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1. LSC17 score complements genetics and measurable residual disease in acute myeloid leukemia: an ALFA study

Author: Loic Vasseur, Laurène Fenwarth, Jérôme Lambert, Stéphane de Botton, Martin Figeac, Céline Villenet, Maël Heiblig, Pierre-yves Dumas, Christian Récher, Celine Berthon, Emilie Lemasle, Delphine Lebon, Juliette Lambert, Christine Terré, Karine Celli-Lebras, Hervé Dombret, Claude Preudhomme, Meyling H Cheok, Raphaël A. Itzykson, Nicolas Duployez, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Département de Génétique [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), and Service de pathologie [CHU Lille]
Subjects: [SDV]Life Sciences [q-bio], Hematology
Abstract: International audience; Whether the LSC17 gene expression can improve risk stratification in the context of NGS-based risk stratification and measurable residual disease (MRD) in AML patients treated intensively has not been explored. We analyzed LSC17 in 504 adult patients prospectively treated in the ALFA-0702 trial. Multiple (cyto)genetic alterations were associated with changes in LSC17, such as higher LSC17 in patients with RUNX1 or TP53 mutations, and lower scores in those with CEBPA and NPM1 mutations. LSC17-high patients had a lower rate of complete response (CR) or CR with incomplete platelet recovery (CRp) after one induction course in a multivariable analysis (OR=0.41, p=0.0007) accounting for European LeukemiaNet 2022 (ELN22) risk groups, age, and white blood cell (WBC) count. The LSC17-high status was associated with shorter overall survival (OS) (3-year OS: 70.0% versus 52.7% in LSC17-low patients, p
Published: 2023
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2. UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

Author: Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli‑Lebras, Lionel Adès, Delphine Lebon, Céline Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Récher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-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), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'hématologie adulte [Hôpital de Saint Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Haut-Lévêque, and Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux]
Subjects: Cancer Research, Oncology, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults.
Published: 2023
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3. Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study

Author: Rémi Lenain, Romain Larrue, François Glowacki, Christelle Cauffiez, Franck Broly, Viviane Gnemmi, Aghilès Hamroun, Myriam Labalette, Mehdi Maanaoui, Cynthia Van der Hauwaert, Nicolas Pottier, Jean-Baptiste Gibier, Benjamin Hennart, Marc Hazzan, Sebastien Gomis, Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Lille Inflammation Research International Center - U 995 (LIRIC), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, and IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Subjects: medicine.medical_specialty, therapeutic drug monitoring, [SDV]Life Sciences [q-bio], Urology, Medicine (miscellaneous), Renal function, chemical and pharmacologic phenomena, Article, polymorphism, Pharmacokinetics, medicine, tacrolimus, pharmacogenetics, integumentary system, medicine.diagnostic_test, business.industry, Incidence (epidemiology), food and beverages, Retrospective cohort study, renal transplantation, Tacrolimus, Transplantation, surgical procedures, operative, Therapeutic drug monitoring, Medicine, business, Pharmacogenetics
Abstract: The pharmacokinetic variability of tacrolimus can be partly explained by CYP3A5 activity. Our objective was to evaluate a tacrolimus sparing policy on renal graft outcome according to CYP3A5 6986A&gt, G genetic polymorphism. This retrospective study included 1114 recipients with a median follow-up of 6.3 years. Genotyping of the 6986A&gt, G allelic variant corresponding to CYP3A5*3 was systematically performed. One year after transplantation, tacrolimus blood trough concentration (C0) target range was 5–7 ng/mL. However, daily dose was capped to 0.10 mg/kg/day regardless of the CYP3A5 genotype. A total 208 CYP3A5*1/- patients were included. Despite a higher daily dose, CYP3A5*1/- recipients exhibited lower C0 during follow-up (p &lt, 0.01). Multivariate analysis did not show any significant influence of CYP3A5*1/- genotype (HR = 0.70, 0.46–1.07, p = 0.10) on patient-graft survival. Glomerular Filtration Rate (GFR) decline was significantly lower for the CYP3A5*1/- group (p = 0.02). The CYP3A5*1/- genotype did not significantly impact the risk of biopsy-proven acute rejection (BPAR) (HR = 1.01, 0.68–1.49, p = 0.97) despite significantly lower C0. Based on our experience, a strategy of tacrolimus capping is associated with a better GFR evolution in CYP3A5*1/- recipients without any significant increase of BPAR incidence. Our study raised some issues about specific therapeutic tacrolimus C0 targets for CYP3A5*1/- patients and suggests to set up randomized control studies in this specific population.
Published: 2021
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4. MUC1 Mitigates Renal Injury and Inflammation in Endotoxin-Induced Acute Kidney Injury by Inhibiting the TLR4-MD2 Axis and Reducing Pro-inflammatory Macrophages Infiltration

Author: Jean-Baptiste Gibier, Isabelle Van Seuningen, Thomas Swierczewski, Patrice Maboudou, Nicolas Pottier, Sébastien Aubert, Brigitte Hémon, François Glowacki, Michael Perrais, Marie Csanyi, Christelle Cauffiez, Viviane Gnemmi, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Service de Néphrologie et Transplantation rénale [CHRU-lille]
Subjects: Male, Lipopolysaccharide, [SDV]Life Sciences [q-bio], Lymphocyte Antigen 96, Inflammation, Critical Care and Intensive Care Medicine, digestive system, Proinflammatory cytokine, Sepsis, Mice, chemistry.chemical_compound, medicine, Animals, Receptor, skin and connective tissue diseases, neoplasms, business.industry, Macrophages, Mucin-1, Mucin, Acute kidney injury, Acute Kidney Injury, medicine.disease, biological factors, digestive system diseases, 3. Good health, Endotoxins, Mice, Inbred C57BL, Toll-Like Receptor 4, chemistry, Emergency Medicine, Cancer research, TLR4, Female, medicine.symptom, business
Abstract: Sepsis is the leading cause of acute kidney injury (AKI) in critical care patients. A cornerstone of sepsis-associated AKI is dysregulated inflammation driven by excessive activation of Toll-like receptor 4 (TLR4) pathway. MUC1, a membrane bound mucin expressed in both epithelial tubular cells and renal macrophages, has been shown to be involved in the regulation of TLRs. Therefore we hypothesized that MUC1 could mitigate the renal inflammatory response to TLR4 activation. To test this hypothesis, we used a murine model of endotoxin-induced AKI by intraperitoneal injection of lipopolysaccharide (LPS). We showed that Muc1-/- mice have a more severe renal dysfunction, an increased activation of the tissular NF-kB pathway and secreted more pro inflammatory cytokines compare to Muc1+/+ mice. By flow cytometry, we observed that the proportion of M1 (pro-inflammatory) macrophages in the kidneys of Muc1-/- mice was significantly increased. In human and murine primary macrophages, we showed that MUC1 is only induced in M1 type macrophages and that macrophages derived from Muc1-/- mice secreted more pro-inflammatory cytokines. Eventually, in HEK293 cells, we showed that (i) MUC1 cytosolic domain (CT) seems necessary for the negative regulation of TLR4 (ii) by proximity ligation assay, MUC1-CT is in close relationship with TLR4 and acts as a competitive inhibitor of the recruitment of MYD88. Overall our results support that in the context of endotoxin-induced AKI, MUC1 plays a significant role in controlling disease severity by regulating negatively the TLR4-MD2 axis.
Published: 2021
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5. Visites de reprise pour pathologies ostéoarticulaires ou troubles mentaux en Hauts-de-France : populations concernées, actions réalisées et facteurs liés à la décision d’inaptitude

Author: S. Fantoni Quinton, F. Franz, M. Surquin, Ariane Leroyer, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Centre de recherche Droits et perspectives du droit - ULR 4487 (CRDP), Université de Lille, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Arrêt de travail, 03 medical and health sciences, 0302 clinical medicine, [SHS.DROIT]Humanities and Social Sciences/Law, 8. Economic growth, Sick leave, Public Health, Environmental and Occupational Health, Visite de reprise, 030212 general & internal medicine, Occupational medicine, 030210 environmental & occupational health
Abstract: This study objective was to describe, considering the French legal framework and current practices, the completed actions and the occupational health services resources mobilized during the reinstatement visit, and identify the unfit to work decision associated factors, in particular in case of musculoskeletal and mental health diseases.MethodThe data were collected during the « Remain at work » cross sectional study from March to April 2019 in the Hauts-de-France regional occupational health services. The questionnaires were filled by the occupational health doctors for every worker seen in a reinstatement visit after a sick leave absence longer than 30 days.ResultsIn total, 5032 questionnaires completed by 208 doctors were analysed. The reinstatement visit after a sick leave absence longer than 30 days concluded to an unfit to work decision for 12.3% of all the workers, but it was 21.7% when the sick leave cause was a mental health problem (16.1% of total sick leave) and 10.5% when it was a musculoskeletal disease (56.3% of total sick leave). Factors significantly associated with inability at work in case of a mental health disease were: being an employment obligation recipient, the disease professional origin, a long term sick leave, working in a 50 or less employees company and being exposed to psychological pressure. In case of musculoskeletal disease, these factors were being 50 years old or more, the “clerk/service worker” status, a long term sick leave, being an employment obligation recipient, working in the construction industry and time constraints.ConclusionThe implementation and evaluation of a “return to work plan” are needed to improve job retention.; Cette étude visait à décrire, dans le contexte de la législation et des pratiques actuelles en France, les mesures mises en œuvre et les ressources mobilisées par les services de santé au travail lors des visites de reprise, et à identifier les facteurs en lien avec les décisions d’inaptitudes, en particulier pour les pathologies ostéoarticulaires et les troubles mentaux.MéthodeLes données sont issues de l’étude transversale « Maintien dans l’emploi », s’étant déroulée en mars et avril 2019, dans les services de santé au travail des Hauts-de-France. Le questionnaire était complété par les médecins du travail pour tout salarié vu en visite de reprise après un arrêt de travail d’au moins 30 jours.RésultatsAu total, 5032 questionnaires complétés par 208 médecins du travail ont été analysés. La visite de reprise après un arrêt d’au moins 30 jours se concluait par une inaptitude du salarié au poste de travail dans 12,3 % des cas, mais 21,7 % en cas d’arrêt de travail pour des troubles mentaux (représentant 16,1 % des arrêts) et de 10,5 % en cas d’atteintes du système ostéoarticulaire (56,3 % des arrêts). Les facteurs associés significativement à une inaptitude faisant suite à un arrêt de travail pour troubles mentaux étaient : être bénéficiaire d’une obligation d’emploi, avoir un trouble d’origine professionnelle, une durée d’arrêt importante, travailler dans une entreprise de moins de 50 salariés et être exposé à la pression psychologique ; lors d’atteintes du système ostéoarticulaire, ces facteurs étaient l’âge supérieur ou égal à 50 ans, le statut employé, une durée d’arrêt de travail importante, être bénéficiaire d’une obligation d’emploi, travailler dans le secteur construction et la présence de contraintes horaires.ConclusionLa mise en place et l’évaluation de plans de retour au travail sont nécessaires pour améliorer le maintien en emploi.
Published: 2021
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6. Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements

Author: Aline Tanguy-Schmidt, Sébastien Maury, Paola Ballerini, Nicolas Sirvent, Judith Landman-Parker, Patrice Chevallier, E. Dore, Cédric Duclos, Ibrahima Ba, Hélène Cavé, Jean Soulier, Massimiliano Bonifacio, Nicolas Duployez, Chantal Himberlin, André Baruchel, Hervé Dombret, Thorsten Braun, Ilaria Tanasi, Emmanuelle Clappier, Jerome Tamburini, Nicolas Boissel, Wendy Cuccuini, Philippe Rousselot, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Verona (UNIVR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Recherche clinique appliquée à l'hématologie (URP_3518), Université de Paris (UP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Hôpital Cochin [AP-HP], Hôpital Henri Mondor, Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Reims (CHU Reims), Le CHCB, Centre Hospitalier de la Côte Basque, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier de Versailles André Mignot (CHV), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, Adolescent, Aged, Antineoplastic Agents, Child, Child, Preschool, Female, Gene Rearrangement, Humans, Middle Aged, Oncogene Proteins, Fusion, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-abl, Young Adult, Oncogene Proteins, Immunology, Biochemistry, Precursor Cell Lymphoblastic Leukemia Lymphoma, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Acute lymphocytic leukemia, medicine, Preschool, Fusion, ComputingMilieux_MISCELLANEOUS, ABL, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Gene rearrangement, medicine.disease, Ph-Like Acute Lymphoblastic Leukemia, 3. Good health, 030220 oncology & carcinogenesis, Cancer research, business, Tyrosine kinase, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Tanasi et al present a prospective strategy for identifying patients with Philadelphia-like acute lymphoblastic leukemia, demonstrating the efficacy of early introduction of tyrosine kinase inhibitors in improving outcomes.
Published: 2019
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7. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer

Author: Thomas Boulanger, Jérôme Barrière, Audrey Mailliez, Michael Weller, Emilie Le Rhun, Isabelle Rodrigues, Veronique Lorgis, Yves Marie Robin, Jacques Bonneterre, Marie-Cécile Le Deley, Jennifer Wallet, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, University hospital of Zurich [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Service de neuro-oncologie, de neurochirurgie générale et stéréotaxique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Biostatistiques [CHRU Lille], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Imagerie [Lille] (Cancer Oscar Lambret ), Cancer Oscar Lambret [Lille], Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département Oncologie Médicale [Nice], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), Service de pathologie [CHU Lille], Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service de biostatistiques [CHU Lille] (Centre Oscar Lambret), Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA)-UNICANCER, University of Zurich, and SALZET, Michel
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, brain, [SDV]Life Sciences [q-bio], Population, Clinical Investigations, 610 Medicine & health, Breast Neoplasms, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Internal medicine, depocyte, medicine, Clinical endpoint, Humans, cerebrospinal, Progression-free survival, education, 030304 developmental biology, 0303 health sciences, education.field_of_study, business.industry, Hazard ratio, Cytarabine, meningitis, neoplastic, medicine.disease, Chemotherapy regimen, 10040 Clinic for Neurology, 3. Good health, [SDV] Life Sciences [q-bio], Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Neurology (clinical), business, medicine.drug
Abstract: Background DEPOSEIN (NCT01645839) was a randomized open-label phase III study to explore the role of intrathecal chemotherapy in patients with newly diagnosed leptomeningeal metastasis (LM), a common manifestation of breast cancer. Methods Patients with newly diagnosed LM defined by tumor cells in the cerebrospinal fluid or combination of clinical and neuroimaging signs of LM were randomized to receive systemic therapy alone (control group) or systemic therapy plus intrathecal liposomal cytarabine (experimental group). Progression-free survival related to LM (LM-PFS) was the primary endpoint. Results Thirty-seven and 36 patients were assigned to the control and the experimental groups. Median number of liposomal cytarabine injections in the experimental group was 5 (range 1–20). Focal radiotherapy was performed in 6 (16%) and 3 (8%) patients in the control and experimental groups. In the intent-to-treat population, median LM-PFS was 2.2 months (95% CI: 1.3–3.1) in the control versus 3.8 months (95% CI: 2.3–6.8) in the experimental group (hazard ratio 0.61, 95% CI: 0.38–0.98) (P = 0.04). Seventy-one patients have died. Median overall survival was 4.0 months (95% CI: 2.2–6.3) in the control versus 7.3 months (95% CI: 3.9–9.6) in the experimental group (hazard ratio 0.85, 95% CI: 0.53–1.36) (P = 0.51). Serious adverse events were reported in 22 and 30 patients, respectively. Quality of life until progression did not differ between groups. Conclusion The addition of intrathecal liposomal cytarabine to systemic treatment improves LM-related PFS. Confirmatory trials with optimized patient selection criteria and more active drugs may be required to demonstrate a survival benefit from intrathecal pharmacotherapy.
Published: 2020
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8. Molecular characteristics of multifocal brain histiocytic sarcoma

Author: N. Piton, S. Derrey, Elodie Bohers, A. Zarea, Annie Laquerrière, Homa Adle-Biassette, Florent Marguet, F. Renaud, Thomas Boyer, J. C. Sabourin, Service de santé au travail et pathologie professionnelle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pathologie [CHU Rouen], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe d'étude des proliférations lymphoïdes (GPL), Service d'Hématologie Cellulaire [Lille], Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), and Service de neurochirurgie [CHU Rouen]
Subjects: Pathology, medicine.medical_specialty, Histology, business.industry, Histiocytic sarcoma, medicine.disease, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Neurology, 030220 oncology & carcinogenesis, Physiology (medical), [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Neurology (clinical), business, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery
Abstract: International audience
Published: 2018
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9. Discrepancy Between Clinical and Pathologic Nodal Status of Esophageal Cancer and Impact on Prognosis and Therapeutic Strategy

Author: Alain Duhamel, Christophe Mariette, Bernard Meunier, Gil Lebreton, Denis Collet, Arnaud Pasquer, Cécile Brigand, Hélène Behal, Sheraz R. Markar, Jérémie Thereaux, Caroline Gronnier, Florence Renaud, Johan Gagnière, Guillaume Piessen, Imperial College London, Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Clermont-Ferrand, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de Hautepierre [Strasbourg], Service de pathologie [CHU Lille], CHU Pontchaillou [Rennes], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Herrada, Anthony, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Inserm, Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Centre Hospitalier Régional Universitaire de Brest [CHRU Brest], and Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Subjects: Male, Pathology, Esophageal Neoplasms, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Aucun, Gastroenterology, 0302 clinical medicine, Risk Factors, Surgical oncology, Medicine, 10. No inequality, Neoadjuvant therapy, Hazard ratio, Middle Aged, Esophageal cancer, 3. Good health, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Resection margin, Adenocarcinoma, Female, 030211 gastroenterology & hepatology, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Survival rate, Neoplasm Staging, Retrospective Studies, Gastrointestinal Oncology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, T-stage, Surgery, Lymph Nodes, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: The impact of discrepancies between clinical (c) and pathologic (p) stages of esophageal cancer remains a poorly understood issue. This study aimed to compare the prognosis of patient groups treated by primary surgery including clinical N0/pathologic N0 (cN0pN0), clinical N0/pathologic N+ (cN0pN+), clinical N+/pathologic N0 (cN+pN0), and clinical N+/pathologic N+ (cN+pN+).METHODS: Data were collected from 30 European centers during the years 2000 to 2010. Among 2944 recruited patients, 1554 patients receiving primary surgery met the inclusion criteria including 613 cN0pN0, 403 cN0pN+, 220 cN+pN0, and 318 cN+pN+ patients. Analyses with adjustment of the propensity score were used to compensate for differences in baseline characteristics.RESULTS: Clinical T stages 3 and 4 were increased in cN+pN+ (73.0%), cN0pN+ (49.6%), and cN+pN0 (51.8%) compared with cN0pN0 (32.8%). Compared with cN0pN0, cN+pN+ and cN0pN+ showed an increase in the proportion of adenocarcinoma histologic subtype, poor tumor differentiation, pathologic T3 and T4 stages, and R1/2 resection margin. Adjusted 5-year overall survival (hazard ratio [HR] 3.12; 95% confidence interval [CI] 2.57-3.78; P
Published: 2017
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10. Effect of secondary electron emission on the guiding properties of insulating capillaries

Author: K. Tökési, R. D. Dubois, E. Giglio, Simulation (SIMUL), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institute for Nuclear Research [Budapest] (ATOMKI), Hungarian Academy of Sciences (MTA), Service de pathologie [CHU Lille], and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: History, Materials science, Secondary emission, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], Molecular physics, Computer Science Applications, Education
Abstract: Synopsis The transmission of 1 keV Ar+ ions through a macroscopic glass capillary is simulated by taking explicitly into account the secondary electron (SE) emission generated by ion impacts inside the capillary. The SE emission re-distributes the injected charge in the capillary wall and thus modifies the guiding power of insulating capillaries. Especially for high beam intensities, SE are found to be crucial for explaining the observed time-evolution of the transmitted intensities.
Published: 2020
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11. Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry

Author: Nicolas Franck, E. Maubec, Gaëlle Quéreux, Caroline Ram-Wolff, Philippe Courville, Laurence Lamant, Olivier Dereure, G. Dobos, Isabelle Templier, Florent Grange, Saskia Ingen-Housz-Oro, Jacques Rouanet, Martine Bagot, N. Josselin, O. Augereau, Stéphane Barete, Serge Boulinguez, Isabelle Moulonguet, Marisa Battistella, Nicolas Ortonne, Anne Durlach, A. Carlotti, Pascal Joly, S. Taix, Sophie Dalac, Michel D'Incan, F. Franck, Laurent Mortier, A. de Masson, Marie Beylot-Barry, Charlée Nardin, Jacqueline Rivet, M.-D. Vignon-Pennamen, Laurence Michel, Liliane Laroche, Anne Pham-Ledard, Romain Dubois, T. Petrella, Béatrice Vergier, Florent Amatore, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Cochin [AP-HP], Centre hospitalier de Cahors, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Dermatologie (CHU de Dijon), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Grenoble, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Cahors, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: medicine.medical_specialty, Mycosis fungoides, Heterogeneous group, business.industry, Incidence (epidemiology), [SDV]Life Sciences [q-bio], CBCL, Retrospective cohort study, Dermatology, medicine.disease, Cutaneous lymphoma, 3. Good health, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Male patient, Epidemiology, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. Objectives The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. Methods Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. Results The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. Conclusions Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.
Published: 2020
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12. Clinical, Radiological, Histopathological, Molecular Description and Identification of Prognostic Factors for Desmoplastic Infantile Gangliogliomas and Astrocytomas: A Multicentric Cohort Study

Author: Gourmel, A., Perbet, R., Beccaria, K., Maurage, C. A., Escande, F., Grill, J., Varlet, P., Figarella, D., Vinchon, M., Bourdeaut, F., Devoldere, C., Le Moing, Anne Gaelle, Salamon, A. I. Bertozzi, de Carli, E., Gentet, J. C., Icher, C., Frappaz, D., Silva, K., Leblond, P., Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Amiens-Picardie, Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Léon Bérard [Lyon], Dynamique des Génomes et Adaptation Microbienne (DynAMic), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), and DESSAIVRE, Louise
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

13. Prognostic Significance of Concurrent Gene Mutations in Intensively Treated Patients with IDH1/2 Mutated AML

Author: Raphael Itzykson, Lionel Ades, Hervé Dombret, Jean Valère Malfuson, Juliette Lambert, Céline Berthon, Claude Preudhomme, Christine Terré, Emmanuel Raffoux, Cécile Pautas, Jean-Baptiste Micol, Matthieu Duchmann, Jean-Pierre Marolleau, Nicolas Duployez, Emilie Lemasle, Karine Celli-Lebras, Arnaud Pigneux, Claude Gardin, Christian Recher, Xavier Thomas, Pascal Turlure, Nicolas Boissel, Stéphane de Botton, Thorsten Braun, Denis Caillot, Norbert Vey, Sylvain Chantepie, Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Service d'Hématologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie cellulaire, F-33000, Bordeaux., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Génétique [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service clinique des Maladies du Sang, CHU Amiens-Picardie, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut d'Hématologie de Basse-Normandie (IHBN), 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)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), DESSAIVRE, Louise, and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Mutation, IDH1, business.industry, Point mutation, [SDV]Life Sciences [q-bio], Immunology, DNMT3A Gene, Cell Biology, Hematology, Gene mutation, medicine.disease_cause, Biochemistry, Chemotherapy regimen, [SDV] Life Sciences [q-bio], Isocitrate dehydrogenase, Cancer research, Medicine, business, Gene
Abstract: Background : Point mutations in isocitrate dehydrogenase (IDH) genes are seen in 20% of adult patients (pts) with acute myeloid leukemia (AML). Prognostic significance of each IDH1/2 mutation (mut) analyzed with co-occurring mutations treated with intensive chemotherapy (IC) remains inconsistent, particularly with the advent of IDH inhibitors. Furthermore, the role of allogeneic stem cell transplantation (SCT) in IDH-mutated without favorable-risk features is not known. Patients & Methods: Between 2009 and 2016, 262 pts with IDH1/2 mutated AML (101 IDH1mut, 115 IDH2R140Qmutand 46 IDH2R172mut) were treated with IC in younger ALFA-0702 (NCT00932412, n = 133) and older ALFA-1200 (NCT01966497, n = 129) prospective trials. Median age was 50 [42-54] and 67 y [64-71], respectively (resp). Targeted 37-gene next-generation sequencing (NGS) information was available for all pts. According to ELN 2010 classification, non-favorable CR/CRp pts were eligible for SCT if they had a sibling or matched unrelated donor. Correlation between IDHmutand covariates was realized by Pearson correlation coefficient and point biserial correlation for continuous and dichotomic variables, resp. Impact on response and survival was assessed for all covariates present in at least 10% of patients. SCT was considered as a time-dependent variable. Informative variables selected by LASSO were included in multivariate logistic regression for response and multivariate Cox model for survival. All analyses were stratified on the clinical trial. Results: IDH1 mut was significantly associated with NPM1mut(p=0.025), DNMT3Amut(p=0.009) and mutually exclusive with TET2mut(p=0.009). 80% (81/101) of IDH1 mutated pts achieved CR/CRp [96 % (46/48) if concomitant NPM1mut vs 66% (35/53) if not (p=0.0009)]. With a median FU of 39 months, overall median OS was not reached and median EFS was 15 months (Fig 1A). Presence of NPM1mutwas the only variable associated with longer OS (HR=0.33, p=0.001) and EFS (HR = 0.4, p = 0.001) in multivariate analysis. At 5 years, OS was estimated at 68% and 35% and EFS at 55% and 26%, resp (Fig 1B). Effect of concomitant NPM1mutwas reinforced in the absence of DNMT3Amut(HR=0.14, p=0.0006 and HR=0.16, p IDH2R140Q mut was significantly associated with NPM1mut(p=0.0004) and SRSF2mut(p IDH2R172K mut was significantly associated with DNMT3Amut(p=0.0004) and BCORmut(p Finally, in non-favorable ELN 2010 pts (74, 74 and 46 with IDH1mut, IDH2R140Qmutand IDH2R172Kmut, resp), SCT in first CR only benefited to pts with IDH1mut(p=0.004 for OS) or with IDH2R172Kmut(p=0.03 for EFS). Conclusion: In a large prospective series, NPM1mutis the main better risk factor in the IDH1mutand IDH2R140Qmutsubgroups and may be used as stratification factor in clinical trials testing frontline specific IDH inhibitors with IC. Allogeneic SCT in first CR appears to improve the outcome of pts with non-favorable IDH1 or IDH2R172K mutated AML. Figure 1 Disclosures Micol: Jazz Pharmaceuticals: Consultancy; AbbVie: Consultancy. Thomas:ABBVIE: Honoraria; DAICHI: Honoraria; INCYTE: Honoraria; PFIZER: Honoraria. Braun:Institut de Recherches Internationales Servier (IRIS): Research Funding. Ades:Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Helsinn Healthcare: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Membership on an entity's Board of Directors or advisory committees. Berthon:PFIZER: Other: DISCLOSURE BOARD; JAZZPHARMACEUTICAL: Other: DISCLOSURE BOARD; CELGEN: Other: DISCLOSURE BOARD. Boissel:NOVARTIS: Consultancy. Vey:Janssen: Honoraria; Novartis: Consultancy, Honoraria. Pigneux:Astellas: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Jazz: Honoraria; Abbvie: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Daichi: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria. Recher:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dombret:CELGENE: Consultancy, Honoraria; AGIOS: Honoraria; Institut de Recherches Internationales Servier (IRIS): Research Funding. De Botton:Daiichi: Consultancy; Janssen: Consultancy; Agios: Consultancy, Research Funding; Astellas: Consultancy; Pierre Fabre: Consultancy; Servier: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Forma: Consultancy, Research Funding; Syros: Consultancy; AbbVie: Consultancy; Celgene Corporation: Consultancy, Speakers Bureau; Bayer: Consultancy.
Published: 2019
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14. NEW INSIGTHS IN CELLULAR MECHANISMS INVOLVED IN THE LIVER REGENERATION DEFECT DESCRIBED IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS

Author: Saleh, Mohamed Bou, Lassailly, Guillaume, Ningarhari, Massih, Gnemmi, Viviane, Maggiotto, Francois, Artru, Florent, Boleslawski, Emmanuel, Anglo, Emilie, Sancho-Bru, Pau, Stephanie Truant, Corlu, Anne, Argemi, Josepmaria, Dharancy, Sebastien, Bataller, Ramon, Mathurin, Philippe, Louvet, Alexandre, Dubuquoy, Laurent, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Hôpital Claude Huriez [Lille], CHU Lille, Université Paris 1 Panthéon-Sorbonne (UP1), Service de pathologie [CHU Lille], Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Lille (CHU de Lille), Université Paris Descartes - Paris 5 (UPD5), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas, Partenaires INRAE, CIBER in Epidemiology and Public Health, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: [SDV] Life Sciences [q-bio], hépatite alcoolique, microbiote intestinal, [SDV]Life Sciences [q-bio], rectocolite hémorragique, maladie de Crohn, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

15. The Effect of Lactobacillus fermentum ME‐3 Treatment on Glycation and Diabetes Complications

Author: Eric Boulanger, Axel Guilbaud, Brigitte Onraed, Céline Niquet-Léridon, Patrice Maboudou, Mike Howsam, Susanna Schraen, Sophie Lestavel, Frédéric J. Tessier, Anne Garat, Marc Fremont, Florian Delguste, Benoît Foligné, CHU Lille, Inserm, Institut Pasteur de Lille, Université de Lille, Lille Inflammation Research International Center (LIRIC) - U995, Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167, Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011, Lille Inflammation Research International Center - U 995 [LIRIC], IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483, UniLaSalle, Lille Neurosciences & Cognition (LilNCog) - U 1172, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE], Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Service de pathologie [CHU Lille], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Transformations et Agro-ressources (UT&A), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Glycation End Products, Advanced, Male, 0301 basic medicine, Limosilactobacillus fermentum, Lactobacillus fermentum, [SDV]Life Sciences [q-bio], Type 2 diabetes, carboxymethyllysine, Pharmacology, Gut flora, Kidney, Weight Gain, Diabetes Mellitus, Experimental, law.invention, Diabetes Complications, 03 medical and health sciences, Probiotic, law, Glycation, Diabetes mellitus, medicine, Animals, furosine, Glycated Hemoglobin, 030109 nutrition & dietetics, diabetes, biology, business.industry, Lysine, Probiotics, Diabetic mouse, biology.organism_classification, medicine.disease, Lipids, Gastrointestinal Microbiome, 030104 developmental biology, glycation, probiotics, Liver, Receptors, Leptin, Steatosis, business, Food Science, Biotechnology
Abstract: International audience; ScopeType 2 diabetes (T2D) induces organ damage associated with glycation, among other metabolic pathways. While therapeutic strategies have been tested to reduce the formation and impact of glycation products, results remain equivocal. Anti-diabetic therapies using probiotics have been proposed, but their effect upon glycation has not been reported. Here, the effects of the bacterial strain Lactobacillus fermentum ME-3 on glycation and T2D-related complications in a mouse model of T2D are investigated.Methods & ResultsWild-type LepRdb and diabetic LepRdb littermates receive a daily gavage of either water or the probiotic ME-3 strain (1010 CFU). Glycation markers, fructoselysine-derived furosine (FL-furosine) and carboxymethyllysine (CML), are quantified in four major organs and plasma using stable-isotope dilution LC–MS/MS. After 12 weeks of ME-3 treatment, diabetic mice gain less weight and exhibit an apparently improved glucose tolerance. The ME-3 treatment reduces median renal levels of FL-furosine in both genotypes by 12–15%, and renal and pulmonary free-CML in diabetic mice by 30% and 18%, respectively. Attenuated hepatic steatosis and an improved plasma lipid profile are also observed with treatment in both genotypes, while the gut microbiota profile is unchanged.ConclusionL. fermentum ME-3 has therapeutic potential for reducing the formation/accumulation of some glycation products in kidneys and attenuating some common diabetes-related complications.
Published: 2020
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16. Management of bleeding and emergency invasive procedures in patients on dabigatran: Updated guidelines from the French Working Group on Perioperative Haemostasis (GIHP) – September 2016

Author: Albaladejo, Pierre, Pernod, Gilles, Godier, Anne, De Maistre, Emmanuel, Rosencher, Nadia, Mas, Jean Louis, Fontana, Pierre, Samama, Charles Marc, Steib, Annick, Schlumberger, Sylvie, Marret, Emmanuel, Roullet, Stéphanie, Susen, Sophie, Madi-Jebara, Samia, Nguyen, Philippe, Schved, Jean François, Bonhomme, Fanny, Sié, Pierre, Perioperative Haemostasis, French Working Group on, CHU Grenoble, Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sainte Anne [Paris], Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires de Genève (HUG), CHU Strasbourg, Hôpital Foch [Suresnes], Service Anesthésie - Réanimation [Bordeaux], CHU Bordeaux [Bordeaux], Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Interactions cellules micro-environnement (IFR53), Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and CHU Cochin [AP-HP]
Subjects: medicine.medical_specialty, Emergency Medical Services, Regional anaesthesia, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Antithrombins, Perioperative Care, Dabigatran, 03 medical and health sciences, 0302 clinical medicine, Emergency surgery, Medicine, Humans, In patient, 030212 general & internal medicine, Invasive Procedure, Dabigatran concentration, ddc:616, ddc:617, business.industry, Bleeding, Idarucizumab, General Medicine, Perioperative, Hemostasis, Surgical, 3. Good health, Bleeding complication, Anesthesiology and Pain Medicine, Antidote, Surgical Procedures, Operative, Emergency medicine, Emergency, Surgery, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; In 2013, the GIHP published guidelines for the management of severe haemorrhages and emergency surgery. This update applies to patients treated with dabigatran, with a bleeding complication or undergoing an urgent invasive procedure. It includes how to handle the available specific antidote (idarucizumab), when to measure dabigatran plasmatic concentration and when to use non-specific measures in these situations. It also includes guidelines on how to perform regional anaesthesia and analgesia procedures.
Published: 2018
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17. Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

Author: Denis Collet, Christophe Mariette, Jérémie Thereaux, Caroline Gronnier, Bernard Meunier, Charlotte Cohen, Fregat, Guillaume Piessen, Williams Tessier, Johan Gagnière, Florence Renaud, Arnaud Pasquer, Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), CHU Clermont-Ferrand, CHU Pontchaillou [Rennes], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, Male, medicine.medical_specialty, Neoplasm, Residual, Esophageal Neoplasms, Anastomotic Leak, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Anastomosis, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Hospital Mortality, Stage (cooking), Survival rate, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Salvage Therapy, business.industry, Standard treatment, Radiotherapy Dosage, Retrospective cohort study, Chemoradiotherapy, Middle Aged, Esophageal cancer, medicine.disease, 3. Good health, Surgery, Esophagectomy, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cohort, Carcinoma, Squamous Cell, Female, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business
Abstract: International audience; BACKGROUND:Locoregional recurrence rates after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer (EC) are high. Salvage surgery (SALV) is considered the best treatment option in case of persistent or recurrent disease for operable patients, but SALV has been associated with increased morbidity and mortality. The aim of this study is to identify factors linked to outcomes after SALV to better select candidates and to optimize perioperative care.STUDY DESIGN:We retrospectively analyzed data from 308 consecutive SALV patients from a large multicenter European cohort. Univariate and multivariate analyses were performed to identify factors associated with in-hospital postoperative morbidity, anastomotic leakage (AL), and overall survival (OS).RESULTS:The in-hospital postoperative mortality and morbidity rates were 8.4 and 34.7%, respectively. Squamous cell histology (p = 0.040) and radiation dose ≥ 55 Gy (p = 0.047) were independently associated with major morbidity. The AL rate was 12.7%, and cervical anastomosis was independently associated with AL (p = 0.002). OS at 5 years was 34.0%. Radiation dose ≥ 55 Gy (p = 0.003), occurrence of postoperative complications (p = 0.006), ypTNM stage 3 (p = 0.019), and positive surgical margins (p < 0.001) were linked to poor prognosis.CONCLUSIONS:SALV is a valuable option for patients with persistent or recurrent disease after dCRT and offers long-term survival. Factors such as radiation dose and anastomosis location identified here will help to optimize outcomes after SALV, which may be considered a standard treatment in the EC therapeutic armamentarium.
Published: 2018
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18. Influence of comorbid alcohol use disorders on the clinical patterns of major depressive disorder: a general population-based study

Author: Pierre Thomas, Baptiste Pignon, Imane Benradia, Jean-Luc Roelandt, Pierre-Alexis Geoffroy, Louise Carton, Benjamin Rolland, Philippe de Timary, Alexandre Baguet, Mickaël Naassila, Ali Amad, Guillaume Vaiva, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université Catholique de Louvain (UCL), Alcoolisation précoce et vulnerabilité à la dépendance, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de psychiatrie adulte, and Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Epidemiology, Alcohol abuse, [SDV]Life Sciences [q-bio], Emotions, Alcohol use disorder, Comorbidity, Major depressive disorder, Toxicology, behavioral disciplines and activities, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, mental disorders, medicine, Humans, Pharmacology (medical), Dual diagnosis, Bipolar disorder, Psychiatry, Pharmacology, Depressive Disorder, Major, business.industry, Panic disorder, Alcohol dependence, Middle Aged, medicine.disease, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Alcoholism, Diagnosis, Dual (Psychiatry), Regression Analysis, Female, France, business, 030217 neurology & neurosurgery
Abstract: Background To compare the symptom patterns of major depressive disorder (MDD) among subjects with MDD and 1) no alcohol use disorder (AUD), 2) alcohol abuse and 3) alcohol dependence, respectively. Methods In a general population survey of 38,694 French individuals, MDD and AUDs were assessed using the Mini International Neuropsychiatric Interview 5.0.0 (MINI). A total of 4339 subjects (11.2%) in the sample met the criteria for MDD. Among them, 413 (9.5%) AUD subjects were identified: 138 (3.2%) for alcohol abuse and 275 (6.3%) for alcohol dependence. The associations of each of the ten MDD criteria of the MINI and psychiatric clinical features were compared among the three groups. The relative profiles of ‘MDD + AUD’ vs. ‘MDD alone’ were determined using a multivariable stepwise regression model. Results With the noAUD group as the reference, sadness (OR = 0.46; 95%CI, 0.29–0.74) and anhedonia (OR = 1.66; 95%CI, 1.06–2.73) were only associated with alcohol abuse. Sleep disorders (OR = 2.07; 95%CI, 1.51–2.88), feelings of guilt (OR = 1.41; 95%CI, 1.05–1.90), diminished concentration/indecisiveness (OR = 1.52; 95%CI, 1.12–2.07) and thoughts of death (OR = 1.95; 95%CI 1.49–2.55) were only associated with alcohol dependence. Weight or appetite variations were both associated with alcohol abuse (OR = 1.7; 95%CI, 1.15–2.53) and dependence (OR = 1.41; 95%CI, 1.06–1.88). Bipolar disorder and PTSD were only associated with alcohol dependence. Psychotic features, previous suicide attempts, and panic disorder were more frequent in the MDD-AUD group. Conclusion MDD-AUD subjects displayed a more severe profile with specific symptomatology and comorbidity profiles compared to MDD-only subjects.
Published: 2018
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19. Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation

Author: Delphine Vezzosi, Abir Al Ghuzlan, Delphine Drui, Matthieu Wargny, Sébastien Aubert, Sarra Smati, Olivier Chabre, Laurence Amar, Claire Briet, François Pattou, Rossella Libé, Martine Patey, Bertrand Cariou, Frédérique Tissier, Karine Renaudin, Nathalie Sturm, Jérôme Bertherat, Magalie Haissaguerre, Peggy Pierre, Mathilde Sibony, Jean Christophe Lifante, Claudine Berthozat, Emmanuelle Leteurtre, Christine Do Cao, Eric Baudin, Eric Mirallié, Service de Pathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d’anatomie et cytologie pathologique, Hôpital Robert Debré, CHU de Reims, Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Université Paris-Sorbonne (UP4), Service d'HYPERVASC [CHU HEGP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence pour les Maladies Rares, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'endocrinologie-diabétologie-nutrition [CHU Grenoble-Alpes], Service d’endocrinologie, diabétologie et maladies métaboliques [CHRU LIlle], Département d'endocrinologie - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2, Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie (TOULOUSE - Endocrino), CHU Toulouse [Toulouse], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Chirurgie Générale et Endocrinienne [Lyon], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de chirurgie générale et endocrinienne, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie Digestive et Endocrinienne [Nantes], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Service d'Endocrinologie [Nantes], Unité de recherche de l'institut du thorax (ITX-lab), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire [Grenoble] (CHU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Pathology, Proliferation index, Adenoma, [SDV]Life Sciences [q-bio], Malignancy, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, Biomarkers, Tumor, Adenoma, Oxyphilic, Humans, Stage (cooking), Retrospective Studies, biology, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Adrenal Cortex Neoplasms, 3. Good health, 030104 developmental biology, Ki-67 Antigen, 030220 oncology & carcinogenesis, Ki-67, Cohort, biology.protein, Female, business
Abstract: International audience; Oncocytic adrenocortical tumors are a rare subtype of adrenal tumors with challenging diagnosis and histoprognostic assessment. It is usually believed that oncocytic adrenocortical tumors have a more indolent clinical behavior than conventional adrenocortical tumors. As the Weiss score overestimates the malignancy of oncocytic adrenocortical tumors owing to intrinsic parameters, alternative scores have been proposed. The Lin-Weiss-Bisceglia score is currently recommended. We performed a large nationwide multicenter retrospective clinicopathologic study of oncocytic adrenocortical tumors. Among the 43 patients in our cohort, 40 patients were alive without disease, 2 patients died of their disease and 1 patient was alive with relapse after a median follow-up of 38 months (20-59). Our data revealed that over 50% of the oncocytic adrenocortical tumor cases were diagnosed as carcinoma whatever the classification systems used, including the Lin-Weiss-Bisceglia score. The exception is the Helsinki score, which incorporates the Ki-67 proliferation index and was the most specific prognostic score for oncocytic adrenocortical tumor malignancy without showing a loss in sensitivity. A comparison of malignant oncocytic adrenocortical tumors with conventional adrenocortical carcinomas matched for age, sex, ENS@T stage and surgical resection status showed significant better overall survival of malignant oncocytic adrenocortical tumors.
Published: 2018
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20. Oncogenic Predictors of Outcome in Older AML Patients Treated Intensively. Analysis of the ALFA-1200 Trial

Author: Lauris Gastaud, Sylvain Chantepie, Olivier Nibourel, Karine Celli-Lebras, Christine Terré, Nicolas Boissel, Hervé Dombret, Lionel Ades, Jean-Baptiste Micol, Benjamin Papoular, Raphael Itzykson, Cécile Pautas, Nicolas Duployez, Elise Fournier, Claude Gardin, Céline Berthon, Emilie Lemasle, Thomas Cluzeau, Thorsten Braun, Xavier Thomas, Alice Marceau-Renaut, Emmanuel Raffoux, Jean Valère Malfuson, Philippe Rousselot, Claude Preudhomme, Jean-Pierre Marolleau, Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Claude Huriez [Lille], CHU Lille, Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service de pathologie [CHU Lille], Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service clinique des Maladies du Sang, CHU Amiens-Picardie, Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut d'Hématologie de Basse-Normandie (IHBN), 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)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Mathématiques & Sécurité de l'information (XLIM-MATHIS), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de Génétique [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Service d'Hématologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], and DESSAIVRE, Louise
Subjects: 0301 basic medicine, Oncology, Neuroblastoma RAS viral oncogene homolog, medicine.medical_specialty, Univariate analysis, business.industry, [SDV]Life Sciences [q-bio], Immunology, Hazard ratio, Cell Biology, Hematology, Odds ratio, Gene mutation, medicine.disease_cause, Biochemistry, [SDV] Life Sciences [q-bio], Transplantation, 03 medical and health sciences, 030104 developmental biology, Gene interaction, Internal medicine, medicine, KRAS, business
Abstract: Context. The prognostic value of gene mutations in older AML patients (pts) treated intensively remains unclear. Only one study has explored the role of mutation patterns determined by NGS in older AML pts prospectively treated with various chemotherapies in years 2000-2010 (Eisfeld Leukemia 2018). Methods. Pts older than 60y enrolled in the ALFA-1200 trial (NCT01966497) between 09/2012 and 06/2016 were sequenced with a 37-gene myeloid panel. Pts received one 7+3 course followed by 2 intermediate-dose cytarabine courses. Pts with non-favorable risk were eligible for allogeneic stem cell transplantation (SCT). Variable selection for multivariate analyses was performed by lasso penalized regression including age, gender and log(WBC) as covariates. Results. Sequencing was done in 471 (93%) of the 509 enrolled pts. Median age and WBC count were 68y and 5.3x109/L, respectively (resp). CR (including CRp) was achieved in 341 (72%) pts and 90 underwent RIC-SCT in first CR. With a median follow-up of 25.4 months, median OS was 20.7 months. Pts had a median of 3 mutations (range 1-10). The 17 mostly frequently mutated genes (≥5% of pts, by decreasing frequency: DNMT3A, NPM1, TET2, ASXL1, FLT3, SRSF2, IDH2, RUNX1, NRAS, IDH1, STAG2, BCOR, TP53, PTPN11, U2AF1, EZH2 and KRAS) were retained for prognostic analyses. Genes belonging to a common pathway (eg. NRAS and KRAS) may have divergent prognostic values, preventing biology-informed grouping of mutations. Cytogenetic risk (derived from ELN 2017, Döhner Blood 2017, not considering gene mutations) was favorable (fav), intermediate (int), adverse (adv) and missing in 3%, 72%, 18% and 7% resp. Because of the few pts with fav cytogenetics in our cohort, pts were further grouped into non-adv and adv cytogenetics. CR rates and median OS were 75.6% vs 56.6% and 24.8 vs 9.5 months in pts with non-adv and adv cytogenetics, resp (both p In the 388 pts with non-adv cytogenetics, NPM1 mutations independently predicted improved CR rate (Odds Ratio [OR]=2.3, p=0.014), while mutations in ASXL1 (OR=0.46, p=0.012), RUNX1 (OR=0.46, p=0.013) and NRAS (OR=0.49, p=0.04) had independent adverse predictive value. In univariate analysis the shorter OS of FLT3-ITD pts was confined to allele ratios≥ 0.5 (FLT3-ITDhigh, p=0.02). In a multivariate analysis accounting for clinical covariates, mutations in NPM1 (Hazard Ratio [HR]=0.45, p In the 83 pts with adv cytogenetics, TP53 mutations predicted shorter OS (p=0.004). Among pts with adv cytogenetics, those without TP53 mutation had a median OS of 12.6 months and were thus classified as high risk while the median OS of the 30 pts with adv cytogenetics and TP53 mutations was only 5.4 months, defining very high risk disease. This stratification resulted in improved OS prediction compared to the full molecular ELN 2017 (C-index 0.63 vs 0.58, resp). This stratification also predicted Relapse-Free Survival (RFS, Figure, p Conclusion. In AML patients older than 60y treated intensively, mutations in 7 genes (NPM1, SRSF2, FLT3, DNMT3A, ASLX1, NRAS and TP53) can refine the prognosis of cytogenetic sub-groups. Figure Figure. Disclosures Cluzeau: MENARINI: Consultancy; CELGENE: Consultancy; JAZZ PHARMA: Consultancy.
Published: 2018
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21. CD163-positive tumor-associated macrophages and CD8-positive cytotoxic lymphocytes are powerful diagnostic markers for the therapeutic stratification of osteosarcoma patients: An immunohistochemical analysis of the biopsies fromthe French OS2006 phase 3 trial

Author: Françoise Rédini, Marta Jimenez, Corinne Bouvier, Claire Illac, Laurence Brugieres, Véronique Minard, Béatrice Marie, Vincent Minville, Gonzague de Pinieux, François Gouin, Marie-cecile Ledeley, Julia Gilhodes, Thomas Filleron, Sophie Piperno-Neumann, Natacha Entz-Werle, Frédérique Larousserie, Eric Mascard, Anne Gomez-Brouchet, Jean-Marc Guinebretière, Sébastien Aubert, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de Biostatistiques [Toulouse], Institut Claudius Regaud-Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pathologie [Institut Curie], Institut Curie [Paris], Service de Pathologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Pathologie [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie orthopédique et traumatologie pédiatrique [CHU Necker ], CHU Necker - Enfants Malades [AP-HP], Département d'Orthopédie [CHU Hôtel Dieu, Nantes], Hôtel-Dieu de Nantes, UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'Oncologie Médicale [Institut Curie, Paris], Funding were obtained from the French National Cancer Institute (INCa Novartis Chugai Ligue Nationale contre le Cancer Fédération Enfants et Santé Société Française des Cancers et Leucémies de l’enfant (SFC and the Association Etoile de Martin). The ancillary biological studies were approved by the Sarcoma Group of UNICANCER, the 'Groupe des Sarcomes Français-Groupe d’étude des Tumeurs Osseuses' (GSF-GETO), the SFCE and the InterSarc network., Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT)-Institut Claudius Regaud, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), maurice, sandrine, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Pathology, medicine.medical_treatment, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, cd163, lcsh:RC254-282, Metastasis, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, osteosarcoma, Immunology and Allergy, Medicine, Cytotoxic T cell, Original Research, Chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, CD68, cd8, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, macrophages, 030104 developmental biology, pd1/pdl-1 checkpoint, 030220 oncology & carcinogenesis, Immunohistochemistry, Osteosarcoma, business, lcsh:RC581-607, CD163, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The French phase 3 trial (OS 2006) testing zoledronic acid, an osteoclast inhibitor, with chemotherapy and surgery did not improve the outcome of patients with osteosarcoma (OS). To understand this unexpected result, the presence of infiltrating immune cells was investigated in 124 pre-therapeutic biopsies of patients enrolled in the trial. The percentage of CD68/CD163 tumor-infiltrating macrophages (TAMs), CD8+ lymphocytes, osteoclasts, and the PD1/PDL-1 checkpoint were assessed by immunohistochemistry. M1/M2 macrophage polarization was characterized by pSTAT1/CMAF staining. The expression of these biomarkers was correlated with clinical outcome. No statistical correlations were found with response to chemotherapy. High CD163 levels (>50% of cells per core; 43.8% of patients) were associated with CMAF nuclear expression and significantly correlated with better overall survival (p = 0.0025) and longer metastasis progression-free survival (MPFS, p = 0.0315) independently of metastatic status (p = 0.002). Only a trend was observed for patients with high CD68-positive cells (p = 0.0582). CD8+ staining was positive in >50% of cases with a median staining of 1%. Lower CD8+ levels were associated with metastatic disease at diagnosis and the presence of CD8-positive cells significantly correlated with improved overall survival in zoledronate-treated patients (p = 0.0415). PD1/PDL-1 staining was negative in >80% of cases and was not correlated with outcome. Finally, CD163-positive TAMs and CD8 positive cells are crucial prognostic biomarkers in OS, whereas PD1/PDL-1 checkpoint plays a minor role. For the first time, we described a correlation between CD8 positive cells and survival in zoledronate-treated patients. The immunohistochemical analysis of the microenvironment in biopsies may represent a novel tool for therapeutic stratification.
Published: 2017
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22. SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1- mutated patient's management

Author: C, Colson, E, Aubry, M, Cartigny, A-A, Rémy, H, Franquet, X, Leroy, G, Kéchid, C, Lefèvre, R, Besson, M, Cools, A F, Spinoit, C, Sultan, S, Manouvrier, P, Philibert, J, Ghoumid, Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'endocrinologie pédiatrique [CHU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Heterozygote, Hypospadias, endocrine system, Adolescent, spleen development, Primary Ovarian Insufficiency, Sex Determination Processes, Steroidogenic Factor 1, XY-DSD, SF1, A%22">c.1227C>A, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Humans, Female, Child, Spermatogenesis, Spleen, Adrenal Insufficiency
Abstract: International audience; Steroidogenic factor 1 (encoded by SF1/NR5A1) is a transcription factor with multiple target genes involved in the development and function of multiple steroidogenic and non-steroidogenic tissues. NR5A1 mutations lead to several phenotypes, including sex reversal, spermatogenesis failure, premature ovarian failure and adrenocortical insufficiency. The implication of NR5A1 mutations in spleen development anomalies was recently highlighted. We provide new evidence of this involvement, describing a novel heterozygous non-sense NR5A1 mutation in a 46,XY-DSD with polysplenia female proband and her father, who had hypospadias and asplenia.
Published: 2017
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23. Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer

Author: Sefrioui , France, Vermeulin , France, Blanchard , France, Chapusot , Caroline, Beaussire , Ludivine, Armengol-Debeir , Laura, Sesboué , Richard, Gangloff , Alice, Hebbar , Mohamed, Copin , Marie-Christine, Houivet , Estelle, Schwarz , Lilian, Clatot , Florian, Tuech , Jacques, Bénichou , Jacques, Martin , Laurent, Bouvier , Anne-Marie, Sabourin , Jean-Christophe, Sarafan-Vasseur , Nasrin, Frébourg , Thierry, Lepage , Côme, Michel , Pierre, Di Fiore , Frédéric, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Hôpital Charles Nicolle [Tunis], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pathologie, PRES Université Lille Nord de France-Faculté de Médecine Henri Warembourg-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Charles Nicolle [Rouen], Groupe d'étude des proliférations lymphoïdes (GPL), Unité de biostatistiques [CHU Rouen], Centre Guillaume le Conquérant, Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [Rouen], Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [CHU Lille], Département de chirurgie [Rouen], CRLCC Henri Becquerel, Service de chirurgie digestive [Rouen], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Oncologie Médicale, and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel )
Subjects: Male, Proto-Oncogene Proteins B-raf, MESH: Colon Cancer, DNA Copy Number Variations, Receptor, ErbB-2, MESH: Chromosomal instability, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, MESH: Copy Number Variation, Loss of Heterozygosity, Receptors, Cell Surface, Polymerase Chain Reaction, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Humans, Prospective Studies, Neoplasm Metastasis, Aged, Proportional Hazards Models, Colon Cancer, Tumor Suppressor Proteins, Carcinoma, Middle Aged, DCC Receptor, Prognosis, Copy Number Variation, Chromosomal instability, Microstellite Stable, Phenotype, Treatment Outcome, Colonic Neoplasms, MESH: Disease-Free Survival, Female, MESH: Microstellite Stable, Neoplasm Recurrence, Local, Microsatellite Repeats
Abstract: IF 5.531; International audience; We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p
Published: 2017
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24. The FREGAT biobank: a clinico-biological database dedicated to esophageal and gastric cancers

Author: Stéphanie Clisant, Florence Renaud, Véronique Christophe, Antoine Adenis, Guillaume Piessen, Christine Delaeter, Malek Dib, Patrick Gelé, Valentin Harter, Emmanuelle Leteurtre, Christophe Mariette, Franck Bonnetain, Marie-Christine Copin, Alain Duhamel, Herrada, Anthony, Hôpital Claude Huriez [Lille], CHU Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Traitement des Données du Cancéropôle Nord-Ouest (CTD-CNO), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE)-UNICANCER, UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), CNRS, Inserm, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc], Site de Recherche Intégrée en Cancérologie [SIRIC-ONCOLille], Service de Biologie Moléculaire et Centre de Pathologie [Equipe 1], Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 [CIC Lille], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC], Service d'Oncologie Médicale [CHRU Besançon], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) [CEF2P / CARCINO], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], and Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab]
Subjects: Male, Cancer Research, Databases, Factual, Esophageal Neoplasms, Epidemiology, Esophageal cancer, Disease, Study Protocol, 0302 clinical medicine, Prospective Studies, Biological Specimen Banks, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Biobank, Combined Modality Therapy, 3. Good health, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, Adult, Quality of life, medicine.medical_specialty, FREGAT, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, Therapeutic approach, Young Adult, Quality of life (healthcare), [SDV.CAN] Life Sciences [q-bio]/Cancer, Stomach Neoplasms, Genetics, medicine, Humans, Intensive care medicine, Aged, Internet, business.industry, Research, Cancer, Human and social sciences, Clinico-biological database, medicine.disease, Clinical research, business, Gastric cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: While the incidence of esophageal and gastric cancers is increasing, the prognosis of these cancers remains bleak. Endoscopy and surgery are the standard treatments for localized tumors, but multimodal treatments, associated chemotherapy, targeted therapies, immunotherapy, radiotherapy, and surgery are needed for the vast majority of patients who present with locally advanced or metastatic disease at diagnosis. Although survival has improved, most patients still present with advanced disease at diagnosis. In addition, most patients exhibit a poor or incomplete response to treatment, experience early recurrence and have an impaired quality of life. Compared with several other cancers, the therapeutic approach is not personalized, and research is much less developed. It is, therefore, urgent to hasten the development of research protocols, and consequently, develop a large, ambitious and innovative tool through which future scientific questions may be answered. This research must be patient-related so that rapid feedback to the bedside is achieved and should aim to identify clinical-, biological- and tumor-related factors that are associated with treatment resistance. Finally, this research should also seek to explain epidemiological and social facets of disease behavior. The prospective FREGAT database, established by the French National Cancer Institute, is focused on adult patients with carcinomas of the esophagus and stomach and on whatever might be the tumor stage or therapeutic strategy. The database includes epidemiological, clinical, and tumor characteristics data as well as follow-up, human and social sciences quality of life data, along with a tumor and serum bank. This innovative method of research will allow for the banking of millions of data for the development of excellent basic, translational and clinical research programs for esophageal and gastric cancer. This will ultimately improve general knowledge of these diseases, therapeutic strategies and patient survival. This database was initially developed in France on a nationwide basis, but currently, the database is available for worldwide contributions with respect to the input of patient data or the request for data for scientific projects. The FREGAT database has a dedicated website ( www.fregat-database.org ) and is registered on the Clinicaltrials.gov site, number NCT 02526095 , since August 8, 2015.
Published: 2016
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25. Brentuximab vedotin in refractory or relapsed peripheral T-cell lymphomas: the French named patient program experience in 56 patients

Author: Richard Delarue, Céline Bossard, Emmanuel Bachy, Corinne Haioun, Mathilde Lamarque, Adrien Contejean, Josette Brière, Hervé Tilly, Steven Le Gouill, Marie Parrens, Philippe Gaulard, Pauline Brice, Reda Bouabdallah, Brigitte Bouchindhomme, Danielle Canioni, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'anatomie et cytologie pathologiques, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Necker - Enfants Malades [AP-HP], Département d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], UMR INSERM U955, École nationale vétérinaire - Alfort (ENVA), Service d'hématologie clinique, Département de pathologie [Mondor], Bernardo, Elizabeth, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Centre d’Investigation Clinique de Nantes ( CIC Nantes ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Ecole Nationale Vétérinaire d'Alfort, and École nationale vétérinaire d'Alfort (ENVA)
Subjects: Oncology, medicine.medical_specialty, CD30, T cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, Refractory, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Brentuximab vedotin, Online Only Articles, ComputingMilieux_MISCELLANEOUS, business.industry, Hematology, medicine.disease, Primary cutaneous T-cell lymphoma, 3. Good health, Peripheral, Lymphoma, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, business, 030215 immunology, medicine.drug
Abstract: Brentuximab vedotin (BV) is an antibody-drug-conjugate directed against CD30 antigen, recently approved for the treatment of relapsed anaplastic large-cell lymphomas (ALCL).[1][1] It has further been suggested that a significant proportion of peripheral T-cell lymphomas (PTCL) may be potential
Published: 2016
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26. Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas

Author: Jean Luc Descotes, Eva Comperat, Jean Philippe Spano, Roger Mouawad, Chad J. Creighton, Morgan Rouprêt, Hui Yao, Xavier Leroy, Philippe Barthélémy, Linda Dainese, Mokrane Yacoub, Xiaoping Su, Nathalie Rioux-Leclercq, Marion Classe, Gabriel G. Malouf, Virginie Verkarre, Véronique Lindner, Jean-Christophe Bernhard, David Khayat, Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Service de pathologie [CHU Strasbourg], CHU Strasbourg, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de pathologie [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'urologie [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'oncologie médicale [CHU Strasbourg], Service d'Oncologie Médicale [Bordeaux], Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, French Network for Research on Kidney Cancer (UroCCR), Service d'Urologie [CHU Pitié-Salpêtrière], service d'urologie [CHU Bordeaux], CHU Bordeaux [Bordeaux], Baylor College of Medicine (BCM), Baylor University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Universitaire de Cancérologie [Sorbonne Université] (IUC)
Subjects: Adult, Male, 0301 basic medicine, Urologic Neoplasms, Pathology, medicine.medical_specialty, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Transcriptome, Young Adult, 03 medical and health sciences, Collecting duct carcinoma, 0302 clinical medicine, Renal cell carcinoma, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biomarkers, Tumor, Carcinoma, medicine, Genetics, Humans, Carcinoma, Renal Cell, health care economics and organizations, Aged, Kidney, Multidisciplinary, Tumor-infiltrating lymphocytes, Middle Aged, medicine.disease, Phenotype, Kidney Neoplasms, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Kidney cancer
Abstract: Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Herein, we performed for the first time transcriptome sequencing of CDC and compared them to UTUC and renal cell carcinoma subtypes. We discovered that CDC displays a unique transcriptomic signature among kidney cancer subtypes, with a putative cell of origin in the distal convoluted tubules. Hierarchical unsupervised clustering reveals that the CDC signature is closer to that of other RCC subtypes than to UTUC, which is similar to that of bladder carcinoma. CDC is characterized by a metabolic shift, with impairment of oxidoreductase activity, pyruvate metabolism and the tricarboxlyic acid cycle, as well as an immunogenic response consistent with increased tumor infiltrating lymphocytes, particularly within metastatic cases. In addition, pathways differentially altered between CDC and UTUC point to a basal-like phenotype of CDC in contrast to the luminal-like signature of UTUC. We conclude that CDC harbors a pathognomonic transcriptomic signature characterized by immunogenic and a metabolic aberrations, indicating that targeting these processes might provide therapeutic options for patients.
Published: 2016
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27. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort

Author: Dominique Figarella-Branger, Anh Tuan Nguyen, Hugues Loiseau, Jean-Yves Delattre, Claude-Alain Maurage, Olivier Chinot, François Ducray, Carole Colin, Ahmed Idbaih, Elisabeth Moyal, Emmanuelle Uro-Coste, Emmanuèle Lechapt-Zalcman, Caroline Dehais, Catherine Carpentier, Christine Desenclos, Emeline Tabouret, Karima Mokhtari, Anne Jouvet, David Meyronet, Marc Polivka, Neuro-Oncologie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- 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), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [APHP], 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 [APHP]-Centre National de la Recherche Scientifique (CNRS), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie Raymond Escourolle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CHU Toulouse [Toulouse], Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], CHU de Bordeaux Pellegrin [Bordeaux], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de pathologie, AP-HP Hôpital Lariboisière [Paris], Laboratoire d'Anatomie Pathologique [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), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de neurochirurgie, Hôpital Nord - Amiens, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-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 Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Pathology, IDH1, Adolescent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Oligodendroglioma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 1p/19q Codeletion, Astrocytoma, World Health Organization, Disease-Free Survival, Pathology and Forensic Medicine, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, Oligodendroglial Tumor, neoplasms, Pathological, Grading (tumors), Aged, Aged, 80 and over, business.industry, Brain Neoplasms, Glioma, Middle Aged, medicine.disease, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Mutation, Female, Neurology (clinical), Who classification, business, 030217 neurology & neurosurgery, Anaplastic astrocytoma
Abstract: The new WHO classification of diffuse gliomas has been refined and now includes the 1p/19q codeletion, IDH1/2 mutation, and histone H3-K27M mutation. Our objective was to assess the prognostic value of the updated 2016 WHO classification in the French POLA cohort. All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nationwide POLA cohort were reclassified according to the updated 4th WHO classification. In total, 1041 patients were included, with a median age at diagnosis of 50.4 years (range 17.1–84.4). Based on the new histomolecular classification, diagnoses included anaplastic oligodendroglioma IDH mutant and 1p/19q-codeleted (32.5 %), anaplastic astrocytoma IDH mutant (IDH mut) (11.0 %), anaplastic astrocytoma IDH wild type (IDH wt) (5.3 %), glioblastoma IDH mut (17.1 %), and glioblastoma IDH wt (33.2 %). Ten patients presented with a diffuse midline tumor, H3 K27M mutant. The new WHO classification was prognostic for progression-free survival (PFS) and overall survival (OS) (p
Published: 2016
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28. Central Nervous System and Peripheral Inflammatory Processes in Alzheimer’s Disease: Biomarker Profiling Approach

Author: Constance eDELABY, Audrey eGABELLE, David eBLUM, Susanna eSCHRAEN MASCHKE, Amandine eMOULINIER, Justine eBOULANGIEN, Dany eSEVERAC, Luc eBUEE, Thierry eREME, Sylvain eLEHMANN, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Philips, Alexandre, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Chemokine, [SDV]Life Sciences [q-bio], Central nervous system, Inflammation, Disease, Bioinformatics, lcsh:RC346-429, cerebrospinal fluid, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Medicine, lcsh:Neurology. Diseases of the nervous system, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Original Research, 0303 health sciences, biology, business.industry, Neurodegeneration, biomarkers, medicine.disease, Neural stem cell, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Neurology, inflammation, Immunology, biology.protein, Neurology (clinical), Alzheimer's disease, medicine.symptom, Alzheimer disease, business, serum, 030217 neurology & neurosurgery, Neuroscience
Abstract: Brain inflammation is one of the hallmarks of Alzheimer disease (AD) and a current trend is that inflammatory mediators, particularly cytokines and chemokines, may represent valuable biomarkers for early screening and diagnosis of the disease. Various studies have reported differences in serum level of cytokines, chemokines, and growth factors in patients with MCI (Mild Cognitive Impairment) or AD. However, data were often inconsistent and the exact function of inflammation in neurodegeneration is still a matter of debate.In the present work, we measured the expression of 120 biomarkers (corresponding to cytokines, chemokines, growth factors, and related signalling proteins) in the serum of 49 patients with the following diagnosis distribution: 15 controls, 14 AD and 20 MCI. In addition, we performed the same analysis in the cerebrospinal fluid (CSF) of 20 of these patients (10 AD and 10 controls). Among the biomarkers tested, none showed significant changes in the serum, but 13 were significantly modified in the CSF of AD patients. Interestingly, all of these biomarkers were implicated in neurogenesis or neural stem cells migration and differentiation. In a second part of the study, 10 of these putative biomarkers (plus 4 additional) were quantified using quantitative multiplex ELISA methods in the CSF and the serum of an enlarged cohort composed of 31 AD and 24 control patients.Our results confirm the potential diagnosis interest of previously published blood biomarkers, and proposes new ones (such as IL-8 and TNFR-I). Further studies will be needed to validate these biomarkers which could be used alone, combined, or in association with the classical amyloid and tau biomarkers.
Published: 2015
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29. Impaired processing of self-face recognition in anorexia nervosa

Author: France Hirot, Marine Lesage, Lya Pedron, Isabelle Meyer, Pierre Thomas, Olivier Cottencin, Dewi Guardia, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: Adult, Anorexia Nervosa, Adolescent, Trail Making Test, Neuropsychological Tests, Anorexia nervosa, 050105 experimental psychology, Developmental psychology, Body Mass Index, 03 medical and health sciences, [SCCO]Cognitive science, Young Adult, 0302 clinical medicine, Cognition, Face perception, medicine, Body Image, Humans, 0501 psychology and cognitive sciences, 2. Zero hunger, 05 social sciences, Cognitive flexibility, Recognition, Psychology, Feeding Behavior, Middle Aged, medicine.disease, Body Dysmorphic Disorders, Self Concept, Psychiatry and Mental health, Clinical Psychology, Eating disorders, Body dysmorphic disorder, Female, Psychology, Body mass index, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Body image disturbances and massive weight loss are major clinical symptoms of anorexia nervosa (AN). The aim of the present study was to examine the influence of body changes and eating attitudes on self-face recognition ability in AN. Twenty-seven subjects suffering from AN and 27 control participants performed a self-face recognition task (SFRT). During the task, digital morphs between their own face and a gender-matched unfamiliar face were presented in a random sequence. Participants' self-face recognition failures, cognitive flexibility, body concern and eating habits were assessed with the Self-Face Recognition Questionnaire (SFRQ), Trail Making Test (TMT), Body Shape Questionnaire (BSQ) and Eating Disorder Inventory-2 (EDI-2), respectively. Subjects suffering from AN exhibited significantly greater difficulties than control participants in identifying their own face (p = 0.028). No significant difference was observed between the two groups for TMT (all p > 0.1, non-significant). Regarding predictors of self-face recognition skills, there was a negative correlation between SFRT and body mass index (p = 0.01) and a positive correlation between SFRQ and EDI-2 (p
Published: 2015
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30. The Lymphoid Variant of Hypereosinophilic Syndrome

Author: Lefevre, Guillaume, Copin, Marie-Christine, Staumont-Sallé, Delphine, Avenel-Audran, Martine, Aubert, Hélène, Taïeb, Alain, Salles, Gilles, Maisonneuve, Hervé, Ghomari, Kamel, Ackerman, Felix, Legrand, Fanny, Baruchel, André, Launay, David, Terriou, Louis, Leclech, Christian, Khouatra, Chahera, Morati-Hafsaoui, Chafika, Labalette, Myriam, Borie, Raphaël, Cotton, François, Gouellec, Noémie Le, Morschhauser, Franck, Trauet, Jacques, Roche-Lestienne, Catherine, Capron, Monique, Hatron, Pierre-Yves, Prin, Lionel, Kahn, Jean-Emmanuel, Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Dermatologie pédiatrique - Bordeaux, CHU Bordeaux [Bordeaux], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie, CH La Roche-sur-Yon, Hôpital Foch [Suresnes], Service d'hématologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), MIA Software [Nantes], MIA, Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris Diderot - Paris 7 (UPD7), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie Cellulaire [Lille], Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Claude Huriez [Lille], CHU Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, Adolescent, CD3 Complex, T-Lymphocytes, [SDV]Life Sciences [q-bio], Middle Aged, Article, Young Adult, Phenotype, Child, Preschool, Hypereosinophilic Syndrome, Humans, Female, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies
Abstract: The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network. All patients who met the recent criteria of hypereosinophilia (HE) or HES and who had a persistent CD3-CD4+ T-cell subset on blood T-cell phenotyping were included. Clinical and laboratory data were retrospectively collected by chart review. CD3-CD4+ L-HES was diagnosed in 21 patients (13 females, median age 42 years [range, 5–75 yr]). Half (48%) had a history of atopic manifestations. Clinical manifestations were dermatologic (81%), superficial adenopathy (62%), rheumatologic (29%), gastrointestinal (24%), pulmonary (19%), neurologic (10%), and cardiovascular (5%). The median absolute CD3-CD4+ T-cell count was 0.35 G/L (range, 0.01–28.3), with a clonal TCRγδ rearrangement in 76% of patients. The mean follow-up duration after HES diagnosis was 6.9 ± 5.1 years. All patients treated with oral corticosteroids (CS) (n = 18) obtained remission, but 16 required CS-sparing treatments. One patient had a T-cell lymphoma 8 years after diagnosis, and 3 deaths occurred during follow-up. In conclusion, clinical manifestations related to CD3-CD4+ T cell-associated L-HES are not limited to skin, and can involve all tissue or organs affected in other types of HE. Contrary to FIP1L1-PDGFRA chronic eosinophilic leukemia patients, CS are always effective in these patients, but CS-sparing treatments are frequently needed. The occurrence of T-cell lymphoma, although rare in our cohort, remains a major concern during follow-up.
Published: 2014
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31. Electro-clinical presentation of hereditary transthyretin related amyloidosis when presenting as a polyneuropathy of unknown origin in northern France.

Author: Davion JB, Bocquillon P, Cassim F, Frezel N, Lacour A, Dhaenens CM, Maurage CA, Gibier JB, Hachulla E, Nguyen The Tich S, Defebvre L, Merle PE, and Tard C
Subjects: France epidemiology, Humans, Prealbumin genetics, Amyloid Neuropathies, Familial complications, Amyloid Neuropathies, Familial diagnosis, Amyloid Neuropathies, Familial epidemiology, Polyneuropathies diagnosis, Polyneuropathies epidemiology, Polyneuropathies etiology, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
Abstract: Introduction: Hereditary transthyretin related amyloidosis (h-ATTR) classically presents as a small fiber neuropathy with positive family history, but can also be revealed by various other types of peripheral neuropathy., Objective: To describe the initial electro-clinical presentation of patients from in a single region (northern France) of h-ATTR when it presents as a polyneuropathy of unknown origin., Method: We reviewed the records of patients referred to two neuromuscular centers from northern France with a peripheral neuropathy of unknown origin who were subsequently diagnosed with h-ATTR., Results: Among 26 h-ATTR patients (10 Val30Met, 16 Ser77Tyr), only 14 patients had a suspicious family history (53.8%). The electro-clinical presentation was mostly a large-fiber sensory motor polyneuropathy (92.3%), which could be symmetric or not, length-dependent or not, or associated with nerve entrapment or not. Demyelinating signs were observed in 17 patients (70.8%), among whom nine fulfilled the criteria for a definite diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (37.5%)., Conclusion: h-ATTR may have a wide spectrum of clinical profiles, and should be considered in the screening of polyneuropathies of unknown origin., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Published: 2021
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31 results on '"Service de pathologie [CHU Lille]"'

1. LSC17 score complements genetics and measurable residual disease in acute myeloid leukemia: an ALFA study

2. UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

3. Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study

4. MUC1 Mitigates Renal Injury and Inflammation in Endotoxin-Induced Acute Kidney Injury by Inhibiting the TLR4-MD2 Axis and Reducing Pro-inflammatory Macrophages Infiltration

5. Visites de reprise pour pathologies ostéoarticulaires ou troubles mentaux en Hauts-de-France : populations concernées, actions réalisées et facteurs liés à la décision d’inaptitude

6. Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements

7. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer

8. Molecular characteristics of multifocal brain histiocytic sarcoma

9. Discrepancy Between Clinical and Pathologic Nodal Status of Esophageal Cancer and Impact on Prognosis and Therapeutic Strategy

10. Effect of secondary electron emission on the guiding properties of insulating capillaries

11. Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry

12. Clinical, Radiological, Histopathological, Molecular Description and Identification of Prognostic Factors for Desmoplastic Infantile Gangliogliomas and Astrocytomas: A Multicentric Cohort Study

13. Prognostic Significance of Concurrent Gene Mutations in Intensively Treated Patients with IDH1/2 Mutated AML

14. NEW INSIGTHS IN CELLULAR MECHANISMS INVOLVED IN THE LIVER REGENERATION DEFECT DESCRIBED IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS

15. The Effect of Lactobacillus fermentum ME‐3 Treatment on Glycation and Diabetes Complications

16. Management of bleeding and emergency invasive procedures in patients on dabigatran: Updated guidelines from the French Working Group on Perioperative Haemostasis (GIHP) – September 2016

17. Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

18. Influence of comorbid alcohol use disorders on the clinical patterns of major depressive disorder: a general population-based study

19. Clinicopathological description of 43 oncocytic adrenocortical tumors: importance of Ki-67 in histoprognostic evaluation

20. Oncogenic Predictors of Outcome in Older AML Patients Treated Intensively. Analysis of the ALFA-1200 Trial

21. CD163-positive tumor-associated macrophages and CD8-positive cytotoxic lymphocytes are powerful diagnostic markers for the therapeutic stratification of osteosarcoma patients: An immunohistochemical analysis of the biopsies fromthe French OS2006 phase 3 trial

22. SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1- mutated patient's management

23. Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer

24. The FREGAT biobank: a clinico-biological database dedicated to esophageal and gastric cancers

25. Brentuximab vedotin in refractory or relapsed peripheral T-cell lymphomas: the French named patient program experience in 56 patients

26. Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas

27. Prognostic impact of the 2016 WHO classification of diffuse gliomas in the French POLA cohort

28. Central Nervous System and Peripheral Inflammatory Processes in Alzheimer’s Disease: Biomarker Profiling Approach

29. Impaired processing of self-face recognition in anorexia nervosa

30. The Lymphoid Variant of Hypereosinophilic Syndrome

31. Electro-clinical presentation of hereditary transthyretin related amyloidosis when presenting as a polyneuropathy of unknown origin in northern France.

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31 results on '"Service de pathologie [CHU Lille]"'

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