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Sample records for adult low-grade gliomas

  1. Multidisciplinary management of adult low grade gliomas.

    PubMed

    Mariş, D; Nica, D; Mohan, D; Moisa, H; Ciurea, A V

    2014-01-01

    Adult hemispheric low grade gliomas (LGG) cover a pathologic spectrum which has specific clinical, histological and molecular characteristics. The optimal management of these tumors is still a controversial topic in international literature. We evaluated scientific papers from the literature (Medline and Cochrane Library to date) and we compared the results found there with our experience, trying to create a pattern of treatment of our own. The advances in microsurgical and neuromonitoring techniques, as well as in neuroimaging, allow for a more aggressive resection of LGG with a significant improvement in overall survival and quality of life. The potential risks of the "wait and see" policy and the neurotoxicity of radiotherapy are challenged by the benefits of careful surgical resection and up-front chemotherapy. The present day treatment strategy, based on recent evidence, should include a maximal surgical resection when possible, with the full preservation of the patients ability, and delayed radiotherapy. The role of temozolomide in the management of LGG and the identification of the therapeutic modality with the best quality of life profile will be determined by ongoing trials. The further characterization of prognostic relevance of molecular markers and data from advanced imaging techniques needs an intensification of research and validation efforts. LGG: low grade gliomas, WHO: World Health Organization, OS: overall survival, PFS: progression-free survival, MRI: Magnetic resonance imaging, MRS: Magnetic resonance spectroscopy, MPFS: malignant progression-free survival, rCBV: Relative Cerebral Blood Volume, QOL: quality of life, FLAIR: Fluid attenuated inversion recovery, MGMT: O6-methylguanine DNA methyltransferase enzyme, DSC MR imaging: Dynamic Susceptibility Contrast Perfusion MR imaging, 1H-MRS: Proton Magnetic Resonance Spectroscopy, IDH1: isocitrate dehydrogenase 1 gene, SPECT: Single-photon emission computed tomography, PET: Positron emission

  2. Adult Supratentorial Low-Grade Glioma: Long-Term Experience at a Single Institution

    SciTech Connect

    Bauman, Glenn; Fisher, Barbara; Watling, Christopher; Cairncross, J. Gregory; Macdonald, David

    2009-12-01

    Purpose: To report the long-term follow-up of a cohort of adult patients with supratentorial low-grade glioma treated at a single institution. Methods and Materials: A cohort of 145 adult patients treated at the London Regional Cancer Program between 1979 and 1995 was reviewed. Results: With a median follow-up of 105 months, the median progression-free survival was 61 months (95% confidence interval, 53-77), and the median overall survival was 118 months (95% confidence interval, 93-129). The 10- and 20-year progression-free and overall survival rate was 18% and 0% and 48% and 22%, respectively. Cox regression analysis confirmed the importance of age, histologic type, presence of seizures, Karnofsky performance status, and initial extent of surgery as prognostic variables for overall and cause-specific survival. Function among long-term survivors without tumor progression was good to excellent for most patients. Conclusion: Low-grade glioma is a chronic disease, with most patients dying of their disease. However, long-term survival with good function is possible. Survival is determined primarily by the disease factors with selection and timing of adjuvant treatments having less influence on outcome.

  3. Neurocognitive effects of proton radiation therapy in adults with low-grade glioma.

    PubMed

    Sherman, Janet Cohen; Colvin, Mary K; Mancuso, Sarah M; Batchelor, Tracy T; Oh, Kevin S; Loeffler, Jay S; Yeap, Beow Y; Shih, Helen A

    2016-01-01

    To understand neurocognitive effects of proton radiation therapy (PRT) in patients with low-grade glioma, we evaluated 20 patients who received this therapy prospectively and over 5 years with a comprehensive neuropsychological battery. 20 patients were evaluated at baseline and at yearly intervals for up to 5 years with a battery of neuropsychological measures that assessed intellectual, attention, executive, visuospatial and memory functions as well as mood and functional status. We evaluated change in cognitive functioning over time. We analyzed the relationship between cognitive performance and tumor location and also examined whether patients' performance differed from that reported in a study of normative practice effects. Overall, patients exhibited stability in cognitive functioning. Tumor location played a role in performance; those with tumors in the left hemisphere versus in the right hemisphere were more impaired at baseline on verbal measures (p < .05). However, we found greater improvement in verbal memory over time in patients with left than with right hemisphere tumors (p < .05). Results of our study, the first to investigate, in depth, neurocognitive effects of PRT in adults with low-grade gliomas, are promising. We hypothesize that the conformal advantage of PRT may contribute to preservation of cognitive functioning, although larger sample sizes and a longer period of study are required. Our study also highlights the need to consider normative practice effects when studying neurocognitive functioning in response to treatment over time, and the need to utilize comprehensive neuropsychological batteries given our findings that differentiate patients with left and right hemisphere tumors.

  4. Awake surgery for hemispheric low-grade gliomas: oncological, functional and methodological differences between pediatric and adult populations.

    PubMed

    Trevisi, Gianluca; Roujeau, Thomas; Duffau, Hugues

    2016-10-01

    Brain mapping through a direct cortical and subcortical electrical stimulation during an awake craniotomy has gained an increasing popularity as a powerful tool to prevent neurological deficit while increasing extent of resection of hemispheric diffuse low-grade gliomas in adults. However, few case reports or very limited series of awake surgery in children are currently available in the literature. In this paper, we review the oncological and functional differences between pediatric and adult populations, and the methodological specificities that may limit the use of awake mapping in pediatric low-grade glioma surgery. This could be explained by the fact that pediatric low-grade gliomas have a different epidemiology and biologic behavior in comparison to adults, with pilocytic astrocytomas (WHO grade I glioma) as the most frequent histotype, and with WHO grade II gliomas less prone to anaplastic transformation than their adult counterparts. In addition, aside from the issue of poor collaboration of younger children under 10 years of age, some anatomical and functional peculiarities of children developing brain (cortical and subcortical myelination, maturation of neural networks and of specialized cortical areas) can influence direct electrical stimulation methodology and sensitivity, limiting its use in children. Therefore, even though awake procedure with cortical and axonal stimulation mapping can be adapted in a specific subgroup of children with a diffuse glioma from the age of 10 years, only few pediatric patients are nonetheless candidates for awake brain surgery.

  5. Neurosurgical management of adult diffuse low grade gliomas in Canada: a multi-center survey.

    PubMed

    Khan, Osaama H; Mason, Warren; Kongkham, Paul N; Bernstein, Mark; Zadeh, Gelareh

    2016-01-01

    Adult diffuse low-grade gliomas are slow growing, World Health Organization grade II lesions with insidious onset and ultimate anaplastic transformation. The timing of surgery remains controversial with polarized practices continuing to govern patient management. As a result, the management of these patients is variable. The goal of this questionnaire was to evaluate practice patterns in Canada. An online invitation for a questionnaire including diagnostic, preoperative, perioperative, and postoperative parameters and three cases with magnetic resonance imaging data with questions to various treatment options in these patients was sent to practicing neurosurgeons and trainees. Survey was sent to 356 email addresses with 87 (24.7%) responses collected. The range of years of practice was less than 10 years 36% (n = 23), 11-20 years 28% (n = 18), over 21 years 37% (n = 24). Twenty-two neurosurgery students of various years of training completed the survey. 94% (n = 47) of surgeons and trainees (n = 20) believe that we do not know the "right treatment". 90% of surgeons do not obtain formal preoperative neurocognitive assessments. 21% (n = 13) of surgeons and 23% of trainees (n = 5) perform a biopsy upon first presentation. A gross total resection was believed to increase progression free survival (surgeons: 75%, n = 46; trainees: 95%, n = 21) and to increase overall survival (surgeons: 64%, n = 39, trainees: 68%, n = 15). Intraoperative MRI was only used by 8% of surgeons. Awake craniotomy was the procedure of choice for eloquent tumors by 80% (n = 48) of surgeons and 100% of trainees. Of those surgeons who perform awake craniotomy 93% perform cortical stimulation and 38% performed subcortical stimulation. Using the aid of three hypothetical cases with progressive complexities in tumor eloquence there was a trend for younger surgeons to operate earlier, and use awake craniotomy to obtain greater extent of resection with the aid of cortical stimulation when compared to

  6. Prognostic significance of IDH mutation in adult low-grade gliomas: a meta-analysis.

    PubMed

    Sun, Hairui; Yin, Lianhu; Li, Showwei; Han, Song; Song, Guangrong; Liu, Ning; Yan, Changxiang

    2013-06-01

    Mutations in the gene encoding isocitrate dehydrogenase (IDH) have been identified in approximately 65-90 % of low-grade gliomas (LGGs). Various studies examining the relationship between IDH mutation with the clinical outcome in patients with LGGs have yielded inconclusive results. The purpose of the present meta-analysis of literature is to determine this effect. We conducted a meta-analysis of 10 studies (937 patients) that evaluated the correlation between IDH mutation and overall survival (OS). For the quantitative aggregation of the survival results, the IDH mutation effect was measured by hazard ratio (HR). Overall, the pooled HR was 0.585 (95 % CI, 0.376-0.911, p = 0.025, random effect model) for patients with IDH mutation vs patients without IDH mutation. IDH mutation was associated with better overall survival of LGGs. At least this trend was observed in our analysis.

  7. Surgical management of low-grade gliomas.

    PubMed

    Gerard, Carter S; Straus, David; Byrne, Richard W

    2014-08-01

    Low-grade gliomas represent a wide spectrum of intra-axial brain tumors with diverse presentations, radiographic and surgical appearances, and prognoses. While there remains a role for biopsy, a growing body of evidence shows that aggressive surgical resection of low-grade gliomas may improve symptoms, extend progression-free survival (PFS), and even cure a select few patients. With the application of preoperative functional imaging, intraoperative navigation, and cortical stimulation, neurosurgeons are able to perform more complete resections while limiting the risk to patients. In this article, we describe the surgical management and current operative techniques used in the treatment of low-grade gliomas.

  8. Management of supratentorial recurrent low-grade glioma: A multidisciplinary experience in 35 adult patients.

    PubMed

    Spitaels, Julien; Devriendt, Daniel; Sadeghi, Niloufar; Luce, Sylvie; De Witte, Olivier; Goldman, Serge; Mélot, Christian; Lefranc, Florence

    2017-09-01

    The management of recurrent diffuse low-grade gliomas (LGGs) is controversial. In the present study, the multidisciplinary management of 35 patients with recurrent LGGs was retrospectively analyzed. Tumor progression or recurrence was defined by clinical, radiological and/or metabolic pejorative evolution. All patients were regularly followed up by a multidisciplinary neuro-oncological group at Hôpital Erasme. Patients with histologically confirmed supratentorial LGGs (7 astrocytoma, 22 oligodendrogliomas and 6 oligoastrocytomas) who had undergone surgery between August 2004 and November 2010 were included. A total of 3 patients exhibited no tumor progression (median follow-up (FU), 81 months; range, 68-108 months). Tumor recurrence occurred in the 32 remaining patients [progression-free survival (PFS), 26 months; range, 2-104 months]. In addition, 25/29 (86%) patients who received surgery alone underwent reoperation at the time of tumor recurrence, and high-grade transformation occurred in 6 of these patients (24%). Furthermore, 4/29 (14%) patients were treated with adjuvant therapy alone (3 chemotherapy and 1 radiotherapy). In the 19 patients with no high-grade transformation at reintervention, 3 received adjuvant therapy and 16 were regularly followed up through multimodal imaging. The PFS time of the patients who underwent reoperation with close FU (n=16) and for the patients receiving adjuvant therapy with or without surgery (n=7) at first recurrence was 10 and 24 months (P=0.005), respectively. However, no significant difference was observed for overall survival (P=0.403). At the time of this study, 22 of the 35 patients included were alive following a median FU time of 109 months (range, 55-136). The results of the present study could change the multidisciplinary approach used into a more aggressive approach with adjuvant therapy, with or without surgery, for the treatment of a select subpopulation of patients with LGGs at the first instance of tumor

  9. Updated therapeutic strategy for adult low-grade glioma stratified by resection and tumor subtype.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Iseki, Hiroshi; Ikuta, Soko; Konishi, Yoshiyuki; Saito, Taichi; Tamura, Manabu; Chernov, Michael; Watanabe, Atsushi; Okamoto, Saori; Maebayashi, Katsuya; Mitsuhashi, Norio; Okada, Yoshikazu

    2013-01-01

    The importance of surgical resection for patients with supratentorial low-grade glioma (LGG) remains controversial. This retrospective study of patients (n = 153) treated between 2000 to 2010 at a single institution assessed whether increasing the extent of resection (EOR) was associated with improved progression-free survival (PFS) and overall survival (OS). Histological subtypes of World Health Organization grade II tumors were as follows: diffuse astrocytoma in 49 patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and 95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and 85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%, and 62.7%, respectively. Patients were divided into two groups by EOR ≥90% and <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in patients with ≥90% EOR. Increased EOR resulted in better PFS for diffuse astrocytoma but not for oligodendroglioma. Multivariate analysis identified age and EOR as parameters significantly associated with OS. The only parameter associated with PFS was EOR. Based on these findings, we established updated therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with astrocytoma will require second-look surgery, whereas patients with oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will be treated with chemotherapy.

  10. Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection.

    PubMed

    Nitta, Masayuki; Muragaki, Yoshihiro; Maruyama, Takashi; Ikuta, Soko; Komori, Takashi; Maebayashi, Katsuya; Iseki, Hiroshi; Tamura, Manabu; Saito, Taiichi; Okamoto, Saori; Chernov, Mikhail; Hayashi, Motohiro; Okada, Yoshikazu

    2015-01-01

    OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was

  11. 'Low grade glioma': an update for radiologists.

    PubMed

    Larsen, Jennifer; Wharton, Steve B; McKevitt, Fiona; Romanowski, Charles; Bridgewater, Caroline; Zaki, Hesham; Hoggard, Nigel

    2017-02-01

    With the recent publication of a new World Health Organization brain tumour classification that reflects increased understanding of glioma tumour genetics, there is a need for radiologists to understand the changes and their implications for patient management. There has also been an increasing trend for adopting earlier, more aggressive surgical approaches to low-grade glioma (LGG) treatment. We will summarize these changes, give some context to the increased role of tumour genetics and discuss the associated implications of their adoption for radiologists. We will discuss the earlier and more radical surgical resection of LGG and what it means for patients undergoing imaging.

  12. Low-grade gliomas: introduction and overview.

    PubMed

    Piepmeier, J M; Christopher, S

    1997-08-01

    This issue of the Journal of Neuro-Oncology is devoted to recent investigations of low-grade gliomas. The purpose of this issue is not to debate the relative merits and liabilities of different management strategies for low-grade gliomas, but to present new data concerning novel and innovative approaches to evaluating these lesions. The common theme of many of these reports represents a departure from grading systems that primarily depend on a morphology-based analysis from light microscopy to classify these tumors. The purpose of this review is to present the reasoning behind the selection of authors for this issue of the Journal of Neuro-Oncology and to provide a format for presentation of new ideas concerning these interesting tumors. It is clear that standard classification systems that address only the morphological characteristics of tumor cells can not adequately represent the wide variation in biological activity that is found with these lesions. It is hoped that these articles will stimulate further interest and research into low-grade gliomas that will one day lead to more effective therapy.

  13. Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study.

    PubMed

    You, Gan; Sha, Zhi-Yi; Yan, Wei; Zhang, Wei; Wang, Yong-Zhi; Li, Shao-Wu; Sang, Lin; Wang, Zi; Li, Gui-Lin; Li, Shou-Wei; Song, Yi-Jun; Kang, Chun-Sheng; Jiang, Tao

    2012-02-01

    Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival.

  14. Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study

    PubMed Central

    You, Gan; Sha, Zhi-Yi; Yan, Wei; Zhang, Wei; Wang, Yong-Zhi; Li, Shao-Wu; Sang, Lin; Wang, Zi; Li, Gui-Lin; Li, Shou-Wei; Song, Yi-Jun; Kang, Chun-Sheng; Jiang, Tao

    2012-01-01

    Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival. PMID:22187341

  15. Subjective Quality of Life in Persons with Low-Grade Glioma and Their Next of Kin

    ERIC Educational Resources Information Center

    Edvardsson, Tanja I.; Ahlstrom, Gerd I.

    2009-01-01

    Patients with low-grade glioma have a longer survival than patients with highly malignant glioma, and for this reason questions of quality of life (QoL) are of particular importance to such patients as well as to their next of kin. No studies have been found in which both adult patients with low-grade glioma and their next of kin have estimated…

  16. Subjective Quality of Life in Persons with Low-Grade Glioma and Their Next of Kin

    ERIC Educational Resources Information Center

    Edvardsson, Tanja I.; Ahlstrom, Gerd I.

    2009-01-01

    Patients with low-grade glioma have a longer survival than patients with highly malignant glioma, and for this reason questions of quality of life (QoL) are of particular importance to such patients as well as to their next of kin. No studies have been found in which both adult patients with low-grade glioma and their next of kin have estimated…

  17. Prospective assessment of activities of daily living using modified Barthel's Index in children and young adults with low-grade gliomas treated with stereotactic conformal radiotherapy.

    PubMed

    Jalali, Rakesh; Dutta, Debnarayan; Kamble, Rashmi; Gupta, Tejpal; Munshi, Anusheel; Sarin, Rajiv; Dinshaw, Ketayun

    2008-12-01

    To report prospective evaluations of activities of daily living (ADL) in young patients with low-grade gliomas treated with stereotactic conformal radiotherapy (SCRT). Between April 2001 and February 2008, 38 children and young adults (age 5-25 years, median 12.5 years) with low-grade gliomas with residual/progressive disease and treated with SCRT were accrued in a prospective protocol. Patients underwent baseline and follow-up ADL assessments by the modified Barthel's battery, which comprises domains of personal hygiene, bathing self, feeding, toilet, stair climbing, dressing, bowel control, bladder control, ambulation, and chair-bed transfer. The patient population consisted of 38 patients (male 29, female 9) with a diagnosis of residual or progressive low-grade glioma (pilocytic astrocytoma in 27, fibrillary astrocytoma in 5, ependymoma in 4, and oligodendroglioma and pleomorphic xanthoastrocytoma in 1 each). Three patients were visually handicapped. Mean of total modified Barthel's ADL score (Barthel' Index, BI) at baseline before staring SCRT was 94.5 (standard deviation 14.8, range 45-100). At 2-year and 3-year follow-up, mean BI was 97.1 and 99, respectively. At baseline pre-radiotherapy assessment, patients with impaired visual function and with low performance status (Karnofsky performance score, KPS < 70) had significantly lower BI than those with normal vision (P low-grade gliomas after surgical intervention had a lower than normal BI

  18. Gamma Knife treatment of low-grade gliomas in children.

    PubMed

    Ekşi, Murat Şakir; Yılmaz, Baran; Akakın, Akın; Toktaş, Zafer Orkun; Kaur, Ahmet Cemil; Demir, Mustafa Kemal; Kılıç, Türker

    2015-11-01

    Low-grade gliomas have good overall survival rates in pediatric patients compared to adults. There are some case series that reported the effectiveness and safety of Gamma Knife radiosurgery, yet they are limited in number of patients. We aimed to review the relevant literature for pediatric low-grade glial tumors treated with stereotactic radiosurgery, specifically Gamma Knife radiosurgery, and to present an exemplary case. A 6-year-old boy was admitted to clinic due to head trauma. He was alert, cooperative, and had no obvious motor or sensorial deficit. A head CT scan depicted a hypodense zone at the right caudate nucleus. The brain magnetic resonance imaging (MRI) depicted a mass lesion at the same location. A stereotactic biopsy was performed. Histopathological diagnosis was low-grade astrocytoma (grade II, World Health Organization (WHO) classification, 2007). Gamma Knife radiosurgery was applied to the tumor bed. Tumor volume was 21.85 cm(3). Fourteen gray was given to 50% isodose segment of the lesion (maximal dose of 28 Gy). The tumor has disappeared totally in 4 months, and the patient was tumor-free 21 months after the initial treatment. The presented literature review represents mostly single-center experiences with different patient and treatment characteristics. Accordingly, a mean/median margin dose of 11.3-15 Gy with Gamma Knife radiosurgery (GKRS) is successful in treatment of pediatric and adult low-grade glial tumor patients. However, prospective studies with a large cohort of pediatric patients should be conducted to make a more comprehensive conclusion for effectiveness and safety of GKRS in pediatric low-grade glial tumors.

  19. Validation of EORTC Prognostic Factors for Adults With Low-Grade Glioma: A Report Using Intergroup 86-72-51

    SciTech Connect

    Daniels, Thomas B.; Brown, Paul D.; Felten, Sara J.; Wu, Wenting; Buckner, Jan C.; Arusell, Robert M.; Curran, Walter J.; Abrams, Ross A.; Schiff, David; Shaw, Edward G.

    2011-09-01

    Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of

  20. Neurodevelopmental Outcomes of Children with Low-Grade Gliomas

    ERIC Educational Resources Information Center

    Ris, M. Douglas; Beebe, Dean W.

    2008-01-01

    As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by…

  1. Neurodevelopmental Outcomes of Children with Low-Grade Gliomas

    ERIC Educational Resources Information Center

    Ris, M. Douglas; Beebe, Dean W.

    2008-01-01

    As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by…

  2. Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas.

    PubMed

    Haris, Mohammad; Kumar, Shaleen; Raj, Mani Karthick; Das, Koilpillai Joseph Maria; Sapru, Shantanu; Behari, Sanjay; Rathore, Ram Kishore Singh; Narayana, Ponnada A; Gupta, Rakesh Kumar

    2008-04-01

    The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)-can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT). Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis. Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins >55 Gy and 50-55 Gy. For the 45 50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the >55 Gy and 50-55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT. Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a threshold dose of 45-50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50-55 Gy and >55 Gy, thus providing an objective measure of radiation effect on NAWM.

  3. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802.

    PubMed

    Shaw, Edward G; Wang, Meihua; Coons, Stephen W; Brachman, David G; Buckner, Jan C; Stelzer, Keith J; Barger, Geoffrey R; Brown, Paul D; Gilbert, Mark R; Mehta, Minesh P

    2012-09-01

    A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG). Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests. In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02). PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.

  4. Randomized Trial of Radiation Therapy Plus Procarbazine, Lomustine, and Vincristine Chemotherapy for Supratentorial Adult Low-Grade Glioma: Initial Results of RTOG 9802

    PubMed Central

    Shaw, Edward G.; Wang, Meihua; Coons, Stephen W.; Brachman, David G.; Buckner, Jan C.; Stelzer, Keith J.; Barger, Geoffrey R.; Brown, Paul D.; Gilbert, Mark R.; Mehta, Minesh P.

    2012-01-01

    Purpose A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG). Patients and Methods Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests. Results In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02). Conclusion PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy. PMID:22851558

  5. Molecular neuropathology of low-grade gliomas and its clinical impact.

    PubMed

    Riemenschneider, M J; Reifenberger, G

    2010-01-01

    The term "low-grade glioma" refers to a heterogeneous group of slowly growing glial tumors corresponding histologically to World Health Organization (WHO) grade I or II. This group includes astrocytic, oligodendroglial, oligoastrocytic and ependymal tumor entities, most of which preferentially manifest in children and young adults. Depending on histological type and WHO grade, growth patterns of low-grade gliomas are quite variable, with some tumors diffusely infiltrating the surrounding central nervous system tissue and others showing well demarcated growth. Furthermore, some entities tend to recur and show spontaneous malignant progression while others remain stable for many years. This review provides a condensed overview concerning the molecular genetics of different glioma entities subsumed under the umbrella of low-grade glioma. For a better understanding the cardinal epidemiological, histological and immunohistochemical features of each entity are shortly outlined. Multiple cytogenetic, chromosomal and genetic alterations have been identified in low-grade gliomas to date, with distinct genetic patterns being associated with the individual tumor subtypes. Some of these molecular alterations may serve as a diagnostic adjunct for tumor classification in cases with ambiguous histological features. However, to date only few molecular changes have been associated with clinical outcome, such as the combined losses of chromosome arms 1p and 19q as a favorable prognostic marker in patients with oligodendroglial tumors.

  6. Circulating anti-filamin C autoantibody as a potential serum biomarker for low-grade gliomas

    PubMed Central

    2014-01-01

    Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable due to its invasive nature. Establishment of serum biomarkers for glioma would be beneficial both for early diagnosis and adequate therapeutic intervention. Filamins are an actin cross-linker and filamin C (FLNC), normally restricted in muscle tissues, offers many signaling molecules an essential communication fields. Recently, filamins have been considered important for tumorigenesis in cancers. Methods We searched for novel glioma-associated antigens by serological identification of antigens utilizing recombinant cDNA expression cloning (SEREX), and found FLNC as a candidate protein. Tissue expressions of FLNC (both in normal and tumor tissues) were examined by immunohistochemistry and quantitative RT-PCR analyses. Serum anti-FLNC autoantibody level was measured by ELISA in normal volunteers and in the patients with various grade gliomas. Results FLNC was expressed in glioma tissues and its level got higher as tumor grade advanced. Anti-FLNC autoantibody was also detected in the serum of glioma patients, but its levels were inversely correlated with the tissue expression. Serum anti-FLNC autoantibody level was significantly higher in low-grade glioma patients than in high-grade glioma patients or in normal volunteers, which was confirmed in an independent validation set of patients’ sera. The autoantibody levels in the patients with meningioma or cerebral infarction were at the same level of normal volunteers, and they were significantly lower than that of low-grade gliomas. Total IgG and anti-glutatione S-transferase (GST) antibody level were not altered among the patient groups, which suggest that the autoantibody response was specific for FLNC. Conclusions The present results suggest that serum anti-FLNC autoantibody can be a potential serum biomarker for early diagnosis of low-grade gliomas while it needs a large-scale clinical study

  7. Stereotactic radiosurgery of deeply seated low grade gliomas.

    PubMed

    Barcia, J A; Barcia-Salorio, J L; Ferrer, C; Ferrer, E; Algás, R; Hernández, G

    1994-01-01

    The authors report the results of a series of 16 cases of low-grade gliomas in whom radiosurgery was performed. This series started in 1977. All the tumours received a single radiosurgical session (with a mean dose of 21.7 Gy, 5-10 mm. collimator; one patient received two sessions and in another patient two different targets were irradiated in the same session). Prior to radiosurgery, six patients received conventional external fractionated radiotherapy, with two lateral fields of up to 10 x 10 cm. and a mean dose of 55.1 Gy and another six patients with tumours less than 5 cm. in diameter, received stereotactic radiotherapy using four fields of up to 5 x 5 cm. and a mean dose of 53.1 Gy. In both cases, conventional fractionation was used, giving a dose of 1.8 to 2 Gy/day. The tumour disappeared in 8 cases (50%) and shunk or ceased its growth in 5 additional cases (31%). In 3 cases of brainstem gliomas in which the clinical condition was previously very poor there was no evolutional change and the patients eventually died. We conclude that radiosurgery is effective in the treatment of deeply seated low-grade gliomas, where it may become the treatment of choice in the absence of other more definitive choices.

  8. A comprehensive review of paediatric low-grade diffuse glioma: pathology, molecular genetics and treatment.

    PubMed

    Ryall, Scott; Tabori, Uri; Hawkins, Cynthia

    2017-04-01

    Gliomas are the most common central nervous system neoplasms affecting children and can be both high- and low-grade. Paediatric low-grade glioma may be either World Health Organization grade I or grade II. Despite being classified as grade II diffuse astrocytoma, these neoplasms arising in children are distinct clinically and molecularly from their adult counterparts. They do not tend to progress to higher grade lesions and only rarely harbour an IDH mutation. Here, we review the clinical, histologic and molecular features of paediatric grade II diffuse glioma, highlighting their diagnostic criteria, prevalence across brain locations, their most common molecular features and how to test for them, and lastly the current status of therapeutic options available for their treatment.

  9. Association of carcinoid tumor and low grade glioma

    PubMed Central

    2012-01-01

    Background Lung carcinoid tumor and low grade glioma are two uncommon malignancies. Patients and methods We report the case of 24-year-old man who presented with respiratory disease. Imaging investigations showed a right lung tumor and histological analysis confirmed a typical carcinoid tumor. As part of initial staging, brain MRI revealed an asymptomatic right frontal lesion. First, a right pulmonary lobectomy was performed without adjuvant treatment. In second time, brain tumorectomy was performed. Histological examination confirmed the diagnosis of low grade glioma (LGG). The patient remained in complete remission 2.5 years after the initial diagnosis. Results This is the first case reporting the association between LGG and lung carcinoid tumor, while no association between LGG and a systemic tumor have been published to date. Association of lung carcinoid tumor with other malignant diseases has been reported but remained uncommon. Only minimal data support a potential molecular common origin. Conclusion This exceptional association may be fortuitous. However, their concomitant diagnoses suggest a potential association between both rare diseases. A genetic susceptibility remains possible. PMID:23137305

  10. Association of carcinoid tumor and low grade glioma.

    PubMed

    Tabouret, Emeline; Barrié, Maryline; Vicier, Cecile; Gonçalves, Anthony; Chinot, Olivier; Viens, Patrice; Madroszyk, Anne

    2012-11-08

    Lung carcinoid tumor and low grade glioma are two uncommon malignancies. We report the case of 24-year-old man who presented with respiratory disease. Imaging investigations showed a right lung tumor and histological analysis confirmed a typical carcinoid tumor. As part of initial staging, brain MRI revealed an asymptomatic right frontal lesion. First, a right pulmonary lobectomy was performed without adjuvant treatment. In second time, brain tumorectomy was performed. Histological examination confirmed the diagnosis of low grade glioma (LGG). The patient remained in complete remission 2.5 years after the initial diagnosis. This is the first case reporting the association between LGG and lung carcinoid tumor, while no association between LGG and a systemic tumor have been published to date. Association of lung carcinoid tumor with other malignant diseases has been reported but remained uncommon. Only minimal data support a potential molecular common origin. This exceptional association may be fortuitous. However, their concomitant diagnoses suggest a potential association between both rare diseases. A genetic susceptibility remains possible.

  11. The etiopathogenesis of diffuse low-grade gliomas.

    PubMed

    Darlix, Amélie; Gozé, Catherine; Rigau, Valérie; Bauchet, Luc; Taillandier, Luc; Duffau, Hugues

    2017-01-01

    The origins of diffuse low-grade gliomas (DLGG) are unknown. Beyond some limited data on their temporal and cellular origins, the mechanisms and risk factors involved are poorly known. First, based on strong relationships between DLGG development and the eloquence of brain regions frequently invaded by these tumors, we propose a "functional theory" to explain the origin of DLGG. Second, the biological pathways involved in DLGG genesis may differ according to tumor location (anatomo-molecular correlations). The cellular and molecular mechanisms of such "molecular theory" will be reviewed. Third, the geographical distribution of diffuse WHO grade II-III gliomas within populations is heterogeneous, suggesting possible environmental risk factors. We will discuss this "environmental theory". Finally, we will summarize the current knowledge on genetic susceptibility in gliomas ("genetic predisposition theory"). These crucial issues illustrate the close relationships between the pathophysiology of gliomagenesis, the anatomo-functional organization of the brain, and personalized management of DLGG patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas

    ClinicalTrials.gov

    2015-12-14

    Adult Brain Tumor; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Grade II Meningioma; Adult Melanocytic Lesion; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma; Adult Pineocytoma; Recurrent Adult Brain Tumor

  13. The role of radiotherapy in the management of patients with diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.

    PubMed

    Ryken, Timothy C; Parney, Ian; Buatti, John; Kalkanis, Steven N; Olson, Jeffrey J

    2015-12-01

    (1) What is the optimal role of external beam radiotherapy in the management of adult patients with newly diagnosed low-grade glioma (LGG) in terms of improving outcome (i.e., survival, complications, seizure control or other reported outcomes of interest)? (2) Which radiation strategies (dose, timing, fractionation, stereotactic radiation, brachytherapy, chemotherapy) improve outcomes compared to standard external beam radiation therapy in the initial management of low grade gliomas in adults? (3) Do specific factors (e.g., age, volume, extent of resection, genetic subtype) identify subgroups with better outcomes following radiation therapy than the general population of adults with newly diagnosed low-grade gliomas? These recommendations apply to adults with newly diagnosed diffuse LGG. OUTCOMES IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW GRADE GLIOMA TREATED WITH RADIOTHERAPY: Level I Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong progression free survival, irrespective of extent of resection. Level II Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults as an equivalent alternative to observation in preserving cognitive function, irrespective of extent of resection. Level III Radiotherapy is recommended in the management of newly diagnosed low grade glioma in adults to improve seizure control in patients with epilepsy and subtotal resection. Level III Radiotherapy is recommended in the management of newly diagnosed low-grade glioma in adults to prolong overall survival in patients with subtotal resection. Level III Consideration of the risk of radiation induced morbidity, including cognitive decline, imaging abnormalities, metabolic dysfunction and malignant transformation, is recommended when the delivery of radiotherapy is selected in the management of newly diagnosed low-grade glioma in adults. STRATEGIES OF RADIOTHERAPY IN ADULT PATIENTS WITH NEWLY DIAGNOSED LOW

  14. Molecular classification of low-grade diffuse gliomas.

    PubMed

    Kim, Young-Ho; Nobusawa, Sumihito; Mittelbronn, Michel; Paulus, Werner; Brokinkel, Benjamin; Keyvani, Kathy; Sure, Ulrich; Wrede, Karsten; Nakazato, Yoichi; Tanaka, Yuko; Vital, Anne; Mariani, Luigi; Stawski, Robert; Watanabe, Takuya; De Girolami, Umberto; Kleihues, Paul; Ohgaki, Hiroko

    2010-12-01

    The current World Health Organization classification recognizes three histological types of grade II low-grade diffuse glioma (diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma). However, the diagnostic criteria, in particular for oligoastrocytoma, are highly subjective. The aim of our study was to establish genetic profiles for diffuse gliomas and to estimate their predictive impact. In this study, we screened 360 World Health Organization grade II gliomas for mutations in the IDH1, IDH2, and TP53 genes and for 1p/19q loss and correlated these with clinical outcome. Most tumors (86%) were characterized genetically by TP53 mutation plus IDH1/2 mutation (32%), 1p/19q loss plus IDH1/2 mutation (37%), or IDH1/2 mutation only (17%). TP53 mutations only or 1p/19q loss only was rare (2 and 3%, respectively). The median survival of patients with TP53 mutation ± IDH1/2 mutation was significantly shorter than that of patients with 1p/19q loss ± IDH1/2 mutation (51.8 months vs. 58.7 months, respectively; P = 0.0037). Multivariate analysis with adjustment for age and treatment confirmed these results (P = 0.0087) and also revealed that TP53 mutation is a significant prognostic marker for shorter survival (P = 0.0005) and 1p/19q loss for longer survival (P = 0.0002), while IDH1/2 mutations are not prognostic (P = 0.8737). The molecular classification on the basis of IDH1/2 mutation, TP53 mutation, and 1p/19q loss has power similar to histological classification and avoids the ambiguity inherent to the diagnosis of oligoastrocytoma.

  15. Outcomes of Multidisciplinary Management in Pediatric Low-Grade Gliomas

    SciTech Connect

    Oh, Kevin S.; Hung, Jonathan; Robertson, Patricia L.; Garton, Hugh J.; Muraszko, Karin M.; Sandler, Howard M.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. Methods and Materials: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). Results: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 {+-} 4% (standard error) and 94 {+-} 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age {<=}5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 {+-} 9% and 100%, respectively. Conclusions: Low-grade gliomas in children {<=}5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.

  16. Pediatric low-grade gliomas: implications of the biologic era.

    PubMed

    Packer, Roger J; Pfister, Stephan; Bouffet, Eric; Avery, Robert; Bandopadhayay, Pratiti; Bornhorst, Miriam; Bowers, Daniel C; Ellison, David; Fangusaro, Jason; Foreman, Nicholas; Fouladi, Maryam; Gajjar, Amar; Haas-Kogan, Daphne; Hawkins, Cynthia; Ho, Cheng-Ying; Hwang, Eugene; Jabado, Nada; Kilburn, Lindsay B; Lassaletta, Alvaro; Ligon, Keith L; Massimino, Maura; Meeteren, Schouten-van; Mueller, Sabine; Nicolaides, Theo; Perilongo, Giorgio; Tabori, Uri; Vezina, Gilbert; Warren, Katherine; Witt, Olaf; Zhu, Yuan; Jones, David T; Kieran, Mark

    2017-06-01

    For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management. Molecular-targeted therapies should be integrated expeditiously, but also carefully into the management of these tumors and success measured not only by radiographic responses or stability, but also by functional outcomes. These trials need to be carried out with the caveat that the long-term impact of molecularly targeted therapy on the developing nervous system, especially with long duration treatment, is essentially unknown. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Advances in the management of low-grade gliomas.

    PubMed

    Nageswara Rao, Amulya A; Packer, Roger J

    2014-01-01

    Low-grade gliomas (LGGs) represent the most common childhood brain tumors and are a histologically heterogenous group of tumors. Most LGGs are surgically resectable with excellent 10-year overall survival outcomes of more than 90 % with surgery alone. Tumors not amenable to surgical resection and those with an aggressive biology are more challenging to treat. Conventional radiotherapy is a more efficacious method of long-term tumor control than chemotherapy. However, radiation is associated with significant cognitive, endocrine, and cerebrovascular late effects, making chemotherapy an often-preferred modality over radiotherapy, especially in younger children. Multiple chemotherapy regimens have been evaluated over the past few decades with comparable survival outcomes and differing toxicity profiles. Newer regimens containing antiangiogenic agents also show promise. Recent molecular studies have implicated the BRAF oncogene, a key regulator of the MAPK pathway, and the AKT/mTOR pathway in pediatric LGG tumorigenesis. This has opened up promising new avenues for targeted therapy, with many agents currently under investigation.

  18. Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas

    PubMed Central

    Pallud, Johan; Blonski, Marie; Mandonnet, Emmanuel; Audureau, Etienne; Fontaine, Denys; Sanai, Nader; Bauchet, Luc; Peruzzi, Philippe; Frénay, Marc; Colin, Philippe; Guillevin, Rémy; Bernier, Valérie; Baron, Marie-Hélène; Guyotat, Jacques; Duffau, Hugues; Taillandier, Luc; Capelle, Laurent

    2013-01-01

    Background Supratentorial diffuse low-grade gliomas present a slow macroscopic tumor growth that can be quantified through the measurement of their velocity of diametric expansion. We assessed whether spontaneous velocity of diametric expansion can predict long-term outcomes as a categorical variable and as a continuous predictor. Methods A total of 407 adult patients with newly diagnosed supratentorial diffuse low-grade gliomas in adults were studied. Results The mean spontaneous velocity of diametric expansion before first-line treatment was 5.8 ± 6.3 mm/year. During the follow-up (mean, 86.5 ± 59.4 months), 209 patients presented a malignant transformation, and 87 died. The malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (median, 103 and 249 months, respectively) than in cases of fast velocity of diametric expansion (median, 35 and 91 months, respectively; P < .001). In multivariate analyses, spontaneous velocity of diametric expansion as a categorical variable (<4, ≥4 and <8, ≥8 and <12, ≥12 mm/year) was an independent prognostic factor for malignant progression-free survival (P < .001; hazard ratio, 3.87; 95% confidence interval [CI], 2.67–5.52) and for overall survival (P < .001; hazard ratio, 4.62; 95% CI, 2.58–7.97). Velocity of diametric expansion was also an independent prognostic factor for overall survival as a continuous predictor, showing a linear relationship between overall survival and spontaneous velocity of diametric expansion (hazard ratio, 1.09 per one unit increase; 95% CI, 1.06–1.12; P < .001). Conclusions Independent of the molecular status, the spontaneous velocity of diametric expansion allows the identification of rapidly growing diffuse low-grade gliomas (at higher risk of worsened evolution) during the pretherapeutic period and without delaying treatment. PMID:23393207

  19. Intra-rater variability in low-grade glioma segmentation.

    PubMed

    Bø, Hans Kristian; Solheim, Ole; Jakola, Asgeir Store; Kvistad, Kjell-Arne; Reinertsen, Ingerid; Berntsen, Erik Magnus

    2017-01-01

    Assessment of size and growth are key radiological factors in low-grade gliomas (LGGs), both for prognostication and treatment evaluation, but the reliability of LGG-segmentation is scarcely studied. With a diffuse and invasive growth pattern, usually without contrast enhancement, these tumors can be difficult to delineate. The aim of this study was to investigate the intra-observer variability in LGG-segmentation for a radiologist without prior segmentation experience. Pre-operative 3D FLAIR images of 23 LGGs were segmented three times in the software 3D Slicer. Tumor volumes were calculated, together with the absolute and relative difference between the segmentations. To quantify the intra-rater variability, we used the Jaccard coefficient comparing both two (J2) and three (J3) segmentations as well as the Hausdorff Distance (HD). The variability measured with J2 improved significantly between the two last segmentations compared to the two first, going from 0.87 to 0.90 (p = 0.04). Between the last two segmentations, larger tumors showed a tendency towards smaller relative volume difference (p = 0.07), while tumors with well-defined borders had significantly less variability measured with both J2 (p = 0.04) and HD (p < 0.01). We found no significant relationship between variability and histological sub-types or Apparent Diffusion Coefficients (ADC). We found that the intra-rater variability can be considerable in serial LGG-segmentation, but the variability seems to decrease with experience and higher grade of border conspicuity. Our findings highlight that some criteria defining tumor borders and progression in 3D volumetric segmentation is needed, if moving from 2D to 3D assessment of size and growth of LGGs.

  20. Sexuality after surgery for diffuse low-grade glioma

    PubMed Central

    Surbeck, Werner; Herbet, Guillaume; Duffau, Hugues

    2015-01-01

    Background Although neurological and neurocognitive outcomes have previously been studied after resection of diffuse low-grade glioma (DLGG), the impact of surgery on sexual life has not been investigated. Our aim was to assess whether DLGG surgery could have consequences on sexual experience. Methods Anonymous standardized questionnaires concerning sexual functioning, including the Arizona Sexual Experiences Scale (ASEX) and a subjective statement, were completed by 32 patients who underwent surgery for DLGG. All patients returned to a normal social and professional life following resection, with neither neurological deficits nor depression. No radiotherapy was administered, and patients who received chemotherapy were without treatment for at least 1 year. Results Seventeen patients (53%) reported a postoperative sexual change, with subjective deterioration in 15 (88%) and improvement in 2 (12%). Sexual dysfunction according to ASEX affected 9 of 15 women (60%) and 5 of 17 men (29%). Right-sided resections were associated with more difficulties in reaching orgasm than left-sided resections (P < .02). Men with temporal lobe resection displayed more reduction in sexual drive (P < .003) and sexual arousal (P < .004) than women, resulting in significant higher overall ASEX scores for temporal lobe resections in men (P = .01). Men remaining on antiepileptic drugs who underwent right-sided resection displayed higher overall ASEX scores than women (P = .031). Conclusions This first evaluation of sexual life after surgery for DLGG suggests that sexual dysfunction is common in this population. Therefore, we suggest that sexual health should consistently be addressed during routine pre- and postoperative examination of patients with DLGG. PMID:25699682

  1. Assessment of quality of life in patients treated for low-grade glioma: a preliminary report.

    PubMed Central

    Taphoorn, M J; Heimans, J J; Snoek, F J; Lindeboom, J; Oosterink, B; Wolbers, J G; Karim, A B

    1992-01-01

    In this pilot study quality of life was assessed in fourteen adult patients who were treated for a low-grade glioma with surgery and radiotherapy at least one year previously. Apart from widely used parameters, such as the neurological and functional status, the patients' cognitive functioning and actual affective status were determined. In addition the patients were interviewed to evaluate various aspects of quality of life. Generally no serious focal neurological deficits were found, although psychological examination showed serious cognitive and affective disturbances in most cases. Self report measures concerning cognitive functioning were not in all cases in accordance with objective test results. When the results of treatment in glioma patients are evaluated assessment of quality of life, including neuropsychological functioning, should be performed, especially as new therapeutic strategies are being developed. PMID:1602310

  2. Imaging of adult brainstem gliomas.

    PubMed

    Purohit, Bela; Kamli, Ali A; Kollias, Spyros S

    2015-04-01

    Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as 18F-fluoro-ethyl-tyrosine positron emission tomography (18F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Network Plasticity and Intraoperative Mapping for Personalized Multimodal Management of Diffuse Low-Grade Gliomas.

    PubMed

    Ghinda, Cristina Diana; Duffau, Hugues

    2017-01-01

    Gliomas are the most frequent primary brain tumors and include a variety of different histological tumor types and malignancy grades. Recent achievements in terms of molecular and imaging fields have created an unprecedented opportunity to perform a comprehensive interdisciplinary assessment of the glioma pathophysiology, with direct implications in terms of the medical and surgical treatment strategies available for patients. The current paradigm shift considers glioma management in a comprehensive perspective that takes into account the intricate connectivity of the cerebral networks. This allowed significant improvement in the outcome of patients with lesions previously considered inoperable. The current review summarizes the current theoretical framework integrating the adult human brain plasticity and functional reorganization within a dynamic individualized treatment strategy for patients affected by diffuse low-grade gliomas. The concept of neuro-oncology as a brain network surgery has major implications in terms of the clinical management and ensuing outcomes, as indexed by the increased survival and quality of life of patients managed using such an approach.

  4. Network Plasticity and Intraoperative Mapping for Personalized Multimodal Management of Diffuse Low-Grade Gliomas

    PubMed Central

    Ghinda, Cristina Diana; Duffau, Hugues

    2017-01-01

    Gliomas are the most frequent primary brain tumors and include a variety of different histological tumor types and malignancy grades. Recent achievements in terms of molecular and imaging fields have created an unprecedented opportunity to perform a comprehensive interdisciplinary assessment of the glioma pathophysiology, with direct implications in terms of the medical and surgical treatment strategies available for patients. The current paradigm shift considers glioma management in a comprehensive perspective that takes into account the intricate connectivity of the cerebral networks. This allowed significant improvement in the outcome of patients with lesions previously considered inoperable. The current review summarizes the current theoretical framework integrating the adult human brain plasticity and functional reorganization within a dynamic individualized treatment strategy for patients affected by diffuse low-grade gliomas. The concept of neuro-oncology as a brain network surgery has major implications in terms of the clinical management and ensuing outcomes, as indexed by the increased survival and quality of life of patients managed using such an approach. PMID:28197403

  5. EGFR immunolabeling pattern may discriminate low-grade gliomas from gliosis.

    PubMed

    Burel-Vandenbos, Fanny; Benchetrit, Maxime; Miquel, Catherine; Fontaine, Denys; Auvergne, Romane; Lebrun-Frenay, Christine; Cardot-Leccia, Nathalie; Michiels, Jean-François; Paquis-Flucklinger, Veronique; Virolle, Thierry

    2011-04-01

    Overexpression of epidermal growth factor receptor (EGFR) is common in gliomas. Gliomas are infiltrating tumors in which neoplastic glial cells can be intermingled with reactive glial cells, particularly in diffuse low-grade gliomas. As overexpression of EGFR has also been described in gliosis, it can be difficult to evaluate EGFR immunolabeling in diffuse low-grade gliomas because of this cell mix. We compared EGFR immunolabeling between gliosis and low-grade gliomas in order to identify distinctive criteria. We studied EGFR expression in 28 cases of gliosis and 39 diffuse low-grade gliomas (23 astrocytomas and 16 oligodendrogliomas). EGFR immunohistochemistry staining was performed on paraffin-embedded sections with a mouse monoclonal antibody (clone 2-18C9; Dako). Co-expression of EGFR with Olig2, Mib-1, and p53 was assessed in seven cases of low-grade gliomas using double immunolabeling. Then, EGFR immunostaining was blindly tested on 22 small specimens of indeterminate glial lesions provided by a reference neuropathological center. Two pathologists of our local center were asked to classify the lesions into diffuse low-grade glioma or gliosis according to the pattern of EGFR expression. Weak expression of EGFR was commonly detected in gliosis (23/28 cases). Strongly-stained cells were absent. Positive cells had reactive glial cell morphology. EGFR expression in gliomas was characterized by constant strongly-stained cells (39/39 cases). All strongly-stained cells had a high nucleus-to-cytoplasm ratio, with minimal to moderate nuclear atypia. Most of the strongly EGFR-positive cells were Olig2-positive. All the cases displayed cells co-expressing EGFR and Mib-1. In three p53-positive tumors, many p53-positive cells were strongly EGFR-positive. On the basis of EGFR expression, 14 out of the 22 indeterminate cases were classified as gliomas and eight as gliosis by both pathologists. Concordance with the initial diagnosis established by the reference center and

  6. The role of neuropathology in the management of patients with diffuse low grade glioma: A systematic review and evidence-based clinical practice guideline.

    PubMed

    Cahill, Daniel P; Sloan, Andrew E; Nahed, Brian V; Aldape, Kenneth D; Louis, David N; Ryken, Timothy C; Kalkanis, Steven N; Olson, Jeffrey J

    2015-12-01

    Adult patients (age ≥18 years) who have suspected low-grade diffuse glioma. What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult? LEVEL I: Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma. Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis. A resection specimen is preferred over a biopsy specimen, to minimize the potential for sampling error issues. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for IDH1 mutation (R132H and/or others) warranted? If so, is there a preferred method? IDH gene mutation assessment, via IDH1 R132H antibody and/or IDH1/2 mutation hotspot sequencing, is highly-specific for low-grade diffuse glioma, and is recommended as an additional test for classification and prognosis. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is testing for 1p/19q loss warranted? If so, is there a preferred method? 1p/19q loss-of-heterozygosity testing, by FISH, array-CGH or PCR, is recommended as an additional test in oligodendroglial cases for prognosis and potential treatment planning. Patients with histologically-proven WHO grade II diffuse glioma. In adult patients (age ≥18 years) with histologically-proven WHO grade II diffuse glioma, is MGMT promoter methylation testing warranted? If so, is there a preferred method? There is insufficient evidence to recommend methyl-guanine methyl-transferase (MGMT) promoter methylation testing as a routine for low-grade diffuse gliomas. It is recommended that patients be enrolled in properly designed clinical trials to assess the value of this and related

  7. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1.

    PubMed

    Ramkissoon, Lori A; Horowitz, Peleg M; Craig, Justin M; Ramkissoon, Shakti H; Rich, Benjamin E; Schumacher, Steven E; McKenna, Aaron; Lawrence, Michael S; Bergthold, Guillaume; Brastianos, Priscilla K; Tabak, Barbara; Ducar, Matthew D; Van Hummelen, Paul; MacConaill, Laura E; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J; Hill, D Ashley; Pomeroy, Scott L; Eberhart, Charles G; Dunn, Ian F; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A; Santagata, Sandro; Hahn, William C; Stiles, Charles D; Ligon, Azra H; Kieran, Mark W; Beroukhim, Rameen; Ligon, Keith L

    2013-05-14

    Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas.

  8. Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1

    PubMed Central

    Ramkissoon, Lori A.; Horowitz, Peleg M.; Craig, Justin M.; Ramkissoon, Shakti H.; Rich, Benjamin E.; Schumacher, Steven E.; McKenna, Aaron; Lawrence, Michael S.; Bergthold, Guillaume; Brastianos, Priscilla K.; Tabak, Barbara; Ducar, Matthew D.; Van Hummelen, Paul; MacConaill, Laura E.; Pouissant-Young, Tina; Cho, Yoon-Jae; Taha, Hala; Mahmoud, Madeha; Bowers, Daniel C.; Margraf, Linda; Tabori, Uri; Hawkins, Cynthia; Packer, Roger J.; Hill, D. Ashley; Pomeroy, Scott L.; Eberhart, Charles G.; Dunn, Ian F.; Goumnerova, Liliana; Getz, Gad; Chan, Jennifer A.; Santagata, Sandro; Hahn, William C.; Stiles, Charles D.; Ligon, Azra H.; Kieran, Mark W.; Beroukhim, Rameen; Ligon, Keith L.

    2013-01-01

    Pediatric low-grade gliomas (PLGGs) are among the most common solid tumors in children but, apart from BRAF kinase mutations or duplications in specific subclasses, few genetic driver events are known. Diffuse PLGGs comprise a set of uncommon subtypes that exhibit invasive growth and are therefore especially challenging clinically. We performed high-resolution copy-number analysis on 44 formalin-fixed, paraffin-embedded diffuse PLGGs to identify recurrent alterations. Diffuse PLGGs exhibited fewer such alterations than adult low-grade gliomas, but we identified several significantly recurrent events. The most significant event, 8q13.1 gain, was observed in 28% of diffuse astrocytoma grade IIs and resulted in partial duplication of the transcription factor MYBL1 with truncation of its C-terminal negative-regulatory domain. A similar recurrent deletion-truncation breakpoint was identified in two angiocentric gliomas in the related gene v-myb avian myeloblastosis viral oncogene homolog (MYB) on 6q23.3. Whole-genome sequencing of a MYBL1-rearranged diffuse astrocytoma grade II demonstrated MYBL1 tandem duplication and few other events. Truncated MYBL1 transcripts identified in this tumor induced anchorage-independent growth in 3T3 cells and tumor formation in nude mice. Truncated transcripts were also expressed in two additional tumors with MYBL1 partial duplication. Our results define clinically relevant molecular subclasses of diffuse PLGGs and highlight a potential role for the MYB family in the biology of low-grade gliomas. PMID:23633565

  9. Statistical evaluation of manual segmentation of a diffuse low-grade glioma MRI dataset.

    PubMed

    Ben Abdallah, Meriem; Blonski, Marie; Wantz-Mezieres, Sophie; Gaudeau, Yann; Taillandier, Luc; Moureaux, Jean-Marie

    2016-08-01

    Software-based manual segmentation is critical to the supervision of diffuse low-grade glioma patients and to the optimal treatment's choice. However, manual segmentation being time-consuming, it is difficult to include it in the clinical routine. An alternative to circumvent the time cost of manual segmentation could be to share the task among different practitioners, providing it can be reproduced. The goal of our work is to assess diffuse low-grade gliomas' manual segmentation's reproducibility on MRI scans, with regard to practitioners, their experience and field of expertise. A panel of 13 experts manually segmented 12 diffuse low-grade glioma clinical MRI datasets using the OSIRIX software. A statistical analysis gave promising results, as the practitioner factor, the medical specialty and the years of experience seem to have no significant impact on the average values of the tumor volume variable.

  10. Spontaneous Intracerebral Hematoma in Low-Grade Glioma After 14 Years of Follow-Up.

    PubMed

    Joković, Miloš; Bogosavljević, Vojislav; Nikolić, Igor; Jovanović, Nemanja

    We are reporting the case of a 53-year old woman presenting to our hospital with a hemorrhagic low-grade glioma (LGG). She was admitted to a nearby general hospital where she had presented with aphasia, right hemiplegia and change of mental status. Computer tomography (CT) images showed a left temporo-parietal hemorrhage with mass effect. She was transferred to our hospital neuro-intensive care unit where emergency craniotomy was performed. A tumor with hematoma was removed and further histopathology analysis revealed tumor progression. We reviewed the literature reporting cases of central nervous system tumors hemorrhage and found that these types of events are exquisitely rare in adults with LGG. However these events are possible, suggesting that it should be included in the differential diagnosis of any patient presenting with intracranial hemorrhage. This case raises questions regarding the benefit of early versus late intervention for patients known to have LGG.

  11. Malignant glioblastomatous transformation of a low-grade glioma in a child.

    PubMed

    Unal, Ekrem; Koksal, Yavuz; Cimen, Omer; Paksoy, Yahya; Tavli, Lema

    2008-12-01

    The term of low-grade glioma addresses a favorable clinical outcome with indolent histological features in general consideration; however, recent studies underline the inconsistency, which originates from the accumulation of different histologic subtypes in this terminology. The malignant transformation of a low-grade glioma is unusual but presents a poor prognosis. We report a case of a 12-year-old boy, who was referred for complaints of recurrent seizures. His physical examination was unremarkable, but it was learned that a peripheral mass lesion located on the left posterior parietal lobe--which had been thought to be a low-grade glioma--had been detected on a magnetic resonance imaging 2 years ago at a different hospital. The patient was then treated with valproate and carbamazepine for the seizures and advised to be followed up without any additional diagnostic and therapeutic studies for his suspected low-grade glioma. A recent magnetic resonance imaging study showed enlargements of the mass and surrounding edema with additional necrosis. Surgical excision of the tumor was performed. After the diagnosis of glioblastoma multiforme, the patient received radiation therapy and chemotherapy with a good clinical recovery without any evidence of residue or recurrence at 12-month follow-up. The first line treatment modality in the management of low-grade glioma--especially in suitable patients--is clearly surgery. The gross total resection guarantees the distinguishing of the histological types of the low-grade gliomas and reflects the biologic behavior of these tumors. Observation without surgery must be reserved for selected inoperable cases.

  12. Molecular Markers in Low-Grade Glioma-Toward Tumor Reclassification.

    PubMed

    Olar, Adriana; Sulman, Erik P

    2015-07-01

    Low-grade diffuse gliomas are a heterogeneous group of primary glial brain tumors with highly variable survival. Currently, patients with low-grade diffuse gliomas are stratified into risk subgroups by subjective histopathologic criteria with significant interobserver variability. Several key molecular signatures have emerged as diagnostic, prognostic, and predictor biomarkers for tumor classification and patient risk stratification. In this review, we discuss the effect of the most critical molecular alterations described in diffuse (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, BRAF(V600E), and C11orf95-RELA fusion) gliomas. These molecular features reflect tumor heterogeneity and have specific associations with patient outcome that determine appropriate patient management. This has led to an important, fundamental shift toward developing a molecular classification of World Health Organization grade II-III diffuse glioma.

  13. Assessment of diffusion tensor imaging metrics in differentiating low-grade from high-grade gliomas.

    PubMed

    El-Serougy, Lamiaa; Abdel Razek, Ahmed Abdel Khalek; Ezzat, Amani; Eldawoody, Hany; El-Morsy, Ahmad

    2016-10-01

    The aim of this article is to assess diffusion tensor imaging (DTI) metrics in differentiating low-grade from high-grade gliomas. A prospective study was conducted on 35 patients with gliomas who underwent DTI. Gliomas were classified into low-grade and high-grade gliomas. The fractional anisotropy (FA), mean diffusivity (MD), linear coefficient (CL), planar coefficient (CP) and spherical coefficient (CS) of the solid tumoral part and peri-tumoral regions were calculated. There was significant difference (p = 0.001) in MD of the solid tumoral part of low-grade (1.78 ± 0.33 × 10(-3 )mm(2)/s) and high-grade (1.16 ± 0.22 × 10(-3 )mm(2)/s) gliomas. The selection of 1.42 × 10(-3 )mm(2)/s as a cutoff value of MD of the tumoral part was used to differentiate low-grade and high-grade gliomas; the best results were obtained with area under the curve (AUC) of 0.957 and accuracy of 91.4%. There was a significant difference in FA, MD, CP and CS of peri-tumoral regions of both groups with p values of 0.006, 0.042, 0.030 and 0.037, respectively. The cutoff values of MD, FA, CS and CP of the peri-tumoral region used to differentiate low-grade from high-grade gliomas were 1.24, 0.315, 0.726 and 0.321 with AUC of 0.694, 0.773, 0.734 and 0.724 and accuracy of 68.6%, 80.0%, 74.3% and 74.3%, respectively. The combined MD of the solid tumoral part and FA of the peri-tumoral region used to differentiate low-grade from high-grade gliomas revealed AUC of 0.974 and accuracy of 88.6%. We conclude that the combination of MD of the solid tumoral part and FA of the peri-tumoral region is a noninvasive method to differentiate low-grade from high-grade gliomas. © The Author(s) 2016.

  14. Diagnostic challenges, management and outcomes of midline low-grade gliomas.

    PubMed

    Waqar, Mueez; Hanif, Shahid; Rathi, Nitika; Das, Kumar; Zakaria, Rasheed; Brodbelt, Andrew R; Walker, Carol; Jenkinson, Michael D

    2014-11-01

    Low-grade gliomas (LGGs) are slow-growing and diffusely infiltrating tumours constituting 25-30 % of adult gliomas. Rarely, these tumours may arise in the cerebral midline, including the thalamus, hypothalamus, tectum and brainstem. Here we present a contemporary experience with midline LGGs. Midline LGGs were identified from a retrospective database of adult patients who received a histological diagnosis of WHO grade II glioma between 2006 and 2012 at a single institution. Location, radiological data and clinical outcomes were collected. IDH1 status was assessed by immunohistochemistry. Eighteen patients with midline LGGs were identified, with a median age of 45. Most received biopsy upon diagnosis, though asymptomatic patients with tectal tumours underwent active surveillance. Oligodendroglial tumours were much less common than in a comparable group of lobar tumours (6 vs. 38 %, Fisher's exact test, p = 0.007). Only one tumour was immunopositive for IDH1 (1/17). Radiological diagnosis correlated with histology in only 71 % of patients. Median survival of midline LGGs was 48 months (3-90 months) and radiological features such as contrast enhancement, size and radiological diagnosis did not predict survival in this cohort. Median overall survival of midline LGGs was less than lobar LGGs (log-rank, p = 0.006), though differences became insignificant when considering only biopsied astrocytomas in both locations (log-rank, p = 0.491). Diagnosis of midline LGGs is complicated by both limitations of biopsy and imaging. Midline tumours have a poorer prognosis compared to lobar equivalents and survival differences are probably due to the absence of significant surgical intervention in midline locations.

  15. Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low-Grade Gliomas.

    PubMed

    Patel, Y T; Daryani, V M; Patel, P; Zhou, D; Fangusaro, J; Carlile, D J; Martin, P D; Aarons, L; Stewart, C F

    2017-03-22

    Selumetinib (AZD6244, ARRY-142886), a mitogen activated protein kinases (MEK1 and 2) inhibitor, has been granted orphan drug designation for differentiated thyroid cancer. The primary aim of this analysis was to characterize the population pharmacokinetics of selumetinib and its active metabolite N-desmethyl-selumetinib in patients with cancer. Concentration-time data from adult and pediatric clinical trials were pooled to develop a population pharmacokinetic model using a sequential approach where selumetinib and N-desmethyl-selumetinib data were modeled separately. A sequential zero- and first-order absorption with lag time with a two-compartment model for selumetinib and a two-compartment model for N-desmethyl-selumetinib best described the concentration-time data. Intrapatient variability in absorption was higher than interpatient variability. The apparent drug clearance (CL/F) from the central compartment was 13.5 L/hr (RSE 4.9%). Significant covariates for CL/F were age, alanine aminotransferase, and body surface area. This study confirms that flat dosing is appropriate in adults, whereas body-surface area based dosing should be used in pediatric patients.

  16. A mathematical model describes the malignant transformation of low grade gliomas: Prognostic implications

    PubMed Central

    Bodnar, Marek; Piotrowska, Monika J.; Murek, Michael; Schucht, Philippe; Beck, Jürgen; Martínez-González, Alicia; Pérez-García, Víctor M.

    2017-01-01

    Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose a mathematical model describing the spatio-temporal transition of LGGs into HGGs. Our modelling approach is based on two cellular populations with transitions between them being driven by the tumour microenvironment transformation occurring when the tumour cell density grows beyond a critical level. We show that the proposed model describes real patient data well. We discuss the relationship between patient prognosis and model parameters. We approximate tumour radius and velocity before malignant transformation as well as estimate the onset of this process. PMID:28763450

  17. A mathematical model describes the malignant transformation of low grade gliomas: Prognostic implications.

    PubMed

    Bogdańska, Magdalena U; Bodnar, Marek; Piotrowska, Monika J; Murek, Michael; Schucht, Philippe; Beck, Jürgen; Martínez-González, Alicia; Pérez-García, Víctor M

    2017-01-01

    Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose a mathematical model describing the spatio-temporal transition of LGGs into HGGs. Our modelling approach is based on two cellular populations with transitions between them being driven by the tumour microenvironment transformation occurring when the tumour cell density grows beyond a critical level. We show that the proposed model describes real patient data well. We discuss the relationship between patient prognosis and model parameters. We approximate tumour radius and velocity before malignant transformation as well as estimate the onset of this process.

  18. Efficacy of Perfusion Computed Tomography (PCT) in Differentiating High-Grade Gliomas from Low Grade Gliomas, Lymphomas, Metastases and Abscess.

    PubMed

    Karegowda, Lakshmikanth Halegubbi; Kadavigere, Rajagopal; Shenoy, Poonam Mohan; Paruthikunnan, Samir Mustaffa

    2017-05-01

    Tumoural angioneogenesis and its quantification are important in predicting the tumour grade and in the management with respect to the treatment available and to assess the response to treatment and the prognosis. It also plays major role in the growth and spread of tumours. Hence, a need arises for non-invasive in vivo methods to assess tumour angioneogenesis and tumour grade at the time of presentation and for monitoring the response during treatment and follow up. In this regard Perfusion Computed Tomography (PCT) can be easily added into routine CT studies to obtain such information on lesion physiology along with its morphology. Prospective evaluation of the efficacy of PCT in differentiating high grade gliomas from low grade glioma lymphomas, metastases and abscess. Perfusion CT was performed in 68 patients (17 high-grade gliomas, 10 low-grade gliomas, 7 lymphomas, 27 metastases and 7 abscess). Perfusion parameters which include Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF), Mean Transit Time (MTT) and Time To Peak (TTP) were derived both from the lesion and the normal parenchyma and were Normalized (n) by obtaining the ratio. Statistical analysis for high grade versus low-grade gliomas, high grade gliomas versus lymphomas, metastases and abscess was performed. Difference in the mean nCBV and nCBF in high grade gliomas were statistically significant from low grade gliomas with cut off of > 3.07 for nCBV and > 2.08 for nCBF yielding good sensitivity and specificity. Difference in the mean nCBV and nMTT in the lymphomas were statistically significant from high grade gliomas (p<0.05) with cut off of <3.40 for nCBV and >1.83 for nMTT yielding good sensitivity and specificity. Difference in the mean nCBV and nMTT in the metastases were statistically significant from high grade gliomas (p<0.05) with cut off of >4.95 for nCBV and >1.88 for nMTT yielding a fair sensitivity and specificity. No statistical significant difference seen among the parameters in

  19. BRAF, GNAQ, and GNA11 mutations and copy number in pediatric low-grade glioma.

    PubMed

    Laviv, Yosef; Toledano, Helen; Michowiz, Shalom; Dratviman-Storobinsky, Olga; Turm, Yuval; Fichman-Horn, Suzana; Kagnovski, Ella; Goldenberg-Cohen, Nitza

    2012-01-01

    Fifty-two samples of pediatric low-grade glioma (48 primary, 4 recurrent) were analyzed for BRAF copy number variation (digital PCR analysis, CopyCaller) and point mutations of BRAF V600E, and exon 5 Q209 in GNAQ, and GNA11, using the MALDI-TOF mass spectrometer with validation by direct sequencing. An increased BRAF copy number was found in 18/47 primary samples tested; 15 of them (83.3%) were pilocytic astrocytomas. A BRAF mutation was found in 3/48 primary tumors, all with a normal BRAF copy number and no GNAQ mutation. One sample had a GNAQ209 mutation (Q209P626) with a normal BRAF gene; none of the tumors had a GNA11Q209 mutation. Recurrent or progressive tumors, analyzed in four patients, had the same molecular genotype as their primary. Increased BRAF copy number and activating BRAF mutations may be involved in the development of low-grade glioma via overactivation of the Ras/Raf pathway. This is the first report of a mutation in GNAQ209 in pediatric low-grade glioma. Understanding the molecular mechanisms underlying glioma initiation and growth may assist in the development of targeted therapies.

  20. Putamen involvement and survival outcomes in patients with insular low-grade gliomas.

    PubMed

    Wang, Yongheng; Wang, Yinyan; Fan, Xing; Li, Shaowu; Liu, Xing; Wang, Jiangfei; Jiang, Tao

    2017-06-01

    OBJECTIVE Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system's association with survival outcome. METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil's classification, was examined using multivariate analyses. RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil's classification. CONCLUSIONS The current study's findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

  1. Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: insular lesions.

    PubMed

    Hinojosa, J; Gil-Robles, S; Pascual, B

    2016-10-01

    Insula and paralimbic region represent a common location for gliomas in adulthood. However, limbic and paralimbic tumors are rare in children. Reports of pediatric insular tumors are scarce in literature, and most of them are included in adult's series, so their management and outcome can be outlined only after extracting data from these reports. Due to their predominantly low grade, they usually have a benign course for some time, what make them ideal candidates for total resection. However, their intricate location and spread to key areas, including the temporal lobe, make them a surgical challenge. The transsylvian route, with or without resection of the frontal and/or temporal operculae, which requires exposure of part or all of the insula is commonly selected for insular tumor approaches. Intraoperative functional mapping is a standard procedure for resection of central region tumors in adults. In children and young individuals, awake craniotomy is not always possible and surgical planning usually relay on functional and anatomical preoperative studies. The main goal when approaching an insular tumor is to achieve the largest extent of resection to increase overall patient survival while preserving the functional status, minimizing postoperative morbidity and increasing the quality of life. The extent of resection seems to be correlated also with the control of associated (and usually intractable) epilepsy.

  2. Predictors of seizure freedom after resection of supratentorial low-grade gliomas. A review.

    PubMed

    Englot, Dario J; Berger, Mitchel S; Barbaro, Nicholas M; Chang, Edward F

    2011-08-01

    Seizures are the most frequent presenting symptom in patients with low-grade gliomas (LGGs), and significantly influence quality of life if they are uncontrolled. Achieving freedom from seizures is of utmost importance in surgical planning, but the factors associated with seizure control remain incompletely understood. The authors performed a systematic literature review of seizure outcomes after resection of LGGs causing seizures, examining 773 patients across 20 published series. Rates of seizure freedom were stratified across 7 variables: patient age, tumor location, preoperative seizure control with medication, seizure semiology, epilepsy duration, extent of resection, and the use of intraoperative electrocorticography (ECoG). Gross-total resection was most predictive of complete seizure freedom, when compared with subtotal resection (OR 3.41, 95% CI 2.36-4.93). Other predictors of seizure freedom included preoperative seizure control on antiepileptic medication (OR 2.12, 95% CI 1.33-3.38) and duration of seizures of ≤ 1 year (OR 1.85, 95% CI 1.22-2.79). Patients with simple partial seizure semiology achieved seizure freedom less often than those with complex partial, generalized, or mixed seizure types (OR 0.46, 95% CI 0.26-0.80). No significant differences in seizure outcome were observed between adults versus children, patients with temporal lobe versus extratemporal tumors, or with the use of intraoperative ECoG. Seizure control is one of the most important considerations in planning surgery for low-grade brain tumors. Gross-total resection is a critical factor in achieving seizure freedom.

  3. Exploiting molecular biology for diagnosis and targeted management of pediatric low-grade gliomas.

    PubMed

    Garcia, Michael A; Solomon, David A; Haas-Kogan, Daphne A

    2016-06-01

    The majority of brain tumors arising in children are low-grade gliomas. Although historically categorized together as pediatric low-grade gliomas (PLGGs), there is significant histologic and genetic diversity within this group. In general, prognosis for PLGGs is excellent, and limitation of sequelae from tumor and treatment is paramount. Advances in high-throughput genetic sequencing and gene expression profiling are fundamentally changing the way PLGGs are classified and managed. Here, we review the histologic subtypes and highlight how recent advances in elucidating the molecular pathogenesis of these tumors have refined diagnosis and prognostication. Additionally, we discuss how characterizing specific genetic alterations has paved the way for the rational use of targeted therapies that are currently in various phase clinical trials.

  4. PET AND SPECT STUDIES IN CHILDREN WITH HEMISPHERIC LOW-GRADE GLIOMAS

    PubMed Central

    Juhász, Csaba; Bosnyák, Edit

    2016-01-01

    Molecular imaging is playing an increasing role in the pre-treatment evaluation of low-grade gliomas. While glucose positron emission tomography (PET) can be helpful to differentiate low-grade from high-grade tumors, PET imaging with amino acid radiotracers has several advantages, such as better differentiation between tumors and non-tumorous lesions, optimized biopsy targeting and improved detection of tumor recurrence. This review provides a brief overview of single photon emission computed tomography (SPECT) studies followed by a more detailed review of clinical applications of glucose and amino acid PET imaging in low-grade hemispheric gliomas. We discuss key differences in the performance of the most commonly utilized PET radiotracers and highlight the advantage of PET/MRI fusion to obtain optimal information about tumor extent, heterogeneity and metabolism. Recent data also suggest that simultaneous acquisition of PET/MR images and the combination of advanced MRI techniques with quantitative PET can further improve the pre- and post-treatment evaluation of pediatric brain tumors. PMID:27659825

  5. Cognitive function after radiotherapy for supratentorial low-grade glioma: A North Central Cancer Treatment Group prospective study

    SciTech Connect

    Laack, Nadia N.; Brown, Paul D. . E-mail: brown.paul@mayo.edu; Ivnik, Robert J.; Furth, Alfred F. M.S.; Ballman, Karla V.; Hammack, Julie E.; Arusell, Robert M.; Shaw, Edward G.; Buckner, Jan C.

    2005-11-15

    Purpose: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. Methods and Materials: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. Results: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. Conclusions: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

  6. Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.

    PubMed

    Laack, Nadia N; Brown, Paul D; Ivnik, Robert J; Furth, Alfred F; Ballman, Karla V; Hammack, Julie E; Arusell, Robert M; Shaw, Edward G; Buckner, Jan C

    2005-11-15

    To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

  7. Measuring clinical outcomes in neuro-oncology. A battery to evaluate low-grade gliomas (LGG).

    PubMed

    Papagno, Costanza; Casarotti, Alessandra; Comi, Alessandro; Gallucci, Marcello; Riva, Marco; Bello, Lorenzo

    2012-06-01

    We describe how a neuropsychological evaluation in patients with brain tumors should be performed, specifically in the case of low-grade gliomas. Neuropsychological examination is crucial before starting any treatment as well as during the follow-up, since it can improve neurosurgery techniques and reveal potential cognitive effects of chemotherapy and radiotherapy, besides planning rehabilitation. We underline that sensitive and wide-ranging tests are required; specific tasks based on the lesion site should be added. Moreover, some tests can provide additional information about the evolution of the tumor. A careful, thorough examination improves quality of life.

  8. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments.

    PubMed

    Rudà, Roberta; Bello, Lorenzo; Duffau, Hugues; Soffietti, Riccardo

    2012-09-01

    Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine + CCNU+ vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy.

  9. Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments

    PubMed Central

    Rudà, Roberta; Bello, Lorenzo; Duffau, Hugues; Soffietti, Riccardo

    2012-01-01

    Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine + CCNU+ vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy. PMID:23095831

  10. Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery.

    PubMed

    Kristo, Gert; Raemaekers, Mathijs; Rutten, Geert-Jan; de Gelder, Beatrice; Ramsey, Nick F

    2015-03-01

    Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left hemisphere is linked to inter-hemispheric reorganization. Based on literature, we hypothesized that reorganization would induce changes in the spatial pattern of activation specifically in tumour homologue brain areas in the healthy right hemisphere. An experimental group (EG) of 14 patients with a glioma in the left hemisphere near language related brain areas, and a control group of 6 patients with a glioma in the right, non-language dominant hemisphere were scanned before and after resection. In addition, an age and gender matched second control group of 18 healthy volunteers was scanned twice. A verb generation task was used to map language related areas and a novel technique was used for data analysis. Contrary to our hypothesis, we found that functional recovery following surgery of low-grade gliomas cannot be linked to functional reorganization in language homologue brain areas in the healthy, right hemisphere. Although elevated changes in the activation pattern were found in patients after surgery, these were largest in brain areas in proximity to the surgical resection, and were very similar to the spatial pattern of the brain shift following surgery. This suggests that the apparent perilesional functional reorganization is mostly caused by the brain shift as a consequence of surgery. Perilesional functional reorganization can however not be excluded. The study suggests that language recovery after transient post-surgical language deficits involves recovery of functioning of the presurgical language system.

  11. Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol Specific and Desensitization Shows Poor Efficacy.

    PubMed

    Dodgshun, Andrew J; Hansford, Jordan R; Cole, Theresa; Choo, Sharon; Sullivan, Michael J

    2016-01-01

    The use of carboplatin for the treatment of pediatric low grade gliomas (PLGG) is often limited by the development of carboplatin hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary between 6% and 32% in these patients. Here we report the frequency of carboplatin hypersensitivity reactions depending on the treatment regimen used, and outcomes of carboplatin desensitization. The records of all patients in a single institution who were treated with carboplatin for PLGG were accessed and all patients receiving more than one dose of carboplatin are reported. Thirty four patients with PLGG were treated with carboplatin according to one of the two different regimens. Carboplatin hypersensitivity was documented in 47% of patients, but the frequency differed by treatment protocol. Those patients treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of cases whereas 68% of those treated with combined carboplatin and vincristine (every three weeks, according to the SIOP 2004 low grade glioma protocol) had carboplatin reactions (OR 23.6, P < 0.01). Desensitization was only successful in two out of 10 patients in whom it was attempted. Hypersensitivity reactions to carboplatin are more common in this cohort than previously reported and rates are protocol-dependent. Desensitization showed limited effectiveness in this cohort. © 2015 Wiley Periodicals, Inc.

  12. Decision-making abilities in patients with frontal low-grade glioma.

    PubMed

    Mattavelli, Giulia; Casarotti, Alessandra; Forgiarini, Matteo; Riva, Marco; Bello, Lorenzo; Papagno, Costanza

    2012-10-01

    Decisions in daily life are often quite complex, especially when one has to decide about his/her own health, as it is the case for patients with brain tumours. The integrity of the prefrontal cortex (and of the orbito-frontal in particular) is crucial in humans for practical decision-making. We investigated decision-making in 22 right-handed patients with a left frontal low-grade glioma, by means of a more complex, computerized version of the Iowa gambling task and we compared their performance with that of 26 neurologically-unimpaired subjects. After the experiment, we also administered a questionnaire to evaluate subjects' conscious comprehension level of the task and two self-report scales to verify potential effects of individual personality differences. Patients chose significantly less cards than controls from the advantageous deck, without modifying their behaviour over time, and this correlated with abstract reasoning abilities. In both groups, level of comprehension, significantly affected performance. An improvement was found post-surgery. In conclusion, the performance in the Gambling Task suggests that patients with left frontal low-grade gliomas can be impaired in decision-making, apparently requiring more time to understand the task: therefore, a particular attention and care should be taken to explain risks and consequences of his/her illness and treatment in order to obtain an informed decision from the patient.

  13. Pitfalls in the assessment of disability in individuals with low-grade gliomas.

    PubMed

    Påhlson, Anneli; Ek, Lena; Ahlström, Gerd; Smits, Anja

    2003-11-01

    In this study, the presence of motor and cognitive disability is described in a cohort of patients with low-grade glioma recruited from a geographical area with a well-defined population located in the middle of Sweden. The study group consisted of 35 patients, of which 24 were evaluated by both a neurologist and a neuropsychologist, and 11 only by a neurologist. The test battery according to EFIT (Edinburgh Functional Impairment Test) was used by the neurologist to measure impairments of limb function, memory and speech. Patients were asked to self-evaluate their deficits in motor function and cognition by responding to a specific questionnaire. In addition, a neuropsychological test battery was used by an experienced neuropsychologist who had no previous contact with the patients. In general, motor impairment was mild and predominantly found in the upper limb. Neuropsychological assessment revealed moderate or severe cognitive impairment in more than half of the patients. This impairment was not detected by neurological examination, and only to some extent reported by the patients them selves. The results show statistical differences in cognitive function, memory and language as recorded by the three assessors. In conclusion, this study demonstrates the usefulness of neuropsychological assessment as a complement to neurological examination to detect cognitive dysfunction in patients with low-grade gliomas.

  14. Hypnosis for Awake Surgery of Low-grade Gliomas: Description of the Method and Psychological Assessment.

    PubMed

    Zemmoura, Ilyess; Fournier, Eric; El-Hage, Wissam; Jolly, Virginie; Destrieux, Christophe; Velut, Stéphane

    2016-01-01

    Awake craniotomy with intraoperative electric stimulation is a reliable method for extensive removal of low-grade gliomas while preserving the functional integrity of eloquent surrounding brain structures. Although fully awake procedures have been proposed, asleep-awake-asleep remains the standard technique. Anesthetic contraindications are the only limitation of this method, which is therefore not reliable for older patients with high-grade gliomas. To describe and assess a novel method for awake craniotomy based on hypnosis. We proposed a novel hypnosedation procedure to patients undergoing awake surgery for low-grade gliomas in our institution between May 2011 and April 2015. Surgical data were retrospectively recorded. The subjective experience of hypnosis was assessed by 3 standardized questionnaires: the Cohen Perceived Stress Scale, the Posttraumatic Stress Disorder Checklist Scale, the Peritraumatic Dissociative Experience Questionnaire, and a fourth questionnaire designed specifically for this study. Twenty-eight questionnaires were retrieved from 43 procedures performed on 37 patients. The Peritraumatic Dissociative Experience Questionnaire revealed a dissociation state in 17 cases. The Perceived Stress Scale was pathological in 8 patients. Two patients in this group stated that they would not accept a second hypnosedation procedure. The Posttraumatic Stress Disorder Checklist Scale revealed 1 case of posttraumatic stress disorder. Burr hole and bone flap procedures were the most frequently reported unpleasant events during opening (15 of 52 events). The main findings of our study are the effectiveness of the technique, which in all cases allowed resection of the tumor up to functional boundaries, and the positive psychological impact of the technique in most of the patients.

  15. Analysis of DTI-Derived Tensor Metrics in Differential Diagnosis between Low-grade and High-grade Gliomas

    PubMed Central

    Jiang, Liang; Xiao, Chao-Yong; Xu, Quan; Sun, Jun; Chen, Huiyou; Chen, Yu-Chen; Yin, Xindao

    2017-01-01

    Purpose: It is critical and difficult to accurately discriminate between high- and low-grade gliomas preoperatively. This study aimed to ascertain the role of several scalar measures in distinguishing high-grade from low-grade gliomas, especially the axial diffusivity (AD), radial diffusivity (RD), planar tensor (Cp), spherical tensor (Cs), and linear tensor (Cl) derived from diffusion tensor imaging (DTI). Materials and Methods: Fifty-three patients with pathologically confirmed brain gliomas (21 low-grade and 32 high-grade) were included. Contrast-enhanced T1-weighted images and DTI were performed in all patients. The AD, RD, Cp, Cs, and Cl values in the tumor zone, peritumoral edema zone, white matter (WM) adjacent to edema and contralateral normal-appearing white matter (NAWM) were calculated. The DTI parameters and tumor grades were statistically analyzed, and receiver operating characteristic (ROC) curve analysis was also performed. Results: The DTI metrics in the affected hemisphere showed significant differences from those in the NAWM, except for the AD values in the tumor zone and the RD values in WM adjacent to edema in the low-grade groups, as well as the Cp values in WM adjacent to edema in the high-grade groups. AD in the tumor zone as well as Cs and Cl in WM adjacent to edema revealed significant differences between the low- and high-grade gliomas. The areas under the curve (Az) of all three metrics were greater than 0.5 in distinguishing low-grade from high-grade gliomas by ROC curve analysis, and the best DTI metric was Cs in WM adjacent to edema (Az: 0.692). Conclusion: AD in the tumor zone as well as Cs and Cl in WM adjacent to edema will provide additional information to better classify gliomas and can be used as non-invasive reliable biomarkers in glioma grading. PMID:28848428

  16. Challenges in Drug Discovery for Neurofibromatosis Type 1-Associated Low-Grade Glioma

    PubMed Central

    Ricker, Cora A.; Pan, Yuan; Gutmann, David H.; Keller, Charles

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that results from germline mutations of the NF1 gene, creating a predisposition to low-grade gliomas (LGGs; pilocytic astrocytoma) in young children. Insufficient data and resources represent major challenges to identifying the best possible drug therapies for children with this tumor. Herein, we summarize the currently available cell lines, genetically engineered mouse models, and therapeutic targets for these LGGs. Conspicuously absent are human tumor-derived cell lines or patient-derived xenograft models for NF1-LGG. New collaborative initiatives between patients and their families, research groups, and pharmaceutical companies are needed to create transformative resources and broaden the knowledge base relevant to identifying cooperating genetic drivers and possible drug therapeutics for this common pediatric brain tumor. PMID:28066715

  17. Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.

    PubMed

    Zhang, Jinghui; Wu, Gang; Miller, Claudia P; Tatevossian, Ruth G; Dalton, James D; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S; Fulton, Lucinda L; Dooling, David J; Vadodaria, Bhavin; Mulder, Heather L; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Baker, Suzanne J; Ellison, David W

    2013-06-01

    The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs.

  18. Pathology of low-grade gliomas: an update of emerging concepts.

    PubMed Central

    Perry, Arie

    2003-01-01

    Although the term low-grade glioma (LGG) is useful for its connotation of a slow-growing, better prognosis CNS primary neoplasm typically occurring in a young patient, it also serves as a potential diagnostic wastebasket, occasionally leading to conceptual errors, therapeutic uncertainty, or misinterpretation of clinical data. For example, the LGG designation is occasionally invoked as a justification for lumping together biologically unrelated entities such as pilocytic astrocytoma and diffuse astrocytoma. Whereas the former represents a benign and potentially surgically curable neoplasm that virtually never undergoes malignant transformation, the latter is a surgically incurable low-grade malignancy, prone to further malignant progression and eventual fatality. Therefore, although rare cases lacking a clear distinction may be encountered, the term LGG should be abandoned for a more specific diagnosis whenever possible. The primary goals of this paper are to review practical surgical pathology issues related to the diagnosis of diffuse LGGs and to update the reader on emerging clinicopathologic and molecular genetic concepts. Also discussed are current controversies of classification/grading and the role of ancillary testing via immunohistochemical and genetic techniques. PMID:12816723

  19. Magnetic Resonance of 2-Hydroxyglutarate in IDH1-Mutated Low-Grade Gliomas

    PubMed Central

    Phillips, Joanna J.; Yoshihara, Hikari A. I.; Parvataneni, Rupa; Srinivasan, Radhika; Bourne, Gabriela; Berger, Mitchel S.; Chang, Susan M.; Cha, Soonmee; Nelson, Sarah J.

    2013-01-01

    Recent studies have indicated that a significant survival advantage is conferred to patients with gliomas whose lesions harbor mutations in the genes isocitrate dehydrogenase 1 and 2 (IDH1/2). IDH1/2 mutations result in aberrant enzymatic production of the potential oncometabolite D-2-hydroxyglutarate (2HG). Here, we report on the ex vivo detection of 2HG in IDH1-mutated tissue samples from patients with recurrent low-grade gliomas using the nuclear magnetic resonance technique of proton high-resolution magic angle spinning spectroscopy. Relative 2HG levels from pathologically confirmed mutant IDH1 tissues correlated with levels of other ex vivo metabolites and histopathology parameters associated with increases in mitotic activity, relative tumor content, and cellularity. Ex vivo spectroscopic measurements of choline-containing species and in vivo magnetic resonance measurements of diffusion parameters were also correlated with 2HG levels. These data provide extensive characterization of mutant IDH1 lesions while confirming the potential diagnostic value of 2HG as a surrogate marker of patient survival. Such information may augment the ability of clinicians to monitor therapeutic response and provide criteria for stratifying patients to specific treatment regimens. PMID:22238333

  20. Malignant transformation of low-grade gliomas in patients undergoing adjuvant therapy.

    PubMed

    Rotta, José Marcus; de Oliveira, Matheus Fernandes; Reis, Rodolfo Casimiro; Botelho, Ricardo Vieira

    2017-03-01

    Low-grade gliomas (LGG) comprise nearly 15-20 % of all central nervous system glial tumors. Several factors have been recognized as playing role in LGG malignant transformation (MT). A breakthrough analysis of a multidisciplinary group pointed that temozolomide may play a role in MT of LGGs. We analyzed the prevalence of MT in LGG patients submitted to adjuvant therapy (AT). We analyzed the medical charts of 43 patients with LGG submitted to surgery or biopsy and attending at Hospital do Servidor Público Estadual de São Paulo (São Paulo, Brazil), consecutively diagnosed from 1995 to 2013. 43 patients (24 women and 19 men) were evaluated, with mean age of 45.3 years. According to histology, 30 were astrocytomas (70 %), 12 (27 %) were oligodendrogliomas, and 1 (3 %) were mixed glioma. Mean follow-up time was 4.2 years with the standard deviation of 2.1. Twenty-eight patients did not receive adjuvant therapy and 15 received adjuvant therapy. From 43 patients with complete follow-up, 21 (48 %) experienced malignant transformation. Among such patients, nine were users of AT. Forty-eight percent of patients presented MT, being 60 % in the AT group and 42.8 % without AT. Our analysis revealed a high prevalence of MT in patients undergoing AT, higher than in patients without AT.

  1. Stereotactic brachytherapy of low-grade cerebral glioma after tumor resection.

    PubMed

    Suchorska, Bogdana; Ruge, Maximilian; Treuer, Harald; Sturm, Volker; Voges, Jürgen

    2011-10-01

    The purpose of this study was to assess the impact of stereotactic brachytherapy (SBT) on survival time and outcome when applied after resection of low-grade glioma (LGG) of World Health Organization grade II. From January 1982 through December 2006 we treated 1024 patients who had glioma with stereotactic implantation of iodine-125 seeds and SBT in accordance with a prospective protocol. For the present analysis, we selected 95 of 277 patients with LGG, in whom SBT was applied to treat progressive (43 patients) or recurrent (52 patients) tumor after resection. At 24 months after seed implantation, the tumor response rate was 35.9%, and the tumor control rate was 97.3%. The median progression-free-survival (PFS) duration after SBT was 52.7 ± 7.1 months. Five-year and 10-year PFS probabilities were 43.4% and 10.7%, respectively. Malignant tumor transformation, the diagnosis "astrocytoma," and tumor volume >20 mL were significantly associated with reduced PFS. Tumor progression or relapse after SBT (53 of 95 patients) was treated with tumor resection, a second SBT, chemotherapy, and/or radiotherapy. The median overall survival duration (from the first diagnosis of LGG until the patient's last contact) was 245.0 ± 4.9 months. Patients still under observation after seed implantation had a median follow-up time of 156.4 ± 55.7 months. Perioperative transient morbidity was 1.1%, and the frequency of permanent morbidity caused by SBT was 3.3%. In conclusion, SBT of recurrent or progressive LGG after resection located in functionally critical brain areas has high local efficacy and comparably low morbidity. Referred to individually adopted glioma treatment concepts SBT provides a reasonably long PFS, thus improving overall survival. In selected patients, SBT can lead to delays in the application of chemotherapy and/or radiotherapy.

  2. Extent of resection and survival in supratentorial infiltrative low-grade gliomas: analysis of and adjustment for treatment bias.

    PubMed

    Gousias, Konstantinos; Schramm, Johannes; Simon, Matthias

    2014-02-01

    Any correlation between the extent of resection and the prognosis of patients with supratentorial infiltrative low-grade gliomas may well be related to biased treatment allocation. Patients with an intrinsically better prognosis may undergo more aggressive resections, and better survival may then be falsely attributed to the surgery rather than the biology of the disease. The present study investigates the potential impact of this type of treatment bias on survival in a series of patients with low-grade gliomas treated at the authors' institution. We conducted a retrospective study of 148 patients with low-grade gliomas undergoing primary treatment at our institution from 1996-2011. Potential prognostic factors were studied in order to identify treatment bias and to adjust survival analyses accordingly. Eloquence of tumor location proved the most powerful predictor of the extent of resection, i.e., the principal source of treatment bias. Univariate as well as multivariate Cox regression analyses identified the extent of resection and the presence of a preoperative neurodeficit as the most important predictors of overall survival, tumor recurrence and malignant progression. After stratification for eloquence of tumor location in order to correct for treatment bias, Kaplan-Meier estimates showed a consistent association between the degree of resection and improved survival. Treatment bias was not responsible for the correlation between extent of resection and survival observed in the present series. Our data seem to provide further support for a strategy of maximum safe resections for low-grade gliomas.

  3. Clinical prognostic factors of adjuvant radiation therapy for low-grade gliomas: results of 10 years survival.

    PubMed

    Kaya, Vildan; Aksu, Melek Gamze; Korcum, Aylin Fidan; Ozdemir, Beyza; Ceçen, Yiğit; Sindir, Bora; Genç, Mine

    2014-01-01

    Low-grade gliomas compose 5-20% of all glial tumors. The prognosis of the disease can be anticipated by specific clinical factors determined during diagnosis. For this purpose, our study investigated the clinical prognostic factors for low-grade gliomas. Patients diagnosed with histopathologically confirmed low-grade glioma, followed by Akdeniz University and Süleyman Demirel University School of Medicine, Department of Radiation Oncology between 1999 and 2013 were included in the study. The examination of survival by single variable analyses were performed by log rank test. For the multivariate analysis, independent factors for the prediction of survival by using possible factors determined by previous analyses were examined by using Cox regression analysis. Fifty-five patients were included in the study. The mean follow-up period was determined as 60 ± 57 (4.5-168.1) months. Five-year overall survival was determined as 69% and 10-year overall survival was determined as 40%. When the potential prognostic factors were studied in Cox regression model, pre-radiotherapy age below 40 and gross-total excision were determined as good prognostic factors. We demonstrated that the aggressive surgical resection provided a better survival advantage both in single variable analyses and multivariate analyses. Consequently, although the low number of patients was the most important limitation in our study, we consider that patient age and extent of resection are the most important clinical prognostic factors in low-grade gliomas.

  4. Anatomical location differences between mutated and wild-type isocitrate dehydrogenase 1 in low-grade gliomas.

    PubMed

    Yu, Jinhua; Shi, Zhifeng; Ji, Chunhong; Lian, Yuxi; Wang, Yuanyuan; Chen, Liang; Mao, Ying

    2017-01-06

    Anatomical location of gliomas has been considered as a factor implicating the contributions of a specific precursor cells during the tumor growth. Isocitrate dehydrogenase 1 (IDH1) is a pathognomonic biomarker with a significant impact on the development of gliomas and remarkable prognostic effect. The correlation between anatomical location of tumor and IDH1 states for low-grade gliomas was analyzed quantitatively in this study. Ninety-two patients diagnosed of low-grade glioma pathologically were recruited in this study, including 65 patients with IDH1-mutated glioma and 27 patients with wide-type IDH1. A convolutional neural network was designed to segment the tumor from three-dimensional magnetic resonance imaging images. Voxel-based lesion symptom mapping was then employed to study the tumor location distribution differences between gliomas with mutated and wild-type IDH1. In order to characterize the location differences quantitatively, the Automated Anatomical Labeling Atlas was used to partition the standard brain atlas into 116 anatomical volumes of interests (AVOIs). The percentages of tumors with different IDH1 states in 116 AVOIs were calculated and compared. Support vector machine and AdaBoost algorithms were used to estimate the IDH1 status based on the 116 location features of each patient. Experimental results proved that the quantitative tumor location measurement could be a very important group of imaging features in biomarker estimation based on radiomics analysis of glioma.

  5. Microfoci of malignant progression in diffuse low-grade gliomas: towards the creation of an intermediate grade in glioma classification?

    PubMed

    Pedeutour-Braccini, Zoé; Burel-Vandenbos, Fanny; Gozé, Catherine; Roger, Coralie; Bazin, Audrey; Costes-Martineau, Valérie; Duffau, Hugues; Rigau, Valérie

    2015-04-01

    Low-grade gliomas (GII) inescapably progress to high-grade gliomas (GIII). The duration of this transition is highly variable between patients and reliable predictive markers do not exist. We noticed in a subset of cases of GII, obtained by awake neurosurgery, the presence of microfoci with high cellular density, high vascular density, or minimal endothelial proliferation, which we called GII+. Our aim was to investigate whether these foci display immunohistochemical and molecular characteristics similar to GIII and whether their presence is correlated to poor prognosis. We analyzed cell proliferation, hypoxia, vascularization, and alterations of tumorigenic pathways by immunohistochemistry (Ki-67, CD31, HIF-1-alpha, EGFR, P-AKT, P53, MDM2) and fluorescence in situ hybridization (EGFR, MDM2, PDGFRA) in the hypercellular foci of 16 GII+ cases. We compared overall survival between GII, GII+, and GIII. Ki-67, and CD31 expression was higher in the foci than in the tumor background in all cases. Aberrant expression of protein markers and genomic aberrations were also observed in some foci, distinct from the tumor background. Survival was shorter in GII+ than in GII cases. Our results suggest that these foci are the early histological hallmark of anaplastic transformation, which is supported by molecular aberrations. Our study is the first to demonstrate intratumoral morphological, immunohistochemical, and molecular heterogeneity in resection specimens of GII, the presence of which is correlated to shorter survival. Our findings question the discriminative capacity of the current glioma classification and provide arguments in favor of the creation of a grade intermediate between GII and GIII, to optimize the treatment strategy of GII.

  6. A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas.

    PubMed

    Ponnampalam, Stephen N; Kamaluddin, Nor Rizan; Zakaria, Zubaidah; Matheneswaran, Vickneswaran; Ganesan, Dharmendra; Haspani, Mohammed Saffari; Ryten, Mina; Hardy, John A

    2017-01-01

    The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a p<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (p<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and

  7. A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas

    PubMed Central

    Ponnampalam, Stephen N.; Kamaluddin, Nor Rizan; Zakaria, Zubaidah; Matheneswaran, Vickneswaran; Ganesan, Dharmendra; Haspani, Mohammed Saffari; Ryten, Mina; Hardy, John A.

    2016-01-01

    The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4×44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a P<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (P<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and

  8. First experiences in treatment of low-grade glioma grade I and II with proton therapy

    PubMed Central

    2012-01-01

    Background To retrospectively assess feasibility and toxicity of proton therapy in patients with low-grade glioma (WHO °I/II). Patients and methods Proton beam therapy only administered in 19 patients (median age 29 years; 9 female, 10 male) for low-grade glioma between 2010 and 2011 was reviewed. In 6 cases proton therapy was performed due to tumor progression after biopsy, in 8 cases each due to tumor progression after (partial-) resection, and in 5 cases due to tumor progression after chemotherapy. Median total dose applied was 54 GyE (range, 48,6-54 GyE) in single fractions of median 1.8 GyE. Median clinical target volume was 99 cc (range, 6–463 cc) and treated using median 2 beams (range, 1–2). Results Proton therapy was finished as planned in all cases. At end of proton therapy, 13 patients showed focal alopecia, 6 patients reported mild fatigue, one patient with temporal tumor localization concentration deficits and speech errors and one more patient deficits in short-term memory. Four patients did not report any side effects. During follow-up, one patient presented with pseudo-progression showing worsening of general condition and brain edema 1–2 months after last irradiation and restitution after 6 months. In the present MR imaging (median follow-up 5 months; range 0–22 months) 12 patients had stable disease, 2 (1) patients partial (complete) remission, one more patient pseudo-progression (differential diagnosis: tumor progression) 4 weeks after irradiation without having had further follow-up imaging so far, and one patient tumor progression approximately 9 months after irradiation. Conclusion Regarding early side effects, mild alopecia was the predominant finding. The rate of alopecia seems to be due to large treatment volumes as well as the anatomical locations of the target volumes and might be avoided by using multiple beams and the gantry in the future. Further evaluations including neuropsychological testing are in preparation. PMID

  9. Progressive Low-Grade Glioma: Assessment of Prognostic Importance of Histologic Reassessment and MRI Findings.

    PubMed

    Narang, Amol K; Chaichana, Kaisorn L; Weingart, Jon D; Redmond, Kristin J; Lim, Michael; Olivi, Alessandro; Quinones-Hinojosa, Alfred; Kleinberg, Lawrence R

    2017-03-01

    In patients with progressive low-grade glioma (LGG), the presence of new magnetic resonance imaging (MRI) enhancement is commonly used as an indicator of malignant degeneration, but its accuracy in this setting is uncertain. We characterize the ability of new MRI enhancement to serve as a surrogate for histologic grade in patients with progressive LGG, and to explore the prognostic value of new MRI enhancement, pathologic grade, and extent of resection. Patients at our institution with World Health Organization grade II glioma diagnosed between 1994 and 2010 and who underwent repeat biopsy or resection at progression were retrospectively reviewed (n = 108). The positive predictive value, negative predictive value, sensitivity, and specificity of new MRI enhancement were characterized. A multivariable proportional hazards model was used to test associations with overall survival (OS), and Kaplan-Meier curves were constructed to compare OS between patient subsets. The positive predictive value, negative predictive value, sensitivity, and specificity of new MRI enhancement were 82%, 77%, 92%, and 57%, respectively. In patients without malignant degeneration, new MRI enhancement was associated with inferior median OS (92.5 months vs. not reached; P = 0.03). In patients with malignant degeneration, gross or near total resection was associated with improved median OS (58.8 vs. 28.8 months; P = 0.02). In patients with progressive LGG, new MRI enhancement and pathologic grade were discordant in greater than 20% of cases. Pathologic confirmation of grade should therefore be attempted, when safe, to dictate management. Beyond functioning as a surrogate for pathologic grade, new MRI enhancement may predict for worse outcomes, a concept that merits prospective investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials.

    PubMed

    Avila, Edward K; Chamberlain, Marc; Schiff, David; Reijneveld, Jaap C; Armstrong, Terri S; Ruda, Roberta; Wen, Patrick Y; Weller, Michael; Koekkoek, Johan A F; Mittal, Sandeep; Arakawa, Yoshiki; Choucair, Ali; Gonzalez-Martinez, Jorge; MacDonald, David R; Nishikawa, Ryo; Shah, Aashit; Vecht, Charles J; Warren, Paula; van den Bent, Martin J; DeAngelis, Lisa M

    2017-01-01

    Patients with low-grade glioma frequently have brain tumor-related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Clinical Management of Seizures in Patients With Low-Grade Glioma.

    PubMed

    Piotrowski, Anna F; Blakeley, Jaishri

    2015-07-01

    Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%-2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered. Copyright © 2015. Published by Elsevier Inc.

  12. Clinical Management of Seizures in Patients With Low-Grade Glioma

    PubMed Central

    Piotrowski, Anna F.; Blakeley, Jaishri

    2015-01-01

    Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%–2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered. PMID:26050593

  13. Functional recovery after surgical resection of low grade gliomas in eloquent brain: hypothesis of brain compensation

    PubMed Central

    Duffau, H; Capelle, L; Denvil, D; Sichez, N; Gatignol, P; Lopes, M; Mitchell, M; Sichez, J; Van Effenterre, R

    2003-01-01

    Objectives: To describe functional recovery after surgical resection of low grade gliomas (LGG) in eloquent brain areas, and discuss the mechanisms of compensation. Methods: Seventy-seven right-handed patients without deficit were operated on for a LGG invading primary and/or secondary sensorimotor and/or language areas, as shown anatomically by pre-operative MRI and intraoperatively by electrical brain stimulation and cortico-subcortical mapping. Results: Tumours involved 31 supplementary motor areas, 28 insulas, 8 primary somatosensory areas, 4 primary motor areas, 4 Broca's areas, and 2 left temporal language areas. All patients had immediate post-operative deficits. Recovery occurred within 3 months in all except four cases (definitive morbidity: 5%). Ninety-two percent of the lesions were either totally or extensively resected on post-operative MRI. Conclusions: These findings suggest that spatio-temporal functional re-organisation is possible in peritumoural brain, and that the process is dynamic. The recruitment of compensatory areas with long term perilesional functional reshaping would explain why: before surgery, there is no clinical deficit despite the tumour growth in eloquent regions; immediately after surgery, the occurrence of a deficit, which could be due to the resection of invaded areas participating (but not essential) to the function; and why three months after surgery, almost complete recovery had occurred. This brain plasticity, which decreases the long term risk of surgical morbidity, may be used to extend the limits of surgery in eloquent areas. PMID:12810776

  14. Surgery of insular and paralimbic diffuse low-grade gliomas: technical considerations.

    PubMed

    Michaud, Karine; Duffau, Hugues

    2016-11-01

    Once considered a "no man's land" especially when invaded by a diffuse low grade glioma (DLGG), the insula remains to this day a surgical challenge. Surgery for insular DLGG involves consideration of its hidden location under the potentially eloquent operculae, the proximity to vascular tree and high density of functions not only in the insular cortex but also in the white fiber pathways passing under the insular lobe. The natural history of DLGG and the potential benefits and consequences of the surgical approach also need a close look. In the last decade, a better knowledge of the functional anatomy and connectivity of this region, as well as an improvement in surgical techniques as direct stimulation mapping, combined with an increasing literature showing a favorable impact of maximal resection for DLGG, were deciding factors in the paradigmatic shift from expectative treatment to early surgical management. Here, our goal is to discuss the structural and functional aspects of the insula, the specificities of insular and paralimbic DLGG by emphasizing the technical considerations of surgery in this region, as well as its oncological and functional outcomes. In summary, this new strategy based upon early maximal safe surgical resection showed both oncological benefit and preservation of quality of life-or even an improvement thanks to epilepsy relief.

  15. Fatigue in patients with low grade glioma: systematic evaluation of assessment and prevalence.

    PubMed

    van Coevorden-van Loon, Ellen M P; Coomans, Marijke B; Heijenbrok-Kal, Majanka H; Ribbers, Gerard M; van den Bent, Martin J

    2017-06-01

    Fatigue is the most prevalent and disabling symptom in cancer patients. Yet, scientific literature on this topic is scarce and reports disparate results. This study systematically reviews how fatigue is assessed in patients with low-grade glioma and evaluates its prevalence in LGG patients. A systematic literature search was performed in PubMed, Embase and PsychINFO for articles reporting on fatigue in patients with LGG. Two reviewers independently extracted data from selected articles. Inclusion criteria were: (1) patients with suspected or confirmed LGG; (2) fatigue was assessed as primary or secondary outcome measure; (3) age≥ 18 years; (4) full-length article written in English or Dutch. In total, 19 articles were selected, including 971 patients. Seven self-assessment instruments were identified. Prevalence rates ranged from 39 to 77%. Fatigue was found to be a common side effect of treatment. The prevalence rates ranged from 20 to 76% when fatigue was reported as a mild or moderate side effect and fatigue was prevalent in 4% when reported as a severe side effect. Fatigue is a common problem in LGG patients that warrants more therapeutic and scientific attention. Gaining deeper insight in the underlying mechanisms of fatigue is essential in targeting therapy to individual patients.

  16. A mathematical model of low grade gliomas treated with temozolomide and its therapeutical implications.

    PubMed

    Bogdańska, M U; Bodnar, M; Belmonte-Beitia, J; Murek, M; Schucht, P; Beck, J; Pérez-García, V M

    2017-06-01

    Low grade gliomas (LGGs) are infiltrative and incurable primary brain tumours with typically slow evolution. These tumours usually occur in young and otherwise healthy patients, bringing controversies in treatment planning since aggressive treatment may lead to undesirable side effects. Thus, for management decisions it would be valuable to obtain early estimates of LGG growth potential. Here we propose a simple mathematical model of LGG growth and its response to chemotherapy which allows the growth of LGGs to be described in real patients. The model predicts, and our clinical data confirms, that the speed of response to chemotherapy is related to tumour aggressiveness. Moreover, we provide a formula for the time to radiological progression, which can be possibly used as a measure of tumour aggressiveness. Finally, we suggest that the response to a few chemotherapy cycles upon diagnosis might be used to predict tumour growth and to guide therapeutical actions on the basis of the findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Synchronized brain activity and neurocognitive function in patients with low-grade glioma: a magnetoencephalography study.

    PubMed

    Bosma, Ingeborg; Douw, Linda; Bartolomei, Fabrice; Heimans, Jan J; van Dijk, Bob W; Postma, Tjeerd J; Stam, Cornelis J; Reijneveld, Jaap C; Klein, Martin

    2008-10-01

    We investigated the mechanisms underlying neurocognitive dysfunction in patients with low-grade glioma (LGG) by relating functional connectivity revealed by magnetoencephalography to neurocognitive function. We administered a battery of standardized neurocognitive tests measuring six neurocognitive domains to a group of 17 LGG patients and 17 healthy controls, matched for age, sex, and educational level. Magnetoencephalography recordings were conducted during an eyes-closed "resting state," and synchronization likelihood (a measure of statistical correlation between signals) was computed from the delta to gamma frequency bands to assess functional connectivity between different brain areas. We found that, compared with healthy controls, LGG patients performed more poorly in psychomotor function, attention, information processing, and working memory. LGG patients also had significantly higher long-distance synchronization scores in the delta, theta, and lower gamma frequency bands than did controls. In contrast, patients displayed a decline in synchronization likelihood in the lower alpha frequency band. Within the delta, theta, and lower and upper gamma bands, increasing short- and long-distance connectivity was associated with poorer neurocognitive functioning. In summary, LGG patients showed a complex overall pattern of differences in functional resting-state connectivity compared with healthy controls. The significant correlations between neurocognitive performance and functional connectivity in various frequencies and across multiple brain areas suggest that the observed neurocognitive deficits in these patients can possibly be attributed to differences in functional connectivity due to tumor and/or treatment.

  18. The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study.

    PubMed

    Bosma, I; Stam, C J; Douw, L; Bartolomei, F; Heimans, J J; van Dijk, B W; Postma, T J; Klein, M; Reijneveld, J C

    2008-05-01

    In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits.

  19. Biopsy versus resection for the management of low-grade gliomas.

    PubMed

    Veeravagu, Anand; Jiang, Bowen; Ludwig, Cassie; Chang, Steven D; Black, Keith L; Patil, Chirag G

    2013-04-30

    Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG. To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG. The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to week 3 November 2012), EMBASE (1980 to Week 46 2012). Unpublished and grey literature including Metaregister, Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials were also queried for ongoing trials. Patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT) were included. Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL). A total of 2764 citations were searched and critically analyzed for relevance. This effort was undertaken by three independent review authors. No RCTs of biopsy or resection for LGG were identified. Twenty other studies were retrieved for analysis based on pre-specified selection criteria. Ten studies were retrospective or literature reviews. Three studies were prospective but were limited to tumor recurrence or the extent of

  20. Learning and Memory Following Conformal Radiation Therapy for Pediatric Craniopharyngioma and Low-Grade Glioma

    SciTech Connect

    Di Pinto, Marcos; Conklin, Heather M.; Li, Chenghong; Merchant, Thomas E.

    2012-11-01

    Purpose: The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning. Methods and Materials: Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years. Results: No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy. Conclusions: This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients.

  1. Quality of life in low-grade glioma patients receiving temozolomide.

    PubMed

    Liu, Raymond; Solheim, Karla; Polley, Mei-Yin; Lamborn, Kathleen R; Page, Margaretta; Fedoroff, Anne; Rabbitt, Jane; Butowski, Nicholas; Prados, Michael; Chang, Susan M

    2009-02-01

    The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well-being scores (mean difference = 2.2; p < 0.01) compared to a normal population. Compared to patients with left hemisphere tumors, patients with right hemisphere tumors reported higher physical well-being scores (p = 0.01): 44% could not drive, 26% did not feel independent, and 26% were afraid of having a seizure. Difficulty with work was noted in 24%. Mean change scores at each chemotherapy cycle compared to baseline for all QOL subscales showed either no significant change or were significantly positive (p < 0.01). Patients with LGG on TMZ at baseline prior to chemotherapy reported QOL comparable to a normal population with the exception of social and emotional well-being, and those with right hemisphere tumors reported higher physical well-being scores compared to those with left hemisphere tumors. While remaining on therapy, LGG patients were able to maintain their QOL in all realms. LGG patients' QOL may be further improved by addressing their emotional well-being and their loss of independence in terms of driving or working.

  2. Longitudinal Investigation of Adaptive Functioning Following Conformal Irradiation for Pediatric Craniopharyngioma and Low-Grade Glioma

    SciTech Connect

    Netson, Kelli L.; Conklin, Heather M.; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E.

    2013-04-01

    Purpose: Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Methods and Materials: Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. Results: Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. Conclusions: There was relative sparing of postirradiation functional outcomes over time in this sample

  3. Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

    PubMed

    Lassaletta, Alvaro; Zapotocky, Michal; Mistry, Matthew; Ramaswamy, Vijay; Honnorat, Marion; Krishnatry, Rahul; Guerreiro Stucklin, Ana; Zhukova, Nataliya; Arnoldo, Anthony; Ryall, Scott; Ling, Catriona; McKeown, Tara; Loukides, Jim; Cruz, Ofelia; de Torres, Carmen; Ho, Cheng-Ying; Packer, Roger J; Tatevossian, Ruth; Qaddoumi, Ibrahim; Harreld, Julie H; Dalton, James D; Mulcahy-Levy, Jean; Foreman, Nicholas; Karajannis, Matthias A; Wang, Shiyang; Snuderl, Matija; Nageswara Rao, Amulya; Giannini, Caterina; Kieran, Mark; Ligon, Keith L; Garre, Maria Luisa; Nozza, Paolo; Mascelli, Samantha; Raso, Alessandro; Mueller, Sabine; Nicolaides, Theodore; Silva, Karen; Perbet, Romain; Vasiljevic, Alexandre; Faure Conter, Cécile; Frappaz, Didier; Leary, Sarah; Crane, Courtney; Chan, Aden; Ng, Ho-Keung; Shi, Zhi-Feng; Mao, Ying; Finch, Elizabeth; Eisenstat, David; Wilson, Bev; Carret, Anne Sophie; Hauser, Peter; Sumerauer, David; Krskova, Lenka; Larouche, Valerie; Fleming, Adam; Zelcer, Shayna; Jabado, Nada; Rutka, James T; Dirks, Peter; Taylor, Michael D; Chen, Shiyi; Bartels, Ute; Huang, Annie; Ellison, David W; Bouffet, Eric; Hawkins, Cynthia; Tabori, Uri

    2017-09-01

    Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy.

  4. A disconnection account of subjective empathy impairments in diffuse low-grade glioma patients.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Menjot de Champfleur, Nicolas; Costi, Emanuele; Bonnetblanc, François; Duffau, Hugues

    2015-04-01

    Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (p<0.0005 Bonferroni-corrected). Similarly, we found that disconnection of the right uncinate fasciculus and the right inferior fronto-occipital fasciculus predicted, respectively, a low (p<0.05 Bonferroni-corrected) and a high (p<0.05 Bonferroni-corrected) subjective empathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (p<0.01). Taken as a whole, these findings provide key fundamental insights into the anatomical connectivity of empathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by

  5. Learning and memory following conformal radiation therapy for pediatric craniopharyngioma and low-grade glioma.

    PubMed

    Di Pinto, Marcos; Conklin, Heather M; Li, Chenghong; Merchant, Thomas E

    2012-11-01

    The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning. Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years. No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy. This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Cost-Effectiveness of Radiation and Chemotherapy for High-Risk Low-Grade Glioma.

    PubMed

    Qian, Yushen; Maruyama, Satoshi; Kim, Haju; Pollom, Erqi L; Kumar, Kiran A; Chin, Alexander L; Harris, Jeremy P; Chang, Daniel T; Pitt, Allison; Bendavid, Eran; Owens, Douglas K; Durkee, Ben Y; Soltys, Scott G

    2017-06-28

    The addition of PCV (procarbazine, lomustine, vincristine) chemotherapy to radiotherapy (RT) for patients with high-risk (≥ 40 years old or sub-totally resected) low-grade glioma (LGG) results in an absolute median survival benefit of over 5 years. We evaluated the cost-effectiveness of this treatment strategy. A decision tree with an integrated three-state Markov model was created to follow patients with high risk LGG after surgery treated with RT vs. RT+PCV. Patients existed in one of 3 health states: stable, progressive, and dead. Survival and freedom from progression were modeled to reflect the results of RTOG 9802 using time-dependent transition probabilities. Health utility values and costs of care were derived from the literature and national registry databases. Analysis was conducted from the healthcare perspective. Deterministic and probabilistic sensitivity analysis explored uncertainty in model parameters. Modeled outcomes demonstrated agreement with clinical data in expected benefit of addition of PCV to RT. The addition of PCV to RT yielded an incremental benefit of 4.77 quality-adjusted life-years (QALYs) (9.94 for RT+PCV vs. 5.17 for RT alone) at an incremental cost of $48,635 ($188,234 for RT+PCV vs. $139,598 for RT alone), resulting in an incremental cost-effectiveness ratio of $10,186 per QALY gained. Probabilistic sensitivity analysis demonstrates that within modeled distributions of parameters, RT+PCV has 99.96% probability of being cost-effectiveness at a willingness-to-pay threshold of $100,000 per QALY. The addition of PCV to RT is a cost-effective treatment strategy for patients with high-risk LGG.

  7. Metastatic Low-Grade Gliomas in Children: 20 Years' Experience at St. Jude Children's Research Hospital.

    PubMed

    Chamdine, Omar; Broniscer, Alberto; Wu, Shengjie; Gajjar, Amar; Qaddoumi, Ibrahim

    2016-01-01

    Patients with low-grade gliomas (LGG), which are the most common childhood brain tumors, have excellent long-term survival. Dissemination of LGG is rare. Robust data on the incidence, presentation, patterns of dissemination, disease behavior, outcome, and best-management approaches do not exist. We describe 20 years of follow-up of children with metastatic LGG. Data collected during the period 1990-2010 were retrospectively reviewed for the following inclusion criteria: diagnosis of metastatic LGG, age younger than 21 years at initial diagnosis, and magnetic resonance imaging of the brain and/or spine at diagnosis and/or follow-up. Patient demographics, pathology, treatment modalities, and outcome were reviewed. Of 599 patients with LGG, 38 (6%) had metastatic disease at either diagnosis or follow-up. Most tumors (87%) were located in the brain, and half of the patients had metastatic disease at presentation. The most common diagnosis was pilocytic astrocytoma (55%). Chemotherapy was the most common initial treatment modality. Median survival of the group was 6.2 years (range, 0.1-16.9 years). Fifteen (40%) patients died at a median of 6 years from diagnosis (range, 0.8-15 years). Overall survival at 5, 10, and 15 years was 80.7 ± 6.6%, 63.0 ± 10.2%, and 50.9 ± 16.0%, respectively. This study describes the longest follow-up of children with metastatic LGG. LGG is underestimated and entails major morbidity and mortality. Prospective studies are needed to learn the true incidence, study the biology, and determine the best approaches to diagnosis, treatment, and follow-up. © 2015 Wiley Periodicals, Inc.

  8. Longitudinal investigation of adaptive functioning following conformal irradiation for pediatric craniopharyngioma and low-grade glioma.

    PubMed

    Netson, Kelli L; Conklin, Heather M; Wu, Shengjie; Xiong, Xiaoping; Merchant, Thomas E

    2013-04-01

    Children treated for brain tumors with conformal radiation therapy experience preserved cognitive outcomes. Early evidence suggests that adaptive functions or independent-living skills may be spared. This longitudinal investigation prospectively examined intellectual and adaptive functioning during the first 5 years following irradiation for childhood craniopharyngioma and low-grade glioma (LGG). The effect of visual impairment on adaptive outcomes was investigated. Children with craniopharyngioma (n=62) and LGG (n=77) were treated using conformal or intensity modulated radiation therapy. The median age was 8.05 years (3.21-17.64 years) and 8.09 years (2.20-19.27 years), respectively. Serial cognitive evaluations including measures of intelligence quotient (IQ) and the Vineland Adaptive Behavior Scales (VABS) were conducted at preirradiation baseline, 6 months after treatment, and annually through 5 years. Five hundred eighty-eight evaluations were completed during the follow-up period. Baseline assessment revealed no deficits in IQ and VABS indices for children with craniopharyngioma, with significant (P<.05) longitudinal decline in VABS Communication and Socialization indices. Clinical factors associated with more rapid decline included females and preirradiation chemotherapy (interferon). The only change in VABS Daily Living Skills correlated with IQ change (r=0.34; P=.01) in children with craniopharyngioma. Children with LGG performed below population norms (P<.05) at baseline on VABS Communication, Daily Living Indices, and the Adaptive Behavior Composite, with significant (P<.05) longitudinal decline limited to VABS Communication. Older age at irradiation was a protective factor against longitudinal decline. Severe visual impairment did not independently correlate with poorer adaptive outcomes for either tumor group. There was relative sparing of postirradiation functional outcomes over time in this sample. Baseline differences in functional abilities before

  9. Compromised health-related quality of life in patients with low-grade glioma.

    PubMed

    Aaronson, Neil K; Taphoorn, Martin J B; Heimans, Jan J; Postma, Tjeerd J; Gundy, Chad M; Beute, Guus N; Slotman, Ben J; Klein, Martin

    2011-11-20

    To investigate the generic and condition-specific health-related quality of life (HRQL) of patients with low-grade glioma (LGG). A total of 195 patients with LGG, which was diagnosed, on average, 5.6 years before the study, were compared with 100 patients with hematologic (non-Hodgkin's) lymphoma and chronic lymphatic leukemia cancer (NHL/CLL) and 205 general population controls who were comparable with patients with LGG at the group level for age, sex, and education (healthy controls). Generic HRQL was assessed with the Short Form-36 (SF-36) Health Survey, and condition-specific HRQL was assessed with the Medical Outcomes Study cognitive function questionnaire and the European Organisation for Research and Treatment of Cancer brain cancer module. Objective neurocognitive functioning was assessed with a standardized battery of neuropsychological tests. No statistically significant differences were observed between patients with LGG and patients with NHL/CLL in SF-36 scores. Patients with LGG scored significantly lower than healthy controls on six of eight scales and on the mental health component score of the SF-36. Approximately one quarter of patients with LGG reported serious neurocognitive symptoms. Female sex, epilepsy burden, and number of objectively assessed neurocognitive deficits were associated significantly with both generic and condition-specific HRQL. Clinical variables, including the time since diagnosis, tumor lateralization, extent of surgery, and radiotherapy, did not show a consistent relationship with HRQL. Patients with LGG experienced significant problems across a broad range of HRQL domains, many of which were not condition-specific. However, the neurocognitive deficits and epilepsy that were relatively prevalent among patients with LGG were associated with negative HRQL outcomes and, thus, contributed additionally to the vulnerability of this population of patients with cancer.

  10. Fluorine F 18 Fluorodopa-Labeled PET Scan in Planning Surgery and Radiation Therapy in Treating Patients With Newly Diagnosed High- or Low-Grade Malignant Glioma

    ClinicalTrials.gov

    2016-10-10

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma

  11. Low Grade Gliomas in Eloquent Locations – Implications for Surgical Strategy, Survival and Long Term Quality of Life

    PubMed Central

    Jakola, Asgeir S.; Unsgård, Geirmund; Myrmel, Kristin S.; Kloster, Roar; Torp, Sverre H.; Lindal, Sigurd; Solheim, Ole

    2012-01-01

    Background Surgical management of suspected LGG remains controversial. A key factor when deciding a surgical strategy is often the tumors’ perceived relationship to eloquent brain regions Objective To study the association between tumor location, survival and long-term health related quality of life (HRQL) in patients with supratentorial low-grade gliomas (LGG). Methods Adults (≥18 years) operated due to newly diagnosed LGG from 1998 through 2009 included from two Norwegian university hospitals. After review of initial histopathology, 153 adults with supratentorial WHO grade II LGG were included in the study. Tumors’ anatomical location and the relationship to eloquent regions were graded. Survival analysis was adjusted for known prognostic factors and the initial surgical procedure (biopsy or resection). In long-term survivors, HRQL was assessed with disease specific questionnaires (EORTC QLQ-C30 and BN20) as well as a generic questionnaire (EuroQol 5D). Results There was a significant association between eloquence and survival (log-rank, p<0.001). The estimated 5-year survival was 77% in non-eloquent tumors, 71% in intermediate located tumors and 54% in eloquent tumors. In the adjusted analysis the hazard ratio of increasing eloquence was 1.5 (95% CI 1.1–2.0, p = 0.022). There were no differences in HRQL between patients with eloquent and non-eloquent tumors. The most frequent self-reported symptoms were related to fatigue, cognition, and future uncertainty. Conclusion Eloquently located LGGs are associated with impaired survival compared to non-eloquently located LGG, but in long-term survivors HRQL is similar. Although causal inference from observational data should be done with caution, the findings illuminate the delicate balance in surgical decision making in LGGs, and add support to the probable survival benefits of aggressive surgical strategies, perhaps also in eloquent locations. PMID:23251537

  12. Low grade gliomas in eloquent locations - implications for surgical strategy, survival and long term quality of life.

    PubMed

    Jakola, Asgeir S; Unsgård, Geirmund; Myrmel, Kristin S; Kloster, Roar; Torp, Sverre H; Lindal, Sigurd; Solheim, Ole

    2012-01-01

    Surgical management of suspected LGG remains controversial. A key factor when deciding a surgical strategy is often the tumors' perceived relationship to eloquent brain regions To study the association between tumor location, survival and long-term health related quality of life (HRQL) in patients with supratentorial low-grade gliomas (LGG). Adults (≥18 years) operated due to newly diagnosed LGG from 1998 through 2009 included from two Norwegian university hospitals. After review of initial histopathology, 153 adults with supratentorial WHO grade II LGG were included in the study. Tumors' anatomical location and the relationship to eloquent regions were graded. Survival analysis was adjusted for known prognostic factors and the initial surgical procedure (biopsy or resection). In long-term survivors, HRQL was assessed with disease specific questionnaires (EORTC QLQ-C30 and BN20) as well as a generic questionnaire (EuroQol 5D). There was a significant association between eloquence and survival (log-rank, p<0.001). The estimated 5-year survival was 77% in non-eloquent tumors, 71% in intermediate located tumors and 54% in eloquent tumors. In the adjusted analysis the hazard ratio of increasing eloquence was 1.5 (95% CI 1.1-2.0, p = 0.022). There were no differences in HRQL between patients with eloquent and non-eloquent tumors. The most frequent self-reported symptoms were related to fatigue, cognition, and future uncertainty. Eloquently located LGGs are associated with impaired survival compared to non-eloquently located LGG, but in long-term survivors HRQL is similar. Although causal inference from observational data should be done with caution, the findings illuminate the delicate balance in surgical decision making in LGGs, and add support to the probable survival benefits of aggressive surgical strategies, perhaps also in eloquent locations.

  13. Molecular fingerprinting reflects different histotypes and brain region in low grade gliomas

    PubMed Central

    2013-01-01

    Background Paediatric low-grade gliomas (LGGs) encompass a heterogeneous set of tumours of different histologies, site of lesion, age and gender distribution, growth potential, morphological features, tendency to progression and clinical course. Among LGGs, Pilocytic astrocytomas (PAs) are the most common central nervous system (CNS) tumours in children. They are typically well-circumscribed, classified as grade I by the World Health Organization (WHO), but recurrence or progressive disease occurs in about 10-20% of cases. Despite radiological and neuropathological features deemed as classic are acknowledged, PA may present a bewildering variety of microscopic features. Indeed, tumours containing both neoplastic ganglion and astrocytic cells occur at a lower frequency. Methods Gene expression profiling on 40 primary LGGs including PAs and mixed glial-neuronal tumours comprising gangliogliomas (GG) and desmoplastic infantile gangliogliomas (DIG) using Affymetrix array platform was performed. A biologically validated machine learning workflow for the identification of microarray-based gene signatures was devised. The method is based on a sparsity inducing regularization algorithm l1l2 that selects relevant variables and takes into account their correlation. The most significant genetic signatures emerging from gene-chip analysis were confirmed and validated by qPCR. Results We identified an expression signature composed by a biologically validated list of 15 genes, able to distinguish infratentorial from supratentorial LGGs. In addition, a specific molecular fingerprinting distinguishes the supratentorial PAs from those originating in the posterior fossa. Lastly, within supratentorial tumours, we also identified a gene expression pattern composed by neurogenesis, cell motility and cell growth genes which dichotomize mixed glial-neuronal tumours versus PAs. Our results reinforce previous observations about aberrant activation of the mitogen-activated protein kinase

  14. Biopsy versus resection for the management of low-grade gliomas.

    PubMed

    Jiang, Bowen; Chaichana, Kaisorn; Veeravagu, Anand; Chang, Steven D; Black, Keith L; Patil, Chirag G

    2017-04-27

    This is an updated version of the original Cochrane review published in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG. To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG. The following electronic databases were searched in 2012 for the first version of the review: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to November week 3 2012), Embase (1980 to Week 46 2012). For this updated version, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3 2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified on PubMed and by using the 'related articles' feature. We also searched unpublished and grey literature including ISRCTN-metaRegister of Controled Trials, Physicians Data Query and ClinicalTrials.gov for ongoing trials. We planned to include patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT). Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression-free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL). A total of 1375

  15. Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI.

    PubMed

    Zacà, Domenico; Jovicich, Jorge; Nadar, Sreenivasan R; Voyvodic, James T; Pillai, Jay J

    2014-08-01

    (i) to validate blood oxygenation level dependent (BOLD) breathhold cerebrovascular reactivity (BH CVR) mapping as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional MRI (fMRI) for sensorimotor mapping, and (ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group. We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional). Motor task mean T-value was significantly higher in the contralesional ROIs (6.00 ± 1.74 versus 4.34 ± 1.68; P = 0.00004) as well as the BH mean T-value (4.74 ± 2.30 versus 4.09 ± 2.50; P = 0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z = 2.99; P = 0.03). Actual NVU prevalence was 75%. Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks). © 2013 Wiley Periodicals, Inc.

  16. Cerebrovascular reactivity mapping in patients with low grade gliomas undergoing presurgical sensorimotor mapping with BOLD fMRI

    PubMed Central

    Zacà, Domenico; Jovicich, Jorge; Nadar, Sreenivasan R.; Voyvodic, James T.; Pillai, Jay J.

    2013-01-01

    Purpose i) to validate Blood Oxygenation Level Dependent (BOLD) breath hold cerebrovascular reactivity mapping (BH CVR) as an effective technique for potential detection of neurovascular uncoupling (NVU) in a cohort of patients with perirolandic low grade gliomas undergoing presurgical functional magnetic resonance imaging (fMRI) for sensorimotor mapping, and ii) to determine whether NVU potential, as assessed by BH CVR mapping, is prevalent in this tumor group. Materials and Methods We retrospectively evaluated 12 patients, with histological diagnosis of grade II glioma, who performed multiple motor tasks and a BH task. Sensorimotor activation maps and BH CVR maps were compared in two automatically defined regions of interest (ROIs), ipsilateral to the lesion (i.e., ipsilesional) and contralateral to the lesion (i.e., contralesional). Results Motor task mean T-value was significantly higher in the contralesional ROIs (6.00±1.74 vs 4.34±1.68, p=0.00004) as well as the BH mean T-value (4.74±2.30 vs 4.09±2.50, p=0.009). The number of active voxels was significantly higher in the contralesional ROIs (Z=2.99, p=0.03). Actual NVU prevalence was 75%. Conclusion Presurgical sensorimotor fMRI mapping can be affected by NVU-related false negative activation in low grade gliomas (76% of analyzed tasks). PMID:24338845

  17. Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas

    PubMed Central

    Sarmiento, J Manuel; Venteicher, Andrew S; Patil, Chirag G

    2015-01-01

    Background In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. Objectives To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. Search methods We searched up to September 2014 the following electronic databases: the Cochrane Register of Controlled Trials (CENTRAL, Issue 8, 2014), MEDLINE (1948 to Aug week 3, 2014), and EMBASE (1980 to Aug week 3, 2014) to identify trials for inclusion in this Cochrane review. Selection criteria We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). Data collection and analysis Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. Main results We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy is associated with an increase in time to

  18. Using different schedules of Temozolomide to treat low grade gliomas: systematic review of their efficacy and toxicity.

    PubMed

    Lashkari, Harsha Prasada; Saso, Srdjan; Moreno, Lucas; Athanasiou, Thanos; Zacharoulis, Stergios

    2011-11-01

    Low grade gliomas (LGG) contribute to 50% of all central nervous tumors in children and 15% of all gliomas in adults. Temozolomide (TMZ) is an oral alkylating agent with activity in high and LGG. Various regimens of TMZ are currently in use. We attempted to assess the impact of different TMZ regimens on the treatment of LGG. A systematic review of the literature identified all the studies published in Pubmed, EMBASE and Cochrane databases which met the inclusion criteria. The primary outcome measure was the impact of different TMZ regimens on the 12 month progression-free survival (PFS) rates of patients diagnosed with progressive LGG. Secondary outcome measures looked at the ability of the three regimens to elicit an objective response and the associated toxicity. Statistical pooling and calculation of weighted mean average of each proportion (WMAP) was conducted using a random-effects model. 18 studies (736 patients) were analyzed. PFS at 12 months revealed a WMAP of 0.61 (95% CI 0.44-0.78) for regimen A, 0.59 (0.28-0.89) for regimen B, and 0.91 (95% CI 0.83-0.99) for regimen C (Regimen A--200 mg/m(2)/day for 5 days, repeated every 4 weeks; B--75 mg/m(2)/day for 21 days repeated every 4 weeks; C--75 mg/m(2)/day for 7 weeks with 4 weeks of every 11 weeks). In terms of objective response, WMAP were 0.19 (95% 0.13-0.25), 0.27 (95% CI 0.15-0.39) and 0.21 (95% CI 0.10-0.32) for regimen A, B, C respectively. When analyzing hematological toxicity, WMAPs were 0.14 (95% 0.11-0.18), 0.35 (0.14-0.56) and 0.23 (95% CI 0.03-0.43). The bulk of evidence originates from the standard 5 day/month regimen A but with a lack of comparative studies. Analysis revealed significant heterogeneity. Although there is possibly an indication that metronomic regimens of TMZ result in better PFS and response rate when compared to the conventional standard 5 day regimen, insufficient available data and study heterogeneity preclude any safe conclusions. Well designed randomized controlled

  19. Bevacizumab and Irinotecan in Treating Young Patients With Recurrent, Progressive, or Refractory Glioma, Medulloblastoma, Ependymoma, or Low Grade Glioma

    ClinicalTrials.gov

    2017-08-28

    Childhood Cerebral Anaplastic Astrocytoma; Childhood Oligodendroglioma; Childhood Spinal Cord Neoplasm; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma

  20. Rare synchronous association of vestibular schwannoma and indolent insular oligodendroglioma in a patient without neurofibromatosis: controversial issue of timing for surgical treatment of asymptomatic low-grade gliomas

    PubMed Central

    Iacoangeli, Maurizio; Di Rienzo, Alessandro; Colasanti, Roberto; Alvaro, Lorenzo; Nocchi, Niccolò; Polonara, Gabriele; Di Somma, Lucia Giovanna Maria; Zizzi, Antonio; Scarpelli, Marina; Scerrati, Massimo

    2012-01-01

    The co-occurrence of a vestibular schwannoma and a low-grade glioma is rare, and even rarer is the association with an oligodendroglioma. Although various authors have addressed the problem of treating patients with incidentally discovered indolent low-grade gliomas, an established protocol does not exist to date. The common approach is to reserve surgery until there is radiological evidence of tumor growth or high-grade transformation. However, because incidental low-grade glioma may represent the first stage of unavoidable pathological progression towards high-grade glioma, early and radical surgical resection should be advocated in order to increase the chance of a “cure” and prolonged survival. This case report supports this view, and suggests reflection on a possible change from a conservative philosophy to preventative surgical treatment. PMID:23180968

  1. Detection of KIAA1549-BRAF Fusion Transcripts in Formalin-Fixed Paraffin-Embedded Pediatric Low-Grade Gliomas

    PubMed Central

    Tian, Yongji; Rich, Benjamin E.; Vena, Natalie; Craig, Justin M.; MacConaill, Laura E.; Rajaram, Veena; Goldman, Stewart; Taha, Hala; Mahmoud, Madeha; Ozek, Memet; Sav, Aydin; Longtine, Janina A.; Lindeman, Neal I.; Garraway, Levi A.; Ligon, Azra H.; Stiles, Charles D.; Santagata, Sandro; Chan, Jennifer A.; Kieran, Mark W.; Ligon, Keith L.

    2011-01-01

    Alterations of BRAF are the most common known genetic aberrations in pediatric gliomas. They frequently are found in pilocytic astrocytomas, where genomic duplications involving BRAF and the poorly characterized gene KIAA1549 create fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point mutations are less common and generally occur in nonpilocytic tumors. The development of BRAF inhibitors as drugs has created an urgent need for robust clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion transcripts have been detected in frozen tissue, however, methods for FFPE tissue have not been reported. We developed a panel of FFPE-compatible quantitative RT-PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of these assays to a collection of 51 low-grade pediatric gliomas showed 97% sensitivity and 91% specificity compared with fluorescence in situ hybridization or array comparative genomic hybridization. In parallel, we assayed samples for the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further support previous observations that these two alterations of the BRAF, KIAA1549 fusions and V600E point mutations, are associated primarily with pilocytic astrocytomas and nonpilocytic gliomas, respectively. These results show that fusion transcripts and mutations can be detected reliably in standard FFPE specimens and may be useful for incorporation into future studies of pediatric gliomas in basic science or clinical trials. PMID:21884820

  2. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma.

    PubMed

    Buckner, Jan C; Shaw, Edward G; Pugh, Stephanie L; Chakravarti, Arnab; Gilbert, Mark R; Barger, Geoffrey R; Coons, Stephen; Ricci, Peter; Bullard, Dennis; Brown, Paul D; Stelzer, Keith; Brachman, David; Suh, John H; Schultz, Christopher J; Bahary, Jean-Paul; Fisher, Barbara J; Kim, Harold; Murtha, Albert D; Bell, Erica H; Won, Minhee; Mehta, Minesh P; Curran, Walter J

    2016-04-07

    Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and

  3. Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma

    PubMed Central

    Buckner, Jan C.; Shaw, Edward G.; Pugh, Stephanie L.; Chakravarti, Arnab; Gilbert, Mark R.; Barger, Geoffrey R.; Coons, Stephen; Ricci, Peter; Bullard, Dennis; Brown, Paul D.; Stelzer, Keith; Brachman, David; Suh, John H.; Schultz, Christopher J.; Bahary, Jean-Paul; Fisher, Barbara J.; Kim, Harold; Murtha, Albert D.; Bell, Erica H.; Won, Minhee; Mehta, Minesh P.; Curran, Walter J.

    2016-01-01

    BACKGROUND Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or

  4. Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom.

    PubMed

    Meguins, Lucas Crociati; Adry, Rodrigo Antônio Rocha da Cruz; Silva Júnior, Sebastião Carlos da; Pereira, Carlos Umberto; Oliveira, Jean Gonçalves de; Morais, Dionei Freitas de; Araújo Filho, Gerardo Maria de; Marques, Lúcia Helena Neves

    2015-11-01

    To present a surgical series of patients with low grade temporal gliomas causing intractable epilepsy, focusing on long-term seizure outcome. A retrospective study was conducted with patients with temporal low-grade gliomas (LGG). Sixty five patients with were operated in our institution. Males were more affected than females and the mean age at surgery was 32.3 ± 8.4 (9-68 years). The mean age at seizure onset was 25.7 ± 9.2 (11-66 years). Seizure outcome was classified according with Engel classification. After one year of follow up, forty two patients (64.6%) were Engel I; seventeen (26.2%) Engel II; four (6.2%) Engel III and two (3.1%) Engel IV. Statistically significant difference in seizure outcome was obtained when comparing the extension of resection. Engel I was observed in 39 patients (69.6%) with total resection and in only 3 (33.3%) patients with partial resection. Gross-total resection of temporal LGGs is a critically important factor in achieving seizure-freedom.

  5. Olig2 labeling index is correlated with histological and molecular classifications in low-grade diffuse gliomas.

    PubMed

    Suzuki, Aya; Nobusawa, Sumihito; Natsume, Atsushi; Suzuki, Hiromichi; Kim, Young-Ho; Yokoo, Hideaki; Nagaishi, Masaya; Ikota, Hayato; Nakazawa, Takuro; Wakabayashi, Toshihiko; Ohgaki, Hiroko; Nakazato, Yoichi

    2014-11-01

    Diagnosis of low-grade diffuse gliomas based on morphology is highly subjective and, therefore, is often difficult, with significant intra- and interobserver variability. Here, we investigated WHO grade II diffuse astrocytomas, oligoastrocytomas and oligodendrogliomas for immunohistochemical expression of Olig2, measuring its labeling index (LI), and evaluated the significance of Olig2 LI in the histological and molecular classifications. The means of Olig2 LI in glioma cells were 43.7 % in diffuse astrocytomas, 59.3 % in oligoastrocytomas and 76.1 % in oligodendrogliomas. There was a statistically significant difference between all pairs of histological types. The mean of Olig2 LI of gliomas with 1p/19q loss ± IDH1/2 mutation, the majority of them being oligodendrogliomas, was significantly higher than the means of those with TP53 mutation ± IDH1/2 mutation and IDH1/2 mutation only, the majority of which were diffuse astrocytomas (70.1 vs. 47.2 and 46.5 %, respectively). When categorized according to the classification of Jiao et al., Olig2 LI of I-CF gliomas (cases with IDH and one or more of CIC, FUBP1 or combined 1p/19q loss; mean 71.0 %) was significantly higher than that of I-A gliomas (cases with IDH and ATRX alterations; mean 45.3 %). These molecular classifications were reported to correlate well with clinical outcome. However, borderlines of Olig2 LI were broad and could not clearly distinguish genotypes in the molecular classifications. In conclusion, Olig2 LI cannot be taken as a complete surrogate marker for molecular genotype, but could possibly provide some ancillary information when molecular assay is not availabe.

  6. Genetics of adult glioma.

    PubMed

    Goodenberger, McKinsey L; Jenkins, Robert B

    2012-12-01

    Gliomas make up approximately 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors. Despite the frequency of gliomas, the etiology of these tumors remains largely unknown. Diffuse gliomas, including astrocytomas and oligodendrogliomas, belong to a single pathologic class but have very different histologies and molecular etiologies. Recent genomic studies have identified separate molecular subtypes within the glioma classification that appear to correlate with biological etiology, prognosis, and response to therapy. The discovery of these subtypes suggests that molecular genetic tests are and will be useful, beyond classical histology, for the clinical classification of gliomas. While a familial susceptibility to glioma has been identified, only a small percentage of gliomas are thought to be due to single-gene hereditary cancer syndromes. Through the use of linkage studies and genome-wide association studies, multiple germline variants have been identified that are beginning to define the genetic susceptibility to glioma.

  7. Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies.

    PubMed

    Delgado-López, P D; Corrales-García, E M; Martino, J; Lastra-Aras, E; Dueñas-Polo, M T

    2017-03-02

    The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

  8. Occupation and adult gliomas.

    PubMed

    Carozza, S E; Wrensch, M; Miike, R; Newman, B; Olshan, A F; Savitz, D A; Yost, M; Lee, M

    2000-11-01

    Lifetime job histories from a population-based, case-control study of gliomas diagnosed among adults in the San Francisco Bay area between August 1991 and April 1994 were evaluated to assess occupational risk factors. Occupational data for 476 cases and 462 controls were analyzed, with adjustment for age, gender, education, and race. Imprecise increased risks were observed for physicians and surgeons (odds ratio (OR) = 3.5, 95% confidence interval (CI): 0.7, 17.6), artists (OR = 1.9, 95% CI: 0.5, 6.5), foundry and smelter workers (OR = 2.6, 95% CI: 0.5, 13.1), petroleum and gas workers (OR = 4.9, 95% CI: 0.6, 42.2), and painters (OR = 1.6, 95% CI: 0.5, 4.9). Legal and social service workers, shippers, janitors, motor vehicle operators, and aircraft operators had increased odds ratios only with longer duration of employment. Physicians and surgeons, foundry and smelter workers, petroleum and gas workers, and painters showed increased risk for both astrocytic and nonastrocytic tumors. Artists and firemen had increased risk for astrocytic tumors only, while messengers, textile workers, aircraft operators, and vehicle manufacturing workers showed increased risk only for nonastrocytic tumors. Despite study limitations, including small numbers for many of the occupational groups, a high percentage of proxy respondents among cases, and lack of specific exposure information, associations were observed for several occupations previously reported to be at higher risk for brain tumors generally and gliomas specifically.

  9. Glioma-associated stem cells: a novel class of tumor-supporting cells able to predict prognosis of human low-grade gliomas.

    PubMed

    Bourkoula, Evgenia; Mangoni, Damiano; Ius, Tamara; Pucer, Anja; Isola, Miriam; Musiello, Daniela; Marzinotto, Stefania; Toffoletto, Barbara; Sorrentino, Marisa; Palma, Anita; Caponnetto, Federica; Gregoraci, Giorgia; Vindigni, Marco; Pizzolitto, Stefano; Falconieri, Giovanni; De Maglio, Giovanna; Pecile, Vanna; Ruaro, Maria Elisabetta; Gri, Giorgia; Parisse, Pietro; Casalis, Loredana; Scoles, Giacinto; Skrap, Miran; Beltrami, Carlo Alberto; Beltrami, Antonio Paolo; Cesselli, Daniela

    2014-05-01

    Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-the-art markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. We isolated glioma-associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASC-based score was the only independent predictor of overall survival and malignant progression free-survival. The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of glioma-initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient-based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. © 2013 AlphaMed Press.

  10. Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

    SciTech Connect

    Greenberger, Benjamin A.; Pulsifer, Margaret B.; Ebb, David H.; MacDonald, Shannon M.; Jones, Robin M.; Butler, William E.; Huang, Mary S.; Marcus, Karen J.; Oberg, Jennifer A.; Tarbell, Nancy J.; Yock, Torunn I.

    2014-08-01

    Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy{sub RBE} (48.6-54 Gy{sub RBE}). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 Gy{sub RBE} to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.

  11. Intraoperative Probe-Based Confocal Laser Endomicroscopy in Surgery and Stereotactic Biopsy of Low-Grade and High-Grade Gliomas: A Feasibility Study in Humans.

    PubMed

    Pavlov, Vladislav; Meyronet, David; Meyer-Bisch, Vincent; Armoiry, Xavier; Pikul, Brian; Dumot, Chloé; Beuriat, Pierre-Aurelien; Signorelli, Francesco; Guyotat, Jacques

    2016-10-01

    The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection. To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas. In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment. The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy "normal" tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed. We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins. 5-ALA, 5-aminolevulinic acidpCLE, probe-based confocal laser endomicroscopyPpIX, protoporphyrin IX.

  12. CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles.

    PubMed

    Jain, P; Fierst, T M; Han, H J; Smith, T E; Vakil, A; Storm, P J; Resnick, A C; Waanders, A J

    2017-08-14

    Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways. Although ATP-competitive, first-generation RAF inhibitors (vemurafenib/PLX4720, RAFi) cause paradoxical activation of the MAPK pathway in BRAF-fusion tumors, inhibition can be achieved with 'paradox breaker' RAFi, such as PLX8394. Here we report that, unlike BRAF fusions, CRAF fusions are unresponsive to both generations of RAFi, vemurafenib and PLX8394, highlighting a distinct responsiveness of CRAF fusions to clinically relevant RAFi. Whereas PLX8394 decreased BRAF-fusion dimerization, CRAF-fusion dimerization is unaffected primarily because of robust protein-protein interactions mediated by the N-terminal non-kinase fusion partner, such as QKI. The pan-RAF dimer inhibitor, LY3009120, could suppress CRAF-fusion oncogenicity by inhibiting dimer-mediated signaling. In addition, as CRAF fusions activate both the MAPK and PI3K/mTOR signaling pathways, we identify combinatorial inhibition of the MAPK/mTOR pathway as a potential therapeutic strategy for CRAF-fusion-driven tumors. Overall, we define a mechanistic distinction between PLGG-associated BRAF- and CRAF/RAF1 fusions in response to RAFi, highlighting the importance of molecularly classifying PLGG patients for targeted therapy. Furthermore, our study uncovers an important contribution of the non-kinase fusion partner to oncogenesis and potential therapeutic strategies against PLGG

  13. Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity.

    PubMed

    Duffau, Hugues

    2005-08-01

    Surgical treatment of low-grade gliomas (LGGs) aims to maximise the amount of tumour tissue resected, while minimising the risk of functional sequelae. In this review I address the issue of how to reconcile these two conflicting goals. First, I review the natural history of LGG-growth, invasion, and anaplastic transformation. Second, I discuss the contribution of new techniques, such as functional mapping, to our understanding of brain reorganisation in response to progressive growth of LGG. Third, I consider the clinical implications of interactions between tumour progression and brain plasticity. In particular, I show how longitudinal studies (preoperative, intraoperative, and postoperative) could allow us to optimise the surgical risk-to-benefit ratios. I will also discuss controversial issues such as defining surgical indications for LGGs, predicting the risk of postoperative deficit, aspects of operative surgical neuro-oncology (eg, preoperative planning and preservation of functional areas and tracts), and postoperative functional recovery.

  14. An inverse problem formulation for parameter estimation of a reaction-diffusion model of low grade gliomas

    PubMed Central

    Gholami, Amir; Mang, Andreas; Biros, George

    2015-01-01

    We present a numerical scheme for solving a parameter estimation problem for a model of low-grade glioma growth. Our goal is to estimate the spatial distribution of tumor concentration, as well as the magnitude of anisotropic tumor diffusion. We use a constrained optimization formulation with a reaction-diffusion model that results in a system of nonlinear partial differential equations (PDEs). In our formulation, we estimate the parameters using partially observed, noisy tumor concentration data at two different time instances, along with white matter fiber directions derived from diffusion tensor imaging (DTI). The optimization problem is solved with a Gauss-Newton reduced space algorithm. We present the formulation and outline the numerical algorithms for solving the resulting equations. We test the method using synthetic dataset and compute the reconstruction error for different noise levels and detection thresholds for monofocal and multifocal test cases. PMID:25963601

  15. Stochastic modelling of slow-progressing tumors: Analysis and applications to the cell interplay and control of low grade gliomas

    NASA Astrophysics Data System (ADS)

    Rodríguez, Clara Rojas; Fernández Calvo, Gabriel; Ramis-Conde, Ignacio; Belmonte-Beitia, Juan

    2017-08-01

    Tumor-normal cell interplay defines the course of a neoplastic malignancy. The outcome of this dual relation is the ultimate prevailing of one of the cells and the death or retreat of the other. In this paper we study the mathematical principles that underlay one important scenario: that of slow-progressing cancers. For this, we develop, within a stochastic framework, a mathematical model to account for tumor-normal cell interaction in such a clinically relevant situation and derive a number of deterministic approximations from the stochastic model. We consider in detail the existence and uniqueness of the solutions of the deterministic model and study the stability analysis. We then focus our model to the specific case of low grade gliomas, where we introduce an optimal control problem for different objective functionals under the administration of chemotherapy. We derive the conditions for which singular and bang-bang control exist and calculate the optimal control and states.

  16. Long-Term Results of Brachytherapy With Temporary Iodine-125 Seeds in Children With Low-Grade Gliomas

    SciTech Connect

    Korinthenberg, Rudolf; Neuburger, Daniela; Trippel, Michael; Ostertag, Christoph; Nikkhah, Guido

    2011-03-15

    Purpose: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. Methods and Materials: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. Results: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. Conclusions: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.

  17. Proton magnetic resonance spectroscopic imaging in pediatric low-grade gliomas.

    PubMed

    Porto, Luciana; Kieslich, Matthias; Franz, Kea; Lehrbecher, Thomas; Pilatus, Ulrich; Hattingen, Elke

    2010-10-01

    Our purpose was to investigate whether in vivo proton magnetic resonance spectroscopic imaging, using normalized concentrations of total choline (tCho) and total creatine (tCr), can differentiate between WHO grade I pilocytic astrocytoma (PA) and diffuse, fibrillary WHO grade II astrocytoma (DA) in children. Data from 16 children with astrocytomas (11 children with PA and 5 children with DA) were evaluated retrospectively. MRS was performed before treatment in all patients with histologically proven low-grade astrocytomas. Metabolite concentrations of tCho and tCr were normalized to the respective concentration in contralateral brain tissue. The Mann-Whitney U test was performed to evaluate differences between these two groups. Normalized tCho did not show any statistically significant difference between the two groups. There was a strong trend (P = 0.07) toward higher values of normalized tCr in the DA group. For 3 of 5 children with DA, lactate was detectable, but only 1 of 11 children with PA showed lactate. We concluded that choline as a single parameter is not reliable in the differential diagnosis of low-grade astrocytomas in children. Our results suggest that tCr concentrations combined with lactate will be helpful in the differential diagnosis of PA and DA in children.

  18. New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach

    PubMed Central

    Duffau, Hugues; Taillandier, Luc

    2015-01-01

    Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a “wait and see” policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology. PMID:25087230

  19. New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach.

    PubMed

    Duffau, Hugues; Taillandier, Luc

    2015-03-01

    Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Differentiation of high-grade and low-grade diffuse gliomas by intravoxel incoherent motion MR imaging

    PubMed Central

    Togao, Osamu; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Mizoguchi, Masahiro; Yoshimoto, Koji; Suzuki, Satoshi O.; Iwaki, Toru; Obara, Makoto; Van Cauteren, Marc; Honda, Hiroshi

    2016-01-01

    Background Our aim was to assess the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). Methods Forty-five patients with diffuse glioma (age 50.9 ± 20.4 y; 26 males, 19 females) were assessed with IVIM imaging using 13 b-values (0–1000 s/mm2) at 3T. The perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were calculated by fitting the bi-exponential model. The apparent diffusion coefficient (ADC) was obtained with 2 b-values (0 and 1000 s/mm2). Relative cerebral blood volume was measured by the dynamic susceptibility contrast method. Two observers independently measured D, ADC, D*, and f, and these measurements were compared between the LGG group (n = 16) and the HGG group (n = 29). Results Both D (1.26 ± 0.37 mm2/s in LGG, 0.94 ± 0.19 mm2/s in HGG; P < .001) and ADC (1.28 ± 0.35 mm2/s in LGG, 1.03 ± 0.19 mm2/s in HGG; P < .01) were lower in the HGG group. D was lower than ADC in the LGG (P < .05) and HGG groups (P < .0001). D* was not different between the groups. The f-values were significantly larger in HGG (17.5 ± 6.3%) than in LGG (5.8 ± 3.8%; P < .0001) and correlated with relative cerebral blood volume (r = 0.85; P < .0001). Receiver operating characteristic analyses showed areas under curve of 0.95 with f, 0.78 with D, 0.73 with ADC, and 0.60 with D*. Conclusion IVIM imaging is useful in differentiating HGGs from LGGs. PMID:26243792

  1. Late sequela after treatment of childhood low-grade gliomas: a retrospective analysis of 69 long-term survivors treated between 1983 and 2003.

    PubMed

    Benesch, Martin; Lackner, Herwig; Sovinz, Petra; Suppan, Elisabeth; Schwinger, Wolfgang; Eder, Hans-Georg; Dornbusch, Hans Jürgen; Moser, Andrea; Triebl-Roth, Karin; Urban, Christian

    2006-06-01

    The aim of the present study was to evaluate the spectrum of late effects in a large cohort of pediatric patients with low-grade gliomas (WHO grade I and II) during an observation period of 20 years. Eighty-seven patients with low-grade gliomas grouped according to tumor location (cerebellum: n=28; cerebral hemispheres: n=21; central midline: n=15; brainstem: n=12; tectum: n=5; other locations: n=6) were evaluated for tumor- and/or treatment-related late effects by analysis of medical and computer records, and personal interviews. Seventy patients underwent neurosurgery, 29 patients received additional radiotherapy and 20 additional chemotherapy. Median follow-up of survivors is 96 months with an overall survival of 79% (cerebellum: 89%; cerebral hemispheres: 95%; central midline: 80%; brainstem: 25%; tectum: 100%; other locations: 66%). Chronic medical problems (mild ataxia to multiple severe neuroendocrine deficits) are observed in 100% of patients with brainstem/central midline tumors and in 40-50% of patients with low-grade gliomas of other locations. Endocrine deficiencies were observed in 15/17 (88%) of long-term survivors who received radiotherapy. In contrast, none of the patients who underwent surgery only had endocrine deficiencies. Seven long-term survivors (10.1%) are severely disabled with permanent need of medical help. Tumor- and treatment-related late effects are common in patients with low-grade gliomas with the most severe occurring in patients with brainstem or central midline tumors. As long-term survival is excellent in patients with low-grade gliomas except for tumors located in the brainstem, future treatment studies should focus on avoiding long-term late effects.

  2. Viability screen on pediatric low grade glioma cell lines unveils a novel anti-cancer drug of the steroid biosynthesis inhibitor family.

    PubMed

    Ajeawung, Norbert Fonya; Maltais, René; Jones, Chris; Poirier, Donald; Kamnasaran, Deepak

    2013-03-01

    Pediatric low grade gliomas are the most common central nervous system tumors and are still incurable among a subset of patients despite current treatment modalities. Steroid biosynthesis occurs in a wide variety of organs including the brain, to mediate an assortment of functions, including a proposed role in the growth of gliomas. Hence, targeting steroid biosynthesis and/or their signaling pathways, is anticipated as an effective approach for treating gliomas. In this study, we investigated whether our chemical library of steroid inhibitors can modulate the growth of pediatric low grade glioma cell lines (Res186, Res259, R286), and subsequently identified a potent inhibitor of 17β-hydroxysteroid dehydrogenase type 3, referred to as DK16, which functions by attenuating cell viability, proliferation, migration/invasion and anchorage independent growth and conversely induces apoptosis and cell cycle arrest in a dose and duration dependent manner. Further investigations into the mechanisms of how DK16 functions showed that this drug increased the BAX/BCL2 expression ratio, induced phosphatidylserine externalization, and mitochondrial membrane depolarizations culminating to the release and nuclear translocation of AIF. In addition, treatments of low grade glioma cell lines with DK16 increased the expression of pro-apoptotic mediators including CDK2 and CTSL1, and with the converse diminished expression of pro-survival and migratory/invasion genes like PRKCA, TERT, MAPK8, MMP1 and MMP2. Our findings collectively demonstrate the potent anti-neoplastic properties of DK16, a steroid biosynthesis inhibitor, on the growth of pediatric low grade gliomas.

  3. BI-05MOLECULAR PROFILING OF LOW GRADE GLIOMAS (LGG) IN COLOMBIA (ONCOLGROUP)

    PubMed Central

    Cardona, Andres; Jimenez, Enrique; Hakim, Fernando; Useche, Nicolas; Bermudez, Sonia; Arrieta, Oscar; Behaine, Jose; Rodriguez, July; Carranza, Hernan; Otero, Jorge; Vargas, Carlos; Rojas, Leornardo; Ortiz, Leon Dario

    2014-01-01

    BACKGROUND: LGG are classified as being astrocytoma (DA), oligodendroglioma (OD) or mixed glioma (OA). TP53-m and 1p19q codeletion have been the main molecular abnormalities recorded to date. IDH1/2 mutations have been described in up to 85% of LGG. It has recently been found that ATRX plays a significant role in glioma oncogenesis. METHODS: We searched for P53 and Olig2 protein expression, MGMT methylation status (pMGMT), 1p19q codeletion and IDH/ATRX status in 63 Colombian LGG patients (pts). Overall survival (OS) rate was estimated and compared between groups and according to genotype. RESULTS: Mean age was 40.1-yo (±12.3), 50% of the pts were male, mean lesion diameter was 41.7 mm (±17.2 mm) and histological distribution was 61.9%, 25.4% and 12.7% for AD, OD and OA, respectively. Surgical resection was total in 47.6%, subtotal in 31.7% and biopsy was performed in 20.6% of the cases. Alterations in IDH1/2 were found in 57.1%, pMGMT+ in 65.1%, overexpression of p53 and Olig2 in 30.2% and 44.4%, and 1p19q codeletion in 34.9%. The presence of alterations in ATRX was analysed in 25 patients, being positive in 16% (all IDH1 + /1p19q-). Median follow-up was 15.8 months (95%CI 7.6-42.0), OS was 39.2 months (95%CI 1.3-114) and the variables positively modifying OS were pMGMT+ (p = 0.004), 1p19q codeletion (p = 0.015), the extension of surgical intervention (p = 0.011) and the number of lobes involved (p = 0.021). Multivariate analysis showed that pMGMT and 1p19q codeletion modified the OS in our population (p = 0.039 and 0.047, respectively). CONCLUSIONS: This is the first study which has evaluated the molecular profile in LGG pts from Latin-America. Our findings confirmed the prognostic relevance of pMGMT and 1p19q codeletion, without finding a positive relation for IDH1/2 mutations. This finding could have been explained by sample size and selection bias. Alterations in ATRX are limited to the population of pts having AD/OA and IDH1 + /1p19q-.

  4. Extreme protraction for low-grade gliomas: theoretical proof of concept of a novel therapeutical strategy.

    PubMed

    Pérez-García, Víctor M; Pérez-Romasanta, Luis A

    2016-09-01

    Grade II gliomas are slowly growing primary brain tumours that affect mostly young patients and become fatal after a variable time period. Current clinical handling includes surgery as first-line treatment. Cytotoxic therapies (radiotherapy RT or chemotherapy QT) are used initially only for patients having a bad prognosis. Therapies are administered following the 'maximum dose in minimum time' principle, which is the same schedule used for high-grade brain tumours. Using mathematical models describing the growth of these tumours in response to radiotherapy, we find that an extreme protraction therapeutical strategy, i.e. enlarging substantially the time interval between RT fractions, may lead to better tumour control. Explicit formulas are found providing the optimal spacing between doses in a very good agreement with the simulations of the full 3D mathematical model approximating the tumour spatiotemporal dynamics. This idea, although breaking the well-established paradigm, has biological meaning since, in these slowly growing tumours, it may be more favourable to treat the tumour as the tumour cells leave the quiescent compartment and move into the cell cycle.

  5. Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps.

    PubMed

    Castellano, Antonella; Donativi, Marina; Rudà, Roberta; De Nunzio, Giorgio; Riva, Marco; Iadanza, Antonella; Bertero, Luca; Rucco, Matteo; Bello, Lorenzo; Soffietti, Riccardo; Falini, Andrea

    2016-05-01

    To explore the role of diffusion tensor imaging (DTI)-based histogram analysis and functional diffusion maps (fDMs) in evaluating structural changes of low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy. Twenty-one LGG patients underwent 3T-MR examinations before and after three and six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery (FLAIR) sequences and DTI (b = 1000 s/mm(2), 32 directions). Mean diffusivity (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q) were obtained. Histogram and fDM analyses were performed on co-registered baseline and post-chemotherapy maps. DTI changes were compared with modifications of tumour area and volume [according to Response Assessment in Neuro-Oncology (RANO) criteria], and seizure response. After three cycles of TMZ, 20/21 patients were stable according to RANO criteria, but DTI changes were observed in all patients (Wilcoxon test, P ≤ 0.03). After six cycles, DTI changes were more pronounced (P ≤ 0.005). Seventy-five percent of patients had early seizure response with significant improvement of DTI values, maintaining stability on FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume change (R(2) = 0.614 and 0.561, P < 0.0005, respectively). TMZ-related changes were located mainly at tumour borders on p and MD fDMs. DTI-based histogram and fDM analyses are useful techniques to evaluate the early effects of TMZ chemotherapy in LGG patients. • DTI helps to assess the efficacy of chemotherapy in low-grade gliomas. • Histogram analysis of DTI metrics quantifies structural changes in tumour tissue. • Functional diffusion maps (fDMs) spatially localize the changes of DTI metrics. • Changes in DTI histograms and fDMs precede changes in conventional MRI. • Early changes in DTI histograms and fDMs correlate with seizure response.

  6. Resecting diffuse low-grade gliomas to the boundaries of brain functions: a new concept in surgical neuro-oncology.

    PubMed

    Duffau, H

    2015-12-01

    The traditional dilemma making surgery for diffuse low-grade gliomas (DLGGs) challenging is underlain by the need to optimize tumor resection in order to significantly increase survival versus the risk of permanent neurological morbidity. Development of neuroimaging led neurosurgeons to achieve tumorectomy according to the oncological limits provided by preoperative or intraoperative structural and metabolic imaging. However, this principle is not coherent, neither with the infiltrative nature of DLGGs nor with the limited resolution of current neuroimaging. Indeed, despite technical advances, MRI still underestimates the actual spatial extent of gliomas, since tumoral cells are present several millimeters to centimeters beyond the area of signal abnormalities. Furthermore, cortical and subcortical structures may be still crucial for brain functions despite their invasion by this diffuse tumoral disease. Finally, the lack of reliability of functional MRI has also been demonstrated. Therefore, to talk about "maximal safe resection" based upon neuroimaging is a non-sense, because oncological MRI does not show the tumor and functional MRI does not show critical neural pathways. This review proposes an original concept in neuro-oncological surgery, i.e. to resect DLGG to the boundaries of brain functions, thanks to intraoperative electrical mapping performed in awake patients. This paradigmatic shift from image-guided resection to functional mapping-guided resection, based upon an accurate study of brain connectomics and neuroplasticity in each patient throughout tumor removal has permitted to solve the classical dilemma, by increasing both survival and quality of life in DLGG patients. With this in mind, brain surgeons should also be neuroscientists.

  7. Endocrine outcome in long-term survivors of low-grade hypothalamic/chiasmatic glioma.

    PubMed

    Collet-Solberg, P F; Sernyak, H; Satin-Smith, M; Katz, L L; Sutton, L; Molloy, P; Moshang, T

    1997-07-01

    We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy. Descriptive retrospective study using case note review analysis. The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment. Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function. Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery. Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than

  8. The Role of Telomere Maintenance in the Spontaneous Growth Arrest of Pediatric Low-Grade Gliomas1

    PubMed Central

    Tabori, Uri; Vukovic, Bisera; Zielenska, Maria; Hawkins, Cynthia; Braude, Ilan; Rutka, James; Bouffet, Eric; Squire, Jeremy; Malkin, David

    2006-01-01

    Abstract Spontaneous tumor regression is a unique feature of pediatric low-grade gliomas (PLGG). We speculated that lack of telomere maintenance is responsible for this behavior. We first looked for evidence of telomerase activity and alternative-lengthening telomeres (ALT) in 56 PLGG. Telomerase activity was observed in 0 of 11 PLGG in contrast to 10 of 13 high-grade pediatric brain tumors. There was no ALT in 45 of 45 samples. We applied Q-FISH to eight patients whose indolent PLGG underwent two metachronous biopsies over a lag of several years. Telomere shortening was observed in the second biopsy in all tumors but not in a normal brain control (P < .0001), indicating that lack of telomere maintenance is associated with continuous telomere erosion. Based on these observations, we observed that younger PLGG patients who exhibit more aggressive and frequently recurrent tumors had significantly longer telomeres than older ones (P = .00014). Tumors with a terminal restriction fragment length of <7.5 did not recur, whereas the presence of longer telomeres (>8.0) conferred a high likelihood of late recurrences in PLGG. Our findings provide a plausible biological mechanism to explain the tendency of PLGG to exhibit growth arrest and spontaneous regression. Telomere maintenance may therefore represent the first known biologic prognostic marker in PLGG. PMID:16611406

  9. Deep Learning based Radiomics (DLR) and its usage in noninvasive IDH1 prediction for low grade glioma.

    PubMed

    Li, Zeju; Wang, Yuanyuan; Yu, Jinhua; Guo, Yi; Cao, Wei

    2017-07-14

    Deep learning-based radiomics (DLR) was developed to extract deep information from multiple modalities of magnetic resonance (MR) images. The performance of DLR for predicting the mutation status of isocitrate dehydrogenase 1 (IDH1) was validated in a dataset of 151 patients with low-grade glioma. A modified convolutional neural network (CNN) structure with 6 convolutional layers and a fully connected layer with 4096 neurons was used to segment tumors. Instead of calculating image features from segmented images, as typically performed for normal radiomics approaches, image features were obtained by normalizing the information of the last convolutional layers of the CNN. Fisher vector was used to encode the CNN features from image slices of different sizes. High-throughput features with dimensionality greater than 1.6*10(4) were obtained from the CNN. Paired t-tests and F-scores were used to select CNN features that were able to discriminate IDH1. With the same dataset, the area under the operating characteristic curve (AUC) of the normal radiomics method was 86% for IDH1 estimation, whereas for DLR the AUC was 92%. The AUC of IDH1 estimation was further improved to 95% using DLR based on multiple-modality MR images. DLR could be a powerful way to extract deep information from medical images.

  10. Beneficial impact of high-field intraoperative magnetic resonance imaging on the efficacy of pediatric low-grade glioma surgery.

    PubMed

    Roder, Constantin; Breitkopf, Martin; Ms; Bisdas, Sotirios; Freitas, Rousinelle da Silva; Dimostheni, Artemisia; Ebinger, Martin; Wolff, Markus; Tatagiba, Marcos; Schuhmann, Martin U

    2016-03-01

    Intraoperative MRI (iMRI) is assumed to safely improve the extent of resection (EOR) in patients with gliomas. This study focuses on advantages of this imaging technology in elective low-grade glioma (LGG) surgery in pediatric patients. The surgical results of conventional and 1.5-T iMRI-guided elective LGG surgery in pediatric patients were retrospectively compared. Tumor volumes, general clinical data, EOR according to reference radiology assessment, and progression-free survival (PFS) were analyzed. Sixty-five patients were included in the study, of whom 34 had undergone conventional surgery before the iMRI unit opened (pre-iMRI period) and 31 had undergone surgery with iMRI guidance (iMRI period). Perioperative data were comparable between the 2 cohorts, apart from larger preoperative tumor volumes in the pre-iMRI period, a difference without statistical significance, and (as expected) significantly longer surgeries in the iMRI group. According to 3-month postoperative MRI studies, an intended complete resection (CR) was achieved in 41% (12 of 29) of the patients in the pre-iMRI period and in 71% (17 of 24) of those in the iMRI period (p = 0.05). Of those cases in which the surgeon was postoperatively convinced that he had successfully achieved CR, this proved to be true in only 50% of cases in the pre-iMRI period but in 81% of cases in the iMRI period (p = 0.055). Residual tumor volumes on 3-month postoperative MRI were significantly smaller in the iMRI cohort (p < 0.03). By continuing the resection of residual tumor after the intraoperative scan (when the surgeon assumed that he had achieved CR), the rate of CR was increased from 30% at the time of the scan to 85% at the 3-month postoperative MRI. The mean follow-up for the entire study cohort was 36.9 months (3-79 months). Progression-free survival after surgery was noticeably better for the entire iMRI cohort and in iMRI patients with postoperatively assumed CR, but did not quite reach statistical

  11. Residual Tumor Volume as Best Outcome Predictor in Low Grade Glioma – A Nine-Years Near-Randomized Survey of Surgery vs. Biopsy

    PubMed Central

    Roelz, Roland; Strohmaier, David; Jabbarli, Ramazan; Kraeutle, Rainer; Egger, Karl; Coenen, Volker A.; Weyerbrock, Astrid; Reinacher, Peter C.

    2016-01-01

    Diffuse low grade gliomas (DLGG) are continuously progressive primary brain neoplasms that lead to neurological deficits and death. Treatment strategies are controversial. Randomized trials establishing the prognostic value of surgery do not exist. Here, we report the results of a nine-year near-randomized patient distribution between resection and biopsy. Until 2012, the Department of Neurosurgery and the Department of Stereotactic Neurosurgery at the University Medical Center Freiburg were organized as separate administrative units both coordinating DLGG patient treatment independently. All consecutive adult patients with a new diagnosis of DLGG by either stereotactic biopsy or resection were included. Pre- and post-operative tumor volumetry was performed. 126 patients, 87 men (69%), 39 women (31%), median age 41 years, were included. 77 (61%) were initially managed by biopsy, 49 (39%) by resection. A significant survival benefit was found for patients with an initial management by resection (5-year OS 82% vs. 54%). The survival benefit of patients with initial resection was reserved to patients with a residual tumor volume of less than 15 cm3. Maximum safe resection is the first therapy of choice in DLGG patients if a near-complete tumor removal can be achieved. Accurate prediction of the extent-of-resection is required for selection of surgical candidates. PMID:27574036

  12. Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery.

    PubMed

    Kunz, Mathias; Nachbichler, Silke B; Ertl, Lorenz; Fesl, Gunther; Egensperger, Rupert; Niyazi, Maximilian; Schmid, Irene; Tonn, Joerg Christian; Peraud, Aurelia; Kreth, Friedrich Wilhelm

    2016-03-01

    To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen. Temporary Iodine-125 seeds were used (median reference dose: 54 Gy). Treatment response was estimated with the modified MacDonald criteria. Analysis of functional outcome included ophthalmological, endocrinological and neurological evaluation. Survival was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. Toxicity was categorized according to the Common Terminology Criteria for Adverse Events. Fifty-eight patients were included treated either with SBT alone (n = 39) or with SBT plus microsurgery (n = 19). Five-year progression-free survival was 87%. Two patients had died due to tumor progression. Among survivors, improvement/stabilization/deterioration of functional deficits was seen in 20/14/5 patients, respectively. Complete/partial response had beneficial impact on functional scores (P = 0.02). The 5-year estimated risk to receive adjuvant radiotherapy/chemotherapy was 5.2%. The overall early (delayed) toxicity rate was 8.6% (10.3%), respectively. No permanent morbidity occurred. In complex located PLGGs, early SBT alone or combined with best safe resection preserves/improves functional scores and results in tumor control rates usually achieved with complete resection. Long-term analysis is necessary for confirmation of these results.

  13. Long-Term Cognitive Functioning and Psychological Well-Being in Surgically Treated Patients with Low-Grade Glioma.

    PubMed

    Campanella, Fabio; Palese, Alvisa; Del Missier, Fabio; Moreale, Renzo; Ius, Tamara; Shallice, Tim; Fabbro, Franco; Skrap, Miran

    2017-07-01

    The aim of this work is to provide an in-depth investigation of the impact of low-grade gliomas (LGG) and their surgery on patients' cognitive and emotional functioning and well-being, carried out via a comprehensive and multiple-measure psychological and neuropsychological assessment. Fifty surgically treated patients with LGG were evaluated 40 months after surgery on their functioning over 6 different cognitive domains, 3 core affective/emotional aspects, and 3 different psychological well-being measures to obtain a clearer picture of the long-term impact of illness and surgery on their psychological and relational world. Close relatives were also involved to obtain an independent measure of the psychological dimensions investigated. Cognitive status was satisfactory, with only mild short-term memory difficulties. The affective and well-being profile was characterized by mild signs of depression, good satisfaction with life and psychological well-being, and good personality development, with patients perceiving themselves as stronger and better persons after illness. However, patients showed higher emotional reactivity, and psychological well-being measures were negatively affected by epileptic burden. Well-being was related to positive affective/emotional functioning and unrelated to cognitive functioning. Good agreement between patients and relatives was found. In the long-term, patients operated on for LGG showed good cognitive functioning, with no significant long-term cognitive sequelae for the extensive surgical approach. Psychologically, patients appear to experience a deep psychological change and maturation, closely resembling that of so-called posttraumatic growth, which, to our knowledge, is for the first time described and quantified in patients with LGG. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

    PubMed

    Miotto, Eliane C; Balardin, Joana B; Vieira, Gilson; Sato, Joao R; Martin, Maria da Graça M; Scaff, Milberto; Teixeira, Manoel J; Junior, Edson Amaro

    2014-01-01

    Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

  15. Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype

    PubMed Central

    Bergthold, Guillaume; Bandopadhayay, Pratiti; Hoshida, Yujin; Ramkissoon, Shakti; Ramkissoon, Lori; Rich, Benjamin; Maire, Cecile L.; Paolella, Brenton R.; Schumacher, Steven E.; Tabak, Barbara; Ferrer-Luna, Ruben; Ozek, Memet; Sav, Aydin; Santagata, Sandro; Wen, Patrick Yung; Goumnerova, Liliana C.; Ligon, Azra H.; Stiles, Charles; Segal, Rosalind; Golub, Todd; Grill, Jacques; Ligon, Keith L.; Chan, Jennifer A.; Kieran, Mark W.; Beroukhim, Rameen

    2015-01-01

    Background Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity. Methods We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain. Results Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. “Not otherwise specified” (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs. Conclusion Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related. PMID:25825052

  16. The Value of Intraoperative and Early Postoperative Magnetic Resonance Imaging in Low-Grade Glioma Surgery: A Retrospective Study.

    PubMed

    Pala, Andrej; Brand, Christine; Kapapa, Thomas; Hlavac, Michal; König, Ralph; Schmitz, Bernd; Wirtz, Christian Rainer; Coburger, Jan

    2016-09-01

    The presence of residual tumor is crucial in decision-making for low-grade gliomas (LGGs), because patients older than 40 years of age with residual tumor are considered for adjuvant treatment. There are hints that early postoperative fluid-attenuated inversion recovery (FLAIR) and T2 (within 48 hours) may overestimate residual tumor volume in LGG. Intraoperative magnetic resonance imaging (MRI) without subsequent resection or ultra-early postoperative MRI may assess the amount of residual tumor more adequately. To evaluate the utility of postoperative imaging in LGG, we volumetrically analyzed intraoperative, early, and late (3-4 months after surgery) postoperative MRIs of LGGs. A total of 33 patients with LGG were assessed retrospectively. Residual tumor was defined as signal-enhanced tissue in T2 and FLAIR. Volumetric assessment was performed with intraoperative, early, and late postoperative T2/FLAIR via Brainlab-iPlan 3.0. Wilcoxon and χ(2) tests were used for statistical analysis. A significant difference of FLAIR/T2 abnormalities was found in intraoperative and early postoperative MRIs (FLAIR mean volume = 5.433 cm(3), T2 mean volume = 3.374 cm(3) vs. FLAIR mean volume = 14.090 cm(3), P = 0.002, T2 mean volume = 7.597 cm(3), P = 0.006). There was no significant difference between intraoperative and late postoperative FLAIR/T2 abnormalities (late postoperative FLAIR/T2 mean volume = 5.560 cm(3) and 2.370 cm(3), P = 0.520, P = 0.398), whereas a significant difference was detected between early and late postoperative images (FLAIR, P < 0.0001; T2, P < 0.00001). Intraoperative MRI without further resection or ultra-early postoperative MRI seems to reflect the actual volume of residual tumor in LGG more precisely compared with early postoperative MRI and therefore seems to be more useful regarding decisions for adjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Subgroup characteristics of insular low-grade glioma based on clinical and molecular analysis of 42 cases.

    PubMed

    Tang, Chao; Zhang, Zhen-yu; Chen, Ling-chao; Sun, Zelin; Zhang, Yi; Qin, Zhiyong; Yao, Yu; Zhou, Liang-fu

    2016-02-01

    Although the classification of insular glioma has been established based on the anatomical location in order to facilitate personalized surgical resection, the diagnosis based on anatomical and functional characteristics becomes more complex when insular tumors extend into either the frontobasal brain region and/or the temporal lobe, as part of the limbic system. Moreover, prognosis of insular tumor resection is still controversial. Further analysis of subgroup characteristics of insular grade II gliomas based on clinical and molecular analysis is required to reliably determine patients' survival rates. In this retrospective study 20 purely insular grade II gliomas patients and 22 paralimbic grade II gliomas that involved frontal and/or temporal lobes were compared with regard to epidemiological and clinical characteristics. The molecular profiles including Isocitrate dehydrogenase 1 (IDH1), telomerase reverse transcriptase (TERT) promoter, and P53 mutations, 1p19q co-deletion were analyzed, and microRNA profiles were assessed by microarray and bioinformatics analysis. Purely insular grade II gliomas displayed a high frequency of IDH1 mutations with favorable outcome. IDH1 mutated paralimbic glioma shared many parameters with the purely insular glioma in respect to growth patterns, survival, and microRNA profile, but differed significantly from the IDH1 wild type paralimbic gliomas. Our findings suggest that IDH1 mutations can define subpopulations of insular gliomas with distinct disease entities regardless of tumor extension patterns. These findings could be useful to develop a customized treatment strategy for insular glioma patients.

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

    PubMed Central

    Chang, Edward F.; Clark, Aaron; Smith, Justin S.; Polley, Mei-Yin; Chang, Susan M.; Barbaro, Nicholas M.; Parsa, Andrew T.; McDermott, Michael W.; Berger, Mitchel S.

    2013-01-01

    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. PMID

  19. Imaging signatures of meningioma and low-grade glioma: a diffusion tensor, magnetization transfer and quantitative longitudinal relaxation time MRI study.

    PubMed

    Piper, Rory J; Mikhael, Shadia; Wardlaw, Joanna M; Laidlaw, David H; Whittle, Ian R; Bastin, Mark E

    2016-05-01

    Differentiation of cerebral tumor pathology currently relies on interpretation of conventional structural MRI and in some cases histology. However, more advanced MRI methods may provide further insight into the organization of cerebral tumors and have the potential to aid diagnosis. The objective of this study was to use multimodal quantitative MRI to measure the imaging signatures of meningioma and low-grade glioma (LGG). Nine adults with meningioma and 11 with LGG were identified, and underwent standard structural, quantitative longitudinal relaxation time (T1) mapping, magnetization transfer and diffusion tensor MRI. Maps of mean (〈D〉), axial (λAX) and radial (λRAD) diffusivity, fractional anisotropy (FA), magnetization transfer ratio (MTR) and T1 were generated on a voxel-by-voxel basis. Using structural and echo-planar T2-weighted MRI, manual region-of-interest segmentation of brain tumor, edema, ipsilateral and contralateral normal-appearing white matter (NAWM) was performed. Differences in imaging signatures between the different tissue types, both absolute mean values and ratios relative to contralateral NAWM, were assessed using t-tests with statistical significance set at p<0.05. For both absolute mean values and ratios relative to contralateral NAWM, there were significant differences in 〈D〉, λAX, λRAD, FA, MTR and T1 between meningioma and LGG tumor tissue, respectively. Only T1 and FA differed significantly between edematous tissue associated with the two tumor types. These results suggest that multimodal MRI biomarkers are significantly different, particularly in tumor tissue, between meningioma and LGG. By using quantitative multimodal MRI it may be possible to identify tumor pathology non-invasively. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Symptomatic Adjacent Segment Pathology after Posterior Lumbar Interbody Fusion for Adult Low-Grade Isthmic Spondylolisthesis

    PubMed Central

    Sakaura, Hironobu; Yamashita, Tomoya; Miwa, Toshitada; Ohzono, Kenji; Ohwada, Tetsuo

    2013-01-01

    The incidence of symptomatic adjacent segment pathology (ASP) after fusion surgery for adult low-grade isthmic spondylolisthesis (IS) has been reported to be relatively low compared with other lumbar disease entities. However, there has been no study of symptomatic ASP incidence using posterior lumbar interbody fusion (PLIF) with pedicle screw instrumentation. We investigated the incidence of symptomatic ASP after PLIF with pedicle screw instrumentation for adult low-grade IS and identified significant risk factors for symptomatic ASP. We retrospectively studied records of 40 consecutive patients who underwent PLIF with pedicle screw instrumentation at the Department of Orthopaedic Surgery, Kansai Rosai Hospital, Amagasaki, Japan. The patients were followed for ≥ 4 years. Patients' medical records were retrospectively examined for evidence of symptomatic ASP. Age at time of surgery, sex, fusion level, whole lumbar lordosis, segmental lordosis, preexisting laminar inclination angle, and facet tropism at the cranial fusion segment were analyzed to identify risk factors for symptomatic ASP. Four patients (ASP group) developed symptomatic ASP at the cranial segment adjacent to the fusion. There were no significant differences in age, sex, fusion level, lumbar lordosis, segmental lordosis, or facet tropism at the cranial segment adjacent to the fusion between the ASP and the non-ASP groups. In contrast, laminar inclination angle at the cranial vertebra adjacent to the fusion was significantly higher in the ASP group than in the non-ASP group. Four patients (10%) developed symptomatic ASP after PLIF with transpedicular fixation for adult low-grade IS. Preexisting laminar horizontalization at the cranial vertebra adjacent to the fusion was a significant risk factor for symptomatic ASP. PMID:24436872

  1. Recovery of functional connectivity of the sensorimotor network after surgery for diffuse low-grade gliomas involving the supplementary motor area.

    PubMed

    Vassal, Matthieu; Charroud, Céline; Deverdun, Jérémy; Le Bars, Emmanuelle; Molino, François; Bonnetblanc, Francois; Boyer, Anthony; Dutta, Anirban; Herbet, Guillaume; Moritz-Gasser, Sylvie; Bonafé, Alain; Duffau, Hugues; de Champfleur, Nicolas Menjot

    2017-04-01

    OBJECTIVE The supplementary motor area (SMA) syndrome is a well-studied lesional model of brain plasticity involving the sensorimotor network. Patients with diffuse low-grade gliomas in the SMA may exhibit this syndrome after resective surgery. They experience a temporary loss of motor function, which completely resolves within 3 months. The authors used functional MRI (fMRI) resting state analysis of the sensorimotor network to investigate large-scale brain plasticity between the immediate postoperative period and 3 months' follow-up. METHODS Resting state fMRI was performed preoperatively, during the immediate postoperative period, and 3 months postoperatively in 6 patients with diffuse low-grade gliomas who underwent partial surgical excision of the SMA. Correlation analysis within the sensorimotor network was carried out on those 3 time points to study modifications of its functional connectivity. RESULTS The results showed a large-scale reorganization of the sensorimotor network. Interhemispheric connectivity was decreased in the postoperative period, and increased again during the recovery process. Connectivity between the lesion side motor area and the contralateral SMA rose to higher values than in the preoperative period. Intrahemispheric connectivity was decreased during the immediate postoperative period and had returned to preoperative values at 3 months after surgery. CONCLUSIONS These results confirm the findings reported in the existing literature on the plasticity of the SMA, showing large-scale modifications of the sensorimotor network, at both inter- and intrahemispheric levels. They suggest that interhemispheric connectivity might be a correlate of SMA syndrome recovery.

  2. Association of fear of terror with low-grade inflammation among apparently healthy employed adults.

    PubMed

    Melamed, Samuel; Shirom, Arie; Toker, Sharon; Berliner, Shlomo; Shapira, Itzhak

    2004-01-01

    Based on evidence that psychological stress may induce a chronic inflammatory process, we hypothesized that the stress caused by chronic fear of terror may be associated with low-grade inflammation. This hypothesis was examined in employed men and women with the presence of low-grade inflammation measured by high sensitivity C-reactive protein (CRP). Apparently healthy employed adults (N = 1153) undergoing periodic health check-ups in a tertiary hospital in Israel completed a questionnaire. Fear of terror (scored 1-5) was assessed by three items measuring the extent to which respondents have deep concern for personal safety, elevated tension in crowded places, and fear of terror strikes causing harm to one's self or one's family members. The main outcome measure was the presence or absence of an elevated CRP level (>3.0 mg/L). Women scored significantly higher on fear of terror compared with men (M = 2.16 vs. M = 1.68, respectively; p <.0001). Most of the study participants who scored high (4 or 5) on fear of terror, reported having experienced this feeling for 1 year or more. In women only, there was a positive association between fear of terror and risk of elevated CRP level (adjusted OR = 1.7, 95% CI 1.2-2.4) in a multivariate model adjusting for generalized anxiety, depressive symptoms, and potentially confounding demographic and biomedical variables. Chronic fear of terror in women, but not in men, is associated with elevated CRP levels, which suggests the presence of low-grade inflammation and a potential risk of cardiovascular disease.

  3. Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) low-grade glioma research workshop.

    PubMed

    Huse, Jason T; Wallace, Max; Aldape, Kenneth D; Berger, Mitchel S; Bettegowda, Chetan; Brat, Daniel J; Cahill, Daniel P; Cloughesy, Timothy; Haas-Kogan, Daphne A; Marra, Marco; Miller, C Ryan; Nelson, Sarah J; Salama, Sofie R; Soffietti, Riccardo; Wen, Patrick Y; Yip, Stephen; Yen, Katharine; Costello, Joseph F; Chang, Susan

    2014-01-01

    Diffuse gliomas consist of both low- and high-grade varieties, each with distinct morphological and biological features. The often extended periods of relative indolence exhibited by low-grade gliomas (LGG; WHO grade II) differ sharply from the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO grade IV). Nevertheless, until recently, the molecular foundations underlying this stark biological contrast between glioma variants remained largely unknown. The discoveries of distinctive and highly recurrent genomic and epigenomic abnormalities in LGG have both informed a more accurate classification scheme and pointed to viable avenues for therapeutic development. As such, the field of neuro-oncology now seems poised to capitalize on these gains to achieve significant benefit for LGG patients. This report will briefly recount the proceedings of a workshop held in January 2013 and hosted by Accelerate Brain Cancer Cure (ABC(2)) on the subject of LGG. While much of the meeting covered recent insights into LGG biology, its focus remained on how best to advance the clinical management, whether by improved preclinical modeling, more effective targeted therapeutics and clinical trial design, or innovative imaging technology.

  4. Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system.

    PubMed

    Figarella-Branger, Dominique; Bouvier, Corinne; de Paula, André Maues; Mokhtari, Karima; Colin, Carole; Loundou, Anderson; Chinot, Olivier; Metellus, Philippe

    2012-11-01

    Adult grade II low-grade gliomas (LGG) are classified according to the WHO as astrocytomas, oligodendrogliomas or mixed gliomas. TP53 mutations and 1p19q codeletion are the main molecular abnormalities recorded, respectively, in astrocytomas and oligodendrogliomas and in mixed gliomas. Although IDH mutations (IDH1 or IDH2) are recorded in up to 85 % of low-grade gliomas, IDH negative gliomas do occur. We have searched for p53 expression, 1p19q codeletion and IDH status (immunohistochemical detection of the common R132H IDH1 mutation and IDH direct sequencing). Internexin alpha (INA) expression previously recorded to be associated with 1p19q codeletion (1p19q+) gliomas was also analysed. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53-/1p19q-; group 2, IDH+/p53-/1p19q+; group 3, IDH+/p53+/1p19q-; and group 4, triple negative gliomas. In contrast to the WHO classification, this molecular classification predicts overall survival on uni- and multivariate analysis (P = 0.001 and P = 0.007, respectively). Group 4 carries the worst prognosis and group 2 the best. Interestingly, p53 +/INA- expression predicts lack of 1p19q codeletion (specificity 100 %, VPP 100 %). The combined use of these three molecular markers allow for an accurate prediction of survival in LGG. These findings could significantly modify LGG classification and may represent a new tool to guide patient-tailored therapy. Moreover, immunohistochemical detection of p53, INA and mR132H IDH1 expression could represent an interesting prescreening test to be performed before 1p19q codeletion, IDH1 minor mutation and IDH2 mutation detection.

  5. Low-grade inflammation in overweight and obese adults is affected by weight loss program.

    PubMed

    Petelin, Ana; Bizjak, Mojca; Černelič-Bizjak, Maša; Jurdana, Mihaela; Jakus, Tadeja; Jenko-Pražnikar, Zala

    2014-08-01

    Low-grade systemic inflammation due to obesity is considered to be the key link between obesity and obesity-related disorders. The hypothesis was tested that significant alterations in inflammatory markers and adipokines would occur over a multidisciplinary intervention and that these changes might also be important for improvement of cardiovascular risk factors. Thirty-tree overweight adults completed a 6-month multidisciplinary intervention program to evaluate the effects of a personalized dietary program based on the individual's resting metabolic rate (RMR) on anthropometric parameters, aerobic and anaerobic capabilities, metabolic profile, inflammation, and body image satisfaction. Body composition, physical activity, anaerobic capabilities, RMR, metabolic profile, and low-grade inflammation were measured. Diet composition and body image dissatisfaction were also assessed. After 6 months of multidisciplinary intervention the participants showed significantly decreased body weight, waist circumference (WC), and the inflammatory markers tumor necrosis factor-α, C-reactive protein, and visfatin. They also showed increased anti-inflammatory adiponectin and consequently decreased serum insulin, HOMA-IR, and total cholesterol. The important findings of the study were that reduction of sugars and saturated fatty acids in the diet, coupled with an increase in exercise, significantly correlated with reduction of WC and body mass index. In addition, positive correlations between ∆ BMI, ∆ WC, ∆ trunk fat, inflammation, and cardiovascular risk factors were demonstrated. Weight loss in combination with increased physical activity, a negative energy balance, and diet adjustment was associated with lower inflammation and consequently with lower cardiovascular risk factors.

  6. MR spectroscopy differentiation between high and low grade astrocytomas: a comparison between paediatric and adult tumours.

    PubMed

    Porto, Luciana; Kieslich, Matthias; Franz, Kea; Lehrnbecher, Thomas; Zanella, Friedhelm; Pilatus, Ulrich; Hattingen, Elke

    2011-05-01

    To investigate whether pathologically similar astrocytomas in adults and children may also show metabolic similarities in proton magnetic resonance spectroscopy ((1)H-MRS) and whether the MRS data could help to differentiate between low and high grade gliomas for the different groups. Twelve children (5 WHO II astrocytomas, 7 WHO III astrocytomas) and 37 adults (21 WHO II astrocytomas, 16 WHO III astrocytomas) were included in this study. MR spectroscopic data were evaluated retrospectively using normalized measures of total choline (tCho), N-acetyl-aspartate (NAA) and total creatine (tCr). These metabolites were used to differentiate between WHO II and WHO III astrocytomas in children and adults. Histopathological grading was performed using WHO criteria. (1)H-MRS was carried out prior to the commencement of any treatment. Signal intensities of tCho, NAA and tCr were normalized to their values in contralateral brain tissue. The resulting concentration ratios were then used to calculate the change in the intratumoural ratio of NAA to tCho. A Mann-Whitney U-Test was performed to evaluate differences within the respective groups. In both groups, loss of NAA and increase of tCho were more pronounced in WHO III than in WHO II astrocytoma. The best discriminator to differentiate between low and high grade gliomas was found to be the ratio of NAA/tCho (p < 0.01). The normalized metabolite signal intensities ratio NAA to tCho is the most accurate in differentiating between low and high grade astrocytomas in both children and adults. Copyright © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. A multivariate analysis of factors determining tumor progression in childhood low-grade glioma: a population-based cohort study (CCLG CNS9702)

    PubMed Central

    Stokland, Tore; Liu, Jo-Fen; Ironside, James W.; Ellison, David W.; Taylor, Roger; Robinson, Kathryn J.; Picton, Susan V.; Walker, David A.

    2010-01-01

    The purpose of this study was to identify risk factors for the progression of low-grade glioma in children from a large population-based cohort. Patient and tumor details of a national cohort of children with low-grade glioma, recruited into an international multidisciplinary clinical strategy, were subjected to univariate and multivariate analyses of progression-free survival and overall survival. From the cohort of 798 patients, 639 patients were eligible, with a median age 6.71 years (0.26–16.75 years); 49% were males; 15.9% had neurofibromatosis type 1, 63.7% pilocytic astrocytoma, 5.9% fibrillary astrocytoma, 4.2% mixed neuronal-glial tumors, and 3.6% others; 21.1% were diagnosed clinically. Anatomically implicated were 31.6% cerebellum, 24.6% chiasma/hypothalamus, 16.0% cerebral hemispheres, 9.9% brain stem, 6.1% other supratentorial midline structures, 5.9% optic nerve only, 4.5% spinal cord, and 1.4% others. The 5-year overall survival and progression-free survival in the whole cohort were 94.6% and 69.4%, respectively. There was a significant association between age and site (P < .001) and extent of tumor resection and site (P < .001). Multivariate analysis identified young age, fibrillary astrocytoma, and extent of surgical resection as significant independent risk factors for progression. Hypothalamic/chiasmatic tumors demonstrated the most sustained tendency to progress. In conclusion, the influence of age and anatomical site upon the risk of tumor progression suggests that these factors strongly influence tumor behavior for the majority of pilocytic tumors. Age <1 year and 1–5 years, fibrillary histology, completeness of resection, and chiasmatic location are candidates for stratification in future studies. PMID:20861086

  8. Dynamic aphasia following low-grade glioma surgery near the supplementary motor area: a selective spontaneous speech deficit.

    PubMed

    Satoer, Djaina; Kloet, Alfred; Vincent, Arnaud; Dirven, Clemens; Visch-Brink, Evy

    2014-01-01

    We describe a patient (KO) with reduced spontaneous speech, resembling dynamic aphasia, after awake glioma surgery in the proximity of the supplementary motor area. Naming, repetition, and comprehension were intact. He was tested with an extensive neuropsychological test-battery and a protocol for dynamic aphasia at 1 year. He presented with postoperative reduced spontaneous speech and selective executive function deficits. Most language recovery took place at 3 months postoperatively, whereas the executive functions improved between 3 months and 1 year. Results suggest that resection near the supplementary motor area could increase the risk of cognitive disturbances at long term, especially language.

  9. Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis.

    PubMed

    Reon, Brian J; Anaya, Jordan; Zhang, Ying; Mandell, James; Purow, Benjamin; Abounader, Roger; Dutta, Anindya

    2016-12-01

    Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles in regulating neurogenesis and brain tumor progression. To better understand the role of lncRNAs in brain cancer, we performed a global analysis to identify and characterize all annotated and novel lncRNAs in both grade II and III gliomas as well as grade IV glioblastomas (glioblastoma multiforme [GBM]). We determined the expression of all lncRNAs in over 650 brain cancer and 70 normal brain tissue RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and other publicly available datasets. We identified 611 induced and 677 repressed lncRNAs in glial tumors relative to normal brains. Hundreds of lncRNAs were specifically expressed in each of the three lower grade glioma (LGG) subtypes (IDH1/2 wt, IDH1/2 mut, and IDH1/2 mut 1p19q codeletion) and the four subtypes of GBMs (classical, mesenchymal, neural, and proneural). Overlap between the subtype-specific lncRNAs in GBMs and LGGs demonstrated similarities between mesenchymal GBMs and IDH1/2 wt LGGs, with 2-fold higher overlap than would be expected by random chance. Using a multivariate Cox regression survival model, we identified 584 and 282 lncRNAs that were associated with a poor and good prognosis, respectively, in GBM patients. We developed a survival algorithm for LGGs based on the expression of 64 lncRNAs that was associated with patient prognosis in a test set (hazard ratio [HR] = 2.168, 95% CI = 1.765-2.807, p < 0.001) and validation set (HR = 1.921, 95% CI = 1.333-2.767, p < 0.001) of patients from TCGA. The main limitations of this study are that further work is needed to investigate the clinical relevance of our findings, and that validation in an independent dataset is needed to determine the robustness of our survival algorithm. This work identifies a panel of lncRNAs that appear to be prognostic in gliomas and provides a critical resource for

  10. Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis

    PubMed Central

    Reon, Brian J.; Anaya, Jordan; Zhang, Ying; Abounader, Roger; Dutta, Anindya

    2016-01-01

    Background Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles in regulating neurogenesis and brain tumor progression. To better understand the role of lncRNAs in brain cancer, we performed a global analysis to identify and characterize all annotated and novel lncRNAs in both grade II and III gliomas as well as grade IV glioblastomas (glioblastoma multiforme [GBM]). Methods and Findings We determined the expression of all lncRNAs in over 650 brain cancer and 70 normal brain tissue RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and other publicly available datasets. We identified 611 induced and 677 repressed lncRNAs in glial tumors relative to normal brains. Hundreds of lncRNAs were specifically expressed in each of the three lower grade glioma (LGG) subtypes (IDH1/2 wt, IDH1/2 mut, and IDH1/2 mut 1p19q codeletion) and the four subtypes of GBMs (classical, mesenchymal, neural, and proneural). Overlap between the subtype-specific lncRNAs in GBMs and LGGs demonstrated similarities between mesenchymal GBMs and IDH1/2 wt LGGs, with 2-fold higher overlap than would be expected by random chance. Using a multivariate Cox regression survival model, we identified 584 and 282 lncRNAs that were associated with a poor and good prognosis, respectively, in GBM patients. We developed a survival algorithm for LGGs based on the expression of 64 lncRNAs that was associated with patient prognosis in a test set (hazard ratio [HR] = 2.168, 95% CI = 1.765–2.807, p < 0.001) and validation set (HR = 1.921, 95% CI = 1.333–2.767, p < 0.001) of patients from TCGA. The main limitations of this study are that further work is needed to investigate the clinical relevance of our findings, and that validation in an independent dataset is needed to determine the robustness of our survival algorithm. Conclusions This work identifies a panel of lncRNAs that appear to be prognostic in

  11. Early Detection of Malignant Transformation in Resected WHO II Low-Grade Glioma Using Diffusion Tensor-Derived Quantitative Measures

    PubMed Central

    Freitag, Martin T.; Maier-Hein, Klaus H.; Binczyk, Francisczek; Laun, Frederik B.; Weber, Christian; Bonekamp, David; Tarnawski, Rafal; Bobek-Billewicz, Barbara; Polanska, Joanna; Majchrzak, Henryk; Stieltjes, Bram

    2016-01-01

    Objective Here, we retrospectively investigate the value of voxel-wisely plotted diffusion tensor-derived (DTI) axial, radial and mean diffusivity for the early detection of malignant transformation (MT) in WHO II glioma compared to contrast-enhanced images. Materials and Methods Forty-seven patients underwent brain magnetic resonance imaging follow-up between 2006–2014 after gross-tumor resection of intra-axial WHO II glioma. Axial/Mean/Radial diffusivity maps (AD/MD/RD) were generated from DTI data. ADmin/MDmin/RDmin values were quantified within tumor regions-of-interest generated by two independent readers including tumor contrast-to-noise (CNR). Sensitivity/specificity and area-under-the-curve (AUC) were calculated using receiver-operating-characteristic analysis. Inter-reader agreement was assessed (Cohen’s kappa). Results Eighteen patients demonstrated malignant transformation (MT) confirmed in 8/18 by histopathology and in 10/18 through imaging follow-up. Twelve of 18 patients (66.6%) with MT showed diffusion restriction timely coincidental with contrast-enhancement (CE). In the remaining six patients (33.3%), the diffusion restriction preceded the CE. The mean gain in detection time using DTI was (0.8±0.5 years, p = 0.028). Compared to MDmin and RDmin, ROC-analysis showed best diagnostic value for ADmin (sensitivity/specificity 94.94%/89.7%, AUC 0.96; p<0.0001) to detect MT. CNR was highest for AD (1.83±0.14), compared to MD (1.31±0.19; p<0.003) and RD (0.90±0.23; p<0.0001). Cohen’s Kappa was 0.77 for ADmin, 0.71 for MDmin and 0.65 for RDmin (p<0.0001, respectively). Conclusion MT is detectable at the same time point or earlier compared to T1w-CE by diffusion restriction in diffusion-tensor-derived maps. AD demonstrated highest sensitivity/specificity/tumor-contrast compared to radial or mean diffusivity (= apparent diffusion coefficient) to detect MT. PMID:27741525

  12. Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data.

    PubMed

    Zetterling, Maria; Roodakker, Kenney R; Berntsson, Shala Ghaderi; Edqvist, Per-Henrik; Latini, Francesco; Landtblom, Anne-Marie; Pontén, Fredrik; Alafuzoff, Irina; Larsson, Elna-Marie; Smits, Anja

    2016-11-01

    OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H-positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc-removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

  13. Image fusion analysis of volumetric changes after interstitial low-dose-rate iodine-125 irradiation of supratentorial low-grade gliomas.

    PubMed

    Julow, Jeno; Major, Tibor; Mangel, László; Bajzik, Gábor; Viola, Arpad

    2007-04-01

    The aim of this study was to compare the volumes of tumor necrosis, reactive zone and edema with the three-dimensional dose distributions after brachytherapy treatments of gliomas. The investigation was performed an average of 14.2 months after low-dose-rate (125)I interstitial irradiation of 25 inoperable low-grade gliomas. The prescribed dose was 50-60 Gy to the tumor surface. Dose planning and image fusion were performed with the BrainLab-Target 1.19 software. In the CT/ MRI images, the "triple ring" (tumor necrosis, reactive ring and edema) developing after the interstitial irradiation of the brain tumors was examined. The images with the triple ring were fused with the planning images, and the isodose curves were superimposed on them. The volumes of the three regions were measured. The average dose at the necrosis border was determined from the isodose distribution. For quantitative assessment of the dose distributions, the dose nonuniformity ratio (DNR), homogeneity index (HI), coverage index (CI) and conformal index (COIN) were calculated. The relative volumes of the different parts of the triple ring after the interstitial irradiation compared to the reference dose volume were the following: necrosis, 40.9%, reactive zone, 47.1%, and edema, 367%. The tumor necrosis developed at 79.1 Gy on average. The average DNR, HI, CI and COIN were 0.45, 0.24, 0.94 and 0.57, respectively. The image fusion analysis of the volume of tumor necrosis, reactive ring and edema caused by interstitial irradiation and their correlation with the dose distribution provide valuable information for patient follow-up, treatment options, and effects and side effects of radio therapy.

  14. THE VALUE OF PRE- AND INTRA-OPERATIVE ADJUNCTS ON THE EXTENT OF RESECTION OF HEMISPHERIC LOW GRADE GLIOMAS; A RETROSPECTIVE ANALYSIS

    PubMed Central

    Incekara, Fatih; Olubiyi, Olutayo; Ozdemir, Aysegul; Lee, Tom; Rigolo, Laura; Golby, Alexandra

    2016-01-01

    Background To achieve maximal resection with minimal risk of postoperative neurological morbidity, different neurosurgical adjuncts are being used during low grade glioma (LGG) surgery. Objectives The goal of this study was to investigate the effect of pre- and intra-operative adjuncts on the extent of resection (EOR) of hemispheric LGGs. Methods Medical records were reviewed to identify patients of any sex, 18 years or older, who underwent LGG surgery at ‘X’ Hospital between January 2005 and July 2013. Patients were divided in 8 subgroups based on the use of neuronavigation system alone (NN), functional MRI-diffusion tensor imaging (fMRI-DTI) guided neuronavigation (FD), intra-operative MRI (MR) and direct electrical stimulation (DES). Initial and residual tumors were measured and mean EOR was compared between groups. Results Of all 128 patients, gross total resection was achieved in 23.4%. Overall mean EOR was 81.3% ± 20.5%. Using DES in combination with fMRI-DTI (mean EOR 86.7% ± 12.4%) on eloquent tumors improved mean EOR significantly after adjustment for potential confounders, when compared with neuronavigation alone (mean EOR 76.4% ± 25.5%, p = 0.001). Conclusions Using DES in combination with fMRI and DTI significantly improves EOR when LGGs are located in eloquent areas, compared with craniotomies were only neuronavigation was used. PMID:26216736

  15. Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning.

    PubMed

    Musat, Elena; Roelofs, Erik; Bar-Deroma, Raquel; Fenton, Paul; Gulyban, Akos; Collette, Laurence; Stupp, Roger; Weber, Damien C; Bernard Davis, J; Aird, Edwin; Baumert, Brigitta G

    2010-05-01

    Early assessment of radiotherapy (RT) quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas. RT plans provided for dummy cases were evaluated and compared against expert plans. We analysed: (1) tumour and organs-at-risk delineation, (2) geometric and dosimetric characteristics, (3) planning parameters, compliance with dose prescription and Dmax for OAR (4) indices: RTOG conformity index (CI), coverage factor (CF), tissue protection factor (PF); conformity number (CN = PF x CF); dose homogeneity in PTV (U). Forty-one RT plans were evaluated. Only two (5%) centres were requested to repeat CTV-PTV delineations. Three (7%) plans had a significant under-dosage and dose homogeneity in one deviated > 10%. Dose distribution was good with mean values of 1.5, 1, 0.68, and 0.68 (ideal values = 1) for CI, CF, PF, and CN, respectively. CI and CN strongly correlated with PF and they correlated with PTV. Planning with more beams seems to increase PTV(Dmin), improving CF. U correlated with PTV(Dmax). Preliminary results of the dummy run procedure indicate that most centres conformed to protocol requirements. To quantify plan quality we recommend systematic calculation of U and either CI or CN, both of which measure the amount of irradiated normal brain tissue. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery.

    PubMed

    Valdés, Pablo A; Jacobs, Valerie; Harris, Brent T; Wilson, Brian C; Leblond, Frederic; Paulsen, Keith D; Roberts, David W

    2015-09-01

    Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)-induced PpIX fluorescence in a series of patients with LGG. Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 mg/kg of ALA approximately 3 hours prior to surgery under an institutional review board-approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively

  17. Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

    PubMed Central

    Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

    2015-01-01

    OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were

  18. Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target

    PubMed Central

    Hütt-Cabezas, Marianne; Karajannis, Matthias A.; Zagzag, David; Shah, Smit; Horkayne-Szakaly, Iren; Rushing, Elisabeth J.; Cameron, J. Douglas; Jain, Deepali; Eberhart, Charles G.; Raabe, Eric H.; Rodriguez, Fausto J.

    2013-01-01

    Background Previous studies support a role for mitogen-activated protein kinase pathway signaling, and more recently Akt/mammalian target of rapamycin (mTOR), in pediatric low-grade glioma (PLGG), including pilocytic astrocytoma (PA). Here we further evaluate the role of the mTORC1/mTORC2 pathway in order to better direct pharmacologic blockade in these common childhood tumors. Methods We studied 177 PLGGs and PAs using immunohistochemistry and tested the effect of mTOR blockade on 2 PLGG cell lines (Res186 and Res259) in vitro. Results Moderate (2+) to strong (3+) immunostaining was observed for pS6 in 107/177 (59%) PAs and other PLGGs, while p4EBP1 was observed in 35/115 (30%), pElF4G in 66/112 (59%), mTOR (total) in 53/113 (47%), RAPTOR (mTORC1 component) in 64/102 (63%), RICTOR (mTORC2 component) in 48/101 (48%), and pAkt (S473) in 63/103 (61%). Complete phosphatase and tensin homolog protein loss was identified in only 7/101 (7%) of cases. In PA of the optic pathways, compared with other anatomic sites, there was increased immunoreactivity for pS6, pElF4G, mTOR (total), RICTOR, and pAkt (P < .05). We also observed increased pS6 (P = .01), p4EBP1 (P = .029), and RICTOR (P = .05) in neurofibromatosis type 1 compared with sporadic tumors. Treatment of the PLGG cell lines Res186 (PA derived) and Res259 (diffuse astrocytoma derived) with the rapalog MK8669 (ridaforolimus) led to decreased mTOR pathway activation and growth. Conclusions These findings suggest that the mTOR pathway is active in PLGG but varies by clinicopathologic subtype. Additionally, our data suggest that mTORC2 is differentially active in optic pathway and neurofibromatosis type 1–associated gliomas. MTOR represents a potential therapeutic target in PLGG that merits further investigation. PMID:24203892

  19. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group.

    PubMed

    Ater, Joann L; Zhou, Tianni; Holmes, Emiko; Mazewski, Claire M; Booth, Timothy N; Freyer, David R; Lazarus, Ken H; Packer, Roger J; Prados, Michael; Sposto, Richard; Vezina, Gilbert; Wisoff, Jeffrey H; Pollack, Ian F

    2012-07-20

    PURPOSE Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. PATIENTS AND METHODS Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm(2). Tumor location in the thalamus was also associated with poor OS. CONCLUSION The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.

  20. IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas.

    PubMed

    Juratli, Tareq A; Kirsch, Matthias; Robel, Katja; Soucek, Silke; Geiger, Kathrin; von Kummer, Rüdiger; Schackert, Gabriele; Krex, Dietmar

    2012-07-01

    This study investigated the prognostic and predictive significance of IDH1 and IDH2 mutations in low-grade astrocytomas (LGA). The presence and consistency of IDH mutations during the progression of LGA to secondary high-grade gliomas (sHGG) were detected. Samples of patients with LGA and sHGG were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. Furthermore, the MGMT promoter status was provided using the methylation-specific PCR. Our population comprised 71 patients with a total of 45 pairs of LGA and their consecutive sHGG. Median follow-up was 9.6 years. IDH mutations were found in 36/45 LGA (80%) and their sHGG without changes in the mutation status. A total of 71 patients with LGA were analyzed according to clinical and molecular tumor-related factors: 56/71 patients (78.8%) had an IDH mutation without significant influence on the progression-free or overall survival (OS), and 22/71 (31%) of the patients received postoperative radiotherapy (RT) after diagnosis of LGA. Patients with early RT but without IDH mutations had the shortest survival. Our study shows that IDH mutation status is stable during the progression course of LGA to sHGG. The presence of IDH mutations fails to demonstrate a significant influence on survival in the multivariate analysis of LGA patients. Early RT appears to be beneficial only LGA patients with IDH-mutations.

  1. Connectivity in MEG resting-state networks increases after resective surgery for low-grade glioma and correlates with improved cognitive performance☆

    PubMed Central

    van Dellen, E.; de Witt Hamer, P.C.; Douw, L.; Klein, M.; Heimans, J.J.; Stam, C.J.; Reijneveld, J.C.; Hillebrand, A.

    2012-01-01

    Purpose Low-grade glioma (LGG) patients often have cognitive deficits. Several disease- and treatment related factors affect cognitive processing. Cognitive outcome of resective surgery is unpredictable, both for improvement and deterioration, especially for complex domains such as attention and executive functioning. MEG analysis of resting-state networks (RSNs) is a good candidate for presurgical prediction of cognitive outcome. In this study, we explore the relation between alterations in connectivity of RSNs and changes in cognitive processing after resective surgery, as a stepping stone to ultimately predict postsurgical cognitive outcome. Methods Ten patients with LGG were included, who had no adjuvant therapy. MEG recording and neuropsychological assessment were obtained before and after resective surgery. MEG data were recorded during a no-task eyes-closed condition, and projected to the anatomical space of the AAL atlas. Alterations in functional connectivity, as characterized by the phase lag index (PLI), within the default mode network (DMN), executive control network (ECN), and left- and right-sided frontoparietal networks (FPN) were compared to cognitive changes. Results Lower alpha band DMN connectivity was increased after surgery, and this increase was related to improved verbal memory functioning. Similarly, right FPN connectivity was increased after resection in the upper alpha band, which correlated with improved attention, working memory and executive functioning. Discussion Increased alpha band RSN functional connectivity in MEG recordings correlates with improved cognitive outcome after resective surgery. The mechanisms resulting in functional connectivity alterations after resection remain to be elucidated. Importantly, our findings indicate that connectivity of MEG RSNs may be used for presurgical prediction of cognitive outcome in future studies. PMID:24179752

  2. Phase 2 Study of Temozolomide-Based Chemoradiation Therapy for High-Risk Low-Grade Gliomas: Preliminary Results of Radiation Therapy Oncology Group 0424

    SciTech Connect

    Fisher, Barbara J.; Hu, Chen; Macdonald, David R.; Lesser, Glenn J.; Coons, Stephen W.; Brachman, David G.; Ryu, Samuel; Werner-Wasik, Maria; Bahary, Jean-Paul; Liu, Junfeng; Chakravarti, Arnab; Mehta, Minesh

    2015-03-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power. Methods and Materials: Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of >1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ. Results: From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P<.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis. Conclusions: The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P<.001) and the study-hypothesized rate of 65%.

  3. Spontaneous involution of pediatric low-grade gliomas: high expression of cannabinoid receptor 1 (CNR1) at the time of diagnosis may indicate involvement of the endocannabinoid system.

    PubMed

    Sredni, Simone Treiger; Huang, Chiang-Ching; Suzuki, Mario; Pundy, Tatiana; Chou, Pauline; Tomita, Tadanori

    2016-11-01

    Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children. Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG. We performed an integrated molecular analysis including high throughput gene expression (GE), microRNA (miRNA) expression data of primary, untreated tumors from patients with P-LGG who underwent STR at our institution, with at least 10 years follow-up. We identified a set of protein-coding genes and miRNAs significantly differentially expressed in P-LGG that presented spontaneous involution (involution-I) or without progression (stable-S) after STR alone. The cannabinoid receptor 1 (CNR1 or CB1) gene (FC = 2.374; p value = 0.007) was at the top of the list and predicted to be regulated by hsa-miR-29b-3p (FC = -2.353, p value = 0.0001). CNR1 also showed a trend to be higher expressed in S/I by immunohistochemistry. The P-LGG, which remained stable or that presented spontaneous involution after STR, showed significantly higher CNR1 expression at the time of diagnosis. We hypothesize that high expression levels of CNR1 provide tumor susceptibility to the antitumor effects of circulating endocannabinoids like anandamide, resulting in tumor involution. This corroborates with reports suggesting that CNR1 agonists and activators of the endocannabinoid system may represent therapeutic opportunities for children with LGG. We also suggest that CNR1 may be a prognostic marker for P-LGG. This is the first time spontaneous involution of P-LGG has been suggested to be induced by endocannabinoids.

  4. A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas

    ClinicalTrials.gov

    2017-01-30

    Pilomyxoid Astrocytoma; Pilocytic Astrocytoma; Glioma, Astrocytic; Optic Nerve Glioma; Pleomorphic Xanthoastrocytoma; Glioblastoma Multiforme; Anaplastic Astrocytoma; Gliosarcoma; Diffuse Intrinsic Pontine Glioma; DIPG; Low-grade Glioma; Brainstem Glioma

  5. Neuropsychological status in children and young adults with benign and low-grade brain tumors treated prospectively with focal stereotactic conformal radiotherapy

    SciTech Connect

    Jalali, Rakesh . E-mail: rjalali@medscape.com; Goswami, Savita; Sarin, Rajiv; More, Niteen; Siddha, Manish; Kamble, Rashmi

    2006-11-15

    Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score in

  6. ¹⁸F-Fluorocholine PET/CT as a complementary tool in the follow-up of low-grade glioma: diagnostic accuracy and clinical utility.

    PubMed

    Gómez-Río, Manuel; Testart Dardel, Nathalie; Santiago Chinchilla, Alicia; Rodríguez-Fernández, Antonio; Olivares Granados, Gonzalo; Luque Caro, Raquel; Zurita Herrera, Mercedes; Chamorro Santos, Clara E; Lardelli-Claret, Pablo; Llamas-Elvira, José M

    2015-05-01

    The follow-up of treated low-grade glioma (LGG) requires the evaluation of subtle clinical changes and MRI results. When the result is inconclusive, additional procedures are required to assist decision-making, such as the use of advanced MRI (aMRI) sequences and nuclear medicine scans (SPECT and PET). The aim of this study was to determine whether incorporating (18)F-fluorocholine PET/CT in the follow-up protocol for treated LGG improves diagnostic accuracy and clinical utility. This was a prospective case-series study in patients with treated LGG during standard follow-up with indeterminate clinical and/or radiological findings of tumour activity. All patients underwent clinical evaluation, aMRI, (201)Tl-SPECT and (18)F-fluorocholine PET/CT. Images were interpreted by visual evaluation complemented with semiquantitative analysis. Between January 2012 and December 2013, 18 patients were included in this study. The final diagnosis was established by histology (five surgical specimens, one biopsy specimen) or by consensus of the Neuro-Oncology Group (11 patients) after a follow-up of >6 months (mean 14.9 ± 2.72 months). The global diagnostic accuracies were 90.9% for aMRI (38.8% inconclusive), 69.2 % for (201)Tl-SPECT (11.1% inconclusive), and 100% for (18)F-fluorocholine PET/CT. (201)Tl-SPECT led correctly to a change in the initial approach in 38.9% of patients but might have led to error in 27.8%. The use of (18)F-fluorocholine PET/CT alone rather than (201)Tl-SPECT led correctly to a change in the approach suggested by routine follow-up in 72.2% of patients and endorsed the approach in the remaining 27.8%. Our results support the need to complement structural MRI with aMRI and nuclear medicine procedures in selected patients. (18)F-Fluorocholine PET/CT can be useful in the individualized management of patients with treated LGG with uncertain clinical and/or radiological evidence of tumour activity.

  7. Impact of 14-day bed rest on serum adipokines and low-grade inflammation in younger and older adults.

    PubMed

    Jurdana, Mihaela; Jenko-Pražnikar, Zala; Mohorko, Nina; Petelin, Ana; Jakus, Tadeja; Šimunič, Boštjan; Pišot, Rado

    2015-12-01

    Ageing and inactivity both contribute to systemic inflammation, but the effects of inactivity on inflammation in healthy elderly individuals have not been elucidated. We hypothesised that 14-day bed rest could affect the pro- and anti-inflammatory markers in young subjects differently than in older adults. A short-term 14-day horizontal bed rest study (BR14) has been used as a model of inactivity in two groups of healthy male volunteers: 7 aged 18-30 years (young) and 16 aged 55-65 years (older adults). The effects of inactivity on inflammation were compared. Key low-grade inflammation mediators, tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), visfatin, resistin, and anti-inflammatory adiponectin were measured in fasting serum samples, collected at baseline (BDC) and post BR14. Young responded to BR14 by increasing serum visfatin and resistin while older adults responded to BR14 by increasing IL-6 and TNF-α. In addition, serum adiponectin increased in all participants. Data from correlation analysis demonstrated positive association between Δ serum visfatin and Δ IL-6 in both groups, while Δ serum adiponectin was negatively associated with Δ TNF-α in young and positively associated with Δ resistin in the older adults. As little as 14 days of complete physical inactivity (BR14) negatively affected markers of low-grade inflammation in both groups, but the inflammation after BR14 was more pronounced in older adults. The effect of BR14 on IL-6 and resistin differed between young and older adults. Inflammatory responses to BR14 in older adults differed from those reported in the literature for obese or subjects in pathological states, suggesting potentially different mechanisms between inactivity- and obesity-induced inflammations.

  8. O8.04TEMOZOLOMIDE AFTER RADIOTHERAPY IN RECURRENT “LOW-GRADE” DIFFUSE BRAINSTEM GLIOMA IN ADULTS

    PubMed Central

    Reyes-Botero, G.; Laigle-Donadey, F.; Mokhtari, K.; Martin-Duverneuil, N.; Delattre, J.Y.

    2014-01-01

    INTRODUCTION: Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is frequently used as initial treatment. However, only limited data is available concerning chemotherapy efficacy at relapse after RT. Temozolomide (TMZ) is frequently used in progressive supratentorial gliomas after RT, but its efficacy in diffuse brainstem gliomas in adults has not been reported. PATIENTS AND METHODS: We conducted a retrospective analysis including patients from our database with non-enhancing diffuse brainstem glioma (histological or MRI criteria compatible with low-grade glioma) who received TMZ at relapse after RT. Tumors localized in the pons, medulla oblongata or midbrain were analyzed excluding supratentorial or infratentorial tumors secondary infiltrating the brainstem. Clinical and radiological responses were assessed and progression-free survival (PFS) and overall survival (OS) time were estimated. RESULTS: In total, 15 adult patients (median age 34 years) were selected. Histological analysis was available in 5 cases showing grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment obtaining a median PFS of 34.2 months (95% CI 24.1-44.2). Median KPS at the time of relapse after RT was 80. TMZ was administered orally at 150-200mg/m2 for 5 days every 28 days at progression disease after RT. Clinical improvement after TMZ was observed in 9 cases (60%) whereas radiological assessment detected 6 partial responses. Estimated median PFS after TMZ was 9.5 months (95% CI 7.9-11) and median OS was 14.4 months (95% CI 10.5-18.2). Grade 3 thrombocytopenia was observed in 26% of cases. CONCLUSIONS: TMZ could be useful in adult patients with progressive diffuse low-grade brainstem glioma after RT failure. Further studies are warranted to detect clinical and biological markers of response to TMZ.

  9. Moving toward molecular classification of diffuse gliomas in adults.

    PubMed

    Theeler, Brett J; Yung, W K Alfred; Fuller, Gregory N; De Groot, John F

    2012-10-30

    Diffuse gliomas are a heterogenous group of neoplasms traditionally classified as grades II to IV based on histologic features, and with prognosis determined mainly by histologic grade and pretreatment clinical factors. Our understanding of the molecular basis of glioma initiation, tumor progression, and treatment failure is rapidly evolving. A molecular profile of diffuse gliomas is emerging. Studies evaluating gene expression and DNA methylation profile have found multiple glioma subtypes and an association between subtype and survival. The recent discovery of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations in glioma has provided reproducible prognostic biomarkers and novel therapeutic targets. Glioblastomas that exhibit CpG island hypermethylator phenotype, proneural gene expression, or IDH1 mutation identify a subset of patients with markedly improved prognosis. Accumulated evidence supports the stratification of both low-grade and anaplastic diffuse gliomas into prognostic groups using 1p/19q codeletion and IDH mutation status. A classification scheme incorporating clinical, pathologic, and molecular information may facilitate improved prognostication for patients treated in the clinic, the development of more effective clinical trials, and rational testing of targeted therapeutics.

  10. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  11. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  12. Understanding inherited genetic risk of adult glioma – a review

    PubMed Central

    Rice, Terri; Lachance, Daniel H.; Molinaro, Annette M.; Eckel-Passow, Jeanette E.; Walsh, Kyle M.; Barnholtz-Sloan, Jill; Ostrom, Quinn T.; Francis, Stephen S.; Wiemels, Joseph; Jenkins, Robert B.; Wiencke, John K.; Wrensch, Margaret R.

    2016-01-01

    During the past six years, researchers have made major progress identifying common inherited genetic variation that increases risk for primary adult glioma. This paper summarizes knowledge about rare familial cancer syndromes that include adult glioma and reviews the available literature on the more recently discovered common inherited variation. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. Most of these variants increase relative risk of primary adult glioma by 20% to 40%, but the TP53 variant rs78378222 confers a two-fold relative risk (ie, 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk of IDH-mutated astrocytomas and oligodendroglial tumors (ie, 600%). Even with a six-fold relative risk, the overall risk of developing adult glioma is too low for screening for the high-risk variant on chromosome 8. Future studies will help clarify which inherited adult glioma risk variants are associated with subtypes defined by histology and/or acquired tumor mutations. This review also provides an information sheet for primary adult glioma patients and their families. PMID:26941959

  13. Understanding inherited genetic risk of adult glioma - a review.

    PubMed

    Rice, Terri; Lachance, Daniel H; Molinaro, Annette M; Eckel-Passow, Jeanette E; Walsh, Kyle M; Barnholtz-Sloan, Jill; Ostrom, Quinn T; Francis, Stephen S; Wiemels, Joseph; Jenkins, Robert B; Wiencke, John K; Wrensch, Margaret R

    2016-03-01

    During the past six years, researchers have made major progress identifying common inherited genetic variation that increases risk for primary adult glioma. This paper summarizes knowledge about rare familial cancer syndromes that include adult glioma and reviews the available literature on the more recently discovered common inherited variation. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. Most of these variants increase relative risk of primary adult glioma by 20% to 40%, but the TP53 variant rs78378222 confers a two-fold relative risk (ie, 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk of IDH-mutated astrocytomas and oligodendroglial tumors (ie, 600%). Even with a six-fold relative risk, the overall risk of developing adult glioma is too low for screening for the high-risk variant on chromosome 8. Future studies will help clarify which inherited adult glioma risk variants are associated with subtypes defined by histology and/or acquired tumor mutations. This review also provides an information sheet for primary adult glioma patients and their families.

  14. Season of Birth and Risk for Adult Onset Glioma

    PubMed Central

    Efird, Jimmy T.

    2010-01-01

    Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive. PMID:20623001

  15. P17.41CLINICAL MANAGEMENT AND OUTCOME OF HISTOLOGICALLY VERIFIED ADULT BRAINSTEM GLIOMAS IN SWITZERLAND: A RETROSPECTIVE ANALYSIS OF 21 PATIENTS

    PubMed Central

    Hundsberger, T.; Tonder, M.; Andreas, H.; Brügge, D.; Roelcke, U.; Putora, P.M.; Stupp, R.; Weller, M.

    2014-01-01

    BACKGROUND: Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult brainstem gliomas. METHODS: A retrospective chart review of adults (>age 18 years) was conducted. Brainstem glioma was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. RESULTS: 21 patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 versus 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (3 in each group), radiochemotherapy (2 versus 6), chemotherapy alone (0 versus 2) or no postoperative therapy (3 versus 1). Median PFS (24.1 versus 5.8 months; log-rank, p = 0.009) and mOS (30.5 versus 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. CONCLUSIONS: Histologically verification of adult brainstem glioma is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

  16. Insights From Molecular Profiling of Adult Glioma.

    PubMed

    Diamandis, Phedias; Aldape, Kenneth D

    2017-07-20

    The comprehensive molecular profiling of cancer has resulted in new insights into the biology and classification of numerous tumor types. In the case of primary brain tumors that commonly affect adults, an emerging set of disease-defining biomarker sets is reshaping existing diagnostic entities that had previously been defined on the basis of their microscopic appearance. Substantial progress has been made in this regard for common primary brain tumors in adults, especially diffuse gliomas, where large-scale profiling efforts have led to the incorporation of highly prevalent molecular alterations that promote a biologically based classification as an adjunct to the traditional histopathologic approach. The growing awareness that histologically indistinguishable tumors can be divided into more precise and biologically relevant subgroups has demanded a more global routine approach to biomarker assessment. These considerations have begun to intersect with the decreasing costs and availability of genome-wide analysis tools and, thus, incorporation into routine practice. We review how molecular profiling already has led to an evolution in the classification of brain tumors. In addition, we discuss the likely trajectory of incorporation of global molecular profiling platforms into the routine clinical classification of adult brain tumors.

  17. BRAF V600E-mutated diffuse glioma in an adult patient: a case report and review.

    PubMed

    Suzuki, Yuta; Takahashi-Fujigasaki, Junko; Akasaki, Yasuharu; Matsushima, Satoshi; Mori, Ryosuke; Karagiozov, Kostadin; Joki, Tatsuhiro; Ikeuchi, Satoshi; Ikegami, Masahiro; Manome, Yoshinobu; Murayama, Yuichi

    2016-01-01

    Recent advances in genomic technology and genome-wide analysis have identified key molecular alterations that are relevant to the diagnosis and prognosis of brain tumors. Molecular information such as mutations in isocitrate dehydrogenase (IDH) genes or 1p/19q co-deletion status will be more actively incorporated into the histological classification of diffuse gliomas. BRAF V600E mutations are found frequently in circumscribed low-grade gliomas such as pleomorphic xanthoastrocytoma (PXA) and extra-cerebellar pilocytic astrocytoma, or epithelioid glioblastomas (E-GBM), a rare variant of GBM. This mutation is relatively rare in other types of diffuse gliomas, especially in adult onset cases. Here, we present an adult onset case of IDH wild-type/BRAF V600E-mutated diffuse glioma, evolving from grade III to grade IV. The tumor displayed atypical exophytic growth and had unusual histological features not fully compatible with, but indicative of PXA and E-GBM. We discuss differential diagnosis of the tumor, and review previously described diffuse gliomas with the BRAF V600E mutation.

  18. Involvement of the neural stem cell compartment by pediatric and adult gliomas: a retrospective review of 377 cases.

    PubMed

    Marsh, James C; Goldman, Stewart; Ziel, Ellis; Bregman, Corey; Diaz, Aidnag; Byrne, Richard; Fangusaro, Jason

    2015-03-01

    To assess frequency of neural stem cell compartment (NSC) involvement in adult and pediatric gliomas [World Health Organization (WHO) grades 1-4], and to assess whether NSC involvement at presentation impacts on survival, recurrence rates, and/or transformation from low grade (WHO grade 1-2) to high grade disease (WHO grades 3-4). Cranial MRIs for 154 pediatric and 223 adult glioma patients treated from 2000 to 2012 were reviewed. NSC involvement was documented. Tumors were stratified by age (adult vs. pediatric), histology, tumor grade, tumor location, and involvement of midline structures. Odds ratios (OR) for death were calculated based on NSC status at presentation. Rates of transformation and recurrence rates (ORR) were compared using Fisher's Exact Test. Time to recurrence (TTR) was calculated using student t test. Among recurrent and transformed tumors, we also assessed the rate of NSC involvement at time of recurrence or transformation. 74.8 % of tumors had NSC involvement. Higher rates of NSC involvement were seen among adult (p = .0001); high grade (p = .0001)); grade 2 versus grade 1 (p = .0001) and other grade 1 histologies (p = .0001) versus JPA (juvenile pilocytic astrocytoma) patients); grade 2-4 tumors (p = .0001); and supratentorial tumors (p < .0001). No transformation was noted among pediatric low grade tumors or adult grade 1 tumors. 22/119 (18.5 %) adult grade 2 tumors transformed. Rates of transformation were not impacted by NSC status (p = .47). ORR was 15.1 %, and was greater for NSC+ tumors at presentation (p = .05). 36/41 recurrences (87.8 %) involved NSC at time of recurrence. OR for death was 2.62 (1.16-5.9), p = .02 for NSC+ tumors at presentation. Adult and pediatric gliomas (all grades) frequently involve NSC at presentation, although rates are lower in pediatric JPA and all infratentorial tumors. NSC involvement at presentation increases OR death and reduces TTR for pediatric gliomas (all grades) and adult low grade gliomas, and

  19. MRI in treatment of adult gliomas.

    PubMed

    Henson, John W; Gaviani, Paola; Gonzalez, R Gilberto

    2005-03-01

    Diffuse astrocytomas of the adult cerebral hemispheres are unique among tumours in human beings in the extent to which their imaging features are related to histopathological characteristics and clinical behaviour. However, understanding is still restricted about the value of imaging features in the measurement of response and of progression in these tumours. The present approach used in clinical trials, which consists of an anatomical measurement of the enhancing tumour on MRI, has many problems, and might not be acceptable as a surrogate endpoint for survival in patients with glioblastoma who are enrolled in clinical trials. Dynamic imaging techniques, such as capillary permeability mapping, are being used in studies of new drugs that target specific molecular features of gliomas; however, the validity of these techniques has not been elucidated. Diffusion imaging can be valuable for fibre-tract mapping to assist surgical planning and might become useful in measuring early response to treatment in densely cellular tumours. Functional imaging techniques can be used to localise motor, sensory, and language-control areas before surgery. Intraoperative MRI has produced improvements in the extent of tumour resection, and molecular imaging is another technique on the horizon, which could come to have a role in clinical trials in the near future. Thus, as a rapidly expanding sphere of investigation, brain-tumour imaging is producing great excitement. The aim of these new techniques is to aid the identification of more effective treatments.

  20. Telomere maintenance and the etiology of adult glioma.

    PubMed

    Walsh, Kyle M; Wiencke, John K; Lachance, Daniel H; Wiemels, Joseph L; Molinaro, Annette M; Eckel-Passow, Jeanette E; Jenkins, Robert B; Wrensch, Margaret R

    2015-11-01

    A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk has remained elusive. Recent data address this question and are reviewed here. Common inherited variants near the telomerase-component genes TERC and TERT are associated both with longer telomere length and increased risk of glioma. Exome sequencing of glioma patients from families with multiple affected members has identified rare inherited mutations in POT1 (protection of telomeres protein 1) as high-penetrance glioma risk factors. These heritable POT1 mutations are also associated with increased telomere length in leukocytes. Tumor sequencing studies further indicate that acquired somatic mutations of TERT and ATRX are among the most frequent alterations found in adult gliomas. These mutations facilitate telomere lengthening, thus bypassing a critical mechanism of apoptosis. Although future research is needed, mounting evidence suggests that glioma is, at least in part, a disease of telomere dysregulation. Specifically, several inherited and acquired variants underlying gliomagenesis affect telomere pathways and are also associated with increased telomere length. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Association between adult height, genetic susceptibility and risk of glioma

    PubMed Central

    Kitahara, Cari M; Wang, Sophia S; Melin, Beatrice S; Wang, Zhaoming; Braganza, Melissa; Inskip, Peter D; Albanes, Demetrius; Andersson, Ulrika; Beane Freeman, Laura E; Buring, Julie E; Carreón, Tania; Feychting, Maria; Gapstur, Susan M; Gaziano, J Michael; Giles, Graham G; Hallmans, Goran; Hankinson, Susan E; Henriksson, Roger; Hsing, Ann W; Johansen, Christoffer; Linet, Martha S; McKean-Cowdin, Roberta; Michaud, Dominique S; Peters, Ulrike; Purdue, Mark P; Rothman, Nathaniel; Ruder, Avima M; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Stevens, Victoria L; Visvanathan, Kala; Waters, Martha A; White, Emily; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Hoover, Robert; Fraumeni, Joseph F; Chatterjee, Nilanjan; Yeager, Meredith; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

    2012-01-01

    Background Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub-types, and investigated effect modification by genetic susceptibility to the disease. Methods We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case–control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. Results Among men, we found a positive association between height and glioma risk (≥190 vs 170–174 cm, pooled OR = 1.70, 95% CI: 1.11–2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17–3.38; P-trend = 0.02). Among women, these associations were less clear (≥175 vs 160–164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70–1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77–2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. Conclusion An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease. PMID:22933650

  2. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors.

    PubMed

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias; Stummer, Walter

    2016-03-01

    Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether

  3. Natural history and management of brainstem gliomas in adults. A retrospective Italian study.

    PubMed

    Salmaggi, A; Fariselli, L; Milanesi, I; Lamperti, E; Silvani, A; Bizzi, A; Maccagnano, E; Trevisan, E; Laguzzi, E; Rudà, R; Boiardi, A; Soffietti, R

    2008-02-01

    Brainstem gliomas in adults are rare tumors, with heterogeneous clinical course; only a few studies in the MRI era describe the features in consistent groups of patients. In this retrospective study, we report clinical features at onset, imaging characteristics and subsequent course in a group of 34 adult patients with either histologically proven or clinico-radiologically diagnosed brainstem gliomas followed at two centers in Northern Italy. Of the patients 18 were male, 14 female, with a median age of 31. In 21 of the patients histology was obtained and in 20 it was informative (2 pilocytic astrocytoma, 9 low-grade astrocytoma, 8 anaplastic astrocytoma and 1 glioblastoma). Contrast enhancement at MRI was present in 14 patients. In all of the 9 patients who were investigated with MR spectroscopy, the Cho/NAA ratio was elevated at diagnosis. In 8 of the patients, an initial watch and wait policy was adopted, while 24 were treated shortly after diagnosis with either radiotherapy alone [4] or radiotherapy and chemotherapy [20] (mostly temozolomide). Only minor radiological responses were observed after treatments; in a significant proportion of patients (9 out of 15) clinical improvement during therapy occurred in the context of radiologically (MRI) stable disease. Grade III or IV myelotoxicity was observed in 6 patients. After a follow-up ranging from 9 to 180 months, all but 2 patients have progressed and 14 have died (12 for disease progression, 2 for pulmonary embolism). Median overall survival time was of 59 months. Investigation of putative prognostically relevant parameters showed that a short time between disease onset and diagnosis was related to a shorter survival. Compared with literature data, our study confirms the clinical and radiological heterogeneity of adult brainstem gliomas and underscores the need for multicenter trials in order to assess the efficacy of treatments in these tumors.

  4. Glioma

    MedlinePlus

    ... come from ependymal cells. Tumors that display a mixture of these different cells are called mixed gliomas. ... oligodendrocytes, and ependymal cells. Tumors that display a mixture of these cells are called mixed gliomas. Astrocytoma: ...

  5. The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.

    PubMed

    Feng, Jie; Hao, Shuyu; Pan, Changcun; Wang, Yu; Wu, Zhen; Zhang, Junting; Yan, Hai; Zhang, Liwei; Wan, Hong

    2015-11-01

    Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets.

  6. The Value of 5-Aminolevulinic Acid in Low-grade Gliomas and High-grade Gliomas Lacking Glioblastoma Imaging Features: An Analysis Based on Fluorescence, Magnetic Resonance Imaging, 18F-Fluoroethyl Tyrosine Positron Emission Tomography, and Tumor Molecular Factors

    PubMed Central

    Jaber, Mohammed; Wölfer, Johannes; Ewelt, Christian; Holling, Markus; Hasselblatt, Martin; Niederstadt, Thomas; Zoubi, Tarek; Weckesser, Matthias

    2015-01-01

    BACKGROUND: Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade. OBJECTIVE: The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [18F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics. METHODS: Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and 18F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors. RESULTS: Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and 18F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted. CONCLUSION: Age, tumor volume, and 18F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased

  7. Adjacent segment degeneration after lumbar interbody fusion with percutaneous pedicle screw fixation for adult low-grade isthmic spondylolisthesis: minimum 3 years of follow-up.

    PubMed

    Bae, Jun Seok; Lee, Sang-Ho; Kim, Jin-Sung; Jung, Byungjoo; Choi, Gun

    2010-12-01

    Although favorable clinical outcomes have been reported for instrumented lumbar interbody fusion (LIF), adjacent segment degeneration (ASD) has been reported as a long-term complication after LIF. To investigate ASD after instrumented LIF performed at a single level and only for the homogeneous disease of adult low-grade isthmic spondylolisthesis. A total of 128 patients who had undergone LIF for the treatment of adult low-grade isthmic spondylolisthesis involving the lower lumbar spine at our institution between February 2001 and December 2004 were retrospectively reviewed by chart review and telephone survey. Of them, 103 patients with a minimum of a 36-month follow-up period were enrolled in this study. The mean age was 48.5 years. The average follow-up period was 59 months. Clinical and radiological data related to segmental lordosis (SL), whole lumbar lordosis, sacral slope, pelvic tilt, pelvic incidence, and L1 axis S1 distance were analyzed to identify significant risk factors for ASD. The overall incidence of ASD was 10.6% (11/103). The incidences of radiographic and symptomatic ASD were 8.7% (9/103) and 1.9% (2/103), respectively. All patients improved clinically and functionally during the follow-up period. Postoperative SL, preoperative SL, whole lumbar lordosis, and L1 axis S1 distance were significant risk factors for ASD. Only SL was a significant risk factor for both the preoperative and postoperative states. ASD may occur at a relatively lower incidence in adult low-grade isthmic spondylolisthesis compared with other degenerative lumbar spinal diseases. SL is significantly correlated with ASD, whereas mechanical alterations caused by LIF are less likely to affect the adjacent segment. Restoration of normal SL is important for preventing ASD, and long-term follow-up is necessary.

  8. Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA.

    PubMed

    Costello-White, Reagan; Ryff, Carol D; Coe, Christopher L

    2015-08-01

    The objective of this study was to investigate the effects of low-grade inflammation on age-related changes in glomerular filtration rate (GFR) in middle-aged and older white Americans, African-Americans, and Japanese adults. Serum creatinine, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were determined for 1570 adult participants in two surveys of aging in the USA and Japan (N = 1188 and 382, respectively). Kidney function declined with age in both countries and was associated with IL-6 and CRP. IL-6 and CRP also influenced the extent of the arithmetic bias when calculating the GFR using the chronic kidney disease epidemiology (CKD-EPI) formula with just serum creatinine. Younger African-Americans initially had the highest GFR but showed a steep age-related decrement that was associated with elevated inflammation. Japanese adults had the lowest average GFR but evinced a large effect of increased inflammatory activity when over 70 years of age. Importantly, our results also indicate that low-grade inflammation is important to consider when evaluating kidney function solely from serum creatinine.

  9. Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease.

    PubMed

    Giordano, Mauro; Ciarambino, Tiziana; Castellino, Pietro; Cataliotti, Alessandro; Malatino, Lorenzo; Ferrara, Nicola; Politi, Cecilia; Paolisso, Giuseppe

    2014-09-01

    The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear. Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b-G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo. During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD). In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Treatment of Adult Lower-Grade Glioma in the Era of Genomic Medicine.

    PubMed

    Chang, Susan M; Cahill, Daniel P; Aldape, Kenneth D; Mehta, Minesh P

    2016-01-01

    By convention, gliomas are histopathologically classified into four grades by the World Health Organization (WHO) legacy criteria, in which increasing grade is associated with worse prognosis and grades also are subtyped by presumed cell of origin. This classification has prognostic value but is limited by wide variability of outcome within each grade, so the classification is rapidly undergoing dramatic re-evaluation in the context of a superior understanding of the biologic heterogeneity and molecular make-up of these tumors, such that we now recognize that some low-grade gliomas behave almost like malignant glioblastoma, whereas other anaplastic gliomas have outcomes comparable to favorable low-grade gliomas. This clinical spectrum is partly accounted for by the dispersion of several molecular genetic alterations inherent to clinical tumor behavior. These molecular biomarkers have become important not only as prognostic factors but also, more critically, as predictive markers to drive therapeutic decision making. Some of these, in the near future, will likely also serve as potential therapeutic targets. In this article, we summarize the key molecular features of clinical significance for WHO grades II and III gliomas and underscore how the therapeutic landscape is changing.

  11. Radiation combined with temozolomide contraindicated for young adults diagnosed with anaplastic glioma

    PubMed Central

    Cai, Jinquan; You, Gan; Wang, Yinyan; Qiu, Xiaoguang; Li, Shouwei; Wu, Chenxing; Yao, Kun; Li, Wenbin; Peng, Xiaoxia; Zhang, Wei; Jiang, Tao

    2016-01-01

    Purpose Age is a major prognostic factor for malignant gliomas. However, few studies have investigated the management of gliomas in young adults. We determined the role of survival and treatment in young adults with advanced gliomas in a large population from the Chinese Glioma Genome Atlas (CGGA). Methods This study included 726 adults (age ≥ 18) with histologically proven anaplastic glioma or glioblastoma multiforme (GBM). The overall and progression-free survival was determined in young (age < 50) and older groups (age ≥ 50). Results The study included an older group (OP) of 264 patients and a younger group (YP) of 462patients. In the OP group with GBM and anaplastic glioma, patients treated with RT combined with temozolomide (TMZ) manifested significantly longer OS and PFS compared with patients assigned to RT alone (P < 0.05). In contrast, the YP group diagnosed with anaplastic glioma failed to show any survival advantage with RT plus TMZ compared with RT alone. Conclusions We observed no survival benefit in young adults (age < 50) with anaplastic glioma when treated with TMZ combined with RT. Our findings warrant further investigation of younger patients diagnosed with anaplastic glioma treated with radiotherapy plus TMZ chemotherapy. PMID:27590514

  12. Low grade mosaic for a complex supernumerary ring chromosome 18 in an adult patient with multiple congenital anomalies

    PubMed Central

    2010-01-01

    Background Several cases have been reported of patients with a ring chromosome 18 replacing one of the normal chromosomes 18. Less common are patients with a supernumerary ring chromosomes 18. High resolution whole genome examination in patients with multiple congenital abnormalities might reveal cytogenetic abnormalities of an unexpected complexity. Results We report a 24 years old male patient with lower spinal anomalies, hypospadia, bifid scrotum, cryptorchism, anal atresia, kidney stones, urethra anomalies, radial dysplasia, and a hypoplastic thumb. Some of the anomalies overlap with the VACTERL association. Chromosome analysis of cultured peripheral blood lymphocytes revealed an additional ring chromosome in 13% of the metaphases. Both parents had a normal karyotype, demonstrating the de novo origin of this ring chromosome. FISH analysis using whole chromosome paints showed that the additional chromosomal material was derived from chromosome 18. Chromosome analysis of cultured fibroblasts revealed only one cell with the supernumerary ring chromosome in the 400 analyzed. To characterize the ring chromosome in more detail peripheral blood derived DNA was analyzed using SNP-arrays. The array results indicated a 5 Mb gain of the pericentromeric region of chromosome 18q10-q11.2. FISH analysis using BAC-probes located in the region indicated the presence of 6 signals on the r(18) chromosome. In addition, microsatellite analysis demonstrated that the unique supernumerary ring chromosome was paternally derived and both normal copies showed biparental disomy. Conclusions We report on an adult patient with multiple congenital abnormalities who had in 13% of his cells a unique supernumerary ring chromosome 18 that was composed of 6 copies of the 5 Mb gene rich region of 18q11. PMID:20618949

  13. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

    ClinicalTrials.gov

    2017-01-30

    Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood

  14. Changing incidence and improved survival of gliomas.

    PubMed

    Ho, Vincent K Y; Reijneveld, Jaap C; Enting, Roelien H; Bienfait, Henri P; Robe, Pierre; Baumert, Brigitta G; Visser, Otto

    2014-09-01

    Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma and low-grade gliomas. Data on 21,085 gliomas (excluding grade I tumours) were obtained from the Netherlands Cancer Registry, including tumours of the CNS without pathological confirmation. We calculated the age-standardised incidence rates and the estimated annual percentage change (EAPC) for all glioma subtypes. Crude and relative survival rates were estimated using information on the vital status obtained from the Dutch Municipal Personal Records Database. Incidence of gliomas in adults increased over time, from 4.9 per 100,000 in 1989 to 5.9 in 2010 (EAPC 0.7%, p<0.001). Two thirds were astrocytoma, 10% oligodendroglioma/oligoastrocytoma, 3% ependymoma and 21% were unspecified. Within the group of astrocytic tumours, the proportion of glioblastoma rose, while the proportion of anaplastic and unspecified astrocytoma decreased. Unspecified neoplasms also decreased, but this was significant only after 2005. Over the course of the study period, glioblastoma patients more often received multimodality treatment with chemotherapy concomitant and adjuvant to radiotherapy. The crude two-year survival rate of glioblastoma patients improved significantly, from 5% in the time period 1989-1994 to 15% in 2006-2010, with median survival increasing from 5.5 to 9 months. The incidence of low-grade gliomas did not change over time. Survival rates for low-grade oligodendroglial and mixed tumours show a modest improvement. The incidence rate for the total group of gliomas slightly increased, with a decrease of anaplastic and unspecified tumours and an increase of glioblastoma. Following the introduction of combined chemoradiation, two-year survival rates for glioblastoma significantly improved

  15. Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process.

    PubMed

    Galvao, Rui Pedro; Kasina, Anita; McNeill, Robert S; Harbin, Jordan E; Foreman, Oded; Verhaak, Roel G W; Nishiyama, Akiko; Miller, C Ryan; Zong, Hui

    2014-10-07

    How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the premalignant events taking place between initial mutation and a fully developed tumor mass are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas.

  16. Pediatric high-grade glioma: current molecular landscape and therapeutic approaches.

    PubMed

    Braunstein, Steve; Raleigh, David; Bindra, Ranjit; Mueller, Sabine; Haas-Kogan, Daphne

    2017-03-29

    High-grade pediatric central nervous system glial tumors are comprised primarily of anaplastic astrocytomas (AA, WHO grade III) and glioblastomas (GBM, WHO grade IV). High-grade gliomas are most commonly diagnosed in the primary setting in children, but as in adults, they can also arise as a result of transformation of a low-grade malignancy, though with limited frequency in the pediatric population. The molecular genetics of high-grade gliomas in the pediatric population are distinct from their adult counterparts. In contrast to the adult population, high-grade gliomas in children are relatively infrequent, representing less than 20% of cases.

  17. The epidemiology of glioma in adults: a “state of the science” review

    PubMed Central

    Ostrom, Quinn T.; Bauchet, Luc; Davis, Faith G.; Deltour, Isabelle; Fisher, James L.; Langer, Chelsea Eastman; Pekmezci, Melike; Schwartzbaum, Judith A.; Turner, Michelle C.; Walsh, Kyle M.; Wrensch, Margaret R.; Barnholtz-Sloan, Jill S.

    2014-01-01

    Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O6-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine–phosphate–guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults. PMID:24842956

  18. The epidemiology of glioma in adults: a "state of the science" review.

    PubMed

    Ostrom, Quinn T; Bauchet, Luc; Davis, Faith G; Deltour, Isabelle; Fisher, James L; Langer, Chelsea Eastman; Pekmezci, Melike; Schwartzbaum, Judith A; Turner, Michelle C; Walsh, Kyle M; Wrensch, Margaret R; Barnholtz-Sloan, Jill S

    2014-07-01

    Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults.

  19. Association between Serum Ferritin Concentrations and Depressive Symptoms among Chinese Adults: A Population Study from the Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIHealth) Cohort Study

    PubMed Central

    Yu, Bin; Yu, Fei; He, Haiyan; Zhang, Qing; Meng, Ge; Wu, Hongmei; Du, Huanmin; Liu, Li; Shi, Hongbin; Xia, Yang; Guo, Xiaoyan; Liu, Xing; Li, Chunlei; Bao, Xue; Liu, Fangfang; Fang, Liyun; Yang, Huijun; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Zhao, Honglin; Song, Kun; Niu, Kaijun

    2016-01-01

    Depressive symptoms have become the most important global public health issue. Iron plays an important role in brain function, cognition, and behavior, and its impacts on depressive symptoms may be multifactorial with both positive and negative effects. Previous observational studies focusing on the association between iron status and depressive symptoms showed inconsistent results. Ferritin is a ubiquitous intracellular protein that can store and release iron and is widely used as a clinical biomarker to evaluate iron status. We performed a cross-sectional study to examine the relationship between serum ferritin and depressive symptoms among 3,839 subjects who were from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIHealth) cohort. Depressive symptoms were assessed using the Chinese version of 20-item self-rating Depression Scale (SDS) with 4 cutoffs (40, 45, 48 and 50) to indicate elevated depressive symptoms (40 was the primary cut-off). The prevalence of depressive symptoms was 36.5%, 17.6%, 11.0% and 7.0% for SDS ≥40, ≥45, ≥48 and ≥50, respectively. With the primary cut-off point of 40, multiple potential confounding factors were adjusted and the odds ratios (95% confidence interval) of having elevated depressive symptoms by quartiles of serum ferritin concentrations were 1.00 (reference), 1.10 (0.91, 1.34), 0.81 (0.66, 1.01) and 1.02 (0.81, 1.28) for the first, second, third and fourth quartile, respectively (P for trend = 0.76). Similar relations were observed with the use of other cut-offs as a definition of depressive symptoms. In conclusion, there is no significant relationship between serum ferritin concentrations and depressive symptoms among Chinese adults. PMID:27611581

  20. Radiotherapy for diffuse brainstem glioma in children and young adults.

    PubMed

    Hu, Xin; Fang, Yuan; Hui, Xuhui; Jv, Yan; You, Chao

    2016-06-27

    Diffuse brainstem glioma is a devastating disease with very poor prognosis. The most commonly used radiological treatment is conventional fractionated radiation. So far, there is no meta-analysis or systematic review available that assesses the benefits or harms of radiation in people with diffuse brainstem glioma. To assess the effects of conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem gliomas in children and young adults aged 0 to 21 years. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, and EMBASE to 19 August 2015. We scanned conference proceedings from the International Society for Paediatric Oncology (SIOP), International Symposium on Paediatric Neuro-Oncology (ISPNO), Society of Neuro-Oncology (SNO), and European Association of Neuro-Oncology (EANO) from 1 January 2010 to 19 August 2015. We searched trial registers including the International Standard Randomised Controlled Trial Number (ISRCTN) Register, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the register of the National Institutes of Health to 19 August 2015. We imposed no language restrictions. All randomised controlled trials (RCTs), quasi-randomised trials (QRCTs), or controlled clinical trials (CCTs) that compared conventional fractionated radiotherapy (with or without chemotherapy) versus other therapies (including different radiotherapy techniques) for newly diagnosed diffuse brainstem glioma in children and young adults aged 0 to 21 years. Two review authors independently screened studies for inclusion, extracted data, assessed the risk of bias in each eligible trial, and conducted GRADE assessment of included studies. We resolved disagreements through discussion. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of

  1. A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method.

    PubMed

    Walker, David A; Liu, JoFen; Kieran, Mark; Jabado, Nada; Picton, Susan; Packer, Roger; St Rose, Christian

    2013-04-01

    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.

  2. Characteristics of gliomas in patients with somatic IDH mosaicism.

    PubMed

    Bonnet, Charlotte; Thomas, Laure; Psimaras, Dimitri; Bielle, Franck; Vauléon, Elodie; Loiseau, Hugues; Cartalat-Carel, Stéphanie; Meyronet, David; Dehais, Caroline; Honnorat, Jérôme; Sanson, Marc; Ducray, François

    2016-03-31

    IDH mutations are found in the majority of adult, diffuse, low-grade and anaplastic gliomas and are also frequently found in cartilaginous tumors. Ollier disease and Maffucci syndrome are two enchondromatosis syndromes characterized by the development of multiple benign cartilaginous tumors due to post-zygotic acquisition of IDH mutations. In addition to skeletal tumors, enchondromatosis patients sometimes develop gliomas. The aim of the present study was to determine whether gliomas in enchondromatosis patients might also result from somatic IDH mosaicism and whether their characteristics are similar to those of sporadic IDH-mutated gliomas. For this purpose, we analyzed the characteristics of 6 newly diagnosed and 32 previously reported cases of enchondromatosis patients who developed gliomas and compared them to those of a consecutive series of 159 patients with sporadic IDH-mutated gliomas. As was the case with sporadic IDH mutated gliomas, enchondromatosis gliomas were frequently located in the frontal lobe (54 %) and consisted of diffuse low-grade (73 %) or anaplastic gliomas (21 %). However, they were diagnosed at an earlier age (25.6 years versus 44 years, p < 0.001) and were more frequently multicentric (32 % versus 1 %, p < 0.001) and more frequently located within the brainstem than sporadic IDH mutated gliomas (21 % versus 1 %, p < 0.001). Their molecular profile was characterized by IDH mutations and loss of ATRX expression. In two patients, the same IDH mutation was demonstrated in the glioma and in a cartilaginous tumor. In contrast to sporadic IDH mutated gliomas, no enchondromatosis glioma harbored a 1p/19q co-deletion (0/6 versus 59/123, p = 0.03). The characteristics of gliomas in patients with enchondromatosis suggest that these tumors, as cartilaginous tumors, result from somatic IDH mosaicism and that the timing of IDH mutation acquisition might affect the location and molecular characteristics of gliomas. Early

  3. Genome-Wide Analyses Identify Recurrent Amplifications of Receptor Tyrosine Kinases and Cell-Cycle Regulatory Genes in Diffuse Intrinsic Pontine Glioma

    PubMed Central

    Paugh, Barbara S.; Broniscer, Alberto; Qu, Chunxu; Miller, Claudia P.; Zhang, Junyuan; Tatevossian, Ruth G.; Olson, James M.; Geyer, J. Russell; Chi, Susan N.; da Silva, Nasjla Saba; Onar-Thomas, Arzu; Baker, Justin N.; Gajjar, Amar; Ellison, David W.; Baker, Suzanne J.

    2011-01-01

    Purpose Long-term survival for children with diffuse intrinsic pontine glioma (DIPG) is less than 10%, and new therapeutic targets are urgently required. We evaluated a large cohort of DIPGs to identify recurrent genomic abnormalities and gene expression signatures underlying DIPG. Patients and Methods Single-nucleotide polymorphism arrays were used to compare the frequencies of genomic copy number abnormalities in 43 DIPGs and eight low-grade brainstem gliomas with data from adult and pediatric (non-DIPG) glioblastomas, and expression profiles were evaluated using gene expression arrays for 27 DIPGs, six low-grade brainstem gliomas, and 66 nonbrainstem low-grade gliomas. Results Frequencies of specific large-scale and focal imbalances varied significantly between DIPGs and nonbrainstem pediatric glioblastomas. Focal amplifications of genes within the receptor tyrosine kinase–Ras–phosphoinositide 3-kinase signaling pathway were found in 47% of DIPGs, the most common of which involved PDGFRA and MET. Thirty percent of DIPGs contained focal amplifications of cell-cycle regulatory genes controlling retinoblastoma protein (RB) phosphorylation, and 21% had concurrent amplification of genes from both pathways. Some tumors showed heterogeneity in amplification patterns. DIPGs showed distinct gene expression signatures related to developmental processes compared with nonbrainstem pediatric high-grade gliomas, whereas expression signatures of low-grade brainstem and nonbrainstem gliomas were similar. Conclusion DIPGs comprise a molecularly related but distinct subgroup of pediatric gliomas. Genomic studies suggest that targeted inhibition of receptor tyrosine kinases and RB regulatory proteins may be useful therapies for DIPG. PMID:21931021

  4. White Matter Change Revealed by Diffusion Tensor Imaging in Gliomas

    PubMed Central

    Won, Young Il; Kim, Chi Heon; Park, Chul-Kee; Koo, Bang-Bon; Lee, Jong-Min; Jung, Hee-Won

    2016-01-01

    Background Tumor-related white matter change is detected at late stages with magnetic resonance imaging (MRI), when mass effect or prominent edema is present. We analyzed if diffusion tensor imaging (DTI) white matter change earlier than conventional MRI. Methods Twenty-six patients with gliomas (World Health Organization grade II, 5; grade III, 12; and grade IV, 9) within 2 cm from the posterior limb of the internal capsule (IC) were studied. Fifteen normal adults were enrolled as controls. Fluid attenuation inversion recovery MRI showed a high signal change at the posterior limb of the IC (HSIC) in 9 patients with grade III or IV gliomas. We classified the gliomas as WHO grade II (gliomas II), grade III or IV without HSIC [gliomas III/IV(-)] and grade III or IV with HSIC [gliomas III/IV(+)], as an indicator of the increase in the severity of the white matter changes. Fractional anisotropy (FA) and apparent diffusion coefficients (ADC) were calculated for the pyramidal tract. Tumor progression along pyramidal tract was evaluated by follow-up MRI in 16 patients at 40±18 months. Results FA showed no significant difference between gliomas II and control (p=0.694), but was lower in gliomas III/IV(-) and gliomas III/IV(+) (p<0.001). ADCs were higher in gliomas II, gliomas III/IV(-) and gliomas III/IV(+) than control (p<0.001). Tumor progression was detected in 2/16 patients. Conclusion DTI detected white matter changes that appeared to be normal in MRI. ADC changed even in low grade glioma, indicating ADC may be a better parameter for the early detection of white matter change. PMID:27867919

  5. A case report of pseudoprogression followed by complete remission after proton-beam irradiation for a low-grade glioma in a teenager: the value of dynamic contrast-enhanced MRI.

    PubMed

    Meyzer, Candice; Dhermain, Frédéric; Ducreux, Denis; Habrand, Jean-Louis; Varlet, Pascale; Sainte-Rose, Christian; Dufour, Christelle; Grill, Jacques

    2010-02-04

    A fourteen years-old boy was treated post-operatively with proton therapy for a recurrent low-grade oligodendroglioma located in the tectal region. Six months after the end of irradiation (RT), a new enhancing lesion appeared within the radiation fields. To differentiate disease progression from radiation-induced changes, dynamic susceptibility contrast-enhanced (DSCE) MRI was used with a T2* sequence to study perfusion and permeability characteristics simultaneously. Typically, the lesion showed hypoperfusion and hyperpermeability compared to the controlateral normal brain. Without additional treatment but a short course of steroids, the image disappeared over a six months period allowing us to conclude for a pseudo-progression. The patient is alive in complete remission more than 2 years post-RT.

  6. Prognostic and Predictive Biomarkers in Adult and Pediatric Gliomas: Toward Personalized Treatment

    PubMed Central

    Haynes, Harry R.; Camelo-Piragua, Sandra; Kurian, Kathreena M.

    2014-01-01

    It is increasingly clear that both adult and pediatric glial tumor entities represent collections of neoplastic lesions, each with individual pathological molecular events and treatment responses. In this review, we discuss the current prognostic biomarkers validated for clinical use or with future clinical validity for gliomas. Accurate prognostication is crucial for managing patients as treatments may be associated with high morbidity and the benefits of high risk interventions must be judged by the treating clinicians. We also review biomarkers with predictive validity, which may become clinically relevant with the development of targeted therapies for adult and pediatric gliomas. PMID:24716189

  7. A glioma classification scheme based on coexpression modules of EGFR and PDGFRA.

    PubMed

    Sun, Yingyu; Zhang, Wei; Chen, Dongfeng; Lv, Yuhong; Zheng, Junxiong; Lilljebjörn, Henrik; Ran, Liang; Bao, Zhaoshi; Soneson, Charlotte; Sjögren, Hans Olov; Salford, Leif G; Ji, Jianguang; French, Pim J; Fioretos, Thoas; Jiang, Tao; Fan, Xiaolong

    2014-03-04

    We hypothesized that key signaling pathways of glioma genesis might enable the molecular classification of gliomas. Gene coexpression modules around epidermal growth factor receptor (EGFR) (EM, 29 genes) or platelet derived growth factor receptor A (PDGFRA) (PM, 40 genes) in gliomas were identified. Based on EM and PM expression signatures, nonnegative matrix factorization reproducibly clustered 1,369 adult diffuse gliomas WHO grades II-IV from four independent databases generated in three continents, into the subtypes (EM, PM and EM(low)PM(low) gliomas) in a morphology-independent manner. Besides their distinct patterns of genomic alterations, EM gliomas were associated with higher age at diagnosis, poorer prognosis, and stronger expression of neural stem cell and astrogenesis genes. Both PM and EM(low)PM(low) gliomas were associated with younger age at diagnosis and better prognosis. PM gliomas were enriched in the expression of oligodendrogenesis genes, whereas EM(low)PM(low) gliomas were enriched in the signatures of mature neurons and oligodendrocytes. The EM/PM-based molecular classification scheme is applicable to adult low-grade and high-grade diffuse gliomas, and outperforms existing classification schemes in assigning diffuse gliomas to subtypes with distinct transcriptomic and genomic profiles. The majority of the EM/PM classifiers, including regulators of glial fate decisions, have not been extensively studied in glioma biology. Subsets of these classifiers were coexpressed in mouse glial precursor cells, and frequently amplified or lost in an EM/PM glioma subtype-specific manner, resulting in somatic copy number alteration-dependent gene expression that contributes to EM/PM signatures in glioma samples. EM/PM-based molecular classification provides a molecular diagnostic framework to expedite the search for new glioma therapeutic targets.

  8. Coffee, tea, caffeine intake, and risk of adult glioma in three prospective cohort studies.

    PubMed

    Holick, Crystal N; Smith, Scott G; Giovannucci, Edward; Michaud, Dominique S

    2010-01-01

    Current data suggest that caffeinated beverages may be associated with lower risk of glioma. Caffeine has different effects on the brain, some of which could play a role in brain carcinogenesis, and coffee has been consistently associated with reduced risk of liver cancer, thus suggesting a potential anticarcinogenic effect. A total of 335 incident cases of gliomas (men, 133; women, 202) were available from three independent cohort studies. Dietary intake was assessed by food frequency questionnaires obtained at baseline and during follow-up. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between consumption of coffee, tea, carbonated beverages, caffeine, and glioma risk adjusting for age and total caloric intake. Estimates from each cohort were pooled using a random-effects model. Consumption of five or more cups of coffee and tea daily compared with no consumption was associated with a decrease risk of glioma (RR, 0.60; 95% CI, 0.41-0.87; P(trend) = 0.04). Inverse, although weaker, associations were also observed between coffee, caffeinated coffee, tea, and carbonated beverages and glioma risk. No association was observed between decaffeinated coffee and glioma risk. Among men, a statistically significant inverse association was observed between caffeine consumption and risk of glioma (RR, 0.46; 95% CI, 0.26-0.81; P(trend) = 0.03); the association was weaker among women. Our findings suggest that consumption of caffeinated beverages, including coffee and tea, may reduce the risk of adult glioma, but further research is warranted to confirm these findings in other populations.

  9. Coffee, tea, caffeine intake and risk of adult glioma in 3 prospective cohort studies

    PubMed Central

    Holick, Crystal N.; Smith, Scott G.; Giovannucci, Edward; Michaud, Dominique S.

    2009-01-01

    Current data suggest that caffeinated beverages may be associated with lower risk of glioma. Caffeine has different effects on the brain, some which could play a role in brain carcinogenesis, and coffee has been consistently associated with reduced risk of liver cancer, thus suggesting a potential anticarcinogenic effect. A total of 335 incident cases of gliomas (men = 133, women = 202) were available from three independent cohort studies. Dietary intake was assessed by food-frequency questionnaires obtained at baseline and during follow-up. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) between consumption of coffee, tea, carbonated beverages, caffeine, and glioma risk adjusting for age and total caloric intake. Estimates from each cohort were pooled using a random-effects model. Consumption of five or more cups of coffee and tea a day compared to no consumption was associated with a decrease risk of glioma (RR = 0.60; 95% CI: 0.41–0.87; p-trend = 0.04). Inverse, although weaker, associations were also observed between coffee, caffeinated coffee, tea, carbonated beverages and glioma risk. No association was observed between decaffeinated coffee and glioma risk. Among men, a statistically significant inverse association was observed between caffeine consumption and risk of glioma (RR = 0.46; 95% CI: 0.26–0.81; p-trend = 0.03); the association was weaker among women. Our findings suggest that consumption of caffeinated beverages, including coffee and tea, may reduce the risk of adult glioma, but further research is warranted to confirm these findings in other populations. PMID:20056621

  10. A healthy diet is associated with less endothelial dysfunction and less low-grade inflammation over a 7-year period in adults at risk of cardiovascular disease.

    PubMed

    van Bussel, Bas C T; Henry, Ronald M A; Ferreira, Isabel; van Greevenbroek, Marleen M J; van der Kallen, Carla J H; Twisk, Jos W R; Feskens, Edith J M; Schalkwijk, Casper G; Stehouwer, Coen D A

    2015-03-01

    A healthy diet rich in fish, fruit, and vegetables, but moderate in alcohol and low in dairy products and meat, has been associated with a lower rate of incident cardiovascular disease (CVD). The underlying mechanisms, however, remain unclear. Endothelial dysfunction and low-grade inflammation play important roles in CVD. A healthy diet might modify these phenomena. We investigated the associations between the above food groups and overall biomarker scores of endothelial dysfunction and low-grade inflammation in a 7-y longitudinal study. Using longitudinal data from 557 participants at increased CVD risk from the CODAM (Cohort on Diabetes and Atherosclerosis Maastricht) Study, we assessed diet intake by food-frequency questionnaire and measured plasma biomarkers of endothelial dysfunction [von Willebrand factor, soluble vascular cell adhesion molecule 1, soluble endothelial selectin, soluble thrombomodulin, soluble intercellular adhesion molecule 1 (sICAM-1)] and low-grade inflammation [C-reactive protein, serum amyloid A, interleukin (IL)-6, IL-8, tumor necrosis factor α, and sICAM-1]. At baseline, participants were aged 59.6 ± 6.9 y. Measurements were performed then and after 7 y. Biomarkers were combined into overall scores (sum of z scores; higher scores indicating worse function). Longitudinal data were analyzed with generalized estimating equations and adjusted for sex, age, glucose metabolism, energy intake, body mass index, physical activity, alcohol consumption, and smoking. Higher consumption of fish (per 100 g/wk), but not total consumption of vegetables, fruit, alcohol-containing beverages, dairy products, or meat, was associated with a lower overall endothelial dysfunction score over 7 y (β: -0.027; 95% CI: -0.051, -0.004). No associations were observed with the overall low-grade inflammation score. Further food component analyses indicated that consumption of more lean fish (per 100 g/wk) and raw vegetables (per 100 g/d), and fewer high-fat dairy

  11. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk.

    PubMed

    Walsh, Kyle M; Codd, Veryan; Rice, Terri; Nelson, Christopher P; Smirnov, Ivan V; McCoy, Lucie S; Hansen, Helen M; Elhauge, Edward; Ojha, Juhi; Francis, Stephen S; Madsen, Nils R; Bracci, Paige M; Pico, Alexander R; Molinaro, Annette M; Tihan, Tarik; Berger, Mitchel S; Chang, Susan M; Prados, Michael D; Jenkins, Robert B; Wiemels, Joseph L; Samani, Nilesh J; Wiencke, John K; Wrensch, Margaret R

    2015-12-15

    Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82x10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48x10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83x10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.

  12. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

    PubMed Central

    Walsh, Kyle M.; Codd, Veryan; Rice, Terri; Nelson, Christopher P.; Smirnov, Ivan V.; McCoy, Lucie S.; Hansen, Helen M.; Elhauge, Edward; Ojha, Juhi; Francis, Stephen S.; Madsen, Nils R.; Bracci, Paige M.; Pico, Alexander R.; Molinaro, Annette M.; Tihan, Tarik; Berger, Mitchel S.; Chang, Susan M.; Prados, Michael D.; Jenkins, Robert B.; Wiemels, Joseph L.; Samani, Nilesh J.; Wiencke, John K.; Wrensch, Margaret R.

    2015-01-01

    Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82×10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48×10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83×10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis. PMID:26646793

  13. TERT promoter mutations and telomere length in adult malignant gliomas and recurrences

    PubMed Central

    Heidenreich, Barbara; Rachakonda, P. Sivaramakrishna; Hosen, Ismail; Volz, Florian; Hemminki, Kari; Weyerbrock, Astrid; Kumar, Rajiv

    2015-01-01

    In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5–250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03–0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 – 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome. PMID:25797251

  14. TERT promoter mutations and telomere length in adult malignant gliomas and recurrences.

    PubMed

    Heidenreich, Barbara; Rachakonda, P Sivaramakrishna; Hosen, Ismail; Volz, Florian; Hemminki, Kari; Weyerbrock, Astrid; Kumar, Rajiv

    2015-04-30

    In this report on 303 gliomas we show the highest frequency of TERT promoter mutations in gliobastomas (80%) followed by oligodendrogliomas (70%) and astrocytomas (39%). We observed positive association between TERT promoter and IDH mutations in oligodendroglial tumors (OR = 26.3; 95% CI 2.5-250.2) and inverse association in primary glioblastomas (OR = 0.13; 95% CI 0.03-0.58). Tumors with TERT promoter mutations compared to those without showed increased TERT transcription; we also showed difference in the transcription levels due to the two main mutations. Tumors with TERT promoter mutations had shorter telomeres than those without. The patients with only TERT promoter mutations showed worst survival (median survival 14.6 months) and patients with both IDH and TERT promoter mutations showed best survival (246.5 months). In patients with astrocytoma, the TERT promoter mutations only associated with poor survival (P < 0.0001); IDH mutations and 1p/19q deletions associated with increased survival (P = 0.0004). TERT promoter mutations in low grade gliomas associated with reduced progression free survival (HR 10.2; 95% CI 1.9 - 55.9). While our data affirm the role of TERT promoter mutations in glial tumors, effects on transcription and telomere length emphasise the importance of telomere biology in disease genesis and outcome.

  15. Emerging targeted therapies for glioma.

    PubMed

    Miller, Julie J; Wen, Patrick Y

    2016-12-01

    Gliomas are the most common malignant primary brain tumors in adults. Despite aggressive treatment with surgery, radiation and chemotherapy, these tumors are incurable and invariably recur. Molecular characterization of these tumors in recent years has advanced our understanding of gliomagenesis and offered an array of pathways that can be specifically targeted. Areas covered: The most commonly dysregulated signaling pathways found in gliomas will be discussed, as well as the biologic importance of these disrupted pathways and how each may contribute to tumor development. Our knowledge regarding these pathways are most relevant to Grade IV glioma/glioblastoma, but we will also discuss genomic categorization of low grade glioma. Further, drugs targeting single pathways, which have undergone early phase clinical trials will be reviewed, followed by an in depth discussion of emerging treatments on the horizon, which will include inhibitors of Epidermal Growth Factor Receptor (EGFR) and receptor tyrosine kinases, Phosphoinositide-3-Kinase (PI3K), angiogenesis, cell cycle and mutant Isocitrate Dehydrogenase (IDH) mutations. Expert opinion: Results from single agent targeted therapy trials have been modest. Lack of efficacy may stem from a combination of poor blood brain barrier penetration, the genetically heterogeneous make-up of the tumors and the emergence of resistance mechanisms. These factors can be overcome by rational drug design that capitalizes on ways to target critical pathways and limits upregulation of redundant pathways.

  16. The molecular biology of WHO grade II gliomas.

    PubMed

    Marko, Nicholas F; Weil, Robert J

    2013-02-01

    The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

  17. Occupation and adult gliomas in the San Francisco Bay Area.

    PubMed

    Krishnan, Geetha; Felini, Martha; Carozza, Susan E; Miike, Rei; Chew, Terri; Wrensch, Margaret

    2003-06-01

    The etiology of gliomas is not well understood. Some jobs might involve sustained and elevated exposures to carcinogens. This study compares lifetime job histories of 879 glioma cases diagnosed between August 1991 to April 1994 and May 1997 to August 1999 in the San Francisco Bay Area and 864 controls. Logistic analyses compared longest and ever held occupations of 1 year or more for all astrocytic and nonastrocytic cases and controls overall with adjustment for age, gender, and ethnicity and separately for men and women. Two-fold or higher or statistically significant elevated odds ratios were found overall and in men among those with longest held occupations, as firefighters, physicians, material moving equipment operators, and janitors; such elevated odds ratios were also observed for longest-held occupations among male motor vehicle operators and personal service workers and female messengers, legal/social service workers, electronic equipment operators, painters, and food processors. Odds ratios of 0.50 or less, but not statistically significant, were found for those with longest held jobs as writers/journalists, biological scientists, paper workers, mechanics, chemists, and photographers/photoprocessors. This study supports previously observed occupational associations and is one of the few studies with sufficient numbers to separately analyze occupations by gender.

  18. A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically-Modified Neural Stem Cells Expressing E.Coli Cytosine Deaminase for Treatment of Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2015-03-02

    Adult Anaplastic Astrocytoma; Recurrent Grade III Glioma; Recurrent Grade IV Glioma; Adult Anaplastic Oligodendroglioma; Adult Brain Tumor; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Adult Anaplastic Oligoastrocytoma; Recurrent High Grade Glioma

  19. Application of technical strategies for surgical management of adult intrinsic pontine gliomas: a retrospective series.

    PubMed

    Yang, Xiang; Ren, Yan-Ming; Hui, Xu-Hui; Liu, Xue-Song; Wu, Wen-Tao; Zhang, Yue-Kang

    2015-01-01

    The authors retrospectively analyzed the surgical treatment of adult intrinsic pontine gliomas in their department, and to enhance the understanding of technical strategies to treat this disease. 7 patients with intrinsic pontine gliomas were recruited for this study, between January 2011 and June 2013. All patients underwent preoperative MRI and Diffusion Tensor Imaging Fiber Tracking (DTI-FT). In addition, multimodal Intraoperative Neuromonitoring (IOM) and Intraoperative Neuronavigation were also applied during microsurgery. 7 patients with intrinsic pontine gliomas were treated at the West China Hospital of Sichuan University. Mean age, mean duration of symptoms prior to diagnosis, and mean duration of follow-up average time were 38.0 years, 2.0 months, and 23.4 months, respectively. The main presentations were progressive cranial nerve deficits and long tract signs. Total resection was achieved in 3 patients, subtotal resection in 2, and partial resection in 2. Postoperative pathological examination revealed: astrocytoma (WHO II) in 4 cases, anaplastic oligoastrocytoma (AO, WHO III) in one case, and anaplastic astrocytoma (AA, WHO III) in two cases. Postoperative radiotherapy were administered to all patients, and 4 patients with astrocytoma (WHO II) rejected chemotherapy. After 11-39 months of follow-up, patient symptoms were resolved or stable without aggravation except one patient died because of rapidly progressive glioma at 11 months after operation. MRI in other patients showed residual tumor size to be unchanged or without obviously recurrence. Combining preoperative MRI with preoperative DTI-FT, surgery can be better assessed and the operation for adult intrinsic pontine gliomas can be maximally and safely resected with the aid of Multimodal IOMs and Intraoperative Navigation during microsurgery.

  20. Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma.

    PubMed

    Carceller, Fernando; Fowkes, Lucy A; Khabra, Komel; Moreno, Lucas; Saran, Frank; Burford, Anna; Mackay, Alan; Jones, David T W; Hovestadt, Volker; Marshall, Lynley V; Vaidya, Sucheta; Mandeville, Henry; Jerome, Neil; Bridges, Leslie R; Laxton, Ross; Al-Sarraj, Safa; Pfister, Stefan M; Leach, Martin O; Pearson, Andrew D J; Jones, Chris; Koh, Dow-Mu; Zacharoulis, Stergios

    2016-08-01

    Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1-21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival. Ninety-one patients (47 HGG, 44 DIPG) were evaluable. Median age: 10 years (range, 2-20). Eleven episodes of PsP were observed in 10 patients (4 HGG, 6 DIPG). Rates of PsP: 8.5 % (HGG); 13.6 % (DIPG). Two episodes of PsP were based on clinical findings alone; nine episodes had concurrent radiological changes: increased size of lesions (n = 5), new focal enhancement (n = 4). Temozolomide, MGMT methylation or H3F3A mutations were not found to be associated with increased occurrence of PsP. For HGG, 1-year progression-free survival (PFS) was 41.9 % no-PsP versus 100 % PsP (p = 0.041); differences in 1-year overall survival (OS) were not significant. For DIPG, differences in 1-year PFS and OS were not statistically significant. Hazard ratio (95 %CI) of PsP for OS was 0.551 (0.168-1.803; p = 0.325) in HGG; and 0.308 (0.107-0.882; p = 0.028) in DIPG. PsP occurred in both pediatric HGG and DIPG patients at a comparable rate to adult HGG. PsP was associated with improved 1-yr PFS in HGG patients. PsP had a protective effect upon OS in DIPG patients.

  1. Morbidity profile following aggressive resection of parietal lobe gliomas.

    PubMed

    Sanai, Nader; Martino, Juan; Berger, Mitchel S

    2012-06-01

    The impact of parietal lobe gliomas is typically studied in the context of parietal lobe syndromes. However, critical language pathways traverse the parietal lobe and are susceptible during tumor resection. The authors of this study reviewed their experience with parietal gliomas to characterize the impact of resection and the morbidity associated with language. The study population included adults who had undergone resection of parietal gliomas of all grades. Tumor location was identified according to a proposed classification system for parietal region gliomas. Low- and high-grade tumors were volumetrically analyzed using FLAIR and T1-weighted contrast-enhanced MR imaging. One hundred nineteen patients with parietal gliomas were identified--34 with low-grade gliomas and 85 with high-grade gliomas. The median patient age was 45 years, and most patients (53) presented with seizures, whereas only 4 patients had an appreciable parietal lobe syndrome. The median preoperative tumor volume was 31.3 cm(3), the median extent of resection was 96%, and the median postoperative tumor volume was 0.9 cm(3). Surprisingly, the most common early postoperative neurological deficit was dysphasia (16 patients), not weakness (12 patients), sensory deficits (14 patients), or parietal lobe syndrome (10 patients). A proposed parietal glioma classification system, based on surgical anatomy, was predictive of language deficits. This is the largest reported experience with parietal lobe gliomas. The findings suggested that parietal language pathways are compromised at a surprisingly high rate. The proposed parietal glioma classification system is predictive of postoperative morbidity associated with language and can assist with preoperative planning. Taken together, these data emphasize the value of identifying language pathways when operating within the parietal lobe.

  2. Co-expression modules of NF1, PTEN and sprouty enable distinction of adult diffuse gliomas according to pathway activities of receptor tyrosine kinases

    PubMed Central

    Xue, Yang; Wu, Chenxing; Yao, Kun; Zhang, Chuanbao; Jin, Qiang; Huang, Rong; Li, Jiuyi; Sun, Yingyu; Su, Xiaodong; Jiang, Tao; Fan, Xiaolong

    2016-01-01

    Inter-individual variability causing elevated signaling of receptor tyrosine kinases (RTK) may have hampered the efficacy of targeted therapies. We developed a molecular signature for clustering adult diffuse gliomas based on the extent of RTK pathway activities. Glioma gene modules co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) were identified, their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV from five independent data sets into two subtypes with distinct activities of RAS-RAF-MEK-MAPK cascade and PI3K-AKT pathway (named RMPAhigh and RMPAlow subtypes) in a morphology-independent manner. The RMPAhigh gliomas were associated with poor prognosis compared to the RMPAlow gliomas. The RMPAhigh and RMPAlow glioma subtypes harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPAhigh gliomas were enriched in immature vessel cells and tumor associated macrophages, and both cell types expressed high levels of pro-angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. In gliomas with major genomic lesions unrelated to RTK pathway, high RMPA signature was associated with short survival. Thus, the RMPA signatures capture RTK activities in both glioma cells and glioma microenvironment, and RTK signaling in the glioma microenvironment contributes to glioma progression. PMID:27385209

  3. SOX2 immunity and tissue resident memory in children and young adults with glioma.

    PubMed

    Vasquez, Juan C; Huttner, Anita; Zhang, Lin; Marks, Asher; Chan, Amy; Baehring, Joachim M; Kahle, Kristopher T; Dhodapkar, Kavita M

    2017-08-01

    Therapies targeting immune checkpoints are effective in tumors with a high mutation burden that express multiple neo-antigens. However, glial tumors including those seen in children carry fewer mutations and there is an unmet need to identify new antigenic targets of anti-tumor immunity. SOX2 is an embryonal stem cell antigen implicated in the biology of glioma initiating cells. Expression of SOX2 by pediatric glial tumors and the capacity of the immune system in these patients to recognize SOX2 has not been previously studied. We examined the expression of SOX2 on archived paraffin-embedded tissue from pediatric glial tumors. The presence of T-cell immunity to SOX2 was examined in both blood and tumor-infiltrating T-cells in children and young adults with glioma. The nature of tumor-infiltrating immune cells was analyzed with a 37-marker panel using single-cell mass cytometry. SOX2 is expressed by tumor cells but not surrounding normal tissue in pediatric gliomas of all grades. T-cells against this antigen can be detected in blood and tumor tissue in glioma patients. Glial tumors are enriched for CD8/CD4 T-cells with tissue resident memory (TRM; CD45RO(+), CD69(+), CCR7(-)) phenotype, which co-express multiple inhibitory checkpoints including PD-1, PD-L1 and TIGIT. Tumors also contain natural killer cells with reduced expression of lytic granzyme. Our data demonstrate immunogenicity of SOX2, which is specifically overexpressed on pediatric glial tumor cells. Harnessing tumor immunity in glioma will likely require the combined targeting of multiple inhibitory checkpoints.

  4. Optic glioma

    MedlinePlus

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  5. Occupation and the risk of adult glioma in the United States.

    PubMed

    De Roos, A J; Stewart, P A; Linet, M S; Heineman, E F; Dosemeci, M; Wilcosky, T; Shapiro, W R; Selker, R G; Fine, H A; Black, P M; Inskip, P D

    2003-03-01

    Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. This is our first analysis of occupation and will guide future exposure-specific assessments.

  6. [Therapeutic strategies and prospects of gliomas].

    PubMed

    Taillibert, Sophie; Pedretti, Marta; Sanson, Marc

    2004-10-23

    The prognosis and the treatment of gliomas depend on age, performance status and histological grade. Symptomatic treatment relies on steroids against cerebral edema, anti-epileptic drugs for seizures and perioperatively, prevention of thrombo-embolism and digestive complications, physiotherapy. Specific therapies include surgery, radiotherapy and chemotherapy. Surgery is necessary for histological diagnosis. In low grade gliomas, it has a significant impact in terms of survival. In malignant gliomas, surgery provides symptomic relief without clearly improving survival. Radiation therapy has been shown to improve survival in malignant glioma, but not in asymptomatic low grade tumors. Chemotherapy has a modest efficacy in glioblastomas, whereas oligodendrogliomas with 1p 19q deletion are chemosensitive tumors.

  7. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma.

    PubMed

    Pace, Andrea; Dirven, Linda; Koekkoek, Johan A F; Golla, Heidrun; Fleming, Jane; Rudà, Roberta; Marosi, Christine; Le Rhun, Emilie; Grant, Robin; Oliver, Kathy; Oberg, Ingela; Bulbeck, Helen J; Rooney, Alasdair G; Henriksson, Roger; Pasman, H Roeline W; Oberndorfer, Stefan; Weller, Michael; Taphoorn, Martin J B

    2017-06-01

    Patients with glioma present with complex palliative care needs throughout their disease trajectory. The life-limiting nature of gliomas and the presence of specific symptoms related to neurological deterioration necessitate an appropriate and early palliative care approach. The multidisciplinary palliative care task force of the European Association of Neuro-Oncology did a systematic review of the available scientific literature to formulate the best possible evidence-based recommendations for the palliative care of adult patients with glioma, with the aim to reduce symptom burden and improve the quality of life of patients and their caregivers, particularly in the end-of-life phase. When recommendations could not be made because of the scarcity of evidence, the task force either used evidence from studies of patients with systemic cancer or formulated expert opinion. Areas of palliative care that currently lack evidence and thus deserve attention for further research are fatigue, disorders of behaviour and mood, interventions for the needs of caregivers, and timing of advance care planning. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The relationship between sagittal spinopelvic parameters and the degree of lumbar intervertebral disc degeneration in young adult patients with low-grade spondylolytic spondylolisthesis.

    PubMed

    Oh, Y-M; Eun, J-P

    2013-09-01

    We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration. There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration.

  9. The combination of novel targeted molecular agents and radiation in the treatment of pediatric gliomas.

    PubMed

    Dasgupta, Tina; Haas-Kogan, Daphne A

    2013-01-01

    Brain tumors are the most common solid pediatric malignancy. For high-grade, recurrent, or refractory pediatric brain tumors, radiation therapy (XRT) is an integral treatment modality. In the era of personalized cancer therapy, molecularly targeted agents have been designed to inhibit pathways critical to tumorigenesis. Our evolving knowledge of genetic aberrations in pediatric gliomas is being exploited with the use of specific targeted inhibitors. These agents are additionally being combined with XRT to increase the efficacy and duration of local control. In this review, we discuss novel agents targeting three different pathways in gliomas, and their potential combination with XRT. BRAF is a serine/threonine kinase in the RAS/RAF/MAPK kinase pathway, which is integral to cellular division, survival, and metabolism. Two-thirds of pilocytic astrocytomas, a low-grade pediatric glioma, contain a translocation within the BRAF gene called KIAA1549:BRAF that causes an overactivation of the MEK/MAPK signaling cascade. In vitro and in vivo data support the use of MEK or mammalian target of rapamycin (mTOR) inhibitors in low-grade gliomas expressing this translocation. Additionally, 15-20% of high-grade pediatric gliomas express BRAF V600E, an activating mutation of the BRAF gene. Pre-clinical in vivo and in vitro data in BRAF V600E gliomas demonstrate dramatic cooperation between XRT and small molecule inhibitors of BRAF V600E. Another major signaling cascade that plays a role in pediatric glioma pathogenesis is the PI3-kinase (PI3K)/mTOR pathway, known to be upregulated in the majority of high- and low-grade pediatric gliomas. Dual PI3K/mTOR inhibitors are in clinical trials for adult high-grade gliomas and are poised to enter studies of pediatric tumors. Finally, many brain tumors express potent stimulators of angiogenesis that render them refractory to treatment. An analog of thalidomide, CC-5103 increases the secretion of critical cytokines of the tumor

  10. Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma.

    PubMed

    Agnihotri, Sameer; Aldape, Kenneth D; Zadeh, Gelareh

    2014-12-01

    Diffuse gliomas and secondary glioblastomas (GBMs) that develop from low-grade gliomas are a common and incurable class of brain tumor. Mutations in the metabolic enzyme glioblastomas (IDH1) represent a distinguishing feature of low-grade gliomas and secondary GBMs. IDH1 mutations are one of the most common and earliest detectable genetic alterations in low-grade diffuse gliomas, and evidence supports this mutation as a driver of gliomagenesis. Here, the authors highlight the biological consequences of IDH1 mutations in gliomas, the clinical and therapeutic/diagnostic implications, and the molecular subtypes of these tumors. They also explore, in brief, the non-IDH1-mutated gliomas, including primary GBMs, and the molecular subtypes and drivers of these tumors. A fundamental understanding of the diversity of GBMs and lower-grade gliomas will ultimately allow for more effective treatments and predictors of survival.

  11. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas

    PubMed Central

    Healy, Patrick; Reitman, Zachary J.; Lipp, Eric; Rasheed, B. Ahmed; Yang, Rui; Diplas, Bill H.; Wang, Zhaohui; Greer, Paula K.; Zhu, Huishan; Wang, Catherine Y.; Carpenter, Austin B.; Friedman, Henry; Friedman, Allan H.; Keir, Stephen T.; He, Jie; He, Yiping; McLendon, Roger E.; Herndon II, James E.; Yan, Hai; Bigner, Darell D.

    2014-01-01

    Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival. PMID:24722048

  12. Carboxyl terminus of Hsp70-interacting protein (CHIP) contributes to human glioma oncogenesis.

    PubMed

    Xu, Tao; Zhou, Quan; Zhou, Jingxu; Huang, Yan; Yan, Yong; Li, Weiqing; Wang, Chunlin; Hu, Guohan; Lu, Yicheng; Chen, Juxiang

    2011-05-01

    Malignant glioma is the most common adult primary brain tumor, and the mechanism of its oncogenesis is poorly understood. Growing evidence has shown that E3 ubiquitin ligases can promote tumorgenesis of glioma. CHIP is an E3 ubiquitin ligase that can induce ubiquitylation and degradation of many tumor-related proteins, and it has been reported to act as an upstream regulator in breast cancer; however, its role in human gliomas has not been evaluated yet. In this study, the expression of CHIP in glioma tissues was studied using immunohistochemistry. CHIP expression in glioma cells was studied by real-time RT-PCR, western blot and double immunofluorescence staining. The role of CHIP in glioma oncogenesis was investigated by lentivirus-mediated RNA interference (RNAi) and overexpression in vitro and in vivo. We showed CHIP expression in glioma samples was related to tumor grades, with stronger staining in high-grade gliomas than in low-grade gliomas. Knocking down of CHIP suppressed proliferation, colony formation of U251 and U87 glioma cells, while overexpression of CHIP resulted in enhanced proliferation and colony formation in vitro. In a nude mouse xenograft model, intratumoral injection of CHIP RNAi lentivirus significantly delayed tumor growth. In contrast, overexpression of CHIP resulted in enhanced tumor growth in vivo. After CHIP RNAi, both survivin mRNA and protein were decreased, while CHIP overexpression induced increased mRNA and protein levels of survivin. This is the first study demonstrating CHIP contributes to oncogenesis of glioma. © 2011 Japanese Cancer Association.

  13. Sunitinib in Treating Patients With Recurrent Malignant Gliomas

    ClinicalTrials.gov

    2016-01-29

    Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma

  14. Supratotal resection of diffuse gliomas - an overview of its multifaceted implications.

    PubMed

    Yordanova, Y N; Duffau, H

    2017-02-06

    Successful management of diffuse low-grade and high-grade gliomas in adults is a challenge for neuro-oncologists. Indeed, due to their highly infiltrative feature, these diseases remain incurable despite therapeutic advances. Nevertheless, the elaboration of individualized therapeutic strategies has led to an improvement of both overall survival and quality of life. In particular, the impact of surgical resection on diffuse glioma survival has been extensively demonstrated. However, this impact is significant only when the resection is total (i.e., complete removal of the T2-hyperintensity in diffuse low-grade gliomas, or complete removal of the enhancement in high-grade gliomas), or at least subtotal. Interestingly, biopsy samples within and beyond the abnormalities, defined by magnetic resonance imaging, have shown that the actual spatial extent of gliomas was underestimated by this conventional imaging modality, since glioma cells were present outside the signal abnormalities. Thus, it was suggested that the removal of a margin around the tumor visible on magnetic resonance imaging, i.e. "supratotal resection", might improve the outcomes in diffuse gliomas. To achieve this type of supramaximal resection, while preserving the quality of life, a new concept is to switch from an image-guided surgery to a functional-guided surgery, i.e. to pursue the resection up to the eloquent neural networks using intraoperative direct electrical stimulation mapping in awake patients. The aim of this article was to review the recent data about supratotal resection, including both oncological and functional results. Favorable outcomes have recently opened the door to the principle of "preventive surgery" in incidentally discovered gliomas, and to the proposal of a medical screening.

  15. Low-grade astrocytomas of childhood.

    PubMed

    Rekate, H L; Rakfal, S M

    1991-05-01

    Low-grade astrocytomas are the single most common form of pediatric brain tumor, representing 28% of the total. Prolonged survival and even cures can be expected in a substantial proportion of patients who present with these tumors. For a variety of reasons, the overall oncologic management of children with low-grade astrocytomas is extremely controversial. This article analyzes the available information related to the management of various forms of low-grade astrocytoma in childhood while awaiting the performance of a long-term national cooperative study on the natural history and management of this common pediatric brain tumor.

  16. KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.

    PubMed

    Badiali, Manuela; Gleize, Vincent; Paris, Sophie; Moi, Loredana; Elhouadani, Selma; Arcella, Antonietta; Morace, Roberta; Antonelli, Manila; Buttarelli, Francesca Romana; Figarella-Branger, Dominique; Kim, Young-Ho; Ohgaki, Hiroko; Mokhtari, Karima; Sanson, Marc; Giangaspero, Felice

    2012-11-01

    KIAA1549-BRAF fusion gene and isocitrate dehydrogenase (IDH) mutations are considered two mutually exclusive genetic events in pilocytic astrocytomas and diffuse gliomas, respectively. We investigated the presence of the KIAA1549-BRAF fusion gene in conjunction with IDH mutations and 1p/19q loss in 185 adult diffuse gliomas. Moreover BRAF(v600E) mutation was also screened. The KIAA1549-BRAF fusion gene was evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and sequencing. We found IDH mutations in 125 out 175 cases (71.4%). There were KIAA1549-BRAF fusion gene in 17 out of 180 (9.4%) cases and BRAF(v600E) in 2 out of 133 (1.5%) cases. In 11 of these 17 cases, both IDH mutations and the KIAA1549-BRAF fusion were present, as independent molecular events. Moreover, 6 of 17 cases showed co-presence of 1p/19q loss, IDH mutations and KIAA1549-BRAF fusion. Among the 17 cases with KIAA1549-BRAF fusion gene 15 (88.2%) were oligodendroglial neoplasms. Similarly, the two cases with BRAF(v600E) mutation were both oligodendroglioma and one had IDH mutations and 1p/19q co-deletion. Our results suggest that in a small fraction of diffuse gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E) mutation may be responsible for deregulation of the Ras-RAF-ERK signaling pathway. Such alterations are more frequent in oligodendroglial neoplasm and may be co-present with IDH mutations and 1p/19q loss.

  17. Seizure prognosis of patients with low-grade tumors.

    PubMed

    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

    2012-09-01

    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  18. Histologic classification of gliomas.

    PubMed

    Perry, Arie; Wesseling, Pieter

    2016-01-01

    Gliomas form a heterogeneous group of tumors of the central nervous system (CNS) and are traditionally classified based on histologic type and malignancy grade. Most gliomas, the diffuse gliomas, show extensive infiltration in the CNS parenchyma. Diffuse gliomas can be further typed as astrocytic, oligodendroglial, or rare mixed oligodendroglial-astrocytic of World Health Organization (WHO) grade II (low grade), III (anaplastic), or IV (glioblastoma). Other gliomas generally have a more circumscribed growth pattern, with pilocytic astrocytomas (WHO grade I) and ependymal tumors (WHO grade I, II, or III) as the most frequent representatives. This chapter provides an overview of the histology of all glial neoplasms listed in the WHO 2016 classification, including the less frequent "nondiffuse" gliomas and mixed neuronal-glial tumors. For multiple decades the histologic diagnosis of these tumors formed a useful basis for assessment of prognosis and therapeutic management. However, it is now fully clear that information on the molecular underpinnings often allows for a more robust classification of (glial) neoplasms. Indeed, in the WHO 2016 classification, histologic and molecular findings are integrated in the definition of several gliomas. As such, this chapter and Chapter 6 are highly interrelated and neither should be considered in isolation.

  19. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

    PubMed Central

    2015-01-01

    BACKGROUND Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. METHODS We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. RESULTS Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. CONCLUSIONS The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q

  20. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas.

    PubMed

    Brat, Daniel J; Verhaak, Roel G W; Aldape, Kenneth D; Yung, W K Alfred; Salama, Sofie R; Cooper, Lee A D; Rheinbay, Esther; Miller, C Ryan; Vitucci, Mark; Morozova, Olena; Robertson, A Gordon; Noushmehr, Houtan; Laird, Peter W; Cherniack, Andrew D; Akbani, Rehan; Huse, Jason T; Ciriello, Giovanni; Poisson, Laila M; Barnholtz-Sloan, Jill S; Berger, Mitchel S; Brennan, Cameron; Colen, Rivka R; Colman, Howard; Flanders, Adam E; Giannini, Caterina; Grifford, Mia; Iavarone, Antonio; Jain, Rajan; Joseph, Isaac; Kim, Jaegil; Kasaian, Katayoon; Mikkelsen, Tom; Murray, Bradley A; O'Neill, Brian Patrick; Pachter, Lior; Parsons, Donald W; Sougnez, Carrie; Sulman, Erik P; Vandenberg, Scott R; Van Meir, Erwin G; von Deimling, Andreas; Zhang, Hailei; Crain, Daniel; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron; Bowen, Jay; Dicostanzo, Katie; Gastier-Foster, Julie; Leraas, Kristen M; Lichtenberg, Tara M; Pierson, Christopher R; Ramirez, Nilsa C; Taylor, Cynthia; Weaver, Stephanie; Wise, Lisa; Zmuda, Erik; Davidsen, Tanja; Demchok, John A; Eley, Greg; Ferguson, Martin L; Hutter, Carolyn M; Mills Shaw, Kenna R; Ozenberger, Bradley A; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Jensen, Mark A; Liu, Jia; Pihl, Todd; Raman, Rohini; Wan, Yunhu; Wu, Ye; Ally, Adrian; Auman, J Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B; Beroukhim, Rameen; Bootwalla, Moiz S; Bowlby, Reanne; Bristow, Christopher A; Brooks, Denise; Butterfield, Yaron; Carlsen, Rebecca; Carter, Scott; Chin, Lynda; Chu, Andy; Chuah, Eric; Cibulskis, Kristian; Clarke, Amanda; Coetzee, Simon G; Dhalla, Noreen; Fennell, Tim; Fisher, Sheila; Gabriel, Stacey; Getz, Gad; Gibbs, Richard; Guin, Ranabir; Hadjipanayis, Angela; Hayes, D Neil; Hinoue, Toshinori; Hoadley, Katherine; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven; Jones, Corbin D; Kucherlapati, Raju; Lai, Phillip H; Lander, Eric; Lee, Semin; Lichtenstein, Lee; Ma, Yussanne; Maglinte, Dennis T; Mahadeshwar, Harshad S; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew L; Mieczkowski, Piotr A; Moore, Richard A; Mose, Lisle E; Mungall, Andrew J; Pantazi, Angeliki; Parfenov, Michael; Park, Peter J; Parker, Joel S; Perou, Charles M; Protopopov, Alexei; Ren, Xiaojia; Roach, Jeffrey; Sabedot, Thaís S; Schein, Jacqueline; Schumacher, Steven E; Seidman, Jonathan G; Seth, Sahil; Shen, Hui; Simons, Janae V; Sipahimalani, Payal; Soloway, Matthew G; Song, Xingzhi; Sun, Huandong; Tabak, Barbara; Tam, Angela; Tan, Donghui; Tang, Jiabin; Thiessen, Nina; Triche, Timothy; Van Den Berg, David J; Veluvolu, Umadevi; Waring, Scot; Weisenberger, Daniel J; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Xu, Andrew W; Yang, Lixing; Zack, Travis I; Zhang, Jianhua; Aksoy, B Arman; Arachchi, Harindra; Benz, Chris; Bernard, Brady; Carlin, Daniel; Cho, Juok; DiCara, Daniel; Frazer, Scott; Fuller, Gregory N; Gao, JianJiong; Gehlenborg, Nils; Haussler, David; Heiman, David I; Iype, Lisa; Jacobsen, Anders; Ju, Zhenlin; Katzman, Sol; Kim, Hoon; Knijnenburg, Theo; Kreisberg, Richard Bailey; Lawrence, Michael S; Lee, William; Leinonen, Kalle; Lin, Pei; Ling, Shiyun; Liu, Wenbin; Liu, Yingchun; Liu, Yuexin; Lu, Yiling; Mills, Gordon; Ng, Sam; Noble, Michael S; Paull, Evan; Rao, Arvind; Reynolds, Sheila; Saksena, Gordon; Sanborn, Zack; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Shen, Ronglai; Shmulevich, Ilya; Sinha, Rileen; Stuart, Josh; Sumer, S Onur; Sun, Yichao; Tasman, Natalie; Taylor, Barry S; Voet, Doug; Weinhold, Nils; Weinstein, John N; Yang, Da; Yoshihara, Kosuke; Zheng, Siyuan; Zhang, Wei; Zou, Lihua; Abel, Ty; Sadeghi, Sara; Cohen, Mark L; Eschbacher, Jenny; Hattab, Eyas M; Raghunathan, Aditya; Schniederjan, Matthew J; Aziz, Dina; Barnett, Gene; Barrett, Wendi; Bigner, Darell D; Boice, Lori; Brewer, Cathy; Calatozzolo, Chiara; Campos, Benito; Carlotti, Carlos Gilberto; Chan, Timothy A; Cuppini, Lucia; Curley, Erin; Cuzzubbo, Stefania; Devine, Karen; DiMeco, Francesco; Duell, Rebecca; Elder, J Bradley; Fehrenbach, Ashley; Finocchiaro, Gaetano; Friedman, William; Fulop, Jordonna; Gardner, Johanna; Hermes, Beth; Herold-Mende, Christel; Jungk, Christine; Kendler, Ady; Lehman, Norman L; Lipp, Eric; Liu, Ouida; Mandt, Randy; McGraw, Mary; Mclendon, Roger; McPherson, Christopher; Neder, Luciano; Nguyen, Phuong; Noss, Ardene; Nunziata, Raffaele; Ostrom, Quinn T; Palmer, Cheryl; Perin, Alessandro; Pollo, Bianca; Potapov, Alexander; Potapova, Olga; Rathmell, W Kimryn; Rotin, Daniil; Scarpace, Lisa; Schilero, Cathy; Senecal, Kelly; Shimmel, Kristen; Shurkhay, Vsevolod; Sifri, Suzanne; Singh, Rosy; Sloan, Andrew E; Smolenski, Kathy; Staugaitis, Susan M; Steele, Ruth; Thorne, Leigh; Tirapelli, Daniela P C; Unterberg, Andreas; Vallurupalli, Mahitha; Wang, Yun; Warnick, Ronald; Williams, Felicia; Wolinsky, Yingli; Bell, Sue; Rosenberg, Mara; Stewart, Chip; Huang, Franklin; Grimsby, Jonna L; Radenbaugh, Amie J; Zhang, Jianan

    2015-06-25

    Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas. We performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes. Unsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma. The integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most

  1. Radiotherapy for brainstem gliomas in children and adults: A single-institution experience and literature review.

    PubMed

    Yoshida, Kenji; Sulaiman, Nor Shazrina; Miyawaki, Daisuke; Ejima, Yasuo; Nishimura, Hideki; Ishihara, Takeaki; Matsuo, Yoshiro; Nishikawa, Ryo; Sasayama, Takashi; Hayakawa, Akira; Kohmura, Eiji; Sasaki, Ryohei

    2017-04-01

    To evaluate the treatment results of radiotherapy (RT) in children and adults with brainstem gliomas (BSGs) and review the previous literature. Thirty patients (14 children, 16 adults) with BSG treated using RT were retrospectively evaluated. The median ages of the children and adults were 8 years (range: 2-16 years) and 49 years (range: 19-75 years), respectively. A histological diagnosis was obtained in 11 patients. The median total radiation dose was 56 Gy (range: 50-70 Gy) with a single fraction size of 1.8-2.0 Gy. Temozolomide was administered concurrently with RT in 14 patients. Tumor progression after RT occurred in 26 patients (14 children and 12 adults). Four adults survived without tumor progression. The median survival times for children and adults were 8.5 and 39 months, respectively. The 1-, 2- and 3-year overall survival rates for children/adults were 29%/75%, 14%/68% and 0%/53%, respectively (P = 0.001), and the 1-, 2- and 3-year progression-free survival rates for children/adults were 14%/69%, 0%/49% and 0%/35%, respectively (P < 0.001). Grade 3 or higher acute and late toxicities did not occur. In this study, the prognosis of children with BSGs was considerably poorer than that of adults, and our results are consistent with those of previous studies. Efforts should be made to improve the survival outcomes of patients with BSGs, especially children. © 2016 The Authors. Asia-Pacific Journal of Clinical Oncology Published by John Wiley & Sons Australia, Ltd.

  2. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  3. Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT.

    PubMed

    Pekmezci, Melike; Rice, Terri; Molinaro, Annette M; Walsh, Kyle M; Decker, Paul A; Hansen, Helen; Sicotte, Hugues; Kollmeyer, Thomas M; McCoy, Lucie S; Sarkar, Gobinda; Perry, Arie; Giannini, Caterina; Tihan, Tarik; Berger, Mitchel S; Wiemels, Joseph L; Bracci, Paige M; Eckel-Passow, Jeanette E; Lachance, Daniel H; Clarke, Jennifer; Taylor, Jennie W; Luks, Tracy; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2017-03-02

    The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in

  4. Adult diffuse gliomas produce mRNA transcripts encoding EGFR isoforms lacking a tyrosine kinase domain

    PubMed Central

    GUILLAUDEAU, ANGÉLIQUE; DURAND, KARINE; RABINOVITCH-CHABLE, HÉLÈNE; POMMEPUY, ISABELLE; MESTUROUX, LAURA; ROBERT, SANDRINE; CHAUNAVEL, ALAIN; MOREAU, JEAN-JACQUES; LABROUSSE, FRANÇOIS

    2012-01-01

    The epidermal growth factor receptor (EGFR) gene encodes four alternatively spliced mRNA, variants 1, 2, 3 and 4, respectively, encoding the whole isoform a (EGFR) and truncated isoforms b, c and d, all of which lack the receptor’s intracellular domain. In addition, a mutant EGFRvIII differs from isoform a in a truncated extracellular domain. The expression pattern of these isoforms is unknown in adult diffuse gliomas. Thus, we investigated in 47 cases: i) EGFR protein expression by immunohistochemistry using an extracellular domain-recognizing antibody (Ext-Ab) and an intracellular domain specific one (Int-Ab), ii) mRNA expression of EGFRv1, -v2, -v3, -v4 and -vIII by RT-PCR and iii) EGFR amplification by fluorescent in situ hybridization. The relation of these data with histological criteria and patient outcome was studied. The immunostaining was stronger with the Ext-Ab than with the Int-Ab. EGFRv1, -v2, -v3 and -v4 mRNA expression were highly correlated. They were expressed in all tumors, with highest levels in glioblastomas. EGFRv1 strong levels and the presence of vIII mRNAs were more closely associated with Int-Ab staining. EGFR gene amplification concerned only glioblastomas and was associated with the presence of EGFRvIII and high levels of EGFRv2, -v3 and -v4 transcripts. A pejorative outcome was associated with: histology (glioblastomas), EGFR amplification, strong Int-Ab labeling and high levels of variant mRNAs. Our results indicated that the full-length EGFR and mutant EGFRvIII are not the sole EGFR isoform expressed in diffuse gliomas. This could explain discordant immunohistochemical results reported in the literature and may have therapeutic implications. PMID:22159595

  5. Molecular signalling pathways in canine gliomas.

    PubMed

    Boudreau, C E; York, D; Higgins, R J; LeCouteur, R A; Dickinson, P J

    2017-03-01

    In this study, we determined the expression of key signalling pathway proteins TP53, MDM2, P21, AKT, PTEN, RB1, P16, MTOR and MAPK in canine gliomas using western blotting. Protein expression was defined in three canine astrocytic glioma cell lines treated with CCNU, temozolamide or CPT-11 and was further evaluated in 22 spontaneous gliomas including high and low grade astrocytomas, high grade oligodendrogliomas and mixed oligoastrocytomas. Response to chemotherapeutic agents and cell survival were similar to that reported in human glioma cell lines. Alterations in expression of key human gliomagenesis pathway proteins were common in canine glioma tumour samples and segregated between oligodendroglial and astrocytic tumour types for some pathways. Both similarities and differences in protein expression were defined for canine gliomas compared to those reported in human tumour counterparts. The findings may inform more defined assessment of specific signalling pathways for targeted therapy of canine gliomas.

  6. Better utilization of low-grade woods

    Treesearch

    Peter Koch

    1957-01-01

    The objective of this paper is threefold: to outline briefly some of the avenues of approach so far employed in utilizing low-grade wood, to comment on the economic aspects of the problem, and finally, to speculate about what developments the future might bring to the field of utilization.

  7. EEG, transmission computed tomography, and positron emission tomography with fluorodeoxyglucose /sup 18/F. Their use in adults with gliomas

    SciTech Connect

    Newmark, M.E.; Theodore, W.H.; Sato, S.; De La Paz, R.; Patronas, N.; Brooks, R.; Jabbari, B.; Di Chiro, G.

    1983-10-01

    We evaluated the relationship between findings from EEG, transmission computed tomography (CT), and positron emission tomography in 23 adults with gliomas. The cortical metabolic rate was suppressed in patients with and without focal slowing. Focal delta activity was not related to involvement of gray or white matter. Rhythmic delta activity and focal attenuation of background amplitude on EEG, however, were correlated with involvement of the thalamus.

  8. Therapeutic Targeting of Histone Modifications in Adult and Pediatric High-Grade Glioma

    PubMed Central

    Williams, Maria J.; Singleton, Will G. B.; Lowis, Stephen P.; Malik, Karim; Kurian, Kathreena M.

    2017-01-01

    Recent exciting work partly through The Cancer Genome Atlas has implicated epigenetic mechanisms including histone modifications in the development of both pediatric and adult high-grade glioma (HGG). Histone lysine methylation has emerged as an important player in regulating gene expression and chromatin function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3 variants and the subject of posttranslational histone modifications, as it can be both methylated and acetylated. In pediatric HGG, two critical single-point mutations occur in the H3F3A gene encoding the regulatory histone variant H3.3. These mutations occur at lysine (K) 27 (K27M) and glycine (G) 34 (G34R/V), both of which are involved with key regulatory posttranscriptional modifications. Therefore, these mutations effect gene expression, cell differentiation, and telomere maintenance. In recent years, alterations in histone acetylation have provided novel opportunities to explore new pharmacological targeting, with histone deacetylase (HDAC) overexpression reported in high-grade, late-stage proliferative tumors. HDAC inhibitors have shown promising therapeutic potential in many malignancies. This review focuses on the epigenetic mechanisms propagating pediatric and adult HGGs, as well as summarizing the current advances in clinical trials using HDAC inhibitors. PMID:28401060

  9. Plerixafor After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed High Grade Glioma

    ClinicalTrials.gov

    2016-11-08

    Adult Ependymoblastoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglial Tumors; Adult Pineoblastoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET)

  10. Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2017-02-20

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Tumor

  11. [Controversy on treatments for gliomas].

    PubMed

    Nomura, K

    1998-09-01

    Gliomas are representative primary malignant brain tumors, and with such tumors it is difficult to define the advanced stage. If the advanced stage indicates no curability by surgery alone, most gliomas would belong to this criterion because of their poor prognosis without any completely effective treatment. In this sense, no one could show a standard therapy to treat these unfortunate patients, for example, patients with glioblastoma, they could permit only 1 year survived even they had any applicable treatments to the lesions, these days. Treatment for low-grade gliomas has been most controversial for a long time, and no standard treatments have been determined so far. In this paper, as the treatment of low-grade gliomas it was intended to report what must be done for this patient and the present results of opinion survey for the treatment of gliomas which was done to professors of 80 institutes, from schools of medicine at all universities and medical colleges in Japan. For high-grade gliomas, some effectiveness of radiation therapy was disclosed as well as chemotherapy from recent papers. Gene therapy was also discussed briefly, its present status and future.

  12. Up-regulation of USP2a and FASN in gliomas correlates strongly with glioma grade.

    PubMed

    Tao, Bang-Bao; He, Hua; Shi, Xiu-hua; Wang, Chun-lin; Li, Wei-qing; Li, Bing; Dong, Yan; Hu, Guo-Han; Hou, Li-Jun; Luo, Chun; Chen, Ju-xiang; Chen, Huai-rui; Yu, Yu-hong; Sun, Qing-fang; Lu, Yi-Cheng

    2013-05-01

    Gliomas are the most common neoplasms in the central nervous system. The lack of efficacy of glioma therapies necessitates in-depth studies of glioma pathology, especially of the underlying molecular mechanisms that transform normal glial cells into tumor cells. Here we report that a deubiquitinating enzyme, ubiquitin-specific protease 2a (USP2a), and its substrate, fatty acid synthase (FASN), are over-expressed in glioma tissue. Using real-time quantitative polymerase chain reaction (PCR), Western blot and immunohistochemistry, we examined the expression and cellular distribution of USP2a and FASN in human glioma tissues. The expression patterns of USP2a and FASN correlated with the pathologic and clinical characteristics of the patients. Real-time PCR analysis showed that the expression levels of USP2a and its substrate FASN were higher in high-grade (World Health Organization [WHO] grades III and IV) glioma tissues than in low-grade (WHO grades I and II) glioma tissues. Western blot analysis indicated that the average optical densitometry ratio of USP2a and its substrate FASN in high-grade gliomas was higher than in low-grade gliomas. Moreover, statistical analysis of grade-classified glioma samples showed that the level of USP2a and FASN expression increased with the elevation of the WHO grade of glioma. USP2a protein expression was detected in the nucleus of glioma tissues and an increase in expression was significantly associated with the elevation of the WHO grade of glioma by immunohistochemistry. These findings expand our understanding of the molecular profiling of glioma and could shed light on new diagnostic criteria for gliomas.

  13. [Value of MDM2, CDK4 and SATB2 immunohistochemistry in histologic diagnosis of low-grade osteosarcoma].

    PubMed

    Chen, C Y; Zhang, H Z; Jiang, Z M; Zhou, J; Chen, J; Liu, L

    2016-06-08

    To investigate the value of combined application of MDM2, CDK4 and SATB2 immunohistochemistry in pathological diagnosis of low-grade osteosarcoma. Forty-seven cases of low grade osteosarcoma, including low grade central osteosarcoma (n=20) and parosteal osteosarcoma (n=27), were selected from Shanghai Jiaotong University Affiliated the Sixth People's Hospital. The clinical, radiography and histopathology were reviewed. The sensitivity and specificity of MDM2, CDK4 and SATB2 immunohistochemistry in the diagnosis of low-grade osteosarcoma were assessed along with an evaluation of their expressions in fibrous dysplasia, desmoplastic fibroma, low-grade fibrosarcoma and other fibrous tumors. Low-grade osteosarcoma had protracted clinical course, occurring mostly in elder adults and mainly involving long bones. Radiographic studies showed that low-grade central osteosarcoma had a mainly malignant lytic presentation, however about 5/18 of tumors overlapping with intermediate and benign bone diseases, while parosteal osteosarcoma was characterized by a densely sclerotic malignant appearance. Histologically, low-grade osteosarcomas were characterized by well-differentiated spindle tumor cells, various mature tumor bones and an aggressive growth pattern. The positive expression rates of MDM2 and CDK4 in low-grade osteosarcoma were 74.5% and 55.3%, respectively. Eighty-three percent of low-grade osteosarcoma expressed one or both markers. Low-grade osteosarcoma and fibrous dysplasia were both positive for SATB2, while desmoplastic fibroma, low-grade fibrosacoma and other fibrous tumors were negative for SATB2. Accurate diagnosis of low-grade osteosarcoma should be based on combination of clinical presentation, imaging and histopathology, with immunohistochemistry as a diagnostic adjunct. Positive immunostaining for CDK4 and/or MDM2 supports the diagnosis of low-grade osteosarcoma, but the negative one does not rule out such lesion. The negative expression of SATB2 is helpful

  14. Low grade metamorphism of mafic rocks

    NASA Astrophysics Data System (ADS)

    Schiffman, Peter

    1995-07-01

    Through most of this past century, metamorphic petrologists in the United States have paid their greatest attention to high grade rocks, especially those which constitute the core zones of exhumed, mountain belts. The pioneering studies of the 50's through the 80's, those which applied the principles of thermodynamics to metamorphic rocks, focused almost exclusively on high temperature systems, for which equilibrium processes could be demonstrated. By the 1980's, metamorphic petrologists had developed the methodologies for deciphering the thermal and baric histories of mountain belts through the study of high grade rocks. Of course, low grade metamorphic rocks - here defined as those which form at pressures and temperatures up to and including the greenschist facies - had been well known and described as well, initially through the efforts of Alpine and Circum-Pacific geologists who recognized that they constituted an integral and contiguous portion of mountain belts, and that they underlay large portions of accreted terranes, many of oceanic origins. But until the mid 80's, much of the effort in studying low grade rocks - for a comprehensive review of the literature to that point see Frey (1987) - had been concentrated on mudstones, volcanoclastic rocks, and associated lithologies common to continental mountain belts and arcs. In the mid 80's, results of the Deep Sea Drilling Project (DSDP) rather dramatically mitigated a shift in the study of low grade metamorphic rocks.

  15. Body mass index, physical activity, and risk of adult meningioma and glioma: A meta-analysis.

    PubMed

    Niedermaier, Tobias; Behrens, Gundula; Schmid, Daniela; Schlecht, Inga; Fischer, Beate; Leitzmann, Michael F

    2015-10-13

    Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77-1.07). Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma. © 2015 American Academy of Neurology.

  16. Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007.

    PubMed

    Dubrow, Robert; Darefsky, Amy S

    2011-07-29

    We hypothesized that race/ethnic group, sex, age, and/or calendar period variation in adult glioma incidence differs between the two broad subtypes of glioblastoma (GBM) and non-GBM. Primary GBM, which constitute 90-95% of GBM, differ from non-GBM with respect to a number of molecular characteristics, providing a molecular rationale for these two broad glioma subtypes. We utilized data from the Surveillance, Epidemiology, and End Results Program for 1992-2007, ages 30-69 years. We compared 15,088 GBM cases with 9,252 non-GBM cases. We used Poisson regression to calculate adjusted rate ratios and 95% confidence intervals. The GBM incidence rate increased proportionally with the 4th power of age, whereas the non-GBM rate increased proportionally with the square root of age. For each subtype, compared to non-Hispanic Whites, the incidence rate among Blacks, Asians/Pacific Islanders, and American Indians/Alaskan Natives was substantially lower (one-fourth to one-half for GBM; about two-fifths for non-GBM). Secondary to this primary effect, race/ethnic group variation in incidence was significantly less for non-GBM than for GBM. For each subtype, the incidence rate was higher for males than for females, with the male/female rate ratio being significantly higher for GBM (1.6) than for non-GBM (1.4). We observed significant calendar period trends of increasing incidence for GBM and decreasing incidence for non-GBM. For the two subtypes combined, we observed a 3% decrease in incidence between 1992-1995 and 2004-2007. The substantial difference in age effect between GBM and non-GBM suggests a fundamental difference in the genesis of primary GBM (the driver of GBM incidence) versus non-GBM. However, the commonalities between GBM and non-GBM with respect to race/ethnic group and sex variation, more notable than the somewhat subtle, albeit statistically significant, differences, suggest that within the context of a fundamental difference, some aspects of the complex process of

  17. Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

    ClinicalTrials.gov

    2015-05-29

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  18. Terahertz reflectometry imaging for low and high grade gliomas

    PubMed Central

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-01-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes. PMID:27782153

  19. Terahertz reflectometry imaging for low and high grade gliomas

    NASA Astrophysics Data System (ADS)

    Ji, Young Bin; Oh, Seung Jae; Kang, Seok-Gu; Heo, Jung; Kim, Sang-Hoon; Choi, Yuna; Song, Seungri; Son, Hye Young; Kim, Se Hoon; Lee, Ji Hyun; Haam, Seung Joo; Huh, Yong Min; Chang, Jong Hee; Joo, Chulmin; Suh, Jin-Suck

    2016-10-01

    Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

  20. Utilization of low grade coal. Final report

    SciTech Connect

    Wells, C.E.

    1981-12-01

    Purpose was to construct and use a pilot furnace that could utilize low-grade coal (steam coal and coal fines) in place of oil or natural gas. This pilot furnace was tested on a 66-inch Raymond H.S. Roller Mill at the No. 1 plant of the James River Limestone Co. Results indicate that the commercial use is feasible; drying costs average $0.36 per ton with coal vs $0.80 per ton on annual basis when oil fired. Results are applicable to limestone manufacturers producing dry pulverized products. (DLC)

  1. Diffusion tensor imaging suggests extrapontine extension of pediatric diffuse intrinsic pontine gliomas

    PubMed Central

    Wagner, Matthias W.; Bell, W. Robert; Kern, Jason; Bosemani, Thangamadhan; Mhlanga, Joyce; Carson, Kathryn A.; Cohen, Kenneth J.; Raabe, Eric H.; Rodriguez, Fausto; Huisman, Thierry A.G.M.; Poretti, Andrea

    2016-01-01

    Purpose To apply DTI to detect early extrapontine extension of pediatric diffuse intrinsic pontine glioma along the corticospinal tracts. Methods In children with diffuse intrinsic pontine glioma, low-grade brainstem glioma, and age-matched controls, DTI metrics were measured in the posterior limb of the internal capsule and posterior centrum semiovale. Histological examination was available in one patient. Results 6 diffuse intrinsic pontine glioma, 8 low-grade brainstem glioma, and two groups of 25 controls were included. In diffuse intrinsic pontine glioma compared to controls, fractional anisotropy was lower in the bilateral posterior limb of the internal capsule, axial diffusivity was lower in the bilateral posterior centrum semiovale and posterior limb of the internal capsule, while radial diffusivity was higher in the bilateral posterior limb of the internal capsule. No significant differences were found between low-grade brainstem glioma and controls. In diffuse intrinsic pontine glioma compared to low-grade brainstem glioma, axial diffusivity was lower in the bilateral posterior limb of the internal capsule. Histological examination in one child showed tumor cells in the posterior limb of the internal capsule. Conclusion Reduction in fractional anisotropy and axial diffusivity and increase in radial diffusivity in diffuse intrinsic pontine glioma may reflect tumor extension along the corticospinal tracts as shown by histology. DTI may detect early extrapontine tumor extension in diffuse intrinsic pontine glioma before it becomes apparent on conventional MRI sequences. PMID:26971411

  2. Prevalence and profile of cognitive impairment in adult glioma: a sensitivity analysis.

    PubMed

    Boone, Mathieu; Roussel, Martine; Chauffert, Bruno; Le Gars, Daniel; Godefroy, Olivier

    2016-08-01

    Cognitive impairment has been reported in 27-83 % of adults with World Health Organization (WHO) grade I-III glioma. However, the few studies in this field used different methods for cognitive assessment. The objective of the present study was to establish the prevalence of cognitive impairment in patients with WHO grade I-III primary brain tumors and determine the effect sizes of a comprehensive battery of tests. This study used a comprehensive neuropsychological battery to examine 27 patients. To control for false positives, prevalence was estimated from the overall neuropsychological score. Size effects were determined using Cohen's d. Cognitive impairment was observed in 51.9 % (95 % CI 33-70.7 %) of the patients; the impairment affected action speed (38.5 %), cognitive (33 %) and behavioral (21.7 %) executive functions, oral expression (29.6 %), episodic memory (29.6 %) and visuoconstructive abilities (19.2 %). The largest effect sizes (d ≥ 1.645) were observed for the Digit Symbol Substitution test, global hypoactivity, free recall, Stroop time, the Boston Naming test (BNT), the Trail Making test B (TMTB), verbal fluency and the Rey-Osterrieth Complex Figure Test. Four of these scores (global hypoactivity, the Digit Symbol Substitution test, the TMTB perseveration, and the BNT) were combined to make a shortened battery (AUC 0.872; 95 % CI 0.795-0.949). The overall neuropsychological score was the sole factor associated with the functional outcome. Our results suggest that about half of survivors with a grade I-III primary brain tumor suffer from cognitive impairment. Tests with a large effect size should be included in future large-scale studies.

  3. Local image variance of 7 Tesla SWI is a new technique for preoperative characterization of diffusely infiltrating gliomas: correlation with tumour grade and IDH1 mutational status.

    PubMed

    Grabner, Günther; Kiesel, Barbara; Wöhrer, Adelheid; Millesi, Matthias; Wurzer, Aygül; Göd, Sabine; Mallouhi, Ammar; Knosp, Engelbert; Marosi, Christine; Trattnig, Siegfried; Wolfsberger, Stefan; Preusser, Matthias; Widhalm, Georg

    2017-04-01

    To investigate the value of local image variance (LIV) as a new technique for quantification of hypointense microvascular susceptibility-weighted imaging (SWI) structures at 7 Tesla for preoperative glioma characterization. Adult patients with neuroradiologically suspected diffusely infiltrating gliomas were prospectively recruited and 7 Tesla SWI was performed in addition to standard imaging. After tumour segmentation, quantification of intratumoural SWI hypointensities was conducted by the SWI-LIV technique. Following surgery, the histopathological tumour grade and isocitrate dehydrogenase 1 (IDH1)-R132H mutational status was determined and SWI-LIV values were compared between low-grade gliomas (LGG) and high-grade gliomas (HGG), IDH1-R132H negative and positive tumours, as well as gliomas with significant and non-significant contrast-enhancement (CE) on MRI. In 30 patients, 9 LGG and 21 HGG were diagnosed. The calculation of SWI-LIV values was feasible in all tumours. Significantly higher mean SWI-LIV values were found in HGG compared to LGG (92.7 versus 30.8; p < 0.0001), IDH1-R132H negative compared to IDH1-R132H positive gliomas (109.9 versus 38.3; p < 0.0001) and tumours with significant CE compared to non-significant CE (120.1 versus 39.0; p < 0.0001). Our data indicate that 7 Tesla SWI-LIV might improve preoperative characterization of diffusely infiltrating gliomas and thus optimize patient management by quantification of hypointense microvascular structures. • 7 Tesla local image variance helps to quantify hypointense susceptibility-weighted imaging structures. • SWI-LIV is significantly increased in high-grade and IDH1-R132H negative gliomas. • SWI-LIV is a promising technique for improved preoperative glioma characterization. • Preoperative management of diffusely infiltrating gliomas will be optimized.

  4. Large retroperitoneal low-grade extraskeletal osteosarcoma

    PubMed Central

    Jaipuria, Jiten; Kumar, Ashok; Rao, Adla Satyanarayan; Kataria, Satya Pal

    2014-01-01

    Low-grade extraskeletal osteosarcoma is an extremely rare neoplasm with only nine cases reported in the literature, in which only one case involved the retroperitoneum. Tendency to dedifferentiate as well as recur with high-grade variant is known and management principles are not well defined, necessitating a continuous review of literature. We report management of the largest such retroperitoneal tumour (18.0 cm× 18.3 cm×17.8 cm) in a 38-year-old man, which was treated with surgery followed by six cycles of cisplatin (90 mg/m2 days 1 and 2) and doxorubicin (75 mg/m2 day 3), cycled every 3 weeks (with granulocyte colony stimulating factor support as necessary). The patient is disease free after 3 years of follow-up. PMID:24658529

  5. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2017-04-27

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  6. Red and processed meat consumption and risk of glioma in adults: A systematic review and meta-analysis of observational studies

    PubMed Central

    Saneei, Parvane; Willett, Walter; Esmaillzadeh, Ahmad

    2015-01-01

    Background: These findings from several observational studies, investigated the association between red meat consumption and gliomas, were inconsistent. We conducted a systematic review and meta-analysis of observational studies to summarize available date on the relation between meat intake and risk of glioma. Materials and Methods: A systematic literature search of relevant reports published until May 2014 of the PubMed/Medline, ISI Web of Knowledge, Excerpta Medica database, Ovid database, Google Scholar, and Scopus databases was conducted. From 723 articles yielded in the preliminary literature search, data from eighteen publications (14 case-control, three cohort, and one nested case-control study) on unprocessed red meat, processed meat, and/or total red meat consumption in relation to glioma in adults were included in the analysis. Quality assessment of studies was performed. Random effects model was used to conduct the meta-analysis. Results: We found a positive significant association between unprocessed red meat intake and risk of glioma (relative risk [RR] = 1.30; 95% confidence interval [CI]: 1.08-1.58) after excluding three studies with uncertain type of brain cancer. This analysis included only one cohort study which revealed no relation between unprocessed red meat intake and glioma (RR = 1.75; 95% CI: 0.35-8.77). Consumption of processed meats was not related to increased risk of glioma in population-based case-control studies (RR = 1.26; 95% CI: 1.05-1.51) and reduced risk in hospital-based case-controls (RR = 0.79; 95% CI: 0.65-0.97). No significant association was seen between processed red meat intake and risk of glioma in cohort studies (RR: 1.08; 95% CI: 0.84-1.37). Total red meat consumption was not associated with risk of adult glioma in case-control or cohort studies. Conclusion: In this meta-analysis of 18 observational studies, we found a modest positive association between unprocessed red meat intake and risk of gliomas based almost

  7. Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

    PubMed Central

    Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

    2014-01-01

    Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

  8. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1

    PubMed Central

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R.; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-01-01

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) “stem-like” cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance. PMID:27213425

  9. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.

    PubMed

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-05-19

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) "stem-like" cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  10. A Prospective Study of Height and Body Mass Index in Childhood, Birth Weight, and Risk of Adult Glioma Over 40 Years of Follow-up

    PubMed Central

    Kitahara, Cari M.; Gamborg, Michael; Rajaraman, Preetha; Sørensen, Thorkild I. A.; Baker, Jennifer L.

    2014-01-01

    Greater attained height and greater body mass index (BMI; weight (kg)/height (m)2) in young adulthood have been associated with glioma risk, but few studies have investigated the association with body size at birth or during childhood, when the brain undergoes rapid cell growth and differentiation. The Copenhagen School Health Records Register includes data on 320,425 Danish schoolchildren born between 1930 and 1989, with height and weight measurements from ages 7–13 years and parentally recorded birth weights. We prospectively evaluated associations between childhood height and BMI, birth weight, and adult glioma risk. During follow-up (1968–2010), 355 men and 253 women aged ≥18 years were diagnosed with glioma. In boys, height at each age between 7 and 13 years was positively associated with glioma risk; hazard ratios per standard-deviation score at ages 7 (approximately 5.1 cm) and 13 (approximately 7.6 cm) years were 1.17 (95% confidence interval (CI): 1.05, 1.30) and 1.21 (95% CI: 1.09, 1.35), respectively. No associations were observed for childhood height in girls or for BMI. Birth weight was positively associated with risk (per 0.5 kg: hazard ratio = 1.13, 95% CI: 1.04, 1.24). These results suggest that exposures associated with higher birth weight and, in boys, greater height during childhood may contribute to the etiology of adult glioma. PMID:25205831

  11. Low-grade oligodendroglioma of the pineal gland: a case report and review of the literature

    PubMed Central

    2010-01-01

    Background Gliomas are a very rare subtype of pineal region tumours, whereas oligodendrogliomas of the pineal region are exceedingly rare, since there have been only 3 cases of anaplastic oligodedrogliomas reported this far. Methods-Results We present a case of a low-grade oligodendroglioma arising in the pineal gland of a 37 year-old woman. The patient presented with diplopia associated with a cystic pineal region mass demonstrated on MRI. Total resection was performed and histological examination showed that the cystic wall consisted of tumour cells with a central nucleus a perinuclear halo and minimal pleomorphism. Immnunohistochemical analysis showed that these cells were diffusely positive for CD57, and negative for GFAP, CD10, CD99, cytokeratins, neurofilaments and synaptophysin. FISH analysis was performed in a small number of neoplastic cells, which were not exhausted after immunohistochemistry and did not reveal deletion of 1p and 19q chromosome arms. However, the diagnosis of a low grade oligodendroglioma of the pineal gland was assigned. Conclusion Although the spectrum of tumours arising in the pineal gland is broad, the reports of oligodendrogliomas confined to this location are exceedingly rare, and to the best of our knowledge there is no report of a low-grade oligodendroglioma. However, they should be added in the long list of tumours arising in the pineal gland. PMID:20849631

  12. Extent of surgical resection predicts seizure freedom in low-grade temporal lobe brain tumors.

    PubMed

    Englot, Dario J; Han, Seunggu J; Berger, Mitchel S; Barbaro, Nicholas M; Chang, Edward F

    2012-04-01

    Achieving seizure control in patients with low-grade temporal lobe gliomas or glioneuronal tumors remains highly underappreciated, because seizures are the most frequent presenting symptom and significantly impact patient quality-of-life. To assess how the extent of temporal lobe resection influences seizure outcome. We performed a quantitative, comprehensive systematic literature review of seizure control outcomes in 1181 patients with epilepsy across 41 studies after surgical resection of low-grade temporal lobe gliomas and glioneuronal tumors. We measured seizure-freedom rates after subtotal resection vs gross-total lesionectomy alone vs tailored resection, including gross-total lesionectomy with hippocampectomy and/or anterior temporal lobe corticectomy. Included studies were observational case series, and no randomized, controlled trials were identified. Although only 43% of patients were seizure-free after subtotal tumor resection, 79% of individuals were seizure-free after gross-total lesionectomy (OR = 5.00, 95% confidence interval [CI]: 3.33-7.14). Furthermore, tailored resection with hippocampectomy plus corticectomy conferred additional benefit over gross-total lesionectomy alone, with 87% of patients achieving seizure freedom (OR = 1.82, 95% CI: 1.23-2.70). Overall, extended resection with hippocampectomy and/or corticectomy over gross-total lesionectomy alone significantly predicted seizure freedom (OR = 1.18, 95% CI: 1.11-1.26). Age <18 years and mesial temporal location also prognosticated favorable seizure outcome. Gross-total lesionectomy of low-grade temporal lobe tumors results in significantly improved seizure control over subtotal resection. Additional tailored resection including the hippocampus and/or adjacent cortex may further improve seizure control, suggesting dual pathology may sometimes allow continued seizures after lesional excision.

  13. Dietary factors and the risk of glioma in adults: results of a case-control study in Melbourne, Australia.

    PubMed

    Giles, G G; McNeil, J J; Donnan, G; Webley, C; Staples, M P; Ireland, P D; Hurley, S F; Salzberg, M

    1994-11-01

    In a population-based case-control study of 416 incident gliomas in adults carried out in Melbourne, Australia, between 1987 and 1991, 409 age-sex-matched case-control pairs (243 male and 166 female) had adequate data available to examine associations between the dietary intake of N-nitroso compounds, N-nitroso precursors, other nutrients including N-nitroso inhibitors, and the risk of glioma. Dietary intakes were based on the reported frequency of consumption of 59 food items. Increased odds ratio (OR) were observed in males who consumed high levels of bacon, corned meats, apples, melons and oil. OR less than unity were observed in men consuming cabbage and cola drinks, and in women who consumed wholegrain bread, pasta, corned meat, bananas, cauliflower, brocoli, cola drinks and nuts. Generally, N-nitroso associations were greater in men and micronutrient associations were greater in women. Elevated OR in men, but not women, were associated with the intake of N-nitroso dimethylamine (NDMA), retinol and vitamin E. The intake of nitrate (largely of vegetable origin) was protective in women but not in men. When analyzed using multiple logistic regression, the association with NDMA intake in males was not modified by dietary micronutrient intakes. In females, beta carotene alone, though not directly associated with risk, modified the effect of NDMA. On balance, this study added only limited support to the N-nitroso hypothesis of glial carcinogenesis.

  14. Expression of indoleamine 2,3-dioxygenase and correlation with pathological malignancy in gliomas.

    PubMed

    Mitsuka, Kentaro; Kawataki, Tomoyuki; Satoh, Eiji; Asahara, Takayuki; Horikoshi, Toru; Kinouchi, Hiroyuki

    2013-06-01

    : Indoleamine 2,3-dioxygenase (IDO) is a tryptophan catabolic enzyme involved in immune tolerance and tumor immune escape processes. Recently, IDO expression has been found to correlate with the prognosis of malignant tumors, but the implication of IDO in glioma progression remains unknown. : To investigate the relationship between IDO expression and histological malignancy in gliomas. : IDO expression was examined in a total of 75 surgical specimens obtained from 68 patients with glioma using immunohistochemical staining. The 75 specimens included 15 diffuse astrocytomas, 21 anaplastic astrocytomas, and 39 glioblastomas. Six of 39 glioblastomas were secondary glioblastomas, transforming from grade II or III gliomas that had been determined at the first surgery. IDO expression rate was compared in each histological grade, and patient survival was analyzed. : Expression of IDO was found in 72 of 75 gliomas at varying intensities. Stronger expression of IDO was more likely to be observed in malignant gliomas compared with low-grade gliomas. IDO expression in the 6 cases of secondary glioblastoma was stronger than in the initial low-grade glioma. Survival analysis using the Kaplan-Meier method revealed that grade IV patients with strong IDO expression had significantly worse overall survival rates (P = .04) than patients with weak IDO expression. : IDO is expressed more strongly in both primary and secondary glioblastoma tissue than low-grade glioma and may affect clinical outcome. If IDO promotes glioma cells to escape from the immune system, IDO may be a crucial therapeutic target for malignant gliomas.

  15. Radiation-induced gliomas

    PubMed Central

    Prasad, Gautam; Haas-Kogan, Daphne A.

    2013-01-01

    Radiation-induced gliomas represent a relatively rare but well-characterized entity in the neuro-oncologic literature. Extensive retrospective cohort data in pediatric populations after therapeutic intracranial radiation show a clearly increased risk in glioma incidence that is both patient age- and radiation dose/volume-dependent. Data in adults are more limited but show heightened risk in certain groups exposed to radiation. In both populations, there is no evidence linking increased risk associated with routine exposure to diagnostic radiation. At the molecular level, recent studies have found distinct genetic differences between radiation-induced gliomas and their spontaneously-occurring counterparts. Clinically, there is understandable reluctance on the part of clinicians to re-treat patients due to concern for cumulative neurotoxicity. However, available data suggest that aggressive intervention can lead to improved outcomes in patients with radiation-induced gliomas. PMID:19831840

  16. High-Grade Glioma of the Ventrolateral Medulla in an Adult: Case Presentation and Discussion of Surgical Considerations

    PubMed Central

    Spurgeon, Angela; Le, Viet; Konakondla, Sanjay; Miller, Douglas C.; Hopkins, Tamera; Litofsky, N. Scott

    2016-01-01

    Background. High-grade gliomas of the brainstem are rare in adults and are particularly rare in the anterolateral medulla. We describe an illustrative case and discuss the diagnostic and treatment issues associated with a tumor in this location, including differential diagnosis, anatomical considerations for options for surgical management, multimodality treatment, and prognosis. Case Description. A 69-year-old woman presented with a 3-week history of progressive right lower extremity weakness. She underwent an open biopsy via a far lateral approach with partial condylectomy, which revealed a glioblastoma. Concurrent temozolomide and radiation were completed; however, she elected to stop her chemotherapy after 5.5 weeks of treatment. She succumbed to her disease 11 months after diagnosis. Conclusions. Biopsy can be performed relatively safely to provide definitive diagnosis to guide treatment, but long-term prognosis is poor. PMID:27242937

  17. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

    ClinicalTrials.gov

    2016-10-19

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  18. A meta-analysis of coffee and tea consumption and the risk of glioma in adults.

    PubMed

    Malerba, Stefano; Galeone, Carlotta; Pelucchi, Claudio; Turati, Federica; Hashibe, Mia; La Vecchia, Carlo; Tavani, Alessandra

    2013-02-01

    Coffee contains many compounds, including antioxidants, which could prevent cancerogenesis, and coffee has been related with lower incidence of cancer at several sites. Tea is also rich in antioxidants, mainly polyphenols. To provide a quantitative overall estimate on the relation between coffee and tea consumption and glioma, we combined all published data, using a meta-analytic approach. In September 2012, a bibliography search was carried out in both PubMed and Embase to identify observational studies providing quantitative estimates on the issue. Pooled estimates of the relative risks (RR) and the corresponding 95 % confidence intervals (CI) were calculated using random-effects models. Six studies (four cohort and two case-control studies) were available for meta-analysis, for a total of about 2100 cases. The summary RRs and 95 % CIs of glioma for drinkers versus non/occasional drinkers were 0.96 (95 % CI: 0.81-1.13) for coffee and 0.86 (95 % CI: 0.78-0.94) for tea, with no heterogeneity between studies. When we compared the highest versus the lowest categories of consumption, the RRs were 1.01 (95 % CI: 0.83-1.22) for coffee, 0.88 (95 % CI: 0.69-1.12) for tea, and 0.75 (95 % CI: 0.54-1.05) for coffee plus tea. This meta-analysis, although based on few studies, suggests a lack of association between coffee intake and glioma risk, and a tendency, if any, to a lower risk for tea and coffee plus tea drinkers.

  19. Coffee, tea, soda, and caffeine intake in relation to risk of adult glioma in the NIH-AARP Diet and Health Study.

    PubMed

    Dubrow, Robert; Darefsky, Amy S; Freedman, Neal D; Hollenbeck, Albert R; Sinha, Rashmi

    2012-05-01

    We utilized the large, prospective NIH-AARP Diet and Health Study to further explore the hypothesis, suggested by two recent prospective cohort studies, that increased intake of coffee, tea, soda, and/or caffeine is associated with reduced adult glioma risk. At baseline in 1995-1996, dietary intake, including coffee, tea, and soda, was assessed with a food frequency questionnaire. We used Cox proportional hazards models to calculate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for glioma risk in relation to beverage intake. During follow-up of 545,771 participants through 2006, 904 participants were diagnosed with glioma. We found no trends of decreasing glioma risk with increasing intake of specific beverages or total caffeine. HR patterns for consumption of the caffeinated versus decaffeinated form of each beverage were inconsistent with a specific caffeine effect. HR patterns of reduced glioma risk for most categories of beverage intake greater than "none" prompted a post hoc analysis that revealed borderline-significant inverse associations for any versus no intake of tea (HR = 0.84; 95 % CI, 0.69-1.03), total coffee plus tea (HR = 0.70; 95 % CI, 0.48-1.03), and soda (HR = 0.82; 95 % CI, 0.67-1.01). The borderline-significant inverse associations could be explained by a threshold effect in which any beverage intake above a low level confers a beneficial effect, most likely due to beverage constituents other than caffeine. They could also be explained by non-drinkers of these beverages sharing unknown extraneous characteristics associated with increased glioma risk, or by chance.

  20. Coffee, tea, soda, and caffeine intake in relation to risk of adult glioma in the NIH-AARP Diet and Health Study

    PubMed Central

    Dubrow, Robert; Darefsky, Amy S.; Freedman, Neal D.; Hollenbeck, Albert R.; Sinha, Rashmi

    2012-01-01

    Purpose We utilized the large, prospective NIH-AARP Diet and Health Study to further explore the hypothesis, suggested by two recent prospective cohort studies, that increased intake of coffee, tea, soda, and/or caffeine is associated with reduced adult glioma risk. Methods At baseline in 1995–1996, dietary intake, including coffee, tea, and soda, was assessed with a food frequency questionnaire. We used Cox proportional hazards models to calculate adjusted hazard ratios (HR) and 95 percent confidence intervals (CI) for glioma risk in relation to beverage intake. Results During follow-up of 545,771 participants through 2006, 904 participants were diagnosed with glioma. We found no trends of decreasing glioma risk with increasing intake of specific beverages or total caffeine. HR patterns for consumption of the caffeinated versus decaffeinated form of each beverage were inconsistent with a specific caffeine effect. HR patterns of reduced glioma risk for most categories of beverage intake greater than “none” prompted a post hoc analysis that revealed borderline-significant inverse associations for any versus no intake of tea (HR = 0.84; 95% CI, 0.69–1.03), total coffee plus tea (HR = 0.70; 95% CI, 0.48–1.03), and soda (HR = 0.82; 95% CI, 0.67–1.01). Conclusions The borderline-significant inverse associations could be explained by a threshold effect in which any beverage intake above a low level confers a beneficial effect, most likely due to beverage constituents other than caffeine. They also could be explained by non-drinkers of these beverages sharing unknown extraneous characteristics associated with increased glioma risk, or by chance. PMID:22457000

  1. Genetic alterations in uncommon low-grade neuroepithelial tumors: BRAF, FGFR1, and MYB mutations occur at high frequency and align with morphology.

    PubMed

    Qaddoumi, Ibrahim; Orisme, Wilda; Wen, Ji; Santiago, Teresa; Gupta, Kirti; Dalton, James D; Tang, Bo; Haupfear, Kelly; Punchihewa, Chandanamali; Easton, John; Mulder, Heather; Boggs, Kristy; Shao, Ying; Rusch, Michael; Becksfort, Jared; Gupta, Pankaj; Wang, Shuoguo; Lee, Ryan P; Brat, Daniel; Peter Collins, V; Dahiya, Sonika; George, David; Konomos, William; Kurian, Kathreena M; McFadden, Kathryn; Serafini, Luciano Neder; Nickols, Hilary; Perry, Arie; Shurtleff, Sheila; Gajjar, Amar; Boop, Fredrick A; Klimo, Paul D; Mardis, Elaine R; Wilson, Richard K; Baker, Suzanne J; Zhang, Jinghui; Wu, Gang; Downing, James R; Tatevossian, Ruth G; Ellison, David W

    2016-06-01

    Low-grade neuroepithelial tumors (LGNTs) are diverse CNS tumors presenting in children and young adults, often with a history of epilepsy. While the genetic profiles of common LGNTs, such as the pilocytic astrocytoma and 'adult-type' diffuse gliomas, are largely established, those of uncommon LGNTs remain to be defined. In this study, we have used massively parallel sequencing and various targeted molecular genetic approaches to study alterations in 91 LGNTs, mostly from children but including young adult patients. These tumors comprise dysembryoplastic neuroepithelial tumors (DNETs; n = 22), diffuse oligodendroglial tumors (d-OTs; n = 20), diffuse astrocytomas (DAs; n = 17), angiocentric gliomas (n = 15), and gangliogliomas (n = 17). Most LGNTs (84 %) analyzed by whole-genome sequencing (WGS) were characterized by a single driver genetic alteration. Alterations of FGFR1 occurred frequently in LGNTs composed of oligodendrocyte-like cells, being present in 82 % of DNETs and 40 % of d-OTs. In contrast, a MYB-QKI fusion characterized almost all angiocentric gliomas (87 %), and MYB fusion genes were the most common genetic alteration in DAs (41 %). A BRAF:p.V600E mutation was present in 35 % of gangliogliomas and 18 % of DAs. Pathogenic alterations in FGFR1/2/3, BRAF, or MYB/MYBL1 occurred in 78 % of the series. Adult-type d-OTs with an IDH1/2 mutation occurred in four adolescents, the youngest aged 15 years at biopsy. Despite a detailed analysis, novel genetic alterations were limited to two fusion genes, EWSR1-PATZ1 and SLMAP-NTRK2, both in gangliogliomas. Alterations in BRAF, FGFR1, or MYB account for most pathogenic alterations in LGNTs, including pilocytic astrocytomas, and alignment of these genetic alterations and cytologic features across LGNTs has diagnostic implications. Additionally, therapeutic options based upon targeting the effects of these alterations are already in clinical trials.

  2. The Art of Intraoperative Glioma Identification

    PubMed Central

    Zhang, Zoe Z.; Shields, Lisa B. E.; Sun, David A.; Zhang, Yi Ping; Hunt, Matthew A.; Shields, Christopher B.

    2015-01-01

    A major dilemma in brain-tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture, which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of (1) image-based navigation, (2) intraoperative sampling, (3) electrophysiological monitoring, and (4) enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease. PMID:26284196

  3. Elevated serum complement C3 levels are related to the development of prediabetes in an adult population: the Tianjin Chronic Low-Grade Systematic Inflammation and Health Cohort Study.

    PubMed

    Bao, X; Xia, Y; Zhang, Q; Wu, H M; Du, H M; Liu, L; Wang, C J; Shi, H B; Guo, X Y; Liu, X; Li, C L; Su, Q; Meng, G; Yu, B; Sun, S M; Wang, X; Zhou, M; Jia, Q Y; Song, K; Niu, K J

    2016-04-01

    To investigate whether serum complement C3 is related to the prevalence and incidence of prediabetes in an adult population. A cross-sectional (n = 10 206) and prospective cohort study (n = 3333), with a mean (range; 95% CI) follow-up of 2.63 (1-6; 2.58-2.68) years, was conducted in people recruited from the Health Management Centre of Tianjin Medical University General Hospital in Tianjin, China. Measurement of serum C3 concentration, blood fasting glucose, oral glucose tolerance, HbA1c and other potential confounding factors was performed at baseline and each year during the follow-up. Prediabetes was defined according to the criteria of the American Diabetes Association. Adjusted logistic and Cox proportional hazards regression models were used to assess the relationships between C3 quintiles and prediabetes. The prevalence and incidence of prediabetes were 38.5% and 119 per 1000 person-years, respectively. In cross-sectional analysis, after adjustment for potential confounders, the odds ratios of prediabetes for increasing quintiles of C3 were 1.00 (reference), 1.32 (95% CI 1.14-1.53), 1.37 (95% CI 1.18-1.59), 1.75 (95% CI 1.51-2.03), 2.25 (95% CI 1.93-2.62; P for trend < 0.0001). In the cohort analysis, the multiple-adjusted hazard ratio of prediabetes in the highest quintile of baseline C3 was 1.43 (95% CI 1.15, 1.78; P for trend < 0.001), when compared with the lowest quintile. These findings indicate that elevated serum C3 levels are significantly related to an increased risk of developing prediabetes in an adult population, suggesting that C3 can be used as a biomarker in high-risk individuals to improve primary prevention of prediabetes and diabetes. © 2015 Diabetes UK.

  4. Desalination using low grade heat sources

    NASA Astrophysics Data System (ADS)

    Gude, Veera Gnaneswar

    A new, low temperature, energy-efficient and sustainable desalination system has been developed in this research. This system operates under near-vacuum conditions created by exploiting natural means of gravity and barometric pressure head. The system can be driven by low grade heat sources such as solar energy or waste heat streams. Both theoretical and experimental studies were conducted under this research to evaluate and demonstrate the feasibility of the proposed process. Theoretical studies included thermodynamic analysis and process modeling to evaluate the performance of the process using the following alternate energy sources for driving the process: solar thermal energy, solar photovoltaic/thermal energy, geothermal energy, and process waste heat emissions. Experimental studies included prototype scale demonstration of the process using grid power as well as solar photovoltaic/thermal sources. Finally, the feasibility of the process in reclaiming potable-quality water from the effluent of the city wastewater treatment plant was studied. The following results have been obtained from theoretical analysis and modeling: (1) The proposed process can produce up to 8 L/d of freshwater for 1 m2 area of solar collector and evaporation chamber respectively with a specific energy requirement of 3122 kJ for 1 kg of freshwater production. (2) Photovoltaic/thermal (PV/T) energy can produce up to 200 L/d of freshwater with a 25 m2 PV/T module which meets the electricity needs of 21 kWh/d of a typical household as well. This configuration requires a specific energy of 3122 kJ for 1 kg of freshwater production. (3) 100 kg/hr of geothermal water at 60°C as heat source can produce up to 60 L/d of freshwater with a specific energy requirement of 3078 kJ for 1 kg of freshwater production. (4) Waste heat released from an air conditioning system rated at 3.25 kW cooling, can produce up to 125 L/d of freshwater. This configuration requires an additional energy of 208 kJ/kg of

  5. Low-grade myofibroblastic sarcoma of the parapharyngeal space.

    PubMed

    Takahama, A; Nascimento, A G; Brum, M C; Vargas, P A; Lopes, M A

    2006-10-01

    Low-grade myofibroblastic sarcoma was recently described as representing malignant mesenchymal tumours that show myofibroblastic differentiation; few cases have been reported. Here, a low-grade myofibroblastic sarcoma of the parapharyngeal space is described. A 42-year-old man presented with swelling on the right side of the temporal bone. Based on histological and immunohistochemical features, the diagnosis of low-grade myofibroblastic sarcoma was established. The tumour had invaded the orbit and the brain, and therefore surgical excision was not possible. There are thought to have been no cases affecting this region reported previously in the English-language literature.

  6. Intraoperative monitoring of an aspect of executive functions: administration of the Stroop test in 9 adult patients during awake surgery for resection of frontal glioma.

    PubMed

    Wager, Michel; Du Boisgueheneuc, Foucaud; Pluchon, Claudette; Bouyer, Coline; Stal, Veronique; Bataille, Benoit; Guillevin, Carole Menuel; Gil, Roger

    2013-06-01

    Awake brain surgery allows extensive intraoperative monitoring of not only motor and sensory functions and language but also executive functions. To administer the Stroop test intraoperatively to avoid dramatic side effects such as akinetic mutism and to monitor executive functions in an attempt to optimize the benefit/risk balance of surgery. A series of 9 adult patients with frontal glioma were operated on for gross tumor resection under local anesthesia. All procedures involved the anterior cingulate cortex (ACC). Three types of response to the Stroop test were observed: 3 patients had a Stroop effect only for stimulation of the contralateral ACC; 3 patients had a Stroop effect for stimulation of the ipsilateral ACC; and 3 patients had no Stroop effect. Preoperative and postoperative neuropsychological and surgical results are presented and discussed. Stimulation sites eliciting a Stroop effect are compared with published image-based data, and insight provided by these surgical data regarding ACC function and plasticity is discussed. No operative complication related to intraoperative administration of the Stroop test was observed. Administration of the Stroop test during resection of gliomas involving the ACC in adult patients is an option for intraoperative monitoring of executive functions during awake surgery. Globally, these results suggest functional compensation, mediated by plasticity mechanisms, by contralateral homologous regions of the ACC in adult patients with frontal glioma.

  7. Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

    ClinicalTrials.gov

    2014-07-09

    Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Grade III Meningioma; Adult Mixed Glioma; Recurrent Adult Brain Tumor

  8. Functionally Active Gap Junctions between Connexin 43-Positive Mesenchymal Stem Cells and Glioma Cells.

    PubMed

    Gabashvili, A N; Baklaushev, V P; Grinenko, N F; Levinskii, A B; Mel'nikov, P A; Cherepanov, S A; Chekhonin, V P

    2015-05-01

    The formation of functional gap junctions between mesenchymal stem cells and cells of low-grade rat glioma C6 cells was studied in in vitro experiments. Immunocytochemical analysis with antibodies to connexin 43 extracellular loop 2 showed that mesenchymal stem cells as well as C6 glioma cells express the main astroglial gap junction protein connexin 43. Analysis of migration activity showed that mesenchymal stem cells actively migrate towards C6 glioma cells. During co-culturing, mesenchymal stem cells and glioma C6 form functionally active gap junctions mediating the transport of cytoplasmic dye from glioma cells to mesenchymal stem cells in the opposite direction. Fluorometry showed that the intensity of transport of low-molecular substances through heterologous gap junctions between mesenchymal stem cells and glioma cells is similar to that through homologous gap junctions between glioma cells. This phenomenon can be used for the development of new methods of cell therapy of high-grade gliomas.

  9. A score of low-grade inflammation and risk of mortality: prospective findings from the Moli-sani study.

    PubMed

    Bonaccio, Marialaura; Di Castelnuovo, Augusto; Pounis, George; De Curtis, Amalia; Costanzo, Simona; Persichillo, Mariarosaria; Cerletti, Chiara; Donati, Maria Benedetta; de Gaetano, Giovanni; Iacoviello, Licia

    2016-11-01

    Low-grade inflammation is associated with an increased risk of chronic degenerative disease, but its relationship with mortality is less well explored. We aimed at evaluating, at a large epidemiological level, the possible association of low-grade inflammation, as measured by a composite score, with overall mortality risk. We conducted a population-based prospective investigation on 20,337 adult subjects free from major hematological disease and acute inflammatory status, randomly recruited from the general population of the Moli-sani study. A low-grade inflammation score was obtained from the sum of 10-tiles of plasmatic (C-reactive protein) and cellular (leukocyte and platelet counts, granulocyte/lymphocyte ratio) biomarkers of low-grade inflammation; higher levels indicated increased low-grade inflammation. Hazard ratios were calculated using multivariable Cox proportional hazard models with 95% confidence intervals. At the end of follow-up (median 7.6 years), 837 all-cause deaths were recorded. As compared to subjects in the lowest quartile of the low-grade inflammation score, those in the highest category had a significantly increased risk in overall mortality (HR=1.44; 1.17-1.77), independently of possible confounders, including the presence of chronic diseases and a number of health-related behaviors. The magnitude of the association of low-grade inflammation with mortality was relatively higher in type 2 diabetic patients (HR=2.90; 1.74-4.84) and in individuals with a history of cardiovascular disease (HR=2.48; 1.50-4.11) as compared to their counterparts who were free from the disease. In conclusion, an elevated degree of low-grade inflammation, as measured by a composite score of inflammatory biomarkers, is an independent risk factor for total mortality in an apparently healthy adult general population. Copyright© Ferrata Storti Foundation.

  10. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss.

    PubMed

    Arita, Hideyuki; Narita, Yoshitaka; Fukushima, Shintaro; Tateishi, Kensuke; Matsushita, Yuko; Yoshida, Akihiko; Miyakita, Yasuji; Ohno, Makoto; Collins, V Peter; Kawahara, Nobutaka; Shibui, Soichiro; Ichimura, Koichi

    2013-08-01

    Telomere lengthening is one of the key events in most cancers, and depends largely on telomerase activation. Telomerase activation is a well-known phenomenon in gliomas; however, its mechanism remains obscure. In this study, we investigated the presence of mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in a series of 546 gliomas. We found a high incidence of mutually exclusive mutations located at two hot spots, C228T and C250T, in all subtypes of gliomas (55 %). The frequency of mutation was particularly high among primary glioblastomas (70 %) and pure oligodendroglial tumors (74 %), while relatively low in diffuse astrocytomas and anaplastic astrocytomas (19 and 25 %, respectively). The expression level of TERT in tumors carrying those mutations was on average 6.1 times higher than that of wild-type tumors, indicating that the mutated promoter leads to upregulation of TERT. TERT promoter mutations were observed in almost all tumors harboring concurrent total 1p19q loss and IDH1/2 mutations (98 %). Otherwise TERT promoter mutations were mostly observed among IDH wild-type tumors. Most EGFR amplifications (92 %) were also associated with TERT promoter mutations. Our data indicate that mutation of the TERT promoter is one of the major mechanisms of telomerase activation in gliomas. The unique pattern of TERT promoter mutations in relation to other genetic alterations suggests that they play distinct roles in the pathogenesis of oligodendroglial and astrocytic tumors. Our results shed a new light on the role of telomerase activation in the development of adult gliomas.

  11. Management and outcome of focal low-grade brainstem tumors in pediatric patients: the St. Jude experience.

    PubMed

    Klimo, Paul; Pai Panandiker, Atmaram S; Thompson, Clinton J; Boop, Frederick A; Qaddoumi, Ibrahim; Gajjar, Amar; Armstrong, Gregory T; Ellison, David W; Kun, Larry E; Ogg, Robert J; Sanford, Robert A

    2013-03-01

    Whereas diffuse intrinsic pontine gliomas generally have a short symptom duration and more cranial nerve involvement, focal brainstem gliomas are commonly low grade, with fewer cranial neuropathies. Although these phenotypic distinctions are not absolute predictors of outcome, they do demonstrate correlation in most cases. Because there is a limited literature on focal brainstem gliomas in pediatric patients, the objective of this paper was to report the management and outcome of these tumors. The authors reviewed the records of all children diagnosed with radiographically confirmed low-grade focal brainstem gliomas from 1986 to 2010. Each patient underwent biopsy or resection for tissue diagnosis. Event-free survival (EFS) and overall survival were evaluated. Univariate analysis was conducted to identify demographic and treatment variables that may affect EFS. Fifty-two patients (20 girls, 32 boys) with follow-up data were identified. Median follow-up was 10.0 years, and the median age at diagnosis was 6.5 years (range 1-17 years). The tumor locations were midbrain (n = 22, 42%), pons (n = 15, 29%), and medulla (n = 15, 29%). Surgical extirpation was the primary treatment in 25 patients (48%). The 5- and 10-year EFS and overall survival were 59%/98% and 52%/90%, respectively. An event or treatment failure occurred in 24 patients (46%), including 5 deaths. Median time to treatment failure was 3.4 years. Disease progression in the other 19 patients transpired within 25.1 months of diagnosis. Thirteen of these patients received radiation, including 11 within 2 months of primary treatment failure. Although children with intrinsic tumors had slightly better EFS at 5 years compared with those with exophytic tumors (p = 0.054), this difference was not significant at 10 years (p = 0.147). No other variables were predictive of EFS. Surgery suffices in many children with low-grade focal brainstem gliomas. Radiation treatment is often reserved for disease progression but

  12. Cognitive outcomes among survivors of focal low-grade brainstem tumors diagnosed in childhood.

    PubMed

    Clark, Kellie N; Ashford, Jason M; Pai Panandiker, Atmaram S; Klimo, Paul; Merchant, Thomas E; Billups, Catherine A; Conklin, Heather M

    2016-09-01

    Pediatric focal low-grade brainstem tumors are associated with excellent prognosis. Surgical resection and conformal radiation therapy are front-line treatment options; radiation therapy (RT) serves as an excellent treatment for disease progression. Given high survival rates and limited research regarding functional outcomes, the current study examined neurocognitive outcomes in a group of low-grade brainstem glioma survivors. Forty-three survivors of focal low-grade brainstem gliomas underwent neurocognitive assessment (58 % male; median = 6.9 years at diagnosis; median = 14.9 years at latest assessment). Treatment included combinations of surgery, chemotherapy, and RT with 70 % ultimately receiving RT. Neurocognitive outcomes were evaluated through retrospective chart review. Intellectual and academic performance were significantly different from normative expectations (full scale IQ = 86.5 ± 16.8; reading comprehension = 91.3 ± 16.4; math reasoning = 88.2 ± 18.9; reference group = 100 ± 15). Further, the percentage performing below average exceeded the expected 16 % in the normative sample (full scale IQ = 43 %; reading comprehension = 37 %; math reasoning = 50 %). Mean parent ratings did not reflect concerns regarding internalizing and externalizing behaviors or executive functioning (internalizing = 54.9 ± 12.7; externalizing = 51.6 ± 14.6, global executive composite = 57.1 ± 16.0; reference group = 50 ± 10); however, the proportion with clinically elevated scores was higher than the expected 16 % (internalizing = 42 %; externalizing = 26 %; global executive composite = 38 %). Mean performance fell below average for visual-motor coordination (81.8 ± 13.2) and parent ratings of adaptive functioning (73.4 ± 24.2), with 65 and 62 % falling outside the average range, respectively. There were no significant differences between

  13. Molecular classification of gliomas.

    PubMed

    Masui, Kenta; Mischel, Paul S; Reifenberger, Guido

    2016-01-01

    The identification of distinct genetic and epigenetic profiles in different types of gliomas has revealed novel diagnostic, prognostic, and predictive molecular biomarkers for refinement of glioma classification and improved prediction of therapy response and outcome. Therefore, the new (2016) World Health Organization (WHO) classification of tumors of the central nervous system breaks with the traditional principle of diagnosis based on histologic criteria only and incorporates molecular markers. This will involve a multilayered approach combining histologic features and molecular information in an "integrated diagnosis". We review the current state of diagnostic molecular markers for gliomas, focusing on isocitrate dehydrogenase 1 or 2 (IDH1/IDH2) gene mutation, α-thalassemia/mental retardation syndrome X-linked (ATRX) gene mutation, 1p/19q co-deletion and telomerase reverse transcriptase (TERT) promoter mutation in adult tumors, as well as v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and H3 histone family 3A (H3F3A) aberrations in pediatric gliomas. We also outline prognostic and predictive molecular markers, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and discuss the potential clinical relevance of biologic glioblastoma subtypes defined by integration of multiomics data. Commonly used methods for individual marker detection as well as novel large-scale DNA methylation profiling and next-generation sequencing approaches are discussed. Finally, we illustrate how advances in molecular diagnostics affect novel strategies of targeted therapy, thereby raising new challenges and identifying new leads for personalized treatment of glioma patients.

  14. Primary Gliosarcoma of the Optic Nerve: A Unique Adult Optic Pathway Glioma.

    PubMed

    Cimino, Patrick J; Sychev, Yevgeniy V; Gonzalez-Cuyar, Luis F; Mudumbai, Raghu C; Keene, C Dirk

    2016-10-11

    A 90-year-old woman presented with 1-year history of right-sided progressive proptosis, neovascular glaucoma, blindness, and worsening ocular pain. No funduscopic examination was possible because of a corneal opacity. Head CT scan without contrast demonstrated a heterogeneous 4.1 cm (anterior-posterior) by 1.7 cm (transverse) cylindrical mass arising in the right optic nerve and extending from the retrobulbar globe to the optic canal. She underwent palliative enucleation with subtotal resection of the orbital optic nerve and tumor. Pathological examination showed effacement of the optic nerve by an infiltrative high-grade glial neoplasm with biphasic sarcomeric differentiation. Invasion into the uvea and retina was present. The neoplasm was negative for melan-A, HMB45, tyrosinase, synaptophysin, smooth muscle actin, and epithelial membrane antigen. The glioma had strongly intense, but patchy immunopositivity for glial fibrillary acidic protein. Multiple foci of neoplastic cells had pericellular reticulin staining. The overall features were diagnostic of a gliosarcoma (World Health Organization grade IV) of the optic nerve. Postoperative MRI demonstrated postsurgical changes and residual gliosarcoma with extension into the optic chiasm. The patient died 2 and a half months after her enucleation surgery at her nursing home. Autopsy was unavailable due to the caregiver wishes, making a definitive cause of death unknown. Gliosarcoma is a rare variant of glioblastoma, and this is the first documented case presenting as a primary neoplasm of the optic nerve.

  15. [Cognitive disorders and adult grade II and III gliomas: analysis of a series of 15 patients].

    PubMed

    Le Rhun, E; Delbeuck, X; Devos, P; Pasquier, F; Dubois, F

    2009-06-01

    Correlated with better follow-up of gliomas, cognitive disorders are increasingly studied. The aim of this study was to describe the cognitive disorders presented by these patients at baseline, before any treatment, and to evaluate the relations between cognitive disorders and return to work. A detailed neuropsychological evaluation was administrated to 15 newly diagnosed patients with a grade II or III glial tumor before any treatment. Patients also completed the quality of life and depression scales. All patients in our study presented with at least one failed cognitive domain during the detailed examination, while the scores on the MMSE scale were within the norm. The most deteriorated functions were divided attention and episodic verbal and nonverbal memory. Moreover, a significant link was found between the number of failed cognitive functions and quality of life. Cognitive disorders are frequent with glial tumors and impact patients' quality of life. Simple tests of global cognitive status are not sufficient to detect cognitive difficulties in these patients. Consequently, detailed and adapted neuropsychological assessment is necessary, especially to detect deteriorated problems with memory, divided attention, or processing speed in this population.

  16. Area-based socioeconomic position and adult glioma: a hierarchical analysis of surveillance epidemiology and end results data.

    PubMed

    Plascak, Jesse J; Fisher, James L

    2013-01-01

    Glioma rates vary by demographic factors and geo-political boundaries and this variation suggests higher glioma rates in groups of higher socioeconomic position. The primary goal of this analysis is to investigate the relationship between glioma and county socioeconomic position using U.S. Surveillance Epidemiology and End Results (SEER) data. Cases were individuals 25+ years diagnosed with glioma between 2000 and 2006 and residing within the SEER-17 catchment area. County-, sex-, race-, age-specific rates were created in order to investigate individual-level associations (population data from U.S. Census 2000). A Bayesian hierarchical Poisson spatial conditionally autoregressive (CAR) model was utilized to simultaneously estimate individual- and county-level associations while controlling for county spatial dependence. Those residing in counties of the second, third, and fourth highest quartiles of socioeconomic position have glioma incidence rates that are 1.10 (95% CI: 1.02,1.19), 1.11 (95% CI: 1.02,1.20), 1.14 (95% CI: 1.05,1.23) times that of the first quartile, respectively. A CAR model properly controlled for error spatial dependence. Investigated lag times suggest year 2000 census data yields superior model fit. Demographically adjusted rates of glioma are elevated in counties of higher socioeconomic position. More well-grounded theory concerning the glioma-socioeconomic position association along with socioeconomic data collected at multiple levels is recommended for future studies investigating this relationship.

  17. Low-grade proteinuria and microalbuminuria in renal transplantation.

    PubMed

    Halimi, Jean-Michel

    2013-07-27

    Nephrotic-range proteinuria has been known for years to be associated with poor renal outcome. Newer evidence indicates that early (1-3 months after transplantation) low-grade proteinuria and microalbuminuria (1) provide information on the graft in terms of donor characteristics and ischemia/reperfusion injury, (2) may occur before the development of donor-specific antibodies, (3) predict the development of diabetes and cardiovascular events, and (4) are associated with reduced long-term graft and patient survivals. Low-grade proteinuria and microalbuminuria are also predictive of diabetes, cardiovascular morbidity, and death in nontransplanted populations, which may help us to understand the pathophysiology of low-grade proteinuria or microalbuminuria in renal transplantation. The impact of immunosuppressive medications, including mammalian target of rapamycin inhibitors, on graft survival is still discussed, and the effect on proteinuria is crucial to the debate. The fact that chronic allograft rejection may exist as early as 3 months after renal transplantation indicates that optimal management of low-grade proteinuria or microalbuminuria should occur very early after transplantation to improve long-term renal function and the overall outcome of renal transplant recipients. The presence of low-grade proteinuria or microalbuminuria early after transplantation must be taken into account to choose adequate immunosuppressive and antihypertensive medications. Limited information exists regarding the benefit of therapeutic interventions to reduce low-grade proteinuria or microalbuminuria. Whether renin angiotensin blockade results in optimal nephroprotection in patients with low-grade proteinuria or microalbuminuria is not proven, especially in the absence of chronic allograft nephropathy. Observational studies and randomized clinical trials yield conflicting results. Finally, randomized clinical trials are urgently needed.

  18. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    ClinicalTrials.gov

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  19. Use of EF5 to Measure the Oxygen Level in Tumor Cells of Patients Undergoing Surgery or Biopsy for Newly Diagnosed Supratentorial Malignant Glioma

    ClinicalTrials.gov

    2013-01-15

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymoma

  20. Phase II trial of intratumoral BCNU injection and radiotherapy on untreated adult malignant glioma.

    PubMed

    Jenkinson, Michael D; Smith, Trevor S; Haylock, Brian; Husband, David; Shenoy, Aditya; Vinjamuri, Sobhan; Walker, Carol; Pietronigro, Denis; Warnke, Peter C

    2010-08-01

    DTI-015 (BCNU dissolved in ethanol) utilizes solvent facilitated perfusion (SFP) for intratumoral drug delivery. A phase II clinical trial of DTI-015 and fractionated external beam radiotherapy on newly diagnosed, malignant gliomas investigated early changes in tumour physiology and metabolism, clinical outcome and safety. Pre- and post DTI-015 injection neuro-imaging included computed tomography (CT) cerebral blood flow and volume, glucose and thallium single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Clinical status was determined before and after DTI-015, prior to radiotherapy and 3 monthly thereafter until progression (defined by Macdonald criteria). Primary endpoint was radiographic response. Secondary endpoints were progression free (PFS) and overall survival (OS). Twelve patients were enrolled; eight glioblastoma multiforme (GBM), four anaplastic astrocytoma (AA). Three days after DTI-015 injection, mean tumour blood flow (Paired t-test; P < 0.001) and blood volume (Paired t-test; P = 0.001) were significantly reduced. There was a significant decrease in glucose utilization (Paired t-test; P < 0.001) and thallium uptake (Paired t-test; P < 0.001) at 6 days. Tumour blood volume had a sustained reduction (Paired t-test; P = 0.001) at 26 days after DTI-015. There were two serious adverse events. Two patients with AA achieved a partial response. Median PFS was 39 weeks for AA and 27 weeks for GBM; median OS for GBM was 47 weeks and 132 weeks for AA. The imaging data forms a biological basis for understanding the effects of high dose BCNU delivered intratumorally by SFP, and suggests early effects on tumour vasculature and metabolism.

  1. Ischemic stroke in patients with gliomas at The University of Texas-M.D. Anderson Cancer Center.

    PubMed

    Kamiya-Matsuoka, Carlos; Cachia, David; Yust-Katz, Shlomit; Rodriguez, Yvo A; Garciarena, Pedro; Rodarte, Elsa M; Tremont-Lukats, Ivo W

    2015-10-01

    Patients with gliomas are at risk of cerebrovascular accidents (CVA) with potential consequences on survival, function, and local tumor control. Our objective was to provide information about CVA in patients with gliomas and to estimate survival in this group. We reviewed all adult glioma patients with ischemic CVA at the University of Texas-M.D. Anderson Cancer Center from 2003 through 2014. We extracted demographic, clinical, imaging, treatment and outcome data. We used descriptive summary data and estimated or compared survival rates where appropriate. 60 of 6500 patients (0.1%) with high-grade (HGG, n = 47) or low-grade glioma (LGG, n = 13) had ischemic CVA Thirty-two (53%) patients had postoperative strokes, and 20 (33%) had CVA after 2 weeks of surgery. Forty-one patients (68%) had gross total resection. For HGG and CVA, the poststroke median overall survival was 17 months versus 61 months in LGG and CVA (P = 0.03; hazard ratio (HR): 2.8; 95% CI 1.07-4.60). Survival stratified by modified Rankin Scale grade was significant (X(2) = 9.8, P = 0.007). Five patients received bevacizumab before stroke onset; none responded to antiangiogenic therapy. There was no stroke-related death. At our institution for 10 years, ischemic CVA in glioma patients was a rare complication, clearly associated in half of cases to surgery, and with a variable negative impact on performance status and neurologic function. In this group, patients with more neurological deficits lived less. The survival difference between and within subgroups was most likely due to tumor grade. More research is necessary to improve prevention of postoperative stroke in glioma patients.

  2. Low-grade serous ovarian cancer: A review.

    PubMed

    Kaldawy, Anis; Segev, Yakir; Lavie, Ofer; Auslender, Ron; Sopik, Victoria; Narod, Steven A

    2016-11-01

    Epithelial ovarian cancers can be divided into the more common, aggressive type II cancers and the less common, slow-growing type I cancers. Under this model, serous ovarian carcinomas can be subdivided into high-grade (type II) and low-grade (type I) tumours. The two-tier system for grading serous ovarian carcinomas is superior to more detailed grading systems in terms of predicting survival. Low-grade serous carcinomas typically present in young women and have a relatively good prognosis, despite being resistant to chemotherapy. Low-grade serous cancers have a high prevalence of KRAS and BRAF mutations, but a low prevalence of TP53 mutations (which are characteristic of high-grade serous cancers). Among women with low-grade serous ovarian cancer, the presence of a KRAS/BRAF mutation is a favorable prognostic factor. Studies of the mitogen-activated protein kinase (MAPK) inhibitor in low-grade serous ovarian cancer suggest that identifying MAPK mutations might eventually be useful in guiding treatment.

  3. Current Management of Low-Grade Dysplasia in Barrett Esophagus

    PubMed Central

    2017-01-01

    Low-grade dysplasia in Barrett esophagus remains an ongoing challenge in clinical management. Recent studies suggest an increased risk in progression of low-grade dysplasia to high-grade dysplasia and/or adenocarcinoma. This is especially seen when 1 or more expert gastrointestinal pathologist confirms the diagnosis and in the setting of low-grade dysplasia that persists on more than 1 endoscopy. In the setting of confirmed and persistent low-grade dysplasia, level 1 evidence supports endoscopic ablation as a treatment option for these patients, although continued surveillance remains a viable option. Current management of these patients emphasizes the importance of the following principles: (1) biopsies should not be obtained in the setting of erosive esophagitis; (2) any diagnosis of low-grade dysplasia should be confirmed by a second pathologist with extensive expertise in Barrett esophagus; (3) surveillance endoscopy should be repeated within 3 to 6 months of the initial diagnosis with rigorous visual inspection to exclude higher-level lesions; and (4) the advantages and disadvantages of both endoscopic ablation and continued surveillance should be reviewed with the patient. PMID:28546793

  4. Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives.

    PubMed

    Marlow, Megan M; Shah, Sumedh S; Véliz, Eduardo A; Ivan, Michael E; Graham, Regina M

    2017-01-01

    Resistance mechanisms employed by high-grade gliomas allow them to successfully evade current standard treatment of chemotherapy and radiation treatment. Withaferin A (WA), utilized in Ayurvedic medicine for centuries, is attracting attention for its antitumor capabilities. Here we review pertinent literature on WA as a high-grade glioma treatment, and discuss the cancerous mechanisms it affects. WA is relatively nontoxic and has shown potential in crossing the blood-brain barrier. WA prevents p53 alterations and inactivates overexpressed MDM2 through ARF and ROS production. Furthermore, WA upregulates Bax, inducing mitochondrial death cascades, inhibits mutated Akt, mTOR, and NF-κB pathways, and inhibits angiogenesis in tumors. Therapy with WA for high-grade gliomas is supported through the literature. Further investigation is warranted and encouraged to fully unearth its abilities against malignant gliomas.

  5. Mutations in chromatin machinery and pediatric high-grade glioma

    PubMed Central

    Lulla, Rishi R.; Saratsis, Amanda Muhs; Hashizume, Rintaro

    2016-01-01

    Pediatric central nervous system tumors are the most common solid tumor of childhood. Of these, approximately one-third are gliomas that exhibit diverse biological behaviors in the unique context of the developing nervous system. Although low-grade gliomas predominate and have favorable outcomes, up to 20% of pediatric gliomas are high-grade. These tumors are a major contributor to cancer-related morbidity and mortality in infants, children, and adolescents, with long-term survival rates of only 10 to 15%. The recent discovery of somatic oncogenic mutations affecting chromatin regulation in pediatric high-grade glioma has markedly improved our understanding of disease pathogenesis, and these findings have stimulated the development of novel therapeutic approaches targeting epigenetic regulators for disease treatment. We review the current perspective on pediatric high-grade glioma genetics and epigenetics, and discuss the emerging and experimental therapeutics targeting the unique molecular abnormalities present in these deadly childhood brain tumors. PMID:27034984

  6. Is seborrhoeic dermatitis associated with a diffuse, low-grade folliculitis and progressive cicatricial alopecia?

    PubMed

    Pitney, Lucy; Weedon, David; Pitney, Michael

    2016-08-01

    An association between adult scalp seborrhoeic dermatitis and cicatricial hair loss has not previously been convincingly established. This study seeks to demonstrate a unique relationship between a clinically identifiable chronic scalp dermatitis-folliculitis with the characteristic histological features of low-grade inflammatory fibrosing alopecia, resulting in a distinctive progressive cicatricial alopecia which we believe is prevalent and hitherto unrecognised, and befits the description of seborrhoeic folliculitis. The clinical, epidemiological and histopathological features of seborrhoeic folliculitis are demonstrated to establish its unique status among the disorders of adult diffuse cicatricial alopecia. © 2015 The Australasian College of Dermatologists.

  7. Number of glioma polyploid giant cancer cells (PGCCs) associated with vasculogenic mimicry formation and tumor grade in human glioma

    PubMed Central

    2013-01-01

    Background Polyploid giant cancer cells (PGCCs) contribute to solid tumor heterogeneity. This study investigated the relationships among PGCCs numbers, vasculogenic mimicry (VM) formation, and tumor grades in glioma. Methods A total of 76 paraffin-embedded glioma tissue samples, including 28 cases of low grade and 48 cases of high grade gliomas, were performed with H&E and immunohistochemical staining for Ki-67 and hemoglobin. The size of PGCCs nuclei was measured by a micrometer using H&E section and defined as at least three times larger than the nuclei of regular diploid cancer cells. The number of PGCCs and different blood supply patterns were compared in different grade gliomas. Microcirculation patterns in tumors were assessed using CD31 immunohistochemical and PAS histochemical double staining. Human glioma cancer cell line C6 was injected into the chicken embryonating eggs to form xenografts, which was used to observe the PGCCs and microcirculation patterns. Results In human glioma, the number of PGCCs increased with the grade of tumors (χ2 = 4.781, P = 0.015). There were three kinds of microcirculation pattern in human glioma including VM, mosaic vessel (MV) and endothelium dependent vessel. PGCCs were able to generate erythrocytes via budding to form VM. The walls of VM were positive (or negative) for PAS staining and negative for CD31 staining. There were more VM and MVs in high grade gliomas than those in low grade gliomas. The differences have statistical significances for VM (t = 3.745, P = 0.000) and MVs (t = 4.789, P = 0.000). PGCCs, VM and MVs can also be observed in C6 chicken embryonating eggs xenografts. Conclusions The data demonstrated presence of PGCCs, VM and MVs in glioma and PGCCs generating erythrocytes contribute the formation of VM and MVs. PMID:24422894

  8. Re-irradiation with hypo-fractionated stereotactic robotic radiotherapy for salvage in adult patients with brainstem glioma

    PubMed Central

    Susheela, Sridhar P; Revannasiddaiah, Swaroop; Muzumder, Sandeep; Mallarajapatna, Govindarajan; Kallur, Kumar; Basavalingaiah, Ajaikumar S

    2013-01-01

    Purpose Brainstem glioma (BSG) is often treated with definitive irradiation. However, subsequent progression and death occur as a rule rather than the exception, after varying periods of control. The outlook of patients with post-irradiation progression is dismal, and most of these patients are treated with supportive care alone. Despite the obvious risks with an area as critical as the brainstem, it is a possibility to encounter situations wherein the patients (themselves or their associates) ask for re-irradiation, with the hope of a few extra months of life. The risk of radiation-induced brainstem toxicity may be justifiable under the strict assumption that the patients stand a chance of benefiting from re-irradiation but still may not live long enough to manifest brainstem toxicity. Methods Five adult BSG patients were treated with re-irradiation using robotic-arm stereotactic radiation therapy (SRT) between September 2009 and July 2012, primarily at the request of the concerned patient parties. Re-irradiation doses ranged from 16 to 25 Gray (Gy) delivered by robotic arm stereotactic irradiation in 2–5 fractions. Results Four out of five patients enjoyed a prolongation of survival in the order of months (three, five, six, and 14 months), which was very significant given that all patients had severe neurological compromise and poor performance status prior to re-irradiation. One patient has survived 36 months after re-irradiation and thus has lived long enough to manifest late radiation-induced brainstem toxicity. Conclusion Despite the obvious risks of brainstem toxicity associated with the use of re-irradiation for BSG, the use of fractionated stereotactic re-irradiation seems to offers prospects of additional periods of local control and augments duration of life. PMID:24171050

  9. A phase II trial of thalidomide and procarbazine in adult patients with recurrent or progressive malignant gliomas.

    PubMed

    Ruiz, Jimmy; Case, Doug; Enevold, Gina; Rosdhal, Robin; Tatter, Stephen B; Ellis, Thomas L; McQuellon, Richard P; McMullen, Kevin P; Stieber, Volker W; Shaw, Edward G; Lesser, Glenn J

    2012-02-01

    Thalidomide and procarbazine have demonstrated single agent activity against malignant gliomas (MG). We evaluated the combination of thalidomide and procarbazine with a single arm phase II trial in adults with recurrent or progressive MG. Procarbazine was given at a dose of 250 mg/m(2)/d × 5day q 28 days. Thalidomide was administered at a dose of 200 mg/day continuously. Intrapatient dose escalation of thalidomide was attempted (increase by 100 mg/day weekly as tolerated) to a maximum of 800 mg/day. The primary outcome was tumor response, assessed by MRI and CT. Secondary outcomes were progression free survival (PFS), overall survival (OS) and toxicity. In addition, quality of life questionnaires were performed at baseline and prior to each odd cycle in all treated patients. Eighteen patients (median age of 50) were accrued and received a total of 36 cycles (median 2) of therapy. The median maximum thalidomide dose achieved was 400 mg (range 0-800). No complete or partial responses were seen. One patient (6%) experienced stable disease, fourteen (78%) progressed as best response and three (17%) were not evaluable for response. Median time to progression was 2.1 months (95% CI, 1.5-2.5). Seventeen patients have died (one patient lost to follow-up after progression); median survival from enrollment was 7.6 months (95% CI, 3.5-9.4). Grade 3/4 drug related toxicity was minimal. Quality of life diminished over time. The combination of thalidomide and procarbazine demonstrated no efficacy in this trial.

  10. MYB-QKI rearrangements in Angiocentric Glioma drive tumorigenicity through a tripartite mechanism

    PubMed Central

    Bandopadhayay, Pratiti; Ramkissoon, Lori A.; Jain, Payal; Bergthold, Guillaume; Wala, Jeremiah; Zeid, Rhamy; Schumacher, Steven E.; Urbanski, Laura; O’Rourke, Ryan; Gibson, William J.; Pelton, Kristine; Ramkissoon, Shakti H.; Han, Harry J.; Zhu, Yuankun; Choudhari, Namrata; Silva, Amanda; Boucher, Katie; Henn, Rosemary E.; Kang, Yun Jee; Knoff, David; Paolella, Brenton R.; Gladden-Young, Adrianne; Varlet, Pascale; Pages, Melanie; Horowitz, Peleg M.; Federation, Alexander; Malkin, Hayley; Tracy, Adam; Seepo, Sara; Ducar, Matthew; Hummelen, Paul Van; Santi, Mariarita; Buccoliero, Anna Maria; Scagnet, Mirko; Bowers, Daniel C.; Giannini, Caterina; Puget, Stephanie; Hawkins, Cynthia; Tabori, Uri; Klekner, Almos; Bognar, Laszlo; Burger, Peter C.; Eberhart, Charles; Rodriguez, Fausto J.; Hill, D. Ashley; Mueller, Sabine; Haas-Kogan, Daphne A.; Phillips, Joanna J.; Santagata, Sandro; Stiles, Charles D.; Bradner, James E.; Jabado, Nada; Goren, Alon; Grill, Jacques; Ligon, Azra H.; Goumnerova, Liliana; Waanders, Angela J.; Storm, Phillip B.; Kieran, Mark W.; Ligon, Keith L.; Beroukhim, Rameen; Resnick, Adam C.

    2016-01-01

    Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs including 19 Angiocentric Gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in Angiocentric Gliomas. In vitro and in vivo functional studies show MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of the tumor suppressor QKI. This represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor. PMID:26829751

  11. Rheology and extrusion of low-grade paper and sludge

    Treesearch

    C. Tim. Scott; Stefan. Zauscher; Daniel J. Klingenberg

    1999-01-01

    This paper discusses efforts to characterize the rheological properties of pulps that include low-grade wastepapers and papermill sludges to determine their potential for extrusion and conversion into useful products. We investigated apparent changes in viscosity associated with the addition of typical inorganic paper fillers (calcium carbonate, kaolin clay, and...

  12. Polymorphous low-grade adenocarcinoma of the nasal fossa.

    PubMed

    González-Lagunas, Javier; Alasà-Caparrós, Cristian; Vendrell-Escofet, Gerard; Huguet-Redecilla, Pere; Raspall-Martin, Guillermo

    2005-01-01

    An unusual case of a T4N2CMx polymorphous low grade adenocarcinoma located in the nasal fossae and extending to the pterygoid area is presented. The primary tumor was excised through a Lefort I maxillotomy and the neck was managed with a supraomohyoid neck dissection. Adjuntive postoperative radiotherapy was also administered to the patient.

  13. New technology for low-grade hardwood utilization: System 6

    Treesearch

    Hugh W. Reynolds; Charles J. Gatchell

    1982-01-01

    System 6 is a technology for converting low-grade hardwood to high-valued end products such as furniture and kitchen cabinets. Among its concepts are: (1) a new, nonlumber product called standard-size blanks; (2) highly automated methods of converting the logs to blanks; (3) total processing of every board that contains a minimum-size cutting; and (4) minimized machine...

  14. Low-grade hardwood lumber production, markets, and issues

    Treesearch

    Dan Cumbo; Robert Smith; Philip A. Araman

    2003-01-01

    Due to recent downturn in the economy and changes in traditional hardwood markets. U.S. hardwood manufacturers are facing significant difficulties. In particular, markets for low-grade lumber have been diminishing, while increased levels of the material are being produced at hardwood sawmills in the United States. A nationwide survey of hardwood lumber manufacturers...

  15. FBC could give new life to low-grade coal

    SciTech Connect

    Not Available

    1984-08-01

    Fluidised-bed combustion is gaining a foothold in the US industrial steam boiler market because of the wide range of coals that can be utilised, including those which are of very low grade. The prospects for using this technology for electricity generation are also considered to be good, and information is given on several demonstration plants which are planned.

  16. Low-Grade Epithelial Proliferations of the Sinonasal Tract.

    PubMed

    Bullock, Martin J

    2016-03-01

    Low-grade epithelial proliferations of the sinonasal tract include Schneiderian papillomas, respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma and low-grade non-intestinal adenocarcinoma. There is considerable overlap in their clinical presentation, endoscopic appearance, and imaging features. Although well-described diagnostic criteria exist, a definitive diagnosis may be difficult to reach on a small biopsy. Schneiderian papillomas are divided into fungiform, inverted, and oncocytic types, each with characteristic clinical and morphological features. The latter two may progress to malignancy. The majority are still considered to be HPV-related. Two lesions are designated as hamartomas, but their pathogenesis remains uncertain, with inflammatory and neoplastic origins proposed. Respiratory epithelial adenomatoid hamartoma is increasingly being recognized for its association with chronic rhinosinusitis and olfactory cleft site of origin. Seromucinous hamartoma has gained attention in recent years and overlaps with both respiratory epithelial adenomatoid hamartoma and low-grade non-intestinal adenocarcinoma. Controversy surrounds their distinction, particularly from low-grade adenocarcinoma. The latter generally is cured by complete excision, with a 26 % risk of recurrence but rare metastases and deaths from disease.

  17. Do Low Grades Cause College Students to Give up?

    ERIC Educational Resources Information Center

    Thayer, Robert E.

    The thesis that low grades cause college students to give up receives some support from early psychological research and from current reinforcement theories. This study investigates the effects on subsequent grades of low, average, and high first-exam grades for 192 students in a traditional grading system and 52 students in a pass-fail grading…

  18. Circulating levels of the innate and humoral immune regulators CD14 and CD23 are associated with adult glioma.

    PubMed

    Zhou, Mi; Wiemels, Joseph L; Bracci, Paige M; Wrensch, Margaret R; McCoy, Lucie S; Rice, Terri; Sison, Jennette D; Patoka, Joseph S; Wiencke, John K

    2010-10-01

    Allergy history has been consistently inversely associated with glioma risk. Two serologic markers, soluble CD23 (sCD23) and soluble CD14 (sCD14), are part of the innate and adaptive humoral immune systems and modulate allergic responses in opposite directions, with sCD23 enhancing and sCD14 blunting inflammatory responses. We measured sCD23 and sCD14 in serum from blood that was drawn at a single time point from 1,079 glioma patients postdiagnosis and 736 healthy controls. Glioma was strongly associated with high sCD14 [highest versus lowest quartile odds ratio (OR), 3.94; 95% confidence interval (95% CI), 2.98-5.21] and low sCD23 (lowest versus highest quartile OR, 2.5; 95% CI, 1.89-3.23). Results were consistent across glioma histologic types and grades, but were strongest for glioblastoma. Whereas temozolomide treatment was not associated with either sCD14 or sCD23 levels among cases, those taking dexamethasone had somewhat lower sCD23 levels than those not taking dexamethasone. However, sCD23 was associated with case status regardless of dexamethasone treatment. These results augment the long-observed association between allergies and glioma and support a role for the innate and adaptive humoral functions of the immune system, in particular immunoregulatory proteins, in gliomagenesis.

  19. Is Invasive Micropapillary Serous Carcinoma a Low-grade Carcinoma?

    PubMed

    Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kaku, Tsunehisa; Kato, Kiyoko; Oda, Yoshinao

    2016-01-01

    "Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.

  20. Low-grade infections in nonarthroplasty shoulder surgery.

    PubMed

    Khan, Umair; Torrance, Emma; Townsend, Robert; Davies, Steve; Mackenzie, Tanya; Funk, Lennard

    2017-09-01

    Recent studies have identified the diagnostic challenge of low-grade infections after shoulder arthroplasty surgery. Infections after nonarthroplasty procedures have not been reported. This study assessed patient-related risk factors, outcomes, and clinical presentation of low-grade infection after open and arthroscopic nonarthroplasty shoulder surgery. The cases of 35 patients presenting with suspected low-grade infection were reviewed. Biopsy specimens taken at revision surgery were cultured in the sterile environment of a class II laminar flow cabinet and incubated for a minimum of 14 days at a specialist orthopedic microbiology laboratory. Patient-related factors (age, occupation, injection), index surgery, and infection characteristics (onset of symptoms, duration to diagnosis, treatment) were analyzed. Positive cultures were identified in 21 cases (60.0%), of which 15 were male patients (71%). Of all patients with low-grade infection, 47.6% were male patients between 16 and 35 years of age. Propionibacterium acnes and coagulase-negative staphylococcus were the most common organisms isolated (81.1% [n = 17] and 23.8% [n = 5], respectively). Of 14 negative culture cases, 9 were treated with early empirical antibiotics (64.3%); 7 patients reported symptomatic improvement (77.8%). Of 5 patients treated with late empirical antibiotics, 4 stated improvement. Patients presented with symptoms akin to resistant postoperative frozen shoulder (persistent pain and stiffness, unresponsive to usual treatments). Young male patients are at greatest risk for low-grade infections after arthroscopic and open nonarthroplasty shoulder surgery. P. acnes was the most prevalent organism. Patients presented with classic postoperative frozen shoulder symptoms, resistant to usual treatments. Interestingly, 78.6% of patients with negative cultures responded positively to empirical treatment. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  1. Circulating biomarkers for discrimination between aseptic joint failure, low-grade infection, and high-grade septic failure.

    PubMed

    Ettinger, Max; Calliess, Tilman; Kielstein, Jan T; Sibai, Jasmin; Brückner, Thomas; Lichtinghagen, Ralf; Windhagen, Henning; Lukasz, Alexander

    2015-08-01

    Late-onset chronic (low-grade) periprosthetic joint infections are often accompanied by unspecific symptoms, false-negative cultures or nonspecific low values of serum biomarkers. This may lead to the unintended implantation of a revision prosthesis into an infected surgical site with the risk of short-term failure developing again. Conversely, false diagnosis of joint infection may result in multistage revision procedures, which expose the patient to unnecessary surgical procedures and inappropriate antibiotic treatment. Here, we investigated whether circulating biomarkers can preoperatively distinguish between aseptic prosthesis loosening and low-grade joint infection, and which biomarker combinations are most accurate. Inclusion criteria for the study were indication for revision arthroplasty due to aseptic implant failure, acute high-grade infection, or (suspected) low-grade infection. C-reactive protein (CRP), procalcitonin, tumor necrosis factor α, interleukin 6 (IL-6), interleukin 10, and lipopolysaccharide binding protein were assessed preoperatively in the serum of 98 adult patients. The classification tree method revealed IL-6 and CRP as the most suitable biomarker combination for the discrimination of aseptic loosening vs low-grade joint infection. The combination of IL-6 >5.12 pg/mL and CRP >0.3 mg/dL correctly identified 15 of 16 patients as having low-grade infection (94%) whereas just one patient was aseptic (6%). This is the first comprehensive prospective clinical study to our knowledge investigating the significance of a combined biomarker approach in differentiating between aseptic prosthesis loosening and low-grade joint infection. CRP plus IL-6 seems to be the most helpful combination for preoperative discrimination of aseptic loosening vs low-grade joint infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Altered Resting-State Functional Connectivity in the Hand Motor Network in Glioma Patients.

    PubMed

    Mallela, Arka N; Peck, Kyung K; Petrovich-Brennan, Nicole M; Zhang, Zhigang; Lou, William; Holodny, Andrei I

    2016-08-22

    To examine the functional connectivity of the primary and supplementary motor areas (SMA) in glioma patients using resting-state functional MRI (rfMRI). To correlate rfMRI data with tumor characteristics and clinical information to characterize functional reorganization of resting-state networks (RSN) and the limitations of this method. This study was IRB approved and in compliance with Health Insurance Portability and Accountability Act. Informed consent was waived in this retrospective study. We analyzed rfMRI in 24 glioma patients and 12 age- and sex-matched controls. We compared global activation, interhemispheric connectivity, and functional connectivity in the hand motor RSNs using hemispheric voxel counts, pairwise Pearson correlation, and pairwise total spectral coherence. We explored the relationship between tumor grade, volume, location, and the patient's clinical status to functional connectivity. Global network activation and interhemispheric connectivity were reduced in gliomas (p < 0.05). Functional connectivity between the bilateral motor cortices and the SMA was reduced in gliomas (p < 0.01). High-grade gliomas had lower functional connectivity than low-grade gliomas (p < 0.05). Tumor volume and distance to ipsilateral motor cortex demonstrated no association with functional connectivity loss. Functional connectivity loss is associated with motor deficits in low-grade gliomas, but not in high-grade gliomas. Global reduction in resting-state connectivity in areas distal to tumor suggests that radiological tumor boundaries underestimate areas affected by glioma. Association between motor deficits and rfMRI suggests that rfMRI may accurately reflect functional changes in low-grade gliomas. Lack of association between rfMRI and clinical motor deficits implies decreased sensitivity of rfMRI in high-grade gliomas, possibly due to neurovascular uncoupling.

  3. RO4929097, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Malignant Glioma

    ClinicalTrials.gov

    2015-09-28

    Acoustic Schwannoma; Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Primary Melanocytic Lesion of Meninges; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma

  4. Malignant Transformation in Glioma Steered by an Angiogenic Switch: Defining a Role for Bone Marrow-Derived Cells

    PubMed Central

    Pisapia, David; Greenfield, Jeffrey P

    2016-01-01

    Low-grade gliomas, such as pilocytic astrocytoma and subependymoma, are often characterized as benign tumors due to their relative circumscription radiologically and typically non-aggressive biologic behavior. In contrast, low-grades that are by their nature diffusely infiltrative, such as diffuse astrocytomas and oligodendrogliomas, have the potential to transform into malignant high-grade counterparts and, given sufficient time, invariably do so. These high-grade gliomas carry very poor prognoses and are largely incurable, warranting a closer look at what causes this adverse transition. A key characteristic that distinguishes low- and high-grade gliomas is neovascularization: it is absent in low-grade gliomas, but prolific in high-grade gliomas, providing the tumor with ample blood supply for exponential growth. It has been well described in the literature that bone marrow-derived cells (BMDCs) may contribute to the angiogenic switch that is responsible for malignant transformation of low-grade gliomas. In this review, we will summarize the current literature on BMDCs and their known contribution to angiogenesis-associated tumor growth in gliomas. PMID:26973806

  5. Tissue Proteome Analysis of Different Grades of Human Gliomas Provides Major Cues for Glioma Pathogenesis.

    PubMed

    Gollapalli, Kishore; Ghantasala, Saicharan; Atak, Apurva; Rapole, Srikanth; Moiyadi, Aliasgar; Epari, Sridhar; Srivastava, Sanjeeva

    2017-05-01

    Gliomas are heterogeneous and most commonly occurring brain tumors. Blood-brain barrier restricts the entry of brain tumor proteins into blood stream thus limiting the usage of serum or plasma for proteomic analysis. Our study aimed at understanding the molecular basis of aggressiveness of various grades of brain tumors using isobaric tagging for relative and absolute quantification (iTRAQ) based mass spectrometry. Tissue proteomic analysis of various grades of gliomas was performed using four-plex iTRAQ. We labeled five sets (each set consists of control, grade-II, III, and IV tumor samples) of individual glioma patients using iTRAQ reagents. Significantly altered proteins were subjected to bioinformatics analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID). Various metabolic pathways like glycolysis, TCA-cycle, electron transport chain, lactate metabolism, and blood coagulation pathways were majorly observed to be perturbed in gliomas. Most of the identified proteins involved in redox reactions, protein folding, pre-messenger RNA (mRNA) processing, antiapoptosis, and blood coagulation were found to be upregulated in gliomas. Transcriptomics data of glioblastoma multiforme (GBM), low-grade gliomas (LGGs), and controls were downloaded from The Cancer Genome Atlas (TCGA) data portal and further analyzed using BRB-Array tools. Expression levels of a few significantly altered proteins like lactate dehydrogenase, alpha-1 antitrypsin, fibrinogen alpha chain, nucleophosmin, annexin A5, thioredoxin, ferritin light chain, thymosin beta-4-like protein 3, superoxide dismutase-2, and peroxiredoxin-1 and 6 showed a positive correlation with increasing grade of gliomas thereby offering an insight into molecular basis behind their aggressive nature. Several proteins identified in different grades of gliomas are potential grade-specific markers, and perturbed pathways provide comprehensive overview of molecular cues involved in glioma

  6. Polymorphous low grade adenocarcinoma presenting an uncommon radiographic aspect.

    PubMed

    de Magalhães, M H C G; de Magalhães, R P; de Araújo, V C; de Sousa, S O M

    2006-05-01

    The aim of this study was to present clinical, histological and immunohistochemical aspects of a polymorphous low grade adenocarcinoma occurring in the mandible. A radiolucent tumour, located in the right mandible, was removed from a 40-year-old woman. Radiographic and CT exams revealed that the lesion expanded bucco-lingual cortical plates and presented an irregular scalloping of the bone. The surrounding lining mucosa was intact. The patient underwent total surgical removal of the lesion with an intraoperative biopsy. Histological diagnosis was polymorphous low-grade adenocarcinoma confirmed by immunohistochemical study. One-year follow up was uneventful. The accurate diagnosis of lesions presenting unusual clinical aspects, as the one presented here, is critical for correctly handling treatment.

  7. Low-Grade Myofibroblastic Sarcoma of the Larynx.

    PubMed

    Vlad, Diana; Albu, Silviu

    2016-05-01

    Low-grade myofibroblastic sarcoma is a malignant tumor of myofibroblasts, which has only recently become more clearly defined. It represents a rare entity that progresses in a slow-growing infiltrative pattern inside deep soft tissues. Due to its rarity and the plasticity of the myofibroblast, it can cause significant diagnostic difficulties. Differencing this neoplasm from other spindle cell tumors requires the use of ancillary techniques such as immunohistochemistry and/or electron microscopy. The authors report an unusual case of low-grade myofibroblastic sarcoma of the larynx in a 24-year-old woman, with atypical clinicopathologic presentation. The patient underwent direct laryngoscopy with excision of the malignant mass followed by adjuvant radiation therapy. The authors emphasize the uncommon location of this tumor type and discuss management options.

  8. Properties of concrete blocks prepared with low grade recycled aggregates.

    PubMed

    Poon, Chi-Sun; Kou, Shi-cong; Wan, Hui-wen; Etxeberria, Miren

    2009-08-01

    Low grade recycled aggregates obtained from a construction waste sorting facility were tested to assess the feasibility of using these in the production of concrete blocks. The characteristics of the sorted construction waste are significantly different from that of crushed concrete rubbles that are mostly derived from demolition waste streams. This is due to the presence of higher percentages of non-concrete components (e.g. >10% soil, brick, tiles etc.) in the sorted construction waste. In the study reported in this paper, three series of concrete block mixtures were prepared by using the low grade recycled aggregates to replace (i) natural coarse granite (10mm), and (ii) 0, 25, 50, 75 and 100% replacement levels of crushed stone fine (crushed natural granite <5mm) in the concrete blocks. Test results on properties such as density, compressive strength, transverse strength and drying shrinkage as well as strength reduction after exposure to 800 degrees C are presented below. The results show that the soil content in the recycled fine aggregate was an important factor in affecting the properties of the blocks produced and the mechanical strength deceased with increasing low grade recycled fine aggregate content. But the higher soil content in the recycled aggregates reduced the reduction of compressive strength of the blocks after exposure to high temperature due probably to the formation of a new crystalline phase. The results show that the low grade recycled aggregates obtained from the construction waste sorting facility has potential to be used as aggregates for making non-structural pre-cast concrete blocks.

  9. [Low grade parosteal osteosarcoma. Clinical and oncological outcomes].

    PubMed

    Albergo, José I; Farfalli, Germán L; Ayerza, Miguel A; Muscolo, Domingo L; Aponte-Tinao, Luis A

    2015-01-01

    The objective of the study was to analyze a group of patients with low grade parosteal osteosarcoma treated with limb salvage surgery and reconstructed with bone allograft. A retrospective review from our oncologic data base between 1980 and 2010 was done and all patients with diagnosis of low grade parosteal osteosarcoma, treated with limb salvage surgery and reconstructed with allograft were included. Twenty-two patients were included for the analysis. The mean age was 32±11 years (10-59) y the mean follow-up 93±69 months (8-237). Ten year overall survival of the series was 91% (95% CI: 79-100). Four patients developed local recurrence, 2 of them histological classified after the resection dedifferentiated parosteal osteosarcoma. Two patients developed distant recurrence, being the lung the only site of metastasis. Ten year limb salvage reconstruction survival was 65% (95% CI: 44-86). Long term survival rate in low grade parosteal osteosarcoma is over 90%. Surgical resection wide margin should be the elective treatment and biological limb salvage reconstruction is a good alternative.

  10. Recovery of Tungsten and Molybdenum from Low-Grade Scheelite

    NASA Astrophysics Data System (ADS)

    Li, Yongli; Yang, Jinhong; Zhao, Zhongwei

    2017-10-01

    With most high-quality tungsten ores being exhausted, the enhancement of low-grade scheelite concentrates processing has attracted a great deal of attention. The objective of this study is to develop a method to maximize the recovery tungsten and molybdenum from a low-grade scheelite via a new acid leaching process followed by solvent extraction. Under optimal conditions (350 g/L H2SO4, 95°C, and 2 h), approximately 99.8% of tungsten and 98% of molybdenum were leached out. In the subsequent solvent extraction process, more than 99% of the tungsten and molybdenum were extracted with a co-extraction system (50% TBP, 30% HDEHP, and 10% 2-octanol in kerosene) using a three-stage cross-flow extraction. The raffinate can be recycled for the next leaching process after replenishing the H2SO4 to the initial value (approximately 350 g/L). Based on these results, a conceptual flowsheet is presented to recover tungsten and molybdenum from the low-grade scheelite.

  11. Notch signaling activation in pediatric low-grade astrocytoma.

    PubMed

    Brandt, William D; Schreck, Karisa C; Bar, Eli E; Taylor, Isabella; Marchionni, Luigi; Raabe, Eric; Eberhart, Charles G; Rodriguez, Fausto J

    2015-02-01

    Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in the development, stem cell biology, and pathogenesis of several cancers, but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomic sites compared with non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res186 and Res259 using either RNA interference or a γ-secretase inhibitor resulted in variable, but significant, reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target.

  12. Notch Signaling Activation in Pediatric Low-Grade Astrocytoma

    PubMed Central

    Brandt, William D.; Schreck, Karisa C.; Bar, Eli E.; Taylor, Isabella; Marchionni, Luigi; Raabe, Eric; Eberhart, Charles G.; Rodriguez, Fausto J.

    2014-01-01

    Pilocytic astrocytoma (PA) is the most common primary brain tumor in children; various signaling pathways have been implicated in its biology. The Notch signaling pathway has been found to play a role in development, stem cell biology, and the pathogenesis of several cancers but its role in PA has not been investigated. We studied alterations in Notch signaling components in tumor tissue from 18 patients with PA and 4 with other low-grade astrocytomas to identify much needed therapeutic targets. We found that Notch pathway members were overexpressed at the mRNA (NOTCH1, NOTCH2, HEY1, HEY2) and protein (HES1) levels in PAs at various anatomical sites compared to non-neoplastic brain samples. These changes were not associated with specific BRAF alterations. Inhibiting the Notch pathway in the pediatric low-grade astrocytoma cell lines Res 186 and Res 259 using either RNA interference or a γ-secretase inhibitor resulted in variable but significant reduction in cell growth and migration. This study suggests a potential role for Notch signaling in pediatric low-grade astrocytoma tumorigenesis and that Notch signaling may be a viable pathway therapeutic target. PMID:25575134

  13. Diagnostic flow cytometry for low-grade myelodysplastic syndromes.

    PubMed

    Ogata, Kiyoyuki

    2008-12-01

    It has long been considered that flow cytometry (FCM) has little role in clinical practice in the diagnosis of myelodysplastic syndromes (MDS). However, recent advances in the analytical method and knowledge of MDS FCM are changing this stereotype. This paper reviews the concept and current status of FCM in the diagnosis of low-grade MDS. The diagnosis of low-grade MDS in the absence of ringed sideroblasts and chromosomal aberration is not always straightforward, and a report from a recent international working conference has proposed FCM as an adjunctive diagnostic test for such cases. Currently, only a limited number of laboratories are applying FCM to the diagnosis of MDS. Furthermore, standard analytical methods in FCM for MDS have not been established, and no single FCM parameter is sufficiently sensitive and specific to make the diagnosis of MDS. To establish MDS FCM as a widely accepted, dependable diagnostic tool, prospective studies should increase flow parameters that can be analysed reproducibly and determine their sensitivity and specificity, either alone or in combination. CD34+ cell-related parameters that are applicable for diagnosing low-grade MDS in many laboratories are introduced here.

  14. Recovery of Tungsten and Molybdenum from Low-Grade Scheelite

    NASA Astrophysics Data System (ADS)

    Li, Yongli; Yang, Jinhong; Zhao, Zhongwei

    2017-07-01

    With most high-quality tungsten ores being exhausted, the enhancement of low-grade scheelite concentrates processing has attracted a great deal of attention. The objective of this study is to develop a method to maximize the recovery tungsten and molybdenum from a low-grade scheelite via a new acid leaching process followed by solvent extraction. Under optimal conditions (350 g/L H2SO4, 95°C, and 2 h), approximately 99.8% of tungsten and 98% of molybdenum were leached out. In the subsequent solvent extraction process, more than 99% of the tungsten and molybdenum were extracted with a co-extraction system (50% TBP, 30% HDEHP, and 10% 2-octanol in kerosene) using a three-stage cross-flow extraction. The raffinate can be recycled for the next leaching process after replenishing the H2SO4 to the initial value (approximately 350 g/L). Based on these results, a conceptual flowsheet is presented to recover tungsten and molybdenum from the low-grade scheelite.

  15. High-grade focal areas in low-grade central osteosarcoma: high-grade or still low-grade osteosarcoma?

    PubMed

    Righi, Alberto; Paioli, Anna; Dei Tos, Angelo Paolo; Gambarotti, Marco; Palmerini, Emanuela; Cesari, Manuela; Marchesi, Emanuela; Donati, Davide Maria; Picci, Piero; Ferrari, Stefano

    2015-01-01

    High-grade foci (grade 3 according to Broder's grading system) are sometimes detected in low-grade (grade 1 and 2) central osteosarcoma. The aim of this study was to retrospectively evaluate the clinical outcome in patients upgraded to high grade (grade 3) after a first diagnosis of low-grade osteosarcoma, following the detection of high-grade areas (grade 3) in the resected specimen. Of the 132 patients with a diagnosis of low-grade central osteosarcoma at surgical biopsy at our Institute, 33 patients were considered eligible for the study. Median age was 37 (range 13-58 years). Location was in an extremity in 29 patients (88 %). Post-operative chemotherapy was given in 22 (67 %) patients. Follow-up data were available for all patients, with a median observation time of 115 months (range 4-322 months). After histological revision, areas of high-grade (grade 3) osteosarcoma accounting for less than 50 % of the tumor were found in 20 (61 %) patients, whereas the majority of the tumor was composed of a high-grade (grade 3) component in 13 (39 %) patients. In the 20 cases of low-grade osteosarcoma with high-grade foci (grade 3) in less than 50 % of the tumor, 9 patients did not receive adjuvant chemotherapy; only one of them died, of unrelated causes. In the adjuvant chemotherapy group (11 out of 20 patients), one patient developed multiple lung metastases and died of disease 39 months after the first diagnosis. In the other 13 cases of low-grade osteosarcoma with high-grade foci (grade 3) in more than 50 % of the tumor, 12 patients received adjuvant chemotherapy: 2 had recurrence, 4 developed multiple lung metastases and 3 died of disease. The only patient who did not receive chemotherapy is alive without disease 232 months after complete surgical remission. Our data indicate that patients with a diagnosis of low-grade osteosarcoma where the high-grade (grade 3) component is lower than 50 % of the resected specimen, may not require chemotherapy

  16. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    ClinicalTrials.gov

    2017-03-22

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  17. Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma.

    PubMed

    Qu, Min; Qiu, B O; Xiong, Wende; Chen, Dong; Wu, Anhua

    2015-05-01

    The aim of the present study was to determine the expression of a-disintegrin and metalloproteinase 10 (ADAM10) in human glioma tissues from surgical specimens and discuss its possible significance in glioma biology. A total of 43 glioma specimens obtained from patients between 2007 and 2010 were collected and a series of assays were performed. Of these, 22 cases were low-grade gliomas, while 21 cases were high-grade gliomas. In addition, 20 cases of meningioma were used as the control group. Reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry were used to determine the mRNA and protein expression levels of ADAM10. Besides the quantitative analysis, histological observations were also performed to localize ADAM10 expression in glioma cells. The RT-PCR and western blot analysis results demonstrated increased ADAM10 expression in the low-grade glioma samples compared with the control (P<0.05), while ADAM10 expression was further increased in the high-grade glioma samples (P<0.01 vs. control; P<0.05 vs. low-grade glioma), indicating that the mRNA and protein expression levels of ADAM10 were malignancy-dependent. The immunohistochemical analysis revealed that the ADAM10 protein was located on both the tumor cell membrane and blood vessel walls within tumor tissues. In conclusion, these results indicated that ADAM10 expression correlates with the grade of malignancy in human glioma from surgical specimens. In addition, the fact that ADAM10 protein was expressed on cell membranes and blood vessel walls within tumor tissues, indicates that its expression may be associated with invasive tumor growth and peritumoral edema formation.

  18. ENabling Reduction of Low-grade Inflammation in SEniors Pilot Study: Concept, Rationale, and Design.

    PubMed

    Manini, Todd M; Anton, Stephen D; Beavers, Daniel P; Cauley, Jane A; Espeland, Mark A; Fielding, Roger A; Kritchevsky, Stephen B; Leeuwenburgh, Christiaan; Lewis, Kristina H; Liu, Christine; McDermott, Mary M; Miller, Michael E; Tracy, Russell P; Walston, Jeremy D; Radziszewska, Barbara; Lu, Jane; Stowe, Cindy; Wu, Samuel; Newman, Anne B; Ambrosius, Walter T; Pahor, Marco

    2017-09-01

    To test two interventions to reduce interleukin (IL)-6 levels, an indicator of low-grade chronic inflammation and an independent risk factor for impaired mobility and slow walking speed in older adults. The ENabling Reduction of low-Grade Inflammation in SEniors (ENRGISE) Pilot Study was a multicenter, double-blind, placebo-controlled randomized pilot trial of two interventions to reduce IL-6 levels. Five university-based research centers. Target enrollment was 300 men and women aged 70 and older with an average plasma IL-6 level between 2.5 and 30 pg/mL measured twice at least 1 week apart. Participants had low to moderate physical function, defined as self-reported difficulty walking one-quarter of a mile or climbing a flight of stairs and usual walk speed of less than 1 m/s on a 4-m usual-pace walk. Participants were randomized to losartan, omega-3 fish oil (ω-3), combined losartan and ω-3, or placebo. Randomization was stratified depending on eligibility for each group. A titration schedule was implemented to reach a dose that was safe and effective for IL-6 reduction. Maximal doses were 100 mg/d for losartan and 2.8 g/d for ω-3. IL-6, walking speed over 400 m, physical function (Short Physical Performance Battery), other inflammatory markers, safety, tolerability, frailty domains, and maximal leg strength were measured. Results from the ENRGISE Pilot Study will provide recruitment yields, feasibility, medication tolerance and adherence, and preliminary data to help justify a sample size for a more definitive randomized trial. The ENRGISE Pilot Study will inform a larger subsequent trial that is expected to have important clinical and public health implications for the growing population of older adults with low-grade chronic inflammation and mobility limitations. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  19. BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas.

    PubMed

    Olow, Aleksandra; Mueller, Sabine; Yang, Xiaodong; Hashizume, Rintaro; Meyerowitz, Justin; Weiss, William; Resnick, Adam C; Waanders, Angela J; Stalpers, Lukas J A; Berger, Mitchel S; Gupta, Nalin; James, C David; Petritsch, Claudia K; Haas-Kogan, Daphne A

    2016-11-01

    Alteration of the BRAF/MEK/MAPK pathway is the hallmark of pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in the majority of these tumors. We investigated combinations of MEK1/2, BRAF(V600E) and mTOR inhibitors in gliomas carrying specific genetic alterations of the MAPK pathway. We used human glioma lines containing BRAF(V600E) (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric high-grade: SF188, SF9427, SF8628) and isogenic systems of KIAA1549:BRAF-expressing NIH/3T3 cells and BRAF(V600E)-expressing murine brain cells. Signaling inhibitors included everolimus (mTOR), PLX4720 (BRAF(V600E)), and AZD6244 (MEK1/2). Proliferation was determined using ATP-based assays. In vivo inhibitor activities were assessed in the BT40 PLGG xenograft model. In BRAF(V600E) cells, the three possible doublet combinations of AZD6244, everolimus, and PLX4720 exhibited significantly greater effects on cell viability. In BRAF(WT) cells, everolimus + AZD6244 was superior compared with respective monotherapies. Similar results were found using isogenic murine cells. In KIAA1549:BRAF cells, MEK1/2 inhibition reduced cell viability and S-phase content, effects that were modestly augmented by mTOR inhibition. In vivo experiments in the BRAF(V600E) pediatric xenograft model BT40 showed the greatest survival advantage in mice treated with AZD6244 + PLX4720 (P < 0.01). In BRAF(V600E) tumors, combination of AZD6244 + PLX4720 is superior to monotherapy and to other combinatorial approaches. In BRAF(WT) pediatric gliomas, everolimus + AZD6244 is superior to either agent alone. KIAA1549:BRAF-expressing tumors display marked sensitivity to MEK1/2 inhibition. Application of these results to PLGG treatment must be exercised with caution because the dearth of PLGG models necessitated only a single patient-derived PLGG (BT40) in this study. Clin Cancer Res; 22(21); 5312-21. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Introduction of novel semiquantitative evaluation of (99m)Tc-MIBI SPECT before and after treatment of glioma.

    PubMed

    Deltuva, Vytenis Pranas; Jurkienė, Nemira; Kulakienė, Ilona; Bunevičius, Adomas; Matukevičius, Algimantas; Tamašauskas, Arimantas

    2012-01-01

    BACKGROUND AND OBJECTIVE. There is a need for objective semiquantitative indexes for the evaluation of results of single-photon emission tomography (SPECT) in patients with brain glioma. The aim of this study was to validate the total size index (TSI) and total intensity index (TII) based on technetium-99m-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT scans to discriminate the patients with high-grade glioma versus low-grade glioma and to evaluate the changes of viable glioma tissue by the means of TSI and TII after surgery and after radiation treatment. MATERIAL AND METHODS. Thirty-two patients (mean age, 55 years [SD, 18]; 20 men) underwent a (99m)Tc-MIBI-SPECT scan before surgery. Of these patients, 27 underwent a postoperative (99m)Tc-MIBI-SPECT scan and 7 patients with grade IV glioma underwent a third (99m)Tc-MIBI-SPECT scan after radiation treatment. TII that corresponds to the area and intensity of tracer uptake and TSI that corresponds to the area of tracer uptake were calculated before surgery, after surgery, and after radiation treatment. RESULTS. The TII and TSI were found to be valid in discriminating the patients with high-grade versus low-grade glioma with optimal cutoff values of 3.0 and 2.5, respectively. Glioma grade correlated with the preoperative TSI score (r=0.76, P<0.001) and preoperative TII score (r=0.64, P<0.001). There was a significant decrease in the TII and TSI after surgery in patients with grade IV glioma. After radiation treatment, there was a significant increase in the TII in patients with grade IV glioma. CONCLUSIONS. TSI and TII were found to be reliable in discriminating the patients with high-grade versus low-grade glioma and allowed for the semiquantitative evaluation of change in viable glioma tissue after surgery and after radiation treatment in patients with grade IV glioma.

  1. Patterns of diagnostic marker assessment in adult diffuse glioma: a survey of the European Confederation of Neuropathological Societies (Euro-CNS)

    PubMed Central

    Woehrer, Adelheid; Kristensen, Bjarne W.; Vital, Anne; Hainfellner, Johannes A.

    2017-01-01

    The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field. Based on 130 responses from participants across 40 nations neuropathologists uniformly rate molecular marker testing as highly relevant and already incorporate molecular information in their diagnostic assessments. At the same time however, the survey documents substantial differences in access to crucial biomarkers and molecular techniques across geographic regions and within individual countries. Concerns are raised concerning the validity of test assays with MGMT, 1p19q, and ATRX; being perceived as most problematic. Neuropathologists advocate the need for international harmonization of standards and consensus guidelines, and the majority is willing to actively engage in interlaboratory trials aiming at quality control (Figure 1). PMID:27966427

  2. Patterns of diagnostic marker assessment in adult diffuse glioma: a survey of the European Confederation of Neuropathological Societies (Euro-CNS).

    PubMed

    Woehrer, Adelheid; Kristensen, Bjarne W; Vital, Anne; Hainfellner, Johannes A

    The 2016 update of the WHO classification has introduced an integrated diagnostic approach that incorporates both tumor morphology and molecular information. This conceptual change has far-reaching implications, especially for neuropathologists who are in the forefront of translating molecular markers to routine diagnostic use. Adult diffuse glioma is a prototypic example for a group of tumors that underwent substantial regrouping, and it represents a major workload for surgical neuropathologists. Hence, we conducted a survey among members of the European Confederation of Neuropathological Societies (Euro-CNS) in order to assess 1) the extent to which molecular markers have already been incorporated in glioma diagnoses, 2) which molecular techniques are in daily use, and 3) to set a baseline for future surveys in this field. Based on 130 responses from participants across 40 nations neuropathologists uniformly rate molecular marker testing as highly relevant and already incorporate molecular information in their diagnostic assessments. At the same time however, the survey documents substantial differences in access to crucial biomarkers and molecular techniques across geographic regions and within individual countries. Concerns are raised concerning the validity of test assays with MGMT, 1p19q, and ATRX; being perceived as most problematic. Neuropathologists advocate the need for international harmonization of standards and consensus guidelines, and the majority is willing to actively engage in interlaboratory trials aiming at quality control (Figure 1).
.

  3. Stereotactic biopsy in gliomas guided by 3-tesla 1H-chemical-shift imaging of choline.

    PubMed

    Hermann, Elvis J; Hattingen, Elke; Krauss, Joachim K; Marquardt, Gerhard; Pilatus, Ulrich; Franz, Kea; Setzer, Matthias; Gasser, Thomas; Tews, Dominique S; Zanella, Friedhelm E; Seifert, Volker; Lanfermann, Heinrich

    2008-01-01

    To investigate chemical-shift imaging (CSI) to guide stereotactic biopsy of the choline 'hot spot' in cerebral lesions suggestive of low-grade glioma. Nine patients with hyperintense lesions on T(2)-weighted images of standard magnetic resonance imaging without contrast enhancement underwent advanced magnetic resonance studies. These studies included 3-dimensional T(1)-weighted sequences with contrast enhancement and 2-dimensional (1)H-CSI spectroscopy at 3 T. Signal intensity maps with relative signal intensities for choline were generated. The region with the highest choline signal intensity (the hot spot) was chosen as the target for stereotactic biopsy. The histopathological results were correlated with the increase in choline. All spectroscopic data were of sufficient quality. In 5 instances the neuropathological diagnosis was grade II glioma, according to the WHO classification, and in 4 instances it was grade III glioma. According to the CSI criteria, all grade III gliomas and 4 of the 5 grade II gliomas were classified correctly. One grade II glioma was overestimated by CSI as a high-grade glioma. (1)H-CSI-guided stereotactic biopsy may offer advantages as compared to conventional stereotactic biopsy. The biopsy of the choline hot spot in suggestive low-grade gliomas may help to identify focal points of higher tumor malignancy independent of contrast enhancement. Copyright 2008 S. Karger AG, Basel.

  4. Factors Influencing Neurocognitive Outcomes in Young Patients With Benign and Low-Grade Brain Tumors Treated With Stereotactic Conformal Radiotherapy

    SciTech Connect

    Jalali, Rakesh; Mallick, Indranil; Dutta, Debnarayan

    2010-07-15

    Purpose: To present the effect of radiotherapy doses to different volumes of normal structures on neurocognitive outcomes in young patients with benign and low-grade brain tumors treated prospectively with stereotactic conformal radiotherapy (SCRT). Methods and Materials: Twenty-eight patients (median age, 13 years) with residual/progressive brain tumors (10 craniopharyngioma, 8 cerebellar astrocytoma, 6 optic pathway glioma and 4 cerebral low-grade glioma) were treated with SCRT to a dose of 54 Gy in 30 fractions over 6 weeks. Prospective neuropsychological assessments were done at baseline before RT and at subsequent follow-up examinations. The change in intelligence quotient (IQ) scores was correlated with various factors, including dose-volume to normal structures. Results: Although the overall mean full-scale IQ (FSIQ) at baseline before RT remained unchanged at 2-year follow-up after SCRT, one third of patients did show a >10% decline in FSIQ as compared with baseline. Logistic regression analysis demonstrated that patients aged <15 years had a significantly higher chance of developing a >10% drop in FSIQ than older patients (53% vs. 10%, p = 0.03). Dosimetric comparison in patients showing a >10% decline vs. patients showing a <10% decline in IQ revealed that patients receiving >43.2 Gy to >13% of volume of the left temporal lobe were the ones to show a significant drop in FSIQ (p = 0.048). Radiotherapy doses to other normal structures, including supratentorial brain, right temporal lobe, and frontal lobes, did not reveal any significant correlation. Conclusion: Our prospectively collected dosimetric data show younger age and radiotherapy doses to left temporal lobe to be predictors of neurocognitive decline, and may well be used as possible dose constraints for high-precision radiotherapy planning.

  5. Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas—a Pediatric Brain Tumor Consortium study

    PubMed Central

    Gururangan, Sridharan; Fangusaro, Jason; Poussaint, Tina Young; McLendon, Roger E.; Onar-Thomas, Arzu; Wu, Shengjie; Packer, Roger J.; Banerjee, Anu; Gilbertson, Richard J.; Fahey, Frederic; Vajapeyam, Sridhar; Jakacki, Regina; Gajjar, Amar; Goldman, Stewart; Pollack, Ian F.; Friedman, Henry S.; Boyett, James M.; Fouladi, Maryam; Kun, Larry E.

    2014-01-01

    Background A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival. Methods Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9). Results Thirty-five evaluable patients (median age 8.4 y [range, 0.6–17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2–26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1–17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6–49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE ± 5.96%) and 47.8% (SE ± 9.27%), respectively. The commonest toxicities related to BVZ included grades 1–2 hypertension in 24, grades 1–2 fatigue in 23, grades 1–2 epistaxis in 18, and grades 1–4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037). Conclusion The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas. PMID:24311632

  6. Changes in brain glioma incidence and laterality correlates with use of mobile phones--a nationwide population based study in Israel.

    PubMed

    Barchana, Micha; Margaliot, Menahem; Liphshitz, Irena

    2012-01-01

    Mobile phones are in extensive use worldwide and concerns regarding their role in tumor formation were raised. Over the years multiple studies were published in order to investigate this issue using several approaches. The current study looks at secular trends of brain gliomas (low and high grade) incidence and changes in tumor's laterality over 30 years in a population extensively using this technology with a possible correlation to the spread of use of mobile phones. All brain gliomas that were diagnosed from 1980-2009 were included and subdivided into two groups--low and high grade. Secular and periodic time trend analyses of incidence rates and changes in laterality were performed. Preferred side of head using mobile phones was assessed with a questionnaire in a sample of adult individuals. A decrease in incidence of low grade giomas (LGG) that correlated with introduction of mobile technology was found from 2.57, 2.34 and 2.79 for every 100,000 in the period 1980 to the end of 1994 to 1.72, 1.82 and 1.57, respectively, over the last three 5-years periods (1995-2009). High-grade glioma incidences increased significantly from 1980-2009 but in the period after mobile phones were introduced (1994-2009) a lower, non significant, rate of increase was observed in males and a lower one (significant) in females. A shift towards left sided tumor location for all adult gliomas combined and separately for LGG and HGG was noted from 1995 onward. The shift was more marked for those who were diagnosed in ages 20-49 (p=0.03). We found a statistically significant decrease in LGG's over 30-years period that correlates with introducing of mobile phones technology and a shift in laterality towards left-sided tumors, the latter occurred in both low and high-grade gliomas.

  7. Decompression without Fusion for Low-Grade Degenerative Spondylolisthesis

    PubMed Central

    Cheung, Jason Pui Yin; Cheung, Prudence Wing Hang; Cheung, Kenneth Man Chee

    2016-01-01

    Study Design Retrospective series. Purpose Assess results of decompression-only surgery for low-grade degenerative spondylolisthesis with consideration of instability. Overview of Literature There is no consensus on whether fusion or decompression-only surgery leads to better outcomes for patients with low-grade degenerative spondylolisthesis. Current trends support fusion but many studies are flawed due to over-generalization without consideration of radiological instability and their variable presentations and natural history. Methods Patients with surgically treated degenerative spondylolisthesis from 1990–2013 were included. Clinical and radiological instability measures were included. Any residual or recurrence of symptoms, revision surgery performed and functional outcome scores including the numerical global rate of change scale, visual analogue scale, and modified Barthel index were measured. Follow-up periods for patients were divided into short-term (<5 years), mid-term (5–10 years) and long-term (>10 years). Results A total of 64 patients were recruited. Mechanical low back pain was noted in 48 patients and most (85.4%) had relief of back pain postoperatively. Radiological instability was noted in 4 subjects by flexion-extension radiographs and 12 subjects with prone traction radiographs by increased disc height and reduction of olisthesis and slip angle. From the results of the short-term, mid-term and long-term follow-up, reoperation only occurred within the first 5-year follow-up period. All functional scores improved from preoperative to postoperative 1-year follow-up. Conclusions Decompression-only for low-grade degenerative spondylolisthesis has good long-term results despite instability. Further higher-level studies should be performed on this patient group with radiological instability to suggest the superior surgical option. PMID:26949462

  8. Low-grade myofibroblastic sarcoma of the palate.

    PubMed

    Yamada, Tomohiro; Yoshimura, Tomohide; Kitamura, Naoya; Sasabe, Eri; Ohno, Seiji; Yamamoto, Tetsuya

    2012-09-01

    Low-grade myofibroblastic sarcoma (LGMS) is a rare, malignant tumor with myofibroblastic differentiation. Despite it being classified as a distinct entity by the World Health Organization, a few cases were reported in the oral and maxillofacial region. Here, a LGMS developed on the palate of a 73-year-old man who presented with a 1-cm tumor on the posterior border of the palate. Based on the histological and immunohistochemical features, a diagnosis of LGMS was established. The tumor was resected, and no recurrence was observed over 2 years. Although the tongue is the most preferred site for LGMS, it may occur in any region of the oral cavity.

  9. Low-grade myofibroblastic sarcoma of the oral cavity.

    PubMed

    Demarosi, Frederica; Bay, Alessandro; Moneghini, Laura; Carrassi, Antonio

    2009-08-01

    Two cases of low-grade myofibroblastic sarcoma (LGMS) are presented: one of lateral tongue, the other of lower buccal vestibule. LGMS represents a distinct atypical myofibroblastic tumor that occurs in several sites, primarily within the head and neck regions. A painless, enlarging mass is the most common clinical presentation, but a definitive diagnosis requires both histopathological and immunohistochemical analyses. Histologically, LGMS commonly presents as a cellular lesion composed of spindle-shaped tumor cells arranged primarily in fascicles with a diffusely infiltrative pattern. Immunohistochemically, LGMS shows positive staining for at least one myogenic marker, such as desmin, and muscle actin.

  10. Experimental Study on Purification of Low Grade Diatomite

    NASA Astrophysics Data System (ADS)

    Xiao, Liguang; Pang, Bo

    2017-04-01

    This paper presented an innovation for purification of low grade diatomite(DE) by grinding, ultrasonic pretreatment, acid leaching of closed stirring and calcination. The optimum process parameters of DE purification were obtained, the characterizations of original and purified DE were determined by SEM and BET. The results showed that the specific surface area of DE increased from 12.65m2/g to 23.23m2/g, which increased by 45.54%. SEM analysis revealed that the pore structure of purified DE was dredged highly.

  11. Intrinsic tectal low grade astrocytomas: is surgical removal an alternative treatment? Long-term outcome of eight cases.

    PubMed

    Ramina, Ricardo; Coelho Neto, Mauricio; Fernandes, Yvens Barbosa; Borges, Guilherme; Honorato, Donizeti Cesar; Arruda, Walter Oleschko

    2005-03-01

    Low-grade gliomas arising in dorsal midbrain in children and young patients usually present few neurological symptoms and findings, and patients management is controversial. Some authors propose only clinical observation until the patient present signs of increased intracranial pressure when a shunt with or without biopsy, is inserted; others recommend radiotherapy after stereotactic or open biopsy. Microsurgical total removal of tumor may be curative. We present a retrospective analysis of eight patients (mean age 16.6 +/- 11.5 years-old) with low-grade astrocytoma of the tectal region operated on using an infratentorial/supracerebellar approach between 1981 and 2002. All patients presented hydrocephalus and had a shunt insertion before surgical resection of the lesion. The tumour could be totally resected in seven patients. In one case radical removal was not possible due to infiltrative pattern of the lesion. Postoperative radiotherapy was performed in two cases, one patient at the beginning of this series and in the case with infiltrative tumor. This patient presented progressive tumor growth and died five years after surgery. No recurrence occurred after total removal. Post-surgical follow-up time ranged from 2 1/2 to 22 1/2 years (mean 9.9 +/- 5.9 years). Radical microsurgical removal of non invasive tumors is possible without mortality or significant morbidity. It may be curative and should remain as an alternative to be discussed with the patient.

  12. Improving vaccine efficacy against malignant glioma

    PubMed Central

    Ladomersky, Erik; Genet, Matthew; Zhai, Lijie; Gritsina, Galina; Lauing, Kristen L.; Lulla, Rishi R.; Fangusaro, Jason; Lenzen, Alicia; Kumthekar, Priya; Raizer, Jeffrey J.; Binder, David C.; James, C. David; Wainwright, Derek A.

    2016-01-01

    ABSTRACT The effective treatment of adult and pediatric malignant glioma is a significant clinical challenge. In adults, glioblastoma (GBM) accounts for the majority of malignant glioma diagnoses with a median survival of 14.6 mo. In children, malignant glioma accounts for 20% of primary CNS tumors with a median survival of less than 1 y. Here, we discuss vaccine treatment for children diagnosed with malignant glioma, through targeting EphA2, IL-13Rα2 and/or histone H3 K27M, while in adults, treatments with RINTEGA, Prophage Series G-100 and dendritic cells are explored. We conclude by proposing new strategies that are built on current vaccine technologies and improved upon with novel combinatorial approaches. PMID:27622066

  13. Polymorphous low grade adenocarcinoma: review and case report.

    PubMed

    Pintor, María Fernanda; Figueroa, Liberto; Martínez, Benjamín

    2007-12-01

    Polymorphous Low-Grade Adenocarcinoma is a rare, malignant salivary gland tumor, which is found almost exclusively in minor salivary glands. It is more frequent in the age range from 30 to 70, with a clear female predilection in a 2:1 ratio. It is usually located in the hard or soft palate, although it may be found in the rest of the oral cavity too. It is rare in major salivary glands. In general it has good prognosis, with recurrence rates in the range of 17% - 24%. Although rare, metastasis to regional lymph nodes may occur in 9% of the cases. This report describes the case of a patient that consulted at the Military Odontological Center (Central Odontológica del Ejército) due to an esthetic alteration of her dental prosthesis, which had been made 8 years before. The patient was sent to the Maxillofacial Surgery Service, where the intraoral examination showed a big mass compromising the hard palate and the alveolar ridge. During examination, a dent in her prosthesis was found to correspond to the tumor mass; it was therefore concluded that the tumor had at least an eight-year-old evolution. An incisional biopsy was carried out, and once the polymorphous low-grade adenocarcinoma diagnosis had been stated, the patient was sent to the Head and Neck Surgery Service of the Military Hospital, where the lesion was treated by wide surgical excision followed by radiation therapy.

  14. Ethanol and other oxygenateds from low grade carbonaceous resources

    SciTech Connect

    Joo, O.S.; Jung, K.D.; Han, S.H.

    1995-12-31

    Anhydrous ethanol and other oxygenates of C2 up can be produced quite competitively from low grade carbonaceous resources in high yield via gasification, methanol synthesis, carbonylation of methanol an hydrogenation consecutively. Gas phase carbonylation of methanol to form methyl acetate is the key step for the whole process. Methyl acetate can be produced very selectively in one step gas phase reaction on a fixed bed column reactor with GHSV over 5,000. The consecutive hydrogenation of methyl or ethyl acetate produce anhydrous ethanol in high purity. It is also attempted to co-produce methanol and DME in IGCC, in which low grade carbonaceous resources are used as energy sources, and the surplus power and pre-power gas can be stored in liquid form of methanol and DME during base load time. Further integration of C2 up oxygenate production with IGCC can improve its economics. The attempt of above extensive technology integration can generate significant industrial profitability as well as reduce the environmental complication related with massive energy consumption.

  15. Low-grade fibrosarcoma of the proximal humerus.

    PubMed

    Saito, Tsuyoshi; Oda, Yoshinao; Tanaka, Kazuhiro; Matsuda, Shuichi; Sakamoto, Akio; Yamamoto, Hidetaka; Iwamoto, Yukihide; Tsuneyoshi, Masazumi

    2003-02-01

    We present the clinical, radiographical and pathological features of low-grade fibrosarcoma of the left proximal humerus in a 23-year-old man in whom it was necessary to distinguish the tumor from desmoplastic fibroma, malignant fibrous histiocytoma and intramedullary well-differentiated osteosarcoma. The patient presented with a 10-day history of pain in his left upper arm sustained when trying to break his fall with his left hand when slipping in the street. Plain radiography revealed an expanding multilobular osteolytic lesion from the proximal metaphysis to the diaphysis of his left humerus, accompanied by a pathological fracture at the distal portion of the lesion. Open biopsy of the lesion was performed twice; however, a conclusive diagnosis could not be obtained. The patient underwent wide excision and prosthetic replacement of the left proximal humerus. Histologically, the resected tumor was composed of both cellular areas and hypocellular areas. Cellular areas revealed a proliferation of bundles of uniform fibroblastic spindle-shaped cells with minimal cellular atypia, mixed with abundant intercellular collagenization. Mitotic figures were occasionally seen. Hypocellular areas showed myxoid features with loose bundles of collagen fibers. The patient demonstrates no evidence of disease 42 months after surgery. It is important to detect the scant atypical cells for the differential diagnosis of low-grade fibrosarcoma and desmoplastic fibroma of bone.

  16. Low-grade serous carcinoma: new concepts and emerging therapies.

    PubMed

    Romero, Ignacio; Sun, Charlotte C; Wong, Kwong K; Bast, Robert C; Gershenson, David M

    2013-09-01

    For the past several years, all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance leading to separate clinical trials for patients with this subtype originating from the Gynecologic Oncology Group's Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20-40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare - about 5%. Primary treatment of low-grade serous carcinoma includes surgery+platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormonal therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Assessment of low-grade hepatic encephalopathy: a critical analysis.

    PubMed

    Kircheis, Gerald; Fleig, Wolfgang E; Görtelmeyer, Roman; Grafe, Susanne; Häussinger, Dieter

    2007-11-01

    The value of paper-pencil tests and West-Haven-criteria for assessment of low-grade hepatic encephalopathy under conditions of a randomized, double-blind, placebo-controlled, clinical trial was evaluated in a cohort of 217 cirrhotics. Patients were graded at least twice clinically for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery. Re-evaluation of the study documentation showed that at study entry 33% and during the study even 50% of the patients were wrongly allocated to minimal or overt hepatic encephalopathy. Despite the participating physicians' training, 31% of the number-connection-tests-A, 20% of the number-connection-tests-B and 28% of the line-tracing-test were in retrospect considered invalid by an independent psychologist. Neither the Portosystemic-Encephalopathy-Syndrome (PSE) test nor the Psychometric-Hepatic-Encephalopathy-Sum (PHES)-score reliably picked up clinical improvement in the individual patient. Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy, the clinical classification of individual patients into one of the groups will have a high rate of error. The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test. Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven-criteria and paper-pencil tests including related scores for quantification of low-grade HE at least in multicenter approaches.

  18. Elderly people with low body weight may have subtle low-grade inflammation.

    PubMed

    Nakajima, Kei; Yamaoka, Hiroko; Morita, Kumiko; Ebata, Midori; Eguchi, Satoko; Muneyuki, Toshitaka; Munakata, Hiromi

    2009-04-01

    Low-grade inflammation, which plays important roles in the development of fatal diseases, is commonly observed in obese people. However, this has not been evaluated in lean people, who have relatively increased mortality risk compared with people of normal weight. Here, we elucidate the association between systemic low-grade inflammation and low body weight, with particular emphasis on aging. We examined the relationship between circulating C-reactive protein (CRP) and BMI in a cross-sectional study of 2,675 apparently healthy adults who had undergone a medical check-up. Overall, subjects with low BMI (<21.0 kg/m(2), n = 585) showed a favorable cardiovascular profile without being undernourished. In the elderly (>or=55 years old), logarithmic CRP (LogCRP) showed a sigmoid curve against BMI with a base at BMI 21.0-22.9 kg/m(2), but not against waist circumference (WC), even in nonsmokers. In contrast, in middle-aged people, LogCRP showed an almost linear relationship with both BMI and WC. LogCRP levels in elderly nonsmokers with low BMI, but not normal or high BMI, were significantly higher than those in middle-aged with corresponding BMI (P < 0.05). After adjustment for age, sex, smoking status, and weight change over the past 2 years, the adjusted means of LogCRP still had a similar sigmoid curve against BMI in the elderly. These results suggest that elderly people with low body weight may have subtle low-grade inflammation irrespective of a favorable cardiovascular risk, which remains to be confirmed in further studies.

  19. [Histological and molecular classification of gliomas].

    PubMed

    Figarella-Branger, D; Colin, C; Coulibaly, B; Quilichini, B; Maues De Paula, A; Fernandez, C; Bouvier, C

    2008-01-01

    Gliomas are the most frequent tumors of the central nervous system. The WHO classification, based on the presumed cell origin, distinguishes astrocytic, oligodendrocytic and mixed gliomas. A grading system is based on the presence of the following criteria: increased cellular density, nuclear atypias, mitosis, vascular proliferation and necrosis. The main histological subtype of grade I gliomas are pilocytic astrocytomas, which are benign. Diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas are low-grade (II) or high-grade (III and IV) tumors. Glioblastomas correspond to grade IV astrocytomas. C. Daumas-Duport et al. have proposed another classification based on histology and imaging data, which distinguishes oligodendrogliomas and mixed gliomas of grade A (without endothelial proliferation and/or contrast enhancement), oligodendrogliomas and mixed gliomas of grade B (with endothelial proliferation or contrast enhancement), glioblastomas and glioneuronal malignant tumors. Both classifications lack reproducibility. Many studies have searched for a molecular classification. Recurrent abnormalities in gliomas have been found. They encompassed recurrent chromosomal alterations, such as lost of chromosome 10, gain of chromosome 7, deletion of chromosome 1p and 19q, but also activation of the Akt pathway (amplification of EGFR), dysregulation of the cell cycle (deletion of p16, p53). These studies have enabled the description of two molecular subtypes for glioblastomas. De novo glioblastomas, which occur in young patients without of a prior history of brain tumor and harbor frequent amplification of EGFR, deletion of p16 and mutation of PTEN while mutation of p53 is infrequent. Secondary glioblastomas occur in the context of a preexisting low-grade glioma and are characterized by more frequent mutation of p53. On the other side, combined complete deletion of 1p and 19q as the result of the translocation t(1;19)(q10;p10) is highly specific of oligodendrogliomas

  20. The SHOLO mill: make pallet parts and pulp chips from low-grade hardwoods

    Treesearch

    Hugh W. Reynolds; Charles J. Gatchell; Charles J. Gatchell

    1970-01-01

    SHOLO (from SHOrt Log) is a new solution to the old problem of profitably converting low-grade hardwood logs into products or product parts. It does away with the traditional and often uneconomical procedure of sawing low-grade logs into standard lumber and then converting this standard lumber into product parts. Instead, the SHOLO process is used to convert low-grade...

  1. Characterizing the adoption of low-grade hardwood lumber by the secondary wood processing industry

    Treesearch

    Robert L. Smith; Wibke Pohle; Philip Araman; Dan Cumbo

    2004-01-01

    This study investigated the adoption of low-grade lumber in the secondary hardwood industry. Factors influencing decisions regarding the utilization of low-grade lumber were identified and value-added opportunities to increase the use of low-grade lumber among manufacturers currently using higher grades were evaluated. Data were collected via a nationwide mail survey...

  2. Drug-Loaded Nanoparticle Systems And Adult Stem Cells: A Potential Marriage For The Treatment Of Malignant Glioma?

    PubMed Central

    Auffinger, Brenda; Morshed, Ramin; Tobias, Alex; Cheng, Yu; Ahmed, Atique U; Lesniak, Maciej S

    2013-01-01

    Despite all recent advances in malignant glioma research, only modest progress has been achieved in improving patient prognosis and quality of life. Such a clinical scenario underscores the importance of investing in new therapeutic approaches that, when combined with conventional therapies, are able to effectively eradicate glioma infiltration and target distant tumor foci. Nanoparticle-loaded delivery systems have recently arisen as an exciting alternative to improve targeted anti-glioma drug delivery. As drug carriers, they are able to efficiently protect the therapeutic agent and allow for sustained drug release. In addition, their surface can be easily manipulated with the addition of special ligands, which are responsible for enhancing tumor-specific nanoparticle permeability. However, their inefficient intratumoral distribution and failure to target disseminated tumor burden still pose a big challenge for their implementation as a therapeutic option in the clinical setting. Stem cell-based delivery of drug-loaded nanoparticles offers an interesting option to overcome such issues. Their ability to incorporate nanoparticles and migrate throughout interstitial barriers, together with their inherent tumor-tropic properties and synergistic anti-tumor effects make these stem cell carriers a good fit for such combined therapy. In this review, we will describe the main nanoparticle delivery systems that are presently available in preclinical and clinical studies. We will discuss their mechanisms of targeting, current delivery methods, attractive features and pitfalls. We will also debate the potential applications of stem cell carriers loaded with therapeutic nanoparticles in anticancer therapy and why such an attractive combined approach has not yet reached clinical trials. PMID:23594406

  3. Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation.

    PubMed

    Jiang, Rifeng; Jiang, Jingjing; Zhao, Lingyun; Zhang, Jiaxuan; Zhang, Shun; Yao, Yihao; Yang, Shiqi; Shi, Jingjing; Shen, Nanxi; Su, Changliang; Zhang, Ju; Zhu, Wenzhen

    2015-12-08

    Conventional diffusion imaging techniques are not sufficiently accurate for evaluating glioma grade and cellular proliferation, which are critical for guiding glioma treatment. Diffusion kurtosis imaging (DKI), an advanced non-Gaussian diffusion imaging technique, has shown potential in grading glioma; however, its applications in this tumor have not been fully elucidated. In this study, DKI and diffusion weighted imaging (DWI) were performed on 74 consecutive patients with histopathologically confirmed glioma. The kurtosis and conventional diffusion metric values of the tumor were semi-automatically obtained. The relationships of these metrics with the glioma grade and Ki-67 expression were evaluated. The diagnostic efficiency of these metrics in grading was further compared. It was demonstrated that compared with the conventional diffusion metrics, the kurtosis metrics were more promising imaging markers in distinguishing high-grade from low-grade gliomas and distinguishing among grade II, III and IV gliomas; the kurtosis metrics also showed great potential in the prediction of Ki-67 expression. To our best knowledge, we are the first to reveal the ability of DKI to assess the cellular proliferation of gliomas, and to employ the semi-automatic method for the accurate measurement of gliomas. These results could have a significant impact on the diagnosis and subsequent therapy of glioma.

  4. Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation

    PubMed Central

    Zhao, Lingyun; Zhang, Jiaxuan; Zhang, Shun; Yao, Yihao; Yang, Shiqi; Shi, Jingjing; Shen, Nanxi; Su, Changliang; Zhang, Ju; Zhu, Wenzhen

    2015-01-01

    Conventional diffusion imaging techniques are not sufficiently accurate for evaluating glioma grade and cellular proliferation, which are critical for guiding glioma treatment. Diffusion kurtosis imaging (DKI), an advanced non-Gaussian diffusion imaging technique, has shown potential in grading glioma; however, its applications in this tumor have not been fully elucidated. In this study, DKI and diffusion weighted imaging (DWI) were performed on 74 consecutive patients with histopathologically confirmed glioma. The kurtosis and conventional diffusion metric values of the tumor were semi-automatically obtained. The relationships of these metrics with the glioma grade and Ki-67 expression were evaluated. The diagnostic efficiency of these metrics in grading was further compared. It was demonstrated that compared with the conventional diffusion metrics, the kurtosis metrics were more promising imaging markers in distinguishing high-grade from low-grade gliomas and distinguishing among grade II, III and IV gliomas; the kurtosis metrics also showed great potential in the prediction of Ki-67 expression. To our best knowledge, we are the first to reveal the ability of DKI to assess the cellular proliferation of gliomas, and to employ the semi-automatic method for the accurate measurement of gliomas. These results could have a significant impact on the diagnosis and subsequent therapy of glioma. PMID:26544514

  5. Current surgical results with low-grade arteriovenous malformations

    PubMed Central

    Potts, Matthew B.; Lau, Darryl; Abla, Adib A.; Kim, Helen; Young, William L.; Lawton, Michael T.

    2015-01-01

    OBJECTIVE Surgical resection is an appealing therapy for brain arteriovenous malformations (AVM) because of its high cure rate, low complication rate, and immediacy, becoming the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of ARUBA, we reviewed an experience with low-grade AVMs, the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA’s randomization process. METHODS A prospective AVM registry was searched to identify patients with Spetzler-Martin grade I and II AVMs treated with surgical resection during a 16-year period. RESULTS Of the 232 surgical patients included, 117 (50%) presented with hemorrhage, 33% had Spetzler-Martin grade I, and 67% had grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (mRS 0–1) were found in 78% of patients with 97% improved or unchanged from their pre-operative mRS scores. Unruptured AVM patients had better functional outcomes (91% good outcome compared to 65% in the ruptured group, p=0.0008), while relative outcomes were equivalent (98% improved/unchanged in ruptured AVM patients versus 96% in unruptured AVM patients). CONCLUSION Surgery should be regarded as the “gold standard” therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in both ruptured and unruptured patients support a dominant surgical posture, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate

  6. Evaluation of Eight Plasma Proteins as Candidate Blood-Based Biomarkers for Malignant Gliomas

    PubMed Central

    Lange, Ryan P.; Everett, Allen; Dulloor, Pratima; Korley, Frederick K.; Bettegowda, Chetan; Blair, Cherie; Grossman, Stuart A.; Holdhoff, Matthias

    2015-01-01

    Eight brain-derived proteins were evaluated regarding their potential for further development as a blood-based biomarker for malignant gliomas. Plasma levels for glial fibrillary acidic protein, neurogranin, brain-derived neurotrophic factor, intracellular adhesion molecule 5, metallothionein-3, beta-synuclein, S100 and neuron specific enolase were tested in plasma of 23 patients with high-grade gliomas (WHO grade IV), 11 low-grade gliomas (WHO grade II), and 15 healthy subjects. Compared to the healthy controls, none of the proteins appeared to be specific for glioblastomas. However, the data are suggestive of higher protein levels in gliosarcomas (n = 2), which may deserve further exploration. PMID:25019213

  7. Frontal brain asymmetry, childhood maltreatment, and low-grade inflammation at midlife.

    PubMed

    Hostinar, Camelia E; Davidson, Richard J; Graham, Eileen K; Mroczek, Daniel K; Lachman, Margie E; Seeman, Teresa E; van Reekum, Carien M; Miller, Gregory E

    2017-01-01

    Frontal EEG asymmetry is thought to reflect variations in affective style, such that greater relative right frontal activity at rest predicts enhanced emotional responding to threatening or negative stimuli, and risk of depression and anxiety disorders. A diathesis-stress model has been proposed to explain how this neuro-affective style might predispose to psychopathology, with greater right frontal activity being a vulnerability factor especially under stressful conditions. Less is known about the extent to which greater relative right frontal activity at rest might be associated with or be a diathesis for deleterious physical health outcomes. The present study examined the association between resting frontal EEG asymmetry and systemic, low-grade inflammation and tested the diathesis-stress model by examining whether childhood maltreatment exposure interacts with resting frontal asymmetry in explaining inflammation. Resting EEG, serum inflammatory biomarkers (interleukin-6, C-reactive protein, and fibrinogen) and self-reported psychological measures were available for 314 middle-aged adults (age M=55.3years, SD=11.2, 55.7% female). Analyses supported the diathesis-stress model and revealed that resting frontal EEG asymmetry was significantly associated with inflammation, but only in individuals who had experienced moderate to severe levels of childhood maltreatment. These findings suggest that, in the context of severe adversity, a trait-like tendency towards greater relative right prefrontal activity may predispose to low-grade inflammation, a risk factor for conditions with inflammatory underpinnings such as coronary heart disease.

  8. Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas.

    PubMed

    de la Fuente, Cristian; Pumarola, Martí; Blasco, Ester; Fernández, Francisco; Viu, Judit; Añor, Sònia

    2014-06-01

    In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.

  9. Reductive Leaching of Low-Grade Pyrolusite with Formic Acid

    NASA Astrophysics Data System (ADS)

    Lu, Youzhi; Ma, Huaju; Huang, Runjun; Yuan, Aiqun; Huang, Zengwei; Zhou, Zeguang

    2015-08-01

    The extraction of manganese from low-grade pyrolusite is investigated using formic acid as reductant in sulfuric acid medium. The effects of volumes of formic acid, concentration of sulfuric acid, liquid to solid ratio (L/S), leaching time, and temperature on leaching efficiency of manganese, iron, and aluminum are valuated with single-factor experiments. The results show that the leaching efficiency of manganese reached 90.08 pct with 80.70 pct of iron and 31.55 pct of aluminum under the optical conditions: 15 pct H2SO4(v/v) 60 ml, 4 ml formic acid, and 2 hours leaching time at 363 K (90 °C).

  10. Persistent low-grade inflammation and regular exercise.

    PubMed

    Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2 diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise.

  11. Low-grade heat recuperation by the organic Rankine cycle

    NASA Astrophysics Data System (ADS)

    Verneau, A.

    1980-11-01

    The use of an organic Rankine cycle engine in the conversion of low-grade industrial waste heat into mechanical energy is examined. The principles of a Rankine system using a vapor as the working fluid at operating temperatures from 100 to 500 C are presented, and the advantages of using organic vapors rather than water in the Rankine cycle are pointed out. Attention is then given to the Rankine cycle itself, the organic fluids employed, the multistage low-power turbines and the evaporator, which acts as a countercurrent heat exchanger. Economic aspects of the use of Rankine cycle systems for industrial waste heat recovery are then considered, and examples are presented of the calculation of power recovered and investment costs for the examples of heat recovery from diesel exhaust and from low-pressure steam.

  12. Interaction of low-grade metamorphic coals with methanol

    SciTech Connect

    S.I. Zherebtsov

    2007-06-15

    How conditions of alkylation of low-grade metamorphic coals with methanol in the presence of benzenesulfonic acid influence the yield of extractable matter was experimentally studied and relevant regression equations were obtained. It was shown that catalytic methylation considerably increases the yield of the extractable matter, as well as reducing the thermal stability of modified samples and alters the elemental composition of the samples and their extracts. A possible mechanism of coal methylation is discussed on the basis of regression models and experimental results. The interaction of the coal matter with the alkylating agent presumably involves the formation of the carbocation and its reaction with the coal organic matter. Both depolymerization reactions and the addition reactions of a portion of extractable compounds, the alkylating agent, and the catalyst with the high-molecular mass coal matrix take place.

  13. Factors that may influence polymorphous low-grade adenocarcinoma growth.

    PubMed

    Soares, Andresa Borges; Martinez, Elizabeth Ferreira; Ribeiro, Patricia Fernandes Avila; Barreto, Icleia Siqueira; Aguiar, Maria Cássia; Furuse, Cristiane; Sperandio, Marcelo; Montalli, Victor Angelo; de Araújo, Ney Soares; de Araújo, Vera Cavalcanti

    2017-04-01

    There is mounting evidence on the importance of some biological processes in tumor growth, such as vascular supply, apoptosis, autophagy, and senescence. We have investigated these processes in polymorphous low-grade adenocarcinoma (PLGA), in an attempt to identify those that are relevant for this particular lesion. We analyzed 31 cases of PLGA using immunohistochemistry to antibodies against CD34 and CD105 to detect blood vessels; against D2-40 to detect lymphatic vessels; against Bax, Bcl-2, and survivin to explore cell apoptosis; and against Beclin and LCB3 to investigate autophagy and against p21 and p16 to assess senescence. Our results showed that PLGA growth does not depend on newly formed vessels but only on preexisting vasculature. Furthermore, PLGA is promoted by autophagy, sustained by both anti-apoptotic and anti-senescence signals, and stimulated by Bcl-2 and survivin.

  14. Low Grade Endometrial Stromal Sarcoma: A Case Report

    PubMed Central

    Jain, Reena; Batra, Swaraj; Ahmad, Ayesha; Elahi, Arifa Anwar; Gupta, Monika; Saith, Poonam

    2015-01-01

    Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the endometrium, occurring in the age group of 40–50 years. We report a case of low-grade ESS in a 39-year-old woman, presenting as rapid enlargement of a uterine fibroid polyp associated with irregular and excessive vaginal bleeding. Polypectomy followed by pan hysterectomy was performed. Histopathological examination and immunohistochemistry confirmed LGESS. As the tumor is rarely encountered, management protocols are still questionable. In our case, we tried a different post-surgical protocol and the patient is being closely followed up. Although rare, ESS should be considered in the differential diagnosis of all women who present with a rapid enlargement of a uterine leiomyoma. PMID:25648534

  15. Comparison of the Effect of Vessel Size Imaging and Cerebral Blood Volume Derived from Perfusion MR Imaging on Glioma Grading.

    PubMed

    Kang, H-Y; Xiao, H-L; Chen, J-H; Tan, Y; Chen, X; Xie, T; Fang, J-Q; Wang, S; Yang, Y; Zhang, W-G

    2016-01-01

    Vascular proliferation is a major criterion for grading gliomas on the basis of histology. Relative cerebral blood volume can provide pathophysiologic information about glioma grading. Vessel size imaging, in some animals, can be used to estimate the microvascular caliber of a glioma, but its clinical use remains unclear. Herein, we aimed to compare the predictive power of relative cerebral blood volume and vessel size imaging in glioma grading, with grading based on histology. Seventy patients with glioma participated in the study; 30 patients underwent MR perfusion imaging with a spin-echo sequence and vessel size imaging with a gradient-echo and spin-echo sequence successively at 24-hour intervals before surgery. We analyzed the vessel size imaging values and relative cerebral blood volume of differently graded gliomas. The microvessel parameters were histologically evaluated and compared with those on MR imaging. The cutoff values of vessel size imaging and relative cerebral blood volume obtained from receiver operating characteristic curve analyses were used to predict glioma grading in another 40 patients. Vessel size imaging values and relative cerebral blood volume were both increased in high-grade gliomas compared with low-grade gliomas (P < .01). Moreover, vessel size imaging values had higher specificity and sensitivity in differentiating high-grade from low-grade gliomas compared with relative cerebral blood volume. In addition, a significant correlation was observed between vessel size imaging values and microvessel diameters (r > 0.8, P < .05) and between relative cerebral blood volume and microvessel area (r = 0.6579, P < .05). Most important, the use of vessel size imaging cutoff values to predict glioma grading was more accurate (100%) than use of relative cerebral blood volume (85%) values. Vessel size imaging can provide more accurate information on glioma grading and may serve as an effective biomarker for the prognosis of patients with gliomas

  16. Radiation therapy for localized duodenal low-grade follicular lymphoma

    PubMed Central

    Harada, Arisa; Oguchi, Masahiko; Terui, Yasuhito; Takeuchi, Kengo; Igarashi, Masahiro; Kozuka, Takuyo; Harada, Ken; Uno, Takashi; Hatake, Kiyohiko

    2016-01-01

    The aim of this study was to evaluate the initial treatment results and toxicities of radiation therapy for patients with early stage low-grade follicular lymphoma (FL) arising from the duodenum. We reviewed 21 consecutive patients with early stage duodenal FL treated with radiation therapy between January 2005 and December 2013 at the Cancer Institute Hospital, Tokyo. The characteristics of patients were: median age 62 years (range, 46–79 years), gender (male, 6; female, 15), clinical stage (I, 20; II1, 1), histological grade (I, 17; II, 4). All patients were treated with radiation therapy alone. The median radiation dose was 30.6 Gy (range, 30.6–39.6) in 17 fractions. The involved-site radiation therapy was delivered to the whole duodenum. The median follow-up time was 43.2 months (range 21.4–109.3). The 3-year overall survival (OS), relapse-free survival (RFS) and local control (LC) rates were 94.7%, 79.3% and 100%, respectively. There were four relapses documented outside the treated volumes: two in the gastrointestinal tract (jejunum, terminal ileum), one in an abdominal lymph node (mesenteric lymph node) and one in the bone marrow. None died of the disease; one death was due to acute myeloid leukemia. No toxicities greater than Grade 1 were observed during treatment and over the follow-up time. The 30.6 Gy of involved-site radiation therapy provided excellent local control with very low toxicities. Radiation therapy could be an effective and safe treatment option for patients with localized low grade FL arising from the duodenum. PMID:27009323

  17. Severe hypomagnesemia and low-grade inflammation in metabolic syndrome.

    PubMed

    Guerrero-Romero, Fernando; Bermudez-Peña, Carmen; Rodríguez-Morán, Martha

    2011-06-01

    To evaluate the association between severe hypomagnesemia and the low-grade inflammatory response in subjects with metabolic syndrome (MetS), ninety-eight individuals with new diagnosis of MetS were enrolled in a cross-sectional study. Pregnancy, smoking, alcohol intake, renal damage, hepatic disorders, infectious or chronic inflammatory diseases, malignancy, use of diuretics, statins, calcium antagonist, antioxidants, vitamins, anti-inflammatory drugs, or previous oral magnesium supplementation were exclusion criteria. According serum magnesium levels, participants were assigned to the following groups: 1) severe hypomagnesemia (≤1.2 mg/dL); 2) hypomagnesemia (>1.2≤1.8 mg/dL); 3) Normal serum magnesium levels (>1.8 mg/dL). The low-grade inflammatory response was defined by elevation of serum levels of (hsCRP >1.0 ≤10.0 mg/L) or TNF-alpha (TNF-α ≥3.5 pg/mL). Severe hypomagnesemia, hypomagnesemia, and normomagnesemia were identified in 21 (21.4%), 38 (38.8%), and 39 (39.8%) individuals. The ORs, adjusted by WC, showed that severe hypomagnesemia (OR: 8.1; CI 95%: 3.6-19.4 and OR: 3.7; CI 95%: 1.1-12.1), but not hypomagnesemia (OR: 1.8; CI 95%: 0.9-15.5 and OR: 1.6; CI 95%: 0.7-3.6), was strongly associated with elevated hsCRP and TNF-α levels, and that normomagnesemia exhibited a protective role (OR: 0.32; CI 95%: 0.1-0.7 and OR: 0.28; CI 95%: 0.1-0.6) for elevation of CRP and TNF-α. Results of this study show that, in subjects with MetS, severe hypomagnesemia, but not hypomagnesemia, is associated with elevated concentrations of CRP and TNF-α.

  18. The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.

    PubMed

    Ohka, Fumiharu; Natsume, Atsushi; Motomura, Kazuya; Kishida, Yugo; Kondo, Yutaka; Abe, Tatsuya; Nakasu, Yoko; Namba, Hiroki; Wakai, Kenji; Fukui, Takashi; Momota, Hiroyuki; Iwami, Kenichiro; Kinjo, Sayano; Ito, Maki; Fujii, Masazumi; Wakabayashi, Toshihiko

    2011-01-01

    Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4) have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ), and even low grade gliomas (LGGs, WHO grade 2) eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP) in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1) IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2) LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3) LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4) higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.

  19. A novel, integrated PET-guided MRS technique resulting in more accurate initial diagnosis of high-grade glioma.

    PubMed

    Kim, Ellen S; Satter, Martin; Reed, Marilyn; Fadell, Ronald; Kardan, Arash

    2016-06-01

    Glioblastoma multiforme (GBM) is the most common and lethal malignant glioma in adults. Currently, the modality of choice for diagnosing brain tumor is high-resolution magnetic resonance imaging (MRI) with contrast, which provides anatomic detail and localization. Studies have demonstrated, however, that MRI may have limited utility in delineating the full tumor extent precisely. Studies suggest that MR spectroscopy (MRS) can also be used to distinguish high-grade from low-grade gliomas. However, due to operator dependent variables and the heterogeneous nature of gliomas, the potential for error in diagnostic accuracy with MRS is a concern. Positron emission tomography (PET) imaging with (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) has been shown to add additional information with respect to tumor grade, extent, and prognosis based on the premise of biochemical changes preceding anatomic changes. Combined PET/MRS is a technique that integrates information from PET in guiding the location for the most accurate metabolic characterization of a lesion via MRS. We describe a case of glioblastoma multiforme in which MRS was initially non-diagnostic for malignancy, but when MRS was repeated with PET guidance, demonstrated elevated choline/N-acetylaspartate (Cho/NAA) ratio in the right parietal mass consistent with a high-grade malignancy. Stereotactic biopsy, followed by PET image-guided resection, confirmed the diagnosis of grade IV GBM. To our knowledge, this is the first reported case of an integrated PET/MRS technique for the voxel placement of MRS. Our findings suggest that integrated PET/MRS may potentially improve diagnostic accuracy in high-grade gliomas.

  20. [The clinical application of hydrogen magnetic resonance spectroscopy combining with diffusion weight imaging in brain gliomas grading].

    PubMed

    Xu, Shengsheng; Ouyang, Yu; Luo, Tianyou; Zeng, Yongming; Zhou, Xiangping; Xiao, Jiahe

    2011-06-01

    The present study was aimed to investigate the function of diffusion weight imaging (DWI) combining with magnetic resonance spectroscopy (MRS) in the grading of brain gliomas. 12 cases low grade and 17 cases high grade of brain gliomas patients were examined with DWI and MRS, with all tumors confirmed by pathology in advance. The apparent diffusion coefficient (ADC) values, their corresponding metabolite ratios of Cho/Cr, Cho/NAA and tumor cellularities of tumor solid enhanced parts were measured. The ratios of Cho/Cr and Cho/NAA and their corresponding ADC values had significant differences between their high and low grade gliomas values, respectively. The ADC values demonstrated a negative correlation with Cho/Cr, Cho/NAA, and a significant negative correlated with Cho/Cr. And the ADC values demonstrated strong negative correlations with tumor cellularities. DWI combining with MRS could provide more valuable information in evaluating gliomas grading.

  1. Diffusion Tensor Imaging for Glioma Grading: Analysis of Fiber Density Index.

    PubMed

    Davanian, Fariba; Faeghi, Fariborz; Shahzadi, Sohrab; Farshifar, Zahra

    2017-01-01

    The most common primary tumors of brain are gliomas and tumor grading is essential for designing proper treatment strategies. The gold standard choice to determine grade of glial tumor is biopsy which is an invasive method. The purpose of this study was to investigate the role of fiber density index (FDi) by means of diffusion tensor imaging (DTI) (as a noninvasive method) in glial tumor grading. A group of 20 patients with histologically confirmed diagnosis of gliomas were evaluated in this study. We used a 1.5 Tesla MR system (AVANTO; Siemens, Germany) with a standard head coil for scanning. Multidirectional diffusion weighted imaging (measured in 12 noncollinear directions), and T1 weighted nonenhanced were performed for all patients. We defined two regions of interest (ROIs); 1) White matter fibers near the tumor and 2) Similar fibers in the contralateral hemisphere. FDi of the low-grade gliomas was higher than those of high-grade gliomas, which was significant (P=0.017). FDi ratio (ratio of fiber density in vicinity of the tumor to homologous fiber tracts in the contralateral hemisphere) is higher in low-grade than high-grade tumors, (P=0.05). In addition, we performed ROC (receiver operating characteristic) curve and the area under curve (AUC) was 0.813(P=0.013). Our findings prove significant difference in FDi near by low-grade and high-grade gliomas. Therefore, FDi values and ratios are helpful in glial tumor grading.

  2. Low-Grade Myofibroblastic Sarcoma in the Mandibular Canal: A Case Report.

    PubMed

    Yu, Yueyuan; Xiao, Jin; Wang, Lan; Yang, Guiqiang

    2016-07-01

    Low-grade myofibroblastic sarcoma (LGMS) represents an atypical myofibroblastic tumor characterized by a diffusely infiltrating pattern of spindle-shaped tumor cells. It was classified as a distinct soft tissue tumor by the World Health Organization in 2002. LGMS occurs mostly in adult patients and has a predilection for the head and neck region. So far, only a few cases of LGMS located in the mandible have been reported. Aggressive surgical resection with clear margins is the primary treatment for LGMS. Because of its rarity, reports of radiation therapy are limited, and the therapeutic effect is still controversial. We present the case of an 8-year-old girl with LGMS of the mandibular canal to highlight the clinical features and rarity and to improve the understanding of the therapeutic effect of radiotherapy on LGMS.

  3. Low-Grade Systemic Inflammation Profile, Unrelated to Homocysteinemia, in Obese Children

    PubMed Central

    V. Economou, Emanuel; V. Malamitsi-Puchner, Ariadne; P. Pitsavos, Christos; E. Kouskouni, Evangelia; Magaziotou-Elefsinioti, Ioanna; Creatsas, George

    2005-01-01

    To investigate in prepubertal obese children (POC) the profile of chronic low-grade systemic inflammation (CLGSI) and its relation to homocysteinemia, 72 POC were evaluated for serum C-reactive protein (CRP) and amyloid A (SAA) levels, both markers of CLGSI, and plasma levels of total homocysteine (tHcy), an independent risk factor for adult atherosclerosis, in comparison to 42 prepubertal lean children (PLC). The main observations in POC were higher CRP levels compared to PLC, positive association of SAA levels to CRP levels, no association of CRP or SAA levels to tHcy levels. Thus, in POC, positively interrelated to each other, elevated CRP and unaltered SAA levels reveal a unique profile of the CLGSI, not explaining homocysteinemia-induced risk for future atherosclerosis. PMID:16489253

  4. Primary Role for Kinin B1 and B2 Receptors in Glioma Proliferation.

    PubMed

    Nicoletti, Natália Fontana; Sénécal, Jacques; da Silva, Vinicius Duval; Roxo, Marcelo R; Ferreira, Nelson Pires; de Morais, Rafael Leite T; Pesquero, João Bosco; Campos, Maria Martha; Couture, Réjean; Morrone, Fernanda Bueno

    2016-11-16

    This study investigated the role of kinins and their receptors in malignant brain tumors. As a first approach, GL-261 glioma cells were injected (2 × 10(5) cells in 2 μl/2 min) into the right striatum of adult C57/BL6 wild-type, kinin B1 and B2 receptor knockout (KOB1R and KOB2R) and B1 and B2 receptor double knockout mice (KOB1B2R). The animals received the selective B1R (SSR240612) and/or B2R (HOE-140) antagonists by intracerebroventricular (i.c.v.) route at 5, 10, and 15 days. The tumor size quantification, mitotic index, western blot analysis, quantitative autoradiography, immunofluorescence, and confocal microscopy were carried out in brain tumor samples, 20 days after tumor induction. Our results revealed an uncontrolled tumor growing in KOB1R or SSR240612-treated mice, which was blunted by B2R blockade with HOE-140, suggesting a crosstalk between B1R and B2R in tumor growing. Combined treatment with B1R and B2R antagonists normalized the upregulation of tumor B1R and decreased the tumor size and the mitotic index, as was seen in double KOB1B2R. The B1R was detected on astrocytes in the tumor, indicating a close relationship between this receptor and astroglial cells. Noteworthy, an immunohistochemistry analysis of tumor samples from 16 patients with glioma diagnosis revealed a marked B1R immunopositivity in low-grade gliomas or in older glioblastoma individuals. Furthermore, the clinical data revealed a significantly higher immunopositivity for B1R, when compared to a lower B2R immunolabeling. Taken together, our results show that blocking simultaneously both kinin receptors or alternatively stimulating B1R may be of therapeutic value in the treatment of brain glioblastoma growth and malignancy.

  5. Incidence of gliomas by anatomic location

    PubMed Central

    Larjavaara, Suvi; Mäntylä, Riitta; Salminen, Tiina; Haapasalo, Hannu; Raitanen, Jani; Jääskeläinen, Juha; Auvinen, Anssi

    2007-01-01

    The anatomic location of a glioma influences prognosis and treatment options. The aim of our study was to describe the distribution of gliomas in different anatomic areas of the brain. A representative population-based sample of 331 adults with glioma was used for preliminary analyses. The anatomic locations for 89 patients from a single center were analyzed in more detail from radiologic imaging and recorded on a three-dimensional 1 × 1 × 1– cm grid. The age-standardized incidence rate of gliomas was 4.7 per 100,000 person-years. The most frequent subtypes were glioblastoma (47%) and grade II–III astrocytoma (23%), followed by oligodendroglioma and mixed glioma. The gliomas were located in the frontal lobe in 40% of the cases, temporal in 29%, parietal in 14%, and occipital lobe in 3%, with 14% in the deeper structures. The difference in distribution between lobes remained after adjustment for their tissue volume: the tumor:volume ratio was 4.5 for frontal, 4.8 for temporal, and 2.3 for parietal relative to the occipital lobe. The area with the densest occurrence was the anterior subcortical brain. Statistically significant spatial clustering was found in the three-dimensional analysis. No differences in location were found among glioblastoma, diffuse astrocytoma, and oligodendroglioma. Our results demonstrate considerable heterogeneity in the anatomic distribution of gliomas within the brain. PMID:17522333

  6. Mechanism of SEMA3B gene silencing and clinical significance in glioma.

    PubMed

    Pang, C H; Du, W; Long, J; Song, L J

    2016-03-18

    The aim of the current study was to explore mechanisms of SEMA3B gene expression and its clinical significance in glioma, and provide a theoretical foundation for investigating individualized treatment in glioma. Paraffin-embedded tissues from 43 patients with a confirmed clinical diagnosis of glioma following neurosurgery at the First Affiliated Hospital of Zhengzhou University from December 2013 to April 2014 were selected randomly. An additional three normal brain tissues were obtained following encephalic decompression excision due to acute craniocerebral injury in the same period, which were used as the control group. Immunohistochemical staining for vascular endothelial growth factor was performed on the glioma tissues from the 43 patients. Genomic DNA was extracted for bisulfate conversion and sequencing. SEMA3B was fully expressed in the three normal brain tissues, and incompletely expressed in the 43 glioma tissues, with a lack of expression in 48.8% (21/43) of samples. Moreover, 58% of high-grade gliomas (grade III and IV) lacked SEMA3B expression, which was significantly more than those that lacked expression (20%) in low-grade gliomas (grade I and II), indicating that, as the clinical pathological grade increased, SEMA3B expression decreased. The occurrence and development of malignant tumors is a product of multiple genes and other factors. Here, we provide theoretical basis for glioma development and prognosis involving DNA-methylation driven silencing of SEMA3B, and thus, SEMA3B is a potential target for directed treatments against glioma.

  7. Paradoxical prognostic impact of TERT promoter mutations in gliomas depends on different histological and genetic backgrounds.

    PubMed

    You, Hao; Wu, Yao; Chang, Kai; Shi, Xiao; Chen, Xin-Da; Yan, Wei; Li, Rui

    2017-10-01

    The purpose of this study was to explore the clinical significance of telomerase reverse transcriptase (TERT) promoter mutations in gliomas. We used DNA sequencing data to analyze 887 gliomas for TERT promoter mutations based on histological and genetic backgrounds. TERT promoter mutations were detected in 39.6% of low-grade gliomas, 40.3% of anaplastic gliomas, 44.7% of primary glioblastomas, 29.4% of secondary glioblastomas, and in 29.7% of Proneural, 38.6% of Neural, 41.8% of Classical, and 41.6% of Mesenchymal subtypes. Frequency of C250T mutation in recurrent gliomas was approximately half that in newly diagnosed gliomas. TERT exhibited improved prognosis when co-occurred with isocitrate dehydrogenase 1 (IDH1) and 1p19q alteration, but experienced inverse survival in the Mesenchymal subtype or tumor protein p53 (TP53) and epidermal growth factor receptor (EGFR) alteration. Furthermore, the five subtypes were classified based on the prognostic impact of the TERT mutation with different genetic backgrounds of glioma. We describe the TERT promoter mutation spectrum according to the histological, genetic, and molecular subtypes of glioma, which may aid in glioma subtype classification and have clinical implications. © 2017 John Wiley & Sons Ltd.

  8. Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas.

    PubMed

    Takano, Shingo; Ishikawa, Eiichi; Sakamoto, Noriaki; Matsuda, Masahide; Akutsu, Hiroyoshi; Noguchi, Masayuki; Kato, Yukinari; Yamamoto, Tetsuya; Matsumura, Akira

    2016-04-01

    The molecular subgrouping of diffuse gliomas was recently found to stratify patients into prognostically distinct groups better than histological classification. Among several molecular parameters, the key molecules for the subtype diagnosis of diffuse gliomas are IDH mutation, 1p/19q co-deletion, and ATRX mutation; 1p/19q co-deletion is undetectable by immunohistochemistry, but is mutually exclusive with ATRX and p53 mutation in IDH mutant gliomas. Therefore, we applied ATRX and p53 immunohistochemistry instead of 1p/19q co-deletion analysis. The prognostic value of immunohistochemical diagnosis for Grade III gliomas was subsequently investigated. Then, the same immunohistochmical diagnostic approach was expanded for the evaluation of Grade II and IV diffuse glioma prognosis. The results indicate immunohistochemical analysis including IDH1/2, ATRX, p53, and Ki-67 index is valuable for the classification of diffuse gliomas, which is useful for the evaluation of prognosis, especially Grade III gliomas and lower-grade gliomas (i.e., Grade II and III).

  9. Characterization and Beneficiation Studies of a Low Grade Bauxite Ore

    NASA Astrophysics Data System (ADS)

    Rao, D. S.; Das, B.

    2014-10-01

    A low grade bauxite sample of central India was thoroughly characterized with the help of stereomicroscope, reflected light microscope and electron microscope using QEMSCAN. A few hand picked samples were collected from different places of the mine and were subjected to geochemical characterization studies. The geochemical studies indicated that most of the samples contain high silica and low alumina, except a few which are high grade. Mineralogically the samples consist of bauxite (gibbsite and boehmite), ferruginous mineral phases (goethite and hematite), clay and silicate (quartz), and titanium bearing minerals like rutile and ilmenite. Majority of the gibbsite, boehmite and gibbsitic oolites contain clay, quartz and iron and titanium mineral phases within the sample as inclusions. The sample on an average contains 39.1 % Al2O3 and 12.3 % SiO2, and 20.08 % of Fe2O3. Beneficiation techniques like size classification, sorting, scrubbing, hydrocyclone and magnetic separation were employed to reduce the silica content suitable for Bayer process. The studies indicated that, 50 % by weight with 41 % Al2O3 containing less than 5 % SiO2 could be achieved. The finer sized sample after physical beneficiation still contains high silica due to complex mineralogical associations.

  10. Clean-burning fuels produced from low-grade coal

    SciTech Connect

    1995-03-01

    Under the acid rain program, operators of large combustion units are required to reduce their emissions of sulfur oxides (SO{sub x}) and nitrogen oxides (NO{sub x}). Although the program provides significant flexibility through its system of marketable emission allowances, regulated sources needing to reduce SO{sub x} emissions typically choose one of the following two options: (1) switch to a low-sulfur fuel, or (2) add end-of-pipe controls. Because it is naturally low in sulfur, one good candidate for fuel switching is coal mined from the Powder River basin in northeast Wyoming. The Encoal Corporation (Gillette, Wyoming) has attempted to improve the economics of using Powder River coal by installing a coal liquification plant at an existing mine near Gillette. The plant, cofunded by the Department of Energy (DOE) and Zeigler Coal Holding Company (the parent company to Encoal), has demonstrated commercial-scale application of a liquids-from-coal (LFC) process developed by SGI International. The LFC process represents a middle-of-the-road approach to coal treatment. As described, here, the process converts high-moisture, low-grade coal into process-derived fuel (PDF-an upgraded solid coal product) and coal-derived liquids (CDL-fuel-oil type liquids). The LFC process also produces an organic gas stream, which is burned internally as an energy source. Finally, the LFC process can be adapted, if necessary, to remove sulfur from high-sulfur coal. 1 ref., 1 fig.

  11. Low grade thermal energy harvester using graphene-based thermocells

    NASA Astrophysics Data System (ADS)

    Sindhuja, M.; Lohith, B.; Sudha, V.; Manjunath, G. R.; Harinipriya, S.

    2017-07-01

    Graphene-based thermocells for the conversion of low grade waste heat into electrical energy are investigated. A maximum current and power density of 0.63 A m-2 and 0.19 W m-2 respectively for 1 mV s-1 at a temperature gradient of 50 °C is obtained. The maximum energy conversion efficiency relative to Carnot efficiency is 1.57% which is 1.1 times higher than the literature data. A constant ohmic overpotential of 0.07 V is calculated from equivalent circuit analysis. This low value of ohmic overpotential indicates higher ionic conductivity in the electrolyte medium. The mass transfer overpotential is low and is calculated as 0.2133 V for all load variations, indicating constant redox behaviour and an increased energy conversion efficiency of the device. The double layer capacitance is estimated as 3.72 F at a very low load (ca. 1 mV s-1) and 0.32 F at a very high load (ca. 100 mV s-1) thereby demonstrating the functioning ability of the device at higher loads. The Seebeck coefficient for a graphene electrode is evaluated to be 0.0117 V K-1 and is in satisfactory agreement with the literature value of 0.02 V K-1 for carbon-based devices.

  12. Nimotuzumab treatment of malignant gliomas.

    PubMed

    Bode, Udo; Massimino, Maura; Bach, Ferdinand; Zimmermann, Martina; Khuhlaeva, Elena; Westphal, Manfred; Fleischhack, Gudrun

    2012-12-01

    In spite of new alkylating medication and recently accumulated knowledge about genomics, the prognosis of malignant gliomas remains poor. The introduction of single substances interfering with tumour proliferation dynamics has been disappointing and the lessons learned indicate that a complicated network of proliferation needs time consuming, in-depth analysis in order to more specifically treat now distinguishable subgroups of a disease, which too long was thought of as a uniform entity. The clinical trials using the EGFR antibody nimotuzumab in the treatment of malignant gliomas are reviewed. Pending conformation in future studies the antibody might be part of the treatment of MGMT-negative, EGFR-amplified, not completely resected gliomas of adulthood and juvenile DIPG (pontine gliomas). Upcoming genomic results of the different tumour entities may suggest certain combination partners of the antibody. Recent studies of nimotuzumab indicate the reason for the lack of toxicity, which is the most attractive argument for its clinical use besides modest efficacy. We await the final results on the use of the antibody together with vinorelbine and radiation therapy for the therapy of DIPG. Adult patients with MGMT-negative, EGFR amplified, not totally resected GBM may also profit from this combination therapy. TK-inhibitors combined with the antibody and irradiation may be an option for a therapeutic trial in paediatric patients.

  13. Low Grade Juvenile Osteochondritis Dissecans of the Knee

    PubMed Central

    Etcheto, H. Rivarola; Blanchod, C. Collazo; Palanconi, M.; Zordan, J.; Salinas, E. Alvarez; Autorino, C.

    2017-01-01

    Juvenile osteochondritis dissecans (OCD) of the knee is a nosological entity acquired, idiopathic and potentially reversible. Dissects the subchondral bone tissue plane from the underlying bone, making a partial or complete osteochondral detachment, with a loose body. Consensus to treat none surgically poor symptomatic and stable lesions. If the lesion becomes instable or more symptomatic, surgical treatment will be best the option. Recently histological evidence holds is possible find sources of instability in deep layers sub chondral bone, even in patients with ¨stables lesions¨. This condition might be the reason of unfavorable evolution certain cases previously considered as ¨stable or incipient¨, treated with the classic non operative protocols. Objectives: The purpose of the present study consist in present a series of cases of young patients with symptomatic low grade juvenile OCD (grade I-II), treated surgically with subchondral debridement and fixation ¨in situ¨ describing the clinical and imaging findings. Methods: We evaluated 15 cases of symptomatic juvenile OCD of the knee, stables lesion (grade I/ II) according to Di Paola´s classification, who have not responded to conservative therapy for at least 6 months. Results: All patients were treated surgical consecutively with arthroscopically assisted ¨in situ¨ fixation with pins Smart Nail NR, ConMed-Linvatex and for the same group of surgeons. We evaluated the clinical and imagenologic outcomes with MRI for a minimum follow up of six month to one year. No looseness of fastening material or loose bodies in the submitted sample were recorded. The study by MRI imaging techniques using high definition chondral identification evidence allowed the consolidation of the fragment to the 6th month. Conclusion: All patients evolved asymptomatic and returned to the previous activity, with high level of satisfaction.

  14. Rotational thyrotracheopexy after cricoidectomy for low-grade laryngeal chrondrosarcoma.

    PubMed

    Rovó, László; Bach, Ádám; Sztanó, Balázs; Matievics, Vera; Szegesdi, Ilona; Castellanos, Paul F

    2017-05-01

    The complex laryngeal functions are fundamentally defined by the cricoid cartilage. Thus, lesions requiring subtotal or total resection of the cricoid cartilage commonly warrant total laryngectomy. However, from an oncological perspective, the resection of the cricoid cartilage would be an optimal solution in these cases. The poor functional results of the few reported cases of total and subtotal cricoidectomy with different reconstruction techniques confirm the need for new approaches to reconstruct the infrastructure of the larynx post cricoidectomy. Retrospective case series review. Four consecutive patients with low-grade chondrosarcoma were treated by cricoidectomy with rotational thyrotracheopexy reconstruction to enable the functional creation of a complete cartilaginous ring that can substitute the functions of the cricoid cartilage. The glottic structures were stabilized with endoscopic arytenoid abduction lateropexy. Patients were evaluated with objective and subjective function tests. Tumor-free margins were proven; patients were successfully decannulated within 3 weeks. Voice outcomes were adequate for social conversation in all cases. Oral feeding was possible in three patients. Total and subtotal cricoidectomy can be a surgical option to avoid total laryngectomy in cases of large chondrosarcomas destroying the cricoid cartilage. The thyrotracheopexy rotational advancement technique enables the effective reconstruction of the structural deficit of the resected cricoid cartilage in cases of total and subtotal cricoidectomy. An adequate airway for breathing, swallowing, and voice production can be reconstructed with good oncological control. In cases where the pharynx is not involved, good swallowing function can also be achieved. 4. Laryngoscope, 127:1109-1115, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  15. Progress on molecular biomarkers and classification of malignant gliomas.

    PubMed

    Zhang, Chuanbao; Bao, Zhaoshi; Zhang, Wei; Jiang, Tao

    2013-06-01

    Gliomas are the most common primary intracranial tumors in adults. Anaplastic gliomas (WHO grade III) and glioblastomas (WHO grade IV) represent the major groups of malignant gliomas in the brain. Several diagnostic, predictive, and prognostic biomarkers for malignant gliomas have been reported over the last few decades, and these markers have made great contributions to the accuracy of diagnosis, therapeutic decision making, and prognosis of patients. However, heterogeneity in patient outcomes may still be observed, which highlights the insufficiency of a classification system based purely on histopathology. Great efforts have been made to incorporate new information about the molecular landscape of gliomas into novel classifications that may potentially guide treatment. In this review, we summarize three distinctive biomarkers, three most commonly altered pathways, and three classifications based on microarray data in malignant gliomas.

  16. Genomic dynamics associated with malignant transformation in IDH1 mutated gliomas

    PubMed Central

    Sun, Choong-Hyun; Koh, Youngil; Park, Sung-Hye; Kim, Ja Eun; Yun, Hongseok; Lee, Se-Hoon

    2015-01-01

    The genomic mechanism responsible for malignant transformation remains an open question for glioma researchers, where differing conclusions have been drawn based on diverse study conditions. Therefore, it is essential to secure direct evidence using longitudinal samples from the same patient. Moreover, malignant transformation of IDH1-mutated gliomas is of potential interest, as its genomic mechanism under influence of oncometabolite remains unclear, and even higher rate of malignant transformation was reported in IDH1-mutated low grade gliomas than in wild-type IDH1 tumors. We have analyzed genomic data using next-generation sequencing technology for longitudinal samples from 3 patients with IDH1-mutated gliomas whose disease had progressed from a low grade to a high grade phenotype. Comprehensive analysis included chromosomal aberrations as well as whole exome and transcriptome sequencing, and the candidate driver genes for malignant transformation were validated with public database. Integrated analysis of genomic dynamics in clonal evolution during the malignant transformation revealed alterations in the machinery regulating gene expression, including the spliceosome complex (U2AF2), transcription factors (TCF12), and chromatin remodelers (ARID1A). Moreover, consequential expression changes implied the activation of genes associated with the restoration of the stemness of cancer cells. The alterations in genetic regulatory mechanisms may be the key factor for the major phenotypic changes in IDH1 mutated gliomas. Despite being limited to a small number of cases, this analysis provides a direct example of the genomic changes responsible for malignant transformation in gliomas. PMID:26524630

  17. Childhood bullying involvement predicts low-grade systemic inflammation into adulthood

    PubMed Central

    Copeland, William E.; Wolke, Dieter; Lereya, Suzet Tanya; Shanahan, Lilly; Worthman, Carol; Costello, E. Jane

    2014-01-01

    Bullying is a common childhood experience that involves repeated mistreatment to improve or maintain one’s status. Victims display long-term social, psychological, and health consequences, whereas bullies display minimal ill effects. The aim of this study is to test how this adverse social experience is biologically embedded to affect short- or long-term levels of C-reactive protein (CRP), a marker of low-grade systemic inflammation. The prospective population-based Great Smoky Mountains Study (n = 1,420), with up to nine waves of data per subject, was used, covering childhood/adolescence (ages 9–16) and young adulthood (ages 19 and 21). Structured interviews were used to assess bullying involvement and relevant covariates at all childhood/adolescent observations. Blood spots were collected at each observation and assayed for CRP levels. During childhood and adolescence, the number of waves at which the child was bullied predicted increasing levels of CRP. Although CRP levels rose for all participants from childhood into adulthood, being bullied predicted greater increases in CRP levels, whereas bullying others predicted lower increases in CRP compared with those uninvolved in bullying. This pattern was robust, controlling for body mass index, substance use, physical and mental health status, and exposures to other childhood psychosocial adversities. A child’s role in bullying may serve as either a risk or a protective factor for adult low-grade inflammation, independent of other factors. Inflammation is a physiological response that mediates the effects of both social adversity and dominance on decreases in health. PMID:24821813

  18. Childhood bullying involvement predicts low-grade systemic inflammation into adulthood.

    PubMed

    Copeland, William E; Wolke, Dieter; Lereya, Suzet Tanya; Shanahan, Lilly; Worthman, Carol; Costello, E Jane

    2014-05-27

    Bullying is a common childhood experience that involves repeated mistreatment to improve or maintain one's status. Victims display long-term social, psychological, and health consequences, whereas bullies display minimal ill effects. The aim of this study is to test how this adverse social experience is biologically embedded to affect short- or long-term levels of C-reactive protein (CRP), a marker of low-grade systemic inflammation. The prospective population-based Great Smoky Mountains Study (n = 1,420), with up to nine waves of data per subject, was used, covering childhood/adolescence (ages 9-16) and young adulthood (ages 19 and 21). Structured interviews were used to assess bullying involvement and relevant covariates at all childhood/adolescent observations. Blood spots were collected at each observation and assayed for CRP levels. During childhood and adolescence, the number of waves at which the child was bullied predicted increasing levels of CRP. Although CRP levels rose for all participants from childhood into adulthood, being bullied predicted greater increases in CRP levels, whereas bullying others predicted lower increases in CRP compared with those uninvolved in bullying. This pattern was robust, controlling for body mass index, substance use, physical and mental health status, and exposures to other childhood psychosocial adversities. A child's role in bullying may serve as either a risk or a protective factor for adult low-grade inflammation, independent of other factors. Inflammation is a physiological response that mediates the effects of both social adversity and dominance on decreases in health.

  19. PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas.

    PubMed

    Nakae, Shunsuke; Sasaki, Hikaru; Hayashi, Saeko; Hattori, Natsuki; Kumon, Masanobu; Nishiyama, Yuya; Adachi, Kazuhide; Nagahisa, Shinya; Hayashi, Takuro; Inamasu, Joji; Abe, Masato; Hasegawa, Mitsuhiro; Hirose, Yuichi

    2015-01-01

    Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.

  20. PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas

    PubMed Central

    Nakae, Shunsuke; Sasaki, Hikaru; Hayashi, Saeko; Hattori, Natsuki; Kumon, Masanobu; Nishiyama, Yuya; Adachi, Kazuhide; Nagahisa, Shinya; Hayashi, Takuro; Inamasu, Joji; Abe, Masato; Hasegawa, Mitsuhiro; Hirose, Yuichi

    2015-01-01

    Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, −9p, and −11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas. PMID:26558387

  1. Impact of epidemiological characteristics of supratentorial gliomas in adults brought about by the 2016 world health organization classification of tumors of the central nervous system.

    PubMed

    Jiang, Haihui; Cui, Yong; Wang, Junmei; Lin, Song

    2016-11-24

    The latest World Health Organization (WHO) classification of tumors of the central nervous system (CNS) integrates both histological and molecular features in the definition of diagnostic entities. This new approach enrolls novel entities of gliomas. In this study, we aimed to reveal the epidemiological characteristics, including age at diagnosis, gender ratio, tumor distribution and survival, of these new entities. We retrospectively reclassified 1210 glioma samples according to the 2016 CNS WHO diagnostic criteria. In our cohort, glioblastoma multiforme (GBM) with wildtype isocitrate dehydrogenase (IDH) was the most common malignant tumor in the brain. Almost all gliomas were more prevalent in males, especially in the cluster of WHO grade III gliomas and IDH-wildtype GBM. Age at diagnosis was directly proportional to tumor grade. With respect to the distribution by histology, we found that gliomas concurrent with IDH-mutant and 1p/19q-codeleted or with single IDH-mutant were mainly distributed in frontal lobe, while those with IDH-wildtype were dominant in temporal lobe. Lesions located in insular lobe were more likely to be IDH-mutant astrocytoma. In summary, our results elucidated the epidemiological characteristics as well as the regional constituents of these new gliomas entities, which could bring insights into tumorigenesis and personalized treatment of Chinese glioma population.

  2. Metabolomics profiling in plasma samples from glioma patients correlates with tumor phenotypes

    PubMed Central

    Zhao, Hua; Heimberger, Amy B.; Lu, Zhimin; Wu, Xifeng; Hodges, Tiffany R.; Song, Renduo; Shen, Jie

    2016-01-01

    Background Tumor-based molecular biomarkers have redefined in the classification gliomas. However, the association of systemic metabolomics with glioma phenotype has not been explored yet. Methods In this study, we conducted two-step (discovery and validation) metabolomic profiling in plasma samples from 87 glioma patients. The metabolomics data were tested for correlation with glioma grade (high vs low), glioblastoma (GBM) versus malignant gliomas, and IDH mutation status. Results Five metabolites, namely uracil, arginine, lactate, cystamine, and ornithine, significantly differed between high- and low-grade glioma patients in both the discovery and validation cohorts. When the di