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1. Comparison of the management of Helicobacter pylori infection between the older and younger European populations

Author

Paulius Jonaitis, Olga P. Nyssen, Ilaria Maria Saracino, Giulia Fiorini, Dino Vaira, Ángeles Pérez-Aísa, Bojan Tepes, Manuel Castro-Fernandez, Manuel Pabón-Carrasco, Alma Keco-Huerga, Irina Voynovan, Alfredo J. Lucendo, Ángel Lanas, Samuel J. Martínez-Domínguez, Enrique Alfaro Almajano, Luis Rodrigo, Ludmila Vologzanina, Natasa Brglez Jurecic, Maja Denkovski, Luis Bujanda, Umud Mahmudov, Mārcis Leja, Frode Lerang, Gülüstan Babayeva, Dmitry S. Bordin, Antonio Gasbarrini, Juozas Kupcinskas, Oleksiy Gridnyev, Theodore Rokkas, Ricardo Marcos-Pinto, Perminder S. Phull, Sinead M. Smith, Ante Tonkić, Doron Boltin, György Miklós Buzás, Štěpán Šembera, Halis Şimşek, Tamara Matysiak-Budnik, Vladimir Milivojevic, Wojciech Marlicz, Marino Venerito, Lyudmila Boyanova, Michael Doulberis, Lisette G. Capelle, Anna Cano-Català, Leticia Moreira, Francis Mégraud, Colm O’Morain, Javier P. Gisbert, Laimas Jonaitis, and Hp-EuReg investigators

Subjects
Medicine, Science
Abstract

Abstract The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. “European Registry on H. pylori Management (Hp-EuReg)” data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18–59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p

Published
2023
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2. Author Correction: Comparison of the management of Helicobacter pylori infection between the older and younger European populations

Author

Paulius Jonaitis, Olga P. Nyssen, Ilaria Maria Saracino, Giulia Fiorini, Dino Vaira, Ángeles Pérez-Aísa, Bojan Tepes, Manuel Castro-Fernandez, Manuel Pabón-Carrasco, Alma Keco-Huerga, Irina Voynovan, Alfredo J. Lucendo, Ángel Lanas, Samuel J. Martínez-Domínguez, Enrique Alfaro Almajano, Luis Rodrigo, Ludmila Vologzanina, Natasa Brglez Jurecic, Maja Denkovski, Luis Bujanda, Umud Mahmudov, Mārcis Leja, Frode Lerang, Gülüstan Babayeva, Dmitry S. Bordin, Antonio Gasbarrini, Juozas Kupcinskas, Oleksiy Gridnyev, Theodore Rokkas, Ricardo Marcos-Pinto, Perminder S. Phull, Sinead M. Smith, Ante Tonkić, Doron Boltin, György Miklós Buzás, Štěpán Šembera, Halis Şimşek, Tamara Matysiak-Budnik, Vladimir Milivojevic, Wojciech Marlicz, Marino Venerito, Lyudmila Boyanova, Michael Doulberis, Lisette G. Capelle, Anna Cano-Català, Leticia Moreira, Francis Mégraud, Colm O’Morain, Javier P. Gisbert, Laimas Jonaitis, and Hp-EuReg investigators

Subjects
Medicine, Science
Published
2023
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3. Primary Gastrointestinal Follicular Lymphomas: A Prospective Study of 31 Patients with Long-term Follow-up Registered in the French Gastrointestinal Lymphoma Study Group (GELD) of the French Federation of Digestive Oncology (FFCD)

Author

Tamara Matysiak-Budnik, Philippe Jamet, Nicolas Chapelle, Bettina Fabiani, Paul Coppo, and Agnès Ruskoné-Fourmestraux

Subjects
primary gastrointestinal follicular lymphoma, follicular lymphoma, transformation, clinical management, follow-up, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background/Aims: Primary gastrointestinal follicular lymphomas (PGFL) are very rare. Our aim was to analyze the clinical features, management, and long-term outcomes in a prospective series of patients diagnosed with PGFL. Methods: All adult patients with PGFL, consecutively enrolled into the multicenter French study between 1990 and 2017, were evaluated and followed up prospectively after undergoing a complete work-up. Clinical, pathological and endoscopic features, as well as treatment outcomes, were analyzed. Results: Thirty-one patients (16 men, median age 62 years, range 33 to 79 years) with PGFL were included. The median follow-up was 92 months (range, 6 to 218 months). In the majority of patients (n=14), lymphoma was incidentally diagnosed during endoscopy. Otherwise, the most frequent circumstances of diagnosis were abdominal pain (n=7) and dyspepsia (n=5). The duodenum was the most common site of involvement (n=19) and multifocal localizations were seen in seven patients (22%). The most frequent first line strategy was surveillance applied in 22 patients (71%), of whom nine reached spontaneous, complete remission and 11 had stable disease. Seven patients (23%) received chemotherapy as first line treatment, and two underwent resection. Of seven patients who received chemotherapy, four achieved complete remission. In three patients, transformation into a high-grade lymphoma occurred. Conclusions: The diagnosis of PGFL is frequently fortuitous. The most common localization is in the duodenum. The disease has an indolent course and a good prognosis, however, rare cases of transformation into aggressive high-grade lymphoma may occur. An appropriate characterization and follow-up of these lymphomas is mandatory for their optimal management.

Published
2022
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4. Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013–2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

Author

Olga P. Nyssen, Pietro Pratesi, Miguel A. Spínola, Laimas Jonaitis, Ángeles Pérez-Aísa, Dino Vaira, Ilaria Maria Saracino, Matteo Pavoni, Giulia Fiorini, Bojan Tepes, Dmitry S. Bordin, Irina Voynovan, Ángel Lanas, Samuel J. Martínez-Domínguez, Enrique Alfaro, Luis Bujanda, Manuel Pabón-Carrasco, Luis Hernández, Antonio Gasbarrini, Juozas Kupcinskas, Frode Lerang, Sinead M. Smith, Oleksiy Gridnyev, Mārcis Leja, Theodore Rokkas, Ricardo Marcos-Pinto, Antonio Meštrović, Wojciech Marlicz, Vladimir Milivojevic, Halis Simsek, Lumir Kunovsky, Veronika Papp, Perminder S. Phull, Marino Venerito, Lyudmila Boyanova, Doron Boltin, Yaron Niv, Tamara Matysiak-Budnik, Michael Doulberis, Daniela Dobru, Vincent Lamy, Lisette G. Capelle, Emilija Nikolovska Trpchevska, Leticia Moreira, Anna Cano-Català, Pablo Parra, Francis Mégraud, Colm O’Morain, Guillermo J. Ortega, Javier P. Gisbert, and on behalf of the Hp-EuReg Investigators

Subjects
Helicobacter pylori, clustering, phenotyping, machine learning, treatment, eradication, Therapeutics. Pharmacology, RM1-950
Abstract

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.

Published
2023
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5. Prolonged response on olaparib maintenance in metastatic pancreatic acinar cell carcinoma associated with a germline BRCA 2 mutation, revealed by severe panniculitis

Author

Margaux Lelong, Jean‐Luc Raoul, Yann Touchefeu, Jean‐Marie Berthelot, Paul Arnolfo, Tamara Matysiak‐Budnik, and Hélène Senellart

Subjects
BRCA mutation, lipase, long survival, pancreatic acinar cell cancer, panniculitis, Medicine, Medicine (General), R5-920
Abstract

Abstract This 38‐year‐old man has a familial BRCA2 mutation. He presented with skin erythema, polyarthritis, dactylitis, and febrile erythema nodosum; a biopsy of a liver metastase revealed acinar cell carcinoma of the pancreas. After FOLFIRINOX, olaparib was initiated, and 24 months after, the patient was PS 0 and asymptomatic.

Published
2022
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6. 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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7. Nivolumab‐induced celiac‐like enteropathy in patient with metastatic renal cell carcinoma: Case report and review of the literature

Author

Lucie Duval, Sarah Habes, Thierry Chatellier, Pascale Guerzider, Céline Bossard, Claude Masliah, Isabelle Archambeaud, Yann Touchefeu, and Tamara Matysiak‐Budnik

Subjects
celiac‐like enteropathy, immune‐related adverse effects, immunotherapy, nivolumab, PD‐1 inhibitors, Medicine, Medicine (General), R5-920
Abstract

Abstract Nivolumab may induce severe celiac‐like enteropathy, that may appear very rapidly, after only two injections of nivolumab, and may be successfully treated with corticosteroids. This observation underlines the importance of histological analysis of duodenal biopsies and the necessity to rule out a real celiac disease in patients with nivolumab‐induced diarrhea.

Published
2019
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8. 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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9. Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type

Author

Phu Hung Nguyen, Yann Touchefeu, Tony Durand, Philippe Aubert, Emilie Duchalais, Stanislas Bruley des Varannes, Christine Varon, Michel Neunlist, and Tamara Matysiak-Budnik

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Gastric cancer is the third leading cause of cancer-related death worldwide, but the mechanisms of gastric carcinogenesis are not completely understood. Recently, the role of cholinergic neuronal pathways in promoting this process has been demonstrated. Our aim was to extend these studies and to evaluate, using an in vitro model of tumorspheres, the effect of acetylcholine on human gastric cancer cells, and the role of acetylcholine receptors and of the nitric oxide pathway, in this effect. The gastric cancer cell line MKN-45 of the diffuse type of gastric cancer was cultured in the presence of acetylcholine, or different agonists or inhibitors of muscarinic and nicotinic acetylcholine receptors, or nitric oxide donor or inhibitor of the nitric oxide pathway, and the number and size of tumorspheres were assessed. The expression of cancer stem cell markers (CD44 and aldehyde dehydrogenase) was also evaluated by immunofluorescence and quantitative reverse transcription polymerase chain reaction. We showed that acetylcholine increased both the number and size of tumorspheres and that this effect was reproduced with both muscarinic and nicotinic acetylcholine receptors agonists and was inhibited by both receptor antagonists. The nitric oxide donor stimulated the tumorsphere formation, while the nitric oxide synthesis inhibitor inhibited the stimulatory effect of acetylcholine. Moreover, acetylcholine increased the expression of stem cell markers on gastric cancer cells. These results indicate that acetylcholine induces the stem cell properties of gastric cancer cells and both muscarinic and nicotinic receptors and a nitrergic pathway might be involved in this effect.

Published
2018
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10. Specific IgG response against Mycobacterium avium paratuberculosis in children and adults with Crohn's disease.

Author

Julien Verdier, Louis Deroche, Matthieu Allez, Caroline Loy, Franck Biet, Christelle C Bodier, Sylvie Bay, Christelle Ganneau, Tamara Matysiak-Budnik, Jean Marc Reyrat, Martine Heyman, Nadine Cerf-Bensussan, Frank M Ruemmele, and Sandrine Ménard

Subjects
Medicine, Science
Abstract

Background and aimsPresence of serum antibodies against Mycobacterium avium paratuberculosis (MAP) in Crohn's Disease (CD) as a disease characteristic remains controversial. In the present work, we assessed antibody reactivity of serum and intestinal fluid against four distinct MAP-antigens, including the recently identified MAP-specific lipopentapeptide (L5P).MethodsImmunoglobulin concentrations and specificity against 3 non MAP-specific antigens: glycosyl-transferase-d (GSD), purified protein derivative from MAP (Johnin-PPD), heparin binding haemagglutinin (MAP-HBHA) and one MAP-specific antigen: synthetic L5P were determined by ELISA in gut lavage fluids from adult controls or patients with CD, and in sera of children or adult controls or patients with CD, ulcerative colitis or celiac disease.ResultsTotal IgA and IgG concentrations were increased in sera of children with CD but were decreased in sera of adults with CD, thereof specificity against MAP antigens was assessed by normalizing immunoglobulin concentrations between samples. In CD patients, IgG reactivity was increased against the four MAP antigens, including L5P in gut lavage fluids but it was only increased against L5P in sera. By contrast, anti-L5P IgG were not increased in patients with ulcerative colitis or celiac disease.ConclusionsA significant increase in anti-L5P IgG is observed in sera of children and adults with CD but not in patients with other intestinal inflammatory diseases. Anti-L5P antibodies may serve as serological marker for CD.

Published
2013
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11. Defibrotide for Sinusoidal Obstruction Syndrome and Nodular Regenerative Hyperplasia After Oxaliplatin-Based Hepatic Intra-Arterial Chemotherapy: A Case Report

Author

Amaury Druet, Caroline Viala, Yann Touchefeu, Jean-François Mosnier, Tamara Matysiak-Budnik, and Erwan Corbineau

Subjects
medicine.medical_specialty, Chemotherapy, Colorectal cancer, business.industry, medicine.medical_treatment, Gastroenterology, Defibrotide, medicine.disease, Oxaliplatin, Hepatic arterial infusion, Oncology, Internal medicine, medicine, bacteria, Portal hypertension, Complication, business, Nodular regenerative hyperplasia, medicine.drug
Abstract

Clinical Practice Points • Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of oxaliplatin-based chemotherapy. • Nodular regenerative hyperplasia can be associated at a late stage of SOS, and should be suspected in case of signs of portal hypertension such as thrombocytopenia or splenomegaly. • To our knowledge, this is the first report of SOS occurring after oxaliplatin hepatic arterial infusion (HAI). • We report a case of a 43-year-old man, with colorectal liver metastases with SOS associated with nodular regenerative hyperplasia, diagnosed after 28 cycles of oxaliplatin-based HAI, treated with defibrotide but with a fatal outcome.

Published
2022

12. Supplementary Figure from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Laurence Zitvogel, Lisa Derosa, Edoardo Pasolli, Jean-Yves Scoazec, Hans Clevers, Fjodor Yousef Yengej, Nicola Segata, Mohamed-Amine Bani, Leonardo Lordello, Bertrand Routy, Guido Kroemer, Oliver Kepp, Bernhard Ryffel, Sylvie Berrard, Valentin Quiniou, Sophie Ugolini, Connie P.M. Duong, Paul Hofman, Jacques Bosq, Tamara Matysiak-Budnik, Laetitia Aymeric, Anne Bessard, Michel Neunlist, Fanny Mann, Angélique Puget, Paule Opolon, Nathalie Droin, Marine Aglave, Marc Deloger, Jérôme Cartry, Fanny Jaulin, Marine Fidelle, Cassandra Thelemaque, Marine Mazzenga, Pierre Ly, Eugénie Pizzato, Gibrail Mansouri, Kousuke Ueda, Imran Lahmar, Jean-Eudes Fahrner, Anne-Gaëlle Goubet, Gladys Ferrere, Valerio Iebba, Antoine Lafarge, Carolina Alves Costa Silva, Safae Terrisse, and Satoru Yonekura

Abstract

Supplementary Figure from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Published
2023

13. Data from Cancer Induces a Stress Ileopathy Depending on β-Adrenergic Receptors and Promoting Dysbiosis that Contributes to Carcinogenesis

Author

Laurence Zitvogel, Lisa Derosa, Edoardo Pasolli, Jean-Yves Scoazec, Hans Clevers, Fjodor Yousef Yengej, Nicola Segata, Mohamed-Amine Bani, Leonardo Lordello, Bertrand Routy, Guido Kroemer, Oliver Kepp, Bernhard Ryffel, Sylvie Berrard, Valentin Quiniou, Sophie Ugolini, Connie P.M. Duong, Paul Hofman, Jacques Bosq, Tamara Matysiak-Budnik, Laetitia Aymeric, Anne Bessard, Michel Neunlist, Fanny Mann, Angélique Puget, Paule Opolon, Nathalie Droin, Marine Aglave, Marc Deloger, Jérôme Cartry, Fanny Jaulin, Marine Fidelle, Cassandra Thelemaque, Marine Mazzenga, Pierre Ly, Eugénie Pizzato, Gibrail Mansouri, Kousuke Ueda, Imran Lahmar, Jean-Eudes Fahrner, Anne-Gaëlle Goubet, Gladys Ferrere, Valerio Iebba, Antoine Lafarge, Carolina Alves Costa Silva, Safae Terrisse, and Satoru Yonekura

Abstract

Gut dysbiosis has been associated with intestinal and extraintestinal malignancies, but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here, we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. The rapid onset of tumorigenesis induced a burst of REG3γ release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long-lasting dysbiosis dominated by Gram-positive Clostridium species. Pharmacologic blockade of β-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin, or cohousing of tumor bearers with tumor-free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Patients with cancer harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extraintestinal malignancies requiring specific therapies.Significance:Whether gut dysbiosis promotes tumorigenesis and how it controls tumor progression remain open questions. We show that 50% of transplantable extraintestinal malignancies triggered a β-adrenergic receptor–dependent ileal mucosa atrophy, associated with increased gut permeability, sustained Clostridium spp.–related dysbiosis, and cancer growth. Vancomycin or propranolol prevented cancer-associated stress ileopathy.This article is highlighted in the In This Issue feature, p. 873

Published
2023

16. 133 - PATRÓN DE PRESCRIPCIÓN DE PROBIÓTICOS ADYUVANTES A LA TERAPIA ERRADICADORA FRENTE A HELICOBACTER PYLORI: RESULTADOS DEL REGISTRO EUROPEO SOBRE EL MANEJO DE LA INFECCIÓN POR HELICOBACTER PYLORI (HP-EUREG)

Author

Diego Casas, Javier Alcedo, Miguel Lafuente, F. Javier López, Angeles Pérez-Aisa, Matteo Pavoni, Ilaria Maria Saracino, Bojan Tepes, Laimas Jonaitis, Manuel Castro-Fernández, Manuel Pabón-Carrasco, Alma Keco-Huerga, Irina Voynovan, Luis Bujanda, Alfredo J. Lucendo, Natasa Brglez Jurecic, Maja Denkovski, Perminder S. Phull, Luis Rodrigo, Angel Lanas, Samuel J. Martínez-Domínguez, Enrique Alfaro, Galina D Fadieienko, José M. Huguet, Dmitry S. Bordin, Antonio Gasbarrini, Juozas Kupcinskas, Gülüstan Babayeva, Oleksiy Gridnyev, Mrcis Leja, Theodore Rokkas, Ricardo Marcos-Pinto, Frode Lerang, Doron Boltin, Veronika Papp, Ante Tonki, Sinead M. Smith, Halis Simsek, Marino Venerito, Lyudmila Boyanova, Vladimir Milivojevic, Lumir Kunovsky, Tamara Matysiak-Budnik, Wojciech Marlicz, Michael Doulberis, Anna Cano-Català, Luis Hernández, Leticia Moreira, Olga P. Nyssen, Francis Megraud, Colm O. Morain, and Javier P. Gisbert

Subjects
Hepatology, Gastroenterology
Published
2023

17. 130 - COMPARACIÓN DE LA EFECTIVIDAD DE LOS TRATAMIENTOS ERRADICADORES MÁS FRECUENTES ENTRE LAS POBLACIONES MÁS MAYORES Y MÁS JÓVENES DE EUROPA: DATOS DEL REGISTRO EUROPEO SOBRE EL MANEJO DE LA INFECCIÓN POR HELICOBACTER PYLORI (HP-EUREG)

Author

Paulius Jonaitis, Olga P. Nyssen, Ilaria Maria Saracino, Giulia Fiorini, Dino Vaira, Ángeles Pérez-Aísa, Bojan Tepes, M. Castro-Fernández, Manuel Pabón-Carrasco, Alma Keco-Huerga, Irina Voynovan, Alfredo J Lucendo, Ángel Lanas, Samuel J Martínez-Domínguez, Enrique Alfaro Almajano, Luis Rodrigo, Ludmila Vologzanina, Natasa Brglez Jurecic, Maja Denkovski, Luis Bujanda, Umud Mahmudov, Mrcis Leja, Frode Lerang, Gülüstan Babayeva, Dmitry S. Bordin, Antonio Gasbarrini, Juozas Kupcinskas, Oleksiy Gridnyev, Theodore Rokkas, Ricardo Marcos-Pinto, Perminder S. Phull, Sinead M. Smith, Ante Tonki, Doron Boltin, György Miklós Buzás, Lumír Kunovský, Halis imek, Tamara Matysiak-Budnik, Vladimir Milivojevic, Wojciech Marlicz, Marino Venerito, Lyudmila Boyanova, Michael Doulberis, Lisette G. Capelle, Anna Cano-Català, Leticia Moreira, Francis Mégraud, Colm O’Morain, Javier P. Gisbert, and Laimas Jonaitis

Subjects
Hepatology, Gastroenterology
Published
2023

18. PAPEL DEL USO DE PROBIÓTICOS EN LA EFECTIVIDAD DE LOS TRATAMIENTOS FRENTE A HELICOBACTER PYLORI: RESULTADOS DEL REGISTRO EUROPEO SOBRE EL MANEJO DE LA INFECCIÓN POR HELICOBACTER PYLORI (HP-EUREG)

Author

Diego Casas, Javier Alcedo, Miguel Lafuente, F. Javier López, Angeles Pérez-Aisa, Matteo Pavoni, Ilaria Maria Saracino, Bojan Tepes, Laimas Jonaitis, Manuel Castro-Fernández, Manuel Pabón Carrasco, Alma Keco- Huerga, Irina Voynovan, Luis Bujanda, Alfredo J. Lucendo, Natasa Brglez Jurecic, Maja Denkovski, Perminder S. Phull, Luis Rodrigo, Angel Lanas, Samuel J. Martínez-Domínguez, Enrique Alfaro, Galina D Fadieienko, José M. Huguet, Dmitry S. Bordin, Antonio Gasbarrini, Juozas Kupcinskas, Gülüstan Babayeva, Oleksiy Gridnyev, Mrcis Leja, Theodore Rokkas, Ricardo Marcos-Pinto, Frode Lerang, Doron Boltin, Veronika Papp, Ante Tonki, Sinead M. Smith, Halis Simsek, Marino Venerito, Lyudmila Boyanova, Vladimir Milivojevic, Lumir Kunovsky, Tamara Matysiak-Budnik, Wojciech Marlicz, Michael Doulberis, Anna Cano-Català, Luis Hernández, Leticia Moreira, Olga P. Nyssen, Francis Megraud, Colm O. Morain, and Javier P. Gisbert

Subjects
Hepatology, Gastroenterology
Published
2023

19. 127 - IMPACTO DEL USO DE PROBIÓTICOS EN LA SEGURIDAD DE LOS TRATAMIENTOS FRENTE A HELICOBACTER PYLORI: RESULTADOS DEL REGISTRO EUROPEO SOBRE EL MANEJO DE LA INFECCIÓN POR HELICOBACTER PYLORI (HP-EUREG)

Author

Diego Casas, Javier Alcedo, Miguel Lafuente, F. Javier López, Angeles Pérez-Aisa, Matteo Pavoni, Ilaria Maria Saracino, Bojan Tepes, Laimas Jonaitis, Manuel Castro-Fernández, Manuel Pabón-Carrasco, Alma Keco-Huerga, Irina Voynovan, Luis Bujanda, Alfredo J. Lucendo, Natasa Brglez Jurecic, Maja Denkovski, Perminder S. Phull, Luis Rodrigo, Angel Lanas, Samuel J. Martínez-Domínguez, Enrique Alfaro, Galina D. Fadieienko, Jose M. Huguet, Dmitry S. Bordin, Antonio Gasbarrini, Juozas Kupcinskas, Gülüstan Babayeva, Oleksiy Gridnyev, Mrcis Leja, Theodore Rokkas, Ricardo Marcos-Pinto, Frode Lerang, Doron Boltin, Veronika Papp, Ante Tonki, Sinead M. Smith, Halis Simsek, Marino Venerito, Lyudmila Boyanova, Vladimir Milivojevic, Lumir Kunovsky, Tamara Matysiak-Budnik, Wojciech Marlicz, Michael Doulberis, Anna Cano-Català, Luis Hernández, Leticia Moreira, Olga P. Nyssen, Francis Megraud, Colm O. Morain, and Javier P. Gisbert

Subjects
Hepatology, Gastroenterology
Published
2023

20. Cancer induces a stress ileopathy depending on B-adrenergic receptors and promoting dysbiosis that contribute to carcinogenesis

Author

Satoru Yonekura, Safae Terrisse, Carolina Alves Costa Silva, Antoine Lafarge, Valerio Iebba, Gladys Ferrere, Anne-Gaëlle Goubet, Jean-Eudes Fahrner, Imran Lahmar, Kousuke Ueda, Gibrail Mansouri, Eugénie Pizzato, Pierre Ly, Marine Mazzenga, Cassandra Thelemaque, Marine Fidelle, Fanny Jaulin, Jérôme Cartry, Marc Deloger, Marine Aglave, Nathalie Droin, Paule Opolon, Angélique Puget, Fanny Mann, Michel Neunlist, Anne Bessard, Laetitia Aymeric, Tamara Matysiak-Budnik, Jacques Bosq, Paul Hofman, Connie P.M. Duong, Sophie Ugolini, Valentin Quiniou, Sylvie Berrard, Bernhard Ryffel, Oliver Kepp, Guido Kroemer, Bertrand Routy, Leonardo Lordello, Mohamed-Amine Bani, Nicola Segata, Fjodor Yousef Yengej, Hans Clevers, Jean-Yves Scoazec, Edoardo Pasolli, Lisa Derosa, Laurence Zitvogel, Hubrecht Institute for Developmental Biology and Stem Cell Research, Yonekura, Satoru, Terrisse, Safae, Alves Costa Silva, Carolina, Lafarge, Antoine, Iebba, Valerio, Ferrere, Glady, Goubet, Anne-Gaelle, Fahrner, Jean-Eude, Lahmar, Imran, Ueda, Kosuke, Mansouri, Gibrail, Pizzato, Eugenie, Ly, Pierre, Mazzenga, Marine, Thelemaque, Cassandra, Fidelle, Marine, Jaulin, Fanny, Cartry, Jerome, Deloger, Marc, Aglave, Marine, Droin, Nathalie, Opolon, Paule, Puget, Angelique, Mann, Fanny, Neunlist, Michel, Bessard, Anne, Aymeric, Laetitia, Matysiak-Budnik, Tamara, Bosq, Jacque, Hofman, Paul, Duong, Connie P M, Ugolini, Sophie, Quiniou, Valentin, Berrard, Sylvie, Ryffel, Bernhard, Kepp, Oliver, Kroemer, Guido, Routy, Bertrand, Lordello, Leonardo, Bani, Mohamed-Amine, Segata, Nicola, Yousef Yengej, Fjodor, Clevers, Han, Scoazec, Jean-Yve, Pasolli, Edoardo, Derosa, Lisa, Zitvogel, Laurence, Institut de Biologie du Développement de Marseille (IBDM), and Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)

Subjects
metagenomics, bioinformatic, Carcinogenesis, [SDV]Life Sciences [q-bio], microbiome, bioinformatics, Gut dysbiosi, B-adrenergic receptors, Gut dysbiosis, Oncology, epithelial barrier permeability, chemiotherapy, Receptors, Adrenergic, beta, microbiota, carcinogenesis, stress ileopathy, immunotherapy, Dysbiosis, Humans, carcinogenesi, Intestinal Mucosa, metagenomic, B-adrenergic receptor, Signal Transduction
Abstract

Gut dysbiosis has been associated with intestinal and extraintestinal malignancies, but whether and how carcinogenesis drives compositional shifts of the microbiome to its own benefit remains an open conundrum. Here, we show that malignant processes can cause ileal mucosa atrophy, with villous microvascular constriction associated with dominance of sympathetic over cholinergic signaling. The rapid onset of tumorigenesis induced a burst of REG3γ release by ileal cells, and transient epithelial barrier permeability that culminated in overt and long-lasting dysbiosis dominated by Gram-positive Clostridium species. Pharmacologic blockade of β-adrenergic receptors or genetic deficiency in Adrb2 gene, vancomycin, or cohousing of tumor bearers with tumor-free littermates prevented cancer-induced ileopathy, eventually slowing tumor growth kinetics. Patients with cancer harbor distinct hallmarks of this stress ileopathy dominated by Clostridium species. Hence, stress ileopathy is a corollary disease of extraintestinal malignancies requiring specific therapies. Significance: Whether gut dysbiosis promotes tumorigenesis and how it controls tumor progression remain open questions. We show that 50% of transplantable extraintestinal malignancies triggered a β-adrenergic receptor–dependent ileal mucosa atrophy, associated with increased gut permeability, sustained Clostridium spp.–related dysbiosis, and cancer growth. Vancomycin or propranolol prevented cancer-associated stress ileopathy. This article is highlighted in the In This Issue feature, p. 873

Published
2022

21. Concomitant decrease of double-positive lymphocyte population CD4CD8αα and Faecalibacterium prausnitzii in patients with colorectal cancer

Author

Quentin Le Bastard, Yann Touchefeu, Emilie Duchalais, Joudy Alameddine, Eric Mirallié, Tamara Matysiak-Budnik, Francine Jotereau, Marie Rimbert, Emmanuel Montassier, François Javaudin, Stanislas Bruley des Varannes, Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d’Immunologie [CHU Nantes] (Centre d’Immunomonitorage Nantes Atlantique - CIMNA), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Hôtel-Dieu de Nantes, and Dupuis, Christine

Subjects
medicine.medical_specialty, Colorectal cancer, [SDV]Life Sciences [q-bio], T cell, Lymphocyte, Population, Faecalibacterium prausnitzii, Gut flora, T-Lymphocytes, Regulatory, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Bacteroides, Humans, Microbiome, education, education.field_of_study, Hepatology, biology, Bacteroidetes, business.industry, medicine.disease, biology.organism_classification, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Colorectal Neoplasms, business, Dysbiosis
Abstract

International audience; Introduction and aims: Changes in the composition of the gut microbiota in patients with colorectal cancer (CRC) compatible with a contribution of the gut microbiota in carcinogenesis have been reported. In particular, a decrease Faecalibacterium prausnitzii has been identified. A CD4CD8αα, double-positive lymphocyte population (DP8α) has recently been demonstrated in the human colon and blood with regulatory functions and specificity for F. prausnitzii. Here, we aimed to detect dysbiosis in the fecal microbiome of patients with CRC by metagenomic analysis, and to look for changes in the levels of DP8α circulating T cells specific for F. prausnitzii in these patients.Patients and methods: Patients with CRC and control subjects were prospectively included. None had received antibiotics in the previous month or any anti-tumor treatment. A stool sample was collected for each participant, and analyzed by shotgun sequencing. The DP8α T cell population was identified and quantified on fresh whole blood by flow cytometry with anti-CD45, anti-CD3, anti-CD4 and anti-CD8α co-labeling.Results: Twenty-one patients with CRC and 20 controls subjects were included. We found that mean relative abundance of five species was significantly decreased in CRC patients compared with controls, including F. prausnitzii, Barnesiella intestinihominis, Alistipes finegoldii, Bacteroides eggerthii and Eubacterium siraeum. We also found that the DP8α T cell population was significantly decreased in the blood of CRC patients compared with controls.Conclusion: In our work, we showed that a reduced abundance of F. prausnitzii in CRC patients was associated to a significant decrease in the circulating DP8α Treg population, suggesting a potential involvement of reduced activity of DP8α T cells in colonic carcinogenesis. These findings open new diagnostic and therapeutic strategies for CRC.

Published
2020

22. Evaluation of a Phone Call Reminder Strategy in the Surveillance of Patients with Gastric Precancerous Lesions Lost to Follow-Up

Author

Emmanuel Coron, Estelle Cauchin, Iva Jirka, Jean-François Mosnier, Tamara Matysiak-Budnik, Yann Touchefeu, Matthieu Péron, Lucille Quénéhervé, and Nicolas Chapelle

Subjects
medicine.medical_specialty, medicine.diagnostic_test, Atrophic gastritis, business.industry, Pharmaceutical Science, Intestinal metaplasia, Cancer, medicine.disease, Phone call, Endoscopy, Surveillance endoscopy, Dysplasia, Internal medicine, medicine, Lost to follow-up, business, Research Article
Abstract

Background: Surveillance of gastric precancerous lesions (GPL) may reduce gastric cancer (GC)-related mortality, but some patients with GPL are lost to follow-up. Objective: The aim of this study was to evaluate the feasibility and efficacy of a “phone-call” strategy in surveillance of the lost to follow-up patients. Patients and Methods: Among all the patients diagnosed with GPL (atrophic gastritis, intestinal metaplasia, low-grade dysplasia) between 2000 and 2015, we identified those who should undergo surveillance endoscopy according to the current guidelines. They were contacted by telephone and invited to undergo endoscopy with gastric biopsies for histological analysis. Results: Among 535 patients with GPL, 134 were contacted. Sixty-two (46%) could not be joined, 36 did not have endoscopy for other reasons, and finally, 36 patients (22 males, median age 65 years) were included. After the median time interval of 57 months between 2 endoscopies, 18 patients showed stability, 11 regression, and 7 progression of GPL, including 1 patient who developed GC. Conclusion: Despite several telephone calls, only one-third of the contacted patients could be brought to surveillance endoscopy. Most of the patients showed stability of GPL, but 1 progressed to GC and could be successfully treated.

Published
2020

23. Digestive cancer screening across Europe

Author

Patrizia Burra, Michael Bretthauer, Maria Buti Ferret, Ana Dugic, Pierluigi Fracasso, Marcis Leja, Tamara Matysiak Budnik, Patrick Michl, Luigi Ricciardiello, Thomas Seufferlein, Monique van Leerdam, Andreea Botos, Institut Català de la Salut, [Burra P] Department of Surgery, Oncology and Gastroenterology, Multivisceral Transplant Unit, Padua University Hospital, Padua, Italy. [Bretthauer M] Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway. [Buti Ferret M] Servei d'Hepatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Dugic A] Department of Gastroenterology, Klinikum Bayreuth Friedrich‐ Alexander‐University Erlangen‐Nürnberg, Bayreuth, Germany. [Fracasso P] Department of Gastroenterology, Ospedale Sandro Pertini, Rome, Italy. [Leja M] Institute of Clinical and Preventive Medicine, University of Latvia and Riga East University Hospital, Riga, Latvia, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Oncology, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms [DISEASES], Aparell digestiu - Càncer - Diagnòstic, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales [ENFERMEDADES], Cribatge (Medicina), diagnóstico::técnicas y procedimientos diagnósticos::cribado sistemático [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Gastroenterology, diagnóstico::diagnóstico precoz::detección precoz del cáncer [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Diagnostic Techniques and Procedures::Mass Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Diagnosis::Early Diagnosis::Early Detection of Cancer [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract

Digestive cancer; Screening; Europe Cáncer digestivo; Cribado; Europa Càncer digestiu; Cribratge; Europa

Published
2022

24. Targeting DNA damage repair mechanisms in pancreas cancer

Author

Eric Van Cutsem, Teresa Macarulla, Pascal Hammel, Albrecht Stenzinger, Thomas Seufferlein, Jean-Luc Van Laethem, Eileen M. O'Reilly, Alexander Kleger, Pieter-Jan Cuyle, Joaquim Bellmunt, Estelle Cauchin, Lukas Perkhofer, Tamara Matysiak-Budnik, Johann Gout, Alica K Beutel, Talia Golan, Institut Català de la Salut, [Perkhofer L] Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany. [Golan T] Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. [Cuyle PJ] Digestive Oncology Department, Imelda General Hospital, Bonheiden, Belgium. University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. [Matysiak-Budnik T] IMAD, Department of Gastroenterology and Digestive Oncology, Hôtel Dieu, CHU de Nantes, Nantes, France. [Van Laethem JL] GI Cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. [Macarulla T] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Oncology, ADN - Reparació, Cancer Research, BRCA1/2, endocrine system diseases, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Chemical Phenomena::Biochemical Phenomena::DNA Repair [PHENOMENA AND PROCESSES], Germline, Medicine, DNA damage repair, platinum, Gen BRCA 2, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas [ENFERMEDADES], Gen BRCA 1, RC254-282, fenómenos químicos::fenómenos bioquímicos::reparación del ADN [FENÓMENOS Y PROCESOS], DNS-Reparatur, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Conference Report, Sciences bio-médicales et agricoles, homologous repair deficiency, Pàncrees - Càncer - Prognosi, PARP inhibitor, medicine.medical_specialty, Pancreatic neoplasms, PALB2, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], pancreatic ductal adenocarcinoma, DNA repair, MLH1, Germline mutation, Internal medicine, ddc:610, Homologous recombination, Bauchspeicheldrüsenkrebs, Diagnosis::Prognosis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], diagnóstico::pronóstico [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms [DISEASES], business.industry, PARP inhibition, Cancer, medicine.disease, digestive system diseases, MSH6, body regions, Cancérologie, MSH2, DNA damage, DNS-Schädigung, business, DDC 610 / Medicine & health
Abstract

Impaired DNA damage repair (DDR) is increasingly recognised as a hallmark in pancreatic ductal adenocarcinoma (PDAC). It is estimated that around 14% of human PDACs harbour mutations in genes involved in DDR, including, amongst others, BRCA1/2, PALB2, ATM, MSH2, MSH6 and MLH1. Recently, DDR intervention by PARP inhibitor therapy has demonstrated effectiveness in germline BRCA1/2-mutated PDAC. Extending this outcome to the significant proportion of human PDACs with somatic or germline mutations in DDR genes beyond BRCA1/2 might be beneficial, but there is a lack of data, and consequently, no clear recommendations are provided in the field. Therefore, an expert panel was invited by the European Society of Digestive Oncology (ESDO) to assess the current knowledge and significance of DDR as a target in PDAC treatment. The aim of this virtual, international expert meeting was to elaborate a set of consensus recommendations on testing, diagnosis and treatment of PDAC patients with alterations in DDR pathways. Ahead of the meeting, experts completed a 27-question survey evaluating the key issues. The final recommendations herein should aid in facilitating clinical practice decisions on the management of DDR-deficient PDAC., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

25. Predictive Factors of Chemotherapy Initiation after Biliary Drainage for Advanced Biliary Tract Cancer: A Retrospective Multicenter Study

Author

Brigitte Dessomme, Julien Edeline, Jaafar Bennouna, Astrid Lièvre, Maëva Salimon, Thimothee Wallenhorst, Pauline Guillouche, Yann Touchefeu, Annie Lim, Jérôme Gournay, Miloud Azarfane, Jeremy Meyer, Tamara Matysiak-Budnik, Hélène Senellart, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre René Gauducheau, CRLCC René Gauducheau, Clinique Jules Verne, Centre Eugène Marquis (CRLCC), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, predictive factors, Multivariate analysis, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, jaundice, biliary tract cancer, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Univariate analysis, Chemotherapy, Biliary drainage, Cholestasis, Biliary tract cancer, business.industry, prognostic factors, Bilirubin, Jaundice, 3. Good health, Biliary Tract Neoplasms, Bile Duct Neoplasms, Multicenter study, Biliary tract, Drainage, medicine.symptom, business
Abstract

International audience; Background and Aims: In unresectable biliary tract cancers, the management of biliary obstruction is often the first step before introduction of chemotherapy. Our aim was to study the predictive factors of chemotherapy initiation after biliary drainage in a series of patients presenting with advanced biliary tract cancer and obstructive jaundice. Methods: Data of all patients treated for unresectable biliary tract cancer with initial biliary obstruction requiring a drainage in six institutions, from January 2009 to January 2019, were retrospectively collected. Results: Among 82 patients included in this study (median age 68 years, men 61%), 48 (59%) received chemotherapy. Median overall survival was 4.9 months (0.2-38.7) in the group of patients who did not receive chemotherapy and 12.2 months (1.9-61.0) in chemotherapy group (HR=2.93; 95%CI: 1.6-5.3; p

Published
2021

26. Adhesion of Gastric Cancer Cells to the Enteric Nervous System: Comparison between the Intestinal Type and Diffuse Type of Gastric Cancer

Author

Paul Girot, Nicolas Chapelle, Laetitia Aymeric, Anne Bessard, Alice Prigent, Yann Touchefeu, Christine Varon, Michel Neunlist, Emilie Duchalais, and Tamara Matysiak-Budnik

Subjects
Cancer Research, Oncology, gastric cancer, enteric nervous system, cell-adhesion molecules, diffuse type, intestinal type
Abstract

Background: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. The enteric nervous system (ENS) has been suggested to be involved in cancer development and spread. Objective: To analyze the GC cell adhesion to the ENS in a model of co-culture of gastric ENS with GC cells. Methods: Primary culture of gastric ENS (pcgENS), derived from a rat embryo stomach, was developed. The adhesion of GC cells to pcgENS was studied using a co-culture model. The role of N-Cadherin, a cell-adhesion protein, was evaluated. Results: Compared to intestinal-type GC cells, the diffuse-type GC cancer cells showed higher adhesion to pcgENS (55.9% ± 1.075 vs. 38.9% ± 0.6611, respectively, p < 0.001). The number of diffuse-type GC cells adherent to pcgENS was significantly lower in neuron-free pcgENS compared to neuron-containing pcgENS (p = 0.0261 and 0.0329 for AGS and MKN45, respectively). Confocal microscopy showed that GC cells adhere preferentially to the neurons of the pcgENS. N-Cadherin blockage resulted in significantly decreased adhesion of the GC cells to the pcgENS (p < 0.01). Conclusion: These results suggest a potential role of enteric neurons in the dissemination of GC cells, especially of the diffuse-type, partly through N-Cadherin.

Published
2022

27. Long-Term Follow-up of Gastric Precancerous Lesions in a Low GC Incidence Area

Author

Yann Touchefeu, Lucille Quénéhervé, Estelle Cauchin, Alice Bourget, Matthieu Péron, Tamara Matysiak-Budnik, Emmanuel Coron, Maxime Leroy, Nicolas Chapelle, and jean François Mosnier

Subjects
Adult, Gastritis, Atrophic, Male, medicine.medical_specialty, Atrophic gastritis, Biopsy, Gastroenterology, Risk Assessment, Article, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Stomach Neoplasms, Internal medicine, Gastroscopy, medicine, Humans, Stage (cooking), Aged, Aged, 80 and over, Metaplasia, Helicobacter pylori, business.industry, Incidence (epidemiology), Incidence, Stomach, Intestinal metaplasia, Cancer, Middle Aged, medicine.disease, Confidence interval, Dysplasia, Gastric Mucosa, 030220 oncology & carcinogenesis, Relative risk, Disease Progression, 030211 gastroenterology & hepatology, Female, France, business, Precancerous Conditions, Follow-Up Studies
Abstract

Introduction Data on the evolution of gastric precancerous lesions (GPL), especially in countries of a Low gastric cancer incidence area are limited. Our objective was to study a long-term evolution of GPL in France. Methods All the patients diagnosed with GPL (atrophic gastritis, intestinal metaplasia [IM], and dysplasia) between 2000 and 2015 and fulfilling criteria for evolution assessment (at least 2 endoscopies, minimal follow-up of 6 months, and at least 2 biopsies obtained from the antrum and corpus) were included. Clinical and endoscopic data were analyzed, and histological samples were reviewed by an expert pathologist with evaluation of the Operative Link on Gastric Intestinal Metaplasia Assessment stage and type of IM. Results From the 507 patients with GPL, 79 fulfilled the strict criteria. During a mean follow-up of 66 months, during which the patients had a mean number of 4 endoscopies (min-max: 2-21) with 9 biopsies/endoscopy, a stability was observed in 70% of patients. Progression occurred in 14% of patients, within a mean delay of 62.1 months (min-max: 17-99). Progression of the lesions was significantly higher in patients with incomplete type of IM (relative risk of progression for incomplete IM: 11.5; 95% confidence interval 2.5-53.1). Regression of IM occurred in 16% of the patients, after a mean delay of 90 months. Discussion This study shows that the patients with antrum-limited IM, especially of incomplete type, are at the highest risk of developing gastric cancer. In most patients, however, the lesions remain stable, which highlights the need for additional markers to better target the patients at risk of progression.

Published
2020

28. Oxaliplatin and 5-Fluorouracil in Advanced Well-Differentiated Digestive Neuroendocrine Tumors: A Multicenter National Retrospective Study from the French Group of Endocrine Tumors

Author

Guillaume Cadiot, Tamara Matysiak-Budnik, Aurélie Ferru, Michel Ducreux, Guillaume Roquin, Jaafar Bennouna, Hélène Senellart, Marc Pracht, Yann Touchefeu, Olivia Hentic, Jean-Baptiste Girot, Paul Girot, Eric Baudin, Thomas Walter, Julien Hadoux, Rosine Guimbaud, David Malka, and Nadia Bouarioua

Subjects
Oncology, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Neuroendocrine tumors, Cellular and Molecular Neuroscience, Endocrinology, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Endocrine system, Humans, Retrospective Studies, Endocrine and Autonomic Systems, business.industry, Retrospective cohort study, medicine.disease, Well differentiated, Oxaliplatin, Pancreatic Neoplasms, Neuroendocrine Tumors, Treatment Outcome, Fluorouracil, Insulinoma, business, medicine.drug
Abstract

Introduction: Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs); however, the available data are limited. Our aim was to assess the efficacy of FOLFOX (association of 5-fluorouracil with oxaliplatin) in a large series of patients with advanced digestive NETs. Methods: All patients with advanced digestive well-differentiated NETs treated with at least 3 cycles of FOLFOX between January 2004 and December 2018 in 12 centers from the French Group of Endocrine Tumors were included. Tumor response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria, progression free survival (PFS), and overall survival, as well as prognostic factors, were analyzed retrospectively. Results: One hundred fifty-five patients were included. Primary tumor locations were pancreas (n = 89), small intestine (n = 40), unknown with no evidence for lung primary (n = 13), stomach (n = 7), and rectum (n = 6). Median Ki-67 was 10%, and 65% of the tumors were grade 2. The partial response rate was 30% for pancreatic NETs, 12.5% for small intestine NETs, 38.5% for unknown primary NETs, 14% for gastric NETs, and 17% for rectal NETs. Significant prognostic factors for poor PFS after FOLFOX were progressive disease at the beginning of treatment (hazard ratio [HR] = 1.83, p = 0.007), hepatic involvement superior to 50% (HR = 2.67, p = 0.0001), and rectal primary tumor location (HR = 2.6, p = 0.0036). Among pancreatic NETs, insulinomas had a better median PFS (22 months) than other pancreatic NETs (9 months, p = 0.026) and showed a high rate (8/9) of serum glucose normalization. Conclusions: FOLFOX shows a promising antitumor activity in advanced digestive NETs. Rapid symptomatic response is observed in metastatic insulinomas.

Published
2020

29. Recent Guidelines on the Management of Patients with Gastric Atrophy: Common Points and Controversies

Author

Tamara Matysiak-Budnik, Maria Constanza Camargo, Marcis Leja, and Maria Blanca Piazuelo

Subjects
Gastritis, Atrophic, medicine.medical_specialty, Physiology, Atrophic gastritis, Adenocarcinoma, Article, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Internal medicine, Health care, Gastroscopy, Medicine, Humans, Intensive care medicine, Societies, Medical, Metaplasia, biology, Helicobacter pylori, business.industry, Stomach, Gastroenterology, Intestinal metaplasia, Cancer, Disease Management, Hepatology, medicine.disease, biology.organism_classification, United States, Europe, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, 030211 gastroenterology & hepatology, Observational study, business, Precancerous Conditions, Cohort study
Abstract

Patients with gastric precancerous lesions (atrophic gastritis and intestinal metaplasia) have increased risk of developing gastric cancer, and adequate management and surveillance of these patients should allow to reduce gastric cancer-related mortality. The guidelines on the management of these patients have been recently published by the European Societies (MAPS II guidelines) and by the American Gastroenterological Association (AGA). The aim of this commentary is to compare these two guidelines by highlighting the common points and differences between them. Both guidelines recommend a systematic detection and eradication of Helicobacter pylori in all patients with gastric atrophy. However, there is a major difference in the recommendations for surveillance: while the MAPS II guidelines recommend systematic endoscopic surveillance in all patients with severe gastric atrophy (with or without intestinal metaplasia), the AGA guidelines focus only on intestinal metaplasia and plead against systematic surveillance, leaving the possibility of surveillance in individual patients based on shared decision between clinicians and patients. The difference between two guidelines comes essentially from the different arguments used by two authorities (randomized control studies by AGA and observational cohort studies by the European Societies), and may be, at least in part, related to the difference between the European and American health care systems and potential economic burden.

Published
2020

30. SYSTEMATIC UPPER ENDOSCOPY CONCOMITANT WITH COLONOSCOPY PERFORMED WITHIN THE COLO-RECTAL CANCER SCREENING PROGRAM: IMPACT ON THE PATIENT-MANAGEMENT STRATEGY

Author

E Duchalais, Y Touchefeu, O Planade, Tamara Matysiak-Budnik, JF Mosnier, N Chapelle, E Coron, M Verdier, and B Dessomme

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, General surgery, Concomitant, Upper endoscopy, medicine, Colonoscopy, Colo-rectal cancer, business, Patient management
Published
2020

31. Systematic upper endoscopy concomitant with colonoscopy performed within the colorectal cancer screening program: Impact on the patients' management

Author

Yann Touchefeu, Emmanuel Coron, Lucille Quénéhervé, Emilie Duchalais, Jean-François Mosnier, Nicolas Chapelle, Marine Verdier, Brigitte Dessomme, Marc Le Rhun, Tamara Matysiak-Budnik, and Orianne Planade

Subjects
Adenoma, medicine.medical_specialty, Atrophic gastritis, Gastrointestinal Diseases, Colonoscopy, Gastroenterology, Helicobacter Infections, 03 medical and health sciences, Duodenal Adenoma, 0302 clinical medicine, Internal medicine, medicine, Humans, Esophagus, Early Detection of Cancer, Retrospective Studies, Hepatology, medicine.diagnostic_test, Helicobacter pylori, business.industry, Intestinal metaplasia, medicine.disease, medicine.anatomical_structure, Dysplasia, 030220 oncology & carcinogenesis, Concomitant, Occult Blood, 030211 gastroenterology & hepatology, business, Colorectal Neoplasms
Abstract

Background and aims The French colorectal cancer screening program is based on a fecal immunochemical test, followed by colonoscopy in case of positivity. The benefit of adding a concomitant upper endoscopy to detect upper digestive lesions (precancerous or others) is still debated. Our aim was to evaluate the frequency of upper digestive lesions detected by upper endoscopy performed concomitantly with colonoscopy following a positive fecal immunochemical test, and their impact on the patients’ management (i.e., surveillance, medical treatment, endoscopic or surgical procedure). Methods Data of all the patients who consulted for a positive test between May 2016 and May 2019 in our center, and for whom concomitant upper endoscopy and colonoscopy were performed, were analyzed retrospectively. Patients with significant history of upper gastrointestinal diseases or with current gastrointestinal symptoms were excluded. Results One hundred patients were included [median age (min–max): 62 (50–75), men 64%]. Macroscopic and/or microscopic upper digestive lesions were found in 58 of them (58%): Helicobacter pylori infection in 17 patients, gastric precancerous lesions in 9 patients (chronic atrophic gastritis with intestinal metaplasia, n = 8, low grade dysplasia, n = 1), Barrett's esophagus requiring surveillance in 4 patients, and 1 duodenal adenoma with low-grade dysplasia. In 44 patients (44%), the upper endoscopy findings had an impact on patients’ management, with no significant difference between the groups with positive (CRC or advanced adenoma)- or negative (any other lesions or normal) colonoscopy. Conclusion A systematic upper endoscopy combined with colonoscopy for positive fecal immunochemical test could represent an efficient strategy for upper digestive lesions screening in France. Further studies are necessary to confirm these results and to evaluate cost-effectiveness of this approach.

Published
2020

32. 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

34. Gastric Cancer: Where Are We Heading?

Author

Pawel Petryszyn, Nicolas Chapelle, and Tamara Matysiak-Budnik

Subjects
medicine.medical_specialty, medicine.disease_cause, Bioinformatics, Helicobacter Infections, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, Epidemiology, medicine, Prevalence, Humans, Early Detection of Cancer, biology, business.industry, Incidence (epidemiology), Mortality rate, Incidence, Gastroenterology, Cancer, General Medicine, Helicobacter pylori, medicine.disease, biology.organism_classification, Epstein–Barr virus, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business, Carcinogenesis
Abstract

Background: Despite its decreasing incidence, gastric cancer (GC) remains one of the leading cancers in the world and an important global healthcare problem due to its overall high prevalence and high mortality rate. Summary: GC is a consequence of Helicobacter pylori infection in 90% of cases, while in 10% Epstein Barr Virus may be responsible. Moreover, some recent epidemiological data suggest an increasing incidence in some young patients groups possibly due to autoimmunity, and if this tendency is confirmed, it may change the epidemiology of GC in the future. The pathogenesis of GC is mainly related to H. pylori infection, but recent data indicate the possible role of other bacteria and their metabolites, like N-nitrosocompounds or acetaldehyde, interfering during the last steps of carcinogenesis. The new molecular classifications of GCs show a great heterogeneity of this neoplasia, which may in the future help to define personalized treatment strategies for the patients. Early detection and proper surveillance of high risk patients should be our major objectives. Key Messages: GC is still an important healthcare problem, with its several aspects which remain the major challenges for the future.

Published
2019

35. Hepatic arterial infusion in the management of colorectal cancer liver metastasis: Current and future perspectives

Author

Nicolas Chapelle, Tamara Matysiak-Budnik, Philippe Rougier, Sylvie Metairie, Frédéric Douane, and Yann Touchefeu

Subjects
medicine.medical_specialty, animal structures, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, Metastasis, 03 medical and health sciences, Hepatic Artery, 0302 clinical medicine, Hepatic arterial infusion, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Infusions, Intra-Arterial, Intensive care medicine, Hepatology, business.industry, Systemic chemotherapy, Liver Neoplasms, Gastroenterology, virus diseases, medicine.disease, Patient management, Oxaliplatin, 030220 oncology & carcinogenesis, Colorectal Neoplasms, business, Catheter placement, Adjuvant, medicine.drug
Abstract

The technique of hepatic arterial infusion (HAI) for the treatment of liver metastases from colorectal cancer has been developed over more than 30 years. Although the indications and protocols for this technique have evolved with time, HAI is not routinely performed in clinical practice. Studies have been heterogeneous, with different regimens of intra-arterial drugs, associated or not with systemic chemotherapy, and with unconvincing outcomes. Technical difficulties for catheter placement have limited the implementation of this method in routine practice. The aim of this review is to present recent studies, highlighting technical improvements and promising combinations of oxaliplatin-based HAI with systemic treatments. HAI is being investigated in both the metastatic setting - in the first line and beyond - and in the adjuvant setting, and we will discuss its potential place in current and future patient management.

Published
2018

36. Survival and prognostic factors analysis of 151 intestinal and pancreatic neuroendocrine tumors: a single center experience

Author

Tamara Matysiak-Budnik, Hélène Senellart, Paul Girot, Marie-Françoise Heymann, Aurélien Venara, Clotilde Dumars, Yann Touchefeu, Fanny Foubert, Nicolas Regenet, and Maëva Salimon

Subjects
medicine.medical_specialty, Mitotic index, business.industry, Proportional hazards model, Gastroenterology, Neuroendocrine tumors, University hospital, medicine.disease, Single Center, Primary tumor, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, Original Article, 030211 gastroenterology & hepatology, business, Multiple endocrine neoplasia, Pathological
Abstract

BACKGROUND: Intestinal and pancreatic neuroendocrine tumors (IP-NETs) are rare tumors with heterogeneous outcomes. The aim of our study was to determine the clinical, therapeutic and pathological factors which impact the overall survival (OS) in IP-NETs. METHODS: All the patients diagnosed with IP-NETs at the Nantes University Hospital between October 1994 and October 2013 were retrospectively analysed. Patients with MEN-1 (Type 1 Multiple Endocrine Neoplasia) or Von Hippel-Lindau syndrome were excluded. Additionally, a prospective analysis of tumor grade (mitotic index and Ki67 index) was performed on tumor samples. OS was evaluated by Kaplan-Meier method and prognostic factors by log-rank test and Cox model. RESULTS: The study included 151 patients. Median age was 60 (range, 14–81). Primary tumor was pancreatic in 86 patients (56.95%) and intestinal in 65 patients (43.05%). Tumors were metastatic (synchronous or metachronous) in 72 patients (47.7%). The median OS was 157 months. For all IP-NETs, age >65 years (P5% (P=0.03), synchronous metastases (P=0.016), primary tumor size >25 mm (P=0.03) and emergency surgery (P=0.007) were independent poor prognostic factors. CONCLUSIONS: In this large series of patients with IP-NET, age >65 years, Ki67 >5%, primary tumor size >25 mm, synchronous metastases and emergency surgery for acute complications have been identified as independent poor prognostic factors.

Published
2018

37. Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study

Author

Estelle Cauchin, Yann Touchefeu, Philippe Rougier, Sylvie Metairie, Frédéric Douane, Tamara Matysiak-Budnik, Antoine Bouvier, Christophe Perret, Hélène Senellart, Dominique Luet, Samuel Le Sourd, and Annie Lim

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Organoplatinum Compounds, Colorectal cancer, Leucovorin, Neutropenia, Gastroenterology, Disease-Free Survival, 03 medical and health sciences, Hepatic Artery, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Hepatic arterial infusion chemotherapy, medicine, Humans, Infusions, Intra-Arterial, In patient, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Liver Neoplasms, Hazard ratio, Retrospective cohort study, Middle Aged, medicine.disease, Confidence interval, Oxaliplatin, Survival Rate, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, France, Colorectal Neoplasms, business, medicine.drug
Abstract

Introduction Hepatic arterial infusion chemotherapy (HAIC) is a treatment used for liver metastases (LM) of colorectal cancer (CRC). Because of its technical conditions, it has been used in only a few experienced centers in France. Our aim was to evaluate its feasibility, efficacy and tolerance in 4 centers. Methods Clinical, biological, and radiological data of patients treated with HAIC for unresectable LM from CRC in 4 institutions from October 2011 to January 2016 were retrospectively analyzed. Results Sixty-one patients with unresectable LM from CRC were included. Patients had previously received systemic chemotherapy in 95% of patients and 82.8% had previous oxaliplatin treatment. Oxaliplatin was administered using an intra-arterial route combined with intravenous (I.V.) Five-fluorouracil (5-FU) with leucovorin alone in 43.3% of patients, or combined with other I.V. chemotherapies or monoclonal antibodies in 56.7% of patients. Grade 3 to 4 clinical toxicities were reported in 16% of patients, including 9.8% of neurotoxicity, and Grade 3 to 4 biological toxicities were reported in 24.6% of patients including 22.2% with neutropenia. Catheter-related complications were observed in 31.1%. Tumor response rate in first- and second-line was 26.5% and third- and fourth-line was 11%. Median overall survival (OS) in first- and second-line was 13.5 months and third- and fourth-line was 8.3 months (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.39-1.12; P = .1729). Median progression-free survival (PFS) in first- and second-line was 9 months and third- and fourth-line were 6 months (HR, 0.53; 95% CI, 0.18-0.659; P = .0037). A secondary R0 resection was possible in 10 cases (16.4%) allowing a 2-year survival of 80%. Conclusion These data confirm that in centers that recently developed HAIC using oxaliplatin, this treatment is feasible and has acceptable tolerance. The results, in terms of hepatic PFS, PFS, OS, and the rate of secondary resections of LM, are in the range of published data, and they confirm the interest of HAIC in patients in progression after multiple I.V. treatments.

Published
2017

38. Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona

Author

Fátima Carneiro, Jean-Luc Van Laethem, Thomas Seufferlein, Ulrich Güller, Thomas Gruenberger, Harpreet Wasan, Michel Ducreux, Eric Van Cutsem, Alexander Baraniskin, Tamara Matysiak-Budnik, Wolff Schmiegel, and Lucjan Wyrwicz

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Consensus, Alternative medicine, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Genetic Predisposition to Disease, Clinical significance, Gastrointestinal cancer, Precision Medicine, Gastrointestinal Neoplasms, business.industry, Opinion leadership, Prognosis, Precision medicine, medicine.disease, Molecular diagnostics, Phenotype, 030104 developmental biology, Molecular Diagnostic Techniques, 030220 oncology & carcinogenesis, Position paper, Interdisciplinary Communication, business, Medical literature
Abstract

Background and scope In the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use. Methodology Opinion leaders and experts from diverse nationalities selected on scientific merit were asked to answer to a prepared set of questions about the current status of molecular diagnostics in different GI cancers. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. Results Preselected molecular genetic biomarkers that are described and disputed in the current medical literature in different GI cancers were debated, and recommendations for clinical routine practice were made whenever possible. Furthermore, the preanalytical variations were commented and proposals for quality controls of biospecimens were made. Conclusion The current article summarises the recommendations of the expert committee regarding prognostic and predictive molecular genetic biomarkers in different entities of GI cancers. The briefly and comprehensively formulated guidelines should assist clinicians in the process of decision making in daily clinical practice.

Published
2017

39. Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study

Author

Jaafar Bennouna, Aziz Zaanan, Caroline Prieux-Klotz, Manuela Tiako Meyo, Thierry Lecomte, Vincent Hautefeuille, Jérôme Gournay, David Tougeron, Maëva Salimon, Tamara Matysiak-Budnik, Yann Touchefeu, and Morgane Caulet

Subjects
Oncology, Male, Cancer Research, endocrine system diseases, medicine.medical_treatment, chemotherapy, Deoxycytidine, Cholangiocarcinoma, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, Aged, 80 and over, Liver Neoplasms, Middle Aged, humanities, Progression-Free Survival, Bevacizumab, Oxaliplatin, Survival Rate, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Disease Progression, 030211 gastroenterology & hepatology, Female, France, medicine.drug, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, MEDLINE, 03 medical and health sciences, hepatocholangiocarcinoma, Internal medicine, Carcinoma, Humans, Progression-free survival, Hepatitis B Antibodies, Survival rate, Aged, Retrospective Studies, Chemotherapy, business.industry, prognostic factors, Retrospective cohort study, Bilirubin, Hepatitis C Antibodies, medicine.disease, Neoplasms, Complex and Mixed, Gemcitabine, body regions, Clinical Study, Cisplatin, business
Abstract

Background: Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which no data on chemosensitivity exist. The aims of this multicentre study were to evaluate overall survival (OS), progression-free survival (PFS), and prognostic factors in cHCC-ICC treated by gemcitabine plus platinum as first-line. Methods: Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy between 2008 and 2017 were retrospectively analysed. Diagnosis was based on histology or, in case of ICC or HCC histology, on discordant computerised tomography scan enhancement patterns associated with discordant serum tumour marker elevation suggesting the alternative tumour. OS and PFS were evaluated by Kaplan–Meier method and prognostic factors by Log-rank test and Cox model. Results: Among 30 patients included, cHCC-ICC was histologically proven in 22 (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS were 9.0 and 16.2 months, respectively. Serum bilirubin ⩾30 μmol l−1 (P=0.001) and positive serology for HBV and/or HCV (P=0.014) were independent poor prognostic factors for OS. Conclusions: Gemcitabine plus platinum-based chemotherapy is effective as first-line for advanced cHCC-ICC.

Published
2017

40. The multidisciplinary management of gastro-oesophageal junction tumours

Author

Andrés Cervantes, Th. Seufferlein, D.H. Ilson, W. Schmiegel, Michel Ducreux, J.-L. Van Laethem, Florian Lordick, Ph. Rougier, Karin Haustermans, Fátima Carneiro, Tamara Matysiak-Budnik, Annemieke Cats, H. Messman, E. Van Cutsem, Côme Lepage, and William H. Allum

Subjects
medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, Multimodal therapy, Gastro oesophageal junction, Plenary session, medicine.disease, Surgery, Clinical expertise, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, 030220 oncology & carcinogenesis, medicine, Position paper, 030211 gastroenterology & hepatology, Medical physics, Gastrointestinal cancer, business, Endoscopic treatment
Abstract

Background and scope The management of GOJ cancers remains controversial and may vary between countries. Evidence-based attitudes and guidelines are not easy to elaborate since most of the trials and studies reported mixed cases of oesophageal (both adenocarcinoma and squamous cell tumours), GOJ and gastric cancers. The aim of this expert discussion and position paper is to elaborate practical recommendations that integrate evidence-reported literature and experience-based attitude covering all clinical aspects of GOJ cancer across different specialities and countries in Europe. Methodology Opinion leaders, selected on scientific merit were asked to answer to a prepared set of questions covering the approach of GOJ tumours from definition to therapeutic strategies. All answers were then discussed during a plenary session and reported here in providing a well-balanced reflection of both clinical expertise and updated evidence-based medicine. Results Definition, classification, diagnosis and staging of GOJ tumours were updated and debated. Therapeutic aspects including endoscopic therapy, surgical management, both multimodal curative and palliative management were also reviewed for proposing practical and consensual positions and recommendations whenever possible. Conclusion GOJ tumours deserve specific attention,not only for uniformising clinical management across countries but also for performing specific clinical and translational research,mainly in the curative perioperative setting.

Published
2016

41. Nivolumab‐induced celiac‐like enteropathy in patient with metastatic renal cell carcinoma: Case report and review of the literature

Author

Yann Touchefeu, Tamara Matysiak-Budnik, Isabelle Archambeaud, Claude Masliah, Thierry Chatellier, Céline Bossard, Sarah Habes, Lucie Duval, Pascale Guerzider, Institut des maladies de l'appareil digestif [Nantes] (IMAD), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, Clinique Mutualiste de l'Estuaire Cité Sanitaire [Saint Nazaire], Centre hospitalier de Saint-Nazaire, The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and NantesU M, Dépôt

Subjects
PD‐1 inhibitors, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, Case Report, Disease, Case Reports, 030204 cardiovascular system & hematology, Gastroenterology, nivolumab, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Internal medicine, medicine, celiac‐like enteropathy, Enteropathy, In patient, lcsh:R5-920, business.industry, lcsh:R, nutritional and metabolic diseases, General Medicine, Immunotherapy, medicine.disease, digestive system diseases, [SDV] Life Sciences [q-bio], Diarrhea, 030220 oncology & carcinogenesis, immune‐related adverse effects, immunotherapy, medicine.symptom, Nivolumab, lcsh:Medicine (General), business
Abstract

International audience; Nivolumab may induce severe celiac-like enteropathy, that may appear very rapidly, after only two injections of nivolumab, and may be successfully treated with corticosteroids. This observation underlines the importance of histological analysis of duodenal biopsies and the necessity to rule out a real celiac disease in patients with nivolumab-induced diarrhea.

Published
2019

42. Gastric MALT lymphoma in a population-based study in France: clinical features, treatments and survival

Author

Alain Monnereau, Sébastien Orazio, Karine Ligier, Philippe Jamet, Emilie Marrer, Patricia Delafosse, Michel Velten, Agnès Ruskoné-Fourmestraux, Marc Maynadié, Laïla Bouzid, Anne Cowppli-Bony, Brigitte Trétarre, Tamara Matysiak-Budnik, Bénédicte Lapôtre Ledoux, Laetitia Daubisse, Antoine de Mascarel, and Anne-Sophie Woronoff

Subjects
Adult, Male, medicine.medical_specialty, Population, Helicobacter Infections, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Young adult, Stage (cooking), education, Survival analysis, Aged, Aged, 80 and over, education.field_of_study, Hepatology, biology, Helicobacter pylori, business.industry, Remission Induction, Gastroenterology, Lymphoma, B-Cell, Marginal Zone, Middle Aged, biology.organism_classification, medicine.disease, Survival Analysis, Lymphoma, Gastric Mucosa, 030211 gastroenterology & hepatology, Female, France, business, Diffuse large B-cell lymphoma, Rare disease
Abstract

Background Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and most available data on gastric MALT lymphoma (GML) come from clinical studies of selected patients treated in centres of excellence. Aims To analyse the clinical features, management and survival of GML patients in a population-based study in France METHODS: All new cases of GML diagnosed between 2002 and 2010 in 11 French areas covered by cancer registries were included. Pathology reports were verified and, if necessary, reviewed by an expert pathologist. All clinical data were retrospectively collected from medical files and analysed using stata V. 14 software. Results Four hundred and sixteen patients with confirmed GML (50% male, median age 67 years) were identified. Among them, 44 showed an early transformation into diffuse large B cell lymphoma and were considered to have had an initially missed high-grade lymphoma. At diagnosis, 76% of patients were at stage IE/II, and 24% at stage III/IV of the disease. Helicobacter pylori infection was found in 57% of the patients. Eradication treatment was administered to 76% of patients and complete remission (CR) was obtained in 39%. One hundred and ninety patients received at least one other treatment, including 10 already in CR after eradication. Altogether, CR was obtained in 70% of patients and the 5-year overall survival was 79% (95% CI [75-83]). Conclusions In comparison to clinical series, in the general population, GMLs are more frequently diagnosed at an advanced stage, their clinical management is heterogeneous, and there is a risk of misdiagnosis and overtreatment. These results highlight the necessity of following currently available guidelines in this field.

Published
2019

43. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019

Author

Gianluca Esposito, Ilze Kikuste, Miguel Areia, Rita Barros, Marcis Leja, Diogo Libânio, Bruno Annibale, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Mónica Garrido, Francis Mégraud, Tamara Matysiak-Budnik, Fátima Carneiro, Ernst J. Kuipers, Jeanin E. van Hooft, Jean-François Fléjou, Jean-Marc Dumonceau, Ricardo Marcos-Pinto, Gastroenterology and Hepatology, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and Quality of Life, and Gastroenterology & Hepatology

Subjects
Gastritis, Atrophic, medicine.medical_specialty, Atrophic gastritis, Biopsy, Chronic gastritis, gastroenterology, Gastroenterology, Risk Assessment, Endoscopy, Gastrointestinal, Chromoendoscopy, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, Stomach Neoplasms, precancerous conditions, stomach, gastric cancer, Internal medicine, medicine, Humans, Metaplasia, medicine.diagnostic_test, business.industry, Stomach, Intestinal metaplasia, medicine.disease, Endoscopy, Patient Care Management, Europe, medicine.anatomical_structure, Dysplasia, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Gastritis, medicine.symptom, business
Abstract

Main RecommendationsPatients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent Helicobacter pylori gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. H. pylori eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. H. pylori eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective.

Published
2019

44. Can PPH3 be helpful to assess the discordant grade in primary and metastatic enteropancreatic neuroendocrine tumors?

Author

Tamara Matysiak-Budnik, Yann Touchefeu, Clotilde Dumars, Fanny Foubert, Marie-Françoise Heymann, Hélène Senellart, Nicolas Regenet, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Service d'Anatomopathologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), CRNH IMAD, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Chirurgie Digestive et Endocrinienne [Nantes], Centre René Gauducheau, CRLCC René Gauducheau, 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), Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], Bernardo, Elizabeth, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Adult, 0301 basic medicine, Pathology, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Intestinal Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, Phospho-histone H3, Metastases, Neuroendocrine tumors, Gastroenterology, Histones, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Intestinal Neoplasms, Biomarkers, Tumor, Humans, Medicine, Phosphorylation, Mitotic count, Young adult, Grading (tumors), Aged, Neoplasm Grading, biology, business.industry, Enteropancreatic neuroendocrine tumor (EPNET), Middle Aged, medicine.disease, Primary tumor, 3. Good health, Pancreatic Neoplasms, Neuroendocrine Tumors, Grading, Ki-67 Antigen, 030104 developmental biology, 030220 oncology & carcinogenesis, Ki-67, biology.protein, Immunohistochemistry, business
Abstract

International audience; Therapeutic strategy in neuroendocrine tumors (NETs) is based on histological characteristics of the primary tumor (PT), even in case of metastatic disease. Our aim was to compare the tumor grade between PT and their liver metastases (LM) in patients with enteropancreatic NETs. Forty-one patients treated for sporadic NETs (10 pancreatic, 31 intestinal) were included. All presented synchronous (35) or metachronous (6) LM. Tumor grade was evaluated for PT and LM according to the WHO classification, using Ki-67 labeling and mitotic count (MC) evaluated with or without phospho-histone H3 (PPH3). Tumor grade differed between primary and metastatic tumor in 16/41 patients (39 %), with an increase of grade in 13 of them (32 %). The median Ki-67, MC, and PPH3 in metastases were statistically higher than in PT (p = 0.0002, 0.02, and 0.01). In 17 of 65 cases tested with PPH3 (26 %), this antibody was more efficient in assessing the grade compared to the usual MC, and in 2/65 casescompared to the Ki-67. A better correlation was observed between Ki-67 and PPH3 (p = 0.0001) than between Ki-67and MC without immunohistochemistry. There is a significant difference in tumor grade between primary and metastatic NETs, underlining the necessity of a systematic biopsy on LM for patient management. Moreover, PPH3 appears to be a powerful antibody to assess the MC and the tumor grade much more accurately when associated with Ki-67

Published
2016

45. Comparison of 4 Screening Methods for Detecting Fluoropyrimidine Toxicity Risk: Identification of the Most Effective, Cost-Efficient Method to Save Lives

Author

Tamara Matysiak Budnik, Jean-Philippe Metges, Hélène Senellart, Olivier Capitain, Roger Faroux, Marc Ferec, Mario Campone, Jonathan Dauve, Nadege Blouin, Valérie Rossi, Valérie Seegers, and Claire Stampfli

Subjects
Oncology, medicine.medical_specialty, Health, Toxicology and Mutagenesis, DPD deficiency, fluoropyrimidines, Toxicology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Screening method, medicine, Dihydropyrimidine dehydrogenase, Chemical Health and Safety, Cost efficiency, business.industry, screening, lcsh:RM1-950, Public Health, Environmental and Occupational Health, Risk identification, toxicity, risk assessment, lcsh:Therapeutics. Pharmacology, comparison, 030220 oncology & carcinogenesis, Toxicity, Original Article, Risk of death, Risk assessment, business
Abstract

Background: Fluoropyrimidines (FPs) carry around 20% risk of G3-5 toxicity and 0.2-1% risk of death, due to dihydropyrimidine dehydrogenase (DPD) deficiency. Several screening approaches exist for predicting toxicity, however there is ongoing debate over which method is best. This study compares 4 screening approaches. Method: 472 patients treated for colorectal, head-and-neck, breast, or pancreatic cancers, who had not been tested pre-treatment for FP toxicity risk, were screened using: DPYD genotyping (G); phenotyping via plasma Uracil (U); phenotyping via plasma-dihydrouracil/uracil ratio (UH2/U); and a Multi-Parametric Method (MPM) using genotype, phenotype, and epigenetic data. Performance was compared, particularly the inability to detect at-risk patients (false negatives). Results: False negative rates for detecting G5 toxicity risk were 51.2%, 19.5%, 9.8% and 2.4%, for G, U, UH2/U and MPM, respectively. False negative rates for detecting G4-5 toxicity risk were 59.8%, 36.1%, 21.3% and 4.7%, respectively. MPM demonstrated significantly (p < 0.001) better prediction performance. Conclusion: MPM is the most effective method for limiting G4-5 toxicity. Its systematic implementation is cost-effective and significantly improves the risk-benefit ratio of FP-treatment. The use of MPM, rather than G or U testing, would avoid nearly 8,000 FP-related deaths per year globally (500 in France), and spare hundreds of thousands from G4 toxicity.

Published
2020

46. Screening and surveillance in hereditary gastrointestinal cancers: Recommendations from the European Society of Digestive Oncology (ESDO) expert discussion at the 20th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona, June 2018

Author

Fátima Carneiro, Michel Ducreux, Antoni Castells, Ulrich Güller, Eric Van Cutsem, Estelle Cauchin, Wolff Schmiegel, Judith Balmaña, Jean-Luc Van Laethem, Deepak Vangala, Tamara Matysiak-Budnik, Lucian Wyrwicz, and Pascal Hammel

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Population, DNA Mutational Analysis, Genetic Counseling, Chemoprevention, Risk Assessment, Clinical expertise, 03 medical and health sciences, 0302 clinical medicine, Neoplastic Syndromes, Hereditary, Internal medicine, Familial Pancreatic Cancer, medicine, Humans, Gastrointestinal cancer, Genetic Testing, Age of Onset, education, Early Detection of Cancer, Germ-Line Mutation, Gastrointestinal Neoplasms, education.field_of_study, business.industry, Colonoscopy, Oncogenes, Sequence Analysis, DNA, Clinical routine, medicine.disease, Lynch syndrome, Pancreatic Neoplasms, Molecular Diagnostic Techniques, Organ Specificity, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Hereditary diffuse gastric cancer, business, Gi cancer
Abstract

Patients with hereditary gastrointestinal (GI) cancers represent a substantial fraction of the overall affected population. Although awareness for hereditary GI cancer syndromes is on the rise, identification of patients and measures of surveillance are often unclear in everyday clinical routine. Therefore, the European Society of Digestive Oncology expert discussion 2018 at the World Congress on Gastrointestinal Cancer focussed on screening and surveillance of hereditary colorectal, gastric and pancreatic cancers. An international panel of experts and opinion leaders developed the here presented recommendations based on published evidence and on profound clinical expertise to facilitate clinical routine in identification and caretaking of patients with familial GI cancers.

Published
2018

48. Confocal laser endomicroscopy: A new gold standard for the assessment of mucosal healing in ulcerative colitis

Author

Vincent Macé, Andrzej S. Tarnawski, Arnaud Boureille, Amrita Ahluwalia, Jean-François Mosnier, Emmanuel Coron, Tamara Matysiak-Budnik, Marc Le Rhun, and Céline Bossard

Subjects
medicine.medical_specialty, Pathology, Hepatology, medicine.diagnostic_test, business.industry, Angiogenesis, Crypt, Gastroenterology, Colonoscopy, Inflammation, Vascular permeability, medicine.disease, Ulcerative colitis, Endoscopy, In vivo, Internal medicine, medicine, medicine.symptom, business
Abstract

Background and Aim Endoscopic assessment of mucosal healing in ulcerative colitis (UC) is increasingly accepted as a measure of disease activity, therapeutic goal, and the key prognostic indicator. While regular endoscopy evaluates appearance of the mucosal surface, confocal laser endomicroscopy (CLE) enables in vivo visualization of subepithelial mucosa at 1000× magnification during ongoing endoscopy. Our aims were to determine using CLE whether endoscopically normal appearing colonic mucosa in patients with UC in remission (UC-IR) has fully regenerated mucosal structures, resolved inflammation, and to identify the mechanisms. Methods Twelve patients (six controls and six with UC-IR) underwent colonoscopy using CLE and intravenous fluorescein infusion. During colonoscopy, CLE images of colonic mucosa and conventional mucosal biopsies were obtained and evaluated using image-analysis systems. We quantified; (i) regeneration of colonic crypts and blood microvessels; (ii) cyclooxygenase 2 (COX2) expression; (iii) mitochondrial DNA (mtDNA) mutations; (iv) inflammatory infiltration; and (v) vascular permeability (VP). Results In control subjects, CLE demonstrated normal colonic crypts and microvasculature. COX2 expression was minimal, and

Published
2015

49. Hamartomatous Tumors in the Gastrointestinal Tract

Author

Tamara Matysiak-Budnik, Yann Touchefeu, and Estelle Cauchin

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Juvenile Polyp, medicine.medical_treatment, Pharmaceutical Science, Physical examination, Peutz–Jeghers syndrome, Cowden syndrome, Mini-Review, medicine.disease, Dermatology, Gastroenterology, digestive system diseases, Polypectomy, Hamartomatous Polyp, Hamartomatous polyposis, Internal medicine, medicine, Genetic predisposition, business
Abstract

Background: Digestive hamartomatous polyps are a rare entity. They may be sporadic (solitary Peutz-Jeghers polyp or solitary juvenile polyp) or reveal genetic predisposition like Peutz-Jeghers syndrome, juvenile polyposis or Cowden disease. Summary: Diagnosis is based on personal and family history and on clinical data including physical signs (in particular dermatological), endoscopic findings (the number of polyps) and histological features of the polyps. The risk of complications and of digestive and extra-digestive cancers may be high, especially in case of genetic predisposition syndromes, and requires multidisciplinary management of the patients (oncogenetic counseling, gastroenterologist, pathologist, dermatologist, gynecologist and endocrinologist). Endoscopic evaluation is very helpful to establish the current situation, to perform polypectomy and to allow for good histological examination of the polyps, whose degeneration has been exceptionally described. The recent development of new molecular techniques (next-generation DNA sequencing) allows for rapid multiple gene sequencing and facilitates diagnosis. Key Message: Discovery of a hamartomatous polyp requires a rigorous work-up which should be performed by a multidisciplinary team, including a genetic oncologist, experienced in this pathology. Practical Implications: The diagnostic procedure in hamartomatous polyps should be based on the number of polyps identified during endoscopy (solitary versus multiple) and on their histological characteristics. The clinical examination must search for mucosal and skin lesions. If a polyposis syndrome is identified, oncogenetic consultation is necessary in order to define screening modalities for family members, aiming at preventing cancer development. Endoscopic resection (polypectomy) of the lesions may prevent complications like bleeding and degeneration and also diminish the risk of surgery and subsequent short bowel syndrome.

Published
2015

50. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author

Jean-François Emile, Catherine Julié, Karine Le Malicot, Come Lepage, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Stéphanie Dimet, Camille Boulagnon-Rombi, Marc-Antoine Allard, Frédérique Penault-Llorca, Jaafar Bennouna, Pierre Laurent-Puig, Julien Taieb, Josef Thaler, Richard Greil, Johannes Gaenzer, Wolfgang Eisterer, Joerg Tschmelitsch, Felix Keil, Hellmut Samonigg, August Zabernigg, Franz Schmid, Günther Steger, Robert Steinacher, Johannes Andel, Björn Jagdt, Alois Lang, Michael Fridrik, Reinhold Függer, Friedrich Hofbauer, Ewald Woell, Dietmar Geissler, Alfred Lenauer, Manfred Prager, Geert D'Haens, Gauthier Demolin, Joseph Kerger, Guido Deboever, Gilbert Ghillebert, Marc Polus, Eric Van Cutsem, Hassan Rezaie Kalantari, Thierry Delaunoit, Jean Charles Goeminne, Marc Peeters, Philippe Vergauwe, Ghislain Houbiers, Yves Humblet, Jos Janssens, Dirk Schrijvers, Erik Vanderstraeten, Jan Vermorken, Daniel Van Daele, Michel Ferrante, Frederic Forget, Alain Hendlisz, Mette Yilmaz, Svend Erik Nielsen, Lene Vestermark, Jim Larsen, Mohamed-Ayman Zawadi, Olivier Bouche, Laurent Mineur, Jaafar Bennouna-Louridi, Louis Marie Dourthe, Marc Ychou, Eveline Boucher, Denis Pezet, Francoise Desseigne, Michel Ducreux, Patrick Texereau, Laurent Miglianico, Philippe Rougier, Serge Fratte, Charles-Briac Levache, Yacine Merrouche, Stephen Ellis, Christophe Locher, Jean-Francois Ramee, Claire Garnier, Frederic Viret, Bruno Chauffert, Isabelle Cojean-Zelek, Pierre Michel, Cedric Lecaille, Christian Borel, Jean-Francois Seitz, Denis Smith, Catherine Lombard-Bohas, Thierry Andre, Jean-Marc Gornet, Francine Fein, Marie-Aude Coulon-Sfairi, Marie-Christine Kaminsky, Jean-Paul Lagasse, Dominique Luet, Pierre-Luc Etienne, Mohamed Gasmi, Andre Vanoli, Suzanne Nguyen, Thomas Aparicio, Hervé Perrier, Noel Stremsdoerfer, Philippe Laplaige, Dominique Arsene, Dominique Auby, Laurent Bedenne, Romain Coriat, Bernard Denis, Patrick Geoffroy, Gilles Piot, Yves Becouarn, Gilbert Bordes, Gael Deplanque, Olivier Dupuis, Frederic Fruge, Rosine Guimbaud, Thierry Lecomte, Gérard Lledo, Iradej Sobhani, Amani Asnacios, Ahmed Azzedine, Christophe Desauw, Marie-Pierre Galais, Dany Gargot, You-Heng Lam, Abakar Abakar-Mahamat, Jean-Francois Berdah, Sylviane Catteau, Marie-Christine Clavero-Fabri, Jean-Francois Codoul, Jean-Louis Legoux, Denis Goldfain, Pierre Guichard, Denis Pere Verge, Jocelyne Provencal, Bruno Vedrenne, Catherine Brezault-Bonnet, Denis Cleau, Jean-Paul Desir, David Fallik, Bruno Garcia, Marie-Hélène Gaspard, Dominique Genet, Johannes Hartwig, Yves Krummel, Tamara Matysiak Budnik, Vanessa Palascak-Juif, Harizo Randrianarivelo, Yves Rinaldi, Albert Aleba, Ariane Darut-Jouve, Aimery de Gramont, Herve Hamon, Frederic Wendehenne, Axel Matzdorff, Michael Konrad Stahl, Wolfgang Schepp, Martin Burk, Lothar Mueller, Michael Geissler, Luisa Mantovani-Loeffler, Thomas Hoehler, Walter Asperger, Hendrik Kroening, Ludwig Fischer von Weikersthal, Stefan Fuxius, Matthias Groschek, Johannes Meiler, Tanja Trarbach, Jacqueline Rauh, Nicolas Ziegenhagen, Albrecht Kretzschmar, Ullrich Graeven, Arnd Nusch, Goetz von Wichert, Ralf-Dieter Hofheinz, Gerhard Kleber, Karl-Heinz Schmidt, Ursula Vehling-Kaiser, Claudia Baum, Jochen Schuette, Georg Martin Haag, Wilhelm Holtkamp, Jochen Potenberg, Tobias Reiber, Georg Schliesser, Hans-Joachim Schmoll, Wolfgang Schneider-Kappus, Wolfgang Abenhardt, Claudio Denzlinger, Jan Henning, Bartscht Marxsen, Hans Guenter Derigs, Helmut Lambertz, Ingulf Becker-Boost, Karel Caca, Christian Constantin, Thomas Decker, Henning Eschenburg, Sigrun Gabius, Holger Hebart, Albrecht Hoffmeister, Heinz-August Horst, Stephan Kremers, Malte Leithaeuser, Sebastian Mueller, Siegfried Wagner, Severin Daum, Frank Schlegel, Martina Stauch, Volker Heinemann, Evaristo Maiello, Luciano Latini, Alberto Zaniboni, Dino Amadori, Giuseppe Aprile, Sandro Barni, Rodolfo Mattioli, Andrea Martoni, Rodolfo Passalacqua, Mario Nicolini, Enzo Pasquini, Carla Rabbi, Enrico Aitini, Alberto Ravaioli, Carlo Barone, Guido Biasco, Stefano Tamberi, Angelo Gambi, Claudio Verusio, Marina Marzola, Giorgio Lelli, Corrado Boni, Stefano Cascinu, Paolo Bidoli, Massimo Vaghi, Giorgio Cruciani, Francesco Di Costanzo, Alberto Sobrero, Roberto Petrioli, Massimo Aglietta, Oscar Alabiso, Federico Capuzzo, Alfredo Falcone, Domenico Cristi Corsi, Roberto Labianca, Stefania Salvagni, Silvana Chiara, Libero Ciuffreda, Francesco Ferraù, Francesco Giuliani, Sara Lonardi, Nicola Gebbia, Giovanni Mantovani, Evaristo Sanches, Juan Carlos Mellidez, Pedro Santos, Joao Freire, Cristina Sarmento, Luis Costa, Antonio Moreira Pinto, Sergio Barroso, Jorge Espirito Santo, Fátima Guedes, Amélia Monteiro, Anabela Sa, Irene Furtado, Ramon Salazar, Enrique Aranda Aguilar, Fernando Rivera Herrero, Javier Sastre Valera, Manuel Valladares Ayerbes, Jaime Feliu Batlle, Silvia Gil, Albert Abad Esteve, Carlos Garcia-Giron, Guillermo Lopez Vivanco, Antonia Salud Salvia, Vicente Alonso Orduña, Ruth Vera Garcia, Javier Gallego, Bartomeu Massuti Sureda, Jordi Remon, Maria Jose Safont Aguilera, Luis Cirera Nogueras, Bernado Queralt Merino, Cristina Gravalos Castro, Purificacion Martinez de Prado, Carlos Pijaume Pericay, Manuel Constenla Figueiras, Inmaculada Guasch Jordan, Maria Jose Gome Reina, Amelia Lopez-Ladron Garcia, Antonio Arrivi Garcia-Ramos, Andres Cervantes, Carlos Fernandez Martos, Eugenio Marcuello Gaspar, Ines Cabezas Montero, Pilar Escudero Emperador, Ana Leon Carbonero, Manuel Gallen Castillo, Teresa Garcia Garcia, Jose Garcia Lopez, Encarnacion Gonzalez Flores, Monica Guillot Morales, Marta Llanos Muñoz, Ana López Martín, Joan Maurel, Juan Carlos Camara, Rosario Dueñas Garcia, Mercedes Salgado, Isabel Hernandez Busquier, Teresa Checa Ruiz, Adelaida Lacasta Muñoa, Miquel Nogue Aliguer, Amalia Velasco Ortiz de Taranco, Miguel Mendez Ureña, Ferran Losa Gaspa, Jose Juan Ponce, Carlos Bosch Roig, Pedro Valero Jimenez, Antonio Galan Brotons, Santiago Albiol Rodriguez, Jose Ales Martinez, Liliana Canosa Ruiz, Margarita Centelles Ruiz, John Bridgewater, Rob Glynne-Jones, Saad Tahir, Tamas Hickish, Jim Cassidy, Leslie Samuel, UE 1373 Fourrages Environnement Ruminants Lusignan, Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Environnement et Agronomie ( E.A. ) -Biologie et Amélioration des Plantes ( BAP ) -Fourrages Environnement Ruminants Lusignan ( FERLUS ), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Service de Biostatistique, Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hépato-gastroentérologie et cancérologie digestive (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Vall d'Hebron University Hospital [Barcelona], Dpt of Internal Medicine, Section of Immunoallergology and Respiratory [Florence] Diseases, University of Florence, Carl Gustav Carus University Hospital, Erasme Hospital, Brussels, Centre Hepato-Biliaire, AP-HP Hôpital Paul Brousse, Modèles de Cellules Souches Malignes et Thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne ( IMoST ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université de Nantes ( UN ), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Klinikum Wels Grieskirchen, Oncology department [Salzburg], Salzburger Landesklinikum - Uniklinikum Salzburg ( SALK ), Institute of Chemical Reaction Engineering, Hamburg University of Technology, Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung ( AWI ), Department of Medical Oncology, Medical University Vienna, Department of Internal Medicine, Hospital of Steyr, Department Internal Medicine 3, Centre for Hematology and Medical Oncology, General Hospital Linz, Department Medicine LKH, Institut für Festköperfirschung, Institut des Sciences Moléculaires de Marseille ( ISM2 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Marseille ( ECM ) -Aix Marseille Université ( AMU ), University Hospitals Leuven [Leuven], Katholieke Universiteit Leuven ( KU Leuven ), Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Institut de Biologie Computationnelle ( IBC ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Sciences Moléculaires ( ISM ), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique ( CNRS ), Faculty of Veterinary Medicine, Ghent University [Belgium] ( UGENT ), Medical Oncology, Antwerp University Hospital [Edegem], Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier de L'Ardenne (Libramont), Department of Cardiology [Sivas, Turkey], Cumhuriyet University [Sivas, Turkey], Department of Earth Sciences, Durham University, Department of Oncology, Rigshospitalet [Copenhagen], Odense Hospital, CP Kelco ApS, Centre Hospitalier Universitaire de Reims ( CHU Reims ), 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 ), Université du Québec à Montréal ( UQAM ), Université Panthéon-Sorbonne ( UP1 ), École nationale supérieure d'architecture de Nantes ( ENSA Nantes ), Department of Hepatogastroenterology and Oncology, Hopital Ambroise Pare, 9, Avenue Charles de Gaulle, 92104, Boulogne Cedex, France., Hôpital Ambroise Paré, CH Belfort-Montbéliard, Polyclinique Francheville, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Centre Hospitalier de Meaux, Service d'hématologie, Clinique Catherine de Sienne, Unité de recherche sur les Biopolymères, Interactions Assemblages ( BIA ), Institut National de la Recherche Agronomique ( INRA ), Université de la Méditerranée - Aix-Marseille 2, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), CHU Amiens-Picardie, Pôle oncologie médicale, Hôpital des Diaconesses, Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Bretagne Occidentale - École de sages-femmes ( UBO UFR MSS ESF ), Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Service Gastro-Entérologie, CHU Besançon, Université de Franche-Comté ( UFC ) -Université de Franche-Comté ( UFC ), Centre Alexis Vautrin ( CAV ), Ecophysiologie Végétale, Agronomie et Nutritions ( EVA ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Recherche Agronomique ( INRA ), Image et ville ( IV ), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Département informatique ( INFO ), Université européenne de Bretagne ( UEB ) -Télécom Bretagne-Institut Mines-Télécom [Paris], Service de Gastro-entérologie [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Agence de l'Environnement et de la Maîtrise de l'Energie - ADEME, Service d'hépato-gastroentérologie, CHU Caen-Hôpital côte de nacre, Département de Médecine, Centre hospitalier de Libourne, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Fondation FondaMental, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Variabilité de réponse aux psychotropes ( VariaPsy - U1144 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ), Département d'oncologie digestive, Institut Bergonié - CRLCC Bordeaux, Hôpital St Joseph, Service de Gynécologie et d'Obstétrique ( CHU Lyon ), Hospices Civils de Lyon ( HCL ), Gastro - Entérologie et Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, Immunothérapie, Chimie et Cancer ( GICC ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Université Montpellier 1 ( UM1 ), Service de gastro-entérologie - Hôpital Henri Mondor, Laboratoire Matière et Systèmes Complexes ( Laboratoire MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -UFR de Physique, France, Amériques, Espagne – Sociétés, pouvoirs, acteurs ( FRAMESPA ), Université Toulouse - Jean Jaurès ( UT2J ) -Centre National de la Recherche Scientifique ( CNRS ), Regional Hospital of Orleans, Histoire, Archéologie et littératures des Mondes chrétiens et musulmans médiévaux ( CIHAM ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -École des hautes études en sciences sociales ( EHESS ) -Université Jean Moulin - Lyon III ( UJML ) -Université d'Avignon et des Pays de Vaucluse ( UAPV ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Dept Med Genet, Hôpital Erasme (Bruxelles), Polyclinique de Limoges - site François Chénieux [Limoges], Clinique Médicale B, CHU Strasbourg, Service de gastro-entérologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Hôpital Européen [Fondation Ambroise Paré - Marseille], Asklepios Klinikum Uckermark GmbH, DESY, Notkestr 85, D-22607 Hamburg, Germany, NASA Ames Research Center ( ARC ), Department of Chemistry, Center for Structural Biology, Vanderbilt University [Nashville], Biostatistique et Processus Spatiaux ( BIOSP ), Institute of Ecology [Jena], Friedrich-Schiller-Universität Jena, University of Rostock [Germany], Universität Stuttgart [Stuttgart], Oneonta, Zentrum für Innere Medizin, Klinikum Schwäbisch Gmünd/Stauferklinik, Physiopathologie du stress pancréatique, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Mathématiques de Marseille ( I2M ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Department of Computer Science [Freiburg], University of Freiburg [Freiburg], Institut für Mathematik [Berlin], Technische Universität Berlin ( TUB ), Department of Information Engineering, Computer Science and Mathematics, Università degli Studi dell'Aquila [L'Aquila] ( UNIVAQ.IT ), Department of Animal Sciences, North Carolina Agricultural and Technical State University, FEEM, Romagna Cancer Registry, IRST, Luigi Pierantoni Hospital, Observatoire sociologique du changement ( OSC ), Sciences Po-Centre National de la Recherche Scientifique ( CNRS ), Dipartimento di Chimica, Fisica e Ambiente, Università degli Studi di Udine - University of Udine [Italie], Department of Nuclear Medicine, PET/CT Centre, Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche [Ancona] ( UNIVPM ), Universidade Nova de Lisboa ( UNINOVA ), Ottawa Hospital Research Institute [Ottawa] ( OHRI ), Oncologia Medica, Ospedali Riuniti, Ospedale 'San Vincenzo', NIPE, CIPES, European Synchrotron Radiation Facility ( ESRF ), Departamento de Engenharia Informática, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto]-Universidade do Porto [Porto], 3Decide, Unité de recherche Amélioration, Génétique et Physiologie Forestières ( UAGPF ), Universidade Federal de Campina Grande [Campina Grande] ( UFCG ), Instituto de Engenharia de Sistemas e Computadores ( INESC ), Departamento de Ciências Biológicas, Universidade Regional do Cariri ( URCA Brasil ), Department of Biochemistry and Molecular Biology [Barcelona, Spain], Universitat de Barcelona ( UB ), Associated Unit to Consejo Superior de Investigaciones Científicas - CSIC [Barcelona, Spain], University of Barcelona-Institute of Biomedicine - IBUB [Barcelona, Spain], IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau ( CARE ), Institut de recherches sur la catalyse et l'environnement de Lyon ( IRCELYON ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] ( LAAS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Institut National Polytechnique [Toulouse] ( INP ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Instituto de Ciencia de Materiales de Madrid [Madrid] ( ICMM ), Interactions, Corpus, Apprentissages, Représentations ( ICAR ), École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique ( CNRS ), Institut d'Investigacions Biomèdiques August Pi i Sunyer ( IDIBAPS ), North Region Cancer Registry of Portugal, UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Paediatrics and Intensive Care, Hospital Universitari Sant Joan de Deu, Laboratoire de Psychologie Sociale ( LPS ), Aix Marseille Université ( AMU ), Universitat de València ( UV ), Instituto de Cienca de Materiales de Madrid [Madrid] ( ICMM ), Biology, New Mexico State University, New Mexico State University, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department - Carnegie Mellon University, University of Pittsburgh, Laboratoire de Sciences Actuarielle et Financière ( SAF ), Université de Lyon-Université de Lyon, Instituto de Oncologia Corachan ( IDOC ), Laboratoire d'informatique de l'école normale supérieure ( LIENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Experimental Quantum Optics and Photonics Group, University of Strathclyde, Institut de recherches Asiatiques ( IrAsia ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Européen de Réalité Virtuelle ( CERV ), École Nationale d'Ingénieurs de Brest ( ENIB ), Sol Agro et hydrosystème Spatialisation ( SAS ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de recherche cerveau et cognition ( CERCO ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Géomatériaux et Environnement ( LGE ), Université Paris-Est Marne-la-Vallée ( UPEM ), Hôpital Ambroise Paré [AP-HP], Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université de Nantes (UN), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Salzburger Landesklinikum - Uniklinikum Salzburg (SALK), Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Biologie Computationnelle (IBC), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires (ISM), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universiteit Gent = Ghent University [Belgium] (UGENT), Antwerp University Hospital [Edegem] (UZA), Hillerød Hospital, Copenhagen University Hospital-Copenhagen University Hospital, Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Université Paris 1 Panthéon-Sorbonne (UP1), École nationale supérieure d'architecture de Nantes (ENSA Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bretagne Occidentale - École de sages-femmes (UBO UFR MSS ESF), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Alexis Vautrin (CAV), Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Image et ville (IV), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Département informatique (INFO), Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Libourne, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation FondaMental [Créteil], Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service de Gynécologie et d'Obstétrique (CHU Lyon), Hospices Civils de Lyon (HCL), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital privé Toulon Hyères : Sainte Marguerite, Clinique des Quatre Pavillons, Lormont, France, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), NASA Ames Research Center (ARC), Biostatistique et Processus Spatiaux (BioSP), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University of Rostock, State University of New York at Oneonta (SUNY Oneonta), State University of New York (SUNY), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Klinikum Deggendorf, Technische Universität Berlin (TU), Università degli Studi dell'Aquila (UNIVAQ), North Carolina A&T State University, University of North Carolina System (UNC)-University of North Carolina System (UNC), Observatoire sociologique du changement (OSC), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Università Politecnica delle Marche [Ancona] (UNIVPM), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Ottawa Hospital Research Institute [Ottawa] (OHRI), European Synchrotron Radiation Facility (ESRF), Departamento de Engenharia Informática [Porto], Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto-Universidade do Porto, Universidade Federal de Campina Grande [Campina Grande] (UFCG), Instituto de Engenharia de Sistemas e Computadores (INESC), Universidade Regional do Cariri (URCA Brasil), Universitat de Barcelona (UB), IRCELYON-Catalytic and Atmospheric Reactivity for the Environment (CARE), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Interactions, Corpus, Apprentissages, Représentations (ICAR), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines (ENS LSH)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitario de Valme, Anenida de Bellavista s/n, Sevilla 41014, Spain, Hospital Son Llatzer, Universitat de València (UV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hospital Universitari Son Espases, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto de Oncologia Corachan (IDOC), Laboratoire d'informatique de l'école normale supérieure (LIENS), École normale supérieure - Paris (ENS Paris), Institut de recherches Asiatiques (IrAsia), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Sol Agro et hydrosystème Spatialisation (SAS), 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), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est Marne-la-Vallée (UPEM), Fédération Francophone de Cancérologie Digestive (FFCD), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Department of Information Engineering, Computer Science and Mathematics = Dipartimento di Ingegneria e Scienze dell'Informazione e Matematica [L'Aquila] (DISIM), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'informatique - ENS Paris (DI-ENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institute of Biomedicine - IBUB [Barcelona, Spain]-University of Barcelona, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), 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 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 National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Environnement et Agronomie (E.A.)-Biologie et Amélioration des Plantes (BAP)-Fourrages Environnement Ruminants Lusignan (FERLUS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, University of Florence (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), Université Montesquieu - Bordeaux 4-Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Ghent University [Belgium] (UGENT), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal (UQAM), Université Panthéon-Sorbonne (UP1), Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Franche-Comté (UFC)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Biostatistique et Processus Spatiaux (BIOSP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Technische Universität Berlin (TUB), Università degli Studi dell'Aquila [L'Aquila] (UNIVAQ.IT), Universidade Nova de Lisboa (NOVA), Faculdade de Engenharia [Porto] (FEUP), Unité de recherche Amélioration, Génétique et Physiologie Forestières (UAGPF), IRCELYON-Caractérisation et remédiation des polluants dans l'air et l'eau (CARE), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-INRP-Ecole Normale Supérieure Lettres et Sciences Humaines-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, J. -F., Julie, C., Le Malicot, K., Lepage, C., Tabernero, J., Mini, E., Folprecht, G., Van Laethem, J. -L., Dimet, S., Boulagnon-Rombi, C., Allard, M. -A., Penault-Llorca, F., Bennouna, J., Laurent-Puig, P., Taieb, J., Thaler, J., Greil, R., Gaenzer, J., Eisterer, W., Tschmelitsch, J., Keil, F., Samonigg, H., Zabernigg, A., Schmid, F., Steger, G., Steinacher, R., Andel, J., Jagdt, B., Lang, A., Fridrik, M., Fugger, R., Hofbauer, F., Woell, E., Geissler, D., Lenauer, A., Prager, M., D'Haens, G., Demolin, G., Kerger, J., Deboever, G., Ghillebert, G., Polus, M., Van Cutsem, E., Kalantari, H. R., Delaunoit, T., Goeminne, J. C., Peeters, M., Vergauwe, P., Houbiers, G., Humblet, Y., Janssens, J., Schrijvers, D., Vanderstraeten, E., Vermorken, J., Van Daele, D., Ferrante, M., Forget, F., Hendlisz, A., Yilmaz, M., Nielsen, S. E., Vestermark, L., Larsen, J., Zawadi, M. -A., Bouche, O., Mineur, L., Bennouna-Louridi, J., Dourthe, L. M., Ychou, M., Boucher, E., Pezet, D., Desseigne, F., Ducreux, M., Texereau, P., Miglianico, L., Rougier, P., Fratte, S., Levache, C. -B., Merrouche, Y., Ellis, S., Locher, C., Ramee, J. -F., Garnier, C., Viret, F., Chauffert, B., Cojean-Zelek, I., Michel, P., Lecaille, C., Borel, C., Seitz, J. -F., Smith, D., Lombard-Bohas, C., Andre, T., Gornet, J. -M., Fein, F., Coulon-Sfairi, M. -A., Kaminsky, M. -C., Lagasse, J. -P., Luet, D., Etienne, P. -L., Gasmi, M., Vanoli, A., Nguyen, S., Aparicio, T., Perrier, H., Stremsdoerfer, N., Laplaige, P., Arsene, D., Auby, D., Bedenne, L., Coriat, R., Denis, B., Geoffroy, P., Piot, G., Becouarn, Y., Bordes, G., Deplanque, G., Dupuis, O., Fruge, F., Guimbaud, R., Lecomte, T., Lledo, G., Sobhani, I., Asnacios, A., Azzedine, A., Desauw, C., Galais, M. -P., Gargot, D., Lam, Y. -H., Abakar-Mahamat, A., Berdah, J. -F., Catteau, S., Clavero-Fabri, M. -C., Codoul, J. -F., Legoux, J. -L., Goldfain, D., Guichard, P., Verge, D. P., Provencal, J., Vedrenne, B., Brezault-Bonnet, C., Cleau, D., Desir, J. -P., Fallik, D., Garcia, B., Gaspard, M. -H., Genet, D., Hartwig, J., Krummel, Y., Budnik, T. M., Palascak-Juif, V., Randrianarivelo, H., Rinaldi, Y., Aleba, A., Darut-Jouve, A., de Gramont, A., Hamon, H., Wendehenne, F., Matzdorff, A., Stahl, M. K., Schepp, W., Burk, M., Mueller, L., Geissler, M., Mantovani-Loeffler, L., Hoehler, T., Asperger, W., Kroening, H., von Weikersthal, L. F., Fuxius, S., Groschek, M., Meiler, J., Trarbach, T., Rauh, J., Ziegenhagen, N., Kretzschmar, A., Graeven, U., Nusch, A., von Wichert, G., Hofheinz, R. -D., Kleber, G., Schmidt, K. -H., Vehling-Kaiser, U., Baum, C., Schuette, J., Haag, G. M., Holtkamp, W., Potenberg, J., Reiber, T., Schliesser, G., Schmoll, H. -J., Schneider-Kappus, W., Abenhardt, W., Denzlinger, C., Henning, J., Marxsen, B., Derigs, H. G., Lambertz, H., Becker-Boost, I., Caca, K., Constantin, C., Decker, T., Eschenburg, H., Gabius, S., Hebart, H., Hoffmeister, A., Horst, H. -A., Kremers, S., Leithaeuser, M., Mueller, S., Wagner, S., Daum, S., Schlegel, F., Stauch, M., Heinemann, V., Maiello, E., Latini, L., Zaniboni, A., Amadori, D., Aprile, G., Barni, S., Mattioli, R., Martoni, A., Passalacqua, R., Nicolini, M., Pasquini, E., Rabbi, C., Aitini, E., Ravaioli, A., Barone, C., Biasco, G., Tamberi, S., Gambi, A., Verusio, C., Marzola, M., Lelli, G., Boni, C., Cascinu, S., Bidoli, P., Vaghi, M., Cruciani, G., Di Costanzo, F., Sobrero, A., Petrioli, R., Aglietta, M., Alabiso, O., Capuzzo, F., Falcone, A., Corsi, D. C., Labianca, R., Salvagni, S., Chiara, S., Ciuffreda, L., Ferrau, F., Giuliani, F., Lonardi, S., Gebbia, N., Mantovani, G., Sanches, E., Mellidez, J. C., Santos, P., Freire, J., Sarmento, C., Costa, L., Pinto, A. M., Barroso, S., Santo, J. E., Guedes, F., Monteiro, A., Sa, A., Furtado, I., Salazar, R., Aguilar, E. A., Herrero, F. R., Valera, J. S., Ayerbes, M. V., Batlle, J. F., Gil, S., Esteve, A. A., Garcia-Giron, C., Vivanco, G. L., Salvia, A. S., Orduna, V. A., Garcia, R. V., Gallego, J., Sureda, B. M., Remon, J., Safont Aguilera, M. J., Nogueras, L. C., Merino, B. Q., Castro, C. G., de Prado, P. M., Pericay, C. P., Figueiras, M. C., Jordan, I. G., Gome Reina, M. J., Garcia, A. L. -L., Garcia-Ramos, A. A., Cervantes, A., Martos, C. F., Gaspar, E. M., Montero, I. C., Emperador, P. E., Carbonero, A. L., Castillo, M. G., Garcia, T. G., Lopez, J. G., Flores, E. G., Morales, M. G., Munoz, M. L., Martin, A. L., Maurel, J., Camara, J. C., Garcia, R. D., Salgado, M., Busquier, I. H., Ruiz, T. C., Munoa, A. L., Aliguer, M. N., de Taranco, A. V. O., Urena, M. M., Gaspa, F. L., Ponce, J. J., Roig, C. B., Jimenez, P. V., Brotons, A. G., Rodriguez, S. A., Martinez, J. A., Ruiz, L. C., Ruiz, M. C., Bridgewater, J., Glynne-Jones, R., Tahir, S., Hickish, T., Cassidy, J., and Samuel, L.

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Organoplatinum Compounds, Colorectal cancer, medicine.medical_treatment, Medizin, Leucovorin, Prospective cohort study, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, FOLFOX, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, tudy, Lymphocytes, Prospective Studies, Leucovorin/therapeutic use, Middle Aged, Prognosis, 3. Good health, Colorectal carcinoma, Fluorouracil, 030220 oncology & carcinogenesis, Predictive value of tests, Colonic Neoplasms, Biomarker (medicine), Lymphocytes/pathology, Female, Adjuvant, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Fluorouracil/therapeutic use, Biomarkers, Tumor/analysis, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Predictive Value of Tests, Biomarker, Immune response, Internal medicine, medicine, Biomarkers, Tumor, Humans, Survival analysis, Aged, business.industry, medicine.disease, Survival Analysis, Surgery, 030104 developmental biology, Prospective cohort&nbsp, Multivariate Analysis, Colonic Neoplasms/diagnosis, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, business
Abstract

IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data.ResultsAmong the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients.ConclusionAlthough this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients.

Published
2017

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