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54. Advanced risk management in offshore terminals and marine ports

Author

Mokhtari, K

Subjects
TC Hydraulic engineering. Ocean engineering, HD61, HE, HD61 Risk Management, TC, HE Transportation and Communications
Abstract

This research aims to propose a Risk Management (RM) framework and develop a generic risk-based model for dealing with potential hazards and risk factors associated with offshore terminals' and marine ports' operations and management. Hazard identification was conducted through an appropriate literature review of major risk factors of these logistic infrastructures. As a result in the first phase of this research a Fuzzy Analytical Hierarchal Process (FAHP) method was used for determining the relative weights of the risk factors identified via the literature review. This has led to the development of a generic risk -based model which can help related industrial professionals and risk managers assess the risk factors and develop appropriate strategies to take preventive/corrective actions for mitigation purposes, with a view of maintaining efficient offshore terminals' and marine ports' operations and management. In the second phase of the research the developed risk-based model incorporating Fuzzy Set Theory (FST), an Evidential Reasoning (ER) approach and the IDS software were used to evaluate the risk levels of different ports in real situations using a case study. The IDS software based on an ER approach was used to aggregate the previously determined relative weights of the risk factors with the new evaluation results of risk levels for the real ports. The third phase of the research made use of the Cause and Consequence Analysis (CCA) including the Fault Tree Analysis (FTA) and Event Tree Analysis (ETA) under a fuzzy environment, to analyse in detail the most significant risk factors determined from the first phase of the research, using appropriate case-studies. In the fourth phase of the research an individual RM strategy was tailored and implemented on the most significant risk factor identified previously. In the last phase of the research and in order to complete the RM cycle, the best mitigation strategies were introduced and evaluated in the form of ideal solutions for mitigating the identified risk factors. All methods used in this research have quantitative and qualitative nature. Expert judgements carried out for gathering the required information accounted for the majority of data collected. The proposed RM framework can be a useful method for managers and auditors when conducting their RM programmes in the offshore and marine industries. The novelty of this research can help the Quality, Health, Safety, Environment and Security (QHSES) managers, insurers and risk managers in the offshore and marine industries investigate the potential hazards more appropriately if there is uncertainty of data sources. In this research with considering strategic management approaches to RM development the proposed RM framework and risk based model contribute to knowledge by developing and evaluating an effective methodology for future use of the RM professionals.

Published
2017
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60. Genome-wide association study identifies multiple susceptibility loci for glioma

Author

Kinnersley, B, Labussière, M, Holroyd, A, Di Stefano, A-L, Broderick, P, Vijayakrishnan, J, Mokhtari, K, Delattre, J-Y, Gousias, K, Schramm, J, Schoemaker, MJ, Fleming, SJ, Herms, S, Heilmann, S, Schreiber, S, Wichmann, H-E, Nöthen, MM, Swerdlow, A, Lathrop, M, Simon, M, Bondy, M, Sanson, M, and Houlston, RS

Abstract

Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10−9) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10−8), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10−11), 12q21.2 (rs12230172, P=7.53 × 10−11) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10−9). Our findings provide further insights into the genetic basis of the different glioma subtypes.

Published
2015

61. Chordoid Gliomas of the Third Ventricle Share TTF-1 Expression With Organum Vasculosum of the Lamina Terminalis

Author

Bielle, F, Villa, C, Giry, M, Bergemer-Fouquet, AM, Polivka, M, Vasiljevic, A, Aubriot-Lorton, MH, Bernier, M, Lechapt-Zalcman, E, Viennet, G, Sazdovitch, V, Duyckaerts, C, Sanson, M, Figarella-Branger, D, Mokhtari , K., on behalf of the RENOP, ., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropathology Department Raymond-Escourolle, departement Raymont escourelle, Pathology Department, Hôpital Bretonneau, CHRU Tours, Tours, Pathology Department, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathology and Neuropathology Department, Centre de Biologie et Pathologie Est, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, Hospices Civiles de Lyon, Plateau technique de Biologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département de Pathologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Pathology Department, CHU Besançon, Besançon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathology and Neuropathology Department, Assistance Publique-Hôpitaux de Marseille, AP-HM CHU, Timone, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU Pitié-Salpêtrière [APHP] - Centre National de la Recherche Scientifique (CNRS), Sorbonne Universités, UPMC Univ Paris 06, UM 75, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, U 1127, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique, UMR 7225, ICM, Centre National de la Recherche Scientifique (CNRS), Department of Anatomical and Cytological Pathology, Hôpital Foch, Suresnes, Hôpital Foch [Suresnes], Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Université Paris Descartes, Paris, Centre Hospitalier Régional Universitaire de Tours (CHRU), Hôpital Lariboisière, Pathology Department, Plateau technique de Biologie, CHU, Dijon, Department of Pathology, Caen University Hospital, Avenue de la Côte de Nacre, 14000, Caen, France., CHU Caen, Centre National de la Recherche Scientifique, UMR 6301 ISTCT CERVOxy Group, Caen, CNRS ISTCT, CHU Besançon, AP-HP, Neurology 2 Mazarin Department, Pitié-Salpêtrière Hospital, Hôpital la Pitié-Salpétrière, Aix-Marseille university, INSERM U911, Marseille, France, Onconeurotek, Pitié-Salpêtrière Hospital, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)

Subjects
Adult, Male, Thyroid Nuclear Factor 1, IDH1, [SDV]Life Sciences [q-bio], Clone (cell biology), Biology, medicine.disease_cause, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Organum Vasculosum, Aged, Retrospective Studies, Third Ventricle, Third ventricle, Lamina terminalis, Nuclear Proteins, Anatomy, Glioma, respiratory system, Middle Aged, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Forebrain, Immunohistochemistry, Surgery, Female, Carcinogenesis, Cerebral Ventricle Neoplasms, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; Chordoid glioma of the third ventricle (CG3V) is a rare tumor developing in a stereotyped localization. It has been related to the circumventricular organ of the lamina terminalis, in the anterior part of the third ventricle, but its oncogenesis is poorly understood. TTF-1 transcription factor is involved in the development and adult physiology of the ventral forebrain. We studied the histopathologic and immunohistochemical features of a multicentric series of 17 cases of CG3V. We described additional histologic patterns (solid, fibrosing, and fusiform) to the typical chordoid pattern. TTF-1 was constantly expressed in CG3V, as in developing and adult lamina terminalis. The anti-TTF-1 SPT24 clone was more sensitive than the 8G7G3/1 clone. No mutation of IDH1 R132, IDH2 R172, or BRAF V600 codons was found. We showed TTF-1 as a useful marker for the diagnosis of CG3V and the understanding of its oncogenesis.

Published
2015
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62. Quantifying the heritability of glioma using genome-wide complex trait analysis

Author

Kinnersley, B., Mitchell, J.S., Gousias, K., Schramm, J., Idbaih, A., Labussière, M., Marie, Y., Rahimian, A., Wichmann, H.-E., Schreiber, S., Hoang-Xuan, K., Delattre, J.Y., Nöthen, M.M., Mokhtari, K., Lathrop, M, Bondy, M., Simon, M., and Houlston, R.S.

Abstract

Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) influencing glioma risk. While these SNPs only explain a small proportion of the genetic risk it is unclear how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to three GWAS datasets totalling 3,373 cases and 4,571 controls and performed a meta-analysis to estimate the heritability of glioma. Our results identify heritability estimates of 25% (95% CI: 20-31%, P = 1.15 × 10-17) for all forms of glioma - 26% (95% CI: 17-35%, P = 1.05 × 10-8) for glioblastoma multiforme (GBM) and 25% (95% CI: 17-32%, P = 1.26 × 10-10) for non-GBM tumors. This is a substantial increase from the genetic variance identified by the currently identified GWAS risk loci (∼6% of common heritability), indicating that most of the heritable risk attributable to common genetic variants remains to be identified.

Published
2015

70. Alpha-Internexin Expression Predicts Outcome in Anaplastic Oligodendroglial Tumors and May Positively Impact the Efficacy of Chemotherapy

Author

Mokhtari, K, Ducray, F, Kros, J.M., Gorlia, T, Idbaih, A, Taphoorn, M, Wesseling, P, Hoang-Xuan, K, van den Bent, Martin, Sanson, M, Neurology, CCA - Innovative therapy, and Pathology

Subjects
SDG 3 - Good Health and Well-being
Abstract

BACKGROUND: Although it has been demonstrated that the neuronal intermediate filament alpha-internexin (INA) is closely related to 1p19q codeletion in gliomas, its prognostic and predictive value has not yet been confirmed in a prospective trial. The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospective, randomized European Organization for Research and Treatment of Cancer (EORTC) 26951 trial of adjuvant procarbazine, lomustine, and vincristine (PCV) in patients with anaplastic oligodendroglial tumors (AOTs). METHODS: INA immunohistochemistry expression in tumors from 92 patients who were included in the EORTC 26951 trial was analyzed independently by 2 observers and was correlated with relevant clinical characteristics, including progression-free survival (PFS) and overall survival (OS), and with molecular features, including 1p/19q codeletion, isocitrate dehydrogenase 1 and 2 gene (IDH7/IDH2) mutation, and O-6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status. RESULTS: INA expression was observed in 33 tumors and was strongly correlated with 1p/19q codeletion, IDH1 mutations, and MGMT promoter methylation. It was associated with significantly better PFS and OS independent of the treatment received. By using Cox proportional hazard modeling for OS with stepwise selection, INA expression, patient age, and performance status were identified as independent prognostic factors. The results indicated that INA expression may have an impact on the efficacy of combined radiotherapy plus PCV. CONCLUSIONS: In a homogeneously treated group of patients with grade III AOTs, INA expression had strong favorable prognostic significance for OS and may have predictive value for sensitivity to chemotherapy. Cancer 2011;117:3014-26. (C) 2011 American Cancer Society.

Published
2011
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71. Hypoxia and Metabolism Regulation in Chordomas: Correlation Between Biology and Clinical Features for Potential Targeted Therapy

Author

Mammar, H., primary, Polivka, M., additional, Belkacemi, Y., additional, Lot, G., additional, Froelich, S., additional, Carpentier, A., additional, Clemenceau, S., additional, Gaillard, S., additional, Paquis, P., additional, Birtwisle-Peyrottes, I., additional, Burel-Vandenbos, F., additional, Mokhtari, K., additional, Kerrou, K., additional, Talbot, J.N., additional, Dendale, R., additional, Bondiau, P.Y., additional, Pouyssegur, J., additional, and Mazure, N., additional

Published
2015
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72. Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas

Author

Alentorn, A., Thuijl, H.F. van, Marie, Y., Alshehhi, H., Carpentier, C., Boisselier, B., Laigle-Donadey, F., Mokhtari, K., Scheinin, I., Wesseling, P., Ylstra, B., Capelle, L., Hoang-Xuan, K., Sanson, M., Delattre, J.Y., Reijneveld, J.C., Idbaih, A., Alentorn, A., Thuijl, H.F. van, Marie, Y., Alshehhi, H., Carpentier, C., Boisselier, B., Laigle-Donadey, F., Mokhtari, K., Scheinin, I., Wesseling, P., Ylstra, B., Capelle, L., Hoang-Xuan, K., Sanson, M., Delattre, J.Y., Reijneveld, J.C., and Idbaih, A.

Abstract

Item does not contain fulltext, BACKGROUND: Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. METHODS: We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. RESULTS: Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. CONCLUSION: Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.

Published
2014

73. Spatial and temporal evolution of distal 10q deletion, a prognostically unfavorable event in diffuse low-grade gliomas

Author

Thuijl, H.F. van, Scheinin, I., Sie, D., Alentorn, A., Essen, H.F. van, Cordes, M., Fleischeuer, R., Gijtenbeek, A., Beute, G., Brink, W.A. van den, Meijer, G.A., Havenith, M., Idbaih, A., Hoang-Xuan, K., Mokhtari, K., Verhaak, R., Valk, P. van der, Wiel, M.A. van de, Heimans, J.J., Aronica, E., Reijneveld, J.C., Wesseling, P., Ylstra, B., Thuijl, H.F. van, Scheinin, I., Sie, D., Alentorn, A., Essen, H.F. van, Cordes, M., Fleischeuer, R., Gijtenbeek, A., Beute, G., Brink, W.A. van den, Meijer, G.A., Havenith, M., Idbaih, A., Hoang-Xuan, K., Mokhtari, K., Verhaak, R., Valk, P. van der, Wiel, M.A. van de, Heimans, J.J., Aronica, E., Reijneveld, J.C., Wesseling, P., and Ylstra, B.

Abstract

Contains fulltext : 136086.pdf (publisher's version ) (Open Access), BackgroundThe disease course of patients with diffuse low-grade glioma is notoriously unpredictable. Temporal and spatially distinct samples may provide insight into the evolution of clinically relevant copy number aberrations (CNAs). The purpose of this study is to identify CNAs that are indicative of aggressive tumor behaviour and can thereby complement the prognostically favorable 1p/19q co-deletion.ResultsGenome-wide, 50 base pair single-end, sequencing was performed to detect CNAs in a clinically well-characterized cohort of 98 formalin-fixed paraffin-embedded low-grade gliomas. CNAs are correlated with overall survival as an endpoint. Seventy-five additional samples from spatially distinct regions and paired recurrent tumors of the discovery cohort were analysed to interrogate the intratumoral heterogeneity and spatial evolution. Loss of 10q25.2-qter is a frequent subclonal event and significantly correlates with an unfavorable prognosis. A significant correlation is furthermore observed in a validation set of 126 and confirmation set of 184 patients. Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/ 19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors.ConclusionsCNAs in low-grade gliomas display extensive intratumoral heterogeneity. Distal loss of 10q is a late onset event and a marker for reduced overall survival in low-grade glioma patients. Intratumoral heterogeneity and higher frequencies of distal 10q loss in recurrences suggest this event is involved in outgrowth to the recurrent tumor.

Published
2014

74. Plasma cell Granuloma of the Brain in a Cat

Author

Belluco, S, Thibaud, J-L, Mokhtari, K, WYERS, Monique, Blot, Stéphane, Colle, Marie-Anne, Inconnu, and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

77. Méningiomes multi-récidivants : établissement de critères de réponse thérapeutiques après analyse des cinétiques de croissance et des types de récidive

Author

Zanello, M., primary, Peyre, M., additional, Mokhtari, K., additional, Boch, A., additional, Capelle, L., additional, Carpentier, A., additional, Clemenceau, S., additional, Karachi, C., additional, Navarro, S., additional, Nouet, A., additional, Reina, V., additional, Sanson, M., additional, Cornu, P., additional, and Kalamarides, M., additional

Published
2014
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79. ET-62 * HIGHLY SELECTIVE ACTIVITY OF MDM2 INHIBITOR RG7112 AGAINST MDM2-AMPLIFIED/TP53 WILD-TYPE GLIOBLASTOMAS

Author

Verreault, M., primary, Levasseur, C., additional, Schmitt, C., additional, Guehennec, J., additional, Labussiere, M., additional, Marie, Y., additional, Haidar, S., additional, Mokhtari, K., additional, Hoang-Xuan, K., additional, Sanson, M., additional, Ligon, K., additional, Delattre, J.-Y., additional, and Idbaih, A., additional

Published
2014
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80. TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations

Author

Labussière, M, primary, Di Stefano, A L, additional, Gleize, V, additional, Boisselier, B, additional, Giry, M, additional, Mangesius, S, additional, Bruno, A, additional, Paterra, R, additional, Marie, Y, additional, Rahimian, A, additional, Finocchiaro, G, additional, Houlston, R S, additional, Hoang-Xuan, K, additional, Idbaih, A, additional, Delattre, J-Y, additional, Mokhtari, K, additional, and Sanson, M, additional

Published
2014
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81. Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib

Author

Idbaih, A., primary, Mokhtari, K., additional, Emile, J.-F., additional, Galanaud, D., additional, Belaid, H., additional, de Bernard, S., additional, Benameur, N., additional, Barlog, V.-C., additional, Psimaras, D., additional, Donadieu, J., additional, Carpentier, C., additional, Martin-Duverneuil, N., additional, Haroche, J., additional, Feuvret, L., additional, Zahr, N., additional, Delattre, J.-Y., additional, and Hoang-Xuan, K., additional

Published
2014
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86. P11.04 * MALT CNS LYMPHOMAS: A MONOCENTRIC EXPERIENCE

Author

Larrieu, D., primary, Choquet, S., additional, Hoang-Xuan, K., additional, Mokhtari, K., additional, Navarro, S., additional, Martin-Duverneuil, N., additional, Leblond, V., additional, Charlotte, F., additional, and Houillier, C., additional

Published
2014
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92. Intracranial extra-axial cavernous (HEM) angiomas: tumors or vascular malformations?

Author

Alessandra Biondi, Clemenceau S, Dormont D, Deladoeuille M, Gk, Ricciardi, Mokhtari K, Jp, Sichez, and Marsault C

Subjects
Adult, Central Nervous System Vascular Malformations, Diagnosis, Differential, Male, Radiography, Hemangioma, Cavernous, Central Nervous System, Brain Neoplasms, Humans, Female, Middle Aged
Abstract

Extra-axial cavernous hemangiomas or angiomas [(hem)angiomas] are relatively rare lesions. They usually arise in relation to the dura mater intracranially or at the spinal level. Most of these lesions have been described in the middle cranial fossa at level of the cavernous sinus. Controversy still exists regarding the exact nature of these extra-axial cavernous angiomas: vascular tumor versus vascular malformation similar to intra-axial cavernomas. It has been suggested that they could represent an adult form of the hemangioma of infancy. Extra-axial cavernous (hem)angiomas often mimic meningiomas and their clinical behavior and imaging appearance are quite different than those of intra-axial cavernous angiomas.Five patients ranging in age from 24 to 63 years with a histologically proven dural cavernous angioma were retrospectively included. The lesions were located at level of the cavernous sinus (4 cases) and falx. CT and MR scans were performed in all cases and angiography in three patients. Four patients underwent surgery and a biopsy was performed in one case. One lesion was embolized before biopsy. Histology was available in all patients.In the operated patients, the lesion was totally resected in 2 cases and partially in the other 2. No postsurgical complication was noted. Histology revealed a vascular malformation composed of large vascular channels lined by flat endothelium and separated by fibroconnective tissue stroma. The pathological diagnosis was cavernous angioma.On the basis of the analysis of the literature and of our cases, intra-cranial extra-cerebral so-called cavernous (hem)angiomas present findings suggesting that they are vascular malformative lesions, analogous to the intra-axial cavernous angioma. A relationship with the hemangiomas of infancy seems unlikely. Correct terms for extra-cerebral cavernous (hem)angiomas are cavernoma, cavernous angioma, or venous vascular malformation of cavernous type . The term hemangioma should be avoided and reserved for the common vascular tumor of infancy.

Published
2002

93. [Cerebral glioblastomas and systemic metastases]

Author

Denier C, Antoine Carpentier, Mokhtari K, and Jy, Delattre

Subjects
Male, Lung Neoplasms, Brain Neoplasms, Liver Neoplasms, Disease Progression, Humans, Bone Neoplasms, Middle Aged, Glioblastoma, Tomography, X-Ray Computed, Magnetic Resonance Imaging, Kidney Neoplasms
Abstract

Glioblastomas are highly malignant but locally invasive tumors. In only rare instances do extra-neural metastasis occur. We report herein 2 cases of such dissemination occurring 9 and 15 month after the initial diagnosis and treatment of supratentorial gliomas. Metastasis involved the lung, the kidney and the liver in one case and the bones in the other case. Both patients died within 3 month after diagnosis of the systemic metastasis despite chemotherapy.

Published
2002

94. Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial.

Author

Hegi, M.E., Janzer, R.C., Lambiv, W.L., Gorlia, T., Kouwenhoven, M.C., Hartmann, C., Deimling, A. Von, Martinet, D., Besuchet Schmutz, N., Diserens, A.C., Hamou, M.F., Bady, P., Weller, M., Bent, M.J. van den, Mason, W.P., Mirimanoff, R.O., Stupp, R., Mokhtari, K., Wesseling, P., Hegi, M.E., Janzer, R.C., Lambiv, W.L., Gorlia, T., Kouwenhoven, M.C., Hartmann, C., Deimling, A. Von, Martinet, D., Besuchet Schmutz, N., Diserens, A.C., Hamou, M.F., Bady, P., Weller, M., Bent, M.J. van den, Mason, W.P., Mirimanoff, R.O., Stupp, R., Mokhtari, K., and Wesseling, P.

Abstract

1 juni 2012, Item does not contain fulltext, Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as classical GBM. The detection of pseudo-palisading necrosis (PPN) was associated with benefit from chemotherapy (p = 0.0002), while no such effect was present in the absence of PPN (p = 0.86). In the adjusted interaction model including clinical prognostic factors and MGMT status, PPN was borderline nonsignificant (p = 0.063). Taken together, recognition of an oligodendroglioma-like component in an otherwise classic GBM identifies a pathogenetically mixed group without prognostic significance. However, the presence of PPN may indicate biological features of clinical relevance for further improvement of therapy.

Published
2012

95. Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial

Author

Hegi, M E, Janzer, R C, Lambiv, W L, Gorlia, T, Kouwenhoven, M C M, Hartmann, C, von Deimling, A, Martinet, D, Besuchet Schmutz, N, Diserens, A C, Hamou, M F, Bady, P, Weller, M, van den Bent, M J, Mason, W P, Mirimanoff, R O, Stupp, R, Mokhtari, K, Wesseling, P, Hegi, M E, Janzer, R C, Lambiv, W L, Gorlia, T, Kouwenhoven, M C M, Hartmann, C, von Deimling, A, Martinet, D, Besuchet Schmutz, N, Diserens, A C, Hamou, M F, Bady, P, Weller, M, van den Bent, M J, Mason, W P, Mirimanoff, R O, Stupp, R, Mokhtari, K, and Wesseling, P

Abstract

Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as classical GBM. The detection of pseudo-palisading necrosis (PPN) was associated with benefit from chemotherapy (p = 0.0002), while no such effect was present in the absence of PPN (p = 0.86). In the adjusted interaction model including clinical prognostic factors and MGMT status, PPN was borderline nonsignificant (p = 0.063). Taken together, recognition of an oligodendroglioma-like component in an otherwise classic GBM identifies a pathogenetically mixed group without prognostic significance. However, the presence of PPN may indicate biological features of clinical relevance for further improvement of therapy.

Published
2012

96. Successful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs

Author

Antoine Carpentier, Xie J, Mokhtari K, and Jy, Delattre

Subjects
Male, Time Factors, Brain Neoplasms, CD8 Antigens, Macrophages, Oligonucleotides, Mice, Nude, Glioma, Cancer Vaccines, Immunohistochemistry, Rats, Killer Cells, Natural, Mice, Rats, Inbred Lew, Tumor Cells, Cultured, Animals, Humans, CpG Islands, Microglia, Neoplasm Transplantation
Abstract

Phosphorothioate oligodeoxynucleotides with CpG motifs (CpG-ODNs) activate various immune cell subsets and induce production of numerous cytokines. To evaluate whether CpG-ODNs can induce rejection of established tumors, Lewis rats were inoculated intracerebrally with syngeneic CNS-1 glioma cells and subsequently injected with CpG-ODNs into the tumor bed. Although all of the control rats (n = 14) died within 23 days, 88% of the animals (n = 8) treated with a single CpG-ODN injection 5 days after tumor inoculation showed long-term survival (90 days; P0.002). CpG-ODNs increased tumoral infiltration with macrophage/microglial cells, CD8, and natural killer lymphocytes. CpG-ODN-cured animals were further protected against a second tumor challenge. CpG-ODNs had no effect on a s.c. CNS1 tumor in nude mice, which suggested that CpG-ODN is not directly cytotoxic and that immunostimulation is required for the antitumoral effect. These findings suggest that intratumoral injections of CpG-ODNs represent a new immunotherapeutic approach in human gliomas, which overcome the need for the selection and purification of a tumoral antigen.

Published
2000

97. Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951

Author

Mokhtari, K., Ducray, F., Kros, J.M., Gorlia, T., Idbaih, A., Taphoorn, M., Wesseling, P., Hoang-Xuan, K., Bent, M.J. van den, Sanson, M., Mokhtari, K., Ducray, F., Kros, J.M., Gorlia, T., Idbaih, A., Taphoorn, M., Wesseling, P., Hoang-Xuan, K., Bent, M.J. van den, and Sanson, M.

Abstract

Item does not contain fulltext, BACKGROUND: Although it has been demonstrated that the neuronal intermediate filament alpha-internexin (INA) is closely related to 1p19q codeletion in gliomas, its prognostic and predictive value has not yet been confirmed in a prospective trial. The authors of this report assessed the prognostic significance of INA expression and its correlation with relevant clinical and molecular characteristics in the prospective, randomized European Organization for Research and Treatment of Cancer (EORTC) 26951 trial of adjuvant procarbazine, lomustine, and vincristine (PCV) in patients with anaplastic oligodendroglial tumors (AOTs). METHODS: INA immunohistochemistry expression in tumors from 92 patients who were included in the EORTC 26951 trial was analyzed independently by 2 observers and was correlated with relevant clinical characteristics, including progression-free survival (PFS) and overall survival (OS), and with molecular features, including 1p/19q codeletion, isocitrate dehydrogenase 1 and 2 gene (IDH1/IDH2) mutation, and O-6 methylguanine-DNA methyltransferase (MGMT) promoter methylation status. RESULTS: INA expression was observed in 33 tumors and was strongly correlated with 1p/19q codeletion, IDH1 mutations, and MGMT promoter methylation. It was associated with significantly better PFS and OS independent of the treatment received. By using Cox proportional hazard modeling for OS with stepwise selection, INA expression, patient age, and performance status were identified as independent prognostic factors. The results indicated that INA expression may have an impact on the efficacy of combined radiotherapy plus PCV. CONCLUSIONS: In a homogeneously treated group of patients with grade III AOTs, INA expression had strong favorable prognostic significance for OS and may have predictive value for sensitivity to chemotherapy.

Published
2011

98. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951.

Author

Idbaih, A., Dalmasso, C., Kouwenhoven, M., Jeuken, J.W.M., Carpentier, C., Gorlia, T., Kros, J.M., French, P., Teepen, J., Broet, P., Delattre, O., Mokhtari, K., Sanson, M., Delattre, J.Y., Bent, M. van den, Hoang-Xuan, K., Idbaih, A., Dalmasso, C., Kouwenhoven, M., Jeuken, J.W.M., Carpentier, C., Gorlia, T., Kros, J.M., French, P., Teepen, J., Broet, P., Delattre, O., Mokhtari, K., Sanson, M., Delattre, J.Y., Bent, M. van den, and Hoang-Xuan, K.

Abstract

1 juni 2011, Item does not contain fulltext, Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

Published
2011

99. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

Author

Idbaih, A. (Ahmed), Dalmasso, C. (Cyril), Kouwenhoven, M.C.M. (Mathilde), Jeuken, J. (Judith), Carpentier, C. (Catherine), Gorlia, T.S. (Thierry), Kros, J.M. (Johan), French, P.J. (Pim), Teepen, J.L.J.M., Broët, P. (Philippe), Delattre, O. (Olivier), Mokhtari, K. (Karima), Sanson, M. (Marc), Bent, M.J. (Martin) van den, Hoang-Xuan, K. (Khe), Idbaih, A. (Ahmed), Dalmasso, C. (Cyril), Kouwenhoven, M.C.M. (Mathilde), Jeuken, J. (Judith), Carpentier, C. (Catherine), Gorlia, T.S. (Thierry), Kros, J.M. (Johan), French, P.J. (Pim), Teepen, J.L.J.M., Broët, P. (Philippe), Delattre, O. (Olivier), Mokhtari, K. (Karima), Sanson, M. (Marc), Bent, M.J. (Martin) van den, and Hoang-Xuan, K. (Khe)

Abstract

Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

Published
2011
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100. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951

Author

Idbaih, A, Dalmasso, C, Kouwenhoven, Mathilde, Jeuken, J, Carpentier, C, Gorlia, T, Kros, J.M., French, Pim, Teepen, J, Broet, P, Delattre, O, Mokhtari, K, Sanson, M, Delattre, JY, van den Bent, Martin, Hoang-Xuan, K, Idbaih, A, Dalmasso, C, Kouwenhoven, Mathilde, Jeuken, J, Carpentier, C, Gorlia, T, Kros, J.M., French, Pim, Teepen, J, Broet, P, Delattre, O, Mokhtari, K, Sanson, M, Delattre, JY, van den Bent, Martin, and Hoang-Xuan, K

Abstract

Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

Published
2011

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