Glioblastoma-associated stromal cells (GASCs) from histologically normal surgical margins have a myofibroblast phenotype and angiogenic properties.

Glioblastoma (GB) displays diffusely infiltrative growth patterns. Dispersive cells escape surgical resection and contribute to tumour recurrence within a few centimeters of the resection cavity in 90% of cases. We know that the non-neoplastic stromal compartment, in addition to infiltrative tumour cells, plays an active role in tumour recurrence. We isolated a new stromal cell population from the histologically normal surgical margins of GB by computer-guided stereotaxic biopsies and primary culture. These GB-associated stromal cells (GASCs) share phenotypic and functional properties with the cancer-associated fibroblasts (CAFs) described in the stroma of carcinomas. In particular, GASCs have tumour-promoting effects on glioma cells in vitro and in vivo. Here, we describe a quantitative proteomic analysis, using iTRAQ labelling and mass spectrometry, to compare GASCs with control stromal cells derived from non-GB peripheral brain tissues. A total of 1077 proteins were quantified and 67 proteins were found to differ between GASCs and control stromal cells. Several proteins changed in GASCs are related to a highly motile myofibroblast phenotype, and to wound healing and angiogenesis. The results for several selected proteins were validated by western blotting or flow cytometry. Furthermore, the effect of GASCs on angiogenesis was confirmed using the orthotopic U87MG glioma model. In conclusion, GASCs, isolated from GB histologically normal surgical margins and found mostly near blood vessels, could be a vascular niche constituent establishing a permissive environment, facilitating angiogenesis and possibly colonization of recurrence-initiating cells. We identify various proteins as being expressed in GASCs: some of these proteins may serve as prognostic factors for GB and/or targets for anti-glioma treatment.

[Brain metastases: surgery and stereotactic radiosurgery]. / Chirurgie et radiochirurgie des métastases cérébrales.

Recent progresses in treatment of brain metastases have improved survival and quality of life in cancer patients. Surgery and stereotactic radiosurgery are two validated technics for brain metastases treatment. Actually, these two modalities of treatment could be used separately or in combination depending on the clinical situation (age, primitive disease status, type of primitive cancer, Karnofsky performance status) and radiological situation (number of brain metastases, localization). In this article, data from trials that examine the role of surgery and stereotactic radiosurgery in the management of brain metastases are reviewed.

Clinical guidelines and care pathway for management of low back pain with or without radicular pain.

OBJECTIVE: To develop guidelines for low back pain management according to previous international guidelines and the updated literature. METHODS: A report was compiled from a review of systematic reviews of guidelines published between 2013 and 2018 and meta-analysis of the management of low back pain published between 2015 and 2018. This report summarized the state-of-the-art scientific knowledge for each predefined area of the guidelines from a critical review of selected literature. A multidisciplinary panel of experts including 17 health professionals involved in low back pain management and 2 patient representatives formulated preliminary guidelines based on the compilation report and a care pathway. The compilation report and preliminary guidelines were submitted to 25 academic institutions and stakeholders for the consultation phase. From responses of academic institutions and stakeholders, the final guidelines were developed. For each area of the guidelines, agreement between experts was assessed by the RAND/UCLA method. RESULTS: The expert panel drafted 32 preliminary recommendations including a care pathway, which was amended after academic institution and stakeholder consultation. The consensus of the multidisciplinary expert panel was assessed for each final guideline: 32 recommendations were assessed as appropriate; none was assessed as uncertain or inappropriate. Strong approval was obtained for 27 recommendations and weak for 5. CONCLUSION: These new guidelines introduce several concepts, including the need to early identify low back pain at risk of chronicity to provide quicker intensive and multidisciplinary management if necessary.

Lessons to Be Remembered from a Dural Arteriovenous Fistula Mimicking Medulla and High Cervical Cord Glioma.

The radiological signs of intracranial dural arteriovenous fistulas (ICDAVFs) are heterogenous. While it is commonly accepted that hyper intense T2 wedge magnetic resonance imaging of the brainstem and cervical cord mainly concern gliomas, it is so far uncommon and probably unknown that ICDAVFs can imitate similar radiological pattern, especially with gadolinium contrast enhancement and cord enlargement. Thus the angiography is poorly documented in the diagnostic workup. We report the unusual history of ICDAVFs, revealed by clinical and radiological features that mimicked a medulla or cervical spinal cord glioma. This observation provides information on the management of atypical lesions mimicking medulla or cervical cord glioma and arguments for a careful radiological study. Looking for dilated veins around the brainstem and the cord is mandatory in the workup of a supposed infiltrating brainstem or spinal cord lesion, in order to rule out an ICDAVF. Even if the hyperintense T2 images associated with contrast enhancement is in favor of a brainstem or spinal cord glioma, additional cerebral angiography should be mandatory. Moreover, this clinical case highlights the need for a multidisciplinary approach including neuroradiologist, oncologist and neurosurgeon.

Optic nerve and visual pathways primary glioblastoma treated with radiotherapy and temozolomide chemotherapy.

PURPOSE: Primary malignant gliomas of the optic nerves are rare tumors of adulthood, progressing rapidly to blindness and to death within several months, regardless of the type of treatment. Recently, treatments associating radiotherapy and temozolomide have been used in other types of glioblastomas, but their impact on optic nerve malignant gliomas is not known. METHODS: This was a retrospective case series of 2 patients diagnosed with primary optic nerve and chiasm glioblastoma (GBM), treated with radiotherapy and concomitant temozolomide. RESULTS: A 74-year-old man presented with visual loss caused by an infiltrative and enhancing lesion, affecting the left optic nerve and the chiasm, subsequently confirmed as GBM World Health Organization (WHO) grade IV. The patient was treated with external conformal radiotherapy (54 Gy over 42 days) and concomitant chemotherapy with temozolomide (75 mg/m2/day), followed by 6 monthly cycles of adjuvant treatment (250 mg/day for 5 days). The second patient was a 74-year-old woman diagnosed with bilateral visual loss due to pathologically confirmed GBM (WHO grade IV). She was treated with temozolomide (220 mg/day) for 1 month, followed by radiotherapy (54 Gy over 42 days) and temozolomide chemotherapy (75 mg/m2/day). There was no adjuvant regimen. This treatment resulted in disease stabilization and partial preservation of vision during 12 months for patient 1, 8 months for patient 2. Survival after first examination was 15 and 11 months, respectively. CONCLUSIONS: Combined radiotherapy and temozolomide may be an alternative treatment in optic nerve and visual pathways primary GBM, potentially providing a longer survival.