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51 results on '"Laurent Hannoun"'

1. Variant on Manifestation of Duodenal Metastasis 26 Years after Initial Diagnosis of Primary Cutaneous Melanoma

Author: Kumiko Kitajima, Armelle Bardier-Dupas, Sylvie Breton, Géraldine Rousseau, Jean-Michel Siksik, Jean-Christophe Vaillant, and Laurent Hannoun
Subjects: Nonampullary duodenal neoplasm, Amelanotic melanoma, Metastatic duodenal tumor, Malignant melanoma, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Malignant duodenal neoplasms are relatively rare, and the diagnosis is often delayed because of their vague and nonspecific symptoms. We report the case of a 79-year-old female who had a medical history of malignant melanoma of the cheek that had initially been diagnosed at 53 years of age. Work-up revealed severe stenosis of the duodenum caused by a large mass with ulceration at the tip of its mucosal surface. Tumor biopsy led to a histological diagnosis of extremely poorly differentiated carcinoma, but it was impossible to determine whether the lesion was a primary neoplasm or represented secondary involvement. Pancreatoduodenectomy was performed, and the surgical specimen showed a protuberant tumor in the nonampullary region of the second portion of the duodenum. Final diagnosis of metastatic duodenal melanoma was made by immunohistological examination. She is currently alive without recurrence 28 months after the surgical treatment.
Published: 2010
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2. Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.

Author: Nadya Depinay, Jean Francois Franetich, Anne Charlotte Grüner, Marjorie Mauduit, Jean-Marc Chavatte, Adrian J F Luty, Geert-Jan van Gemert, Robert W Sauerwein, Jean-Michel Siksik, Laurent Hannoun, Dominique Mazier, Georges Snounou, and Laurent Rénia
Subjects: Medicine, Science
Abstract: BackgroundThe liver stages of malaria parasites are inhibited by cytokines such as interferon-γ or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-α possibly because of differences in the models used. We have reassessed the role of TNF-α in the different cellular systems used to study the Plasmodium pre-erythrocytic stages.Methods and findingsHuman or mouse TNF-α were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-α treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-α inhibition was mediated by a soluble factor present in the supernatant of TNF-α stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified.ConclusionsTreatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection.
Published: 2011
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3. Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice.

Author: Nicolas Brezillon, Marie-Noëlle Brunelle, Hélène Massinet, Eric Giang, Céline Lamant, Lucie DaSilva, Sophie Berissi, Jacques Belghiti, Laurent Hannoun, Gherard Puerstinger, Eva Wimmer, Johan Neyts, Olivier Hantz, Patrick Soussan, Serban Morosan, and Dina Kremsdorf
Subjects: Medicine, Science
Abstract: Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC(50) of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy.
Published: 2011
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4. Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection.

Author: Anthony Siau, Olivier Silvie, Jean-François Franetich, Samir Yalaoui, Carine Marinach, Laurent Hannoun, Geert-Jaan van Gemert, Adrian J F Luty, Emmanuel Bischoff, Peter H David, Georges Snounou, Catherine Vaquero, Patrick Froissard, and Dominique Mazier
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface proteins involved in hepatocyte invasion, while the other two were predominantly expressed during hepatic parasite development. The genome-wide up-regulation of expression observed supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes validated our approach as one means to determine the repertoire of proteins implicated during the early events of the Plasmodium infection, and in this case that of P. falciparum, the species responsible for the severest forms of malaria.
Published: 2008
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5. A plant-derived morphinan as a novel lead compound active against malaria liver stages.

Author: Maëlle Carraz, Akino Jossang, Jean-François Franetich, Anthony Siau, Liliane Ciceron, Laurent Hannoun, Robert Sauerwein, François Frappier, Philippe Rasoanaivo, Georges Snounou, and Dominique Mazier
Subjects: Medicine
Abstract: BACKGROUND: The global spread of multidrug-resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. METHODS AND FINDINGS: Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 muM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 muM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 muM, TI 46, and IC50 42.4 muM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. CONCLUSIONS: A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs.
Published: 2006
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6. Surgically treated oesophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes

Author: Sheraz R. Markar, Caroline Gronnier, Arnaud Pasquer, Alain Duhamel, Hélène Behal, Jérémie Théreaux, Johan Gagnière, Gil Lebreton, Cécile Brigand, Bernard Meunier, Denis Collet, Christophe Mariette, Guillaume Luc, Magalie Cabau, Jacques Jougon, Bogdan Badic, Patrick Lozach, Serge Cappeliez, Arnaud Alves, Renaud Flamein, Denis Pezet, Federica Pipitone, Bogdan Stan Iuga, Nicolas Contival, Eric Pappalardo, Styliani Mantziari, Flora Hec, Marguerite Vanderbeken, Williams Tessier, Nicolas Briez, Fabien Fredon, Alain Gainant, Muriel Mathonnet, Jean-Marc Bigourdan, Salim Mezoughi, Christian Ducerf, Jacques Baulieux, Oussama Baraket, Gilles Poncet, Delphine Vaudoyer, Peggy Jourdan Enfer, Laurent Villeneuve, Olivier Glehen, Thibault Coste, Jean Michel Fabre, Frédéric Marchal, Romain Frisoni, Ahmet Ayav, Laurent Brunaud, Laurent Bresler, Charlotte Cohen, Olivier Aze, Nicolas Venissac, Daniel Pop, Jérôme Mouroux, Ion Donici, Michel Prudhomme, Emanuele Felli, Stéphanie Lisunfui, Marie Seman, Gaelle Godiris Petit, Mehdi Karoui, Christophe Tresallet, Fabrice Ménégaux, Laurent Hannoun, Brice Malgras, Denis Lantuas, Karine Pautrat, Marc Pocard, Patrice Valleur, Imperial College London, 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, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU 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), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital de Hautepierre [Strasbourg], Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CIC-IT Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Générale et Viscérale (CGV - BREST), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Département de chirurgie digestive, CHU Clermont-Ferrand, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Claude Huriez [Lille], CHU Lille, Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Médico-Chirurgical des Maladies de l'Appareil Digestif et de Transplantation Hépatique, Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Thoracic Surgery, Louis Pasteur Hospital, Groupe de Recherche Angevin en Economie et Management (GRANEM), Université d'Angers (UA)-AGROCAMPUS OUEST-Institut National de l'Horticulture et du Paysage, Service de Chirurgie thoracique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'hépato-gastro-entérologie [APHP 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Gastroenterological Surgery, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Santé publique : épidémiologie et qualité des soins-EA 2694 (CERIM), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Universitaire Estaing, Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB), UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical (UMR PVBMT - INRA), Institut National de la Recherche Agronomique (INRA), Hôpital Claude Huriez, Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, CHU Saint-Eloi, Université de Lorraine (UL), Faculté de Médecine [Nancy], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [APHP], Service de chirurgie générale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre d'Etude et Recherche en Informatique Médicale, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de chirurgie digestive, Service de Médecine Interne, PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Digestive Surgery, University Medical Hospital, Unité de Chirurgie Colorectale, CHU Grenoble, Unité de Méthodologie en Recherche Clinique, Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Chelsea and Westminster Hospital, Service de Chirurgie Thoracique (NICE - Chirurgie Thoracique), West University of Timisoara [Roumanie] (UVT), Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de l'Horticulture et du Paysage-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université d'Angers (UA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Université d'Angers (UA)-AGROCAMPUS OUEST, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de l'Horticulture et du Paysage
Subjects: Male, Cancer Research, medicine.medical_specialty, Neoplasms, Radiation-Induced, Esophageal Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Adenocarcinoma, Eighty Nine, Radiated field, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Breast cancer, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, Radiotherapy, business.industry, Incidence (epidemiology), Cancer, Neoplasms, Second Primary, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Chemoradiotherapy, Perioperative, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, Radiation therapy, Treatment Outcome, Editorial, Oncology, 030220 oncology & carcinogenesis, Propensity score matching, Carcinoma, Squamous Cell, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The objectives of this study were to compare peri-operative and long-term outcomes from oesophageal cancer (EC) (i) that arose in a previously radiated field (ECRF) versus primary (PEC) and among ECRF patients and (ii) radiotherapy-induced (RIEC) versus non-radiotherapy-induced EC (NRIEC).Data were collected from 30 European centres from 2000 to 2010. Two thousand four hundred eighty nine EC patients surgically treated were included in the PEC group and 136 in the ECRF group, NRIEC group (n = 61) and RIEC group (n = 75). Propensity score matching analyses were used to compensate for differences in baseline characteristics.Compared to the PEC group, the ECRF group was characterised by less use of neoadjuvant chemoradiotherapy (0% versus 29.5%; P 0.001), less pathological stage III/IV (31.6% versus 39.2%, P = 0.036), greater incidence of R1/2 margins (21.3% versus 10.9%; P 0.001), increased in-hospital mortality (14.0% versus 7.1%; P = 0.003) and overall morbidity (68.4% versus 56.4%, P = 0.006). After matching, 5-year overall (28.8% versus 50.5%; hazard ratio [HR] = 1.53, 95% confidence interval [CI]: 1.15-2.04; P = 0.003) and event-free (32.2% versus 42.5%; HR = 1.56, 95% CI: 1.18-2.05; P = 0.002) survivals were significantly reduced in the ECRF group. There were no significant differences in incidence or pattern of tumour recurrence. Comparing RIEC and NRIEC groups, there were no significant differences in short- or long-term outcomes before and after matching.ECRF is associated with poorer long-term survival related to a reduced utilisation of neoadjuvant chemoradiotherapy and an increased incidence of tumour margin involvement at surgery. Outcomes appear to be dictated by the limitations related to previous radiotherapy administration more than the radiotherapy-induced carcinogenesis.
Published: 2017

7. Fistules aorto-intestinales après remplacement prothétique de l’aorte abdominale : résultats chirurgicaux et suivi à long terme chez 32 patients

Author: Hadrien Gibert, Thibaut Schoell, Fabien Koskas, Mehdi Karoui, Jean-Christophe Vaillant, Christophe Trésallet, Laurent Chiche, Laurent Hannoun, and Julien Gaudric
Subjects: Aorta, medicine.medical_specialty, business.industry, Fistula, Stomach, Retrospective cohort study, General Medicine, Anastomosis, medicine.disease, Comorbidity, Surgery, medicine.anatomical_structure, medicine.artery, Duodenum, Medicine, business, Abdominal surgery
Abstract: Management of patients with abdominal secondary aorto-entericfistulae (SAEF) complicating aortic graft replacement is controversial. We retrospectively analyzed the postope- rative and long-term outcomes of all consecutive patients operated on for SAEF betwveen 2002 and2012. All were managed by in situ replacement with a cryopreserved allograft and treatment of the affected digestive tract. Thirty-two patients (median age 65 years) underwent aortic replacement for SAEFa median of 5 years after initial aortic surgery. The fistulae were located in the duodenum (n = 20), small bowel (n = 6), colon (n = 5) or stomach (n = 1). Treatment of the digestive tract included suture (n = 16), resection with anastomosis (n = 12) covered by a defunctioning stoma (n = 1), and Hartmann's procedure (n = 3). Omentoplasty was performed in 18 patients (56 %), and 17 patients (53 %) had afeedingjejunostomy. Eight patients (25 %) died post-operatively, 3 with a recurrent aorto-enteric fistula. Fifteen (62.5 %) of the remaining patients developed 27 complications, including 6 patients (19 %) with severe morbidity (Dindo III-IV). The reoperation rate was 21 %. The median hospital stay was 33 days. During follow-up (median 15 months), no further patients had a recurrent aorto-enteric fistula. We conclude that surgery for SAEF is a major procedure associated with high mortality and morbidity. Good long-term results can be obtained by excision of the prosthetic graft with cryopreserved allograft replacement, and by management in a tertialy referral center with expertise in both vascular and digestive surgery.
Published: 2013

8. Role of neoadjuvant treatment in clinical T2N0M0 oesophageal cancer: results from a retrospective multi-center European study

Author: Sheraz R. Markar, Caroline Gronnier, Arnaud Pasquer, Alain Duhamel, Hélène Beal, Jérémie Théreaux, Johan Gagnière, Gil Lebreton, Cécile Brigand, Bernard Meunier, Denis Collet, Christophe Mariette, Abdennahceur Dhahri, Delphine Lignier, Cyril Cossé, Jean-Marc Regimbeau, Magalie Cabau, Jacques Jougon, Bogdan Badic, Patrick Lozach, Jean Pierre Bail, Serge Cappeliez, Issam El Nakadi, Arnaud Alves, Renaud Flamein, Denis Pezet, Federica Pipitone, Bogdan Stan-Iuga, Nicolas Contival, Eric Pappalardo, Simon Msika, Styliani Mantziari, Nicolas Demartines, Flora Hec, Marguerite Vanderbeken, Williams Tessier, Nicolas Briez, Fabien Fredon, Alain Gainant, Muriel Mathonnet, Jean Marc Bigourdan, Salim Mezoughi, Christian Ducerf, Jacques Baulieux, Jean-Yves Mabrut, Oussama Baraket, Gilles Poncet, Mustapha Adham, Delphine Vaudoyer, Peggy Jourdan Enfer, Laurent Villeneuve, Olivier Glehen, Thibault Coste, Jean-Michel Fabre, Frédéric Marchal, Romain Frisoni, Ahmet Ayav, Laurent Brunaud, Laurent Bresler, Charlotte Cohen, Olivier Aze, Nicolas Venissac, Daniel Pop, Jérôme Mouroux, Ion Donici, Michel Prudhomme, Emanuele Felli, Stéphanie Lisunfui, Marie Seman, Gaelle Godiris Petit, Mehdi Karoui, Christophe Tresallet, Fabrice Ménégaux, Jean-Christophe Vaillant, Laurent Hannoun, Brice Malgras, Denis Lantuas, Karine Pautrat, Marc Pocard, Patrice Valleur, Najim Chafai, Pierre Balladur, Magalie Lefrançois, Yann Parc, François Paye, Emmanuel Tiret, Marius Nedelcu, Letizia Laface, Thierry Perniceni, Brice Gayet, Alexandre Filipello, Jack Porcheron, Olivier Tiffet, Noémie Kamlet, Rodrigue Chemaly, Amandine Klipfel, Patrick Pessaux, Cecile Brigand, Serge Rohr, Nicolas Carrère, Chiara Da Re, Frédéric Dumont, Diane Goéré, Dominique Elias, Claude Bertrand, Imperial College London, 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, Hôpital Claude Huriez [Lille], CHU 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), Service de Biostatistiques [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie Générale et Viscérale (CGV - BREST), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital de Hautepierre [Strasbourg], Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Service de chirurgie digestive, CHU Bordeaux [Bordeaux], Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), 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 de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CIC-IT Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO), Département de chirurgie digestive, CHU Clermont-Ferrand, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Unité de Chirurgie Colorectale, CHU Grenoble, Environnement Ville Société (EVS), École normale supérieure - Lyon (ENS Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Unité de Méthodologie en Recherche Clinique, Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Chelsea and Westminster Hospital, Service de Chirurgie Thoracique (NICE - Chirurgie Thoracique), Centre Hospitalier Universitaire de Nice (CHU Nice), West University of Timișoara [Roumanie] (WUT), Service de Chirurgie thoracique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Lab-STICC_UBS_CID_DECIDE, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (UMR 3192) (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastro-entérologie [APHP 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), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], 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), Laboratoire de Mathématiques Informatique et Applications (LAMIA), Université des Antilles et de la Guyane (UAG), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Department of Gastroenterological Surgery, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Mutualiste de Montsouris (IMM), Departement medico-chirurgical de pathologie digestive, Chirurgie digestive, Centre Hospitalier Universitaire de Saint-Etienne, Départment de Statistiques Bio-médicales, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de chirurgie digestive [Strasbourg-Hautepierre], Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), R&D, centre de Fresnes, Pfizer, 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), Service de biostatistiques [CHU Lille], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-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, Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Hôpital Claude Huriez, Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire Estaing, UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical (UMR PVBMT - INRA), Institut National de la Recherche Agronomique (INRA), Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hopital Louis Mourier - AP-HP [Colombes], École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS)-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 de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), West University of Timisoara [Roumanie] (UVT), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'endocrinologie-métabolisme [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), ONERA, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Environnement, Ville, Société (EVS), École normale supérieure de Lyon (ENS de Lyon)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-École Nationale des Travaux Publics de l'État (ENTPE)-École nationale supérieure d'architecture de Lyon (ENSAL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), 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-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Chirurgie Générale et Viscérale ( CGV - BREST ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Université de Brest ( UBO ), UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical ( UMR PVBMT - INRA ), Institut National de la Recherche Agronomique ( INRA ), Hôpital de la Côte de Nacre, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Ingénierie des Matériaux Polymères - Site Université Claude Bernard Lyon 1 ( IMP ), Université Claude Bernard Lyon 1 ( UCBL ), 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 ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux ( UB ), Université de Brest ( UBO ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Environnement Ville Société ( EVS ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -Université Jean Moulin - Lyon III-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 Jean Monnet [Saint-Étienne] ( UJM ) -École Nationale des Travaux Publics de l'État ( ENTPE ) -Ecole Nationale Supérieure des Mines de Saint-Etienne-École nationale supérieure d'architecture de Lyon ( ENSAL ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Centre de recherche en éducation de Nantes ( CREN ), Université de Nantes ( UN ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Université de Lorraine ( UL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Chelsea and Westminster Hospital NHS Foundation Trust, Service de Chirurgie Thoracique ( NICE - Chirurgie Thoracique ), CHU Nice, West University of Timisoara [Roumanie], West University of Timisoara, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (UMR 3192) ( Lab-STICC ), Université européenne de Bretagne ( UEB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -Université européenne de Bretagne ( UEB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance ( Lab-STICC ), École Nationale d'Ingénieurs de Brest ( ENIB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -ENSTA Bretagne-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ) -École Nationale d'Ingénieurs de Brest ( ENIB ) -ENSTA Bretagne-Centre National de la Recherche Scientifique ( CNRS ), 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)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Mathématiques Informatique et Applications ( LAMIA ), Université des Antilles et de la Guyane ( UAG ), Angiogenese et recherche translationnelle ( CART U965 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Institut Mutualiste de Montsouris ( IMM ), CHU Angers, ONERA - The French Aerospace Lab ( Chatillon ), Procédés Alimentaires et Microbiologiques [Dijon] ( PAM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté ( UBFC ), and Institut Gustave Roussy ( IGR )
Subjects: Oncology, Subset Analysis, Cancer Research, medicine.medical_specialty, Neoadjuvant treatment, Survival, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Neoadjuvant therapy, [ SDV ] Life Sciences [q-bio], business.industry, Oesophageal cancer, Carcinoma, Phase-III Trial, Cancer, Retrospective cohort study, Chemoradiotherapy, cT2N0M0, medicine.disease, Resection, 3. Good health, Postoperative Mortality, Esophagectomy, 030220 oncology & carcinogenesis, Propensity score matching, Adenocarcinoma, 030211 gastroenterology & hepatology, Surgery, Therapy, business
Abstract: International audience; Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
Published: 2016

9. Incidence and Risk Factors Related to Symptomatic Venous Thromboembolic Events After Esophagectomy for Cancer

Author: Jean-Michel Fabre, Delphine Lignier, Claude Bertrand, Xaviéra Coueffé, Brice Gayet, Marie Seman, Peggy Jourdan Enfer, Gainant A, Christophe Trésallet, Magalie Cabau, Jacques Jougon, Magalie Lefrançois, Gil Lebreton, Emmanuel Tiret, Nicolas Contival, Styliani Mantziari, Bernard Meunier, Nicolas Demartines, Flora Hec, Alexandre Filipello, Denis Lantuas, Federica Pipitone, Chiara Da Re, Renaud Flamein, François Paye, Denis Collet, Patrick Pessaux, Karine Pautrat, Jean-Marc Bigourdan, Simon Msika, Michel Prudhomme, Johan Gagnière, Jérémie Thereaux, Mehdi Karoui, Patrice Valleur, Diane Goéré, Yann Parc, Mael Chalret du Rieu, Jean-Pierre Bail, Jacques Baulieux, Denis Pezet, Stéphanie Lisunfui, Williams Tessier, Laurent Brunaud, Ion Donici, Marguerite Vanderbeken, Fabien Fredon, N. Chafai, Gilles Poncet, Charlotte Cohen, Jérémie H. Lefevre, Guillaume Luc, Letizia Laface, Serge Rohr, Frédéric Dumont, Jean-Marc Regimbeau, Oussama Baraket, R Frisoni, Serge Cappeliez, Issam El Nakadi, Eric Pappalardo, Marius Nedelcu, Thibault Coste, Marc Pocard, Cécile Brigand, N. Briez, Patrick Lozach, Amandine Klipfel, Gaelle Godiris Petit, Olivier Tiffet, Daniel Pop, Arnaud Alves, Jack Porcheron, Christophe Mariette, Delphine Vaudoyer, Arnaud Pasquer, Frédéric Marchal, Bogdan Stan-Iuga, Thierry Perniceni, Nicolas Carrere, Laurent Villeneuve, Jean-Christophe Vaillant, Caroline Gronnier, Olivier Glehen, B. Malgras, Muriel Mathonnet, Nicolas Venissac, Pierre Balladur, Markus Schäfer, Noémie Kamlet, Olivier Aze, Laurent Bresler, C. Ducerf, Jérôme Mouroux, Dominique Elias, Cyril Cosse, Bogdan Badic, Salim Mezoughi, Jean-Yves Mabrut, Emanuele Felli, Abdennahceur Dhahri, Fabrice Menegaux, Laurent Hannoun, Kathleen Turner, Ahmet Ayav, Mustapha Adam, Rodrigue Chemaly, 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, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service de Chirurgie Générale et Viscérale (CGV - BREST), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne, PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CIC-IT Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO), Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Département de chirurgie digestive, CHU Clermont-Ferrand, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Montreal Heart Institute, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de recherche en éducation de Nantes (CREN), Le Mans Université (UM)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Thoracique (NICE - Chirurgie Thoracique), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU), Babes-Bolyai University [Cluj-Napoca] (UBB), Service de Chirurgie thoracique, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Lab-STICC_UBS_CID_DECIDE, Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (UMR 3192) (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Mathématiques Informatique et Applications (LAMIA), Université des Antilles et de la Guyane (UAG), Université des Antilles (Pôle Guadeloupe), Université des Antilles (UA), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Association Pro Pictura Antiqua (APPA-CEPMR), Ville de Soissons, CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Hubert Curien (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Mutualiste de Montsouris (IMM), Departement medico-chirurgical de pathologie digestive, Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Strasbourg, Laboratoire brestois de mécanique et des systèmes (LBMS), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne), Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), Chercheur indépendant, Hospices Civils de Lyon (HCL), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Universitaire Estaing, Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), UMR Peuplement Végétaux et Bioagresseurs en Milieu Tropical (UMR PVBMT - INRA), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hopital Louis Mourier - AP-HP [Colombes], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), equipe 4, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), 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)-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), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université européenne de Bretagne - European University of Brittany (UEB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université européenne de Bretagne - European University of Brittany (UEB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École Nationale d'Ingénieurs de Brest (ENIB)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de chirurgie générale viscérale et endocrinienne [CHU Pitié-Sapêtrière], Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne, 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, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Edouard Herriot [CHU - HCL], École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], 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 Chirurgie Générale, Viscérale et Endocrinienne [CHU Pitié-Sapêtrière], Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN)-Le Mans Université (UM), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Service de Chirurgie Hépatobiliaire et Digestive [Rennes], FREGAT Working Group-FRENCH-AFC, Dhahri, A., Lignier, D., Cossé, C., Regimbeau, J.M., Luc, G., Collet, D., Cabau, M., Jougon, J., Badic, B., Lozach, P., Bail, J.P., Cappeliez, S., El Nakadi, I., Lebreton, G., Alves, A., Flamein, R., Pezet, D., Pipitone, F., Stan-Iuga, B., Coueffé, X., Contival, N., Pappalardo, E., Msika, S., Hec, F., Vanderbeken, M., Tessier, W., Briez, N., Fredon, F., Gainant, A., Mathonnet, M., Bigourdan, J.M., Mezoughi, S., Ducerf, C., Baulieux, J., Mabrut, J.Y., Pasquer, A., Baraket, O., Poncet, G., Adam, M., Vaudoyer, D., Enfer, P.J., Villeneuve, L., Glehen, O., Coste, T., Fabre, J.M., Marchal, F., Frisoni, R., Ayav, A., Brunaud, L., Bresler, L., Cohen, C., Aze, O., Venissac, N., Pop, D., Mouroux, J., Donici, I., Prudhomme, M., Felli, E., Lisunfui, S., Seman, M., Petit, G.G., Karoui, M., Tresallet, C., Ménégaux, F., Vaillant, J.C., Hannoun, L., Malgras, B., Lantuas, D., Pautrat, K., Pocard, M., Valleur, P., Lefevre, J., Chafai, N., Balladur, P., Lefranéois, M., Parc, Y., Paye, F., Tiret, E., Nedelcu, M., Laface, L., Perniceni, T., Gayet, B., Turner, K., Meunier, B., Filipello, A., Porcheron, J., Tiffet, O., Kamlet, N., Chemaly, R., Klipfel, A., Pessaux, P., Brigand, C., Rohr, S., Chalret du Rieu, M., Carrére, N., Da Re, C., Dumont, F., Goéré, D., Elias, D., and Bertrand, C.
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, ARDS, medicine.medical_specialty, Esophageal Neoplasms, medicine.drug_class, medicine.medical_treatment, Low molecular weight heparin, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030204 cardiovascular system & hematology, Aged, Aged, 80 and over, Esophageal Neoplasms/surgery, Esophagectomy/adverse effects, Female, Hospital Mortality, Humans, Incidence, Length of Stay, Middle Aged, Postoperative Complications/etiology, Risk Factors, Venous Thromboembolism/epidemiology, Venous Thromboembolism/etiology, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Internal medicine, Medicine, cardiovascular diseases, ComputingMilieux_MISCELLANEOUS, business.industry, Incidence (epidemiology), Cancer, Venous Thromboembolism, Esophageal cancer, equipment and supplies, medicine.disease, 3. Good health, Pulmonary embolism, Surgery, Esophagectomy, Venous thrombosis, 030220 oncology & carcinogenesis, Cardiology and Cardiovascular Medicine, business
Abstract: Background Major oncologic surgery is associated with a high incidence of venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE). However, the incidence and risk factors for symptomatic VTE during curative treatment for patients with esophageal cancer are poorly documented. Methods Data were collected from 30 European centers from 2000 to 2010. The incidence of in-hospital VTE was assessed in 2,944 patients with esophageal cancer having surgery with curative intent, and 50 clinically relevant parameters were assessed as potential risk factors for VTE. Patients received low molecular weight heparin prophylaxis during hospital stay and for 4 weeks after surgery. Results Eighty-four patients (2.9%) developed a symptomatic VTE; all of them had a DVT and 44 were also diagnosed with a PE. In the VTE group there were 19 postoperative deaths recorded, 5 of which (26.3%) were directly caused by PE at postoperative days 7, 10, 21, 45, and 48 despite VTE prophylaxis. In-hospital postoperative mortality was significantly higher in VTE patients (23% versus 7%, p 0.001) and mean hospital stay was also longer in this group (33 ± 24 versus 25 ± 21 days, p 0.001). Multivariable analysis showed that high American Society of Anesthesiologists (ASA) class ( p = 0.008), pneumopathy ( p = 0.002), or an acute respiratory distress syndrome (ARDS) ( p = 0.015) were significantly associated with VTE. Conclusions Patients with ASA class III or IV and those who present a postoperative pneumopathy or ARDS seem to be at higher risk for VTE. Thus, current VTE screening and thromboprophylaxis for these patients might be inadequate and needs further investigation.
Published: 2016

10. Thrombocytopenia, splenomegaly, and portal blood flow in patients who have undergone liver transplantation for cirrhosis

Author: Laurent Hannoun, Silvia Fratéa, Christian Ionescu, Pierre Coriat, Jean-Michel Siksik, Sabine Darnat, Benjamin Granger, Daniel Eyraud, and Jean-Christophe Vaillant
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Liver transplantation, Gastroenterology, Internal medicine, medicine, Humans, Platelet, Aged, Transplantation, Hepatology, Platelet Count, Portal Vein, business.industry, Hepatitis C, Perioperative, Middle Aged, medicine.disease, Thrombocytopenia, Liver Transplantation, Surgery, surgical procedures, operative, Regional Blood Flow, Splenomegaly, Portal blood, Portal hypertension, Female, business
Abstract: The platelet count (PC), the spleen size (SS), and the portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT) for cirrhosis, but these parameters have not been described and analyzed in combination. We analyzed PC data and Doppler sonography measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used. PCs increased significantly from 101.5 ± 68.5 × 10(9) /L before OLT to 162.4 ± 86 × 10(9) /L 1 month after OLT and remained stable for 1 year after the operation. PBF increased significantly from 619 ± 239 mL/minute before OLT to 1379 ± 491 mL/minute after OLT and remained stable during the first year. SS slowly decreased after OLT, but the decrease became significant only 9 months after the operation (13.8 ± 4.2 cm before OLT versus 11.7 ± 3.7 cm at 9 months, P < 0.05). The cirrhosis etiology did not influence the evolution of the parameters. With or without replication or interferon treatment before OLT, the hepatitis C group viruses did not influence PCs postoperatively. The evolution of SS was correlated to the evolution of PCs in the year after transplantation. In conclusion, PCs and PBF increase rapidly after OLT, whereas SS slowly decreases. The cirrhosis etiology does not influence the evolution of PCs. Thrombocytopenia and splenomegaly are 2 results of portal hypertension, but the rapid normalization of PBF does not completely or rapidly reverse these 2 phenomena.
Published: 2012

11. Vascular exclusion of the liver

Author: Laurent Hannoun, Eric Savier, and Jean-Michel Siksik
Subjects: Text mining, Liver, business.industry, Hepatectomy, Humans, Medicine, Vena Cava, Inferior, General Medicine, Hepatic Veins, business, Bioinformatics, Hemostasis, Surgical
Published: 2011

12. Variant on Manifestation of Duodenal Metastasis 26 Years after Initial Diagnosis of Primary Cutaneous Melanoma

Author: Sylvie Breton, Jean-Christophe Vaillant, G. Rousseau, Laurent Hannoun, Kumiko Kitajima, Jean-Michel Siksik, and Armelle Bardier-Dupas
Subjects: Metastatic duodenal tumor, Amelanotic melanoma, Pathology, medicine.medical_specialty, Malignant melanoma, business.industry, Melanoma, Gastroenterology, Published: March 2010, Cheek, medicine.disease, Primary Neoplasm, Nonampullary duodenal neoplasm, medicine.anatomical_structure, Cutaneous melanoma, Duodenum, medicine, lcsh:Diseases of the digestive system. Gastroenterology, Medical history, lcsh:RC799-869, business, Duodenal Neoplasm
Abstract: Malignant duodenal neoplasms are relatively rare, and the diagnosis is often delayed because of their vague and nonspecific symptoms. We report the case of a 79-year-old female who had a medical history of malignant melanoma of the cheek that had initially been diagnosed at 53 years of age. Work-up revealed severe stenosis of the duodenum caused by a large mass with ulceration at the tip of its mucosal surface. Tumor biopsy led to a histological diagnosis of extremely poorly differentiated carcinoma, but it was impossible to determine whether the lesion was a primary neoplasm or represented secondary involvement. Pancreatoduodenectomy was performed, and the surgical specimen showed a protuberant tumor in the nonampullary region of the second portion of the duodenum. Final diagnosis of metastatic duodenal melanoma was made by immunohistological examination. She is currently alive without recurrence 28 months after the surgical treatment.
Published: 2010

13. Patients with acute liver failure listed for superurgent liver transplantation in France: Reevaluation of the clichy-villejuif criteria

Author: Bertrand Suc, Teresa Antonini, Philippe Ichai, François-René Pruvot, Olivier Boillot, Christian Ducerf, Christian Letoublon, Jean Gugenheim, Olivier Soubrane, Didier Samuel, Philippe Mathurin, Laurent Hannoun, Jean Saric, Daniel Cherqui, Christian Jacquelinet, Denis Castaing, Armand Abergel, Vincent Di Martino, Philippe Wolf, Claire Francoz, Yves Patrice Le Treut, Karim Boudjema, Laurence Chiche, Georges-Philippe Pageaux, Camille Legeai, Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Digestive Surgery and Transplantation, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chirurgie Générale et Digestive [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Chirurgie Générale et Transplantation Multi Organes, CHU Strasbourg, Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Chirurgie, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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 Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Digestif, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital de l'Archet, Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Service de chirurgie digestive, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Département de Chirurgie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Direction Médicale et Scientifique, Agence de la biomédecine [Saint-Denis la Plaine], Service de chirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), 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), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: medicine.medical_specialty, Time Factors, Waiting Lists, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Renal function, Kaplan-Meier Estimate, Liver transplantation, Risk Assessment, Severity of Illness Index, Gastroenterology, Decision Support Techniques, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Interquartile range, Internal medicine, Odds Ratio, medicine, Humans, Survival rate, Hepatic encephalopathy, Acetaminophen, Transplantation, Creatinine, Chi-Square Distribution, Hepatology, business.industry, Patient Selection, digestive, oral, and skin physiology, Odds ratio, Liver Failure, Acute, medicine.disease, Liver Transplantation, Surgery, Logistic Models, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Multivariate Analysis, 030211 gastroenterology & hepatology, France, Chemical and Drug Induced Liver Injury, Emergencies, business
Abstract: International audience; In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non–paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance ≥ 60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level \textless 200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level \textgreater 20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level \textless 200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non–paracetamol-induced ALF were split and 2 other items were included in this model: the bilirubin level and creatinine clearance. Liver Transpl 21:512-523, 2015. © 2015 AASLD.
Published: 2015

14. Measurement of Indoleamine 2, 3 Dioxygenase Activity in Colorectal Cancer: A Controlled Group Study

Author: Gaëlle Gottr, Armelle Bardier, Laurent Hannoun, Daniel Eyraud, Frédéric Charlotte, Audrey Perez-Lascar, Louis Lemoine, David Klatzmann, Noël Zahr, Benjamin Granger, Mehdi Karoui, Pierre Coriat, Jean-Christophe Vaillant, Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], 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), Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Sorbonne Université - Faculté de médecine Pitié Salpétrière, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, Immune system, Internal medicine, medicine, Serum concentration, Indoleamine 2,3-dioxygenase, chemistry.chemical_classification, business.industry, Kynurénine, Tryptophan, Biomarker, medicine.disease, digestive system diseases, 3. Good health, Enzyme, Endocrinology, chemistry, Indoleamine 2,3, Immunology, dioxygenase activity, Biomarker (medicine), [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Kynurenine
Abstract: International audience; Background: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan (Trp) to kynurenine (Kyn), suppresses antitumor immune responses via depletion of Trp and accumulation of Kyn. We hypothesized that, in colorectal cancer (CRC), IDO activity may serve as a biomarker and thus we compared the IDO activity between patients with CRC and those without CRC. We further assessed the effect of surgical treatment of CRC on IDO activity.Methods: Serum concentrations of Trp and Kyn were measured by high performance liquid chromatography in the sera of 68 patients with CRC (CRC group) and 38 without CRC (Control group) prior surgery (D0) and 7 days after surgery (D7). The IDO activity was estimated by the serum Kyn-to-Trp ratio (Kyn/Trp ratio).Results: At Day 0, serum Kyn concentration was higher in the CRC group than in Control group (1.7 [1.4;2.1] μM vs 1.25 [0.9;1.78] μM, respectively; p=0.004) while no difference in serum concentration of Trp was observed between the two groups. Kyn/Trp ratio (IDO activity) was significantly higher in the CRC group than in Control group. At Day 7 serum concentrations of Trp, Kyn and the Kyn/Trp ratio were not statistically different between the two groups.Conclusion: This study indicates that IDO activity is higher in patients with CRC compared with those without CRC. Surgical treatment impacts the IDO activity with a similar Kyn/Trp ratio in both groups. This study is the first step to larger studies to establish the Kyn/Trp ratio as a reliable serum marker of CRC.
Published: 2015

15. [Abdominal secondary aorto-enteric fistulae complicating aortic graft replacement: postoperative and long-term outcomes in 32 patients]

Author: Jean-christophe, Vaillant, Thibaut, Schoell, Mehdi, Karoui, Laurent, Chiche, Julien, Gaudric, Hadrien, Gibert, Christophe, Tresallet, Fabien, Koskas, and Laurent, Hannoun
Subjects: Adult, Aged, 80 and over, Male, Fistula, Multiple Organ Failure, Suture Techniques, Aortic Diseases, Comorbidity, Length of Stay, Middle Aged, Allografts, Shock, Septic, Blood Vessel Prosthesis Implantation, Postoperative Complications, Treatment Outcome, Intestinal Fistula, Humans, Female, Aorta, Abdominal, Gastrointestinal Hemorrhage, Digestive System Surgical Procedures, Aged, Retrospective Studies
Abstract: Management of patients with abdominal secondary aorto-entericfistulae (SAEF) complicating aortic graft replacement is controversial. We retrospectively analyzed the postope- rative and long-term outcomes of all consecutive patients operated on for SAEF betwveen 2002 and2012. All were managed by in situ replacement with a cryopreserved allograft and treatment of the affected digestive tract. Thirty-two patients (median age 65 years) underwent aortic replacement for SAEFa median of 5 years after initial aortic surgery. The fistulae were located in the duodenum (n = 20), small bowel (n = 6), colon (n = 5) or stomach (n = 1). Treatment of the digestive tract included suture (n = 16), resection with anastomosis (n = 12) covered by a defunctioning stoma (n = 1), and Hartmann's procedure (n = 3). Omentoplasty was performed in 18 patients (56 %), and 17 patients (53 %) had afeedingjejunostomy. Eight patients (25 %) died post-operatively, 3 with a recurrent aorto-enteric fistula. Fifteen (62.5 %) of the remaining patients developed 27 complications, including 6 patients (19 %) with severe morbidity (Dindo III-IV). The reoperation rate was 21 %. The median hospital stay was 33 days. During follow-up (median 15 months), no further patients had a recurrent aorto-enteric fistula. We conclude that surgery for SAEF is a major procedure associated with high mortality and morbidity. Good long-term results can be obtained by excision of the prosthetic graft with cryopreserved allograft replacement, and by management in a tertialy referral center with expertise in both vascular and digestive surgery.
Published: 2014

16. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study

Author: Houry S, C. Louvet, F. Maindrault-Goebel, François Paye, Brice Gayet, A. de Gramont, Olivier Rosmorduc, D. Avenin, Frédéric Selle, Laurent Hannoun, Christophe Tournigand, S. Provent, Thierry André, and J. P. Lotz
Subjects: Adult, Male, medicine.medical_specialty, Lung Neoplasms, Neutropenia, Organoplatinum Compounds, Vomiting, Intrahepatic bile ducts, GemOx, Adenocarcinoma, Deoxycytidine, Gastroenterology, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Survival rate, Aged, business.industry, Gallbladder, Liver Neoplasms, Anemia, Nausea, Hematology, Middle Aged, medicine.disease, Thrombocytopenia, Gemcitabine, Oxaliplatin, Survival Rate, Biliary Tract Neoplasms, Treatment Outcome, medicine.anatomical_structure, Oncology, Biliary tract, Female, business, Progressive disease, medicine.drug
Abstract: Since gemcitabine-oxaliplatin (GEMOX) has been used in pancreatic adenocarcinoma, we studied its activity and tolerability in advanced biliary tract adenocarcinoma (ABTA).Consecutive adult patients with confirmed ABTA were recruited from four centers. Those in group A had performance status (PS) 0-2, bilirubin2.5x normal and received GEMOX as first-line chemotherapy. Those in group B had PS2 and/or bilirubin2.5x normal and/or prior chemotherapy. All received gemcitabine 1000 mg/m2 as a 10 mg/m2/min infusion on day 1, followed by oxaliplatin 100 mg/m2 as a 2-h infusion on day 2, every 2 weeks.Tumor sites were gallbladder (19), extrahepatic bile ducts (5), ampulla of vater (3) and intrahepatic bile ducts (29). Results for group A (n = 3) were: objective response 36% [95% confidence interval (CI) 18.7% to 52.3%], stable disease 26%, progressive disease 39%, median progression-free survival (PFS) 5.7 months and overall survival (OS) 15.4 months. Results for group B (n = 23) were: objective response 22% (95% CI 6.5% to 37.4%), stable disease 30%, progressive disease 48%, PFS 3.9 months and OS 7.6 months. National Cancer Institute Common Toxicity Criteria grade 3-4 toxicities were neutropenia 14% of patients, thrombocytopenia 9%, nausea/vomiting 5% and peripheral neuropathy 7%.The GEMOX combination is active and well tolerated in ABTA.
Published: 2004

17. Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures

Author: Jean-François Franetich, Audrey Lorthiois, Laurent Hannoun, Artur Scherf, Matthew J. Fuchter, Roger Le Grand, Thierry T. Diagana, Nicholas A. Malmquist, Jean-Christophe Vaillant, Dominique Mazier, Anne-Marie Zeeman, Geert-Jan van Gemert, Georges Snounou, Audrey Gego, Nathalie Dereuddre-Bosquet, Clemens H. M. Kocken, Robert W. Sauerwein, and Laurent Dembele
Subjects: Male, Time Factors, Primaquine, Green Fluorescent Proteins, Plasmodium vivax, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], General Biochemistry, Genetics and Molecular Biology, Cell Line, Epigenesis, Genetic, Persistence (computer science), Histones, Mice, 03 medical and health sciences, Recurrence, parasitic diseases, medicine, Animals, Humans, Epigenetics, Cells, Cultured, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, biology, 030306 microbiology, Histone-Lysine N-Methyltransferase, General Medicine, biology.organism_classification, Plasmodium ovale, medicine.disease, Malaria, 3. Good health, medicine.anatomical_structure, Microscopy, Fluorescence, Sporozoites, Hepatocyte, Histone methyltransferase, Immunology, Hepatocytes, Histone Methyltransferases, Macaca, Female, Plasmodium cynomolgi, medicine.drug
Abstract: Malaria relapses, resulting from the activation of quiescent hepatic hypnozoites of Plasmodium vivax and Plasmodium ovale, hinder global efforts to control and eliminate malaria. As primaquine, the only drug capable of eliminating hypnozoites, is unsuitable for mass administration, an alternative drug is needed urgently. Currently, analyses of hypnozoites, including screening of compounds that would eliminate them, can only be made using common macaque models, principally Macaca rhesus and Macaca fascicularis, experimentally infected with the relapsing Plasmodium cynomolgi. Here, we present a protocol for long-term in vitro cultivation of P. cynomolgi-infected M. fascicularis primary hepatocytes during which hypnozoites persist and activate to resume normal development. In a proof-of-concept experiment, we obtained evidence that exposure to an inhibitor of histone modification enzymes implicated in epigenetic control of gene expression induces an accelerated rate of hypnozoite activation. The protocol presented may further enable investigations of hypnozoite biology and the search for compounds that kill hypnozoites or disrupt their quiescence.
Published: 2014

18. Expansion of CMV-mediated NKG2C+ NK cells associates with the development of specific de novo malignancies in liver-transplanted patients

Author: Vincent Vieillard, Patrice Debré, Laurent Hannoun, Didier Samuel, Florence Baychelier, Abla Achour, Armelle Arnoux, Michel Marty, and Caroline Besson
Subjects: Adult, Male, medicine.medical_treatment, T cell, Immunology, Cytomegalovirus, Biology, Immunophenotyping, Young Adult, Antigen, Risk Factors, Cell Line, Tumor, Neoplasms, medicine, Immunology and Allergy, Cluster Analysis, Humans, Aged, Innate immune system, Immunosuppression, Middle Aged, Liver Transplantation, Transplantation, Killer Cells, Natural, Cytokine, medicine.anatomical_structure, Phenotype, Antigens, Surface, Cytomegalovirus Infections, Cytokines, Female, NK Cell Lectin-Like Receptor Subfamily C
Abstract: Solid cancers are a major adverse outcome of orthotopic liver transplantation (OLT). Although the use of chronic immunosuppression is known to play a role in T cell impairment, recent insights into the specificities of NK cells led us to reassess the potential modulation of this innate immune cell compartment after transplantation. Our extensive phenotypic and functional study reveals that the development of specific de novo noncutaneous tumors post-OLT is linked to unusual NK cell subsets with maturation defects and to uncommon cytokine production associated with the development of specific cancers. Remarkably, in CMV+ patients, the development de novo head/neck or colorectal tumors is linked to an aberrant expansion of NK cells expressing NKG2C and a high level of intracellular TNF-α, which impact on their polyfunctional capacities. In contrast, NK cells from patients diagnosed with genitourinary tumors possessed a standard immature signature, including high expression of NKG2A and a robust production of IFN-γ. Taken together, our results suggest that under an immunosuppressive environment, the interplay between the modulation of NK repertoire and CMV status may greatly hamper the spectrum of immune surveillance and thus favor outgrowth and the development of specific de novo tumors after OLT.
Published: 2013

19. Microbiological Hazards Related to Xenotransplantation of Porcine Organs into Man

Author: Donald V. Cramer, Jean-Christophe Vaillant, Dominic C. Borie, Laurent Hannoun, Jean Louis Bequet, Luu Phan-Thanh, and Leonard Makowka
Subjects: Microbiology (medical), medicine.medical_specialty, Swine, Epidemiology, Xenotransplantation, medicine.medical_treatment, Bovine spongiform encephalopathy, Transplantation, Heterologous, Population, Biology, Diagnostic tools, Communicable Diseases, 03 medical and health sciences, Zoonoses, medicine, Animals, Humans, Intensive care medicine, education, 030304 developmental biology, Swine Diseases, education.field_of_study, 0303 health sciences, Transmission (medicine), 030306 microbiology, medicine.disease, 3. Good health, Clinical trial, Transplantation, Infectious Diseases, Communicable disease transmission, Immunology
Abstract: Pigs are emerging as the most likely providers of genetically engineered organs and cells for the purpose of clinical xenotransplantation. Introduction of clinical trials has been delayed primarily by uncertainties regarding the risk of swine pathogen transmission that could harm the recipient. The concern that xenotransplantation carries the potential for a new epidemic has been highlighted by recent experiences with both bovine spongiform encephalopathy and human immunodeficiency diseases. As clinical trials have been postponed and xenotransplantation teams are working actively to gather data for an estimation of the risk, this review provides the reader with a state-of-the-art estimation of the microbiological hazards related to xenotransplantation of porcine organs to man. Particular emphasis is put on viral and retroviral hazards. Both current diagnostic tools and those under development are described, along with breeding strategies to provide donor animals that would not put the recipient or the general population at risk.
Published: 1998

20. Primary tumor resection in colorectal cancer with unresectable synchronous metastases: A review

Author: Reza Kianmanesh, Jean-Baptiste Bachet, Cindy Neuzillet, Mehdi Karoui, Jean-Christophe Vaillant, Laurent Hannoun, Gilles Manceau, Olivier Bouché, Louis de Mestier, and Jean Philippe Spano
Subjects: Oncology, medicine.medical_specialty, Chemotherapy, Colorectal cancer, business.industry, medicine.medical_treatment, Gastroenterology, Review, medicine.disease, Primary tumor, Asymptomatic, Colorectal surgery, Surgery, Resection, law.invention, Randomized controlled trial, Quality of life, law, Internal medicine, medicine, medicine.symptom, business
Abstract: At the time of diagnosis, 25% of patients with colorectal cancer (CRC) present with synchronous metastases, which are unresectable in the majority of patients. Whether primary tumor resection (PTR) followed by chemotherapy or immediate chemotherapy without PTR is the best therapeutic option in patients with asymptomatic CRC and unresectable metastases is a major issue, although unanswered to date. The aim of this study was to review all published data on whether PTR should be performed in patients with CRC and unresectable synchronous metastases. All aspects of the management of CRC were taken into account, especially prognostic factors in patients with CRC and unresectable metastases. The impact of PTR on survival and quality of life were reviewed, in addition to the characteristics of patients that could benefit from PTR and the possible underlying mechanisms. The risks of both approaches are reported. As no randomized study has been performed to date, we finally discussed how a therapeutic strategy’s trial should be designed to provide answer to this issue.
Published: 2013

21. Malignant Intrahepatic Biliary Papillomatosis Associated With Viral C Cirrhosis

Author: Jean-François Fléjou, Najat Mourra, Laurent Hannoun, Rolland Parc, and Geraldine Rousvoal
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Pathology, Lung Neoplasms, Cirrhosis, Caroli disease, Intrahepatic bile ducts, Hepacivirus, Papillomatosis, Adenocarcinoma, Gastroenterology, Pathology and Forensic Medicine, Malignant transformation, Adenoma, Bile Duct, Fatal Outcome, Internal medicine, medicine, Humans, Choledochal cysts, Aged, Hepatitis, Papilloma, business.industry, General Medicine, medicine.disease, Hepatitis C, Medical Laboratory Technology, Bile Ducts, Intrahepatic, Biliary Tract Neoplasms, Biliary tract, medicine.symptom, business
Abstract: Biliary papillomatosis is a rare entity characterized by multiple papillary adenomas involving extensive areas of the biliary tract with a great potential for recurrence and malignant transformation. It has been reported in association with Caroli disease and a choledochal cyst. We report herein a case of malignant intrahepatic biliary papillomatosis associated with cirrhosis secondary to hepatitis C. To the best of our knowledge, this is the first report of this association.
Published: 2002

22. Antiviral activity of Bay 41-4109 on hepatitis B virus in humanized Alb-uPA/SCID mice

Author: Eric Giang, Jacques Belghiti, Serban Morosan, Sophie Berissi, Céline Lamant, Johan Neyts, Eva Wimmer, Gherard Puerstinger, Patrick Soussan, Lucie DaSilva, Olivier Hantz, Marie-Noëlle Brunelle, Laurent Hannoun, Dina Kremsdorf, Hélène Massinet, Nicolas Brezillon, IFR Laennec (IL), Institut National de la Recherche Agronomique (INRA)-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), neuroscience and barin technology, Service de chirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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), Department of Microbiology and Immunology, Rega Institute for Medical Research, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), equipe 16, Physiopathologie moléculaire et nouveaux traitements des hépatites virales, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM)-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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogenèse Hépatique et Virologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénèse des Hépatites Virales B et Immunothérapie (UMR_S 812), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR Laennec ( IL ), Institut National de la Recherche Agronomique ( INRA ) -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)-Hôpital Beaujon, Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Catholic University of Leuven ( KU Leuven ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -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 ) -Centre Léon Bérard [Lyon]-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 ), Pathogénèse des Hépatites Virales B et Immunothérapie ( UMR_S 812 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université de Lyon-Université de Lyon-IFR62-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Cancérologie de Lyon (CRCL), and 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)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Mouse, Pyridines, Gastroenterology and hepatology, Biopsy, medicine.medical_treatment, MESH : Immunohistochemistry, MESH : Pyrimidines, MESH : Hepatitis B virus, MESH : Viral Load, Mice, SCID, MESH : Hepatocytes, Liver transplantation, medicine.disease_cause, Hepatitis, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hepatocytes, Mice, MESH: Biopsy, 0302 clinical medicine, MESH : Albumins, MESH: Animals, MESH : DNA, Viral, MESH: Mice, SCID, 0303 health sciences, Multidisciplinary, MESH: Kinetics, virus diseases, Animal Models, Viral Load, Hepatitis B, Antivirals, Immunohistochemistry, 3. Good health, MESH : Antiviral Agents, Infectious hepatitis, MESH: Hepatitis B virus, Real-time polymerase chain reaction, Liver, Capsid, 030220 oncology & carcinogenesis, Infectious diseases, Medicine, MESH : Kinetics, MESH: Viral Load, Viral load, Research Article, MESH: Antiviral Agents, Hepatitis B virus, MESH : Pyridines, Science, Alpha interferon, Viremia, [SDV.CAN]Life Sciences [q-bio]/Cancer, Viral diseases, Biology, Antiviral Agents, Microbiology, 03 medical and health sciences, Model Organisms, Albumins, Virology, MESH : Mice, medicine, Animals, Humans, MESH: Mice, Liver diseases, 030304 developmental biology, MESH: Humans, MESH: Hepatitis B, MESH : Humans, MESH: Pyridines, MESH : Liver, MESH : Hepatitis B, MESH: Immunohistochemistry, medicine.disease, MESH : Mice, SCID, digestive system diseases, MESH: DNA, Viral, Kinetics, Animal Models of Infection, Pyrimidines, Viral replication, MESH : Biopsy, MESH: Pyrimidines, DNA, Viral, Immunology, Hepatocytes, MESH : Animals, MESH: Albumins, MESH: Liver
Abstract: International audience; Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC(50) of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy.
Published: 2011

23. Liver resection with normothermic ischaemia exceeding 1 h

Author: Borie D, Jean-Christophe Vaillant, D. Jones, E. Delva, Rolland Parc, Nordlinger B, and Laurent Hannoun
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Blood transfusion, Portal triad, Pleural effusion, medicine.medical_treatment, Blood Loss, Surgical, Ischemia, Vascular occlusion, Asymptomatic, Body Temperature, Postoperative Complications, medicine, Humans, Blood Transfusion, Aged, Retrospective Studies, Proaccelerin, business.industry, Middle Aged, medicine.disease, Constriction, Hemostasis, Surgical, Surgery, medicine.anatomical_structure, Liver, Anesthesia, Hemostasis, Female, medicine.symptom, business, Liver Circulation
Abstract: A retrospective study was made of 34 patients who underwent major liver resection with a single period of vascular occlusion exceeding 60 min. The liver remnant was normal in all cases. Vascular occlusion was achieved by continuous portal trial clamping (15 patients), hepatic vascular exclusion (15) or a sequential combination of both procedures (four). Liver cooling was not used. The mean(s.e.m.) duration of continuous normothermic liver ischaemia was 73·6(2·5) (range 60–127) min. The mean(s.e.m.) amount of blood transfused during operation was 5·3(0·8) units packed red cells. There were no deaths after surgery and the postoperative course was uneventful, or limited to asymptomatic pleural effusion, in 18 patients. Three patients suffered postoperative bleeding necessitating further surgery and one of these required reintervention for a prolonged bile leak. Four patients had transient liver failure that resolved spontaneously within 15 days. There was a 13-fold increase in serum transaminase activities and the proaccelerin level was 45 per cent that of normal on day 1 after operation. These changes were returning to normal levels within 15 days. Continuous vascular occlusion during major liver resection is a useful manoeuvre that may be performed safely on normal hepatic parenchyma for up to 90 min.
Published: 1993

24. 5-Fluorourcil combined with the [6S]-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma

Author: J. Richaud, E. Goldschmidt, Thierry André, Laurent Hannoun, A. Sezeur, X. Grison, S. Mauban, M. Bardon, V. Izrael, R. Parc, T. Guillot, D. Machover, G Metzger, R. Salmon, J. P. Lotz, J Zittoun, and J. Marquet
Subjects: medicine.medical_specialty, Chemotherapy, biology, business.industry, medicine.medical_treatment, Hematology, Thymidylate synthase, Gastroenterology, Chemotherapy regimen, Surgery, Folinic acid, Regimen, Oncology, Pharmacokinetics, Fluorouracil, Internal medicine, Concomitant, medicine, biology.protein, business, medicine.drug
Abstract: Summary Background Potentiation of the antitumor activity of 5-fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase (TS), fluorodeoxyuridylate (FdUMP), and methylene tetrahydrofolate (5,10-CH2-FH4), which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C6 carbon of the pteridine ring. Only the levorotatory [6S]-folinic acid is transformed into active folate cofactors. However, the [6R]-stereoisomer is not inert; it was shown to interfere with the [6S] form at the cellular level. The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out 2 consecutive phase I-II studies of 5-FU combined with the [6S]-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. Patients and methods Treatment comprised 5-FU by i.v. infusion for 2 hours (the initial dose was 350 mg/m2/d; it was incremented by 25 mg/m2/d until a maximal dose of 550 mg/m2/d) and [6S]-folinic acid (100 mg/m2/d by rapid i.v. injection in Regimen 1, and 100 mg/m2 by rapid i.v. injection followed by a 2-hour infusion of 250 mg/m2 in Regimen 2) for 5 days, every 21 days. Twenty-five pts and 27 pts were assessed in Regimen 1 and in Regimen 2, respectively. They had had no prior chemotherapy. The median follow-up time was 9 months and 15.5 months for patients treated with Regimen 1 and Regimen 2, respectively. For pts treated with Regimen 1, the response rate was 52% (CR, 12%; PR, 40%). The median time to disease progression was 9.2 months. The probability of survival at 12 months was 73%. For pts treated with Regimen 2, the response rate was 37% (CR, 7%; PR, 30%). The median time to disease progression was 8.9 months. The probability of survival at 12 months was 67%. Improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects (WHO grades ≥ 3) were diarrhea, dermatitis, and mucositis. One single episode of grade 4 diarrhea occurred. After injection according to the schema in Regimen 1, [6S]-folinic acid was rapidly cleared from plasma (mean t 1/2 a and t ½ α and t ½ β of 7.2 and 126 minutes, respectively). The mean concentration of the [6S]-stereoisomer two hours after injection was 5.8 mmol/L. After a rapid i.v. injection of 100 mg/m2 followed by a 2-hour infusion of 250 mg/m2, the mean concentration of [6S]-folinic acid two hours after the injection was 57.5 mmol/L. Pharmacokinetic data suggests saturation of the metabolic conversion of [6S]-foli-nic acid when large doses are administered. Conclusions The [6S]-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. However, increase of the daily dose of the folate did not result in a therapeutic improvement. The present results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.
Published: 1993

25. Influence of geriatric consultation with comprehensive geriatric assessment on final therapeutic decision in elderly cancer patients

Author: François Piette, Nicolas Magné, Laurent Hannoun, Fabrice Menegaux, Jean-Pierre Lefranc, Jean-Philippe Spano, Jean-Jacques Duron, Sylvie Breton, Pascal Chaïbi, Sarah Watson, and Amale Chebib
Subjects: Male, medicine.medical_specialty, Activities of daily living, MEDLINE, Comorbidity, Internal medicine, Neoplasms, Activities of Daily Living, medicine, Humans, Geriatric Assessment, Referral and Consultation, Depression (differential diagnoses), Aged, Retrospective Studies, Aged, 80 and over, business.industry, Depression, Malnutrition, Age Factors, Cancer, Geriatric assessment, Retrospective cohort study, Hematology, medicine.disease, Causality, Oncology, Physical therapy, Disease Progression, Female, Comprehensive Health Care, business, Follow-Up Studies
Abstract: Elderly patients represent a heterogeneous population in which decisions on cancer treatment are often difficult. The present study aims to report a 2-year period of the activity of geriatric assessment consultations and the impact on treatment decisions. Since January 2007, we have systematically carried out geriatric consultations, using well-known international scales, for elderly patients in whom treatment decisions appear complex to oncologists. From January 2007 to November 2008, 161 patients (57 men, 104 women; median age 82.4 years, range 73-97) were seen at geriatric consultations. Most of the patients (134/161) were undergoing first-line treatment and cancer was metastatic in 86 patients (53%). Geriatric assessment found severe comorbidities (grade 3 or 4 in CIRS-G scale) in 75 patients, dependence for at least one activity of daily living (ADL) in 52 patients, cognitive impairment in 42 patients, malnutrition in 104 patients (65%) and depression in 39 patients. According to the oncologists' prior decisions, there were no changes in treatment decisions in only 29 patients. Cancer treatment was changed in 79 patients (49%), including delayed therapy in 5 patients, less intensive therapy in 29 patients and more intensive therapy in 45 patients. Patients for whom the final decision was delayed or who underwent less intensive therapy had significantly more frequent severe comorbidities (23/34, p
Published: 2010

26. Temperature shift and host cell contact up-regulate sporozoite expression of Plasmodium falciparum genes involved in hepatocyte infection

Author: Geert-Jaan van Gemert, Emmanuel Bischoff, Samir Yalaoui, Dominique Mazier, Patrick Froissard, Carine Marinach, Jean-François Franetich, Georges Snounou, Catherine Vaquero, Olivier Silvie, Anthony Siau, Peter H. David, Laurent Hannoun, Adrian J. F. Luty, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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), Department of Medical Microbiology [Nijmegen], Radboud University Medical Center [Nijmegen], Génopole, Institut Pasteur [Paris] (IP), Parasitologie moléculaire et Signalisation, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Parasitologie Comparée et Modèles Expérimentaux, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Plasmodium pan genomic microarrays were financed by grants from the Délégation Générale pour l’Armement (DGA verst.nu22120/DSP/SREAF and Contract no 0434025), Programme PAL+/Fond National pour la Science, the Institut Pasteur and the Programme Génopole. The work was in part supported by the European Union (MALINV project no 012199). A. Siau was supported by MENRT, Fondation de la Recherche Médicale (FRM), and by the Fondation des Treilles., The authors are grateful to Anne Charlotte Grüner for constructive comments and criticisms of the manuscript and to Emilie Duvaltier, Anna Engström, and Marga van de Vegte-Bolmer for their technical help. Microarray analysis and confocal microscopy were performed using the Pitié-Salpêtrière genomic core facility (P3S) and the Plate-forme d'Imagerie Cellulaire, respectively., Vaquero, Catherine, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Plasmodium, Hot Temperature, Host cells, [SDV]Life Sciences [q-bio], MESH: Malaria, Falciparum/metabolism, Protozoan Proteins, MESH: Plasmodium falciparum/metabolism, MESH: Hepatocytes/parasitology, Transcriptome, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, Microbiology/Parasitology, Malaria, Falciparum, Biology (General), Cells, Cultured, Oligonucleotide Array Sequence Analysis, Infectivity, 0303 health sciences, MESH: Plasmodium falciparum/genetics, Reverse Transcriptase Polymerase Chain Reaction, MESH: Protozoan Proteins/biosynthesis, MESH: Gene Expression Profiling/methods, MESH: Hepatocytes/metabolism, 030302 biochemistry & molecular biology, Anopheles, MESH: Malaria, Falciparum/genetics, Genetics and Genomics/Gene Expression, Parasitic diseases, Up-Regulation, 3. Good health, Cell biology, Pathogenesis and modulation of inflammation [N4i 1], [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Sporozoites, Hepatocyte, MESH: Up-Regulation*/genetics, Transcriptome analysis, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, Infectious Diseases/Tropical and Travel-Associated Diseases, MESH: Cells, Cultured, QH301-705.5, Plasmodium falciparum, Immunology, MESH: Protozoan Proteins/genetics, Biology, Salivary glands, MESH: Hot Temperature, Microbiology, MESH: Oligonucleotide Array Sequence Analysis/methods, 03 medical and health sciences, Virology, Genetics, medicine, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, MESH: Humans, Microarray analysis techniques, Gene Expression Profiling, Infectious Diseases/Protozoal Infections, RC581-607, biology.organism_classification, Gene expression profiling, Hepatocytes, Parasitology, Microbial pathogenesis and host defense [UMCN 4.1], Gene expression, Immunologic diseases. Allergy, Immunity, infection and tissue repair [NCMLS 1]
Abstract: Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface proteins involved in hepatocyte invasion, while the other two were predominantly expressed during hepatic parasite development. The genome-wide up-regulation of expression observed supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes validated our approach as one means to determine the repertoire of proteins implicated during the early events of the Plasmodium infection, and in this case that of P. falciparum, the species responsible for the severest forms of malaria., Author Summary Sporozoites, the infective form of the malaria parasites Plasmodium, are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver where they specifically invade hepatocytes, in which they develop to yield another form, the merozoite, infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. We studied the changes in gene expression in sporozoites, from the parasite species P. falciparum that infects humans, in an in vitro system where they were co-cultured with their natural host cells, primary human hepatocytes. The whole genome transcriptome profiling carried out led to the identification of 532 genes that were up-regulated following co-culture. This genome-wide up-regulation of expression supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes we identified validated our approach as one means to determine the repertoire of proteins implicated during the early events in the infection by P. falciparum, the species responsible for the severest forms of malaria.
Published: 2008

27. Procalcitonin in liver transplantation: are high levels due to donors or recipients?

Author: Corinne Vezinet, Pierre Coriat, Marie Laure Tanguy, Jean-Christophe Vaillant, Daniel Eyraud, Laurent Hannoun, S. Fratea, Said Ben Ayed, Jean Michel Siksik, Maguy Bernard, and Marie Movschin
Subjects: Adult, Calcitonin, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, medicine.medical_treatment, Calcitonin Gene-Related Peptide, Liver transplantation, Critical Care and Intensive Care Medicine, Procalcitonin, law.invention, Postoperative Complications, law, parasitic diseases, medicine, Humans, Prospective Studies, Protein Precursors, Prospective cohort study, Transplantation, business.industry, Research, Graft Survival, Postoperative complication, Middle Aged, bacterial infections and mycoses, Intensive care unit, Tissue Donors, Surgery, Liver Transplantation, surgical procedures, operative, Anesthesia, Female, business, Complication, Perfusion, hormones, hormone substitutes, and hormone antagonists, Biomarkers
Abstract: Introduction To date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications. Methods PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction. Results In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest. Conclusion PCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.
Published: 2008

28. New active drugs against liver stages of Plasmodium predicted by molecular topology

Author: Laurent Hannoun, Robert W. Sauerwein, Martin Danis, Francis Derouin, Dominique Mazier, Nassira Mahmoudi, Ramón García-Domenech, Jorge Galvez, Jean-François Franetich, and Khemais Farhati
Subjects: Quantitative structure–activity relationship, Stereochemistry, Antiparasitic, medicine.drug_class, Models, Biological, Auto-immunity, transplantation and immunotherapy [N4i 4], Antimalarials, Mice, Structure-Activity Relationship, Parasitic Sensitivity Tests, parasitic diseases, medicine, Animals, Humans, Structure–activity relationship, Pharmacology (medical), Pharmacology, biology, Poverty-related infectious diseases [N4i 3], Plasmodium falciparum, Plasmodium yoelii, biology.organism_classification, In vitro, Infectious Diseases, medicine.anatomical_structure, Liver, Biochemistry, Susceptibility, Hepatocyte, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1], Infection and autoimmunity [NCMLS 1], Function (biology), Immunity, infection and tissue repair [NCMLS 1]
Abstract: We conducted a quantitative structure-activity relationship (QSAR) study based on a database of 127 compounds previously tested against the liver stage of Plasmodium yoelii in order to develop a model capable of predicting the in vitro antimalarial activities of new compounds. Topological indices were used as structural descriptors, and their relation to antimalarial activity was determined by using linear discriminant analysis. A topological model consisting of two discriminant functions was created. The first function discriminated between active and inactive compounds, and the second identified the most active among the active compounds. The model was then applied sequentially to a large database of compounds with unknown activity against liver stages of Plasmodium . Seventeen drugs that were predicted to be active or inactive were selected for testing against the hepatic stage of P. yoelii in vitro. Antiretroviral, antifungal, and cardiotonic drugs were found to be highly active (nanomolar 50% inhibitory concentration values), and two ionophores completely inhibited parasite development. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed on hepatocyte cultures for all compounds, and none of these compounds were toxic in vitro. For both ionophores, the same in vitro assay as those for P. yoelii has confirmed their in vitro activities on Plasmodium falciparum . A similar topological model was used to estimate the octanol/water partition of each compound. These results demonstrate the utility of the QSAR and molecular topology approaches for identifying new drugs that are active against the hepatic stage of malaria parasites. We also show the remarkable efficacy of some drugs that were not previously reported to have antiparasitic activity.
Published: 2008

29. Scavenger receptor BI boosts hepatocyte permissiveness to Plasmodium infection

Author: Xavier Collet, Anthony Siau, Laurent Hannoun, Jean-Christophe Vaillant, Adrian J. F. Luty, Samir Yalaoui, Audrey Gego, Jean-François Franetich, Geert-Jan van Gemert, Martine Moreau, Thierry Huby, John Chapman, Dominique Mazier, Patrick Froissard, Robert W. Sauerwein, and Armelle Rametti
Subjects: Male, Permissiveness, Cancer Research, Plasmodium, MICROBIO, Hepatitis C virus, Schizonts, medicine.disease_cause, Microbiology, Auto-immunity, transplantation and immunotherapy [N4i 4], Host-Parasite Interactions, Tetraspanin 28, Mice, Tetraspanin, Antigens, CD, Immunology and Microbiology(all), Virology, parasitic diseases, medicine, Animals, Humans, Scavenger receptor, Receptor, Molecular Biology, Cells, Cultured, Mice, Knockout, biology, Liver Diseases, Poverty-related infectious diseases [N4i 3], Plasmodium falciparum, Scavenger Receptors, Class B, biology.organism_classification, Malaria, Cell biology, Mice, Inbred C57BL, Pathogenesis and modulation of inflammation [N4i 1], Cholesterol, medicine.anatomical_structure, Sporozoites, Hepatocyte, Hepatocytes, Female, CELLBIO, Parasitology, Microbial pathogenesis and host defense [UMCN 4.1], Infection and autoimmunity [NCMLS 1], CD81, Immunity, infection and tissue repair [NCMLS 1]
Abstract: Contains fulltext : 71106.pdf (Publisher’s version ) (Closed access) Infection of hepatocytes by Plasmodium falciparum sporozoites requires the host tetraspanin CD81. CD81 is also predicted to be a coreceptor, along with scavenger receptor BI (SR-BI), for hepatitis C virus. Using SR-BI-knockout, SR-BI-hypomorphic and SR-BI-transgenic primary hepatocytes, as well as specific SR-BI-blocking antibodies, we demonstrate that SR-BI significantly boosts hepatocyte permissiveness to P. falciparum, P. yoelii, and P. berghei entry and promotes parasite development. We show that SR-BI, but not the low-density lipoprotein receptor, acts as a major cholesterol provider that enhances Plasmodium infection. SR-BI regulates the organization of CD81 at the plasma membrane, mediating an arrangement that is highly permissive to penetration by sporozoites. Concomitantly, SR-BI upregulates the expression of the liver fatty-acid carrier L-FABP, a protein implicated in Plasmodium liver-stage maturation. These findings establish the mechanistic basis of the CD81-dependent Plasmodium sporozoite invasion pathway.
Published: 2008

30. Nonalcoholic Fatty Liver Disease Increases the Risk of Hepatocellular Carcinoma in Patients With Alcohol-Associated Cirrhosis Awaiting Liver Transplants

Author: Ghizlaine Esselma, Corinne Vezinet, Marika Rudler, Raluca Pais, Jean-Michel Siksik, Thierry Poynard, Daniel Eyraud, Vlad Ratziu, Jean-Christophe Vaillant, G. Rousseau, Laurent Hannoun, Eric Savier, Frédéric Charlotte, Pascal Lebray, and Dominique Thabut
Subjects: Male, Paris, medicine.medical_specialty, Alcoholic liver disease, Carcinoma, Hepatocellular, Cirrhosis, medicine.medical_treatment, Liver transplantation, Risk Assessment, Gastroenterology, Liver disease, Model for End-Stage Liver Disease, Liver Cirrhosis, Alcoholic, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, Prevalence, Humans, Medicine, Obesity, Aged, Retrospective Studies, Hepatology, business.industry, Liver Neoplasms, Fatty liver, Middle Aged, medicine.disease, Fatty Liver, Diabetes Mellitus, Type 2, Female, France, Steatosis, business
Abstract: Many patients with alcohol-associated cirrhosis also have diabetes, obesity, or insulin resistance-mediated steatosis, but little is known about how these disorders affect the severity of liver disease. We analyzed the prevalence and prognostic implications of metabolic risk factors (MRFs) such as overweight, diabetes, dyslipidemia, and hypertension in patients with alcohol-associated cirrhosis awaiting liver transplants.We performed a retrospective study of 110 patients with alcohol-associated cirrhosis (77% male; mean age, 55 y; 71% with6 mo of abstinence) who received liver transplants at a single center in Paris, France, from 2000 through 2013. We collected data on previous exposure to MRFs, steatosis (10% in the explant), and histologically confirmed hepatocellular carcinoma (HCC).HCC was detected in explants from 29 patients (26%). Steatosis was detected in explants from 47 patients (70% were abstinent for ≥6 mo); 50% had a history of overweight or type 2 diabetes. Fifty-two patients (47%) had a history of MRFs and therefore were at risk for nonalcoholic fatty liver disease. A higher proportion of patients with MRF had HCC than those without MRF (46% vs 9%; P.001). A previous history of overweight or type 2 diabetes significantly increased the risk for HCC (odds ratio, 6.23; 95% confidence interval [CI], 2.47-15.76, and odds ratio, 4.63; 95% CI, 1.87-11.47, respectively; P.001). MRF, but not steatosis, was associated with the development of HCC (odds ratio, 11.76; 95% CI, 2.60-53; P = .001) independent of age, sex, amount of alcohol intake, or severity of liver disease.Patients with alcohol-associated cirrhosis who received transplants frequently also had nonalcoholic fatty liver disease. MRFs, particularly overweight, obesity, and type 2 diabetes, significantly increase the risk of HCC.
Published: 2015

31. Expression of human CD81 differently affects host cell susceptibility to malaria sporozoites depending on the Plasmodium species

Author: Geert-Jan van Gemert, Jean-François Franetich, Laurent Hannoun, Anne Dubart-Kupperschmitt, Shoshana Levy, Olivier Silvie, Eric Rubinstein, Claude Boucheix, Dominique Mazier, Céline Greco, Robert W. Sauerwein, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-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), Department of Medical Microbiology, Radboud University Medical Center [Nijmegen], Division of Oncology, Department of Medicine, Stanford University Medical Center, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Garcia, Marie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
Subjects: MESH : Sporozoites, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH : Animals, Genetically Modified, Host tropism, MESH: Sporozoites, MESH: Host-Parasite Relations, Plasmodium, Animals, Genetically Modified, Mice, Tetraspanin, MESH : Plasmodium falciparum, MESH: Animals, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, MESH: Antigens, CD, MESH: Plasmodium falciparum, MESH: Plasmodium yoelii, MESH : Cell Nucleus, 0303 health sciences, biology, 3. Good health, Sporozoites, Infection and autoimmunity [NCMLS 1], [ INFO.INFO-BT ] Computer Science [cs]/Biotechnology, Plasmodium yoelii, MESH: Cell Nucleus, MESH: Cell Line, Tumor, Plasmodium falciparum, Immunology, Auto-immunity, transplantation and immunotherapy [N4i 4], Microbiology, Host-Parasite Interactions, Tetraspanin 28, MESH: Animals, Genetically Modified, 03 medical and health sciences, Species Specificity, Antigen, Antigens, CD, Cell Line, Tumor, Virology, MESH : Mice, parasitic diseases, MESH : Antigens, CD, Animals, Humans, MESH : Species Specificity, MESH: Species Specificity, MESH: Mice, 030304 developmental biology, Cell Nucleus, MESH: Humans, MESH : Cell Line, Tumor, 030306 microbiology, MESH : Humans, fungi, Poverty-related infectious diseases [N4i 3], [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, MESH : Plasmodium yoelii, MESH : Host-Parasite Relations, biology.organism_classification, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [INFO.INFO-BT] Computer Science [cs]/Biotechnology, Cell culture, MESH : Animals, Microbial pathogenesis and host defense [UMCN 4.1], Immunity, infection and tissue repair [NCMLS 1], CD81
Abstract: Contains fulltext : 49897.pdf (Publisher’s version ) (Closed access) Plasmodium sporozoites can enter host cells by two distinct pathways, either through disruption of the plasma membrane followed by parasite transmigration through cells, or by formation of a parasitophorous vacuole (PV) where the parasite further differentiates into a replicative exo-erythrocytic form (EEF). We now provide evidence that following invasion without PV formation, transmigrating Plasmodium falciparum and Plasmodium yoelii sporozoites can partially develop into EEFs inside hepatocarcinoma cell nuclei. We also found that rodent P. yoelii sporozoites can infect both mouse and human hepatocytes, while human P. falciparum sporozoites infect human but not mouse hepatocytes. We have previously reported that the host tetraspanin CD81 is required for PV formation by P. falciparum and P. yoelii sporozoites. Here we show that expression of human CD81 in CD81-knockout mouse hepatocytes is sufficient to confer susceptibility to P. yoelii but not P. falciparum sporozoite infection, showing that the narrow P. falciparum host tropism does not rely on CD81 only. Also, expression of CD81 in a human hepatocarcinoma cell line is sufficient to promote the formation of a PV by P. yoelii but not P. falciparum sporozoites. These results highlight critical differences between P. yoelii and P. falciparum sporozoite infection, and suggest that in addition to CD81, other molecules are specifically required for PV formation during infection by the human malaria parasite.
Published: 2006

32. New approach for high-throughput screening of drug activity on Plasmodium liver stages

Author: Olivier Silvie, Claude Boucheix, Laurent Hannoun, Khemais Farhati, Robert W. Sauerwein, Dominique Mazier, Audrey Gego, Jean-François Franetich, Adrian J. F. Luty, and Eric Rubinstein
Subjects: Drug, Plasmodium, High-throughput screening, media_common.quotation_subject, Auto-immunity, transplantation and immunotherapy [N4i 4], Apicomplexa, Antimalarials, parasitic diseases, medicine, Animals, Humans, Pharmacology (medical), Cells, Cultured, media_common, Pharmacology, biology, Poverty-related infectious diseases [N4i 3], Plasmodium falciparum, Biological activity, medicine.disease, biology.organism_classification, Pathogenesis and modulation of inflammation [N4i 1], Infectious Diseases, Biochemistry, Immunology, Hepatic stellate cell, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1], Infection and autoimmunity [NCMLS 1], Malaria, Immunity, infection and tissue repair [NCMLS 1]
Abstract: Plasmodiumliver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity onPlasmodiumliver stages in vitro, based on an infrared fluorescence scanning system. This method allowed us to count automatically and rapidlyPlasmodium-infected hepatocytes, using different hepatic cells and differentPlasmodiumspecies, includingPlasmodium falciparum. This new technique is well adapted for high-throughput drug screening and should facilitate the identification of new antimalarial compounds active onPlasmodiumliver stages.
Published: 2006

33. Liver-stage development of Plasmodium falciparum, in a humanized mouse model

Author: Wijnand Eling, Carlo Giannini, Laurent Hannoun, Serban Morosan, Françoise Lunel, Catherine Blanc, Laurent Renia, Dina Kremsdorf, Serena Battaglia, Nico van Rooijen, Pierre Druilhe, Robert W. Sauerwein, Jacques Belghiti, Christian Bréchot, and Stéphanie Hez-Deroubaix
Subjects: Xenotransplantation, medicine.medical_treatment, Plasmodium falciparum, Transplantation, Heterologous, Mice, Transgenic, Mice, SCID, Auto-immunity, transplantation and immunotherapy [N4i 4], Mice, In vivo, Immunity, medicine, Animals, Immunology and Allergy, Serum Albumin, Urokinase, Hepatitis, biology, Macrophages, Poverty-related infectious diseases [N4i 3], biology.organism_classification, medicine.disease, Virology, Killer Cells, Natural, Infectious Diseases, medicine.anatomical_structure, Liver, alpha 1-Antitrypsin, Hepatocyte, Models, Animal, Immunology, Humanized mouse, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1], Clodronic Acid, Infection and autoimmunity [NCMLS 1], medicine.drug, Immunity, infection and tissue repair [NCMLS 1]
Abstract: Item does not contain fulltext BACKGROUND: The liver stage of the human malaria parasite Plasmodium falciparum is the least known, yet it holds the greatest promise for the induction of sterile immunity and the development of novel drugs. Progress has been severely limited by the lack of adequate in vitro and in vivo models. METHODS: Recently, it was found that immunodeficient mice transgenic for the urokinase plasminogen activator allow survival of differentiated human hepatocytes. We confirm this finding but show that hepatocyte survival is short lived unless nonadaptive defenses are simultaneously depleted. RESULTS: By controlling macrophages and NK cells, we readily effected the long-term secretion of human serum albumin and human alpha-1 antitrypsin in mouse serum (at 3 months, the proportion of repopulated mice increased from 0% to 60% and from 22% to 80%, respectively; P
Published: 2006

34. Drug Development Papers in PLoS Medicine: How We Try to Spot a Winner

Author: Robert W. Sauerwein, Akino Jossang, François Frappier, Anthony Siau, Laurent Hannoun, Jean-François Franetich, Georges Snounou, Dominique Mazier, Liliane Ciceron, Philippe Rasoanaivo, Maëlle Carraz, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de chimie et biochimie des substances naturelles, Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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), Department of Medical Microbiology, Radboud University Medical Center [Nijmegen], Laboratoire de Pharmacognosie Appliquée aux Maladies Infectieuses, Institut Malgache de Recherches Appliquées, Parasitologie et modèles expérimentaux, This work was supported in part by grants from the Ministère Délégué à la Recherche et aux Nouvelles Technologies (Programme Pal+) and the Fondation pour la Recherche Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Peduzzi, Jean
Subjects: Morphinan, Primaquine, lcsh:Medicine, Plasmodium, MESH: Hepatocytes, chemistry.chemical_compound, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Cells, Cultured, MESH: Plasmodium falciparum, MESH: Plasmodium yoelii, MESH: Inhibitory Concentration 50, 0303 health sciences, biology, Drug discovery, General Medicine, 3. Good health, MESH: Morphinans, Liver, Morphinans, MESH: Phytotherapy, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Plant Bark, MESH: Cell Fractionation, Biological Assay, Lead compound, Infection and autoimmunity [NCMLS 1], Plasmodium yoelii, MESH: Plant Bark, medicine.drug, Research Article, MESH: Cells, Cultured, 030231 tropical medicine, Molecular Sequence Data, Plasmodium falciparum, MESH: Malaria, Cell Fractionation, MESH: Biological Assay, Auto-immunity, transplantation and immunotherapy [N4i 4], Microbiology, 03 medical and health sciences, Antimalarials, Inhibitory Concentration 50, Drugs and Adverse Drug Reactions, parasitic diseases, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, lcsh:R, Poverty-related infectious diseases [N4i 3], medicine.disease, biology.organism_classification, Virology, MESH: Antimalarials, Malaria, chemistry, Immunology, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1], Immunity, infection and tissue repair [NCMLS 1], Phytotherapy, MESH: Liver
Abstract: Background The global spread of multidrug–resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. Methods and Findings Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 μM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 μM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 μM, TI 46, and IC50 42.4 μM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. Conclusions A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs., A derivative of a morphinan alkaloid, tazopsine, from a plant used against malaria in Madagascar, is active against the hepatic stages ofPlasmodium species., Editors' Summary Background. The parasite that causes malaria has quickly developed resistance to many of the drugs that are commonly used to treat this disease. As a result, new drugs and drug combinations are needed. In some parts of the world where antimalarial drugs are failing due to resistance, or are not available to everyone, people often turn to traditional herbal remedies instead. These traditional plant remedies can be a useful starting point for development of new drugs, but the process of developing effective new drugs from plant remedies is long and complicated. An important initial step is to isolate and identify the active compounds from plants and then see how well these compounds perform against malaria parasites in laboratory tests. If the tests are successful, such compounds could then progress to experiments in animals and possibly eventually human trials. One plant used widely in Madagascar for treatment of malaria is Strychnopsis thouarsii; the traditional remedy consists of the plant stem bark boiled in water. Why Was This Study Done? The group of researchers doing this study wanted to discover candidates for new malaria drugs. They therefore wanted to find out which molecular compounds in the stem bark of S. thouarsii contained antimalarial activity, and what particular stage of the malaria parasite's life cycle these compounds had an effect on. The researchers suspected that the agents in this plant bark had some activity against the “liver stage” of malaria infection in humans. This is the first stage of infection, after a person has been bitten by a malaria-infected mosquito, and before blood cells are invaded by malaria parasites (which then causes the disease symptoms). Very few drugs currently in existence have an effect on the “liver stage” of infection, but activity at this stage would be tremendously useful because it could mean a drug is better for prevention of malaria than others in existence. What Did the Researchers Do and Find? First, the researchers wanted to take the traditional herbal remedy—of S. thouarsii bark boiled in water—and find out precisely which molecule in that remedy was responsible for the antimalarial activity. They therefore used a method called chromatography to progressively separate the herbal extract into its distinct components. At each stage of separation, the extract was checked for activity against malaria using a laboratory test. Inactive extracts were disregarded, and the active component then taken on to a further separation round. After many rounds of separation and testing, the researchers got down to a single, apparently new, molecule that was active against malaria in the laboratory test, and this molecule was named tazopsine (in the Malagasy language the word Tazo refers to malaria). In order to find out how effective the molecule was at killing malaria parasites, the researchers took human or mouse liver cells cultured in the laboratory, infected them with malaria parasites (either the malaria parasite that normally infects humans, or a related species that infects mice), and then added tazopsine at different concentrations. The compound completely killed the malaria parasites even at very low concentrations, and had activity against malaria infecting either liver cells or red blood cells. Tazopsine was then given to mice injected with a species of the malaria parasite. The compound protected most mice against malaria infection when it was used at a dosage level lower than the toxic dose. The researchers then tried making a series of different variants of tazopsine in the hope that some variants would be less toxic, but equally active as, the original compound. They found one variant, named NCP-tazopsine, that was much less toxic but just as active as tazopsine, but only against the malaria infecting liver cells. What Do These Findings Mean? In these experiments a new molecule, tazopsine, was discovered from a Malagasy plant, and it was found to be active against liver-stage malaria parasites, in laboratory experiments and in mice. This molecule or variants of it could in future become candidate antimalarial drugs in humans. However, much work would need to be done before testing could get to that stage. Different variants of molecules related to tazopsine would need to be tested to find one that has low toxicity, and these variants would need to be fully evaluated in animals to see how they are handled in the body before any trials could begin in humans. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030513 The World Health Organization publishes a minisite containing links to information about all aspects of malaria worldwide, including treatment, prevention, and current programmes for malaria control Medicines for Malaria Venture is a collaboration between public and private organizations (including the pharmaceutical industry) that aims to fund and manage the development of new drugs for treatment and prevention of malaria Wikipedia entries for drug discovery and drug development (note: Wikipedia is an internet encyclopedia that anyone can edit)
Published: 2006

35. A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozites

Author: Robert W. Sauerwein, Robin F. Anders, Eric Rubinstein, Gerd Pluschke, Dominique Mazier, Markus S. Mueller, Michael J. Blackman, Myriam Bodescot, Olivier Silvie, Geert-Jan van Gemert, Stéphanie Charrin, Anthony Siau, Jean-François Franetich, Laurent Hannoun, Alan W. Thomas, Yupin Charoenvit, and Clemens H. M. Kocken
Subjects: Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, Biochemistry, Plasmodium, Exocytosis, Microneme, parasitic diseases, Animals, Humans, Secretion, Apical membrane antigen 1, Molecular Biology, Cells, Cultured, Infectivity, biology, Membrane Proteins, Cell Biology, biology.organism_classification, Cell biology, Rhoptry neck, Sporozoites, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1]
Abstract: Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and invade hepatocytes as a first and obligatory step of the parasite life cycle in man. Hepatocyte invasion involves proteins secreted from parasite vesicles called micronemes, the most characterized being the thrombospondin-related adhesive protein (TRAP). Here we investigated the expression and function of another microneme protein recently identified in Plasmodium falciparum sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1 antibodies inhibit sporozoite invasion, suggesting that the protein is involved during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP relocate to the sporozoite surface, where they are proteolytically cleaved, resulting in the shedding of soluble fragments. A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection.
Published: 2004

36. A highly efficient, stable, and rapid approach for ex vivo human liver gene therapy via a FLAP lentiviral vector

Author: Serban Morosan, Serena Battaglia, Pierre Charneau, Dina Kremsdorf, J. Guilherme Tralhao, Karine Mollier, Carlo Giannini, Hélène Gilgenkrantz, Jacques Emmanuel Guidotti, and Laurent Hannoun
Subjects: Genetic enhancement, Transgene, Genetic Vectors, Mice, SCID, Biology, Viral vector, Mice, Transduction (genetics), Lentivirus/genética, Transduction, Genetic, Vectores Genéticos, medicine, Animals, Humans, Autologous transplantation, Transgenes, Cells, Cultured, Ratos, Hepatology, Lentivirus, Cell Differentiation, Genetic Therapy, Rats, Genetically modified organism, Terapia Genética, Phenotype, medicine.anatomical_structure, Hepatocyte, Immunology, Hepatocytes, Cancer research, Hepatócitos, Cell Division, Ex vivo
Abstract: Allogenic hepatocyte transplantation or autologous transplantation of genetically modified hepatocytes has been used successfully to correct congenital or acquired liver diseases and can be considered as an alternative to orthotopic liver transplantation. However, hepatocytes are neither easily maintained in culture nor efficiently genetically modified and are very sensitive to dissociation before their reimplantation into the recipient. These difficulties have greatly limited the use of an ex vivo approach in clinical trials. In the present study, we have shown that primary human and rat hepatocytes can be efficiently transduced with a FLAP lentiviral vector without the need for plating and culture. Efficient transduction of nonadherent primary hepatocytes was achieved with a short period of contact with vector particles, without modifying hepatocyte viability, and using reduced amounts of vector. We also showed that the presence of the DNA FLAP in the vector construct was essential to reach high levels of transduction. Moreover, transplanted into uPA/SCID mouse liver, lentivirally transduced primary human hepatocytes extensively repopulated their liver and maintained a differentiated and functional phenotype as assessed by the stable detection of human albumin and antitrypsin in the serum of the animals for months. In conclusion, the use of FLAP lentiviral vectors allows, in a short period of time, a high transduction efficiency of human functional and reimplantable hepatocytes. This work therefore opens new perspectives for the development of human clinical trials based on liver-directed ex vivo gene therapy. info:eu-repo/semantics/publishedVersion
Published: 2003

37. Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity

Author: Michel Prenant, Claude Boucheix, Wijnand Eling, Elodie Belnoue, Dominique Mazier, Jean-François Franetich, Olivier Silvie, Laurent Rénia, Laurent Hannoun, Shoshana Levy, and Eric Rubinstein
Subjects: Recombinant Fusion Proteins, Plasmodium falciparum, Protozoan Proteins, Vacuole, Plasmodium, Tetraspanin 29, General Biochemistry, Genetics and Molecular Biology, Tetraspanin 28, Mice, Antigens, CD, Anopheles, parasitic diseases, medicine, Animals, Humans, Malaria, Falciparum, Cells, Cultured, Mice, Knockout, Infectivity, Mice, Inbred BALB C, Membrane Glycoproteins, biology, Membrane Proteins, Plasmodium yoelii, General Medicine, biology.organism_classification, Virology, Malaria, Mice, Inbred C57BL, Circumsporozoite protein, medicine.anatomical_structure, Sporozoites, Hepatocyte, Hepatocytes, Microbial pathogenesis and host defense [UMCN 4.1], CD81
Abstract: Item does not contain fulltext Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and first invade the liver of the mammalian host, as an obligatory step of the life cycle of the malaria parasite. Within hepatocytes, Plasmodium sporozoites reside in a membrane-bound vacuole, where they differentiate into exoerythrocytic forms and merozoites that subsequently infect erythrocytes and cause the malaria disease. Plasmodium sporozoite targeting to the liver is mediated by the specific binding of major sporozoite surface proteins, the circumsporozoite protein and the thrombospondin-related anonymous protein, to glycosaminoglycans on the hepatocyte surface. Still, the molecular mechanisms underlying sporozoite entry and differentiation within hepatocytes are largely unknown. Here we show that the tetraspanin CD81, a putative receptor for hepatitis C virus, is required on hepatocytes for human Plasmodium falciparum and rodent Plasmodium yoelii sporozoite infectivity. P. yoelii sporozoites fail to infect CD81-deficient mouse hepatocytes, in vivo and in vitro, and antibodies against mouse and human CD81 inhibit in vitro the hepatic development of P. yoelii and P. falciparum, respectively. We further demonstrate that the requirement for CD81 is linked to sporozoite entry into hepatocytes by formation of a parasitophorous vacuole, which is essential for parasite differentiation into exoerythrocytic forms.
Published: 2003

38. Hemodynamic and hormonal responses to the sudden interruption of caval flow: insights from a prospective study of hepatic vascular exclusion during major liver resections

Author: Corinne Vezinet, Alain Carayon, Olivier Richard, Pierre Coriat, D. Eyraud, Dominique C. Borie, Barbara Schaup, Jean-Christophe Vaillant, Laurent Hannoun, and Marie Movschin
Subjects: Male, Cardiac output, medicine.medical_specialty, Hemodynamics, Inferior vena cava, Plasma renin activity, medicine.artery, Internal medicine, Monitoring, Intraoperative, Medicine, Humans, Anesthesia, Prospective Studies, Aged, business.industry, Liver Neoplasms, Middle Aged, Hormones, Surgery, Anesthesiology and Pain Medicine, Blood pressure, medicine.anatomical_structure, medicine.vein, Liver, Pulmonary artery, Cardiology, Vascular resistance, Female, Vascular Resistance, Venae Cavae, business, Venous return curve, Liver Circulation
Abstract: UNLABELLED Hepatic vascular exclusion (HVE) combines portal triad clamping and occlusion of the inferior vena cava. Although HVE has been performed for major liver resections during the last 2 decades, little is known about the mechanisms that explain its satisfactory hemodynamic tolerance. Consequently, we performed a comprehensive study of both hemodynamic and hormone responses to HVE. Twenty-two patients who underwent liver resection for secondary tumors developed in noncirrhotic livers were prospectively studied. Heart rate, arterial blood pressure, pulmonary artery pressure, mixed venous saturation, cardiac output, and left ventricular dimensions determined by transesophageal echocardiography were monitored in HVE patients. Blood concentrations of arginine vasopressin (AVP), epinephrine, norepinephrine, dopamine, and atrial natriuretic peptide and plasma renin activity (PRA) were measured before clamping; 5, 15, and 30 min after clamping; and 15 min after unclamping. Hemodynamic response to HVE was characterized by a significant (P < 0.05) decrease in left ventricular dimensions, fractional area change, and pulmonary artery pressure. We also observed a marked decrease in cardiac output (50%) and an increase in heart rate and systemic vascular resistance. After unclamping, there was peripheral vasodilation, assessed by a significant decrease in systemic vascular resistance from the preclamping value to unclamping. An acute and sustained increase in AVP and norepinephrine that returned to baseline after unclamping and the absence of modification in PRA concentrations were noted. The marked decrease in venous return that characterizes HVE is compensated for by an increase in vascular resistance secondary to an important activation of the AVP and sympathetic systems. The PRA system does not play an important role in maintaining arterial blood pressure during HVE. IMPLICATIONS Hemodynamic and hormonal responses to the acute interruption of caval venous return to the heart were investigated in patients undergoing liver resection with hepatic vascular exclusion. A compensatory role for arginine vasopressin and sympathetic systems that provoked increased vascular resistance was demonstrated.
Published: 2002

39. Secondary proctectomy and ileal pouch—anal anastomosis after ileorectal anastomosis for familial adenomatous polyposis

Author: Rolland Parc, Pascal Frileux, Nordlinger B, Emmanuel Tiret, C. Penna, Laurent Hannoun, and Alex Kartheuser
Subjects: Adult, Male, Reoperation, medicine.medical_specialty, Adolescent, Colorectal cancer, medicine.medical_treatment, Rectum, Anastomosis, Gastroenterology, Familial adenomatous polyposis, Surgical anastomosis, Postoperative Complications, Ileum, Internal medicine, medicine, Humans, Child, Defecation, Pelvis, Aged, Rectal Neoplasms, Proctocolectomy, business.industry, Anastomosis, Surgical, Proctocolectomy, Restorative, Middle Aged, medicine.disease, Surgery, medicine.anatomical_structure, Adenomatous Polyposis Coli, Adenocarcinoma, Female, business
Abstract: Conversion of ileorectal anastomosis to ileal pouch—anal anastomosis (IPAA) was indicated in 29 patients with familial adenomatous polyposis but technically impossible in three because of unsuspected pelvic desmoid tumours. There was no operative mortality and overall postoperative morbidity and late complication rates were no different from those in a group of 120 patients who underwent IPAA as a first operative procedure. Unsuspected adenocarcinoma (one invasive, three in situ) was found in four patients. The functional results in patients with IPAA did not differ from those of ileorectal anastomosis before conversion or from those obtained after IPAA as a first-choice procedure. Secondary proctectomy and IPAA can be safely offered to patients with ileorectal anastomosis and a high risk of rectal cancer.
Published: 1993

40. Phase I and phase II drug-metabolizing enzymes are expressed and heterogeneously distributed in the biliary epithelium

Author: Pierre Balladur, Raoul Poupon, Dominique Wendum, François Ballet, Véronique Barbu, Fatima Lakehal, Philippe Beaune, Laurent Hannoun, Laurent Becquemont, and Chantal Housset
Subjects: Liver cytology, Blotting, Western, Gene Expression, Isozyme, Cytochrome P-450 Enzyme System, Microsomes, medicine, Cytochrome P-450 CYP3A, Humans, RNA, Messenger, Biliary Tract, health care economics and organizations, Biotransformation, Cells, Cultured, Glutathione Transferase, Epoxide Hydrolases, Hepatology, biology, CYP1A2, Cytochrome P450, Gallbladder, Cytochrome P-450 CYP2E1, Epithelial Cells, Oxidoreductases, N-Demethylating, CYP2E1, Immunohistochemistry, Epithelium, Blot, Isoenzymes, medicine.anatomical_structure, Biochemistry, Liver, Pharmaceutical Preparations, Microsomal epoxide hydrolase, Steroid Hydroxylases, biology.protein, Aryl Hydrocarbon Hydroxylases
Abstract: Tissue expression of drug-metabolizing enzymes influences susceptibility to drugs and carcinogens. Because the biliary epithelium, exposed to bile-borne chemicals, may give rise to drug-induced cholangiopathies and to cholangiocarcinomas, we determined the pattern of expression of drug-metabolizing enzymes in this epithelium. We first demonstrated by blot analyses that biliary epithelial cells (BEC) isolated from human gallbladders display cytochrome P450 (CYP) 1A, 2E1, and 3A, microsomal epoxide hydrolase (mEH), alpha, mu, and pi glutathione S-transferase (GST), transcripts and proteins. We also identified CYP-associated steroid 6beta-hydroxylase activity in BEC. CYP and mEH expression was 5- to 20-fold lower in BEC than in autologous hepatocytes, and further differed by a higher ratio of CYP3A5/CYP3A4, and by CYP1A1 predominance over CYP1A2. alphaGST was highly expressed in both hepatocytes and BEC, while piGST was restricted to BEC. In approximately 50% of individuals, muGST was expressed in hepatocytes and at lower levels in BEC. By using the same antibodies as those used in immunoblots, we could show by immunohistochemistry that CYP2E1, CYP3A, mEH, alpha, mu, and piGST immunoreactivities are expressed and display a heterogeneous distribution in the epithelium lining the entire biliary tract except for small intrahepatic bile ducts that were devoid of CYP3A and alphaGST immunoreactivities. In conclusion, BEC contribute to phase II, and although to a lesser extent than hepatocytes, to phase I biotransformation. The distribution of drug-metabolizing enzymes in BEC suggest that they are heterogeneous in their ability to generate and detoxicate reactive metabolites, which may contribute to specific distributions of cholangiopathies.
Published: 1999

41. Deletion of hydroxyethylstarch from University of Wisconsin solution induces cell shrinkage and proteolysis during and after cold storage of rat liver

Author: Laurent Hannoun, E. Savier, Jean-Claude Chaumeil, N. Neveux, J.-P. De Bandt, Jacqueline Giboudeau, Christine Charrueau, and Luc Cynober
Subjects: Cryopreservation, Male, Hepatology, Organ Preservation Solutions, Cold storage, Proteins, Stimulation, Biology, Protein degradation, Rats, Andrology, Hydroxyethyl Starch Derivatives, Rats, Sprague-Dawley, medicine.anatomical_structure, Biochemistry, Liver, Hepatocyte, medicine, Animals, Viaspan, Liver preservation, Intracellular, Drug metabolism
Abstract: Among the numerous components of the University of Wisconsin (UW) solution used for organ preservation, the usefulness of hydroxyethylstarch (HES), the colloido-osmotic support of this solution, is controversial. The aim of our study was to determine the influence of HES on hepatic metabolism and intracellular hydration state during hypothermic preservation and after reperfusion in a model of isolated perfused rat liver. Three groups of eight livers were perfused either immediately or after 18 hours of cold storage in a UW-based preservation solution with or without HES. Omission of HES results in 1) a stimulation of protein degradation shown by the marked increase in branched-chain amino acid (BCAA) release (211 +/- 55 vs. 87 +/- 28 nmol/min/g; P < .05, modified UW group vs. UW group), 2) an increase in oxygen consumption (81.7 +/- 4.8 vs. 61.5 +/- 5.0 micromol/h/g; P < .05), 3) a decrease in glucose production (2.3 +/- 0.6 vs. 5.0 +/- 0.6 micromol/min/g; P < .05), and 4) a reduction in intracellular volume (414 +/- 36 vs. 557 +/- 41 microL/g; P < .05). We conclude that HES plays an important role in liver preservation by limiting proteolysis, possibly through the observed preservation of cell volume.
Published: 1997

42. Tandem high-dose chemotherapy with ifosfamide, carboplatin, and teniposide with autologous bone marrow transplantation for the treatment of poor prognosis common epithelial ovarian carcinoma

Author: Carmen Macovei, Emmanuel Touboul, Jean-Pierre Lefranc, Jean-Pierre Lotz, Sidney Houry, Carole Bouleuc, Serge Uzan, Thierry André, Laurent Hannoun, and Victor Izrael
Subjects: Adult, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Population, Gastroenterology, Transplantation, Autologous, Carboplatin, chemistry.chemical_compound, Autologous stem-cell transplantation, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Ifosfamide, education, Survival rate, Bone Marrow Transplantation, Teniposide, Ovarian Neoplasms, education.field_of_study, Chemotherapy, business.industry, Carcinoma, Middle Aged, Combined Modality Therapy, Survival Analysis, Surgery, Regimen, Oncology, chemistry, Female, business, medicine.drug
Abstract: BACKGROUND A Phase I or II trial was conducted to assess the toxicity and the efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and teniposide in patients with poor prognosis ovarian carcinoma. METHODS Thirty-seven patients were scheduled to receive tandem high dose therapy combining ifosfamide 7500 to 11250 mg/m2, carboplatin 875 to 1000 mg/m2 and teniposide 750 to 1000 mg/m2, followed by autologous bone marrow transplantation (ABMT). Eight patients were refractory to the platin-based regimen, 7 were treated in chemosensitive relapse, and 22 in partial or complete response (PR/CR) were treated. Sixty-six cycles were administered. Sixteen patients were evaluated for response. RESULTS The overall response rate was 56% (CR rate: 12%). Toxic effects consisted of mainly renal toxicity, esophagitis, and enterocolitis. Three patients died of therapy-related complications. Since the time of ABMT, the median overall survival (OS) duration of the whole population was 18 months and the survival rate was 14% at 60 months. For the 22 patients treated after PR or CR, the median OS duration was 24 months and the survival rate was 32% at 60 months. Tandem high dose therapy with ABMT was unable to circumvent resistance to conventional chemotherapy or to prolong the duration of survival for patients treated in chemosensitive relapse. For patients treated after CR or PR, the survival results were similar to that achieved with conventional therapy. CONCLUSIONS Prospective, randomized studies, including patients only after CR or with minimal residual disease, are urgently required to evaluate the activity of high dose therapy in the treatment of advanced ovarian carcinoma. Cancer 1996;77:2550-9.
Published: 1996

43. Liver Biopsy Analysis Has a Low Level of Performance for Diagnosis of Intermediate Stages of Fibrosis

Author: Gilles Lenaour, Daniel Eyraud, Laurent Hannoun, Yen Ngo, Frédéric Charlotte, Helmi M'Kada, Frédérique Capron, Vlad Ratziu, Mona Munteanu, Thierry Poynard, and Jean-Christophe Vaillant
Subjects: Adult, Liver Cirrhosis, Male, Alcoholic liver disease, medicine.medical_specialty, Biopsy, Chronic liver disease, Gastroenterology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Internal medicine, Severity of illness, Nonalcoholic fatty liver disease, Medicine, Humans, Aged, Hepatology, medicine.diagnostic_test, business.industry, FibroTest, Histocytochemistry, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, 030220 oncology & carcinogenesis, Liver biopsy, 030211 gastroenterology & hepatology, Female, business
Abstract: There is controversy about the performance of noninvasive tests such as FibroTest in diagnosing intermediate stages of fibrosis. We investigated whether this controversy results from limitations of biopsy analysis for intermediate-stage fibrosis and inappropriate determination of the standard area under the receiver-operator characteristic curve (AUROC).To determine whether biopsy has a lower diagnostic performance for fibrosis stage F2 (few septa) vs F1 (fibrosis without septa), compared with its performance for F1 vs F0 or F4 vs F3, we determined the fibrotic areas of large surgical samples collected from 20 consecutive patients with chronic liver disease or normal liver tissue that surrounded tumors. We analyzed digitized images of 27,869 virtual biopsies of increasing length and also analyzed data from 6500 patients with interpretable FibroTest results who also underwent biopsy analysis.The overall performance of biopsy analysis (by Obuchowski measure) increased with biopsy length from 0.885 for 5-mm to 0.912 for 30-mm samples (P.0001). The performance of biopsy was lower for the diagnosis of F2 vs F1 samples (weighted AUROC [wAUROC] = 0.505) than for F1 vs F0 (wAUROC = 0.773; 53% difference; P.0001) or F4 vs F3 (wAUROC = 0.700; 39% difference; P.0001), even when 30-mm biopsy samples were used. The performance of FibroTest was also lower for the diagnosis of F2 vs F1 samples (wAUROC = 0.512) than for F1 vs F0 samples (wAUROC = 0.626; 22% difference; P.0001) or F4 vs F3 (wAUROC = 0.628; 23% difference; P.0001). However, the FibroTest had smaller percentage differences among wAUROC values than biopsy.Biopsy has a low level of diagnostic performance for fibrosis stages F2 and F1. The recommendation for biopsy analysis, instead of a validated biomarker panel such as FibroTest, for the diagnosis of intermediate stages of fibrosis is therefore misleading.
Published: 2012
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44. Inhibitory Effect of TNF-α on Malaria Pre-Erythrocytic Stage Development: Influence of Host Hepatocyte/Parasite Combinations

Author: Jean-Marc Chavatte, Laurent Rénia, Jean Francois Franetich, Robert W. Sauerwein, Nadya Depinay, Marjorie Mauduit, Dominique Mazier, Laurent Hannoun, Adrian J. F. Luty, Anne Charlotte Grüner, Georges Snounou, Jean-Michel Siksik, and Geert-Jan van Gemert
Subjects: Erythrocytes, medicine.medical_treatment, Protozoology, Mice, Molecular Cell Biology, Receptor, Multidisciplinary, Interleukin, Host-Pathogen Interaction, Infectious Diseases, medicine.anatomical_structure, Cytokine, Medical Microbiology, Hepatocyte, Cytokines, Medicine, Tumor necrosis factor alpha, Plasmodium yoelii, Research Article, Clinical Research Design, Preclinical Models, Science, Plasmodium falciparum, Immunology, Gastroenterology and Hepatology, Biology, Nitric Oxide, Microbiology, Host-Parasite Interactions, Tetraspanin 28, Antigens, CD, Cell Line, Tumor, Parasitic Diseases, medicine, Animals, Humans, Life Cycle Stages, Tumor Necrosis Factor-alpha, Immunity, Tropical Diseases (Non-Neglected), Immune Defense, Pathogenesis and modulation of inflammation Infection and autoimmunity [N4i 1], biology.organism_classification, medicine.disease, Malaria, Solubility, Immune System, Hepatocytes, Parastic Protozoans, Parasitology, Clinical Immunology, Reactive Oxygen Species
Abstract: Contains fulltext : 97044.pdf (Publisher’s version ) (Open Access) BACKGROUND: The liver stages of malaria parasites are inhibited by cytokines such as interferon-gamma or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-alpha possibly because of differences in the models used. We have reassessed the role of TNF-alpha in the different cellular systems used to study the Plasmodium pre-erythrocytic stages. METHODS AND FINDINGS: Human or mouse TNF-alpha were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-alpha treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-alpha inhibition was mediated by a soluble factor present in the supernatant of TNF-alpha stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. CONCLUSIONS: Treatment TNF-alpha prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection.
Published: 2011

45. Extracorporeal membrane oxygenation as a bridge to liver transplantation for acute respiratory distress syndrome-induced life-threatening hypoxaemia aggravated by hepatopulmonary syndrome

Author: Chung Hi Do, Hélène Brisson, Jean-Jacques Rouby, Pauline Houssel, Laurent Hannoun, Daniel Eyraud, Qin Lu, Jean-Christophe Vaillant, Rubin Luo, Antoine Monsel, Hervé Mal, Corinne Vezinet, and François Durand
Subjects: Male, medicine.medical_specialty, Waiting Lists, medicine.medical_treatment, Liver transplantation, Critical Care and Intensive Care Medicine, hypoxaemia, Liver disease, orthotopic liver transplantation, hepatopulmonary syndrome, Extracorporeal membrane oxygenation, Humans, Medicine, Respiratory system, Hypoxia, Diffuse alveolar damage, Hepatopulmonary syndrome, Mechanical ventilation, Respiratory Distress Syndrome, Lung, Acute respiratory distress syndrome, business.industry, Research, Middle Aged, extracorporeal membrane oxygenation, medicine.disease, Liver Transplantation, Surgery, medicine.anatomical_structure, Anesthesia, business
Abstract: Introduction: Combined with massive lung aeration loss resulting from acute respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular lung disorder characterized by diffuse or localized dilated pulmonary capillaries, may induce hypoxaemia and death in patients with end-stage liver disease. Methods: The case of such a patient presenting with both disorders and in whom an extracorporeal membrane oxygenation was used is described. Results: A 51-year-old man with a five-year history of alcoholic cirrhosis was admitted for acute respiratory failure, platypnoea and severe hypoxaemia requiring emergency tracheal intubation. Following mechanical ventilation, hypoxaemia remained refractory to positive end-expiratory pressure, 100% of inspired oxygen and inhaled nitric oxide. Two-dimensional contrast-enhanced (agitated saline) transthoracic echocardiography disclosed a massive right-to-left extracardiac shunt, without patent foramen ovale. Contrast computed tomography (CT) of the thorax using quantitative analysis and colour encoding system established the diagnosis of acute respiratory distress syndrome aggravated by hepatopulmonary syndrome. According to the severity of the respiratory condition, a veno-venous extracorporeal membrane oxygenation was implemented and the patient was listed for emergency liver transplantation. Orthotopic liver transplantation was performed at Day 13. At the end of the surgical procedure, the improvement in oxygenation allowed removal of extracorporeal membrane oxygenation (Day 5). The patient was discharged from hospital at Day 48. Three months after hospital discharge, the patient recovered a correct physical autonomy status without supplemental O2. Conclusions: In a cirrhotic patient, acute respiratory distress syndrome was aggravated by hepatopulmonary syndrome causing life-threatening hypoxaemia not controlled by standard supportive measures. The use of extracorporeal membrane oxygenation, by controlling gas exchange, allowed the performing of a successful liver transplantation and final recovery.
Published: 2011

46. Repeat liver resection for recurrent colorectal metastases

Author: I. Karaitianos, Laurent Hannoun, P. Balladur, Nordlinger B, Huguet C, Rolland Parc, and Jean-Christophe Vaillant
Subjects: Adult, Male, Reoperation, medicine.medical_specialty, Palliative care, medicine.medical_treatment, Liver transplantation, Resection, Metastasis, medicine, Hepatectomy, Humans, Survival rate, Aged, Lung, business.industry, Rectal Neoplasms, Liver Neoplasms, Middle Aged, medicine.disease, Surgery, medicine.anatomical_structure, Liver, Colonic Neoplasms, Female, Operative risk, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract: Sixteen patients underwent 18 repeat liver resections for recurrence of colorectal hepatic metastases that had been previously resected. Only minor liver resection had been undertaken at the first operation; three were palliative. The second operation was major hepatectomy in ten patients, minor resection in five and orthotopic liver transplantation in one. In one patient, lung metastases were resected before the second operation. One repeat hepatectomy was palliative. After partial liver resection, there were no deaths and complications were observed in six of 15 patients. One patient died 2 weeks after liver transplantation. After the second resection, 2-, 3- and 5-year survival rates were 67, 57 and 30 per cent; the mean survival time was 33 (range 8–93) months. Tumour recurrence was observed in 11 of 14 patients 4–32 (mean 13) months after a second curative liver resection; two patients received a third curative operation for recurrent liver metastases. After the second curative hepatectomy, seven patients died from disease after a mean of 36 (range 14–61) months and seven are currently alive at a mean of 33 (range 8–93) months. Four of these patients are free from disease 26–93 months after resection and three are alive with recurrence. Repeat hepatectomy for recurrent colorectal metastases can prolong survival in selected patients and has low operative risk.
Published: 1993

47. Vascular Occlusions for Liver Resections

Author: Laurent Hannoun, H. Deriaz, Delva E, Y. Camus, André Lienhart, Bernard Nordlinger, Claude Huguet, and Rolland Parc
Subjects: medicine.medical_specialty, Blood transfusion, Cirrhosis, Portal triad, business.industry, medicine.medical_treatment, Ischemia, medicine.disease, Inferior vena cava, Surgery, medicine.anatomical_structure, medicine.vein, medicine, Hepatectomy, Packed red blood cells, business, Vein
Abstract: The intra- and early postoperative courses of 142 consecutive patients who underwent liver resections using vascular occlusions to reduce bleeding were reviewed. In 127 patients, the remnant liver parenchyma was normal, and 15 patients had liver cirrhosis. Eighty-five patients underwent major liver resections: right, extended right, or left lobectomies. Portal triad clamping (PTC) was used alone in 107 cases. Complete hepatic vascular exclusion (HVE) combining PTC and occlusion of the inferior vena cava below and above the liver was used for 35 major liver resections. These 35 patients had large or posterior liver tumors, and HVE was used to reduce the risks of massive bleeding or air embolism caused by an accidental tear of the vena cava or a hepatic vein. Duration of normothermic liver ischemia was 32.3 +/- 1.2 minutes (mean +/- SEM) and ranged from 8 to 90 minutes. Amount of blood transfusion was 5.5 +/- 0.5 (mean +/- SEM) units of packed red blood cells. There were eight operative deaths (5.6%). Overall, postoperative complications occurred in 46 patients (32%). The patients who experienced complications after surgery had received more blood transfusion than those with an uneventful postoperative course (p less than 0.001). The length of postoperative hospital stay was also correlated with the amount of blood transfused during surgery (p less than 0.001). On the other hand, there was no correlation between the durations of liver ischemia of up to 90 minutes and the lengths of postoperative hospital stay. The longest periods of ischemia were not associated with increased rates of postoperative complications, liver failures, or deaths. There was no difference in mortality or morbidity after major liver resections performed with the use of HVE as compared with major liver resections carried out with PTC alone, although the lesions were larger in the former group. It is concluded that the main priority during liver resections is to reduce operative bleeding. Vascular occlusions aim at achieving this goal and can be extended safely for up to 60 minutes.
Published: 1989

48. Septic Necrosis of the Midline Wound in Postoperative Peritonitis

Author: Rolland Parc, Jiri Honiger, Etienne Levy, Laurent Hannoun, Pascal Frileux, Donald L. Palmer, Bernard Nordlinger, and Emmanuel Tiret
Subjects: Male, Reoperation, medicine.medical_specialty, medicine.medical_treatment, Peritonitis, Dehiscence, Surgical Flaps, Abdominal wall, Laparotomy, Surgical Wound Dehiscence, medicine, Humans, Surgical Wound Infection, Hernia, Wound Healing, integumentary system, business.industry, Suture Techniques, Middle Aged, medicine.disease, Surgery, medicine.anatomical_structure, Debridement, Anesthesia, Abdomen, Female, Complication, business, Surgical incision, Research Article
Abstract: Wound management following laparotomy for postoperative peritonitis and varying degrees of parietal necrosis remains a challenging and controversial problem. Because maintained peritoneal integrity and primary wound closure offer the best opportunity for survival, an original technique involving bilateral incisions to relax skin and rectus fascia is proposed. This technique permits medial myocutaneous advancement and primary tension-free skin closure of midline laparotomy incisions. Sixty-nine patients with severe postoperative peritonitis were treated according from 1980 through 1985. Nine of these patients died of advanced multiple organ failure soon after referral, and eight more died after prolonged treatment. Fourteen patients had one or more reoperations for complications. Only nine wound failures resulted, including five eviscerations and four wound infections followed by progressive dehiscence. The bilateral relaxing incisions healed secondarily without complication. Survivors developed midline wound hernia; ten of the 52 surviving patients have had these repaired. This method of primary closure is safe when performed in conjunction with rigorous surgical care of intraperitoneal infection and may enhance survival. We recommend the technique to surgeons who treat severe postoperative peritonitis and septic necrosis of midline laparotomy wounds.
Published: 1988

49. Continuous enteral nutrition during the early adaptive stage of the short bowel syndrome

Author: Rolland Parc, Etienne Levy, Cosnes J, J. P. Masini, J M Ollivier, Pascal Frileux, Sergio Sandrucci, Laurent Hannoun, Perron, Nicolas, and Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Enterocutaneous fistula, Adult, Male, Short Bowel Syndrome, medicine.medical_specialty, Resuscitation, Elemental diet, Adolescent, Gastroenterology, Enteral administration, Feces, Enteral Nutrition, Malabsorption Syndromes, Internal medicine, medicine, Humans, Child, Serum Albumin, Aged, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Body Weight, Middle Aged, Short bowel syndrome, medicine.disease, Prognosis, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Small intestine, Surgery, medicine.anatomical_structure, Parenteral nutrition, Female, business, Complication
Abstract: Sixty-two patients with the short bowel syndrome (30–150 cm) were managed by continuous enteral nutrition (CEN) in the early adaptive phase. In all, 82 per cent were referrals from other units and 85 per cent of referrals had failure of one or more organ systems on admission. There were intra-abdominal abscesses in 41 per cent of patients and 37 per cent had an enterocutaneous fistula. The diet included polysaccharides, medium chain triglycerides and protein hydrolysates, mixed with a high-viscosity tapioca suspension. An elemental diet was used initially in 15 per cent of patients. Thirty-three patients had an interruption of the gastrointestinal tract by a temporary enterostomy. Chyme was re-infused into the distal intestine in 20 cases. ‘Zero-time’ was taken as the time of operation or, for referred patients treated conservatively, the date of admission. CEN was commenced at a mean of 14 days from zero-time. Total parenteral nutrition could be discontinued at a mean of 36 days and exclusive oral alimentation was resumed at a mean of 87 days. Patients with small bowel longer than 80 cm attained enteral autonomy earlier than patients with a shorter length. Mean faecal volume did not increase following institution of CEN, suggesting tolerance to the high-viscosity diet. In cases with re-infusion of enteric content, the distal circuit (length of distal small intestine 46 cm) was able to absorb 70 per cent of the volume re-infused (mean volume 2700 ml). Body weight and nutritional markers increased significantly during the course of CEN. This study suggests that enteral autonomy can be attained early in the short bowel syndrome, even under challenging conditions. Elemental formulae do not appear to offer a benefit over polymeric diets.
Published: 1988

50. Hepatic resection for colorectal liver metastases. Influence on survival of preoperative factors and surgery for recurrences in 80 patients

Author: Bernard Nordlinger, Rolland Parc, Laurent Hannoun, Marc-Antoine Quilichini, Eric Delva, and Claude Huguet
Subjects: Adult, Male, medicine.medical_specialty, Portal triad, Colorectal cancer, medicine.medical_treatment, Rectum, Metastasis, Actuarial Analysis, Occlusion, medicine, Hepatectomy, Humans, Stage (cooking), Aged, business.industry, Rectal Neoplasms, Mortality rate, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, Surgery, medicine.anatomical_structure, Colonic Neoplasms, Female, Neoplasm Recurrence, Local, business, Follow-Up Studies, Research Article
Abstract: This report analyses an experience with 80 liver resections for metastatic colorectal carcinoma. Primary colorectal cancers had all been resected. Liver metastases were solitary in 44 patients, multiple in 36 patients, unilobar in 76 patients, and bilobar in 4 patients. Tumor size was less than 5 cm in 33 patients, 5-10 cm in 30 patients, and larger than 10 cm in 17 patients. There were 43 synchronous and 37 metachronous liver metastases with a delay of 2-70 months. The surgical procedures included more major liver resections (55 patients) than wedge resections (25 patients). Portal triad occlusion was used in most cases, and complete vascular exclusion of the liver was performed for resection of the larger tumors. In-hospital mortality rate was 5%. Three- and 5-year survival rates were 40.5% and 24.9%, respectively. None of the analysed criteria: size and number of liver metastases, delay after diagnosis of the primary cancer, Duke's stage, could differentiate long survivors from patients who did not benefit much from liver surgery due to early recurrence. Recurrences were observed in 51 patients during the study, two thirds occurring during the first year after liver surgery. Eight patients had resection of "secondary" metastases after a first liver resection: two patients for extrahepatic recurrences and six patients for liver recurrences. Encouraging results raise the question of how far agressive surgery for liver metastases should go.
Published: 1987

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