Showing papers by "Stephen Attwood published in 2016"
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University of Bern1, Praxis2, University Hospital of Basel3, Mayo Clinic4, University of North Carolina at Chapel Hill5, Northwestern University6, Floating Hospital for Children7, Cincinnati Children's Hospital Medical Center8, University of California, San Diego9, University of Colorado Denver10, Indiana University11, Icahn School of Medicine at Mount Sinai12, Children's Hospital of Philadelphia13, University Hospital of Lausanne14
TL;DR: In patients with EoE, endoscopic or histologic remission can be identified with only modest accuracy based on symptoms alone, and physicians cannot rely on lack of symptoms to make assumptions about lack of biologic disease activity in adults withEoE.
202 citations
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QIMR Berghofer Medical Research Institute1, Medical Research Council2, Fred Hutchinson Cancer Research Center3, Wellcome Trust Centre for Human Genetics4, University of Hamburg5, University of Bonn6, Otto-von-Guericke University Magdeburg7, Heidelberg University8, University of Cologne9, University of Mainz10, St John of God Health Care11, Durham University12, University of Plymouth13, University of Leicester14, Leicester Royal Infirmary15, University of Oxford16, University of British Columbia17, McMaster University18, Katholieke Universiteit Leuven19, Queen's University Belfast20, Mayo Clinic21, Beckman Research Institute22, University of Texas MD Anderson Cancer Center23, University of Leeds24, Karolinska Institutet25, King's College London26, Ontario Institute for Cancer Research27, Yale University28, University of Southern California29, University of Sheffield30, University of North Carolina at Chapel Hill31, University of California, San Francisco32, University of Cambridge33, Radboud University Nijmegen34, University of Warwick35, University of Central Lancashire36
TL;DR: The meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesphageal adenocarcinoma and revealed new insights into causes of these diseases.
Abstract: Summary Background Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. Methods We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p −8 ). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches—including functional annotation databases and gene-based and pathway-based methods—to identify pathophysiologically relevant cellular mechanisms. Findings Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10 −10 ), MSRA (rs17749155; p=5·2 × 10 −10 ), LINC00208 and BLK (rs10108511; p=2·1 × 10 −9 ), KHDRBS2 (rs62423175; p=3·0 × 10 −9 ), TPPP and CEP72 (rs9918259; p=3·2 × 10 −9 ), TMOD1 (rs7852462; p=1·5 × 10 −8 ), SATB2 (rs139606545; p=2·0 × 10 −8 ), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10 −8 ). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10 −8 ) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p −6 ) belonged to muscle cell differentiation and to mesenchyme development and differentiation. Interpretation Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. Funding US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kroner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.
120 citations
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TL;DR: In a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy, however, patients receiving LARS had significantly greater reductions in 24-hour esophagal acid exposure after 6 months and 5 years.
50 citations
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TL;DR: Endoscopic therapy is preferred over esophagectomy for most patients with HGD or intramucosal adenocarcinoma, and may be applicable to select patients with submucosal tumors.
15 citations
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TL;DR: Magnetic augmentation and electrical stimulation of the lower esophageal sphincter represent promising innovative procedures in the field of anti-reflux surgery.
Abstract: Reflux symptoms are very common, and despite modern medication they are a major cause of disease burden and loss of quality of life worldwide. Laparoscopic anti-reflux surgery is the only current effective alternative but suffers from the risks of long-term side effects. Surgery also suffers variation in standards and outcomes. Magnetic augmentation and electrical stimulation of the lower esophageal sphincter represent promising innovative procedures in the field.
11 citations