[Impact of NGS results on patient outcome with a multiform glioblastoma]. / Analyse de l'impact des résultats du séquençage de nouvelle génération chez les patients atteints de glioblastome.

PURPOSE: Although some genetic alterations in glioblastoma (GBM) have been characterized, the prognostic value of these gene mutations is not yet established in patients treated with standard therapy. PATIENTS AND METHOD: 40 patients with newly diagnosed GBM, treated between July 2017 and December 2019, and who had genomic analysis were analyzed. Next-generation sequencing techniques (NGS) were used with a panel of 26 genes. Patients were grouped according to MGMT status, the presence or absence of at least one mutated gene on the panel, and p53 expression by immunohistochemistry. RESULTS: the median follow-up was 11.5 months (1.0-37). For all patients, the median duration of progression-free survival was 8 months (95% CI, 5.3-10.7) and the median overall survival (OS) was 17 months (95% CI, 7.5-26.5). Progression-free and overall survival were significantly different according to MGMT status but not according to NGS and p53 status. Three groups of patients according to different combined status could be distinguished due to significant differences in overall survival. CONCLUSION: we have shown that the presence of MGMT promoter methylation is a good prognostic factor. By grouping the patients according to their MGMT, NGS and p53 status, three groups of patients could be separated according to their overall survival. However, these results must be confirmed on a larger number of patients.

Interventional magnetic-resonance-guided cryotherapy combined with microsurgery for recurrent glioblastoma: An innovative treatment?

BACKGROUND: Glioblastoma invariably recurs after primary Stupp tumor therapy and portends a poor prognosis. Cryoablation is a well-established treatment strategy for extra-cranial tumors. The safety and efficacy of interventional MR-guided cryoablation (iMRgC) has not been explored in recurrent glioblastoma. METHODS: A retrospective analysis of data collected over a period of 24 months was performed. The inclusion criteria were: (I) recurrent glioblastoma despite Stupp protocol; (II) MRI followed by histological confirmation of recurrent glioblastoma; (III) location allowing iMRgC followed by microsurgical resection; and (IV) patient's consent. The primary objective was to assess feasibility in terms of complications. The secondary objective was to analyze progression-free survival (PFS), post-iMRgC survival and overall survival (OS). RESULTS: The study included 6 patients, with a mean age of 67±7.6 years [range, 54-70 years]. No major complications were observed. Median PFS was 7.5 months [IQR 3.75-9.75] and 6-month PFS was 50%. Median post-iMRgC survival was 9 months [IQR 7.5-15.25] and 6-month post-iMRgC survival was 80%. Median OS was 22.5 months [IQR 21.75-30]. CONCLUSION: iMRgC for recurrent glioblastoma demonstrated a good safety profile, with no major complications. Our data suggest improved PFS and OS. TRIAL REGISTRATION NUMBER: No. IRB00011687 retrospectively registred on July 7th 2021.

Signaling pathway deregulation and molecular alterations across pediatric medulloblastomas.

Medulloblastomas (MBs) account for 15% of brain tumors in children under the age of 15. To date, the overall 5-year survival rate for all children is only around 60%. Recent advances in cancer genomics have led to a fundamental change in medulloblastoma classification and is evolving along with the genomic discoveries, allowing to regularly reclassify this disease. The previous molecular classification defined 4 groups (WNT-activated MB, SHH-activated MB and the groups 3 and 4 characterized partially by NMYC and MYC driven MBs). This stratification moved forward recently to better define these groups and their correlation to outcome. This new stratification into 7 novel subgroups was helpful to lay foundations and complementary data on the understanding regarding molecular pathways and gene mutations underlying medulloblastoma biology. This review was aimed at answering the recent key questions on MB genomics and go further in the relevance of those genes in MB development as well as in their targeted therapies.

[Choice optimisation of radiation therapy technique for central neurocytomas from literature data]. / Optimisation du choix de la technique d'irradiation des neurocytomes centraux à partir des données de la littérature.

Neurocytomas represent 0,25 to 0,5 of brain tumours. These tumours have neuronal differentiation. It's a young adult disease. The main treatment is neurosurgery. The place of other therapies is still unclear, noticeably with regards to radiotherapy. This review aim is to determine the place and the modalities of radiotherapy in the management of neurocytomas. A literature search using PubMed allowed to select the most relevant studies. Finally, 22 studies were selected according to pre-established criteria to answer the problem. All studies were retrospective studies except one. The analysis conclusion defined radiotherapy as a treatment of choice in selected patients, when surgical resection was incomplete or when tumour was atypical.

Diagnostic value of fusion of metabolic and structural images for stereotactic biopsy of brain tumors without enhancement after contrast medium injection.

BACKGROUND: The heterogeneous nature of glioma makes it difficult to select a target for stereotactic biopsy that will be representative of grade severity on non-contrast-enhanced lesion imaging. The objective of this study was to evaluate the benefit of fusion of metabolic images (PET 18F-DOPA) with magnetic resonance imaging (MRI) morphological images for cerebral biopsy under stereotactic conditions of glioma without contrast enhancement. PATIENTS AND METHODS: This single-center prospective observational study conducted between January 2016 and April 2018 included 20 consecutive patients (mean age: 45±19.5 years; range, 9-80 years) who underwent cerebral biopsy for a tumor without MRI enhancement but with hypermetabolism on 18F-FDOPA PET (positron emission tomography). Standard 18F-FDOPA uptake value (SUVmax) was determined for diagnosis of high-grade glioma, with comparison to histomolecular results. RESULTS: Histological diagnosis was made in all patients (100%). Samples from hypermetabolism areas revealed high-grade glial tumor in 16 patients (80%). For a SUVmax threshold of 1.75, sensitivity was 81.2%, specificity 50%, PPV 86.7% and VPN 40% for diagnosis of high-grade glioma. No significant association between SUVmax and histomolecular mutation was found. CONCLUSION: 18F-FDOPA metabolic imaging is an aid in choosing the target to be biopsied under stereotactic conditions in tumors without MR enhancement. Nevertheless, despite good sensitivity, 18F-FDOPA PET is insufficient for definitive diagnosis of high-grade tumor.

Multidisciplinary management of an intra-sellar cavernous hemangioma: Case report and review of the literature.

Extra-axial cavernous hemangiomas (ECH) are rare vascular lesions with a tendency to grow within the medial structures of the middle cranial fossa. This pathological entity lacks specific symptoms, and falls into the category of differential diagnosis of space occupying lesions in the cavernous sinus (CS) with or without sellar involvement, including those of tumoral, vascular and inflammatory nature. Of note, ECH can also be indolent, and is at times discovered incidentally during autopsy investigations. On radiological studies, ECH with sellar extension are frequently mistaken at first for pituitary adenomas. Total removal of intrasellar-CS ECH is technically demanding and burdened by remarkable morbidity and mortality rates, mostly related to the complex neuroanatomy of the CS-sellar region (i.e., peri and postoperative bleeding, and transitory or permanent nerve palsies, hormonal deficits). Consequently, only a few cases of successful total removal have been reported so far in the literature. Surgical debulking with cranial nerve decompression followed by stereotactic radiosurgery is currently considered the best alternative to total removal when the latter carries excessive perioperative risks. We present a rare case of a mainly located intrasellar ECH extending to the left CS discussing its clinical features and focusing on the most relevant aspects of the surgical management along with a review of the pertinent literature.

Differentiation of vestibular schwannomas from meningiomas of the internal auditory canal using perilymphatic signal evaluation on T2-weighted gradient-echo fast imaging employing steady state acquisition at 3T.

BACKGROUND: Our aim was to confirm the usefulness of the perilymphatic signal changes on T2-weighted (T2W) gradient-echo sequence to differentiate vestibular schwannomas from internal auditory canal (IAC) meningiomas, through a compartmental analysis of inner ear fluids signal intensity. METHODS: A total of 203 patients with all criteria for typical vestibular schwannoma on T1-weighted contrast-enhanced sequences were retrospectively enrolled (190 schwannomas and 13 meningiomas). All patients underwent a T2W gradient-echo steady state free precession (SSFP) acquisition at 3T. Two radiologists analysed the signal intensity of the perilymph (cistern and cochlea) and endolymph (saccule and utricle) using a region of interest-based method for obtaining ratios between the analysed structures and the cerebrospinal fluid (CSF). RESULTS: Obstructive vestibular schwannomas showed a markedly decreased perilymphatic signal in both cistern and cochlea; the cistern/CSF ratio (Ci/CSF) was 0.62. The decrease was more moderate in IAC meningiomas (Ci/CSF = 0.81). For Ci/CSF > 0.70, the tumour was more likely a meningioma, with a 92% sensitivity and 83% specificity. No endolymphatic signal changes were observed. CONCLUSION: The pronounced decrease in perilymphatic signal on a T2W SSFP sequence in obstructive vestibular schwannoma provides a new tool to differentiate schwannomas from IAC meningiomas, which may be useful to overcome the insufficiencies of morphological analysis.

An unusual pituitary stalk lesion: What is the place of surgery?

BACKGROUND: Sellar and suprasellar primary melanocytic tumors are exceptional occurrences. Besides the difficulty of differential diagnosis between a primary and secondary lesion, treatment of these pathologies is still unclear and controversial. CASE REPORT: We describe the case of a 36-year-old woman with no relevant previous medical history who presented with 1 month history of diabetes insipidus, blurred vision and generalized weakness; a brain MRI disclosed an atypical pituitary stalk lesion; initially the tumor was biopsied through an endonasal endoscopic approach that revealed a melanocytic tumor; the patient was afterwards managed by a second stage extended endonasal endoscopic approach achieving a subtotal tumor removal. The overall survival was of 14 months due to the multidisciplinary management including surgery, radio and chemotherapy. CONCLUSION: If a biopsy is essential to deal with these invasive lesions, treatment including surgical resection should be part of a multidisciplinary approach.

Biphasic response of a tecto-mesencephalic pilocytic astrocytoma after Gamma Knife surgery--A case report.

Biphasic response (shrinkage-regrowth-shrinkage) of tumors has never previously been reported in the postoperative course, neither after microsurgery, nor after Gamma Knife surgery (GKS). We present the case of an adult with dorsal midbrain syndrome resulting from a pilocytic astrocytoma centered on the mesencephalic tectum. The tumor extended to the third ventricle and the thalamus. Initially, due to tumor growth, a biopsy was performed and histology established. Later, a ventriculocisternostomy for obstructive hydrocephalus was performed. Finally, GKS was performed, as the tumor continued to grow. After GKS, the lesion exhibited a biphasic response, with a major shrinkage at 3 months, regrowth within the target volume at 6 and 9 months and a second phase of important shrinkage at 12 months, which persisted for the next two years. The possible mechanisms for this particular response pattern are discussed.

Combination of MRI and dynamic FET PET for initial glioma grading.

AIM: MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading. PATIENTS, METHODS: 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated. RESULTS: Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022). CONCLUSION: Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.

Decision making and management of gliomas: practical considerations.

Over the last decade, diagnostic options and introduction of novel treatments have expanded the armamentarium in the management of malignant glioma. Combined chemoradiotherapy has become the standard of care in glioblastoma up to the age of 70 years, while treatment in elderly patients or with lower grade glioma is less well defined. Molecular markers define different disease subtypes and allow for adapted treatment selection. This review focuses on simple questions arising in the daily management of patients.

Finasteride-related Leydig cell tumour: report of a case and literature review.

Leydig cell tumours (LCTs) of the testis are rare. Their origin is still unknown. This case report describes a potential relationship between LCT and prolonged exposure to Finasteride.

Diffusion-weighted MRI, dynamic susceptibility contrast MRI and ultrasound perfusion quantification of denervated muscle in rabbits.

OBJECTIVE: The purpose of this study was to assess denervated muscle perfusion using dynamic susceptibility contrast MRI (DSCMRI) and contrast-enhanced ultrasound (CEUS), and to measure denervated muscle apparent diffusion coefficient (ADC) on b1000 diffusion-weighted MRI (DWMRI) at 3 T in order to clarify whether muscle denervation leads to an increase in the extracellular extravascular space, or an increase in blood flow-or both. MATERIALS AND METHODS: Axotomy of the right sciatic nerve of six white rabbits was performed at day 0. At day 9, hind limb muscles MRI and CEUS were performed to assess the consequences of denervation and both semimembranosus muscles of each rabbit were explanted for histological studies. Signal intensity on T2- and T1-weighted MRI, ADC on DWMRI, maximum signal drop (MSD) on DSCMRI and the area under the curve (AUC) on CEUS were measured over circular regions of interest (ROI), in both semimembranosus muscles. Non-parametric Wilcoxon matched-pairs tests were used to assess the mean differences between denervated and normal muscles. RESULTS: T2 fat-saturated (FS) MRI studies showed a strong signal in the right semimembranosus muscles compared with the left side, and gadolinium enhancement was observed on T1 FS MRI. Denervated muscles show a significant increase in ADC on DWMRI (p < 0.01) and a significant signal enhancement on DSCMR imaging (p < 0.05) and on first-pass CEUS (p < 0.05). CONCLUSION: The results of this study--based on perfusion- and diffusion-weighted images--suggest that, after denervation, both increased blood flow through muscle tissue and expansion of the extracellular water volume are present.

[Active surveillance for early-stage prostate cancer]. / La surveillance active dans la prise en charge du cancer de la prostate précoce.

Diagnostic and treatment management of prostate cancer at its initial stage continues to raise important debates within the involved medical community. To establish a protocol for active surveillance, a validated option in specific conditions of localised prostate cancer management for eight years, is a unique opportunity to gather different specialists in this field. This paper presents this concept.

[Purulent corneal melting secondary to multidrug-resistant Fusarium oxysporum aggravated by topical corticosteroid therapy]. / Fonte purulente de la cornée secondaire à une infection à Fusarium oxysporum polyrésistant favorisée par une corticothérapie topique.

Keratomycosis is a rare sight-threatening infection of the cornea. Predisposing factors in its pathogenesis are corneal trauma, mostly of plant origin, contact lenses, and overuse of topical corticosteroids. We report a case of a 44-year-old woman, with no ophthalmologic history, who developed severe keratitis 7 days after beginning topical therapy with a corticosteroid and antibiotic. Microbiological analysis revealed Fusarium oxysporum keratitis. Despite aggressive antifungal therapy with Voriconazole and Amphotericin B, she required a penetrating keratoplasty for impending corneal perforation. A second keratoplasty was performed because of corneal-transplant rejection after 6 months. There was no recurrence of Fusarium infection.

Different effects of the Cdx1 and Cdx2 homeobox genes in a murine model of intestinal inflammation.

AIMS: The CDX1 and CDX2 homeoproteins are intestine-specific transcription factors regulating homeostasis. We investigated their relevance in experimentally-induced intestinal inflammation. METHODS: The response to intestinal inflammation induced by dextran sodium sulfate (DSS) was compared in wild type, Cdx1(-/-) and Cdx2(+/-) mice. Intestinal permeability was determined in wild type and Cdx2(+/-) mice. Protein-protein interactions were investigated by co-immunoprecipitation and GST-pulldown, and their functional consequences were assessed using Luciferase reporter systems. RESULTS: Heterozygous Cdx2(+/-) mice, but not Cdx1(-/-) mice, were hypersensitive to DSS-induced acute inflammation as all these mice showed blood in the stools at day 1 of DSS treatment. Hypersensitivity was associated to a 50% higher intestinal permeability. In Cdx2(+/-) mice, the colonic epithelium was repaired during the week after the end of DSS treatment, whereas two weeks were required for wild type animals. Subsequently, no colonic tumour was observed in Cdx2(+/-) mice subjected to 5 repeated cycles of DSS, in contrast to the 2.7 tumours found per wild type mouse. Based on the fact that Smad3(+/-) mice, like Cdx2(+/-) mice, better repair the damaged intestinal epithelium, we found that the CDX2 protein interacts with SMAD3, independently of SMAD4, resulting in a 5-fold stimulation of SMAD3 transcriptional activity. CDX1 also interacted with SMAD3 but it inhibited by 10-fold the SMAD3/SMAD4-dependent transcription. CONCLUSION: The Cdx1 and Cdx2 homeobox genes have distinct effects on the outcome of a pro-inflammatory challenge. This is mirrored by different functional interactions of the CDX1 and CDX2 proteins with SMAD3, a major element of the TGFbeta signalling pathway.