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1. Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre studyResearch in context

Author

Rémy Nicolle, Cindy Canivet, Laurent Palazzo, Bertrand Napoléon, Mira Ayadi, Camille Pignolet, Jérôme Cros, Sophie Gourgou, Janick Selves, Jérôme Torrisani, Nelson Dusetti, Pierre Cordelier, Louis Buscail, Barbara Bournet, Nicolas Carrère, Fabrice Muscari, Bertrand Suc, Rosine Guimbaud, Corinne Couteau, Marion Deslandres, Pascale Rivera, Emily Alouany, Nadim Fares, Karl Barange, Anne Gomez-Brouchet, Adrian Culetto, Guillaume Le Cosquer, Marion Jaffrelot, Bertrand Pujol, Fabien Fumex, Jérôme Desrame, Christine Lefort, Vincent Lepilliez, Rodica Gincul, Pascal Artru, Léa Clavel, Anne-Isabelle Lemaistre, Sarah Tubiana, Nicolas Flori, Pierre Senesse, Pierre-Emmanuel Colombo, Emmanuelle Samalin-Scalzi, Fabienne Portales, Lise Roca, Claire Honfo Ga, Carinne Plassot, Marc Ychou, Pierre Guibert, Christelle De La Fouchardière, Mathieu Sarabi, Patrice Peyrat, Séverine Tabone-Eglinger, Caroline Renard, Guillaume Piessen, Stéphanie Truant, Alain Saudemont, Guillaume Millet, Florence Renaud, Emmanuelle Leteurtre, Patrick Gelé, Eric Assenat, Jean-Michel Fabre, François-Régis Souche, Marie Dupuy, Anne-Marie Gorce-Dupuy, Jeanne Ramos, Jean-François Seitz, Jean Hardwigsen, Emmanuelle Norguet-Monnereau, Philippe Grandval, Muriel Duluc, Dominique Figarella-Branger, Véronique Vendrely, Clément Subtil, Eric Terrebonne, Jean-Frédéric Blanc, Jean-Philippe Merlio, Dominique Farges-Bancel, Jean-Marc Gornet, Daniela Geromin, Geoffroy Vanbiervliet, Anne-Claire Frin, Delphine Ouvrier, Marie-Christine Saint-Paul, Philippe Berthélémy, Chelbabi Fouad, Stéphane Garcia, Nathalie Lesavre, Mohamed Gasmi, Marc Barthet, Vanessa Cottet, and Cyrille Delpierre

Subjects
Pancreatic cancer, RNA sequencing, Targeted DNA deep sequencing, Translational medicine, Predictive medicine, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Published
2024
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2. Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study

Author

Aurelien Amiot, Anne Bourrier, Jean-Marc Gornet, Olivier Dewit, Stephane Nancey, Romain Altwegg, Vered Abitbol, David Laharie, Catherine Reenaers, Charlotte Gagnière, Anthony Buisson, Maria Nachury, Stephanie Viennot, Lucine Vuitton, Carmen Stefanescu, Philippe Marteau, Guillaume Bouguen, and Philippe Seksik

Subjects
Crohn's disease, Ulcerative colitis, Inflammatory bowel disease, Healthcare worker, SARS-CoV-2, Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13–5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Published
2023
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3. Autologous organoid co-culture model reveals T cell-driven epithelial cell death in Crohn’s Disease

Author

Nassim Hammoudi, Sarah Hamoudi, Julie Bonnereau, Hugo Bottois, Kevin Pérez, Madeleine Bezault, Déborah Hassid, Victor Chardiny, Céline Grand, Brice Gergaud, Joëlle Bonnet, Leila Chedouba, My-Linh Tran Minh, Jean-Marc Gornet, Clotilde Baudry, Hélène Corte, Léon Maggiori, Antoine Toubert, Jacqueline McBride, Camille Brochier, Margaret Neighbors, Lionel Le Bourhis, and Matthieu Allez

Subjects
lymphoepithelial interactions, crohn’s disease, inflammatory bowel diseases, organoids, CD103, NKG2D, Immunologic diseases. Allergy, RC581-607
Abstract

Lympho-epithelial interactions between intestinal T resident memory cells (Trm) and the epithelium have been associated with inflammatory bowel disease (IBD) activity. We developed ex vivo autologous organoid-mucosal T cell cocultures to functionally assess lymphoepithelial interactions in Crohn’s Disease (CD) patients compared to controls. We demonstrate the direct epithelial cell death induced by autologous mucosal T cells in CD patients but not in controls. These findings were positively correlated with T cell infiltration of the organoids. This potential was inhibited by limiting lympho-epithelial interactions through CD103 and NKG2D blocking antibodies. These data directly demonstrate for the first time the direct deleterious effect of mucosal T cells on the epithelium of CD patients. Such ex-vivo models are promising techniques to unravel the pathophysiology of these diseases and the potential mode of action of current and future therapies.

Published
2022
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4. Gastrointestinal bleeding in critically ill immunocompromised patients

Author

Jennifer Catano, Sophie Caroline Sacleux, Jean-Marc Gornet, Marine Camus, Naike Bigé, Faouzi Saliba, Elie Azoulay, Guillaume Dumas, and Lara Zafrani

Subjects
Gastrointestinal bleeding, Intensive care unit, Immunocompromised host, Lymphoma, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Acute gastrointestinal bleeding (GIB) may be a severe condition in immunocompromised patients and may require intensive care unit (ICU) admission. We aimed to describe the clinical spectrum of critically ill immunocompromised patients with GIB and identify risk factors associated with mortality and severe GIB defined by hemorrhagic shock, hyperlactatemia and/or the transfusion of more than 5 red blood cells units. Finally, we compared this cohort with a control population of non-immunocompromised admitted in ICU for GIB. Results Retrospective study in 3 centers including immunocompromised patients with GIB admitted in ICU from January, 1st 2010 to December, 31rd 2019. Risk factors for mortality and severe GIB were assessed by logistic regression. Immunocompromised patients were matched with a control group of patients admitted in ICU with GIB. A total of 292 patients were analyzed in the study, including 141 immunocompromised patients (compared to a control group of 151 patients). Among immunocompromised patients, upper GIB was more frequent (73%) than lower GIB (27%). By multivariate analysis, severe GIB was associated with male gender (OR 4.48, CI95% 1.75–11.42, p = 0.00), upper GIB (OR 2.88, CI95% 1.11–7.46, p = 0.03) and digestive malignant infiltration (OR 5.85, CI95% 1.45–23.56, p = 0.01). Conversely, proton pump inhibitor treatment before hospitalization was significantly associated with decreased risk of severe GIB (OR 0.25, IC95% 0.10–0.65, p

Published
2021
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6. Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)

Author

Stefano Kim, Marine Jary, Thierry André, Véronique Vendrely, Bruno Buecher, Eric François, François-Clément Bidard, Sarah Dumont, Emmanuelle Samalin, Didier Peiffert, Simon Pernot, Nabil Baba-Hamed, Farid El Hajbi, Olivier Bouché, Jérôme Desrame, Aurélie Parzy, Mustapha Zoubir, Christophe Louvet, Jean-Baptiste Bachet, Thierry Nguyen, Meher Ben Abdelghani, Denis Smith, Christelle De La Fouchardière, Thomas Aparicio, Jaafar Bennouna, Jean-Marc Gornet, Marion Jacquin, Franck Bonnetain, and Christophe Borg

Subjects
Anal carcinoma, Advanced, Metastatic, Docetaxel, And chemotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients. Methods This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon’s optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy. Discussion Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA. Trial registration NCT02402842 , EudraCT: 2014–001789-81.

Published
2017
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7. Predictive factors for the success of endoscopic dilation of esophageal caustic stricture: the experience of a French tertiary reference center

Author

Nassim Hammoudi, Audrey Giaoui, Jérôme Lambert, Marion Dhooge, Hélène Corte, My-Linh Tran-Minh, Pierre Cattan, and Jean-Marc Gornet

Subjects
Adult, Treatment Outcome, Caustics, Esophageal Stenosis, Humans, Female, Surgery, Constriction, Pathologic, Dilatation, Retrospective Studies
Abstract

Predictors of the efficacy of endoscopic dilation for caustic esophageal stricture have been poorly studied.All patients undergoing an endoscopic dilation for an esophageal caustic stricture between 1990 and 2015 in a French national reference center were included. Success of dilation was defined by self-food autonomy without the need for reconstructive esophageal surgery.During the study period, 894 patients were admitted after caustic ingestion. Among them, 101 patients developed esophageal stricture and 92 patients were eligible for analysis (missing data in 8 cases, 1 patient died before endoscopic dilation). In this cohort (median age 42 years, women 53%, strong alkali 74%, suicide attempt 77%, hydrostatic balloon use 93%), the overall success rate of dilation was 57% with a median number of 3 dilation sessions (274 sessions, range 1-17). Factors predicting the success of the procedure were: non-inflammatory stricture or non-inflammatory intercalated mucosa between stricture (88% vs 47%, p = 0.001), a single stricture versus 2 or more strictures (69% vs 47% vs 33%, respectively, p = 0.04), a stricture of less than 5 cm (70% vs 27%, p 0.001) and the existence of mild/ moderately tight or very tight stricture (70% vs 21% of success, p 0.001). Perforation rate was 6.5% (18/274) requiring emergency surgery in 2 cases.Several characteristics of caustic esophageal strictures are significantly associated with the success rate of endoscopic dilation. Our data may be useful for customizing treatment strategies in patients with a caustic stricture.

Published
2022
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9. Obesity in adult patients with inflammatory bowel disease: Clinical features and impact on disability. A cross-sectional survey from the GETAID

Author

Rose Al Bacha, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Anne Bourrier, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Mathieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Matthieu Allez, Stephanie Viennot, Catherine Le Berre, David Laharie, Maria Nachury, Aurelien Amiot, Sara Tadbiri, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Carole Martins, Mathieu Uzzan, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Cecilia Landmann, Julien Kirchgesner, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Sandie Pestour, Thomas Chateau, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Arnaud Bourreille, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], Immunité muqueuse et vaccination, 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)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Grenoble, Service d'Hépato-gastro-entérologie [CHRU Nancy], 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 Toulouse (CHU Toulouse), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), and This study was supported by Abbvie.

Subjects
Crohn's disease, Disability, Ulcerative colitis, Hepatology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fatigue, Inflammatory bowel disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability.Aims: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability.Patients and methods: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals).Results: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3).Conclusion: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications.

Published
2023
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10. Kidney function monitoring in inflammatory bowel disease: The MONITORED consensus

Author

Lucas Guillo, Pierre Delanaye, Martin Flamant, Lucile Figueres, Sabine Karam, Sandrine Lemoine, Alban Benezech, Anne-Laure Pelletier, Aurélien Amiot, Bénédicte Caron, Carmen Stefanescu, Gilles Boschetti, Guillaume Bouguen, Jean-François Rahier, Jean-Marc Gornet, Jean-Pierre Hugot, Joëlle Bonnet, Lucine Vuitton, Maria Nachury, Mathias Vidon, Mathieu Uzzan, Mélanie Serrero, Nina Dib, Philippe Seksik, Xavier Hebuterne, Jean-Philippe Bertocchio, Christophe Mariat, Laurent Peyrin-Biroulet, CHU Marseille, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CRHU Nancy, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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 Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU UCL Namur, AP-HP Hôpital universitaire Robert-Debré [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHI Créteil, Hôpital Beaujon [AP-HP], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), No funding, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (MGD) Service de gastro-entérologie

Subjects
Kidney diseases, Consensus, Monitoring, Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, Inflammatory bowel diseases, Inflammatory Bowel Diseases, Kidney, Kidney Function Tests, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Humans, Kidney Diseases, 030211 gastroenterology & hepatology
Abstract

International audience; BACKGROUND AND AIMS: Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD. METHODS: A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement. RESULTS: Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient. CONCLUSION: The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients.

Published
2022
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11. Haemorrhagic shock secondary to a diffuse ulcerative enteritis after Ipilimumab and Nivolumab treatment for metastatic melanoma: a case report

Author

Thomas Aparicio, Noémie Trystram, Pauline Laly, Barouyr Baroudjian, Philippe Bertheau, and Jean-Marc Gornet

Subjects
Advanced and Specialized Nursing, Enteroscopy, Enterocolitis, medicine.medical_specialty, business.industry, Ipilimumab, medicine.disease, Gastroenterology, Infliximab, Enteritis, 03 medical and health sciences, 0302 clinical medicine, Anesthesiology and Pain Medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Ileitis, Nivolumab, medicine.symptom, Colitis, business, medicine.drug
Abstract

We provide a unique case of haemorrhagic shock complicating a corticosteroid-resistant diffuse ulcerative enteritis in a patient treated with a combination of an anti CTLA-4 and an anti PD-1 for metastatic melanoma. Immunotherapy has changed the perspective for the management of patients with metastatic melanoma but are also responsible for digestive complications mainly represented by immunomediated colitis. Digestive bleeding is common in patients with extensive colonic lesions but has never been described in enteritis independent of colitis. The patient with acute intestinal obstruction related ileitis without evidence of stricture on imaging and then had a gastro-intestinal bleed. In the absence of haemorrhagic lesions on upper gastrointestinal endoscopy, colonoscopy and CT angiography, a surgical exploration with enteroscopy was performed. This revealed an extensive ulcerated jejunoileitis, with active bleeding, within a Meckel's diverticulum. Management included resection of the Meckel diverticulum with a transient double barrel ileostomy. Two infliximab infusions were given due to persistent bleeding. We observed a dramatic improvement after infliximab treatment with complete cessation of bleeding and no further need for transfusions. A complete mucosal healing has been achieved on enteroscopy at 3 months with disappearance of histological inflammatory lesions. This observation suggests that infliximab represents a therapeutic option in severe enteritis and may be as effective as in more moderate immune-mediated enterocolitis.

Published
2022
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12. Appendiceal tumors and pseudomyxoma peritonei: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (RENAPE, RENAPATH, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR)

Author

Vahan Kepenekian, Frédéric Bibeau, Anthony Dohan, Juliette Fontaine, Olivier Bouché, Peggy Dartigues, Jean-Baptiste Delhorme, Diane Goéré, François Quenet, Gerlinde Averous, Clarisse Eveno, Benoit You, Pascal Rousset, Jean-Marc Gornet, Laurent Villeneuve, Pascale Mariani, Olivier Glehen, and Marc Pocard

Subjects
medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, General surgery, Gastroenterology, Physical examination, Evidence-based medicine, Pseudomyxoma Peritonei, medicine.disease, Clinical Practice, Appendiceal Neoplasms, Radiological weapon, medicine, Humans, Pseudomyxoma peritonei, Hyperthermic intraperitoneal chemotherapy, France, business, Cytoreductive surgery, Pathological, Peritoneal Neoplasms, Societies, Medical
Abstract

Introduction This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) ( www.tncd.org ). Methods All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence. Results AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies. Conclusion These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.

Published
2022
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14. Predictive factors of severe early treatment-related toxicity in patients receiving first-line treatment for metastatic colorectal cancer: Pooled analysis of 2190 patients enrolled in Fédération Francophone de Cancérologie Digestive (FFCD) trials

Author

Clémence Breton, Jean-Baptiste Bachet, Jaafar Bennouna, Sylvain Manfredi, Jean-Louis Legoux, Aimery de Gramont, Karine Le Malicot, Thomas Aparicio, Thierry Lecomte, Olivier Bouché, Michel Ducreux, Olayidé Boussari, Julien Taieb, and Jean-Marc Gornet

Subjects
Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Neoplasm Metastasis, Aged, Aflibercept, Chemotherapy, Performance status, business.industry, Middle Aged, Prognosis, medicine.disease, Oxaliplatin, Irinotecan, Treatment Outcome, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Toxicity, Female, Colorectal Neoplasms, business, medicine.drug
Abstract

Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC).Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3).Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0-1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80-0.96]; p = 0.004).ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation.

Published
2021
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15. Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study

Author

Mathurin Fumery, Jérôme Filippi, Vered Abitbol, Amélie Biron, David Laharie, Melanie Serrero, Romain Altwegg, Yoram Bouhnik, Laurent Peyrin‐Biroulet, Cyrielle Gilletta, Xavier Roblin, Guillaume Pineton de Chambrun, Lucine Vuitton, Anne Bourrier, Stephane Nancey, Jean‐Marc Gornet, Stephane Nahon, Guillaume Bouguen, Stephanie Viennot, Maria Nachury, Aurelien Amiot, Franck Brazier, Clara Yzet, Xavier Hebuterne, Guillaume Cadiot, Hedia Brixi, Pauline Rivière, Florian Poullenot, Xavier Treton, Carmen Stefanescu, Camille Zallot, Laurent Beaugerie, Philippe Seksik, Harry Sokol, Julien Kirchgesner, Gilles Boschetti, Bernard Flourié, Claire Gay, Pauline Danion, Chloe Venturin, Matthieu Allez, Clotilde Baudry, Benjamin Pariente, Pauline Wils, Charlotte Gagnière, Jenny Tannoury, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], CHU Marseille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, CHI Créteil, GETAID, Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Adult, Male, medicine.medical_specialty, Pancolitis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Ustekinumab, Humans, Medicine, Pharmacology (medical), Adverse effect, Colectomy, Hepatology, business.industry, Remission Induction, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug, Cohort study
Abstract

International audience; Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. Aims To assess the real-world effectiveness and safety of ustekinumab in patients with UC. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score

Published
2021
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16. Cephalic Duodenopancreatectomy for Hyperalgic Duodenal Crohn's Disease Fistulized in the Pancreatic Gland

Author

Sabra Guellouz, Benjamin Pariente, Claire Benet, Clotilde Baudry, Nelson Lourenco, Aurore Kraemer, Matthieu Allez, and Jean-Marc Gornet

Subjects
Cephalic duodenopancreatectomy, Crohn’s disease, Fistula, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Upper gastrointestinal (GI) tract involvement in adult Crohn's disease (CD) is rare and severe complications unusual. Stenosis has been reported, but gastroduodenal fistulae are seldom detected during surgery and most of the fistulae are cologastric or ileogastric. In complicated gastroduodenal CD, medical treatments are often effective and surgery is only considered in exceptional cases. We here report the unusual case of a 23-year-old patient with upper GI CD presenting a hyperalgic giant ulcer of the bulb fistulized in the pancreatic gland. The failure of steroids and two lines of combined treatment led us to a salvage surgical option. Abdominal exploration showed a plate stomach with an inflammatory bulboduodenal block. Cephalic duodenopancreatectomy and cholecystectomy were performed; histological analysis reported large fissuring pylorus ulceration with micro abscesses reaching the pancreas and the presence of non-caseating granulomas. Six months after the surgery, the patient had stopped antalgic treatment and did not have residual abdominal pain. He had gained 11 kg in weight and had no diarrhea with pancreatic enzymes. To our knowledge, we report the first case of an upper GI and fistulizing CD patient heavily treated with steroids and combined immunosuppressant agents requiring salvage cephalic duodenopancreatectomy.

Published
2014
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17. Prevalence of anti-TNF contraindications in Crohn’s disease: A cross-sectional survey from the GETAID

Author

Aurelien Amiot, Philippe Seksik, Jean-Marie Reimund, Maria Nachury, Romain Altwegg, Arnaud Bourreille, Stephanie Viennot, Mathurin Fumery, Xavier Roblin, Melanie Serrero, Matthieu Allez, Claire Painchart, Elise Chanteloup, Lucine Vuitton, Ginette Fotsing, Anthony Buisson, Baya Coulibaly, Stephane Nancey, Cyrielle Gilletta, Laurianne Plastaras, Vered Abitbol, Lucas Guillo, Marion Simon, Stephane Nahon, David Laharie, Laurent Peyrin-Biroulet, Guillaume Bouguen, Charlotte Gagniere, Pauline Wils, Yoram Bouhnik, Carmen Stefanescu, Xavier Treton, Carole Martins, Mathieu Uzzan, Emilie Del Tedesco, Laurent Beaugerie, Anne Bourrier, Cecilia Landmann, Julien Kirchgesner, Harry Sokol, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Medina Boualit, Lucile Boivineau, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Hospital of Montpellier, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Aix Marseille Université (AMU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier [Valenciennes, Nord], Hôpital Saint-Joseph [Marseille], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Clermont-Ferrand, Centre Hospitalier Henri Duffaut (Avignon), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CH Colmar, Hôpital Cochin [AP-HP], Institut Mutualiste de Montsouris (IMM), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Bordeaux [Bordeaux], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], This study was supported by an institutional grant by Takeda, CRHU Nancy, 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Etienne, and CHU Toulouse [Toulouse]

Subjects
Crohn’s disease, Hepatology, Contraindications, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Inflammatory bowel disease, Anti-TNF, Cross-Sectional Studies, Treatment Outcome, Crohn Disease, Prevalence, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Contraindication
Abstract

International audience; BACKGROUND: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. METHODS: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn’s disease, assessing each patient’s potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. RESULTS: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians’ preferred first-line biological therapy choice for 78.2%. CONCLUSION: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn’s disease. Physicians’ choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age.

Published
2022
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18. Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

Author

Xavier Treton, Helene Corte, Jean-Marc Gornet, Jérôme Lambert, Nicolas Munoz-Bongrand, Mathias Vidon, Yves Panis, Jean-David Zeitoun, Philippe Seksik, Laurent Abramowitz, Matthieu Allez, and Léon Maggiori

Subjects
Adult, Anal fistula, medicine.medical_specialty, Combination therapy, Fistula, Population, Fibrin Tissue Adhesive, law.invention, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Randomized controlled trial, law, Humans, Rectal Fistula, Medicine, Cumulative incidence, education, Fibrin glue, Retrospective Studies, education.field_of_study, Crohn's disease, business.industry, Gastroenterology, medicine.disease, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Tissue Adhesives, 030211 gastroenterology & hepatology, business
Abstract

Aim The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. Methods This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. Results In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. Conclusion An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.

Published
2020
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19. Une complication digestive rare sous anti-PD-1 (pembrolizumab)

Author

Jean-Marc Gornet, Maxime Battistella, Julien Calvani, Justine Vivier-Chicoteau, Barouyr Baroudjian, Céleste Lebbé, Julie Delyon, Philippe Bertheau, and Rémie Elia

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Pathology and Forensic Medicine
Abstract

Resume Le type de colite le plus frequemment observe sous immunotherapie anti-PD-1 est celui d’une colite aigue active a polynucleaires neutrophiles. A l’inverse, la colite collagene, qui appartient a la famille des colites microscopiques, est exceptionnelle. Nous rapportons un cas de colite collagene chez un homme de 76 ans, traite par pembrolizumab pour un melanome cutane multimetastatique. Quatorze mois apres l’introduction du pembrolizumab, le patient a developpe une diarrhee de grade 3 (jusqu’a 9 selles liquides non glairo-sanglantes/j), associee a une profonde hypokaliemie. Aucun agent infectieux n’a ete identifie. La rectosigmoidoscopie a mis en evidence une congestion colique diffuse, sans ulceration. Les biopsies coliques systematiques ont revele un epaississement de la bande collagene sous-epitheliale, mesurant entre 20 et 30 μm d’epaisseur, associe a une augmentation moderee de la cellularite inflammatoire du chorion, avec presence de lymphocytes et plasmocytes. Le patient a ete efficacement traite par un arret temporaire du pembrolizumab et la mise en place d’une corticotherapie (prednisone) a la dose de 0,8 mg/kg/j, d’abord intraveineuse, puis par voie orale, avec decroissance progressive sur 6 semaines. Lors de la decroissance de la prednisone, une recidive des diarrhees a ete observee. Il a donc ete propose un relais par budesonide 9 mg/j permettant une resolution complete et definitive des diarrhees. Le budesonide a depuis ete stoppe. Le pembrolizumab n’a pour l’instant pas ete repris. Il existe actuellement une progression osseuse localisee du melanome, traitee par radiotherapie seule. En cas de reprise evolutive plus importante, un nouveau traitement systemique pourra etre discute.

Published
2020
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20. Long-term outcome of patients with acute severe ulcerative colitis responding to intravenous steroids

Author

Julien Kirchgesner, Antoine Meyer, Jean-Marc Gornet, Aurelien Amiot, Laurent Beaugerie, Matthieu Allez, Franck Carbonnel, and Robert Salameh

Subjects
medicine.medical_specialty, Multivariate analysis, Hepatology, business.industry, medicine.medical_treatment, Hazard ratio, Gastroenterology, Retrospective cohort study, medicine.disease, Ulcerative colitis, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Medicine, 030211 gastroenterology & hepatology, Pharmacology (medical), 030212 general & internal medicine, business, Intravenous steroids, medicine.drug, Colectomy
Abstract

BACKGROUND The long-term outcome of patients with acute severe ulcerative colitis (ASUC) responding to intravenous steroids (IVS) has been poorly reported. AIMS To assess relapse-free survival in patients with ASUC responding to IVS. METHODS Between January 2006 and December 2017, 142 consecutive patients with ASUC (according to modified Truelove-and-Witts criteria) responding to IVS were included in this multicentre retrospective study. Relapse was defined by a partial Mayo Clinic score >4 and/or the need for another maintenance therapy. RESULTS Among the 142 included patients (100 naive of immunomodulator and/or biological agent) hospitalised for ASUC, 59 (41.5%) were treated at discharge with 5-aminosalicylic acid, 60 (42%) with immunomodulators, 18 (13%) with anti-tumour necrosis factor (TNF) agents and 5 (3.5%) with vedolizumab. After a median follow-up of 4.8 (2.6-7.3) years, 90 (63.4%) had relapsed and 12 (8.5%) had required colectomy. The probabilities of relapse-free survival were 58%, 48% and 40% at 1, 2 and 5 years respectively. The multivariate analysis demonstrated that patients with

Published
2020
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21. Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study

Author

Vered Abitbol, Aurelien Amiot, Caroline Besson, Xavier Treton, Laurent Beaugerie, Catherine Thieblemont, Paul Coppo, Anouk Walter-Petrich, Thomas Aparicio, Georgia Malamut, Julien Kirchgesner, Lionel Galicier, Dominique Cazals-Hatem, Bénédicte Deau-Fischer, Matthieu Allez, Jean Marc Gornet, T. Severyns, Jérôme Lambert, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Henri Mondor AP-HP/UPEC, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Hôpital Beaujon, 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), Unité de neurophysiologie [CHU Saint-Antoine], 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), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Male, medicine.medical_specialty, Lymphoma, [SDV]Life Sciences [q-bio], medicine.medical_treatment, IBD, Population, Antineoplastic Agents, Lymphoma, T-Cell, Inflammatory bowel disease, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Interquartile range, hemic and lymphatic diseases, Internal medicine, medicine, Humans, B-cell lymphoma, education, Digestive System Surgical Procedures, Neoplasm Staging, Biological Products, education.field_of_study, Chemotherapy, business.industry, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, Hodgkin Disease, Chemotherapy regimen, 3. Good health, Intestines, 030220 oncology & carcinogenesis, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, France, Lymphoma, Large B-Cell, Diffuse, business, Immunosuppressive Agents
Abstract

Background and Aims The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. Methods A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. Results A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. Conclusions In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

Published
2020
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22. Predictive factors for early progression during induction chemotherapy and chemotherapy-free interval: analysis from PRODIGE 9 trial

Author

Jean-Marc Phelip, Valérie Boige, Karine Le Malicot, Julien Taieb, Jean-Marc Gornet, Jaafar Bennouna, Olivier Bouché, Eric Francois, for Prodige investigators, Veronique Guerin-Meyer, Oana Cojocarasu, Marie-Christine Kaminsky, Joëlle Egreteau, Laetitia Dahan, Jean-Baptiste Bachet, François Ghiringhelli, Roger Faroux, Mohamed Gasmi, Thomas Aparicio, Christian Borel, and Côme Lepage

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Multivariate analysis, Colorectal cancer, medicine.medical_treatment, Logistic regression, Article, law.invention, Free interval, Prognostic markers, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Aged, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, medicine.disease, Clinical trial, 030220 oncology & carcinogenesis, Disease Progression, Female, Colorectal Neoplasms, business
Abstract

Background Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges. Methods A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10. Results In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02–3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68–7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92–3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96–3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058). Conclusion High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC. Clinical trial number NCT00952029.

Published
2020
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23. Management of immune checkpoint inhibitor in patients with cancer and pre-existing inflammatory bowel disease: Recommendations from the GETAID

Author

Aurelien Amiot, David Laharie, Georgia Malamut, Melanie Serrero, Florian Poullenot, Laurent Peyrin-Biroulet, Arnaud Bourreille, Lucine Vuitton, Guillaume Bouguen, Vered Abitbol, Amelie Biron, Anne Bourrier, Ludovic Caillo, Mathurin Fumery, Cyrielle Gilletta, Laurianne Plastaras, Marion Simon, Stephanie Viennot, Philippe Seksik, Alain Attar, Anthony Buisson, Benedicte Caron, Maeva Charkaoui, Jean-Marc Gornet, Lucas Guillo, Catherine Le Berre, Edouard Louis, Nicolas Mathieu, Maria Nachury, Stephane Nancey, Stephane Paul, Catherine Reenaers, Xavier Treton, Mathieu Uzzan, and Pauline Wils

Subjects
Diarrhea, Hepatology, Recurrence, Neoplasms, Gastroenterology, Humans, Colitis, Inflammatory Bowel Diseases, Immune Checkpoint Inhibitors, Retrospective Studies
Abstract

There is no consensus on the management of immune checkpoint inhibitor (ICI) for treating cancer in patients with pre-existing inflammatory bowel disease (IBD). The Groupe d'Étude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) aimed to provide recommendations on this topic.A dedicated working group performed a comprehensive expert-based review of the literature, generated clinical key question and shaped recommendations that were further voted for approval by the educational and scientific committees of the GETAID. Using consensus methods, treatment modalities were defined by vote.Majority of patients with IBD in clinical remission can be treated with ICI after cancer diagnosis. The rate of relapse or immune-related diarrhoea or colitis upon ICI treatment is up to 39.8% and is maximal with ICI combination therapy compared to monotherapies. When starting ICI in a patient with IBD, it is recommended to assess disease activity and pursue ongoing maintenance therapy. In case of relapse or immune-related diarrhoea or colitis upon ICI treatment, treatment depends on grading of diarrhoea or colitis and may include corticosteroid therapy, infliximab and/or vedolizumab.In the present publication, we provided recommendations, which may assist gastroenterologists, haematologists, and oncologists for a better management of patients with pre-existing IBD before and during cancer treatment with ICI.

Published
2022

24. Impact of HIV Infection on the Course of Inflammatory Bowel Disease and Drug Safety Profile: A Multicenter GETAID Study

Author

Lucas Guillo, David Laharie, Mélanie Serrero, Anne-Laure Pelletier, Hélène Rousseau, Laurent Peyrin-Biroulet, Mathieu Uzzan, Christian Rabaud, Stephanie Viennot, Laurence Picon, Vered Abitbol, Mathias Vidon, Ludovic Caillo, Aurelien Amiot, Laurent Beaugerie, Morgane Amil, Maria Nachury, Jérôme Filippi, Jean-Marc Gornet, Stéphane Nancey, Romain Altwegg, Michael T. Collins, Catherine Reenaers, Felix Goutorbe, Alban Benezech, Grégory Dubourg, Anthony Buisson, Cédric Baumann, Hôpital Nord [CHU - APHM], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Hopital Saint-Louis [AP-HP] (AP-HP), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Bordeaux [Bordeaux], Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier de la Côte Basque (CHCB), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Henri Duffaut (Avignon), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Délégation à la Recherche Clinique et à l'Innovation [CHRU Nancy] (DRCI), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], HIV Infections, Disease, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, Crohn Disease, Internal medicine, medicine, Humans, Retrospective Studies, Crohn's disease, Hepatology, business.industry, Hazard ratio, Gastroenterology, Retrospective cohort study, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 030220 oncology & carcinogenesis, Concomitant, 030211 gastroenterology & hepatology, Colitis, Ulcerative, business
Abstract

Background and aims Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. Methods We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. Results Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. Conclusion Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations.

Published
2022
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25. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Author

Laurent Peyrin-Biroulet, Jean-François Rahier, Julien Kirchgesner, Vered Abitbol, Sebastian Shaji, Alessandro Armuzzi, Konstantinos Karmiris, Javier P. Gisbert, Peter Bossuyt, Ulf Helwig, Johan Burisch, Henit Yanai, Glen A. Doherty, Fernando Magro, Tamás Molnar, Mark Löwenberg, Jonas Halfvarson, Edyta Zagorowicz, Hélène Rousseau, Cédric Baumann, Filip Baert, Laurent Beaugerie, Jean-Marc Gornet, Jean-Marie Reimund, Xavier Hebuterne, Aurélien Amiot, Franco Armelao, Pierre Blanc, Claudio Papi, Guillaume Pineton De Chambrun, Xavier Roblin, null Chu, Sohail Shariq, Nikolaos Viazis, Jimmy Limdi, Piotr Eder H, Georgios Michalopoulos, Andrew Bell, Livia Biancone, Marie Dewitte, Zia Mazhar, Denis Franchimont, Stephane Nancey, Gilles Macaigne, Maria Beatrice Principi, Mathurin Fumery, Gareth Parkes, Jean-Christophe Valats, Glen Doherty, Guillaume Bouguen, Hersin Tsai, Mohsin Gangi, Natalia Pedersen, Frédéric Heluwaert, Richard Shenderey, Sebastian Zeissig, Jeffrey Butterworth, Fabiana Castiglione, Lynsey Corless, Camille Zallot, Salil Singh, Sunil Sonwalkar, Elizabeth Clayton, Deven Vani, Guy Bellaiche, Martine De Vos, Uri Kopylov, Triana Lobaton, Christophe Locher, Gerassimos Mantzaris, George Abouda, Katie Smith, Michael Sprakes, Angeliki Theodoropoulou, Emma Wesley, Joëlle Bonnet, David Elphick, Cyrielle Gilletta, John Gordon, David Laharie, Antoine Nakad, Ambrogio Orlando, Patrick Dubois, Peter Hasselblatt, Christophe Michiels, Cathryn Preston, Anca Staicu, Lucine Vuitton, Mehdi Kaassis, Ally Speight, Deb Ghosh, Nicolas Mathieu, Anne-Laure Pelletier, Anne Phillips, Romain Altwegg, Irit Avni, null biron, Jonathon Landy, Maria Nachury, Achuth Shenoy, Caroline Trang, Georgios Bamias, Klaudia Farkas, Christian Maaser, Ariella Shitrit, Britta Siegmund, Jérôme Filippi, Colm O'morain, Laurent Costes, David Hobday, Zoltán Szepes, Emma Calabrese, Helen Dallal, Michael Fung, Arvind Ramadas, Bijay Baburajan, Konrad Koss, Christophe Barberis, Anthony Buisson, Morgane Amil, Paola Balestrieri, Matthew Johnson, Maria Tzouvala, Stéphanie Viennot, Ferenc Nagy, Nick Thompson, Laurent Alric, Sunil Samuel, Anne Bourrier, Elise Chanteloup, Emilie Del Tedesco, Marcus Harbord, Alan Lobo, Sally Myers, Richard Pollok, Tariq Ahmad, Rakesh Chaudhary, Christos Karakoidas, Ashraf Soliman, Carmen Stefanescu, Georgios Theocharis, Stijn Vanden Branden, Belén Beltran, Yoram Bouhnik, Arnaud Bourreille, Joana Branco, Ben Colleypriest, Rami Eliakim, Paul Knight, Aoibhlinn O'toole, Virgina Robles, Konstantinos Triantafyllou, Marta Maia Bosca, Guy Lambrecht, Lucia Marquez Mosquera, Simon Panter, Aikaterini Pappa, Marion Simon, Ganesh Sivaji, Christophe Bellanger, Arthur Belle, Natalia Borruel, Laurence Egan, Harald Peeters, Daniel Sharpstone, Ramesh Arasaradnam, José Manuel Benitez, Jens Frederik Dahlerup, Olga Giouleme, Miguel Minguez, Eftychia Tsironi, Angela Variola, Patrick Allen, Lucille Boivineau, Andy Cole, Nina Dib, Fernando Gomollon, Richard Johnston, Konstantinos Katsanos, Nick Kennedy, Marianne Kiszka-Kanowitz, Ignacio Marin-Jimenez, Pál Miheller, Pilar Nos, Othman Saraj, Lars Vinter-Jensen, Eran Zittan, Clotilde Baudry, Xavier Calvet, Marie-Christine Cazelles-Boudier, Jean-Louis Coenegrachts, Garret Cullen, Marco Daperno, Anjan Dhar, Romain Gerard, Nanna Jensen, Nitsan Maharshak, Mark Mcalindon, Simon Mcloughlin, Miles Parkes, Kamal Patel, Armando Peixoto, Dimitrios Polymeros, Francisco Portela, Rodolfo Rocca, Philippe Seksik, Sreedhar Subramanian, Ruth Tennenbaum, Raja Atreya, Oliver Bachmann, Arthur Berger, Renáta Bor, Maire Buckley, Daniel Carpio, María Chaparro, Francesco Costa, Eugeni Domenech, Maria Esteve, Stephen Foley, Jordi Guardiola, Ioannis Koutroubakis, Tanja Kuehbacher, Cécilia Landman, Alessandro Lavagna, Noemí Manceñido, Míriam Mañosa, Maria Dolores Martín-Arranz, Laurianne Plastaras, Maria Lia Scribano, Subhasish Sengupta, Nils Teich, My-Linh Tran-Minh, Evanthia Zampeli, Leila Amininejad, Teresa Arroyo, Alain Attar, Ann-Sofie Backman, Anita Bálint, John Beckly, Shomron Ben Horin, Sónia Bernardo, Ludovic Caillo, Bénédicte Caron, María Shanika de Silva, Anna FábiáN, Gionata Fiorino, Ana Gutierrez, Adi Lahat, Mohamed Masmoudi, Marco Mendolaro, Vinciane Muls, Florian Poullenot, Christopher Probert, Catherine Reenaers, Mariann Rutka, Zaman Sarwari, Joanne Sayer, Beatriz Sicilia, Helena Sousa, Catherine van Kemseke, Yamile Zabana, Marco Astegiano, Paul Banim, Dominik Bettenworth, Médina Boualit, Jacob Broder Brodersen, Angeliki Christidou, Rachel Cooney, João Cortez Pinto, Portugal Marília Cravo, Anneline Cremer, Silvio Danese, Antonio di Sabatino, Jan Fallingborg, Antonio Ferronato, Esther Garcia Planella, Sanjay Gupta, Eran Israeli, Samantha Kestenbaum, Lone Larsen, Elisabeth Macken, Nicoletta Mathou, Ágnes Milassin, Joanna Pofelski, Chiara Ricci, Francisco Rodriguez-Moranta, Martin Schmidt-Lauber, Ian Shaw, Marta Soares, Heithem Soliman, Christos Triantos, Konstantinos Zografos, Anurag Agrawal, Alexandre Aubourg, Manuel Barreiro-de Acosta, Jesús Barrio, Daniel Bergemalm, Fernando Bermejo, Giorgia Bodini, Johan Bohr, Dimitrios Christodoulou, Christophe Claessens, Paul Collins, Ruth de Francisco, Santiago Garcia, Sotirios Georgopoulos, Felix Goutorbe, Chrisostomos Kalantzis, Anastasia Kourikou, Vincent Mace, Georgia Malamut, Paula Ministro, Isabelle Nion Larmurier, Elena Ricart, Mélanie Serrero, Juliette Sheridan, Petra Weimers, Vibeke Andersen, Bruno Arroja, Bernd Bokemeyer, Luis Bujanda, Thibault Degand, Carl Eriksson, Cécile Garceau, Henning Glerup, Idan Goren, Lucina Jackson, Stéphane Koch, Francisco Mesonero, Ingrid Ordas, Pauline Riviere, Simone Saibeni, João Soares, Noémie Tavernier, Klaus Theede, Bella Ungar, Elke Bästlein, Antonio Gasbarrini, Andreas Protopapas, Wolfgang Reindl, Fabrizio Bossa, Ailsa Hart, Franz-Josef Heil, Anthony O'Connor, Bas Oldenburg, Luca Pastorelli, null Stephen patchett, Subramaniam Ramakrishnan, John de Caestecker, Ana Echarri, David Kevans, Jürgen Büning, Rosa Coelho, Jeroen Jansen, Benjamin Koslowski, Christopher Wells, Daniel Ceballos, Ingrid König, Hari Padmanabhan, Timi Patani, Raheel Qureshi, Matthieu Allez, Emmanouil Archavlis, Delphine Bonnet, Luisa Guidi, Deirdre Mcnamara, Piero Vernia, Michael Weidenhiller, Lang Alon, Trine Boysen, Charlotte Delattre, Richard Farrell, Rolf-Achim Krüger, Thierry Paupard, Ida Vind, Flavio Caprioli, Vladimir Gancho, Vincent Quentin, Benjamin Avidan, Geert D’Haens, Jane Mccarthy, Jonathon Snook, Konstantinos Soufleris, Frank Zerbib, Dan Carter, Annekatrien Depla, Thomas Eisenbach, Walter Fries, Nikolaos Grammatikos, Saskia Ilegems, Antonio Lopez-Sanroman, Jacques Moreau, Gabriele Riegler, Svend Rietdijk, Marta Rocha, Isabelle Rosa, Barbara Ryan, Yelena Yeremenko, Arnaud Boruchowicz, Filipe Damião, Foteini Laoudi, Andreas Lügering, Giampiero Macarri, Konstantinos Thomopoulos, Luísa Barros, Thomas Blixt, Aurélien Garros, Sam Khorrami, Harry Sokol, Andreas Sturm, Dan Livovsky, Jochen Maul, Heinrich Miks, Vasileios Papadopoulos, Carsten Schmidt, Yifat Snir, Lise Svenningsen, Wafaa Ahmed, Yelena Broitman, Emmanuel Cuillerier, Prashant Kant, Jan Leyden, Lev Lichtenstein, Susana Lopes, Chloé Martineau, Hugh Mulcahy, Axel Schweitzer, Fiona Van Schaik, Hagar Banai, Pauline Danion, Charlotte Dulery, Herma Fidder, Claire Gay, Hervé Hagege, Florence Harnois, Søren Peter Jørgensen, Jens Müller-Ziehm, Michail Oikonomou, Carolina Palmela, Jörg Schulze/Röske, Mark Smith, Tamar Thurm, Francesca Bresso, Hedia Brixi, John Jones, Padraig Macmathuna, Claire Painchart, Yulia Ron, Marianne Vester-Andersen, Gonçalo Alexandrino, Norbert Börner, Mariana Cardoso, Cristina Chagas, Axel Dignaß, Iris Dotan, Charlotte Hedin, Pantelis Karatzas, Panagiotis Kasapidis, Károly Palatka, Georgios Sakizlis, Ana Wilson, Nick Bosanko, Paulo Caldeira, Charlotte Gagniere, Louise Libier, Camille Meunier, Gero Moog, Audrey Pasquion, Roberta Pica, Ayesha Akbar, Nadia Arab, Guillaume Cadiot, João Carvalho, Claire Charpignon, Laus Fellermann, Sigal Fishman, Gerald Fraser, Nathan Gluck, Mark Hoesl, Jarosław Kierkus, Maria Klopocka, Eduardo Martin Arranz, Luis Menchen, Susanna Nikolaus, Anca Petrache, Cyriel Ponsioen, Sabino Riestra, Pilar Robledo, Cristina Rodriguez, Misheal Samer, Matthias Tischer, Joanna Wypych, Julien Baudon, Cristina Bezzio, Gilles Boschetti, Tom Creed, Maria Giulia Demarzo, Stefano Festa, Andrés Figueroa, Mette Julsgaard, Pablo Navarro, Pablo Perez-Galindo, Cléa Rouillon, Emanuele Sablich, Joan Tosca, Mathias Vidon, Marine Vidon, René-Louis Vitte, Anne Wampach, Isabelle Clerc Urmes, Marc Borie, Mathieu Uzzan, Kelly Chatten, Rimmer Peter, Iqbal Tariq, Marta Cossignani, Fiorella Cañete, Tom Holvoet, Susanne Krasz, Sandra Dias, Hadas Abalia, Aziza Abaza, Gal Abramovich, Ingrid Ackzell, Carol Adams, Catherine Addleton, Erika Alfambra, Alicia Algaba, Clare Allcock, Joanna Allison, Karine Amouriaux, Julie Anderson, Emma Anderson, Saskia Appelmans, Lisa Armstrong, Stacey Atkins, Masoumeh Attaran-Bandarabadi, Yvonne Bailey, Stephanie Bardot, Natasha Beck, Lillie Bennett, Jonathan Phil Bergfeld, Ramdane Berkane, Hanne Boey, Louise Bowlas, Joanne Bradley-Potts, Tracy Brear, Nicole Bretlander-Peters, Ellen Brown, Johanna Brown, Elizabeth Buckingham, Katrien Buellens, Rhian Bull, Maura Burke, Leighanne Burns, Julie Burton, Agness Bwalya, Karine Cabanas, Muriel Callaghan, Océane Camou, Debbie Campbell, Elvira Capoferro, Mandy Carnahan, Cornelia Carnio, Anne Carter, Concetta Casali Clack, Leïla Chedouba, Bessie Cipriano, Sophie Claeys, Manon Closset, Dilek Coban, Sara Cococcia, Carolann Coe, Helen Cole, Emilie Collet, Kayleigh Collins, Isabelle Combes, Emma Connor, Kathryn Constantin, Susan Cooke, Nathanaëlle Cornet, Estelle Corrihons, Pilar Corsino, Rosie Cortaville, Donna Cotterill, Amanda Cowton, Harriet Cox, Viktoria Cripps, Amanda Crowder, Tzufit Cukier, Amelia Daniel, Chris Dawe, Jose de Haan, Rosanna de la Croix, Evva Dejonckheere, Juan Delare Villanegro, Guillaume Delaval, Mariangela Delliponti, Aude Delommez, Emilie Detry, Melanie Dhanaratne, Laura Diez Galan, Marie Dodel, Emma Dooks, Joseph Du Cheyron, Linda Duane, Jennifer Dulling Vulgo Cochran, Simona Dyer, Harvey Dymond, Charlotte Ekblad, Kerry Elliott, Ingrid Emmerson, Irène Eugene-Jolchine, Lorna Fleming, Eve Fletcher, Sarah Ford, Greg Forshaw, Angela Foulds, Caroline Francois, Nicole Fuge, Gal Gafni, Miri Ganon, Olga Garcia Nuñez, Laura Garcia Ramirez, Sophie Gelder, Raimonda Gettkowski, Daniela Gilardi, Paolo Giuffrida, Vincent Gobert, Jo Godden, Nuala Godwin, Kay Goulden, Sharon Graham, Charlotte Green, Marie Green, Aboubakar Gueye, Tuba Guler, Ida Gustavsson, Helena Hadjisavvas, Fiona Hammonds, Christina Hantzi, Marion Hauke, Julie Haydock, Orla Hayes, Lizette Helbo Nislev, Jessica Hochstodter, Ashleigh Hogg, Manuela Hölbing, Maureen Holland, Maartje Holsbergen, Linda Howard, Aviya Hoyda, Robert Hull, Jane Irish, Wendy Jackson, Wendy Janssen, Lesley Jeffrey, Sofia Jourdan, Izabela Jutrowska, Chava Kaniel, Theofilos Karezos, Niamh Kelly, Jessica Kelly, Mary Kennedy, Una Kennedy, Joyce Kibaru, Gemma Kirkman, Janine Klaproth, Corinna Kneese, Andrea Koch, Kathleen Kokke, Martha Koppelow, Sabine Krause, Sabine Krauspe, Petra Kwakkenbos, Nunzia Labarile, Hannah Lang, Marianne Lassailly, Martine Leconte, Linda Lepczynski, Emma Levell, Nina Levhar, Kerstin Lindhort, Jessica Lisle, Beatriz Lopez Cauce, Gabriele Lorenz, Ambra Lovati, Tracey Lowry, Margareta Lund, Anne Lutz Vorderbrügge, Suzanne Maansson, Videsheka Madapathage, Maelys Cheviakoff, Alison Magness, Orla Manley, Catherine Manyoni, Ingke Marg, Antonella Marra, Carole Martins, Arianna Massella, Aurore Mathias, Danielle Mervyn, Charlotte Minsart, Sally Mitchell, Kathleen Monks, Mélanie Montero, Alson Moore, Maren Moser, Alison Moss, Angela Mullen, M. Francisca Murciano, Deanna Naylor, Ansgar Nehus, Anne Nicholson, Sarah Nöding, Sinead Nolan, Janet Nörenberg, Clare Northcott, Jim O'Connell, Alison O’Kelly, Noam Orbach-Zingboim, Judit Orobitg, Charlene Otieno, Charlotte Owen, Sarah Patch, Maor Pauker, Renate Pauli, Harriet Pearson, Falgon Peggy, Séverine Petit, Christine Petrissans, Simona Piergallini, Lucy Pippard, Laura Pitt, Gabriella Pócsik, Yoann Poher, Chloé Pomes, Lucy Pritchard, Laura Puchades, Sheena Quaid, Aleem Rana, Dana Raynard, Mykla Reilly, Sonja Reinert, Manuela Reinknecht, Baerbel Renner, Rob Reynolds, Giulia Rizzuto, Matthew Robinson, Joke Robrechts, Eva M. Rodriguez, Efrat Rosenblum, Tamlyn Russel, Ibiyemi Sadare, Noa Salama, Toos Schakel, Anja Schauer, Elisa Schiavoni, Caroline Shaw, Sarah Shelton, Virginie Sicart, Elodie Siouville, Orla Smith, Théo Soude, Sophie Stephenson, Elaine Stephenson, Marjan Steppe, An Sterkx, Jo Stickley, Kathleen Sugrue, Natalia Swietec, Charlotte Tasiaux, Bhavneet Thamu, Susane Thomas, Ogwa Tobi, Kahina Touabi, Shifra Tovi, Julie Tregonning, Laura Turchini, Julia Unkhoff, Olesya Unruh, Nurcan Uzun, Frauke Van Aert, Sandrine Vanden Bergh, Louise Vandenbroucke, Laura Vansteenkiste, Shay Vardit, Valentin Vergriete, Elaine Walker, Eleanor Warner, Olivia Watchorn, Ekaterina Watson, Marie-Claire Wauthier, Belgium Maria Weetman, Margaret Weston, Wiebke West-Petroschka, Susann Wienecke, Kerstin Wierling, Miriam Wiestler, Rebecca Wilcox, Elva Wilhelmsen, Angharad Williams, Georgina Williamson, Deborah Wilson, Kate Wistance, Nicolas Wortmann, Subie Wurie, Karin Yadgar, Gail Young, Megan Young, Julien Aucouturier, Marie- Jo Bertin, Hasnae Bougrine, Marie Coisnon, Antoine Defrance, Kati Gutierrez, Amel Harouz, Laure Jerber, Aida Khlifi, Amina Kirati, Nasaladjine Liworo, Maude Logoltat, Charlotte Mailhat, Chancely M'Bayi, Yasmina Medane, Dalal Merkhoufa, Saouda Mohamed Elhad, Bertille Monthe, Fanny Moyon, Pascaline Rabiega, Jennifer Sekela, Charlotte Thilloy, Naima Hamamouche, Frederic Partisotti, Patrick Blandin, Hocine Mokhtari, Laure Coutard, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Gastroenterology and hepatology, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Biological Products, Hepatology, Efficacy, Lymphoma, Tumor Necrosis Factor-alpha, Inflammatory Bowel Disease, Gastroenterology, Biologics, Crohn Disease/diagnosis, Inflammatory Bowel Diseases/chemically induced, Colitis, Ulcerative/diagnosis, Cohort Studies, Necrosis, Immunologic Factors/adverse effects, Humans, Female, 03.02. Klinikai orvostan, Prospective Studies, Safety, I-CARE, Cancer, Immunosuppressive Agents
Abstract

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Published
2022
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26. Patients’ real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group

Author

Maria Nachury, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Sara Tadbiri, Matthieu Allez, Stephanie Viennot, Arnaud Bourreille, David Laharie, Aurelien Amiot, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Anne Bourrier, Cecilia Landmann, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Nicolas Mathieu, Sandie Pestour, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), 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)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), AbbVie, GETAID-patient experience study group: Aurelien Amiot , Sara Tadbiri , Charlotte Gagniere , Jenny Tannoury , Maria Nachury , Benjamin Pariente , Pauline Wils , Yoram Bouhnik , Carmen Stefanescu , Xavier Treton , Melanie Serrero , Jerome Filippi , Xavier Hébuterne , Nadia Arab , Virginie Cluzeau , Xavier Roblin , Emilie Del Tedesco , Laurent Beaugerie , Philippe Seksik , Anne Bourrier , Cecilia Landmann , Julien Kirchgesner , Harry Sokol , Guillaume Bouguen , Laurent Siproudhis , Marie DeWitte , Denis Franchimont , Guillaume Savoye , Anthony Buisson , Edouard Louis , Catherine Reenaers , Stephane Nancey , Gilles Boschetti , Claire Gay , Pauline Danion , Bernard Flourié , Vered Abitbol , Georgia Malamut , Jean-Marie Reimund , Benedicte Caron , Olivier DeWitt , Lucine Vuitton , Nicolas Mathieu , Sandie Pestour , Laurent Peyrin-Biroulet , Camille Zallot , Cyrielle Gilletta , Matthieu Allez , Jean-Marc Gornet , Clotilde Baudry , Stephanie Viennot , Arnaud Bourreille , Caroline Trang-Poisson , Nina Dib , Hedi Brixi , Guillaume Cadiot , Medina Boualit , Claire Painchart , Laurianne Plastaras , Romain Altwegg , Lucile Boivineau , Mathurin Fumery , Ludovic Caillo , David Laharie , Pauline Riviere , Florian Poullenot , Benoit Coffin , Henri Duboc , Stephane Nahon , Noemie Tavernier , Marion Simon , Baya Coulibaly , Morgane Amil , Duveau Nicolas , Sherine Khater , Mehdi Kaassis , Felix Goutorbe , Driffa Moussata , Laurence Picon, CHU Saint-Etienne, 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)-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), 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Toulouse [Toulouse], CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, 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), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Crohn’s disease, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Cross-sectional study, [SDV]Life Sciences [q-bio], Disease, Patients experience, Inflammatory bowel disease, Tertiary care, digestive system, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physicians, Outpatients, medicine, Quantitative assessment, Humans, Adverse effect, Crohn's disease, Physician-Patient Relations, Hepatology, business.industry, Gastroenterology, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, France, Self Report, business
Abstract

International audience; BACKGROUND: Patients’ experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients’ experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients’ knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.

Published
2021
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27. Prevalence of Self-Reported Venous Thromboembolism and Cardiovascular Risk Factors in Patients with Ulcerative Colitis: The GETAID FOCUS Study

Author

Lucas, Guillo, Aurélien, Amiot, Mélanie, Serrero, Romain, Altwegg, Xavier, Roblin, Calina, Atanasiu, Anthony, Buisson, Catherine, Le Berre, Catherine, Reenaers, Jean-Marc, Gornet, David, Laharie, Vered, Abitbol, Amélie, Biron, Bénédicte, Caron, Stéphane, Nancey, Antoine, Chupin, Antoine, Blain, Lucine, Vuitton, Ludovic, Caillo, Julien, Kirchgesner, Maria, Nachury, Laurent, Peyrin-Biroulet, and Marie, Bonnet-Dodel

Subjects
Adult, Cross-Sectional Studies, Cardiovascular Diseases, Risk Factors, Prevalence, Humans, Colitis, Ulcerative, Female, Self Report, Venous Thromboembolism
Abstract

Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC).We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC.A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor.This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients.

Published
2021

28. Withholding the Introduction of Anti-Epidermal Growth Factor Receptor: Impact on Outcomes in RAS Wild-Type Metastatic Colorectal Tumors: A Multicenter AGEO Study (the WAIT or ACT Study)

Author

Isabelle Trouilloud, Nabil Baba-Hamed, Marie-Pierre Galais, David Tougeron, Romain Coriat, Jean-Philippe Metges, Olivier Bouché, Jean-Marc Phelip, Lola-Jade Palmieri, Laurent Mineur, Benoit Rousseau, Victoire Granger, Lea Saban-Roche, Pierre Michel, Julie Henriques, Jean-Marc Gornet, Emilie Soularue, Astrid Lièvre, Denis Smith, Dewi Vernery, Stéphane Obled, Gael Goujon, Christophe Locher, Anne-Laure Bignon-Bretagne, Gaetan Des Guetz, Sylvain Manfredi, Solene Doat, Bruno Buecher, Marie Dior, Carole Vitellius, Simon Pernot, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut Curie [Paris], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier de Meaux, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Louis Mourier - AP-HP [Colombes], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Michallon, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-Gastroentérologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Growth factor receptor, Interquartile range, Internal medicine, Gastrointestinal Cancer, Antineoplastic Combined Chemotherapy Protocols, Anti‐epidermal growth factor receptor, Humans, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Chemotherapy, Metastatic colorectal cancer, business.industry, Hazard ratio, Antibodies, Monoclonal, medicine.disease, RAS status, 3. Good health, 030220 oncology & carcinogenesis, Propensity score matching, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract

Background Patients with RAS wild‐type (WT) nonresectable metastatic colorectal cancer (mCRC) may receive either bevacizumab or an anti‐epidermal growth factor receptor (EGFR) combined with first‐line, 5‐fluorouracil‐based chemotherapy. Without the RAS status information, the oncologist can either start chemotherapy with bevacizumab or wait for the introduction of the anti‐EGFR. Our objective was to compare both strategies in a routine practice setting. Materials and Methods This multicenter, retrospective, propensity score–weighted study included patients with a RAS WT nonresectable mCRC, treated between 2013 and 2016 by a 5‐FU‐based chemotherapy, with either delayed anti‐EGFR or immediate anti‐vascular endothelial growth factor (VEGF). Primary criterion was overall survival (OS). Secondary criteria were progression‐free survival (PFS) and objective response rate (ORR). Results A total of 262 patients (129 in the anti‐VEGF group and 133 in the anti‐EGFR group) were included. Patients receiving an anti‐VEGF were more often men (68% vs. 56%), with more metastatic sites (>2 sites: 15% vs. 9%). The median delay to obtain the RAS status was 19 days (interquartile range: 13–26). Median OS was not significantly different in the two groups (29 vs. 30.5 months, p = .299), even after weighting on the propensity score (hazard ratio [HR] = 0.86, 95% confidence interval [CI], 0.69–1.08, p = .2024). The delayed introduction of anti‐EGFR was associated with better median PFS (13.8 vs. 11.0 months, p = .0244), even after weighting on the propensity score (HR = 0.74, 95% CI, 0.61–0.90, p = .0024). ORR was significantly higher in the anti‐EGFR group (66.7% vs. 45.6%, p = .0007). Conclusion Delayed introduction of anti‐EGFR had no deleterious effect on OS, PFS, and ORR, compared with doublet chemotherapy with anti‐VEGF. Implications for Practice For RAS/RAF wild‐type metastatic colorectal cancer, patients may receive 5‐fluorouracil‐based chemotherapy plus either bevacizumab or an anti‐epidermal growth factor receptor (EGFR). In daily practice, the time to obtain the RAS status might be long enough to consider two options: to start the chemotherapy with bevacizumab, or to start without a targeted therapy and to add the anti‐EGFR at reception of the RAS status. This study found no deleterious effect of the delayed introduction of an anti‐EGFR on survival, compared with the introduction of an anti‐vascular endothelial growth factor from cycle 1. It is possible to wait one or two cycles to introduce the anti‐EGFR while waiting for RAS status., More than half of the cases of metastatic colorectal cancer harbor a RAS mutation; however, the time to obtain RAS status might be long enough to consider delayed anti‐EGFR treatment. This article reports on the two main treatment strategies for these cases.

Published
2019
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29. Accord d’experts français pour la prise en charge des métastases péritonéales de cancers colo-rectaux

Author

Pascale Mariani, Marc Ychou, François Quenet, Jérémie H. Lefevre, Diane Goéré, Michel Ducreux, Olivier Glehen, Thierry André, M. Brunel, Karine Abboud, Marc Pocard, C. Eveno, A. Pinto, Jean-Marc Gornet, and Olivia Sgarbura

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Surgery
Abstract

Resume En cas de diagnostic de metastases peritoneales (accord fort des experts) : i) prendre avis aupres d’une RCP ayant une forte experience en pathologie du peritoine (reseau BIG RENAPE), ii) Transfert ou non du patient a une equipe referente de la CHIP, selon proposition de la RCP. Concernant la chimiotherapie systemique (accord fort des experts) : i) elle est realisee en pre et postoperatoire, ii) Pour une duree totale n’excedant pas 6 mois, iii) pas d’anti-angiogenique en postoperatoire. Concernant la chirurgie d’exerese (accord fort des experts) : i) elle doit etre radicale menee par mediane xyphopubienne, ii) pas de cytoreduction par cœlioscopie. Une CHIP peut etre proposee en dehors d’un essai par une equipe referente de la CHIP (accord faible des d’expert) : i) Si l’exerese est radicale, ii) si la morbidite attendue est « raisonnable », iii) Si l’indication de CHIP a ete posee en RCP et iv) l’utilisation de la mitomycine est preferee a l’utilisation de la l’oxaliplatine qui est deconseillee pour cette indication.

Published
2019
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30. Ustekinumab treatment for neutrophilic dermatoses associated with Crohn's disease: A multicenter retrospective study

Author

Tullia de Risi-Pugliese, Philippe Seksik, Jean-David Bouaziz, François Chasset, Philippe Moguelet, Jean-Marc Gornet, Anne Bourrier, Aurélien Amiot, Laurent Beaugerie, Camille Francès, Sarah Guégan, Benoit Coffin, Benjamin Pariente, Vered Abitbol, Marion Simon, Elise Chantelou, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Université Paris Descartes - Paris 5 (UPD5)

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], MEDLINE, Dermatology, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Ustekinumab, medicine, Humans, Young adult, Child, Retrospective Studies, Crohn's disease, business.industry, Crohn disease, Sweet Syndrome, Retrospective cohort study, medicine.disease, Pyoderma Gangrenosum, Female, 030211 gastroenterology & hepatology, Dermatologic Agents, business, Pyoderma gangrenosum, medicine.drug
Published
2019
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31. Gastrointestinal bleeding in critically ill immunocompromised patients

Author

Sophie Caroline Sacleux, Jennifer Catano, Jean-Marc Gornet, Marine Camus, Guillaume Dumas, Faouzi Saliba, Elie Azoulay, Naïke Bigé, Lara Zafrani, Gestionnaire, Hal Sorbonne Université, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Paul Brousse, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des Soins Intensifs [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), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Gastrointestinal bleeding, medicine.medical_specialty, Lymphoma, medicine.drug_class, Population, Proton-pump inhibitor, Critical Care and Intensive Care Medicine, 01 natural sciences, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Anesthesiology, medicine, Intensive care unit, 030212 general & internal medicine, 0101 mathematics, education, Immunocompromised host, education.field_of_study, business.industry, RC86-88.9, Research, 010102 general mathematics, Retrospective cohort study, Medical emergencies. Critical care. Intensive care. First aid, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, Hyperlactatemia, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Background Acute gastrointestinal bleeding (GIB) may be a severe condition in immunocompromised patients and may require intensive care unit (ICU) admission. We aimed to describe the clinical spectrum of critically ill immunocompromised patients with GIB and identify risk factors associated with mortality and severe GIB defined by hemorrhagic shock, hyperlactatemia and/or the transfusion of more than 5 red blood cells units. Finally, we compared this cohort with a control population of non-immunocompromised admitted in ICU for GIB. Results Retrospective study in 3 centers including immunocompromised patients with GIB admitted in ICU from January, 1st 2010 to December, 31rd 2019. Risk factors for mortality and severe GIB were assessed by logistic regression. Immunocompromised patients were matched with a control group of patients admitted in ICU with GIB. A total of 292 patients were analyzed in the study, including 141 immunocompromised patients (compared to a control group of 151 patients). Among immunocompromised patients, upper GIB was more frequent (73%) than lower GIB (27%). By multivariate analysis, severe GIB was associated with male gender (OR 4.48, CI95% 1.75–11.42, p = 0.00), upper GIB (OR 2.88, CI95% 1.11–7.46, p = 0.03) and digestive malignant infiltration (OR 5.85, CI95% 1.45–23.56, p = 0.01). Conversely, proton pump inhibitor treatment before hospitalization was significantly associated with decreased risk of severe GIB (OR 0.25, IC95% 0.10–0.65, p p = 0 .01), upper GIB (OR 4.33, CI95% 1.50–12.47, p = 0.01), and long-term corticosteroid therapy before admission (OR 2.98, CI95% 1.32–6.71, p = 0.01). Albuminemia (per 5 g/l increase) was associated with lower mortality (OR 0.54, IC95% 0.35–0.84, p = 0.01). After matching with a control group of non-immunocompromised patients, severity of bleeding was increased in immunocompromised patients, but mortality was not different between the 2 groups. Conclusion Mortality is high in immunocompromised patients with GIB in ICU, especially in patients receiving long term corticosteroids. Mortality of GIB is not different from mortality of non-immunocompromised patients in ICU. The prophylactic administration of proton pump inhibitors should be considered in this population.

Published
2021
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32. Safety of Hydrocortisone Premedication Discontinuation in Patients with Inflammatory Bowel Disease on Maintenance Therapy with Infliximab: a Prospective Clinical and Pharmacological Study

Author

Pascal Houzé, Clotilde Baudry, Deborah Hassid, Marion Simon, Matthieu Allez, Marianne Maillet, Justine Vivier-Chicoteau, Nassim Hammoudi, My-Linh Tran-Minh, Jean-Marc Gornet, and Paul McLellan

Subjects
Adult, Male, medicine.medical_specialty, Combination therapy, Hydrocortisone, Premedication, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Gastrointestinal Agents, Internal medicine, medicine, Humans, Prospective Studies, 030203 arthritis & rheumatology, business.industry, Gastroenterology, General Medicine, medicine.disease, Inflammatory Bowel Diseases, Infliximab, Discontinuation, Cohort, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract

Background Hydrocortisone premedication reduces the risk of antibodies to infliximab [ATIs] formation in patients receiving infliximab [IFX] therapy for inflammatory bowel disease [IBD]. Aim We aimed to determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX. Methods We performed an observational prospective pharmacoclinical study in a tertiary referral centre, including all consecutive IBD outpatients with no previous IFX infusion reaction and in clinical remission on maintenance IFX [alone or in combination therapy] for at least 6 months. This cohort was followed for 1 year after discontinuation of hydrocortisone premedication. Results Among the 268 IBD outpatients, 95 patients met the inclusion criteria [mean age 38 years; 64% male; 80% Crohn’s disease; 45% combination therapy]. The median IFX duration was 5 years [0.54–14] with a mean infused dose of 533 mg [200–1000] and a mean interval duration of 7.9 weeks [4–10]. None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of infliximab serum trough levels [5.5 µg/mL vs 5.9 µg/mL] measured at the time of the three IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at 1 year. Conclusions Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy.

Published
2020

33. Que doivent savoir les chirurgiens à propos des troubles digestifs et des anomalies paracliniques induits par le COVID 19 ?

Author

Deborah Hassid, F. Leleu, M.L. Tran Minh, and Jean-Marc Gornet

Subjects
03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery
Abstract

Resume Les symptomes lies du COVID-19 sont principalement caracterises par la triade fievre, toux seche et dyspnee. Toutefois, des symptomes digestifs ont egalement ete rapportes dont la frequence, initialement consideree comme faible, semble toucher plus de la moitie des patients a des degres divers. Ceux-ci se manifestent principalement par une anorexie, une diarrhee, des nausees et ou vomissements et des douleurs abdominales. Bien que le pronostic soit lie a l’atteinte pulmonaire, les troubles digestifs semblent significativement plus frequents chez les patients ayant une infection severe COVID-19. Des formes digestives isolees ou pouvant preceder les symptomes pulmonaires sont desormais bien decrites avec de la diarrhee au premier plan clinique. Les principales anomalies biologiques pouvant orienter precocement vers une infection COVID-19 sont la lymphopenie, une CRP augmentee et une augmentation des transaminases predominant sur les ASAT. Le scanner thoraco-abdominal semble utile pour eliminer une pathologie digestive non liee au coronavirus et pour rechercher des images pulmonaires compatibles avec une infection COVID-19. Il n’existe pas de donnees sur l’interet de l’endoscopie digestive en cas de symptomes digestifs persistants. Le risque de contamination de l’endoscopiste semble par ailleurs significatif. Un mode de transmission oro-fecale de l’infection est possible ce d’autant que l’excretion virale dans les selles semble frequente et plus longue qu’au niveau ORL, y compris chez des patients avec prelevement pharynge negatif ou sans symptomes digestifs. Ainsi, dans certains cas douteux, une analyse virologique des selles peut permettre de porter un diagnostic de certitude. La contagiosite persistante d’un patient en cas d’excretion virale prolongee dans les selles est possible mais pas parfaitement etablie. L’avenement proche de la serologie devrait permettre d’identifier les malades ayant ete infectes par l’epidemie de COVID-19 notamment les sujets pauci-symptomatiques non detectes au sein du personnel de sante. La reprise de l’activite medico-chirurgicale devra faire l’objet d’une strategie dediee en amont du deconfinement.

Published
2020
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34. [What do surgeons need to know about the digestive disorders and paraclinical abnormalities induced by COVID-19?]

Author

M.L. Tran Minh, Deborah Hassid, F. Leleu, Jean-Marc Gornet, Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Abdominal pain, medicine.medical_specialty, Nausea, [SDV]Life Sciences [q-bio], Digestive System Diseases, Pneumonia, Viral, Anorexia, Lung injury, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Viral shedding, Pandemics, Digestive System Surgical Procedures, Transmission (medicine), business.industry, COVID-19, General Medicine, 3. Good health, Diarrhea, 030220 oncology & carcinogenesis, Vomiting, 030211 gastroenterology & hepatology, medicine.symptom, Coronavirus Infections, business
Abstract

The symptoms associated with COVID-19 are mainly characterized by a triad composed of fever, dry cough and dyspnea. However, digestive symptoms have also been reported. At first considered as infrequent, they in fact seem to affect more than half of patients. The symptoms mainly include anorexia, diarrhea, nausea and/or vomiting and abdominal pain. Even though prognosis is associated with lung injury, digestive symptoms seem significantly more frequent in patients presenting with severe COVID-19 infection. Digestive presentations, which may be isolated or which can precede pulmonary symptoms, have indeed been reported, with diarrhea as a leading clinical sign. The main biological abnormalities that can suggest COVID-19 infection at an early stage are lymphopenia, elevated CRP and heightened ASAT transaminases. Thoraco-abdominal scan seems useful as a means of on the one hand ruling out digestive pathology not connected with coronavirus and on the other hand searching for pulmonary images consistent with COVID-19 infection. No data exist on the value of digestive endoscopy in cases of persistent digestive symptoms. Moreover, the endoscopists may themselves be at significant risk of contamination. Fecal-oral transmission of the infection is possible, especially insofar as viral shedding in stools seems frequent and of longer duration than at the ENT level, including in patients with negative throat swab and without digestive symptoms. In some doubtful cases, virologic assessment of stool samples can yield definitive diagnosis. In the event of prolonged viral shedding in stools, a patient's persistent contagiousness is conceivable but not conclusively established. Upcoming serology should enable identification of the patients having been infected by the COVID-19 epidemic, particularly among previously undetected pauci-symptomatic members of a health care staff. Resumption of medico-surgical activity should be the object of a dedicated strategy preceding deconfinement.

Published
2020
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35. Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study

Author

S. Nguyen, Quentin Klopfenstein, Oana Cojocarasu, Francis Fein, Mohamed Gasmi, Cynthia Reichling, Pierre-Laurent Puig, Karine Le Malicot, Jean Paul Lagasse, Côme Lepage, Pierre-Luc Etienne, Jean-Marc Gornet, Julien Taieb, Jean-François Emile, Hakim Becheur, Dominique Luet, François Ghiringhelli, André Vanoli, Hervé Perrier, Marie Christine Kaminsky, Valentin Derangère, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER

Subjects
0301 basic medicine, Colorectal cancer, Lymphocyte, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, immunohistopathology, MESH: Lymphocytes, Tumor-Infiltrating, biology, Gastroenterology, MESH: Neoplasm Staging, Prognosis, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Colonic Neoplasms, Stromal cell, CD3, adjuvant treatment, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Disease-Free Survival, MESH: Prognosis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Immune system, computerised image analysis, Stroma, Artificial Intelligence, Image Interpretation, Computer-Assisted, Humans, MESH: Artificial Intelligence, Neoplasm Invasiveness, Pathological, Neoplasm Staging, MESH: Colonic Neoplasms, MESH: Humans, business.industry, MESH: Adenocarcinoma, MESH: Neoplasm Invasiveness, medicine.disease, 030104 developmental biology, MESH: Disease-Free Survival, biology.protein, Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Image Interpretation, Computer-Assisted, CD8
Abstract

ObjectiveDiagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools.DesignWe have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes.ResultsWithin the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; pConclusionThese findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients’ prognosis.

Published
2020
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36. Development and internal validation of a diagnostic score for gastric linitis plastica

Author

Pierre-Emmanuel Bonnot, Romain Coriat, Gaël Goujon, Diane Goéré, Jean-Marc Gornet, Thomas Aparicio, Olivier Glehen, Marc Pocard, Justine Vivier-Chicoteau, Stephanie Morgant, Jérôme Lambert, Marie Dior, B Roche, pocard, marc, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Southern Mississippi (USM), 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), Centre Hospitalier Lyon Sud, Service de Chirurgie Digestive, Hospices Civils de Lyon (HCL), Hôpital Louis-Mourier, Colombes, France., AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CArcinose Péritoine Paris-Technologies (ex-CART) (CAP Paris-Tech (UMR_S_1275)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Endoscopic ultrasound, Male, Cancer Research, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Linitis plastica, medicine.medical_treatment, MESH: gastric cancer, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Logistic regression, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], 10. No inequality, medicine.diagnostic_test, Signet ring cell, Gastroenterology, General Medicine, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Oncology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Radiology, medicine.medical_specialty, MESH: diagnostic score, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Stomach Neoplasms, Diagnostic score, Gastrectomy, medicine, Humans, Pathological, Aged, Retrospective Studies, business.industry, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, ROC Curve, business, Abdominal surgery, Follow-Up Studies
Abstract

International audience; Background: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas.Methods: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was perfomed using bootstrapping methods to correct for overoptimism.Results:220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9-97.3] and a specificity of 88.7% [81.7-95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959.Conclusion: It’s the first study validating a pre-therapeutic diagnostic score (Saint-Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data.

Published
2020
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37. Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.

Author

Camille Jung, Jean-Frédéric Colombel, Marc Lemann, Laurent Beaugerie, Matthieu Allez, Jacques Cosnes, Gwenola Vernier-Massouille, Jean-Marc Gornet, Jean-Pierre Gendre, Jean-Pierre Cezard, Frank M Ruemmele, Dominique Turck, Françoise Merlin, Habib Zouali, Christian Libersa, Philippe Dieudé, Nadem Soufir, Gilles Thomas, and Jean-Pierre Hugot

Subjects
Medicine, Science
Abstract

Background & aimsRecent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.MethodA cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations.ResultsThe NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03).ConclusionsIt is not recommended to genotype the studied polymorphisms in routine practice.

Published
2012
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38. ERBB3-Activating Mutations in Small Bowel Adenocarcinomas

Author

Ivan Bieche, Frédéric Di Fiore, Virginie Bernard, Sophie Vacher, Céline Callens, A. Zaanan, Thomas Aparicio, Pauline Afchain, Delphine Le Corre, Luc Cabel, Pierre Laurent-Puig, Jean-Marc Gornet, François-Clément Bidard, and Magali Svrcek

Subjects
Cancer Research, Mutation, Afatinib, ERBB Family Signaling Pathway, Biology, medicine.disease_cause, Lapatinib, Exon, Oncology, Trastuzumab, Cancer research, medicine, DNA mismatch repair, ERBB3, medicine.drug
Abstract

Purpose Functional studies have demonstrated that some mutations of ERBB3, which encodes for human epidermal growth factor receptor (HER) 3, are oncogenic via activation of the ErbB family signaling pathway. Significant clinical activity of anti-HER2 therapies (trastuzumab plus lapatinib combination or afatinib) has been reported in patients with ERBB3-mutated cancers. This study was designed to report the rate of activating ERBB3 mutations in small bowel adenocarcinoma (SBA), a rare tumor type in which we previously reported a high rate (12%) of ERBB2-activating mutations. Materials and Methods DNA from 74 SBAs, previously characterized for ERBB2 mutations and mismatch repair status, was submitted for sequencing of ERBB3 exons 3, 6, 7, 8, and 23. Orthogonal validation by targeted next-generation sequencing was performed. Results Four of 74 SBAs (5.4%) displayed ERBB3-activating mutations, including three p.V104M mutations (c.310 G>A) in exon 3 and one p.E928G mutation (c.2783 A>G) in exon 23. No mutations were detected in exons 6, 7, and 8. ERBB3-activating mutations were associated with microsatellite instability ( P = .002) and the presence of ERBB2-activating mutations ( P = .002). Two SBAs with co-occurrence of ERBB2 and ERBB3 mutations were further analyzed by targeted next-generation sequencing. Mutant allelic frequencies suggested that both mutations were shared by the same clone rather than being harbored by mutually exclusive tumor subclones. Conclusion SBAs display a high rate of ERBB3-activating mutations, which have been shown to be targetable by anti-HER2 therapies. Strikingly, ERBB3 was frequently comutated with ERBB2, suggesting a strong oncogenic addiction of these SBAs to the HER2 pathway.

Published
2018
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39. Rare cause of rectal stenosis in a patient with long-term use of Infliximab and Mercaptopurine for ulcerative colitis

Author

Charlotte Gardair, Jean-Marc Gornet, My-Linh Tran-Minh, Matthieu Allez, and Nassim Hammoudi

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Combination therapy, Constriction, Pathologic, Proctoscopy, Risk Assessment, Severity of Illness Index, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Pharmacotherapy, Internal medicine, Severity of illness, medicine, Humans, Colitis, Sigmoidoscopy, Dose-Response Relationship, Drug, Mercaptopurine, business.industry, Biopsy, Needle, Middle Aged, medicine.disease, Immunohistochemistry, Ulcerative colitis, Infliximab, Golimumab, Rectal Diseases, 030104 developmental biology, Colitis, Ulcerative, Drug Therapy, Combination, 030211 gastroenterology & hepatology, business, Follow-Up Studies, medicine.drug
Abstract

A 58-year-old, non-smoker male patient with no family history was followed up since 2002 for ulcerative colitis (UC) located in the rectosigmoid. He was initially treated by salicylates alone until November 2008. Mercaptopurine was started in August 2009 for steroid dependence with primary failure despite adequate 6 thioguanine nucleotides (6 TGN) level. He was included in February 2010 in the PURSUIT trial testing Golimumab with only partial response. A combination therapy with Mercaptopurine and Infliximab was then started in December 2010 with a long-term clinical, biological and endoscopic steroid-free remission. A pan-chromoendoscopy performed in June 2016 showed a complete mucosal healing with no histological activity …

Published
2018
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40. Anti-TNF therapy for genital fistulas in female patients with Crohn's disease: a nationwide study from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID)

Author

Caroline Trang, Stephanie Viennot, Stéphane Nahon, Aurelien Amiot, Guillaume Le Baut, Philippe Seksik, Lucine Vuitton, Laurent Peyrin-Biroulet, Marion Simon, Alexandre Aubourg, Carmen Stefanescu, Guillaume Pineton de Chambrun, Ludovic Caillo, Guillaume Bouguen, Cyrielle Gilletta de Saint Joseph, Jean-Marc Gornet, Mathurin Fumery, Emilie Del Tedesco, David Laharie, Laurianne Plastaras, Romain Altwegg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Male, Fistula, MESH: Immunotherapy, MESH: Infliximab, MESH: Adalimumab, 0302 clinical medicine, Crohn Disease, Pharmacology (medical), MESH: Treatment Outcome, Crohn's disease, Gastroenterology, 3. Good health, Treatment Outcome, MESH: Young Adult, 030220 oncology & carcinogenesis, Drainage, Female, 030211 gastroenterology & hepatology, MESH: Immunosuppressive Agents, Immunotherapy, MESH: Certolizumab Pegol, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Drainage, Young Adult, 03 medical and health sciences, medicine, Adalimumab, Humans, Retrospective Studies, MESH: Humans, MESH: Crohn Disease, MESH: Fistula, Hepatology, Tumor Necrosis Factor-alpha, business.industry, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, MESH: Male, Infliximab, Surgery, MESH: Tumor Necrosis Factor-alpha, Concomitant, Relative risk, Certolizumab Pegol, Complication, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

BACKGROUND: Genital fistulas represent a devastating complication of Crohn's disease. Only studies with small sample sizes have evaluated the efficacy of anti-TNF therapy for this complication. AIMS: To assess the efficacy of anti-TNF therapy for genital fistulas complicating Crohn's disease and to identify predictive factors associated with clinical response at 1 year. METHODS: Consecutive patients treated with anti-TNF therapy for genital fistulas complicating Crohn's disease from 1999 to 2016 in 19 French centres from the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif were included in a retrospective cohort study. Outcome was clinical fistula closure at 1 year. RESULTS: Among the 204 women with genital fistulas who received anti-TNF therapy, 131 were analysed. The first anti-TNF given was infliximab (79%), adalimumab (20%), or certolizumab (1%). At start of anti-TNF therapy, 56% of patients had seton drainage and 53% had concomitant immunosuppressive treatment. A complementary surgery was performed during the first year in 10 patients (8%). At 1 year, 37% of patients had complete clinical fistula closure, 22% had a partial response, and 41% had no response. Among patients without complementary surgery, 34% (41/121) had complete clinical fistula closure. Only complementary surgery was associated with better response on multivariate analysis (adjusted relative risk: 2.02, 95% CI: 1.25-3.26, P = 0.0043). CONCLUSIONS: In the anti-TNF era, approximately one-third of patients with genital fistula in Crohn's disease had complete fistula closure at 1 year. Collaboration between surgeons and gastroenterologists appears to be very important to improve the rate of fistula closure.

Published
2018
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41. Inflammatory bowel disease drastically affects the prognosis of patients treated for peritoneal metastases with combined cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A multicenter study

Author

Clarisse Eveno, Diane Goéré, Nassim Hammoudi, Jérôme Lambert, Thomas Aparicio, Marc Pocard, Matthieu Allez, Nelson Lourenco, Marianne Maillet, Jean-Marc Gornet, and Olivier Glehen

Subjects
medicine.medical_specialty, Colorectal cancer, business.industry, General Medicine, Disease, medicine.disease, Gastroenterology, Inflammatory bowel disease, digestive system diseases, Oxaliplatin, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, Peritoneal Cancer Index, 030211 gastroenterology & hepatology, Surgery, Hyperthermic intraperitoneal chemotherapy, Cytoreductive surgery, business, medicine.drug
Abstract

Background Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown. Methods IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer. Results 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1–30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment. Conclusion CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed.

Published
2018
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42. P504 Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with real-world ulcerative colitis: A GETAID multicentre cohort study

Author

D. Laharie, Anne Bourrier, Lucine Vuitton, L Peyrin-Biroulet, Stéphane Nahon, Mathurin Fumery, Aurelien Amiot, Stephanie Viennot, Jérôme Filippi, Yoram Bouhnik, G Pineton de Chambrun, Benjamin Pariente, Jean-Marc Gornet, Xavier Roblin, Mélanie Serrero, Stéphane Nancey, Romain Altwegg, Abitbol, Guillaume Bouguen, Cyrielle Gilletta, A Biron, and Getaid

Subjects
medicine.medical_specialty, Pancolitis, business.industry, medicine.medical_treatment, Gastroenterology, General Medicine, medicine.disease, Ulcerative colitis, Vedolizumab, Maintenance therapy, Internal medicine, Ustekinumab, medicine, medicine.symptom, Adverse effect, business, Colectomy, medicine.drug, Cohort study
Abstract

Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but no real-life long-term data is currently available. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined by a partial Mayo Clinic score ≤ 2. The aim of the present study was to assess long-term effectiveness and safety of ustekinumab in UC. Results 103 UC patients (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) were included in 21 centres. History of immunomodulator, anti-TNF and vedolizumab therapies was noted in 84.5%, 99.0% and 85.4% of the cases, respectively. At week 54, 44 (43%) patients discontinued ustekinumab, for lack of efficacy (n=41), pregnancy (n=1), persistence of eczematiform lesions (n=1) or personal decision (n=1). Cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7%, and 58.4% after 3, 6, 9, and 12 months, respectively. In multivariate analysis, a CRP>5 mg/L at week 0 (OR=2.91, CI95%[1.15–7.36]; p=0.02) and concomitant steroids at week 0 (OR=3.05, CI95%[1.30–7.14]; p=0.01) were significantly associated with ustekinumab discontinuation within one year. The overall rate of steroid-free clinical remission at week 52 was 32% of whom 71% had null rectal bleeding and stool frequency subscores. Ten patients (9.7%) underwent colectomy within a median of 6.7 [4.3–10.6] months. Adverse events were observed in 15 (16.9%) patients, of whom 4 (4.5%) had severe adverse events including three patients with exacerbation of UC leading to hospitalization, and a 62 years-old men who died from a myocardial infarction four months after ustekinumab initiation. Conclusion In this real-world cohort study that included patients with refractory ulcerative colitis to multiple therapies, more than one-half of patients were still treated by ustekinumab and one-third were in steroid-free clinical remission, after 52 weeks.

Published
2021
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43. Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency

Author

Rachid Kaci, Magali Svrcek, Dewi Vernerey, Pascale Cervera, Alex Duval, Philippe Bertheau, Yann Parc, Sylvie Dumont, Thierry André, Frédéric Bibeau, Romain Cohen, Daniel Lopez-Trabada, Jean-Marc Gornet, J-B. Bachet, Armelle Bardier, Elisabeth Hain, Olivier Buhard, Florence Renaud, 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), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Pathologie [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), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastroentérologie, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), 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, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Service de chirurgie générale et digestive [CHU Saint-Antoine], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Oncologie Médicale [CHU Saint -Antoine], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'Oncologie Médicale [CHU Saint-Antoine]

Subjects
Male, 0301 basic medicine, Cancer Research, Heredity, Time Factors, Colorectal cancer, Kaplan-Meier Estimate, DNA Mismatch Repair, 0302 clinical medicine, Risk Factors, PMS2, Neoplasm Metastasis, Middle Aged, Lynch syndrome, Pedigree, 3. Good health, Phenotype, Treatment Outcome, Molecular Diagnostic Techniques, Oncology, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, DNA mismatch repair, France, Colorectal Neoplasms, MutL Protein Homolog 1, Adult, Proto-Oncogene Proteins B-raf, congenital, hereditary, and neonatal diseases and abnormalities, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MLH1, Disease-Free Survival, Diagnosis, Differential, 03 medical and health sciences, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Predictive Value of Tests, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, neoplasms, Aged, Proportional Hazards Models, Retrospective Studies, nutritional and metabolic diseases, Cancer, Microsatellite instability, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, DNA Methylation, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, 030104 developmental biology, Multivariate Analysis, Mutation, Cancer research
Abstract

International audience; Background: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs.Patients and methods: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation.Results: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (31%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44).Conclusions: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.

Published
2017
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44. Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)

Author

Christophe Borg, Jaafar Bennouna, Aurélie Parzy, Didier Peiffert, François-Clément Bidard, Christelle De La Fouchardiere, Olivier Bouché, Simon Pernot, Stefano Kim, Marion Jacquin, Denis Smith, Sarah Dumont, Mustapha Zoubir, Franck Bonnetain, Thomas Aparicio, Emmanuelle Samalin, Thierry André, Marine Jary, Farid El Hajbi, Véronique Vendrely, Jean-Marc Gornet, Bruno Buecher, Thierry Nguyen, Eric Francois, Jean-Baptiste Bachet, Nabil Baba-Hamed, Christophe Louvet, Meher Ben Abdelghani, and Jérôme Desramé

Subjects
0301 basic medicine, Oncology, Adult, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Phases of clinical research, Docetaxel, lcsh:RC254-282, 03 medical and health sciences, Young Adult, Study Protocol, 0302 clinical medicine, Anal carcinoma, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Genetics, medicine, Clinical endpoint, Humans, Aged, Aged, 80 and over, Chemotherapy, business.industry, Middle Aged, Interim analysis, Anus Neoplasms, Prognosis, And chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030104 developmental biology, Fluorouracil, Research Design, 030220 oncology & carcinogenesis, Localized disease, Carcinoma, Squamous Cell, Metastatic, Taxoids, Advanced, France, Cisplatin, Neoplasm Recurrence, Local, business, Chemoradiotherapy, medicine.drug
Abstract

Background The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients. Methods This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon’s optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy. Discussion Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA. Trial registration NCT02402842 , EudraCT: 2014–001789-81.

Published
2017
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45. Postoperative Complications after Ileocecal Resection in Crohn’s Disease: A Prospective Study From the REMIND Group

Author

Benjamin Pariente, Claire Auzolle, Philippe Zerbib, Anne Dubois, Yves Panis, Philippe Marteau, Jérôme Filippi, Eddy Cotte, Mathurin Fumery, Nicolas Munoz-Bongrand, Jean-Marc Gornet, Philippe Seksik, Xavier Treton, Pascal Houzé, Gilles Boschetti, Matthieu Allez, Charles Sabbagh, Carmen Stefanescu, Karine Pautrat, Marc Chevrier, Anthony Buisson, Xavier Jouven, Najim Chafai, Département de Gastroentérologie, Hôpital Européen [Fondation Ambroise Paré - Marseille], Laboratoire d'Analyses Médicales, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Department of Gastroenterological Surgery, Hop St Louis, Hospices Civils de Lyon (HCL), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Départment de Gastroentérologie, Université de Lille, Droit et Santé, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department Colorectal Surgery, Department of Gastroenterological Surgery and Transplantation, Université Lille Nord de France (COMUE), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department Digestion and Oncology Surgery, Université de Picardie Jules Verne (UPJV), Département de Gastroentérogie et Clinique Nutrition, Université de Nice Sophia-Antipolis (UNSA), CHU Trousseau [APHP], Department Gastroenteroly IBD and Nutrition Support, Association Francois Aupetit, MSD France, Helmsley Charitable Trust, 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), Centre Hospitalier Universitaire Estaing, Department Digestion Surgery, Hopital Saint Antoine, Hôpital Lariboisière, Biochimie, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP]

Subjects
medicine.medical_specialty, medicine.medical_treatment, chirurgie, 03 medical and health sciences, Ileostomy, 0302 clinical medicine, intestin, Interquartile range, medicine, Risk factor, Prospective cohort study, intestine, maladie inflammatoire, Crohn's disease, Hepatology, business.industry, Gastroenterology, Postoperative complication, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, maladie de crohn, Odds ratio, crohn disease, medicine.disease, inflammatory disease, 3. Good health, Surgery, facteur de risque, risk factor, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, thérapie, Cohort study
Abstract

OBJECTIVES: We sought to determine the frequency of and risk factors for early (30-day) postoperative complications after ileocecal resection in a well-characterized, prospective cohort of Crohn's disease patients. METHODS: The REMIND group performed a nationwide study in 9 French university medical centers. Clinical-, biological-, surgical-, and treatment-related data on the 3 months before surgery were collected prospectively. Patients operated on between 1 September 2010 and 30 August 2014 were included. RESULTS: A total of 209 patients were included. The indication for ileocecal resection was stricturing disease in 109 (52%) cases, penetrating complications in 88 (42%), and medication-refractory inflammatory disease in 12 (6%). A two-stage procedure was performed in 33 (16%) patients. There were no postoperative deaths. Forty-three (21%) patients (23% of the patients with a one-stage procedure vs. 9% of those with a two-stage procedure, P=0.28) experienced a total of 54 early postoperative complications after a median time interval of 5 days (interquartile range, 4-12): intra-abdominal septic complications (n=38), extraintestinal infections (n=10), and hemorrhage (n=6). Eighteen complications (33%) were severe (Dindo-Clavien III-IV). Reoperation was necessary in 14 (7%) patients, and secondary stomy was performed in 8 (4.5%). In a multivariate analysis, corticosteroid treatment in the 4 weeks before surgery was significantly associated with an elevated postoperative complication rate (odds ratio (95% confidence interval)=2.69 (1.15-6.29); P=0.022). Neither preoperative exposure to anti-tumor necrosis factor (TNF) agents (n=93, 44%) nor trough serum anti-TNF levels were significant risk factors for postoperative complications. CONCLUSIONS: In this large, nationwide, prospective cohort, postoperative complications were observed after 21% of the ileocecal resections. Corticosteroid treatment in the 4 weeks before surgery was significantly associated with an elevated postoperative complication rate. In contrast, preoperative anti-TNF therapy (regardless of the serum level or the time interval between last administration and surgery) was not associated with an elevated risk of postoperative complications.

Published
2017
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46. An Unusual Case of Chronic Cough Revealing Ulcerative Colitis

Author

Louise Bondeelle, Nassim Hammoudi, and Jean-Marc Gornet

Subjects
medicine.medical_specialty, Colon, Biopsy, Colonoscopy, Bronchi, Gastroenterology, Pulmonary Disease, Chronic Obstructive, Young Adult, X ray computed, Internal medicine, medicine, Humans, Young adult, Colitis, Bronchiolitis Obliterans, Unusual case, Hepatology, medicine.diagnostic_test, business.industry, medicine.disease, Ulcerative colitis, Respiratory Function Tests, Chronic cough, Cough, Colitis, Ulcerative, Female, medicine.symptom, Tomography, X-Ray Computed, business, Immunosuppressive Agents
Published
2020
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47. Bidirectional chemotherapy combining intraperitoneal docetaxel with intravenous 5-fluorouracil and oxaliplatin for patients with unresectable peritoneal metastasis from gastric cancer: the first study in Western countries

Author

Rea Lo Dico, Nicola Guglielmo, Julien Taieb, Jean Marc Gornet, Aziz Zaanan, and Marc Pocard

Subjects
medicine.medical_specialty, medicine.medical_treatment, intraperitoneal chemotherapy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Internal medicine, Internal Medicine, medicine, cytoreductive surgery, advanced gastric cancer, Chemotherapy, HIPEC, business.industry, Oxaliplatin, Regimen, Docetaxel, Fluorouracil, 030220 oncology & carcinogenesis, peritoneal metastasis, Conventional PCI, Peritoneal Cancer Index, 030211 gastroenterology & hepatology, business, medicine.drug, Research Article, bidirectional chemotherapy
Abstract

BackgroundA new treatment using bidirectional intraperitoneal (IP) and intravenous (IV) chemotherapy developed by Asiatic surgeons improves outcomes in patients with synchronous peritoneal metastasis (PM) from gastric cancer (GC).MethodsWe enrolled six consecutive patients with unresectable PM from GC who underwent bidirectional chemotherapy using IP docetaxel and IV FOLFOX or LV5FU2. In one course, IP docetaxel 30 mg/m2 was administrated on days 1, 8 and 15, and IV FOLFOX or LV5FU2 was administered on days 1 and 15, followed by 7 days of rest. Before and after a complete bidirectional cycle of three courses, the peritoneal cancer index (PCI) was evaluated by laparoscopy. The primary endpoint was to evaluate the feasibility and safety of bidirectional chemotherapy. Secondary endpoints were overall survival (OS), and the success of the therapeutic strategy was reflected by a decrease of 25% of the initial PCI.ResultsAll patients completed one bidirectional cycle. The regimen was well tolerated. The median OS was 13 months [range 5–18], and the 1-year OS rate was 67%. After the first bidirectional cycle, the PCI decrease ≥25% of the initial value in four patients. A major histological response was observed in four patients.ConclusionsThis is the first Western study and confirms the feasibility and safety of bidirectional treatment using IP and IV chemotherapy for patients with unresectable PM from GC, resulting in a 13-month median OS with limited morbidity. The decrease in PCI after one bidirectional cycle is promising.

Published
2019

48. Impact of tobacco smoking on the patient's outcome after (chemo)radiotherapy for anal cancer

Author

Christophe Hennequin, Thomas Aparicio, Jean-Marc Gornet, Jacques Lerman, Laurent Quero, Sophie Guillerm, Alain Valverde, Gaël Goujon, Laurent Abramowitz, Pierre Cattan, Isabelle Etienney, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe Hospitalier Diaconesses Croix Saint-Simon, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CCSD, Accord Elsevier, Clinique Blomet, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Tobacco, Tobacco Smoking, Medicine, Anal cancer, Humans, Cancer, Aged, Retrospective Studies, Aged, 80 and over, Univariate analysis, Radiotherapy, business.industry, Anal Squamous Cell Carcinoma, Chemoradiotherapy, Middle Aged, medicine.disease, Anus Neoplasms, Prognosis, Confidence interval, 3. Good health, Anal, [SDV] Life Sciences [q-bio], Radiation therapy, 030104 developmental biology, Treatment Outcome, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, Neoplasm Recurrence, Local, business
Abstract

International audience; Purpose: Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer.Methods: We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival (OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS).Results: Patients' characteristics were as follows: median age, 62 years (range = 36-89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86 patients (50%), among whom 28 patients and 58 patients were current and former smokers, respectively. Tumours were classified as locally limited (T1-2, N0, M0) for 86 patients (50%) and locally advanced (T3-4 or N+, M0) for 85 patients (50%). The median total dose was 64.4 Gy (range = 54-76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4 cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio = 2.85, 95% confidence interval [1.25-6.50], p = 0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p = 0.038). Tobacco smoking was also associated with poor overall survival (p = 0.03), locoregional relapse-free survival (LRFS; p = 0.05) and CFS (p = 0.02).Conclusions: Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose ± chemotherapy.

Published
2019
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49. Management of colorectal peritoneal metastases: Expert opinion

Author

Marc Ychou, François Quenet, Pascale Mariani, Olivia Sgarbura, Jérémie H. Lefevre, Thierry André, M. Brunel, Jean-Marc Gornet, Karine Abboud, A. Pinto, Marc Pocard, Michel Ducreux, C. Eveno, Olivier Glehen, Diane Goéré, Service d'Oncologie Médicale [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), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de chirurgie générale et digestive [CHU Saint-Antoine], Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier de Versailles André Mignot (CHV), Institut Gustave Roussy (IGR), Université Paris-Saclay, Lille Neurosciences & Cognition - U 1172 (LilNCog), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], CArcinose Péritoine Paris-Technologies (ex-CART) (CAP Paris-Tech (UMR_S_1275)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], CCSD, Accord Elsevier, CHU Saint-Etienne, Service d'Oncologie Médicale [CHU Saint-Antoine], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, Colorectal cancer, [SDV]Life Sciences [q-bio], Antineoplastic Agents, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cytoreductive surgery, Radical surgery, Laparoscopy, Peritoneal Neoplasms, Carcinomatosis, medicine.diagnostic_test, HIPEC, business.industry, General surgery, Carcinoma, Cytoreduction Surgical Procedures, Hyperthermia, Induced, General Medicine, medicine.disease, Combined Modality Therapy, 3. Good health, Oxaliplatin, Colon cancer, [SDV] Life Sciences [q-bio], Chemotherapy, Cancer, Regional Perfusion, 030220 oncology & carcinogenesis, Expert opinion, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, Peritoneal diseases, Colorectal Neoplasms, business, medicine.drug
Abstract

International audience; When peritoneal metastases are diagnosed (strong agreement of experts): (i) seek advice from a multidisciplinary coordination meeting (MCM) with large experience in peritoneal disease (e.g. BIG RENAPE network); (ii) transfer (or not) the patient to a referral center with experience in hyperthermic intraperitoneal chemotherapy (HIPEC), according to the advice of the MCM. With regard to systemic chemotherapy (strong agreement of experts): (i) it should be performed both before and after surgery, (ii) for no longer than 6 months; (iii) without postoperative anti-angiogenetic drugs. With regard to cytoreductive surgery (strong agreement of experts): (i) Radical surgery requires a xiphopubic midline incision; (ii) no cytoreductive surgery via laparoscopy. With regard to HIPEC: HIPEC can be proposed for trials outside an HIPEC referral center (weak agreement between experts): (i) if surgery is radical; (ii) if the expected morbidity is "reasonable"; (iii) if the indication for HIPEC was suggested by a MCM, and; (iv) mitomycin is preferred to oxaliplatin (which cannot be recommended) for this indication.

Published
2019
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50. Possible Paradoxical Photosensitive Psoriasis Induced by Tumour Necrosis Factor-alpha Inhibitors

Author

Jean-Marc Gornet, Marie-Dominique Vignon-Pennamen, Jean-David Bouaziz, Pauline Bataille, and Adèle de Masson

Subjects
Male, Administration, Topical, Dermatology, Tumour necrosis factor alpha, Risk Assessment, Tacrolimus, Young Adult, Crohn Disease, Psoriasis, medicine, lcsh:Dermatology, Humans, Photosensitivity Disorders, business.industry, Tumor Necrosis Factor-alpha, Biopsy, Needle, General Medicine, lcsh:RL1-803, medicine.disease, Immunohistochemistry, Infliximab, Treatment Outcome, Cancer research, business, Blood Chemical Analysis, Facial Dermatoses, Follow-Up Studies
Published
2019

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