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Sample records for temporal high-grade gliomas

  1. Contemporary management of high-grade gliomas.

    Science.gov (United States)

    Sim, Hao-Wen; Morgan, Erin R; Mason, Warren P

    2018-01-01

    High-grade gliomas, including glioblastoma, are the most common malignant brain tumors in adults. Despite intensive efforts to develop new therapies for these diseases, treatment options remain limited and prognosis is poor. Recently, there have been important advances in our understanding of the molecular basis of glioma, leading to refinements in our diagnostic and management approach. There is new evidence to guide the treatment of elderly patients. A multitude of new agents have been investigated, including targeted therapies, immunotherapeutics and tumor-treating fields. This review summarizes the key findings from this research, and presents a perspective on future opportunities to advance the field.

  2. Adult high-grade malignant gliomas

    Directory of Open Access Journals (Sweden)

    Fable Zustovich

    2011-12-01

    Full Text Available Central nervous system (CNS malignant gliomas are relatively rare diseases. Prognosis is poor but has improved over recent years due to the improvement in the multi-disciplinary treatment: surgery, radiotherapy and chemotherapy...

  3. Terahertz reflectometry imaging for low and high grade gliomas

    Science.gov (United States)

    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

  4. Levetiracetam improves verbal memory in high-grade glioma patients

    NARCIS (Netherlands)

    de Groot, Marjolein; Douw, Linda; Sizoo, Eefje M; Bosma, Ingeborg; Froklage, Femke E; Heimans, Jan J; Postma, Tjeerd J; Klein, Martin; Reijneveld, Jaap C

    BACKGROUND: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of

  5. Management of Patients with High-Grade Glioma

    Directory of Open Access Journals (Sweden)

    Simge Yukse

    2014-11-01

    Full Text Available The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient’s care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient’s journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome, and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical management of patients with high-grade glioma.

  6. Concurrent thermochemoradiotherapy for brain high-grade glioma

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    Ryabova, A. I., E-mail: ranigor@mail.ru; Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Choinzonov, E. L. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Tomsk, 634050 (Russian Federation); Gribova, O. V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Baranova, A. V. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  7. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Science.gov (United States)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  8. Irradiation and Bevacizumab in High-Grade Glioma Retreatment Settings

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    Niyazi, Maximilian; Ganswindt, Ute; Schwarz, Silke Birgit [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany); Kreth, Friedrich-Wilhelm; Tonn, Joerg-Christian [Department of Neurosurgery, Ludwig-Maximilians-University Munich, Munich (Germany); Geisler, Julia; Fougere, Christian la [Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich (Germany); Ertl, Lorenz; Linn, Jennifer [Department of Neuroradiology, Ludwig-Maximilians-University Munich, Munich (Germany); Siefert, Axel [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany); Belka, Claus, E-mail: claus.belka@med.uni-muenchen.de [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany)

    2012-01-01

    Purpose: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. Patients and Methods: After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. Results: The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. Conclusion: Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting.

  9. Cognitive impairments in patients with low grade gliomas and high grade gliomas

    Directory of Open Access Journals (Sweden)

    Eliane C. Miotto

    2011-08-01

    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

  10. Cerebral Connectivity and High-grade Gliomas: Evolving Concepts of Eloquent Brain in Surgery for Glioma

    Directory of Open Access Journals (Sweden)

    Sanjay Konakondla

    2017-02-01

    Full Text Available Technological advances in imaging the human brain help us map and understand the intricacies of cerebral connectivity. Current techniques and specific imaging sequences, however, do come with limitations. Image resolution, variability of techniques and interpretation of images across institutions are just a few concerns. In the setting of high-grade gliomas, understanding how these pathways are affected during tumor growth, surgical resection, and in the brain plasticity presents an even greater challenge. Clinical symptoms, tumor growth, and intraoperative electrical stimulation are important peri-operative considerations to assist in determining neuronal re-wiring and establish a basis of anatomic and functional correlation. The application of functional mapping coupled with the understanding of the natural history of gliomas and implications of neural plasticity, is critical in achieving the goals of maximal tumor resection while minimizing post operative deficits and improving quality of life.

  11. International Differences in Treatment and Clinical Outcomes for High Grade Glioma

    OpenAIRE

    Chien, Li-Nien; Ostrom, Quinn T.; Gittleman, Haley; Lin, Jia-Wei; Sloan, Andrew E.; Barnett, Gene H.; Elder, J. Bradley; McPherson, Christopher; Warnick, Ronald; Chiang, Yung-Hsiao; Lin, Chieh-Min; Rogers, Lisa R.; Chiou, Hung-Yi; Barnholtz-Sloan, Jill S.

    2015-01-01

    Background High grade gliomas are the most common type of malignant brain tumor, and despite their rarity, cause significant morbidity and mortality. This study aimed to compare the treatment patterns of high grade glioma to examine survival patterns in patients who receive specific treatments between cohorts in Ohio and Taiwan. Method Patients aged 18 years and older at age of diagnosis with World Health Organization (WHO) grade III or IV astrocytoma from 2007-2012 were selected from the Ohi...

  12. A population-based study of high-grade gliomas and mutated isocitrate dehydrogenase 1

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Kristensen, Bjarne W; Hjelmborg, Jacob

    2012-01-01

    High-grade gliomas have a dismal prognosis, and prognostic factors are needed to optimize treatment algorithms. In this study we identified clinical prognostic factors as well as the prognostic value of isocitrate dehydrogenase 1 (IDH1) status in a population-based group of patients with high......-grade gliomas. Using the Danish Cancer Registry and the Danish Pathology Databank we identified 359 patients: 234 had WHO grade IV gliomas, 58 had WHO grade III gliomas, and 67 were diagnosed clinically. Mutated IDH1 was predominantly observed in oligodendroglial tumors (WHO grade III). Patients with mutated...... IDH1 had a significantly better outcome than patients with wildtype IDH1: 2-year OS 59% and 18%, respectively (HR 0.38, 95% CI 0.21-0.68). However, when adjusting for other prognostic factors, IDH1 status was not a significant independent prognostic factor (HR=0.58, 95% CI 0.32-1.07). Young age...

  13. 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

    Science.gov (United States)

    2017-11-07

    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

  14. Preclinical evaluation of convection-enhanced delivery of liposomal doxorubicin to treat pediatric diffuse intrinsic pontine glioma and thalamic high-grade glioma

    NARCIS (Netherlands)

    Sewing, A.C.; Lagerweij, T.; Vuurden, D.G. van; Meel, M.H.; Veringa, S.J.; Carcaboso, A.M.; Gaillard, P.J.; Vandertop, W. Peter; Wesseling, P.; Noske, D.; Kaspers, G.J.; Hulleman, E.

    2017-01-01

    OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however,

  15. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  16. Radio-fluoro guided surgery in high grade gliomas

    International Nuclear Information System (INIS)

    Lopez Piloto, Orestes; Salva Camano, Silvia; Gonzalez Gonzalez, Justo; Cruz Hernandez, Tania Margarita; Martinez Suarez, Eduardo; Lopez Arbolay, Omar; Ardisana Santana, Ernesto

    2015-01-01

    The MIBI (99mTc MIBI, methoxyisobutylisonitrile, MIBI, or sestamibi): is a wide readiness to the rich flow of photons, which improves the detection of pathological uptake with gamma probe, these physical properties make of this radiotracer the election to radioguided surgery. The sodium fluorescein is a water-soluble organic coloring substance used in the exam of the sanguine glasses of the eye. We carried out the report of five cases diagnosed with brain tumor of high grade of malignancy, with the objective to demonstrated that use of Radio-Fluro-guided Surgery (RFGS) we can achieve gross total resections without bigger deficit, completing the inclusion and exclusion criteria. The technique of RFGS demonstrated utility in the gross total resection, diminishing the residual tumor, without increasing surgery complexity and surgical times. In our study doesn't evidence of adverse effects for the administration of the radiopharmaceuticals and fluorescein

  17. Immunotherapy for high-grade glioma: how to go beyond Phase I/II clinical trials.

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    van Gool, Stefaan

    2013-10-01

    Evaluation of: Lasky JL 3rd, Panosyan EH, Plant A et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 33, 2047-2056 (2013). Immunotherapy for children and adults with high-grade glioma (HGG) is an emerging innovative treatment approach, which aims at stimulating the body's own immune system against HGG by using autologous dendritic cells pulsed with autologous tumor lysate as a therapeutic vaccine. This is the third report on immunotherapy for HGG in children, bringing additional knowledge and experience to the scientific community. However, at the same time, this and other manuscripts urge for the next step in treatment development.

  18. Venous thromboembolism and survival in patients with high-grade glioma

    OpenAIRE

    Simanek, Ralph; Vormittag, Rainer; Hassler, Marco; Roessler, Karl; Schwarz, Martin; Zielinski, Christoph; Pabinger, Ingrid; Marosi, Christine

    2007-01-01

    Patients with malignancy, particularly patients with high-grade glioma (HGG; WHO grade III/IV), have an increased risk of venous thromboembolism (VTE). It has been suggested that VTE predicts survival in cancer patients. The aim of our study was to investigate the occurrence of symptomatic VTE and its impact on survival in patients with HGG. Consecutive patients (n = 63; 36 female, 27 male; median age, 58 years) who had neurosurgical intervention between October 2003 and December 2004 were fo...

  19. O9.04HIGH GRADE GLIOMAS AND CAREGIVERS' PSYCHOLOGICAL BURDEN

    OpenAIRE

    Petruzzi, A.; Finocchiaro, C.Y.; Vistalli, G.; Botturi, A.; Milanesi, I.; Silvani, A.; Lamperti, E.

    2014-01-01

    The diagnosis of a brain tumor is particularly stressful both for patients and their caregivers because the prognosis is poor and life expectancy is short. This is especially true when caregivers deal with high-grade gliomas (HGG). Despite treatment advances, median survival remains low, ranging from 1 to 5 years. Focal neurological deficits, epilepsy, cognitive dysfunction and symptoms of increased intracranial pressure are prominent symptoms in HHG and they may arise in any stage of the dis...

  20. A dosimetric comparison of four treatment planning methods for high grade glioma

    Directory of Open Access Journals (Sweden)

    Miller Robert W

    2009-10-01

    Full Text Available Abstract Background High grade gliomas (HGG are typically treated with a combination of surgery, radiotherapy and chemotherapy. Three dimensional (3D conformal radiotherapy treatment planning is still the main stay of treatment for these patients. New treatment planning methods suggest better dose distributions and organ sparing but their clinical benefit is unclear. The purpose of the current study was to compare normal tissue sparing and tumor coverage using four different radiotherapy planning methods in patients with high grade glioma. Methods Three dimensional conformal (3D, sequential boost IMRT, integrated boost (IB IMRT and Tomotherapy (TOMO treatment plans were generated for 20 high grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively. Results The mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe were highest with 3D plans and least with IB plans. The mean dose to the contralateral globe was highest with TOMO plans. The mean of the integral dose (ID to the brain was least with the IB plan and was lower with IMRT compared to 3D plans. The TOMO plans had the least mean D10 to the normal brain but higher mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90 were significantly lower with the IMRT plans compared to the 3D plans. Conclusion No single treatment planning method was found to be superior to all others and a personalized approach is advised for planning and treating high-grade glioma patients with radiotherapy. Integral dose did not reflect accurately the dose volume histogram (DVH of the normal brain and may not be a good indicator of delayed radiation toxicity.

  1. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

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    Karunamuni, Roshan [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bartsch, Hauke; White, Nathan S. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McDonald, Carrie R. [Department of Psychiatry, University of California San Diego, La Jolla, California (United States); Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua [Department of Radiology, University of California San Diego, La Jolla, California (United States); Mell, Loren [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Brewer, James B.; Dale, Anders M. [Department of Radiology, University of California San Diego, La Jolla, California (United States); Hattangadi-Gluth, Jona A., E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2016-02-01

    Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

  2. Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma

    International Nuclear Information System (INIS)

    Karunamuni, Roshan; Bartsch, Hauke; White, Nathan S.; Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah C.; Seibert, Tyler M.; McDonald, Carrie R.; Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua; Mell, Loren; Brewer, James B.; Dale, Anders M.; Hattangadi-Gluth, Jona A.

    2016-01-01

    Purpose: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. Results: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. Conclusions: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT.

  3. High grade glioma: Imaging combined with pathological grade defines management and predicts prognosis

    International Nuclear Information System (INIS)

    Burnet, Neil G.; Lynch, Andrew G.; Jefferies, Sarah J.; Price, Stephen J.; Jones, Phil H.; Antoun, Nagui M.; Xuereb, John H.; Pohl, Ute

    2007-01-01

    Introduction: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. Patients and methods: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. Results: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. Conclusions: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma

  4. Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

    LENUS (Irish Health Repository)

    Howley, R

    2012-10-15

    Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR\\/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.

  5. Daily Life Experiences of Patients With a High-Grade Glioma and Their Caregivers

    DEFF Research Database (Denmark)

    Piil, Karin; Juhler, Marianne; Jakobsen, Johannes

    2015-01-01

    BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs...... for rehabilitation and supportive care in patients with HGG and their caregivers. METHODS: Patients with malignant glioma (N = 30) and their caregivers (N = 33) were interviewed five times during the first year of the HGG trajectory. A thematic analysis of interviews at five time points revealed five main themes......, the need for information and guidance regarding symptoms and supportive care interventions became evident. Caregivers play a significant supporting role for the patients and need special support themselves and practical assistance especially when symptoms progress. Finally, there is a need...

  6. International Differences in Treatment and Clinical Outcomes for High Grade Glioma.

    Directory of Open Access Journals (Sweden)

    Li-Nien Chien

    Full Text Available High grade gliomas are the most common type of malignant brain tumor, and despite their rarity, cause significant morbidity and mortality. This study aimed to compare the treatment patterns of high grade glioma to examine survival patterns in patients who receive specific treatments between cohorts in Ohio and Taiwan.Patients aged 18 years and older at age of diagnosis with World Health Organization (WHO grade III or IV astrocytoma from 2007-2012 were selected from the Ohio Brain Tumor Study and the Taiwan Cancer Registry. The treatment information was derived from medical chart reviews in Ohio and National Health Insurance Research Data in Taiwan. Treatment examined included surgical procedure (brain biopsy and/or resection, radiotherapy (radiation and/or radiosurgery, and alkylating chemotherapy. Kaplan-Meier and parametric survival models were used to examine the effect of treatment on survival, adjusted for age, sex, and comorbidities.294 patients in Ohio and 1,097 patients in Taiwan met the inclusion criteria. 70.3% patients in Ohio and 51.4% in Taiwan received surgical resection, followed by concurrent chemoradiation. Patients who received this treatment had the highest survival rate, with a 1-year survival rate of 72.8% in Ohio and 73.4% in Taiwan. Patients who did not receive surgical resection, followed by concurrent chemoradiation had an increased risk of death (hazard ratio of 5.03 [95% confidence interval (CI: 3.61-7.02] in Ohio and 1.49 [95% CI: 1.31-1.71] in Taiwan after adjustment for age, sex, and comorbidities.Surgical resection followed by concurrent chemoradiation was associated with higher survival rate of patients with high grade glioma in both Ohio and Taiwan; however, one-third of patients in Ohio and half in Taiwan did not receive this treatment.

  7. In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma

    NARCIS (Netherlands)

    Veringa, S.J.; Biesmans, D.; Vuurden, D.G. van; Jansen, M.H.; Wedekind, L.E.; Horsman, I.; Wesseling, P.; Vandertop, W.P.; Noske, D.P.; Kaspers, G.J.L.; Hulleman, E.

    2013-01-01

    Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the leading cause of cancer-related death in children. While it is clear that surgery (if possible), and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear.

  8. Intensity-modulated radiotherapy in high-grade gliomas: Clinical and dosimetric results

    International Nuclear Information System (INIS)

    Narayana, Ashwatha; Yamada, Josh; Berry, Sean; Shah, Priti B.S.; Hunt, Margie; Gutin, Philip H.; Leibel, Steven A.

    2006-01-01

    Purpose: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. Methods and Materials: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. Results: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. Conclusions: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy

  9. MEG network differences between low- and high-grade glioma related to epilepsy and cognition.

    Directory of Open Access Journals (Sweden)

    Edwin van Dellen

    Full Text Available OBJECTIVE: To reveal possible differences in whole brain topology of epileptic glioma patients, being low-grade glioma (LGG and high-grade glioma (HGG patients. We studied functional networks in these patients and compared them to those in epilepsy patients with non-glial lesions (NGL and healthy controls. Finally, we related network characteristics to seizure frequency and cognitive performance within patient groups. METHODS: We constructed functional networks from pre-surgical resting-state magnetoencephalography (MEG recordings of 13 LGG patients, 12 HGG patients, 10 NGL patients, and 36 healthy controls. Normalized clustering coefficient and average shortest path length as well as modular structure and network synchronizability were computed for each group. Cognitive performance was assessed in a subset of 11 LGG and 10 HGG patients. RESULTS: LGG patients showed decreased network synchronizability and decreased global integration compared to healthy controls in the theta frequency range (4-8 Hz, similar to NGL patients. HGG patients' networks did not significantly differ from those in controls. Network characteristics correlated with clinical presentation regarding seizure frequency in LGG patients, and with poorer cognitive performance in both LGG and HGG glioma patients. CONCLUSION: Lesion histology partly determines differences in functional networks in glioma patients suffering from epilepsy. We suggest that differences between LGG and HGG patients' networks are explained by differences in plasticity, guided by the particular lesional growth pattern. Interestingly, decreased synchronizability and decreased global integration in the theta band seem to make LGG and NGL patients more prone to the occurrence of seizures and cognitive decline.

  10. Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas

    International Nuclear Information System (INIS)

    Baumert, Brigitta G.; Lutterbach, Johannes; Bernays, Rene; Davis, J. Bernard; Heppner, Frank L.

    2003-01-01

    Purpose: To determine the value and the toxicity of an additional fractionated stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in patients with malignant gliomas. Materials and methods: Seventeen patients (11 male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) ≤4 cm in maximum diameter, with a good performance status (WHO ≥2), were treated with a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions following partial brain irradiation to a dose of 60 Gy in 30 fractions. This patient group was compared with historical data in a matched-pair analysis. Results: All patients were treated by conventional radiotherapy and a SRT boost (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included fatigue (two), impairment of short-term memory (one) and worsening of pre-existing symptoms (one). No patient developed steroid dependence after SRT. One patient was re-operated for radiation necrosis. At a median follow-up of 25 months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and 42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years for all patients, respectively. Median survival for the whole patient group is 20 months. Comparison with a matched historical group showed a significantly better survival for the group treated with a stereotactic boost (P<0.0001). Conclusion: A fractionated stereotactic boost after standard external beam radiotherapy in selected patients with high-grade glioma is feasible and well tolerated with low toxicity. Compared to historical data survival is significantly better with an additional SRT boost. However, its effectiveness has to be proven in a randomized trial

  11. Comparison of T2 and FLAIR imaging for target delineation in high grade gliomas

    Directory of Open Access Journals (Sweden)

    Miller Robert W

    2010-01-01

    Full Text Available Abstract Background FLAIR and T2 weighted MRIs are used based on institutional preference to delineate high grade gliomas and surrounding edema for radiation treatment planning. Although these sequences have inherent physical differences there is limited data on the clinical and dosimetric impact of using either or both sequences. Methods 40 patients with high grade gliomas consecutively treated between 2002 and 2008 of which 32 had pretreatment MRIs with T1, T2 and FLAIR available for review were selected for this study. These MRIs were fused with the treatment planning CT. Normal structures, clinical tumor volume (CTV and planning tumor volume (PTV were then defined on the T2 and FLAIR sequences. A Venn diagram analysis was performed for each pair of tumor volumes as well as a fractional component analysis to assess the contribution of each sequence to the union volume. For each patient the tumor volumes were compared in terms of total volume in cubic centimeters as well as anatomic location using a discordance index. The overlap of the tumor volumes with critical structures was calculated as a measure of predicted toxicity. For patients with MRI documented failures, the tumor volumes obtained using the different sequences were compared with the recurrent gross tumor volume (rGTV. Results The FLAIR CTVs and PTVs were significantly larger than the T2 CTVs and PTVs (p Conclusions Although both T2 and FLAIR MRI sequences are used to define high grade glial neoplasm and surrounding edema, our results show that the volumes generated using these techniques are different and not interchangeable. These differences have bearing on the use of intensity modulated radiation therapy (IMRT and highly conformal treatment as well as on future clinical trials where the bias of using one technique over the other may influence the study outcome.

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

    Science.gov (United States)

    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.

  13. Proton magnetic resonance spectroscopy in the distinction of high-grade cerebral gliomas from single metastatic brain tumors

    International Nuclear Information System (INIS)

    Server, Andres; Schellhorn, Till; Haakonsen, Monika; Nakstad, Per H.; Josefsen, Roger; Kulle, Bettina; Maehlen, Jan; Kumar, Theresa; Gadmar, Oeystein; Langberg, Carl W.

    2010-01-01

    Background: Brain metastases and primary high-grade gliomas, including glioblastomas multiforme (GBM) and anaplastic astrocytomas (AA), may be indistinguishable by conventional magnetic resonance (MR) imaging. Identification of these tumors may have therapeutic consequences. Purpose: To assess the value of MR spectroscopy (MRS) using short and intermediate echo time (TE) in differentiating solitary brain metastases and high-grade gliomas on the basis of differences in metabolite ratios in the intratumoral and peritumoral region. Material and Methods: We performed MR imaging and MRS in 73 patients with histologically verified intraaxial brain tumors: 53 patients with high-grade gliomas (34 GBM and 19 AA) and 20 patients with metastatic brain tumors. The metabolite ratios of Cho/Cr, Cho/NAA, and NAA/Cr at intermediate TE and the presence of lipids at short TE were assessed from spectral maps in the tumoral core, peritumoral edema, and contralateral normal-appearing white matter. The differences in the metabolite ratios between high-grade gliomas/GBM/AA and metastases were analyzed statistically. Cutoff values of Cho/Cr, Cho/NAA, and NAA/Cr ratios in the peritumoral edema, as well as Cho/Cr and NAA/Cr ratios in the tumoral core for distinguishing high-grade gliomas/GBM/AA from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Significant differences were noted in the peritumoral Cho/Cr, Cho/NAA, and NAA/ Cr ratios between high-grade gliomas/GBM/AA and metastases. ROC analysis demonstrated a cutoff value of 1.24 for peritumoral Cho/Cr ratio to provide sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 100%, 88.9%, 80.0%, and 100%, respectively, for discrimination between high-grade gliomas and metastases. By using a cutoff value of 1.11 for peritumoral Cho/NAA ratio, the sensitivity was 100%, the specificity was 91.1%, the PPV was 83.3%, and the NPV was 100%. Conclusion: The results of this

  14. Proton magnetic resonance spectroscopy in the distinction of high-grade cerebral gliomas from single metastatic brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Server, Andres; Schellhorn, Till; Haakonsen, Monika; Nakstad, Per H. (Section of Neuroradiology, Dept. of Medical Imaging and Intervention, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)), e-mail: a.s.alonso@medisin.uio.no; Josefsen, Roger (Dept. of Neurosurgery, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)); Kulle, Bettina (Epi-Gen Faculty Division, Akershus Univ. Hospital, and Dept. of Biostatistics, Univ. of Oslo, Oslo (Norway)); Maehlen, Jan; Kumar, Theresa (Dept. of Pathology, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)); Gadmar, Oeystein (Dept. of Diagnostic Physics, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway)); Langberg, Carl W. (Cancer Center, Oslo Univ. Hospital, Ullevaal, Univ. of Oslo, Oslo (Norway))

    2010-04-15

    Background: Brain metastases and primary high-grade gliomas, including glioblastomas multiforme (GBM) and anaplastic astrocytomas (AA), may be indistinguishable by conventional magnetic resonance (MR) imaging. Identification of these tumors may have therapeutic consequences. Purpose: To assess the value of MR spectroscopy (MRS) using short and intermediate echo time (TE) in differentiating solitary brain metastases and high-grade gliomas on the basis of differences in metabolite ratios in the intratumoral and peritumoral region. Material and Methods: We performed MR imaging and MRS in 73 patients with histologically verified intraaxial brain tumors: 53 patients with high-grade gliomas (34 GBM and 19 AA) and 20 patients with metastatic brain tumors. The metabolite ratios of Cho/Cr, Cho/NAA, and NAA/Cr at intermediate TE and the presence of lipids at short TE were assessed from spectral maps in the tumoral core, peritumoral edema, and contralateral normal-appearing white matter. The differences in the metabolite ratios between high-grade gliomas/GBM/AA and metastases were analyzed statistically. Cutoff values of Cho/Cr, Cho/NAA, and NAA/Cr ratios in the peritumoral edema, as well as Cho/Cr and NAA/Cr ratios in the tumoral core for distinguishing high-grade gliomas/GBM/AA from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Significant differences were noted in the peritumoral Cho/Cr, Cho/NAA, and NAA/ Cr ratios between high-grade gliomas/GBM/AA and metastases. ROC analysis demonstrated a cutoff value of 1.24 for peritumoral Cho/Cr ratio to provide sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 100%, 88.9%, 80.0%, and 100%, respectively, for discrimination between high-grade gliomas and metastases. By using a cutoff value of 1.11 for peritumoral Cho/NAA ratio, the sensitivity was 100%, the specificity was 91.1%, the PPV was 83.3%, and the NPV was 100%. Conclusion: The results of this

  15. Health-related quality of life in patients with high-grade gliomas

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, Karl Bang

    2015-01-01

    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity......-being increased significant, indicating a better HRQOL attend of followup. The diagnosis of a HGG leads to an ongoing functional decline measured as a decline of the KPS and a reduced physical activity during leisure time. Supportive care combined with rehabilitative and palliative approaches might well...... follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did...

  16. The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

    Science.gov (United States)

    Juratli, T A; Kirsch, M; Geiger, K; Klink, B; Leipnitz, E; Pinzer, T; Soucek, S; Schrock, E; Schrok, E; Schackert, G; Krex, D

    2012-12-01

    Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

  17. The challenges of management of high-grade gliomas in Nigeria

    Directory of Open Access Journals (Sweden)

    Chika Anele Ndubuisi

    2017-01-01

    Full Text Available Background: High-grade gliomas (HGG are among the most challenging brain tumors despite many research efforts worldwide. Aim: The aim of this study was to evaluate the local challenges that may influence outcome of HGG managed in a neurosurgical center in Nigeria. Methodology: Retrospective analysis of prospectively recorded data of patients managed for intracranial HGG at Memfys Hospital for Neurosurgery, Enugu, Nigeria, between the year 2006 and 2015. Only cases with conclusive histology following surgery were analyzed. Results: Glioma was 60 (23.8% of 252 histology confirmed brain tumors. HGG represented 53.8% of gliomas with male:female ratio of 2.2:1.0 and peaked from fifth decade of life. Glioblastoma multiforme accounted for 69% of HGG. At 1-year postsurgery, 53% of HGGs were dead and 88% of these deaths were in the World Health Organization Grade IV group. Only 40% of cases could receive adjuvant treatment with only 15% mortality at 1 year in this subgroup that received adjuvant therapy. In addition, 19% of cases had surgery at Karnofsky score (Ks of ≥70%. However, 94% of mortality at 1 year was related to surgery at Ks of ≤60%. Only four patients had a tumor volume of ≤50 cm3, and among these cases, three patients were independent at 1 year. Patients with tumor volume above 50 cm3 accounted for 94% of mortality. Conclusion: The peak age incidence for HGG seems to be lower than in Caucasians. Most cases present late with poor Ks and big tumor volume. The proportion with access to adjuvant treatment is still poor. Preoperative Karnofsky, extent of resection, duration of hospital, and Intensive Care Unit stay have impact on outcome.

  18. Reirradiation with concurrent bevacizumab for recurrent high-grade gliomas in adult patients.

    Science.gov (United States)

    Schernberg, A; Dhermain, F; Ammari, S; Dumont, S N; Domont, J; Patrikidou, A; Pallud, J; Dezamis, É; Deutsch, É; Louvel, G

    2018-02-01

    To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas. Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy). The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003), and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P0.05). Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50Gy. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  19. Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, G.; Grana, C.; Chinol, M.; Cremonesi, M.; De Cicco, C.; Zoboli, S. [Div. of Nuclear Medicine, European Inst. of Oncology, Milan (Italy); De Braud, F. [Div. of Medical Oncology, European Inst. of Oncology, Milan (Italy); Robertson, C. [Div. of Epidemiology and Biostatistics, European Inst. of Oncology, Milan (Italy); Zurrida, S.; Veronesi, U. [Scientific Director Office, European Institute of Oncology, Milan (Italy); Casadio, C. [Div. of Pathology and Lab. Medicine, European Inst. of Oncology, Milan (Italy); Siccardi, A.G. [San Raffaele Scientific Institute and University of Milan (Italy)

    1999-04-29

    While the incidence of brain tumours seems to be increasing, median survival in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatment. We have developed an avidin-biotin pre-targeting approach for delivering therapeutic radionuclides to gliomas, using anti-tenascin monoclonal antibodies, which seems potentially effective for treating these tumours. We treated 48 eligible patients with histologically confirmed grade III or IV glioma and documented residual disease or recurrence after conventional treatment. Three-step radionuclide therapy was performed by intravenous administration of 35 mg/m{sup 2} of biotinylated anti-tenascin monoclonal antibody (1st step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2nd step), and 18-24 h later by 1-2 mg of yttrium-90-labelled biotin (3rd step). {sup 90}Y doses of 2.22-2.96 GBq/m{sup 2} were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m{sup 2}. Tumour mass reduction (>25%-100%), documented by computed tomography or magnetic resonance imaging, occurred in 12/48 patients (25%), with 8/48 having a duration of response of at least 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a minor response and four with stable disease. Median survival from {sup 90}Y treatment is 11 months for grade IV glioblastoma and 19 months for grade III anaplastic gliomas. Avidin-biotin based three-step radionuclide therapy is well tolerated at the dose of 2.2 GBq/m{sup 2}, allowing the injection of {sup 90}Y-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in patients no longer responsive to other therapies. (orig.) With 5 figs., 4 tabs., 34 refs.

  20. In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.

    Directory of Open Access Journals (Sweden)

    Susanna J E Veringa

    Full Text Available Pediatric high-grade gliomas (pHGG, including diffuse intrinsic pontine gliomas (DIPG, are the leading cause of cancer-related death in children. While it is clear that surgery (if possible, and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.

  1. Solitary metastases and high-grade gliomas: radiological differentiation by morphometric analysis and perfusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hakyemez, B., E-mail: bahattinh@hotmail.co [Uludag University School of Medicine, Department of Radiology, Division of Neuroradiology, Bursa (Turkey); Erdogan, C.; Gokalp, G.; Dusak, A.; Parlak, M. [Uludag University School of Medicine, Department of Radiology, Division of Neuroradiology, Bursa (Turkey)

    2010-01-15

    Aim: To evaluate the value of morphometric analysis and perfusion-weighted magnetic resonance imaging (MRI) in differentiating solitary metastases from high-grade gliomas. Materials and methods: Forty-eight tumours (22 high-grade gliomas and 26 solitary hemispheric metastases) were evaluated using conventional and perfusion-weighted MRI. T2-weighted, gradient-echo, echo-planar sequences were used for perfusion-weighted MRI. Relative cerebral blood volume (rCBV) ratios were calculated by dividing the rCBV of the intratumoural and peritumoural areas with the average CBV value of the normal white matter areas. Morphometric analysis was carried out by proportioning the area of peritumoural oedema to the mass area. Mann-Whitney U test and ROC curve analysis were applied for statistical analysis. P < 0.05 was accepted as statistically significant. Results: Mean rCBV ratios of intratumoural areas of high-grade gliomas and metastases were 5.02 +- 2.47 and 4.62 +- 2.46, respectively. No statistically significant difference was found (p = 0.515). rCBV ratios of peritumoural oedema were 0.89 +- 0.51 in high-grade gliomas and 0.31 +- 0.12 in metastases. The difference was statistically significant (p < 0.001). According to the results of morphometric analysis, a statistically significant difference was present between the two tumour types (p < 0.001). Conclusion: Measuring the oedema: mass and rCBV ratios of the oedema surrounding the tumour prior to operation in solitary masses proved to be useful for differentiating metastases from high-grade gliomas.

  2. MGMT promoter methylation determined by HRM in comparison to MSP and pyrosequencing for predicting high-grade glioma response.

    Science.gov (United States)

    Switzeny, Olivier J; Christmann, Markus; Renovanz, Mirjam; Giese, Alf; Sommer, Clemens; Kaina, Bernd

    2016-01-01

    The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value. We analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan-Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP. Compared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

  3. Signaling pathways and mesenchymal transition in pediatric high-grade glioma.

    Science.gov (United States)

    Meel, Michaël H; Schaper, Sophie A; Kaspers, Gertjan J L; Hulleman, Esther

    2018-03-01

    Pediatric high-grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPG), are the most lethal types of cancer in children. In recent years, it has become evident that these tumors are driven by epigenetic events, mainly mutations involving genes encoding Histone 3, setting them apart from their adult counterparts. These tumors are exceptionally resistant to chemotherapy and respond only temporarily to radiotherapy. Moreover, their delicate location and diffuse growth pattern make complete surgical resection impossible. In many other forms of cancer, chemo- and radioresistance, in combination with a diffuse, invasive phenotype, are associated with a transcriptional program termed the epithelial-to-mesenchymal transition (EMT). Activation of this program allows cancer cells to survive individually, invade surrounding tissues and metastasize. It also enables them to survive exposure to cytotoxic therapy, including chemotherapeutic drugs and radiation. We here suggest that EMT plays an important, yet poorly understood role in the biology and therapy resistance of pHGG and DIPG. This review summarizes the current knowledge on the major signal transduction pathways and transcription factors involved in the epithelial-to-mesenchymal transition in cancer in general and in pediatric HGG and DIPG in particular. Despite the fact that the mesenchymal transition has not yet been specifically studied in pHGG and DIPG, activation of pathways and high levels of transcription factors involved in EMT have been described. We conclude that the mesenchymal transition is likely to be an important element of the biology of pHGG and DIPG and warrants further investigation for the development of novel therapeutics.

  4. Surgery of high grade gliomas - pros in favor of maximal cytoreductive surgery

    Directory of Open Access Journals (Sweden)

    C. Abrudan

    2011-03-01

    Full Text Available Background: Malignant glioma is themost common primary brain tumour inadults. More and more studies are focusedon the role of surgery in prolonged medianof survival and survival at two years. Thepurpose of this study is to add somearguments in favour of radical surgery inmalignant glioma.Material and Methods: The study is based433 cases of high grade cerebral gliomaoperated between 01.01.2000-31.12.2009 atthe Department of Neurosurgery, ClujCounty Emergency Hospital. We analyzedage, gender, type and duration ofsymptoms, type of surgery, pathologicaldiagnosis and the correlation of thesefactors with overall survival. Data for longterm follow up were available for 266patients.Results: The results shows, according totheir histological features, the fallowingdispersions: astrocitomas grade III (28%,glioblastoma multiforme (64%, high gradeoligodendrogliomas (5% and high gradeependimomas (3%. The global survivalrate was 47 % at 12 months, 26,3% at 18months and 16,7% at 24 months. The ageand type of surgery are prognostic factorsthat significantly influenced the survival at12, 18 and 24 months (9,3 months age 65 years; 9,2months GTR versus 6,4 months STR-at 12months monitoring; 11,7 months age 65; 11,5 monthsGTR versus 7,1 months STR-at 18 monthsmonitoring; 12,8 months age 65; 12,6 months GTR versus7,5 months STR –at 24 monthsmonitoring.Conclusions: Our study shows that longterm postoperative outcome after radicalsurgical resection are better than the resultsof either partial resection or simple biopsy;in terms of duration of survival (thedifference of mean survival at 12, 18 and 24months monitoring was 2,8 months, 4,4months and 5,1 months respectively infavour of patients with gross total removal .

  5. Dynamic CT perfusion imaging of intra-axial brain tumours: differentiation of high-grade gliomas from primary CNS lymphomas

    International Nuclear Information System (INIS)

    Schramm, Peter; Xyda, Argyro; Knauth, Michael; Klotz, Ernst; Tronnier, Volker; Hartmann, Marius

    2010-01-01

    Perfusion computed tomography (PCT) allows to quantitatively assess haemodynamic characteristics of brain tissue. We investigated if different brain tumor types can be distinguished from each other using Patlak analysis of PCT data. PCT data from 43 patients with brain tumours were analysed with a commercial implementation of the Patlak method. Four patients had low-grade glioma (WHO II), 31 patients had glioblastoma (WHO IV) and eight patients had intracerebral lymphoma. Tumour regions of interest (ROIs) were drawn in a morphological image and automatically transferred to maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and permeability (K Trans ). Mean values were calculated, group differences were tested using Wilcoxon and Mann Whitney U-tests. In comparison with normal parenchyma, low-grade gliomas showed no significant difference of perfusion parameters (p > 0.05), whereas high-grade gliomas demonstrated significantly higher values (p Trans , p Trans values compared with unaffected cerebral parenchyma (p = 0.0078) but no elevation of CBV. High-grade gliomas show significant higher CBV values than lymphomas (p = 0.0078). PCT allows to reliably classify gliomas and lymphomas based on quantitative measurements of CBV and K Trans . (orig.)

  6. CyberKnife® enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures

    Directory of Open Access Journals (Sweden)

    Oermann Eric

    2010-06-01

    Full Text Available Abstract Introduction With conventional radiation technique alone, it is difficult to deliver radical treatment (≥ 60 Gy to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. Methods Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy. Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife® image-guided radiosurgical system. The majority of patients (88% received concurrent and/or adjuvant Temozolmide. Results During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. Conclusion We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting

  7. Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC.

    Science.gov (United States)

    Heute, Dirk; Kostron, Herwig; von Guggenberg, Elisabeth; Ingorokva, Shota; Gabriel, Michael; Dobrozemsky, Georg; Stockhammer, Günther; Virgolini, Irene J

    2010-03-01

    The treatment of patients with high-grade malignant glioma still represents an unsolved clinical problem. We report the treatment of 3 patients who had World Health Organization grade IV recurrent glioblastoma: a 23-y-old woman and 2 men aged 61 and 62 y. All 3 patients were treated with the somatostatin receptor radiopharmaceutical (90)Y-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid(0)-d-Phe(1),Tyr(3)]octreotide (DOTATOC). A cumulated dose of 1.7-2.2 GBq given in 3 or 4 cycles was locally injected into a previously implanted catheter system. Treatment was successful in all 3 patients, with only minor side effects reported. After treatment, MRI and PET showed complete remission in one patient and partial remission in the other patients. These findings correlated well with clinical improvement and improved quality of life. Receptor-mediated radionuclide therapy by locally injected (90)Y-DOTATOC is feasible and well tolerated. This approach represents an attractive strategy for the treatment of locally recurring or progressing glioblastoma.

  8. Recent Application of Advanced MR Imaging to Predict Pseudoprogression in High-grade Glioma Patients.

    Science.gov (United States)

    Yoo, Roh-Eul; Choi, Seung Hong

    2016-01-01

    Pseudoprogression is regarded as a subacute form of treatment-related change with a reported incidence of 20-30%, occurring predominantly within the first three months after the completion of concurrent chemoradiotherapy (CCRT) in glioblastoma multiforme (GBM) patients. Occurrence of progressive lesions on conventional contrast-enhanced MR imaging may also accompany clinical deterioration, posing considerable diagnostic challenges to clinicians and radiologists. False interpretation of treatment-related change as true progression may lead to the cessation of effective first-line therapy (i.e., adjuvant temozolomide) and unnecessary surgery. Increasing awareness of the diagnostic challenge of the phenomenon has underscored the need for better imaging techniques that may aid in differentiating the treatment-related change from true progression. In this review, we discuss the recent applications of advanced MR imaging such as diffusion-weighted and perfusion-weighted imaging in the evaluation of treatment response in high-grade glioma patients and highlight their potential role in differentiating pseudoprogression from true progression.

  9. 5-Aminolevulinic Acid Fluorescence in High Grade Glioma Surgery: Surgical Outcome, Intraoperative Findings, and Fluorescence Patterns

    Directory of Open Access Journals (Sweden)

    Alessandro Della Puppa

    2014-01-01

    Full Text Available Background. 5-Aminolevulinic acid (5-ALA fluorescence is a validated technique for resection of high grade gliomas (HGG; the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Methods. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR>98% and GTR>90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO. Results. 94 patients were finally enrolled. Overall GTR>98% and GTR>90% was achieved in 93% and 100% of patients. Extent of resection (GTR>98% was dependent on tumor location, tumor grade (P<0.05, and tumor size (P<0.05. In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57% (P<0.01 and recurrent (60% tumors. Conclusions. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

  10. Comparison of T2 and FLAIR imaging for target delineation in high grade gliomas

    International Nuclear Information System (INIS)

    Stall, Bronwyn; Zach, Leor; Ning, Holly; Ondos, John; Arora, Barbara; Shankavaram, Uma; Miller, Robert W; Citrin, Deborah; Camphausen, Kevin

    2010-01-01

    FLAIR and T2 weighted MRIs are used based on institutional preference to delineate high grade gliomas and surrounding edema for radiation treatment planning. Although these sequences have inherent physical differences there is limited data on the clinical and dosimetric impact of using either or both sequences. 40 patients with high grade gliomas consecutively treated between 2002 and 2008 of which 32 had pretreatment MRIs with T1, T2 and FLAIR available for review were selected for this study. These MRIs were fused with the treatment planning CT. Normal structures, clinical tumor volume (CTV) and planning tumor volume (PTV) were then defined on the T2 and FLAIR sequences. A Venn diagram analysis was performed for each pair of tumor volumes as well as a fractional component analysis to assess the contribution of each sequence to the union volume. For each patient the tumor volumes were compared in terms of total volume in cubic centimeters as well as anatomic location using a discordance index. The overlap of the tumor volumes with critical structures was calculated as a measure of predicted toxicity. For patients with MRI documented failures, the tumor volumes obtained using the different sequences were compared with the recurrent gross tumor volume (rGTV). The FLAIR CTVs and PTVs were significantly larger than the T2 CTVs and PTVs (p < 0.0001 and p = 0.0001 respectively). Based on the discordance index, the abnormality identified using the different sequences also differed in location. Fractional component analysis showed that the intersection of the tumor volumes as defined on both T2 and FLAIR defined the majority of the union volume contributing 63.6% to the CTV union and 82.1% to the PTV union. T2 alone uniquely identified 12.9% and 5.2% of the CTV and PTV unions respectively while FLAIR alone uniquely identified 25.7% and 12% of the CTV and PTV unions respectively. There was no difference in predicted toxicity to normal structures using T2 or FLAIR. At the

  11. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges

    OpenAIRE

    Rahmathulla G; Hovey EJ; Hashemi-Sadraei N; Ahluwalia MS

    2013-01-01

    Gazanfar Rahmathulla,1 Elizabeth J Hovey,2,3 Neda Hashemi-Sadraei,4 Manmeet S Ahluwalia4 1Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, 2Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia; 3School of Medicine, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Neurological and Taussig Cancer Institutes, Cleveland Clinic, Cleveland, OH, USA Abstract: High-grade gliomas continue to have dismal prognosis d...

  12. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges.

    Science.gov (United States)

    Rahmathulla, Gazanfar; Hovey, Elizabeth J; Hashemi-Sadraei, Neda; Ahluwalia, Manmeet S

    2013-01-01

    High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV) are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas.

  13. Differentiation of intracranial tuberculomas and high grade gliomas using proton MR spectroscopy and diffusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Juan, E-mail: pengjuan1209@126.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Ouyang, Yu, E-mail: 1957ouyangyu@sina.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Fang, Wei-Dong, E-mail: fwd9707@yahoo.com.cn [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Luo, Tian-You, E-mail: ltychy@sina.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Li, Yong-Mei, E-mail: lymzhang70@yahoo.com.cn [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Lv, Fa-Jin, E-mail: fajinlv@hotmail.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Zhang, Zhi-Wei, E-mail: jintianzzw@163.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China); Li, Xin-You, E-mail: lixinyou666@163.com [Department of Radiology, the First Affiliated Hospital, Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing 400016 (China)

    2012-12-15

    Objective: The purpose of this study was to determine whether proton MR spectroscopy ({sup 1}H MRS) and diffusion-weighted (DW) imaging can be used to differentiate intracranial tuberculomas from high grade gliomas (HGGs). Materials and methods: A total of 41 patients (19 with intracranial tuberculomas and 22 with HGGs) were examined in our study. {sup 1}H MRS and DW imaging were performed at a 1.5T MR scanner before operation or treatment. Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lipid and lactate (LL) in the contrast-enhancing rim of each lesion were expressed as metabolite ratios and were normalized to the contralateral hemisphere. The apparent diffusion coefficient (ADC) was also calculated. The metabolite ratios and ADC values in the enhancing rim of intracranial tuberculomas and HGGs were compared using the Wilcoxon rank sum test. Diagnostic accuracy was compared using receiver operating characteristic (ROC) analysis. Results: Significant differences were found in the maximum Cho/Cr (P = 0.015), Cho/NAA (P = 0.001) and Cho/Cho-n ratios (P = 0.002), and minimum ADC value (P < 0.001) between the intracranial tuberculomas and HGGs. Diagnostic accuracy was higher by minimum ADC value than maximum Cho/Cr, Cho/NAA and Cho/Cho-n ratios (93.8% versus 75.7%, 80.8% and 78.1%). Conclusion: These results suggest a promising role for {sup 1}H MRS and DW imaging in the differentiation between the intracranial tuberculomas and HGGs.

  14. Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Narayana, Ashwatha, E-mail: ashwatha.narayana@nyumc.org [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Kunnakkat, Saroj D. [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Medabalmi, Praveen [Department of Biostatistics, New York University Langone Medical Center, New York, NY (United States); Golfinos, John; Parker, Erik [Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Knopp, Edmond [Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Zagzag, David [Department of Pathology, New York University Langone Medical Center, New York, NY (United States); Eagan, Patricia [Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Atlantic Health System, Overlook Hospital, Summit, NJ (United States); Gruber, Deborah [Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Gruber, Michael L. [Department of Neurosurgery, New York University Langone Medical Center, New York, NY (United States); Department of Neuro-Oncology, New York University Langone Medical Center, New York, NY (United States); Atlantic Health System, Overlook Hospital, Summit, NJ (United States)

    2012-01-01

    Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R{sup 2} = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

  15. The End-of-Life Phase of High-Grade Glioma Patients: Dying With Dignity?

    Science.gov (United States)

    Taphoorn, Martin J.B.; Uitdehaag, Bernard; Heimans, Jan J.; Deliens, Luc; Reijneveld, Jaap C.; Pasman, H. Roeline W.

    2013-01-01

    Background. In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. Methods. We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. Results. Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. Conclusions. Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life. PMID:23335620

  16. Integrin alpha 5 beta 1 Plays a Critical Role in Resistance to Temozolomide by Interfering with the p53 Pathway in High-Grade Glioma

    Czech Academy of Sciences Publication Activity Database

    Janoušková, Hana; Maglott, A.; Leger, D.Y.; Bossert, C.; Noulet, F.; Guerin, E.; Guenot, D.; Pinel, S.; Chastagner, P.; Plenat, F.; Entz-Werle, N.; Lehmann-Che, J.; Godet, J.; Martin, S.; Teisinger, Jan; Dontenwill, M.

    2012-01-01

    Roč. 72, č. 14 (2012), s. 3463-3470 ISSN 0008-5472 Institutional support: RVO:67985823 Keywords : cancer * integrins * high-grade glioma Subject RIV: CE - Biochemistry Impact factor: 8.650, year: 2012

  17. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges

    Directory of Open Access Journals (Sweden)

    Rahmathulla G

    2013-04-01

    Full Text Available Gazanfar Rahmathulla,1 Elizabeth J Hovey,2,3 Neda Hashemi-Sadraei,4 Manmeet S Ahluwalia4 1Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, 2Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia; 3School of Medicine, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Neurological and Taussig Cancer Institutes, Cleveland Clinic, Cleveland, OH, USA Abstract: High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas. Keywords: bevacizumab, antiangiogenesis, glioma, glioblastoma, vascular endothelial growth factor

  18. Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas

    OpenAIRE

    Lin, Yi; Jiang, Tao; Zhou, Kaijia; Xu, Li; Chen, Baoshi; Li, Guilin; Qiu, Xiaoguang; Jiang, Tianzi; Zhang, Wei; Song, Sonya W.

    2009-01-01

    Insulin-like growth factor binding protein 2 (IGFBP-2) is a malignancy-associated protein measurable in tumors and blood. Increased IGFBP-2 is associated with shortened survival of advanced glioma patients. Thus, we examined plasma IGFBP-2 levels in glioma patients and healthy controls to evaluate its value as a plasma bio-marker for glioma. Plasma IGFBP-2 levels in 196 patients with newly diagnosed glioma and 55 healthy controls were analyzed using an IGFBP-2 ELISA kit. Blood was collected b...

  19. Simultaneous integrated vs. sequential boost in VMAT radiotherapy of high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Farzin, Mostafa [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Tehran University of Medical Science, Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran (Iran, Islamic Republic of); Molls, Michael; Astner, Sabrina; Oechsner, Markus [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Radiation Oncology, Munich (Germany); Rondak, Ina-Christine [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institut fuer Medizinische Statistik und Epidemiologie, Munich (Germany)

    2015-12-15

    In 20 patients with high-grade gliomas, we compared two methods of planning for volumetric-modulated arc therapy (VMAT): simultaneous integrated boost (SIB) vs. sequential boost (SEB). The investigation focused on the analysis of dose distributions in the target volumes and the organs at risk (OARs). After contouring the target volumes [planning target volumes (PTVs) and boost volumes (BVs)] and OARs, SIB planning and SEB planning were performed. The SEB method consisted of two plans: in the first plan the PTV received 50 Gy in 25 fractions with a 2-Gy dose per fraction. In the second plan the BV received 10 Gy in 5 fractions with a dose per fraction of 2 Gy. The doses of both plans were summed up to show the total doses delivered. In the SIB method the PTV received 54 Gy in 30 fractions with a dose per fraction of 1.8 Gy, while the BV received 60 Gy in the same fraction number but with a dose per fraction of 2 Gy. All of the OARs showed higher doses (D{sub max} and D{sub mean}) in the SEB method when compared with the SIB technique. The differences between the two methods were statistically significant in almost all of the OARs. Analysing the total doses of the target volumes we found dose distributions with similar homogeneities and comparable total doses. Our analysis shows that the SIB method offers advantages over the SEB method in terms of sparing OARs. (orig.) [German] Es wurden 2 Arten der Planung fuer die volumetrisch modulierte Rotationsbestrahlung (VMAT) bei 20 Patienten mit hochgradigen Gliomen verglichen: simultan integrierter Boost (SIB) und sequenzieller Boost (SEB). Dazu wurde die Dosisverteilung in den Zielvolumina und den Risikoorganen analysiert. Es wurden Planungsvolumina (PTV), Boostvolumina (BV) und Risikoorgane konturiert sowie SIB- und SEB-Plaene erstellt. Der SEB besteht aus 2 Plaenen. Im ersten Plan erhaelt das PTV 50 Gy in 25 Fraktionen. Im zweiten Plan erhaelt das Boostvolumen 10 Gy in 5 Fraktionen (Einzeldosis jeweils 2 Gy). Die Dosis

  20. O9.04HIGH GRADE GLIOMAS AND CAREGIVERS' PSYCHOLOGICAL BURDEN

    Science.gov (United States)

    Petruzzi, A.; Finocchiaro, C.Y.; Vistalli, G.; Botturi, A.; Milanesi, I.; Silvani, A.; Lamperti, E.

    2014-01-01

    The diagnosis of a brain tumor is particularly stressful both for patients and their caregivers because the prognosis is poor and life expectancy is short. This is especially true when caregivers deal with high-grade gliomas (HGG). Despite treatment advances, median survival remains low, ranging from 1 to 5 years. Focal neurological deficits, epilepsy, cognitive dysfunction and symptoms of increased intracranial pressure are prominent symptoms in HHG and they may arise in any stage of the disease. Moreover, fatigue, mood disturbance, and anxiety are often reported. All these factors negatively affect patients' and caregivers' overall quality of life. Few studies have investigated, to date, the quality of life of the caregivers who take care of HGG patients. Thus, we sought to evaluate their quality of life and their specific reactions to caregiving. We recruited 91 caregivers of HGG patients. We used the following questionnaires in order to detect quality of life, anxiety, depression and specific reactions to patients' disease: 36-Item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), Caregiver Reaction Assessment Scale (CRA). These psychological questionnaires were administered in the form of an interview by a psychologist. The present study shows that caregivers experience higher levels of anxiety (t (90) = 11.3, p < .01) and depression (t (90) = 9.26, p < .01) than the normative sample. Also caregivers' mental health (“Vitality”, “Social Functioning”, “Role-Emotional”, “Mental Health”) appeared to be compromised as compared to the normative sample. As specific reactions to caregiving our caregivers presented “loss of physical strength” and “financial problems”. Caregiving experience did not negatively influence “caregivers' self-esteem”, “lack of family support” and “disrupted schedule”. Although a highly positive perception of the caregivers' self-esteem is reported, the impact of HGG diagnosis

  1. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk

    NARCIS (Netherlands)

    Walsh, Kyle M.; Codd, Veryan; Smirnov, Ivan V.; Rice, Terri; Decker, Paul A.; Hansen, Helen M.; Kollmeyer, Thomas; Kosel, Matthew L.; Molinaro, Annette M.; McCoy, Lucie S.; Bracci, Paige M.; Cabriga, Belinda S.; Pekmezci, Melike; Zheng, Shichun; Wiemels, Joseph L.; Pico, Alexander R.; Tihan, Tarik; Berger, Mitchell S.; Chang, Susan M.; Prados, Michael D.; Lachance, Daniel H.; O'Neill, Brain Patrick; Sicotte, Hugues; Eckel-Passow, Jeanette E.; van der Harst, Pim; Wiencke, John K.; Samani, Nilesh J.; Jenkins, Robert B.; Wrensch, Margaret R.

    Glioma, the most common central nervous system cancer in adults, has poor prognosis. Here we identify a new SNP associated with glioma risk, rs1920116 (near TERC), that reached genome-wide significance (P-combined = 8.3 x 10(-9)) in a meta-analysis of genome-wide association studies (GWAS) of

  2. Magnetic resonance perfusion for differentiating low-grade from high-grade gliomas at first presentation.

    Science.gov (United States)

    Abrigo, Jill M; Fountain, Daniel M; Provenzale, James M; Law, Eric K; Kwong, Joey Sw; Hart, Michael G; Tam, Wilson Wai San

    2018-01-22

    Gliomas are the most common primary brain tumour. They are graded using the WHO classification system, with Grade II-IV astrocytomas, oligodendrogliomas and oligoastrocytomas. Low-grade gliomas (LGGs) are WHO Grade II infiltrative brain tumours that typically appear solid and non-enhancing on magnetic resonance imaging (MRI) scans. People with LGG often have little or no neurologic deficit, so may opt for a watch-and-wait-approach over surgical resection, radiotherapy or both, as surgery can result in early neurologic disability. Occasionally, high-grade gliomas (HGGs, WHO Grade III and IV) may have the same MRI appearance as LGGs. Taking a watch-and-wait approach could be detrimental for the patient if the tumour progresses quickly. Advanced imaging techniques are increasingly used in clinical practice to predict the grade of the tumour and to aid clinical decision of when to intervene surgically. One such advanced imaging technique is magnetic resonance (MR) perfusion, which detects abnormal haemodynamic changes related to increased angiogenesis and vascular permeability, or "leakiness" that occur with aggressive tumour histology. These are reflected by changes in cerebral blood volume (CBV) expressed as rCBV (ratio of tumoural CBV to normal appearing white matter CBV) and permeability, measured by K trans . To determine the diagnostic test accuracy of MR perfusion for identifying patients with primary solid and non-enhancing LGGs (WHO Grade II) at first presentation in children and adults. In performing the quantitative analysis for this review, patients with LGGs were considered disease positive while patients with HGGs were considered disease negative.To determine what clinical features and methodological features affect the accuracy of MR perfusion. Our search strategy used two concepts: (1) glioma and the various histologies of interest, and (2) MR perfusion. We used structured search strategies appropriate for each database searched, which included: MEDLINE

  3. Combining Diffusion Tensor Metrics and DSC Perfusion Imaging: Can It Improve the Diagnostic Accuracy in Differentiating Tumefactive Demyelination from High-Grade Glioma?

    Science.gov (United States)

    Hiremath, S B; Muraleedharan, A; Kumar, S; Nagesh, C; Kesavadas, C; Abraham, M; Kapilamoorthy, T R; Thomas, B

    2017-04-01

    Tumefactive demyelinating lesions with atypical features can mimic high-grade gliomas on conventional imaging sequences. The aim of this study was to assess the role of conventional imaging, DTI metrics ( p:q tensor decomposition), and DSC perfusion in differentiating tumefactive demyelinating lesions and high-grade gliomas. Fourteen patients with tumefactive demyelinating lesions and 21 patients with high-grade gliomas underwent brain MR imaging with conventional, DTI, and DSC perfusion imaging. Imaging sequences were assessed for differentiation of the lesions. DTI metrics in the enhancing areas and perilesional hyperintensity were obtained by ROI analysis, and the relative CBV values in enhancing areas were calculated on DSC perfusion imaging. Conventional imaging sequences had a sensitivity of 80.9% and specificity of 57.1% in differentiating high-grade gliomas ( P = .049) from tumefactive demyelinating lesions. DTI metrics ( p : q tensor decomposition) and DSC perfusion demonstrated a statistically significant difference in the mean values of ADC, the isotropic component of the diffusion tensor, the anisotropic component of the diffusion tensor, the total magnitude of the diffusion tensor, and rCBV among enhancing portions in tumefactive demyelinating lesions and high-grade gliomas ( P ≤ .02), with the highest specificity for ADC, the anisotropic component of the diffusion tensor, and relative CBV (92.9%). Mean fractional anisotropy values showed no significant statistical difference between tumefactive demyelinating lesions and high-grade gliomas. The combination of DTI and DSC parameters improved the diagnostic accuracy (area under the curve = 0.901). Addition of a heterogeneous enhancement pattern to DTI and DSC parameters improved it further (area under the curve = 0.966). The sensitivity increased from 71.4% to 85.7% after the addition of the enhancement pattern. DTI and DSC perfusion add profoundly to conventional imaging in differentiating tumefactive

  4. Dynamic Contrast-Enhanced Perfusion MRI of High Grade Brain Gliomas Obtained with Arterial or Venous Waveform Input Function.

    Science.gov (United States)

    Filice, Silvano; Crisi, Girolamo

    2016-01-01

    The aim of this study was to evaluate the differences in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) perfusion estimates of high-grade brain gliomas (HGG) due to the use of an input function (IF) obtained respectively from arterial (AIF) and venous (VIF) approaches by two different commercially available software applications. This prospective study includes 20 patients with pathologically confirmed diagnosis of high-grade gliomas. The data source was processed by using two DCE dedicated commercial packages, both based on the extended Toft model, but the first customized to obtain input function from arterial measurement and the second from sagittal sinus sampling. The quantitative parametric perfusion maps estimated from the two software packages were compared by means of a region of interest (ROI) analysis. The resulting input functions from venous and arterial data were also compared. No significant difference has been found between the perfusion parameters obtained with the two different software packages (P-value < .05). The comparison of the VIFs and AIFs obtained by the two packages showed no statistical differences. Direct comparison of DCE-MRI measurements with IF generated by means of arterial or venous waveform led to no statistical difference in quantitative metrics for evaluating HGG. However, additional research involving DCE-MRI acquisition protocols and post-processing would be beneficial to further substantiate the effectiveness of venous approach as the IF method compared with arterial-based IF measurement. Copyright © 2015 by the American Society of Neuroimaging.

  5. The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients.

    Science.gov (United States)

    Chen, Jian-Wu; Zhou, Chang-Fu; Lin, Zhi-Xiong

    2015-09-15

    Although age is thought to correlate with the prognosis of glioma patients, the most appropriate age-group classification standard to evaluate prognosis had not been fully studied. This study aimed to investigate the influence of age-group classification standards on the prognosis of patients with high-grade hemispheric glioma (HGG). This retrospective study of 125 HGG patients used three different classification standards of age-groups (≤ 50 and >50 years old, ≤ 60 and >60 years old, ≤ 45 and 45-65 and ≥ 65 years old) to evaluate the impact of age on prognosis. The primary end-point was overall survival (OS). The Kaplan-Meier method was applied for univariate analysis and Cox proportional hazards model for multivariate analysis. Univariate analysis showed a significant correlation between OS and all three classification standards of age-groups as well as between OS and pathological grade, gender, location of glioma, and regular chemotherapy and radiotherapy treatment. Multivariate analysis showed that the only independent predictors of OS were classification standard of age-groups ≤ 50 and > 50 years old, pathological grade and regular chemotherapy. In summary, the most appropriate classification standard of age-groups as an independent prognostic factor was ≤ 50 and > 50 years old. Pathological grade and chemotherapy were also independent predictors of OS in post-operative HGG patients. Copyright © 2015. Published by Elsevier B.V.

  6. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib.

    LENUS (Irish Health Repository)

    Kinsella, Paula

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC(50)). Response for each culture was compared with the EGFR\\/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile.

  7. Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Ulyte, Agne [Vilnius University, Faculty of Medicine, Vilnius (Lithuania); Katsaros, Vasileios K. [General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Advanced Imaging Modalities - CT and MRI, Athens (Greece); University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Liouta, Evangelia; Stranjalis, Georgios [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Boskos, Christos [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Radiation Oncology, Athens (Greece); Papanikolaou, Nickolas [Champalimaud Foundation, Department of Radiology, Centre for the Unknown, Lisbon (Portugal); Usinskiene, Jurgita [National Cancer Institute, Vilnius (Lithuania); Affidea Lietuva, Vilnius (Lithuania); Bisdas, Sotirios [University College London Hospitals, Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, London (United Kingdom)

    2016-12-15

    The prognostic value of the dynamic contrast-enhanced (DCE) MRI perfusion and its histogram analysis-derived metrics is not well established for high-grade glioma (HGG) patients. The aim of this prospective study was to investigate DCE perfusion transfer coefficient (K{sup trans}), vascular plasma volume fraction (v{sub p}), extracellular volume fraction (v{sub e}), reverse transfer constant (k{sub ep}), and initial area under gadolinium concentration time curve (IAUGC) as predictors of progression-free (PFS) and overall survival (OS) in HGG patients. Sixty-nine patients with suspected anaplastic astrocytoma or glioblastoma underwent preoperative DCE-MRI scans. DCE perfusion whole tumor region histogram parameters, clinical details, and PFS and OS data were obtained. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify perfusion parameters with the best differentiation performance. On univariate analysis, v{sub e} and skewness of v{sub p} had significant negative impacts, while k{sub ep} had significant positive impact on OS (P < 0.05). v{sub e} was also a negative predictor of PFS (P < 0.05). Patients with lower v{sub e} and IAUGC had longer median PFS and OS on Kaplan-Meier analysis (P < 0.05). K{sup trans} and v{sub e} could also differentiate grade III from IV gliomas (area under the curve 0.819 and 0.791, respectively). High v{sub e} is a consistent predictor of worse PFS and OS in HGG glioma patients. v{sub p} skewness and k{sub ep} are also predictive for OS. K{sup trans} and v{sub e} demonstrated the best diagnostic performance for differentiating grade III from IV gliomas. (orig.)

  8. Basic Principles of Creation of Topometrical Cards of Beam Therapy in the Cases of High-grade Malignant Supratentorial Gliomas

    International Nuclear Information System (INIS)

    Liepa, Z.; Platkajis, A.; Apskalne, D.

    2007-01-01

    Background. High-grade malignant supratentorial gliomas: anaplastic astrocytomas (AA), anaplastic oligodendrogliomas (AO), anaplastic oligoatrocitomas (AOA), anaplastic ependimomas (AE), glioblastomas (GB) and other less occasional forms of gliomas are approximately 1,82% of all cases of malignant tumors. Life expectancy for such patients still is very low, for several forms of tumors -12-18 months. High-grade malignant gliomas need for combined approach, and one part of such approach is beam therapy. For reaching qualitative results of beam therapy, method of topometrical planning of beam therapy is crucial, because it allow planning therapy due to anatomic features of every patient. The aim of work was comparison of basic principles of creation of 2-dimensional (2D) and 3-dimensional (3D) topometrical cards of beam therapy. Material and methods. In the process of research, analyse of creation of 2D and 3D cards for patients in period 2000-2005 were made. For creation of 2D cards pelviometer, conturometer of head (Picture 1), pictures of tests of brains in the biggest cross - section of tumor (Picture 2) were used. For creation 3D cards computertomography LightSpeed Rt, which is suitable for topometry (Picture 3), planning system of 3D reconstruction ECLIPSE (Picture 4), 3D reconstruction by data from pre - surgery and/or after - surgery tests of brain (Picture 5), and matching in format of DICOM (Picture 6) were used. In this research 214 patients with supratentorial malign gliomas were covered (Table 1,2). Results. In 98 cases 2D topometrical cards were made, which allows creating only two contrary areas of entry of beams or two areas of entry under angle (Picture 7, 8). In 55 cases in 2D topographic cards two contrary areas of entry were made and in 43 cases plan of beam therapy with areas of entry under angle were made. 3D cards anatomic features of patient as well as location of critical organs were taken into account (picture 10). In case of 3D the number of

  9. 18F-Fluorocholine PET/CT, Brain MRI, and 5-Aminolevulinic Acid for the Assessment of Tumor Resection in High-Grade Glioma.

    Science.gov (United States)

    García Vicente, Ana María; Jiménez Aragón, Fátima; Villena Martín, Maikal; Jiménez Londoño, German Andrés; Borrás Moreno, Jose María

    2017-06-01

    High-grade glioma is a very aggressive and infiltrative tumor in which complete resection is a chance for a better outcome. We present the case of a 57-year-old man with a brain lesion suggestive of high-grade glioma. Brain MRI and F-fluorocholine PET/CT were performed previously to plan the surgery. Surgery was microscope assisted after the administration of 5-aminolevulinic acid. Postsurgery brain MRI and PET were blind evaluated to the surgery results and reported as probably gross total resection.

  10. High bone sialoprotein (BSP expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

    Directory of Open Access Journals (Sweden)

    Tao Xu

    Full Text Available OBJECTIVES: To investigate the expression and prognostic value of bone sialoprotein (BSP in glioma patients. METHODS: We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001. Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS and overall survival (OS in both grade III and grade IV glioma patients [hazard ratio (HR = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6-methylguanine (O(6-meG DNA methyltransferase (MGMT methylation and Karnofsky performance score (KPS less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

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

    Directory of Open Access Journals (Sweden)

    Angela Spurgeon

    2016-01-01

    Full Text Available 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.

  12. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Wuthrick, Evan J., E-mail: evan.wuthrick@osumc.edu [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Curran, Walter J. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Department of Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland (United States); Lin, Alexander [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Glass, Jon; Evans, James; Andrews, David W. [Department of Neurological Surgery, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Axelrod, Rita [Department of Medical Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Shi, Wenyin; Werner-Wasik, Maria [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Haacke, E. Mark [Department of Radiology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Department of Biomedical Engineering, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Hillman, Gilda G. [Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan (United States); Dicker, Adam P. [Department of Radiation Oncology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-10-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival.

  13. A Pilot Study of Hypofractionated Stereotactic Radiation Therapy and Sunitinib in Previously Irradiated Patients With Recurrent High-Grade Glioma

    International Nuclear Information System (INIS)

    Wuthrick, Evan J.; Curran, Walter J.; Camphausen, Kevin; Lin, Alexander; Glass, Jon; Evans, James; Andrews, David W.; Axelrod, Rita; Shi, Wenyin; Werner-Wasik, Maria; Haacke, E. Mark; Hillman, Gilda G.; Dicker, Adam P.

    2014-01-01

    Purpose/Objective(s): Angiogenic blockade with irradiation may enhance the therapeutic ratio of radiation therapy (RT) through vascular normalization. We sought to determine the safety and toxicity profile of continuous daily-dosed sunitinib when combined with hypofractionated stereotactic RT (fSRT) for recurrent high-grade gliomas (rHGG). Methods and Materials: Eligible patients had malignant high-grade glioma that recurred or progressed after primary surgery and RT. All patients received a minimum of a 10-day course of fSRT, had World Health Organization performance status of 0 to 1, and a life expectancy of >3 months. During fSRT, sunitinib was administered at 37.5 mg daily. The primary endpoint was acute toxicity, and response was assessed via serial magnetic resonance imaging. Results: Eleven patients with rHGG were enrolled. The fSRT doses delivered ranged from 30 to 42 Gy in 2.5- to 3.75-Gy fractions. The median follow-up time was 40 months. Common acute toxicities included hematologic disorders, fatigue, hypertension, and elevated liver transaminases. Sunitinib and fSRT were well tolerated. One grade 4 mucositis toxicity occurred, and no grade 4 or 5 hypertensive events or intracerebral hemorrhages occurred. One patient had a nearly complete response, and 4 patients had stable disease for >9 months. Two patients (18%) remain alive and progression-free >3 years from enrollment. The 6-month progression-free survival was 45%. Conclusions: Sunitinib at a daily dose of 37.5 mg given concurrently with hypofractionated stereotactic reirradiation for rHGG yields acceptable toxicities and an encouraging 6-month progression-free survival

  14. Needs and preferences among patients with high-grade glioma and their caregivers - A longitudinal mixed methods study.

    Science.gov (United States)

    Piil, K; Jakobsen, J; Christensen, K B; Juhler, M; Guetterman, T C; Fetters, M D; Jarden, M

    2018-01-04

    Previous reports on the patient perspective of daily life during a 1-year high-grade glioma (HGG) trajectory from the time of diagnosis are sparse. The aim of this longitudinal mixed methods study is to identify the specific needs and preferences for rehabilitation and supportive care and how it links with physical activity, psychological measures and health quality longitudinally over the first year after diagnosis among patients with HGG and their caregivers by integrating qualitative and quantitative findings. Using a longitudinal mixed methods design, patients with malignant glioma (n = 30) and their caregivers (n = 33) were interviewed and completed questionnaires (patients only) about physical activity level, anxiety/depression and quality of life five times during the 1-year period. Their needs and preferences included interventions designed to re-define hope after diagnosis, health promoting physical activities initiated early, psychological symptom management strategies, and life planning. Caregivers are committed to their caregiving role, but their engagement is nonetheless challenged over time by enormous caregiver burdens. The identified specific needs and preferences favour supportive care, education, information and rehabilitation. Guidelines attentive to these needs and implemented in clinical practice have the potential to improve patients' health-related quality of life and support caregivers by involving them more actively in care and management. © 2018 The Authors. European Journal of Cancer Care Published by John Wiley & Sons Ltd.

  15. Revisit the Candidacy of Brain Cell Types as the Cell(s) of Origin for Human High-Grade Glioma.

    Science.gov (United States)

    Shao, Fangjie; Liu, Chong

    2018-01-01

    High-grade glioma, particularly, glioblastoma, is the most aggressive cancer of the central nervous system (CNS) in adults. Due to its heterogeneous nature, glioblastoma almost inevitably relapses after surgical resection and radio-/chemotherapy, and is thus highly lethal and associated with a dismal prognosis. Identifying the cell of origin has been considered an important aspect in understanding tumor heterogeneity, thereby holding great promise in designing novel therapeutic strategies for glioblastoma. Taking advantage of genetic lineage-tracing techniques, performed mainly on genetically engineered mouse models (GEMMs), multiple cell types in the CNS have been suggested as potential cells of origin for glioblastoma, among which adult neural stem cells (NSCs) and oligodendrocyte precursor cells (OPCs) are the major candidates. However, it remains highly debated whether these cell types are equally capable of transforming in patients, given that in the human brain, some cell types divide so slowly, therefore may never have a chance to transform. With the recent advances in studying adult NSCs and OPCs, particularly from the perspective of comparative biology, we now realize that notable differences exist among mammalian species. These differences have critical impacts on shaping our understanding of the cell of origin of glioma in humans. In this perspective, we update the current progress in this field and clarify some misconceptions with inputs from important findings about the biology of adult NSCs and OPCs. We propose to re-evaluate the cellular origin candidacy of these cells, with an emphasis on comparative studies between animal models and humans.

  16. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    International Nuclear Information System (INIS)

    Kinsella, Paula; Howley, Rachel; Doolan, Padraig; Clarke, Colin; Madden, Stephen F.; Clynes, Martin; Farrell, Michael; Amberger-Murphy, Verena

    2012-01-01

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC 50 ). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-α expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: ► Non-responders had low EGFR expression, high PDGFR-β, and a low proliferation rate. ► PTEN is not indicative of response to a TKI. ► Erlotinib response was not associated with expression of the proteins examined. ► Imatinib-response correlated with expression of PDGFR-α. ► Gefitinib response correlated with increased expression of EGFR.

  17. Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, Paula, E-mail: paula.kinsella@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Howley, Rachel, E-mail: rhowley@rcsi.ie [Department of Neuropathology, Beaumont Hospital, Dublin 9 (Ireland); Doolan, Padraig, E-mail: padraig.doolan@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Clarke, Colin, E-mail: colin.clarke@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Madden, Stephen F., E-mail: maddens@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Clynes, Martin, E-mail: Martin.Clynes@dcu.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); Farrell, Michael, E-mail: michaelfarrell@beaumont.ie [Department of Neuropathology, Beaumont Hospital, Dublin 9 (Ireland); Amberger-Murphy, Verena, E-mail: Verena.Murphy@icorg.ie [National Institute for Cellular Biotechnology, Dublin City University, Dublin 9 (Ireland); All Ireland Co-operative, Oncology Research Group, 60 Fitzwilliam Square, Dublin 2 (Ireland)

    2012-03-10

    High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Response to TKIs was assessed using 50% inhibitory concentrations (IC{sub 50}). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-{alpha} expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: Black-Right-Pointing-Pointer Non-responders had low EGFR expression, high PDGFR-{beta}, and a low proliferation rate. Black-Right-Pointing-Pointer PTEN is not indicative of response to a TKI. Black-Right-Pointing-Pointer Erlotinib response was not associated with expression of the proteins examined. Black-Right-Pointing-Pointer Imatinib-response correlated with expression of PDGFR-{alpha}. Black-Right-Pointing-Pointer Gefitinib response correlated with increased expression of EGFR.

  18. Profiling Hsp90 differential expression and the molecular effects of the Hsp90 inhibitor IPI-504 in high-grade glioma models.

    Science.gov (United States)

    Di, Kaijun; Keir, Stephen T; Alexandru-Abrams, Daniela; Gong, Xing; Nguyen, Howard; Friedman, Henry S; Bota, Daniela A

    2014-12-01

    Retaspimycin hydrochloride (IPI-504), an Hsp90 (heat shock protein 90) inhibitor, has shown activity in multiple preclinical cancer models, such as lung, breast and ovarian cancers. However, its biological effects in gliomas and normal brain derived cellular populations remain unknown. In this study, we profiled the expression pattern of Hsp90α/β mRNA in stable glioma cell lines, multiple glioma-derived primary cultures and human neural stem/progenitor cells. The effects of IPI-504 on cell proliferation, apoptosis, motility and expression of Hsp90 client proteins were evaluated in glioma cell lines. In vivo activity of IPI-504 was investigated in subcutaneous glioma xenografts. Our results showed Hsp90α and Hsp90β expression levels to be patient-specific, higher in high-grade glioma-derived primary cells than in low-grade glioma-derived primary cells, and strongly correlated with CD133 expression and differentiation status of cells. Hsp90 inhibition by IPI-504 induced apoptosis, blocked migration and invasion, and significantly decreased epidermal growth factor receptor levels, mitogen-activated protein kinase and/or Akt activities, and secretion of vascular endothelial growth factor in glioma cell lines. In vivo study showed that IPI-504 could mildly attenuate tumor growth in immunocompromised mice. These findings suggest that targeting Hsp90 by IPI-504 has the potential to become an active therapeutic strategy in gliomas in a selective group of patients, but further research into combination therapies is still needed.

  19. Trends in peri-operative performance status following resection of high grade glioma and brain metastases: The impact on survival.

    Science.gov (United States)

    Patel, Chirag K; Vemaraju, Ravi; Glasbey, James; Shires, Joanne; Northmore, Tessa; Zaben, Malik; Hayhurst, Caroline

    2018-01-01

    Maximal surgical resection of high grade brain tumours is associated with improved overall survival (OS). It carries the risk of neurological deterioration leading to worsening performance status (PS), which may affect overall survival and preclude patients from adjuvant therapy. We aim to review the changes in performance status of patients undergoing resection of high grade tumours and metastases and the impact of changes on overall survival. A prospective study of the perioperative performance status of 75 patients who underwent primary resection of malignant primary brain tumour or solitary metastasis in a single centre. Data on patients' demographics, tumour histology and overall survival were also collected. WHO performance status was recorded pre-operatively and at intervals following surgery. Of the 75 patients (35 males, 40 females, median age 61 years at diagnosis), 50 had primary malignant brain tumours, 25 had metastasis. Although PS dropped at postoperative day 1 in 14 patients (18.7%), 28% improved by day 5 and there was significant improvement by day 14 (41%, p=0.02). The number of patients with PS 3 or worse changed from 4% pre-operatively (n=3) to 8% (n=6). Overall survival is better in those whose PS remained improved or unchanged at 2 weeks after surgery compared to those whose PS deteriorated; high grade glioma median survival 15.67 vs. 2.4 months (p=0.005) and metastasis median survival 8.53 vs.2.33 months (p=0.001). Our data demonstrates that although PS may deteriorate immediately after surgery, the majority of patients regain their baseline PS or improve by 2 weeks postoperatively; decisions on fitness for adjuvant treatment should therefore be delayed until then. In those patients whose PS declines following surgery overall survival is poor. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  20. Advanced PET and MR imaging in re-irradiation of high grade glioma

    DEFF Research Database (Denmark)

    Møller, Søren

    2014-01-01

    . The goal of this Ph.D. project was to evaluate the side-effects and efficacy of re-irradiation of highgrade glioma and to determine the value of positron emission tomography (PET) using an amino acid tracer for re-irradiation. Moreover, to identify imaging biomarkers capable of predicting the clinical....... The patients in the re-irradiation study underwent cognitive testing as a means of assessing side effects. The studies showed that the side effects of re-irradiation were acceptable but not negligible. Tumor size evaluated by PET was prognostic for survival following radiotherapy and it PET likely contributed......Primary brain cancer is rare but devastating disease. The cancer infiltrates healthy brain tissue and causes neurological symptoms, seizures and cognitive dysfunction. The treatment is aggressive and may have late adverse effects that mimic the symptoms of the disease. Recurrence is almost...

  1. In vivo single-voxel proton MR spectroscopy in the differentiation of high-grade gliomas and solitary metastases

    International Nuclear Information System (INIS)

    Fan, G.; Sun, B.; Wu, Z.; Guo, Q.; Guo, Y.

    2004-01-01

    AIM: To determine whether single-voxel proton magnetic resonance spectroscopy (1HMRS) could be used to differentiate gliomas from metastases on the basis of differences in metabolite levels in the different involved regions. MATERIALS AND METHODS: Twenty-two patients (age range from 32 to 62 years, with a median age of 46.7 years) with a solitary brain tumour (14 gliomas, eight metastases) underwent conventional, gadolinium-DTPA enhanced T1-weighted images, and 1HMRS before surgical resection. Spectra from the enhancing tumour, the peritumoural region, and normal brain were obtained from 1HMRS. A point resolved spectroscopy sequence was required for 1HMRS. The metabolites in the spectra include: N-acetylaspartate (NAA), choline (CHO), creatine compounds (CR), myo-inositol (MI), lactate (LAC), glutamate and glutamine (Glu-n). Relative concentrations of metabolites were related to the peak area, and expressed with reference to CR. Student's t-test was used to determine whether there was a statistically significant difference in relative metabolic ratios between high-grade gliomas and metastases. Meanwhile, 16 of all 22 patients were re-examined using magnetic resonance imaging (MRI) within 6 months of surgical resection. Recurrence was present in three patients (two gliomas, one metastasis). RESULTS: Of the 14 patients with gliomas, the peaks of NAA were reduced in three cases; the peaks of LAC, which were elevated, appeared as typical double-peaks in the peritumoural region in nine cases; the peaks of Glu-n, which were also elevated, had a zigzag appearance in seven cases. The peaks of MI were increased in the tumoural region in eight cases, and CHO levels were elevated in all 14 cases. Of the eight patients with metastases, Glu-n peaks in the tumoural region in three cases and CHO peaks in the tumoural region in four cases were elevated, respectively, while the peaks of CR were reduced in three cases, and the peaks of NAA were markedly reduced in four cases within

  2. Metabolic syndrome factors and risk of postoperative depression in high-grade glioma patients in a 1.5-year prospective study.

    Science.gov (United States)

    Jiao, Jian-Tong; Jiang, Chen; Huang, Jin; Dai, Min-Chao; Wang, Cheng; Cheng, Chao; Shao, Jun-Fei

    2014-10-01

    To date, the relationship between metabolic syndrome factors and the risk of glioma-related depression is still unclear, and no study investigates this relationship. Our aim was to investigate the relationship between metabolic syndrome factors and the risk of postoperative depression in high-grade patients. A total of 386 high-grade glioma patients participated in blood sample collection for metabolic syndrome factors analysis and the hospital anxiety and depression scale testing. The association between metabolic syndrome factors and the risk of postoperative depression was assessed using Cox regression proportional hazards models, and Student's t tests were used to evaluate the differences in demographic variables and clinical characteristics in subgroups. The incidence of postoperative depression in our 1.5-year follow-up was 30.5%. We found the risk of postoperative depression was elevated with increased blood glucose level [hazard ratios (HR) 2.277, 95% confidence interval (CI) 1.201-4.320, top vs. bottom quartile]. The hazard ratio was increased for z-scores of blood glucose (HR 1.672 per unit standard deviation, 95% CI 1.311-2.133] and of the combined metabolic syndrome score (HR 1.080, 95% CI 1.000-1.167). In addition, risk of postoperative depression risk was increased in high-grade glioma patients with high blood glucose levels (≥6.0 mmol/l) (HR 2.084, 95% CI 1.235-3.515). However, we did not find significant associations between postoperative depression and other metabolic syndrome factors, including body mass index, systolic blood pressure, diastolic blood pressure, cholesterol, and triglycerides. Depression is prevalent among patients with high-grade glioma after operation. Blood glucose level is positively associated with the risk of postoperative depression, and might be involved in the etiology of postoperative depression, and may predict its development in high-grade glioma patients.

  3. Health-related quality of life in patients with high-grade gliomas: a quantitative longitudinal study.

    Science.gov (United States)

    Piil, K; Jakobsen, J; Christensen, K B; Juhler, M; Jarden, M

    2015-09-01

    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did not report any depressive symptoms, eight individuals (26.7 %) being depressed at various time points. Among a sub-group of participants who completed all study requirements for the entire study period the level of anxiety decreased significantly during the study. The FACT-Br sub-scale of emotional well-being increased significant, indicating a better HRQOL attend of followup. The diagnosis of a HGG leads to an ongoing functional decline measured as a decline of the KPS and a reduced physical activity during leisure time. Supportive care combined with rehabilitative and palliative approaches might well be valuable along the trajectory especially during the post-surgery period when anxiety is at its highest peak.

  4. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

    Directory of Open Access Journals (Sweden)

    Barth Rolf F

    2012-08-01

    Full Text Available Abstract Boron neutron capture therapy (BNCT is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH. In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger

  5. Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Seong; Ahn, Sung Soo; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, College of Medicine, Seoul (Korea, Republic of); Chang, Jong Hee; Kang, Seok-Gu [Yonsei University College of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Se Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Zhou, Jinyuan [Johns Hopkins University School of Medicine, Division of MRI Research, Department of Radiology, Baltimore, MD (United States)

    2017-08-15

    To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. (orig.)

  6. Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume

    International Nuclear Information System (INIS)

    Choi, Yoon Seong; Ahn, Sung Soo; Lee, Seung-Koo; Chang, Jong Hee; Kang, Seok-Gu; Kim, Se Hoon; Zhou, Jinyuan

    2017-01-01

    To evaluate the added value of amide proton transfer (APT) imaging to the apparent diffusion coefficient (ADC) from diffusion tensor imaging (DTI) and the relative cerebral blood volume (rCBV) from perfusion magnetic resonance imaging (MRI) for discriminating between high- and low-grade gliomas. Forty-six consecutive adult patients with diffuse gliomas who underwent preoperative APT imaging, DTI and perfusion MRI were enrolled. APT signals were compared according to the World Health Organization grade. The diagnostic ability and added value of the APT signal to the ADC and rCBV for discriminating between low- and high-grade gliomas were evaluated using receiver operating characteristic (ROC) analyses and integrated discrimination improvement. The APT signal increased as the glioma grade increased. The discrimination abilities of the APT, ADC and rCBV values were not significantly different. Using both the APT signal and ADC significantly improved discrimination vs. the ADC alone (area under the ROC curve [AUC], 0.888 vs. 0.910; P = 0.007), whereas using both the APT signal and rCBV did not improve discrimination vs. the rCBV alone (AUC, 0.927 vs. 0.923; P = 0.222). APT imaging may be a useful imaging biomarker that adds value to the ADC for discriminating between low- and high-grade gliomas. (orig.)

  7. Radiotherapy in the management of high-grade gliomas diagnosed in Western Australia: a patterns of care study

    International Nuclear Information System (INIS)

    Jackson, Melanie; Taylor, Mandy; Bydder, Sean; Maujean, Eric; Nowak, Anna

    2012-01-01

    Radiotherapy (RT) plays an integral role in the management of high-grade glioma (HGG). However, there is little information on the patterns of care in unselected Australian patients with HGG. This prospective cohort study collected information on patients with a diagnosis of HGG managed in Western Australia over a 25-month period from 2006 to 2008. RT treatment and survival data were analysed. 86% of Western Australian patients with HGG were treated at the study site over this period. Of these, 80% were reviewed by a radiation oncologist with RT recommended in 88% of cases. One hundred eighty-seven patients proceeded to have RT, with most receiving 60 Gy in 30 fractions with limited field external beam radiotherapy (LFRT). Median survival from diagnosis was 13.6 months for all patients and 15.4 months for those planned for treatment with 60 Gy in 30 fractions. The median time from surgery to the start of RT was 41 days. Longer waiting times were not predictors of poor survival. Failure to receive all planned treatment (13% of patients) predicted for poor survival (hazard ratio 0.38). Dose and fractionation practices show concordance with published data and guidelines. Survival is also consistent with clinical trial data for patients planned for aggressive therapy. Nevertheless, a substantial number of patients are not suited to aggressive therapy or fail to complete planned therapy, and these patients have poor outcomes. Treatment delays did not affect survival outcomes but are confounded by earlier treatment of those unsuited to LFRT.

  8. Protoporphyrin-IX fluorescence guided surgical resection in high-grade gliomas: The potential impact of human colour perception.

    Science.gov (United States)

    Petterssen, Max; Eljamel, Sarah; Eljamel, Sam

    2014-09-01

    Protoporphyrin-IX (Pp-IX) fluorescence had been used frequently in recent years to guide microsurgical resection of high-grade gliomas (HGG), particularly following the publication of a randomized controlled trial demonstrating its advantages. However, Pp-IX fluorescence is dependent upon the surgeons' eyes' perception of red fluorescent colour. This study was designed to evaluate human eye fluorescence perception and establish a fluorescence scale. 20 of 108 pre-recorded images from intraoperative fluorescence of HGG were used to construct an 8-panel visual analogue fluorescence scale. The scale was validated by testing 56 participants with normal colour vision and three red-green colour-blind participants. For intra-rater agreement ten participants were tested twice and for inter-observer reliability the whole cohort were tested. The intra- and inter-observer reliability of the scale in normal colour vision participants was excellent. The scale was less reliable in the violet-blue panels of the scale. Colour-blind participants were not able to distinguish between red fluorescence and blue-violet colours. The 8-panel fluorescence scale is valid in differentiating red, pink and blue colours in a fluorescence surgical field among participants with normal colour perception and potentially useful to standardize fluorescence-guided surgery. However, colourblind surgeons should not use fluorescence-guided surgery. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Survival in adult patients with diagnosis of high-grade glioma located in the central nervous system, who were treated with radiotherapy and temozolamide at Hospital Mexico during the period from January 2009 to December 2011

    International Nuclear Information System (INIS)

    Chaves Porras, Jorge Alvaro

    2013-01-01

    The impact of survival is determined by the incorporation of the chemotherapeutic temozolamide into the therapy regimen of patients with high grade gliomas. Overall survival is determined in patients with high grade gliomas. The investigation is performed with the total of patients with high grade gliomas, with treatment of radiotherapy and temozolamide. Progression-free survival is determined in the population with high-grade gliomas at Hospital Mexico, from January 2009 to December 2011. The diagnosis of glioblastoma is given in 86% and astrocytoma grade III in 14% of the cases. The concomitance of radiotherapy with temozolomide is received by 33 of 37 patients. Seventy-six percent of patients completed the 6 cycles of adjuvant therapy. The overall survival rate was 14.39 months. Patients with grade III gliomas have had a better prognosis [es

  10. Unsupervised consensus cluster analysis of [18F]-fluoroethyl-L-tyrosine positron emission tomography identified textural features for the diagnosis of pseudoprogression in high-grade glioma

    OpenAIRE

    Kebir, Sied; Khurshid, Zain; Gaertner, Florian C.; Essler, Markus; Hattingen, Elke; Fimmers, Rolf; Scheffler, Bj?rn; Herrlinger, Ulrich; Bundschuh, Ralph A.; Glas, Martin

    2016-01-01

    Rationale Timely detection of pseudoprogression (PSP) is crucial for the management of patients with high-grade glioma (HGG) but remains difficult. Textural features of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) mirror tumor uptake heterogeneity; some of them may be associated with tumor progression. Methods Fourteen patients with HGG and suspected of PSP underwent FET-PET imaging. A set of 19 conventional and textural FET-PET features were evaluated and subjecte...

  11. EORTC 22972-26991/MRC BR10 trial: Fractionated stereotactic boost following conventional radiotherapy of high grade gliomas

    International Nuclear Information System (INIS)

    Baumert, Brigitta G.; Brada, Michael; Bernier, Jacques; Kortmann, Rolf D.; Dehing-Oberije, Cary; Collette, Laurence; Davis, J. Bernard

    2008-01-01

    Background and purpose: The EORTC trial No. 22972 investigated the role of an additional fractionated stereotactic boost (fSRT) to conventional radiotherapy for patients with high grade gliomas. A quality-assurance (QA) programme was run in conjunction with the study and was the first within the EORTC addressing the quality of a supposedly highly accurate treatment technique such as stereotactic radiotherapy. A second aim was to investigate a possible relation between the clinical results of the stereotactic boost arm and the results of the QA. Materials and methods: The trial was closed in 2001 due to low accrual. In total, 25 patients were randomized: 14 into the experimental arm and 11 into the control arm. Six centres randomized patients, 8 centres had completed the dummy run (DR) for the stereotactic boost part. All participating centres (9) were asked to complete a quality-assurance questionnaire. The DR consisted of treatment planning according to the guidelines of the protocol on 3 different tumour volumes drawn on CT images of a humanized phantom. The SRT technique to be used was evaluated by the questionnaire. Clinical data from patients recruited to the boost arm from 6 participating centres were analysed. Results: There was a full compliance to the protocol requirements for 5 centres. Major and minor deviations in conformality were observed for 2 and 3 centres, respectively. Of the 8 centres which completed the DR, one centre did not comply with the requirements of stereotactic radiotherapy concerning accuracy, dosimetry and planning. Median follow-up and median overall survival were 39.2 and 21.4 months, respectively. Acute and late toxicities of the stereotactic boost were low. One radiation necrosis was seen for a patient who has not received the SRT boost. Three reported serious adverse events were all seizures and probably therapy-related. Conclusions: Overall compliance was good but not ideal from the point of view of this highly precise radiation

  12. Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics.

    Science.gov (United States)

    Hoffman, Lindsey M; DeWire, Mariko; Ryall, Scott; Buczkowicz, Pawel; Leach, James; Miles, Lili; Ramani, Arun; Brudno, Michael; Kumar, Shiva Senthil; Drissi, Rachid; Dexheimer, Phillip; Salloum, Ralph; Chow, Lionel; Hummel, Trent; Stevenson, Charles; Lu, Q Richard; Jones, Blaise; Witte, David; Aronow, Bruce; Hawkins, Cynthia E; Fouladi, Maryam

    2016-01-04

    Diffuse intrinsic pontine glioma (DIPG) and midline high-grade glioma (mHGG) are lethal childhood brain tumors. Spatial genomic heterogeneity has been well-described in adult HGG but has not been comprehensively characterized in pediatric HGG. We performed whole exome sequencing on 38-matched primary, contiguous, and metastatic tumor sites from eight children with DIPG (n = 7) or mHGG (n = 1) collected using a unique MRI-guided autopsy protocol. Validation was performed using Sanger sequencing, Droplet Digital polymerase-chain reaction, immunohistochemistry, and fluorescent in-situ hybridization. Median age at diagnosis was 6.1 years (range: 2.9-23.3 years). Median overall survival was 13.2 months (range: 11.2-32.2 months). Contiguous tumor infiltration and distant metastases were observed in seven and six patients, respectively, including leptomeningeal dissemination in three DIPGs. Histopathological heterogeneity was evident in seven patients, including intra-pontine heterogeneity in two DIPGs, ranging from World Health Organization grade II to IV astrocytoma. We found conservation of heterozygous K27M mutations in H3F3A (n = 4) or HIST1H3B (n = 3) across all primary, contiguous, and metastatic tumor sites in all DIPGs. ACVR1 (n = 2), PIK3CA (n = 2), FGFR1 (n = 2), and MET (n = 1) were also intra-tumorally conserved. ACVR1 was co-mutated with HIST1H3B (n = 2). In contrast, PDGFRA amplification and mutation were spatially heterogeneous, as were mutations in BCOR (n = 1), ATRX (n = 2), and MYC (n = 1). TP53 aberrations (n = 3 patients) varied by type and location between primary and metastatic tumors sites but were intra-tumorally conserved. Spatial conservation of prognostically-relevant and therapeutically-targetable somatic mutations in DIPG and mHGG contrasts the significant heterogeneity of driver mutations seen in adult HGG and supports uniform implementation of diagnostic biopsy in DIPG and mHGG to

  13. Phase II Trial of Radiotherapy After Hyperbaric Oxygenation With Multiagent Chemotherapy (Procarbazine, Nimustine, and Vincristine) for High-Grade Gliomas: Long-Term Results

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuhiko, E-mail: kogawa@med.u-ryukyu.ac.jp [Department of Radiology, University of the Ryukyus, Okinawa (Japan); Ishiuchi, Shogo [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Inoue, Osamu [Department of Hyperbaric Medicine, University of the Ryukyus, Okinawa (Japan); Yoshii, Yoshihiko [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Department of Neurosurgery, Tsukuba Memorial Hospital, Tsukuba (Japan); Saito, Atsushi [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Department of Neurosurgery, Tsukuba Medical Center Hospital, Tsukuba (Japan); Watanabe, Takashi [Department of Neurosurgery, University of the Ryukyus, Okinawa (Japan); Iraha, Shiro [Department of Radiology, Okinawa South Medical Center, Okinawa (Japan); Department of Radiology, University of the Ryukyus, Okinawa (Japan); Toita, Takafumi; Kakinohana, Yasumasa; Ariga, Takuro; Kasuya, Goro; Murayama, Sadayuki [Department of Radiology, University of the Ryukyus, Okinawa (Japan)

    2012-02-01

    Purpose: To analyze the long-term results of a Phase II trial of radiotherapy given immediately after hyperbaric oxygenation (HBO) with multiagent chemotherapy in adults with high-grade gliomas. Methods and Materials: Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. Results: A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range, 43.2-119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multivariate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious nonhematologic or late toxicities were seen in any of the 57 patients. Conclusions: Radiotherapy delivered immediately after HBO with multiagent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas.

  14. A Phase I Study of the Combination of Sorafenib With Temozolomide and Radiation Therapy for the Treatment of Primary and Recurrent High-Grade Gliomas

    International Nuclear Information System (INIS)

    Den, Robert B.; Kamrava, Mitchell; Sheng, Zhi; Werner-Wasik, Maria; Dougherty, Erin; Marinucchi, Michelle; Lawrence, Yaacov R.; Hegarty, Sarah; Hyslop, Terry; Andrews, David W.; Glass, Jon; Friedman, David P.; Green, Michael R.; Camphausen, Kevin; Dicker, Adam P.

    2013-01-01

    Purpose: Despite recent advances in the management of high-grade and recurrent gliomas, survival remains poor. Antiangiogenic therapy has been shown to be efficacious in the treatment of high-grade gliomas both in preclinical models and in clinical trials. We sought to determine the safety and maximum tolerated dose of sorafenib when combined with both radiation and temozolomide in the primary setting or radiation alone in the recurrent setting. Methods and Materials: This was a preclinical study and an open-label phase I dose escalation trial. Multiple glioma cell lines were analyzed for viability after treatment with radiation, temozolomide, or sorafenib or combinations of them. For patients with primary disease, sorafenib was given concurrently with temozolomide (75 mg/m 2 ) and 60 Gy radiation, for 30 days after completion of radiation. For patients with recurrent disease, sorafenib was combined with a hypofractionated course of radiation (35 Gy in 10 fractions). Results: Cell viability was significantly reduced with the combination of radiation, temozolomide, and sorafenib or radiation and sorafenib. Eighteen patients (11 in the primary cohort, 7 in the recurrent cohort) were enrolled onto this trial approved by the institutional review board. All patients completed the planned course of radiation therapy. The most common toxicities were hematologic, fatigue, and rash. There were 18 grade 3 or higher toxicities. The median overall survival was 18 months for the entire population. Conclusions: Sorafenib can be safely combined with radiation and temozolomide in patients with high-grade glioma and with radiation alone in patients with recurrent glioma. The recommended phase II dose of sorafenib is 200 mg twice daily when combined with temozolomide and radiation and 400 mg with radiation alone. To our knowledge, this is the first publication of concurrent sorafenib with radiation monotherapy or combined with radiation and temozolomide.

  15. Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Dijken, Bart R.J. van [University of Groningen, University Medical Center Groningen Department of Radiology, Groningen (Netherlands); Laar, Peter Jan van; Hoorn, Anouk van der [University of Groningen, University Medical Center Groningen Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Holtman, Gea A. [University of Groningen, University Medical Center Groningen, Department of General Practice, Groningen (Netherlands)

    2017-10-15

    Treatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas. Databases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included. Anatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51-81) and 77% (45-93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60-80) and specificity of 87% (77-93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82-91) with a specificity of 86% (77-91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73-98) and specificity was 85% (76-92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79-97) and specificity was 95% (65-99). Advanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas. (orig.)

  16. Distress and psychological morbidity do not reduce over time in carers of patients with high-grade glioma.

    Science.gov (United States)

    Halkett, Georgia K B; Lobb, Elizabeth A; Shaw, Thèrése; Sinclair, Michelle M; Miller, Lisa; Hovey, Elizabeth; Nowak, Anna K

    2017-03-01

    This study aimed to determine how carer distress and psychological morbidity change over time following a patient's diagnosis of high-grade glioma (HGG) and identify factors associated with changes in carers' psychological status. Carers of patients with HGG planned for chemoradiotherapy were recruited to this longitudinal cohort study. Carers completed questionnaires during patients' chemoradiotherapy and 3 and 6 months later including the following: the Distress Thermometer (DT); General Health Questionnaire-12 (GHQ-12); and three single-item questions about understanding of information presented by health professionals, confidence to care and preparedness to care for their relative/friend. Linear latent growth models were applied. The time 1 questionnaire was completed by 118 carers, of these 70 carers provided responses to the third time point. Carer distress and psychological morbidity were most prominent proximal to diagnosis, but remained high over time. Sixty-two percent of participants had moderate or high distress on the DT at time 1, 61% at time 2 and 58% at time 3. Scores on the DT and the GHQ-12 correlated significantly at all time points as did changes in scores over time (p GHQ-12 scores at one time point did not strongly predict scores at subsequent time points. In carers of patients with HGG, distress levels are consistently high and cannot be predicted at any time point. Carers should be monitored over time to identify evolving psychological morbidity. The single-item DT correlates highly with GHQ-12 scores and is a suitable tool for rapid repeated screening.

  17. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

    Directory of Open Access Journals (Sweden)

    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  18. ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Nowosielski, Martha; Tinkhauser, Gerd; Stockhammer, Guenther [Innsbruck Medical University, Department of Neurology, Innsbruck (Austria); Recheis, Wolfgang; Schocke, Michael; Gotwald, Thaddaeus [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Goebel, Georg [Innsbruck Medical University, Department of Medical Statistics, Informatics and Health Economics, Innsbruck (Austria); Gueler, Oezguer [Innsbruck Medical University, 4D Visualization Laboratory, University Clinic of Oto-, Rhino- and Laryngology, Innsbruck (Austria); Kostron, Herwig [Innsbruck Medical University, Department of Neurosurgery, Innsbruck (Austria); Hutterer, Markus [Innsbruck Medical University, Department of Neurology, Innsbruck (Austria); Paracelsus Medical University Salzburg-Christian Doppler Hospital, Department of Neurology, Salzburg (Austria)

    2011-04-15

    The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI). This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated. hT2 were defined as regions of interest (ROI) and registered to corresponding ADC maps (hT2-ADC). Histograms were calculated from hT2-ADC ROIs. Thereafter, histogram asymmetry termed ''skewness'' was calculated and compared to progression-free survival (PFS) as defined by the Response Assessment Neuro-Oncology (RANO) Working Group criteria. At 8-12 weeks follow-up, seven (50%) patients showed a partial response, three (21.4%) patients were stable, and four (28.6%) patients progressed according to RANO criteria. hT2-ADC histograms demonstrated statistically significant changes in skewness in relation to PFS at 6 months. Patients with increasing skewness (n = 11) following B/I therapy had significantly shorter PFS than did patients with decreasing or stable skewness values (n = 3, median percentage change in skewness 54% versus -3%, p = 0.04). In rHGG patients, the change in ADC histogram skewness may be predictive for treatment response early in the course of anti-angiogenic therapy and more sensitive than treatment assessment based solely on RANO criteria. (orig.)

  19. Patterns of Failure After Concurrent Bevacizumab and Hypofractionated Stereotactic Radiation Therapy for Recurrent High-Grade Glioma

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    Shapiro, Lauren Q. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn, E-mail: bealk@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goenka, Anuj [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Karimi, Sasan [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Iwamoto, Fabio M. [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lassman, Andrew B.; Abrey, Lauren E. [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gutin, Philip H. [Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-01

    Purpose: Concurrent bevacizumab with hypofractionated stereotactic radiation therapy (HSRT) is safe and effective for the treatment of recurrent high-grade gliomas (HGG). The objective of this study was to characterize the patterns of failure after this treatment regimen. Methods and Materials: Twenty-four patients with recurrent enhancing HGG were previously treated on an institutional review board-approved protocol of concurrent bevacizumab and reirradiation. Patients received 30 Gy in 5 fractions to the recurrent tumor with HSRT. Brain magnetic resonance imaging (MRI) was performed every 2 cycles, and bevacizumab was continued until clinical or radiographic tumor progression according to the criteria of Macdonald et al. MRI at the time of progression was fused to the HSRT treatment plan, and the location of recurrence was classified on the basis of volume within the 95% isodose line. Outcomes based on patient characteristics, tumor grade, recurrence pattern, and best response to treatment were analyzed by the Kaplan-Meier method. Results: Twenty-two patients experienced either clinical or radiographic progression. Recurrent tumor was enhancing in 15 (71.4%) and nonenhancing in 6 (28.6%) patients. Eleven patients (52.4%) had recurrence within the radiation field, 5 patients (23.8%) had marginal recurrence, and 5 patients had recurrence outside the radiation field. Pattern of enhancement and location of failure did not correlate with overall survival or progression-free survival. Radiographic response was the only variable to significantly correlate with progression-free survival. Conclusions: Despite the promising initial response seen with the addition of HSRT to bevacizumab as salvage treatment for recurrent HGG, approximately half of patients ultimately still experience failure within the radiation field. The rate of local failure with the addition of HSRT seems to be lower than that seen with bevacizumab alone in the salvage setting. Our data underscore the

  20. Proliferation Index Predicts Survival after Second Craniotomy within 6 Months of Adjuvant Radiotherapy for High-grade Glioma.

    Science.gov (United States)

    Gzell, C; Wheeler, H; Huang, D; Gaur, P; Chen, J; Kastelan, M; Back, M

    2016-03-01

    To determine pathological features that predict survival in patients having repeat craniotomy within 6 months of radiotherapy for high-grade glioma (HGG). HGG patients (World Health Organization grade 3/4) managed with repeat craniotomy within 6 months of completing radiotherapy between 2008 and 2012 were included. Based on the presence of residual tumour cells, the pathology was reported as pathological progression or pathological pseudoprogression. The proliferation index (Ki67) was reported and compared with initial pathology as a percentage change. Tumour necrosis was estimated as a percentage of the specimen. Overall survival was calculated in months. Of 327 patients managed with HGG, 27 patients underwent repeat craniotomy within 6 months of radiotherapy. The median survival after reoperation was 11 months (95% confidence interval 1-22). Ki67 at reoperation of 0%, 1-9% and >10% was associated with survival with a median survival of 13, 13 and 3 months, respectively (P = 0.007). Change in Ki67 was also associated with median survival, with 80% reduction median survival 13 months, P = 0.02. Widespread treatment-related necrosis improved outcome, with >80% necrosis having a median survival of 13 months versus 3 months in those with craniotomy within 6 months of radiotherapy is not an independent indicator of prognosis. Patients with residual tumour that had a low Ki67 had a similar median survival as those with only treatment necrosis. Reduced proliferation of residual tumour cells and widespread necrosis may be more important indicators for future outcome. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  1. Phase II Trial of Erlotinib during and after Radiotherapy in Children with Newly Diagnosed High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Ibrahim eQaddoumi

    2014-04-01

    Full Text Available Background. Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG. Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy in children with newly diagnosed HGG. Methods. Following maximum surgical resection, patients between 3 and 21 years with nonmetastatic HGG received local radiotherapy at 59.4 Gy (54 Gy for spinal tumors and those with ≥70% brain involvement. Erlotinib started on day 1 of radiotherapy (120 mg/m2 per day and continued for 2 years unless there was tumor progression or intolerable toxicities. The 2-year progression-free survival (PFS was estimated for patients with intracranial anaplastic astrocytoma (AA and glioblastoma.Results. Median age at diagnosis for 41 patients with intracranial tumors (21 with glioblastoma and 20 with AA was 10.9 years (range, 3.3 to 19 years. The 2-year PFS for patients with AA and glioblastoma was 15% ± 7% and 19% ± 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n=11, dermatologic (n=5, and metabolic (n=4. One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis. Conclusions. Although therapy with erlotinib was mostly well tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and glioblastoma.

  2. Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

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    Huang, Jiayi, E-mail: jhuang@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); DeWees, Todd A.; Badiyan, Shahed N.; Speirs, Christina K.; Mullen, Daniel F.; Fergus, Sandra [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Tran, David D.; Linette, Gerry; Campian, Jian L. [Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri (United States); Chicoine, Michael R.; Kim, Albert H.; Dunn, Gavin [Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri (United States); Simpson, Joseph R.; Robinson, Clifford G. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States)

    2015-08-01

    Purpose: Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters. Methods and Materials: From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL. Results: Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V{sub 25Gy}) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V{sub 25Gy} <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006). Conclusions: Female sex, older age, lower baseline TLC, and higher brain V{sub 25Gy} are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V{sub 25Gy} of brain below 56% may reduce the risk of ASL.

  3. Altered Expression of MGMT in High-Grade Gliomas Results from the Combined Effect of Epigenetic and Genetic Aberrations

    Science.gov (United States)

    Ramalho-Carvalho, João; Pires, Malini; Lisboa, Susana; Graça, Inês; Rocha, Patrícia; Barros-Silva, João Diogo; Savva-Bordalo, Joana; Maurício, Joaquina; Resende, Mário; Teixeira, Manuel R.; Honavar, Mrinalini; Henrique, Rui; Jerónimo, Carmen

    2013-01-01

    MGMT downregulation in high-grade gliomas (HGG) has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP) or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA). By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation) and genetic (monosomy, locus deletion) changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy. PMID:23505468

  4. Fluorescein-Guided Surgery for Resection of High-Grade Gliomas: A Multicentric Prospective Phase II Study (FLUOGLIO).

    Science.gov (United States)

    Acerbi, Francesco; Broggi, Morgan; Schebesch, Karl-Michael; Höhne, Julius; Cavallo, Claudio; De Laurentis, Camilla; Eoli, Marica; Anghileri, Elena; Servida, Maura; Boffano, Carlo; Pollo, Bianca; Schiariti, Marco; Visintini, Sergio; Montomoli, Cristina; Bosio, Lorenzo; La Corte, Emanuele; Broggi, Giovanni; Brawanski, Alexander; Ferroli, Paolo

    2018-01-01

    Purpose: Sodium fluorescein is a dye that, intravenously injected, selectively accumulates in high-grade glioma (HGG) tissue through a damaged blood-brain barrier. In this article, the final results of a multicentric prospective phase II trial (FLUOGLIO) on fluorescein-guided HGG resection through a dedicated filter on the surgical microscope were reported. Methods: Patients with suspected HGGs considered suitable for removal were eligible to participate in this trial. Fluorescein was intravenously injected at a dose of 5 to 10 mg/kg. The primary endpoint was the percentage of patients with histologically confirmed HGGs, without contrast-enhancing tumor at the immediate postoperative MRI. Secondary endpoints were PFS, residual tumor on postoperative MRI, overall survival, neurologic deficits, and fluorescein-related toxicity. The sensitivity and specificity of fluorescein in identifying tumor tissue were estimated by fluorescent and nonfluorescent biopsies at the tumor margin. The study was registered on the European Regulatory Authorities website (EudraCT 2011-002527-18). Results: Fifty-seven patients aged 45 to 75 years were screened for participation, and 46 were considered for primary and secondary endpoints. Mean preoperative tumor volume was 28.75 cm 3 (range, 1.3-87.8 cm 3 ). Thirty-eight patients (82.6%) underwent a complete tumor removal. Median follow-up was 11 months. PFS-6 and PFS-12 were 56.6% and 15.2%. Median survival was 12 months. No adverse reaction related to SF administration was recorded. The sensitivity and specificity of fluorescein in identifying tumor tissue were respectively 80.8% and 79.1%. Conclusions: Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and enables a high percentage of contrast-enhancing tumor in patients with HGGs. Clin Cancer Res; 24(1); 52-61. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. High grade hemangioendothelioma of the temporal bone in a child: a case report

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    Kim, Hyo Lim; Im, Soo Ah; Lim, Gye Yeon; Chun, Ho Jong; Lee, Hee Jeong; Park, Hyun Jin; Byun, Jae Young [The Catholic University of Korea, College of Medicine, Seoul (Korea, Republic of)

    2004-09-15

    Hemangioendothelioma is a rare vascular tumor characterized by endothelial tumor cells and variable malignant behavior, and it's not common for this lesion to involve the bone. Although there are a few reports of cranial involvement by hemangioendothelioma, only rare cases arising in temporal bone have been published. We present the radiologic findings of a 7-year-old boy who had a high grade hemangioendothelioma involving the temporal bone with intracranial extension. Evidence of flow voids on MR images suggested a tumor of vascular origin, and the ill-defined margins, cortical destruction and intracranial extension on the CT and MR images were correlated with the tumor's high histologic grade.

  6. Association between small heat shock protein B11 and the prognostic value of MGMT promoter methylation in patients with high-grade glioma.

    Science.gov (United States)

    Cheng, Wen; Li, Mingyang; Jiang, Yang; Zhang, Chuanbao; Cai, Jinquan; Wang, Kuanyu; Wu, Anhua

    2016-07-01

    OBJECT This study investigated the role and prognostic value of heat shock proteins (HSPs) in glioma. METHODS Data from 3 large databases of glioma samples (Chinese Glioma Genome Atlas, Repository for Molecular Brain Neoplasia Data, and GSE16011), which contained whole-genome messenger RNA microarray expression data and patients' clinical data, were analyzed. Immunohistochemical analysis was performed to validate protein expression in another set of 50 glioma specimens. RESULTS Of 28 HSPs, 11 were overexpressed in high-grade glioma (HGG) compared with low-grade glioma. A univariate Cox analysis revealed that HSPB11 has significant prognostic value for each glioma grade, which was validated by a Kaplan-Meier survival analysis. HSPB11 expression was associated with poor prognosis and was independently correlated with overall survival (OS) in HGG. This study further explored the combined role of HSPB11 and other molecular markers in HGG, such as isocitrate dehydrogenase 1 (IDH1) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. HSPB11 expression was able to refine the prognostic value of IDH1 mutation in patients with HGG. However, when combined with MGMT promoter methylation status, among patients with a methylated MGMT promoter, those with lower levels of HSPB11 expression had longer OS and progression-free survival than patients with higher levels of HSPB11 expression or with an unmethylated MGMT promoter. Moreover, within the MGMT promoter methylation group, patients with low levels of HSPB11 expression were more sensitive to combined radiochemotherapy than those with high levels of HSPB11 expression, which may explain why some patients with HGG with a methylated MGMT promoter show tolerance to radiochemotherapy. CONCLUSIONS HSPB11 was identified as a novel prognostic marker in patients with HGG. Together with MGMT promoter methylation status, HSPB11 expression can predict outcome for patients with HGG and identify those who

  7. Diagnostic Values of DCE-MRI and DSC-MRI for Differentiation Between High-grade and Low-grade Gliomas: A Comprehensive Meta-analysis.

    Science.gov (United States)

    Liang, Jianye; Liu, Dexiang; Gao, Peng; Zhang, Dong; Chen, Hanwei; Shi, Changzheng; Luo, Liangping

    2018-03-01

    This study aimed to collect the studies on the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and dynamic susceptibility contrast MRI (DSC-MRI) in differentiating the grades of gliomas, and evaluate the diagnostic performances of relevant quantitative parameters in glioma grading. We systematically searched studies on the diagnosis of gliomas with DCE-MRI or DSC-MRI in Medline, PubMed, China National Knowledge Infrastructure database, Cochrane Library, and Embase published between January 2005 and December 2016. Standardized mean differences and 95% confidence intervals were calculated for volume transfer coefficient (K trans ), volume fraction of extravascular extracellular space (V e ), rate constant of backflux (K ep ), relative cerebral blood volume (rCBV), and relative cerebral blood flow (rCBF) using Review Manager 5.2 software. Sensitivity, specificity, area under the curve (AUC), and Begg test were calculated by Stata 12.0. Twenty-two studies with available outcome data were included in the analysis. The standardized mean difference of K trans values between high-grade glioma and low-grade glioma were 1.18 (0.91, 1.45); V e values were 1.43 (1.06, 1.80); K ep values were 0.65 (-0.05, 1.36); rCBV values were 1.44 (1.08, 1.81); and rCBF values were 1.17 (0.68, 1.67), respectively. The results were all significant statistically (P values (P = .07), and high-grade glioma had higher K trans , V e , rCBV, and rCBF values than low-grade glioma. AUC values of K trans , V e , rCBV, and rCBF were 0.90, 0.88, 0.93, and 0.73, respectively; rCBV had the largest AUC among the four parameters (P < .05). Both DCE-MRI and DSC-MRI are reliable techniques in differentiating the grades of gliomas, and rCBV was found to be the most sensitive one. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  8. Inhibitors of GLUT/SLC2A Enhance the Action of BCNU and Temozolomide against High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Alberto Azzalin

    2017-04-01

    Full Text Available Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV and ritonavir (RTV, and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2 superfamily, phlorizin (PHZ, in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma. PHZ was inactive on the same cells. Similar results were obtained when cells were grown in adherence or as 3D multicellular tumor spheroids. RTV treatment but not IDV treatment induced AMP-activated protein kinase (AMPKα phosphorylation that paralleled the decrease in glycolytic activity and cell growth. IDV, but not RTV, induced an increase in GLUT1/SLC2A1 whose activity could compensate for the inhibition of GLUT4/SLC2A4 by IDV. RTV and IDV pass poorly the blood brain barrier and are unlikely to reach sufficient liquoral concentrations in vivo to inhibit glioblastoma growth as single agents. Isobologram analysis of the association of RTV or IDV and 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU or 4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo[4.3.0]nona-2,7,9-triene-9-carboxamide (TMZ indicated synergy only with RTV on inhibition of glioblastoma cells. Finally, we tested in vivo the combination of RTV and BCNU on established GL261 tumors. This drug combination increased the overall survival and allowed a five-fold reduction in the dose of BCNU.

  9. Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index

    International Nuclear Information System (INIS)

    Uehara, Kazuyuki; Fujii, Osamu; Soejima, Toshinori; Sugimura, Kazuro; Kohmura, Eiji; Sasaki, Ryohei; Sasayama, Takashi; Miyawaki, Daisuke; Nishimura, Hideki; Yoshida, Kenji; Okamoto, Yoshiaki; Mukumoto, Naritoshi; Akasaka, Hiroaki; Nishihara, Masamitsu

    2012-01-01

    The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB). We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field). The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not. MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease

  10. Downregulation of miR-137 and miR-6500-3p promotes cell proliferation in pediatric high-grade gliomas.

    Science.gov (United States)

    Liang, Muh-Lii; Hsieh, Tsung-Han; Ng, Kim-Hai; Tsai, Ya-Ni; Tsai, Cheng-Fong; Chao, Meng-En; Liu, Da-Jung; Chu, Shing-Shiung; Chen, Wan; Liu, Yun-Ru; Liu, Ren-Shyan; Lin, Shih-Chieh; Ho, Donald Ming-Tak; Wong, Tai-Tong; Yang, Muh-Hwa; Wang, Hsei-Wei

    2016-04-12

    Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors affecting children, and outcomes have remained dismal, even with access to new multimodal therapies. In this study, we compared the miRNomes and transcriptomes of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p as significantly downregulated in pHGGs. miR-137 or miR-6500-3p overexpression reduced cell proliferation in two pHGG cell lines, SF188 and UW479. CENPE, KIF14 and NCAPG levels were significantly higher in pHGGs than pLGGs, and were direct targets of miR-137 or miR-6500-3p. Furthermore, knockdown of CENPE, KIF14 or NCAPG combined with temozolomide treatment resulted in a combined suppressive effect on pHGG cell proliferation. In summary, our results identify novel mRNA/miRNA interactions that contribute to pediatric glioma malignancy and represent potential targets for the development of new therapeutic strategies.

  11. Safety and efficacy of a novel cannabinoid chemotherapeutic, KM-233, for the treatment of high-grade glioma.

    Science.gov (United States)

    Duntsch, Christopher; Divi, Murali Krishna; Jones, Terreia; Zhou, Qihong; Krishnamurthy, Mathangi; Boehm, Peter; Wood, George; Sills, Allen; Moore, Bob M

    2006-04-01

    To test in vitro and in vivo the safety and efficacy of a novel chemotherapeutic agent, KM-233, for the treatment of glioma. In vitro cell cytotoxicity assays were used to measure and compare the cytotoxic effects of KM-233, Delta(8)-tetrahydrocannabinol (THC), and bis-chloroethyl-nitrosurea (BCNU) against human U87 glioma cells. An organotypic brain slice culture model was used for safety and toxicity studies. A human glioma-SCID mouse side-pocket tumor model was used to test in vivo the safety and efficacy of KM-233 with intratumoral and intra-peritoneal administration. KM-233 is a classical cannabinoid with good blood brain barrier penetration that possesses a selective affinity for the CB2 receptors relative to THC. KM-233 was as efficacious in its cytotoxicity against human U87 glioma as Delta(8)-tetrahydrocannabinol, and superior to the commonly used anti-glioma chemotherapeutic agent, BCNU. The cytotoxic effects of KM-233 against human glioma cells in vitro occur as early as two hours after administration, and dosing of KM-233 can be cycled without compromising cytotoxic efficacy and while improving safety. Cyclical dosing of KM-233 to treat U87 glioma in a SCID mouse xenograft side pocket model was effective at reducing the tumor burden with both systemic and intratumoral administration. These studies provide both in vitro and in vivo evidence that KM-233 shows promising efficacy against human glioma cell lines in both in vitro and in vivo studies, minimal toxicity to healthy cultured brain tissue, and should be considered for definitive preclinical development in animal models of glioma.

  12. With a Little Help from My Friends: The Role of Intraoperative Fluorescent Dyes in the Surgical Management of High-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Rosario Maugeri

    2018-02-01

    Full Text Available High-grade gliomas (HGGs are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS and progression-free survival (PFS, but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA or fluorescein sodium (FS have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS, on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.

  13. A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors.

    Science.gov (United States)

    Streiff, Michael B; Ye, Xiaobu; Kickler, Thomas S; Desideri, Serena; Jani, Jayesh; Fisher, Joy; Grossman, Stuart A

    2015-09-01

    Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29-85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17-34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3-126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be primarily responsible for any patient deaths. Therefore, outpatient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.

  14. Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients.

    Science.gov (United States)

    Vees, Hansjörg; Senthamizhchelvan, Srinivasan; Miralbell, Raymond; Weber, Damien C; Ratib, Osman; Zaidi, Habib

    2009-02-01

    The purpose of the study is to assess the contribution of (18)F-fluoro-ethyl-tyrosine ((18)F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone. The study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate (18)F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTV(MRI)). PET image segmentation techniques included manual delineation of contours (GTV(man)), a 2.5 standardized uptake value (SUV) cutoff (GTV(2.5)), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio (SBR)-based adaptive thresholding (GTV(SBR)), gradient find (GTV(GF)), and region growing (GTV(RG)). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques. Contours defined using GTV(2.5) failed to provide successful delineation technically in three patients (18% of cases) as SUV(max) segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation.

  15. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-01-15

    Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

  16. Fluorescein for resection of high-grade gliomas: A safety study control in a single center and review of the literature.

    Science.gov (United States)

    Francaviglia, Natale; Iacopino, Domenico Gerardo; Costantino, Gabriele; Villa, Alessandro; Impallaria, Pietro; Meli, Francesco; Maugeri, Rosario

    2017-01-01

    The importance of a complete resection of high-grade gliomas (HGGs) has been highlighted in scientific literature, in order to limit tumor recurrence and above all to improve disease-free survival rates. Several fluorescent biomarkers have been tested to improve intraoperative identification of residual tumor; 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) are now starting to play a central role in glioma surgery. We performed a retrospective analysis on 47 patients operated for HGGs. Here we report our preliminary data. Data of 47 consecutive patients with HGG have been collected in our study (25 males, 22 females; mean age: 60.3 years, range: 27-86 years). Fluorescein (5 mg/kg of body weight) was injected intravenously right after the induction of general anesthesia. A YELLOW 560 filter was used on an OPMI Pentero 900 microscope (Carl Zeiss Meditec, Oberkochen, Germany) to complete a microsurgical tumor removal. Glioma resection and quality of life were evaluated preoperative and postoperatively. Gross total resection (GTR) was achieved in 53.2% ( n = 25) of patients. A subtotal resection (STR) (>95%) was achieved in 29.8% ( n = 14), while a partial resection (PR) (95%. No adverse effects correlated to fluorescein have been recorded. Fluorescein seems to be safe and effective in the resection of HGGs, allowing a high rate of gross total removal of contrast enhanced areas.

  17. Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

    Directory of Open Access Journals (Sweden)

    Garcia Juan L

    2010-08-01

    Full Text Available Abstract Background Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Results Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders. Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups

  18. TH-E-BRF-05: Comparison of Survival-Time Prediction Models After Radiotherapy for High-Grade Glioma Patients Based On Clinical and DVH Features

    International Nuclear Information System (INIS)

    Magome, T; Haga, A; Igaki, H; Sekiya, N; Masutani, Y; Sakumi, A; Mukasa, A; Nakagawa, K

    2014-01-01

    Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R 2 ) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R 2 between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R 2 was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by the JSPS Core

  19. A comprehensive approach in high-grade glioma management: position statement from the Neuro-Oncology Scientific Club (NOSC), Shiraz, Iran.

    Science.gov (United States)

    Ansari, Mansour; Mosalaei, Ahmad; Ahmadloo, Niloufar; Rasekhi, Alireza; Geramizadeh, Bita; Razmkon, Ali; Anvari, Kazem; Afarid, Mohammad; Dadras, Ali; Nafarieh, Leila; Mohammadianpanah, Mohammad; Nasrolahi, Hamid; Hamedi, Seyed Hasan; Omidvari, Shapour; Nami, Mohammad

    2017-01-01

    Establishing a robust teamwork model in the practice of neuro-oncology requires continued interdisciplinary efforts. The Neuro-Oncology Scientific Club (NOSC) initiative is an interdisciplinary clinical forum promoting the comprehensive approach across involved disciplines in the management of central nervous system (CNS) malignancies. With its provincial founding panels and national steering board, NOSC has been operational in Iran since 2011. This initiative has pursued its mission through interval strategic meetings, tumor boards, case discussions as well as publishing neuro-oncology updates, case study periodicals, and newsletters. A provincial meeting of NOSC in Shiraz put together insights from international practice guidelines, emerging evidence, and expert opinions to draw a position statement on high-grade glioma management in adults. The present report summarizes key highlights from the above clinical forum.

  20. A comprehensive approach in high-grade glioma management: position statement from the Neuro-Oncology Scientific Club (NOSC, Shiraz, Iran

    Directory of Open Access Journals (Sweden)

    Ansari, Mansour

    2017-02-01

    Full Text Available Establishing a robust teamwork model in the practice of neuro-oncology requires continued interdisciplinary efforts. The Neuro-Oncology Scientific Club (NOSC initiative is an interdisciplinary clinical forum promoting the comprehensive approach across involved disciplines in the management of central nervous system (CNS malignancies. With its provincial founding panels and national steering board, NOSC has been operational in Iran since 2011. This initiative has pursued its mission through interval strategic meetings, tumor boards, case discussions as well as publishing neuro-oncology updates, case study periodicals, and newsletters. A provincial meeting of NOSC in Shiraz put together insights from international practice guidelines, emerging evidence, and expert opinions to draw a position statement on high-grade glioma management in adults. The present report summarizes key highlights from the above clinical forum.

  1. Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures.

    Science.gov (United States)

    Johnson, Adrienne; Severson, Eric; Gay, Laurie; Vergilio, Jo-Anne; Elvin, Julia; Suh, James; Daniel, Sugganth; Covert, Mandy; Frampton, Garrett M; Hsu, Sigmund; Lesser, Glenn J; Stogner-Underwood, Kimberly; Mott, Ryan T; Rush, Sarah Z; Stanke, Jennifer J; Dahiya, Sonika; Sun, James; Reddy, Prasanth; Chalmers, Zachary R; Erlich, Rachel; Chudnovsky, Yakov; Fabrizio, David; Schrock, Alexa B; Ali, Siraj; Miller, Vincent; Stephens, Philip J; Ross, Jeffrey; Crawford, John R; Ramkissoon, Shakti H

    2017-12-01

    Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb]). In pLGGs, we detected genomic alterations (GA) in 95.2% (119/125) of tumors. BRAF was most frequently altered (48%; 60/125), and FGFR1 missense (17.6%; 22/125), NF1 loss of function (8.8%; 11/125), and TP53 (5.6%; 7/125) mutations were also detected. Rearrangements were identified in 35% of pLGGs, including KIAA1549-BRAF , QKI-RAF1 , FGFR3-TACC3 , CEP85L-ROS1 , and GOPC-ROS1 fusions. Among pHGGs, GA were identified in 96.8% (152/157). The genes most frequently mutated were TP53 (49%; 77/157), H3F3A (37.6%; 59/157), ATRX (24.2%; 38/157), NF1 (22.2%; 35/157), and PDGFRA (21.7%; 34/157). Interestingly, most H3F3A mutations (81.4%; 35/43) were the variant K28M. Midline tumor analysis revealed H3F3A mutations (40%; 40/100) consisted solely of the K28M variant. Pediatric high-grade gliomas harbored oncogenic EML4-ALK , DGKB-ETV1 , ATG7-RAF1 , and EWSR1-PATZ1 fusions. Six percent (9/157) of pHGGs were hypermutated (TMB >20 mutations per Mb; range 43-581 mutations per Mb), harboring mutations deleterious for DNA repair in MSH6, MSH2, MLH1, PMS2, POLE , and POLD1 genes (78% of cases). Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision-making. Additionally, TMB could be a biomarker to identify pediatric glioblastoma (GBM) patients who may benefit from immunotherapy. By providing objective data to support diagnostic, prognostic, and therapeutic decision-making, comprehensive genomic profiling is necessary for

  2. Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis.

    Directory of Open Access Journals (Sweden)

    Roland F Schwarz

    2015-02-01

    Full Text Available The major clinical challenge in the treatment of high-grade serous ovarian cancer (HGSOC is the development of progressive resistance to platinum-based chemotherapy. The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the development of resistant disease.Evolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide sequencing of 135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy. Samples were obtained from the clinical CTCR-OV03/04 studies, and patients were enrolled between 20 July 2007 and 22 October 2009. Median follow-up of the cohort was 31 mo (interquartile range 22-46 mo, censored after 26 October 2013. Outcome measures were overall survival (OS and progression-free survival (PFS. There were marked differences in the degree of clonal expansion (CE between patients (median 0.74, interquartile range 0.66-1.15, and dichotimization by median CE showed worse survival in CE-high cases (PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003. Bootstrap analysis with resampling showed that the 95% confidence intervals for the hazard ratios for PFS and OS in the CE-high group were greater than 1.0. These data support a relationship between heterogeneity and survival but do not precisely determine its effect size. Relapsed tissue was available for two patients in the CE-high group, and phylogenetic analysis showed that the prevalent clonal population at clinical recurrence arose from early divergence events. A subclonal population marked by a NF1 deletion showed a progressive increase in tumour allele fraction during chemotherapy.This study demonstrates that quantitative measures of intra

  3. Residual Convolutional Neural Network for the Determination ofIDHStatus in Low- and High-Grade Gliomas from MR Imaging.

    Science.gov (United States)

    Chang, Ken; Bai, Harrison X; Zhou, Hao; Su, Chang; Bi, Wenya Linda; Agbodza, Ena; Kavouridis, Vasileios K; Senders, Joeky T; Boaro, Alessandro; Beers, Andrew; Zhang, Biqi; Capellini, Alexandra; Liao, Weihua; Shen, Qin; Li, Xuejun; Xiao, Bo; Cryan, Jane; Ramkissoon, Shakti; Ramkissoon, Lori; Ligon, Keith; Wen, Patrick Y; Bindra, Ranjit S; Woo, John; Arnaout, Omar; Gerstner, Elizabeth R; Zhang, Paul J; Rosen, Bruce R; Yang, Li; Huang, Raymond Y; Kalpathy-Cramer, Jayashree

    2017-11-22

    Purpose: Isocitrate dehydrogenase ( IDH ) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data. Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming. Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively. Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional data set. Clin Cancer Res; 1-9. ©2017 AACR. ©2017 American Association for Cancer Research.

  4. Middle Temporal Gyrus Versus Inferior Temporal Gyrus Transcortical Approaches to High-Grade Astrocytomas in the Mediobasal Temporal Lobe: A Comparison of Outcomes, Functional Restoration, and Surgical Considerations.

    Science.gov (United States)

    Quinones-Hinojosa, Alfredo; Raza, Shaan M; Ahmed, Ishrat; Rincon-Torroella, Jordina; Chaichana, Kaisorn; Olivi, Alessandro

    2017-01-01

    High-grade astrocytomas of the mesial temporal lobe may pose surgical challenges. Several approaches (trans-sylvian, subtemporal, and transcortical) have been designed to circumnavigate the critical neurovascular structures and white fiber tracts that surround this area. Considering the paucity of literature on the transcortical approach for these lesions, we describe our institutional experience with transcortical approaches to Grade III/IV astrocytomas in the mesial temporal lobe. Between 1999 and 2009, 23 patients underwent surgery at the Johns Hopkins Medical Institutions for Grade III/IV astrocytomas involving the mesial temporal lobe (without involvement of the temporal neocortex). Clinical notes, operative records, and imaging were reviewed. Thirteen patients had tumors in the dominant hemisphere. All patients underwent surgery via a transcortical approach (14 via the inferior temporal gyrus and 9 via the middle temporal gyrus). Gross total resection was obtained in 92 % of the cohort. Neurological outcomes were: clinically significant stroke (2 patients), new visual deficits (2 patients), new speech deficit (1 patient); seizure control (53 %). In comparison to reported results in the literature for the transylvian and subtemporal approaches, the transcortical approach may provide the access necessary for a gross total resection with minimal neurological consequences. In our series of patients, there was no statistically significant difference in outcomes between the middle temporal gyrus versus the inferior temporal gyrus trajectories.

  5. Use of peri-operative anti-epileptic drugs in patients with newly diagnosed high grade malignant glioma: a single center experience.

    Science.gov (United States)

    Lwu, Shelly; Hamilton, Mark G; Forsyth, Peter A; Cairncross, J Gregory; Parney, Ian F

    2010-02-01

    An American Academy of Neurology practice parameter recommends that long-term prophylactic anti-epileptic drugs (AED) should not be routine in patients with newly diagnosed brain tumors. However, prospective multi-center North American data shows that most newly diagnosed glioma patients receive prophylactic AED. We examined our own peri-operative AED practice patterns in newly-diagnosed patients with malignant glioma to determine if we deviate from published guidelines. A retrospective chart review was performed in adult patients with newly diagnosed malignant gliomas undergoing surgery in southern Alberta between January 2003 and December 2005. Demographic information, AED use, seizure incidence, adverse effects, tumor size, and tumor location were recorded. Of 164 eligible patients, 54 (33%) presented with seizures and all received AED. Prophylactic AED were given to 44 patients (27%). Peri-operative seizures (within 1 week) occurred in two patients without (3%) and no patients with seizure prophylaxis. Adverse AED reactions and adverse effects attributable to seizures were both rare. Prophylactic AED were continued >1 week post-op in 30 patients (18%). Patients receiving prophylactic AED were more likely to have had tumors involving the temporal lobe than those who did not (50 vs. 20%; P < 0.01). Patients receiving peri-operative AED prophylaxis were common, had a trend to reduced peri-operative seizures, and had few adverse effects. However, most of these patients were maintained on prophylactic AED continued beyond the first peri-operative week, contradicting published guidelines. Increased awareness of practice guidelines may help modify AED prescription patterns in malignant glioma patients.

  6. Reirradiation in progressive high-grade gliomas: outcome, role of concurrent chemotherapy, prognostic factors and validation of a new prognostic score with an independent patient cohort

    International Nuclear Information System (INIS)

    Scholtyssek, Felix; Kortmann, Rolf-Dieter; Müller, Klaus; Zwiener, Isabella; Schlamann, Annika; Seidel, Clemens; Meixensberger, Jürgen; Bauer, Manfred; Hoffmann, Karl-Titus; Combs, Stephanie E; Bueren, André O von

    2013-01-01

    First, to evaluate outcome, the benefit of concurrent chemotherapy and prognostic factors in a cohort of sixty-four high-grade glioma patients who underwent a second course of radiation therapy at progression. Second, to validate a new prognostic score for overall survival after reirradiation of progressive gliomas with an independent patient cohort. All patients underwent fractionated reirradiation with a median physical dose of 36 Gy. Median planned target volume was 110.4 ml. Thirty-six patients received concurrent chemotherapy consisting in 24/36 cases (67%) of carboplatin and etoposide and in 12/36 cases (33%) of temozolomide. We used the Kaplan Meier method, log rank test and proportional hazards regression analysis for statistical assessment. Median overall survival from the start of reirradiation was 7.7 ± 0.7 months. Overall survival rates at 6 and 12 months were 60 ± 6% and 24 ± 6%, respectively. Despite relatively large target volumes we did not observe any major acute toxicity. Concurrent chemotherapy did not appear to improve outcome. In contrast, female gender, young age, WHO grade III histology, favorable Karnofsky performance score and complete resection of the tumor prior to reirradiation were identified as positive prognostic factors for overall survival. We finally validated a recent suggestion for a prognostic score with our independent but small patient cohort. Our preliminary findings suggest that its ability to discriminate between different prognostic groups is limited. Outcome of our patients was comparable to previous studies. Even in case of large target volumes reirradiation seems to be feasible without observing major toxicity. The benefit of concurrent chemotherapy is still elusive. A reassessment of the prognostic score, tested in this study, using a larger patient cohort is needed

  7. Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma

    International Nuclear Information System (INIS)

    Rajkumar, S. Vincent; Buckner, Jan C.; Schomberg, Paula J.; Reid, Joel M.; Bagniewski, Pamela J.; Ames, Matthew M.; Cascino, Terrence L.; Marks, Randolph S.

    1998-01-01

    Purpose: We conducted a Phase I study of bischloroethylnitrosourea (BCNU), cisplatin, and oral etoposide administered prior to and during accelerated hyperfractionated radiation therapy in newly diagnosed high-grade glioma. Pharmacokinetic studies of oral etoposide were also done. Methods and Materials: Patients started chemotherapy after surgery but prior to definitive radiation therapy (160 cGy twice daily x 15 days; 4800 cGy total). Initial chemotherapy consisted of BCNU 40 mg/m 2 days 1-3, cisplatin 30 mg/m 2 days 1-3 and 29-31, and etoposide 50 mg orally days 1-14 and 29-42, repeated in 8 weeks concurrent with radiation therapy. BCNU 200 mg/m 2 every 8 weeks x 4 cycles was given after radiation therapy. Results: Sixteen patients, 5 with grade 3 anaplastic astrocytoma and 11 with glioblastoma were studied. Grade 3-4 leukopenia (38%) and thrombocytopenia (31%) were dose-limiting. Other toxicities were anorexia (81%), nausea (94%), emesis (56%), alopecia (88%), and ototoxicity (38%). The maximum tolerated dose was BCNU 40 mg/m 2 days 1-3, cisplatin 20 mg/m 2 days 1-3 and 29-31, and oral etoposide 50 mg days 1-21 and 29-49 prior to radiation therapy and repeated in 8 weeks with the start of radiation therapy followed by BCNU 200 mg/m 2 every 8 weeks for 4 cycles. Median time to progression and survival were 13 and 14 months respectively. Responses occurred in 2 of 9 (22%) patients with evaluable disease. In pharmacokinetic studies, all patients achieved plasma concentrations of >0.1 μg/ml etoposide (the in vitro radiosensitizing threshold), following a 50 mg oral dose. The mean ± SD 2 hr and 6 hr plasma concentrations were 0.92 ± 0.43 μg/ml and 0.36 ± 0.12 μg/ml, respectively. Estimated duration of exposure to >0.1 μg/ml etoposide was 10-17 hr. Conclusions: Preirradiation chemotherapy with BCNU, cisplatin, and oral etoposide with accelerated hyperfractionated radiation therapy in high-grade gliomas is feasible and merits further investigation. Sustained

  8. Measuring health-related quality of life in high-grade glioma patients at the end of life using a proxy-reported retrospective questionnaire.

    Science.gov (United States)

    Sizoo, Eefje M; Dirven, Linda; Reijneveld, Jaap C; Postma, Tjeerd J; Heimans, Jan J; Deliens, Luc; Pasman, H Roeline W; Taphoorn, Martin J B

    2014-01-01

    To develop, validate, and report on the use of a retrospective proxy-reported questionnaire measuring health-related quality of life (HRQoL) in the end-of-life (EOL) phase of high-grade glioma (HGG) patients. Items relevant for the defined construct were selected using existing questionnaires, topics identified as important in literature, and expert opinion (experienced neuro-oncologists and EOL experts). Psychometric properties, content validity and internal consistency, were determined and the questionnaire was subsequently adapted. Proxy-reported HRQoL data of HGG patients in the EOL, including changes over time, were analyzed. Twenty-nine items were selected covering seven domains; physical comfort, physical and cognitive functioning, psychological, social and spiritual well-being, and overall quality of life. Relatives of 83 deceased HGG patients completed the questionnaire. Content validity was assessed to be adequate. Internal consistency in the domains varied from reasonable to good. Two items were excluded due to poor psychometric properties. Symptom burden increased (p 50). Overall quality of life was rated as poor, mean (SD) of 29 (26). Measuring HRQoL at the EOL of HGG patients with a retrospective, proxy-reported questionnaire was feasible, yielding a validated instrument. HRQoL was reported as poor and deteriorated as death approached.

  9. Toxicity and efficacy of re-irradiation of high-grade glioma in a phase I dose- and volume escalation trial

    DEFF Research Database (Denmark)

    Møller, Søren; Munck Af Rosenschöld, Per; Costa, Junia

    2017-01-01

    INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy of PET and MRI guided re-irradiation of recurrent high-grade glioma (HGG) and to assess the impact of radiotherapy dose, fractionation and irradiated volume. MATERIAL AND METHODS: Patients with localized, recurrent HGG...... (grades III-IV) and no other treatment options were eligible for a prospective phase I trial. Gross tumor volumes for radiotherapy were defined using T1-contrast enhanced MRI and (18)F-fluoro-ethyl tyrosine PET. Radiotherapy was delivered using volumetric modulated arc therapy with a 2-mm margin. The dose...... prescription of four consecutive groups was (1) 35 Gy/10fr., (2) 42 Gy/10fr., (3) 29.5 Gy/5fr. and (4) 35 Gy/10fr. to larger tumor volumes (100-300 cm(3)), respectively. RESULTS: Thirty-one patients were treated of which 81% had glioblastoma. The median progression-free survival was 2.8 months (95%CI: 2.1-3...

  10. Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Franceschi, E; Cavallo, G; Lonardi, S; Magrini, E; Tosoni, A; Grosso, D; Scopece, L; Blatt, V; Urbini, B; Pession, A; Tallini, G; Crinò, L; Brandes, A A

    2007-04-10

    To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mg day(-1)) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1-36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2-104+) weeks and PFS-6 was 14.3% (95% CI 4.0-32.7%). The median overall survival was 24.6 weeks (range 4-104+). No grade 3-4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.

  11. Unsupervised consensus cluster analysis of [18F]-fluoroethyl-L-tyrosine positron emission tomography identified textural features for the diagnosis of pseudoprogression in high-grade glioma.

    Science.gov (United States)

    Kebir, Sied; Khurshid, Zain; Gaertner, Florian C; Essler, Markus; Hattingen, Elke; Fimmers, Rolf; Scheffler, Björn; Herrlinger, Ulrich; Bundschuh, Ralph A; Glas, Martin

    2017-01-31

    Timely detection of pseudoprogression (PSP) is crucial for the management of patients with high-grade glioma (HGG) but remains difficult. Textural features of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) mirror tumor uptake heterogeneity; some of them may be associated with tumor progression. Fourteen patients with HGG and suspected of PSP underwent FET-PET imaging. A set of 19 conventional and textural FET-PET features were evaluated and subjected to unsupervised consensus clustering. The final diagnosis of true progression vs. PSP was based on follow-up MRI using RANO criteria. Three robust clusters have been identified based on 10 predominantly textural FET-PET features. None of the patients with PSP fell into cluster 2, which was associated with high values for textural FET-PET markers of uptake heterogeneity. Three out of 4 patients with PSP were assigned to cluster 3 that was largely associated with low values of textural FET-PET features. By comparison, tumor-to-normal brain ratio (TNRmax) at the optimal cutoff 2.1 was less predictive of PSP (negative predictive value 57% for detecting true progression, p=0.07 vs. 75% with cluster 3, p=0.04). Clustering based on textural O-(2-[18F]fluoroethyl)-L-tyrosine PET features may provide valuable information in assessing the elusive phenomenon of pseudoprogression.

  12. Outcome of secondary high-grade glioma in children previously treated for a malignant condition: A study of the Canadian Pediatric Brain Tumour Consortium

    International Nuclear Information System (INIS)

    Carret, Anne-Sophie; Tabori, Uri; Crooks, Bruce; Hukin, Juliette; Odame, Isaac; Johnston, Donna L.; Keene, Daniel L.; Freeman, Carolyn; Bouffet, Eric

    2006-01-01

    Background and purpose: Reports of secondary high-grade glioma (HGG) in survivors of childhood cancer are scarce. The aim of this study was to review the pattern of diagnosis, the treatment, and outcome of secondary pediatric HGG. Patients and methods: We performed a multi-center retrospective study among the 17 paediatric institutions participating in the Canadian Pediatric Brain Tumour Consortium (CPBTC). Results: We report on 18 patients (14 males, 4 females) treated in childhood for a primary cancer, who subsequently developed a HGG as a second malignancy. All patients had previously received radiation therapy +/- chemotherapy for either acute lymphoblastic leukaemia (n = 9) or solid tumour (n = 9). All HGG occurred within the previous radiation fields. At the last follow-up, 17 patients have died and the median survival time is 9.75 months. Conclusion: Although aggressive treatment seems to provide sustained remissions in some patients, the optimal management is still to be defined. Further documentation of such cases is necessary in order to better understand the pathogenesis, the natural history and the prevention of these tumours

  13. Follow-up Results and Clinical Significance of Magnetic Resonance Spectroscopy Combined with Fluorescence Microscopy in Resection of High Grade Supra-tentoria Gliomas.

    Science.gov (United States)

    Tian, Hai-Long; Zu, Yu-Liang; He, Wei; Zhang, Ning-Ning; Wang, Yi-Hua; Guo, Zhen-Tao; Wang, Chao-Chao; Jiang, Bin; Yin, Xin; Wang, Zhi-Gang

    2017-10-30

    Objective To investigate the clinical effectiveness of magnetic resonance spectroscopy (MRS) combined with sodium fluorescein(FL) in the treatment of high grade gliomas(HGG). Methods From August 2013 to 2015 November,the clinical data of 72 supratentorial HGG(WHO grade Ⅲ-Ⅳ) patients who had received surgical treatment in our hospital were retrospectively studied,among whom 43 cases received MRS combined with intra-perative FL navigation(observation group),and 29 cases only received conventional surgery(control group). Post-operative radiotherapy and chemotherapy were applied for more than 3 months. Routine enhanced MRI were performed 24-48 hours after the operation to investigate the extent of tumor resection. Six months after the operation,the quality of life of patients was evaluated by using the Karnofsky score,and 1-year postoperative survival rate and progression-free survival(PFS) were observed. Results Postoperative MRI showed that the rate of gross total resection(GTR) in observation group was significantly higher than that in control group(72.09%vs.51.72%;χ 2 =23.88,P=0.001),and the GTR rate of WHO grade Ⅳ tumors was significantly higher than that of WHO grade Ⅲ tumors in observation group(92.86% vs.62.07%;χ 2 =6.06,P=0.042). The postoperative Karnofsky score in the observation group was significantly higher than that in control group(μ=2.34,P=0.021). The mean time of follow-up was(16.4±2.4) months(8-21 months) and there was no statistical significant difference between observation group and control group in 1-year survival rate(74.07% vs.77.50%;χ 2 =4.90,P=0.165) and PFS [(13.2±1.2) months vs.(12.7±2.0) months;χ 2 =7.26,P=0.067]. In observation group,the PFS of WHO grade Ⅳ patients was significantly higher than that in control group [(14.2±0.3) months vs.(10.0±1.1) months;χ 2 =11.03,P=0.031]. There was also no statistical significant difference between WHO grade Ⅳ tumors in two groups in terms of 1-year survival rate(71.43% vs.72

  14. Prognostic value of metabolic tumor volume on {sup 11}C-methionine PET in predicting progression-free survival in high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Min Young; Paeng, Jin Chul; Cheon, Gi Jeong; Lee, Dong Soo; Chung, June Key; Kang, Keon Wook [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, E. Edmund [Dept. of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul (Korea, Republic of)

    2015-12-15

    C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG. A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNR{sub max}, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNR{sub max}, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS). Median PFS of all patients was 7.9 months (range 1.0–53.8 months). In univariate analysis, MTV (cutoff 35 cm{sup 3}) was a significant prognostic factor for PFS (P = 0.01), whereas TNR{sub max} (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03). MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNR{sub max} is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.

  15. Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Piludu, Francesca; Vidiri, Antonello [Regina Elena National Cancer Institute, Radiology and Diagnostic Imaging Department, Rome (Italy); Marzi, Simona [Regina Elena National Cancer Institute, Medical Physics Laboratory, Rome (Italy); Pace, Andrea; Villani, Veronica [Regina Elena National Cancer Institute, Neurology Division, Rome (Italy); Fabi, Alessandra [Regina Elena National Cancer Institute, Oncology Department, Rome (Italy); Carapella, Carmine Maria [Regina Elena National Cancer Institute, Oncologic Surgery Department, Rome (Italy); Terrenato, Irene [Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome (Italy); Antenucci, Anna [Regina Elena National Cancer Institute, Clinical Pathology, Rome (Italy)

    2015-12-15

    The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V{sub tot}), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V{sub CE-T1} and V{sub NON-CE-T1}, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K{sup trans} maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V{sub NON-CE-T1} after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K{sup trans}, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V{sub tot} was predictive of overall survival (OS), while V{sub CE-T1} showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K{sup trans} showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. (orig.)

  16. Imaging parameters of high grade gliomas in relation to the MGMT promoter methylation status: the CT, diffusion tensor imaging, and perfusion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won-Jin; Choi, Jin Woo; Roh, Hong Gee [Konkuk University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Lim, So Dug [Konkuk University School of Medicine, Department of Pathology, Seoul (Korea, Republic of); Koh, Young-Cho [Konkuk University School of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of)

    2012-06-15

    We hypothesized that methyl-guanine methyl transferase (MGMT) promoter methylation status, a predictor of the chemosensitivity for high grade gliomas (HGGs), may be associated with computed tomography (CT)/magnetic resonance (MR) imaging variables. Out of 38 consecutive patients with HGGs, 24 patients whose MGMT promoter methylation status was available [12 men and 12 women; median age, 49 years; age range, 22-79 years; WHO grade III (n = 7), WHO grade IV (n = 17)] were enrolled retrospectively. CT attenuation, apparent diffusion coefficient (ADC), fractional anisotropy (FA), and relative cerebral blood volume (rCBV) were measured for enhancing tumors. Qualitative imaging features were also analyzed. Mann-Whitney and Fisher's exact tests were used to evaluate relationships between MGMT promoter methylation status and imaging variables. Maximum CT attenuation was significantly lower in the methylated MGMT promoter group than that in the unmethylated MGMT promoter group (30.3 {+-} 9.5 HU versus 39.2 {+-} 4.7 HU, respectively, p = 0.009). While ADC values tended to be higher in the methylated group than in the unmethylated group (p = 0.055), ADC ratio was significantly higher, and the FA and FA ratios were significantly lower in the methylated group than in the unmethylated group (p = 0.032, p = 0.006 and p = 0.007, respectively). In contrast, rCBV ratio did not differ between the two groups (p = 0.380). Regarding imaging features, only ill-defined margin was seen more frequently in the methylated group than in the unmethylated group (45.5% versus 7.7%, respectively, p = 0.048). Preoperative imaging can predict MGMT promoter methylation status, which is of paramount importance for predicting treatment response to chemotherapy with an alkylating agent. (orig.)

  17. Diffuse, non-traumatic, non-aneurysmal subarachnoid haemorrhage during bevacizumab treatment of high grade glioma: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Arosha S. Dissanayake, MBBS

    2015-06-01

    Full Text Available Background: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor approved by the United States Food and Drug Administration for the treatment of various cancers including refractory high grade glioma. There are case reports of subarachnoid haemorrhage (SAH during bevacizumab treatment though the causative role of the drug in these cases has been obscured by the presence of alternative aetiologies or incomplete investigation. Furthermore, there is no consensus regarding the risk of Central Nervous System (CNS haemorrhage during bevacizumab treatment due to limited available study data. Case Description: A 53 year old female with recurrent gliosarcoma refractory to standard, temozolamide based chemo-radiotherapy presented to our facility in a post-ictal state 16 days after her second dose of intravenous bevacizumab. A Fisher grade III SAH was found on computerised tomography scanning with no causative vascular lesion found on two subsequent digital subtraction angiograms separated by a 10 day period and a Magnetic Resonance Imaging (MRI scan 20 days post-bleed. Given the resolution of symptoms over an uncomplicated 13 day admission, she was discharged home with bevacizumab ceased prior to her scheduled third dose. Conclusion: We discuss here a case of diffuse, non-traumatic SAH during bevacizumab treatment of recurrent gliosarcoma in which alternative aetiologies of haemorrhage were excluded, to our knowledge the first such case in the English language literature. This adverse event is compatible with the known molecular mechanisms of bevacizumab and clinicians should be cognisant of the potential risk of CNS haemorrhage until larger studies are available to quantify this risk.

  18. Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03.

    Science.gov (United States)

    Lee, Eudocia Q; Puduvalli, Vinay K; Reid, Joel M; Kuhn, John G; Lamborn, Kathleen R; Cloughesy, Timothy F; Chang, Susan M; Drappatz, Jan; Yung, W K Alfred; Gilbert, Mark R; Robins, H Ian; Lieberman, Frank S; Lassman, Andrew B; McGovern, Renee M; Xu, Jihong; Desideri, Serena; Ye, Xiabu; Ames, Matthew M; Espinoza-Delgado, Igor; Prados, Michael D; Wen, Patrick Y

    2012-11-01

    A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles. In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. ©2012 AACR.

  19. Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K.; Schlamann, A.; Pietschmann, S.; Kortmann, R.D. [University Medical Center Leipzig, Department of Radiation Oncology, Leipzig (Germany); Guckenberger, M. [University Medical Center Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Warmuth-Metz, M. [University Medical Center Wuerzburg, Department of Neuroradiology, Wuerzburg (Germany); Glueck, A. [Clinic for Radiation Oncology Schwabing, Muenchen (Germany); Wawer, A. [University Medical Center Muenchen Schwabing, Department of Pediatric Hematology and Oncology, Muenchen (Germany); Kramm, C.; Bueren, A.O. von [University Medical Center Goettingen, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Goettingen (Germany)

    2014-04-15

    High-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated. Between March 2007 and December 2012, six children with primary metastatic HGG (n=4) or DIPG (n=2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated. All patients received irradiation to the entire craniospinal axis (35.2 Gy, n=5; 36 Gy, n=1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m{sup 2}/day, n=5; 60 mg/m{sup 2}/day, n=1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0±0.8 months (range 2.4-10.7 months) and median overall survival was 7.6±3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (= grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases. Concurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study. (orig.)

  20. Gliomas

    OpenAIRE

    Berger, M; Weller, M

    2016-01-01

    Key Features •Synthesizes widely dispersed information on the management of gliomas into one comprehensive resource •Chapters written by international authors who are preeminent researchers in the field •Fully explores the therapeutic options for patient care, from chemotherapy to radiotherapy to personalized approaches Description Researchers’ knowledge of gliomas continues to advance rapidly at both the basic and translational levels, and Gliomas provides a thorough overview ...

  1. The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation.

    Science.gov (United States)

    Garside, R; Pitt, M; Anderson, R; Rogers, G; Dyer, M; Mealing, S; Somerville, M; Price, A; Stein, K

    2007-11-01

    To assess the clinical and cost-effectiveness of adjuvant carmustine wafers (BCNU-W) and also of adjuvant and concomitant temozolomide (TMZ), compared with surgery with radiotherapy. Electronic databases were searched up to August 2005. Included trials were critically appraised for key elements of internal and external validity. Relevant data were extracted and a narrative synthesis of the evidence produced. Where possible, data on absolute survival at a fixed time point were meta-analysed using a random effects model. A Markov (state transition) model was developed to assess the cost-utility of the two interventions. The model compared BCNU-W or TMZ separately with current standard treatment with surgery and radiotherapy. The simulated cohort had a mean age of 55 years and was modelled over 5 years. Two randomised controlled trials (RCTs) (n = 32, n = 240) and two observational studies of BCNU-W compared with placebo wafers as adjuvant therapy to surgery and radiotherapy for newly diagnosed high-grade glioma were identified. All the studies were in adults and provided data on 193 patients who had received BCNU-W. The RCT findings excluded under 65-year-olds and those with a Karnofsky Performance Status of less than 60. The largest multi-centre RCT suggested a possible survival advantage with BCNU-W among a cohort of patients with grade III and IV tumours, adding a median of 2.3 months [95% confidence interval (CI) -0.5 to 5.1]. However, analysis using per-protocol, unstratified methods shows this difference to be not statistically significant (HR 0.77, 95% CI 0.57 to 1.03, p = 0.08). Long-term follow-up suggests a significant survival advantage using unstratified analysis. No difference in progression-free survival (PFS) was demonstrated. Subgroup analysis of those with grade IV tumours also showed no significant survival advantage with BCNU-W [hazard ratio (HR) 0.82, 95% CI 0.55 to 1.11, p = 0.20, unstratified analysis]. It is estimated that the cost of surgery

  2. Early Changes in Tumor Perfusion from T1-Weighted Dynamic Contrast-Enhanced MRI following Neural Stem Cell-Mediated Therapy of Recurrent High-Grade Glioma Correlate with Overall Survival

    Directory of Open Access Journals (Sweden)

    Prativa Sahoo

    2018-01-01

    Full Text Available Background. The aim of this study was to correlate T1-weighted dynamic contrast-enhanced MRI- (DCE-MRI- derived perfusion parameters with overall survival of recurrent high-grade glioma patients who received neural stem cell- (NSC- mediated enzyme/prodrug gene therapy. Methods. A total of 12 patients were included in this retrospective study. All patients were enrolled in a first-in-human study (NCT01172964 of NSC-mediated therapy for recurrent high-grade glioma. DCE-MRI data from all patients were collected and analyzed at three time points: MRI#1—day 1 postsurgery/treatment, MRI#2— day 7 ± 3 posttreatment, and MRI#3—one-month follow-up. Plasma volume (Vp, permeability (Ktr, and leakage (λtr perfusion parameters were calculated by fitting a pharmacokinetic model to the DCE-MRI data. The contrast-enhancing (CE volume was measured from the last dynamic phase acquired in the DCE sequence. Perfusion parameters and CE at each MRI time point were recorded along with their relative change between MRI#2 and MRI#3 (Δ32. Cox regression was used to analyze patient survival. Results. At MRI#1 and at MRI#3, none of the parameters showed a significant correlation with overall survival (OS. However, at MRI#2, CE and λtr were significantly associated with OS (p<0.05. The relative λtr and Vp from timepoint 2 to timepoint 3 (Δ32λtr and Δ32Vp were each associated with a higher hazard ratio (p<0.05. All parameters were highly correlated, resulting in a multivariate model for OS including only CE at MRI#2 and Δ32Vp, with an R2 of 0.89. Conclusion. The change in perfusion parameter values from 1 week to 1 month following NSC-mediated therapy combined with contrast-enhancing volume may be a useful biomarker to predict overall survival in patients with recurrent high-grade glioma.

  3. The PET-F.D.G. predicts the high grade recurrent gliomas survival treated by the association of bevacizumab-irinotecan; La TEP-FDG predit la survie des gliomes de haut grade recidivants traites par l'association bevacizumab-irinotecan

    Energy Technology Data Exchange (ETDEWEB)

    Colavolpe, C.; Guedj, E.; Mancini, J.; Bequet-Boucard, C.; Metellus, P.; Barrie, M.; Figarella-Branger, D.; Chinot, O.; Mundler, O. [CHU La Timone, Marseille, (France)

    2009-05-15

    The objective is to evaluate the prognosis value independent of the PET-F.D.G. on the global survival and without progression of recurred high grade gliomas treated by bevacizumab and irinotecan, in comparison with the others prognosis factors of the recurrence. In conclusions, the comparison of the F.D.G. fixation between the tumor area and contralateral one before anti-angiogenic treatment has a prognosis value independent on the global survival and without progression of recurred high grade gliomas treated by bevacizumab/irinotecan. (N.C.)

  4. Phase I dose-escalation study of the PI3K/mTOR inhibitor voxtalisib (SAR245409, XL765) plus temozolomide with or without radiotherapy in patients with high-grade glioma.

    Science.gov (United States)

    Wen, Patrick Y; Omuro, Antonio; Ahluwalia, Manmeet S; Fathallah-Shaykh, Hassan M; Mohile, Nimish; Lager, Joanne J; Laird, A Douglas; Tang, Jiali; Jiang, Jason; Egile, Coumaran; Cloughesy, Timothy F

    2015-09-01

    This phase I study aimed to evaluate safety, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of voxtalisib (SAR245409, XL765), a pan-class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, in combination with temozolomide (TMZ), with or without radiation therapy (RT), in patients with high-grade glioma. Patients received voxtalisib 30-90 mg once daily (q.d.) or 20-50 mg twice daily (b.i.d.), in combination with 200 mg/m(2) TMZ (n = 49), or voxtalisib 20 mg q.d. with 75 mg/m(2) TMZ and RT (n = 5). A standard 3 + 3 dose-escalation design was used to determine the maximum tolerated dose. Patients were evaluated for adverse events (AEs), plasma pharmacokinetics, pharmacodynamic effects in skin biopsies, and tumor response. The maximum tolerated doses were 90 mg q.d. and 40 mg b.i.d. for voxtalisib in combination with TMZ. The most frequently reported treatment-related AEs were nausea (48%), fatigue (43%), thrombocytopenia (26%), and diarrhea (24%). The most frequently reported treatment-related grade ≥3 AEs were lymphopenia (13%), thrombocytopenia, and decreased platelet count (9% each). Pharmacokinetic parameters were similar to previous studies with voxtalisib monotherapy. Moderate inhibition of PI3K signaling was observed in skin biopsies. Best response was partial response in 4% of evaluable patients, with stable disease observed in 68%. Voxtalisib in combination with TMZ with or without RT in patients with high-grade gliomas demonstrated a favorable safety profile and a moderate level of PI3K/mTOR pathway inhibition. © 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.

  5. Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

    DEFF Research Database (Denmark)

    Sørensen, M D; Dahlrot, R H; Boldt, H B

    2018-01-01

    (+) TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold......AIMS: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using...

  6. 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

    Science.gov (United States)

    Walker, David A.; Liu, JoFen; Kieran, Mark; Jabado, Nada; Picton, Susan; Packer, Roger; St. Rose, Christian; Van Meeteren, Antoinette Schouten; Carvalho, Alice; Van Damme, An; Depreitere, Bart; Gustavsson, Bengt; Due Tonnessen, Bernt J; Bertozzi-Salamon, Anne Isabelle; Brentrup, Angela; Raybaud, Charles; Jones, Chris; Dufour, Christelle; Dorfer, Christian; Sainte-Rose, Christian; Malluci, Conor; Hargrave, Darren; Walker, David; Van Vuurden, Dannis; De Carli, Emilie; Bouffet, Eric; Van Calenbergh, Frank; Frappaz, Didier; Frassanito, Paolo; Goodrich, James; Baechli, Heidi; Grill, Jacques; Ternier, Jessica; Cappelen, Johan; Caird, John; Pereira, Josué; Riffaud, Laurent; Baroncini, Marc; Walker, Marion; Kieran, Mark; Ozek, Memet; Jabado, Nada; Nysom, Karsten; Varlet, Pascale; Goodden, John; Bertolini, Patricia; Perilongo, Giorgio; Mercier, Philippe; Grundy, Richard; Kortmann, Rolf Dieter; Packer, Roger; Pfister, Stefan; Constantini, Shlomi; Sgouros, Spyros; Holm, Stefan; Czech, Thomas; Merchant, Thomas; Stokland, Tore; Ridola, Vita; Vandertop, Peter

    2013-01-01

    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. PMID:23502427

  7. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta [G. d' Annunzio Univ. of Chieti, SS. Annunziata Hospital, Chieti (Italy). Dept. of Radiation Oncology; Buonaguidi, Roberto [G. d' Annunzio Univ. of Chieti, Spirito Santo Hospital, Pescara (Italy). Dept. of Neurosurgery; Galzio, Renato J. [Univ. of L' Aquila, San Salvatore Hospital, L' Aquila (Italy). Dept. of Operative Unit of Neurosurgery and Health Sciences; Di Nicola, Marta [G. d' Annunzio Univ. of Chieti (Italy). Lab. of Biostatistics

    2011-12-15

    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level {<=} 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level {<=} 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  8. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    International Nuclear Information System (INIS)

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta; Buonaguidi, Roberto; Galzio, Renato J.; Di Nicola, Marta

    2011-01-01

    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level ≤ 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level ≤ 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  9. Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Michelle M., E-mail: michekim@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Camelo-Piragua, Sandra [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew; Tao, Yebin [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Junck, Larry; Mammoser, Aaron [Department of Neurology, University of Michigan, Ann Arbor, Michigan (United States); Betz, Bryan L. [Department of Pathology, University of Michigan, Ann Arbor, Michigan (United States); Cao, Yue [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan (United States); Kim, Christopher J. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Heth, Jason; Sagher, Oren [Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Tsien, Christina I. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

    2016-02-01

    Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

  10. Hypoxic cell radiosensitizers in the treatment of high grade gliomas: a new direction using combined Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole)

    International Nuclear Information System (INIS)

    Newman, H.F.; Bleehen, N.M.; Ward, R.; Workman, P.

    1988-01-01

    The hypoxic cell radiosensitizers Ro 03-8799 (pimonidazole) and SR 2508 (etanidazole) have been evaluated for their simultaneous penetration into human brain tumors and surrounding normal tissue. Thirteen patients received a dose of 1 g of each agent, infused over a 10 minute period during neurosurgery. Samples of glioma (20), brain (10) and cerebrospinal fluid (1) were obtained at a mean time (+/- SD) of 31 +/- 18 min from the end of infusion. A 24 hr plasma time course was measured in six patients. Nitroimidazole concentrations were determined by HPLC. For a mean dose of 0.55 g/m2 of each agent, the mean tumor concentrations (+/- SD) were 17.0 +/- 12.0 micrograms/g for Ro 03-8799 and 13.5 +/- 10.9 micrograms/g for SR 2508. The tumor/plasma ratios were 279 +/- 230% and 47 +/- 34% respectively. For adjacent 'normal' brain tissue, the radiosensitizer concentrations were 29.9 +/- 13.1 micrograms/g for Ro 03-8799, and 4.0 +/- 1.7 micrograms/g for SR 2508, and the brain/plasma ratios were 430 +/- 29% and 14 +/- 8% respectively. There was a significant trend towards increasing accumulation of both agents with time, in both tumor and normal brain. Concentrations in cerebrospinal fluid were very low. Plasma pharmacokinetics for Ro 03-8799 were similar to previous experience, but for SR 2508 the terminal half-life was greater in this series by a factor of 1.3. The results confirm that Ro 03-8799 is distributed widely in the central nervous system, and demonstrate that SR 2508 can achieve high tumor concentrations when the blood-brain barrier is compromised. The concentrations achieved with the combination are indicative of a significant advantage over metronidazole, misonidazole, or either agent alone, and normalized to the therapeutic dose of 0.75 g/m2 plus 2.0 g/m2 SR 2508 are consistent with those giving additive sensitization in an in vivo mouse tumor model

  11. Loss of miR-107, miR-181c and miR-29a-3p Promote Activation of Notch2 Signaling in Pediatric High-Grade Gliomas (pHGGs

    Directory of Open Access Journals (Sweden)

    Giuseppina Catanzaro

    2017-12-01

    Full Text Available The mechanisms by which microRNAs control pediatric high-grade gliomas (pHGGs have yet to be fully elucidated. Our studies of patient-derived pHGG tissues and of the pHGG cell line KNS42 revealed down-regulation in these tumors of three microRNAs, specifically miR-107, miR-181c, and miR-29a-3p. This down-regulation increases the proliferation of KNS42 cells by de-repressing expression of the Notch2 receptor (Notch2, a validated target of miR-107 and miR-181c and a putative target of miR-29a-3p. Inhibition (either pharmacologic or genetic of Notch2 or re-expression of the implicated microRNAs (all three combined but also individually significantly reduced KNS42 cell proliferation. These findings suggest that Notch2 pathway activation plays a critical role in pHGGs growth and reveal a direct epigenetic mechanism that controls Notch2 expression, which could potentially be targeted by novel forms of therapy for these childhood tumors characterized by high-morbidity and high-mortality.

  12. Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

    NARCIS (Netherlands)

    Thuijl, H.F. van; Scheinin, I.; Sie, D.; Alentorn, A.; Essen, H.F. van; Cordes, M.; Fleischeuer, R.; Gijtenbeek, A.; Beute, G.; Brink, W.A. van den; Meijer, G.A.; Havenith, M.; Idbaih, A.; Hoang-Xuan, K.; Mokhtari, K.; Verhaak, R.; Valk, P. van der; Wiel, M.A. van de; Heimans, J.J.; Aronica, E.; Reijneveld, J.C.; Wesseling, P.; Ylstra, B.

    2014-01-01

    BackgroundThe disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative

  13. Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment

    International Nuclear Information System (INIS)

    Marsh, James C.; Ziel, Ellis G; Diaz, Aidnag Z; Turian, Julius V; Wendt, Julie A.; Gobole, Rohit

    2013-01-01

    We compared integral dose with uninvolved brain (ID brain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. We prepared four PBRT treatment plans for four patients with high-grade gliomas (60Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and ID brain for all plans. There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. ID brain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean ID brain 23.64Gy vs. 28Gy and 18.7Gy vs. 24.5Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7Gy vs. 23.64Gy and 24.5Gy vs. 28Gy, respectively). n the setting of PBRT for high-grade gliomas, IMRT reduces ID brain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces ID brain compared with STD PBRT delivered with either traditional IMRT or HT.

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

    Directory of Open Access Journals (Sweden)

    Magdalena U Bogdańska

    Full Text Available 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.

  15. High-grade glioma in a patient with breast cancer

    Directory of Open Access Journals (Sweden)

    Che-Chao Chang

    2014-07-01

    Full Text Available Breast cancer is one of the most common origins of metastatic lesions in the central nervous system. Many patients with a breast cancer and concurrent brain tumor(s were diagnosed to have a metastatic lesion or lesions in the brain, based exclusively on their image findings without further pathologic verification, and received radiotherapy alone thereafter. It is, however, possible that a different pathology such as primary brain malignancy, which actually warrants a specific treatment modality, may occur in such patients with an already known malignancy. We, herein, reported a 61-year-old female patient who suffered from an anaplastic oligodendroglioma 1 year after her diagnosis of breast cancer. Demographic data, characteristic imaging findings, treatment, and outcome of the patient were discussed.

  16. Bereaved caregivers of patients with high-grade glioma

    DEFF Research Database (Denmark)

    Piil, Karin; Nordentoft, Sara; Larsen, Anders

    2018-01-01

    database, Scopus, PsycINFO and The Social Sciences Citation Index. Studies eligible for inclusion met the following criteria: (1) included bereaved caregivers to patients diagnosed with HGG ≥18 years, (2) described the caregiver's perspective at post bereavement (3) had been peer-reviewed. The papers...

  17. Intraoperative photodynamic treatment for high-grade gliomas

    Science.gov (United States)

    Dupont, C.; Reyns, N.; Deleporte, P.; Mordon, S.; Vermandel, M.

    2017-02-01

    Glioblastoma (GBM) is the most common primary brain tumor. Its incidence is estimated at 5 to 7 new cases each year for 100 000 inhabitants. Despite reference treatment, including surgery, radiation oncology and chemotherapy, GBM still has a very poor prognosis (median survival of 15 months). Because of a systematic relapse of the tumor, the main challenge is to improve local control. In this context, PhotoDynamic Therapy (PDT) may offer a new treatment modality. GBM recurrence mainly occurs inside the surgical cavity borders. Thus, a new light applicator was designed for delivering light during a PDT procedure on surgical cavity borders after Fluorescence Guided Resection. This device combines an inflatable balloon and a light source. Several experimentations (temperature and impermeability tests, homogeneity of the light distribution and ex-vivo studies) were conducted to characterize the device. An abacus was created to determine illumination time from the balloon volume in order to reach a therapeutic fluence value inside the borders of the surgical cavity. According to our experience, cavity volumes usually observed in the neurosurgery department lead to an acceptable average lighting duration, from 20 to 40 minutes. Thus, extra-time needed for PDT remains suitable with anesthesia constraints. A pilot clinical trial is planned to start in 2017 in our institution. In view of the encouraging results observed in preclinical or clinical, this intraoperative PDT treatment can be easily included in the current standard of care.

  18. Paediatric and adult malignant glioma

    DEFF Research Database (Denmark)

    Jones, Chris; Perryman, Lara; Hargrave, Darren

    2012-01-01

    Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

  19. Temozolomide in malignant gliomas.

    Science.gov (United States)

    Yung, W K

    2000-06-01

    Glioblastoma multiforme and anaplastic astrocytoma are the most common primary central nervous system malignancies and are the major cause of morbidity/ mortality despite combined modality approaches. Temozolomide (TMZ), a novel, oral, second-generation alkylating agent, has demonstrated antitumor activity against a broad range of solid tumors and highly resistant malignancies, including high-grade glioma Temozolomide does not require hepatic metabolism for activation, rapidly penetrates the cerebrospinal fluid, and consistently demonstrates reproducible linear pharmacokinetics with approximately 100% oral bioavailability. In preliminary clinical studies, TMZ has demonstrated meaningful efficacy and an acceptable safety profile in the treatment of patients with malignant glioma. These results have been recently confirmed in three open-label, multi-institutional studies that evaluated the use of TMZ in 525 malignant glioma patients. These studies represent the largest evaluation of a single agent in patients with recurrent malignant gliomas and were rigorously controlled with strict, prospectively defined criteria for assessment of tumor response, central review of histology, and validated instruments to assess health-related quality of life. Temozolomide was effective in delaying disease progression and maintaining health-related quality of life. Temozolomide represents a promising new agent in the treatment of malignant glioma.

  20. Aphasia induced by gliomas growing in the ventrolateral frontal region: assessment with diffusion MR tractography, functional MR imaging and neuropsychology.

    Science.gov (United States)

    Bizzi, Alberto; Nava, Simone; Ferrè, Francesca; Castelli, Gianmarco; Aquino, Domenico; Ciaraffa, Francesca; Broggi, Giovanni; DiMeco, Francesco; Piacentini, Sylvie

    2012-02-01

    Lesions in the ventrolateral region of the dominant frontal lobe have been historically associated with aphasia. Recent imaging results suggest that frontal language regions extend beyond classically defined Broca's area to include the ventral precentral gyrus (VPCG) and the arcuate fasciculus (AF). Frontal gliomas offer a unique opportunity to identify structures that are essential for speech production. The aim of this prospective study was to investigate the correlation between language deficits and lesion location in patients with gliomas. Nineteen patients with glioma and 10 healthy subjects were evaluated with diffusion tensor imaging magnetic resonance (MR) tractography, functional MR (verb generation task) and the Aachener Aphasie Test. Patients were divided into two groups according to lesion location with respect to the ventral precentral sulcus: (i) anterior (n=8) with glioma growing in the inferior frontal gyrus (IFG) and underlying white matter; (ii) posterior (n=11) with glioma growing in the VPCG and underlying white matter. Virtual dissection of the AF, frontal intralobar tract, uncinate fasciculus (UF) and inferior frontal occipital fasciculus (IFOF) was performed with a deterministic approach. Seven posterior patients showed aphasia classified as conduction (4), Broca (1), transcortical motor (1) and an isolated deficit of semantic fluency; one anterior patient had transcortical mixed aphasia. All posterior patients had invasion of the VPCG, however only patients with aphasia had also lesion extension to the AF as demonstrated by tractography dissections. All patients with language deficits had high grade glioma. Groups did not differ regarding tumour volume. A functional pars opercularis was identified with functional MR imaging (fMRI) in 17 patients. Gliomas growing in the left VPCG are much more likely to cause speech deficits than gliomas infiltrating the IFG, including Broca's area. Lesion extension to the AF connecting frontal to parietal

  1. Microglia immunophenotyping in gliomas.

    Science.gov (United States)

    Annovazzi, Laura; Mellai, Marta; Bovio, Enrica; Mazzetti, Samanta; Pollo, Bianca; Schiffer, Davide

    2018-01-01

    Microglia, once assimilated to peripheral macrophages, in gliomas has long been discussed and currently it is hypothesized to play a pro-tumor role in tumor progression. Uncertain between M1 and M2 polarization, it exchanges signals with glioma cells to create an immunosuppressive microenvironment and stimulates cell proliferation and migration. Four antibodies are currently used for microglia/macrophage identification in tissues that exhibit different cell forms and cell localization. The aim of the present work was to describe the distribution of the different cell forms and to deduce their significance on the basis of what is known on their function from the literature. Normal resting microglia, reactive microglia, intermediate and bumpy forms and macrophage-like cells can be distinguished by Iba1, CD68, CD16 and CD163 and further categorized by CD11b, CD45, c-MAF and CD98. The number of microglia/macrophages strongly increased from normal cortex and white matter to infiltrating and solid tumors. The ramified microglia accumulated in infiltration areas of both high- and low-grade gliomas, when hypertrophy and hyperplasia occur. In solid tumors, intermediate and bumpy forms prevailed and there is a large increase of macrophage-like cells in glioblastoma. The total number of microglia cells did not vary among the three grades of malignancy, but macrophage-like cells definitely prevailed in high-grade gliomas and frequently expressed CD45 and c-MAF. CD98 + cells were present. Microglia favors tumor progression, but many aspects suggest that the phagocytosing function is maintained. CD98 + cells can be the product of fusion, but also of phagocytosis. Microglia correlated with poorer survival in glioblastoma, when considering CD163 + cells, whereas it did not change prognosis in isocitrate dehydrogenase-mutant low grade gliomas.

  2. Mean Diffusional Kurtosis in Patients with Glioma

    DEFF Research Database (Denmark)

    Tietze, A.; Hansen, Mikkel Bo; Østergaard, Leif

    2015-01-01

    , and the contralateral normal appearing white and grey matter of 34 patients (22 high-grade, 12 low-grade gliomas). MK’ and MD in different grades were compared using a Wilcoxon rank-sum test. Receiver Operating Characteristic curves and the area under the curve were calculated to determine the diagnostic accuracy of MK...

  3. Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

    International Nuclear Information System (INIS)

    Kuwert, T.; Morgenroth, C.; Woesler, B.; Matheja, P.; Palkovic, S.; Vollet, B.; Samnick, S.; Maasjosthusmann, U.; Lerch, H.; Gildehaus, F.J.; Wassmann, H.; Schober, O.

    1996-01-01

    Using single-photon emission tomography (SPET), the radiopharmaceutical L-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating higc-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. (orig.)

  4. High grade magnesium from waste bittern

    International Nuclear Information System (INIS)

    El-Yamani, I.S.; Farah, M.Y.; Isaac, S.L.

    1979-01-01

    The production of high grade magnesia for nuclear purposes from sea water by use of both aqueous and gaseous ammonia has been described. The effect of precipitating conditions on the settling rate and magnesium recovery, was thoroughly examined. Ammonia gas approach was recommended and justified

  5. TWIST is Expressed in Human Gliomas, Promotes Invasion

    Directory of Open Access Journals (Sweden)

    Maria C. Elias

    2005-09-01

    Full Text Available TWIST is a basic helix-loop-helix (bHLH transcription factor that regulates mesodermal development, promotes tumor cell metastasis, and, in response to cytotoxic stress, enhances cell survival. Our screen for bHLH gene expression in rat C6 glioma revealed TWIST. To delineate a possible oncogenic role for TWIST in the human central nervous system (CNS, we analyzed TWIST message, protein expression in gliomas, normal brain. TWIST was detected in the large majority of human glioma-derived cell lines, human gliomas examined. Increased TWIST mRNA levels were associated with the highest grade gliomas, increased TWIST expression accompanied transition from low grade to high grade in vivo, suggesting a role for TWIST in promoting malignant progression. In accord, elevated TWIST mRNA abundance preceded the spontaneous malignant transformation of cultured mouse astrocytes hemizygous for p53. Overexpression of TWIST protein in a human glioma cell line significantly enhanced tumor cell invasion, a hallmark of high-grade gliomas. These findings support roles for TWIST both in early glial tumorigenesis, subsequent malignant progression. TWIST was also expressed in embryonic, fetal human brain, in neurons, but not glia, of mature brain, indicating that, in gliomas, TWIST may promote the functions also critical for CNS development or normal neuronal physiology.

  6. Survival advantage combining a BRAF inhibitor and radiation in BRAF V600E-mutant glioma

    NARCIS (Netherlands)

    Dasgupta, Tina; Olow, Aleksandra K.; Yang, Xiaodong; Hashizume, Rintaro; Nicolaides, Theodore P.; Tom, Maxwell; Aoki, Yasuyuki; Berger, Mitchel S.; Weiss, William A.; Stalpers, Lukas J. A.; Prados, Michael; James, C. David; Mueller, Sabine; Haas-Kogan, Daphne A.

    2016-01-01

    Radiation (RT) is critical to the treatment of high-grade gliomas (HGGs) but cures remain elusive. The BRAF mutation V600E is critical to the pathogenesis of 10-20% of pediatric gliomas, and a small proportion of adult HGGs. Here we aim to determine whether PLX4720, a specific BRAF V600E inhibitor,

  7. New similarity search based glioma grading

    Energy Technology Data Exchange (ETDEWEB)

    Haegler, Katrin; Brueckmann, Hartmut; Linn, Jennifer [Ludwig-Maximilians-University of Munich, Department of Neuroradiology, Munich (Germany); Wiesmann, Martin; Freiherr, Jessica [RWTH Aachen University, Department of Neuroradiology, Aachen (Germany); Boehm, Christian [Ludwig-Maximilians-University of Munich, Department of Computer Science, Munich (Germany); Schnell, Oliver; Tonn, Joerg-Christian [Ludwig-Maximilians-University of Munich, Department of Neurosurgery, Munich (Germany)

    2012-08-15

    MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone. (orig.)

  8. New similarity search based glioma grading.

    Science.gov (United States)

    Haegler, Katrin; Wiesmann, Martin; Böhm, Christian; Freiherr, Jessica; Schnell, Oliver; Brückmann, Hartmut; Tonn, Jörg-Christian; Linn, Jennifer

    2012-08-01

    MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone.

  9. Metal recovery from high-grade WEEE

    DEFF Research Database (Denmark)

    Bigum, Marianne; Brogaard, Line Kai-Sørensen; Christensen, Thomas Højlund

    2012-01-01

    Based on available data in the literature the recovery of aluminium, copper, gold, iron, nickel, palladium and silver from high-grade WEEE was modeled by LCA. The pre-treatment of WEEE included manual sorting, shredding, magnetic sorting, Eddy-current sorting, air classification and optical sorting...... and refining of ore. The resource recovery per tonne of high-grade WEEE ranged from 2 g of palladium to 386 kg of iron. Quantified in terms of person-equivalents the recovery of palladium, gold, silver, nickel and copper constituted the major environmental benefit of the recovery of metals from WEEE...... effect compared to the metallurgical treatment. However only 12-26% of silver, gold and palladium are recovered during pre-treatment, which suggest that the reduction of the apparent losses of precious metals as palladium, gold and silver during pre-treatment of WEEE is of environmental importance. Our...

  10. Spina bifida occulta in high grade spondylolisthesis.

    Science.gov (United States)

    Babbi, L; Terzi, S; Bandiera, S; Barbanti Brodano, G

    2014-01-01

    A 14-year-old boy presented with symptomatic high-grade dysplastic type spondylolisthesis, with a presence of spina bifida occulta, not diagnosed by plain radiographs, but confirmed on preoperative CT and MR. Circumferential fusion with partial reduction of L5/S1 was performed. Awareness of the coexistence of spondylolisthesis and spina bifida by an accurate preoperative planning is paramount to avoid iatrogenic damage to neural elements during surgery.

  11. IDH1 and IDH2 Mutations in Gliomas

    Science.gov (United States)

    Cohen, Adam; Holmen, Sheri; Colman, Howard

    2014-01-01

    Mutations in isocitrate dehydrogenase (IDH) 1 and 2, originally discovered in 2009, occur in the vast majority of low grade gliomas and secondary high grade gliomas. These mutations, which occur early in gliomagenesis, change the function of the enzymes, causing them to produce 2-hydroxyglutarate, a possible oncometabolite, and to not produce NADPH. IDH mutations are oncogenic, although whether the mechanism is through alterations in hydroxylases, redox potential, cellular metabolism, or gene expression is not clear. The mutations also drive increased methylation in gliomas. Gliomas with mutated IDH1 and IDH2 have improved prognosis compared to gliomas with wild-type IDH. Mutated IDH can now be detected by immunohistochemistry and magnetic resonance spectroscopy. No drugs currently target mutated IDH, although this remains an area of active research. PMID:23532369

  12. Cilengitide-induced temporal variations in transvascular transfer parameters of tumor vasculature in a rat glioma model: identifying potential MRI biomarkers of acute effects.

    Directory of Open Access Journals (Sweden)

    Tavarekere N Nagaraja

    Full Text Available Increased efficacy of radiotherapy (RT 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects of Cilengitide on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 days after implantation using dynamic contrast-enhanced (DCE-MRI. Vascular parameters, viz: plasma volume fraction (v(p, forward volume transfer constant (K(trans and interstitial volume fraction (v(e of a contrast agent, were determined in tumor vasculature once before, and again in cohorts 2, 4, 8, 12 and 24 h after Cilengitide administration (4 mg/kg; N = 31; 6-7 per cohort. Perfusion-fixed brain sections were stained for von Willebrand factor to visualize vascular segments. A comparison of pre- and post-treatment parameters showed that the differences between MR indices before and after Cilengitide treatment pivoted around the 8 h time point, with 2 and 4 h groups showing increases, 12 and 24 h groups showing decreases, and values at the 8 h time point close to the baseline. The vascular parameter differences between group of 2 and 4 h and group of 12 and 24 h were significant for K(trans (p = 0.0001 and v(e (p = 0,0271. Vascular staining showed little variation with time after Cilengitide. The vascular normalization occurring 8 h after Cilengitide treatment coincided with similar previous reports of increased treatment efficacy when RT followed Cilengitide by 8 h. Pharmacological normalization of vasculature has the potential to increase sensitivity to RT. Evaluating acute temporal responses of tumor vasculature to putative anti-angiogenic drugs may help in optimizing their combination with other treatment modalities.

  13. Differential expression of centrosomal proteins at different stages of human glioma

    Directory of Open Access Journals (Sweden)

    Lin Fang-Yi

    2010-06-01

    Full Text Available Abstract Background High-grade gliomas have poor prognosis, requiring aggressive treatment. The aim of this study is to explore mitotic and centrosomal dysregulation in gliomas, which may provide novel targets for treatment. Methods A case-control study was performed using 34 resected gliomas, which were separated into low- and high-grade groups. Normal human brain tissue was used as a control. Using immunohistochemical analysis, immunofluorescent microscopy, and RT-PCR, detection of centrins 1 and 2, γ-tubulin, hNinein, Aurora A, and Aurora B, expression was performed. Analysis of the GBM8401 glioma cell line was also undertaken to complement the in vivo studies. Results In high-grade gliomas, the cells had greater than two very brightly staining centrioles within large, atypical nuclei, and moderate-to-strong Aurora A staining. Comparing with normal human brain tissue, most of the mRNAs expression in gliomas for centrosomal structural proteins, including centrin 3, γ-tubulin, and hNinein isoforms 1, 2, 5 and 6, Aurora A and Aurora B were elevated. The significant different expression was observed between high- and low-grade glioma in both γ-tubulin and Aurora A mRNA s. In the high-grade glioma group, 78.6% of the samples had higher than normal expression of γ-tubulin mRNA, which was significantly higher than in the low-grade glioma group (18.2%, p Conclusions Markers for mitotic dysregulation, such as supernumerary centrosomes and altered expression of centrosome-related mRNA and proteins were more frequently detected in higher grade gliomas. Therefore, these results are clinically useful for glioma staging as well as the development of novel treatments strategies.

  14. Intraoperative Contrast Enhanced Ultrasound Evaluates the Grade of Glioma

    Directory of Open Access Journals (Sweden)

    Ling-Gang Cheng

    2016-01-01

    Full Text Available Objective. The aim of our study was to investigate the value of intraoperative contrast enhanced ultrasound (CEUS for evaluating the grade of glioma and the correlation between microvessel density (MVD and vascular endothelial growth factor (VEGF. Methods. We performed intraoperative conventional ultrasound (CUS and CEUS on 88 patients with gliomas. All of the patients have undergone surgery and obtained the results of pathology. All patients have undergone intraoperative CUS and CEUS to compare the characteristics of different grade gliomas and the results of CUS and CEUS were compared with pathological results. Results. The time to start (TTS and time to peak (TTP of low grade glioma (LGG were similar to those of edema and normal brain surrounding glioma. The enhanced extent of LGG was higher than that of the normal brain and edema. The TTS and TTP of high grade glioma were earlier than those of the edema and normal brain surrounding glioma. The enhancement of HGG was higher than that of LGG. The absolute peak intensity (API was correlated with MVD and VEGF. Conclusion. Intraoperative CEUS could help in determining boundary of peritumoral brain edema of glioma. Intraoperative CEUS parameters in cerebral gliomas could indirectly reflect the information of MVD and VEGF.

  15. Comparison of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Arterial Spin Labeling MR Imaging in Gliomas

    Directory of Open Access Journals (Sweden)

    Yuankai Lin

    2015-01-01

    Full Text Available Gliomas grading is important for treatment plan; we aimed to investigate the application of intravoxel incoherent motion (IVIM diffusion-weighted imaging (DWI in gliomas grading, by comparing with the three-dimensional pseudocontinuous arterial spin labeling (3D pCASL. 24 patients (13 high grade gliomas and 11 low grade gliomas underwent IVIM DWI and 3D pCASL imaging before operation; maps of fast diffusion coefficient (D∗, slow diffusion coefficient (D, fractional perfusion-related volume (f, and apparent diffusion coefficient (ADC as well as cerebral blood flow (CBF were calculated and then coregistered to generate the corresponding parameter values. We found CBF and D∗ were higher in the high grade gliomas, whereas ADC, D, and f were lower (all P0.05. IVIM DWI showed more efficiency than 3D pCASL but less validity than conventional DWI in differentiating the high from low grade gliomas.

  16. Tumor localization of boronated porphyrins in an intracerebral model of glioma

    International Nuclear Information System (INIS)

    Hill, J.S.; Kaye, A.H.; Gonzales, M.F.; Stylli, S.S.; Nakamura, Y.; Kahl, S.B.; Vardaxis, N.J.; Johnson, C.I.

    1992-01-01

    Treatment of the most common cerebral tumor, cerebral glioma, is unsatisfactory as the tumor recurs due to inadequate local control. Photodynamic therapy (PDT) and Boron Neutron Capture Therapy (BNCT) offer some promise as adjuvant treatments for cerebral glioma. Several clinical trials have been reported utilizing PDT and BNCT to treat the high grade glioma, glioblastoma multiforme. The authors have investigated the pharmacokinetic tissue distribution of the photosensitizer Haematoporphyrin derivative (HpD), the nido carboranyl porphyrin, boron tetraphenyl porphine (BTPP) and the closo carboranyl monomeric protoporphyrin (BOPP) in CBA mice bearing the intracerebral C6 glioma xenograft

  17. Cloning of a novel transcription factor-like gene amplified in human glioma including astrocytoma grade I

    NARCIS (Netherlands)

    Fischer, U.; Heckel, D.; Michel, A.; Janka, M.; Hulsebos, T.; Meese, E.

    1997-01-01

    Gene amplification, which is generally considered to occur late in tumor development, is a common feature of high grade glioma. Up until now, there have been no reports on amplification in astrocytoma grade I. In this study, we report cloning and sequencing of a cDNA termed glioma-amplified sequence

  18. High-grade primary pulmonary leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Rodrigo Afonso da Silva Sardenberg

    2011-12-01

    Full Text Available Primary sarcomas of the lung are rare and account for 0.5% of all primary lung tumors. There were approximately 300 cases described in the literature as of 2006. All histologic types of sarcoma were described, and the most common intrathoracic types reported were angiosarcoma, leiomyosarcoma, fibrosarcoma, hemangiopericytoma, and rhabdomyosarcoma. The biological behavior of these tumors is not well-known due to their low frequency. Leiomyosarcomas represent one of the most common subtypes encountered in the lungs, and usually occur during the sixth decade, with male predominance. Although the frequency of metastatic disease is not related to tumor size, prognosis was reported to be poorer in high-grade tumors. In comparison with other sarcomas, survival after complete resection of pulmonary leiomyosarcoma was reported as longer. We report on a patient with primary leiomyosarcoma originating from the bronchus with complete resection and long-term follow-up.

  19. Posterior surgery in high-grade spondylolisthesis.

    Science.gov (United States)

    Lengert, R; Charles, Y P; Walter, A; Schuller, S; Godet, J; Steib, J-P

    2014-09-01

    High-grade L5-S1 spondylolisthesis alters sagittal spinopelvic balance, which can cause low back pain and progressive neurologic disorder. The present study assessed spondylolisthesis reduction and maintenance over time with L4-S1 versus L5-S1 fusion using a lever-arm system and posterior fusion combined with lumbosacral graft. Forty patients were operated on for symptomatic high-grade spondylolisthesis, 34 of whom had full pre- and post-operative radiological analysis, with a mean follow-up of 5.4years. There were 9 L5-S1 and 25 L4-S1 instrumentations. Analysis of spinopelvic and slipping parameters and the evolution of segmental lordosis compared results between L5-S1 and L4-S1 instrumentation. Mean Taillard spondylolisthesis index decreased from 64% to 37% (P=0.0001). Overall sagittal spinopelvic balance was not significantly changed. Overall L1-S1 and segmental L4-L5 lordosis were not affected by instrumentation. Mean L5-S1 segmental lordosis increased from 11° to 18°. There was loss of reduction from 19° to 14° with L5-S1 instrumentation, in contrast to maintained reduction with L4-S1 instrumentation (P=0.006). The lever-arm system provided anterior-posterior reduction of spondylolisthesis and corrected slippage. Postoperative change in overall sagittal spinopelvic balance was slight and constant. Posterior L4-S1 fusion provided better long-term control of L5-S1 lordosis reduction than the shorter L5-S1 fusion. Retrospective study of level IV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Molecular and Morphologic Correlates of the Alternative Lengthening of Telomeres Phenotype in High Grade Astrocytomas

    Science.gov (United States)

    Nguyen, Doreen N.; Heaphy, Christopher M.; de Wilde, Roeland F.; Orr, Brent A.; Odia, Yazmin; Eberhart, Charles G.; Meeker, Alan K.; Rodriguez, Fausto J.

    2013-01-01

    Recent studies suggest that the telomere maintenance mechanism known as Alternative Lengthening of Telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas,19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1R132H mutant protein. EGFR amplification was evaluated by FISH. When focusing on histologic subtypes, almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n=4), epithelioid (n=2), giant cell (n=2) and adult small cell astrocytomas (n=7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (p=0.002), microcysts (p<0.0002), IDH1 mutant protein (p<0.0001), ATRX protein loss (p<0.0001), strong P53 expression (p<0.0001), and absence of EGFR amplification (p=0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high grade astrocytomas, and its possible utility as a diagnostic and/or therapeutic target. PMID:22928601

  1. Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas.

    Science.gov (United States)

    Nguyen, Doreen N; Heaphy, Christopher M; de Wilde, Roeland F; Orr, Brent A; Odia, Yazmin; Eberhart, Charles G; Meeker, Alan K; Rodriguez, Fausto J

    2013-05-01

    Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high-grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas, 19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1(R132H) mutant protein. EGFR amplification was evaluated by fluorescence in situ hybridization (FISH). Almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n = 4), epithelioid (n = 2), giant cell (n = 2) and adult small cell astrocytomas (n = 7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (P = 0.002), microcysts (P < 0.0002), IDH1 mutant protein (P < 0.0001), ATRX protein loss (P < 0.0001), strong P53 immunostaining (P < 0.0001) and absence of EGFR amplification (P = 0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high-grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high-grade astrocytomas. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

  2. Histologic classification of gliomas

    NARCIS (Netherlands)

    Perry, Arie; Wesseling, Pieter|info:eu-repo/dai/nl/157872866

    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,

  3. Risk assessment in paediatric glioma-Time to move on from the binary classification.

    Science.gov (United States)

    Dodgshun, A J; Hansford, J R; Sullivan, M J

    2017-03-01

    Paediatric glioma encompasses a wide range of entities with highly variable prognoses. Gliomas are grouped by histopathological features into high- and low-grade glioma but this classification until recently has not taken into account many emerging risk factors in this disease. A comprehensive risk classification has not been published for paediatric glioma despite many risk factors being established in this disease. A comprehensive literature review was carried out identifying risk factors for paediatric low-grade and high-grade glioma. The most consistently described risk factors in high-grade glioma included midline location and extent of surgical resection. For patients with progressive unresectable low-grade glioma, age under 1, neurofibromatosis type I status and location were the most consistently prognostic. Molecular classification shows promise in accurately reassigning diagnosis for some gliomas. Risk profiling in paediatric glioma will require a focused multinational effort but will result in a more accurate and nuanced assessment of prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. ABCG2 is related with the grade of glioma and resistance to mitoxantone, a chemotherapeutic drug for glioma.

    Science.gov (United States)

    Jin, Yao; Bin, Zhang Quan; Qiang, Huang; Liang, Chu; Hua, Chen; Jun, Dong; Dong, Wang Ai; Qing, Lan

    2009-10-01

    The aim of this study is to explore if ABCG2 is related to the grade of glioma and resistance to chemotherapeutic drug for glioma. The ABCG2 expression and distribution among glioma tissues of different grades and other samples were examined using tissue microarray technique. The enhancement of sensitivity of CD133+ glioma stem cells to chemotherapeutic agent, mitoxantone through addition of ABCG2 competitive inhibitor nicardipine was testified by MTT assay and FACS analysis. The positive immunostaining of ABCG2 was observed in less than 10% of low-grade gliomas (3/31 in grade I + II) and in more than 40% of high-grade gliomas (16/37 in grade III + IV), which was statistically different (chi (2) = 10.710, P = 0.0011). In samples consisting of glioma stem cells (CD133+), the positive-straining rate was 100% (4/4), while in CD133- fraction, no positive staining was observed. A simultaneous treatment of CD133+ tumor cells with concentration-dependent mitoxantone (10(-5)-1 microM) and 2.5/5.0 microM nicardipine resulted in synergistic cytotoxicity. The apoptotic rate of CD133+ cells treated with mitoxantone plus nicardipine was significantly higher than that treated with mitoxantone alone (58.54 +/- 7.06% vs. 30.7 +/- 3.79%, P level of ABCG2 is positively associated with the increasing pathological grade of glioma (poor cell differentiation). ABCG2 plays a key role in glioma cells resistance to mitoxantone, chemotherapeutic drug for glioma. Thus, inhibition of ABCG2 protein activity by nicardipine in glioma can sensitize it to mitoxantone, which may lead to better treatment strategies for cancers.

  5. Voxel-based clustered imaging by multiparameter diffusion tensor images for glioma grading.

    Science.gov (United States)

    Inano, Rika; Oishi, Naoya; Kunieda, Takeharu; Arakawa, Yoshiki; Yamao, Yukihiro; Shibata, Sumiya; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu

    2014-01-01

    Gliomas are the most common intra-axial primary brain tumour; therefore, predicting glioma grade would influence therapeutic strategies. Although several methods based on single or multiple parameters from diagnostic images exist, a definitive method for pre-operatively determining glioma grade remains unknown. We aimed to develop an unsupervised method using multiple parameters from pre-operative diffusion tensor images for obtaining a clustered image that could enable visual grading of gliomas. Fourteen patients with low-grade gliomas and 19 with high-grade gliomas underwent diffusion tensor imaging and three-dimensional T1-weighted magnetic resonance imaging before tumour resection. Seven features including diffusion-weighted imaging, fractional anisotropy, first eigenvalue, second eigenvalue, third eigenvalue, mean diffusivity and raw T2 signal with no diffusion weighting, were extracted as multiple parameters from diffusion tensor imaging. We developed a two-level clustering approach for a self-organizing map followed by the K-means algorithm to enable unsupervised clustering of a large number of input vectors with the seven features for the whole brain. The vectors were grouped by the self-organizing map as protoclusters, which were classified into the smaller number of clusters by K-means to make a voxel-based diffusion tensor-based clustered image. Furthermore, we also determined if the diffusion tensor-based clustered image was really helpful for predicting pre-operative glioma grade in a supervised manner. The ratio of each class in the diffusion tensor-based clustered images was calculated from the regions of interest manually traced on the diffusion tensor imaging space, and the common logarithmic ratio scales were calculated. We then applied support vector machine as a classifier for distinguishing between low- and high-grade gliomas. Consequently, the sensitivity, specificity, accuracy and area under the curve of receiver operating characteristic

  6. Comparison of language cortex reorganization patterns between cerebral arteriovenous malformations and gliomas: a functional MRI study.

    Science.gov (United States)

    Deng, Xiaofeng; Zhang, Yan; Xu, Long; Wang, Bo; Wang, Shuo; Wu, Jun; Zhang, Dong; Wang, Rong; Wang, Jia; Zhao, Jizong

    2015-05-01

    , 6 patients (15.8%) showed right-sided lateralization of the Wernicke area, including 2 patients in the glioma-BA subgroup and 4 patients in the glioma-WA subgroup. No patient showed right-sided lateralization of the Broca area. Moreover, although the incidence of right-sided lateralization was higher in cases of low-grade gliomas (5 in 26 [19.2%]) than in high-grade gliomas (1 in 12 [8.3%]), no significant difference was detected between them (p = 0.643). Compared with the AVM group, the incidence of aphasia was significantly higher (p reorganization may occur with both diseases. However, the potential of reorganization in patients with gliomas seems to be insufficient compared with patients AVMs, which is suggested by clinical manifestations and the fMRI findings. Moreover, this study seems to indicate that in patients with an AVM, a nidus near the Broca area mainly leads to right-sided lateralization of the Broca area, and a nidus near the Wernicke area mainly leads to right-sided lateralization of the Wernicke area.

  7. Glioma epidemiology in the central Tunisian population: 1993-2012.

    Science.gov (United States)

    Trabelsi, Saoussen; Brahim, Dorra H'mida-Ben; Ladib, Mohamed; Mama, Nadia; Harrabi, Imed; Tlili, Kalthoum; Yacoubi, Mohamed Tahar; Krifa, Hedi; Hmissa, Sihem; Saad, Ali; Mokni, Moncef

    2014-01-01

    Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

  8. Molecular Alterations of KIT Oncogene in Gliomas

    Directory of Open Access Journals (Sweden)

    Ana L. Gomes

    2007-01-01

    Full Text Available Gliomas are the most common and devastating primary brain tumours. Despite therapeutic advances, the majority of gliomas do not respond either to chemo or radiotherapy. KIT, a class III receptor tyrosine kinase (RTK, is frequently involved in tumourigenic processes. Currently, KIT constitutes an attractive therapeutic target. In the present study we assessed the frequency of KIT overexpression in gliomas and investigated the genetic mechanisms underlying KIT overexpression. KIT (CD117 immunohistochemistry was performed in a series of 179 gliomas of various grades. KIT activating gene mutations (exons 9, 11, 13 and 17 and gene amplification analysis, as defined by chromogenic in situ hybridization (CISH and quantitative real-time PCR (qRT-PCR were performed in CD117 positive cases. Tumour cell immunopositivity was detected in 15.6% (28/179 of cases, namely in 25% (1/4 of pilocytic astrocytomas, 25% (5/20 of diffuse astrocytomas, 20% (1/5 of anaplastic astrocytomas, 19.5% (15/77 of glioblastomas and one third (3/9 of anaplastic oligoastrocytomas. Only 5.7% (2/35 of anaplastic oligodendrogliomas showed CD117 immunoreactivity. No association was found between tumour CD117 overexpression and patient survival. In addition, we also observed CD117 overexpression in endothelial cells, which varied from 0–22.2% of cases, being more frequent in high-grade lesions. No KIT activating mutations were identified. Interestingly, CISH and/or qRT-PCR analysis revealed the presence of KIT gene amplification in 6 glioblastomas and 2 anaplastic oligoastrocytomas, corresponding to 33% (8/24 of CD117 positive cases. In conclusion, our results demonstrate that KIT gene amplification rather than gene mutation is a common genetic mechanism underlying KIT expression in subset of malignant gliomas. Further studies are warranted to determine whether glioma patients exhibiting KIT overexpression and KIT gene amplification may benefit from therapy with anti-KIT RTK

  9. Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation.

    Science.gov (United States)

    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.

  10. An integrated transcriptomic and computational analysis for biomarker identification in human glioma.

    Science.gov (United States)

    Xing, Wenli; Zeng, Chun

    2016-06-01

    Malignant glioma is one of the most common primary brain tumors and is among the deadliest of human cancers. The molecular mechanism for human glioma is poorly understood. Early prognosis of this disease and early treatment are vital. Thus, it is crucial to target the key genes controlling pathogenesis in the early stage of glioma. In this study, differentially expressed genes in human glioma and paired peritumoral tissues were detected by transcriptome microarray analysis. Following gene microarray analysis, the gene expression profile in the differential grade glioma was further validated by bioinformatic analyses, co-expression network construction. Microarray analysis revealed that 1725 genes were differentially expressed and classified into different glioma stage. The analysis revealed 14 genes that were significantly associated with survival with a false discovery rate. Among these genes, macrophage capping protein (CAPG), a member of the actin-regulatory protein, was the key gene in a 20-gene network that modulates cell motility by interacting with the cytoskeleton. Furthermore, the prognostic impact of CAPG was validated by use of quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry on human glioma tissue. CAPG protein was significantly upregulated in clinical high-grade glioblastoma as compared with normal brain tissues. Overexpression of CAPG levels also predict shorter overall survival of glioma patients. These data demonstrated CAPG protein expression in human glioma was associated with tumorigenesis and may be a biomarker for identification of the pathological grade of glioma.

  11. Growth of cultured human glioma tumour cells can be regulated with histamine and histamine antagonists.

    OpenAIRE

    Van der Ven, L. T.; Prinsen, I. M.; Jansen, G. H.; Roholl, P. J.; Defferrari, R.; Slater, R.; Den Otter, W.

    1993-01-01

    The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures. Twelve freshly excised human gliomas were cultured and tested for thei...

  12. Clinical and molecular features of high-grade osteosarcoma

    NARCIS (Netherlands)

    Anninga, Jakob Klaas

    2013-01-01

    It can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant chemotherapy should be combined with radical surgery, irrespective the localization. There are only 4 effective

  13. Clinical utility of 18F-FDG PET in grading gliomas

    International Nuclear Information System (INIS)

    Li Zugui; Cai Li; Gao Shuo

    2004-01-01

    Purpose: To compare 18 F-FDG PET with MRI in grading gliomas. Methods: Ten patients (male 6, female 4, mean age 4.5.0 yrs, range 24.0 yrs to 65.0 yrs) were included in this study. MRI and 18 FDG PET was performed within one week in all patients. 18 FDG attenuation-correction brain images were acquired with a dedicated PET scanner. Visual and semi-qualitative evaluation (T/WM, T/GM) was used and compared with the pre- and post-contrast MRI. Base on the MRI appearance, all patients were divided into two groups (A: high-grade gliomas; B: low-grade gliomas), which were histopathologically proved. Results: In the group A (high-grade, n=4), all lesions were characterized by obviously enhanced in MRI; the group B (low-grade, n= 6) does not enhanced or only slightly enhanced after administration of contrast media, which means that there is no blood-brain-barrier (BBB) damage, but low vascularisation and proliferation rate and slow growing. In the group A, PET can detect all the 4 lesions diagnosed by MRI. In the group B, the diagnostic results of 4 cases by PET were accordance with those of MRI. The results of high ratio of T/W and T/G in PET were disaccordance with the grading of enhanced MRI examination in two cases.They were finally histopathologically proved high-grade gliomas (WHOIII). Because of focal proliferation and malignant differentiation, the demonstrations of the two high-grade gliomas in MRI were similar with those of low-grade gliomas. However, the metabolism of primary brain tumor is different from the normal brain tissue, so it's possible for PET to detect all the high-grade gliomas (n=6). Conclusions: 18 FDG PET is also an important modality in grading gliomas in addition to MRI, especially in grading some mixed gliomas. In the cases that clinically suspected high-grade gliomas but there were no enhancement in MRI examination, PET imaging was suggested. (authors)

  14. Glioma grading capability: Comparisons among parameters from dynamic contrast-enhanced MRI and ADC value on DWI

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyun Seok; Kim, Ah Hyun; Ahn, Sung Soo; Shin, Na Young; Kim, Jin Na; Lee, Seung Koo [Dept. of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul , (Korea, Republic of)

    2013-06-15

    Permeability parameters from dynamic contrast-enhanced MRI (DCE-MRI) and apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI) can be quantitative physiologic metrics for gliomas. The transfer constant (K{sup trans}) has shown efficacy in grading gliomas. Volume fraction of extravascular extracellular space (v{sub e}) has been underutilized to grade gliomas. The purpose of this study was to evaluate v{sub e} in its ability to grade gliomas and to assess the correlation with other permeability parameters and ADC values. A total of 33 patients diagnosed with pathologically-confirmed gliomas were examined by 3 T MRI including DCE-MRI and ADC map. A region of interest analyses for permeability parameters from DCE-MRI and ADC were performed on the enhancing solid portion of the tumors. Permeability parameters form DCE-MRI and ADC between low- and high-grade gliomas; the diagnostic performances of presumptive metrics and correlation among those metrics were statistically analyzed. High-grade gliomas showed higher K{sup trans} (0.050 vs. 0.010 in median value, p = 0.002) and higher v{sub e} (0.170 vs. 0.015 in median value, p = 0.001) than low-grade gliomas. Receiver operating characteristic curve analysis showed significance in both K{sup trans} and v{sub e} for glioma grading. However, there was no significant difference in diagnostic performance between K{sup trans} and v{sub e}. ADC value did not correlate with any of the permeability parameters from DCE-MRI. Extravascular extracellular space (v{sub e}) appears to be comparable with transfer constant (K{sup trans}) in differentiating high-grade gliomas from low-grade gliomas. ADC value does not show correlation with any permeability parameters from DCE-MRI.

  15. Optic radiation fiber tractography in glioma patients based on high angular resolution diffusion imaging with compressed sensing compared with diffusion tensor imaging - initial experience.

    Directory of Open Access Journals (Sweden)

    Daniela Kuhnt

    Full Text Available OBJECTIVE: Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI. However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine. METHODS: Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR, underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS. RESULTS: HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract. CONCLUSIONS: Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.

  16. Glioma Grading and Determination of IDH Mutation Status and ATRX loss by DCE and ASL Perfusion.

    Science.gov (United States)

    Brendle, Cornelia; Hempel, Johann-Martin; Schittenhelm, Jens; Skardelly, Marco; Tabatabai, Ghazaleh; Bender, Benjamin; Ernemann, Ulrike; Klose, Uwe

    2017-05-09

    To evaluate arterial spin labeling (ASL) perfusion and dynamic contrast-enhanced (DCE) perfusion in glioma grading according to the previous WHO classification of 2007, as well as concerning isocitrate dehydrogenase (IDH) mutation status and ATRX expression as required by the new WHO 2016 brain tumor classification. The mean values of Ktrans, Kep, Ve, and Vp by DCE perfusion, and cerebral blood flow (CBF) by ASL perfusion were assessed retrospectively in 40 patients with initial glioma diagnosis. Perfusion parameters were correlated and compared concerning glioma grading, IDH mutation status and ATRX expression. The DCE and ASL perfusion parameters showed merely moderate correlation. The Ktrans, Ve, and CBF by DCE perfusion were different in low-grade and high-grade gliomas (p = 0.0018, p IDH mutation (p = 0.014, sensitivity = 0.75, specificity = 0.88) and showed a trend for the discrimination of astrocytomas with IDH mutation from oligodendrogliomas (p = 0.074). In conclusion, DCE and ASL perfusion are complementary in the differentiation of gliomas. The discrimination of low- and high-grade gliomas is possible by the DCE perfusion parameter Ve, while ASL perfusion shows potential for the differentiation of the IDH and ATRX mutation status of gliomas following the new WHO classification 2016. Both perfusion techniques might represent different aspects of brain tumor perfusion.

  17. Biomarker discovery in high grade sarcomas by mass spectrometry imaging

    OpenAIRE

    Lou, S.

    2017-01-01

    This thesis demonstrates a detailed biomarker discovery Mass Spectrometry Imaging workflow for histologically heterogeneous high grade sarcomas. Panels of protein and metabolite signatures were discovered either distinguishing different histological subtypes or stratifying high risk patients with poor survival.

  18. 40 CFR 246.200 - High-grade paper recovery.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false High-grade paper recovery. 246.200 Section 246.200 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES SOURCE... paper recovery. ...

  19. Post-treatment changes of tumour perfusion parameters can help to predict survival in patients with high-grade astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Sanz-Requena, Roberto; Marti-Bonmati, Luis [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Revert-Ventura, Antonio J.; Salame-Gamarra, Fares [Hospital de Manises, Radiology Department, Manises (Spain); Garcia-Marti, Gracian [Hospital Quironsalud Valencia, Radiology Department, Valencia (Spain); Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); CIBER-SAM, Instituto de Salud Carlos III, Madrid (Spain); Perez-Girbes, Alexandre [Hospital Universitari i Politecnic La Fe, Grupo de Investigacion Biomedica en Imagen, Valencia (Spain); Molla-Olmos, Enrique [Hospital La Ribera, Radiology Department, Alzira (Spain)

    2017-08-15

    Vascular characteristics of tumour and peritumoral volumes of high-grade gliomas change with treatment. This work evaluates the variations of T2*-weighted perfusion parameters as overall survival (OS) predictors. Forty-five patients with histologically confirmed high-grade astrocytoma (8 grade III and 37 grade IV) were included. All patients underwent pre- and post-treatment T2*-weighted contrast-enhanced magnetic resonance (MR) imaging. Tumour, peritumoral and control volumes were segmented. Relative variations of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), K{sup trans-T2*}, k{sub ep-T2*}, v{sub e-T2*} and v{sub p-T2*} were calculated. Differences regarding tumour grade and surgical resection extension were evaluated with ANOVA tests. For each parameter, two groups were defined by non-supervised clusterisation. Survival analysis were performed on these groups. For the tumour region, the 90th percentile increase or stagnation of CBV was associated with shorter survival, while a decrease related to longer survival (393 ± 189 vs 594 ± 294 days; log-rank p = 0.019; Cox hazard-ratio, 2.31; 95% confidence interval [CI], 1.12-4.74). K{sup trans-T2*} showed similar results (414 ± 177 vs 553 ± 312 days; log-rank p = 0.037; hazard-ratio, 2.19; 95% CI, 1.03-4.65). The peritumoral area values showed no relationship with OS. Post-treatment variations of the highest CBV and K{sup trans-T2*} values in the tumour volume are predictive factors of OS in patients with high-grade gliomas. (orig.)

  20. Malignant Transformation of High-Grade Osteoblastoma of the Petrous Apex with Subcutaneous Metastasis

    Science.gov (United States)

    Kraft, Casey T.; Morrison, Robert J.; Arts, H. Alexander

    2015-01-01

    Objectives To present the clinical presentation, management, and pathological findings of a patient with osteosarcoma of the petrous apex with atypical metastasis to the lower abdominal wall. Methods Retrospective review of the records of a case of osteosarcoma of the petrous apex. Results A 49-year old man with facial pain is diagnosed with a right petrous apex lesion with biopsy demonstrating high-grade osteoblastoma. Multiple attempts at en bloc resection were not curative, therefore radiation and chemotherapy was recommended after two surgical attempts. The patient subsequently developed a cutaneous, lower abdominal wall mass which demonstrated osteosarcoma. Petrous apex tumor growth progressed despite treatment until the patient expired from burden of disease. Conclusions Temporal bone osteoblastoma and osteosarcoma are both extremely rare, and can be difficult to differentiate histologically. The present case illustrates these difficulties and demonstrates the possibility of malignant conversion from high-grade osteobastoma to osteosarcoma. PMID:27304442

  1. Malignant transformation of a high-grade osteoblastoma of the petrous apex with subcutaneous metastasis.

    Science.gov (United States)

    Kraft, Casey T; Morrison, Robert J; Arts, H Alexander

    2016-06-01

    We describe the clinical presentation, management, and pathologic findings in a case of osteosarcoma of the petrous apex with an atypical metastasis to the lower abdominal wall. We retrospectively reviewed the record of a 49-year-old man who was diagnosed with a right petrous apex lesion, which biopsy identified as a high-grade osteoblastoma. After two attempts at en bloc resection were not curative, radiation and chemotherapy were recommended. The patient subsequently developed a cutaneous lower abdominal mass that was diagnosed as an osteosarcoma. Meanwhile, the petrous apex tumor continued to grow despite treatment until the patient died from the burden of disease. Temporal bone osteoblastomas and osteosarcomas are both extremely rare, and they can be difficult to differentiate histologically. Our case illustrates this difficulty and demonstrates the possibility of a high-grade osteoblastoma's malignant conversion to an osteosarcoma.

  2. Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study.

    Science.gov (United States)

    Amirian, E Susan; Zhou, Renke; Wrensch, Margaret R; Olson, Sara H; Scheurer, Michael E; Il'yasova, Dora; Lachance, Daniel; Armstrong, Georgina N; McCoy, Lucie S; Lau, Ching C; Claus, Elizabeth B; Barnholtz-Sloan, Jill S; Schildkraut, Joellen; Ali-Osman, Francis; Sadetzki, Siegal; Johansen, Christoffer; Houlston, Richard S; Jenkins, Robert B; Bernstein, Jonine L; Merrell, Ryan T; Davis, Faith G; Lai, Rose; Shete, Sanjay; Amos, Christopher I; Melin, Beatrice S; Bondy, Melissa L

    2016-02-01

    Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. ©2016 American Association for Cancer Research.

  3. PET for gliomas

    International Nuclear Information System (INIS)

    Shinoura, Nobusada; Momose, Toshimitsu

    1999-01-01

    CT and MRI imaging, which essentially provide the physical status of tissue, give important information on the histopathology and extent of gliomas. On the contrary, PET is a biochemical and physiologic technology and is beginning to give more precise information about gliomas, which allows the distinction between gliomas and normal brains, the supply of histopathologic and prognostic information, and the assessment of the response to the therapy. To date, fluorine-18fluorodeoxy-glucose (FDG) and 11C-methionine (MET) are widely used PET tracers for gliomas. Recent studies have demonstrated that the degree of the increase in the glycolytic rate in gliomas, as measured with FDG, is correlated with the histologic grade and prognosis. However, MET is superior to FDG in delineation of the boundaries of gliomas, because MET sometimes shows the lesion invaded by gliomas, which is usually wider than that detected by CT or MRI imaging. Finally, we discussed about 11C-Choline PET, in which T/N ratio of gliomas was remarkably high, and residual tumors were easily distinguished from surrounding normal tissues after surgery. In conclusion, it is important to know the advantage of individual PET tracers and combine a couple of tracers to obtain accurate information about gliomas. (author)

  4. Fine mapping of a region of common deletion on chromosome arm 10p in human glioma

    NARCIS (Netherlands)

    Voesten, A. M.; Bijleveld, E. H.; Westerveld, A.; Hulsebos, T. J.

    1997-01-01

    Allelic loss on chromosome 10 is a frequent event in high grade gliomas. Earlier studies have shown that in most cases a complete copy of chromosome 10 is lost in the tumor. To define more accurately and specifically the region of common deletion on chromosome arm 10p, we have screened a large

  5. Grading of Cerebral Glioma with Multiparametric MR Imaging and {sup 18}F-FDG-PET: Concordance and Accuracy

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jeong Hee; Kim, Ji-hoon; Sohn, Chul-Ho; Choi, Seung Hong; Yun, Tae Jin; Song, Yong Sub [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kang, Won Jun [Seoul National University Hospital, Department of Nuclear Medicine, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Eun, Yong [Seoul National University, College of Medicine, Seoul (Korea, Republic of); Chang, Kee-Hyun [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Soonchunhyang University Bucheon Hospital, Department of Radiology, Bucheon (Korea, Republic of)

    2014-02-15

    To retrospectively evaluate concordance rates and predictive values in concordant cases among multiparametric MR techniques and FDG-PET to grade cerebral gliomas. Multiparametric MR imaging and FDG-PET were performed in 60 consecutive patients with cerebral gliomas (12 low-grade and 48 high-grade gliomas). As the dichotomic variables, conventional MRI, minimum apparent diffusion coefficient in diffusion-weighted imaging, maximum relative cerebral blood volume ratio in perfusion-weighted imaging, choline/creatine ratio and (lipid and lactate)/creatine ratio in MR spectroscopy, and maximum standardised uptake value ratio in FDG-PET in low- and high-grade gliomas were compared. Their concordance rates and positive/negative predictive values (PPV/NPV) in concordant cases were obtained for the various combinations of multiparametric MR techniques and FDG-PET. There were significant differences between low- and high-grade gliomas in all techniques. Combinations of two, three, four, and five out of the five techniques showed concordance rates of 77.0 ± 4.8 %, 65.5 ± 4.0 %, 58.3 ± 2.6 % and 53.3 %, PPV in high-grade concordant cases of 97.3 ± 1.7 %, 99.1 ± 1.4 %, 100.0 ± 0 % and 100.0 % and NPV in low-grade concordant cases of 70.2 ± 7.5 %, 78.0 ± 6.0 %, 80.3 ± 3.4 % and 80.0 %, respectively. Multiparametric MR techniques and FDG-PET have a concordant tendency in a two-tiered classification for the grading of cerebral glioma. If at least two examinations concordantly indicated high-grade gliomas, the PPV was about 95 %. (orig.)

  6. Therapeutic options for recurrent malignant glioma.

    Science.gov (United States)

    Niyazi, Maximilian; Siefert, Axel; Schwarz, Silke Birgit; Ganswindt, Ute; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Belka, Claus

    2011-01-01

    Despite the given advances in neuro-oncology most patients with high grade malignant glioma ultimately fail locally or locoregionally. In parallel with improvements of initial treatment options, several salvage strategies have been elucidated and already entered clinical practice. Aim of this article is to review the current status of salvage strategies in recurrent high grade glioma. Using the following MESH headings and combinations of these terms the pubmed database was searched: "Glioma", "Recurrence", "Neoplasm Recurrence, Local", "Radiosurgery", "Brachytherapy", "Neurosurgical Procedures" and "Drug Therapy". For citation crosscheck the ISI web of science database was used employing the same search terms. In parallel, the abstracts of ASCO 2008-2009 were analyzed accordingly. Currently the following options for salvage entered clinical practice: re-resection, re-irradiation (stereotactic radiosurgery, (hypo-)fractionated (stereotactic) radiotherapy, interstitial brachytherapy) or single/poly-chemotherapy schedules including new dose-intensified or alternative treatment protocols employing targeted drugs. Re-operation is associated with high morbidity and mortality, however, is an option in a highly selected patient cohort. Since toxicity has been overestimated, re-irradiation is an increasingly used option with precise fractionated radiotherapy being the most optimal technique. On average, time to secondary progression is in the range of several months. Conventional chemotherapy regimens also improve time to secondary progression; however the efficacy is only modest and treatment-related toxicities like myelo-suppression occur very frequently. Molecular targeted agents/kinases are undergoing clinical testing; however no final recommendations can be made. Currently, several re-treatment options with only modest efficacy exist. The relative value of each approach compared to other options is unknown as well as it remains open which sequence of modalities should

  7. Expression of WW domain-containing protein 2 is correlated with pathological grade and recurrence of glioma.

    Science.gov (United States)

    Liang, Jun; Qi, Wei-Feng; Xie, Shao; Wang, Wei-Feng; Zhang, Xian-Li; Zhou, Xiu-Ping; Hu, Jin-Xia; Yu, Ru-Tong

    2017-01-01

    WW domain-containing protein 2 (WWP2) is an E3 ubiquitin ligase, which belongs to the NEDD4-like protein family. Recently, it is reported to play a key role in tumorigenesis and development of tumors such as prostate and lung cancer. However, there has been not related report on glioma until now. The aim of this study is to detect the expression of WWP2 and analyze its correlation to the pathological grade and tumor recurrence in patients with glioma. Western blot and immunohistochemistry were separately used to detect the expression of WWP2 protein in 31 brain glioma tissue samples and 80 brain glioma paraffin specimens. The method of Kaplan-Meier was used to analyze the correlation between the WWP2 expression and glioma recurrence. The protein expression level of WWP2 in glioma tissue was significantly higher than that in nontumorous brain tissue (P level of WWP2 in high-grade glioma (Grade III-IV) was significantly higher than that in low-grade glioma (Grade I-II) (P study suggests that WWP2 may play a role in the genesis and development of glioma; it may be a potential biomarker to predict pathological grade and tumor recurrence in patients with glioma.

  8. Chemotherapy in Glioma

    NARCIS (Netherlands)

    W. Taal (Walter)

    2015-01-01

    markdownabstractGliomas are primary brain tumors and include astrocytomas, oligodendrogliomas, and mixed oligo-astrocytomas. Currently, treatment of newly diagnosed diffuse adult gliomas exists of surgery, radiotherapy and chemotherapy. We were the first to show a high incidence of progressive MRI

  9. Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

    Science.gov (United States)

    Siegal, Tali

    2016-01-01

    Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.

  10. [How to biopsy only men with high grade prostate cancer].

    Science.gov (United States)

    Benecchi, Luigi; Bocchi, Francesca; Martinotti, Mario; Perucchini, Laura; Quarta, Matteo; Russo, Fabrizio; Tonghini, Mario; Del Boca, Carlo

    2013-04-24

    Fuzzy logic and Artificial Neural Networks (ANN) are complementary technologies that together generate neuro-fuzzy system. The aim of our study is to compare 2 models for predicting the presence of high-grade prostate cancer (Gleason score 7 or more). We evaluated data from 1000 men with PSA less than 50 ng/mL, who underwent prostate biopsy. A prostate cancer was found in 313 (31%), and in 172 (17.2%) we detected high-grade prostate cancer. With those data, we developed 2 Co-Active Neuro-Fuzzy Inference Systems to predict the presence of high-grade prostate cancer. The first model had four input neurons (PSA, free PSA percentage [%freePSA], PSA density, and age) and the second model had three input neurons (PSA, %freePSA, and age). The model with four input neurons (PSA, %freePSA, PSA density, and age) showed better performances than the one with three input neurons (PSA, %freePSA, and age). In fact the average testing error was 0.42 for the model with four input neurons and 0.44 for the other model. The addition of PSA density to the model has allowed to obtain better results for the diagnosis of high grade prostate cancer.

  11. Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

    Science.gov (United States)

    Andolfi, Laura; Bourkoula, Eugenia; Migliorini, Elisa; Palma, Anita; Pucer, Anja; Skrap, Miran; Scoles, Giacinto; Beltrami, Antonio Paolo; Cesselli, Daniela; Lazzarino, Marco

    2014-01-01

    Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

  12. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report1

    Science.gov (United States)

    Pollack, Ian F.; Jakacki, Regina I.; Blaney, Susan M.; Hancock, Michael L.; Kieran, Mark W.; Phillips, Peter; Kun, Larry E.; Friedman, Henry; Packer, Roger; Banerjee, Anu; Geyer, J. Russell; Goldman, Stewart; Poussaint, Tina Young; Krasin, Matthew J.; Wang, Yanfeng; Hayes, Michael; Murgo, Anthony; Weiner, Susan; Boyett, James M.

    2007-01-01

    This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation. The protocol was also amended to exclude children with prior hemorrhage. Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency. None of 18 patients with recurrent glioma experienced DLT. After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic. In addition to the six patients with hemorrhages during the DLT monitoring period, 10 experienced ITH (eight patients were symptomatic) thereafter. The recommended phase II dose for brainstem gliomas was 265 mg/m2. Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib. The MTD for recurrent high-grade gliomas without EIACDs was 465 mg/m2, but the MTD was not established with EIACDs, with no DLTs at 800 mg/m2. In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs. Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern. PMID

  13. High Grade Leiomyosarcoma Mimicking a Recurrent Angiomyxoma in the Perineum.

    Science.gov (United States)

    Sood, Neha; Swaika, Abhisek; Hanooshi, Bashar; Waldorf, James; Peterson, Jennifer; Wu, Kevin; Attia, Steven; Dinh, Tri A

    2015-05-05

    Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six) reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

  14. High grade leiomyosarcoma mimicking a recurrent angiomyxoma in the perineum

    Directory of Open Access Journals (Sweden)

    Neha Sood

    2015-05-01

    Full Text Available Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma.

  15. Eosinophilic endomyocardial disease due to high grade chest wall sarcoma.

    Science.gov (United States)

    Hussain, A.; Brown, P. J.; Thwaites, B. C.; Hastings, A. G.

    1994-01-01

    Eosinophilic endomyocardial disease is characterised by persisting blood eosinophilia and acute endocardial lesions which progress to endomyocardial fibrosis. In most cases the cause is unknown but it has been described in association with malignant tumours. A fatal case is presented of a 64 year old woman with this disease due to a high grade sarcoma of the chest wall, an association not previously reported. Images PMID:7974303

  16. Diagnostic value of plasma and urinary 2-hydroxyglutarate to identify patients with isocitrate dehydrogenase-mutated glioma.

    Science.gov (United States)

    Lombardi, Giuseppe; Corona, Giuseppe; Bellu, Luisa; Della Puppa, Alessandro; Pambuku, Ardi; Fiduccia, Pasquale; Bertorelle, Roberta; Gardiman, Marina Paola; D'Avella, Domenico; Toffoli, Giuseppe; Zagonel, Vittorina

    2015-05-01

    Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment. Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients. ©AlphaMed Press.

  17. Mobile phone use and glioma risk: A systematic review and meta-analysis.

    Science.gov (United States)

    Yang, Ming; Guo, WenWen; Yang, ChunSheng; Tang, JianQin; Huang, Qian; Feng, ShouXin; Jiang, AiJun; Xu, XiFeng; Jiang, Guan

    2017-01-01

    Many studies have previously investigated the potential association between mobile phone use and the risk of glioma. However, results from these individual studies are inconclusive and controversial. The objective of our study was to investigate the potential association between mobile phone use and subsequent glioma risk using meta-analysis. We performed a systematic search of the Science Citation Index Embase and PubMed databases for studies reporting relevant data on mobile phone use and glioma in 1980-2016. The data were extracted and measured in terms of the odds ratio (OR) and 95% confidence interval (CI) using the random effects model. Subgroup analyses were also carried out. This meta-analysis eventually included 11 studies comprising a total 6028 cases and 11488 controls. There was a significant positive association between long-term mobile phone use (minimum, 10 years) and glioma (OR = 1.44, 95% CI = 1.08-1.91). And there was a significant positive association between long-term ipsilateral mobile phone use and the risk of glioma (OR = 1.46, 95% CI = 1.12-1.92). Long-term mobile phone use was associated with 2.22 times greater odds of low-grade glioma occurrence (OR = 2.22, 95% CI = 1.69-2.92). Mobile phone use of any duration was not associated with the odds of high-grade glioma (OR = 0.81, 95% CI = 0.72-0.92). Contralateral mobile phone use was not associated with glioma regardless of the duration of use. Similarly, this association was not observed when the analysis was limited to high-grade glioma. Our results suggest that long-term mobile phone use may be associated with an increased risk of glioma. There was also an association between mobile phone use and low-grade glioma in the regular use or long-term use subgroups. However, current evidence is of poor quality and limited quantity. It is therefore necessary to conduct large sample, high quality research or better characterization of any potential association between long-term ipsilateral mobile

  18. Isolation and characterization of bone marrow-derived progenitor cells from malignant gliomas.

    Science.gov (United States)

    Guo, Ke-Tai; Juerchott, Kathrin; Fu, Peng; Selbig, Joachim; Eigenbrod, Sabina; Tonn, Jörg-Christian; Schichor, Christian

    2012-11-01

    Malignant gliomas are highly-vascularised tumours. Neoangiogenesis is a crucial factor in the malignant behaviour of tumour and prognosis of patients. Several mechanisms are suspected to lead to neoangiogenesis, one of them is the recruitment of multipotent progenitor cells towards the tumour. Factors such as Vascular endothelial growth factor-A (VEGF-A) were described to recruit bone marrow-derived endothelial progenitor cells (EPCs) to the glioma stroma and vasculature. Little is known about isolating EPCs from normal or malignant tissues. In this study, we addressed the topic of characterization of tumour-isolated EPCs and re-defined the clonal relationship between EPCs and hematopoietic stem cells (HSCs) in gliomas. We first checked public gene expression data of glioma for putative marker expression, pointing towards a prevalence of EPCs and HSCs in glioma. Immunohistochemical staining of glioma tissue confirmed the higher expression of these progenitor markers in glioma tissue. EPCs and HSCs were consequently isolated and characterized at the phenotypic and functional levels. We applied a new isolation method, for the first time, to specimen from patients with high grade glioma including seven grade IV glioblastoma, five-grade III astrocytoma, and three grade III oligoastrocytoma. In all samples, we were able to isolate the tumour-derived EPCs, which were positive for characteristic markers: CD31, CD34 and VEGFR2. The EPCs formed capillary networks in vitro and had the ability to take up acetylated low-density lipoprotein. Glioma-derived HSCs were positive for CD34 and CD45, but they were unable to form a capillary network in vitro. These findings on tumour-derived EPCs/HSCs were in concordance with the results, derived from peripheral blood of healthy volunteers. In our study, we established a new method for EPC/HSC isolation from human gliomas, defined the contribution of EPCs and HSCs to the tumour tissue, and highlighted the intense in vivo tumour host

  19. Tumor-derived hepatocyte growth factor is associated with poor prognosis of patients with glioma and influences the chemosensitivity of glioma cell line to cisplatin in vitro

    Directory of Open Access Journals (Sweden)

    Guo You-feng

    2012-06-01

    Full Text Available Abstract Background We examined the association of tumor-derived hepatocyte growth factor (HGF with the clinicopathological features of gliomas and investigated the effect of HGF inhibition on the biological behavior of tumor cells in vitro in order to determine whether HGF is a valuable prognostic predictor for glioma patients. Methods Seventy-six cases of glioma were collected. The tumor-derived HGF expression, cell proliferation index (PI and intratumoral microvessels were evaluated by immunohistochemistry. Correlation between immunostaining and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. U87MG glioma cells were transfected with short interference (si-RNA for HGF, and the cell viability, migratory ability and chemosensitivity to cisplatin were evaluated in vitro. Results Both high HGF expression in tumor cells (59.2%, 45/76 and high PI were significantly associated with high-grade glioma and increased microvessels in tumors (P P = 0.004 and high-expression of HGF (P = 0.008 emerged as independent prognostic factors for the overall survival of glioma patients. The tumor-derived HGF mRNA and protein expressions were significantly decreased in vitro after transfection of HGF siRNA. HGF siRNA inhibited the cell growth and reduced cell migratory ability. Moreover, HGF siRNA transfection enhanced the chemosensitivity of U87MG glioma cells to cisplatin. Conclusion This study indicated that there was significant correlation among tumor cell-derived HGF, cell proliferation and microvessel proliferation in gliomas. HGF might influence tumor progression by modulating the cell growth, migration and chemoresistance to drugs. Increased expression of HGF may be a valuable predictor for prognostic evaluation of glioma patients.

  20. Successful Nonoperative Management of High-Grade Blunt Renal Injuries.

    Science.gov (United States)

    May, Allison M; Darwish, Oussama; Dang, Brian; Monda, John J; Adsul, Prajakta; Syed, Johar; Siddiqui, Sameer A

    2016-01-01

    Current management of high-grade blunt renal trauma favors a nonoperative approach when possible. We performed a retrospective study of high grade blunt renal injuries at our level I trauma center to determine the indications and success of nonoperative management (NOM). 47 patients with blunt grade IV or V injuries were identified between October 2004 and December 2013. Immediate operative patients (IO) were compared to nonoperatively managed (NOM). Of the 47 patients, 3 (6.4%) were IO and 44 (95.6%) NOM. IO patients had a higher heart rate on admission, 133 versus 100 in NOM ( P = 0.01). IO patients had a higher rate of injury to the renal vein or artery (100%) compared to NOM group (18%) ( P = 0.01). NOM failed in 3 of 44 patients (6.8%). Two required nonemergent nephrectomy and one required emergent exploration resulting in nephrectomy. Six NOM patients had kidney-related complications (13.6%). The renal salvage rate for the entire cohort was 87.2% and 93.2% for NOM. Nonoperative management for hemodynamically stable patients with high-grade blunt renal trauma is safe with a low risk of complications. Management decisions should consider hemodynamic status and visualization of active renal bleeding as well as injury grade in determining operative management.

  1. Corpus callosum involvement and postoperative outcomes of patients with gliomas.

    Science.gov (United States)

    Chen, Ko-Ting; Wu, Tai-Wei Erich; Chuang, Chi-Cheng; Hsu, Yung-Hsin; Hsu, Peng-Wei; Huang, Yin-Cheng; Lin, Tzu-Kang; Chang, Chen-Nen; Lee, Shih-Tseng; Wu, Chieh-Tsai; Tseng, Chen-Kan; Wang, Chun-Chieh; Pai, Ping-Ching; Wei, Kuo-Chen; Chen, Pin-Yuan

    2015-09-01

    Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.

  2. Inflammatory demyelinating pseudotumor with hemorrhage masquerading high grade cerebral neoplasm

    Directory of Open Access Journals (Sweden)

    Amit Agrawal

    2015-03-01

    Full Text Available Demyelinating pseudotumors are rare, benign, solitary intracranial space occupying lesions which masquerade cerebral neoplasms. Contrast MRI shows open ring enhancement which is fairly specific for this entity. Advanced MRI techniques like MR spectroscopy and magnetizing transfer techniques can help differentiating these lesions. NAA/Cr ratio is significantly elevated in central regions of demyelinating pseudotumors than in gliomas and other lesions. Presence of abundant foamy macrophages, lymphoid inflammatory infiltrates around blood vessels, sheets of gemistocytic astrocytes with well-developed processes, well defined border of the lesion absence of neovascularity and necrosis should help us diagnose demyelinating pseudotumor fairly confidently on histopathology.

  3. Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy

    Directory of Open Access Journals (Sweden)

    Gregory K Friedman

    2013-02-01

    Full Text Available While glioblastoma multiforme (GBM is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed ‘glioma stem cells’ (GSCs, ‘glioma progenitor cells’, or ‘glioma-initiating cells', which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGGs must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses, genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oncolytic herpes simplex virus (HSV.

  4. Diffuse intrinsic pontine glioma: poised for progress

    International Nuclear Information System (INIS)

    Warren, Katherine E.

    2012-01-01

    Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy. Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success. The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity. Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies.

  5. Midwest Joint Venture high-grade uranium mining

    International Nuclear Information System (INIS)

    Fredrickson, H.K.

    1992-01-01

    Midwest Joint Venture (MJV) owns a high-grade uranium deposit in northern Saskatchewan. The deposit is located too deep below surface to be mined economically by open pit methods, and as a consequence, present plans are that it will be mined by underground methods. High-grade uranium ore of the type at MJV, encased in weak, highly altered ground and with radon-rich water inflows, has not before been mined by underground methods. The test mining phase of the project, completed in 1989, had three objectives: To evaluate radiation protection requirements associated with the handling of large quantities of radon-rich water and mining high-grade uranium ore in an underground environment; to investigate the quantity and quality of water inflows into the mine; and, to investigate ground conditions in and around the ore zone as an aid in determining the production mining method to be used. With information gained from the test mining project, a mining method for the production mine has been devised. Level plans have been drawn up, ventilation system designed, pumping arrangements made and methods of ore handling considered. All this is to be done in a manner that will be safe for those doing the work underground. Some of the mining methods planned are felt to be unique in that they are designed to cope with mining problems not known to have been encountered before. New problems underground have required new methods to handle them. Remote drilling, blasting, mucking and backfilling form the basis of the planned mining method

  6. Molecular Neuropathology of Gliomas

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    Guido Reifenberger

    2009-01-01

    Full Text Available Gliomas are the most common primary human brain tumors. They comprise a heterogeneous group of benign and malignant neoplasms that are histologically classified according to the World Health Organization (WHO classification of tumors of the nervous system. Over the past 20 years the cytogenetic and molecular genetic alterations associated with glioma formation and progression have been intensely studied and genetic profiles as additional aids to the definition of brain tumors have been incorporated in the WHO classification. In fact, first steps have been undertaken in supplementing classical histopathological diagnosis by the use of molecular tests, such as MGMT promoter hypermethylation in glioblastomas or detection of losses of chromosome arms 1p and 19q in oligodendroglial tumors. The tremendous progress that has been made in the use of array-based profiling techniques will likely contribute to a further molecular refinement of glioma classification and lead to the identification of glioma core pathways that can be specifically targeted by more individualized glioma therapies.

  7. DDX3X Biomarker Correlates with Poor Survival in Human Gliomas

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    Dueng-Yuan Hueng

    2015-07-01

    Full Text Available Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp box helicase 3, X-linked (DDX3X controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81 than in non-tumor controls (n = 23, p = 1.13 × 10−10. Moreover, DDX3X level was also higher in WHO grade III (n = 19 than in non-tumor controls (p = 2.43 × 10−5. Kaplan–Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24 than in those with low DDX3X expression (n = 53 (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893–0.6496. Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.

  8. Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas.

    Science.gov (United States)

    Wakimoto, Hiroaki; Tanaka, Shota; Curry, William T; Loebel, Franziska; Zhao, Dan; Tateishi, Kensuke; Chen, Juxiang; Klofas, Lindsay K; Lelic, Nina; Kim, James C; Dias-Santagata, Dora; Ellisen, Leif W; Borger, Darrell R; Fendt, Sarah-Maria; Vander Heiden, Matthew G; Batchelor, Tracy T; Iafrate, A John; Cahill, Daniel P; Chi, Andrew S

    2014-06-01

    Isocitrate dehydrogenase (IDH) gene mutations occur in low-grade and high-grade gliomas. We sought to identify the genetic basis of malignant phenotype heterogeneity in IDH-mutant gliomas. We prospectively implanted tumor specimens from 20 consecutive IDH1-mutant glioma resections into mouse brains and genotyped all resection specimens using a CLIA-certified molecular panel. Gliomas with cancer driver mutations were tested for sensitivity to targeted inhibitors in vitro. Associations between genomic alterations and outcomes were analyzed in patients. By 10 months, 8 of 20 IDH1-mutant gliomas developed intracerebral xenografts. All xenografts maintained mutant IDH1 and high levels of 2-hydroxyglutarate on serial transplantation. All xenograft-producing gliomas harbored "lineage-defining" mutations in CIC (oligodendroglioma) or TP53 (astrocytoma), and 6 of 8 additionally had activating mutations in PIK3CA or amplification of PDGFRA, MET, or N-MYC. Only IDH1 and CIC/TP53 mutations were detected in non-xenograft-forming gliomas (P = 0.0007). Targeted inhibition of the additional alterations decreased proliferation in vitro. Moreover, we detected alterations in known cancer driver genes in 13.4% of IDH-mutant glioma patients, including PIK3CA, KRAS, AKT, or PTEN mutation or PDGFRA, MET, or N-MYC amplification. IDH/CIC mutant tumors were associated with PIK3CA/KRAS mutations whereas IDH/TP53 tumors correlated with PDGFRA/MET amplification. Presence of driver alterations at progression was associated with shorter subsequent progression-free survival (median 9.0 vs. 36.1 months; P = 0.0011). A subset of IDH-mutant gliomas with mutations in driver oncogenes has a more malignant phenotype in patients. Identification of these alterations may provide an opportunity for use of targeted therapies in these patients. Clin Cancer Res; 20(11); 2898-909. ©2014 AACR. ©2014 American Association for Cancer Research.

  9. Biomechanics of high-grade spondylolisthesis with and without reduction.

    Science.gov (United States)

    Wang, Wenhai; Aubin, Carl-Eric; Cahill, Patrick; Baran, George; Arnoux, Pierre-Jean; Parent, Stefan; Labelle, Hubert

    2016-04-01

    The clinical advantages of reducing spondylolisthesis over fusion in situ have several intuitive reasons such as restore the spinal column into a more anatomic relationship and alignment. However, there is only little evidence in the literature supporting the theoretical advantages of reduction, and its effect on spinopelvic alignment remains poorly defined. In this study, a comprehensive finite element model was developed to analyze the biomechanics of the spine after spinal fusion at L5-S1 in both types of high-grade spondylolisthesis (balanced and unbalanced pelvis). The relevant clinical indices (i.e. spondylolisthesis grade and Dubousset lumbosacral angle), the displacement of L4-L5, pressure within the annulus and nucleus, and stress at L4-L5 were evaluated and compared. The model can well predict the changes of the important clinical indices during the surgery. For a balanced pelvis, the reduction has a minimal effect on the biomechanical conditions at the adjacent level during postsurgical activities. In the unbalanced case, reduction induced larger deformation in the lumbosacral region and a higher stress concentration at adjacent level. Whether such a stress concentration can lead to long-term disc degeneration is not known. The results provide additional information for the clinician considering reduction of high-grade spondylolisthesis.

  10. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogeno...... of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  11. Angiogenesis in gliomas.

    Directory of Open Access Journals (Sweden)

    Elzbieta Czykier

    2008-02-01

    Full Text Available Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP and microvessel density (MVD. Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO. Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO. The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.

  12. {sup 18}F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by {sup 18}F-FDOPA PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam; Singh, Harmandeep; Sharma, Punit; Gupta, Deepak Kumar; Bal, Chandrasekhar [All India Institute of Medical Sciences, New Delhi (India)

    2013-12-15

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. {sup 18}F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-{sup 18}F-fluoro-L-phenylalanine ({sup 18}F-FDOPA) PET-CT was done, 5 days after {sup 18}F-FDG PET-CT. The study revealed an {sup 18}F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. {sup 18}F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. {sup 18}F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake

  13. Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas

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    Matsutani Tomoo

    2012-10-01

    Full Text Available Abstract Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. Methods In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines. Results We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1 was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. Conclusion SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.

  14. Migration capacity of human umbilical cord mesenchymal stem cells towards glioma in vivo

    Science.gov (United States)

    Fan, Cungang; Wang, Dongliang; Zhang, Qingjun; Zhou, Jingru

    2013-01-01

    High-grade glioma is the most common malignant primary brain tumor in adults. The poor prognosis of glioma, combined with a resistance to currently available treatments, necessitates the ment of more effective tumor-selective therapies. Stem cell-based therapies are emerging as novel cell-based delivery vehicle for therapeutic agents. In the present study, we successfully isolated human umbilical cord mesenchymal stem cells by explant culture. The human umbilical cord senchymal stem cells were adherent to plastic surfaces, expressed specific surface phenotypes of mesenchymal stem cells as demonstrated by flow cytometry, and possessed multi-differentiation potentials in permissive induction media in vitro. Furthermore, human umbilical cord mesenchymal stem cells demonstrated excellent glioma-specific targeting capacity in established rat glioma models after intratumoral injection or contralateral ventricular administration in vivo. The excellent glioma-specific targeting ability and extensive intratumoral distribution of human umbilical cord mesenchymal stem cells indicate that they may serve as a novel cellular vehicle for delivering therapeutic molecules in glioma therapy. PMID:25206518

  15. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma

    Science.gov (United States)

    Ceccarelli, Michele; Barthel, Floris P.; Malta, Tathiane M.; Sabedot, Thais S.; Salama, Sofie R.; Murray, Bradley A.; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M.; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyung; Rao, Arjun A.; Grifford, Mia; Cherniack, Andrew D.; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Pretti da Cunha Tirapelli, Daniela; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C.; Yung, W.K. Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J.; Lehman, Norman L.; Barnholtz-Sloan, Jill S.; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D.; Laird, Peter W.; Gutmann, David H.; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G.W.

    2015-01-01

    SUMMARY Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH-mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wildtype diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID:26824661

  16. MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR

    Science.gov (United States)

    2012-01-01

    Background Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. Method We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. Results When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. Conclusion In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method. PMID:22390413

  17. MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR

    Directory of Open Access Journals (Sweden)

    Håvik Annette

    2012-03-01

    Full Text Available Abstract Background Methylation of the O6-methylguanine-DNA methyltransferase (MGMT gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. Method We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. Results When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06. One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. Conclusion In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.

  18. Comparison of Different Post-Processing Algorithms for Dynamic Susceptibility Contrast Perfusion Imaging of Cerebral Gliomas.

    Science.gov (United States)

    Kudo, Kohsuke; Uwano, Ikuko; Hirai, Toshinori; Murakami, Ryuji; Nakamura, Hideo; Fujima, Noriyuki; Yamashita, Fumio; Goodwin, Jonathan; Higuchi, Satomi; Sasaki, Makoto

    2017-04-10

    The purpose of the present study was to compare different software algorithms for processing DSC perfusion images of cerebral tumors with respect to i) the relative CBV (rCBV) calculated, ii) the cutoff value for discriminating low- and high-grade gliomas, and iii) the diagnostic performance for differentiating these tumors. Following approval of institutional review board, informed consent was obtained from all patients. Thirty-five patients with primary glioma (grade II, 9; grade III, 8; and grade IV, 18 patients) were included. DSC perfusion imaging was performed with 3-Tesla MRI scanner. CBV maps were generated by using 11 different algorithms of four commercially available software and one academic program. rCBV of each tumor compared to normal white matter was calculated by ROI measurements. Differences in rCBV value were compared between algorithms for each tumor grade. Receiver operator characteristics analysis was conducted for the evaluation of diagnostic performance of different algorithms for differentiating between different grades. Several algorithms showed significant differences in rCBV, especially for grade IV tumors. When differentiating between low- (II) and high-grade (III/IV) tumors, the area under the ROC curve (Az) was similar (range 0.85-0.87), and there were no significant differences in Az between any pair of algorithms. In contrast, the optimal cutoff values varied between algorithms (range 4.18-6.53). rCBV values of tumor and cutoff values for discriminating low- and high-grade gliomas differed between software packages, suggesting that optimal software-specific cutoff values should be used for diagnosis of high-grade gliomas.

  19. PAI-1 and EGFR expression in adult glioma tumors: toward a molecular prognostic classification

    International Nuclear Information System (INIS)

    Muracciole, Xavier; Romain, Sylvie; Dufour, Henri; Palmari, Jacqueline; Chinot, Olivier; Ouafik, L'Houcine; Grisoli, Francois; Figarella-Branger, Dominique; Martin, Pierre-Marie

    2002-01-01

    Purpose: Molecular classification of gliomas is a major challenge in the effort to improve therapeutic decisions. The plasminogen activator system, including plasminogen activator inhibitor type 1 (PAI-1), plays a key role in tumor invasion and neoangiogenesis. Epidermal growth factor receptor (EGFR) is involved in the control of proliferation. The contribution of PAI-1 and EGFR to the survival of gliomas was retrospectively investigated. Methods and Materials: Fifty-nine adult gliomas treated by neurosurgery and conventional irradiation were analyzed, including 9 low-grade (2) and 50 high-grade (3-4) tumors (WHO classification). PAI-1 was measured on cytosols and EGFR on solubilized membranes using ELISA methods. Results: High PAI-1 levels were strongly associated with high histologic grade (p<0.001) and histologic necrosis (p<0.001). PAI-1 also correlated positively with patient age (p=0.05) and negatively with Karnofsky index (p=0.01). By univariate analysis of the high-grade population, higher PAI-1 (p<0.0001) and EGFR values (p=0.02) were associated with shorter overall survival. Only PAI-1 was an independent factor in multivariate analysis. Grade 3 tumors with low PAI-1 (100% 3-year overall survival rate) presented the same clinical outcome as the low-grade tumors. Conclusions: In this prognostic study, PAI-1 and EGFR expression revealed similarities and differences between high-grade gliomas that were not apparent by traditional clinical criteria. These data strongly support that biologic factors should be included in glioma classification and the design of clinical trials to treat more homogeneous populations

  20. High grade serous ovarian carcinomas originate in the fallopian tube.

    Science.gov (United States)

    Labidi-Galy, S Intidhar; Papp, Eniko; Hallberg, Dorothy; Niknafs, Noushin; Adleff, Vilmos; Noe, Michael; Bhattacharya, Rohit; Novak, Marian; Jones, Siân; Phallen, Jillian; Hruban, Carolyn A; Hirsch, Michelle S; Lin, Douglas I; Schwartz, Lauren; Maire, Cecile L; Tille, Jean-Christophe; Bowden, Michaela; Ayhan, Ayse; Wood, Laura D; Scharpf, Robert B; Kurman, Robert; Wang, Tian-Li; Shih, Ie-Ming; Karchin, Rachel; Drapkin, Ronny; Velculescu, Victor E

    2017-10-23

    High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease.

  1. Heap leaching process of high-grade uranium ore

    International Nuclear Information System (INIS)

    Lin Sirong; Gao Xizheng; Guo Erhua; Lu Shijie

    1994-08-01

    A heap leaching process for high-grade primary uranium ore has been studied. The minerals mainly are uraninite. In the process the manganese dioxide is used as oxidant and ferric sulphate solution as leaching agent. The two-stage counter current heap leach method is used in the process. The leached liquor which contains dissolved uranium and iron returns to the neutralizing stage and the iron in the leached liquor is precipitated in the stage. The acid is added to the main stage and the precipitated iron is dissolved as Fe 2 (SO 4 ) 3 in the stage. Comparing with conventional agitation acid leaching method, this process decreases the consumption of acid by 21% and manganese dioxide by 29%. The extraction rate of uranium reduces 1.86%. (3 figs., 12 tabs.)

  2. Transition of endometrial stromal sarcoma into high-grade sarcoma.

    Science.gov (United States)

    Amant, Frederic; Woestenborghs, Heidi; Vandenbroucke, Vanessa; Berteloot, Patrick; Neven, Patrick; Moerman, Philippe; Vergote, Ignace

    2006-12-01

    Endometrial stromal sarcoma typically is of low grade and hormone-sensitive. Although these characteristics result in an indolent behavior, little data are available on the evolution over time. We report on two cases where microscopic and immunohistochemic assessment of the tumor on several occasions during 8 and 25 years of follow up enabled us to document a transition of a low-grade into a high-grade malignancy. These were mainly characterized by increased cellular atypia, absence of spiral arterioles and an increased mitotic index and proliferation index (MIB1). Since this transition was related to clinical loss of hormone sensitivity, the therapeutic approach consisting of hormonal treatment in combination with repetitive surgery was switched to chemotherapy only. These long-term follow up data provide insight in endometrial stromal sarcoma tumor biology and highlight the importance of sampling recurrent tumors to estimate biologic behavior in order to tailor subsequent treatment.

  3. High Grade Infective Spondylolisthesis of Cervical Spine Secondary to Tuberculosis.

    Science.gov (United States)

    Hadgaonkar, Shailesh; Shah, Kunal; Shyam, Ashok; Sancheti, Parag

    2015-12-01

    Spondylolisthesis coexisting with tuberculosis is rarely reported. There is a controversy whether spondylolisthesis coexists or precedes tuberculosis. Few cases of pathological spondylolisthesis secondary to tuberculous spondylodiscitis have been reported in the lumbar and lumbosacral spine. All cases in the literature presented as anterolisthesis, except one which presented as posterolisthesis of lumbar spine. Spondylolisthesis in the cervical spine is mainly degenerative and traumatic. Spondylolisthesis due to tuberculosis is not reported in the lower cervical spine. The exact mechanism of such an occurrence of spondylolisthesis with tuberculosis is sparsely reported in the literature and inadequately understood. We report a rare case of high grade pathological posterolisthesis of the lower cervical spine due to tubercular spondylodiscitis in a 67-year-old woman managed surgically with a three-year follow-up period. This case highlights the varied and complex presentation of tuberculosis of the lower cervical spine and gives insight into its pathogenesis, diagnosis, and management.

  4. Alkali control of high-grade metamorphism and granitization

    Directory of Open Access Journals (Sweden)

    Oleg G. Safonov

    2014-09-01

    Full Text Available We review petrologic observations of reaction textures from high-grade rocks that suggest the passage of fluids with variable alkali activities. Development of these reaction textures is accompanied by regular compositional variations in plagioclase, pyroxenes, biotite, amphibole and garnet. The textures are interpreted in terms of exchange and net-transfer reactions controlled by the K and Na activities in the fluids. On the regional scale, these reactions operate in granitized, charnockitized, syenitized etc. shear zones within high-grade complexes. Thermodynamic calculations in simple chemical systems show that changes in mineral assemblages, including the transition from the hydrous to the anhydrous ones, may occur at constant pressure and temperature due only to variations in the H2O and the alkali activities. A simple procedure for estimating the activity of the two major alkali oxides, K2O and Na2O, is implemented in the TWQ software. Examples of calculations are presented for well-documented dehydration zones from South Africa, southern India, and Sri Lanka. The calculations have revealed two end-member regimes of alkalis during specific metamorphic processes: rock buffered, which is characteristic for the precursor rocks containing two feldspars, and fluid-buffered for the precursor rocks without K-feldspar. The observed reaction textures and the results of thermodynamic modeling are compared with the results of available experimental studies on the interaction of the alkali chloride and carbonate-bearing fluids with metamorphic rocks at mid-crustal conditions. The experiments show the complex effect of alkali activities in the fluid phase on the mineral assemblages. Both thermodynamic calculations and experiments closely reproduce paragenetic relations theoretically predicted by D.S. Korzhinskii in the 1940s.

  5. Epidemiology of glioma

    DEFF Research Database (Denmark)

    Rasmussen, Birthe Krogh; Hansen, Steinbjorn; Laursen, Rene J.

    2017-01-01

    predominated in all grades. Focal deficits were the most frequent presenting symptom, but among patients with glioma, grade II epileptic seizures were the most frequent symptom. Headache was a rare mono-symptomatic onset symptom. At presentation, higher age, focal deficits and cognitive change for ... duration, and headache

  6. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227 ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  7. Metabolic Reprogramming in Glioma

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Stoll

    2017-04-01

    Full Text Available Many cancers have long been thought to primarily metabolize glucose for energy production—a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor. Multiple catabolic pathways are used for energy production within glioma cells, and are linked in many ways to anabolic pathways supporting cellular function. For example: glycolysis both supports energy production and provides carbon skeletons for the synthesis of nucleic acids; meanwhile fatty acids are used both as energetic substrates and as raw materials for lipid membranes. Furthermore, bio-energetic pathways are connected to pro-oncogenic signaling within glioma cells. For example: AMPK signaling links catabolism with cell cycle progression; mTOR signaling contributes to metabolic flexibility and cancer cell survival; the electron transport chain produces ATP and reactive oxygen species (ROS which act as signaling molecules; Hypoxia Inducible Factors (HIFs mediate interactions with cells and vasculature within the tumor environment. Mutations in the tumor suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase 1 and 2 have been implicated in oncogenic signaling as well as establishing metabolic phenotypes in genetically-defined subsets of malignant glioma. These pathways critically contribute to tumor biology. The aim of this review is two-fold. Firstly, we present the current state of knowledge regarding the metabolic strategies employed by malignant glioma cells, including aerobic glycolysis; the pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle, which is

  8. Metabolic Reprogramming in Glioma.

    Science.gov (United States)

    Strickland, Marie; Stoll, Elizabeth A

    2017-01-01

    Many cancers have long been thought to primarily metabolize glucose for energy production-a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor. Multiple catabolic pathways are used for energy production within glioma cells, and are linked in many ways to anabolic pathways supporting cellular function. For example: glycolysis both supports energy production and provides carbon skeletons for the synthesis of nucleic acids; meanwhile fatty acids are used both as energetic substrates and as raw materials for lipid membranes. Furthermore, bio-energetic pathways are connected to pro-oncogenic signaling within glioma cells. For example: AMPK signaling links catabolism with cell cycle progression; mTOR signaling contributes to metabolic flexibility and cancer cell survival; the electron transport chain produces ATP and reactive oxygen species (ROS) which act as signaling molecules; Hypoxia Inducible Factors (HIFs) mediate interactions with cells and vasculature within the tumor environment. Mutations in the tumor suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase 1 and 2 have been implicated in oncogenic signaling as well as establishing metabolic phenotypes in genetically-defined subsets of malignant glioma. These pathways critically contribute to tumor biology. The aim of this review is two-fold. Firstly, we present the current state of knowledge regarding the metabolic strategies employed by malignant glioma cells, including aerobic glycolysis; the pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle, which is central to amino acid

  9. Re-evaluating TTF-1 immunohistochemistry in diffuse gliomas: Expression is clone-dependent and associated with tumor location.

    Science.gov (United States)

    Pratt, Drew; Afsar, Nina; Allgauer, Michael; Fetsch, Patricia; Palisoc, Maryknoll; Pittaluga, Stefania; Quezado, Martha

    TTF-1 is widely used as a marker in routine surgical pathology in the work-up of malignancy. Aberrant expression of TTF-1 in extrapulmonary and extrathyroidal malignancies is a frequently reported phenomenon. In addition to the recently characterized pituicyte-derived tumors of the sella, immunoreactivity has been reported in diffuse gliomas with the SPT24 clone. Here, we sought to evaluate TTF-1 expression with three commercially available clones in a large series of gliomas. Expression was compared across the newly defined diagnostic entities in the 2016 WHO Classification of CNS Tumors. Using tissue microarrays (TMA), 212 diffuse gliomas (WHO grades II - IV) were systematically evaluated with TTF-1 immunohistochemistry using three clones: SPT24, 8G7G3/1, and SP141, and results correlated with clinicopathologic features. 14 high-grade diffuse gliomas demonstrated nuclear staining with the SP141 and SPT24 clones. Two tumors showed weak positivity with the 8G7G3/1 clone. All tumors were high grade by histology (WHO grades III and IV). 86% (12/14) of TTF-1-positive gliomas involved the frontal lobes at diagnosis. No relationship with IDH R132H, ATRX, p53, H3K27M, or EGFR immunohistochemistry was identified. TTF-1 expression in gliomas was not independently prognostic of overall survival. TTF-1 expression in diffuse gliomas is a rare but potentially misleading occurrence. In our cohort, staining occurred with both the SPT24 and SP141 clones at equal intensity and frequency. Clustering of TTF-1-positive tumors in the frontal lobe(s) suggests lineage-specific expression. Due to clone-specific expression in diffuse gliomas, caution must be exercised in the work-up of intracranial tumors with TTF-1.
.

  10. Signal intensity in T2' magnetic resonance imaging is related to brain glioma grade

    Energy Technology Data Exchange (ETDEWEB)

    Saitta, Laura; Castellan, Lucio [San Martino Hospital, Department of Diagnostic and Interventional Neuroradiology, Genoa (Italy); Heese, Oliver; Westphal, Manfred [UKE, Department of Neurosurgery, Hamburg (Germany); Foerster, Ann-Freya; Siemonsen, Susanne; Fiehler, Jens; Goebell, Einar [University Medical Center Hamburg-Eppendorf (UKE), Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); Matschke, Jakob [UKE, Department of Neuropathology, Hamburg (Germany)

    2011-05-15

    T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas. MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis. Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p < 0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875). High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism. (orig.)

  11. Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma

    Directory of Open Access Journals (Sweden)

    Fujita Mitsugu

    2007-12-01

    Full Text Available Abstract Background In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs. In this report, we characterized GAA-specific CD8+ T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA for over 12 years without recurrence. Methods Peripheral blood mononuclear cells (PBMCs derived from the long term survivor with AA were evaluated for the frequency, cytotoxic T lymphocyte (CTL activity and differentiation status of CD8+ cells recognizing GAA-derived epitopes as well as relative numbers of other immune cell subsets. This patient's AA tissue was evaluated for expression of two GAAs EphA2 and interleukin-13 receptor α2 subunit (IL-13Rα2 by immunohistochemistry. Results The patient's tumor expressed both EphA2 and IL-13Rα2, and in vitro stimulated PBMC demonstrated superior EphA2883–891 and IL-13Rα2345–353-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2883–891-reactive CD8+ T cells contained high numbers of CD45RA-/CCR7- late effector and CD45RA-/CCR7+ central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found. Conclusion To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8+ T cells in a patient who has survived with AA for over 12 years without recurrence. Further studies are warranted to determine whether the status of GAA-reactive CD8+ T cells dictates survival of patients and/or response to therapeutic vaccines.

  12. Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

    Directory of Open Access Journals (Sweden)

    Silke Wemmert

    2005-10-01

    Full Text Available Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group and 30 patients received radiotherapy alone (RT group. The most common aberrations detected were gains of parts of chromosome 7 and losses of 10% 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months. Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.

  13. Controlled rehabilitative and supportive care intervention trials in patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Juhler, M; Jakobsen, J

    2016-01-01

    and Embase were searched for literature published from 1995 to May 2013. Data from eight studies were reviewed for substantive methods and results. Methodological quality was described and assessed using the scoring system for appraising mixed methods research and concomitantly appraising qualitative...... training improves functional outcome and massage therapy reduces stress. Patients and caregivers found that telephone follow-up and a specialist nurse function was an effective and useful way to achieve information and support. Finally, psycho-education increased feelings of mastery among caregivers...

  14. Volumetric index of Tl-201 uptake in symptomatic patients after high - dose radiation treatment for high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, P.A.; Garada, B.M.; Loeffler, J.S. [Brigham and Womens Hospital, Boston, MA (United States)]|[Harvard Medical School, Boston, MA (United States)] [and others

    1995-05-01

    To verify the utility of a volumetric estimation of Tl-201 uptake in the context of possible astrocytoma recurrence after surgery, radiotherapy plus stereotactic boost (radiosurgery/brachitherapy), we analyzed sequential Tl-201/Tc99m-HMPAO brain SPECT studies of 28 patients (18 m/10 f). These were categorized as having tumor mass recurrence (TM), infiltrating tumor cells but no definite tumor mass (IT), or radiation changes and necrosis (RCN) after stereotactic biopsy and/or craniotomy. SPECT studies were obtained with a high-resolution dedicated gamma camera (CERASPECT, Digital Scinitgraphics, Inc.) and image acquisition was performed after intravenous Tl-201 (18.5 MBq) and Tc-99m HMPAO (740 MBq). In order to include relevant information about tumor burden, a volumetric index of Tl-201 uptake was expressed in cm{sup 3} related to voxel size (4.6 x 10{sup -3} cc) within an elliptical ROI that included the tumor area. Only voxels with a threshold {ge} 2 in relation to the average scalp Tl-201 uptake were included and this total number of voxels expressed in cc was compared to previously established maximal tumor/scalp Tl-201 uptake ratios (T/S) and histopathology. Results are presented as the median (min-max) and differences were considered significant for p<0.05. Differences were significant between all groups for both ratios and volume indices and correlation between the two variables was 0.90. In conclusion, the volumetric index of Tl-201 is similar to the maximal Tl-201 T/S ratios in discriminating tumor recurrence and radiation necrosis, suggesting a future role for the volumetric index estimation in the evaluation of treatment efficacy and patient follow-up.

  15. Fractal analysis: fractal dimension and lacunarity from MR images for differentiating the grades of glioma

    International Nuclear Information System (INIS)

    Smitha, K A; Gupta, A K; Jayasree, R S

    2015-01-01

    Glioma, the heterogeneous tumors originating from glial cells, generally exhibit varied grades and are difficult to differentiate using conventional MR imaging techniques. When this differentiation is crucial in the disease prognosis and treatment, even the advanced MR imaging techniques fail to provide a higher discriminative power for the differentiation of malignant tumor from benign ones. A powerful image processing technique applied to the imaging techniques is expected to provide a better differentiation. The present study focuses on the fractal analysis of fluid attenuation inversion recovery MR images, for the differentiation of glioma. For this, we have considered the most important parameters of fractal analysis, fractal dimension and lacunarity. While fractal analysis assesses the malignancy and complexity of a fractal object, lacunarity gives an indication on the empty space and the degree of inhomogeneity in the fractal objects. Box counting method with the preprocessing steps namely binarization, dilation and outlining was used to obtain the fractal dimension and lacunarity in glioma. Statistical analysis such as one-way analysis of variance and receiver operating characteristic (ROC) curve analysis helped to compare the mean and to find discriminative sensitivity of the results. It was found that the lacunarity of low and high grade gliomas vary significantly. ROC curve analysis between low and high grade glioma for fractal dimension and lacunarity yielded 70.3% sensitivity and 66.7% specificity and 70.3% sensitivity and 88.9% specificity, respectively. The study observes that fractal dimension and lacunarity increases with an increase in the grade of glioma and lacunarity is helpful in identifying most malignant grades. (paper)

  16. Fractal analysis: fractal dimension and lacunarity from MR images for differentiating the grades of glioma.

    Science.gov (United States)

    Smitha, K A; Gupta, A K; Jayasree, R S

    2015-09-07

    Glioma, the heterogeneous tumors originating from glial cells, generally exhibit varied grades and are difficult to differentiate using conventional MR imaging techniques. When this differentiation is crucial in the disease prognosis and treatment, even the advanced MR imaging techniques fail to provide a higher discriminative power for the differentiation of malignant tumor from benign ones. A powerful image processing technique applied to the imaging techniques is expected to provide a better differentiation. The present study focuses on the fractal analysis of fluid attenuation inversion recovery MR images, for the differentiation of glioma. For this, we have considered the most important parameters of fractal analysis, fractal dimension and lacunarity. While fractal analysis assesses the malignancy and complexity of a fractal object, lacunarity gives an indication on the empty space and the degree of inhomogeneity in the fractal objects. Box counting method with the preprocessing steps namely binarization, dilation and outlining was used to obtain the fractal dimension and lacunarity in glioma. Statistical analysis such as one-way analysis of variance and receiver operating characteristic (ROC) curve analysis helped to compare the mean and to find discriminative sensitivity of the results. It was found that the lacunarity of low and high grade gliomas vary significantly. ROC curve analysis between low and high grade glioma for fractal dimension and lacunarity yielded 70.3% sensitivity and 66.7% specificity and 70.3% sensitivity and 88.9% specificity, respectively. The study observes that fractal dimension and lacunarity increases with an increase in the grade of glioma and lacunarity is helpful in identifying most malignant grades.

  17. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    Science.gov (United States)

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  18. Molecular Imaging of Gliomas

    Directory of Open Access Journals (Sweden)

    A. H. Jacobs

    2002-10-01

    Full Text Available Gliomas are the most common types of brain tumors. Although sophisticated regimens of conventional therapies are being carried out to treat patients with gliomas, the disease invariably leads to death over months or years. Before new and potentially more effective treatment strategies, such as gene- and cell-based therapies, can be effectively implemented in the clinical application, certain prerequisites have to be established. First of all, the exact localization, extent, and metabolic activity of the glioma must be determined to identify the biologically active target tissue for a biological treatment regimen; this is usually performed by imaging the expression of up-regulated endogenous genes coding for glucose or amino acid transporters and cellular hexokinase and thymidine kinase genes, respectively. Second, neuronal function and functional changes within the surrounding brain tissue have to be assessed in order to save this tissue from therapy-induced damage. Third, pathognomonic genetic changes leading to disease have to be explored on the molecular level to serve as specific targets for patient-tailored therapies. Last, a concerted noninvasive analysis of both endogenous and exogenous gene expression in animal models as well as the clinical setting is desirable to effectively translate new treatment strategies from experimental into clinical application. All of these issues can be addressed by multimodal radionuclide and magnetic resonance imaging techniques and fall into the exciting and fast growing field of molecular and functional imaging. Noninvasive imaging of endogenous gene expression by means of positron emission tomography (PET may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging may reveal the assessment of the “location,” “magnitude,” and

  19. Model-based, semiquantitative and time intensity curve shape analysis of dynamic contrast-enhanced MRI: a comparison in patients undergoing antiangiogenic treatment for recurrent glioma

    NARCIS (Netherlands)

    Lavini, Cristina; Verhoeff, Joost J. C.; Majoie, Charles B.; Stalpers, Lukas J. A.; Richel, Dick J.; Maas, Mario

    2011-01-01

    To compare time intensity curve (TIC)-shape analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data with model-based analysis and semiquantitative analysis in patients with high-grade glioma treated with the antiangiogenic drug bevacizumab. Fifteen patients had a pretreatment

  20. Photon and proton therapy planning comparison for malignant glioma based on CT, FDG-PET, DTI-MRI and fiber tracking

    DEFF Research Database (Denmark)

    Munck af Rosenschöld, Per; Engelholm, Silke; Ohlhues, Lars

    2011-01-01

    The purpose of this study was to compare treatment plans generated using fixed beam Intensity Modulated photon Radiation Therapy (IMRT), inversely optimized arc therapy (RapidArc(R), RA) with spot-scanned Intensity Modulated Proton Therapy (IMPT) for high-grade glioma patients. Plans were compared...

  1. Evaluation of single-photon emission tomography imaging of supratentorial brain gliomas with technetium-99m sestamibi

    International Nuclear Information System (INIS)

    Baillet, G.; Albuquerque, L.; Chen Qiming; Poisson, M.; Delattre, J.Y.

    1994-01-01

    Single-photon emission tomography (SPET) with technetium-99m sestamibi (MIBI) was carried out in 61 adult patients with supratentorial expanding brain lesions. Thirty-one patients had pathologically proven malignant glioma. Ten patients had pathologically proven low-grade glioma, while another 12 patients had a clinical diagnosis of low-grade glioma. The other eight patients had a variety of lesions including radiation necrosis (3), abscess (2), ischaemic stroke (2) and primary brain lymphoma (1). SPET was performed 15 min after administration of 740-930 MBq MIBI and transverse, sagittal and coronal views were reconstructed. Using computed tomography or magnetic resonance imaging guidance, a MIBI uptake index was computed as the ratio of counts in the lesion to counts in the contralateral homologous region. In high-grade gliomas, the MIBI index ranged from 1.9 to 6.6 (mean 3.6 ± 1.4) whereas it ranged from 0.8 to 1.7 (1.1 ± 0.2) in the pathologically proven low-grade group (P < 0.01). No significant difference was found between the two low-grade groups (1.1 ± 0.2 vs 1.1 ± 0.2). No overlap was found between high-grade and low-grade glioma index values. Patients with suspected radiation necrosis, cerebral abscess or ischaemic stroke did not demonstrate high MIBI uptake (0.9-2.2), whereas one patient with brain lymphoma did (3.9). This study suggests that MIBI SPET imaging is of value in distinguishing low-from high-grade supratentorial gliomas in adults. (orig.)

  2. Predicting patterns of glioma recurrence using diffusion tensor imaging

    International Nuclear Information System (INIS)

    Price, Stephen J.; Pickard, John D.; Jena, Rajesh; Burnet, Neil G.; Carpenter, T.A.; Gillard, Jonathan H.

    2007-01-01

    Although multimodality therapy for high-grade gliomas is making some improvement in outcome, most patients will still die from their disease within a short time. We need tools that allow treatments to be tailored to an individual. In this study we used diffusion tensor imaging (DTI), a technique sensitive to subtle disruption of white-matter tracts due to tumour infiltration, to see if it can be used to predict patterns of glioma recurrence. In this study we imaged 26 patients with gliomas using DTI. Patients were imaged after 2 years or on symptomatic tumour recurrence. The diffusion tensor was split into its isotropic (p) and anisotropic (q) components, and these were plotted on T 2 -weighted images to show the pattern of DTI abnormality. This was compared to the pattern of recurrence. Three DTI patterns could be identified: (a) a diffuse pattern of abnormality where p exceeded q in all directions and was associated with diffuse increase in tumour size; (b) a localised pattern of abnormality where the tumour recurred in one particular direction; and (c) a pattern of minimal abnormality seen in some patients with or without evidence of recurrence. Diffusion tensor imaging is able to predict patterns of tumour recurrence and may allow better individualisation of tumour management and stratification for randomised controlled trials. (orig.)

  3. Second Surgery in Insular Low-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Tamara Ius

    2015-01-01

    Full Text Available Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs. Univariate analysis showed that TR is influenced by the following: extent of resection (EOR (P<0.002, ΔVT2T1 value (P<0.001, histological diagnosis of oligodendroglioma (P=0.017, and mutation of IDH1 (P=0.022. The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P<0.001. Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery.

  4. High-Grade Leiomyosarcoma Arising in a Previously Replanted Limb

    Directory of Open Access Journals (Sweden)

    Tiffany J. Pan

    2015-01-01

    Full Text Available Sarcoma development has been associated with genetics, irradiation, viral infections, and immunodeficiency. Reports of sarcomas arising in the setting of prior trauma, as in burn scars or fracture sites, are rare. We report a case of a leiomyosarcoma arising in an arm that had previously been replanted at the level of the elbow joint following traumatic amputation when the patient was eight years old. He presented twenty-four years later with a 10.8 cm mass in the replanted arm located on the volar forearm. The tumor was completely resected and pathology examination showed a high-grade, subfascial spindle cell sarcoma diagnosed as a grade 3 leiomyosarcoma with stage pT2bNxMx. The patient underwent treatment with brachytherapy, reconstruction with a free flap, and subsequently chemotherapy. To the best of our knowledge, this is the first case report of leiomyosarcoma developing in a replanted extremity. Development of leiomyosarcoma in this case could be related to revascularization, scar formation, or chronic injury after replantation. The patient remains healthy without signs of recurrence at three-year follow-up.

  5. Pharmacokinetic MRI of the prostate. Parameters for differentiating low-grade and high-grade prostate cancer

    International Nuclear Information System (INIS)

    Franiel, T.; Taupitz, M.; Asbach, P.; Beyersdorff, D.; Luedemann, L.; Rost, J.

    2009-01-01

    Purpose: to investigate whether pharmacokinetic MRI parameters ''perfusion, blood volume, mean transit time (MTT), interstitial volume, permeability, extraction coefficient, delay, and dispersion'' allow the differentiation of low-grade (Gleason score ≤ 6) and high-grade (Gleason score ≥ 7) prostate cancer. Materials and method: forty-two patients with prostate cancer verified by biopsy (PSA 2.7 to 31.4ng/ml) and scheduled for prostatectomy underwent MRI at 1.5 Tesla using the dynamic contrast-enhanced inversion-prepared dual-contrast gradient echo sequence (temporal resolution, 1.65 s) and a combined endorectal body phased array coil. Parametric maps were computed using a sequential 3-compartment model and the corresponding post-processing algorithms. A total of 41 areas of prostate cancer (15 low-grade, 26 high-grade cancers) in 32 patients were able to be correlated with the prostatectomy specimens and were included in the analysis. Results: low-grade prostate cancers had a higher mean blood volume (1.76% vs. 1.64%, p = 0.039), longer MTT (6.39 s vs. 3.25 s, p -1 vs. 3.86 min -1 , p = 0.011) than high-grade cancers. No statistically significant difference was found for perfusion (p = 0.069), interstitial volume (p = 0.849), extraction coefficient (p = 0.615), delay (p = 0.489), and dispersion (p = 0.306). (orig.)

  6. World wide web-based cytological analysis of atypical squamous cells cannot exclude high-grade intraepithelial lesions.

    Science.gov (United States)

    Washiya, Kiyotada; Takamizu, Ryuichi; Kumagai, Yukie; Himeji, Yukari; Kobayashi, Takako; Iwai, Muneo; Watanabe, Jun

    2012-01-01

    It has been reported that the low level of consistency of diagnosis of atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions (ASC-H) in uterine cervical cancer screening using the Bethesda System, indicating the necessity of a large-scale survey. We presented cases cytologically judged as ASC-H on our website and invited our members to give their opinions regarding the diagnosis by voting online. The Web voting results were analyzed and ASC-H was cytologically investigated. Virtual slides of atypical cells in cytology preparations of 53 cases were prepared and presented on a website. ASC-H cases were divided into 42 cases sampled by brush scraping and 11 cases sampled by cotton swab scraping. Fifty-three cases cytologically judged as ASC-H were classified into benign and CIN2/3, and their patterns of arrangement of atypical cells and 8 cytological parameters were morphologically investigated. The frequency of ASC-H diagnosis in the Web votes was low: 29.2% for brush-scraped and 26.2% for cotton swab-scraped cases. Three-dimensionality, coarse chromatin and irregular nuclei were significantly different between high-grade squamous intraepithelial lesions and benign cases. Web-based surveys showed the difference of cytological findings between high-grade squamous intraepithelial lesions and benign cases. To increase interobserver consistency, it may be useful to share information online, which avoids geographical and temporal limitations. Copyright © 2012 S. Karger AG, Basel.

  7. 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.

    Science.gov (United States)

    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 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.

  8. Preserved splenic function after angioembolisation of high grade injury.

    Science.gov (United States)

    Skattum, Jorunn; Titze, Thomas Larsen; Dormagen, Johann Baptist; Aaberge, Ingeborg S; Bechensteen, Anne Grete; Gaarder, Per Ivar; Gaarder, Christine; Heier, Hans Erik; Næss, Pål Aksel

    2012-01-01

    After introducing splenic artery embolisation (SAE) in the institutional treatment protocol for splenic injury, we wanted to evaluate the effects of SAE on splenic function and assess the need for immunisation in SAE treated patients. 15 SAE patients and 14 splenectomised (SPL) patients were included and 29 healthy blood donors volunteered as controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears from all patients and controls were examined for Howell-Jolly (H-J) bodies. Abdominal doppler, gray scale and contrast enhanced ultrasound (CEUS) were performed on all the SAE patients. Leukocyte and platelet counts were elevated in both SAE and SPL individuals compared to controls. The proportion of memory B-lymphocytes did not differ significantly from controls in either group. In the SAE group total IgA, IgM and IgG levels as well as pneumococcal serotype specific IgG and IgM antibody levels did not differ from the control group. In the SPL group total IgA and IgG Pneumovax(®) (PPV23) antibody levels were significantly increased, and 5 of 12 pneumococcal serotype specific IgGs and IgMs were significantly elevated. H-J bodies were only detected in the SPL group. CEUS confirmed normal sized and well perfused spleens in all SAE patients. In our study non-operative management (NOM) of high grade splenic injuries including SAE, was followed by an increase in total leukocyte and platelet counts. Normal levels of immunoglobulins and memory B cells, absence of H-J bodies and preserved splenic size and intraparenchymal blood flow suggest that SAE has only minor impact on splenic function and that immunisation probably is unnecessary. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Primary balloon angioplasty for symptomatic, high-grade intracranial stenosis.

    Science.gov (United States)

    Tomycz, Luke; Bansal, Neil K; Lockney, Tim; Strothers, Megan; Connors, John J; Shay, Scott; Singer, Robert J

    2013-01-01

    In light of recent controversy about the safety and efficacy of intracranial stenting, we sought to evaluate our experience with primary balloon angioplasty for symptomatic, high-grade intracranial stenosis. All intracranial angioplasty cases performed at Vanderbilt University Medical Center from 2006 to 2011 were retrospectively reviewed for degree of stenosis pre- and post-procedure. Immediate peri-procedural complications were evaluated as well as one-month and long-term outcomes. A total of 26 patients were included in the study with a mean age of 63.0 years and a mean follow-up of 350.2 days. The average pre-procedure stenosis was 71.2%. The immediate, average post-procedure stenosis was 46.6%, and the average post-procedure stenosis at last angiographic follow-up was 44.5%. Retreatment was required in only 3.8% of patients. The primary end-point of major stroke or death at 30 days was observed in 11.5%, and the overall intra-procedural complication rate was 7.7%. The incidence of stroke or death at last follow-up was 15.4%, which is comparable to the one-year stroke or death rate in the medical arm of the SAMPRISS trial. In this retrospective series, primary balloon angioplasty was found to be effective as a treatment option for symptomatic intracranial stenosis with the risk of stroke or death at 30 days higher than the medical arm of SAMPRIS but lower than the stenting arm. The one-year risk of stroke was comparable to that reported for the one-year outcomes in the SAMPRISS medical arm.

  10. MR Imaging-derived Oxygen Metabolism and Neovascularization Characterization for Grading and IDH Gene Mutation Detection of Gliomas.

    Science.gov (United States)

    Stadlbauer, Andreas; Zimmermann, Max; Kitzwögerer, Melitta; Oberndorfer, Stefan; Rössler, Karl; Dörfler, Arnd; Buchfelder, Michael; Heinz, Gertraud

    2017-06-01

    Purpose To explore the diagnostic performance of physiological magnetic resonance (MR) imaging of oxygen metabolism and neovascularization activity for grading and characterization of isocitrate dehydrogenase (IDH) gene mutation status of gliomas. Materials and Methods This retrospective study had institutional review board approval; written informed consent was obtained from all patients. Eighty-three patients with histopathologically proven glioma (World Health Organization [WHO] grade II-IV) were examined with quantitative blood oxygen level-dependent imaging and vascular architecture mapping. Biomarker maps of neovascularization activity (microvessel radius, microvessel density, and microvessel type indicator [MTI]) and oxygen metabolism (oxygen extraction fraction [OEF] and cerebral metabolic rate of oxygen [CMRO 2 ]) were calculated. Receiver operating characteristic analysis was used to determine diagnostic performance for grading and detection of IDH gene mutation status. Results Low-grade (WHO grade II) glioma showed areas with increased OEF (+18%, P < .001, n = 20), whereas anaplastic glioma (WHO grade III) and glioblastoma (WHO grade IV) showed decreased OEF when compared with normal brain tissue (-54% [P < .001, n = 21] and -49% [P < .001, n = 41], respectively). This allowed clear differentiation between low- and high-grade glioma (area under the receiver operating characteristic curve [AUC], 1) for the patient cohort. MTI had the highest diagnostic performance (AUC, 0.782) for differentiation between gliomas of grades III and IV among all biomarkers. CMRO 2 was decreased (P = .037) in low-grade glioma with a mutated IDH gene, and MTI was significantly increased in glioma grade III with IDH mutation (P = .013) when compared with the IDH wild-type counterparts. CMRO 2 showed the highest diagnostic performance for IDH gene mutation detection in low-grade glioma (AUC, 0.818) and MTI in high-grade glioma (AUC, 0.854) and for all WHO grades (AUC, 0

  11. Ex vivo malignant glioma cells are sensitive to Fas (CD95/APO-1) ligand-mediated apoptosis.

    Science.gov (United States)

    Frei, K; Ambar, B; Adachi, N; Yonekawa, Y; Fontana, A

    1998-07-01

    Fas (also known as CD95/APO-1) is a cell surface receptor and member of the tumor necrosis factor receptor superfamily which mediates apoptosis in sensitive cells upon oligomerization by specific antibodies or by its ligand (FasL). Recently, human glioma cell lines were found to be susceptible to Fas-mediated apoptosis triggered by alpha-Fas antibodies. However, whether the Fas system can also be targeted in ex vivo high grade gliomas is at present unknown. In the present investigation, alpha-Fas antibodies and FasL were tested in short-term monolayer cultures or in colony forming assays established from freshly resected tumors of patients with anaplastic astrocytomas (WHO grade III) and glioblastoma multiforme (WHO grade IV). Anti-Fas antibodies induced only moderate apoptosis in four of the 19 tested glioma cell cultures. This contrasts FasL which induced apoptosis in all of the 19 tumor cell cultures analyzed. Mean cytotoxicity of glioma cell cultures treated for 48 h with alpha-Fas antibodies or FasL was 9.6% and 44.3%, respectively. Irrespective of whether alpha-Fas antibodies or FasL were used, pretreatment with recombinant hu (rhu) IFN-gamma and rhuTNF-alpha for 48 h did not sensitize glioma cells to Fas-mediated cytotoxicity. The long-term effect by FasL on tumor colony formation was more striking. FasL treatment resulted in more than 90% inhibition of clonal tumor cell growth of all the eight high grade gliomas analyzed. These results suggest that Fas targeting by FasL but not by alpha-Fas antibodies may provide a promising approach for locoregional glioma treatment.

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

    International Nuclear Information System (INIS)

    Zou, Q.-G.; Xu, H.-B.; Liu, F.; Guo, W.; Kong, X.-C.; Wu, Y.

    2011-01-01

    Aim: To detect a difference in the parameters derived from proton magnetic resonance spectroscopy ( 1 H-MRS) and diffusion tensor imaging (DTI) between low-grade and high-grade gliomas, and to evaluate whether the combination of these two techniques can improve the diagnostic accuracy of conventional magnetic resonance imaging (MRI) in supratentorial glioma grading. Materials and methods: Thirty patients with histologically proved supratentorial brain gliomas (12 low grade, 18 high grade) were prospectively evaluated with contrast material-enhanced MRI, DTI, and multivoxel 1 H-MRS (135 ms echo time). The tumour grades determined using the three methods were then compared with those obtained at histopathology. Receiver operating characteristic (ROC) analyses were performed to determine the optimum thresholds for glioma grading. Independent sample t-test, Spearman's rank correlation, and the Fisher's exact test were also carried out for statistical analysis. p -6 mm 2 /s for the calculated ADC value, corresponding to the maximum Youden index from the ROC curve of the above-selected parameters, the resultant sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and Kappa values were all higher and the fraction of misclassified tumour was lower when compared with conventional MRI. However, only NAA/Cho and ADC calculation contributed to the significant difference (p < 0.01) in the assessment of glioma grade compared to conventional MRI alone, and the grading results of statistical tests comparing those two parameters were highly consistent (kappa value = 0.798). Conclusion: Thresholds for NAA/Cho and calculated ADC values, corresponding to maximum Youden index from ROC curve analyses, helped to improve the accuracy of supratentorial glioma grading when compared with conventional MRI alone. In addition, a combination of NAA/Cho and ADC calculation were more useful together than each alone in a clinical setting to evaluate

  13. Multiple Daily Fractionated RT for Malignant Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kang Mo; Chang, Hye Sook; Ahn, Seoung Do; Choi, Eun Kyung [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Since Jan. 1992, authors have conducted a pilot study to treat malignant glioma with multiple daily fractionated (MDF) radiation therapy and this paper presents the outcome compared MDF to conventional fractionated (CF) radiation therapy. Between Sep. 1989 and Jan. 1993, forty-three patients with high grade glioma of brain except brain stem glioma were treated: nineteen patients were treated with CF radiation therapy and 24 patients were treated with MDF radiation therapy. In CF radiation therapy, total dose was 6300cHy/35fx in 7 weeks, which 5040cGy was delivered to the initial target volume and 1260cGy to reduced target volume. And in MDF radiation therapy, total dose was 6400cGy/40fx in 4 weeks, which 3200cGy was delivered to the initial target volume as 160cGy 2 times daily 6hr apart. All patients had histologically confirmed anaplastic astrocytoma (AA) of glioblastoma multiforme(GBM) with stereotactic biopsy or craniotomy for subtotal or gross tumor resection. The rage of follow-up was 7 months to 4 years with a median follow-up of 9 months. The Median survival from surgery was 9 months for all patients. The median survival was 9 months and 10 months for MDF group and CF group and 10 months and 9.5 months for glioblastoma multiforme and anaplastic astrocytoma, respectively. In 36 patients with follow-up CT scan or MRI scan, disease status was evaluated according to treatment group. Four patients (GBM:3, AA:1) of 21 patients in MDF group, were alive with no evidence of disease, while none of patient was alive with no evidence of disease in CF group. The progression of disease had occurred in 20 patients, 11 patients and 9 patients in MDF group and CF group, respectively. All of these patients showed in-field progression of disease. Four of 11 patients (27%) in MDF group showed the new lesion outside of the treatment field, while 5 of 9 patients(56%) in CF group. In our study the prognosis was not influenced by age, KPS, grade, extent of surgery and different

  14. The expression of cytoglobin as a prognostic factor in gliomas: a retrospective analysis of 88 patients

    International Nuclear Information System (INIS)

    Xu, Hong-Wu; Huang, Hai-Hua; Wei, Xiao-Long; Man, Kwan; Zhang, Guo-Jun; Huang, Yue-Jun; Xie, Ze-Yu; Lin, Lan; Guo, Yan-Chun; Zhuang, Ze-Rui; Lin, Xin-Peng; Zhou, Wen; Li, Mu

    2013-01-01

    Evidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene. We immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors. Low expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFα or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFα and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients’ overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis. Cygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients

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

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Q.-G. [Department of Neuroradiology, Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xu, H.-B., E-mail: xuhaibo1120@hotmail.com [Department of Neuroradiology, Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Liu, F.; Guo, W. [Department of Neuroradiology, Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Kong, X.-C. [Department of Imaging technology, Union hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Wu, Y. [Department of Maternal and Child Health Care, Public Health School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China)

    2011-10-15

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

  16. Optimizing a machine learning based glioma grading system using multi-parametric MRI histogram and texture features.

    Science.gov (United States)

    Zhang, Xin; Yan, Lin-Feng; Hu, Yu-Chuan; Li, Gang; Yang, Yang; Han, Yu; Sun, Ying-Zhi; Liu, Zhi-Cheng; Tian, Qiang; Han, Zi-Yang; Liu, Le-De; Hu, Bin-Quan; Qiu, Zi-Yu; Wang, Wen; Cui, Guang-Bin

    2017-07-18

    Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study. The parametric histogram and image texture attributes of 120 glioma patients were extracted from the perfusion, diffusion and permeability parametric maps of preoperative MRI. Then, 25 commonly used machine learning classifiers combined with 8 independent attribute selection methods were applied and evaluated using leave-one-out cross validation (LOOCV) strategy. Besides, the influences of parameter selection on the classifying performances were investigated. We found that support vector machine (SVM) exhibited superior performance to other classifiers. By combining all tumor attributes with synthetic minority over-sampling technique (SMOTE), the highest classifying accuracy of 0.945 or 0.961 for LGG and HGG or grade II, III and IV gliomas was achieved. Application of Recursive Feature Elimination (RFE) attribute selection strategy further improved the classifying accuracies. Besides, the performances of LibSVM, SMO, IBk classifiers were influenced by some key parameters such as kernel type, c, gama, K, etc. SVM is a promising tool in developing automated preoperative glioma grading system, especially when being combined with RFE strategy. Model parameters should be considered in glioma grading model optimization.

  17. Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study.

    Science.gov (United States)

    Seagle, Brandon-Luke L; Shilpi, Arunima; Buchanan, Samuel; Goodman, Chelain; Shahabi, Shohreh

    2017-08-01

    To provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). We performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. We identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1-35.3%) versus 90.5% (89.3-91.8%), PTR) (95% CI): 1.36 (1.17-1.58), PTR (95% CI): 1.57 (1.32-1.87), P<0.001) were associated with increased survival for high-grade ESS. The contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Volumetric Analysis of Extent of Resection, Survival, and Surgical Outcomes for Insular Gliomas.

    Science.gov (United States)

    Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; Raghuraman, Gugan; Quinones-Hinojosa, Alfredo

    2017-07-01

    Insular gliomas are challenging tumors to surgically resect owing to the anatomy surrounding them. This study evaluates the role of extent of resection (EOR) and molecular markers in surgical outcome and survival for insular gliomas. Seventy-four patients who had undergone initial resection for insular glioma by the same surgeon between 2006 and 2016 were analyzed. Low-grade gliomas (LGGs) (grade II) and high-grade gliomas (HGGs) (grade III/IV) were analyzed for the prognostic role of volumetric EOR and molecular markers in patient survival outcomes. The cohort included 25 patients with LGGs (33.8%) and 49 patients with HGGs (66.2%). Median EOR was 91.7% (range, 10%-100%). New permanent postoperative deficits were found in 2.7% of patients. Patients with LGGs with ≥90% EOR had 5-year survival of 100%, and patients with <90% EOR had 5-year survival of 80%. Patients with HGGs with ≥90% EOR had 2-year survival of 83.7%, and patients with <90% EOR had 2-year survival of 43.8%. For LGGs, EOR was predictive of overall survival (P = 0.017), progression-free survival (PFS) (P = 0.039), and malignant PFS (P = 0.014), whereas 1p/19q codeletion was predictive of PFS (P = 0.014). For HGGs, EOR was predictive of overall survival (P = 0.020) and PFS (P = 0.024). Preoperative tumor volume most significantly affected EOR for insular gliomas (R 2  = 0.053, P = 0.048). Extensive resections of insular gliomas can be achieved with low morbidity and can improve overall survival and PFS. In this series of LGGs, EOR was associated with longer malignant PFS, and 1p/19q codeletion was predictive of PFS. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Tina eDasgupta

    2013-05-01

    Full Text Available 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 low-grade gliomas is being exploited with targeted inhibitors. These agents are also being combined with XRT to increase their efficacy. In this review, we discuss novel agents targeting three different pathways in low-grade gliomas, and their potential combination with XRT. B-Raf is a kinase in the Ras/Raf/MAPK kinase pathway, which is integral to cellular division, survival and metabolism. In low-grade pediatric gliomas, point mutations in BRAF (BRAF V600E or a BRAF fusion mutation (KIAA1549:BRAF causes overactivation of the MEK/MAPK pathway. Pre-clinical data shows cooperation between XRT and tagrgeted inhibitors of BRAF V600E, and MEK and mTOR inhibitors in the gliomas with the BRAF fusion. A second important signaling cascade in pediatric glioma pathogenesis is the PI3 kinase (PI3K/mTOR pathway. Dual PI3K/mTOR inhibitors are poised to enter studies of pediatric tumors. Finally, many brain tumors express potent stimulators of angiogenesis. Several inhibitors of immunomodulators are currently being evaluated in in clinical trials for the treatment of recurrent or refractory pediatric central nervous system (CNS tumors. In summary, combinations of these targeted inhibitors with radiation are currently under investigation in both translational bench research and early clinical trials. We summarize the molecular rationale for, and the pre-clinical data supporting the combinations of these targeted agents with other anti-cancer agents and XRT in pediatric gliomas. Parallels are drawn to adult gliomas, and the molecular mechanisms underlying the efficacy of these agents is discussed

  20. RETRACTED: Downregulation of miR-204 expression correlates with poor clinical outcome of glioma patients.

    Science.gov (United States)

    Ye, Zhen-Nan; Liu, Jing-Peng; Wu, Ling-Yun; Zhang, Xiang-Sheng; Zhuang, Zong; Chen, Qiang; Lu, Yue; Liu, Ce-Gang; Zhang, Zi-Huan; Zhang, Hua-Sheng; Hou, Wen-Zhong; Hang, Chun-Hua

    2017-05-01

    Glioma is the most common type of malignant neoplasm in the central nervous system, with high incidence and mortality rate. MicroRNAs, as a class of small noncoding RNAs, play an important role in carcinogenesis and correlate with glioma diagnosis and prognosis. In this study, we investigated the microRNA-204 (miR-204) concentration in glioma tissues and its relation to the expression of ezrin and bcl-2 mRNA, as well as its potential predictive and prognostic values in glioma. The concentrations of miR-204 were significantly lower in glioma tissues than in nontumor brain tissues and also were lower in high-grade than in low-grade gliomas (World Health Organization grades III and IV versus grades I and II). The miR-204 concentration was inversely correlated with the ezrin and bcl-2 concentrations. The miR-204 concentration was classified as high or low according to the median value, and low miR-204 correlated with higher World Health Organization grade, larger tumor, and worse Karnofsky performance score. Kaplan-Meier survival analysis demonstrated that patients with low miR-204 expression had shorter progression-free survival and overall survival than patients with high miR-204 expression. In addition, univariate and multivariate analyses showed that miR-204 expression was an independent prognostic feature of overall survival and progression-free survival. In conclusion, our study indicates that miR-204 is downregulated in glioma and may be a biomarker of poor prognosis in patients with this cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. F11R is a novel monocyte prognostic biomarker for malignant glioma.

    Directory of Open Access Journals (Sweden)

    Winnie W Pong

    Full Text Available Brain tumors (gliomas contain large populations of infiltrating macrophages and recruited microglia, which in experimental murine glioma models promote tumor formation and progression. Among the barriers to understanding the contributions of these stromal elements to high-grade glioma (glioblastoma; GBM biology is the relative paucity of tools to characterize infiltrating macrophages and resident microglia. In this study, we leveraged multiple RNA analysis platforms to identify new monocyte markers relevant to GBM patient outcome.High-confidence lists of mouse resident microglia- and bone marrow-derived macrophage-specific transcripts were generated using converging RNA-seq and microarray technologies and validated using qRT-PCR and flow cytometry. Expression of select cell surface markers was analyzed in brain-infiltrating macrophages and resident microglia in an induced GBM mouse model, while allogeneic bone marrow transplantation was performed to trace the origins of infiltrating and resident macrophages. Glioma tissue microarrays were examined by immunohistochemistry, and the Gene Expression Omnibus (GEO database was queried to determine the prognostic value of identified microglia biomarkers in human GBM.We generated a unique catalog of differentially-expressed bone marrow-derived monocyte and resident microglia transcripts, and demonstrated that brain-infiltrating macrophages acquire F11R expression in GBM and following bone-marrow transplantation. Moreover, mononuclear cell F11R expression positively correlates with human high-grade glioma and additionally serves as a biomarker for GBM patient survival, regardless of GBM molecular subtype.These studies establish F11R as a novel monocyte prognostic marker for GBM critical for defining a subpopulation of stromal cells for future potential therapeutic intervention.

  2. Postoperative radiotherapy of supratentorial anaplastic gliomas

    International Nuclear Information System (INIS)

    Wendt, T.G.; Bacherler, B.; Baumer, K.; Rohloff, R.; Willich, N.

    1986-01-01

    Between 1970 and 1983, 149 patients with high grade anaplastic supratentorial gliomas received a postoperative irradiation during primary treatment. 118 out of these patients had an anaplastic astrocytoma, 18 an anaplastic oligodendroglioma, and 13 an anaplastic ependymoma. Most of these patients were treated by irradiation of a great volume with 50 Gy within five weeks, the others by irradiation of the total brain with 50 Gy within five weeks and saturation with 10 Gy within one week. The one-year survival of the total group was 35.5% and the two-year survival 10.6%. Patients at an age of less than 40 years show a significantly longer survival than older patients (one-year survival rates 40% and 30.7%, respectively). Patients suffering from anaplastic tumors with astrocytic and oligodendrocytic differentiation have a comparable prognosis. Patients suffering from anaplastic tumors with ependymal differentiation, however, have prolonged survival times. The therapy results of different treatment methods are discussed using the communications of literature. (orig.) [de

  3. Treatment of brain gliomas in children

    International Nuclear Information System (INIS)

    Bloom, H.J.G.

    1986-01-01

    Some neurologists and pediatricians regard the great majority of children with brain tumours as being incurable and suspect that in any long-term survivors the quality of remaining life following treatment will inevitably be greatly impaired. This general pessimism is not supported by the current results of modern treatment and past opinions may need to be revised. In fact, the survival outlook for children with intracranial gliomas is considerably better than that for adults, and this applies to tumours of both low-grade and high-grade malignancy. At the Royal Marsden Hospital (RMH) between 1952 and 1976 a total of 461 children under age 16 years with primary intracranial tumours were referred for radiotherapy. The actuarial survival rate for all cases at 5 years was 48%, at 10 years 41% and at 20 years 38%. Of the 415 children who completed a radical course of irradiation, given either post-operatively or as the sole treatment, 53% were still alive at 5 years, 45% at 10 years and 41% at 20 years. Overall survival was influenced by age, the best results being seen in children aged 10-15 years and the worst in children under 3 years

  4. Natural history of high-grade cervical intraepithelial neoplasia : a review of prognostic biomarkers

    NARCIS (Netherlands)

    Koeneman, Margot M.; Kruitwagen, Roy F. P. M.; Nijman, Hans W.; Slangen, Brigitte F. M.; Van Gorp, Toon; Kruse, Arnold-Jan

    The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical

  5. Extent of high-grade prostatic intraepithelial neoplasia is not a ...

    African Journals Online (AJOL)

    Objective: High-grade prostatic intraepithelial neoplasia (PIN) is a well accepted pre-cursor of invasive prostate cancer. Most investigators agree that a diagnosis of high-grade PIN warrants repeat transrectal ultrasound guided biopsy. We set out to investigate risk factors for cancer among a modern cohort of men with ...

  6. Non-standard radiotherapy fractionations delay the time to malignant transformation of low-grade gliomas.

    Directory of Open Access Journals (Sweden)

    Araceli Henares-Molina

    Full Text Available Grade II gliomas are slowly growing primary brain tumors that affect mostly young patients. Cytotoxic therapies (radiotherapy and/or chemotherapy are used initially only for patients having a bad prognosis. These therapies are planned following the "maximum dose in minimum time" principle, i. e. the same schedule used for high-grade brain tumors in spite of their very different behavior. These tumors transform after a variable time into high-grade gliomas, which significantly decreases the patient's life expectancy. In this paper we study mathematical models describing the growth of grade II gliomas in response to radiotherapy. We find that protracted metronomic fractionations, i.e. therapeutical schedules enlarging the time interval between low-dose radiotherapy fractions, may lead to a better tumor control without an increase in toxicity. Other non-standard fractionations such as protracted or hypoprotracted schemes may also be beneficial. The potential survival improvement depends on the tumor's proliferation rate and can be even of the order of years. A conservative metronomic scheme, still being a suboptimal treatment, delays the time to malignant progression by at least one year when compared to the standard scheme.

  7. Malignant gliomas; Gliomes cerebraux

    Energy Technology Data Exchange (ETDEWEB)

    Haberer, S.; Assouline, A.; Mazeron, J.J. [Service d' oncologie radiotherapique, centre des tumeurs, groupe hospitalier Pitie-Salpetriere, 75 - Paris (France)

    2010-07-01

    Glial tumors represent 2000 to 3000 new cases per year in France and 75% of them are of high grade. Recent understanding of the molecular biology of these tumors revealed the importance of 1p19q co-deletion and mgMT promoter methylation. Radiotherapy also recently evolved with the progress in medical imaging which allows a better definition of the target volumes. Even modest, therapeutic progress is based on chemoradiotherapy with temozolomide and on the development of non-coplanar conformational radiotherapy. Knowledge and precise evaluation of potential late effects of our treatments is necessary due to actual improvement of survival with chemoradiotherapy in glioblastoma. (authors)

  8. Brain volume perfusion CT performed with 128-detector row CT system in patients with cerebral gliomas: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Xyda, Argyro [University Hospital of Goettingen, Department of Neuroradiology, Georg-August University, Goettingen (Germany); University Hospital of Heraklion, Department of Radiology, Crete (Greece); Haberland, Ulrike; Klotz, Ernst [Computed Tomography, Siemens AG Healthcare Sector, Forchheim (Germany); Bock, Hans Christoph [University Hospital of Goettingen, Department of Neurosurgery, Georg-August University, Goettingen (Germany); Jung, Klaus [University Hospital of Goettingen, Department of Medical Statistics, Georg-August University, Goettingen (Germany); Knauth, Michael; Schramm, Ramona; Psychogios, Marios Nikos; Schramm, Peter [University Hospital of Goettingen, Department of Neuroradiology, Georg-August University, Goettingen (Germany); Erb, Gunter [Bracco Imaging Deutschland GmbH, Konstanz (Germany)

    2011-09-15

    Validation of the feasibility and efficacy of volume perfusion computed tomography (VPCT) in the preoperative assessment of cerebral gliomas by applying a 128-slice CT covering the entire tumour. Forty-six patients (25 men, 21 women; mean age 52.8 years) with cerebral gliomas were evaluated with VPCT. Two readers independently evaluated VPCT data, drawing volumes of interest (VOIs) around the tumour according to maximum intensity projection volumes, which were mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability (Ktrans) perfusion datasets. As control, a second VOI was placed in the contralateral healthy cortex. Correlation among perfusion parameters, tumour grade, hemisphere and VOIs was assessed. The diagnostic power of perfusion parameters was analysed by receiver operating characteristics curve analyses. VPCT was feasible in the assessment of the entire tumour extent. Mean values of Ktrans, CBV, CBF in high-grade gliomas were significantly higher compared with low-grade (p < 0.01). Ktrans demonstrated the highest diagnostic (97% sensitivity), positive (100%) and negative (94%) prognostic values. VPCT was feasible in all subjects. All areas of different perfusion characteristics are depicted and quantified in colour-coded 3D maps. The derived parameters correlate well with tumour histopathology, differentiating low- from high-grade gliomas. (orig.)

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    Grabner, Guenther [Medical University of Vienna, High Field Magnetic Resonance Centre, Department of Biomedical Imaging and Image-Guided Therapy, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Vienna (Austria); Carinthia University of Applied Sciences, Department of Health Sciences and Social Work, Klagenfurt am Woerthersee (Austria); Kiesel, Barbara; Millesi, Matthias; Wurzer, Ayguel; Knosp, Engelbert; Wolfsberger, Stefan; Widhalm, Georg [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Woehrer, Adelheid [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Institute of Neurology, Vienna (Austria); Goed, Sabine [Medical University of Vienna, High Field Magnetic Resonance Centre, Department of Biomedical Imaging and Image-Guided Therapy, Vienna (Austria); Mallouhi, Ammar [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Radiology, Vienna (Austria); Marosi, Christine; Preusser, Matthias [Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Vienna (Austria); Medical University of Vienna, Department of Internal Medicine I, Vienna (Austria); Trattnig, Siegfried [Medical University of Vienna, High Field Magnetic Resonance Centre, Department of Biomedical Imaging and Image-Guided Therapy, Vienna (Austria); Medical University of Vienna, Comprehensive Cancer Center, Central Nervous System Tumours Unit (CCC-CNS), Vienna (Austria)

    2017-04-15

    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. (orig.)

  10. The ubiquitin-proteasome system in glioma cell cycle control

    Directory of Open Access Journals (Sweden)

    Vlachostergios Panagiotis J

    2012-07-01

    Full Text Available Abstract A major determinant of cell fate is regulation of cell cycle. Tight regulation of this process is lost during the course of development and progression of various tumors. The ubiquitin-proteasome system (UPS constitutes a universal protein degradation pathway, essential for the consistent recycling of a plethora of proteins with distinct structural and functional roles within the cell, including cell cycle regulation. High grade tumors, such as glioblastomas have an inherent potential of escaping cell cycle control mechanisms and are often refractory to conventional treatment. Here, we review the association of UPS with several UPS-targeted proteins and pathways involved in regulation of the cell cycle in malignant gliomas, and discuss the potential role of UPS inhibitors in reinstitution of cell cycle control.

  11. Adult IDH wild-type lower-grade gliomas should be further stratified.

    Science.gov (United States)

    Aibaidula, Abudumijit; Chan, Aden Ka-Yin; Shi, Zhifeng; Li, Yanxi; Zhang, Ruiqi; Yang, Rui; Li, Kay Ka-Wai; Chung, Nellie Yuk-Fei; Yao, Yu; Zhou, Liangfu; Wu, Jinsong; Chen, Hong; Ng, Ho-Keung

    2017-10-01

    Astrocytoma of the isocitrate dehydrogenase (IDH) wild-type gene is described as a provisional entity within the new World Health Organization (WHO) classification. Some groups believe that IDH wild-type lower-grade gliomas, when interrogated for other biomarkers, will mostly turn out to be glioblastoma. We hypothesize that not all IDH wild-type lower-grade gliomas have very poor outcomes and the group could be substratified prognostically. Seven hundred and eighteen adult WHO grades II and III patients with gliomas from our hospitals were re-reviewed and tested for IDH1/2 mutations. One hundred and sixty-six patients with IDH wild-type cases were identified for further studies, and EGFR and MYB amplifications, mutations of histone H3F3A, TERT promoter (TERTp), and BRAF were examined. EGFR amplification, BRAF, and H3F3A mutations were observed in 13.8%, 6.9%, and 9.5% of patients, respectively, in a mutually exclusive pattern in IDH wild-type lower-grade gliomas. TERTp mutations were detected in 26.8% of cases. Favorable outcome was observed in patients with young age, oligodendroglial phenotype, and grade II histology. Independent adverse prognostic values of older age, nontotal resection, grade III histology, EGFR amplification, and H3F3A mutation were confirmed by multivariable analysis. Tumors were further classified into "molecularly" high grade (harboring EGFR, H3F3A, or TERTp) (median overall survival = 1.23 y) and lower grade (lacking all of the 3) (median overall survival = 7.63 y) with independent prognostic relevance. The most favorable survival was noted in molecularly lower-grade gliomas with MYB amplification. Adult IDH wild-type lower-grade gliomas are prognostically heterogeneous and do not have uniformly poor prognosis. Clinical information and additional markers, including MYB, EGFR, TERTp, and H3F3A, should be examined to delineate discrete favorable and unfavorable prognostic groups.

  12. Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

    Energy Technology Data Exchange (ETDEWEB)

    Alpert, Justin S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Boland, Patrick [Memorial Sloan Kettering Cancer Center, Division of Orthopaedic Surgery, Department of Surgery, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Hameed, Meera [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Panicek, David M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States)

    2018-01-15

    Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear ''tail'' of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging ''tail'' should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma. (orig.)

  13. A new anti-glioma therapy, AG119: pre-clinical assessment in a mouse GL261 glioma model

    International Nuclear Information System (INIS)

    Towner, Rheal A.; Ihnat, Michael; Saunders, Debra; Bastian, Anja; Smith, Nataliya; Pavana, Roheeth Kumar; Gangjee, Aleem

    2015-01-01

    High grade gliomas (HGGs; grades III and IV) are the most common primary brain tumors in adults, and their malignant nature ranks them fourth in incidence of cancer death. Standard treatment for glioblastomas (GBM), involving surgical resection followed by radiation and chemotherapy with temozolomide (TMZ) and the anti-angiogenic therapy bevacizumab, have not substantially improved overall survival. New therapeutic agents are desperately needed for this devastating disease. Here we study the potential therapeutic agent AG119 in a pre-clinical model for gliomas. AG119 possesses both anti-angiogenic (RTK inhibition) and antimicrotubule cytotoxic activity in a single molecule. GL261 glioma-bearing mice were either treated with AG119, anti-VEGF (vascular endothelial growth factor) antibody, anti c-Met antibody or TMZ, and compared to untreated tumor-bearing mice. Animal survival was assessed, and tumor volumes and vascular alterations were monitored with morphological magnetic resonance imaging (MRI) and perfusion-weighted imaging, respectively. Percent survival of GL261 HGG-bearing mice treated with AG119 was significantly higher (p < 0.001) compared to untreated tumors. Tumor volumes (21–31 days following intracerebral implantation of GL261 cells) were found to be significantly lower for AG119 (p < 0.001), anti-VEGF (p < 0.05) and anti-c-Met (p < 0.001) antibody treatments, and TMZ-treated (p < 0.05) mice, compared to untreated controls. Perfusion data indicated that both AG119 and TMZ were able to reduce the effect of decreasing perfusion rates significantly (p < 0.05 for both), when compared to untreated tumors. It was also found that IC 50 values for AG119 were much lower than those for TMZ in T98G and U251 cells. These data support further exploration of the anticancer activity AG119 in HGG, as this compound was able to increase animal survival and decrease tumor volumes in a mouse GL261 glioma model, and that AG119 is also not subject to methyl guanine

  14. Use of statins and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; Andersen, L; Hallas, Jesper

    2013-01-01

    Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting.......Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting....

  15. Metabolic regulation of glioma stem-like cells in the tumor micro-environment.

    Science.gov (United States)

    Thomas, Tom M; Yu, John S

    2017-11-01

    Cancer metabolism has emerged as one of the most interesting old ideas being revisited from a new perspective. In the early 20th century Otto Warburg declared metabolism the prime cause in a disease of many secondary causes, and this statement seems more prescient in view of modern expositions into the true nature of tumor evolution. As the complexity of tumor heterogeneity becomes more clear from a genetic perspective, it is important to consider the inevitably heterogeneous metabolic components of the tumor and the tumor microenvironment. High grade gliomas remain one of the most difficult to treat solid tumors, due in part to the highly vascularized nature of the tumor and the maintenance of more resistant stem-like subpopulations within the tumor. Maintenance of glioma stem cells (GSCs) requires specific alterations within the cells and the greater tumor microenvironment with regards to signaling and metabolism. Specific niches within gliomas help foster the survival of stem-like sub-populations of cells with high tumorigenicity and high metabolic plasticity. Understanding these maintenance pathways and the metabolic dependencies within the niche may highlight potential avenues of addressing tumor resistance and recurrence in glioma patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Future directions in the treatment of malignant gliomas with temozolomide.

    Science.gov (United States)

    Prados, M D

    2000-06-01

    Temozolomide (TMZ) is a new, orally administered, second-generation imidazotetrazine prodrug with essentially 100% oral bioavailability that has demonstrated meaningful efficacy and an acceptable safety profile in the treatment of patients with recurrent glioblastoma multiforme. Because of its unique properties and broad spectrum of anticancer activity, preliminary studies are being conducted to evaluate the efficacy of TMZ in combination with other chemotherapeutic agents, radiation, or immunotherapy. The presence of de novo or acquired resistance to alkylating agents exhibited by malignant gliomas represents a serious impediment in the treatment of these tumors. This review discusses the mechanism of action of TMZ and strategies for overcoming pathways of resistance to this promising agent, including the use of TMZ in combination with other chemotherapeutic agents or radiation therapy, and exploration of alternate dosing schedules. Studies that have evaluated some of these strategies indicate that TMZ is a useful therapeutic option in patients with high-grade gliomas. Alternative approaches, including the use of high-dose TMZ with bone marrow transplantation and in combination with gene therapy, will also be discussed.

  17. 188Re-Labeled Nimotuzumab in the Locoregional Treatment of Malignant Gliomas

    International Nuclear Information System (INIS)

    Montana, R. Leyva; Barrabi, M. Zamora; Casaco, A.; Torres, L.; Perera, A.; Lopez, G.

    2009-01-01

    A new formulation of 188 Re-Nimotuzumab was developed to evaluate the biodistribution, internal radiation dosimetry and safety in the locoregional treatment of malignant gliomas. A phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary administration of single dose of Nimotuzumab labeled with 188 Re. Nimotuzumab is a humanized monoclonal antibody directed against epidermal growth factor receptors. Nine patients with anaplastic astrocytoma or glioblastoma multiforme were intended to be treated with 3 mg of mAb labeled with 10 or 15 mCi of 188 Re. The radioimmunoconjugated showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post- administration. No patient developed human anti-mouse antibody response. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. (author)

  18. Imaging of adult brainstem gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Purohit, Bela, E-mail: purohitbela@yahoo.co.in; Kamli, Ali A.; Kollias, Spyros S.

    2015-04-15

    Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: 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 {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-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.

  19. Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.

    Science.gov (United States)

    Yao, Pei-Sen; Kang, De-Zhi; Lin, Ru-Ying; Ye, Bing; Wang, Wei; Ye, Zu-Cheng

    2014-07-18

    Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer

    DEFF Research Database (Denmark)

    Albitar, Maher; Ma, Wanlong; Lund, Lars

    2018-01-01

    . The urine/plasma assay confirmed a previous validation and was highly accurate in predicting the presence of high-grade PCa (Gleason ≥3 + 4) with sensitivity between 88% and 95% as verified by prostatectomy findings. GS was upgraded after prostatectomy in 27% of patients and downgraded in 12% of patients......BACKGROUND: Distinguishing between low- and high-grade prostate cancers (PCa) is important, but biopsy may underestimate the actual grade of cancer. We have previously shown that urine/plasma-based prostate-specific biomarkers can predict high grade PCa. Our objective was to determine the accuracy......, designated a Gleason Score (GS) based on biopsy, and assigned to prostatectomy prior to participation in the study. The primary outcome measure was the urine/plasma test accuracy in predicting high grade PCa on prostatectomy compared with biopsy findings. Sensitivity and specificity were calculated using...

  1. Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mandy Stanske

    2018-03-01

    Full Text Available PURPOSE: Tumor-infiltrating lymphocytes (TILs have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC, however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2 expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each. Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018. There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026 and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031. High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012. CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.

  2. High-grade renal injuries are often isolated in sports-related trauma

    OpenAIRE

    Patel, Darshan P.; Redshaw, Jeffrey D.; Breyer, Benjamin N.; Smith, Thomas G.; Erickson, Bradley A.; Majercik, Sarah D.; Gaither, Thomas W.; Craig, James R.; Gardner, Scott; Presson, Angela P.; Zhang, Chong; Hotaling, James M.; Brant, William O.; Myers, Jeremy B.

    2015-01-01

    © 2015 Elsevier Ltd. All rights reserved. Introduction: Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. Material and methods: We identified patients with AAST grades III...

  3. Isocitrate dehydrogenase mutations in gliomas

    Science.gov (United States)

    Waitkus, Matthew S.; Diplas, Bill H.; Yan, Hai

    2016-01-01

    Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg132 of IDH1 and Arg172 of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy. PMID:26188014

  4. The prostate cancer risk calculator from the Prostate Cancer Prevention Trial underestimates the risk of high grade cancer in contemporary referral patients.

    Science.gov (United States)

    Ngo, Tin C; Turnbull, Brit B; Lavori, Philip W; Presti, Joseph C

    2011-02-01

    The prostate cancer risk calculator from the Prostate Cancer Prevention Trial estimates the risk of positive biopsy and 1 containing high grade disease (Gleason score 7 or greater) based on prostate specific antigen, digital rectal examination, family history, race and prior negative biopsy. Since data used to create the calculator came from an unreferred population that underwent mainly sextant biopsy, to our knowledge its usefulness in the contemporary urology practice is unknown. We performed the same multivariate logistic regression used to derive the prostate cancer risk calculator in a cohort of men from the Stanford Prostate Needle Biopsy Database who underwent initial prostate needle biopsy using an extended 12-core scheme. Our predictions of overall prostate cancer risk did not differ significantly from those of the calculator. Prostate specific antigen, abnormal digital rectal examination and family history were independent risk factors. However, our model predicted a much greater risk of high grade disease than the prostate cancer risk calculator. Prostate specific antigen, abnormal digital rectal examination and age were independent risk factors for high grade disease. The difference between our estimated risk of high grade prostate cancer and that of the prostate cancer risk calculator can be potentially explained by 1) differences between the cohorts (referred vs unreferred) or 2) the difference in grading, ie grading accuracy due to the difference in biopsy schemes or to temporally related grade shifts. Caution should be used when applying the prostate cancer risk calculator to counsel patients referred for suspicion of prostate cancer since it underestimates the risk of high grade disease. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Cellular phones, cordless phones, and the risks of glioma and meningioma (Interphone Study Group, Germany)

    DEFF Research Database (Denmark)

    Schüz, Joachim; Böhler, Eva; Berg, Gabriele

    2006-01-01

    ascertained during 2000-2003. Controls matched on age, gender, and region were randomly drawn from population registries. In total, 366 glioma cases, 381 meningioma cases, and 1,494 controls were interviewed. Overall use of a cellular phone was not associated with brain tumor risk; the respective odds ratios...... were 0.98 (95% confidence interval (CI): 0.74, 1.29) for glioma and 0.84 (95% CI: 0.62, 1.13) for meningioma. Among persons who had used cellular phones for 10 or more years, increased risk was found for glioma (odds ratio = 2.20, 95% CI: 0.94, 5.11) but not for meningioma (odds ratio = 1.09, 95% CI: 0.......35, 3.37). No excess of temporal glioma (p = 0.41) or meningioma (p = 0.43) was observed in cellular phone users as compared with nonusers. Cordless phone use was not related to either glioma risk or meningioma risk. In conclusion, no overall increased risk of glioma or meningioma was observed among...

  6. EGFRvIII promotes glioma angiogenesis and growth through the NF-κB, interleukin-8 pathway.

    Science.gov (United States)

    Bonavia, R; Inda, M M; Vandenberg, S; Cheng, S-Y; Nagane, M; Hadwiger, P; Tan, P; Sah, D W Y; Cavenee, W K; Furnari, F B

    2012-09-06

    Sustaining a high growth rate requires tumors to exploit resources in their microenvironment. One example of this is the extensive angiogenesis that is a typical feature of high-grade gliomas. Here, we show that expression of the constitutively active mutant epidermal growth factor receptor, ΔEGFR (EGFRvIII, EGFR*, de2-7EGFR) is associated with significantly higher expression levels of the pro-angiogenic factor interleukin (IL)-8 in human glioma specimens and glioma stem cells. Furthermore, the ectopic expression of ΔEGFR in different glioma cell lines caused up to 60-fold increases in the secretion of IL-8. Xenografts of these cells exhibit increased neovascularization, which is not elicited by cells overexpressing wild-type (wt)EGFR or ΔEGFR with an additional kinase domain mutation. Analysis of the regulation of IL-8 by site-directed mutagenesis of its promoter showed that ΔEGFR regulates its expression through the transcription factors nuclear factor (NF)-κB, activator protein 1 (AP-1) and CCAAT/enhancer binding protein (C/EBP). Glioma cells overexpressing ΔEGFR showed constitutive activation and DNA binding of NF-κB, overexpression of c-Jun and activation of its upstream kinase c-Jun N-terminal kinase (JNK) and overexpression of C/EBPβ. Selective pharmacological or genetic targeting of the NF-κB or AP-1 pathways efficiently blocked promoter activity and secretion of IL-8. Moreover, RNA interference-mediated knock-down of either IL-8 or the NF-κB subunit p65, in ΔEGFR-expressing cells attenuated their ability to form tumors and to induce angiogenesis when injected subcutaneously into nude mice. On the contrary, the overexpression of IL-8 in glioma cells lacking ΔEGFR potently enhanced their tumorigenicity and produced highly vascularized tumors, suggesting the importance of this cytokine and its transcription regulators in promoting glioma angiogenesis and tumor growth.

  7. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model.

    Science.gov (United States)

    Scott, Katherine A; Dalgleish, Angus G; Liu, Wai M

    2014-12-01

    High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration- and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU50, 0.77-1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 ± 2.2 mm(3) vs. 48.7 ± 24.9 mm(3) in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. ©2014 American Association for Cancer Research.

  8. Frequent Nek1 overexpression in human gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Jun [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Cai, Yu, E-mail: aihaozuqiu22@163.com [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Pin [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Zhao, Weiguo [Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2016-08-05

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  9. ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas

    International Nuclear Information System (INIS)

    Tomaselli, Sara; Galeano, Federica; Massimi, Luca; Di Rocco, Concezio; Lauriola, Libero; Mastronuzzi, Angela; Locatelli, Franco; Gallo, Angela

    2013-01-01

    High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients. Total RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR). A significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival. High-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas

  10. Detection of High Grade Prostate Cancer among PLCO Participants Using a Prespecified 4-Kallikrein Marker Panel.

    Science.gov (United States)

    Kim, Eric H; Andriole, Gerald L; Crawford, E David; Sjoberg, Daniel D; Assel, Melissa; Vickers, Andrew J; Lilja, Hans

    2017-04-01

    We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). Levels of free, intact, total prostate specific antigen, human kallikrein-2 and microseminoprotein-β were measured while blinded to outcomes in cryopreserved serum from men in the intervention arm of PLCO. Marker levels of 946 men, of whom 100 were African American, were incorporated into a prespecified statistical model to predict high grade prostate cancer on biopsy. The detection of high grade prostate cancer in 94 men (10%) was enhanced by the 4-kallikrein panel with an AUC of 0.79 compared to 0.73 for PCPTRC (Prostate Cancer Prevention Trial Risk Calculator), representing a 0.060 increase (95% CI 0.032-0.088, p panel. In African American men, the 4-kallikrein panel model also enhanced high grade prostate cancer detection over that of prostate specific antigen (AUC 0.80 vs 0.67). As an illustration of clinical implications, using 1 cutoff point for biopsy (6% risk of high grade prostate cancer) with the 4-kallikrein panel model would have eliminated unnecessary biopsies in 420 per 1,000 men (42%) while detecting high grade prostate cancer in 83 of 93 (88%). In a multiethnic United States population, the 4-kallikrein panel demonstrated improved risk discrimination for high grade prostate cancer over conventional clinical variables (age, prostate specific antigen and digital rectal examination) as well as PCPTRC. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Tricyclic Neovibsanin Scaffold Inhibits Glioma by Targeting Glioma ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of tricyclic neovibsanin scaffold (TCNS) on cell viability, colony formation capacity and induction of apoptosis in glioma cells. Methods: 3-(4, 5-Dimethylthiazol-2-yl) 2, 5-diphe¬nyltetrazolium bromide (MTT) assay was used to analyze the effect of TCNS on cell proliferation. Light microscopic ...

  12. Gliomas do nervo óptico: estudo de 11 casos Optic nerve gliomas: a study of 11 cases

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Bleggi Torres

    1996-06-01

    Full Text Available Os gliomas do nervo óptico podem apresentar-se esporadicamente ou como componentes da neurofibromatose. São neoplasias raras, correspondendo a 2 a 5% dos tumores intracranianos e cerca de 6% dos tumores intra-orbitários. No presente estudo, analisamos 11 casos de glioma de nervo óptico diagnosticados em Curitiba num período de 25 anos, sendo 10 pacientes do sexo feminino e 1 do sexo masculino. As idades variaram de 3 a 25 anos; 6 pacientes apresentavam idades inferiores a 15 anos. Dos casos desta série, 27,3% (n=3 apresentavam associação com neurofibromatose. Quanto à localização dos tumores, em 5 pacientes a lesão estava restrita ao nervo óptico e no restante havia extensão para o quiasma óptico, região supra-selar, lobo frontal ou temporal. Todos os pacientes tinham astrocitoma pilocítico.Optic nerve gliomas may occur alone or as components of neurofibromatosis. They are rare tumors accounting for 2 to 5% of all intracranial tumors and 6% of the intra-orbitary neoplasms. The authors present 11 cases of optic nerve glioma diagnosed in Curitiba in the last 25 years. Out of these 11 patients there were 10 women and only 1 man. The ages ranged from 3 to 25 years old, and 6 patients were under 15 years. In this series, 27,3% (n=3 of the cases were associated with neurofibromatosis. Five patients had their tumors restricted to the optic nerve while the others had either extension to the optic chiasm, supra-selar region, frontal or temporal lobe. All the patients had pilocytic astrocytomas.

  13. [Experience of diagnosis and treatment of exogenous high-grade fever].

    Science.gov (United States)

    Xiong, Xing-jiang; Wang, Jie

    2011-06-01

    There is a regular pattern in the diagnosis and treatment of exogenous high-grade fever, of which the key point is formula syndrome identification. Syndrome differentiation of the six channels is appropriate for not only exogenous cold but also various other conditions. The diagnosis and treatment of high-grade fever can also follow the law of syndrome differentiation of the six channels. The theory of epidemic febrile diseases stems from and elaborates on an understanding of exogenous febrile conditions, so many effective formulas used to treat epidemic febrile diseases also have great value in the treatment of high-grade fever. Deteriorated syndrome, which is central to this condition, is very commonly seen in cases of high-grade fever, the key therapeutic principle of which is established according to syndromes. Allowing analysis that does not rigidly adhere to either established modern diagnosis or traditional Chinese syndromes, prominent achievements could be made in treating high-grade fever by summarizing the regular presenting patterns in terms of the constitution and symptoms.

  14. High-grade internal rectal prolapse: Does it explain so-called "idiopathic" faecal incontinence?

    Science.gov (United States)

    Bloemendaal, A L A; Buchs, N C; Prapasrivorakul, S; Cunningham, C; Jones, O M; Hompes, R; Lindsey, I

    2016-01-01

    Faecal incontinence is a multifactorial disorder, with multiple treatment options. The role of internal rectal prolapse in the aetiology of faecal incontinence is debated. Recent data has shown the importance of high-grade internal rectal prolapse in case of faecal incontinence. We aimed to determine the incidence and relevance of internal rectal prolapse in patients with faecal incontinence without an anal sphincter defect. Patient data, collected in a prospective pelvic floor database, were assessed. All females with moderate to severe pure faecal incontinence, without obstructed defecation and sphincter muscle defects, were included. Data on defecation proctography, anorectal physiology and incontinence scores were analysed. Of 2082 females in the database, 174 fitted the inclusion criteria. High-grade internal rectal prolapse was found in 49% of patients and was associated predominantly with urge faecal incontinence. Passive faecal incontinence was more common in low-grade compared to high-grade internal rectal prolapse patients. Maximum resting pressure was lower in older patients and in patients with high-grade compared to low-grade internal rectal prolapse. Internal rectal prolapse grade was not significantly correlated with faecal incontinence severity score. High-grade internal rectal prolapse is common in female patients suffering particularly urge faecal incontinence, without anal sphincter lesions. Defecation proctography should be routine in the work up of faecal incontinence. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  15. Iron labeling and pre-clinical MRI visualization of therapeutic human neural stem cells in a murine glioma model.

    Directory of Open Access Journals (Sweden)

    Mya S Thu

    2009-09-01

    supports the use of FE-Pro-labeled NSCs for real-time tracking in the clinical trial under development: "A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically modified Neural Stem Cells Expressing Escherichia coli Cytosine Deaminase for Treatment of Recurrent High-Grade Gliomas".

  16. Malignant glioma after bombshell injury.

    Science.gov (United States)

    Troost, D; Tulleken, C A

    1984-01-01

    A case of post-traumatic glioma is presented. The patient, wounded in the head in World War II by a bombshell, developed symptoms of an intracranial tumor in 1982. Histopathologically the tumor was an astrocytoma grade III. The tumor was in direct continuity with an old abscess membrane.

  17. A computational model incorporating neural stem cell dynamics reproduces glioma incidence across the lifespan in the human population.

    Directory of Open Access Journals (Sweden)

    Roman Bauer

    Full Text Available Glioma is the most common form of primary brain tumor. Demographically, the risk of occurrence increases until old age. Here we present a novel computational model to reproduce the probability of glioma incidence across the lifespan. Previous mathematical models explaining glioma incidence are framed in a rather abstract way, and do not directly relate to empirical findings. To decrease this gap between theory and experimental observations, we incorporate recent data on cellular and molecular factors underlying gliomagenesis. Since evidence implicates the adult neural stem cell as the likely cell-of-origin of glioma, we have incorporated empirically-determined estimates of neural stem cell number, cell division rate, mutation rate and oncogenic potential into our model. We demonstrate that our model yields results which match actual demographic data in the human population. In particular, this model accounts for the observed peak incidence of glioma at approximately 80 years of age, without the need to assert differential susceptibility throughout the population. Overall, our model supports the hypothesis that glioma is caused by randomly-occurring oncogenic mutations within the neural stem cell population. Based on this model, we assess the influence of the (experimentally indicated decrease in the number of neural stem cells and increase of cell division rate during aging. Our model provides multiple testable predictions, and suggests that different temporal sequences of oncogenic mutations can lead to tumorigenesis. Finally, we conclude that four or five oncogenic mutations are sufficient for the formation of glioma.

  18. Research and development of intelligent controller for high-grade sanitary ware

    Science.gov (United States)

    Bao, Kongjun; Shen, Qingping

    2013-03-01

    With the social and economic development and people's living standards improve, more and more emphasis on modern society, people improve the quality of family life, the use of intelligent controller applications in high-grade sanitary ware physiotherapy students. Analysis of high-grade sanitary ware physiotherapy common functions pointed out in the production and use of the possible risks, proposed implementation of the system hardware and matching, given the system software implementation process. High-grade sanitary ware physiotherapy intelligent controller not only to achieve elegant and beautiful, simple, physical therapy, water power, deodorant, multi-function, intelligent control, to meet the consumers, the high-end sanitary ware market, strong demand, Accelerate the enterprise product Upgrade and improve the competitiveness of enterprises.

  19. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia.

    Science.gov (United States)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

    2012-11-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.

  20. Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

    DEFF Research Database (Denmark)

    Tietze, Anna; Mouridsen, Kim; Lassen-Ramshad, Yasmin

    2015-01-01

    Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome...... than does the established PWI angiogenesis marker, cerebral blood volume (CBV). Material and Methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and COV, its ratio to blood mean transit time, provide indices...... of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival...

  1. Response-predictive gene expression profiling of glioma progenitor cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sylvia Moeckel

    Full Text Available High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a to enrich specimens for brain tumor initiating cells and (b to confront cells with a therapeutic agent before expression profiling.As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

  2. The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain

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    Mursch, Kay; Mursch, Julianne Behnke [Dept. of Neurosurgery, Zentralklinik, Bad Berka (Germany); Scholz, Martin [Dept. of Neurosurgery, Klinikum Duisburg, Duisburg (Germany); Brueck, Wolfgang [Dept. of Neuropathology, Georg August Universitaet, Goettingen (Germany)

    2017-01-15

    The aim of this study was to investigate whether intraoperative ultrasonography (IOUS) helped the surgeon navigate towards the tumor as seen in preoperative magnetic resonance imaging and whether IOUS was able to distinguish between tumor margins and the surrounding tissue. Twenty-five patients suffering from high-grade gliomas who were previously treated by surgery and radiotherapy were included. Intraoperatively, two histopathologic samples were obtained a sample of unequivocal tumor tissue (according to anatomical landmarks and the surgeon's visual and tactile impressions) and a small tissue sample obtained using a navigated needle when the surgeon decided to stop the resection. This specimen was considered to be a boundary specimen, where no tumor tissue was apparent. The decision to take the second sample was not influenced by IOUS. The effect of IOUS was analyzed semi-quantitatively. All 25 samples of unequivocal tumor tissue were histopathologically classified as tumor tissue and were hyperechoic on IOUS. Of the boundary specimens, eight were hypoechoic. Only one harbored tumor tissue (P=0.150). Seventeen boundaries were moderately hyperechoic, and these samples contained all possible histological results (i.e., tumor, infiltration, or no tumor). During surgery performed on relapsed, irradiated, high-grade gliomas, IOUS provided a reliable method of navigating towards the core of the tumor. At borders, it did not reliably distinguish between remnants or tumor-free tissue, but hypoechoic areas seldom contained tumor tissue.

  3. The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain

    Directory of Open Access Journals (Sweden)

    Kay Mursch

    2017-01-01

    Full Text Available Purpose The aim of this study was to investigate whether intraoperative ultrasonography (IOUS helped the surgeon navigate towards the tumor as seen in preoperative magnetic resonance imaging and whether IOUS was able to distinguish between tumor margins and the surrounding tissue. Methods Twenty-five patients suffering from high-grade gliomas who were previously treated by surgery and radiotherapy were included. Intraoperatively, two histopathologic samples were obtained a sample of unequivocal tumor tissue (according to anatomical landmarks and the surgeon’s visual and tactile impressions and a small tissue sample obtained using a navigated needle when the surgeon decided to stop the resection. This specimen was considered to be a boundary specimen, where no tumor tissue was apparent. The decision to take the second sample was not influenced by IOUS. The effect of IOUS was analyzed semi-quantitatively. Results All 25 samples of unequivocal tumor tissue were histopathologically classified as tumor tissue and were hyperechoic on IOUS. Of the boundary specimens, eight were hypoechoic. Only one harbored tumor tissue (P=0.150. Seventeen boundaries were moderately hyperechoic, and these samples contained all possible histological results (i.e., tumor, infiltration, or no tumor. Conclusion During surgery performed on relapsed, irradiated, high-grade gliomas, IOUS provided a reliable method of navigating towards the core of the tumor. At borders, it did not reliably distinguish between remnants or tumor-free tissue, but hypoechoic areas seldom contained tumor tissue.

  4. Biological tumour volumes of gliomas in early and standard 20-40 min18F-FET PET images differ according to IDH mutation status.

    Science.gov (United States)

    Unterrrainer, M; Winkelmann, I; Suchorska, B; Giese, A; Wenter, V; Kreth, F W; Herms, J; Bartenstein, P; Tonn, J C; Albert, N L

    2018-02-27

    For the clinical evaluation of O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET images, the use of standard summation images obtained 20-40 min after injection is recommended. However, early summation images obtained 5-15 min after injection have been reported to allow better differentiation between low-grade glioma (LGG) and high-grade glioma (HGG) by capturing the early 18 F-FET uptake peak specific for HGG. We compared early and standard summation images with regard to delineation of the PET-derived biological tumour volume (BTV) in correlation with the molecular genetic profile according the updated 2016 WHO classification. The analysis included 245 patients with newly diagnosed, histologically verified glioma and a positive 18 F-FET PET scan prior to any further treatment. BTVs were delineated during the early 5-15 min and standard 20-40 min time frames using a threshold of 1.6 × background activity and were compared intraindividually. Volume differences between early and late summation images of >20% were considered significant and were correlated with WHO grade and the molecular genetic profile (IDH mutation and 1p/19q codeletion status). In 52.2% of the patients (128/245), a significant difference in BTV of >20% between early and standard summation images was found. While 44.3% of WHO grade II gliomas (31 of 70) showed a significantly smaller BTV in the early summation images, 35.0% of WHO grade III gliomas (28/80) and 37.9% of WHO grade IV gliomas (36/95) had a significantly larger BTVs. Among IDH-wildtype gliomas, an even higher portion (44.4%, 67/151) showed significantly larger BTVs in the early summation images, which was observed in 5.3% (5/94) of IDH-mutant gliomas only: most of the latter had significantly smaller BTVs in the early summation images, i.e. 51.2% of IDH-mutant gliomas without 1p/19q codeletion (21/41) and 39.6% with 1p/19q codeletion (21/53). BTVs delineated in early and standard summation images differed significantly in

  5. Measurements of diagnostic examination performance using quantitative apparent diffusion coefficient and proton MR spectroscopic imaging in the preoperative evaluation of tumor grade in cerebral gliomas

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    Server, Andres, E-mail: a.s.alonso@medisin.uio.no [Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo University Hospital-Ullevaal and University of Oslo, Kirkeveien 166, NO-0407 Oslo (Norway); Kulle, Bettina, E-mail: b.k.andreassen@medisin.uio.no [Department of Biostatistics, University of Oslo, Oslo (Norway); Gadmar, Oystein B., E-mail: gays@uus.no [Interventional Centre, Oslo University Hospital and Institute for Hospital Medicine, University of Oslo, Oslo (Norway); Josefsen, Roger, E-mail: roos@uus.no [Department of Neurosurgery, Oslo University Hospital-Ullevaal, Oslo (Norway); Kumar, Theresa, E-mail: thku@uus.no [Department of Pathology, Oslo University Hospital-Ullevaal, Oslo (Norway); Nakstad, Per H., E-mail: pena@uus.no [Section of Neuroradiology, Department of Radiology and Nuclear Medicine, Oslo University Hospital-Ullevaal and University of Oslo, Kirkeveien 166, NO-0407 Oslo (Norway)

    2011-11-15

    Purpose: Tumor grading is very important both in treatment decision and evaluation of prognosis. While tissue samples are obtained as part of most therapeutic approaches, factors that may result in inaccurate grading due to sampling error (namely, heterogeneity in tissue sampling, as well as tumor-grade heterogeneity within the same tumor specimen), have led to a desire to use imaging better to ascertain tumor grade. The purpose in our study was to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and accuracy of diffusion-weighted MR imaging (DWI), proton MR spectroscopic imaging (MRSI) or both in grading primary cerebral gliomas. Materials and methods: We performed conventional MR imaging (MR), DWI, and MRSI in 74 patients with newly diagnosed brain gliomas: 59 patients had histologically verified high-grade gliomas: 37 glioblastomas multiform (GBM) and 22 anaplastic astrocytomas (AA), and 15 patients had low-grade gliomas. Apparent diffusion coefficient (ADC) values of tumor and peritumoral edema, and ADC ratios (ADC in tumor or peritumoral edema to ADC of contralateral white matter, as well as ADC in tumor to ADC in peritumoral edema) were determined from three regions of interest. The average of the mean, maximum, and minimum for ADC variables was calculated for each patient. The metabolite ratios of Cho/Cr and Cho/NAA at intermediate TE were assessed from spectral maps in the solid portion of tumor, peritumoral edema and contralateral normal-appearing white matter. Tumor grade determined with the two methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed to determine optimum thresholds for tumor grading. Measures of diagnostic examination performance, such as sensitivity, specificity, PPV, NPV, AUC, and accuracy for identifying high-grade gliomas were also calculated

  6. Measurements of diagnostic examination performance using quantitative apparent diffusion coefficient and proton MR spectroscopic imaging in the preoperative evaluation of tumor grade in cerebral gliomas

    International Nuclear Information System (INIS)

    Server, Andres; Kulle, Bettina; Gadmar, Oystein B.; Josefsen, Roger; Kumar, Theresa; Nakstad, Per H.

    2011-01-01

    Purpose: Tumor grading is very important both in treatment decision and evaluation of prognosis. While tissue samples are obtained as part of most therapeutic approaches, factors that may result in inaccurate grading due to sampling error (namely, heterogeneity in tissue sampling, as well as tumor-grade heterogeneity within the same tumor specimen), have led to a desire to use imaging better to ascertain tumor grade. The purpose in our study was to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and accuracy of diffusion-weighted MR imaging (DWI), proton MR spectroscopic imaging (MRSI) or both in grading primary cerebral gliomas. Materials and methods: We performed conventional MR imaging (MR), DWI, and MRSI in 74 patients with newly diagnosed brain gliomas: 59 patients had histologically verified high-grade gliomas: 37 glioblastomas multiform (GBM) and 22 anaplastic astrocytomas (AA), and 15 patients had low-grade gliomas. Apparent diffusion coefficient (ADC) values of tumor and peritumoral edema, and ADC ratios (ADC in tumor or peritumoral edema to ADC of contralateral white matter, as well as ADC in tumor to ADC in peritumoral edema) were determined from three regions of interest. The average of the mean, maximum, and minimum for ADC variables was calculated for each patient. The metabolite ratios of Cho/Cr and Cho/NAA at intermediate TE were assessed from spectral maps in the solid portion of tumor, peritumoral edema and contralateral normal-appearing white matter. Tumor grade determined with the two methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed to determine optimum thresholds for tumor grading. Measures of diagnostic examination performance, such as sensitivity, specificity, PPV, NPV, AUC, and accuracy for identifying high-grade gliomas were also calculated

  7. Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

    NARCIS (Netherlands)

    Costa, A.F.; Altemani, A.; Vékony, H.; Bloemena, E.; Fresno, F.; Suárez, C.; Llorente, J.L.; Hermsen, M.

    2010-01-01

    Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACCHGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGTis generally considered to be an aggressive variant of ACC, even more

  8. Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type

    NARCIS (Netherlands)

    Costa, A.F.; Altemani, A.; Vékony, H.; Bloemena, E.; Fresno, F.; Suárez, C.; Llorente, J.L.; Hermsen, M.

    2011-01-01

    Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more

  9. Survival and prognostic factors at time of diagnosis in high-grade appendicular osteosarcoma

    DEFF Research Database (Denmark)

    Colding-Rasmussen, Thomas; Thorn, Andrea Pohly; Horstmann, Peter

    2018-01-01

    BACKGROUND: Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diag...

  10. Patient Outcomes in the Operative and Nonoperative Management of High-Grade Spondylolisthesis in Children

    DEFF Research Database (Denmark)

    Lundine, K. M.; Lewis, S. J.; Al-Aubaidi, Zaid

    2014-01-01

    Background:The optimal management of high-grade spondylolisthesis in the growing child is controversial. Some authors have advocated for surgery in all cases regardless of symptoms. Surgical intervention results in a >10% risk of complications with increased risk of neurological injury associated...

  11. Multiparametric Magnetic Resonance Imaging for Discriminating Low-Grade From High-Grade Prostate Cancer

    NARCIS (Netherlands)

    Vos, E.K.; Kobus, T.; Litjens, G.J.S.; Hambrock, T.; Hulsbergen-van de Kaa, C.A.; Barentsz, J.O.; Maas, M.C.; Scheenen, T.W.J.

    2015-01-01

    The aim of this study was to determine and validate the optimal combination of parameters derived from 3-T diffusion-weighted imaging, dynamic contrast-enhanced imaging, and magnetic resonance (MR) spectroscopic imaging for discriminating low-grade from high-grade prostate cancer (PCa).The study was

  12. Low- to high-grade metamorphic transition in the Southern part of Karnataka Nucleus, India

    Science.gov (United States)

    Naqvi, S. M.

    1988-01-01

    The southern part of Karnataka Nucleus has a strong imprint of 2.6 Ga metamorphism. This has affected the schist belts of Karnataka Nucleus from greenschist to upper amphibolite facies. The higher grades of metamorphism are in the Holenarasipur, Nuggihalli, Krishnarajpet, Hadnur and Melkote schist belts. In the high grade transition zone, around Sargur only keels of schist belts are preserved and occur as highly dismembered, disconnected belts with the top and bottom of the stratigraphic column obliterated due to high grade metamorphism and accompanying migmatization. Absence of high-grade metamorphic minerals in the sediments of the Dharwar schist belts supports the contention that high grade metamorphism post-dated the Dharwar sedimentation and occurred around 2.6 Ga ago. Sargur type metamorphism occurred at upper crustal levels and charnockite type metamorphism occurred in lower crustal levels. The P-T conditions for the mineral assemblage in metapelites of Sargur Group indicate burial depths up to at least 15 km suggesting that they were subducted and later obducted during the development of Early Proterozoic Mobile Belt along the southern border of the Karnataka Nucleus.

  13. Transition from low-grade endometrial stromal sarcoma to high-grade endometrial stromal sarcoma.

    Science.gov (United States)

    Ohta, Yoshiki; Suzuki, Takao; Omatsu, Mutsuko; Hamatani, Shigeharu; Shiokawa, Akira; Kushima, Miki; Ota, Hidekazu

    2010-07-01

    We report on a case of a primary low-grade endometrial stromal sarcoma (ESS) that progressed to a secondary high-grade ESS. In the secondary tumor, the immunohistochemical profile and focal tumor cell proliferation pattern suggested that this tumor was not truly undifferentiated, but possessed features of endometrial stroma. Low-grade ESS of our patient's primary tumor showed p53 protein overexpression, which is unusual in low-grade ESS, and her secondary high-grade ESS showed more prominent p53 immunoreactivity. This indicates that low-grade ESS that shows p53 immunoreactivity might progress to high-grade ESS, and it is considered that such cases of low-grade ESS should pay attention to the prognosis. Immunoreactivity for epidermal growth factor receptor was observed in both tumors, suggesting a relationship between the primary and secondary tumors in our case. Further study requires more immunohistochemical data for cases in which low-grade ESS transitions to high-grade ESS; in particular, data on epidermal growth factor receptor expression are necessary to define new therapeutic strategies for ESS.

  14. Transition of low-grade to high-grade endometrial stromal sarcoma: a case report.

    Science.gov (United States)

    Kanda, M; Sonoyama, A; Hirano, H; Kizaki, T; Ohara, N

    2013-01-01

    The transition of low-grade endometrial stromal sarcoma (ESS) to high-grade ESS remains a rare clinical event. A patient presented with abdominal pain and abnormal genital bleeding. She underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal disseminated lesions. Pathological examination revealed low-grade ESS in the uterus and omentum. Immunohistochemical examination showed immunoreactivity for CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor, progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative. P53 immunoreactivity was noted only in the omental lesion. Despite performing six courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent ileostomy and resection of peritoneal disseminated lesions. Pathology showed high-grade ESS in the recurrent lesion of the ileum, which was characterized by severe cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index, and immunoreactivity for p53. Although rare, the transition of low-grade ESS to high-grade ESS may occur and suggests the worsening of the prognosis. Pathological examination and immunohistochemistry are useful for the diagnosis of the transition of low-grade ESS to high-grade ESS.

  15. L5 pedicle subtraction osteotomy for high-grade isthmic spondylolisthesis.

    Science.gov (United States)

    Radcliff, Kristen E; Jakoi, Andre M

    2015-04-01

    To the authors' knowledge, this is the first article to present a pedicle subtraction osteotomy in the lumbar spine to correct and stabilize a high-grade isthmic spondylolisthesis, which poses many challenges with regard to treatment options and outcomes. The optimal surgical treatment for high-grade spondylolisthesis is controversial, but the goals of treatment are to stabilize the affected spinal levels and to decompress the neural elements. A pedicle subtraction osteotomy is a reconstructive procedure that addresses fixed sagittal imbalance by increasing lumbar lordosis through posterior spinal column shortening. The authors report a 46-year-old patient with chronic, progressively worsening back and leg radiculopathy accompanied by sagittal plane malalignment and for which a pedicle subtraction osteotomy was performed. The procedure yielded stabilization of the patient's lumbar spondylolisthesis and sagittal plane alignment was restoration. At 3 months postoperatively, the patient's pain had fully resolved and her motor and neurologic examination exhibited no deficits. At 24 months postoperatively, she was still symptom-free and ambulating without assistance. This report is the first documented successful pedicle subtraction osteotomy in the treatment of high-grade spondylolisthesis. This report indicates that certain patient populations may be amenable to pedicle subtraction osteotomy as a treatment option for pathology involving high-grade isthmic spondylolisthesis. Copyright 2015, SLACK Incorporated.

  16. Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Changes

    Science.gov (United States)

    2014-10-01

    iso - form expression in luteal phase fallopian tube epithelium and high-grade serous carcinoma. Endocr Relat Cancer (2011) 18:221–34. doi:10.1530/ERC-10...0 -1 -2 -3 8 norma ] samp1es - ,-, - • • 1 CM Control Lovastatin (50 mg/kg) C on tro l S ta tin (5 0m g/ kg ) S ta

  17. Improving vaccine efficacy against malignant glioma

    OpenAIRE

    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

    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-13R��2 and/or histone H3 K27M, while in adults, treatm...

  18. TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients

    International Nuclear Information System (INIS)

    Wang, Chao; Cao, Shouqiang; Yan, Ying; Ying, Qiao; Jiang, Tao; Xu, Ke; Wu, Anhua

    2010-01-01

    Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro. RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively. RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients(P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro. Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy

  19. Effect of High-Grade Preoperative Knee Laxity on Anterior Cruciate Ligament Reconstruction Outcomes.

    Science.gov (United States)

    Magnussen, Robert A; Reinke, Emily K; Huston, Laura J; Hewett, Timothy E; Spindler, Kurt P

    2016-12-01

    Knee laxity in the setting of suspected anterior cruciate ligament (ACL) injury is frequently assessed through physical examination using the Lachman, pivot-shift, and anterior drawer tests. The degree of laxity noted on these examinations may influence treatment decisions and prognosis. Increased preoperative knee laxity would be associated with increased risk of subsequent revision ACL reconstruction and worse patient-reported outcomes 2 years postoperatively. Cohort study; Level of evidence, 2. From an ongoing prospective cohort study, 2333 patients who underwent primary isolated ACL reconstruction without collateral or posterior cruciate ligament injury were identified. Patients reported by the operating surgeons as having an International Knee Documentation Committee (IKDC) grade D for Lachman, anterior drawer, or pivot-shift examination were classified as having high-grade laxity. Multiple logistic regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with increased odds of undergoing revision ACL reconstruction within 2 years of the index procedure, controlling for patient age, sex, Marx activity level, level of competition, and graft type. Multiple linear regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with worse IKDC score or Knee injury and Osteoarthritis Outcome Score Knee-Related Quality of Life subscale (KOOS-QOL) scores at a minimum 2 years postoperatively, controlling for baseline score, patient age, ethnicity, sex, body mass index, marital status, smoking status, sport participation, competition level, Marx activity rating score, graft type, and articular cartilage and meniscus status. Pre-reconstruction laxity data were available for 2325 patients (99.7%). Two-year revision data were available for 2259 patients (96.8%), and patient-reported outcomes were available for 1979 patients (84.8%). High-grade preoperative laxity was noted in 743 patients

  20. Prevalence of Neurotropic Viruses in Malignant Glioma and Their Onco-Modulatory Potential.

    Science.gov (United States)

    Strojnik, Tadej; Duh, Darja; Lah, Tamara T

    2017-01-01

    the association between infectious agents and tumour aetiology is relevant in about 20% of cases. We tested high-grade glioma tissues from 45 patients for the presence of viral nucleic acids of six herpes viruses, human adenoviruses (A-G), and two neurotropic human viruses (enteroviruses, tick-borne encephalitis virus). Real-time polymerase chain reaction was used with immunolabelling. Three species of herpes viruses were detected: HSV-2, Epstein-Barr virus (EBV), HHV-6, and one human enterovirus. Plasma of these patients was not infected with viruses. In sera of patients, low HSV-1 and HSV-2 immunoreactivity were found in five cases, although these were not detected in their tumour tissue. Certain common viruses (HSV-1, HSV-2, EBV, human cytomegalovirus) are chronically present in the sera of patients with glioblastoma, but not necessarily in their tissues. Possibly both are associated with glioma progression, as we only found viruses in glioblastoma multiforme, but not in lower stages of glioma. Low titres of viruses in the blood indicate chronic viral virulence. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Prevalence of Neurotropic Viruses in Malignant Glioma and Their Onco-Modulatory Potential

    Science.gov (United States)

    STROJNIK, TADEJ; DUH, DARJA; LAH, TAMARA T

    2017-01-01

    Background: the association between infectious agents and tumour aetiology is relevant in about 20% of cases. Patients and Methods. We tested high-grade glioma tissues from 45 patients for the presence of viral nucleic acids of six herpes viruses, human adenoviruses (A-G), and two neurotropic human viruses (enteroviruses, tick-borne encephalitis virus). Real-time polymerase chain reaction was used with immunolabelling. Results: Three species of herpes viruses were detected: HSV-2, Epstein-Barr virus (EBV), HHV-6, and one human enterovirus. Plasma of these patients was not infected with viruses. In sera of patients, low HSV-1 and HSV-2 immunoreactivity were found in five cases, although these were not detected in their tumour tissue. Conclusion: Certain common viruses (HSV-1, HSV-2, EBV, human cytomegalovirus) are chronically present in the sera of patients with glioblastoma, but not necessarily in their tissues. Possibly both are associated with glioma progression, as we only found viruses in glioblastoma multiforme, but not in lower stages of glioma. Low titres of viruses in the blood indicate chronic viral virulence. PMID:28358704

  2. Transforaminal percutaneous endoscopic lumbar discectomy for very high-grade migrated disc herniation.

    Science.gov (United States)

    Ahn, Yong; Jang, Il-Tae; Kim, Woo-Kyung

    2016-08-01

    Transforaminal percutaneous endoscopic lumbar discectomy (PELD) for high-grade migrated disc herniation has been regarded as a challenging task, but because of the remarkable improvement in navigable instruments and advanced epiduroscopic technique, it can be used for the treatment of high- or very high-grade migrated disc herniation. The purpose of this study was to describe in detail the standardized technique of transforaminal PELD for very high-grade migrated disc herniation and demonstrate the clinical results. Very high-grade lumbar migrated disc herniation was defined as a disc migration beyond the inferior margin of the pedicle. Thirteen consecutive patients with very high-grade lumbar migrated disc herniation were treated with transforaminal PELD, which has three stages: (1) direction-oriented transforaminal approach, (2) release of periannular anchorage, and (3) epiduroscopic fragmentectomy with navigable instruments. The surgical outcomes were assessed using the visual analogue pain score (VAS), Oswestry disability index (ODI), and modified Macnab criteria. The operated levels were L3-4 in 2 (15.4%) patients, L4-5 in 10 (76.9%), and L5-S1 in 1 (7.7%). The directions of migration were cranial in 8 patients and caudal in 5. The mean VAS for leg pain improved from 7.86±1.28 preoperatively to 2.54±1.51 at 6 weeks postoperatively and 1.85±1.07 at 1year postoperatively (Pdisc herniation, and a standardized technique may provide a reliable and reproducible result. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Identifying patients at risk for high-grade intra-abdominal hypertension following trauma laparotomy.

    Science.gov (United States)

    Strang, Steven G; Van Imhoff, Diederik L; Van Lieshout, Esther M M; D'Amours, Scott K; Van Waes, Oscar J F

    2015-05-01

    Abdominal Compartment Syndrome (ACS) is an uncommon but deleterious complication after trauma laparotomy. Early recognition of patients at risk of developing ACS is crucial for their outcome. The aim of this study was to compare the characteristics of patients who developed high-grade intra-abdominal hypertension (IAH) (i.e., grade III or IV; intra-abdominal pressure, IAP >20 mm Hg) following an injury-related laparotomy versus those who did not (i.e., IAP ≤20 mm Hg). A retrospective analysis of consecutive trauma patients admitted to a level 1 trauma centre in Australia between January 1, 1995 and January 31, 2010 was performed. A comparison was made between characteristics of patients who developed high-grade IAH following trauma laparotomy versus those who did not. A total of 567 patients (median age 31 years) were included in this study. Of these patients 10.2% (58/567) developed high-grade IAH of which 51.7% (30/58) developed ACS. Patients with high-grade IAH were older (pgrade IAH received larger volumes of crystalloids (pgrade IAH suffered higher mortality rates (25.9% (15/58) vs. 12.2% (62/509); p=0.012). Of all patients who underwent a trauma laparotomy, 10.2% developed high-grade IAH, which increases the risk of mortality. Patients with acidosis, coagulopathy, and hypothermia were especially at risk. In these patients, the abdomen should be left open until adequate resuscitation has been achieved, allowing for definitive surgery. This is a level III retrospective study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Risk factors for high-grade envenomations after French viper bites in children.

    Science.gov (United States)

    Claudet, Isabelle; Maréchal, Céline; Gurrera, Emmanuel; Cordier, Laurie; Honorat, Raphaele; Grouteau, Erick

    2012-07-01

    Viper bites and subsequent evolution to severe envenomations are more frequent in children. The aims of this study were to describe the clinical, biological, and therapeutic characteristics of children bitten by vipers in France and to identify risk factors associated with severe envenomations. A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary-level children hospital. Collected data were age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity; presence of fang marks; prehospital care; use of specific immunotherapy and associated treatments; length of stay; and hospital course. Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8 ± 4.1 years. Bites were most often located on the lower extremities (77%). The classification of envenomation was: 83% low grade (absence or minor envenomation) and 17% high-grade (moderate to severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav). Being bitten on an upper extremity (P level (P = 0.016) were associated with a significant risk of high-grade envenomation. In the multivariate analysis, 3 factors remained significant: upper-extremity location (relative risk [RR], 60.5 [3.5-1040]; P = 0.005), immediate violent pain (RR, 21.5 [1.3-364.5]; P = 0.03), and female sex (RR, 17.5 [0.9-320.3]; P = 0.053). A certain number of criteria seem related to more significant risk of progression to high-grade envenomation. Bites to the upper extremities should be carefully observed because of the risk of evolution to a high-grade envenomation.

  5. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Blood magnesium, and the interaction with calcium, on the risk of high-grade prostate cancer.

    Directory of Open Access Journals (Sweden)

    Qi Dai

    2011-04-01

    Full Text Available Ionized calcium (Ca and magnesium (Mg compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio are associated with greater prostate cancer risk.In this biomarker sub-study of the Nashville Men's Health Study (NMHS, we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7 and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors.Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively. Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85. An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36 adjusted for serum Ca and Mg. In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment.Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca.

  7. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  8. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude...... that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal...... brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...

  9. Body mass index, serum total cholesterol, and risk of gastric high-grade dysplasia

    Science.gov (United States)

    Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun

    2016-01-01

    Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk

  10. Assessment of glioma response to radiotherapy using 3D pulsed-continuous arterial spin labeling and 3D segmented volume

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Peng; Li, Jianrui; Diao, Qiang; Lin, YuanKai; Zhang, Jun; Li, Lin; Yang, Gang; Fang, Xiaokun; Li, Xie; Chen, YingQi; Zheng, Ling, E-mail: lingzheng1989@yeah.net; Lu, Guangming, E-mail: guangminglu1905@163.com

    2016-11-15

    Background: Gliomas are the most common primary brain tumors in adults, in some cases, radiotherapy may be the preferred treatment option especially for elderly people who cannot endure surgery. Therefore, it is necessary to evaluate the effects of radiotherapy on glioma. Arterial spin labeling (ASL) is an MR imaging technique that allows for a quantitative determination of cerebral blood flow (CBF) noninvasively. Tumor volume is still an important determinant for evaluating treatment response. The purpose of this study was to investigate the relationship between the tumor perfusion parameters and tumor volume and assess the effects of radiotherapy on glioma using pulsed-continuous arterial spin labeling (pcASL) technique. Methods: 35 patients with gliomas, histologically classified as low-grade group (n = 16) and high-grade group (n = 19), treated with radiotherapy only or before using other therapies were included in this study. MR examinations, including T1 weighted image and pcASL, were performed before and 4, 8, 12, 16 weeks after radiotherapy. Regional CBF of normal tissue, mean tumor blood flow (TBF{sub mean}), maximum tumor blood flow (TBF{sub max}), and tumor volume were evaluated at each time point. Both the percentage change in CBF (CBF ratio), TBF{sub mean} (TBF{sub mean} ratio), TBF{sub max} (TBF{sub max} ratio) and the percentage change in tumor volume (volume ratio) were calculated using values obtained before and after radiotherapy. The correlation between the volume ratio and CBF ratio, TBF{sub mean} ratio, TBF{sub max} ratio was assessed using linear regression analysis and Pearson’s correlation. Results: The TBF{sub mean} and TBF{sub max} of high-grade gliomas were significantly higher than that of low-grade group. In high-grade group, a strong correlation was demonstrated between the tumor volume and the TBF{sub max} before radiotherapy (R{sup 2} = 0.35, r{sub s} = 0.59, p < 0.05). There was also a significant correlation between the TBF

  11. The Glioma International Case-Control Study

    DEFF Research Database (Denmark)

    Amirian, E. Susan; Armstrong, Georgina N; Zhou, Renke

    2016-01-01

    describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen......Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly...... collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions....

  12. Rare earth element patterns in Archean high-grade metasediments and their tectonic significance

    Science.gov (United States)

    Taylor, Stuart Ross; Rudnick, Roberta L.; Mclennan, Scott M.; Eriksson, Kenneth A.

    1986-01-01

    REE data on metasedimentary rocks from two different types of high-grade Archean terrains are presented and analyzed. The value of REEs as indicators of crustal evolution is explained; the three geologic settings (in North America, Southern Africa, and Australia) from which the samples were obtained are described; and the data are presented in extensive tables and graphs and discussed in terms of metamorphic effects, the role of accessory phases, provenance, and tectonic implications (recycling, the previous extent of high-grade terrains, and a model of Archean crustal growth). The diversity of REE patterns in shallow-shelf metasediments is attributed to local provenance, while the Eu-depleted post-Archean patterns are associated with K-rich plutons from small, stable early Archean terrains.

  13. Histochemical and ultrastructural study of an elastofibroma dorsi coexisting with a high grade spindle cell sarcoma

    Directory of Open Access Journals (Sweden)

    M Alberghini

    2009-06-01

    Full Text Available Elastofibroma dorsi is a pseudotumoral fibroproliferative lesion characterized by polymorphic fiber-like deposits of elastinophilic material. Several theories have been reported explaining the pathogenesis of elastofibroma. Recent cytogenetic studies have demonstrated chromosomal instability in elastofibromas, not normally observed in non-neoplastic tissues. These chromosomal defects are commonly observed in aggressive fibromatosis too. Such clinical observations suggest a multistage pathogenetic mechanism for the onset of elastofibroma. This study, using histochemical, immunohistochemical staining techniques, and ultrastructural examination, describes the detection of an otherwise typical elastofibroma contextual to a high grade sarcoma. Hence, the coexistence of elastofibroma and high-grade sarcoma may suggest a causal link between the two pathological entities. The results obtained suggest that the coexistence of the two pathological entities is conceivably coincidental.

  14. Rare earth element patterns in Archean high-grade metasediments and their tectonic significance

    Science.gov (United States)

    Taylor, Stuart Ross; Rudnick, Roberta L.; McLennan, Scott M.; Eriksson, Kenneth A.

    1986-10-01

    REE data on metasedimentary rocks from two different types of high-grade Archean terrains are presented and analyzed. The value of REEs as indicators of crustal evolution is explained; the three geologic settings (in North America, Southern Africa, and Australia) from which the samples were obtained are described; and the data are presented in extensive tables and graphs and discussed in terms of metamorphic effects, the role of accessory phases, provenance, and tectonic implications (recycling, the previous extent of high-grade terrains, and a model of Archean crustal growth). The diversity of REE patterns in shallow-shelf metasediments is attributed to local provenance, while the Eu-depleted post-Archean patterns are associated with K-rich plutons from small, stable early Archean terrains.

  15. Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

    Science.gov (United States)

    2015-10-01

    that serous tubal intraepithelial carcinoma (STIC) is the precursor and not a metastasis of many, if not most, pelvic high-grade serous carcinomas...HGSCs) but we believe all the other proposed candidates should be investigated in order to determine if STIC is the precursor of all ovarian and pelvic ...regulated process to maintain genetic stability (20). Overexpression of cyclin E1 can be detected in many HGSCs as well as in some STICs (14). In fact

  16. PREVALENCE OF HUMAN PAPILLOMAVIRUS GENOTYPES IN LOW AND HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS AT CERVICAL TISSUE

    OpenAIRE

    Prasetyo, Rizki Eko; Mastutik, Gondo; Mustokoweni, Sjahjenny

    2017-01-01

    HPV infection is known to cause cervical cancer. This study aimed to identify the variant of HPV genotypes of cervical precancerous lesions from low grade squamous intraepithelial lesion  (LSIL) and high grade squamous intraepithelial lesion (HSIL). This was an explorative study using formalin fix paraffin embedded (FFPE) from cervical precancerous lesions at Dr. Soetomo Hospital, Surabaya. DNA was extracted from FFPE and hybridized for HPV genotyping using Ampliquality HPV Type Express kit (...

  17. Radiologic and clinical outcomes of surgery in high grade spondylolisthesis treated with temporary distraction rod.

    Science.gov (United States)

    Omidi-Kashani, Farzad; Hootkani, Alireza; Jarahi, Lida; Rezvan, Manizheh; Moayedpour, Amir

    2015-03-01

    Surgical techniques used in the treatment of patients with high grade lumbar spondylolisthesis (> 50% slippage) are usually associated with a great deal of controversies. We aim to evaluate the surgical outcomes of high grade spondylolisthesis treated with an intraoperative temporary distraction rod. We retrospectively studied 21 patients (14 females and 7 males), aged 50.4 ± 9.2 years, who had high grade lumbar spondylolisthesis that was treated with intraoperative temporary distraction rods, neural decompression, pedicular screw fixation, and posterolateral fusion involving one more intact upper vertebra. The mean follow-up period was 39.2 months. Radiologic and clinical outcomes were measured by slip angle, slip percentage, correction rate, Oswestry Disability Index (ODI), visual analogue scale (VAS), patient's satisfaction rate in the pre- and postoperative period. Data were analyzed by SPSS ver. 11.5. Analysis of the preoperative visits and final follow-up visits indicated that surgery could improve ODI, lumbar VAS, and leg VAS from 60.5% to 8.2%, from 6.7 to 2.2, and from 6.9 to 1.3, respectively. Slip angle and slip percentage were also changed from -8° to -15° and from 59.2% to 21.4%, respectively. Mean correction rate at the final follow-up visit was 64.1%. Loss of correction was insignificant and a neurologic complication occurred in one patient due to misplacement of one screw. Excellent and good levels of satisfaction were observed in 90.5% of the patients. In the surgical treatment of refractory high grade spondylolisthesis, the use of a temporary distraction rod to reduce the slipped vertebra in combination with neural decompression, posterolateral fusion, and longer instrumentation is associated with satisfactory clinical and radiologic outcomes.

  18. Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett’s Esophagus

    Science.gov (United States)

    Whitson, Matthew J.; Falk, Gary W.

    2015-01-01

    Article Synopsis The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett’s esophagus remains the most well established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett’s esophagus. This article will review both risk and protective factors for neoplastic progression in patients with Barrett’s esophagus. PMID:26021196

  19. Radiologic and Clinical Outcomes of Surgery in High Grade Spondylolisthesis Treated with Temporary Distraction Rod

    Science.gov (United States)

    Hootkani, Alireza; Jarahi, Lida; Rezvan, Manizheh; Moayedpour, Amir

    2015-01-01

    Background Surgical techniques used in the treatment of patients with high grade lumbar spondylolisthesis (> 50% slippage) are usually associated with a great deal of controversies. We aim to evaluate the surgical outcomes of high grade spondylolisthesis treated with an intraoperative temporary distraction rod. Methods We retrospectively studied 21 patients (14 females and 7 males), aged 50.4 ± 9.2 years, who had high grade lumbar spondylolisthesis that was treated with intraoperative temporary distraction rods, neural decompression, pedicular screw fixation, and posterolateral fusion involving one more intact upper vertebra. The mean follow-up period was 39.2 months. Radiologic and clinical outcomes were measured by slip angle, slip percentage, correction rate, Oswestry Disability Index (ODI), visual analogue scale (VAS), patient's satisfaction rate in the pre- and postoperative period. Data were analyzed by SPSS ver. 11.5. Results Analysis of the preoperative visits and final follow-up visits indicated that surgery could improve ODI, lumbar VAS, and leg VAS from 60.5% to 8.2%, from 6.7 to 2.2, and from 6.9 to 1.3, respectively. Slip angle and slip percentage were also changed from -8° to -15° and from 59.2% to 21.4%, respectively. Mean correction rate at the final follow-up visit was 64.1%. Loss of correction was insignificant and a neurologic complication occurred in one patient due to misplacement of one screw. Excellent and good levels of satisfaction were observed in 90.5% of the patients. Conclusions In the surgical treatment of refractory high grade spondylolisthesis, the use of a temporary distraction rod to reduce the slipped vertebra in combination with neural decompression, posterolateral fusion, and longer instrumentation is associated with satisfactory clinical and radiologic outcomes. PMID:25729523

  20. Prevention of Ovarian High Grade Serous Carcinoma by Elucidating Its Early Changes

    Science.gov (United States)

    2016-10-01

    pathology. Springer 2015 25 ▪ Other publications, conference papers, and presentations. Abstracts S George , A Milea, N Salman and P Shaw...11-2-0230) Title: Prevention of Ovarian High-Grade Serous Carcinoma by Elucidating Its Early Change 2011-Current 1. George SH, Greenaway J, Milea...Cancer Res 2012, 18:4334-44. PMID: 22753593 4 11. George SH, Milea A, Shaw P: Proliferation in the normal FTE is a hallmark of the follicular phase

  1. A Levering Technique Using Small Parallel Rods for Open Reduction of High-Grade Thoracolumbar Dislocation

    OpenAIRE

    Hadgaonkar, Shailesh; Shah, Kunal; Khurjekar, Ketan; Krishnan, Vibhu; Shyam, Ashok; Sancheti, Parag

    2017-01-01

    Study Design: Technical report. Objective: Dorsolumbar vertebral dislocations, with or without associated fractures, occur secondary to very high velocity trauma. The reduction procedures and techniques, which may be adopted in these situations, have been multifariously discussed in the literature. Our objective was to assess the outcome of a novel reduction maneuver, using parallel rods which we have employed in reduction of high-grade thoracolumbar fractures to achieve precise sagittal bala...

  2. Oncostatin-M Differentially Regulates Mesenchymal and Proneural Signature Genes in Gliomas via STAT3 Signaling

    Directory of Open Access Journals (Sweden)

    Kumar Natesh

    2015-02-01

    Full Text Available Glioblastoma (GBM, the most malignant of the brain tumors is classified on the basis of molecular signature genes using TCGA data into four subtypes- classical, mesenchymal, proneural and neural. The mesenchymal phenotype is associated with greater aggressiveness and low survival in contrast to GBMs enriched with proneural genes. The proinflammatory cytokines secreted in the microenvironment of gliomas play a key role in tumor progression. The study focused on the role of Oncostatin-M (OSM, an IL-6 family cytokine in inducing mesenchymal properties in GBM. Analysis of TCGA and REMBRANDT data revealed that expression of OSMR but not IL-6R or LIFR is upregulated in GBM and has negative correlation with survival. Amongst the GBM subtypes, OSMR level was in the order of mesenchymal > classical > neural > proneural. TCGA data and RT-PCR analysis in primary cultures of low and high grade gliomas showed a positive correlation between OSMR and mesenchymal signature genes-YKL40/CHI3L1, fibronectin and vimentin and a negative correlation with proneural signature genes-DLL3, Olig2 and BCAN. OSM enhanced transcript and protein level of fibronectin and YKL-40 and reduced the expression of Olig2 and DLL3 in GBM cells. OSM-regulated mesenchymal phenotype was associated with enhanced MMP-9 activity, increased cell migration and invasion. Importantly, OSM induced mesenchymal markers and reduced proneural genes even in primary cultures of grade-III glioma cells. We conclude that OSM-mediated signaling contributes to aggressive nature associated with mesenchymal features via STAT3 signaling in glioma cells. The data suggest that OSMR can be explored as potential target for therapeutic intervention.

  3. The management of high-grade spondylolisthesis and co-existent late-onset idiopathic scoliosis.

    Science.gov (United States)

    Srivastava, Abhishek; Bayley, Edward; Boszczyk, Bronek M

    2016-10-01

    It is relatively common for a scoliosis deformity to be associated with a lumbar spondylolisthesis in adolescents (up to 48 % of spondylolistheses). In the literature two types of curve have been described: 'sciatic' or 'olisthetic'. However, there is no consensus in the literature on how best to treat these deformities. Some authors advocate a single surgical intervention, where both deformities are corrected; whereas, others advocate treating them as separate entities. In this situation, it has been shown that the scoliosis will correct with treatment of the spondylolisthesis. We present a 12-year-old girl who had a concomitant high-grade spondylolisthesis and scoliosis. Her main complaints were those of low back pain and an L5 radiculopathy. We took the decision to treat the spondylolisthesis surgically, but observe the scoliosis, rather than correcting them both surgically at the same sitting. Although the immediately post-operative radiographs showed persistence of the scoliosis, 1-year follow-up demonstrated full resolution of the deformity. This young lady also had relief of her low back pain and leg pain following the surgery. There are no standard guidelines and therefore, we discuss the management of this difficult problem, exemplifying a case of a young girl who had high-grade spondylolisthesis along with a clinically non-flexible scoliosis treated at our institution. We demonstrate that it is safe to observe the scoliosis, even in high-grade spondylolistheses.

  4. Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

    Directory of Open Access Journals (Sweden)

    Andrei G. Vlassenko

    2015-01-01

    Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

  5. Proposal for the award of three contracts for the supply of high-grade helium

    CERN Document Server

    2001-01-01

    This document concerns the award of three contracts for the supply of high-grade helium. Following a market survey carried out among 27 firms in ten Member States, a call for tenders (IT-2855/LHC) was sent on 15 November 2000 to five firms in three Member States. By the closing date, CERN had received tenders from four firms in three Member States. For the reasons explained in this document, the Finance Committee is invited to agree to the negotiation of the following three contracts: - a contract with MESSER GRIESHEIM (DE), the lowest bidder, for the supply of up to 26 000 kg of high-grade helium over a period of three years for an estimated amount of 655 200 Swiss francs, not subject to revision. - a contract with BOC (GB), the second lowest bidder, for the supply of up to 26 000 kg of high-grade helium over a period of three years for an estimated amount of 493 300 US dollars (808 080 Swiss francs), not subject to revision. The rate of exchange which has been used is that stipulated in the tender. - a cont...

  6. Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade undifferentiated sarcomas of the uterus

    NARCIS (Netherlands)

    Pautier, Patricia; Nam, Eun Ji; Provencher, Diane M.; Hamilton, Anne L.; Mangili, Giorgia; Siddiqui, Nadeem Ahmad; Westermann, Anneke M.; Reed, Nicholas Simon; Harter, Philipp; Ray-Coquard, Isabelle

    2014-01-01

    High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive

  7. Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008

    DEFF Research Database (Denmark)

    Baldur-Felskov, Birgitte; Hannibal, Charlotte Gerd; Munk, Christian

    2012-01-01

    To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark.......To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark....

  8. Automated discrimination of lower and higher grade gliomas based on histopathological image analysis

    Directory of Open Access Journals (Sweden)

    Hojjat Seyed Mousavi

    2015-01-01

    Full Text Available Introduction: Histopathological images have rich structural information, are multi-channel in nature and contain meaningful pathological information at various scales. Sophisticated image analysis tools that can automatically extract discriminative information from the histopathology image slides for diagnosis remain an area of significant research activity. In this work, we focus on automated brain cancer grading, specifically glioma grading. Grading of a glioma is a highly important problem in pathology and is largely done manually by medical experts based on an examination of pathology slides (images. To complement the efforts of clinicians engaged in brain cancer diagnosis, we develop novel image processing algorithms and systems to automatically grade glioma tumor into two categories: Low-grade glioma (LGG and high-grade glioma (HGG which represent a more advanced stage of the disease. Results: We propose novel image processing algorithms based on spatial domain analysis for glioma tumor grading that will complement the clinical interpretation of the tissue. The image processing techniques are developed in close collaboration with medical experts to mimic the visual cues that a clinician looks for in judging of the grade of the disease. Specifically, two algorithmic techniques are developed: (1 A cell segmentation and cell-count profile creation for identification of Pseudopalisading Necrosis, and (2 a customized operation of spatial and morphological filters to accurately identify microvascular proliferation (MVP. In both techniques, a hierarchical decision is made via a decision tree mechanism. If either Pseudopalisading Necrosis or MVP is found present in any part of the histopathology slide, the whole slide is identified as HGG, which is consistent with World Health Organization guidelines. Experimental results on the Cancer Genome Atlas database are presented in the form of: (1 Successful detection rates of pseudopalisading necrosis

  9. Safety and Efficacy of Stereotactic Radiosurgery and Adjuvant Bevacizumab in Patients With Recurrent Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Vredenburgh, James J.; Sampson, John H.; Reardon, David A.; Desjardins, Annick; Peters, Katherine B.; Friedman, Henry S. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kirkpatrick, John P., E-mail: john.kirkpatrick@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States)

    2012-04-01

    Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant

  10. Apparent diffusion coefficient maps obtained from high b value diffusion-weighted imaging in the preoperative evaluation of gliomas at 3T: comparison with standard b value diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Qiang; Ling, Chenhan; Zhang, Jianmin [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Neurosurgery, Hangzhou, Zhejiang (China); Dong, Fei; Jiang, Biao [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Radiology, Hangzhou, Zhejiang (China); Shi, Feina [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Neurology, Hangzhou, Zhejiang (China)

    2017-12-15

    To assess whether ADC maps obtained from high b value DWI were more valuable in preoperatively evaluating the grade, Ki-67 index and outcome of gliomas. Sixty-three patients with gliomas, who underwent preoperative multi b value DWI at 3 T, were enrolled. The ADC{sub 1000}, ADC{sub 2000} and ADC{sub 3000} maps were generated. Receiver operating characteristic analyses were conducted to determine the area under the curve (AUC) in differentiating high-grade gliomas (HGG) from low-grade gliomas (LGG). Pearson correlation coefficients (R value) were calculated to investigate the correlation between parameters with the Ki-67 proliferation index. Survival analysis was conducted by using Cox regression. The AUC of the mean ADC{sub 1000} value (0.820) was lower than that of the mean ADC{sub 2000} value (0.847) and mean ADC{sub 3000} value (0.875) in differentiating HGG from LGG. The R value of the mean ADC{sub 1000} value (-0.499) was less negative than that of the mean ADC{sub 2000} value (-0.530) and mean ADC{sub 3000} value (-0.567). The mean ADC{sub 3000} value was an independent prognosis factor for gliomas (p = 0.008), while the mean ADC{sub 1000} and ADC{sub 2000} values were not. ADC maps obtained from high b value DWI might be a better imaging biomarker in the preoperative evaluation of gliomas. (orig.)

  11. Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas

    DEFF Research Database (Denmark)

    Bender, Sebastian; Tang, Yujie; Lindroth, Anders M

    2013-01-01

    Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading...... to a global reduction of the repressive histone mark H3K27me3. We demonstrate that this is caused by aberrant recruitment of the PRC2 complex to K27M mutant H3.3 and enzymatic inhibition of the H3K27me3-establishing methyltransferase EZH2. By performing chromatin immunoprecipitation followed by next......-generation sequencing and whole-genome bisulfite sequencing in primary pHGGs, we show that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs....

  12. Impact of [F-18]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma

    DEFF Research Database (Denmark)

    af Rosenschold, Per Munck; Costa, Junia; Engelholm, Svend Aage

    2015-01-01

    . Gross tumor volume and clinical target volumes (CTVs) were defined in a blinded fashion based on MRI and subsequently PET, and volumetric analysis was performed. The extent of the surgical resection was reviewed using postoperative MRI. RESULTS: Overall, for ∼ 90% of the patients, the PET...

  13. A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT

    International Nuclear Information System (INIS)

    Green, S.; James, N.D.; Cruickshank, G.S.

    2006-01-01

    This presentation will describe a human pharmacokinetic study which is scheduled to begin recruitment in Summer 2006. The study has been ongoing for approximately 4 years to develop the necessary protocols, validate boron assays and to develop a new formulation of BPA. The study population will be patients with glioblastoma multiforme and the study focuses on the route of infusion (intra venous or intra carotid artery) and in each will assess the effect of administration of mannitol (as a blood-brain barrier disrupter). Mannitol will be administered as a bolus at the beginning of a two hour infusion of BPA. The BPA formulation (BPA - mannitol) is also new and avoids some of the problems of low solubility associated with BPA-fructose as well as the potential risk of fructose intolerance. The approach will include stereotactic biopsy which is necessary to confirm diagnosis. Tissue samples collected will include needle biopsy samples of tumour and brain around tumour for estimation of BPA transporter expression, together with microdialysis catheter collection of extra-cellular fluid and routine collection of blood and urine for BPA levels. Where possible, according to surgical plan and the route of entry, samples of cerebro-spinal will also be collected. These data will be used to develop a pharmacokinetic model following the general approach already established by others in the field. This paper presents initial pre-clinical studies on the BPA-mannitol formulation and some assay validation work together with suggestions for approaches to normalisation of the macroscopic boron assays using simultaneous measurement of Mg levels in tissue. (author)

  14. Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype

    DEFF Research Database (Denmark)

    Sørensen, M D; Dahlrot, R H; Boldt, H B

    2018-01-01

    and to characterize CD204(+) cells. RESULTS: Our data revealed that the amount of especially CD204(+) TAMs increases with malignancy grade. In grade III-IV, high CD204 expression was associated with shorter survival, while high IBA-1 intensity correlated with a longer survival. In grade IV, CD204 showed independent......(+) TAMs co-expressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxia-inducible factor-1α. CONCLUSIONS: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold...

  15. The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Roberta Sferra

    2017-05-01

    Full Text Available Glioblastoma (GBM is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC dependent epigenetic modifications and transforming growth factor (TGF-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome.  The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS, into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease.

  16. Application of Awake Craniotomy and Intraoperative Brain Mapping for Surgical Resection of Insular Gliomas of the Dominant Hemisphere.

    Science.gov (United States)

    Alimohamadi, Maysam; Shirani, Mohammad; Shariat Moharari, Reza; Pour-Rashidi, Ahmad; Ketabchi, Mehdi; Khajavi, Mohammadreza; Arami, Mohamadali; Amirjamshidi, Abbas

    2016-08-01

    Radical resection of dominant insular gliomas is difficult because of their close vicinity with internal capsule, basal ganglia, and speech centers. Brain mapping techniques can be used to maximize the extent of tumor removal and to minimize postoperative morbidities by precise localization of eloquent cortical and subcortical areas. Patients with newly diagnosed gliomas of dominant insula were enrolled. The exclusion criteria were severe cognitive disturbances, communication difficulty, age greater than 75 years, severe obesity, difficult airways for intubation and severe cardiopulmonary diseases. All were evaluated preoperatively with contrast-enhanced brain magnetic resonance imaging (MRI), functional brain MRI, and diffusion tensor tractography of language and motor systems. All underwent awake craniotomy with the same anesthesiology protocol. Intraoperative monitoring included continuous motor-evoked potential, electromyography, electrocorticography, direct electrical stimulation of cortex, and subcortical tracts. The patients were followed with serial neurologic examination and imaging. Ten patients were enrolled (4 men, 6 women) with a mean age of 43.6 years. Seven patients suffered from low-grade glioma, and 3 patients had high-grade glioma. The most common clinical presentation was seizure followed by speech disturbance, hemiparesis, and memory loss. Extent of tumor resection ranged from 73% to 100%. No mortality or new major postoperative neurologic deficit was encountered. Seizure control improved in three fourths of patients with medical refractory epilepsy. In one patient with speech disorder at presentation, the speech problem became worse after surgery. Brain mapping during awake craniotomy helps to maximize extent of tumor resection while preserving neurologic function in patients with dominant insular lobe glioma. Copyright © 2016. Published by Elsevier Inc.

  17. Pax3 expression enhances PDGF-B-induced brainstem gliomagenesis and characterizes a subset of brainstem glioma.

    Science.gov (United States)

    Misuraca, Katherine L; Barton, Kelly L; Chung, Alexander; Diaz, Alexander K; Conway, Simon J; Corcoran, David L; Baker, Suzanne J; Becher, Oren J

    2014-10-21

    High-grade Brainstem Glioma (BSG), also known as Diffuse Intrinsic Pontine Glioma (DIPG), is an incurable pediatric brain cancer. Increasing evidence supports the existence of regional differences in gliomagenesis such that BSG is considered a distinct disease from glioma of the cerebral cortex (CG). In an effort to elucidate unique characteristics of BSG, we conducted expression analysis of mouse PDGF-B-driven BSG and CG initiated in Nestin progenitor cells and identified a short list of expression changes specific to the brainstem gliomagenesis process, including abnormal upregulation of paired box 3 (Pax3). In the neonatal mouse brain, Pax3 expression marks a subset of brainstem progenitor cells, while it is absent from the cerebral cortex, mirroring its regional expression in glioma. Ectopic expression of Pax3 in normal brainstem progenitors in vitro shows that Pax3 inhibits apoptosis. Pax3-induced inhibition of apoptosis is p53-dependent, however, and in the absence of p53, Pax3 promotes proliferation of brainstem progenitors. In vivo, Pax3 enhances PDGF-B-driven gliomagenesis by shortening tumor latency and increasing tumor penetrance and grade, in a region-specific manner, while loss of Pax3 function extends survival of PDGF-B-driven;p53-deficient BSG-bearing mice by 33%. Importantly, Pax3 is regionally expressed in human glioma as well, with high PAX3 mRNA characterizing 40% of human BSG, revealing a subset of tumors that significantly associates with PDGFRA alterations, amplifications of cell cycle regulatory genes, and is exclusive of ACVR1 mutations. Collectively, these data suggest that regional Pax3 expression not only marks a novel subset of BSG but also contributes to PDGF-B-induced brainstem gliomagenesis.

  18. A report on radiation-induced gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Salvati, M.; Artico, M.; Caruso, R.; Rocchi, G.; Orlando, E.R.; Nucci, F. (Univ. of Rome La Sapienza (Italy))

    1991-01-15

    Radiation-induced gliomas are uncommon, with only 73 cases on record to date. The disease that most frequently occasioned radiation therapy has been acute lymphoblastic leukemia (ALL). Three more cases are added here, two after irradiation for ALL and one after irradiation for tinea capitis. In a review of the relevant literature, the authors stress the possibility that the ALL-glioma and the retinoblastoma-glioma links point to syndromes in their own right that may occur without radiation therapy.56 references.

  19. Combined chemotherapy of malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Jellinger, K.; Volc, D.; Grisold, W.; Flament, H.; Vollmer, R.; Weiss, R. (Krankenhaus der Stadt Wien-Lainz (Austria). Ludwig Boltzmann Inst. fuer Neurobiologie)

    1983-01-01

    A controlled study of 226 age-matched patients with histologically proven grade 3 and 4 supratentorial gliomas with maximum feasible tumour resection, postoperative Karnofsky performance over 50 and minimum survival of 8 weeks compares the results of supportive care (45 cases), high-dose irradiation of 40 to 66 Gy (59 cases), COMP protocol (CCNU, procarbazine, vincristine, methotrexate, prednisone in 15 day cycles-42 cases) and simultaneous irradiation and COMP chemotherapy (80 cases including 30 survivors). Median recurrent-free intervals in the treatment groups (7 to 11.7 months) were significantly longer than after supportive care (4.4 months). Median survival with supportive care (6.7 months) was significantly shorter than after radiation or COMP treatment (11.7 and 12.3 months) and 14.9 to over 19.9 months with combined treatment, where the two-year survival rates were 33 and 67% (for survivors), and the 3-year survival rates 13 to 30%. Toxic side effects of multimodality treatment were more frequent than after chemotherapy. In addition to space-occupying intracranial cysts often simulating tumour recurrence (12%) and rare radiation necrosis, about 15% of long-term survivors developed progressive intellectual dysfunction with brain atrophy, in the absence of tumour regrowth. Despite some promising results of multimodality approaches towards the management of malignant supratentorial gliomas, the overall results are unsatisfactory and need further optimization.

  20. ARID1A loss correlates with mismatch repair deficiency and intact p53 expression in high-grade endometrial carcinomas.

    Science.gov (United States)

    Allo, Ghassan; Bernardini, Marcus Q; Wu, Ren-Chin; Shih, Ie-Ming; Kalloger, Steve; Pollett, Aaron; Gilks, C Blake; Clarke, Blaise A

    2014-02-01

    BAF250a (ARID1A) loss is a frequent event in high-grade endometrial cancers. It has been proposed that ARID1A is a driver gene, with ARID1A mutations occurring secondary to deregulated mismatch repair mechanism in gastric cancers, representing an alternative oncogenic pathway to p53 alteration. The prognostic significance of ARID1A loss is controversial. In this study, we investigated the frequency of BAF250a immunohistochemical loss in a cohort of high-grade endometrial cancers (n=190) and correlated it with mismatch repair (hMLH1, hMSH2, hMSH6, and hPMS2) and p53 protein expression. The 190 cases consisted of 82 high-grade endometrioid, 88 serous, 10 clear cell, and 10 mixed (carcinosarcomas and mixed histology). There was BAF250a loss in 55/190 (29%) cancers, most commonly in high-grade endometrioid carcinomas (46 vs 9% in serous carcinomas, Pmismatch repair proteins was observed in 63/190 (33%) cancers, most commonly in high-grade endometrioid carcinomas (57 vs 10% in serous carcinomas, Pmismatch repair loss (Pgenes; we found that ARID1A mutations were negatively associated with TP53 mutations but were unrelated to mismatch repair gene mutations. In conclusion, BAF250a loss is more common in high-grade endometrioid carcinomas than in other high-grade endometrial cancers and is associated with mismatch repair deficiency and normal p53 expression.

  1. Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients.

    Science.gov (United States)

    Juratli, Tareq A; Lautenschläger, Tim; Geiger, Kathrin D; Pinzer, Thomas; Krause, Mechthild; Schackert, Gabriele; Krex, Dietmar

    2015-09-01

    Isocitrate dehydrogenase (IDH) mutations are beginning to drive decisions on therapy for glioma patients. Here we sought to determine the impact of adjuvant treatment in patients with IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma (sHGA) WHO grades III/IV. Clinical data of 109 sHGA patients grades III/IV, in addition to IDH mutation-, 1p/19q-codeletion- and MGMT-promoter methylation status-were retrospectively analyzed. Survival analysis in relation to adjuvant treatment modalities and molecular profiling were performed. Out of 109 patients, 88 patients (80.7 %) harbored IDH mutations, 30 patients had a 1p/19q-codeletion (27.5 %) and 69 patients (63.3 %) exhibited a methylated MGMT-promoter status. At a median follow-up of 9.8 years, 62 patients (57 %) died. The postsurgical treatment included: radio-chemotherapy (RT-CT; 54.5 %), RT alone (19.3 %), and CT alone (22.7 %). The median overall survival (OS) in the entire group was 3.4 years (1.9-6.7 years). Patients who received RT-CT had a significantly longer OS compared with those who underwent RT alone (6.5 vs. 1.2 years, HR 0.35, CI 0.32-0.51, p = 0.011). In the IDH-mutant 1p/19q non-codeleted sHGA subgroup the RT-CT cohort had a significantly longer OS in comparison to the RT cohort (6.4 vs. 1.2 years, HR 2.7, CI 1.1-6.5, p = 0.022). In the stepwise multivariable Cox model for OS of all 88 IDH-mutant sHGA patients, survival was strongly associated with only one factor, namely, adjuvant RT-CT at diagnosis of a sHGA. This retrospective long-term study demonstrates that RT and CT (mostly PCV) significantly improves progression-free and overall survival in IDH-mutant secondary high-grade astrocytoma patients, regardless of 1p/19q-codeletion status.

  2. High-grade renal injuries are often isolated in sports-related trauma.

    Science.gov (United States)

    Patel, Darshan P; Redshaw, Jeffrey D; Breyer, Benjamin N; Smith, Thomas G; Erickson, Bradley A; Majercik, Sarah D; Gaither, Thomas W; Craig, James R; Gardner, Scott; Presson, Angela P; Zhang, Chong; Hotaling, James M; Brant, William O; Myers, Jeremy B

    2015-07-01

    Most high-grade renal injuries (American Association for Surgery of Trauma (AAST) grades III-V) result from motor vehicle collisions associated with numerous concomitant injuries. Sports-related blunt renal injury tends to have a different mechanism, a solitary blow to the flank. We hypothesized that high-grade renal injury is often isolated in sports-related renal trauma. We identified patients with AAST grades III-V blunt renal injuries from four level 1 trauma centres across the United States between 1/2005 and 1/2014. Patients were divided into "Sport" or "Non-sport" related groups. Outcomes included rates of hypotension (systolic blood pressure 110bpm), concomitant abdominal injury, and procedural/surgical intervention between sports and non-sports related injury. 320 patients met study criteria. 18% (59) were sports-related injuries with the most common mechanisms being skiing, snowboarding and contact sports (25%, 25%, and 24%, respectively). Median age was 24 years for sports and 30 years for non-sports related renal injuries (p=0.049). Males were more commonly involved in sports related injuries (85% vs. 72%, p=0.011). Median injury severity score was lower for sports related injuries (10 vs. 27, pinjury scale scores. Sports related trauma was more likely to be isolated without other significant injury (69% vs. 39% (psports and non-sports renal injuries (p=0.30). Sports injuries had lower transfusion (7% vs. 47%, psports vs. 18% non-sports, p=0.95). High-grade sports-related blunt renal trauma is more likely to occur in isolation without other abdominal or thoracic injuries and clinicians must have a high suspicion of renal injury with significant blows to the flank during sports activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Quantitative genome-wide methylation analysis of high-grade non-muscle invasive bladder cancer.

    Science.gov (United States)

    Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Glossop, John R; Luscombe, Christopher; Cheng, K K; Zeegers, Maurice P; James, Nicholas D; Devall, Adam J; Mein, Charles A; Gommersall, Lyndon; Fryer, Anthony A; Farrell, William E

    2016-03-03

    High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a clinically unpredictable disease with greater risks of recurrence and progression relative to their low-intermediate-grade counterparts. The molecular events, including those affecting the epigenome, that characterize this disease entity in the context of tumor development, recurrence, and progression, are incompletely understood. We therefore interrogated genome-wide DNA methylation using HumanMethylation450 BeadChip arrays in 21 primary HG-NMIBC tumors relative to normal bladder controls. Using strict inclusion-exclusion criteria we identified 1,057 hypermethylated CpGs within gene promoter-associated CpG islands, representing 256 genes. We validated the array data by bisulphite pyrosequencing and examined 25 array-identified candidate genes in an independent cohort of 30 HG-NMIBC and 18 low-intermediate-grade NMIBC. These analyses revealed significantly higher methylation frequencies in high-grade tumors relative to low-intermediate-grade tumors for the ATP5G2, IRX1 and VAX2 genes (P<0.05), and similarly significant increases in mean levels of methylation in high-grade tumors for the ATP5G2, VAX2, INSRR, PRDM14, VSX1, TFAP2b, PRRX1, and HIST1H4F genes (P<0.05). Although inappropriate promoter methylation was not invariantly associated with reduced transcript expression, a significant association was apparent for the ARHGEF4, PON3, STAT5a, and VAX2 gene transcripts (P<0.05). Herein, we present the first genome-wide DNA methylation analysis in a unique HG-NMIBC cohort, showing extensive and discrete methylation changes relative to normal bladder and low-intermediate-grade tumors. The genes we identified hold significant potential as targets for novel therapeutic intervention either alone, or in combination, with more conventional therapeutic options in the treatment of this clinically unpredictable disease.

  4. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  5. Recurrent high-grade meningioma: a phase II trial with somatostatin analogue therapy.

    Science.gov (United States)

    Simó, Marta; Argyriou, Andreas A; Macià, Miquel; Plans, Gerard; Majós, Carles; Vidal, Noemi; Gil, Miguel; Bruna, Jordi

    2014-05-01

    A prospective, two-stage phase II trial with octreotide in patients with recurrent high-grade meningioma was conducted. The radiographic partial response (RPR) was set as the primary study endpoint, whereas progression-free survival at 6 months (PFS6) was defined as the secondary endpoint. Nine patients (eight men; median age 65) with histological high-grade meningioma (five with grade II and four with grade III) and progression after prior surgery and radiotherapy were included. All had positive brain octreotide SPECT scanning. Octreotide was administered intramuscularly once every 28 days at a dose of 30 mg for the first two cycles and 40 mg for subsequent cycles until progression. Magnetic resonance imaging was performed every 3 months. Progression and RPR were defined as an increase of ≥25 % and as a decrease of ≥50 % in two-dimensional maximum diameters, respectively. Patients received a median of three octreotide cycles (range 1-8) without grade ≥2 toxicities. No RPRs were observed. Stable disease was the best response in 33.3 % (n = 3). All patients had progressive disease at 10 months of follow-up. Median time to progression was 4.23 months (range 1-9.4), and the PFS6 was 44.4 % (n = 4). Our study failed to provide evidence to support the use of monthly long-acting somatostatin analogue schedule in recurrent high-grade meningiomas, as none of our patients demonstrated RPR. The modest median PFS of 4-5 months along with the unknown natural history of recurrent meningiomas render the use of this therapy against these aggressive brain tumors uncertain.

  6. Role of combined circumareolar skin excision and liposuction in management of high grade gynaecomastia

    Directory of Open Access Journals (Sweden)

    Arindam Sarkar

    2014-01-01

    Full Text Available Introduction: High-grade gynaecomastia (Simon IIb and III has tissue excess (skin excess, enlarged areola, and displaced nipple, which is best managed surgically; however, results of conventional breast reduction surgeries and liposuction is not very good. Aim of our study was to describe a combined technique to manage these problems to produce a good result. Material and Method: This was a 2-year study among 12 patients of high grade gynaecomastia. Clinical and laboratory findings were normal. Pre-operatively in standing position, diameter of breast and areola, position of nipple, and amount of skin excess were marked. Under general anaesthesia, tumescent infiltration, circumareolar de-epithelisation of skin excess, and liposuction was completed. Redundant portion of the breast was sharply dissected and pulled out. Areola was fixed over pectoralis fascia at mid humerus level, just medial to the mid-clavicular line. Outer borders of the de-epithelised area were apposed by the purse-string effect of a subdermal suture, and further apposed by few half buried horizontal mattress sutures. Drains for 24 hour and compressive dressings for 6 weeks were used. Result: Mean age of presentation was 25.8 year; emotional discomfort was the chief complaint. Among 12 patients, 10 patients had bilateral gynaecomastia and 8 patients had enlarged and displaced nipple-areola complex. Average hospital stay was 2.41 days and recoveries were usually uneventful. Conclusion: The problem of tissue excess and tissue displacement in high grade gynaecomastia can be well managed by this combined circumareolar skin reduction and liposuction technique to achieve a scar-less flat male chest.

  7. Increased variability of watershed areas in patients with high-grade carotid stenosis

    DEFF Research Database (Denmark)

    Kaczmarz, Stephan; Griese, Vanessa; Preibisch, Christine

    2018-01-01

    of individual WSAs. Methods: We defined individual watershed masks based on relative TTP increases in 30 healthy elderly persons and 28 patients with unilateral, high-grade carotid stenosis, being at risk for watershed-related hemodynamic impairment. Determined WSA location was confirmed by an arterial transit...... variability of WSAs than healthy controls. Perfusion on the side of the stenosis was delayed within individual watershed masks as compared to a watershed template derived from controls, being independent from the grade of the stenosis and collateralization status of the circle of Willis. Conclusion: Results...

  8. Application of the CAB process for the manufacture of high-grade forgings

    International Nuclear Information System (INIS)

    Grimm, W.; Feller, J.; Plaul, H.U.

    1981-01-01

    The suitability of the ladle metallurgy CAB process (deoxidation and desulphurization with calcium and degassing with argon) is investigated for the manufacture of high-grade forgings for the construction of power-generating machines. The primary function of the CAB metallurgy, the improvement of the sulphide and oxide cleanness, was combined with established casting parameters so that the macrosegregates too in large forging ingots could be minimized. A comparison of various methods for the manufacture of large forging ingots revealed that the CAB metallurgy can meet demands, which so far could be satisfied by remelting technologies only. (orig.) [de

  9. Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer.

    Science.gov (United States)

    Nordström, Tobias; Van Blarigan, Erin L; Ngo, Vy; Roy, Ritu; Weinberg, Vivian; Song, Xiaoling; Simko, Jeffry; Carroll, Peter R; Chan, June M; Paris, Pamela L

    2016-03-01

    Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers. To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability. We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression. Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and supports the hypothesis that lycopene may inhibit progression of

  10. Improving vaccine efficacy against malignant glioma.

    Science.gov (United States)

    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

    2016-08-01

    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.

  11. Differentiating low- and high-grade pediatric brain tumors using a continuous-time random-walk diffusion model at high b-values.

    Science.gov (United States)

    Karaman, M Muge; Sui, Yi; Wang, He; Magin, Richard L; Li, Yuhua; Zhou, Xiaohong Joe

    2016-10-01

    To demonstrate that a continuous-time random-walk (CTRW) diffusion model can improve diagnostic accuracy of differentiating low- and high-grade pediatric brain tumors. Fifty-four children with histopathologically confirmed brain tumors underwent diffusion MRI scans at 3Twith 12 b-values (0-4000 s/mm(2) ). The diffusion imageswere fit to a simplified CTRW model to extract anomalous diffusion coefficient, Dm , and temporal and spatial heterogeneity parameters, α and β, respectively. Using histopathology results as reference, a k-means clustering algorithm and a receiver operating characteristic (ROC) analysis were employed to determine the sensitivity, specificity, and diagnostic accuracy of the CTRW parameters in differentiating tumor grades. Significant differences between the low- and high-grade tumors were observed in the CTRW parameters (p-valuesCTRW parameters produced higher diagnostic accuracy (85% vs. 75%) and specificity (83% vs. 54%) than the apparent diffusion coefficient (ADC) from a mono-exponential model. The ROC analysis revealed that any combination of the CTRW parameters gave a larger area under the curve (0.90-0.96) than using ADC (0.80). With its sensitivity to intravoxel heterogeneity, the simplified CTRW model is useful for non-invasive grading of pediatric brain tumors, particularly when surgical biopsy is not feasible. Magn Reson Med 76:1149-1157, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  12. Indirect exploration techniques in search for concealed and high grade uranium ore in India

    International Nuclear Information System (INIS)

    Chaki, Anjan

    2009-01-01

    Atomic Minerals Directorate for Exploration and Research is engaged in uranium exploration for nearly six decades. Initial approach was 'from known to the unknown' i.e., to extend exploration to the subsurface, essentially by drilling from the known surface indication. Repeated reconnaissance has more or less identified major deposits in the country from initial surface indication. Now the exploration strategy has been largely oriented more on 'concept based'. The deposits of unconformity type, well known in Canada and Australia, are of high grade and such deposits have little or no surface manifestation, have become the ideal hunt targets. These deposits are known as 'concealed deposits', which warrant exploration largely by indirect techniques. In India, unconformity related type uranium deposits have been targeted in some of the Proterozoic basins like Cuddapah, Bhima, Kaladgi, Chhattisgarh and Vindhyan, to locate high grade large tonnage deposits. Beside extensive surface and borehole core based detailed geochemical studies, remote sensing techniques like airborne gamma ray spectrometric survey, aerial photo interpretation and very recently airborne FEM and TDEM surveys are being conducted to a depth of 5000m. Satpura Gondwana basins in central India as well as Mahadek Basin in Meghalaya are in different stages of integrated exploration programme for uranium and it includes ground geophysical, as well as airborne radiometric magnetic and EM survey

  13. Dating of zircon from high-grade rocks: Which is the most reliable method?

    Directory of Open Access Journals (Sweden)

    Alfred Kröner

    2014-07-01

    Full Text Available Magmatic zircon in high-grade metamorphic rocks is often characterized by complex textures as revealed by cathodoluminenscence (CL that result from multiple episodes of recrystallization, overgrowth, Pb-loss and modifications through fluid-induced disturbances of the crystal structure and the original U-Th-Pb isotopic systematics. Many of these features can be recognized in 2-dimensional CL images, and isotopic analysis of such domains using a high resolution ion-microprobe with only shallow penetration of the zircon surface may be able to reconstruct much of the magmatic and complex post-magmatic history of such grains. In particular it is generally possible to find original magmatic domains yielding concordant ages. In contrast, destructive techniques such as LA-ICP-MS consume a large volume, leave a deep crater in the target grain, and often sample heterogeneous domains that are not visible and thus often yield discordant results which are difficult to interpret. We provide examples of complex magmatic zircon from a southern Indian granulite terrane where SHRIMP II and LA-ICP-MS analyses are compared. The SHRIMP data are shown to be more precise and reliable, and we caution against the use of LA-ICP-MS in deciphering the chronology of complex zircons from high-grade terranes.

  14. Cerebral vasomotor reactivity and apnea test in symptomatic and asymptomatic high-grade carotid stenosis

    Directory of Open Access Journals (Sweden)

    Lučić-Prokin Aleksandra

    2015-01-01

    Full Text Available Introduction. Cerebral vasomotor reactivity (VMR represents an autoregulatory response of the arterial trunks on the specific vasoactive stimuli, most commonly CO2. Objective. The aim of this retrospective study was to compare VMR in high-grade symptomatic (SCAS and asymptomatic carotid stenosis (ACAS, using the apnea test to evaluate the hemodynamic status. Methods. The study included 50 patients who were hospitalized at the neurology and vascular surgery departments as part of preparation for carotid endarterectomy. We evaluated VMR by calculating the breath holding index (BHI in 34 patients with SCAS and 16 patients with ACAS, with isolated high-grade carotid stenosis. We evaluated the impact of risk factors and collateral circulation on BHI, as well as the correlation between the degree of carotid stenosis and BHI. Results. A pathological BHI was more frequent in the SCAS group (p<0.01. There was no difference in the range of BHI values between the groups, both ipsilaterally and contralaterally. Only male gender was associated with pathological BHI in both groups (p<0.05. Collateral circulation did not exist in over 60% of all subjects. We confirmed a negative correlation between the degree of carotid stenosis and BHI. Conclusion. SCAS and ACAS patients present with different hemodynamics. While ACAS patients have stable hemodynamics, combination of hemodynamic and thromboembolic effects is characteristic of SCAS patients.

  15. DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions.

    Science.gov (United States)

    Sun, Yin; Li, Shu; Shen, Keng; Ye, Shuang; Cao, Dongyan; Yang, Jiaxin

    2015-01-01

    Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients' samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P methylated were positive correlated with cervical disease grade (P methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening.

  16. A Levering Technique Using Small Parallel Rods for Open Reduction of High-Grade Thoracolumbar Dislocation.

    Science.gov (United States)

    Hadgaonkar, Shailesh; Shah, Kunal; Khurjekar, Ketan; Krishnan, Vibhu; Shyam, Ashok; Sancheti, Parag

    2017-06-01

    Technical report. Dorsolumbar vertebral dislocations, with or without associated fractures, occur secondary to very high velocity trauma. The reduction procedures and techniques, which may be adopted in these situations, have been multifariously discussed in the literature. Our objective was to assess the outcome of a novel reduction maneuver, using parallel rods which we have employed in reduction of high-grade thoracolumbar fractures to achieve precise sagittal balance as well as accurate vertebral alignment with minimal soft tissue damage. The study included a total of 11 cases of thoracolumbar dislocations, who had presented to our emergency spine services following high-velocity trauma. After appropriate systemic stabilization and necessary investigations, all patients were surgically treated using the described technique. There were no surgical complications at 2-year follow-up. Radiographs showed good reduction and maintained sagittal balance. We believe that this technique is an excellent means of achieving safer, easier, and accurate reduction for restoration of sagittal/coronal balance and alignment in high-grade thoracolumbar dislocations. It is easily reproducible and predictable.

  17. Wilms tumor gene 1 (WT1) is a prognostic marker in high-grade uterine sarcoma.

    Science.gov (United States)

    Coosemans, An; Van Calster, Ben; Verbist, Godelieve; Moerman, Philippe; Vergote, Ignace; Van Gool, Stefaan W; Amant, Frédéric

    2011-02-01

    Wilms tumor gene 1 (WT1) contributes to uterine sarcoma tumor biology. In this study, we aimed to clarify the prognostic value of WT1. A retrospective clinical and histopathological review of 71 women with high-grade uterine sarcoma (leiomyosarcoma [n = 24], undifferentiated sarcoma [n = 9]), and carcinosarcoma (n = 38) was performed. Patients were followed up for at least 12 months. Wilms tumor gene 1 expression was determined by immunohistochemistry. Data on recurrence (progression-free survival) and overall survival (OS) were available for all patients. Univariate and multivariate analyses of WT1 expression were carried out using Kaplan-Meier curves and Cox regression, respectively. Forty-nine (69%) tumors were WT1 positive. Forty-seven (66%) patients died of the disease, with a median OS time of 22 months. Wilms tumor gene 1 was a predictor of survival in the univariate analysis: the hazard ratio of WT1 positivity was 2.44 (95% confidence interval, 1.34-4.71) for progression-free survival and 2.48 (95% confidence interval, 1.26-4.90) for OS. Multivariate analysis including stage, age, tumor size, and sarcoma subtype identified only stage and WT1 positivity as independent prognostic markers for survival. The identification of WT1 as a prognostic marker confirms its role in high-grade uterine sarcoma and carcinosarcoma tumor biology.

  18. The Role of Telomere Maintenance in the Spontaneous Growth Arrest of Pediatric Low-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Uri Tabori

    2006-02-01

    Full Text Available 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 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.

  19. Infection or Glioma? The False Dilemma of Primary Central Nervous System Histiocytic Sarcoma.

    Science.gov (United States)

    Clifton, William; Akinduro, Oluwaseun Oluwadara; Lopez-Chiriboga, Sebastian; Whitaker, Dale Alan; Reimer, Ronald

    2017-10-01

    Primary central nervous system (CNS) histiocytic sarcoma is an extremely rare lymphoproliferative disorder that affects the CNS and behaves aggressively. Only 27 cases of primary CNS histiocytic sarcoma have been reported. The paucity of literature on this entity has made diagnosis and treatment difficult both for the surgeon and the pathologist. In this case of primary CNS histiocytic sarcoma, a middle-aged woman presented from an outside institution with a supposed cerebellar abscess. Intraoperative frozen pathology was initially interpreted as high-grade glioma; however, final pathology demonstrated histiocytic sarcoma. This report makes a significant contribution to the literature on this rare malignant disease by outlining a similar presentation among several cases and providing a thorough overview of existing criteria for diagnosis and management. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effect of smoking on high-grade cervical cancer in women on the basis of human papillomavirus infection studies

    Directory of Open Access Journals (Sweden)

    Jian-Hong Fang

    2018-01-01

    Conclusion: We concluded here that smoking leads to an enhanced risk of high-grade cervical lesions in persistent high-risk HPV-infected women. This makes a good understanding of smoking's role in cervical cancer.

  1. Long-term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Das, P. K.; Leenstra, S.; Bosch, D. A.

    1995-01-01

    Gliomas, as well as other solid tumours, contain tumour stroma composed of connective tissue, macrophages, capillaries and other non-cellular constituents. Therefore, a homogeneous culture of tumour cells alone, as is often used as a culture model for gliomas, is not ideal to study all aspects of

  2. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  3. Comparison of 18F-FET PET and perfusion-weighted MRI for glioma grading. A hybrid PET/MR study

    International Nuclear Information System (INIS)

    Verger, Antoine; Filss, Christian P.; Lohmann, Philipp; Stoffels, Gabriele; Rota Kops, Elena; Sabel, Michael; Wittsack, Hans J.; Galldiks, Norbert; Fink, Gereon R.; Shah, Nadim J.; Langen, Karl-Josef

    2017-01-01

    Both perfusion-weighted MR imaging (PWI) and O-(2- 18 F-fluoroethyl)-L-tyrosine PET ( 18 F-FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of 18 F-FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner. Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with 18 F-FET PET and PWI using a hybrid PET/MR scanner. After visual inspection of PET and PWI maps (rCBV, rCBF, MTT), volumes of interest (VOIs) with a diameter of 16 mm were centered upon the maximum of abnormality in the tumor area in each modality and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios (TBR mean , TBR max ) were calculated. In addition, Time-to-Peak (TTP) and slopes of time-activity curves were calculated for 18 F-FET PET. Diagnostic accuracies of 18 F-FET PET and PWI for differentiating low-grade glioma (LGG) from high-grade glioma (HGG) were evaluated by receiver operating characteristic analyses (area under the curve; AUC). The diagnostic accuracy of 18 F-FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBR mean and TBR max of 18 F-FET PET uptake (0.80, 0.83) and for TBR mean and TBR max of rCBV (0.80, 0.81). In case of increased signal in the tumor area with both methods (n = 32), local hot-spots were incongruent in 25 patients (78%) with a mean distance of 10.6 ± 9.5 mm. Dynamic FET PET and combination of different parameters did not further improve diagnostic accuracy. Both 18 F-FET PET and PWI discriminate LGG from HGG with similar diagnostic performance. Regional abnormalities in the tumor area are usually not congruent indicating that tumor grading by 18 F-FET PET and PWI is based on different pathophysiological phenomena. (orig.)

  4. Comparison of {sup 18}F-FET PET and perfusion-weighted MRI for glioma grading. A hybrid PET/MR study

    Energy Technology Data Exchange (ETDEWEB)

    Verger, Antoine [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, -4), Juelich (Germany); Lorraine University, Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Nancy (France); Lorraine University, IADI, INSERM, UMR 947, Nancy (France); Filss, Christian P. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, -4), Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Lohmann, Philipp; Stoffels, Gabriele; Rota Kops, Elena [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, -4), Juelich (Germany); Sabel, Michael [University of Duesseldorf, Department of Neurosurgery, Duesseldorf (Germany); Wittsack, Hans J. [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Galldiks, Norbert; Fink, Gereon R. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, -4), Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); University of Cologne and Bonn, Center of Integrated Oncology (CIO), Bonn (Germany); Shah, Nadim J. [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, -4), Juelich (Germany); RWTH Aachen University Hospital, Department of Neurology, Aachen (Germany); Juelich-Aachen Research Alliance (JARA), Section JARA-Brain, Juelich (Germany); Langen, Karl-Josef [Forschungszentrum Juelich, Institute of Neuroscience and Medicine (INM-3, -4), Juelich (Germany); RWTH Aachen University Hospital, Department of Nuclear Medicine, Aachen (Germany); Juelich-Aachen Research Alliance (JARA), Section JARA-Brain, Juelich (Germany)

    2017-12-15

    Both perfusion-weighted MR imaging (PWI) and O-(2-{sup 18}F-fluoroethyl)-L-tyrosine PET ({sup 18}F-FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of {sup 18}F-FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner. Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with {sup 18}F-FET PET and PWI using a hybrid PET/MR scanner. After visual inspection of PET and PWI maps (rCBV, rCBF, MTT), volumes of interest (VOIs) with a diameter of 16 mm were centered upon the maximum of abnormality in the tumor area in each modality and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios (TBR{sub mean}, TBR{sub max}) were calculated. In addition, Time-to-Peak (TTP) and slopes of time-activity curves were calculated for {sup 18}F-FET PET. Diagnostic accuracies of {sup 18}F-FET PET and PWI for differentiating low-grade glioma (LGG) from high-grade glioma (HGG) were evaluated by receiver operating characteristic analyses (area under the curve; AUC). The diagnostic accuracy of {sup 18}F-FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBR{sub mean} and TBR{sub max} of {sup 18}F-FET PET uptake (0.80, 0.83) and for TBR{sub mean} and TBR{sub max} of rCBV (0.80, 0.81). In case of increased signal in the tumor area with both methods (n = 32), local hot-spots were incongruent in 25 patients (78%) with a mean distance of 10.6 ± 9.5 mm. Dynamic FET PET and combination of different parameters did not further improve diagnostic accuracy. Both {sup 18}F-FET PET and PWI discriminate LGG from HGG with similar diagnostic performance. Regional abnormalities in the tumor area are usually not congruent indicating that tumor grading by {sup 18}F-FET PET and PWI is based on different pathophysiological phenomena. (orig.)

  5. FasL and FADD delivery by a glioma-specific and cell cycle-dependent HSV-1 amplicon virus enhanced apoptosis in primary human brain tumors

    Directory of Open Access Journals (Sweden)

    Lam Paula Y

    2010-10-01

    Full Text Available Abstract Background Glioblastoma multiforme is the most malignant cancer of the brain and is notoriously difficult to treat due to the highly proliferative and infiltrative nature of the cells. Herein, we explored the combination treatment of pre-established human glioma xenograft using multiple therapeutic genes whereby the gene expression is regulated by both cell-type and cell cycle-dependent transcriptional regulatory mechanism conferred by recombinant HSV-1 amplicon vectors. Results We demonstrated for the first time that Ki67-positive proliferating primary human glioma cells cultured from biopsy samples were effectively induced into cell death by the dual-specific function of the pG8-FasL amplicon vectors. These vectors were relatively stable and exhibited minimal cytotoxicity in vivo. Intracranial implantation of pre-transduced glioma cells resulted in better survival outcome when compared with viral vectors inoculated one week post-implantation of tumor cells, indicating that therapeutic efficacy is dependent on the viral spread and mode of viral vectors administration. We further showed that pG8-FasL amplicon vectors are functional in the presence of commonly used treatment regimens for human brain cancer. In fact, the combined therapies of pG8-FasL and pG8-FADD in the presence of temozolomide significantly improved the survival of mice bearing intracranial high-grade gliomas. Conclusion Taken together, our results showed that the glioma-specific and cell cycle-dependent HSV-1 amplicon vector is potentially useful as an adjuvant therapy to complement the current gene therapy strategy for gliomas.

  6. Impact on prognosis of the regional distribution of MGMT methylation with respect to the CpG island methylator phenotype and age in glioma patients.

    Science.gov (United States)

    Mur, Pilar; Rodríguez de Lope, Ángel; Díaz-Crespo, Francisco Javier; Hernández-Iglesias, Teresa; Ribalta, Teresa; Fiaño, Concepción; García, Juan Fernando; Rey, Juan Antonio; Mollejo, Manuela; Meléndez, Bárbara

    2015-05-01

    Clinical and molecular prognostic factors in gliomas include age, IDH mutation, the glioma CpG island methylator phenotype (G-CIMP+) and promoter methylation of the O(6)-methylguanine DNA-methyltransferase (MGMT) gene. Among these markers, a predictive value was reported in glioblastomas (GBM) for MGMT promoter methylation, in particular in elderly GBM patients. In this study, methylation data from 46 glioma samples with the Illumina 450K platform were obtained and extended using external data to include a total of 247 glioma samples. Methylation analysis of the whole MGMT gene with this platform revealed two strongly survival-associated CpG regions within the promoter and the gene body, which were confirmed in a reported dataset of high grade-gliomas. Methylation at the promoter (CpG 25, cg12981137 and the prognostic model MGMT-STP27) and at the gene body CpG 165 (cg07933035), were significantly associated with better overall survival, and strongly correlated with G-CIMP+ status. In this series, the prognostic value of MGMT methylation at the promoter was not observed in G-CIMP- cases, although around 50 % of them were MGMT-methylated. These results were also obtained in an homogeneously-treated series of chemoradiated G-CIMP- GBMs analyzed by MSP and qMSP, and confirmed in a reported pyrosequencing-analyzed series of gliomas. Interestingly, in contrast to the MGMT promoter, gene body methylation was of prognostic value in G-CIMP-patients older than 65 years. Our study highlights the relevance of the prognostic value of the different regions of methylation throughout the MGMT gene that could be affected by specific G-CIMP profiles and age groups.

  7. Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

    Science.gov (United States)

    Sibai, Mira; Fisher, Carl; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Roberts, David W.; Wilson, Brian C.

    2017-07-01

    5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of two-dimensional images of [PpIX], alleviating the need for time-consuming point sampling of the brain surface. We present first results of this technique modified for in vivo imaging on an RG2 rat brain tumor model. Despite the moderate errors in retrieving the absorption and reduced scattering coefficients in the subdiffusive regime of 14% and 19%, respectively, the recovered [PpIX] maps agree within 10% of the point [PpIX] values measured by the fiber-optic probe, validating its potential as an extension or an alternative to point sampling during glioma resection.

  8. Molecular Diagnostics of Gliomas Using Next Generation Sequencing of a Glioma-Tailored Gene Panel.

    Science.gov (United States)

    Zacher, Angela; Kaulich, Kerstin; Stepanow, Stefanie; Wolter, Marietta; Köhrer, Karl; Felsberg, Jörg; Malzkorn, Bastian; Reifenberger, Guido

    2017-03-01

    Current classification of gliomas is based on histological criteria according to the World Health Organization (WHO) classification of tumors of the central nervous system. Over the past years, characteristic genetic profiles have been identified in various glioma types. These can refine tumor diagnostics and provide important prognostic and predictive information. We report on the establishment and validation of gene panel next generation sequencing (NGS) for the molecular diagnostics of gliomas. We designed a glioma-tailored gene panel covering 660 amplicons derived from 20 genes frequently aberrant in different glioma types. Sensitivity and specificity of glioma gene panel NGS for detection of DNA sequence variants and copy number changes were validated by single gene analyses. NGS-based mutation detection was optimized for application on formalin-fixed paraffin-embedded tissue specimens including small stereotactic biopsy samples. NGS data obtained in a retrospective analysis of 121 gliomas allowed for their molecular classification into distinct biological groups, including (i) isocitrate dehydrogenase gene (IDH) 1 or 2 mutant astrocytic gliomas with frequent α-thalassemia/mental retardation syndrome X-linked (ATRX) and tumor protein p53 (TP53) gene mutations, (ii) IDH mutant oligodendroglial tumors with 1p/19q codeletion, telomerase reverse transcriptase (TERT) promoter mutation and frequent Drosophila homolog of capicua (CIC) gene mutation, as well as (iii) IDH wildtype glioblastomas with frequent TERT promoter mutation, phosphatase and tensin homolog (PTEN) mutation and/or epidermal growth factor receptor (EGFR) amplification. Oligoastrocytic gliomas were genetically assigned to either of these groups. Our findings implicate gene panel NGS as a promising diagnostic technique that may facilitate integrated histological and molecular glioma classification. © 2016 International Society of Neuropathology.

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

    Science.gov (United States)

    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 IDH mutated gliomas (21 % versus 1 %, p 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 acquisition of IDH mutations could shift gliomagenesis towards the brainstem thereby mimicking the regional preference of histone mutated gliomas.

  10. The progress of radiosensitive genes of human brain glioma

    International Nuclear Information System (INIS)

    Wang Xi; Liu Qiang

    2008-01-01

    Human gliomas are one of the most aggressive tumors in brain which grow infiltrativly. Surgery is the mainstay of treatment. But as the tumor could not be entirely cut off, it is easy to relapse. Radiotherapy plays an important role for patients with gliomas after surgery. The efficacy of radiotherapy is associated with radio sensitivity of human gliomas. This paper makes a summary of current situation and progress for radiosensitive genes of human brain gliomas. (authors)

  11. Glioma

    Science.gov (United States)

    ... functioning well. There are three types of normal glial cells that can produce tumors. An astrocyte will produce ... which it originates. Description Three types of normal glial cells can produce tumors—astrocytes, oligodendrocytes, and ependymal cells. ...

  12. Glioma stem cells targeted by oncolytic virus carrying endostatin-angiostatin fusion gene and the expression of its exogenous gene in vitro.

    Science.gov (United States)

    Zhu, Guidong; Su, Wei; Jin, Guishan; Xu, Fujian; Hao, Shuyu; Guan, Fangxia; Jia, William; Liu, Fusheng

    2011-05-16

    The development of the cancer stem cell (CSCs) niche theory has provided a new target for the treatment of gliomas. Gene therapy using oncolytic viral vectors has shown great potential for the therapeutic targeting of CSCs. To explore whether a viral vector carrying an exogenous Endo-Angio fusion gene (VAE) can infect and kill glioma stem cells (GSCs), as well as inhibit their vascular niche in vitro, we have collected surgical specimens of human high-grade glioma (world health organization, WHO Classes III-VI) from which we isolated and cultured GSCs under conditions originally designed for the selective expansion of neural stem cells. Our results demonstrate the following: (1) Four lines of GSCs (isolated from 20 surgical specimens) could grow in suspension, were multipotent, had the ability to self-renew and expressed the neural stem cell markers, CD133 and nestin. (2) VAE could infect GSCs and significantly inhibit their viability. (3) The Endo-Angio fusion gene was expressed in GSCs 48 h after VAE infection and could inhibit the proliferation of human brain microvascular endothelial cells (HBMEC). (4) Residual viable cells lose the ability of self-renewal and adherent differentiation. In conclusion, VAE can significantly inhibit the activity of GSCs in vitro and the expression of exogenous Endo-Angio fusion gene can inhibit HBMEC proliferation. VAE can be used as a novel virus-gene therapy strategy for glioma. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Togao, Osamu; Hiwatashi, Akio; Yamashita, Koji; Kikuchi, Kazufumi; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Fukuoka (Japan); Keupp, Jochen [Philips Research, Hamburg (Germany); Yoshimoto, Koji; Kuga, Daisuke; Iihara, Koji [Kyushu University, Department of Neurosurgery, Graduate School of Medical Sciences, Fukuoka (Japan); Yoneyama, Masami [Philips Electronics Japan, Tokyo (Japan); Suzuki, Satoshi O.; Iwaki, Toru [Kyushu University, Department of Neuropathology, Graduate School of Medical Sciences, Fukuoka (Japan); Takahashi, Masaya [Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX (United States)

    2017-02-15

    To investigate whether amide proton transfer (APT) MR imaging can differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) among gliomas without intense contrast enhancement (CE). This retrospective study evaluated 34 patients (22 males, 12 females; age 36.0 ± 11.3 years) including 20 with LGGs and 14 with HGGs, all scanned on a 3T MR scanner. Only tumours without intense CE were included. Two neuroradiologists independently performed histogram analyses to measure the 90th-percentile (APT{sub 90}) and mean (APT{sub mean}) of the tumours' APT signals. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were also measured. The parameters were compared between the groups with Student's t-test. Diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis. The APT{sub 90} (2.80 ± 0.59 % in LGGs, 3.72 ± 0.89 in HGGs, P = 0.001) and APT{sub mean} (1.87 ± 0.49 % in LGGs, 2.70 ± 0.58 in HGGs, P = 0.0001) were significantly larger in the HGGs compared to the LGGs. The ADC and rCBV values were not significantly different between the groups. Both the APT{sub 90} and APT{sub mean} showed medium diagnostic performance in this discrimination. APT imaging is useful in discriminating HGGs from LGGs among diffuse gliomas without intense CE. (orig.)

  14. Wide-field spectrally resolved quantitative fluorescence imaging system: toward neurosurgical guidance in glioma resection

    Science.gov (United States)

    Xie, Yijing; Thom, Maria; Ebner, Michael; Wykes, Victoria; Desjardins, Adrien; Miserocchi, Anna; Ourselin, Sebastien; McEvoy, Andrew W.; Vercauteren, Tom

    2017-11-01

    In high-grade glioma surgery, tumor resection is often guided by intraoperative fluorescence imaging. 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) provides fluorescent contrast between normal brain tissue and glioma tissue, thus achieving improved tumor delineation and prolonged patient survival compared with conventional white-light-guided resection. However, commercially available fluorescence imaging systems rely solely on visual assessment of fluorescence patterns by the surgeon, which makes the resection more subjective than necessary. We developed a wide-field spectrally resolved fluorescence imaging system utilizing a Generation II scientific CMOS camera and an improved computational model for the precise reconstruction of the PpIX concentration map. In our model, the tissue's optical properties and illumination geometry, which distort the fluorescent emission spectra, are considered. We demonstrate that the CMOS-based system can detect low PpIX concentration at short camera exposure times, while providing high-pixel resolution wide-field images. We show that total variation regularization improves the contrast-to-noise ratio of the reconstructed quantitative concentration map by approximately twofold. Quantitative comparison between the estimated PpIX concentration and tumor histopathology was also investigated to further evaluate the system.

  15. Dose enhancement by synchrotron radiation and heavy atoms for the treatment of gliomas

    International Nuclear Information System (INIS)

    Bobyk, L.

    2010-11-01

    High grade gliomas are brain tumors of bad prognosis. The standard therapeutic treatment combines surgery, radiotherapy and sometimes use of temozolomide (chemotherapy agent). Healthy tissues radio-sensitivity is a major limitation for radiotherapy treatment. The stereotactic radiotherapy by synchrotron radiation is an innovative technique which combines a low energy radiation (lower 100 keV) with the presence of heavy atoms in the tumoral zone. Such an approach is used to increase the differential of dose deposited in the tumor compared to surrounding healthy tissues. In this study, several compounds containing heavy atoms such as chemotherapy agents: cisplatin/carbo-platin, a DNA base analog: 5-iodo-2'-deoxyuridine (IUdR) and gold nano-particles were considered. The dose enhancement factor induced by the presence of these compounds located for some of them in the extracellular medium or inside the cells for others, was determined using in vitro studies. Thereafter, in vivo studies on rats bearing gliomas, were performed to study the toxicity, the kinetic of distribution and the localization of these compounds together with their potential efficacy of treatment combining intracerebral injection with low energy radiation. (author)

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

    Science.gov (United States)

    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

  17. Precursor lesions of high-grade serous ovarian carcinoma: morphological and molecular characteristics.

    Science.gov (United States)

    Gross, Amy L; Kurman, Robert J; Vang, Russell; Shih, Ie-Ming; Visvanathan, Kala

    2010-01-01

    The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).

  18. Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

    Directory of Open Access Journals (Sweden)

    Amy L. Gross

    2010-01-01

    Full Text Available The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC, particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs but our own findings (unpublished data and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs.

  19. Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma

    DEFF Research Database (Denmark)

    Haugvik, Sven-Petter; Janson, Eva Tiensuu; Österlund, Pia

    2016-01-01

    BACKGROUND: This study aimed to evaluate the role of surgery for patients with high-grade pancreatic neuroendocrine carcinoma (hgPNEC) in a large Nordic multicenter cohort study. Prior studies evaluating the role of surgery for patients with hgPNEC are limited, and the benefit of the surgery...... for patients undergoing resection of the primary tumor and resection/radiofrequency ablation of synchronous metastatic liver disease (n = 12), and 13 months for patients with synchronous metastatic disease given systemic chemotherapy alone (n = 78). The 3-year survival rate after surgery of the primary tumor....... Patients selected for resection of the primary tumor and synchronous liver metastases had a high 3-year survival rate. Selected patients with both localized hgPNEC and metastatic hgPNEC should be considered for radical surgical treatment....

  20. Invisible gold and arsenic in pyrite from the high-grade Hishikari gold deposit, Japan

    International Nuclear Information System (INIS)

    Morishita, Y.; Shimada, N.; Shimada, K.

    2008-01-01

    Gold occurs as both electrum (a natural alloy of gold and silver) and invisible gold in arsenian pyrite in the Hishikari epithermal gold deposit in Japan. Microanalyses of arsenian pyrite from the deposit using secondary ion mass spectrometry (SIMS) and electron probe microanalysis (EPMA) revealed that Au concentrations (0.1-2600 ppm) are positively correlated with As concentrations (0.0-6.1%). A small (3 μm) area of pyrite was analyzed because the sample textures were fine and complicated. The Au/As ratio is high in the Sanjin ore zone, which has very high-grade veins, while the ratio is low in the Yamada ore zone, which has average-grade veins

  1. Study on trickle leaching of a high-grade uranium ore

    International Nuclear Information System (INIS)

    Lin Sirong; Gao Xizhen; Guo Erhua; Lu Shijie

    1996-01-01

    The trickle leaching process for a high-grade silicate uranium ore existing mainly as uraninite form has been studied. Two-stage counter-current trickle leaching with manganese dioxide as oxidant and ferric sulphate solution as leaching agent is used in the process. The leached solution which contains dissolved uranium and iron is carried back to the neutralizing stage and the iron is precipitated in this stage. The acid is added to the main stage and the precipitated iron is dissolved into Fe 2 (SO 4 ) 3 serving as lixiviant in the stage. Compared with conventional agitation acid leaching method, this process decreases the acid consumption by 21% and manganese dioxide by 29%, the extraction rate of uranium reduces by 1.86%

  2. Synchronous Penile Metastasis from a High-Grade Adenocarcinoma of the Prostate

    Directory of Open Access Journals (Sweden)

    S. Dijkstra

    2012-01-01

    Full Text Available Metastasis to the glans penis is a rare phenomenon and usually occurs in a late stage of disease. A 68-year-old man was referred to our clinic because of two indurated lesions of the glans penis and minor lower urinary tract symptoms. Digital rectal examination revealed a hard nodular prostate, and serum prostate-specific antigen (sPSA level was 13.3 ng/mL. Biopsies of the penile lesions and transrectal ultrasound-guided prostate biopsies were taken. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue exposed a synchronous penile metastasis from a high-grade adenocarcinoma of the prostate. Except a pathologically enlarged lymph node detected with MRI there was no suspicion on other metastases. Currently this patient is being treated with a Gonadoreline (GnRH antagonist. Nevertheless, the prognosis will be poor.

  3. Isotopic evidence for two neoproterozoic high-grade metamorphic events in the Brazilia belt

    International Nuclear Information System (INIS)

    Pimentel, Marcio Martins; Fuck, Reinhardt Adolfo; Piuzanna, Danielle; Moraes, Renato de; Gioia, Simone Maria C.L

    2001-01-01

    The Brasilia Belt is part of a Brasiliano/Pan African orogen developed between the Amazon and Sao Francisco cratons. The stabilization of the belt occurred after the last metamorphic event at ca. 620 Ma. There has been increasing geochronological evidence, however, for an older Neoproterozoic metamorphic event at ca. 780 Ma, observed mainly in high grade rocks of three large mafic-ultramafic complexes in the northern part of the belt. In this study we present: (i) new U-Pb and Sm-Nd geochronological data, (ii) a review of the existing metamorphic ages in the Brasilia Belt, and (iii) a discussion on the tectonic model to explain the two Neoproterozoic metamorphic ages (au)

  4. Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome

    DEFF Research Database (Denmark)

    Wang, Zhigang C.; Birkbak, Nicolai Juul; Culhane, Aedín C.

    2012-01-01

    Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR cause...... clusters differed with respect to chemotherapy resistance, and the extent of LOH correlated with PFS. LOH burden may indicate vulnerability to treatment targeting DNA repair, such as PARP1 inhibitors. Clin Cancer Res; 18(20); 5806–15. ©2012 AACR....... into two subgroups. The second group contained remarkably less LOH. BRCA1 promoter methylation was associated with the major group. LOH clusters were reproducible when validated in two independent HGSC datasets. LOH burden in the major cluster of HGSC was similar to triple-negative, and distinct from other...

  5. Adenoid cystic carcinoma of the breast, high grade with basal phenotype, literature review

    Directory of Open Access Journals (Sweden)

    Enaam Junainah

    Full Text Available Adenoid cystic carcinoma (ACC is a rare type of breast carcinoma resembling adenoid cystic carcinoma of other sites. this type of tumors usually characterized by the exhibiting dual cell population of luminal and basaloid with specific growth pattern Most of these sub types are triple-negative with basal-like breast features (tumors that are devoid of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, and express basal cell markers, they are usually low-grade but can be high grade, clinical behavior is indolent despite the nuclear grade, lymph node involvement or distant metastases which is rarely occur. Treatment is either simple mastectomy or lumpectomy. Chemotherapy, radiation and hormonal treatment have limited used in those cases. Keywords: Adenoid cystic carcinoma, Breast, Triple-negative and basal-like phenotype

  6. Fusion-segment of high-grade Lumbar Spondylolisthesis: 2-year follow-up.

    Science.gov (United States)

    Li, X; Xu, L; Kong, Q

    2016-12-01

    The clinical efficacy of reduction and fusion surgery and the suitable range of fusion-segment were evaluated in 12 pediatric patients treated for high-grade spondylolisthesis. Pre/post-operative clinical and radiological assessments were analyzed. A transient L5 nerve root paralysis was observed in one patient with L5 spondylolisthesis. No degenerative spondylolisthesis or adjacent segmental instability occurred above the fusion segments. In conclusion, we suggest that, in case of spondylolisthesis without severe structural scoliosis deformity or only associated with lumbosacral deformity, the posterior ligament complex should be protected in case of adjacent segmental instability and spondylolisthesis. If the spondylolisthesis is complicated with severe structural scoliosis deformity (Cobb ≥ 70°), in principle, the treatment should be performed according to the characteristics of the two diseases respectively.

  7. High grade CIN diagnosis by combined visual inspection with Lugol's iodine and cytology in symptomatic women.

    Science.gov (United States)

    Russo, Evandro; Kupek, Emil; Zanine, Rita Maria

    2011-05-01

    To investigate the diagnostic performance of combining the visual inspection with Lugol's iodine (VILI) and cytology screening to detect high-grade cervical intraepithelial neoplasia (CIN-2 or CIN-3) in symptomatic women, using histological examination as the standard reference test. Cross-sectional referral study utilizing secondary data from 538 medical records from a clinic specialized in cervical pathology in Brazil. Although the sensitivity reached 96.8%, the specificity was only 8.1%, with positive predictive value of 18.3% and negative predictive value of 92.3%. The combination of both tests proved to be highly sensitive, leading to a large decrease in the false negative results. This was achieved, however, at the cost of an excess in the rate of false positive results, thus making the combination unviable for screening in symptomatic women. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Efficacy of spermatic vein ligation in patients affected by high grade left varicocele

    Directory of Open Access Journals (Sweden)

    Marco Grasso

    2014-01-01

    Full Text Available Purpose: To study the effect of high grade varicocele treatment in infertile patients. Materials and Methods: Seventy-five patients were selected by the following criteria: infertility persisting for more than 1 year; abnormal semen parameters; no other infertility-related disease; no obvious causes of infertility in the subject’s partner; basal eco-color Doppler ultrasound demonstrating continuous reflux in the spermatic vein. All patients considered for the study had at least a six months period from the diagnosis to the surgery due to waiting list, choice of the patient or time needed to complete diagnostic evaluation of the couple. The surgical procedure was performed through an inguinal approach. All enrolled patients were counseled to have unprotected intercourse during the ovulation period in order to maximize the probability of pregnancy within the 6-month preoperative period. The achievement of pregnancy and semen parameters were recorded during the preoperative and postoperative period. Results: Two of the seventy-five patients were excluded because of persistent varicocele after surgery. The preoperative pregnancy rate was 1.3% (1 couple. The postoperative pregnancy rate was 42.5%. The stratification of pregnancies by semester showed a significantly higher rate in the first postoperative period (p = 0.0012. Mean time to conception was 13.5 months. Mean preoperative sperm count was 17.6x10 6 /mL compared to 19.7x10 6 /mL in the postoperative period (p < 0.0001. Mean percentage of progressive sperm motility was 13.7%, compared to 17.6% in the postoperative period (p < 0.0001. Mean percentage of normal sperm morphology was 7.6%, compared to 15.2% postoperatively (p < 0.0001. Conclusion: Surgical treatment of high grade varicocele proved to effectively treat associated infertility by improving seminal parameters and pregnancy rate in our patient cohort.

  9. STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

    Science.gov (United States)

    Sinreih, Maša; Štupar, Saša; Čemažar, Luka; Verdenik, Ivan; Frković Grazio, Snježana; Smrkolj, Špela; Rižner, Tea Lanišnik

    2017-07-01

    Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as

  10. Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder.

    Science.gov (United States)

    Kim, Philip H; Cha, Eugene K; Sfakianos, John P; Iyer, Gopa; Zabor, Emily C; Scott, Sasinya N; Ostrovnaya, Irina; Ramirez, Ricardo; Sun, Arony; Shah, Ronak; Yee, Alyssa M; Reuter, Victor E; Bajorin, Dean F; Rosenberg, Jonathan E; Schultz, Nikolaus; Berger, Michael F; Al-Ahmadie, Hikmat A; Solit, David B; Bochner, Bernard H

    2015-02-01

    Urothelial carcinoma of the bladder (UCB) is genomically heterogeneous, with frequent alterations in genes regulating chromatin state, cell cycle control, and receptor kinase signaling. To identify prognostic genomic markers in high-grade UCB, we used capture-based massively parallel sequencing to analyze 109 tumors. Mutations were detected in 240 genes, with 23 genes mutated in ≥5% of cases. The presence of a recurrent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation was associated with improved recurrence-free survival (RFS) (hazard ratio [HR]: 0.35; p=0.014) and improved cancer-specific survival (CSS) (HR: 0.35; p=0.040) in patients treated with radical cystectomy (RC). In multivariable analyses controlling for pT and pN stages, PIK3CA mutation remained associated with RFS (HR: 0.39; p=0.032). The most frequent alteration, TP53 mutation (57%), was more common in extravesical disease (69% vs 32%, p=0.005) and lymph node-positive disease (77% vs 56%, p=0.025). Patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-altered tumors experienced worse RFS (HR: 5.76; pHR: 2.94; p=0.029) in multivariable analyses. Mutations in chromatin-modifying genes were highly prevalent but not associated with outcomes. In UCB patients treated with RC, PIK3CA mutations are associated with favorable outcomes, whereas TP53 and CDKN2A alterations are associated with poor outcomes. Genomic profiling may aid in the identification of UCB patients at highest risk following RC. Using next-generation sequencing, we identified genomic subsets of high-grade urothelial bladder cancer associated with favorable and unfavorable outcomes. These findings may aid in the selection of patients most likely to benefit from novel combined modality approaches. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  11. Zircon ion microprobe dating of high-grade rocks in Sri Lanka

    Energy Technology Data Exchange (ETDEWEB)

    Kroener, A.; Williams, I.S.; Compston, W.; Baur, N.; Vitanage, P.W.; Perera, L.R.K.

    1987-11-01

    The high-grade gneisses of Sri Lanka display spectacular in-situ granulitization phenomena similar to those observed in southern India and of current interest for evolutionary models of the lower continental crust. The absolute ages of these rocks are poorly constrained and so, using the SHRIMP ion microprobe, the authors have analyzed small spots on zircons from upper amphibolite to granulite grade quartzitic and pelitic metasediments. Detrital grains from a metaquartzite of the Highland Group preserve premetamorphic U-Pb ages of between 3.17 and 2.4 Ga and indicate derivation of the sediment from an unidentified Archean source terrain. The Pb-loss patterns of these zircons and the other samples suggest severe disturbance at ca 1100 Ma ago, which the authors attribute to high-grade regional metamorphism. Two pelitic gneisses contain detrital zircons with ages up to 2.04 Ga and also record an approx. = 1100 Ma event that is also apparent from metamorphic rims around old cores and new zircon growth. A granite intrusive into the Highland Group granulites records an emplacement age of 1000-1100 Ma as well as metamorphic disturbance some 550 Ma ago but also contains older, crustally derived xenocrysts. Zircons from a metaquartzite xenolith within the granitoid Vijayan Complex are not older than approx. 1100 Ma; therefore the Vijayan is neither Archean in age nor acted as basement to the Highland Group, as previously proposed. The authors suggest that the Vijayan Complex formed significantly later than the Highland Group and that the two units were brought into contact through post-1.1 Ga thrusting. Although the granulitization phenomena in India and Sri Lanka are similar, the granulite event in Sri Lanka is not Archean in age but took place in the late Proterozoic.

  12. Management and prognosis of patients with high-grade soft tissue sarcomas

    International Nuclear Information System (INIS)

    Alvegaard, T.A.

    1989-01-01

    Doxorubicin is one of the most active single agents in metastatic soft tissue sarcoma. This was the rationale for the evaluation og doxorubicin in an adjuvant situation for patients with high-grade soft tissue sarcoma in a randomized, Scandinavian, multicenter joint care program, which was carried out from January 1981 to February 1986, and included 240 patients. These patients comprised the base series for the investigations of the importance of the surgical margin and radiotherapy for local tumor control; the accuracy of malignancy grading and tumor typing; prognostic factors, including DNA content; and epidemiologic risk factors. The results showed that the use of doxorubicin as adjuvant chemotherapy did not have clinical benefit in patients with high-grade soft tissue sarcoma. The overall local tumor control was high (94 %) for radically operated on extremity-located tumors due to strict classification of surgical margins. The only risk factor for local recurrence was marginal surgery without radiotherapy with a four times higher risk than after compartmental or wide surgery. Twelve percent of the operations reported as radical were classified as marginal, demonstrating the importance of reevaluation of surgical margins, and in these patients the local recurrence rate was 37 %. The 5-year metastasis-free survival for the whole patients series was 55 %, with the extremes 79 % for the patients with no or only one risk factor and 0 % for those with four or five risk factors. The five prognostic factors found could be used for selection of high-risk patients for adjuvant chemotherapy in the future. The epidemiologic study gave limited support for an association between occupational phenoxy-acid exposure and soft tissue sarcoma development. (98 refs.)

  13. Surgical Versus Nonsurgical Treatment for High-Grade Spondylolisthesis in Children and Adolescents

    Science.gov (United States)

    Xue, Xuhong; Wei, Xiaochun; Li, Li

    2016-01-01

    Abstract The optimal management of high-grade spondylolisthesis in children and adolescent is controversial. There is a paucity of literature regarding operatively or nonoperative management in this setting. To assessment of the current state of evidence regarding high-grade spondylolisthesis treatment with the goal of obtaining outcome comparisons in these patients managed either operatively or nonoperatively. We performed a systematic literature search up to November 2014, using Medline, Embase, and The Cochrane Library. The analysis and eligibility criteria were documented according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-guidelines) and Cochrane Back Review Group editorial board. We used the Newcastle–Ottawa quality assessment scale (NOS-scale) to assess the quality. Five observational studies were considered eligible for analysis based on the evaluation of 1596 identified papers. The mean overall difference in the Scoliosis Research Society questionnaire 22 between the surgical and nonsurgical groups was not statistically significant (95% CI: −0.17 to 0.21, P = 0.84). The pooled mean difference in progression of slip between the surgical and nonsurgical groups was no significant difference (OR: 0.47, 95% CI: 0.12–1.81, P = 0.27, I2 = 0%). Because of the preponderance of uncontrolled case series, low-quality evidence indicates that the quality of life and progression of slips was no significant difference between surgery and nonoperation group. Nonoperative patients had no radiologic progression of their slip during the follow-up period. PMID:26986134

  14. [SPINO-PELVIC SAGITTAL ALIGNMENT IN PATIENTS WITH HIGH-GRADE L5 ISTHMIC SPONDYLOLISTHESIS].

    Science.gov (United States)

    Yang, Xi; Kong, Qingquan; Song, Yueming; Liu, Limin; Li, Tao; Gong, Quan; Zeng, Jiancheng; Liu, Hao

    2016-01-01

    To observe the character of spino-pelvic sagittal alignment in patients with high-grade L5 isthmic spondylolisthesis, and to analyze the sagittal alignment alteration after operation. Between January 2009 and June 2014, 25 patients with high-grade L5 isthmic spondylolisthesis underwent posterior surgery, and the clinical data were retrospectively analyzed as study group. There were 14 males and 11 females with a mean age of 42.5 years (range, 20-65 years). The mean disease duration was 6 months (range, 3-12 months). According to the Meyerding evaluating system, 15 cases were rated as degree III, and 10 cases as degree IV. Eighty healthy adult volunteers were recruited simultaneously as control group. The lumbar sacral angle (LSA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis (SVA) were measured on preoperative and last follow-up standing full length lateral X-ray films. And these parameters were compared between study group (preoperative parameters) and control group. Then the patients in study group were divided into 2 subgroups according to Hresko's method: the balanced pelvis subgroup (n = 14) and unbalanced pelvis subgroup (n = 11). The sagittal parameters were compared between 2 subgroups, and the alteration of sagittal parameters before surgery and at last follow-up was analyzed in each subgroup respectively. All patients in study group were followed up 18 months on average (range, 6-48 months). After surgery, spondylolisthesis was reduced from degree III to degree 0 in 12 cases and to degree I in 3 cases, and from degree IV to degree 0 in 6 cases and to degree I in 4 cases. Bone fusion was obtained in all patients at last follow-up. The preoperative PI, SS, PT, and SVA of study group were significantly greater than those of control group (P spondylolisthesis have greater PI, abnormal lumbosacral kyphosis, and sagittal imbalance.

  15. Radiological assessment of lumbosacral dystrophic changes in high-grade spondylolisthesis

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    Vialle, Raphael [Armand Trousseau Hospital, Department of Paediatric Orthopaedics, Paris Cedex 12 (France); Schmit, Pierre [Necker-Enfants Malades Hospital, Department of Paediatric Radiology, Paris (France); Dauzac, Cyril; Guigui, Pierre [Beaujon Hospital, Department of Orthopaedic Surgery, Clichy Cedex (France); Wicart, Philippe [Saint-Vincent de Paul Hospital, Department of Paediatric Orthopaedics, Paris (France); Glorion, Christophe [Necker-Enfants Malades Hospital, Department of Paediatric Orthopaedics, Paris (France)

    2005-09-01

    To analyse radiographic correlates for the clinical status of patients and the deformation reducibility of high-grade lumbosacral spondylolisthesis. We also clarify the clinical and radiographic correlates of a new parameter for S1 dystrophy, the ''S1 index''. One hundred cases of high-grade isthmic lumbosacral spondylolisthesis were reviewed. We noted the dystrophic changes in the cranial sacral endplate, and the caudal endplate of L5. The severity of the spondylolisthesis was evaluated by measuring the lumbosacral kyphosis. The clinical status and the deformation reducibility (dependent on the stiffness of the deformation) were compared with these dystrophic patterns, the sagittal slope of S1 and S2 endplates and a sacral morphological marker, the S1 index. Lumbosacral kyphosis was less severe in cases with dystrophic changes of the posterior cranial edge of S1 and/or of the posterior caudal edge of L5 but its reducibility was worse. These patients were more functionally impaired. We describe and analyse this situation as a partial lumbosacral disc failure responsible for the less severe L5 slipping. The S1 index was strongly correlated with the grade of slipping, the lumbosacral kyphosis and its reducibility. We noted the same configuration among patients with a smaller S1 index, i.e. vertical S1 and S2 vertebral bodies associated with more severe but more reducible lumbosacral kyphosis. Analysing specific criteria, we think it is possible to note progressive dystrophic changes according to the natural history of lumbosacral spondylolisthesis. We think that repeated measurements of these morphological parameters in patients diagnosed with a low-grade lumbosacral spondylolisthesis could be helpful in the early detection of evolving lumbosacral kyphosis and L5 slipping. (orig.)

  16. CIP2A protein expression in high-grade, high-stage bladder cancer

    International Nuclear Information System (INIS)

    Huang, Lisa P; Savoly, Diana; Sidi, Abraham A; Adelson, Martin E; Mordechai, Eli; Trama, Jason P

    2012-01-01

    Bladder cancer is one of the most common cancers in the United States. Numerous markers have been evaluated for suitability of bladder cancer detection and surveillance. However, few of them are acceptable as a routine tool. Therefore, there exists a continuing need for an assay that detects the presence of bladder cancer in humans. It would be advantageous to develop an assay with a protein that is associated with the development of bladder cancer. We have identified the cancerous inhibitor of PP2A (CIP2A) protein as a novel bladder cancer biomarker. In this study, Western blot analysis was used to assess the expression level of CIP2A protein in bladder cancer cell lines and bladder cancer patient tissues (n = 43). Our studies indicated CIP2A protein was abundantly expressed in bladder cancer cell lines but not in nontumor epithelial cell lines. Furthermore, CIP2A was specifically expressed in transitional cell carcinoma (TCC) of the bladder tumor tissues but not in adjacent nontumor bladder tissue. Our data showed that CIP2A protein detection in high-grade TCC tissues had a sensitivity of 65%, which is 3.4-fold higher than that seen in low-grade TCC tissues (19%). The level of CIP2A protein expression increased with the stage of disease (12%, 27%, 67%, and 100% for pTa, pT1, pT2, and pT3 tumor, respectively). In conclusion, our studies suggest that CIP2A protein is specifically expressed in human bladder tumors. CIP2A is preferentially expressed in high-grade and high-stage TCC tumors, which are high-risk and invasive tumors. Our studies reported here support the role of CIP2A in bladder cancer progression and its usefulness for the surveillance of recurrence or progression of human bladder cancer

  17. Neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs

    International Nuclear Information System (INIS)

    Ramos, Pedro; Gonzalez, Manuel; Perry, Fernando; Cardona, Andres Felipe

    2005-01-01

    Background: the use of neoadjuvant chemotherapy for high-grade soft-tissue sarcomas of the limbs continues to be an area of controversy; however, the number of clinical studies favoring the use of an anthracycline and iphosphamide-based regimen is increasing steadily. This approach may provide some advantages for facilitating the surgical resection of the tumor and for local disease control. The historical 5-year survival rate of approximately 50% in this high-risk group treated with local therapy alone represents a poor standard of care; thus, there is a need to incorporate systemic therapy early in the management of these patients. Objective: to describe the role of neoadjuvant chemotherapy in the treatment of soft-tissue sarcomas. Materials and methods: the records of 42 patients who attended the national cancer institute of Colombia in search for management of primary soft-tissue sarcomas were retrospectively reviewed. Ten patients with high-grade tumors larger than 8 cm, treated from June 2000 to February 2002 with neoadjuvant chemotherapy based on an anthracycline and iphosphamide regimen, plus vincristin and cisplatinum in selected cases, followed by surgery and adjuvant therapy with chemotherapy combined with local radiotherapy, were included. Evaluations of objective tumor response, survival, and toxicity were carried out. Results: after neoadjuvant therapy, s ix patients underwent conservative and limb-salvage surgery, three required radical interventions, and one refused surgical treatment. Seven experienced an objective response: it was complete in four and partial in three; the disease kept stable in two patients, and the tumor progressed in one case. After an average 46-month follow-up, four patients were permanently free of disease. Hematological and gastrointestinal toxicity was remarkable, and no patient had a long-term morbidity related to the treatment. Conclusions: this limited retrospective review suggests an advantage for the use of

  18. The role of radiotherapy in the management of spinal cord glioma

    International Nuclear Information System (INIS)

    Shirato, Hiroki; Kamada, Tadashi; Hida, Kazutoshi; Koyanagi, Izumi; Iwasaki, Yoshinobu; Miyasaka, Kazuo; Abe, Hiroshi

    1995-01-01

    Purpose: To determine the role of radiotherapy in the management of spinal cord gliomas. Methods and Materials: Thirty-six patients with spinal cord glioma treated between 1979 and 1993 were examined. The patients had 13 astrocytic tumors (7 astrocytomas, 4 anaplastic astrocytomas, 2 glioblastomas), 22 ependymal tumors (18 ependymomas, 4 myxopapillary ependymomas), and 1 unclassified glioma. Fifteen of the patients were treated by surgery alone, but the rema