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1. Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID

Author

Bénédicte Caron, Philippe Seksik, Anthony Buisson, Pauline Wils, Guillaume Savoye, Carmen Stefanescu, David Laharie, Lucas Guillo, Vered Abitbol, Joelle Bonnet, Romain Altwegg, Lucine Vuitton, Driffa Moussata, Arnaud Bourreille, Amélie Biron, Cyrielle Gilletta, Mathurin Fumery, Stephane Nahon, Stephane Nancey, Houda Camara, and Laurent Peyrin-Biroulet

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

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d’Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey’s honest significant difference test. Results: The most commonly used drugs at inclusion were Humira ® (436/941, 46.3%), Amgevita ® (177/941, 18.8%) and Hulio ® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) ( p

Published
2024
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2. Simultaneous or staged resection for synchronous liver metastasis and primary rectal cancer: a propensity score matching analysis

Author

Elias Karam, Petru Bucur, Camille Gil, Remy Sindayigaya, Nicolas Tabchouri, Louise Barbier, Urs Pabst-Giger, Pascal Bourlier, Thierry Lecomte, Driffa Moussata, Sophie Chapet, Gilles Calais, Mehdi Ouaissi, and Ephrem Salamé

Subjects
Rectal cancer, Synchronous liver metastasis, Simultaneous resection, Staged resection, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15–25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. Methods We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. Results There were 70 patients (55/15 males, female respectively) with median age 60 (54–68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). Conclusions Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

Published
2022
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3. Atrophic Gastritis and Autoimmunity: Results from a Prospective, Multicenter Study

Author

Malgorzata Osmola, Caroline Hemont, Nicolas Chapelle, Marie-Anne Vibet, David Tougeron, Driffa Moussata, Dominique Lamarque, Edith Bigot-Corbel, Damien Masson, Justine Blin, Maxime Leroy, Regis Josien, Jean-François Mosnier, Jérôme Martin, and Tamara Matysiak-Budnik

Subjects
autoimmune gastritis, chronic atrophic gastritis, autoimmunity, gastric cancer, H. pylori, Medicine (General), R5-920
Abstract

Despite a global decrease, gastric cancer (GC) incidence appears to be increasing recently in young, particularly female, patients. The causal mechanism for this “new” type of GC is unknown, but a role for autoimmunity is suggested. A cascade of gastric precancerous lesions, beginning with chronic atrophic gastritis (CAG), precedes GC. To test the possible existence of autoimmunity in patients with CAG, we aimed to analyze the prevalence of several autoantibodies in patients with CAG as compared to control patients. Sera of 355 patients included in our previous prospective, multicenter study were tested for 19 autoantibodies (anti-nuclear antibodies, ANA, anti-parietal cell antibody, APCA, anti-intrinsic factor antibody, AIFA, and 16 myositis-associated antibodies). The results were compared between CAG patients (n = 154), including autoimmune gastritis patients (AIG, n = 45), non-autoimmune gastritis patients (NAIG, n = 109), and control patients (n = 201). ANA positivity was significantly higher in AIG than in NAIG or control patients (46.7%, 29%, and 27%, respectively, p = 0.04). Female gender was positively associated with ANA positivity (OR 0.51 (0.31–0.81), p = 0.005), while age and H. pylori infection status were not. Myositis-associated antibodies were found in 8.9% of AIG, 5.5% of NAIG, and 4.4% of control patients, without significant differences among the groups (p = 0.8). Higher APCA and AIFA positivity was confirmed in AIG, and was not associated with H. pylori infection, age, or gender in the multivariate analysis. ANA antibodies are significantly more prevalent in AIG than in control patients, but the clinical significance of this finding remains to be established. H. pylori infection does not affect autoantibody seropositivity (ANA, APCA, AIFA). The positivity of myositis-associated antibodies is not increased in patients with CAG as compared to control patients. Overall, our results do not support an overrepresentation of common autoantibodies in patients with CAG.

Published
2023
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4. Voltage-Gated Sodium Channel NaV1.5 Controls NHE−1−Dependent Invasive Properties in Colon Cancer Cells

Author

Osbaldo Lopez-Charcas, Lucile Poisson, Oumnia Benouna, Roxane Lemoine, Stéphanie Chadet, Adrien Pétereau, Widad Lahlou, Serge Guyétant, Mehdi Ouaissi, Piyasuda Pukkanasut, Shilpa Dutta, Sadanandan E. Velu, Pierre Besson, Driffa Moussata, and Sébastien Roger

Subjects
colon cancer, NaV channels, cell invasiveness, small-molecule inhibitors, proton efflux, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Colorectal cancer (CRC) is the second leading cause of death worldwide, with 0.9 million deaths per year. The metastatic stage of the disease is identified in about 20% of cases at the first diagnosis and is associated with low patient-survival rates. Voltage-gated sodium channels (NaV) are abnormally overexpressed in several carcinomas including CRC and are strongly associated with the metastatic behavior of cancer cells. Acidification of the extracellular space by Na+/H+ exchangers (NHE) contributes to extracellular matrix degradation and cell invasiveness. In this study, we assessed the expression levels of pore-forming α-subunits of NaV channels and NHE exchangers in tumor and adjacent non-malignant tissues from colorectal cancer patients, CRC cell lines and primary tumor cells. In all cases, SCN5A (gene encoding for NaV1.5) was overexpressed and positively correlated with cancer stage and poor survival prognosis for patients. In addition, we identified an anatomical differential expression of SCN5A and SLC9A1 (gene encoding for NHE-1) being particularly relevant for tumors that originated on the sigmoid colon epithelium. The functional activity of NaV1.5 channels was characterized in CRC cell lines and the primary cells of colon tumors obtained using tumor explant methodologies. Furthermore, we assessed the performance of two new small-molecule NaV1.5 inhibitors on the reduction of sodium currents, as well as showed that silencing SCN5A and SLC9A1 substantially reduced the 2D invasive capabilities of cancer cells. Thus, our findings show that both NaV1.5 and NHE-1 represent two promising targetable membrane proteins against the metastatic progression of CRC.

Published
2022
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5. Serum Pepsinogens Combined with New Biomarkers Testing Using Chemiluminescent Enzyme Immunoassay for Non-Invasive Diagnosis of Atrophic Gastritis: A Prospective, Multicenter Study

Author

Nicolas Chapelle, Malgorzata Osmola, Jérôme Martin, Justine Blin, Maxime Leroy, Iva Jirka, Driffa Moussata, Dominique Lamarque, Raphael Olivier, David Tougeron, Anne Hay-Lombardie, Edith Bigot-Corbel, Damien Masson, Jean-François Mosnier, and Tamara Matysiak-Budnik

Subjects
atrophic gastritis, non-invasive markers, pepsinogens, diagnostic performance, Medicine (General), R5-920
Abstract

Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), a gastric precancerous lesion, is of growing interest for identification of patients at increased risk of gastric cancer. The aim was to analyze the diagnostic performance of serum pepsinogen testing using another method, chemiluminescent enzyme immunoassay (CLEIA), as well as of other new potential biomarkers. Material and Methods: The sera of patients considered at increased risk of gastric cancer and undergoing upper endoscopy collected in our previous prospective, multicenter study were tested for pepsinogen I (PGI) and II (PGII), interleukin-6 (IL-6), human epididymal protein 4 (HE-4), adiponectin, ferritin and Krebs von den Lungen (KL-6) using the CLEIA. The diagnostic performance for the detection of AG was calculated by taking histology as the reference. Results: In total, 356 patients (162 men (46%); mean age 58.6 (±14.2) years), including 152 with AG, were included. For the detection of moderate to severe corpus AG, sensitivity and specificity of the pepsinogen I/II ratio were of 75.0% (95%CI 57.8–87.9) and 92.6% (88.2–95.8), respectively. For the detection of moderate to severe antrum AG, sensitivity of IL-6 was of 72.2% (95%CI 46.5–90.3). Combination of pepsinogen I/II ratio or HE-4 showed a sensitivity of 85.2% (95%CI 72.9–93.4) for the detection of moderate to severe AG at any location. Conclusion: This study shows that PG testing by CLEIA represents an accurate assay for the detection of corpus AG. Additionally, IL-6 and HE-4 may be of interest for the detection of antrum AG. Mini-abstract: Pepsinogens testing by chemiluminescent enzyme immunoassay is accurate for the detection of corpus atrophic gastritis. IL-6 and HE-4 maybe of interest for the detection of antrum atrophic gastritis.

Published
2022
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6. Infliximab Efficacy May Be Linked to Full TNF-α Blockade in Peripheral Compartment—A Double Central-Peripheral Target-Mediated Drug Disposition (TMDD) Model

Author

David Ternant, Olivier Le Tilly, Laurence Picon, Driffa Moussata, Christophe Passot, Theodora Bejan-Angoulvant, Céline Desvignes, Denis Mulleman, Philippe Goupille, and Gilles Paintaud

Subjects
infliximab, pharmacokinetics, target-mediated drug disposition, inflammatory bowel diseases, Pharmacy and materia medica, RS1-441
Abstract

Infliximab is an anti-TNF-α monoclonal antibody approved in chronic inflammatory bowel diseases (IBD). This study aimed at providing an in-depth description of infliximab target-mediated pharmacokinetics in 133 IBD patients treated with 5 mg/kg infliximab at weeks 0, 2, 14, and 22. A two-compartment model with double target-mediated drug disposition (TMDD) in both central and peripheral compartments was developed, using a rich database of 26 ankylosing spondylitis patients as a reference for linear elimination kinetics. Population approach and quasi-steady-state (QSS) approximation were used. Concentration-time data were satisfactorily described using the double-TMDD model. Target-mediated parameters of central and peripheral compartments were respectively baseline TNF concentrations (RC0 = 3.3 nM and RP0 = 0.46 nM), steady-stated dissociation rates (KCSS = 15.4 nM and KPSS = 0.49 nM), and first-order elimination rates of complexes (kCint = 0.17 day−1 and kPint = 0.0079 day−1). This model showed slower turnover of targets and infliximab-TNF complex elimination rate in peripheral compartment than in central compartment. This study allowed a better understanding of the multi-scale target-mediated pharmacokinetics of infliximab. This model could be useful to improve model-based therapeutic drug monitoring of infliximab in IBD patients.

Published
2021
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7. Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial

Author

François-Clément Bidard, Nicolas Kiavue, Marc Ychou, Luc Cabel, Marc-Henri Stern, Jordan Madic, Adrien Saliou, Aurore Rampanou, Charles Decraene, Olivier Bouché, Michel Rivoire, François Ghiringhelli, Eric Francois, Rosine Guimbaud, Laurent Mineur, Faiza Khemissa-Akouz, Thibault Mazard, Driffa Moussata, Charlotte Proudhon, Jean-Yves Pierga, Trevor Stanbury, Simon Thézenas, and Pascale Mariani

Subjects
circulating tumor cells, circulating tumor DNA, liquid biopsy, metastatic colorectal cancer, FOLFIRINOX, Cytology, QH573-671
Abstract

The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch®) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (≥3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p < 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.

Published
2019
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8. The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis

Author

Emmanuelle Masson, Maren Ewers, Sumit Paliwal, Kiyoshi Kume, Virginie Scotet, David N. Cooper, Vinciane Rebours, Louis Buscail, Karen Rouault, Amandine Abrantes, Lina Aguilera Munoz, Jérémie Albouys, Laurent Alric, Xavier Amiot, Isabelle Archambeaud, Solène Audiau, Laetitia Bastide, Julien Baudon, Guy Bellaiche, Serge Bellon, Valérie Bertrand, Karine Bideau, Kareen Billiemaz, Claire Billioud, Sabine Bonnefoy, Corinne Borderon, Barbara Bournet, Estelle Breton, Mathias Brugel, Guillaume Cadiot, Marine Camus, Marine Carpentier-Pourquier, Patrick Chamouard, Ulriikka Chaput, Jian-Min Chen, Franck Cholet, Dragos Marius Ciocan, Christine Clavel, Benoit Coffin, Laura Coimet-Berger, Simona Cosconea, Isabelle Creveaux, Adrian Culetto, Oussama Daboussi, Louis De Mestier, Thibault Degand, Christelle D'engremont, Bernard Denis, Solène Dermine, null Desgrippes, Augustin Drouet D'Aubigny, Raphaël Enaud, Alexandre Fabre, Claude Férec, Dany Gargot, Eve Gelsi, Elena Gentilcore, Rodica Gincul, Emmanuelle Ginglinger-Favre, Marc Giovannini, Cécile Gomercic, Hannah Gondran, Thomas Grainville, Philippe Grandval, Denis Grasset, Stéphane Grimaldi, Sylvie Grimbert, Hervé Hagege, Sophie Heissat, Olivia Hentic, Anne Herber-Mayne, Marc Hervouet, Solene Hoibian, Jérémie Jacques, Bénédicte Jais, Mehdi Kaassis, Stéphane Koch, Elodie Lacaze, Joël Lacroute, Thierry Lamireau, Lucie Laurent, Xavier Le Guillou, Marc Le Rhun, Sarah Leblanc, Philippe Levy, Astrid Lievre, Diane Lorenzo, Frédérique Maire, Kévin Marcel, Jacques Mauillon, Stéphanie Morgant, Driffa Moussata, Nelly Muller, Sophie Nambot, Bertrand Napoleon, Anne Olivier, Maël Pagenault, Anne-laure Pelletier, Olivier Pennec, Fabien Pinard, Mathieu Pioche, Bénédicte Prost, Lucille Queneherve, Noemi Reboux, Samia Rekik, Ghassan Riachi, Barbara Rohmer, Bertrand Roquelaure, Isabelle Rosa Hezode, Florian Rostain, Jean-Christophe Saurin, Laure Servais, Roxana Stan-Iuga, Clément Subtil, Jérémy Tanneche, Charles Texier, Lucie Thomassin, David Tougeron, Lucine Vuitton, Timothée Wallenhorst, Marc Wangerme, Hélène Zanaldi, Frank Zerbib, Seema Bhaskar, Kazuhiro Kikuta, G Venkat Rao, Shin Hamada, D Nageshwar Reddy, Atsushi Masamune, Giriraj Ratan Chandak, and Heiko Witt

Subjects
Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Abstract

PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition.We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction.We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression.The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.

Published
2023

10. 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

11. Probe-based Confocal Laser Endomicroscopy for In Vivo Assessment of Histological Healing in Ulcerative Colitis: Development and Validation of the ENHANCE Index

Author

Christophe Cellier, Emmanuel Coron, Laurent Peyrin-Biroulet, Arnaud Bourreille, Aude Marchal, L Quénéhervé, Jacques Moreau, Driffa Moussata, Enrique Pérez-Cuadrado-Robles, Gabriel Rahmi, Antoine Chupin, Michael Levy, and Guillaume Perrod

Subjects
Male, medicine.medical_specialty, Colon, Lumen (anatomy), Colonoscopy, Sensitivity and Specificity, Inflammatory bowel disease, Predictive Value of Tests, Biopsy, medicine, Mucositis, Humans, Intestinal Mucosa, Wound Healing, Microscopy, Confocal, Microscopy, Video, medicine.diagnostic_test, business.industry, Remission Induction, Patient Acuity, Gastroenterology, General Medicine, Gold standard (test), Middle Aged, medicine.disease, Ulcerative colitis, Endoscopy, Colitis, Ulcerative, Female, France, Radiology, business
Abstract

Background and Aims Histological healing may represent the ultimate therapeutic goal in ulcerative colitis [UC], but it requires biopsies. Our aim was to develop a non-invasive index able to assess histological disease activity in ulcerative colitis, using probe-based confocal laser endomicroscopy [pCLE]. Methods One hundred patients with quiescent UC were prospectively included in five French centres. After fluorescein intravenous injection, during colonoscopy, the colorectal mucosa was analysed by white light imaging and pCLE, and then biopsied in different locations. Five endoscopists performed central reading of pCLE images blinded to clinical, endoscopic, and histological data. One expert pathologist performed a central histological reading [Nancy index: gold standard]. Univariate and multivariate analyses were performed to identify the endomicroscopic items associated with the presence of histologically active disease. Results Over 1000 pCLE videos sequences performed in 100 UC patients in endoscopic remission [Mayo 0 and 1] were evaluated. We observed that vessel diameter >20 µm, dilated crypt lumen, fluorescein leakage, and irregular crypt architecture were statistically associated with histologically proven inflammation according to the Nancy index. Hence, we built a pCLE index of mucosal inflammation with overall accuracy of 79.6% and overall sensitivity and specificity of, respectively, 57.8% and 82.8%. Negative predictive value, especially when a pCLE index ≤1 was observed, was high [93.1%]. Conclusions Using a robust methodology, large vessel diameter, dilated crypt lumen, fluorescein leakage,and irregular crypt architecture are reliable endomicroscopic items defining the ENHANCE index for real-time assessment of histological disease activity in UC.

Published
2020

12. Defining and Assessing the Reproducibility of Crohn’s Disease Endoscopic Lesions: A Delphi-like Method from the GETAID

Author

Lucine Vuitton, Edouard Louis, G Pineton de Chambrun, Anne-Laure Pelletier, P. Marteau, A. Buisson, D. Laharie, P. Seksik, Gwenola Vernier-Massouille, Yoram Bouhnik, Aurelien Amiot, Jean-Yves Mary, Jérôme Filippi, Driffa Moussata, Laurent Peyrin-Biroulet, Guillaume Cadiot, Mathieu Allez, Jean-Louis Dupas, Stéphane Nancey, Alain Attar, Maria Nachury, Antoine Blain, Université Clermont Auvergne (UCA), Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Henri Mondor d'Aurillac, Centre Hospitalier Universitaire de Reims (CHU Reims), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Beaujon [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Tourcoing, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Amiens-Picardie, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), and Centre Hospitalier Universitaire de Liège (CHU-Liège)

Subjects
Crohn’s disease, MESH: Terminology as Topic, Delphi Technique, [SDV]Life Sciences [q-bio], MESH: Observer Variation, Severity of Illness Index, Endoscopy, Gastrointestinal, MESH: Delphi Technique, MESH: Quality Improvement, Crohn Disease, Terminology as Topic, MESH: Severity of Illness Index, medicine, Humans, reproducibility, Observer Variation, Crohn's disease, Microscopy, Video, MESH: Humans, MESH: Crohn Disease, business.industry, Gastroenterology, Reproducibility of Results, General Medicine, ulcerations, medicine.disease, Quality Improvement, endoscopic lesions, MESH: Endoscopy, Gastrointestinal, Intestines, MESH: Microscopy, Video, MESH: Reproducibility of Results, business, Nuclear medicine, MESH: Intestines
Abstract

Background and Aims Defining and assessing the reproducibility of Crohn’s disease [CD] endoscopic lesions is essential in assessing endoscopic healing. Methods Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as ‘moderate’ [0.4–0.6], ‘substantial’ [0.6–0.8], or ‘almost perfect’ [0.8–1.0]. Results Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing ‘substantial’ agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from ‘moderate’ to ‘almost perfect’ agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. Conclusions Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided ‘substantial’ inter-observer agreements, especially in case of high-quality videos.

Published
2020

13. 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

14. Sodium Channel Na v 1.5 Controls Epithelial-to-Mesenchymal Transition and Invasiveness in Breast Cancer Cells Through its Regulation by the Salt-Inducible Kinase-1

Author

Frédéric Gradek, Osbaldo Lopez-Charcas, Stéphanie Chadet, Lucile Poisson, Lobna Ouldamer, Caroline Goupille, Marie-Lise Jourdan, Stéphan Chevalier, Driffa Moussata, Pierre Besson, and Sébastien Roger

Subjects
lcsh:R, lcsh:Medicine, lcsh:Q, lcsh:Science
Abstract

Loss of epithelial polarity and gain in invasiveness by carcinoma cells are critical events in the aggressive progression of cancers and depend on phenotypic transition programs such as the epithelial-to-mesenchymal transition (EMT). Many studies have reported the aberrant expression of voltage-gated sodium channels (NaV) in carcinomas and specifically the NaV1.5 isoform, encoded by the SCN5A gene, in breast cancer. NaV1.5 activity, through an entry of sodium ions, in breast cancer cells is associated with increased invasiveness, but its participation to the EMT has to be clarified. In this study, we show that reducing the expression of NaV1.5 in highly aggressive human MDA-MB-231 breast cancer cells reverted the mesenchymal phenotype, reduced cancer cell invasiveness and the expression of the EMT-promoting transcription factor SNAI1. The heterologous expression of NaV1.5 in weakly invasive MCF-7 breast cancer cells induced their expression of both SNAI1 and ZEB1 and increased their invasive capacities. In MCF-7 cells the stimulation with the EMT-activator signal TGF-β1 increased the expression of SCN5A. Moreover, the reduction of the salt-inducible kinase 1 (SIK1) expression promoted NaV1.5-dependent invasiveness and expression of EMT-associated transcription factor SNAI1. Altogether, these results indicated a prominent role of SIK1 in regulating NaV1.5-dependent EMT and invasiveness.

Published
2019

15. Simultaneous or staged resection for synchronous liver metastasis and primary rectal cancer: a propensity score matching analysis

Author

Elias Karam, Petru Bucur, Camille Gil, Remy Sindayigaya, Nicolas Tabchouri, Louise Barbier, Urs Pabst-Giger, Pascal Bourlier, Thierry Lecomte, Driffa Moussata, Sophie Chapet, Gilles Calais, Mehdi Ouaissi, and Ephrem Salamé

Subjects
Male, Rectal Neoplasms, Liver Neoplasms, Gastroenterology, General Medicine, Middle Aged, Treatment Outcome, Hepatectomy, Humans, Female, Prospective Studies, Colorectal Neoplasms, Propensity Score, Retrospective Studies
Abstract

Background Colorectal cancer is the third most common cancer in France and by the time of the diagnosis, 15–25% of patients will suffer from synchronous liver metastases. Surgery associated to neoadjuvant treatment can cure these patients, but few studies focus only on rectal cancer. This study was meant to compare the outcomes of patients who underwent a simultaneous resection to those who underwent a staged resection (rectum first or liver first) in the University Hospital of Tours, France. Methods We assessed retrospectively a prospective maintained data base about the clinical, pathological and survival outcomes of patients who underwent a simultaneous or a staged resection in our center between 2010 and 2018. A propensity score matching was used, considering the initial characteristics of our groups. Results There were 70 patients (55/15 males, female respectively) with median age 60 (54–68) years. After matching 48 (69%) of them underwent a staged approach and 22 (31%) a simultaneous approach were compared. After PSM, there were 22 patients in each group. No differences were found in terms of morbidity (p = 0.210), overall survival (p = 0.517) and disease-free survival (p = 0.691) at 3 years after matching. There were significantly less recurrences in the simultaneous group (50% vs 81.8%, p = 0.026). Conclusions Simultaneous resection of the rectal primary cancer and synchronous liver metastases is safe and feasible with no difference in terms of survival.

Published
2021

16. Prognostic value of primary tumor sidedness in patients with non-metastatic IBD related CRC – Is it the exception to the rule?

Author

Carsten Kamphues, Jeremie H. Lefevre, Jane Wang, Neda Amini, Laurent Beaugerie, Florian Kuehn, Sang Hyoung Park, Nikolaos Andreatos, Johannes C. Lauscher, Diana Enea, Kai S. Lehmann, Nicolas Peru, Benjamin Weixler, Julien Kirchgesner, Claudius E. Degro, Ioannis Pozios, Cornelius J. van Beekum, Sebastian Schölch, Daniela Zambonin, Christian Schineis, Florian N. Loch, Despoina Geka, Maria Theoxari, Bin Wu, Pei-Pei Wang, Efstathios Antoniou, Emmanouil Pikoulis, Driffa Moussata, George Theodoropoulos, Mehdi Ouaissi, Hendrik Seeliger, Yosuke Inaba, Stefano Scaringi, Christoph Reißfelder, Tim O. Vilz, Chen Lin, Suk-Kyun Yang, Katharina Beyer, Bernhard W. Renz, Kazunari Sasaki, Georgios Antonios Margonis, Magali Svrcek, and Martin E. Kreis

Subjects
Oncology, Rectal Neoplasms, Humans, Surgery, Prognosis, Colorectal Neoplasms, Inflammatory Bowel Diseases, Retrospective Studies
Abstract

Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC.All eligible patients with surgically treated, non-metastatic IBD-CRC were retrospectively identified from institutional databases at ten European and Asian academic centers. Long term endpoints included recurrence-free (RFS) and overall survival (OS). Multivariable Cox proportional hazard regression as well as propensity score analyses were performed to evaluate whether PTS was significantly associated with RFS and OS.A total of 213 patients were included in the analysis, of which 32.4% had right-sided (RS) tumors and 67.6% had left-sided (LS) tumors. PTS was not associated with OS and RFS even on univariable analysis (5-year OS for RS vs LS tumors was 68.0% vs 77.3%, respectively, p = 0.31; 5-year RFS for RS vs LS tumors was 62.8% vs 65.4%, respectively, p = 0.51). Similarly, PTS was not associated with OS and RFS on propensity score matched analysis (5-year OS for RS vs LS tumors was 82.9% vs 91.3%, p = 0.79; 5-year RFS for RS vs LS tumors was 85.1% vs 81.5%, p = 0.69). These results were maintained when OS and RFS were calculated in patients with RS vs LS tumors after excluding patients with rectal tumors (5-year OS for RS vs LS tumors was 68.0% vs 77.2%, respectively, p = 0.38; 5-year RFS for RS vs LS tumors was 62.8% vs 59.2%, respectively, p = 0.98).In contrast to sporadic CRC, PTS does not appear to have a prognostic role in IBD-CRC.

Published
2022

17. Usefulness of confocal laser endomicroscopy for predicting postoperative recurrence in patients with Crohn’s disease: a pilot study

Author

Julie Auzoux, Pierre Besson, Gilles Boschetti, Alexandre Aubourg, Sébastien Roger, Morgane Caulet, Thierry Lecomte, Benjamin Anon, Bernard Flourié, Laurence Picon, Driffa Moussata, Stéphane Nancey, Lucile Poisson, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Régional Universitaire de Tours (CHRU de Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hépato-Gastro-Onco-Entérologie [CHRU de Tours], Université de Tours-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-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), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), 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)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and 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)

Subjects
Adult, Male, medicine.medical_specialty, Colon, medicine.medical_treatment, Population, Colonoscopy, Pilot Projects, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Gastroenterology, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Colon surgery, Internal medicine, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Young adult, education, Colectomy, ComputingMilieux_MISCELLANEOUS, Crohn's disease, education.field_of_study, Microscopy, Confocal, medicine.diagnostic_test, business.industry, Middle Aged, Prognosis, medicine.disease, Endoscopy, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Confocal laser endomicroscopy (CLE) has been shown to predict relapse in inflammatory bowel disease, but its value in the detection of postoperative recurrence in Crohn's disease (CD) is unknown. The aims of this pilot study performed in patients with CD after ileocolonic resection were to compare the macroscopic appearance of the neoterminal ileum, according to the endoscopic Rutgeerts score, with the microscopic findings provided by CLE 6 to 12 months after surgery and to assess the predictive values of CLE-generated parameters for predicting further recurrence in patients with postoperative endoscopic remission.In 25 consecutive patients with CD within 6 to 12 months of surgery, the neoterminal ileum was examined by standard white-light endoscopy (Rutgeerts scale) followed by CLE (Watson grade). Only patients without endoscopic recurrence (Rutgeerts i0 and i1) were then followed endoscopically and clinically (median follow-up 38 months).At the time of the first postoperative colonoscopy, 18 patients (72%) were in endoscopic remission, and 7 (28%) experienced an endoscopic recurrence (Rutgeerts ≥i2). The Rutgeerts score was significantly correlated with the Watson score (ρ = 0 .73; P .0001). The Watson scores at baseline were significantly higher in patients with further endoscopic recurrence (median 2.0; interquartile range [IQR] 1.5-2.0) than in those with endoscopic remission (median 1.0; IQR 1.0-1.0; P = .032) and were significantly higher in patients with clinical relapse (medium 2.0, IQR 2.0-2.0) compared with those in clinical remission (median 1.0; IQR 1.0-1.0; P = .036).CLE could be useful in monitoring patients with CD after intestinal resection. Further studies with a larger population are necessary to confirm these preliminary results.

Published
2019

18. Hypercontractile esophagus resolved after radiofrequency catheter ablation for atrial fibrillation: About a case

Author

Benjamin Anon, Driffa Moussata, Laurence Picon, Alexandre Aubourg, and Dominique Babuty

Subjects
Male, medicine.medical_specialty, Manometry, Physiology, Myenteric Plexus, Vagotomy, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Atrial Fibrillation, medicine, Humans, Esophageal Motility Disorders, Stomach Ulcer, Esophagus, High resolution manometry, Aged, Endocrine and Autonomic Systems, business.industry, Gastroenterology, Atrial fibrillation, medicine.disease, Treatment Outcome, medicine.anatomical_structure, Radiofrequency catheter ablation, Catheter Ablation, Cardiology, 030211 gastroenterology & hepatology, Deglutition Disorders, business, Muscle Contraction
Abstract

The pathophysiology of jackhammer esophagus is complex and remains unclear. Radiofrequency catheter ablation is indicated for highly symptomatic and drug-refractory atrial fibrillation. This technique can induce esophageal and nerve lesions, due to thermal injury. In this report, we describe a case of hypercontractile esophagus diagnosed by HRM (high-resolution manometry). Esophageal symptoms and HRM normalized immediately after RFCA, and we discuss the pathophysiology of hypercontractile esophagus.

Published
2020

19. Rock inhibition promotes Na

Author

Lucile, Poisson, Osbaldo, Lopez-Charcas, Stéphanie, Chadet, Emeline, Bon, Roxane, Lemoine, Lucie, Brisson, Mehdi, Ouaissi, Christophe, Baron, Pierre, Besson, Sébastien, Roger, and Driffa, Moussata

Subjects
Pyridines, Protein Serine-Threonine Kinases, Amides, Article, NAV1.5 Voltage-Gated Sodium Channel, Membrane biophysics, Cell Movement, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Cell Line, Tumor, Colonic Neoplasms, Humans, Neoplasm Invasiveness, Signal Transduction, Cancer
Abstract

The acquisition of invasive capacities by carcinoma cells, i.e. their ability to migrate through and to remodel extracellular matrices, is a determinant process leading to their dissemination and to the development of metastases. these cancer cell properties have often been associated with an increased Rho-ROCK signalling, and ROCK inhibitors have been proposed for anticancer therapies. In this study we used the selective ROCK inhibitor, Y-27632, to address the participation of the Rho-ROCK signalling pathway in the invasive properties of SW620 human colon cancer cells. Contrarily to initial assumptions, Y-27632 induced the acquisition of a pro-migratory cell phenotype and increased cancer cell invasiveness in both 3- and 2-dimensions assays. This effect was also obtained using the other ROCK inhibitor Fasudil as well as with knocking down the expression of ROCK-1 or ROCK-2, but was prevented by the inhibition of NaV1.5 voltage-gated sodium channel activity. Indeed, ROCK inhibition enhanced the activity of the pro-invasive NaV1.5 channel through a pathway that was independent of gene expression regulation. In conclusions, our evidence identifies voltage-gated sodium channels as new targets of the ROCK signalling pathway, as well as responsible for possible deleterious effects of the use of ROCK inhibitors in the treatment of cancers.

Published
2020

20. A panel of stomach-specific biomarkers (GastroPanel®) for the diagnosis of atrophic gastritis: A prospective, multicenter study in a low gastric cancer incidence area

Author

Catherine Le Berre-Scoul, Driffa Moussata, Iva Jirka, Raphael Olivier, Maxime Leroy, Jean-François Mosnier, Tamara Matysiak-Budnik, Pawel Petryszyn, Michel Neunlist, Nicolas Chapelle, Dominique Lamarque, David Tougeron, Justine Blin, Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ligue Contre le Cancer, The study was supported by the Ligue contre le Cancer and BIOHIT. We thank all the physicians participating in patient’s inclusion: Benjamin Anon, Isabelle Archambeaud, Thierry Barrioz, Arnaud Bourreille, Estelle Cauchin, Nicolas Chapelle, Emmanuel Coron, Nicolas Etchepare, Ginette Fotsing, Anais Jaillais, Marc Le Rhun, Nicolas Musquer, Lucille Queneherve, Matthieu Peron, Yann Touchefeu, Caroline Trang, Marc Wangermez. We also thank the clinical research assistants for their help: Pierre Boureau, Karine Cabanas, Eliane Hivernaud, Zeineb Lamoureux, Laetitia Rouleau, Olivier Teston, Fabienne Vavasseur., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Male, Atrophic gastritis, Gastroenterology, Serology, 0302 clinical medicine, Pepsin, diagnostic performance, Pepsinogen A, Pepsinogen C, Prospective Studies, noninvasive markers, biology, Stomach, Incidence (epidemiology), Incidence, General Medicine, Middle Aged, Antibodies, Bacterial, 3. Good health, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, France, Adult, Gastritis, Atrophic, medicine.medical_specialty, Enzyme-Linked Immunosorbent Assay, Sensitivity and Specificity, Helicobacter Infections, 03 medical and health sciences, Stomach Neoplasms, Statistical significance, Internal medicine, atrophic gastritis, Gastrins, medicine, Humans, Aged, business.industry, Cancer, Helicobacter pylori, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cross-Sectional Studies, biology.protein, business, Biomarkers, gastropanel
Abstract

International audience; Background: Analysis of serum biomarkers for the assessment of atrophic gastritis (AG), considered as gastric precancerous lesion, is of growing interest and recommended by current guidelines. Our aim was to evaluate the diagnostic performance of a panel of biomarkers (GastroPanel®) for the detection of AG in France, a country of a low gastric cancer (GC) incidence. Material and Methods: In this prospective, multicenter, cross-sectional study, consecutive patients considered at increased risk of GC and undergoing upper endoscopy with gastric biopsies were included. Blood samples were collected for the analysis of GastroPanel® (association of Pepsinogens I and II, Gastrin-17, and Helicobacter pylori serology) using ELISA. The results of GastroPanel® were compared to the results of histology considered as the reference. Results: Between 2016 and 2019, 344 patients (148 cases with AG, 196 controls without AG) were included. Sensitivity, specificity, positive, and negative predictive values for the detection of AG by GastroPanel® were of 39.9% (95% CI 31.9; 48.2), 93.4% (95% CI 88.9; 96.4), 81.9 (95% CI 71.1; 90.0), and 67.3 (95% CI 61.4; 72.8), respectively. The sensitivity was significantly higher for the detection of severe AG [60.8% (95% CI 46.1; 74.6) P =.015] and corpus AG [61.0% (95% CI 49.2; 72.0), P =.004]. Diagnostic performances of GastroPanel® tended to be better than those of Pepsinogen I alone, but the difference did not reach statistical significance (P =.068). Conclusion: Serum pepsinogen and GastroPanel® tests show promising results for the detection of AG, especially of corpus AG and severe AG, in patients at high risk of GC in France.

Published
2020

21. Machine Learning-Based Classification of the Health State of Mice Colon in Cancer Study from Confocal Laser Endomicroscopy

Author

Pejman Rasti, Hugo Dorez, David Rousseau, Salma Samiei, Raphaël Sablong, Christian Wolf, Driffa Moussata, Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, French National Research Agency : ANR-11-LABX-0063 ANR-11-IDEX-0007, DORA plus (Estonian government programme)., Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Extraction de Caractéristiques et Identification (imagine), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Université Lumière - Lyon 2 (UL2), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
endoscopie, 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Computer science, cancer du colon, médecine humaine, lcsh:Medicine, 02 engineering and technology, modèle, computer.software_genre, Interface homme-machine, Machine Learning, Mice, classification biologique, 0202 electrical engineering, electronic engineering, information engineering, lcsh:Science, bioinformatique, ComputingMilieux_MISCELLANEOUS, muqueuse intestinale, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microscopy, Confocal, Multidisciplinary, Emerging diseases, 3. Good health, microscopie laser confocale, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 020201 artificial intelligence & image processing, Transfer of learning, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Algorithms, Colon, education, Médecine humaine et pathologie, Bioengineering, Maladies émergentes, Machine learning, Article, 03 medical and health sciences, intelligence artificielle, Text mining, saisie d'images, medicine, Animals, [INFO.INFO-HC]Computer Science [cs]/Human-Computer Interaction [cs.HC], business.industry, Deep learning, lcsh:R, Cancer, medicine.disease, Ingénierie biomédicale, Human-Computer Interaction, Support vector machine, 030104 developmental biology, Cancer imaging, Human health and pathology, lcsh:Q, Neural Networks, Computer, Artificial intelligence, State (computer science), business, computer, Software, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

In this article, we address the problem of the classification of the health state of the colon’s wall of mice, possibly injured by cancer with machine learning approaches. This problem is essential for translational research on cancer and is a priori challenging since the amount of data is usually limited in all preclinical studies for practical and ethical reasons. Three states considered including cancer, health, and inflammatory on tissues. Fully automated machine learning-based methods are proposed, including deep learning, transfer learning, and shallow learning with SVM. These methods addressed different training strategies corresponding to clinical questions such as the automatic clinical state prediction on unseen data using a pre-trained model, or in an alternative setting, real-time estimation of the clinical state of individual tissue samples during the examination. Experimental results show the best performance of 99.93% correct recognition rate obtained for the second strategy as well as the performance of 98.49% which were achieved for the more difficult first case.

Published
2019

22. Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity

Author

Morgane Caulet, Driffa Moussata, Chantal Barin-Le Guellec, Christophe Vandier, Aurélie Chantôme, Benjamin Anon, Clémence Perray, Bérenger Largeau, Alban Girault, and Thierry Lecomte

Subjects
Adult, Male, 0301 basic medicine, Gene isoform, Cancer Research, Patch-Clamp Techniques, Organoplatinum Compounds, Small-Conductance Calcium-Activated Potassium Channels, Colorectal cancer, Leucovorin, Antineoplastic Agents, Biology, Toxicology, 03 medical and health sciences, 0302 clinical medicine, SK3, Trinucleotide Repeats, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), Allele, Genotyping, Gene, Aged, Pharmacology, Polymorphism, Genetic, HEK 293 cells, Middle Aged, medicine.disease, Molecular biology, Oxaliplatin, HEK293 Cells, 030104 developmental biology, Oncology, Female, Neurotoxicity Syndromes, Fluorouracil, 030217 neurology & neurosurgery, medicine.drug
Abstract

Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density. A retrospective study was carried out on patients with colorectal cancer who had received oxaliplatin-based chemotherapy. DNA for KCNN3 genotyping was extracted from leukocytes. The region containing the CAG repeats was amplified by PCR and the products separated by capillary electrophoresis for length analysis. The patients were divided into three groups depending on whether they carried two short alleles, one short allele and one long allele, or two long alleles. The primary endpoint was the onset of grade 2 or 3 neuropathy to oxaliplatin. There was no difference in current density, but oxaliplatin induced a differential effect on apamin-sensitive current density between the two isoforms expressed in the HEK cell lines. There was a significant reduction of store-operated calcium entry into cells expressing the short and more active isoform only after high concentration of oxaliplatin exposition. Eighty-six patients were included in the clinical study. There was no significant association between OIN and KCNN3 polymorphism for the three groups. We observed a slight association between OIN and CAG repeat polymorphisms of the KCNN3 gene in a preclinical model, but not a clinical study.

Published
2018

23. Doxorubicin-loaded nanoparticles for patients with advanced hepatocellular carcinoma after sorafenib treatment failure (RELIVE): a phase 3 randomised controlled trial

Author

Inmaculada Ales, Hakan Harputluoglu, Marc Peeters, Jean-Marc Phelip, G. Pelletier, Zsuzsanna Kahan, Alice Gangloff, Fadi Farhat, Imam Waked, Luc Lasser, René Gerolami, Giovanni Luca, Thomas Berg, Julie Le Boulicaut, Jean-Pierre Zarski, Ivan Borbath, Wolfgang Sieghart, Ozlem Ata, Howard Ozer, Julie Vincent, Thierry Fontanges, Bartomeu Massuti, Christos Galanopoulos, Mohammed El Kassas, Audrey Molé, Imam Wakid, Philippe Merle, Nasr El Lahlouby, Andreas Maieron, Marilyne Debette-Gratien, Antonio Cubillo, György Bodoky, Sylvain Manfredi, Faiza Khemissa-Akouz, Jawad Makarem, Jean-Frédéric Blanc, Ahmet Coker, Carmen Guillén, Massimo Colombo, Michael Schultheiß, Joerg Trojan, Yann Touchefeu, Isabelle Ollivier-Hourmand, François Habersetzer, Vlad Ratziu, Amr Abdel, Amr S Saad, Miguel Marín, Magdolna Dank, Mohamed Bouattour, Hélène Regnault, Jean-Didier Grangé, Pierluigi Toniutto, Hanaa Kohail, Sameh Shamaa, Carine Richou, Erdem Goker, Eric Nguyen-Khac, Oscar Alabiso, G.-P. Pageaux, Andrea Casadei-Gardini, Moses Raj, Alexander Zipprich, Henning Wege, Ilkay Tugba, Aurore Baron, Victor Navarro, Domenico Amoroso, Issam Chehade, Nashat Gabrail, Pierre Attali, Barbara Dauvois, Stefano Tamberi, Driffa Moussata, Angela Buonadonna, Emiliano Tamburini, Muhammet Ali, Armand Abergel, Albert Tran, Suayib Yalcin, Ursula Ehmer, Hermini Manzano, Jean Delwaide, Andrés Muñoz, Carlos López, Jean-Pierre Bronowicki, Zsolt Horváth, Alper Sevinc, Gloria Sánchez, Ralph Hauke, Gabriele Luppi, Bérangère Vasseur, Nelson S. Yee, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Charles Nicolle [Rouen]-CHU Rouen, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Merle, P., Blanc, J. -F., Phelip, J. -M., Pelletier, G., Bronowicki, J. -P., Touchefeu, Y., Pageaux, G., Gerolami, R., Habersetzer, F., Nguyen-Khac, E., Casadei-Gardini, A., Borbath, I., Tran, A., Wege, H., Saad, A. S., Colombo, M., Abergel, A., Richou, C., Waked, I., Yee, N. S., Mole, A., Attali, P., Le Boulicaut, J., Vasseur, B., Moussata, D., Grange, J. -D., Ratziu, V., Khemissa-Akouz, F., Regnault, H., Dauvois, B., Zarski, J. -P., Ollivier-Hourmand, I., Manfredi, S., Debette-Gratien, M., Gangloff, A., Fontanges, T., Baron, A., Bouattour, M., Vincent, J., Sieghart, W., Maieron, A., Peeters, M., Delwaide, J., Lasser, L., Berg, T., Schultheiss, M., Zipprich, A., Trojan, J., Ehmer, U., Luppi, G., Luca, G., Tamberi, S., Amoroso, D., Alabiso, O., Buonadonna, A., Toniutto, P., Tamburini, E., Cubillo, A., Munoz, A., Guillen, C., Sanchez, G., Manzano, H., Navarro, V., Ales, I., Massuti, B., Dank, M., Bodoky, G., Kahan, Z., Horvath, Z., Gabrail, N., Ozer, H., Galanopoulos, C., Hauke, R., Raj, M., Harputluoglu, H., Sevinc, A., Goker, E., Coker, A., Yalcin, S., Ali, M., Ata, O., Tugba, I., Elkassas, M., Abdel, A., Wakid, I., Shamaa, S., El, N., Kohail, H., Makarem, J., Chehade, I., Farhat, F., Lopez, C., and Marin, M.

Subjects
Male, Gastroenterology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, Treatment Failure, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Antibiotics, Antineoplastic, Liver Neoplasms, Middle Aged, Sorafenib, 3. Good health, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 030211 gastroenterology & hepatology, Female, medicine.drug, medicine.medical_specialty, Carcinoma, Hepatocellular, Neutropenia, Population, Antineoplastic Agents, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Carcinoma, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Adverse effect, Aged, Hepatology, Dose-Response Relationship, Drug, business.industry, medicine.disease, Thrombocytopenia, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Doxorubicin, Asthenia, Nanoparticles, business
Abstract

Summary Background Cytotoxic chemotherapy is generally ineffective in patients with hepatocellular carcinoma. We assessed the intravenous perfusion of doxorubicin-loaded nanoparticles in patients with hepatocellular carcinoma in whom previous sorafenib therapy had failed. Methods We did a multicentre, open-label, randomised, controlled phase 3 trial at 70 sites in 11 countries. Patients with hepatocellular carcinoma with one or more previous systemic therapies, including sorafenib, were randomly assigned to receive 30 mg/m2 doxorubicin-loaded nanoparticles (30 mg/m2 group), 20 mg/m2 doxorubicin-loaded nanoparticles (20 mg/m2 group), or standard care using a computer-generated randomisation list prepared by the funder and stratified by geographic region. Patients in the experimental groups received perfusion of the drug every 4 weeks and those in the control group received any systemic anticancer therapy (except sorafenib) as per investigator decision. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the population of patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov , number NCT01655693 . Findings Between June 15, 2012, and Jan 27, 2017, 541 patients were screened, of whom 144 were excluded and 397 were randomly assigned to one of the groups (133 to the 30 mg/m2 group; 130 to the 20 mg/m2 group; and 134 to the control group). Median follow-up was 22·7 months (IQR 11·2–34·9). After pooling the doxorubicin groups for the efficacy analysis, median overall survival was 9·1 months (95% CI 8·1–10·4) in the pooled doxorubicin-loaded nanoparticles group and 9·0 months (7·1–11·8) in the control group (HR 1·00 [95% CI 0·78–1·28], two-sided p=0·99). 227 (94%) of 242 patients who received doxorubicin-loaded nanoparticles and 100 (75%) of 134 patients in the control group had at least one treatment-emergent adverse event. The most common drug-related grade 3 or 4 treatment-emergent adverse events were neutropenia (25 [10%] of 242 treated with doxorubicin-loaded nanoparticles and eight [6%] of 134 in the control group), asthenia (six [2%] and four [3%]), and thrombocytopenia (three [1%] and ten [7%]). Six (2%) patients treated with doxorubicin-loaded nanoparticles and one (1%) of those in the control group were deemed by investigators to have had a drug-related death. Serious adverse events occurred in 74 (31%) patients who received doxorubicin-loaded nanoparticles and 48 (36%) in the control group. Interpretation Doxorubicin-loaded nanoparticles did not improve overall survival for patients with hepatocellular carcinoma in whom previous sorafenib treatment had failed. Funding Onxeo.

Published
2019

24. Circulating Tumor Cells and Circulating Tumor DNA Detection in Potentially Resectable Metastatic Colorectal Cancer: A Prospective Ancillary Study to the Unicancer Prodige-14 Trial

Author

Laurent Mineur, Charles Decraene, Nicolas Kiavue, Simon Thezenas, François Ghiringhelli, Olivier Bouché, Eric Francois, Adrien Saliou, Marc-Henri Stern, Driffa Moussata, Faiza Khemissa-Akouz, Charlotte Proudhon, Marc Ychou, Thibault Mazard, Jean-Yves Pierga, François-Clément Bidard, Jordan Madic, Rosine Guimbaud, Luc Cabel, Aurore Rampanou, Michel Rivoire, Trevor Stanbury, Pascale Mariani, Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, 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), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Compartimentation et dynamique cellulaires (CDC), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Toulouse [Toulouse], Institut Sainte Catherine [Avignon], Centre Hospitalier Saint Jean de Perpignan, Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), R&D Unicancer [Paris], CRLCC Val d'Aurelle - Paul Lamarque, Herrada, Anthony, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP]

Subjects
0301 basic medicine, Oncology, FOLFIRINOX, Colorectal cancer, medicine.medical_treatment, Kaplan-Meier Estimate, medicine.disease_cause, Targeted therapy, 0302 clinical medicine, Circulating tumor cell, Medicine, Digital polymerase chain reaction, Prospective Studies, Neoplasm Metastasis, lcsh:QH301-705.5, circulating tumor DNA, metastatic colorectal cancer, General Medicine, Middle Aged, Neoplastic Cells, Circulating, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, KRAS, Colorectal Neoplasms, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, circulating tumor cells, Article, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Humans, Liquid biopsy, neoplasms, Aged, Chemotherapy, liquid biopsy, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030104 developmental biology, lcsh:Biology (General), Mutation, business
Abstract

The management of patients with colorectal cancer (CRC) and potentially resectable liver metastases (LM) requires quick assessment of mutational status and of response to pre-operative systemic therapy. In a prospective phase II trial (NCT01442935), we investigated the clinical validity of circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) detection. CRC patients with potentially resectable LM were treated with first-line triplet or doublet chemotherapy combined with targeted therapy. CTC (Cellsearch&reg, ) and Kirsten RAt Sarcoma (KRAS) ctDNA (droplet digital polymerase chain reaction (PCR)) levels were assessed at inclusion, after 4 weeks of therapy and before LM surgery. 153 patients were enrolled. The proportion of patients with high CTC counts (&ge, 3 CTC/7.5mL) decreased during therapy: 19% (25/132) at baseline, 3% (3/108) at week 4 and 0/57 before surgery. ctDNA detection sensitivity at baseline was 91% (N=42/46) and also decreased during treatment. Interestingly, persistently detectable KRAS ctDNA (p = 0.01) at 4 weeks was associated with a lower R0/R1 LM resection rate. Among patients who had a R0/R1 LM resection, those with detectable ctDNA levels before liver surgery had a shorter overall survival (p &lt, 0.001). In CRC patients with limited metastatic spread, ctDNA could be used as liquid biopsy tool. Therefore, ctDNA detection could help to select patients eligible for LM resection.

Published
2019

25. Association Between Microscopic Lesions at Ileal Resection Margin and Recurrence After Surgery in Patients With Crohn’s Disease

Author

Alexandra Traverse-Glehen, Nassim Hammoudi, Olivier Corcos, Philippe Marteau, Julien Loreau, Mariane Maillet, Martine Leconte, Jonathan Catry, Yves Francois, Najim Chafai, Xavier Dray, Marjolaine Ngollo, Philippe Seksik, Pierre Cattan, Benjamin Pariente, Nicolas Munoz-Bongrand, Peggy Falgon, Stéphane Nancey, Nathan Beaupel, Isabelle Nion-Larmurier, Andrée Nisard, Christophe Attencourt, Emmanuel Tiret, Ulrika Chaput, Denis Chatelain, Marion Chauvenet, Dominique Cazals-Hatem, Eddy Cotte, Laurent Beaugerie, Madeleine Bezault, Mircea Chirica, Gilles Boschetti, Sarah Boyer, Loic Brot, Julien Kirchgesner, Hugo Bottois, Anne Dubois, Magali Svrcek, Yoram Bouhnik, Jean-Marc Gornet, Rachid Kaci, Brice Gergaud, Carmen Stefanescu, Helene Corte, Claire Auzolle, Jean-Louis Dupas, Juliette Joubert Zakeyh, Leila Chedouba, Amine Rahili, Elodie Quévrain, Charles Sabbagh, Lionel Le Bourhis, Maria Nachury, Anne Bourrier, Nathalie Guedj, Florence Renaud, Helena Hadjisavvas, Charlotte Gardair, Gilles Bommelaer, Céline Grand, Xavier Treton, Xavier Jouven, Anthony Buisson, Jérémie H. Lefevre, Paul Hofmann, Stéphanie Patouraux, Jérôme Filippi, Xavier Hébuterne, Driffa Moussata, Clotilde Baudry, Nelson Lourenco, Marion Goutte, Harry Sokol, Victor Chardiny, My-Linh Tran-Minh, Bernard Flourié, Pierre Desreumaux, Catherine Godfraind, Coralie Sommeville, Mathurin Fumery, Nicolas Barnich, Joëlle Bonnet, Anne-Laure Charlois, Dilek Coban, Leon Magiorri, Yves Panis, Matthieu Allez, Jean-François Fléjou, Franck Brazier, M. Ferron, Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Département de Pathologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire de pathologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Autophagie infections immunité – Autophagy Infection Immunity, 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), Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Laboratoire des biomolécules (LBM UMR 7203), Université Pierre et Marie Curie - Paris 6 (UPMC)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-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 la Recherche Agronomique (INRA), Hôpital Beaujon [AP-HP], Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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)-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), 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), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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, medicine.medical_specialty, Cryptitis, Ileum, REMIND Trial, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Interquartile range, medicine, Humans, Prospective Studies, Colectomy, Digestive System Surgical Procedures, Outcome, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Prognostic Factor, IBD Surgery, Anastomosis, Surgical, Gastroenterology, Margins of Excision, Histology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Odds ratio, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Endoscopy, Surgery, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Complication, business
Abstract

International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.

Published
2019

27. Recommandations du CDU–HGE, du CNU d’HGE et de la SFED sur la formation en endoscopie digestive

Author

D. Sautereau, Emmanuel Coron, Driffa Moussata, M. Robaszkiewicz, Stanislas Chaussade, P. Bulois, Thierry Lecomte, Xavier Dray, C. Silvain, R. Laugier, Jean-Christophe Saurin, Marc Barthet, M. Dapoigny, T. Ponchon, Jean-Marie Reimund, and Frédéric Prat

Subjects
03 medical and health sciences, 0302 clinical medicine, medicine.diagnostic_test, business.industry, 030220 oncology & carcinogenesis, Medicine, 030211 gastroenterology & hepatology, Radiology, Nuclear Medicine and imaging, Interventional radiology, business, Nuclear medicine, Echo endoscopie, Abdominal surgery
Published
2016

28. L'endomicroscopie confocale par mini-sonde pour évaluer la rémission histologique dans la rectocolite hémorragique: Résultats d'une étude prospective multicentrique sur 100 patients

Author

Michael J. Levy, C Trang Poisson, A Bressenot-Marchal, Guillaume Perrod, Driffa Moussata, Elia Samaha, Laurent Peyrin-Biroulet, L Quénéhervé, Emmanuel Coron, Arnaud Bourreille, Christophe Cellier, G Rahmi, and J Moreau

Subjects
Gynecology, medicine.medical_specialty, business.industry, medicine, business
Published
2018

29. In vivo MRS for the assessment of mouse colon using a dedicated endorectal coil: initial findings

Author

Olivier Beuf, Laurence Canaple, Hugo Dorez, Driffa Moussata, Sophie Gaillard, Hervé Saint-Jalmes, Hélène Ratiney, Raphaël Sablong, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme d'Imagerie Multimodale LyonTech (PILoT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ANR-11-LABX-0063, LabEx PRIMES, ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), 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), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 5 - RMN et optique : De la mesure aux biomarqueurs, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle de Lyon ( IGFL ), École normale supérieure - Lyon ( ENS Lyon ) -Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), 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 ), Plateforme d'Imagerie Multimodale LyonTech ( PILoT ), Centre Hospitalier Régional Universitaire de Tours, CHRU Tours, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Pathology, medicine.medical_specialty, spectroscopy, Magnetic Resonance Spectroscopy, Colorectal cancer, Colon, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, IBD, Lumen (anatomy), Rectum, Inflammatory bowel disease, 030218 nuclear medicine & medical imaging, lipids, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, choline, medicine, Animals, cancer, Radiology, Nuclear Medicine and imaging, Colitis, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Histology, medicine.disease, Magnetic Resonance Imaging, 3. Good health, endorectal coil, medicine.anatomical_structure, Molecular Medicine, 030211 gastroenterology & hepatology, business, MRI
Abstract

International audience; nflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow-up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues.An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B1 magnetic field, and a dedicated ERC was used for signal reception. Colon-wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 μL to 2 μL while keeping acquisition times below 3 min.The acquired spectra show various biochemical contents such as α- and β-methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon-wall complex exhibits both high lipid and high water contents.To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies.

Published
2017

30. Adenoma detection with blue-water infusion colonoscopy: a randomized trial

Author

Marc O’Brien, Olivia Scalone, D. Pere-Verge, Sandrine Baubet, Claire Billioud, Karine Stroeymeyt-Martin, Driffa Moussata, Christine Chambon-Augoyard, Guillermo Aguero Garcete, Stéphane Degeorges, Sandrine Touzet, Adriane Lesne, Thierry Ponchon, Jérôme Rivory, Audrey Pasquion, Claire Cruiziat, Sylvaine Chalumeau, Florence Léger-Nguyen, S. Poupon-Bourdy, Jean-Marc Phelip, Philippe Brulet, Benjamin Hamel, J. C. Souquet, Thierry Fontanges, Laurent Magaud, Fabien Petit-Laurent, Julien Scanzi, Laurent Poincloux, Angélique Denis, Marion Chauvenet, Mathieu Pioche, Olivier Rouquette, Gwenaelle Tourlonias, Elsa Thimonier, Emmanuelle Graillot, CHU Estaing [Clermont-Ferrand], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Gastro-enterology department, CHU Clermont-Ferrand, Hepato-Gastroenterology, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service d'hépato-gastro-entérologie, CH Pierre Oudot Bourgoin-Jallieu, Hôpital de la Croix-Rousse [CHU - HCL], Hôpital Villefranche sur Saône, Université Panthéon-Sorbonne ( UP1 ), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Hôpital Michallon, Institut Pascal - Clermont Auvergne ( IP ), Sigma CLERMONT ( Sigma CLERMONT ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Application des ultrasons à la thérapie ( LabTAU ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris 1 Panthéon-Sorbonne (UP1), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM), and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adenoma, Male, medicine.medical_specialty, medicine.medical_treatment, Operative Time, Color, Colonoscopy, Adenocarcinoma, Gastroenterology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Intubation, Cecum, Intubation, Gastrointestinal, ComputingMilieux_MISCELLANEOUS, Aged, medicine.diagnostic_test, business.industry, Fecal occult blood, Water, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Colorectal Neoplasms, business
Abstract

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 – 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known.Clinical trials registration: EudraCT 2012-A00548 – 35; NCT01937429.

Published
2017

31. Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment

Author

Lucie Brisson, Pierre Besson, Driffa Moussata, Karine Mahéo, Gaëlle Fromont, Stephan Chevalier, Sébastien Roger, Jean-François Dumas, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Brisson, Lucie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Expression des gènes des phosphorylations oxydatives mitochondriales. Maintenance de l'ADN MT, Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm UMR1069, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de résonance magnétique biologique et médicale (CRMBM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Bioenergetics, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cachexia, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer cell metabolism, Neoplasms, Internal medicine, medicine, Humans, Cancer cell invasiveness, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, pH, Autophagy, Cancer, N-3 polyunsaturated fatty acids, Hydrogen-Ion Concentration, medicine.disease, Dietary Fats, Mitochondria, 3. Good health, 030104 developmental biology, Endocrinology, Anaerobic glycolysis, Cancer cell, Disease Progression, Cancer research, Resistance to treatments, Adjuvant
Abstract

International audience; While tumours arise from acquired mutations in oncogenes or tumour-suppressor genes, it is clearly established that cancers are metabolic diseases characterized by metabolic alterations in tumour cells, and also non-tumour cells of the host organism resulting in tumour cachexia and patient weakness. In this review, we aimed at delineating details by which metabolic alterations in cancer cells, characterized by mitochondrial bioenergetics deregulations and the preference for aerobic glycolysis, are critical parameters controlling the aggressive progression of tumours. In particular, metabolic alteration in cancer cells are coupled to the modulation of intracellular and extracellular pH, epithelial-to-mesenchymal transition and associated increased invasiveness, autophagy, and the development of anticancer treatment resistance. Finally, based on mechanistic, pre-clinical and clinical studies, we proposed the adjuvant supplementation of dietary n-3 polyunsaturated fatty acids for a complementary holistic treatment of the cancer disease.

Published
2017

32. Robust graph representation of images with underlying structural networks. Application to the classification of vascular networks of mice’s colon

Author

Warda Boutegrabet, Hugo Dorez, Denis Bujoreanu, David Rousseau, Raphal Sablong, Driffa Moussata, 3 - Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 5 - RMN et optique : De la mesure aux biomarqueurs, Centre Hospitalier Régional Universitaire de Tours, CHRU Tours, 2 - Images et Modèles, ANR-11-IDEX-0007-02/11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation ( 2011 ), Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), RMN et optique : De la mesure au biomarqueur, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Images et Modèles, ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)

Subjects
0301 basic medicine, Power graph analysis, Theoretical computer science, Monte Carlo method, Image processing, 02 engineering and technology, Network classification, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, Geometric networks, 03 medical and health sciences, Spatial network, Artificial Intelligence, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, 0202 electrical engineering, electronic engineering, information engineering, Segmentation, Mathematics, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, business.industry, Pattern recognition, Complex network, Life science applications, Graph-based image representation, 030104 developmental biology, Signal Processing, Graph (abstract data type), 020201 artificial intelligence & image processing, Computer Vision and Pattern Recognition, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Software
Abstract

A robust graph representation of structural networks in images is introduced.This is inspired from Maximally Stable Extremal Region extended to extremal stable graph.The method is illustrated with a classification problem from biomedical images.The performance of the classification problem can be tested on simulated graphs.The method is of broad applicability when structural networks constitute the objects to be characterized. In this letter, we consider scenes constituted by underlying structural networks. This is an important issue since such scenes appear in many domains of sciences with for instance images of road networks, vascular networks, root systems, etc. The extraction of information from such networks requires characterization methods specifically designed to preserve the topological structure of the network hidden in the image. We propose an entire image processing pipeline for this task with a robust joint segmentation and graph-based representation approach. The proposed method relates, in the closest literature, to the so-called Maximally Stable Extremal Region here extended to extremally stable graph. The method is successfully illustrated with a real world biomedical pattern recognition problem solved with our approach. The robustness of the most common graph parameters is discussed from Monte Carlo simulations on synthetic graphs.

Published
2017

33. Assessment of Mucosal Healing in Inflammatory Bowel Disease

Author

Julie Auzoux, Widad Lahlou, Stéphane Nancey, Alex, Gilles Boschetti, Bernard Flourié, Thierry Lecomte, Laurence Picon, re Aubourg, Alban Girault, Driffa Moussata, William Raoul, Departement d'Hépato-Gastroentérologie et Cancérologie Digestive [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Génétique, Immunothérapie, Chimie et Cancer (GICC), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Autophagie infections immunité – Autophagy Infection Immunity, 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-VetAgro Sup (VAS)-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), Université de Lyon-Université de Lyon-VetAgro Sup (VAS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours

Subjects
ECSS: Endocytoscopy System Score, medicine.medical_specialty, Pathology, VCE: Video-capsule Endoscopy, FC: Fecal Calprotectin, CDEAS: Crohn's Disease Endomicroscopy Activity Score, Gastroenterology, Inflammatory bowel disease, Chromoendoscopy, MRE: Magnetic Resonance Enterography, CD: Crohn's Disease, Quality of life, Internal medicine, CLE: Confocal Laser Endomicroscopy, medicine, Histological healing, CE: NBI Narrow Banding Imaging Coupled with Endocytoscopy, PPV: Positive Predictive Value, NPV: Negative Predictive Value, medicine.diagnostic_test, business.industry, Spe: Specificity, CDAS: Crohn's Disease Activity Score, UCEIS: Ulcerative Colitis Endoscopic Index Of Severity, Endoscopy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, UEGW: United European Gastroenterology Week, Gold standard (test), FICE: Fuji Intelligent Chromo Endoscopy, CDEIS: Crohn's Disease Endoscopic Index of Severity, Magnetic resonance enterography, medicine.disease, IBD: Inflammatory Bowel Disease, UC: Ulcerative Colitis, MARIA: Magnetic Resonance Index Of Activity, Mucosal healing, CRP: C-Reactive Protein, Se: Sensitivity, NBI: Narrow Banding Imaging, CECDAI: Capsule Endoscopy Crohn's Disease Activity Index, SES-CD: Simplified Endoscopic Score For Crohn's Disease, Calprotectin, business, Biomarkers, MH: Mucosal Healing, AIS: Histopathological Scoring of Acute Inflammation
Abstract

International audience; In recent decades, the advent of biological therapy has changed the treatment of inflammatory bowel disease (IBD) and has opened new therapeutic endpoints such as mucosal healing (MH). MH incorporated with clinical remission presents a new concept: deep remission, which correlates with a decrease in hospitalization and surgery and improvement in the patient's quality of life. Several techniques can be used to assess mucosal healing such as endoscopy which remains the gold standard. But considerable variations may exist in the interpretation of the definition of mucosal healing which may also be histological or evaluated by radiological or biological methods. Thus, it is important to study mucosal inflammation by endoscopic scores and by new, more sensitive techniques such as videocapsule endoscopy (VCE), magnetic resonance enterography (MRE), chromoendoscopy and confocal laser endomicroscopy (CLE). Biomarkers, such as fecal calprotectin (FC) were also studied in the evaluation of MH and showed positive results. These methods are currently the subject of validation studies.

Published
2017

34. Tu1995 DEVELOPMENT OF AN ENDOMICROSCOPIC INDEX TO EVALUATE IN VIVO HISTOLOGICAL HEALING IN ULCERATIVE COLITIS PATIENTS: THE ENHANCE INDEX FROM THE FRENCH SOCIETY OF ENDOSCOPY (SFED)

Author

Bastien Perrot, Gabriel Rahmi, Arnaud Bourreille, Driffa Moussata, Caroline Trang, Christophe Cellier, Emmanuel Coron, Guillaume Perrod, Laurent Peyrin-Biroulet, Lucille Quénéhervé, Michael J. Levy, and Jacques Moreau

Subjects
medicine.medical_specialty, Index (economics), medicine.diagnostic_test, business.industry, Gastroenterology, medicine.disease, Ulcerative colitis, Endoscopy, In vivo, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, business
Published
2019

35. Effect of short-chain fatty acids and acidification on the phasic and tonic motor activity of the human colon

Author

Benoit Coffin, Jean-Marc Sabaté, Bernard Flourié, Henri Duboc, Driffa Moussata, Gilles Boschetti, P. Jouët, Caroline Gorbatchef, and Alain Attar

Subjects
Adult, Male, Colon, Physiology, medicine.medical_treatment, Stimulation, Pharmacology, Intracolonic, Butyric acid, Young Adult, chemistry.chemical_compound, medicine, Carbohydrate fermentation, Humans, Saline, chemistry.chemical_classification, Endocrine and Autonomic Systems, Gastroenterology, Fatty acid, Fatty Acids, Volatile, Barostat, Healthy Volunteers, chemistry, Biochemistry, Female, Fermentation, Hydrochloric Acid, Gastrointestinal Motility
Abstract

Background The effects of bacterial fermentation on human colonic motor activity could be explained by colonic acidification or short-chain fatty acid (SCFA) production. We compared in healthy volunteers the colonic motor effects of intracolonic infusion of neutral or acidic saline solutions and then of neutral or acidic solutions containing an SCFA mixture. Methods 20 healthy volunteers swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon connected to a barostat) that migrated into the colon. Colonic motor activity was recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0 (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100 mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined for each hour a global motility index (reflecting phasic activity recorded by all catheters), the mean balloon volume (reflecting tonic activity), and the mean number of high-amplitude-propagated contractions (HAPCs). Key Results Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA mixture did not change the global motility index, the barostat balloon volume, or the HAPC number compared with basal values. Conclusions & Inferences Under our experimental conditions, these findings suggest that the stimulation of colonic motor activity induced by carbohydrate fermentation is not explained by the acidification of the colonic contents or the resulting production of SCFAs.

Published
2013

36. Human Herpesvirus 8-Associated Colorectal Kaposiʼs Sarcoma Occurring in a Drug-induced Immunocompromised Patient with Refractory Ulcerative Colitis

Author

Gilles Boschetti, Françoise Berger, Ivan Graber, Mathieu Pioche, Bernard Flourié, Driffa Moussata, Yves Francois, Eddy Cotte, and Stéphane Nancey

Subjects
Drug, medicine.medical_specialty, Pathology, business.industry, media_common.quotation_subject, Gastroenterology, Immunocompromised patient, medicine.disease, Dermatology, Ulcerative colitis, Refractory, medicine, Immunology and Allergy, Sarcoma, Colitis, business, Kaposi's sarcoma, Human herpesvirus, media_common
Published
2013

37. XIAP as a Radioresistance Factor and Prognostic Marker for Radiotherapy in Human Rectal Adenocarcinoma

Author

Pascale Romestaing, Myriam Decaussin, Bernard Flourié, Franz Rödel, Driffa Moussata, Rachel Paul-Bellon, Stephanie Hehlgans, Françoise Mornex, Bénazir Siddeek, Claire Mauduit, Souheila Amara, Jean-Pierre Gerard, and Mohamed Benahmed

Subjects
Oncology, medicine.medical_specialty, Cell Survival, Apoptosis, X-Linked Inhibitor of Apoptosis Protein, Caspase 3, Adenocarcinoma, Biology, Inhibitor of apoptosis, Radiation Tolerance, Pathology and Forensic Medicine, Mitochondrial Proteins, Cell Line, Tumor, Radiation, Ionizing, Internal medicine, Radioresistance, Biopsy, Biomarkers, Tumor, medicine, Rectal Adenocarcinoma, Humans, Caspase 8, medicine.diagnostic_test, Rectal Neoplasms, Prognosis, XIAP, Gene Knockdown Techniques, Immunohistochemistry, Apoptosis Regulatory Proteins, Carrier Proteins
Abstract

A differential responsiveness of patients to ionizing radiation is observed after preoperative radiotherapy for rectal adenocarcinoma that might be related, in part, to an apoptosis defect. To establish if proteins of the apoptotic cascades [pro-apoptotic: active caspase 3, 8, and 9 and DIABLO (direct inhibitor of apoptosis-binding protein with low pI); anti-apoptotic: XIAP (X-linked inhibitor of apoptosis)] are involved, we analyzed their profile in radioresistant (SW480) and radiosensitive (SW48) human colorectal cell lines. We demonstrated that, after irradiation, the SW48 cells increased the expression of the pro-apoptotic proteins, whereas the SW480 cells increased the expression of the anti-apoptotic protein XIAP. Moreover, XIAP knockdown in SW480 cells enhanced the basal and radiation-induced apoptotic index; the propensity of the SW480 cells to undergo apoptosis after radiation was higher compared with SW48 cells. In a translational study of 38 patients with rectal carcinoma, we analyzed the apoptotic profile for tumor and noncancerous tissue for each biopsy specimen using IHC. According to their response to preoperative radiotherapy, patients were classified into two groups: responsive and nonresponsive. Although no difference in expression of caspase 3, 8, or 9 was observed in the tumor/normal tissue ratio between responsive and nonresponsive patients, the ratio decreased for DIABLO and increased for XIAP. In conclusion, inhibition of XIAP rescues cellular radiosensitivity and both DIABLO and XIAP might be potential predictive markers of radiation responsiveness in rectal adenocarcinoma.

Published
2012

38. Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus

Author

A. Van Gossum, Sandro Ardizzone, Hironori Yamamoto, Simon K. Lo, Arnaud Bourreille, Robert Heuschkel, A. Ignjatovic, Rami Eliakim, Graham L. Radford-Smith, Driffa Moussata, Jean-Frederic Colombel, Ernest G. Seidman, V. Paulsen, Jonathan A. Leighton, J. Kammermeier, Lars Aabakken, David S Sanders, Emanuele Rondonotti, Jason M. Swoger, Julián Panés, S. Bar-Meir, Walter Reinisch, Yoram Bouhnik, Gerassimos J. Mantzaris, M. Keuchel, Simon Travis, Raf Bisschops, Edward V. Loftus, P. F. Fortun, Jörg G. Albert, Edward J. Despott, and Marco Pennazio

Subjects
Enteroscopy, Adult, medicine.medical_specialty, Adolescent, Context (language use), Disease, Gastroenterology, Inflammatory bowel disease, Endoscopy, Gastrointestinal, Crohn Disease, Double-balloon enteroscopy, Internal medicine, Intestine, Small, medicine, Humans, Colitis, Child, medicine.diagnostic_test, business.industry, Patient Selection, Reproducibility of Results, medicine.disease, Ulcerative colitis, digestive system diseases, Endoscopy, Practice Guidelines as Topic, Colitis, Ulcerative, business
Abstract

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Published
2016

39. Comparaison prospective randomisée multicentrique de la coloscopie à l'eau bleue et à l'air: étude Grand Bleu

Author

D. Pere-Verge, Mathieu Pioche, T Fontanges, Driffa Moussata, J Rivory, S. Poupon-Bourdy, J. C. Souquet, Sylvaine Chalumeau, Olivier Rouquette, G Tourlonias, Audrey Pasquion, Sandrine Touzet, Stéphane Degeorges, Adriane Lesne, Julien Scanzi, Christine Chambon-Augoyard, Florence Léger-Nguyen, Laurent Poincloux, Marion Chauvenet, G. Aguero Garcete, Fabien Petit-Laurent, Jean-Marc Phelip, Sandrine Baubet, Laurent Magaud, and T. Ponchon

Subjects
Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Medicine, business
Published
2016

40. Isolated ileitis associated with primary sclerosing cholangitis in three patients with Crohn's disease

Author

Gilles Boschetti, Yoram Bouhnik, Carmen Stefanescu, Driffa Moussata, Bernard Flourié, and Stéphane Nancey

Subjects
0301 basic medicine, Adult, medicine.medical_specialty, endocrine system diseases, Cholangitis, Sclerosing, Inflammation, Disease, digestive system, Gastroenterology, Primary sclerosing cholangitis, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Internal medicine, medicine, Terminal ileum, Humans, Ileitis, Aged, Crohn's disease, Crohn disease, business.industry, digestive, oral, and skin physiology, Middle Aged, medicine.disease, Ulcerative colitis, digestive system diseases, 030104 developmental biology, medicine.anatomical_structure, 030211 gastroenterology & hepatology, Female, medicine.symptom, business
Abstract

Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn's disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients.We report three cases of patients with isolated Crohn's ileitis associated with PSC and in whom colonic inflammation was never documented.Patients were followed up 10-23 years and each patient underwent 6-7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9-10 years.Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept that colonic mucosal inflammation is critical for the pathogenesis of PSC in inflammatory bowel disease.

Published
2016

41. Endoluminal high-resolution MR imaging protocol for colon walls analysis in mouse model of colitis

Author

Olivier Beuf, Hervé Saint-Jalmes, Raphaël Sablong, Hugo Dorez, Sophie Gaillard, Driffa Moussata, Laurence Canaple, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle de Lyon (IGFL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), CRLCC Eugène Marquis (CRLCC), Plateforme d'Imagerie Multimodale LyonTech (PILoT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), This work was supported by the LABEX PRIMES (ANR-11-LABX-0063) of 'Université de Lyon', within the program 'Investissements d’Avenir' (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR)., ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR-11-IDEX-0007,Avenir L.S.E.,PROJET AVENIR LYON SAINT-ETIENNE(2011), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), ANR-11-IDEX-0007-02/11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR-11-IDEX-0007-02/11-IDEX-0007,Avenir L.S.E.,Avenir L.S.E.(2011), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), 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), 5 - RMN et optique : De la mesure aux biomarqueurs, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle de Lyon ( IGFL ), École normale supérieure - Lyon ( ENS Lyon ) -Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), 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 ), CRLCC Eugène Marquis ( CRLCC ), Plateforme d'Imagerie Multimodale LyonTech ( PILoT ), DOREZ, Hugo, Physique, Radiobiologie, Imagerie Médicale et Simulation - - PRIMES2011 - ANR-11-LABX-0063 - LABX - VALID, PROJET AVENIR LYON SAINT-ETIENNE - - Avenir L.S.E.2011 - ANR-11-IDEX-0007 - IDEX - VALID, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 Régional Universitaire de Tours, and CHRU Tours

Subjects
medicine.medical_specialty, Materials science, [SPI] Engineering Sciences [physics], Colon, Slice thickness, [SDV]Life Sciences [q-bio], Biomedical Engineering, Biophysics, High resolution, Health Informatics, Signal-To-Noise Ratio, 030218 nuclear medicine & medical imaging, Mice, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Imaging Tool, Onions, [ SPI ] Engineering Sciences [physics], Image Processing, Computer-Assisted, medicine, Solid State Physics, Animals, Radiology, Nuclear Medicine and imaging, Colitis, Image resolution, Instrumentation, [SDV.IB] Life Sciences [q-bio]/Bioengineering, [ SDV ] Life Sciences [q-bio], Radiological and Ultrasound Technology, medicine.diagnostic_test, Phantoms, Imaging, Imaging / Radiology, Rectum, Magnetic resonance imaging, medicine.disease, Mr imaging, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Disease Models, Animal, Electromagnetic coil, 030220 oncology & carcinogenesis, Computer Appl. in Life Sciences, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, Colorectal Neoplasms, Biomedical engineering
Abstract

International audience; Objective - An endoluminal magnetic resonance (MR) imaging protocol including the design of an endoluminal coil (EC) was defined for high-spatial-resolution MR imaging of mice gastrointestinal walls at 4.7 T. Materials and methods - A receive-only radiofrequency single-loop coil was developed for mice colon wall imaging. Combined with a specific protocol, the prototype was first characterized in vitro on phantoms and on vegetables. Signal-to-noise ratio (SNR) profiles were compared with a quadrature volume birdcage coil (QVBC). Endoluminal MR imaging protocol combined with the EC was assessed in vivo on mice. Results - The SNR measured close to the coil is significantly higher (10 times and up to 3 mm of the EC center) than the SNR measured with the QVBC. The gain in SNR can be used to reduce the in-plane pixel size up to 39 × 39 µm(2) (234 µm slice thickness) without time penalty. The different colon wall layers can only be distinguished on images acquired with the EC. Conclusion - Dedicated EC provides suitable images for the assessment of mice colon wall layers. This proof of concept provides gains in spatial resolution and leads to adequate protocols for the assessment of human colorectal cancer, and can now be used as a new imaging tool for a better understanding of the pathology.

Published
2016

42. Colon cancer in inflammatory bowel disease: recent trends, questions and answers

Author

Driffa Moussata, A. Deleporte, Stéphane Nancey, S. Viennot, Bernard Flourié, and Jean-Marie Reimund

Subjects
medicine.medical_specialty, Colorectal cancer, Population, Disease, Gastroenterology, Inflammatory bowel disease, Diagnosis, Differential, Crohn Disease, Risk Factors, Internal medicine, medicine, Humans, Mass Screening, Colitis, education, Early Detection of Cancer, education.field_of_study, Evidence-Based Medicine, business.industry, Incidence, Cancer, Colonoscopy, General Medicine, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, digestive system diseases, Cell Transformation, Neoplastic, Dysplasia, Population Surveillance, Colonic Neoplasms, Colitis, Ulcerative, France, business
Abstract

Patients with chronic colitis (ulcerative colitis or colonic Crohn's disease) have an increased risk of colorectal cancer (CRC). Although most of the molecular alterations reported in sporadic CRC have also been observed in colitis-associated CRC, they do not occur at the same timing and frequency, indicating a different pathophysiology. In particular, recent work highlighted the importance of chronic mucosal inflammation as a key factor favouring colorectal carcinogenesis in these patients. This may also be one of the reasons explaining the role of 5-aminosalicylates as chemopreventive agents for CRC in inflammatory bowel disease (IBD) patients with colonic involvement. Beside chemoprevention, colonoscopic screening and surveillance have been shown to be the cornerstone for CRC prevention and early detection in this particular patients' population. Periodic surveillance colonoscopy to detect dysplasia has been shown to decrease the mortality attributed to CRC. More recently, progress in imaging techniques increased our ability to identify dysplasia, and should probably now be considered to be an integral part of surveillance colonoscopy. In the future, further improvement of our knowledge of CRC biology, refinement of imaging techniques, as well as molecular discovery (e.g. identification of specific mutations in stool DNA extracts), might lead to develop more accurate diagnostic strategies to reduce the morbidity and mortality related to CRC in patients with ulcerative colitis or colonic Crohn's disease.

Published
2009

43. Contents Vol. 79, 2009

Author

Toshifumi Hibi, Hiroshi Nakase, Kensuke Kubota, Kumiko Saito, Yuriko Minegishi, Gundula Straub, Dieter Jüngst, Berthold Schneider, Nobutaka Fujisawa, Yoshihisa Tsuji, Yasser A. Alderlieste, Yoshiyuki Ito, Hiroshi Ichikawa, Yusuke Sekino, Emanuel Burri, Katsura Mizushima, Yukinao Yamazaki, Michael Neubrand, Dirk P. van Asseldonk, Etsuko Kishimoto, Michiro Otaka, Thomas P. Hüttl, Fritz Spelsberg, Sakae Mikami, Fumiyasu Nakamura, Satoshi Kokura, Ikuhiro Hirata, Masahiro Ohtani, Satoru Saito, Keiko Akimoto, Hédia Benmansour, Atsushi Nakajima, Shigeru Koyama, Hirofumi Hara, Ayako Tomimoto, Osamu Handa, Rupert Althaus, Reginald del Pozo, Toshikazu Yoshikawa, Ulrich Beuers, Izumi Nakagawa, Michael Manz, Takeshi Azuma, Ikumi Yoshida, Lukas Degen, Takuji Kato, Stéphane Nancey, Masahiko Inamori, Tatsushi Omatsu, Erik A.J. Rauws, Tetsuya Okayama, Tsutomu Chiba, Yoshihide Ueda, Stephan R. Vavricka, Masaru Kuriyama, Satoko Adachi, Yoshiaki Ohara, Hidekazu Suzuki, Eisuke Iwasaki, Bram D.J. van den Elzen, Denis Gründel, Kouhei Yamashita, Tomohisa Takagi, Tomohiro Watanabe, Sylvette Claudel, Christoph Beglinger, Natsuko Hayashi, Bernard Flourié, Yuji Naito, Atsushi Nakamura, Tatsuhiro Masaoka, Sabine Roman, Kaori Suzuki, Akiyo Yamakawa, Hiroyuki Suto, Bernardina M. Kanis, Ad A. van Bodegraven, Kimiko Hori, Christoph Jüngst, Tomoyuki Akiyama, Driffa Moussata, Toshihiro Nishizawa, and Nanne K. H. de Boer

Subjects
Gastroenterology
Published
2009

44. Frequency and severity of ileal adenomas in familial adenomatous polyposis after colectomy

Author

Driffa Moussata, G. Bernard, Jean-Christophe Saurin, M. G. Lapalus, B. Prost, Stéphane Nancey, A. Chavaillon, and T. Ponchon

Subjects
Adenoma, Adult, Male, medicine.medical_specialty, Adolescent, Adenomatous polyposis coli, Colorectal cancer, medicine.medical_treatment, Colonic Pouches, Anastomosis, Risk Assessment, Ileal Neoplasm, Gastroenterology, Familial adenomatous polyposis, Age Distribution, Internal medicine, medicine, Humans, Sex Distribution, Colectomy, Neoplasm Staging, Probability, Retrospective Studies, biology, business.industry, Incidence, Biopsy, Needle, Proctocolectomy, Restorative, Middle Aged, medicine.disease, Immunohistochemistry, digestive system diseases, Ileal Neoplasms, Adenomatous Polyposis Coli, Dysplasia, biology.protein, Female, business, Follow-Up Studies
Abstract

BACKGROUND AND STUDY AIMS: The high cumulative risk of colorectal cancer in patients with familial adenomatous polyposis (FAP) justifies prophylactic colectomy with either ileorectal (IRA) or ileal-pouch-anal anastomosis (IPAA). Our aim was to evaluate retrospectively the frequency of and time interval to adenoma development in the ileal mucosa of patients with both types of surgery. PATIENTS AND METHODS: Retrospective study of 44 FAP patients with IRA (n = 21) and IPAA (n = 23). All patients were followed with a standardized procedure including chromoscopy and biopsies of visible polyps. In patients with IRA, specific attention was paid to the ileal mucosa above the anastomosis. RESULTS: In the IPAA group, 18/23 patients (78 %) presented with visible polyps [histology: 16 (70 %) had adenoma with low-grade dysplasia; 1 (4 %) had adenoma with high-grade dysplasia; 1 had normal mucosa]. The mean interval between colectomy and the diagnosis of adenoma was 4.7 +/- 3.3 years. In the IRA group, 16/21 patients (77 %) presented visible polyps in the ileal mucosa [adenoma with low-grade dysplasia in 8 patients (38 %), with high-grade dysplasia in 2 (10 %), and lymphoid nodular hyperplasia in 6]. The mean interval between colectomy and adenoma diagnosis was significantly shorter in the IPAA than in the IRA group (4.76 +/- 3.3 vs. 16.4 +/- 8.5 years, P< 0.0001). CONCLUSION: Our results show a high frequency of adenomas in the ileal mucosa of patients with IPAA and IRA (74 % and 48 % respectively), with evolution into high-grade dysplasia in 6.7 % of cases.

Published
2007

45. Differential effects of ionizing radiation and platinum-derivative chemotherapy on apoptotic pathways in testicular germ cells

Author

Aline Bozec, Sonia Chater, Pascale Romestaing, Mohamed Benahmed, Asma Omezzine, Olivier Chapet, Jean-Pierre Gerard, Claire Mauduit, Françoise Mornex, Souheila Amara, and Driffa Moussata

Subjects
Male, Organoplatinum Compounds, Pyridines, medicine.medical_treatment, Antineoplastic Agents, Apoptosis, Radiation Dosage, Ionizing radiation, Mice, Radiation, Ionizing, Testis, medicine, Animals, Radiology, Nuclear Medicine and imaging, Cells, Cultured, Caspase, Messenger RNA, Chemotherapy, Radiological and Ultrasound Technology, biology, Effector, Spermatozoa, Molecular biology, Oxaliplatin, XIAP, Cell biology, biology.protein, Signal Transduction, medicine.drug
Abstract

The purpose here was to identify whether ionizing radiation and oxaliplatin triggered testicular germ cells apoptosis through different executionary pathways.Adult male mice are treated with oxaliplatin (0.5 mg/kg, Ox) 4 h before being locally irradiated (0.5 Gy, IR, considered as time 0 h).The number of apoptotic germ cells was significantly higher for IR (p0.008), Ox (p0.0001) and Ox + IR (p0.0001) groups compared to the untreated mice group. Similarly, the different treatments induced an increase of p53 expression. Downstream p53, IR and Ox used different pathways. Indeed, IR increased effector caspase-3 expression in terms of mRNA (p0.002), pro-enzyme p0.0001) and active (3.7-fold, p0.003) protein levels but not the inhibitors of apoptosis proteins (IAP) including cIAP1, cIAP2 and XIAP. In contrast, while oxaliplatin treatment had no apparent effect on caspase-3 expression, it significantly decreased the cIAP1 (p0.005), cIAP2 (p0.008) and XIAP (p0.02) proteins levels. Finally, the combination of both treatments decreased IAP expression but did not modify caspase-3 levels while it increased the AIF (apoptosis-inducing factor) protein levels (5.5-fold, p0.003). No modification of AIF levels was observed with OX or IR alone.Together, these results indicate that the platinum analogue oxaliplatin and the ionizing radiations trigger apoptosis in the testicular germ cells, probably through different pathways.

Published
2007

46. Rectocolite hémorragique et anti-TNFα

Author

Bernard Flourié, Stéphane Nancey, and Driffa Moussata

Subjects
Chemotherapy, medicine.drug_class, Rectocolite hemorragique, business.industry, medicine.medical_treatment, Gastroenterology, General Medicine, medicine.disease, Monoclonal antibody, Ulcerative colitis, Infliximab, Clinical trial, Cytokine, Immunology, medicine, Tumor necrosis factor alpha, business, medicine.drug
Published
2007

47. Enrichment of Circulating and Mucosal Cytotoxic CD8+ T Cells Is Associated with Postoperative Endoscopic Recurrence in Patients with Crohn's Disease

Author

Stéphane Nancey, Dominique Kaiserlian, Gilles Boschetti, Driffa Moussata, Yves Francois, Eddy Cotte, Bernard Flourié, Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-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), Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Mucosal Immunity, Vaccination, and Biometrics -- Immunité des muqueuses, vaccinations et biothérapies, 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)-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
0301 basic medicine, Male, Pathology, Cytotoxic, T-Lymphocytes, Gastroenterology, 0302 clinical medicine, Intestinal mucosa, Crohn Disease, Recurrence, Cytotoxic T cell, CD8+ cytotoxic T cells, Prospective Studies, Intestinal Mucosa, Colectomy, Crohn's disease, biology, Crohn\textquoterights disease, General Medicine, Colonoscopy, Middle Aged, 3. Good health, medicine.anatomical_structure, Treatment Outcome, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Female, Original Article, Adult, medicine.medical_specialty, Postoperative recurrence, 03 medical and health sciences, Ileum, Internal medicine, medicine, Humans, Aged, Lamina propria, business.industry, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Granzyme B, CTL, 030104 developmental biology, Granzyme, Case-Control Studies, biology.protein, business, CD8, Follow-Up Studies, T-Lymphocytes, Cytotoxic
Abstract

International audience; BACKGROUND AND AIMS: Evidence from mouse colitis models indicates that cytotoxic CD8+ T cells [CTL] play a key role in the initiation of gut lesions. We investigated whether changes in CD8+ CTL in blood or lamina propria [LP] of the neoterminal ileum were associated with postoperative endoscopic recurrence of Crohn's disease [CD]. METHODS: A total of 37 CD patients with ileocolonic resection were endoscopically followed up at 6 and 12 months post-surgery. CD8+ T cells were analysed by flow cytometry in blood and ileal LP. RESULTS: Granzyme B- and perforin-producing CD8+ T cells were significantly increased at 6 months in blood and in ileum LP in patients with endoscopic recurrence, as compared with those in remission. At a cutoff point of 45% of CD8+ CTL, the overall accuracies of the frequency of blood granzyme B+ or perforin+ CD8+ T cells to identify patients with postoperative endoscopic recurrence were 77% and 83%, respectively. Interestingly, patients with endoscopic recurrence at 12 months were those showing the highest mucosal CD8+ CTL frequency at 6 months, while still in remission. CONCLUSIONS: Enrichment of cytotoxic CD8+ T cells in blood and ileal mucosa coincides with CD postoperative endoscopic recurrence. This underscores that CD8 CTL may play a pathophysiological role in the initiation of gut lesions during CD.

Published
2015

48. Levels of Fecal Calprotectin Are Associated With the Severity of Postoperative Endoscopic Recurrence in Asymptomatic Patients With Crohn's Disease

Author

Xavier Roblin, Guillaume Passot, Jocelyne Drai, Bernard Flourié, Driffa Moussata, Gildas Phelip, Carmen Stefanescu, Yves Francois, Emilie Del Tedesco, Stéphane Nancey, Gilles Boschetti, Yoram Bouhnik, Marc'harid Laidet, Eddy Cotte, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, [SDV]Life Sciences [q-bio], Disease, Gastroenterology, Endoscopy, Gastrointestinal, Cohort Studies, Feces, fluids and secretions, Crohn Disease, Recurrence, Leukocyte L1 Antigen Complex/*metabolism, Prospective Studies, Colectomy, Crohn's disease, Remission Induction, C-Reactive Protein/*metabolism, Middle Aged, 3. Good health, C-Reactive Protein, Treatment Outcome, Crohn Disease/metabolism/*surgery, Female, medicine.symptom, Adult, medicine.medical_specialty, Gastrointestinal, Adolescent, macromolecular substances, Asymptomatic, Young Adult, Ileum, Internal medicine, medicine, Humans, Aged, Hepatology, business.industry, Endoscopy, medicine.disease, Ileum/*surgery, digestive system diseases, Surgery, Asymptomatic Diseases, Calprotectin, Feces/*chemistry, business, Leukocyte L1 Antigen Complex
Abstract

International audience; OBJECTIVES: Fecal calprotectin (fCal) is widely used as marker of gut inflammation and is strongly associated with the severity of endoscopic lesions in Crohn's disease (CD). We analyzed the relationships between levels of fCal and high-sensitivity C-reactive protein (hsCRP) and the presence and severity of postoperative endoscopic recurrence in asymptomatic CD patients (Harvey-Bradshaw index\textless/=3). METHODS: Blood and fecal samples were collected in consecutive asymptomatic CD patients (Harvey-Bradshaw index 0.85 +/- 0.19, mean +/- s.e.m.) who had undergone an ileocolonic resection. hsCRP and fCal were measured and a routine ileocolonoscopy was performed within 18 months (median 7 months) from resection, to detect endoscopic recurrence according to the Rutgeerts score. RESULTS: Eighty-six patients were included in this prospective multicenter observational cohort. fCal concentrations differed significantly in patients with endoscopic recurrence when compared with those in endoscopic remission (mean +/- s.e.m.: 473 +/- 78 mug/g vs. 115 +/- 18 mug/g; P\textless0.0001). The area under the receiver operating characteristic (ROC) curve to discriminate between patients in endoscopic remission and recurrence was 0.86 for fCal and lower for hsCRP (0.70). The best cutoff point for fCal to distinguish between endoscopic remission and recurrence was 100 mug/g as determined by the ROC curve, and its sensitivity, specificity, positive and negative predictive values (NPVs), as well as overall accuracy were 95%, 54%, 69%, 93%, and 77%, respectively. CONCLUSION: Measurement of fCal concentrations is a promising and useful tool for monitoring asymptomatic CD patients after ileocolonic resection. Taking into account the high NPV of fCal, a threshold below 100 mug/g could avoid systematic ileocolonoscopies in 30% of patients from this population.

Published
2015

49. Familial adenomatous polyposis and pancreatic cancer

Author

Leila Senouci, Jean-Yves Scoazec, Driffa Moussata, Stéphane Pinson, Françoise Berger, Jean-Christophe Saurin, Catherine Lombard-Bohas, and Thomas Walter

Subjects
Adult, Male, Genes, APC, Endocrinology, Diabetes and Metabolism, Biopsy, Familial adenomatous polyposis, Young Adult, Endocrinology, Pancreatic cancer, Internal Medicine, medicine, Carcinoma, Humans, Genetic Predisposition to Disease, Young adult, Hepatology, medicine.diagnostic_test, business.industry, Carcinoma, Acinar Cell, Middle Aged, medicine.disease, Prognosis, Phenotype, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, Adenomatous Polyposis Coli, Cancer research, Neuroendocrine therapy, business
Published
2015

50. Accuracies of serum and fecal S100 proteins (calprotectin and calgranulin C) to predict the response to TNF antagonists in patients with Crohn's disease

Author

Bernard Flourié, Gilles Boschetti, Patrick Garnero, Remi Duclaux-Loras, Anne Mialon, Jocelyne Drai, Charlotte Cuerq, Corinne Preaudat, Driffa Moussata, Stéphane Nancey, Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-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), Cisbio Bioassays, Service d'Hépatologie et de Gastroentérologie [Lyon], Hospices Civils de Lyon (HCL), Laboratoire de Biochimie et Toxicologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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)-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
Male, Crohn Disease/*drug therapy/metabolism/mortality, [SDV]Life Sciences [q-bio], Monoclonal/metabolism/*therapeutic use, Gastroenterology, Feces, 0302 clinical medicine, fluids and secretions, Crohn Disease, Maintenance therapy, Recurrence, Immunology and Allergy, Prospective Studies, Prospective cohort study, Crohn's disease, S100 Proteins/*analysis, S100 Proteins, Area under the curve, Antibodies, Monoclonal, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Leukocyte L1 Antigen Complex/*analysis, medicine.drug, Adult, medicine.medical_specialty, Tumor Necrosis Factor-alpha/*antagonists & inhibitors, Enzyme-Linked Immunosorbent Assay, Antibodies, 03 medical and health sciences, Internal medicine, medicine, Adalimumab, Humans, Survival rate, Aged, Tumor Necrosis Factor-alpha, business.industry, S100A12 Protein, medicine.disease, Infliximab, ROC Curve, Immunology, Biomarkers/*analysis, Calprotectin, Feces/*chemistry, business, Leukocyte L1 Antigen Complex, Biomarkers, Follow-Up Studies
Abstract

International audience; BACKGROUND: Calprotectin and S100A12 (calgranulin C) are markers of gut inflammation. The aim was to compare the usefulness of serum and fecal calprotectin (fCal) and S100A12 in assessing the response to anti-TNF and in predicting relapse under maintenance therapy in Crohn's diseases (CD). METHODS: Thirty-two consecutive patients with CD were treated with adalimumab or infliximab. All received an induction regimen followed by maintenance therapy with infliximab 5 mg/kg every 8 weeks or adalimumab 40 mg every other week and provided at week 0 and 14 fecal and blood samples for determination serum CRP, serum and fecal calprotectin and S100A12 levels. RESULTS: Clinical remission at week 14 (responders) was achieved in 21 patients and among them, 12 were still in steroid-free clinical remission at week 52. Median serum S100A12 and fCal concentrations significantly drop only in responders from week 0 to week 14 after induction, whereas serum calprotectin and fecal S100A12 levels failed to differ significantly. Fecal calprotectin levels at week 14 had the highest discriminant validity to predict clinical remission within 1 year after induction (area under the curve = 0.87) followed by fecal, serum S100A12, and serum calprotectin (area under the ROC curve = 0.70, 0.70, and 0.68, respectively). A cutoff of 82 mug/g for fCal at week 14 had a sensitivity and specificity of 93% and 75%, respectively, to predict clinical remission within 1 year of therapy. CONCLUSIONS: Serum S100A12 level and fCal are reliable markers associated with response to induction therapy with anti-TNF. Fecal calprotectin was the best for predicting clinical remission in CD under maintenance therapy.

Published
2015

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