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Anthony Dohan, Benoit Gallix, Boris Guiu, Karine Le Malicot, Caroline Reinhold, Philippe Soyer, Jaafar Bennouna, Francois Ghiringhelli, Emilie Barbier, Valérie Boige, Julien Taieb, Olivier Bouché, Eric François, Jean-Marc Phelip, Christian Borel, Roger Faroux, Jean-Francois Seitz, Stéphane Jacquot, Meher Ben Abdelghani, Faiza Khemissa-Akouz, Dominique Genet, Jean Louis Jouve, Yves Rinaldi, Françoise Desseigne, Patrick Texereau, Etienne Suc, Come Lepage, Thomas Aparico, Christine Hoeffel
PURPOSE: The objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders. METHODS: This study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed...
May 17, 2019: Gut
Chuan-Guo Guo, Ka Shing Cheung, Feifei Zhang, Esther W Chan, Lijia Chen, Ian Ck Wong, Wai K Leung
OBJECTIVE: The risk of GI bleeding (GIB) in aspirin users after Helicobacter pylori (HP) eradication remains poorly defined. We characterised the incidences and temporal trends of hospitalisations for all GIB in aspirin users after HP eradication therapy. DESIGN: Based on a territory-wide health database, we identified all patients who had received the first course of clarithromycin-based triple therapy between 2003 and 2012. Patients were divided into three cohorts according to aspirin use: new users (commenced after HP eradication), chronic users (commenced before and resumed after HP eradication) and non-users...
May 17, 2019: Gut
Fanny Er Vuik, Stella Av Nieuwenburg, Marc Bardou, Iris Lansdorp-Vogelaar, Mário Dinis-Ribeiro, Maria J Bento, Vesna Zadnik, María Pellisé, Laura Esteban, Michal F Kaminski, Stepan Suchanek, Ondřej Ngo, Ondřej Májek, Marcis Leja, Ernst J Kuipers, Manon Cw Spaander
OBJECTIVE: The incidence of colorectal cancer (CRC) declines among subjects aged 50 years and above. An opposite trend appears among younger adults. In Europe, data on CRC incidence among younger adults are lacking. We therefore aimed to analyse European trends in CRC incidence and mortality in subjects younger than 50 years. DESIGN: Data on age-related CRC incidence and mortality between 1990 and 2016 were retrieved from national and regional cancer registries...
May 16, 2019: Gut
Rui Sun, Matija Hedl, Clara Abraham
OBJECTIVE: The interleukin (IL)23 pathway contributes to IBD pathogenesis and is being actively studied as a therapeutic target in patients with IBD. Unexpected outcomes in these therapeutic trials have highlighted the importance of understanding the cell types and mechanisms through which IL23 regulates immune outcomes. How IL23 regulates macrophage outcomes and the consequences of the IL23R R381Q IBD-protective variant on macrophages are not well defined; macrophages are key players in IBD pathogenesis and inflammation...
May 16, 2019: Gut
Ola Olén, Johan Askling, Michael C Sachs, Martin Neovius, Karin E Smedby, Anders Ekbom, Jonas F Ludvigsson
OBJECTIVES: To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years. DESIGN: Swedish nationwide register-based cohort study 1964-2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873...
May 15, 2019: Gut
Alasdair J Scott, James L Alexander, Claire A Merrifield, David Cunningham, Christian Jobin, Robert Brown, John Alverdy, Stephen J O'Keefe, Rex Gaskins, Julian Teare, Jun Yu, David J Hughes, Hans Verstraelen, Jeremy Burton, Paul W O'Toole, Daniel W Rosenberg, Julian R Marchesi, James M Kinross
OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis. DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research...
May 15, 2019: Gut
Lena Schleier, Maximilian Wiendl, Karin Heidbreder, Marie-Theres Binder, Raja Atreya, Timo Rath, Emily Becker, Anja Schulz-Kuhnt, Annette Stahl, Lisa Lou Schulze, Karen Ullrich, Simon F Merz, Lea Bornemann, Matthias Gunzer, Alastair J M Watson, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
OBJECTIVE: To study the role of α4β7 integrin for gut homing of monocytes and to explore the biological consequences of therapeutic α4β7 inhibition with regard to intestinal wound healing. DESIGN: We studied the expression of homing markers on monocyte subsets in the peripheral blood and on macrophage subsets in the gut of patients with IBD and controls with flow cytometry and immunohistochemistry. Integrin function was addressed with dynamic adhesion assays and in vivo gut homing assays...
May 15, 2019: Gut
Masahiro Maeda, Hideyuki Takeshima, Naoko Iida, Naoko Hattori, Satoshi Yamashita, Hiroshi Moro, Yoshimi Yasukawa, Kazuhiro Nishiyama, Taiki Hashimoto, Shigeki Sekine, Genichiro Ishii, Atsushi Ochiai, Takeo Fukagawa, Hitoshi Katai, Yoshiharu Sakai, Toshikazu Ushijima
OBJECTIVE: Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, can confer aggressive properties to cancer cells by secreting multiple factors. Their phenotypes are stably maintained, but the mechanisms are not fully understood. We aimed to show the critical role of epigenetic changes in CAFs in maintaining their tumour-promoting capacity and to show the validity of the epigenomic approach in identifying therapeutic targets from CAFs to starve cancer cells. DESIGN: Twelve pairs of primary gastric CAFs and their corresponding non-CAFs (NCAFs) were established from surgical specimens...
May 13, 2019: Gut
Hong Jiang, Xiuting Liu, Brett L Knolhoff, Samarth Hegde, Kyung Bae Lee, Hongmei Jiang, Ryan C Fields, Jonathan A Pachter, Kian-Huat Lim, David G DeNardo
OBJECTIVE: We investigated how pancreatic cancer developed resistance to focal adhesion kinase (FAK) inhibition over time. DESIGN: Pancreatic ductal adenocarcinoma (PDAC) tumours from KPC mice (p48-CRE; LSL-KRasG12D/wt ; p53flox/wt ) treated with FAK inhibitor were analysed for the activation of a compensatory survival pathway in resistant tumours. We identified pathways involved in the regulation of signal transducer and activator of transcription 3 (STAT3) signalling on FAK inhibition by gene set enrichment analysis and verified these outcomes by RNA interference studies...
May 10, 2019: Gut
Oliver Krenkel, Jana Hundertmark, Ali T Abdallah, Marlene Kohlhepp, Tobias Puengel, Tilmann Roth, Diogo Philippini Pontual Branco, Jana C Mossanen, Tom Luedde, Christian Trautwein, Ivan G Costa, Frank Tacke
OBJECTIVE: Bone marrow-derived myeloid cells accumulate in the liver as monocytes and macrophages during the progression of obesity-related non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH). Myeloid cells comprise heterogeneous subsets, and dietary overnutrition may affect macrophages in the liver and bone marrow. We therefore aimed at characterising in depth the functional adaptations of myeloid cells in fatty liver. DESIGN: We employed single-cell RNA sequencing to comprehensively assess the heterogeneity of myeloid cells in the liver and bone marrow during NAFLD, by analysing C57BL/6 mice fed with a high-fat, high-sugar, high-cholesterol 'Western diet' for 16 weeks...
May 10, 2019: Gut
Man Liu, Jingying Zhou, Xiaoyu Liu, Yu Feng, Weiqin Yang, Feng Wu, Otto Ka-Wing Cheung, Hanyong Sun, Xuezhen Zeng, Wenshu Tang, Myth T S Mok, John Wong, Philip Chun Yeung, Paul Bo San Lai, Zhiwei Chen, Hongchuan Jin, Jie Chen, Stephen Lam Chan, Anthony W H Chan, Ka Fai To, Joseph J Y Sung, Minhu Chen, Alfred Sze-Lok Cheng
OBJECTIVE: Hepatocellular carcinoma (HCC), mostly developed in fibrotic/cirrhotic liver, exhibits relatively low responsiveness to immune checkpoint blockade (ICB) therapy. As myeloid-derived suppressor cell (MDSC) is pivotal for immunosuppression, we investigated its role and regulation in the fibrotic microenvironment with an aim of developing mechanism-based combination immunotherapy. DESIGN: Functional significance of MDSCs was evaluated by flow cytometry using two orthotopic HCC models in fibrotic liver setting via carbon tetrachloride or high-fat high-carbohydrate diet and verified by clinical specimens...
May 10, 2019: Gut
Katharina Herzog, Simonetta Bandiera, Sophie Pernot, Catherine Fauvelle, Frank Jühling, Amélie Weiss, Anne Bull, Sarah C Durand, Béatrice Chane-Woon-Ming, Sébastien Pfeffer, Marion Mercey, Hervé Lerat, Jean-Christophe Meunier, Wolfgang Raffelsberger, Laurent Brino, Thomas F Baumert, Mirjam B Zeisel
OBJECTIVE: Infection of human hepatocytes by the hepatitis C virus (HCV) is a multistep process involving both viral and host factors. microRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Given that miRNAs were indicated to regulate between 30% and 75% of all human genes, we aimed to investigate the functional and regulatory role of miRNAs for the HCV life cycle. DESIGN: To systematically reveal human miRNAs affecting the HCV life cycle, we performed a two-step functional high-throughput miRNA mimic screen in Huh7...
May 10, 2019: Gut
Michael Camilleri
The objectives of this review on 'leaky gut' for clinicians are to discuss the components of the intestinal barrier, the diverse measurements of intestinal permeability, their perturbation in non-inflammatory 'stressed states' and the impact of treatment with dietary factors. Information on 'healthy' or 'leaky' gut in the public domain requires confirmation before endorsing dietary exclusions, replacement with non-irritating foods (such as fermented foods) or use of supplements to repair the damage. The intestinal barrier includes surface mucus, epithelial layer and immune defences...
May 10, 2019: Gut
Elsebeth Lynge, Maria Skaalum Petersen, Søren Nymand Lophaven
No abstract text is available yet for this article.
May 10, 2019: Gut
Marina Ruiz de Galarreta, Amaia Lujambio
No abstract text is available yet for this article.
May 10, 2019: Gut
Chang Xu, Wen Fong Ooi, Aditi Qamra, Jing Tan, Benjamin Yan-Jiang Chua, Shamaine Wei Ting Ho, Kakoli Das, Zul Fazreen Adam Isa, Zhimei Li, Xiaosai Yao, Tingdong Yan, Manjie Xing, Kie Kyon Huang, Joyce Suling Lin, Tannistha Nandi, Su Ting Tay, Ming Hui Lee, Angie Lay Keng Tan, Xuewen Ong, Hassan Ashktorab, Duane Smoot, Shang Li, Shyh-Chang Ng, Bin Tean Teh, Patrick Tan
OBJECTIVE: Gastric cancer (GC) is a leading cause of cancer mortality. Previous studies have shown that hepatocyte nuclear factor-4α (HNF4α) is specifically overexpressed in GC and functionally required for GC development. In this study, we investigated, on a genome-wide scale, target genes of HNF4α and oncogenic pathways driven by HNF4α and HNF4α target genes. DESIGN: We performed HNF4α chromatin immunoprecipitation followed by sequencing across multiple GC cell lines, integrating HNF4α occupancy data with (epi)genomic and transcriptome data of primary GCs to define HNF4α target genes of in vitro and in vivo relevance...
May 8, 2019: Gut
Aharon Oren
No abstract text is available yet for this article.
May 3, 2019: Gut
Michael D E Potter, Thomas M Goodsall, Marjorie M Walker, Nicholas J Talley
No abstract text is available yet for this article.
April 30, 2019: Gut
Manuel Zorzi, Marco Zappa
OBJECTIVE: The impact of a screening programme on colorectal cancer (CRC) incidence in its target population depends on several variables, including coverage with invitations, participation rate, positivity rate of the screening test, compliance with an invitation to second-level assessment and endoscopists' sensitivity.We propose a synthetic indicator that may account for all the variables influencing the potential impact of a screening programme on CRC incidence. DESIGN: We defined the 'rate of advanced adenoma on the target population' (AA-TAP) as the rate of patients who received a diagnosis of advanced adenoma within a screening programme, divided by the programme target population...
April 30, 2019: Gut
Joana Torres, Jianzhong Hu, Akihiro Seki, Caroline Eisele, Nilendra Nair, Ruiqi Huang, Leonid Tarassishin, Bindia Jharap, Justin Cote-Daigneault, Qixing Mao, Ilaria Mogno, Graham J Britton, Mathieu Uzzan, Ching-Lynn Chen, Asher Kornbluth, James George, Peter Legnani, Elana Maser, Holly Loudon, Joanne Stone, Marla Dubinsky, Jeremiah J Faith, Jose C Clemente, Saurabh Mehandru, Jean-Frederic Colombel, Inga Peter
BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points...
April 29, 2019: Gut
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