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1. Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma

Author: Julien Calderaro, Narmin Ghaffari Laleh, Qinghe Zeng, Pascale Maille, Loetitia Favre, Anaïs Pujals, Christophe Klein, Céline Bazille, Lara R. Heij, Arnaud Uguen, Tom Luedde, Luca Di Tommaso, Aurélie Beaufrère, Augustin Chatain, Delphine Gastineau, Cong Trung Nguyen, Hiep Nguyen-Canh, Khuyen Nguyen Thi, Viviane Gnemmi, Rondell P. Graham, Frédéric Charlotte, Dominique Wendum, Mukul Vij, Daniela S. Allende, Federico Aucejo, Alba Diaz, Benjamin Rivière, Astrid Herrero, Katja Evert, Diego Francesco Calvisi, Jérémy Augustin, Wei Qiang Leow, Howard Ho Wai Leung, Emmanuel Boleslawski, Mohamed Rela, Arnaud François, Anthony Wing-Hung Cha, Alejandro Forner, Maria Reig, Manon Allaire, Olivier Scatton, Denis Chatelain, Camille Boulagnon-Rombi, Nathalie Sturm, Benjamin Menahem, Eric Frouin, David Tougeron, Christophe Tournigand, Emmanuelle Kempf, Haeryoung Kim, Massih Ningarhari, Sophie Michalak-Provost, Purva Gopal, Raffaele Brustia, Eric Vibert, Kornelius Schulze, Darius F. Rüther, Sören A. Weidemann, Rami Rhaiem, Jean-Michel Pawlotsky, Xuchen Zhang, Alain Luciani, Sébastien Mulé, Alexis Laurent, Giuliana Amaddeo, Hélène Regnault, Eleonora De Martin, Christine Sempoux, Pooja Navale, Maria Westerhoff, Regina Cheuk-Lam Lo, Jan Bednarsch, Annette Gouw, Catherine Guettier, Marie Lequoy, Kenichi Harada, Pimsiri Sripongpun, Poowadon Wetwittayaklang, Nicolas Loménie, Jarukit Tantipisit, Apichat Kaewdech, Jeanne Shen, Valérie Paradis, Stefano Caruso, and Jakob Nikolas Kather
Subjects: Science
Abstract: Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.
Published: 2023
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2. Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests

Author: Jérôme Boursier, Marine Roux, Charlotte Costentin, Julien Chaigneau, Céline Fournier-Poizat, Aldo Trylesinski, Clémence M. Canivet, Sophie Michalak, Brigitte Le Bail, Valérie Paradis, Pierre Bedossa, Nathalie Sturm, Victor de Ledinghen, AFEF group for the study of liver fibrosis, M118 study group, and Philip N. Newsome
Subjects: Science
Abstract: Abstract Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastography-based tests Agile3+ and Agile4 and then the specialized blood tests FibroMeterV3G and CirrhoMeterV3G, provides stratification in four groups, the last of which is enriched in cirrhosis (71% prevalence in the validation set). A risk prediction chart is also derived to allow estimation of the individual probability of cirrhosis. The predicted risk shows excellent calibration in the validation set, and mean difference with perfect prediction is only −2.9%. These tools improve the personalized non-invasive diagnosis of cirrhosis in NAFLD.
Published: 2023
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3. Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease

Author: Norma David, Jean-Philippe Antignac, Marine Roux, Philippe Marchand, Sophie Michalak, Fréderic Oberti, Isabelle Fouchard, Adrien Lannes, Odile Blanchet, Paul Cales, Etienne B. Blanc, Jérôme Boursier, and Clémence M. Canivet
Subjects: NAFLD, NASH, PFAS, PFHpA, Environmental sciences, GE1-350
Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. Objectives: We aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. Methods: One hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0–F1 fibrosis), 33 with fibrotic NASH (NASH and F2–F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at −80 °C. Results: The median age was 60 years, 61 % of patients were male, 46 % had diabetes and the median body mass index (BMI) was 32 kg/m2. Long-chain PFAS were associated with steatosis grade (p = 0.03). Among the nine PFAS detected in > 50 % of the patients, Perfluoro-n-heptanoic acid (PFHpA) showed significantly higher concentrations in grade 3 steatosis versus grade 1 (p = 0.02). Perfluoro-n-dodecanoic acid (PFDoA) concentrations were higher in patients with significant fibrosis (p = 0.04) and PFHpA in patients with advanced fibrosis (p = 0.02). The association between PFHpA and steatosis grade remained significant in multivariate analysis adjusted for age, gender, BMI, diabetes presence and dyslipidemia (p = 0.004). Discussion: Our study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through β-oxidation and biosynthesis of fatty acids.
Published: 2023
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4. Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions

Author: Arnault Tauziède-Espariat, Aurore Siegfried, Yvan Nicaise, Thomas Kergrohen, Philipp Sievers, Alexandre Vasiljevic, Alexandre Roux, Edouard Dezamis, Chiara Benevello, Marie-Christine Machet, Sophie Michalak, Chloe Puiseux, Francisco Llamas-Gutierrez, Pierre Leblond, Franck Bourdeaut, Jacques Grill, Christelle Dufour, Léa Guerrini-Rousseau, Samuel Abbou, Volodia Dangouloff-Ros, Nathalie Boddaert, Raphaël Saffroy, Lauren Hasty, Ellen Wahler, Mélanie Pagès, Felipe Andreiuolo, Emmanuèle Lechapt, Fabrice Chrétien, Thomas Blauwblomme, Kévin Beccaria, Johan Pallud, Stéphanie Puget, Emmanuelle Uro-Coste, Pascale Varlet, and the RENOCLIP-LOC, the BIOMECA (Biomarkers for Ependymomas in Children, Adolescents) consortium
Subjects: Ependymoma, ZFTA, RELA, DNA-methylation, Clusters, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract The cIMPACT-NOW Update 7 has replaced the WHO nosology of “ependymoma, RELA fusion positive” by “Supratentorial-ependymoma, C11orf95-fusion positive”. This modification reinforces the idea that supratentorial-ependymomas exhibiting fusion that implicates the C11orf95 (now called ZFTA) gene with or without the RELA gene, represent the same histomolecular entity. A hot off the press molecular study has identified distinct clusters of the DNA methylation class of ZFTA fusion-positive tumors. Interestingly, clusters 2 and 4 comprised tumors of different morphologies, with various ZFTA fusions without involvement of RELA. In this paper, we present a detailed series of thirteen cases of non-RELA ZFTA-fused supratentorial tumors with extensive clinical, radiological, histopathological, immunohistochemical, genetic and epigenetic (DNA methylation profiling) characterization. Contrary to the age of onset and MRI aspects similar to RELA fusion-positive EPN, we noted significant histopathological heterogeneity (pleomorphic xanthoastrocytoma-like, astroblastoma-like, ependymoma-like, and even sarcoma-like patterns) in this cohort. Immunophenotypically, these NFκB immunonegative tumors expressed GFAP variably, but EMA constantly and L1CAM frequently. Different gene partners were fused with ZFTA: NCOA1/2, MAML2 and for the first time MN1. These tumors had epigenetic homologies within the DNA methylation class of ependymomas-RELA and were classified as satellite clusters 2 and 4. Cluster 2 (n = 9) corresponded to tumors with classic ependymal histological features (n = 4) but also had astroblastic features (n = 5). Various types of ZFTA fusions were associated with cluster 2, but as in the original report, ZFTA:MAML2 fusion was frequent. Cluster 4 was enriched with sarcoma-like tumors. Moreover, we reported a novel anatomy of three ZFTA:NCOA1/2 fusions with only 1 ZFTA zinc finger domain in the putative fusion protein, whereas all previously reported non-RELA ZFTA fusions have 4 ZFTA zinc fingers. All three cases presented a sarcoma-like morphology. This genotype/phenotype association requires further studies for confirmation. Our series is the first to extensively characterize this new subset of supratentorial ZFTA-fused ependymomas and highlights the usefulness of ZFTA FISH analysis to confirm the existence of a rearrangement without RELA abnormality.
Published: 2021
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5. Albendazole-related Loa Loa encephalopathy

Author: Alice Métais, Sophie Michalak, and Audrey Rousseau
Subjects: Loiasis, Filariasis, Encephalopathy, Neurological adverse events, Albendazole, Side effects, Infectious and parasitic diseases, RC109-216
Published: 2021
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6. Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C

Author: Paul Calès, Julien Chaigneau, Gilles Hunault, Sophie Michalak, Christine Cavaro-Menard, Jean-Baptiste Fasquel, Sandrine Bertrais, and Marie-Christine Rousselet
Subjects: Cirrhosis, digital histopathology, image analysis, liver biopsy, METAVIR staging, Computer applications to medicine. Medical informatics, R858-859.7, Pathology, RB1-214
Abstract: Background: Liver fibrosis staging provides prognostic value, although hampered by observer variability. We used digital analysis to develop diagnostic morphometric scores for significant fibrosis, cirrhosis and fibrosis staging in chronic hepatitis C. Materials and Methods: We automated the measurement of 44 classical and new morphometric descriptors. The reference was histological METAVIR fibrosis (F) staging (F0 to F4) on liver biopsies. The derivation population included 416 patients and liver biopsies ≥20 mm-length. Two validation population included 438 patients. Results: In the derivation population, the area under the receiver operating characteristic (AUROC) for clinically significant fibrosis (F stage ≥2) of a logistic score combining 5 new descriptors (stellar fibrosis area, edge linearity, bridge thickness, bridge number, nodularity) was 0.957. The AUROC for cirrhosis of 6 new descriptors (edge linearity, nodularity, portal stellar fibrosis area, portal distance, granularity, fragmentation) was 0.994. Predicted METAVIR F staging combining 8 morphometric descriptors agreed well with METAVIR F staging by pathologists: k = 0.868. Morphometric score of clinically significant fibrosis had a higher correlation with porto-septal fibrosis area (rs = 0.835) than METAVIR F staging (rs = 0.756, P < 0.001) and the same correlations with fibrosis biomarkers, e.g., serum hyaluronate: rs = 0.484 versus rs = 0.476 for METAVIR F (P = 0.862). In the validation population, the AUROCs of clinically significant fibrosis and cirrhosis scores were, respectively: 0.893 and 0.993 in 153 patients (biopsy < 20 mm); 0.955 and 0.994 in 285 patients (biopsy ≥ 20 mm). The three morphometric diagnoses agreed with consensus expert reference as well as or better than diagnoses by first-line pathologists in 285 patients, respectively: significant fibrosis: 0.733 versus 0.733 (k), cirrhosis: 0.900 versus 0.827, METAVIR F: 0.881 versus 0.865. Conclusion: The new automated morphometric scores provide reproducible and accurate diagnoses of fibrosis stages via "virtual expert pathologist."
Published: 2015
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7. Reliability Criteria of Two-Dimensional Shear Wave Elastography: Analysis of 4277 Measurements in 788 Patients

Author: Gilles Hunault, Valérie Vilgrain, Sylvain Lemoine, Victor de Ledinghen, Maxime Ronot, Brigitte Le Bail, Jérôme Lebigot, Marie-Christine Rousselet, Christophe Aubé, Anita Paisant, Valérie Paradis, Clémence M. Canivet, Jérôme Boursier, Anne Crouan, Sophie Michalak, Pierre-Emmanuel Rautou, Christophe Cassinotto, Marie Irles-Depe, BOURGEAIS, Véronique, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépatologie (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Pathologie Cellulaire et Tissulaire, CERCOPAN, Laboratoire d'anatomie pathologique, Service d’Hépatologie [Hôpital Beaujon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Liver Cirrhosis, Cirrhosis, Coefficient of variation, [SDV]Life Sciences [q-bio], Population, Chronic liver disease, Standard deviation, 03 medical and health sciences, 0302 clinical medicine, 2D-SWE, Region of interest, Medicine, Humans, education, Reliability (statistics), ComputingMilieux_MISCELLANEOUS, education.field_of_study, Hepatology, medicine.diagnostic_test, business.industry, Liver Diseases, Gastroenterology, Reproducibility of Results, medicine.disease, Reliability, Liver Stiffness, 3. Good health, [SDV] Life Sciences [q-bio], Liver, 030220 oncology & carcinogenesis, Liver biopsy, Elasticity Imaging Techniques, Liver Fibrosis, 030211 gastroenterology & hepatology, business, Nuclear medicine
Abstract: International audience; Background & aims: Two-dimensional shear wave elastography (2D-SWE) is an accurate method for the non-invasive evaluation of liver fibrosis. We aimed to determine the reliability criteria and the number of necessary reliable measurements for 2D-SWE.Methods: 788 patients with chronic liver disease underwent liver biopsy and 2D-SWE examination in three centers. The 4277 2D-SWE measurements performed were 2:1 randomly divided into derivation (n = 2851) and validation (n = 1426) sets. Reliability criteria for a 2D-SWE measurement were defined in the derivation set from the intrinsic characteristics given by the device (mean liver stiffness, standard deviation, diameter of the region of interest), with further evaluation in the validation set.Results: In the whole population of 4277 measurements, AUROC for bridging fibrosis was 0.825 ± 0.006 and AUROC for cirrhosis was 0.880 ± 0.006. Mean stiffness and coefficient of variation (CV) were independent predictors of bridging fibrosis or cirrhosis. From these two parameters, new criteria were derived to define a reliable 2D-SWE measurement: stiffness
Published: 2022

8. Albendazole-related Loa Loa encephalopathy

Author: Audrey Rousseau, Alice Métais, and Sophie Michalak
Subjects: Pediatrics, medicine.medical_specialty, biology, business.industry, Encephalopathy, Infectious and parasitic diseases, RC109-216, medicine.disease, biology.organism_classification, Albendazole, Filariasis, Neurological adverse events, Infectious Diseases, Loiasis, medicine, Loa loa, business, Side effects, medicine.drug
Published: 2021

9. Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs

Author: Onorina Bruno, Olivier Sutter, Jérémie Riou, Agnès Rodes, Frédéric Oberti, Christophe Aubé, I. Bricault, Valérie Vilgrain, Hervé Trillaud, Anita Paisant, Valérie Laurent, Maxime Ronot, Christophe Cassinotto, Boris Guiu, Sophie Michalak, Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Paris 13 (UP13), Hôpital Jean Verdier [AP-HP], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle d'imagerie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Pathologie [Clichy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, Cirrhosis, Hepatocellular carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Liver neoplasm, 03 medical and health sciences, 0302 clinical medicine, Magnetic resonance imaging, medicine, Hepatology, medicine.diagnostic_test, business.industry, Washout, Nodule (medicine), Gold standard (test), HCCS, medicine.disease, 3. Good health, 030104 developmental biology, Contrast agent, 030211 gastroenterology & hepatology, medicine.symptom, Nuclear medicine, business
Abstract: Background & Aims The aim of this study was to use a head-to-head nodule comparison to compare the performance of extracellular contrast agent MRI (ECA-MRI) with that of hepatobiliary contrast agent MRI (HBA-MRI) for the non-invasive diagnosis of small hepatocellular carcinomas (HCCs). Methods Between August 2014 and October 2017, 171 patients with cirrhosis, each with 1 to 3 nodules measuring 1–3 cm, were enrolled across 8 centers. All patients underwent both an ECA-MRI and an HBA-MRI within a month. A non-invasive diagnosis of HCC was made when a nodule exhibited arterial phase hyper-enhancement (APHE) with washout at the portal venous phase (PVP) and/or delayed phase (DP) for ECA-MRI, or the PVP and/or HB phase (HBP) for HBA-MRI. The gold standard was defined by using a previously published composite algorithm. Results A total of 225 nodules, of which 153 were HCCs and 72 were not, were included. The sensitivites of both MRI techniques were similar. Specificity was 83.3% (95% CI 72.7–91.1) for ECA-MRI and 68.1% (95% CI 56.0–78.6) for HBA-MRI. In terms of HCC diagnosis on ECA-MRI, 138 nodules had APHE, 84 had washout at PVP, and 104 at DP; on HBA-MRI, 128 nodules had APHE, 71 had washout at PVP, and 99 at HBP. For nodules 2–3 cm in size, sensitivity and specificity were similar between the 2 approaches. For nodules 1–2 cm in size, specificity dropped to 66.1% (95% CI 52.2–78.2) for HBA-MRI vs. 85.7% (95% CI 73.8–93.6) for ECA-MRI. Conclusions HBA-MRI specificity is lower than that of ECA-MRI for diagnosing small HCCs in patients with cirrhosis. These results raise the question of the proper use of HBA-MRI in algorithms for the non-invasive diagnosis of small HCCs. Lay summary There are 2 magnetic resonance imaging (MRI)-based approaches available for the non-invasive diagnosis of hepatocellular carcinoma (HCC), using either extracellular or hepatobiliary contrast agents. The current results showed that the sensitivity of MRI with hepatobiliary contrast agents was similar to that with extracellular contrast agents, but the specificity was lower. Thus, hepatobiliary contrast agent-based MRI, although detailed in international guidelines, should be used with caution for the non-invasive diagnosis of HCC. Clinical trial number NCT00848952 .
Published: 2019

10. Adenocarcinoma of the oesophagogastric junction Siewert II: An oesophageal cancer better cured with total gastrectomy

Author: Benjamin Mathieu, Renaud Flamein, Fédérique Peschaud, Kevin Kraft, Diane Goéré, Sylvain Fabre, Basile Tsilividis, Frederic Borie, Florence Vandois, Jean Pierre Arnaud, Damien Louis, Virginie Pichot-Delahaye, Manuel Fernandez, Frank Bonnetain, Marie Guilbert, Sophie Michalak, Marc Pocard, Denis Pezet, Bertrand Millat, Thibault Voron, Brigitte Gillet, Jeremie Thereaux, Jean Yves Mabrut, Emmanuelle Leteurtre, Xavier B. D’Journo, Nicolas Carrere, Michel Prudhomme, Olivier Glehen, Gil Lebreton, Jean-Marc Regimbeau, Arnaud Pasquer, Pascal Thomas, Jean Robert Delpero, Johan Gagnière, Timothée Thiébot, Denis Collet, Aude Glaise, N. Huten, Guillaume Piessen, Ariane Poisson, Cécile Brigand, Mohamed Hebbar, Bernard Meunier, Pierre Dechelotte, Caroline Gronnier, Dorothée Brachet, Jérôme Guiramand, Abdenaceur Dhari, Francis Michot, François Paye, Jean Michel Balon, Jérémie H. Lefevre, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Chirurgie digestive et hépatobiliaire, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Peuplements végétaux et bioagresseurs en milieu tropical (UMR PVBMT), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université de La Réunion (UR), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie digestive, CHU Bordeaux [Bordeaux], Université de Lille, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Chirurgie Digestive et Endocrinienne [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service Chirurgie Digestive et Endocrinienne [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de chirurgie générale et digestive [CHU Strasbourg], Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Département de chirurgie digestive, [CHU Toulouse], Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Éducation et scolarisation (ESCOL), Centre interdisciplinaire de recherche, culture, éducation, formation, travail (CIRCEFT), Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Recherche juridique de la Sorbonne André Tunc (IRJS), Université Paris 1 Panthéon-Sorbonne (UP1), Département de chirurgie digestive, CHU Clermont-Ferrand, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Département de chirurgie digestive, [CHU Montpellier], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), Service de Chirurgie Générale et Digestive[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Inserm UMR837 Team 5, Service d'oncologie médicale, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service de Chirurgie Digestive et Endocrinienne, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Biologie-Pathologie, Département de chirurgie digestive, [CHU Tours], Université d'Orléans (UO), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Department of Digestive Surgery, Rouen University Hospital, CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Service de chirurgie générale, digestive et oncologique [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Lyon Sud, Service de Chirurgie Digestive, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], AP-HM, Department of General and Digestive Surgery, North Hospital, Marseille, France, parent, Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Chirurgie viscérale et digestive [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire Estaing, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and CCSD, Accord Elsevier
Subjects: Male, medicine.medical_specialty, Esophageal Neoplasms, medicine.medical_treatment, 030230 surgery, Adenocarcinoma, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, 0302 clinical medicine, Oesophagogastric junction, Gastrectomy, Medicine, Humans, In patient, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, Retrospective Studies, Surgical approach, business.industry, Cancer, Retrospective cohort study, Cardia, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Neoadjuvant Therapy, 3. Good health, Surgery, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Female, Esophagogastric Junction, France, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, Median survival
Abstract: Introduction Type II AEG is now considered as oesophageal cancer in the seventh and eighth edition of TNM classification but optimal surgical approach for these tumors remains debated. The objective of the study is to assess and compare surgical and oncological outcomes of two surgical approaches: superior polar oesogastrectomy (SPO) or total gastrectomy (TG) in patients with type II adenocarcinoma of the oesophagogastric junction (AEG). Material and methods 183 patients with type II AEG treated from 1997 to 2010 in 21 French centers by SPO or TG were included in a multicenter retrospective study. The surgical and oncological outcomes were compared between these two surgical approaches. Results A TG was performed in 64 (35%) patients whereas 119 (65%) patients were treated by SPO with transthoracic approach in 100 of them (83.2%) and transhiatal approach with cervicotomy in 19 (16.8%). Surgical outcomes were comparable between the two approaches with a postoperative mortality rate of 4.9% and a severe operative morbidity rate within 30 days of 15.3%. Median survival in patients operated on by TG was of 46 months compared to 27 months in patients treated by SPO (p = 0.118). At multivariate analysis, TG appears to be an independent good prognostic factor compared to SPO (HR = 1.847; p = 0.008). However, TG was also associated with a higher rate of incomplete resection, (12.5% vs 5.9%; p = 0.120). Conclusion When TG allows obtaining tumor-free resection margins, this approach should be preferred to SPO.
Published: 2019

11. New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD

Author: Theophile Gerster, Christophe Bureau, Jean-Marie Péron, Justine Barthelon, Isabelle Fouchard, Frédéric Oberti, Juliette Foucher, Maeva Guillaume, Brigitte Le Bail, Marie Irles, Paul Calès, Wassil Merrouche, Adrien Lannes, Floraine Zuberbuhler, Vincent Leroy, Gilles Hunault, Victor de Lédinghen, Laurence Pelade, Sophie Michalak, Jérôme Boursier, Jérémie Riou, Marine Roux, Jean-Baptiste Hiriart, Cyrielle Delabaudière, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES), Département d'hépatologie (CHU Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Institut des sciences juridique et philosophique de la Sorbonne - UMR 8103 (ISJPS), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Haut-Lévêque [CHU Bordeaux]
Subjects: 0301 basic medicine, Adult, Liver Cirrhosis, Male, medicine.medical_specialty, FIBROMETER, Biopsy, Gastroenterology, Cohort Studies, 03 medical and health sciences, Random Allocation, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Blood test, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Hematologic Tests, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, business.industry, FibroTest, Fatty liver, Middle Aged, medicine.disease, Prognosis, 3. Good health, Data Accuracy, [STAT]Statistics [stat], 030104 developmental biology, Liver, Liver biopsy, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, business, Transient elastography, Algorithms, Biomarkers
Abstract: Background & Aims Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease (NAFLD) as it defines the subgroup of patients with impaired prognosis. The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone (representing indeterminate diagnosis) of fibrosis tests. Here, we aimed to determine the best combination of non-invasive tests for the diagnosis of advanced fibrosis in NAFLD. Methods A total of 938 patients with biopsy-proven NAFLD were randomized 2:1 into derivation and validation sets. All patients underwent liver stiffness measurement with vibration controlled transient elastography (VCTE) and blood fibrosis tests (NAFLD fibrosis score, Fibrosis-4 [FIB4], Fibrotest, Hepascore, FibroMeter). FibroMeterVCTE, which combines VCTE results and FibroMeter markers in a single test, was also calculated in all patients. Results For the diagnosis of advanced fibrosis, VCTE was significantly more accurate than the blood tests (area under the receiver operating characteristic curve [AUROC]: 0.840 ± 0.013, p ≤0.005). FibroMeter was the most accurate blood test (AUROC: 0.793 ± 0.015, p ≤0.017). The combinatory test FibroMeterVCTE outperformed VCTE and blood tests (AUROC: 0.866 ± 0.012, p ≤0.005). The sequential combination of FIB4 then FibroMeterVCTE (FIB4-FMVCTE algorithm) or VCTE then FibroMeterVCTE (VCTE-FMVCTE algorithm) provided an excellent diagnostic accuracy of 90% for advanced fibrosis, with liver biopsy only required to confirm the diagnosis in 20% of cases. The FIB4-FMVCTE and VCTE-FMVCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed. Conclusion The sequential combination of fibrosis tests in the FIB4-FMVCTE and VCTE-FMVCTE algorithms provides a highly accurate solution for the diagnosis of advanced fibrosis in NAFLD. These algorithms should now be validated for the diagnosis of advanced liver fibrosis in diabetology or primary care settings. Lay summary The evaluation of liver fibrosis is mandatory in non-alcoholic fatty liver disease (NAFLD), as advanced fibrosis identifies the subgroup of patients with impaired prognosis. FibroMeterVCTE is a new fibrosis test combining blood markers and the result of vibration controlled transient elastography (VCTE) into a single diagnostic test. Our results show that FibroMeterVCTE outperforms other blood fibrosis tests and VCTE alone for the diagnosis of advanced fibrosis in a large multi-centric cohort of 938 patients with biopsy-proven NAFLD. Sequential algorithms using a simple blood test or VCTE as a first-line procedure, then FibroMeterVCTE as a second-line test accurately classified 90% of patients.
Published: 2019

12. Suspicious liver nodule in chronic liver disease: Usefulness of a second biopsy

Author: Sophie Michalak, Boris Guiu, Isabelle Ollivier-Hourmand, B. Patouillard, Guillaume Baudin, Maxime Esvan, Valérie Vilgrain, L. Estivalet, P. Chevallier, A. Crouan, V. Le Pennec, Yves Gandon, C. Sylvain, A. Guillygomarc’h, Benoit Gallix, Eric Frampas, Christophe Duvoux, Franck Pilleul, Anne Minello, Isabelle Archambeaud, V. Cartier, R. Anty, Christophe Aubé, Jean-Pierre Tasu, Anita Paisant, M. Cuilleron, V. Brun, Alain Luciani, Jérôme Lebigot, Frédéric Oberti, Olivier Seror, J. Dumortie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Gabriel Montpied [Clermont-Ferrand], CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC AP-HP (hegp Ex-Broussais)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de radiologie et imagerie médicale [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Beaujon, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Hôpital l'Archet, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Henri Mondor, Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], 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), Service d'Imagerie Diagnostique et de Radiologie Thérapeutique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], CHU Clermont-Ferrand, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], and Hôpital Beaujon [AP-HP]
Subjects: Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biopsy, Chronic liver disease, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Humans, Medicine, Radiology, Nuclear Medicine and imaging, In patient, Prospective Studies, Prospective cohort study, Aged, Aged, 80 and over, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Liver Diseases, Liver Neoplasms, Nodule (medicine), General Medicine, Middle Aged, medicine.disease, 3. Good health, Hepatocellular carcinoma, Chronic Disease, Female, 030211 gastroenterology & hepatology, Radiology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Purpose: To assess the usefulness of a second biopsy when the first one was inconclusive in patients with a liver nodule found during the follow-up for chronic liver disease.Materials and methods: Among 381 patients (544 nodules) included in a prospective study designed to evaluate the accuracy of imaging for the diagnosis of small hepatocellular carcinoma (HCC) in chronic liver disease, 254 nodules were biopsied. The following histological results were considered as conclusive: HCC, dysplastic or regenerative nodule, and other identified tumors (benign or malignant). For nodules with inconclusive results (e.g. fibrosis or no definite focal lesion), a second biopsy was suggested, but was not mandatory.Results: A total of 242 patients (194 men, 48 women; mean age, 61.9 +/- 9.5 [SD]; range: 40.2-89.0years) with 254 nodules underwent a first biopsy. Mean nodule diameter was 19.2 +/- 5.4mm (range: 10-33mm). The first biopsy was conclusive in 189/254 nodules (74.4%): 157 HCCs (83.1%), 11 regenerative nodules (5.8%), 10 dysplastic nodules (5.3%), 3 cholangiocarcinomas (1.6%), and 8 other tumors (4.2%). Among the 65 nodules for which the first biopsy was inconclusive, a second biopsy was performed for 17 nodules in 16 patients within 6 months of the first one. It was conclusive in 13/17 nodules (76.5%): 10 HCCs (76.9%), 2 dysplastic nodules (15.4%), and 1 other tumor (7.7%). In 4/17 nodules (23.5%), no definitive diagnosis could be provided.Conclusion: The diagnostic yield of a second biopsy of a suspicious lesion suggestive of HCC in chronic liver disease is not decreased compared to the first one. Repeated biopsy after a first negative one could be an alternative option to the follow-up of patients with chronic liver disease. (C) 2018 Societe francaise de radiologie
Published: 2018

13. Macrotrabecular-massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance

Author: Boris Guiu, Jean-Charles Nault, Jonathan Derman, Nicolas Poté, Marianne Ziol, Jessica Zucman-Rossi, Cécile Charpy, Thomas Decaens, Sophie Michalak, Claire Francoz, Alexis Laurent, Julien Calderaro, Charlotte Costentin, Jeanne Ramos, Mohamed Bouattour, Valérie Vilgrain, Georges Philippe Pageaux, Nathalie Barget, Giuliana Amaddeo, Valérie Paradis, Nathalie Ganne-Carrié, Olivier Seror, Alain Luciani, Frédéric Oberti, Christophe Aubé, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Henri Mondor, Service de chirurgie digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service d'hépatologie, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, recurrence, Radiofrequency ablation, Gastroenterology, Article, law.invention, histology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, law, Internal medicine, Biopsy, Carcinoma, Humans, Medicine, Clinical significance, biopsy, Retrospective Studies, Radiofrequency Ablation, Hepatology, medicine.diagnostic_test, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, 030112 virology, digestive system diseases, 3. Good health, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, prognosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We recently identified a histological subtype of hepatocellular carcinoma (HCC), designated as "macrotrabecular-massive" (MTM-HCC) and associated with specific molecular features. In order to assess the clinical relevance of this variant, we investigated its prognostic value in two large series of patients with HCC treated by either surgical resection or radiofrequency ablation (RFA). We retrospectively included 237 HCC surgical samples and 284 HCC liver biopsies from patients treated by surgical resection and RFA, respectively. Histological slides were reviewed by pathologists specialized in liver disease, and the MTM-HCC subtype was defined by the presence of a predominant (>50%) macrotrabecular architecture (more than six cells thick). The main clinical and biological features were recorded at baseline. Clinical endpoints were early and overall recurrence. The MTM-HCC subtype was identified in 12% of the whole cohort (16% of surgically resected samples, 8.5% of liver biopsy samples). It was associated at baseline with known poor prognostic factors (tumor size, alpha-fetoprotein level, satellite nodules, and vascular invasion). Multivariate analysis showed that MTM-HCC subtype was an independent predictor of early and overall recurrence (surgical series: hazard ratio, 3.03; 95% confidence interval, 1.38-6.65; P = 0.006; and 2.76; 1.63-4.67; P < 0.001; RFA series: 2.37; 1.36-4.13; P = 0.002; and 2.19; 1.35-3.54; P = 0.001, respectively). Its prognostic value was retained even after patient stratification according to common clinical, biological, and pathological features of aggressiveness. No other baseline parameter was independently associated with recurrence in the RFA series. CONCLUSION The MTM-HCC subtype, reliably observed in 12% of patients eligible for curative treatment, represents an aggressive form of HCC that may require more specific therapeutic strategies. (Hepatology 2018;68:103-112).
Published: 2017

14. BRAF-V600E immunohistochemistry in a large series of glial and glial-neuronal tumors

Author: Hélène Plouhinec, Blandine Boisselier, Sophie Michalak, Delphine Prunier-Mirebeau, Quentin Breton, Audrey Rousseau, Philippe Menei, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Sanger sequencing, medicine.disease_cause, Ganglioglioma, glial–neuronal tumor, Central Nervous System Neoplasms, Behavioral Neuroscience, 0302 clinical medicine, Child, ganglioglioma, Original Research, Mutation, Glioma, E19294, Middle Aged, Immunohistochemistry, 3. Good health, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, Child, Preschool, symbols, Female, Sequence Analysis, clone (Java method), Adult, Proto-Oncogene Proteins B-raf, Adolescent, BRAF‐V600E mutation, Biology, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, 03 medical and health sciences, symbols.namesake, Young Adult, medicine, Humans, Preschool, neoplasms, Aged, Wild type, Infant, Sequence Analysis, DNA, DNA, medicine.disease, allele‐specific quantitative PCR, Cancer research, RRID: AB_11203852, Spring Bioscience VE1, 030217 neurology & neurosurgery, Immunostaining, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; INTRODUCTION: Some glial-neuronal tumors (GNT) (pleomorphic xantho-astrocytoma [PXA], ganglioglioma [GG]) display BRAF-V600E mutation, which represents a diagnostic clue to these entities. Targeted therapies against BRAF-V600 protein have shown promising results in GNT. The aim of this study was to assess the utility of BRAF-V600E immunohistochemistry (IHC, clone VE1) in daily practice in a series of 140 glial, and GNT compared to molecular biology (MB) techniques.METHODS: We performed BRAF-V600E IHC on all 140 cases. We used Sanger sequencing and allele-specific quantitative PCR (ASQ-PCR) to detect BRAF-V600E mutation when sufficient amount of materiel was available.RESULTS: BRAF-V600E immunostaining was detected in 29.5% of cases (41/140 cases; 61.5% GG/GC/AGG (32/52), 33% PXA, 6.6% pilocytic astrocytomas). In 47 cases, MB could be performed: Sanger sequencing and ASQ-PCR in 34 cases, ASQ-PCR only in 11 cases, and Sanger sequencing only in two cases. In initial tumors, Sanger sequencing identified BRAF-V600E mutation in 19.5% tumors (seven of 36 tested cases). ASQ-PCR showed mutation in 48.5% tumors (17/35 tested cases). In six cases (5 GG, one PXA), the results were discordant between IHC and MB; the five GG cases were immunopositive for BRAF-V600E but wild type with both MB techniques. In another 7 GG, the percentage of mutated (ganglion) cells was low, and Sanger sequencing failed to detect the mutation, which was detected by IHC and ASQ-PCR.CONCLUSIONS: In tumors with few mutated cells (e.g., GG), anti-BRAF-V600E IHC appears more sensitive than Sanger sequencing. The latter, although considered as the gold standard, is not to be used up-front to detect BRAF mutation in GG. The combination of IHC and ASQ-PCR appears more efficient to appraise the indication of targeted therapies in these glioneuronal tumors.
Published: 2017

15. A Developmental and Sequenced One-to-One Educational Intervention for Autism Spectrum Disorder: A Randomized Single-Blind Controlled Trial

Author: Marc Colombel, Antoine Tanet, Elisabeth Simonet, Louisa Garnil, Carole Devaux, Danièle Scellier, Sophie Michalak, Jean-François Havreng, Emmanuel Damville, Catherine Saint-Georges, Véronique Bur, Yves Faure, Myriam Garing, Marc Bandelier, Aude Brellier, Isabelle Gylbert, Aurélie Broche, Annik Hubert-Barthelemy, Anne Juteau, Anne Vautrin, Georges Lançon, Claire Ducateau, Christophe Chartier, François Soumille, Nicolas Bodeau, Graciela C. Crespin, Marie-Noëlle Clément, David Cohen, Hélène Petiton, and Jean-Louis Sarradet
Subjects: education, autism, Context (language use), Pediatrics, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Intervention (counseling), Intellectual disability, medicine, 0501 psychology and cognitive sciences, Clinical Study Protocol, 05 social sciences, medicine.disease, Autism spectrum disorder, intellectual disability, Pediatrics, Perinatology and Child Health, randomized controlled trial, Childhood Autism Rating Scale, Autism, Psychology, Inclusion (education), 030217 neurology & neurosurgery, 050104 developmental & child psychology, Clinical psychology
Abstract: Introduction Individuals with autism spectrum disorder (ASD) who also exhibit severe-to-moderate ranges of intellectual disability (ID) still face many challenges (i.e., less evidence-based trials, less inclusion in school with peers). Methods We implemented a novel model called the “Developmental and Sequenced One-to-One Educational Intervention” (DS1-EI) in 5- to 9-year-old children with co-occurring ASD and ID. The treatment protocol was adapted for school implementation by designing it using an educational agenda. The intervention was based on intensity, regular assessments, updating objectives, encouraging spontaneous communication, promoting skills through play with peers, supporting positive behaviors, providing supervision, capitalizing on teachers’ unique skills, and providing developmental and sequenced learning. Developmental learning implies that the focus of training is what is close to the developmental expectations given a child’s development in a specific domain. Sequenced learning means that the teacher changes the learning activities every 10–15 min to maintain the child’s attention in the context of an anticipated time agenda. We selected 11 French institutions in which we implemented the model in small classrooms. Each institution recruited participants per dyads matched by age, sex, and developmental quotient. Patients from each dyad were then randomized to a DS1-EI group or a Treatment as usual (TAU) group for 36 months. The primary variables – the Childhood Autism Rating scale (CARS) and the psychoeducational profile (PEP-3) – will be blindly assessed by independent raters at the 18-month and 36-month follow-up. Discussion and baseline description We enrolled 75 participants: 38 were randomized to the DS1-EI and 37 to the TAU groups. At enrollment, we found no significant differences in participants’ characteristics between groups. As expected, exposure to school was the only significant difference [9.4 (±4.1) h/week in the DS1-EI group vs. 3.4 (±4.5) h/week in the TAU group, Student’s t-test, t = 5.83, p
Published: 2016

16. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease

Author: Isabelle Fouchard-Hubert, Victor de Lédinghen, Sandrine Bertrais, Jérôme Boursier, Maude Charbonnier, Adrien Lannes, Anne Guillet, Juliette Foucher, Frédéric Oberti, Marie-Christine Rousselet, Paul Calès, Julien Vergniol, Brigitte Le Bail, Faiza Chermak, Jean-Baptiste Hiriart, Sophie Michalak, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], INSERM U1053, Université Bordeaux, Bordeaux, France., and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Liver Cirrhosis, medicine.medical_specialty, FIBROMETER, Cross-sectional study, Biopsy, [SDV]Life Sciences [q-bio], Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, Internal medicine, medicine, Blood test, Humans, Longitudinal Studies, Hepatology, medicine.diagnostic_test, FibroTest, business.industry, Fatty liver, medicine.disease, Prognosis, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Liver biopsy, 030211 gastroenterology & hepatology, business, Biomarkers
Abstract: NAFLD is highly prevalent but only a small subset of patients develop advanced liver fibrosis with impaired liver-related prognosis. We aimed to compare blood fibrosis tests and liver stiffness measurement (LSM) by FibroScan for the diagnosis of liver fibrosis and the evaluation of prognosis in NAFLD.Diagnostic accuracy was evaluated in a cross-sectional study including 452 NAFLD patients with liver biopsy (NASH-CRN fibrosis stage), LSM, and eight blood fibrosis tests (BARD, NAFLD fibrosis score, FibroMeter(NAFLD), aspartate aminotransferase to platelet ratio index (APRI), FIB4, FibroTest, Hepascore, FibroMeter(V2G)). Prognostic accuracy was evaluated in a longitudinal study including 360 NAFLD patients.LSM and FibroMeter(V2G) were the two best-performing tests in the cross-sectional study: AUROCs for advanced fibrosis (F3/4) were, respectively, 0.831±0.019 and 0.817±0.020 (p⩽0.041 vs. other tests); rates of patients with ⩾90% negative/positive predictive values for F3/4 were 56.4% and 46.7% (p0.001 vs. other tests); Obuchowski indexes were 0.834±0.014 and 0.798±0.016 (p⩽0.036 vs. other tests). Two fibrosis classifications were developed to precisely estimate the histological fibrosis stage from LSM or FibroMeter(V2G) results without liver biopsy (diagnostic accuracy, respectively: 80.8% vs. 77.4%, p=0.190). Kaplan-Meier curves in the longitudinal study showed that both classifications categorised NAFLD patients into subgroups with significantly different prognoses (p0.001): the higher was the class of the fibrosis classification, the worse was the prognosis.LSM and FibroMeter(V2G) were the most accurate of nine evaluated tests for the non-invasive diagnosis of liver fibrosis in NAFLD. LSM and FibroMeter(V2G) fibrosis classifications help physicians estimate both fibrosis stage and patient prognosis in clinical practice.The amount of liver fibrosis is the main determinant of the liver-related prognosis in patients with non-alcoholic fatty liver disease (NAFLD). We evaluated eight blood tests and FibroScan in a cross-sectional diagnostic study and found that FibroScan and the blood test FibroMeter(V2G) were the two most accurate tests for the non-invasive evaluation of liver fibrosis in NAFLD. A longitudinal prognostic study showed these two tests initially developed for the diagnosis are also prognostic markers as they allow for the stratification of NAFLD patients in several subgroups with significantly different prognosis.
Published: 2016

17. Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease

Author: Antonia Le Gruyer, Edouard Bardou-Jacquet, Anita Kiani, Fabrice Lainé, Bruno Turlin, Vanessa Brun, Ludivine Legros, Jeff Morcet, Yves Gandon, Sophie Michalak, Romain Moirand, Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Laboratoire de Pathologie Cellulaire et Tissulaire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, Alcoholic liver disease, medicine.medical_specialty, Acoustic radiation force impulse, Biopsy, [SDV]Life Sciences [q-bio], Severity of Illness Index, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Liver Cirrhosis, Alcoholic, Predictive Value of Tests, medicine, Humans, Prospective Studies, Non-invasive, Prospective cohort study, Acoustic radiation force impulse imaging, medicine.diagnostic_test, business.industry, Gastroenterology, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, Liver biopsy, Predictive value of tests, Area Under Curve, Elasticity Imaging Techniques, Prospective Study, 030211 gastroenterology & hepatology, Female, Elastography, Radiology, business, Nuclear medicine
Abstract: International audience; AIM: To evaluate the performance of elastography by ultrasound with acoustic radiation force impulse (ARFI) in determining fibrosis stage in patients with alcoholic liver disease (ALD) undergoing alcoholic detoxification in relation to biopsy. METHODS: Eighty-three patients with ALD undergoing detoxification were prospectively enrolled. Each patient underwent ARFI imaging and a liver biopsy on the same day. Fibrosis was staged according to the METAVIR scoring system. The median of 10 valid ARFI measurements was calculated for each patient. RESULTS: Sixty-nine males and thirteen females (one patient excluded due to insufficient biopsy size) were assessed with a mean alcohol consumption of 132.4 ± 128.8 standard drinks per week and mean cumulative year duration of 17.6 ± 9.5 years. Sensitivity and specificity were respectively 82.4% (0.70-0.95) and 83.3% (0.73-0.94) (AUROC = 0.87) for F ≥ 2 with a cut-off value of 1.63m/s; 82.4% (0.64-1.00) and 78.5% (0.69-0.89) (AUROC = 0.86) for F ≥ 3 with a cut-off value of 1.84m/s; and 92.3% (0.78-1.00] and 81.6% (0.72-0.90) (AUROC = 0.89) for F = 4 with a cut-off value of 1.94 m/s. CONCLUSION: ARFI is an accurate, non-invasive and easy method for assessing liver fibrosis in patients with ALD undergoing alcoholic detoxification
Published: 2016

18. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy

Author: Jean-Baptiste Hiriart, Christophe Cassinotto, Isabelle Fouchard-Hubert, Sophie Michalak, Victor de Ledinghen, Frédéric Oberti, Jérôme Lebigot, Amaury Mouries, Brigitte Le Bail, Paul Calès, V. Cartier, Jérôme Boursier, Christophe Aubé, Julien Vergniol, Bruno Lapuyade, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Université de Bordeaux (UB), Laboratoire d'anatomie pathologique, and CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Adolescent, [SDV]Life Sciences [q-bio], Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, medicine, 80 and over, Humans, Prospective Studies, Prospective cohort study, Aged, 2. Zero hunger, Aged, 80 and over, Univariate analysis, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Middle Aged, medicine.disease, 3. Good health, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, business, Body mass index
Abstract: International audience; Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue. The goal of this study was to assess the clinical use of liver stiffness measurement (LSM) evaluated by supersonic shear imaging (SSI), FibroScan, and acoustic radiation force impulse (ARFI) in a cohort of NAFLD patients who underwent liver biopsy. A total of 291 NAFLD patients were prospectively enrolled from November 2011 to February 2015 at 2 French university hospitals. LSM was assessed by SSI, FibroScan (M probe), and ARFI within two weeks prior to liver biopsy. Calculations of the area under the receiver operating curve (AUROC) were performed and compared for the staging of liver fibrosis. AUROC for SSI, FibroScan, and ARFI were 0.86, 0.82, and 0.77 for diagnoses of ≥F2; 0.89, 0.86, and 0.84 for ≥F3; and 0.88, 0.87, and 0.84 for F4, respectively. SSI had a higher accuracy than ARFI for diagnoses of significant fibrosis (≥F2) (P = 0.004). Clinical factors related to obesity such as body mass index ≥ 30 kg/m(2) , waist circumference ≥102 cm or increased parietal wall thickness were associated with LSM failures when using SSI or FibroScan and with unreliable results when using ARFI. In univariate analysis, FibroScan values were slightly correlated with NAFLD activity score and steatosis (R = 0.28 and 0.22, respectively), whereas SSI and ARFI were not; however, these components of NAFLD did not affect LSM results in multivariate analysis. The cutoff values for SSI and FibroScan for staging fibrosis with a sensitivity ≥90% were very close: 6.3/6.2 kPa for ≥F2, 8.3/8.2 kPa for ≥F3, and 10.5/9.5 kPa for F4.CONCLUSION: Although obesity is associated with an increase in LSM failure, the studied techniques and especially SSI provide high value for the diagnosis of liver fibrosis in NAFLD patients. (Hepatology 2016;63:1817-1827).
Published: 2016

19. Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C

Author: Marie-Christine Rousselet, Christine Cavaro-Menard, Julien Chaigneau, Sophie Michalak, Jean-Baptiste Fasquel, Gilles Hunault, Paul Calès, Sandrine Bertrais, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), and Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS)
Subjects: METAVIR staging, medicine.medical_specialty, Cirrhosis, Liver fibrosis, Population, Health Informatics, lcsh:Computer applications to medicine. Medical informatics, Gastroenterology, Pathology and Forensic Medicine, [SPI]Engineering Sciences [physics], 03 medical and health sciences, 0302 clinical medicine, Cirrhosis, digital histopathology, image analysis, liver biopsy, METAVIR staging, Fibrosis, image analysis, Internal medicine, Biopsy, medicine, lcsh:Pathology, Stage (cooking), education, liver biopsy, education.field_of_study, Receiver operating characteristic, medicine.diagnostic_test, business.industry, medicine.disease, 3. Good health, Computer Science Applications, digital histopathology, 030220 oncology & carcinogenesis, Liver biopsy, lcsh:R858-859.7, 030211 gastroenterology & hepatology, Original Article, Radiology, business, lcsh:RB1-214
Abstract: International audience; Background:Liver fibrosis staging provides prognostic value, although hampered by observer variability. We used digital analysis to develop diagnostic morphometric scores for significant fibrosis, cirrhosis and fibrosis staging in chronic hepatitis C.Materials and Methods:We automated the measurement of 44 classical and new morphometric descriptors. The reference was histological METAVIR fibrosis (F) staging (F0 to F4) on liver biopsies. The derivation population included 416 patients and liver biopsies ≥20 mm-length. Two validation population included 438 patients.Results:In the derivation population, the area under the receiver operating characteristic (AUROC) for clinically significant fibrosis (F stage ≥2) of a logistic score combining 5 new descriptors (stellar fibrosis area, edge linearity, bridge thickness, bridge number, nodularity) was 0.957. The AUROC for cirrhosis of 6 new descriptors (edge linearity, nodularity, portal stellar fibrosis area, portal distance, granularity, fragmentation) was 0.994. Predicted METAVIR F staging combining 8 morphometric descriptors agreed well with METAVIR F staging by pathologists: k = 0.868. Morphometric score of clinically significant fibrosis had a higher correlation with porto-septal fibrosis area (rs = 0.835) than METAVIR F staging (rs = 0.756, P < 0.001) and the same correlations with fibrosis biomarkers, e.g., serum hyaluronate: rs = 0.484 versus rs = 0.476 for METAVIR F (P = 0.862). In the validation population, the AUROCs of clinically significant fibrosis and cirrhosis scores were, respectively: 0.893 and 0.993 in 153 patients (biopsy < 20 mm); 0.955 and 0.994 in 285 patients (biopsy ≥ 20 mm). The three morphometric diagnoses agreed with consensus expert reference as well as or better than diagnoses by first-line pathologists in 285 patients, respectively: significant fibrosis: 0.733 versus 0.733 (k), cirrhosis: 0.900 versus 0.827, METAVIR F: 0.881 versus 0.865.Conclusion:The new automated morphometric scores provide reproducible and accurate diagnoses of fibrosis stages via "virtual expert pathologist."
Published: 2015

20. Primary biliary cirrhosis: proposal for a new simple histological scoring system

Author: Dominique Wendum, Christophe Corpechot, Pierre Bedossa, Pierre-Yves Boëlle, Marie-Christine Saint-Paul, Sophie Michalak, Frédéric Charlotte, Elie-Serge Zafrani, Olivier Chazouillères, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
Subjects: Liver Cirrhosis, medicine.medical_specialty, Scoring system, Cirrhosis, Organ Dysfunction Scores, Biopsy, [SDV]Life Sciences [q-bio], Interface hepatitis, Gastroenterology, Hepatitis, Ductopenia, Primary biliary cirrhosis, Fibrosis, Internal medicine, Medicine, Humans, Observer Variation, Hepatology, medicine.diagnostic_test, business.industry, Bile duct, Liver Cirrhosis, Biliary, Reproducibility of Results, medicine.disease, Prognosis, 3. Good health, medicine.anatomical_structure, Liver biopsy, business, Nuclear medicine
Abstract: International audience; Background & AimsA simple and reproducible evaluation of non diagnostic histological lesions related to prognosis remains crucial in primary biliary cirrhosis (PBC). Presently there is no satisfactory simple scoring system analysing them reliably. We elaborated a semi-quantitative scoring system that assesses fibrosis, lymphocytic interface hepatitis (LIH) and ductopenia, separately. This study was aimed to evaluate its intra/interobserver reproducibility and its correlation with the main biochemical data.MethodsLiver biopsies from 33 consecutive newly diagnosed PBC patients were independently analysed by five liver pathologists. Fibrosis was classified into five stages (portal/periportal fibrosis/few septa/numerous septa/cirrhosis) and LIH into four grades. The bile duct ratio (BDR), i.e. ratio of the number of portal tracts with ducts to total number of portal tracts, Ludwig's and Scheuer's stages were evaluated. Intra and interobserver agreements were assessed. Histological results were correlated to the biochemical data.ResultsMost patients had an early disease on clinical and biological parameters. The biopsies measured 23mm on average (range 12 – 40mm). Intraobserver reproducibility was substantial for fibrosis (κ=0.68), LIH (κ=0.69) and BDR (ICC=0.69). Interobserver agreement for fibrosis was fair with the 5-class system (κ=0.36), moderate with a 4-class system (κ=0.56). moderate for LIH (κ=0.59) and BDR (ICC=0.50). Ludwig's and Scheuer's staging showed a fair interobserver agreement (κ=0.32, κ=0.31 respectively). Our system showed better correlations with biochemistry than Ludwig's and Scheuer's systems did.ConclusionsThis simple scoring system, assessing fibrosis, LIH and BDR separately, has a substantial intraobserver and a moderate interobserver reproducibility. Its prognostic relevance has to be evaluated.
Published: 2015

21. Screening for significant chronic liver disease by using three simple ultrasound parameters

Author: Gregoire Lignon, Frédéric Oberti, Jérôme Lebigot, Christophe Aubé, Sophie Michalak-Provost, Jérôme Boursier, Stéphanie Delumeau, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), and Université d'Angers (UA)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Chronic liver disease, Asymptomatic, Gastroenterology, Sensitivity and Specificity, Young Adult, Fibrosis, Internal medicine, Ultrasound, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, Derivation, Aged, Ultrasonography, medicine.diagnostic_test, business.industry, cirrhosis, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, 3. Good health, Liver, Liver biopsy, Chronic Disease, Screening, Female, Radiology, medicine.symptom, business
Abstract: International audience; ObjectivesChronic liver diseases remain asymptomatic for many years. Consequently, patients are diagnosed belatedly, when cirrhosis is unmasked by lifethreatening complications. We aimed to identify simple ultrasound parameters for the screening of patients with unknown significant chronic liver disease.MethodsThree hundred and twenty seven patients with chronic liver disease, liver biopsy, and ultrasound examination were included in the derivation set. 283 consecutive patients referred for ultrasound examination were included in the validation set; those selected according to the ultrasound parameters identified in the derivation set were then referred for specialized consultation including non-invasive fibrosis tests and ultimately liver biopsy if liver fibrosis was suspected.ResultsIn the derivation set, three ultrasound parameters were independent predictors of severe fibrosis: liver surface irregularity, spleen length (>110mm), and demodulation of hepatic veins. The association of ≥2 of the three above parameters provided 49.1% sensitivity and 86.9% specificity. In the validation set, at ≥2 of the three parameters were present in 23 (8%) of the patients. Among these patients, 8 had liver fibrosis (F≥1), 5 had significant fibrosis (F≥2) and two cirrhosis.ConclusionThe generalized search of three simple ultrasound signs in patients referred for abdominal ultrasound examination may be an easy way to detect those with silent but significant chronic liver disease.
Published: 2015

22. P17.03POST-OPERATIVE EXCLUSIVE CHEMOTHERAPY WITH PCV FOR ANAPLASTIC OLIGODENDROGLIOMA: A RETROSPECTIVE STUDY OF 35 CONFIRMED CASES

Author: Philippe Menei, Edmond Nader, P. Soulié, P. Augereau, Sophie Michalak, A. Pavageau, Delphine Loussouarn, Eric Jadaud, and Audrey Rousseau
Subjects: Oncology, Cancer Research, Vincristine, medicine.medical_specialty, Temozolomide, Oligoastrocytoma, business.industry, medicine.medical_treatment, medicine.disease, Single Center, Procarbazine, Chemotherapy regimen, Surgery, Radiation therapy, Poster Presentations, Median follow-up, Internal medicine, medicine, Neurology (clinical), business, medicine.drug
Abstract: INTRODUCTION: Anaplastic oligodendroglioma/oligoastrocytoma (AO/AOA) represent among primary brain tumors a distinct chemosensitive heterogeneous entity with variable prognosis. New insights in biology have shown the prognostic impact of molecular/genomic tests (1p/19q status and IDH1 mutation). For many decades, front line therapy remains surgery followed by radiotherapy. In two recently updated large phase III trials, patients with 1p/19q codeleted tumors and/or IDH1 mutation lived longer after radiotherapy and adjuvant chemotherapy with PCV (Procarbazine, CCNU, Vincristine). Some authors suggest also encouraging outcome with chemotherapy alone with PCV or temozolomide. PATIENTS AND METHODS: We reviewed a serie of 54 patients initially diagnosed with AO or AOA, consecutively treated in a single center and who received PCV first after initial surgery. Radiation was delayed until relapse or when primary chemotherapy failed. All cases were retrospectively reviewed by a second neuropathologist and reclassified according the 2007 WHO criteria as well 1p/19q codeletion and IDH1 mutation were assessed when possible. RESULTS: From 10/2000 to 10/2009, 35 patients (out of 54) have confirmed diagnosis of AO (n = 25) or AOA (n = 10) and were considered for this analysis. Nineteen out of the 30 tested tumors (63%) had 1p/19q codeletion and 27/35 were IDH1 mutated (by IHC). Follow up MRI were scheduled every 3 months. Sixty-seven% of patients were younger than 50 years, 88% had a resection and 100% had a PS 0 or 1. Median number of delivered cycles was 4 (1 to 6) with hematological toxicity being the main cause of early interruption. The median follow-up was 54,7 months [95% CI; 4,7-17,8]. Median PFS and OS were 51,9 months [36,7 to NR] and 89,5 months [61,1 to NR] respectively in all AO/AOA. In the codeleted subgroup, median PFS was not reached [47,2-NR] and OS was 89,5 months [69,5 - NR]. In the non codeleted, median PFS and OS were shorter (11,6 and 39 months). In the IDH1 mutated subgroup, OS and PFS were respectively 89,5 [68,1 to NR] and 51,9 [37,3 to NR] months respectively. For patients with the wild type IDH1, OS and PFS were lower: 32 [6,7 to NR] and 18,7 [2,9 to NR] months. As of February 2014, eleven patients (31%, 10 codeleted tumors, 8 IDH1 mutated) with no disease progression, after a median follow up of 63,3 months, have not yet received salvage radiotherapy. CONCLUSION: Our results produce additional data to support a personalized treatment strategy for AO/AOA based on molecular/genomic analysis. However, omission of adjuvant RT in order to reduce the risk of delayed neurocognitive dysfunctions could not be recommended and should be implemented in clinical trials.
Published: 2014

23. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

Author: Dominique, Figarella-Branger, Karima, Mokhtari, Caroline, Dehais, Anne, Jouvet, Emmanuelle, Uro-Coste, Carole, Colin, Catherine, Carpentier, Fabien, Forest, Claude-Alain, Maurage, Jean-Michel, Vignaud, Marc, Polivka, Emmanuelle, Lechapt-Zalcman, Sandrine, Eimer, Gabriel, Viennet, Isabelle, Quintin-Roué, Marie-Hélène, Aubriot-Lorton, Marie-Danièle, Diebold, Delphine, Loussouarn, Catherine, Lacroix, Valérie, Rigau, Annie, Laquerrière, Fanny, Vandenbos, Sophie, Michalak, Henri, Sevestre, Michel, Peoch, François, Labrousse, Christo, Christov, Jean-Louis, Kemeny, Marie-Pierre, Chenard, Danchristian, Chiforeanu, François, Ducray, Ahmed, Idbaih, Frederic, Dhermain, Laboratoire d'anatomie pathologique - [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon (HCL), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, U975, Université Paris 06, Service d’Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Anatomie Pathologique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Anatomie Pathologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'anatomie et cytologie pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie-Neuropathologie, CHU de Bordeaux Pellegrin [Bordeaux], Histologie et Pathologie Moléculaire, Université Bordeaux Segalen - Bordeaux 2, Service Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'anatomie et cytologie pathologiques [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Anatomie Pathologique B, Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et Cytologie Pathologique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), chu de nice, Hôpital Pasteur, Laboratoire Central d’Anatomo Pathologie, Hôpital Pasteur [Nice] (CHU), Département de pathologie cellulaire et tissulaire, CHU d'Angers, 4, rue Larrey, 49100 Angers, France., Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Anatomie et Cytologie Pathologiques, CHU Amiens-Picardie, Service d'Anatomie Pathologique [CHU Limoges], CHU Limoges, Hôpital Henri Mondor, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'anatomie pathologique - Hôpital de Hautepierre Hôpitaux Universitaires de Strasbourg - Université de Strasbourg, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuropathologie Raymond Escourolle [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie 2 [CHU Pitié-Salpêtrière], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d'Anatomie et Cytologie Pathologique [Rouen], AP-HP Hôpital Henri Mondor (Créteil), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Neuropathologie [CHU Pitié Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM]-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université
Subjects: Cancer Research, Pathology, medicine.medical_specialty, IDH1, Necrosis, Mitotic index, Proliferation index, [SDV]Life Sciences [q-bio], Oligodendroglioma, Biology, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Chromosome instability, medicine, Mitotic Index, Humans, Progression-free survival, ComputingMilieux_MISCELLANEOUS, Neovascularization, Pathologic, Brain Neoplasms, Brain, medicine.disease, Isocitrate Dehydrogenase, 3. Good health, Oncology, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Chromosome abnormality, Neurology (clinical), medicine.symptom, Chromosome Deletion, Chromosomes, Human, Pair 19, 030217 neurology & neurosurgery
Abstract: BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AO). METHODS: The histological characteristics of 203 AO patients enrolled in the French national network POLA were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q co-deletion was present in 79% of cases and was associated with alpha-internexin expression (p < 10-4), IDH1/2 mutation (p < 10-4), chromosome 4 loss (p < 10-3), and better overall survival (p < 10-4). Based on mitotic index, microvascular proliferation (MVP) and necrosis, 3 groups of 1p/19q co-deleted AO were identified: AO with more than 5 mitoses per 10-HPF, no MVP and no necrosis, (1), AO with MVP and no necrosis (2) and AO with MVP and necrosis (3). Compared to group 1, group 2 and 3 AO had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared to group 2, group 3 AO had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q co-deleted AO, chromosomal instability was associated with shorter progression free survival (p = 0.024) and shorter overall survival (p = 0.023). CONCLUSIONS: The present study shows that oligodendroglioma with classic histological features remains a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q co-deleted AO are also heterogeneous. Interestingly, mitotic index, MVP and necrosis help to classify them into three groups associated with distinct genomic alterations.
Published: 2014

24. Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes

Author: François Paraf, Marie Christine Saint Paul, Saïd Taouji, Jeanne Ramos, Nathalie Sturm, Brigitte Bancel, Valérie Paradis, Dominique Wendum, Emmanuelle Leteurtre, Monique Fabre, Jean-Yves Scoazec, Paulette Bioulac-Sage, Charles Balabaud, Jessica Zucman-Rossi, Gaelle Cubel, Brigitte Le Bail, Sophie Michalak, Catherine Guettier, Jeanne Tran Van Nhieu, Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U837 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Albert Bonniot - Ontogénèse et oncogénèse moléculaires, CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Equipe 16, Centre de Recherche en Cancérologie de Lyon (CRCL), Tumorothèque de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Limoges (UNILIM), Hôpital Pasteur [Nice] (CHU), Laboratoire de Pathologie Cellulaire et Tissulaire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Grenoble-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)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Limoges ( UNILIM ), Hôpital Pasteur [Nice] ( CHU ), CHU Angers, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Genomique Fonctionnelle des Tumeurs Solides, and Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Core needle, Male, MESH: Biopsy, Large-Core Needle, Pathology, MESH : Liver Neoplasms, MESH: Focal Nodular Hyperplasia, MESH: beta Catenin, MESH : Hepatocytes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hepatocytes, MESH: Adenoma, Liver Cell, 0302 clinical medicine, MESH: Liver Neoplasms, MESH : Tumor Markers, Biological, MESH : Female, Hepatocyte Nuclear Factor 1-alpha, MESH : Algorithms, beta Catenin, medicine.diagnostic_test, Liver Neoplasms, Focal nodular hyperplasia, MESH : Adult, MESH : Biopsy, Large-Core Needle, MESH : Diagnosis, Differential, MESH: Predictive Value of Tests, 3. Good health, Focal Nodular Hyperplasia, 030220 oncology & carcinogenesis, Immunohistochemistry, 030211 gastroenterology & hepatology, MESH : Hepatocyte Nuclear Factor 1-alpha, Female, Anatomy, Algorithms, Adult, medicine.medical_specialty, MESH : Male, MESH: Algorithms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, Adenoma, Liver Cell, Diagnosis, Differential, 03 medical and health sciences, MESH : Adenoma, Liver Cell, Glutamate-Ammonia Ligase, Predictive Value of Tests, MESH: Diagnosis, Differential, Biopsy, medicine, Biomarkers, Tumor, Humans, MESH: Glutamate-Ammonia Ligase, MESH : Predictive Value of Tests, MESH: Hepatocyte Nuclear Factor 1-alpha, MESH: Humans, business.industry, Significant difference, MESH : Humans, MESH: Adult, MESH : Glutamate-Ammonia Ligase, Hepatocellular adenoma, medicine.disease, MESH : beta Catenin, MESH: Male, Staining, MESH : Focal Nodular Hyperplasia, MESH: Tumor Markers, Biological, Hepatocytes, Surgery, Biopsy, Large-Core Needle, business, MESH: Female, Immunostaining
Abstract: International audience; Phenotypic identification of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) subtypes using immunohistochemical markers has been developed from their molecular characteristics. Our objective was to evaluate the sensitivity of these markers in the definitive diagnosis of these lesions by core needle biopsies. A total of 239 needle biopsies paired with their surgical resection specimen (group A) or without an associated resection specimen (group B) were reviewed. Using a step-by-step algorithm after standard staining, appropriate immunostaining analyses were performed to determine the certainty of diagnosis of FNH, HNF1α-inactivated HCA, inflammatory HCA, β-catenin-activated HCA, or unclassified HCA. The diagnosis of FNH was certain or probable on routine stains in 53% of needle biopsies of group A, whereas after glutamine synthetase staining, the diagnosis was certain in 86.7% as compared with 100% on the corresponding surgical specimen (P=0.04). In needle biopsies of group A, the diagnosis of HCA was certain on routine stains in 58.6% as compared with 94.3% on surgical specimens. After specific immunostaining, diagnosis was established on biopsies with 74.3% certainty, including all HCA subtypes, with similar distribution in surgical specimens. For each "certain diagnosis" paired diagnostic test (biopsy and surgical specimen), a positive correlation was observed (P
Published: 2012

25. Quantitative proteomic Isotope-Coded Protein Label (ICPL) analysis reveals alteration of several functional processes in the glioblastoma

Author: Mélanie Lagarrigue, Philippe Menei, Charles Pineau, Sophie Michalak, Anne Clavreul, Emmanuelle Com, Plateforme Protéomique-Biogenouest (PPB), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Proteomics Core Facility (Protim), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Plateforme Génomique Santé Biogenouest®-Plateforme Génomique Santé Biogenouest®, Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pathologie Cellulaire et Tissulaire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Biogenouest, French National Cancer Institute (INCa), IBiSA, Conseil Régional de Bretagne grants, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Proteomics Core Facility (Protim), and Université de Rennes (UR)-Plateforme Génomique Santé Biogenouest®-Plateforme Génomique Santé Biogenouest®
Subjects: Proteomics, MESH: Neoplasm Proteins, MESH: Deuterium, MESH: Isotope Labeling, Proteome, MESH: Heat-Shock Proteins, Biochemistry, Mass Spectrometry, 0302 clinical medicine, Tandem Mass Spectrometry, MESH: Nerve Tissue Proteins, Heat-Shock Proteins, Cancer, Carbon Isotopes, 0303 health sciences, medicine.diagnostic_test, MESH: Proteomics, MESH: Glioblastoma, Neoplasm Proteins, 3. Good health, Isotope Labeling, 030220 oncology & carcinogenesis, YWHAZ, Biophysics, Nerve Tissue Proteins, Computational biology, Biology, MESH: Actins, 03 medical and health sciences, MESH: Gene Expression Profiling, Western blot, Heat shock protein, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: 14-3-3 Proteins, YWHAG, HSPA8, YWHAB, 030304 developmental biology, MESH: Mass Spectrometry, MESH: Humans, Gene Expression Profiling, MESH: Tandem Mass Spectrometry, MESH: Carbon Isotopes, ICPL, Deuterium, Molecular biology, Actins, Gene expression profiling, 14-3-3 Proteins, Glioblastoma
Abstract: International audience; Glioblastoma (GB), the most frequent primary tumor of the central nervous system, remains one of the most lethal human cancers despite intensive researches. Current paradigm in the study of GB has been focused on inter-patient variability and on trying to isolate new classification elements or prognostic factors. Here, using ICPL, a technique for protein relative quantification by mass spectrometry, we investigated protein expression between the four regions of GB on clinically relevant biopsies from 5 patients. We identified 584 non-redundant proteins and 31 proteins were found to be up-regulated in the tumor region compared to the peri-tumoral brain tissue, among which, 24 proteins belong to an interaction network linked to 4 biological processes. The core of this network is mainly constituted of interactions between beta-actin (ACTB) with heat shock proteins (HSP90AA1, HSPA8) and 14-3-3 proteins (YWHAZ, YWHAG, YWHAB). A cluster of three isoforms of the sodium pump α-subunit (ATP1A1, ATP1A2, ATP1A3) was also identified outside this network. The differential expression observed for ACTB and 14-3-3γ was further validated by western blot and/or immunohistochemistry. Our study confirms the identity of previously proposed molecular targets, highlights several functional processes altered in GB such as energy metabolism and synaptic transmission and could thus provide added value to new therapeutic trails.
Published: 2012

26. Isolation of a new cell population in the glioblastoma microenvironment

Author: Jean-Luc Carré, Jean Mosser, Anne Clavreul, Philippe Menei, Tony Avril, Marie-Lise Jourdan, Agnès Chassevent, Sophie Michalak, Véronique Quillien, Amandine Etcheverry, Patrick François, Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurochirurgie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Plate-forme transcriptome, Université de Rennes 1 (UR1), Service de génétique moléculaire et génomique, Centre Paul Papin, CRLCC Paul Papin, Service de Biologie, CRLCC Eugène Marquis (CRLCC), Nutrition, croissance et cancer (U 1069) (N2C), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, Laboratoire de Pathologie Cellulaire et Tissulaire, Service de neuro-chirurgie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Biochimie et Biologie Moléculaire, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), The Grand Ouest Glioma Project Network, Cancéropôle Grand Ouest, 44093 Nantes, France, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), Service de Génétique moléculaire et Génomique [CHU Rennes], CHU Pontchaillou [Rennes], Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), De Villemeur, Hervé, Service de neurochirurgie [CHU Angers], and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Stromal cell, Microenvironment, Angiogenesis, Biopsy, Population, Translational study, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Separation, Biology, Primary cultures, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Imaging, Three-Dimensional, [SDV.CAN] Life Sciences [q-bio]/Cancer, Stroma, Glioma, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], RNA, Messenger, education, Cancer-associated fibroblasts, 030304 developmental biology, Oligonucleotide Array Sequence Analysis, 0303 health sciences, education.field_of_study, Brain Neoplasms, Gene Expression Profiling, Cell Differentiation, medicine.disease, Flow Cytometry, Magnetic Resonance Imaging, 3. Good health, Neuroepithelial cell, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Phenotype, Neurology, Oncology, 030220 oncology & carcinogenesis, Cancer-Associated Fibroblasts, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Glioblastoma
Abstract: International audience; Glioblastoma (GB) is a highly infiltrative tumor recurring in 90% of cases within a few centimeters of the resection cavity, even in cases of complete tumor resection and adjuvant chemo/radiotherapy. This observation highlights the importance of understanding this special zone of brain tissue surrounding the tumor. It is becoming clear that the nonneoplastic stromal compartment of most solid cancers plays an active role in tumor proliferation, invasion, and metastasis. Very little information, other than that concerning angiogenesis and immune cells, has been collected for stromal cells from GB. As part of a translational research program, we have isolated a new stromal cell population surrounding GB by computer-guided stereotaxic biopsies and primary culture. We named these cells GB-associated stromal cells (GASCs). GASCs are diploid, do not display the genomic alterations typical of GB cells, and have phenotypic and functional properties in common with the cancer-associated fibroblasts (CAFs) described in the stroma of carcinomas. In particular, GASCs express markers associated with CAFs such as fibroblast surface protein, alpha-smooth muscle actin (α-SMA), and platelet-derived growth factor receptor-beta (PDGFRβ). Furthermore, GASCs have a molecular expression profile different from that of control stromal cells derived from non-GB peripheral brain tissues. GASCs were also found to have tumor-promoting effects on glioma cells in vitro and in vivo. The isolation of GASCs in a tumor of neuroepithelial origin was unexpected, and further studies are required to determine their potential as a target for antiglioma treatment.
Published: 2012

27. Histopathologic and Ultrastructural Features and Claudin Expression in Papillary Tumors of the Pineal Region

Author: Dominique Figarella-Branger, Isabelle Pommepuy, Emmanuèle Lechapt-Zalcman, Sophie Michalak, Caroline Salon, Ingrid Kratzer, Alexandre Vasiljevic, Anne Jouvet, Jean-Louis Kemeny, Michèle Bernier, Pascale Varlet, Emmanuelle Uro-Coste, Ghislaine Saint-Pierre, Jacques Champier, Fabrice Chrétien, Anne-Marie Bergemer Fouquet, Audrey Rousseau, Karima Mokthari, Catherine Miquel, Isabelle Quintin Roué, Jean-François Ghersi-Egea, Michelle Fèvre Montange, Brain Dynamics and Cognition Team (U1028 Inserm - UMR5292 CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brain Dynamics and Cognition (DYCOG), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Biology, Pathology and Forensic Medicine, Tight Junctions, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Biomarkers, Tumor, Humans, Papillary tumors of the pineal region, Claudin, PTPRS, Child, ComputingMilieux_MISCELLANEOUS, Aged, Ultrasonography, Papillary tumor, Middle Aged, medicine.disease, Carcinoma, Papillary, Neuroepithelial cell, 030220 oncology & carcinogenesis, Child, Preschool, Claudins, Pinealoma, Surgery, Choroid plexus, Female, Anatomy, 030217 neurology & neurosurgery, Subcommissural organ
Abstract: Neuroepithelial papillary tumor of the pineal region (PTPR) has been defined as a distinct entity that is increasingly being recognized, with 96 cases now reported. This tumor shares morphologic features with both ependymomas and choroid plexus tumors. PTPR is characterized by an epithelial-like growth pattern in which the vessels are covered by layers of tumor cells forming perivascular pseudorosettes. These tumors exhibit various combinations of papillary and solid architecture, making the differential diagnosis of PTPR difficult to establish. We report the detailed description of the histopathologic features of a large series of PTPRs from 20 different centers and distinguish 2 subgroups of tumors with either a striking papillary growth pattern or a papillary and solid growth pattern. We highlight the findings that PTPRs have unusual vessels with multiple lumina and frequently show detachment of the border of the tumoral cells from the vascular wall. The 2 PTPR subgroups present similar clinical characteristics and immunophenotypes. We confirmed and extended the results of previous ultrastructural studies on the presence of intercellular junctions at the apical part of tumoral cells. The expression of the tight junction proteins claudin-1, claudin-2, and claudin-3 was investigated by immunohistochemistry. Claudin-1 and claudin-3, but not claudin-2, were expressed in PTPRs and in the fetal subcommissural organ, potentially the origin of this tumor. In contrast, all 3 claudins were expressed in choroid plexus papillomas. Claudin expression may help in the diagnosis of PTPRs and can be used in combination with other markers, such as CK18, NCAM, E-cadherin, MAP-2, and Kir 7.1.
Published: 2012

28. Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD

Author: Jérôme Boursier, Christine Cavaro-Menard, Julien Chaigneau, Vincent Roullier, Yves Gallois, Sandrine Bertrais, Marie Christine Rousselet, Paul Calès, Frédéric Oberti, Yves Deugnier, Fabrice Lainé, I. Hubert, Jeremy Sandrini, Gilles Hunault, Nina Dib, Sophie Michalak, Christophe Aubé, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Département d'hépato-gastroentérologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), image, Laboratoire d'Ingéniérie des Systèmes Automatisés (LISA), Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Fer et Métabolismes, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], CHU Pontchaillou [Rennes]-CHU Pontchaillou [Rennes], Laboratoire de Pathologie Cellulaire et Tissulaire, Unité d'Investigation Clinique, Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], and Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Liver Cirrhosis, Male, nonalcoholic fatty liver disease, Cirrhosis, Chronic liver disease, MESH: Epidemiologic Methods, Gastroenterology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Fibrosis, MESH: Metabolic Syndrome X, Nonalcoholic fatty liver disease, Medicine, MESH: Fatty Liver, MESH: Middle Aged, Biopsy, Needle, Fatty liver, Middle Aged, liver morphometry, 3. Good health, Liver, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, MESH: Liver Cirrhosis, Algorithms, Adult, medicine.medical_specialty, MESH: Biopsy, Needle, Hepatitis, Viral, Human, MESH: Algorithms, metabolic syndrome, liver steatosis, 03 medical and health sciences, Internal medicine, Image Interpretation, Computer-Assisted, Humans, MESH: Liver Diseases, Alcoholic, Liver Diseases, Alcoholic, MESH: Hepatitis, Viral, Human, Hepatitis, MESH: Humans, Hepatology, business.industry, fibrosis, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, MESH: Male, Fatty Liver, Steatosis, Metabolic syndrome, Epidemiologic Methods, business, MESH: Female, MESH: Image Interpretation, Computer-Assisted, MESH: Liver
Abstract: International audience; BACKGROUND AND AIM: We carried out morphometric measurements of steatosis to evaluate relationships between steatosis degree and other liver lesions or metabolic syndrome components in nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: We developed an algorithm to measure steatosis area. Two hundred and fourteen patients with NAFLD were included in derivation (10) and validation (204) groups. Controls consisted of patients who were steatosis-free (12), patients with chronic hepatitis C (188), and patients with alcoholic chronic liver disease (94). RESULTS: Accuracy of steatosis area was considered as good or very good in at least 72% of cases by three pathologists. Steatosis areas were as follows: NAFLD = 10.3 ± 9.7%, virus = 2.4 ± 3.1%, alcohol = 7.8 ± 8.2% (P
Published: 2011

29. A not so solitary fibrous tumor of the liver

Author: Paul Calès, Christophe Aubé, Jérôme Boursier, H.-D. Fournier, C. Singeorzan, C. Brochard, L. Laccourreye, Sophie Michalak, Département Polluants et Santé, Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Cytokines : structure, signalisation et prolifération tumorale, and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_specialty, Solitary fibrous tumor, Pathology, Liver tumor, [SDV]Life Sciences [q-bio], Skull Base Neoplasms, Metastasis, Lesion, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, Medicine, Right hepatic lobe, Neoplasm, Humans, Histological examination, Neck pain, business.industry, Liver Neoplasms, Gastroenterology, General Medicine, Middle Aged, medicine.disease, 3. Good health, Radiography, 030220 oncology & carcinogenesis, Solitary Fibrous Tumors, 030211 gastroenterology & hepatology, Radiology, medicine.symptom, business
Abstract: International audience; SummarySolitary fibrous tumor (SFT) is a rare neoplasm. Liver parenchyma is a rare location of SFT and, in this case, it usually follows a benign course. We report here the case of a 54-year-old man who presented a large SFT tumor of the right hepatic lobe. The tumor was surgically resected. Local recurrence occurred 6years later as a 15cm diameter liver tumor. Histological examination of the resected lesion showed features of an aggressive form of SFT. Two years later, the patient presented with complaints of neck pain and ensuing examinations revealed a tumor of the cranial base. A new surgical resection was performed and histological examination confirmed a metastasis of the SFT. Few weeks later, the patient presented an irreducible psoitis due to an iliac bone metastasis. He died within 1month.
Published: 2010

30. The combination of a blood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis

Author: Victor de Ledinghen, Anselme Konate, A Sawadogo, Marie Christine Rousselet, Frédéric Oberti, Paul Calès, Isabelle Fouchard-Hubert, Jérôme Boursier, Véronique Le Tallec, Nina Dib, Taoufiq Dakka, Sophie Michalak, Yves Gallois, Julien Vergniol, Naïma Amrani, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Physiopathologie du cancer du foie, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, FIBROMETER, Biopsy, [SDV]Life Sciences [q-bio], Chronic liver disease, Sensitivity and Specificity, Gastroenterology, sequential diagnostic algorithm, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Blood test, Prospective Studies, Aged, liver fibrosis, Hematologic Tests, Hepatology, medicine.diagnostic_test, Receiver operating characteristic, business.industry, FibroTest, FibroMeter, cirrhosis, blood fibrosis test, Middle Aged, medicine.disease, 3. Good health, liver stiffness, Liver, 030220 oncology & carcinogenesis, Liver biopsy, Elasticity Imaging Techniques, Female, 030211 gastroenterology & hepatology, business, ultrasonographic elastometry, Algorithms, non-invasive diagnosis
Abstract: International audience; Background and aims: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm. Methods: Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included. Five blood fibrosis tests were evaluated: APRI, FIB-4, Hepascore, Fibrotest and FibroMeter. The reference was fibrosis Metavir staging. Results: Diagnosis of significant fibrosis (Metavir F≥2). The most accurate synchronous combination was FibroMeter+LSE, which provided a significantly higher area under the receiver operating characteristic curve (0.892) than LSE alone (0.867, P=0.011) or Fibrometer (0.834, P
Published: 2009

31. FibroMeters: a family of blood tests for liver fibrosis

Author: Françoise Lunel, L. Macchi, Paul Calès, Nina Dib, Julien Chaigneau, A. Chevailler, Frédéric Oberti, Yves Gallois, Gilles Hunault, Sophie Michalak, Marie-Christine Rousselet, Valérie Moal, Jérôme Boursier, I. Hubert, A. Sawadogo, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Ischémie - Reperfusion en transplatation rénale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'hématologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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 hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Liver Cirrhosis, Alcoholic liver disease, Pathology, area of fibrosis, Cirrhosis, [SDV]Life Sciences [q-bio], Gastroenterology, Maladie alcoolique du foie, FibroMètres, 0302 clinical medicine, Fibrosis, Tests sanguins, Medicine, liver fibrosis, 0303 health sciences, FibroMeterss, Hematologic Tests, medicine.diagnostic_test, Fatty liver, General Medicine, Hepatitis C, 3. Good health, Aire de fibrose, Stéatose métabolique, Co-infection VIH, Liver biopsy, Predictive value of tests, 030211 gastroenterology & hepatology, Viral hepatitis, medicine.medical_specialty, Metavir, Hépatite chronique virale, Diagnostic non invasif, Fibrose hépatique, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, NAFLD, Humans, Chronic viral hepatitis, 030304 developmental biology, Blood tests, HIV co-infection, business.industry, cirrhosis, Cirrhose, Reproducibility of Results, medicine.disease, Non invasive diagnosis, business, Hepatic fibrosis, Biomarkers
Abstract: International audience; SummaryFibroMeters are blood tests for liver fibrosis with several specificities: two main diagnostic targets (fibrosis stage and area of fibrosis); adaptation to specific causes; and results confirmed by an expert system. Thus, FibroMeters comprise six different tests: one for staging and one for quantitation of liver fibrosis in each of the three main causes of chronic liver disease—chronic viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). FibroMeters display a high overall diagnostic accuracy and are the only tests to correctly classify 100% of HCV patients without fibrosis or with cirrhosis. They have 90% predictive values in a higher proportion of patients than with other usual blood tests. A 90% correct classification is available in 100% of HCV patients with the following reliable diagnostic intervals: F0/1, F1/2, F2±1, F3±1. In real-life conditions, the reproducibility of FibroMeters is higher than that of liver biopsy or ultrasonographic elastometry. FibroMeters are robust tests with the most stable diagnostic performance across different centers. Optional tests are also available, such as a specific one for cirrhosis, which has a diagnostic accuracy of 93.0% (AUROC: 0.92) and a 100% positive predictive value for diagnosis of HCV cirrhosis. Determination by FibroMeters of the area of fibrosis – the only direct, non-invasive, quantitative measurement of liver fibrosis – are especially useful for following-up cirrhosis as it correlates well with clinical events. FibroMeters are also very accurate in HVB or HIV-HCV co-infected patients. The tests specific for ALD and NAFLD also have a high diagnostic accuracy (AUROCs: 0.96 and 0.94, respectively, for significant fibrosis).
Published: 2008

32. Hemodynamic effects of the early and long-term administration of propranolol in rats with intrahepatic portal hypertension

Author: Sophie Michalak, Frédéric Moal, J. Wang, Yves Gallois, Nicolas Régenet, Paul Calès, Frédéric Oberti, Jérôme Roux, Lionel Fizanne, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: medicine.medical_specialty, Mean arterial pressure, Portal venous pressure, [SDV]Life Sciences [q-bio], Cardiac index, Hemodynamics, Propranolol, Placebo, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Heart rate, Medicine, Carbon Tetrachloride, 030304 developmental biology, Collateral venous circulation, 0303 health sciences, Hepatology, business.industry, Splenorenal shunt, Bile duct ligation, medicine.disease, 3. Good health, Endocrinology, Cardiology, Portal hypertension, 030211 gastroenterology & hepatology, Original Article, Surgery, business, Colorectal Surgery, medicine.drug
Abstract: International audience; Background and aims The aims of this study were to evaluate a preventive effect on collateral venous circulation of long-term administration of propranolol in intrahepatic portal hypertensive rats. Methods Eighty-six Sprague–Dawley rats were allocated to two models of hepatic fibrosis, bile duct-ligated (BDL) induced and carbon tetrachloride (CCl4) induced. Each model was divided into two groups: one receiving placebo and the other propranolol (75 mg kg−1 d−1). Mean arterial pressure (MAP), heart rate (HR), portal pressure (PP), cardiac index (CI), vascular systemic resistance, and splenorenal shunt blood flow (SRS-BF) were measured in anesthetized rats. Results In the BDL model, no significant hemodynamic changes were observed in the propranolol group compared with the placebo group. In CCl4-induced rats, HR (390 ± 50 vs. 329 ± 51 beats/min, P = .001), CI (44 ± 11 vs. 34 ± 10 ml/min, P = .004), PP (15.4 ± 3.0 vs. 13.4 ± 1.9 mmHg, P = .045), and SRS-BF (1.4 ± 1.1 vs. 1.0 ± 1.0 ml/min, P = .047) were significantly lower in the propranolol group. Conclusions This study showed that propranolol has a significant hemodynamic effect only in the CCl4 model and suggested a model-dependent effect of propranolol.
Published: 2008

33. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC

Author: Emmanuelle Jeannot, Charles Balabaud, Yannick Bacq, Jeanne Tran Van Nhieu, Emmanuelle Leteurtre, Paulette Bioulac-Sage, Dominique Wendum, Lucille Mellottee, Denis Castaing, Laurence Chiche, Jessica Zucman-Rossi, Christian Partensky, Elie Serge Zafrani, Sandra Rebouissou, Christophe Laurent, Monique Fabre, Valérie Paradis, Jean-Yves Scoazec, Sophie Michalak, Pierre Laurent-Puig, Catherine Guettier, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Saint-André, Toxicologie Moleculaire (U490), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, The authors thank Leigh Pascoe for critical reading of the manuscript. We thank all the other participants to the GENTHEP (Groupe d'e´tude Ge´ne´tique des Tumeurs He´patiques) network: Michel Beaugrand, Jordi Bruix, Christine Bellanne´e-Chantelot, Jacques Belghiti, Jean Fre´de´ric Blanc, Pascal Bourlier, Paul Cale`s, Chen Liu, Marie Pierre Chenard-Neu, Daniel Cherqui, Vale´rie Costes, Thong Dao, Daniel Dhumeaux, Amar Paul Dhillon, Je´roˆme Dumortier, Olivier Ernst, Dominique Franco, Fre´de´ric Gauthier, Jean Gugenheim, Emmanuel Jacquemin, Daniel Jaeck, Brigitte Le Bail, Se´- bastien Lepreux, Anne de Muret, Fre´de´ric Oberti, Danielle Pariente, Franc¸ois Paye, Franc¸ois-Rene´ Pruvost, Alberto Quaglia, Pierre Rousselot, Antonio Sa Cunha, Marie Christine Saint-Paul, Jean Saric, Pierre Rousselot, Anne Rullier, Janick Selves, Nathalie Sturm. We thank the technicians from the CEPH, Fondation Jean Dausset for their help in sequencing and all the clinicians that referred the patients., Zucman-Rossi, Jessica, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), 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-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, CHU Bordeaux [Bordeaux]-Hôpital Saint -André, Toxicologie Moleculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, Pathology, MESH : Liver Neoplasms, MESH : Retrospective Studies, MESH: beta Catenin, MESH : Aged, MESH : Genotype, Malignant transformation, MESH: Genotype, MESH: Adenoma, Liver Cell, 0302 clinical medicine, MESH: Liver Neoplasms, MESH : Female, Hepatocyte Nuclear Factor 1-alpha, MESH: Carcinoma, Hepatocellular, beta Catenin, MESH: Aged, MESH: Middle Aged, Liver Neoplasms, MESH : Adult, Middle Aged, 3. Good health, MESH : Phenotype, Phenotype, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, MESH : Hepatocyte Nuclear Factor 1-alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Female, 030211 gastroenterology & hepatology, MESH : Mutation, MESH : Carcinoma, Hepatocellular, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, MESH: Mutation, Adolescent, Genotype, Adenoma, MESH : Male, Biology, MESH: Phenotype, Adenoma, Liver Cell, 03 medical and health sciences, MESH : Adenoma, Liver Cell, MESH : Adolescent, medicine, Carcinoma, Humans, MESH : Middle Aged, MESH: Hepatocyte Nuclear Factor 1-alpha, Pathological, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, Hepatology, MESH : Humans, MESH: Retrospective Studies, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatocellular adenoma, MESH : beta Catenin, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases, MESH: Male, Mutation, Inflammatory Hepatocellular Adenoma, Steatosis, MESH: Female
Abstract: Hepatocellular adenomas are benign tumors that can be difficult to diagnose. To refine their classification, we performed a comprehensive analysis of their genetic, pathological, and clinical features. A multicentric series of 96 liver tumors with a firm or possible diagnosis of hepatocellular adenoma was reviewed by liver pathologists. In all cases, the genes coding for hepatocyte nuclear factor 1alpha (HNF1alpha) and beta-catenin were sequenced. No tumors were mutated in both HNF1alpha and beta-catenin enabling tumors to be classified into 3 groups, according to genotype. Tumors with HNF1alpha mutations formed the most important group of adenomas (44 cases). They were phenotypically characterized by marked steatosis (P < 10(-4)), lack of cytological abnormalities (P < 10(-6)), and no inflammatory infiltrates (P < 10(-4)). In contrast, the group of tumors defined by beta-catenin activation included 13 lesions with frequent cytological abnormalities and pseudo-glandular formation (P < 10(-5)). The third group of tumors without mutation was divided into two subgroups based on the presence of inflammatory infiltrates. The subgroup of tumors consisting of 17 inflammatory lesions, resembled telangiectatic focal nodular hyperplasias, with frequent cytological abnormalities (P = 10(-3)), ductular reaction (P < 10(-2)), and dystrophic vessels (P = .02). In this classification, hepatocellular carcinoma associated with adenoma or borderline lesions between carcinoma and adenoma is found in 46% of the beta-catenin-mutated tumors whereas they are never observed in inflammatory lesions and are rarely found in HNF1alpha mutated tumors (P = .004). In conclusion, the molecular and pathological classification of hepatocellular adenomas permits the identification of strong genotype-phenotype correlations and suggests that adenomas with beta-catenin activation have a higher risk of malignant transformation.
Published: 2006

34. Stereotaxic implantation of 5-fluorouracil-releasing microspheres in malignant glioma.

Author: Philippe Menei, Eric Jadaud, Nathalie Faisant, Michèle Boisdron-Celle, Sophie Michalak, Dominique Fournier, Manuel Delhaye, and Jean-Pierre Benoit
Published: 2004

35. Respective roles of porto-septal fibrosis and centrilobular fibrosis in alcoholic liver disease.

Author: Sophie Michalak, Marie-Christine Rousselet, Pierre Bedossa, Christophe Pilette, Daniel Chappard, Frédéric Oberti, Yves Gallois, and Paul Calès
Subjects: ALCOHOLIC liver diseases, RETROPERITONEAL fibrosis, COMPLICATIONS of alcoholism, LIVER biopsy, HEPATITIS, PATHOLOGICAL physiology
Abstract: In alcoholic liver disease, fibrosis classically begins around the centrilobular veins, while portal tract fibrosis is described as inconstant and septal fibrosis is a late event. The aim of this study was to compare the roles of centrilobular fibrosis (CLF) and portal tract/septal fibrosis (PTF) especially in alcoholic chronic liver disease. One hundred and sixty patients with alcoholic chronic liver disease and 83 controls with viral chronic hepatitis were included. The PTF score, derived from the Metavir score, CLF and the area of fibrosis, assessed by image analysis, were evaluated on liver biopsies in addition to blood markers of fibrosis. The correlation between the PTF score and the area of fibrosis was higher in alcoholic liver disease (r = 0.87, p < 10-4) than in viral chronic hepatitis (r = 0.66, p < 10-4). The PTF score correlated with the CLF score (r = 0.92, p < 10-4), serum hyaluronate (r = 0.76, p < 10-4), and the prothrombin index (r = -0.77, p < 10-4). Multiple regression analyses showed that the area of fibrosis was explained only by the PTF score and not by the CLF score. PTF appears more frequent than CLF in alcoholic chronic liver disease, suggesting that PTF may precede CLF. PTF is more responsible for the amount of fibrosis than CLF. The results of this study also validate the use of the Metavir fibrosis score in alcoholic chronic liver disease. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
Published: 2003
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35 results on '"Sophie Michalak"'

1. Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma

2. Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests

3. Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease

4. Supratentorial non-RELA, ZFTA-fused ependymomas: a comprehensive phenotype genotype correlation highlighting the number of zinc fingers in ZFTA-NCOA1/2 fusions

5. Albendazole-related Loa Loa encephalopathy

6. Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C

7. Reliability Criteria of Two-Dimensional Shear Wave Elastography: Analysis of 4277 Measurements in 788 Patients

8. Albendazole-related Loa Loa encephalopathy

9. Comparison of extracellular and hepatobiliary MR contrast agents for the diagnosis of small HCCs

10. Adenocarcinoma of the oesophagogastric junction Siewert II: An oesophageal cancer better cured with total gastrectomy

11. New sequential combinations of non-invasive fibrosis tests provide an accurate diagnosis of advanced fibrosis in NAFLD

12. Suspicious liver nodule in chronic liver disease: Usefulness of a second biopsy

13. Macrotrabecular-massive hepatocellular carcinoma: A distinctive histological subtype with clinical relevance

14. BRAF-V600E immunohistochemistry in a large series of glial and glial-neuronal tumors

15. A Developmental and Sequenced One-to-One Educational Intervention for Autism Spectrum Disorder: A Randomized Single-Blind Controlled Trial

16. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease

17. Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease

18. Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy

19. Automated morphometry provides accurate and reproducible virtual staging of liver fibrosis in chronic hepatitis C

20. Primary biliary cirrhosis: proposal for a new simple histological scoring system

21. Screening for significant chronic liver disease by using three simple ultrasound parameters

22. P17.03POST-OPERATIVE EXCLUSIVE CHEMOTHERAPY WITH PCV FOR ANAPLASTIC OLIGODENDROGLIOMA: A RETROSPECTIVE STUDY OF 35 CONFIRMED CASES

23. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

24. Immunohistochemical markers on needle biopsies are helpful for the diagnosis of focal nodular hyperplasia and hepatocellular adenoma subtypes

25. Quantitative proteomic Isotope-Coded Protein Label (ICPL) analysis reveals alteration of several functional processes in the glioblastoma

26. Isolation of a new cell population in the glioblastoma microenvironment

27. Histopathologic and Ultrastructural Features and Claudin Expression in Papillary Tumors of the Pineal Region

28. Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD

29. A not so solitary fibrous tumor of the liver

30. The combination of a blood test and Fibroscan improves the non-invasive diagnosis of liver fibrosis

31. FibroMeters: a family of blood tests for liver fibrosis

32. Hemodynamic effects of the early and long-term administration of propranolol in rats with intrahepatic portal hypertension

33. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC

34. Stereotaxic implantation of 5-fluorouracil-releasing microspheres in malignant glioma.

35. Respective roles of porto-septal fibrosis and centrilobular fibrosis in alcoholic liver disease.

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35 results on '"Sophie Michalak"'

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