Maintenance of Stemlike Glioma Cells and Microglia in an Organotypic Glioma Slice Model.

BACKGROUND: The therapeutic resistance of gliomas is, at least in part, due to stemlike glioma cells (SLGCs), which self-renew, generate the bulk of tumor cells, and sustain tumor growth. SLGCs from glioblastomas (GB) have been studied in cell cultures or mouse models, whereas little is known about SLGCs from lower grade gliomas. OBJECTIVE: To compare cell and organotypic slice cultures from GBs and lower grade gliomas and study the maintenance of SLGCs. METHODS: Cells and tissue slices from astrocytomas, oligodendrogliomas, oligoastrocytomas, and GBs were cultivated in (1) serum-free medium supplemented with the growth factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), (2) medium containing 10% serum plus EGF and bFGF (F+GF medium), or (3) medium containing 10% fetal calf serum (F medium). Maintenance of cells and cytoarchitecture was addressed, using several candidate SLGC markers (Nestin, Sox2, CD133, CD44, CD49f/integrin α6, and Notch) as well as CD31 (endothelial cells), ionized calcium-binding adapter molecule 1 (microglia), and vimentin. Cell vitality was determined. RESULTS: SLGCs were present in tissue slices from lower and higher grade gliomas. Preservation of the cytoarchitecture in slices was possible for >3 weeks. Maintenance of SLGCs required the presence of EGF/bFGF in cell and slice cultures, in which F+GF appeared superior to N medium. Constraints were observed regarding the preservation of the microglia but not of the endothelial cells. Maintenance of the microglia was improved by addition of the cytokine macrophage colony-stimulating factor. CONCLUSION: Medium supplemented with serum and growth factors EGF, bFGF, and macrophage colony-stimulating factor permits the preservation of SLGCs and non-SLGCs in the original glioma microenvironment.

Recurrent Oligodendroglioma Treated with Acupuncture and Pharmacopuncture.

Acupuncture and pharmacopuncture have been shown to be effective in tumor treatment. However, their effectiveness for treating oligodendroglioma has not been reported yet. The purpose of this study was to provide an initial report on the effectiveness of acupuncture and pharmacopuncture for the treatment of an oligodendroglioma by presenting a case that was treated successfully. A 54-year-old man, who had experienced intracranial hemorrhage, was diagnosed with recurrent oligodendroglioma. His expected survival period was 3-6 months. The patient received daily acupuncture and weekly pharmacopuncture of mountain ginseng and bee venom. After treatment for 18 months, the tumor size was decreased markedly on brain magnetic resonance imaging, and severe seizures had disappeared. In this case, a combination of acupuncture and pharmacopuncture was shown to be effective for the treatment of recurrent oligodendroglioma.

Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of High-Grade Glioma.

INTRODUCTION: The SCAN Neuro-Oncology workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for high-grade glioma in Singapore. MATERIALS AND METHODS: The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. RESULTS: Six international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2013), the European Association for Neuro-Oncology (EANO) Task Force on Malignant Glioma (2014), the European Society of Medical Oncology (2014), the Canadian GBM Recommendations Committee (2007) and the Australian Cancer Network (2009). Recommendations on the systemic therapy of high-grade glioma were produced. CONCLUSION: These adapted guidelines form the SCAN Guidelines 2015 for systemic therapy of high-grade glioma.

Thalamic gliomas in children: an extensive clinical, neuroradiological and pathological study of 14 cases.

OBJECT: Thalamic tumors represent only 1 to 5% of brain neoplasms but frequently affect children. However, pediatric series are rare and go back to several years in spite of recent advances in the neuroradiological, pathological, and molecular fields. METHODS: We report a series of 14 pediatric thalamic gliomas with clinical, neuroradiological, and pathological studies including p53 immunostaining in 11 cases and 1p19q status in three cases. RESULTS: Our series included five pilocytic astrocytomas, seven oligodendrogliomas, and two glioblastomas. Pilocytic astrocytomas were characterized by strong contrast enhancement, lack of p53 expression, and excellent prognosis. Oligodendrogliomas frequently demonstrated an aspect of unilateral thalamic enlargement lacking or with slight contrast enhancement. Some of them expressed p53 or demonstrated 1p loss. Anaplastic oligodendrogliomas and glioblastomas displayed a poor outcome, with a mean survival of 8 months after surgery. CONCLUSION: Our series of pediatric thalamic gliomas clearly distinguishes pilocytic astrocytomas from anaplastic oligodendrogliomas regarding neuroimaging, pathology, and prognosis.

Congenital oligodendroglioma with initial manifestation of jaundice.

Neonatal brain tumor is a rare clinical entity. The initial presentation in affected newborn infants is often subtle, nonspecific, and rarely includes focal neurologic signs. We report a 2-day-old male infant with congenital oligodendroglioma with initial manifestations of hyperbilirubinemia. Phototherapy was started immediately after admission. Because of a tense anterior fontanel and irritable crying, head ultrasonography, computed tomography, and magnetic resonance imaging were performed and revealed a heterogenous brain tumor in the left temporoparietal lobe. Craniotomy and tumor evacuation was performed, and WHO grade III anaplastic oligodendroglioma was confirmed by the pathologic studies. The patient was discharged 3 weeks later, and outpatient follow-up examination revealed a normally developed infant at 6 months of age. The cause of jaundice was thought to be secondary to tumor hemorrhage, which was not infrequent in neonatal brain tumor.

Oligodendroglial ganglioglioma with anaplastic features arising from the thalamus.

Anaplastic gangliogliomas with an oligodendroglial component are exceedingly rare tumors of uncertain growth potential. We report a 17-year-old female with a massive ganglioglioma containing anaplastic oligodendroglioma apparently arising from the thalamus. Two weeks after partial resection, she was started on a regimen including escalated doses of topotecan in combination with a fixed-dosage intensification regimen of cisplatin, cyclophosphamide and vincristine with subsequent hyperfractionated external beam radiotherapy. She currently has stable disease.

Patología molecular de los gliomas / Molecular biology of gliomas

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Oligodendroglioma with signet-ring cell morphology: a case report with an immunohistochemical and ultrastructural study.

A case of oligodendroglioma with signet-ring cell (SRC) morphology arising in the right thalamic region in a 12-year-old boy is described. Histopathologically, the tumor was a composite neoplasm consisting of typical oligodendroglioma and anaplastic components with aggregates of SRC. Immunohistochemically the SRC were negative for glial fibrillary acidic protein (GFAP) but surrounded by GFAP-positive anaplastic cells with high-grade nuclear features. Typical oligodendrogliomatous components were negative for GFAP. The Ki-67 labeling index evaluated with MIB-1 antibody was 1.3% in the SRC component, 9.2% in the GFAP-positive anaplastic cell component, and 0.8% in the typical oligodendrogliomatous component. Ultrastructurally, the cytoplasm of the SRC was filled with irregularly and widely dilated cisternae of rough endoplasmic reticulum containing granular material. Intermediate filaments and a small number of other organelles were distributed in the perinuclear and peripheral areas. Both the SRC and anaplastic cells had slender cytoplasmic processes, although those of the SRC were short and few in number. These findings are distinct from those of SRC hitherto described in oligodendrogliomas to date, and suggest that there is a morphological heterogeneity in SRC rarely seen in oligodendrogliomas and that some examples of SRC are related to the anaplastic cells with astrocytic features in their origin.

[Uptake of DL-3-123I-iodo-alpha-methyltyrosine in recurrent brain tumors]. / Anreicherung von DL-3-123I-Jod-alpha-methyltyrosin in Hirntumorrezidiven.

DL-3-123I-iodo-alpha-methyltyrosine (123I-IMT) is a radiopharmacon which concentrates in brain tumors and can be employed in SPECT. We performed 20 studies in 16 patients after neurosurgery for malignant brain tumors (localization of the primary tumor by CT/MRI). Tumor/non-tumor ratios (T/NT) were calculated in ROI-technique. In 17 cases there was a recurrence or tumor remnant. 14/17 were detectable by increased uptake (T/NT 1.43-2.25). The scans were correlated with CT/MRI studies and validated by biopsy (6/14) or follow-up. All 3 patients without recurrence (neuroradiological follow-up over 6-24 months) had a negative scan. 123I-IMT scintigraphy provides complementary information to CT and MRI. In equivocal neuroradiological or clinical cases it may be valuable in the detection of tumor recurrences and allows an earlier onset of therapy.

Early experience with the Gill Thomas Locator for computed tomography-directed stereotactic biopsy of intracranial lesions.

The Gill Thomas Locator is a stereotactic adaptor for the Brown-Roberts-Wells and Cosman-Roberts-Wells systems. It is a noninvasive device that relies on temporary fixation to the maxillary teeth. A series of 20 patients have had stereotactic biopsies with this system. A diagnostic biopsy was obtained in 19 cases. The frame was well tolerated, accurately relocatable, and allowed computed tomographic scanning and surgery to be conducted at different times.

Cortical mapping and local anaesthetic resection as an aid to surgery of low and intermediate grade gliomas.

We report four cases of the use of peroperative cortical mapping during craniotomy under local anaesthesia to define the relationship between the glioma and speech and somatosensory cortex. This enabled a radical subtotal (two cases) or an apparent total (two cases) excision of the tumour close to the somatosensory and speech cortex with no permanent neurological deficit. Use of this technique allows radical excision of intrinsic low and intermediate grade gliomas that would otherwise be considered unexcisable and may lead to an improved survival.

Photodynamic therapy of malignant brain tumors: clinical results of, difficulties with, questions about, and future prospects for the neurosurgical applications.

Photodynamic therapy (PDT) has been applied in a variety of oncological fields with good results. In neurosurgery, the clinical series are limited and the number of treated patients is not statistically significant. This work examines the results of PDT performed in our clinic and discusses some difficulties and causes of failure of this method in neurosurgical patients. Eight patients with malignant brain tumors underwent PDT. All had been treated previously by operation and radiation therapy and one patient had also received chemotherapy. At 24 hours after the i.v. injection of hematoporphyrin (5 mg/kg body weight), the tumor was removed as radically as possible and the residual tumor bed was exposed to either 630-nm light from an argon-dye laser or 600- to 680-nm light isolated from the emission of a quartz-halogen lamp. The type of sensitizer, the irradiation methods, and the peculiarities of glial tumors are examined as possible causes of failure. The longer survivals of some patients with glial tumors treated by PDT may make this treatment suitable when traditional therapies fail.