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12 results on '"Service de gastro-entérologie et assistance nutritive"'

1. Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study

Author

Vered Abitbol, Stephanie Viennot, Catherine Reenaers, Jean-Marie Reimund, Lucine Vuitton, Mélanie Serrero, Philippe Seksik, Jérôme Filippi, Mathurin Fumery, Guillaume Savoye, David Laharie, Bénédicte Caron, Caroline Trang-Poisson, Jean-Pierre Bronowicki, Guillaume Bouguen, Benjamin Pariente, Maud Reymond, Laurent Peyrin-Biroulet, Stéphane Nancey, Romain Altwegg, L Caillo, Franck Carbonnel, Yoram Bouhnik, Aurelien Amiot, Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), 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 Régional Universitaire [Lille] (CHRU Lille), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Gastroentérologie et nutrition [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), Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Université de Montpellier (UM)-CHU Saint-Eloi, Université de Liège, Hôpital Nord [CHU - APHM], Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hépato-gastroentérologie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Gastro-entérologie et hépatologie [AP-HP Hôpital Cochin], Sorbonne Paris Cité-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), douville, sabine, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), CHU Saint-Antoine [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), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Service d'Hépatologie et de Gastroentérologie [Lyon], Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Chimie Moléculaire de Paris Centre (FR 2769), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Paris Cité-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Department of Hepato-Gastroenterology, University Hospital Estaing of Clermont-Ferrand, Université d'Auvergne (Clermont Ferrand 1) (UdA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Fédération de Médecine Translationelle de Strasbourg (FMTS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Université d'Auvergne - Clermont-Ferrand I (UdA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Charles Nicolle [Rouen]-CHU Rouen

Subjects
Adult, Male, Crohn’s disease, vedolizumab, medicine.medical_specialty, Adolescent, Cholangitis, Sclerosing, Population, Antibodies, Monoclonal, Humanized, Malignancy, Gastroenterology, Inflammatory bowel disease, Primary sclerosing cholangitis, Vedolizumab, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, inflammatory bowel disease, Internal medicine, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, ulcerative colitis, education.field_of_study, Crohn's disease, business.industry, primary sclerosing cholangitis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, General Medicine, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Background Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. Methods We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. Results Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0–29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. Conclusions In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population.

Published
2019

2. Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn’s Disease in Sustained Remission

Author

Reenaers, Catherine, Mary, Jean-Yves, Nachury, Maria, Bouhnik, Yoram, Laharie, David, Allez, Matthieu, Fumery, Mathurin, Amiot, Aurélien, Savoye, Guillaume, Altwegg, Romain, Devos, Martine, Malamut, Georgia, Bourreille, Arnaud, Flourie, Bernard, Marteau, Philippe, Vuitton, Lucine, Coffin, Benoit, Viennot, Stéphanie, Lambert, Jérôme, Colombel, Jean-Frédéric, Louis, Edouard, Getaid, Groupe d'Etude Thérapeutique Des Affections, Université de Liège, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de gastro-entérologie et assistance nutritive, 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), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Infection à helicobacter, inflammation et cancer, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Amiens-Picardie, 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'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Hépato-gastro-entérologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universiteit Gent = Ghent University [Belgium] (UGENT), Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), gastroenterology, Lariboisière hospital, Hôpital Lariboisière-Fernand-Widal [APHP], Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Gastroenterology Unit, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Icahn Medical Institute-Mount Sinai School of Medicine, Department of Gene and Cell Medicine and Institute for Immunology, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Faculty of Medicine and Health Science, University of Ghent, Ghent, Belgium, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hépato-Gastroentérologie [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Lariboisière, AP-HP, Paris, Service d'Hépato-gastro-entérologie [Hôpital Jean Minjoz], Hôpital Jean Minjoz, Hopital Louis Mourier - AP-HP [Colombes], GETAID, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
musculoskeletal diseases, Adult, Male, medicine.medical_specialty, Disease, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Belgium, Crohn Disease, Gastrointestinal Agents, Interquartile range, Recurrence, Internal medicine, medicine, Humans, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Crohn's disease, Hepatology, biology, business.industry, C-reactive protein, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Infliximab, 3. Good health, Surgery, Discontinuation, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, biology.protein, 030211 gastroenterology & hepatology, Female, France, business, medicine.drug, Follow-Up Studies
Abstract

Background & Aims Little is known about long-term outcomes of patients with Crohn's disease (CD) after infliximab withdrawal. We aimed to describe the long-term outcomes of patients with CD in clinical remission after infliximab treatment was withdrawn. Methods We performed a retrospective analysis of data from the 115 patients included in the infliximab discontinuation in patients with CD in stable remission on combined therapy with antimetabolites (STORI) study, performed at 20 centers in France and Belgium from March 2006 through December 2009. The STORI cohort was a prospective analysis of risk and factors associated with relapse following withdrawal of maintenance therapy with infliximab, maintained on antimetabolites, while in clinical remission. We collected data from the end of the study until the last available follow-up examination on patient surgeries, new complex perianal lesions (indicating major complications), and need for and outcomes of restarting therapy with infliximab or another biologic agent. The de-escalation strategy was considered to have failed when a major complication or infliximab restart failure occurred. Results Of the 115 patients initially included, data from 102 patients (from 19 of the 20 study centers) were included in the final analysis. The median follow-up time was 7 years. Twenty-one percent of the patients did not restart treatment with infliximab or another biologic agent and did not have a major complication 7 years after infliximab withdrawal (95% CI, 13.1–30.3). Among patients who restarted infliximab, treatment failed for 30.1% 6 years after restarting (95% CI, 18.5–42.5). Overall, at 7 years after stopping infliximab therapy, major complications occurred in 18.5% of patients (95% CI, 10.2–26.8) whereas 70.2% of patients had no failure of the de-escalation strategy (95% CI, 60.2–80.1). Factors independently associated with major complications were upper-gastrointestinal location of disease, white blood cell count ≥ 5.0 × 109/L, and hemoglobin level ≤12.5 g/dL at the time of infliximab withdrawal. Patients with at least 2 of these factors had a more than 40% risk of major complication in the 7 years following infliximab withdrawal. Conclusions In a long-term follow-up of the STORI cohort (7 years) one fifth of the patients did not restart infliximab or another biologic agent and did not develop major complications. Seventy percent of patients had no failure of the de-escalation strategy (no major complication and no failure of infliximab restart).

Published
2018

3. Topological Modelling of Deep Ulcerations in Patients with Ulcerative Colitis

Author

Gilles Wainrib, Eric Ogier-Denis, Ian Morilla, Hatem Zaag, Xavier Treton, Mathieu Uzzan, Dominique Cazals-Hatem, Service d'Anatomo-Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Xavier Bichat, Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
0301 basic medicine, business.industry, Inference, medicine.disease, Topology, Inflammatory bowel disease, Ulcerative colitis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], digestive system diseases, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Cohort, Medicine, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], In patient, business, ComputingMilieux_MISCELLANEOUS
Abstract

Aims: Steadily the clinicians of our team in inflammatory bowel disease encounter ulcerative colitis patients that develop deep ulcers during their treatment. Currently, these practitioners are only equipped with their grade of expertise in inflammatory domains to decide what new therapy maybe use in such cases. Encouraged by the limited knowledge of this frequent pathology, we seek to determine the molecular conditions underlying the recurrent formation of deep ulcerations in certain group of patients. Method: The goal of this strategy is to expose differences between groups of patients based on similarities computed by random walk graph kernels and performing functional inference on those differences. Results: We apply the methodology to a cohort of eleven miRNA microarrays of ulcerative colitis patients. Our results showed how the group of ulcerative colitis patients with presence of deep ulcers is topologically more similar (0.35) than ulcerative colitis patients (0.18) to control. Such topological constraint drove functional inference to complete the information that clinicians need. Conclusions: Our analyses reveal highly interpretable in the guidance of practitioners to eventually correct initial therapies of ulcerative colitis patients that develop deep ulcers. The methodology can provide them with useful molecular hypotheses necessaries prior to make any decision on the newest course of the treatment.

Published
2017

4. Integrative Network-based Analysis of Colonic Detoxification Gene Expression in Ulcerative Colitis According to Smoking Status

Author

Yannick Ladeiro, Yong-Ping Ding, Ian Morilla, Assiya Marah, Xavier Treton, Dominique Cazals-Hatem, Gilles Wainrib, Fanny Daniel, Philippe Seksik, Eric Ogier-Denis, Yoram Bouhnik, Hatem Zaag, Jean-Pierre Hugot, 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), Physiopathologie de la réactivite bronchique et vasculaire, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Service d'Anatomo-Pathologie, Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Recherche pour le Développement, UR 178 Fundamentals & Domains of Disease Emergence (IRD UR178), Faculté de Médecine Xavier Bichat, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), 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), and Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, 0301 basic medicine, Colon, Gene Expression, Disease, Real-Time Polymerase Chain Reaction, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gene interaction, Detoxification, Gene expression, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Principal Component Analysis, business.industry, Smoking, Gastroenterology, General Medicine, Middle Aged, medicine.disease, Ulcerative colitis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, 030104 developmental biology, Real-time polymerase chain reaction, Case-Control Studies, Inactivation, Metabolic, Immunology, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business, Homeostasis
Abstract

Backgrounds and Aims: The effect of cigarette smoking [CS] is ambivalent since smoking improves ulcerative colitis [UC] while it worsens Crohn’s disease [CD]. Although this clinical relationship between inflammatory bowel disease [IBD] and tobacco is well established, only a few experimental works have investigated the effect of smoking on the colonic barrier homeostasis focusing on xenobiotic detoxification genes. Methods: A comprehensive and integrated comparative analysis of the global xenobiotic detoxification capacity of the normal colonic mucosa of healthy smokers [ n = 8] and non-smokers [ n = 9] versus the non-affected colonic mucosa of UC patients [ n = 19] was performed by quantitative real-time polymerase chain reaction [qRT PCR]. The detoxification gene expression profile was analysed in CD patients [ n = 18], in smoking UC patients [ n = 5], and in biopsies from non-smoking UC patients cultured or not with cigarette smoke extract [ n = 8]. Results: Of the 244 detoxification genes investigated, 65 were dysregulated in UC patients in comparison with healthy controls or CD patients. The expression of ≥ 45/65 genes was inversed by CS in biopsies of smoking UC patients in remission and in colonic explants of UC patients exposed to cigarette smoke extract. We devised a network-based data analysis approach for differentially assessing changes in genetic interactions, allowing identification of unexpected regulatory detoxification genes that may play a major role in the beneficial effect of smoking on UC. Conclusions: Non-inflamed colonic mucosa in UC is characterised by a specifically altered detoxification gene network, which is partially restored by tobacco. These mucosal signatures could be useful for developing new therapeutic strategies and biomarkers of drug response in UC.

Published
2016

5. Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study

Author

Catherine Cardot-Bauters, Olivier Chabre, B. Delemer, Emilie Castermans, Eric Clauser, Michel Rodier, Georges Weryha, M.F. Odou, Alain Calender, F. Borson-Chazot, Abderrahmane Bourredjem, F Schillo, H. Du Boullay, Jean-Marc Kuhn, Véronique Kerlan, Anne Barlier, Catherine Lombard-Bohas, P. Lecomte, S. Giraud, B. Goichot, Albert Beckers, Sophie Christin-Maitre, I. Guilhem, F. Archambeaud, A. Tabarin, Hélène Bihan, Eric Pasmant, Jean-Louis Sadoul, Philippe Chanson, Patricia Niccoli, Julien Thevenon, Jérôme Bertherat, Vincent Rohmer, Pierre Goudet, Marc Le Renard, Lionel Groussin, P. Caron, N. Bourcigaux, Christine Binquet, Eric Baudin, Bruno Vergès, Laurence Faivre, Philippe Ruszniewski, M. Le Bras, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, equipe 4, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Institut Cochin (IC UM3 (UMR 8104 / U1016)), 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 d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), centre hospitalier universitaire de liège, Service d'endocrinologie clinique, CHU Pontchaillou [Rennes], Service d'Endocrinologie (ANGERS - Endocrino), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de médecine interne et de nutrition, Hôpital de Hautepierre [Strasbourg], Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de consultations de pathologies professionnelles [CHRU Nancy] (CCPP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Endocrinologie [CHRU Nancy], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cyanobactéries des milieux aquatiques tropicaux peu profonds. Rôles et contrôles (CYROCO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), 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]-Hôpital Edouard Herriot [CHU - HCL], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), FHU TRANSLAD (CHU de Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, 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]-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)-Hôpital Edouard Herriot [CHU - HCL], Laboratoire des Procédés d'Élaboration des Réactifs Fonctionnels (PERF), Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Eq 4, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est-Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, CHU Lyon, Service d'Endocrinologie (GRENOBLE - Endocrino), CHU Grenoble, Institut Cochin (UMR_S567 / UMR 8104), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Pierre Aigrain (LPA), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Brest (UBO)-Université de Brest (UBO), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Agence nationale de la sécurité des systèmes d'information (ANSSI), Service d'Ophtalmologie (CHU de Dijon), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP]

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Adrenal Gland Neoplasm, Adrenal Gland Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Pituitary neoplasm, Neuroendocrine tumors, Metastasis, Cohort Studies, Young Adult, Endocrinology, Age Distribution, Internal medicine, medicine, Multiple Endocrine Neoplasia Type 1, Humans, MEN1, Genetic Predisposition to Disease, Pituitary Neoplasms, Expressivity (genetics), Child, ComputingMilieux_MISCELLANEOUS, [SDV.BA]Life Sciences [q-bio]/Animal biology, Pituitary tumors, Bronchial Neoplasms, Infant, Newborn, Infant, General Medicine, Thymus Neoplasms, Heritability, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Pedigree, Pancreatic Neoplasms, Neuroendocrine Tumors, Parathyroid Neoplasms, Child, Preschool, Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

BackgroundMEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1.MethodsThe study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software.ResultsIntrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; Ps.e.m.=0.21; Ps.e.m.=0.41; P=0.006) for thNETs.ConclusionThe present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

Published
2015

6. Long-Term Outcome of Enterocutaneous Fistula in Patients With Crohn's Disease Treated With Anti-TNF Therapy: A Cohort Study from the GETAID

Author

Vida Setakhr, Vered Abitbol, Xavier Treton, Yoram Bouhnik, Aurelien Amiot, Michel Veyrac, Jean Marie Reimund, Mathieu Allez, Marc Lémann, Philippe Seksik, Jacques Moreau, Jacques Cosnes, Martine De Vos, David Laharie, Bernard Flourié, Jean-Frederic Colombel, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de gastro-entérologie et assistance nutritive, 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), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'Hépato-gastroentérologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Maladies Infectieuses et Tropicales [CHU Hôpital Nord - Marseille] (M.I.T), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Fédération Médico-Chirurgicale des Maladies de l'Appareil Digestif, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Pole des maladies de l'appareil digestif, gastroentérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and AP-HP Hôpital Beaujon

Subjects
Male, Enterocutaneous fistula, Time Factors, Cutaneous Fistula, Gastroenterology, Colonic Diseases, 0302 clinical medicine, Crohn Disease, Colon surgery, Intestine, Small, Young adult, Crohn's disease, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Anastomosis, Surgical, Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Monoclonal, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Colon, Antibodies, Monoclonal, Humanized, Young Adult, 03 medical and health sciences, Ileum, Internal medicine, Intestinal Fistula, medicine, Adalimumab, Humans, Duodenal Diseases, Retrospective Studies, Hepatology, Tumor Necrosis Factor-alpha, business.industry, Retrospective cohort study, medicine.disease, Infliximab, digestive system diseases, Surgery, business, Follow-Up Studies
Abstract

International audience; : OBJECTIVES:Although anti-tumor necrosis factor (TNF) therapy is the treatment of choice for perianal fistulizing Crohn's disease (CD), the efficacy and safety of anti-TNF therapy in enterocutaneous fistula (ECF) remains unclear.METHODS:Between January 2008 and December 2009, we retrospectively reviewed the outcomes of all CD patients with ECF (excluding perianal fistula) treated with anti-TNF therapy followed up in Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) centers. ECF closure and tolerance of anti-TNF therapy were studied using univariate and multivariate analyses.RESULTS:Forty-eight patients (twenty-six women; median age 34.6 (interquartile range=25.0-45.5) years) were included in this study. The median follow-up period was 3.0 (2.0-6.6) years. The fistula was located in the small bowel (n=38), duodenum (n=1), and colon (n=9). The fistula has been developed in ileocolonic anastomosis in 17 (35%) cases. Sixteen patients (33%) had complex fistulas with multiple tracts and eleven patients (23%) had a high ECF output (if wearing an ostomy bag). Complete ECF closure was achieved in 16 (33%) patients, of whom eight relapsed during the follow-up period. In multivariate analysis, complete ECF closure was associated with the absence of multiple ECF tracts and associated stenosis. An abdominal abscess developed in 15 (31%) patients. ECF resection was needed in 26 (54%) patients. One patient died after surgery owing to abdominal sepsis.CONCLUSIONS:In CD patients with ECF, anti-TNF therapy may be effective in up to one-third of patients, especially in the absence of stenosis and complex fistula. A careful selection of patients is mandatory to prevent treatment failure and improves the safety.Am J Gastroenterol advance online publication, 5 August 2014; doi:10.1038/ajg.2014.183.

Published
2014

7. Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study

Author

Anne Laure Pelletier, Vinciane Rebours, Frank Pilleul, Dermot O'Toole, Catherine Lombard-Bohas, Pascal Hammel, Magaly Zappa, Marie-Pierre Vullierme, Frédérique Maire, Philippe Ruszniewski, Anne Couvelard, Olivia Hentic, CHU Lyon, Swiss Federal Research Institute WSL, SWISS FEDERAL RESEARCH INSTITUTE WSL, Departement d'imagerie Digestive, Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon, 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), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon

Subjects
Oncology, Adult, Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Urinary system, Gastroenterology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Hepatic Artery, Internal medicine, medicine, Humans, Infusions, Intra-Arterial, Embolization, Progression-free survival, Prospective Studies, Chemoembolization, Therapeutic, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Gastrointestinal Neoplasms, Chemotherapy, Endocrine and Autonomic Systems, business.industry, Arterial Embolization, Liver Neoplasms, Middle Aged, medicine.disease, Primary tumor, Embolization, Therapeutic, 3. Good health, Neuroendocrine Tumors, Treatment Outcome, Doxorubicin, 030220 oncology & carcinogenesis, Concomitant, Female, business, Follow-Up Studies
Abstract

Background: Liver surgery is the best treatment for endocrine liver metastases, but it is often impossible due to diffuse disease. Systemic chemotherapy is poorly effective. Hepatic arterial embolization (HAE) and chemoembolization (HACE) have shown efficacy but have never been compared. Patients and Methods: Patients with progressive unresectable liver metastases from midgut endocrine tumors were randomly assigned to receive HAE or HACE (two procedures at 3-month interval). The primary end point was the 2-year progression-free survival (PFS) rate. Secondary end points were response rates, overall survival, and safety. Results: Twelve patients were assigned to receive HACE and 14 to receive HAE. The patient characteristics were well matched across the treatment arms. The 2-year PFS rates were 38 and 44% in the HACE and HAE arms, respectively (p = 0.90). Age, gender, previous resection of the primary tumor or liver metastases, extent of liver involvement, and concomitant treatment with somatostatin analogues were not associated with changes in PFS, whereas elevated baseline urinary 5-HIAA and serum chromogranin A levels were associated with shorter PFS. The 2-year overall survival rates were 80 and 100% in the HACE and HAE arms, respectively (p = 0.16). The disease control rate on CT scan was 95%. Grade 3 toxicity occurred in 19% of patients, with no treatment-related deaths and no differences in the treatment arms. Conclusion: HACE and HAE are safe and permit tumor control in 95% of patients with progressive liver metastases from midgut endocrine tumors. The 2-year PFS was not higher among patients receiving HACE, not favoring the hypothesis of an additive efficacy of arterial chemotherapy or embolization alone.

Published
2012

8. Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'etude des Tumeurs Endocrines

Author

Guillaume Cadiot, Gérard Chabrier, Pierre Goudet, Catherine Cardot-Bauters, I. Guilhem, Claire Bonithon-Kopp, Philippe Bouchard, Olivier Chabre, Bruno Vergès, Françoise Borson-Chazot, Albert Beckers, Patricia Niccoli, P. Caron, Philippe Ruszniewski, A. Tabarin, H. Du Boullay, Fabrice Menegaux, Arnaud Murat, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), centre hospitalier universitaire de Nantes ( CHU Nantes ), Clinique d'endocrinologie, Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Astrophysique de Lyon ( CRAL ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Saint-Antoine [APHP], Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, centre hospitalier universitaire de liège, Service d'endocrinologie clinique, ONERA - The French Aerospace Lab ( Palaiseau ), ONERA, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Hôpital de la Timone [CHU - APHM] (TIMONE), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ONERA - The French Aerospace Lab [Palaiseau], Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ONERA-Université Paris Saclay (COmUE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, endocrine system diseases, MESH : Prevalence, Endocrinology, Diabetes and Metabolism, MESH : Thymus Neoplasms, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, 0302 clinical medicine, Endocrinology, Prevalence, MESH : Female, Family history, Multiple endocrine neoplasia, MESH: Cohort Studies, MESH: Middle Aged, General Medicine, Middle Aged, MESH : Adult, MESH : Pituitary Neoplasms, 030220 oncology & carcinogenesis, Female, France, MESH: Pancreatic Neoplasms, medicine.symptom, MESH : Multiple Endocrine Neoplasia Type 1, MESH: Thymus Neoplasms, Cohort study, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, MESH : Sex Factors, MESH : Male, MESH: Multiple Endocrine Neoplasia Type 1, MESH : Cohort Studies, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030209 endocrinology & metabolism, Context (language use), Lesion, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, Internal medicine, Multiple Endocrine Neoplasia Type 1, medicine, Humans, Pituitary Neoplasms, MEN1, MESH : Middle Aged, MESH: Pituitary Neoplasms, MESH : France, MESH: Prevalence, Hyperparathyroidism, MESH: Humans, business.industry, Pituitary tumors, MESH : Humans, MESH: Adult, Thymus Neoplasms, MESH : Gastrinoma, medicine.disease, MESH: Male, Pancreatic Neoplasms, MESH: France, Gastrinoma, MESH: Gastrinoma, business, MESH: Female, MESH : Pancreatic Neoplasms
Abstract

ContextMultiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed.ObjectiveThe aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1.DesignData regarding a study of 734 cases of MEN1 from the multicenter ‘Groupe d'étude des Tumeurs Endocrines’ were analyzed.ResultsThere were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (P=0.06, P=0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (PPP=0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%).ConclusionThe phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.

Published
2011

9. Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy

Author

Rahier, Jean-François, Buche, Sébastien, Peyrin-Biroulet, Laurent, Bouhnik, Yoram, Duclos, Bernard, Louis, Edouard, Papay, Pavol, Allez, Matthieu, Cosnes, Jacques, Cortot, Antoine, Laharie, David, Reimund, Jean-Marie, Lémann, Marc, Delaporte, Emmanuel, Colombel, Jean-Frédéric, Renseigné, Non, Service d'Hépato-gastroentérologie, UCL Mont Godinne, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Nephrology Service, Université de Montréal (UdeM)-Hôpital Notre-Dame de Montréal, Service de Gastro-Entérologie et Nutrition, Université Pierre et Marie Curie - Paris 6 (UPMC), Hepatogastroenterology, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Montréal [Montréal]-Hôpital Notre-Dame de Montréal, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP]

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Inflammatory bowel disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Adalimumab, Humans, Immunologic Factors, Psoriasis, Crohn's disease, Hepatology, integumentary system, Tumor Necrosis Factor-alpha, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Gastroenterology, Dermatology Life Quality Index, Skin Diseases, Eczematous, Inflammatory Bowel Diseases, medicine.disease, Dermatology, Ulcerative colitis, Infliximab, 3. Good health, Anti-Tumor Necrosis Factor Therapy, Treatment Outcome, Withholding Treatment, Female, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, business, medicine.drug
Abstract

International audience; BACKGROUND & AIMS: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-α therapies. We assessed clinical characteristics, risk factors, and outcomes of skin disease in patients with inflammatory bowel diseases that presented with psoriasiform and eczematiform lesions induced by anti-TNF-α agents. METHODS: We studied 85 patients (69 with Crohn's disease, 15 with ulcerative colitis, and 1 with indeterminate colitis; 62 women) with inflammatory skin lesions (62 psoriasiform and 23 eczematiform lesions). RESULTS: Twenty-four patients had a history of inflammatory skin lesions and 15 had a familial history of inflammatory skin disease. Locations of eczematiform lesions varied whereas scalp and flexural varieties were mostly psoriasiform. Skin lesions emerged but inflammatory bowel disease was quiescent in 69 patients following treatment with any type of anti-TNF-α agent (60 with infliximab, 20 with adalimumab, and 5 with certolizumab). Topical therapy resulted in partial or total remission in 41 patients. Patients with psoriasiform lesions that were resistant to topical therapy and that changed anti-TNF-α therapies once or twice developed recurring lesions. Overall, uncontrolled skin lesions caused 29 patients to stop taking TNF-α inhibitors. CONCLUSIONS: Inflammatory skin lesions following therapy with TNF-α inhibitors occurred most frequently among women and patients with a personal or familial history of inflammatory skin disease; lesions did not correlate with intestinal disease activity. Recurring and intense skin lesions caused 34% of patients in this study to discontinue use of anti-TNF-α agents.

Published
2010

10. The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease

Author

Olivier Lambotte, Yoram Bouhnik, Felipe Suarez, Olivier Hermine, Jean-François Viallard, Georgia Malamut, Jacques Cosnes, Dominique Bechade, Anne-Sophie Lascaux, Nadine Cerf-Bensussan, Marianne Ziol, Christophe Cellier, Virginie Verkarre, Anne Lavergne, Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Necker - Enfants Malades [AP-HP], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Médecine Interne, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de Gastro-Entérologie et Nutrition, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Service de médecine interne et maladies infectieuses, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service d'anatomie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), UPRES EA3406, Université Paris 13 (UP13)-UFR SMBH, Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Université Paris Descartes - Paris 5 (UPD5), Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Université Paris 13 ( UP13 ) -UFR SMBH, Réseau International des Instituts Pasteur ( RIIP ), Université Paris Descartes - Paris 5 ( UPD5 ), Interactions de l'épithelium intestinal et du système immunitaire ( UMR_S 793 ), Institut National de la Recherche Agronomique ( INRA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], and Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)

Subjects
Diarrhea, Colon, Plasma Cells, Disease, Medical Records, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, parasitic diseases, Intestine, Small, medicine, Humans, Enteropathy, Intestinal Mucosa, 030304 developmental biology, Retrospective Studies, 0303 health sciences, Hepatology, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Common variable immunodeficiency, Gastroenterology, nutritional and metabolic diseases, medicine.disease, digestive system diseases, 3. Good health, Celiac Disease, Common Variable Immunodeficiency, Gastritis, Immunology, 030211 gastroenterology & hepatology, Atrophy, business
Abstract

International audience; OBJECTIVES: The enteropathy associated with common variable immunodeficiency (CVID) is poorly characterized, and its possible relationships with well-defined causes of enteropathy, such as celiac sprue (CS), remain debated. We aimed to assess the clinical and histopathological features of the enteropathy associated with CVID. METHODS: The medical files of 50 CVID patients with gastrointestinal symptoms were analyzed retrospectively. Histological, phenotypic, and molecular analysis of intestinal endoscopic specimens was centrally performed. RESULTS: Chronic diarrhea was the most frequent gastrointestinal symptom (92%), and biological evidence of malabsorption was observed in 54% of patients. Chronic gastritis associated or not with pernicious anemia and microscopic colitis were the most frequently observed histopathological features in gastric and colonic mucosa, respectively. Small-bowel biopsies available in 41 patients showed moderate increase in intestinal intraepithelial lymphocytes in 31 patients (75.6%) and villous atrophy in 21 patients (51%). Distinctive features from CS were a profound depletion in plasma cells and follicular lymphoid hyperplasia. Presence of peripheral blood CD8+ hyperlymphocytosis was predictive of intestinal intraepithelial hyperlymphocytosis. Intravenous (i.v.) immunoglobulin (Ig) therapy had no effect on enteropathy-related symptoms. Gluten-free diet improved only two out of 12 patients with villous atrophy, whereas all patients (7/7) responded to steroid therapy. CONCLUSIONS: Several distinctive features differentiate CVID enteropathy from other causes of enteropathy including CS. Replacement i.v. Ig therapy is insufficient to improve gastrointestinal symptoms. Steroids are effective in reducing inflammation and restoring mucosal architecture.

Published
2010

11. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study

Author

STEPHANE NANCEY, Francois MION, Nathalie Ganne-Carrié, Dany GARGOT, ANTOINE CORTOT, Laurent Siproudhis, Bernard FLOURIE, ROBERT BENAMOUZIG, Tabassome SIMON, Frederic Gottrand, Guillaume Savoye, Gerard Thiefin, Fabrice Carrat, Jean-Pierre Hugot, Pierre DESREUMAUX, Laurent Peyrin-biroulet, Laurent Michaud, Christos CHRISTIDIS, Olivier Hermine, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service d'Anatomie et Cytologie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hopital Necker-Enfants Malades, Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Hépato-gastroentérologie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Infection bactérienne, inflammation, et carcinogenèse digestive, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -IFR50-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunité muqueuse et vaccination, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR50-Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Service de gastro-entérologie et assistance nutritive, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Registre des hémopathies malignes de Côte d'Or, Service d'hématologie biologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Agents pathogènes et inflammation - UFC (EA 4266) ( API ), Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), 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)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), 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)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Male, Time Factors, MESH : Age Distribution, MESH : Prospective Studies, MESH : Aged, Inflammatory bowel disease, MESH: Proportional Hazards Models, 0302 clinical medicine, MESH: Lymphoproliferative Disorders, Crohn Disease, Risk Factors, MESH: Risk Factors, MESH : Purines, MESH : Female, Prospective Studies, MESH: Incidence, Prospective cohort study, MESH : Immunosuppressive Agents, MESH : Sex Distribution, MESH: Aged, MESH : Tumor Necrosis Factor-alpha, Crohn's disease, MESH: Middle Aged, Thiopurine methyltransferase, biology, MESH : Lymphoproliferative Disorders, Incidence, MESH: Sex Distribution, General Medicine, MESH: Purines, Middle Aged, MESH : Adult, MESH : Colitis, Ulcerative, Ulcerative colitis, MESH : Risk Factors, MESH : Incidence, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, MESH: Immunosuppressive Agents, Immunosuppressive Agents, Cohort study, MESH : Time Factors, Adult, medicine.medical_specialty, MESH : Male, MESH: Colitis, Ulcerative, Lymphoproliferative disorders, MESH : Crohn Disease, MESH: Multivariate Analysis, 03 medical and health sciences, Age Distribution, Internal medicine, medicine, Humans, MESH : Middle Aged, Sex Distribution, MESH : France, MESH: Age Distribution, Aged, Proportional Hazards Models, MESH: Humans, MESH: Crohn Disease, Tumor Necrosis Factor-alpha, business.industry, MESH : Drug Therapy, Combination, MESH: Time Factors, MESH : Humans, MESH : Multivariate Analysis, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, MESH : Proportional Hazards Models, Lymphoproliferative Disorders, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, MESH: Drug Therapy, Combination, Purines, MESH: Tumor Necrosis Factor-alpha, Multivariate Analysis, biology.protein, Colitis, Ulcerative, business, MESH: Female
Abstract

International audience; BACKGROUND: Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial. We assessed this risk in a prospective observational cohort study. METHODS: 19,486 patients with inflammatory bowel disease, of whom 11,759 (60.3%) had Crohn's disease and 7727 (39.7%) had ulcerative colitis or unclassified inflammatory bowel disease, were enrolled in a nationwide French cohort by 680 gastroenterologists, who reported details of immunosuppressive therapy during the observation period, cases of cancer, and deaths. The risk of lymphoproliferative disorder was assessed according to thiopurine exposure. Median follow-up was 35 months (IQR 29-40). FINDINGS: At baseline, 5867 (30.1%) of patients were receiving, 2809 (14.4%) had discontinued, and 10,810 (55.5%) had never received thiopurines. 23 new cases of lymphoproliferative disorder were diagnosed, consisting of one case of Hodgkin's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder. The incidence rates of lymphoproliferative disorder were 0.90 per 1000 (95% CI 0.50-1.49) patient-years in those receiving, 0.20/1000 (0.02-0.72) patient-years in those who had discontinued, and 0.26/1000 (0.10-0.57) patient-years in those who had never received thiopurines (p=0.0054). The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 (2.01-13.9, p=0.0007). Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease. INTERPRETATION: Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders. FUNDING: Programme Hospitalier de Recherche Clinique National (AOM05157), Association François Aupetit, Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris (AP-HP), Ligue contre le Cancer, and Fonds de Recherche de la Société Nationale Française de Gastro-entérologie.

Published
2009

12. Identification of Restricted Subsets of Mature microRNA Abnormally Expressed in Inactive Colonic Mucosa of Patients with Inflammatory Bowel Disease

Author

Christophe Richard, Fanny Daniel, Eric Pedruzzi, Magali Fasseu, Xavier Treton, André Groyer, Eric Ogier-Denis, Thomas Aparicio, Richard Moreau, Yoram Bouhnik, Dominique Cazals-Hatem, Soulé Jc, Marc Laburthe, Cécile Guichard, Groyer, André, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gastro-entérologie et assistance nutritive, 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), Service d'Anatomo-Pathologie, Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Sante et de la Recherche Medicale (Inserm) and in parts by grants from Association Francois Aupetit AFA, Assistance Publique- Hopitaux de Paris, Ferring Laboratories, Ipsen Laboratories, Societe Nationale Francaise de Gastro-enterologie (SNFGE), Association Francaise pour l'etude du foie (AFEF), and Programme National de Recherche en Hepato-Gastroenterologie., Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Colon, lcsh:Medicine, Crohn's Disease, Biology, Polymerase Chain Reaction, Inflammatory bowel disease, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Intestinal mucosa, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Gene expression, medicine, Humans, Intestinal Mucosa, lcsh:Science, Cell Biology/Gene Expression, 030304 developmental biology, 0303 health sciences, Crohn's disease, Gastroenterology and Hepatology/Inflammatory Bowel Disease, Multidisciplinary, Inflammatory Bowel Disease, lcsh:R, Chromosome Mapping, quiescent mucosa, Genetics and Genomics/Gene Expression, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, digestive system diseases, 3. Good health, MicroRNAs, Immunology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], miRNA profiling, Female, lcsh:Q, 030211 gastroenterology & hepatology, Research Article
Abstract

BACKGROUND: Ulcerative Colitis (UC) and Crohn's Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes. METHODOLOGY/FINDINGS: Expression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or 100 -fold and 0.05-0.19 -fold for over- and under- expression, respectively; 0.001

Published
2010

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