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1. Nomenclature and Definition of Atrophic Lesions in Small Bowel Capsule Endoscopy: A Delphi Consensus Statement of the International CApsule endoscopy REsearch (I-CARE) Group

Author

Luca Elli, Beatrice Marinoni, Reena Sidhu, Christian Bojarski, Federica Branchi, Gian Eugenio Tontini, Stefania Chetcuti Zammit, Sherine Khater, Rami Eliakim, Emanuele Rondonotti, Jean Cristhophe Saurin, Mauro Bruno, Juliane Buchkremer, Sergio Cadoni, Flaminia Cavallaro, Xavier Dray, Pierre Ellul, Ignacio Fernandez Urien, Martin Keuchel, Uri Kopylov, Anastasios Koulaouzidis, Romain Leenhardt, Peter Baltes, Hanneke Beaumont, Clelia Marmo, Deirdre McNamara, Alessandro Mussetto, Artur Nemeth, Enrique Perez Cuadrado Robles, Guillame Perrod, Gabriel Rahmi, Maria Elena Riccioni, Alexander Robertson, Cristiano Spada, Ervin Toth, Konstantinos Triantafyllou, Gabriele Wurm Johansson, and Alessandro Rimondi

Subjects
small bowel atrophy, video-capsule enteroscopy, consensus, Medicine (General), R5-920
Abstract

(1) Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; (2) Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; (3) Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); (4) Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.

Published
2022
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2. Effectiveness of a dedicated small bowel neoplasia screening program by capsule endoscopy in Lynch syndrome: 5 years results from a tertiary care center

Author

Guillaume Perrod, Elia Samaha, Enrique Perez-Cuadrado-Robles, Arthur Berger, Hedi Benosman, Sherine Khater, Ariane Vienne, Charles-André Cuenod, Aziz Zaanan, Pierre Laurent-Puig, Gabriel Rahmi, and Christophe Cellier

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and aims: The role of small bowel neoplasia (SBN) screening in asymptomatic patients with Lynch syndrome (LS) is uncertain. The aim of our study was to assess the effectiveness of screening by capsule endoscopy (CE) in these patients. Methods: This study was an observational, analytical, and retrospective single-center study within the PRED-IdF network. All consecutive asymptomatic patients older than 35 years-old with confirmed LS and no personal history of SBN who started the screening from 2010–2015 were included. The baseline screening and 24 months follow-up were performed by CE. The CE diagnostic yield (positive tumor or polyp) and accuracy, using the follow-up as gold standard, were evaluated. Results: A total of 150 patients underwent the SBN screening program and 135 (52.7 ± 11.2 years-old, 37.8% male) met the inclusion criteria. The baseline CE diagnostic yield was 4.4% (3 polyps, 3 tumors) and the proximal small bowel was the most common location ( n = 4, 66.7%). In total, 87 patients underwent follow-up and the diagnostic yield was 4.6%. Four patients were considered positive at follow-up (2 adenomas, 2 adenocarcinomas). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CE were 60%, 100%, 100%, 96.9%, and 97%, respectively. Conclusions: CE is an accurate procedure for baseline screening of SBN in LS patients and may be efficient for follow-up procedures. However, the optimal starting age of screening and intervals of follow-up must be clarified.

Published
2020
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3. A novel data-driven workflow combining literature and electronic health records to estimate comorbidities burden for a specific disease: a case study on autoimmune comorbidities in patients with celiac disease

Author

Jean-Baptiste Escudié, Bastien Rance, Georgia Malamut, Sherine Khater, Anita Burgun, Christophe Cellier, and Anne-Sophie Jannot

Subjects
Autoimmune diseases, Celiac disease, Electronic health records, Icd 10, Phenotype, Prevalence study, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Data collected in EHRs have been widely used to identifying specific conditions; however there is still a need for methods to define comorbidities and sources to identify comorbidities burden. We propose an approach to assess comorbidities burden for a specific disease using the literature and EHR data sources in the case of autoimmune diseases in celiac disease (CD). Methods We generated a restricted set of comorbidities using the literature (via the MeSH® co-occurrence file). We extracted the 15 most co-occurring autoimmune diseases of the CD. We used mappings of the comorbidities to EHR terminologies: ICD-10 (billing codes), ATC (drugs) and UMLS (clinical reports). Finally, we extracted the concepts from the different data sources. We evaluated our approach using the correlation between prevalence estimates in our cohort and co-occurrence ranking in the literature. Results We retrieved the comorbidities for 741 patients with CD. 18.1% of patients had at least one of the 15 studied autoimmune disorders. Overall, 79.3% of the mapped concepts were detected only in text, 5.3% only in ICD codes and/or drugs prescriptions, and 15.4% could be found in both sources. Prevalence in our cohort were correlated with literature (Spearman’s coefficient 0.789, p = 0.0005). The three most prevalent comorbidities were thyroiditis 12.6% (95% CI 10.1–14.9), type 1 diabetes 2.3% (95% CI 1.2–3.4) and dermatitis herpetiformis 2.0% (95% CI 1.0–3.0). Conclusion We introduced a process that leveraged the MeSH terminology to identify relevant autoimmune comorbidities of the CD and several data sources from EHRs to phenotype a large population of CD patients. We achieved prevalence estimates comparable to the literature.

Published
2017
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4. Impact of an optimized colonoscopic screening program for patients with Lynch syndrome: 6-year results of a specialized French network

Author

Guillaume Perrod, Elia Samaha, Gabriel Rahmi, Sherine Khater, Leila Abbes, Camille Savale, Geraldine Perkins, Aziz Zaanan, Gilles Chatellier, Georgia Malamut, and Christophe Cellier

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background: Despite colonoscopic screening, colorectal cancer (CRC) remains frequent in patients with Lynch syndrome (LS). The objective of this study was to evaluate the impact of an optimized colorectal screening program within a French dedicated network. Methods: All LS patients followed at our institution were consecutively included in the Prédisposition au Cancer Colorectal-Ile de France (PRED-IdF) network. Patients were offered an optimized screening program allowing an adjustment of the interval between colonoscopies, depending on bowel preparation, chromoendoscopy achievement and adenoma detection. Colonoscopies were defined as optimal when all the screening criteria were respected. We compared colonoscopy quality and colonoscopy detection rate before and after PRED-IdF inclusion, including polyp detection rate (PDR), adenoma detection rate (ADR) and cancer detection rate (CDR). Results: Between January 2010 and January 2016, 144 LS patients were consecutively included (male/female = 50/94, mean age = 51 ± 13 years and mutations: MLH1 = 39%, MSH2 = 44%, MSH6 = 15%, PMS2 = 1%). A total of 564 colonoscopies were analyzed, 353 after inclusion and 211 before. After PRED-IdF inclusion, 98/144 (68%) patients had optimal screening colonoscopies versus 33/132 (25%) before ( p < 0.0005). The optimal colonoscopy rate was 304/353 (86%) after inclusion versus 87/211 (41%) before, ( p < 0.0001). PRED-IdF inclusion was associated with a reduction of CRC occurrence with a CDR of 1/353 (0.3%) after inclusion versus 6/211 (2.8%) before ( p = 0.012). ADR and PDR were 99/353 (28%) versus 60/211 (28.8%) ( p > 0.05) and 167/353 (48.1%) versus 90/211 (42.2%) ( p > 0.05), respectively after and before inclusion. Conclusions: An optimized colonoscopic surveillance program in LS patients seems to improve colonoscopic screening quality and might possibly decrease colorectal interval cancer occurrence. Long-term cohort studies are needed to confirm these results.

Published
2018
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5. Over-the-scope clip (OTSC) reduces surgery rate in the management of iatrogenic gastrointestinal perforations

Author

Sherine Khater, Gabriel Rahmi, Guillaume Perrod, Elia Samaha, Hedi Benosman, Leila Abbes, Georgia Malamut, and Christophe Cellier

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and study aims Over-the-scope clip (OTSC) has been recently used in management of gastrointestinal perforations, but data on it are still limited. The aim of this study was to compare management of iatrogenic perforations before and after the OTSC was available in our endoscopy unit. Patients and methods We conducted a monocentric retrospective study from June 2007 to June 2015. All iatrogenic gastrointestinal perforations detected during endoscopy were included. Two time periods were compared in terms of surgery and mortality rates: before use of OTSC (June 2007 to June 2011) and after OTSC became available (June 2011 to June 2015). Results During the first period, 24 perforations were recorded. Fifteen (62.5 %) were managed with surgery. The mortality rate was 8 %. During the second period, 16 perforations occurred. In 11 patients (68.7 %), an OTSC was used to close the perforation, with complete sealing of the perforation in 100 % of cases. However, 2 patients with sigmoid perforation had to undergo surgery due to right ureteral obstruction by the clip in 1 case and to presence of a localized peritonitis in the other. The surgery rate during this period was 12.5 % (2 /16), with a statistically significant difference compared to the first period (P = 0.002). There was no mortality in the second period versus 8 % in the first one (P = 0.23). Conclusions OTSC is effective for endoluminal closure of iatrogenic perforations and results in a significant decrease in surgery rate.

Published
2017
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6. 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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7. Small bowel polyp resection using device‐assisted enteroscopy in Peutz‐Jeghers Syndrome: Results of a specialised tertiary care centre

Author

Enrique Pérez-Cuadrado-Robles, A Vienne, Guillaume Perrod, C.A. Cuenod, Christophe Cellier, Hedi Benosman, Elia Samaha, Arthur Berger, Pierre Laurent-Puig, Gabriel Rahmi, Aziz Zaanan, and Sherine Khater

Subjects
Adult, Male, Enteroscopy, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Balloon Enteroscopy, Adolescent, Biopsy, Peutz-Jeghers Syndrome, Peutz–Jeghers syndrome, Capsule Endoscopy, Tertiary care, law.invention, Resection, Tertiary Care Centers, Young Adult, Hamartomatous Polyp, Capsule endoscopy, law, Intestine, Small, medicine, Humans, Intestinal Mucosa, Device assisted enteroscopy, skin and connective tissue diseases, Aged, Retrospective Studies, Intraoperative Care, business.industry, Gastroenterology, Intestinal Polyps, Original Articles, Middle Aged, medicine.disease, Magnetic Resonance Imaging, digestive system diseases, Treatment Outcome, Oncology, Female, Small Bowel Polyp, Radiology, business, Follow-Up Studies
Abstract

INTRODUCTION: Enteroscopy resection of small bowel polyps in Peutz-Jeghers syndrome has only been described in small case series. Herein, we aimed to assess the efficacy of enteroscopy resection of small bowel polyps within a specialised tertiary care centre and the impact on intraoperative enteroscopy. METHODS: This was an observational single-centre study. All adult Peutz-Jeghers syndrome patients followed in the Predisposition Digestive Ile-de-France network who underwent an endoscopic resection of at least one small bowel polyp ≥ 1 cm by enteroscopy between 2002–2015 were included. Small bowel polyps were detected under a dedicated screening programme by previous capsule endoscopy and/or magnetic resonance enterography, performed every 2–3 years. Complete treatment was defined as the absence of polyps ≥ 1 cm after conventional endoscopic resection. Intraoperative enteroscopy or surgical resection were indicated in incomplete treatments. The overall complete treatment rate including conventional enteroscopy and intraoperative enteroscopy was also considered. RESULTS: Endoscopic resection of 216 small bowel polyps (median: 8.6 per patient, size: 6–60 mm) was performed by 50 enteroscopies in 25 patients (mean age: 36 years, range: 18–71, 56% male) with small bowel polyp ≥ 1 cm. Twenty-three patients (92%) underwent 42 screening capsule endoscopies and 14 (57%) had 23 magnetic resonance enterographies during a median follow-up of 60 months. Complete treatment was achieved in 76%. Intraoperative enteroscopy and surgical resection were performed in four (16%) and two (8%) patients. Intraoperative enteroscopy improved by 16% the complete treatment rate and the overall rate was 92%. The complication rate was 6%. CONCLUSION: This long-term study confirmed the efficacy and safety of endoscopic resection of small bowel polyps in Peutz-Jeghers syndrome. Intraoperative enteroscopy can be a complementary approach in selected cases.

Published
2020
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8. 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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10. Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study

Author

Ciaran P. Kelly, Garbiñe Roy Ariño, Anthony J. DiMarino, George Vlad, Laura Crespo, Raquel Perez Maseda, Amélie Trinquand, Ralph Raymond, Michael Schumann, Anne Blanchard, Olivier Hermine, Georgia Malamut, Jane R. Parnes, Samuli Rounioja, Eric Butz, Valerie Byrnes, Hetty J. Bontkes, Wayne Tsuji, Christophe Cellier, Gerd Bouma, Beth Llewellyn, Nadine Cerf-Bensussan, Tom van Gils, Peter H.R. Green, Joseph A. Murray, Govind Bhagat, Jack D. Bui, Ashleigh Palmer, Bana Jabri, Knut E.A. Lundin, Elizabeth Macintyre, Pekka Collin, Carlota García-Hoz, Sherine Khater, Bertrand Meresse, Francisco Leon, Chris J. J. Mulder, Sheila E. Crowe, David S Sanders, Michel Azizi, Marios Hadjivassiliou, Keijo Viiri, Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Columbia University Medical Center (CUMC), Columbia University [New York], Department of Medicine, University of Washington [Seattle], Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CCSD, Accord Elsevier, 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), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Tampere University Hospital, University of California [San Diego] (UC San Diego), University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Amgen Inc., RCD-II Study Group Investigators: Bana Jabri, Joseph Murray, Anthony DiMarino, Ciaran P Kelly, Valerie Byrnes, David Sanders, Knut Ea Lundin, Michael Schumann, Hetty Bontkes, Bertrand Meresse, Garbiñe Roy Ariño, Govind Bhagat, Keijo Viiri, Samuli Rounioja, Jack Bui, Raquel Perez Maseda, Carlota García-Hoz, Amelie Trinquand, George Vlad, Marios Hadjivassiliou, Michel Azizi, Anne Blanchard, Beth Llewellyn, Ashleigh Palmer, Ralph Raymond, Gastroenterology and hepatology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, and AII - Inflammatory diseases

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Placebo, Gastroenterology, Coeliac disease, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Biopsy, medicine, Clinical endpoint, Adverse effect, education, education.field_of_study, Hepatology, medicine.diagnostic_test, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Intraepithelial lymphocyte, 030211 gastroenterology & hepatology, business
Abstract

Summary Background Refractory coeliac disease type 2 is a rare subtype of coeliac disease with high mortality rates; interleukin 15 (IL-15) is strongly implicated in its pathophysiology. This trial aimed to investigate the effects of AMG 714, an anti-IL-15 monoclonal antibody, on the activity and symptoms of refractory coeliac disease type 2. Methods This was a randomised, double-blind, placebo-controlled, phase 2a study of adults with a confirmed diagnosis of refractory coeliac disease type 2. Patients were randomly assigned at a 2:1 ratio to receive seven intravenous doses over 10 weeks of AMG 714 (8 mg/kg) or matching placebo. Biopsy samples were obtained at baseline and week 12 for cellular analysis and histology. The change in the proportion of aberrant intraepithelial lymphocytes from baseline to week 12 with respect to all intraepithelial lymphocytes was the primary endpoint and was quantified using flow cytometry. Secondary endpoints were the change in aberrant intraepithelial lymphocytes with respect to intestinal epithelial cells; intestinal histological scores (villous height-to-crypt depth ratio; VHCD); intraepithelial lymphocyte counts; Marsh score; and patient-reported symptom measures, including the Bristol stool form scale (BSFS) and gastrointestinal symptom rating scale (GSRS). Main analyses were done in the per-protocol population of patients who received their assigned treatment, provided evaluable biopsy samples, and did not have major protocol deviations; only patients with non-atypical disease were included in the analyses of aberrant intraepithelial lymphocytes, including the primary analysis. Safety was assessed in all patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov (NCT02633020) and EudraCT (2015-004063-36). Findings From April 13, 2016, to Jan 19, 2017, 28 patients were enrolled and randomly assigned to AMG 714 (n=19) and placebo (n=9). Six patients were not included in the primary analysis because of protocol deviation (one in the AMG 714 group), insufficient biopsy samples (one in the AMG 714 group), and atypical intraepithelial lymphocytes (three in the AMG 714 group and one in the placebo group). At 12 weeks, the least square mean difference between AMG 714 and placebo in the relative change from baseline in aberrant intraepithelial lymphocyte percentage was −4·85% (90% CI −30·26 to 20·56; p=0·75). The difference between the AMG 714 and placebo groups in aberrant intraepithelial lymphocytes with respect to epithelial cells at 12 weeks was −38·22% (90% CI −95·73 to 19·29; nominal p=0·18); the difference in change in Marsh score from baseline was 0·09% (95% CI −1·60–1·90; nominal p=0·92); the difference in VHCD ratio was 10·67% (95% CI −38·97 to 60·31; nominal p=0·66); and the difference in change in total intraepithelial lymphocyte count was −12·73% (95% CI −77·57–52·12); nominal p=0·69). Regarding symptoms, the proportion of patients with diarrhoea per the BSFS score decreased from ten (53%) of 19 at baseline to seven (37%) of 19 at week 12 in the AMG 714 group and increased from two (22%) of nine at baseline to four (44%) of nine at week 12 in the placebo group (nominal p=0·0008); and the difference between the groups in change in GSRS score was −0·14 (SE 0·19; nominal p=0·48). Eight (89%) patients in the placebo group and 17 (89%) in the AMG 714 group had treatment-emergent adverse events, including one (11%) patient in the placebo group and five (26%) in the AMG 714 group who had serious adverse events. The most common adverse event in the AMG 714 group was nasopharyngitis (eight [42%] patients vs one [11%] in the placebo group). Interpretation In patients with refractory coeliac disease type 2 who were treated with AMG 714 or placebo for 10 weeks, there was no difference between the groups in terms of the primary endpoint of aberrant intraepithelial lymphocyte reduction from baseline. Effects on symptoms and other endpoints suggest that further research of AMG 714 may be warranted in patients with refractory coeliac disease type 2. Funding Celimmune and Amgen.

Published
2019
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11. Oncogenetic Landscape Of Lymphomagenesis In Coeliac Disease

Author

Thierry Jo Molina, Ludovic Lhermitte, Christine Bole-Feysot, Georgia Malamut, Elizabeth Macintyre, Morgane Cheminant, Amélie Trinquand, Sophie Kaltenbach, Bruno Tesson, Olivier Hermine, David Sibon, Sofia Berrabah, Patrick Villarese, Christophe Cellier, Sherine Khater, Nicolas Guegan, Sascha Cording, Julie Bruneau, Marc Bras, Bertrand Meresse, Nadine Cerf-Bensussan, Vahid Asnafi, and Michael Dussiot

Subjects
Bortezomib, medicine, Cancer research, Proteasome inhibitor, Biology, medicine.disease, DDX3X, TNFAIP3, Coeliac disease, Exome sequencing, Comparative genomic hybridization, medicine.drug, Lymphoma
Abstract

ObjectiveEnteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of celiac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis.DesignPure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridization and RNA-sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=7) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines.Results80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase-domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in NFκB-regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines.ConclusionMutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NFκB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL.

Published
2020
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12. Effectiveness of a dedicated small bowel neoplasia screening program by capsule endoscopy in Lynch syndrome: 5 years results from a tertiary care center

Author

Pierre Laurent-Puig, Gabriel Rahmi, Elia Samaha, Sherine Khater, Hedi Benosman, Enrique Pérez-Cuadrado-Robles, C.A. Cuenod, A Vienne, Christophe Cellier, Aziz Zaanan, Guillaume Perrod, and Arthur Berger

Subjects
medicine.medical_specialty, business.industry, General surgery, capsule endoscopy, Gastroenterology, medicine.disease, Tertiary care, Asymptomatic, Lynch syndrome, law.invention, 03 medical and health sciences, smal bowel neoplasia screening, 0302 clinical medicine, Capsule endoscopy, law, diagnostic yield, 030220 oncology & carcinogenesis, Medicine, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, medicine.symptom, lcsh:RC799-869, business, Original Research
Abstract

Background and aims: The role of small bowel neoplasia (SBN) screening in asymptomatic patients with Lynch syndrome (LS) is uncertain. The aim of our study was to assess the effectiveness of screening by capsule endoscopy (CE) in these patients. Methods: This study was an observational, analytical, and retrospective single-center study within the PRED-IdF network. All consecutive asymptomatic patients older than 35 years-old with confirmed LS and no personal history of SBN who started the screening from 2010–2015 were included. The baseline screening and 24 months follow-up were performed by CE. The CE diagnostic yield (positive tumor or polyp) and accuracy, using the follow-up as gold standard, were evaluated. Results: A total of 150 patients underwent the SBN screening program and 135 (52.7 ± 11.2 years-old, 37.8% male) met the inclusion criteria. The baseline CE diagnostic yield was 4.4% (3 polyps, 3 tumors) and the proximal small bowel was the most common location ( n = 4, 66.7%). In total, 87 patients underwent follow-up and the diagnostic yield was 4.6%. Four patients were considered positive at follow-up (2 adenomas, 2 adenocarcinomas). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CE were 60%, 100%, 100%, 96.9%, and 97%, respectively. Conclusions: CE is an accurate procedure for baseline screening of SBN in LS patients and may be efficient for follow-up procedures. However, the optimal starting age of screening and intervals of follow-up must be clarified.

Published
2020

13. Rôle du pathologiste dans le diagnostic de la maladie cœliaque et de ses complications

Author

Julie Bruneau, David Sibon, Olivier Hermine, Christophe Cellier, Thierry Molina, Elizabeth Macintyre, Sherine Khater, Amélie Trinquand, Georgia Malamut, Nadine Cerf-Bensussan, Morgane Cheminant, and Danielle Canioni

Subjects
0301 basic medicine, 03 medical and health sciences, Medical Laboratory Technology, 030104 developmental biology, 0302 clinical medicine, Biochemistry (medical), 030211 gastroenterology & hepatology, Analytical Chemistry
Abstract

Resume La maladie cœliaque (MC), ou intolerance au gluten, est une pathologie multifactorielle developpee sur un terrain genetique predisposant. Aujourd’hui encore sous diagnostiquee, elle toucherait pres de 1 % de la population mondiale. La presentation clinique classique d’enteropathie avec malabsorption n’est pas la plus frequente, elle est souvent asymptomatique, pauci-symptomatique ou de presentation clinique atypique. Son diagnostic est multidisciplinaire, et l’apport de l’histologie bien que discute, est souvent primordial, confirmant le diagnostic suspecte de MC et justifiant ainsi la mise en place d‘un regime sans gluten (RSG) a vie. L’histologie est utile egalement lors du suivi de la MC, afin de mettre en evidence une pathologie associee ou une evolution defavorable vers une MC refractaire au RSG. Enfin, il faut savoir remettre en question le diagnostic de MC si tous les parametres biologiques ne sont pas reunis et notamment un typage HLA compatible. En effet, la premiere cause d’atrophie villositaire est la MC, mais de nombreuses etiologies peuvent etre associees a une atrophie villositaire. Dans cette revue, les points essentiels du diagnostic, de la physiopathologie, de l’histopathologie et des complications de la MC seront developpes.

Published
2018
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14. Over-the-scope clip (OTSC) reduces surgery rate in the management of iatrogenic gastrointestinal perforations

Author

Leila Abbes, Gabriel Rahmi, Hedi Benosman, Georgia Malamut, Elia Samaha, Christophe Cellier, Guillaume Perrod, and Sherine Khater

Subjects
Original article, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Mortality rate, Perforation (oil well), Significant difference, Peritonitis, Retrospective cohort study, Over the scope clip, medicine.disease, Surgery, Endoscopy, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Medicine, lcsh:Diseases of the digestive system. Gastroenterology, 030211 gastroenterology & hepatology, Pharmacology (medical), lcsh:RC799-869, business
Abstract

Background and study aims Over-the-scope clip (OTSC) has been recently used in management of gastrointestinal perforations, but data on it are still limited. The aim of this study was to compare management of iatrogenic perforations before and after the OTSC was available in our endoscopy unit. Patients and methods We conducted a monocentric retrospective study from June 2007 to June 2015. All iatrogenic gastrointestinal perforations detected during endoscopy were included. Two time periods were compared in terms of surgery and mortality rates: before use of OTSC (June 2007 to June 2011) and after OTSC became available (June 2011 to June 2015). Results During the first period, 24 perforations were recorded. Fifteen (62.5 %) were managed with surgery. The mortality rate was 8 %. During the second period, 16 perforations occurred. In 11 patients (68.7 %), an OTSC was used to close the perforation, with complete sealing of the perforation in 100 % of cases. However, 2 patients with sigmoid perforation had to undergo surgery due to right ureteral obstruction by the clip in 1 case and to presence of a localized peritonitis in the other. The surgery rate during this period was 12.5 % (2 /16), with a statistically significant difference compared to the first period (P = 0.002). There was no mortality in the second period versus 8 % in the first one (P = 0.23). Conclusions OTSC is effective for endoluminal closure of iatrogenic perforations and results in a significant decrease in surgery rate.

Published
2017
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15. Cerebral infarction following cyanoacrylate endoscopic therapy of duodenal varices in a patient with a patent foramen ovale

Author

Christophe Cellier, Damien Vimpere, Sherine Khater, Jean-Luc Diehl, and Baptiste Abbar

Subjects
medicine.medical_specialty, business.industry, Cerebral infarction, Duodenal varices, Foramen ovale (skull), 030204 cardiovascular system & hematology, medicine.disease, law.invention, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Cyanoacrylate, law, Emergency Medicine, Internal Medicine, Patent foramen ovale, Medicine, 030211 gastroenterology & hepatology, business
Published
2018
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16. NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: A CELAC study

Author

Nicolas Guegan, Florence Lhospice, Sascha Cording, Amélie Trinquand, Julie Bruneau, Olivier Hermine, Virginie Verkarre, Nicole Brousse, Christophe Cellier, Georgia Malamut, Elizabeth Macintyre, Felipe Suarez, Laurent Frenzel, Vahid Asnafi, Morgane Cheminant, Sherine Khater, Bertrand Meresse, Ambroise Marçais, Nadine Cerf-Bensussan, Tom van Gils, Chris J. J. Mulder, Thierry Jo Molina, Ludovic Lhermitte, C. cile Bonnafous, David Sibon, Anne-Sophie Jannot, Richard Delarue, Laurent Pouyet, Gastroenterology and hepatology, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), 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), VU University Medical Center [Amsterdam], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, Mi-mAbs (C/O CIML), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Innate Pharma, Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, MESH: Biopsy / methods, Enteropathy-Associated T-Cell Lymphoma / diagnosis, Entropathy-Associated T-Cell Lymphoma / etiology, Enteropathy-Associated T-Cell Lymphoma / immunology, T cell, Biopsy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Coeliac Disease, Coeliac disease, 03 medical and health sciences, 0302 clinical medicine, Enteropathy-Associated T-Cell Lymphoma, Intestinal mucosa, Intestine, Small, medicine, Cytotoxic T cell, Humans, Intestinal Mucosa, MESH: Enteropathy-Associated T-Cell Lymphoma / pathology, Intestinal Mucosa / immunology, Intestinal Mucosa / pathology, Killer Cells, Natural / immunology, Antibody Targeted Therapy, Cells, Cultured, business.industry, Natural Cytotoxicity Triggering Receptor 1, Gastroenterology, MESH: Natural Cytotoxicity Triggering Receptor 1 / immunology, Antibodies, Monoclonal, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, NKG2D, Prognosis, 3. Good health, Killer Cells, Natural, Celiac Disease, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Intraepithelial lymphocyte, Enteropathy-associated T-cell lymphoma, Female, France, Gastrointestinal Lymphoma, business, Ex vivo, Biomarkers, Tumour markers
Abstract

ObjectivesPrimary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs).DesignNKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies.ResultsNKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo.ConclusionNKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL.

Published
2019
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18. EVALUATION OF BARRETT'S ESOPHAGUS (BE) USING BLUE LIGHT IMAGING (BLI) AND LINKED COLOR IMAGING (LCI): EXPERIENCE OF 2 UNIVERSITY HOSPITALS

Author

Christophe Cellier, N Etchepare, N Asmar, Emmanuel Coron, G Rahmi, Sherine Khater, Nicolas Musquer, Guillaume Perrod, Elia Samaha, H Benosman, A Vienne, and M Le Rhun

Subjects
medicine.medical_specialty, business.industry, Barrett's esophagus, medicine, Radiology, Color imaging, medicine.disease, University hospital, business, Blue light
Published
2019
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20. Résection endoscopique des tumeurs sous-muqueuses gastriques de petite taille

Author

Elia Samaha, H. Benosman, Georgia Malamut, Guillaume Perrod, C. Savale, A Vienne, B. Landi, Leila Abbes, J.-B. Danset, Sherine Khater, Anne-Laure Pointet, G Rahmi, and C. Cellier

Subjects
Gynecology, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, medicine, 030211 gastroenterology & hepatology, Radiology, Nuclear Medicine and imaging, business
Abstract

Les tumeurs sous-muqueuses (TSM) de l’estomac sont des lesions frequentes de decouverte souvent fortuite. La plupart des TSM sont asymptomatiques et d’evolution benigne, telles que les lipomes, les leiomyomes, les schwannomes, les pancreas aberrants. Certaines TSM gastriques ont un potentiel de malignite, notamment celles developpees a partir de la musculeuse comme les gastrointestinal stromal tumor et les tumeurs neuroendocrines. Le diagnostic de certitude de ces lesions peut etre difficile, meme apres la realisation d’une echoendoscopique et/ou de biopsies. La resection chirurgicale des tumeurs de plus de 2 cm est justifiee car elle permet une analyse histologique et un traitement carcinologique. Concernant les TSM gastriques de petite taille (

Published
2016
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23. Additional file 1: of A novel data-driven workflow combining literature and electronic health records to estimate comorbidities burden for a specific disease: a case study on autoimmune comorbidities in patients with celiac disease

Author

Jean-Baptiste Escudié, Rance, Bastien, Malamut, Georgia, Sherine Khater, Burgun, Anita, Cellier, Christophe, and Anne-Sophie Jannot

Subjects
endocrine system diseases
Abstract

List of ATC codes used. Lists of Anatomical Therapeutic Chemical Classification System (ATC) codes used for autoimmune thyroiditis (levothy*) and for diabetes mellitus, Type 1 (insulin). (DOCX 13 kb)

Published
2017
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24. Additional file 2: of A novel data-driven workflow combining literature and electronic health records to estimate comorbidities burden for a specific disease: a case study on autoimmune comorbidities in patients with celiac disease

Author

Jean-Baptiste Escudié, Rance, Bastien, Malamut, Georgia, Sherine Khater, Burgun, Anita, Cellier, Christophe, and Anne-Sophie Jannot

Abstract

Evolution of the numbers of co-occurrences in time. The 15 first ranked autoimmune diseases (in red) which would have been included based on the literature available at various time points. Numbers of co-occurrences until the specified year, ranks in prevalence estimates from this study, ranks in number of MeSH terms co-occurrence with term ‘Celiac Disease’ in MEDLINE at specified years. First version of the clinical vignette related on a new analgesic to control pain in mild trauma injuries with the four experimental factors tested. Description of first clinical vignette and list of response options. (DOCX 17 kb)

Published
2017
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27. 616 - AMG 714 (Anti-IL-15 MAB) Halts the Progression of Aberrant Intraepithelial Lymphocytes in Refractory Celiac Disease type II (RCD-II): A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Study Evaluating AMG 714 in Adult Patients with RCD-II/Pre-EATL

Author

Peter H.R. Green, Tom van Gils, Francisco León, Sheila E. Crowe, Pekka Collin, Laura Crespo, Georgia Malamut, Chris J. J. Mulder, Gerd Bouma, Sherine Khater, Wayne Tsuji, and Christophe Cellier

Subjects
medicine.medical_specialty, Hepatology, Adult patients, business.industry, medicine.drug_class, Gastroenterology, Placebo-controlled study, Disease, Monoclonal antibody, Double blind, 03 medical and health sciences, 0302 clinical medicine, Refractory, Interleukin 15, 030220 oncology & carcinogenesis, Internal medicine, medicine, Intraepithelial lymphocyte, 030211 gastroenterology & hepatology, business
Published
2018
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28. [Corticosteroids and radiotherapy in the treatment of Graves' ophthalmopathy]

Author

Elie, Nasr, Sherine, Khater, Dolly, Nehme-Nasr, Fares, Azoury, and Selim, Jambart

Subjects
Adult, Graves Ophthalmopathy, Quality of Life, Humans, Female, Radiotherapy Dosage, Glucocorticoids, Methylprednisolone, Retrospective Studies
Abstract

Graves' ophthalmopathy is a debilitating disease impairing the quality of life of affected individuals. The management of moderate-to-severe active Graves' ophthalmopathy is a major therapeutic challenge, and the treatment outcome is often unsatisfactory. We have carried out a retrospective study to assess the efficacy of combined orbital irradiation and systemic corticosteroids. Ten patients were included; all patients had received 20 Grays to the retrobulbar tissues in ten fractions, and oral or intravenous glucocorticoids. The main therapeutic outcome measures were the criteria of Donaldson and co-workers and a self-assessment evaluation. The quality of life outcome was also evaluated by the GO-QOL (Graves' ophthalmopathy quality of life) questionnaire. Seven patients (70%) demonstrated improvement in ocular parameters; the response was excellent in three cases, good in three cases and fair in one case. Three patients showed no response to the treatment. The self-assessment evaluation showed that 75% of patients were satisfied with the results of the treatment. Proptosis was the most responsive sign to radiation and steroids. A duration of the eye disease of more than 18 months was associated with less improvement and a higher failure of the treatment. Concerning the quality of life, the score for visual fonctionning was 882 +/- 18.2 after treatment, while the score for appearance was 63.3 +/- 23.3. In conclusion, a combination of orbital irradiation and systemic steroids is associated with 70% of favorable responses, but the quality of life is not restored in the same proportions and remains impaired after treatment.

Published
2010

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