PubMed Health⌕ Search

Biomedical subjects

F Beuvon

Publications and source records attributed to F Beuvon.

At least 19 recordsLinked to original sources

Functional endothelin ET B receptors are selectively expressed in human oligodendrogliomas.

Endothelin-1 (ET-1), a vasoactive and mitogenic peptide mainly produced by vascular endothelial cells, may be involved in the progression of several human tumors. Here, we present an immunohistochemical analysis of the expression pattern of ET-1 receptor subtypes (ET(A)-R and ET(B)-R) and a functional study of their potential role in human oligodendrogliomas and oligoastrocytomas. By comparison, we assessed the corresponding expression patterns of glioblastomas. Interestingly, a nuclear localization of ET-1 receptor subtypes (associated or not with a cytoplasmic labeling) was constantly observed in tumor cells from all three glioma types. Moreover, we noted a distinct receptor distribution in the different gliomas: a nuclear expression of ET(B)-R by tumor cells was found to be restricted to oligodendrogliomas and oligoastrocytomas, while a nuclear expression of ET(A)-R was only detected in tumor cells from some glioblastomas. Using primary cultures of oligodendroglial tumor cells, we confirmed the selective expression of nuclear ET(B)-R, together with a plasma membrane expression, and further demonstrated that this receptor was functionally coupled to intracellular signaling pathways known to be involved in cell survival and/or proliferation: extracellular signal-regulated kinase and focal adhesion kinase activation, actin cytoskeleton reorganization. In addition, impairment of ET(B)-R activation in these cells by in vitro treatment with an ET(B)-R-specific antagonist induced cell death. These data point to ET-1 as a possible survival factor for oligodendrogliomas via ET(B)-R activation and suggest that ET(B)-R-specific antagonists might constitute a potential therapeutic alternative for oligodendrogliomas.

Actin Cytoskeleton↗

[Cerebral cavernomas, epilepsy and seizures. Natural history and therapeutic strategy].

PURPOSE: To review, from a retrospective series of 48 patients presenting with seizures associated with one or more supratentorial cavernoma(s), the natural history of the seizures and outcome according to medical and surgical treatment. METHODS: Patients were divided into two groups: group A included patients presenting with a single seizure or rare seizures (n=21), and group B patients having intractable epilepsy (n=27). All received antiepileptic drugs and 35 were operated on (12 in the group A and 23 in the group B). Stereo-EEG was performed in 8 patients in group B. Surgery included lesionectomy alone (n=16), resection of the cavernoma and perilesional tissue (n=7) or tailored corticectomy including the cavernoma (n=12). RESULTS: The natural history of seizures was different in the two groups: mean age at seizure onset was 25 years in group B and 33 years in group A (p<0.05), seizures were partial in all patients in group B and 8 patients in group A (p<0.05). Seizure frequency and periodicity also varied. Prolonged seizure-free periods were observed. The cavernoma was temporal in 17 patients in group B and 4 patients in group A (p<0.01). In group A, seizure outcome was favorable following surgery or with antiepileptic medication only (7 patients out of 12 operated were seizure-free, as were 5 out of 7 non-operated). In group B, seizure outcome was better after surgery than with medication only (17 patients out of 23 operated were in Engel's Class I, while 3 patients of 4 non-operated patients had persisting seizures despite antiepileptic polytherapy). CONCLUSION: Variations in seizure severity in patients harboring cavernomas suggest different therapeutic approaches. In case of unique or rare seizures, surgical resection of the cavernoma is appropriate, but benefits of surgery over antiepileptic medication in terms of seizure control remains unclear. Intractable epilepsy associated with cavernomas is better controlled after surgery rather than with medication only. In these patients, a detailed preoperative work-up is necessary and should be followed by wide resection associated or not with corticectomy, especially in the temporal lobe. Evaluation of outcome after surgery should consider the surgical strategy, antiepileptic medications and the patient's seizure history.

Adolescent↗

[Oligodendrogliomas: historical background of classifications].

The story of the classifications for gliomas is related to the development of the techniques used for cytological and histological examination of brain parenchyma. After a review of these techniques and the progressive discovery of the central nervous system cell types, the main classifications are presented. The first classification is due to Bailey and Cushing in 1926. It was based on histoembryogenetic theory. Then Kernohan introduced, in 1938, the concept of anaplasia. The WHO classification was published in 1979, then revised in 1993 and 2000. It took into account some data from both previous systems and introduced gradually the notion of histological criteria of malignancy. More recently; molecular genetics data and clinical evolution were retained. The Sainte-Anne classification for oligodendrogliomas is based on both histological and imaging data. It includes the notion of spatial histological structure of oligodendrogliomas. Contrast enhancement is closely related to endotheliocapillary hyperplasia. Gliomas classifications are changing and confusions can be made because of lack of reproductibility and misinterpretations of samples.

Brain Neoplasms↗

[Criteria of diagnosis and grading of oligodendrogliomas or oligo-astrocytomas according to the WHO and Sainte-Anne classifications].

Two main classification systems are used in France for the histological typing and grading of oligodendrogliomas: the WHO and Sainte-Anne Hospital (SA) classifications. According to the WHO, the typing of diffuse gliomas is based on the predominant cell type, oligodendroglial versus astrocytic. In contrast, the SA classification is based on the distinction of two patterns of tumor growth, solid tumor tissue versus isolated tumor cells and also relies on imaging and clinical features. According to this approach, the SA classification includes in the category of oligodendrogliomas, the fibrillary or gemistocytic diffuse astrocytomas (WHO grade II) as well as a substantial proportion of astrocytomas WHO grade III, 2) the WHO uses multiple histological criteria for the grading of oligodendrogliomas (grade II versus grade III), including the degree of differentiation, cellular atypia, mitotic activity and necrosis. In contrast, the SA grading of these tumors (grade A versus B) only uses two criteria: the presence or absence of endothelial hyperplasia, and the presence or absence of contrast enhancement. This last criterion allows overcoming the problems related to the representativeness of surgical samples. Difficulties and discrepancies regarding the diagnosis of oligodendrogliomas are in part due to the lack of immunomarker for the identification of tumoral oligodendrocytes. The potential interest of new markers of oligodendroglial precursors for the diagnosis of these tumors will further be discussed.

Astrocytoma↗

[Results of the Sainte-Anne - Lyons series of 318 oligodendroglioma in adults].

INTRODUCTION: Incidence of cerebral oligodendrogliomas is increasing because of better recognition made possible by improved classifications. We studied a homogeneous series using the Sainte-Anne grading scale in order to better understanding the history of these tumors with or without treatment and to assess prognosis and associated factors. PATIENTS AND METHODS: A retrospective series of 318 adult patients with oligodendroglioma (OLG) treated at Hôpital Sainte-Anne, Paris (SA) and Hôpital Neurologique, Lyons (L) between 1984 and 2003 was analyzed: 182 grade A OLG (SA + L), 136 grade B among which a homogenous series of 98 (SA) were included. For grade A: age at diagnosis ranged from 21 to 70 (mean: 41), sex ratio was 1.28. For grade B: age at diagnosis ranged from 12 to 75 (mean: 45.5), sex-ratio was 1.58. The main first symptoms were: epilepsy (A: 91.5%; B: 76%), intracranial hypertension (A: 7.9%; B: 14.6%), neurological deficit (A: 5.1%; B: 17.7%). The most frequent locations were: frontal, insular and central for both A and B. Mean size was 55 mm for grade A, 62 mm for B. Calcifications were found in 20% of A, 48.5% of B. No tumor was enhanced on imaging (CT/MRI) in grade A, all but 7 in grade B. All patients underwent surgery either for biopsy (A: 47.2%; B: 53%), or removal which was partial (A: 26.4% vs B: 19.4%) or extended (A: 36.3% vs B: 37.8%). Fifty-six patients underwent 2 procedures and 12 three procedures. Radiotherapy was performed in 76.9% of grade A, and 91% of B patients, in the immediate postoperative period for 71% A and 82.7% B. Chemotherapy was delivered for 36% of grade A (in the event of transformation to grade B or failure of radiotherapy) and 67.5% of B patients. Among grade A tumors, 38% transformed into grade B within a mean delay of 51 months with a mean follow-up of 78 months. RESULTS: Median survival was 136 months for grade A and 52 for grade B. Survival at 5, 10 and 15 was 75.5%, 51% and 22.4% for grade A vs 45.2%, 31.3% and 0% for grade B respectively. In univariate and multivariate analysis, grade A survival was associated with age at diagnosis, tumor size, large removal and response to radiotherapy. Grade B survival was associated with age at diagnosis, wide removal and sharply defined limits of the tumor on imaging. CONCLUSIONS: Analysis of both published data and this series underlines many prognostic parameters. It shows that OLG are heterogeneous tumors even in each grade (A and B). Treatment should consequently progress towards more targeted procedures for patients mainly with postoperative radiotherapy and chemotherapy.

Adolescent↗

The expression of PEA-15 (phosphoprotein enriched in astrocytes of 15 kDa) defines subpopulations of astrocytes and neurons throughout the adult mouse brain.

Phosphoprotein enriched in astrocytes of 15 kDa (PEA-15) is an abundant phosphoprotein in primary cultures of mouse brain astrocytes. Its capability to interact with members of the apoptotic and mitogen activated protein (MAP) kinase cascades endows PEA-15 with anti-apoptotic and anti-proliferative properties. We analyzed the in vivo cellular sources of PEA-15 in the normal adult mouse brain using a novel polyclonal antibody. Immunohistochemical assays revealed numerous PEA-15-immunoreactive cells throughout the brain of wild-type adult mice while no immunoreactive signal was observed in the brain of PEA-15 -/- mice. Cell morphology and double immunofluorescent staining showed that both astrocytes and neurons could be cellular sources of PEA-15. Closer examination revealed that in a given area only part of the astrocytes expressed the protein. The hippocampus was the most striking example of this heterogeneity, a spatial segregation restricting PEA-15 positive astrocytes to the CA1 and CA3 regions. A PEA-15 immunoreactive signal was also observed in a few cells within the subventricular zone and the rostral migratory stream. In vivo analysis of an eventual PEA-15 regulation in astrocytes was performed using a model of astrogliosis occurring along motor neurons degeneration, the transgenic mouse expressing the mutant G93A human superoxyde-dismutase-1, a model of amyotrophic lateral sclerosis. We observed a marked up-regulation of PEA-15 in reactive astrocytes that had developed throughout the ventral horn of the lumbar spinal cord of the transgenic mice. The heterogeneous cellular expression of the protein and its increased expression in pathological situations, combined with the known properties of PEA-15, suggest that PEA-15 expression is associated with a particular metabolic status of cells challenged with potentially apoptotic and/or proliferative signals.

3T3 Cells↗

Stereotactic CT-guided brain biopsy in the dog.

This study evaluated the accuracy of a new stereotactic CT-guided brain biopsy (SCTGBB) device on 23 client-owned dogs which presented with a brain lesion. Biopsy of the lesion was achieved in 95 per cent of cases. The target tissue was not sampled in one dog. Complications were observed in six dogs. Two dogs with highly vascularised brainstem tumours died after SCTGBB. Minor complications (slight variation in the neurological status) were observed in a further four cases. A diagnosis was reached in 16 dogs after cytological examination and in 21 dogs after histological evaluation. SCTGBB is an accurate diagnostic method for the diagnosis of brain lesions.

Animals↗

[Surgical removal of radio-induced lesions after radiosurgery of cerebral arteriovenous malformations].

Radioinduced lesions after radiosurgery of cerebral arteriovenous malformations may be associated with an increased signal on T2-weighted and gadolinium enhancement on T1-weighted MR images. They do not have necessarily a poor prognosis. These lesions are mostly asymptomatic. But in a few cases they can be associated with severe clinical symptoms which can become corticodependant or corticoresistant. We present the 5 cases of such cerebral arteriovenous malformations treated by radiosurgery, out of our series of 705 patients. The removal was easier than that of untreated cerebral arteriovenous malformations, and led to a complete recovery of symptoms and progressive decrease of imaging abnormalities. Such surgery should be proposed in case of symptomatic radioinduced lesions which fail to respond to steroids.

Adult↗

[Parenchymal changes after radiosurgery of cerebral arteriovenous malformations. Clinical and MRI data].

BACKGROUND AND PURPOSE: Purposes of this study are to describe different parenchymal changes seen after radiosurgery of cerebral arteriovenous malformations and the clinical symptoms which can be associated, and risk factors correlated with them. PATIENTS: and method. From the whole population of 705 patients with a cerebral arteriovenous malformations treated by radiosurgery between 1984 and 1998, clinical from 615 patients and post radiosurgery MRI data from 367 patients were reviewed. Neurological deficit occurred in 5.37% of cases and was still persistant in 1.46% of cases. Delay of occurrence of deficits ranged from 6 to 83 months (mean: 27 months, median: 15 months). Parenchymal changes seen in MRI were classified in 4 grades: 1 without parenchymal changes, 2 hypersignal in sp T2, 3=2 with homogenous enhancement with gadolinium, 4 with hyposignal in spT1 and annular irregular enhancement. Several parameters (size, volume, angioarchitecture of the cerebral arteriovenous malformation, dosimetric parameters) were studied and correlations were searched by uni and multivariate analysis with occurrence and delay of occurrence of deficits or parenchymal changes. RESULTS: In multivariate analysis, only size was significantly correlated with occurrence of parenchymal changes (p=0.0016); only size of the malformation was significantly correlated with delay of occurrence of parenchymal changes (p=0.0082); only grade 4 was correlated with occurrence of neurological deficit (p<0.00001). However, when only "a priori" parameters (known before radiosurgery) are introducted in logistic model, size taille (p=0.02) and hypoplasy of a sinus (p=0.0049) are significantly correlated with occurrence of neurological deficit. Only parenchymal changes grade 4 was significantly correlated with delay of occurrence of a neurological deficit (p<0.00001). However, when only a priori parameters (known before radiosurgery) are introducted in logistic model, only arterial steal (p=0.054) was significantly correlated with delay of occurrence of a neurological deficit. CONCLUSION: Parenchymal changes are various in expression, signification and clinical symptoms associated with them. They must be known and recognized for better prevention and symptomatic treatment as well.

Adolescent↗

Dysembryoplastic neuroepithelial tumors: CT, MR findings and imaging follow-up: a study of 53 cases.

PURPOSE: To evaluate CT and MRI features and long term imaging follow-up of a large series of dysembryoplastic neuroepithelial tumors (DNTS). PATIENTS AND METHODS: We retrospectively analyzed CT (100%) and MR imaging (83%) findings of 53 patients with complex (n = 14), simple (n = 6) or non specific histological forms (n = 33) of DNTS. All patients underwent epilepsy surgery for the treatment of drug resistant partial seizures. Preoperative radiological follow-up from two to 10 years (81%) and a post-operative follow-up from one to 13 years (92%) were available. RESULTS: DNTs are intracortical tumors with no mass effect and no peritumoral edema. An associated deformity of the overlying skull was observed in 44% of the 34 patients with a cortical lesion of the convexity. We found a contrast enhancement of the lesion in 21% of cases, a calcic hyperdensity in 36% of cases and a cystic part in 7.5% of cases. DNTs were hypodense (82%) on CT examinations and had a decreased signal on the T1 Weighted Images (95%) and a hypersignal in T2 Weighted Images (100%) on MR imaging. Eighty-one percent of patients had a mean preoperative radiological follow-up of four years and the tumor was stable in size in all cases; 92% of patients had a mean post-operative radiological follow-up of 4.5 years and no recurrence was seen. CONCLUSION: Three radiological features of DNTs are helpful for the diagnosis: cortical location, absence of mass effect and no surrounding edema. Clinical, radiological and histopathological findings have to be considered together in order to assess the diagnosis and to differentiate DNTs, which are stable lesions from gliomas.

Adult↗

Vascular endothelial growth factor expression in oligodendrogliomas: a correlative study with Sainte-Anne malignancy grade, growth fraction and patient survival.

Microangiogenesis is a delayed but crucial event in the malignant progression of oligodendrogliomas. Accord-ingly, in the new Sainte-Anne grading system of oligodendrogliomas, endothelial hyperplasia and contrast enhancement, both being indicators of microangiogenesis, are key criteria for the distinction of grade A from grade B tumours. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor: a strong correlation between VEGF expression, Sainte-Anne malignancy grade and patient outcome might thus be expected. In order to assess this hypothesis, VEGF immunostaining was performed in a series of 34 oligodendrogliomas that included 11 grade B and 23 grade A, of which nine became grade B during the study period (mean clinical and imaging follow-up: 41 months). VEGF expression correlated strongly with Sainte-Anne tumour grade (P < 0.001), and inversely with patient survival (P < 0.001) and recurrence-free survival (P = 0.002). One hundred per cent of grade B but only 17% of grade A were VEGF-positive. By contrast, the MIB-1 labelling index did not correlate with VEGF expression, total survival or recurrence-free survival. In accordance with the grading system, this study showed that, in oligodendrogliomas, VEGF expression and microangiogenesis are progression-related phenomena that confer on these tumours a growth advantage by presumably reducing hypoxia-induced apoptotic cell death. These findings might have important implications in the future for the indication and timing of anti-angiogenic therapies.

Adult↗

[The "smears" technique for the extemporaneous examination: diagnostic contribution to neurosurgical pathology].

Smear preparation is a fairly accurate, simple and reliable tool for rapid intraoperative diagnosis of central nervous system tumors. Compared with frozen sections this technique has the advantage of being both more accurate for cytological details and of requiring less tissue. In addition final histological analysis after direct formalin fixation is of better quality than post freezing fixation. This technique is most helpful in the field of neuro-oncological pathology specially in glial tumors and in stereotactic biopsy procedures. The cytological aspects and smear patterns disclose important complementary diagnostic information for the histopathological examination.

Brain Neoplasms↗

Dysembryoplastic neuroepithelial tumors: nonspecific histological forms -- a study of 40 cases.

OBJECTIVE: To demonstrate that DNTs include a large morphological spectrum of tumors that cannot be histologically distinguished from conventional categories of gliomas. METHODS: All tumors from patients who underwent epilepsy surgery in Sainte-Anne hospital (Paris) that histologically resembled gliomas and did not conform to current histological criteria for DNTs or gangliogliomas were entered in the study. RESULTS: According to the WHO histological classification, the 40 tumors resembled: pilocytic astrocytomas (4 cases), astrocytomas (16 cases), anaplastic astrocytoma (1 case), oligodendrogliomas (10 cases), oligo-astrocytomas (8 cases) or anaplastic oligo-astrocytomas (1 case). However foci of cortical dysplasia could be observed in 47% of the cases. Clinical presentation and imaging features were strikingly similar to that observed in typical DNTs. Although surgical removal was incomplete in 28% of the cases and none of the patients underwent chemo or radiotherapy, none of the tumors recurred (mean follow-up: 7 years). Moreover, serial preoperative imaging in 26 patients (mean follow-up: 4.5 years) demonstrated that these lesions were perfectly stable. CONCLUSIONS: Whatever the histological appearance of a glial tumor, the diagnosis of DNT must be considered when all the following criteria are associated: (1) partial seizures, with or without secondary generalization, beginning before the age 20 years, (2) no neurological deficit or stable congenital deficit, (3) cortical topography of the lesion as better demonstrated by MRI and (4) no mass effect on imaging.

Adolescent↗

[High grade (B) oligodendroglioma. Concerns and pitfalls in the intraoperative examination of smears].

According to the Ste Anne hospital classification and grading system of oligodendrogliomas the presence of contrast enhancement on MRI and/or the presence of an histological endothelial hyperplasia are correlated with a pejorative prognosis (high grade or grade B). Surgical tumoral exerese and adjuvant chemo or radiotherapy are indicated. When clinical and radiological aspects are typical the extemporaneous diagnosis of oligodendroglioma on smear is usually easy (1). In case of atypical forms: unusual localization or cytological appearance, especially with a small cell hyperchromatic undifferenciated tumor few diagnostic hypothesismay be considered. Four cerebellar tumors are presented with relevant and differential cytological diagnostic criteria. A comparative study between clinical and radiological aspects of medulloblastoma, primitive lymphoma, undifferenciated small cell lung carcinoma, and grade B oligodendroglioma is presented.

Brain Neoplasms↗

Oligodendrogliomas. Part I: Patterns of growth, histological diagnosis, clinical and imaging correlations: a study of 153 cases.

The present study has attempted to demonstrate that the morphological spectrum of oligodendrogliomas includes tumors which are traditionally misinterpreted as 'diffuse fibrillary astrocytoma'. We have shown that these tumors are in fact made of isolated neoplastic oligodendrocytes which are entrapped in a fibrillary background composed of axons and fibrillary reactive gliosis. Analysis in a series of 153 'pure' supratentorial oligodendrogliomas composed of 'classical' or pseudo 'diffuse fibrillary oligodendrogliomas' diagnosed by imaging-based serial stereotactic biopsies showed that 2/3 of the tumors were exclusively made of isolated tumor cells (ITCs) (structure type III) and that only 1/3 of them exhibited both ITCs and solid tumor tissue components (structure type II). The tumor tissue destroys the brain parenchyma and contains new formed microblood vessels whereas ITCs do not destroy the parenchyma and are not associated with microangiogenesis. These fundamentally opposite morphological characteristics were reflected by the following findings: 1) contrast enhancement was observed in 64% of structure type II but was never seen in structure type III oligodendrogliomas. 2) a neurological deficit occurred in 57% of structure type II but in only 8% of structure type III oligodendrogliomas. 3) using the new grading system described in the companion paper to this study, we found that the biological behavior of oligodendrogliomas was also closely related to the patterns of tumor growth. From a synthesis of data gathered in this study it is suggested that emergence of microangiogenesis within a tumor which at first grows slowly with a structure type III pattern is a crucial event toward more aggressive behavior.

Astrocytoma↗