Jean-Jacques Moreau

Centre Hospitalier Universitaire de Limoges, Limages, Limousin, France

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Publications (13)20.09 Total impact

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    ABSTRACT: Sinonasal intestinal-type adenocarcinomas (ITACs) are uncommon tumors of poor prognosis defined by their similarities to colorectal adenocarcinomas. The involvement of the epidermal growth factor receptor (EGFR) pathway in colorectal adenocarcinoma oncogenesis is well established, and the same is expected to apply to ITACs. In a series of 39 ITACs, we investigated EGFR amplification and chromosome 7 polysomy by fluorescence in situ hybridization; EGFR, KRAS, and BRAF mutational status by polymerase chain reaction sequencing; EGFR variant messenger RNA expression by quantitative reverse transcriptase polymerase chain reaction; and EGFR protein expression by immunohistochemistry with antibodies targeting the extracellular domain, the intracellular domain, and the phosphorylated isoform. The findings were analyzed with respect to clinical data, histologic typing, and patient outcome. EGFR amplification was observed in 3 cases with a focal distribution. EGFR proteins were overexpressed in all these foci with both extracellular domain and intracellular domain antibodies, suggesting involvement of the whole receptor. Chromosome 7 polysomy was observed in 15 cases and was not associated with EGFR protein expression. EGFR, KRAS, or BRAF mutations were observed in 5 different cases. The EGFRvIII mutant was not detected. In all cases, EGFR variants were expressed. There was no association between these molecular features and patient survival. In conclusion, (1) our study revealed various EGFR expression patterns in ITACs, indicating tumor heterogeneity; (2) EGFR amplification should be distinguished from chromosome 7 polysomy; (3) fluorescence in situ hybridization analysis could be guided by immunohistochemistry; and (4) ITACs share common alterations of the EGFR pathway with colorectal adenocarcinomas, except for a lower frequency of KRAS and BRAF mutations.
    Human pathology 06/2013; · 3.03 Impact Factor
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    ABSTRACT: INTRODUCTION: Neurosurgery and Maxillofacial Surgery Departments of Limoges University Hospital Centre have developed a new concept of a custom made ceramic implant in hydroxyapatite (HA) for the reconstruction of large and complex craniofacial bone defects (more than 25 cm(2)). MATERIALS AND METHODS: The manufacturing process of the implants used a stereolithography technique that produces implants with three-dimensional shapes derived directly from the scan file of the patient's skull without moulding or machining. Eight patients received 8 implants between 2005 and 2008. RESULTS: The surgical procedure is simple and fast. The post-operative follow-up was 12 months. No major complications (infection or fracture of the implant) were observed. The cosmetic result was considered satisfactory by both patients and surgeons. CONCLUSIONS: These new implants are well suited for reconstruction of large craniofacial bone defects (greater than 25 cm(2)) in adults and children over 8 years.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 12/2012; · 1.25 Impact Factor
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    ABSTRACT: The epidermal growth factor receptor (EGFR) gene encodes four alternatively spliced mRNA, variants 1, 2, 3 and 4, respectively, encoding the whole isoform a (EGFR) and truncated isoforms b, c and d, all of which lack the receptor's intracellular domain. In addition, a mutant EGFRvIII differs from isoform a in a truncated extracellular domain. The expression pattern of these isoforms is unknown in adult diffuse gliomas. Thus, we investigated in 47 cases: i) EGFR protein expression by immunohistochemistry using an extracellular domain-recognizing antibody (Ext-Ab) and an intracellular domain specific one (Int-Ab), ii) mRNA expression of EGFRv1, -v2, -v3, -v4 and -vIII by RT-PCR and iii) EGFR amplification by fluorescent in situ hybridization. The relation of these data with histological criteria and patient outcome was studied. The immunostaining was stronger with the Ext-Ab than with the Int-Ab. EGFRv1, -v2, -v3 and -v4 mRNA expression were highly correlated. They were expressed in all tumors, with highest levels in glioblastomas. EGFRv1 strong levels and the presence of vIII mRNAs were more closely associated with Int-Ab staining. EGFR gene amplification concerned only glioblastomas and was associated with the presence of EGFRvIII and high levels of EGFRv2, -v3 and -v4 transcripts. A pejorative outcome was associated with: histology (glioblastomas), EGFR amplification, strong Int-Ab labeling and high levels of variant mRNAs. Our results indicated that the full-length EGFR and mutant EGFRvIII are not the sole EGFR isoform expressed in diffuse gliomas. This could explain discordant immunohistochemical results reported in the literature and may have therapeutic implications.
    International Journal of Oncology 12/2011; 40(4):1142-52. · 2.66 Impact Factor
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    ABSTRACT: Identification of the subthalamic nucleus (STN) on MR images is difficult, and the use of external landmarks could be of interest for STN targeting in deep brain stimulation (DBS). Our aim was to explore the relationship between the anteroposterior coordinates of (1) the center of the mamillothalamic tract and (2) the anterior border of the STN on axial MR images. The brains of 16 healthy volunteers were imaged on a 3T MR system. Four millimeters under the anterior-posterior commissure plane, we noted the y coordinates of (1) the center of the mamillothalamic tract and (2) the anterior border of the STN. The coordinates were y(STN) = 14.7 ± 1.23 mm and y(Tmth) = 14.3 ± 1.13 mm from the posterior commissure for the STN and the mamillothalamic tract, respectively. The mean difference was 0.4 mm (range 0-1 mm). Pearson's coefficient was 0.97 (p < 0.01). We observed a strong correlation between the anteroposterior coordinates of the mamillothalamic tract and the anterior border of the STN (which is located between 0 and 1 mm in front of the mamillothalamic tract). The mamillothalamic tract could be a good anterior landmark for STN targeting. It could also be tested for target determination in DBS for severe obsessive-compulsive disorder.
    Stereotactic and Functional Neurosurgery 08/2011; 89(5):286-90. · 1.46 Impact Factor
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    ABSTRACT: The alpha-internexin (INA) gene encodes an intermediate filament involved in neurogenesis and maps in 10q24.33. A strong INA protein expression has been reported in oligodendroglial tumours and was associated with 1p19q deletion. To assess the relevance of INA immunohistochemistry in glioma typing, this paper studied the relationship between INA expression, histological type, genomic status and patient outcome. The study analysed INA, nestin, Olig2 and p53 expression, loss of heterozygosity of microsatellite markers from telomere to centromere of 10p, 10q, 1p and 19q chromosomes and epidermal growth factor receptor gene (EGFR) amplification in 40 gliomas (five astrocytomas, 12 oligodendrogliomas, 11 oligoastrocytomas, 12 glioblastomas). INA expression was scored as absent, weak (<10% of labelled tumour cells) or strong (>10%). Oligodendrogliomas showed strong INA and Olig2 expression, and 1p19q whole loss of heterozygosity (wLOH). Astrocytomas and glioblastomas were characterised by no or weak INA expression, high p53 and nestin expression, 10p10q wLOH, and epidermal growth factor receptor amplification. Most oligoastrocytomas had characteristics of astrocytic tumours. All tumours with strong INA expression retained the 10q chromosome arm and, except for one, had a 1p19q wLOH status. However, despite a strong link between INA expression, 1p19q wLOH and 10q retention, discrepancies were observed in 10% of cases. The presence of INA expression, whether weak or strong, was related to a better prognosis. INA expression study can be helpful for glioma typing and prognosis determination in combination with other markers. Nevertheless, INA immunohistochemistry cannot replace the genomic analysis to determine 1p19q and 10p10q status.
    Journal of clinical pathology 06/2011; 64(9):793-801. · 2.43 Impact Factor
  • François Caire, Jean-Jacques Moreau
    La Revue du praticien 10/2010; 60(8):1144-8.
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    ABSTRACT: Gliomas are tumors of the central nervous system derived from glial cells. They show cellular heterogeneity and lack specific diagnostic markers. Although a possible role for the eicosanoid cascade has been suggested in glioma tumorigenesis, the relationship between enzymes and receptors implicated in arachidonic acid metabolism, with histological tumor type has not yet been determined. Quantitative real-time reverse transcription-polymerase chain reaction was performed to measure and compare transcript levels of enzymes and receptors implicated in both lipoxygenase and cyclooxygenase pathways between oligodendrogliomas, astrocytomas, glioblastomas and mixed oligoastrocytomas. Arachidonic acid metabolism-related enzymes and receptor transcripts (i) were underexpressed in classical oligodendrogliomas compared to astrocytomas and/or glioblastomas, (ii) differed between astrocytomas and glioblastomas and (iii) had an intermediate expression in mixed oligoastrocytomas. mRNA levels of enzymes and receptors implicated both in lipoxygenase and cyclooxygenase pathways differed significantly in gliomas according to the histological type.
    Clinical biochemistry 04/2010; 43(10-11):827-35. · 2.02 Impact Factor
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    ABSTRACT: A digital campus is a distance learning site that uses the potential of information and communication technologies to disseminate and improve educational services. This website, with open and free access, is built from free software with Web 2.0 technology. It is hosted at the University of Limoges. It functions as a digital library, containing scanned books, slide shows, more than 200 hours of recorded courses and round tables accessible by streaming video. The site is indexed according to the users’ needs, by level of knowledge, specialty, keywords, and supplementary MeSH terms. The campus is organized as the College of Neurosurgery (http://college.neurochirurgie.fr). The durability of this type of training (in existence for 9 years now) is made possible by a powerful and committed consortium: the French Society of Neurosurgery, which has created high-quality intellectual and scientific resources, the University of Limoges, the Dupuytren University Hospital Center in Limoges, the region of Limousin, and the French-language Virtual Medical University, which have provided logistic and financial support. To target appropriate levels at various users, we distinguished four groups: medical students, neurosurgery students, neurosurgeons (continuing medical education), and students in allied health fields. All areas of neurosurgery are concerned. All the courses, including tests for self-evaluation and scientific meetings (organized with information and communication technologies) are digitally recorded for the site. The principles that make it possible for a medical discipline to organize around an online project are: a pedagogical conception of projects built in the form of models reusable by other health specialties; a stronghold within professional societies of the relevant specialties able to create high-quality intellectual and scientific resources; an organization by educational levels that can be extended transversally to other health disciplines; and free access to the digital campus, the durability of which depends on the dissemination and dynamism of its consortium.
    La Presse Médicale 10/2009; 38(10):1425-1433. · 0.87 Impact Factor
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    ABSTRACT: A digital campus is a distance learning site that uses the potential of information and communication technologies to disseminate and improve educational services. This website, with open and free access, is built from free software with Web 2.0 technology. It is hosted at the University of Limoges. It functions as a digital library, containing scanned books, slide shows, more than 200 hours of recorded courses and round tables accessible by streaming video. The site is indexed according to the users' needs, by level of knowledge, specialty, keywords, and supplementary MeSH terms. The campus is organized as the College of Neurosurgery (http://college.neurochirurgie.fr). The durability of this type of training (in existence for 9 years now) is made possible by a powerful and committed consortium: the French Society of Neurosurgery, which has created high-quality intellectual and scientific resources, the University of Limoges, the Dupuytren University Hospital Center in Limoges, the region of Limousin, and the French-language Virtual Medical University, which have provided logistic and financial support. To target appropriate levels at various users, we distinguished four groups: medical students, neurosurgery students, neurosurgeons (continuing medical education), and students in allied health fields. All areas of neurosurgery are concerned. All the courses, including tests for self-evaluation and scientific meetings (organized with information and communication technologies) are digitally recorded for the site. The principles that make it possible for a medical discipline to organize around an online project are: a pedagogical conception of projects built in the form of models reusable by other health specialties; a stronghold within professional societies of the relevant specialties able to create high-quality intellectual and scientific resources; an organization by educational levels that can be extended transversally to other health disciplines; and free access to the digital campus, the durability of which depends on the dissemination and dynamism of its consortium.
    La Presse Médicale 09/2009; 38(10):1425-33. · 0.87 Impact Factor
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    ABSTRACT: Epidermal growth factor receptor (EGFR) is produced during the molecular pathogenesis of glioma, and new anti-EGFR molecules are available for therapeutics. Consequently, analyses of the EGFR gene and protein are frequently used for glioma characterization. We compare the accuracy and the usefulness of 2 currently used techniques for histologic classification of gliomas. Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) techniques were used to assess EGFR gene amplification and protein abundance in a series of 35 gliomas, including World Health Organization (WHO) grade I, II, and III astrocytomas (AI, AII, AIII), grade II and III tumors with oligodendroglial component (OII, OIII) and grade IV glioblastomas (GBs). EGFR gene amplification was found in one-third of the tumors studied. It was frequent in GB and OIII but was never found in AI, AII, AIII, and OII tumors. IHC and FISH provided similar findings for grade of tumor, despite the fact that, in contrast to the FISH gene amplification, EGFR protein was overexpressed in AIII and in GB. EGFR gene amplification was never observed in tumors not containing EGFR protein: therefore FISH is unnecessary when IHC shows no EGFR protein expression. EGFR gene amplification seems to be restricted to high-grade tumors, WHO grade IV astrocytomas, and grade III oligodendroglial tumors.
    Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 06/2009; 17(3):220-6. · 1.63 Impact Factor
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    ABSTRACT: In view of the important oncogenic action of phospholipase A(2)(PLA(2)) we investigated PLA(2) transcripts in human meningiomas. Real-time PCR was used to investigate PLA(2) transcripts in 26 human meningioma tumors. Results indicated that three Ca(2+)-dependent high molecular weight PLA(2) (PLA(2)-IVA, PLA(2)-IVB, PLA(2)-IVC), one Ca(2+)-independent high molecular weight PLA(2) (PLA(2)-VI) and five low molecular weight secreted forms of PLA(2) (PLA(2)-IB, PLA(2)-IIA, PLA(2)-III, PLA(2)-V, and PLA(2)-XII) are expressed with PLA(2)-IVA, PLA(2)-IVB, PLA(2)-VI, and PLA(2)-XIIA as the major expressed forms. PLA(2)-IIE, PLA(2)-IIF, PLA(2)-IVD, and PLA(2)-XIIB are not detected. Plasma (PLA(2)-VIIA) and intracellular (PLA(2)-VIIB) platelet-activating factor acetylhydrolase transcripts are expressed in human meningiomas. However no difference was found for PLA(2) transcript amounts in relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. In conclusion numerous genes encoding multiples forms of PLA(2) are expressed in meningiomas where they might act on the phospholipid remodeling and on the local eicosanoid and/or cytokine networks.
    Mediators of Inflammation 01/2009; 2009:689430. · 3.88 Impact Factor
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    ABSTRACT: Contexte : Un campus numérique a été créé au début des années 2000 dans l’intention d’utiliser le potentiel des technologies de l’information et de la communication (TIC) pour diffuser et améliorer l’enseignement de la neurochirurgie. Afin de répondre à la diversité des besoins, ce campus a évolué rapidement. Buts : Faire percevoir l’apport du numérique dans les différents pôles d’enseignement d’une spécialité médicale ; souligner l’intérêt de se structurer en consortium pour dynamiser et capitaliser les recherches en TIC appliquées aux sciences de la santé. Moyens : Les outils numériques choisis pour optimiser la démarche pédagogique sont présentés, puis les quatre modèles de formation mis en place sont décrits. Conclusion : Les principes qui permettent à une discipline médicale de se mobiliser autour d’un projet numérique sont : une conception pédagogique des projets construits sous forme de modèles réutilisables par d’autres spécialités des disciplines de santé ; un ancrage fort du campus numérique au sein du collège et de la société savante de la spécialité créateurs de ressources intellectuelles et scientifiques de qualité ; une organisation par pôles d’enseignement permettant une transversalité aux autres disciplines de santé ; un accès libre au campus numérique dont la pérennité est fonction de la diffusion et du dynamisme de son consortium et de l’action de l’Université médicale virtuelle francophone (UMVF). Background: In the early 2000’s, a digital campus was created in order to improve neurosurgery teaching and learning by using technologies of information and communication (TIC). This digital campus has quickly evolved in response to various needs. Goal: To promote the recognition of the contribution of digital technology to different topics of learning of a medical specialty; to highlight the interest to organize a consortium that would encourage research in TIC applied to the field of health sciences. Method: We present digital tools we have chosen in accordance to the educational approach. Also, we describe four models of formation we have developed. Conclusion: Principles that allow the mobilisation of a medical discipline around an educational digital project are the following: 1) projects created with an educational conception have to represent models that can be reused by other specialties of health disciplines; 2) a strong anchorage towards a digital campus must exist among the neurosurgeons college and the scholar society comprised of qualified intellectual and scientific resource creators; 3) teaching should be organize by topics in order to allow a transfer towards other health disciplines; 4) durability of free access of the digital campus depends on the broadcasting and the dynamism of its consortium and the actions undertaken by the French-speaking virtual medical University (FVMU).
    Pédagogie médicale 08/2008;
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    ABSTRACT: Contexte : Le test de concordance de script (TCS) a été choisi par le Collège des enseignants de neurochirurgie comme outil d’auto-évaluation des internes. Jusqu’à présent, ceux-ci ne disposaient en effet d’aucun système d’ é valuation formative leur permettant de faire le point sur leurs forces et leurs faiblesses en cours de formation. But : Rapporter les étapes de mise en place du TCS pour l’auto-évaluation de l’ensemble des internes en formation. Le test est accessible sur Internet dans le cadre du campus numérique de neurochirurgie. L’administration régulière de tests permettra à chacun de suivre l’évolution de ses résultats au cours de sa formation. Mise en place : La rédaction d’une banque de questions a débuté, tous les domaines de la spécialité n’étant pas encore couverts. Le logiciel permettant l’informatisation des tests a par ailleurs été mis au point, permettant la réalisation d’une première évaluation par TCS au cours des « Deuxièmes Journées de Neurochirurgie » en mars 2003. Conclusion : Les internes en neurochirurgie disposent donc désormais d’un mode d’auto-évaluation facilement accessible puisque informatisé. Les efforts porteront désormais sur la diffusion de cet outil et sa pérennisation. Background: No effective tool was up to now available for form ativeassessment of neurosurgery residents during their training. The script concordance test (SCT) was there f o re chosen by the Collège des Enseignants to allow them to assess themselves their clinical competence. Aim: The aim of this work is to describe the constitution of a data bank available for further building of script concordance tests. The test is available on the web. The evolution of the results of each student will be followed up by regular assessment during the residency. Method: A first series of about 200 tests was created between may and novembre 2002, covering the main fields of neurosurgery. The first assessment of neurosurgery residents by script concordance test was carried out in march 2003, during the second « Journées de Neurochirurgie ». Conclusion: A new tool is now available for auto-assessment of neurosurgery residents, easy to use on the web. Diffusion to other branches and perennity of this work are now our main aims.
    http://dx.doi.org/10.1051/pmed:2004018.

Publication Stats

38 Citations
20.09 Total Impact Points

Institutions

  • 2009–2012
    • Centre Hospitalier Universitaire de Limoges
      • Department of Neurosurgery
      Limages, Limousin, France
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2009–2011
    • University of Limoges
      Limages, Limousin, France