Gut

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

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...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

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...

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...