Chronicles of a cancer foretold: 35 years of gastric cancer risk assessment
Introduction In 1980, an international group of pathologists and clinicians led by Basil Morson published a critical review entitled Precancerous Conditions and Epithelial Dysplasia in the Stomach.1 This seminal article attempted to merge Eastern and Western pathological experiences in the evaluation of preneoplastic conditions into a systematic approach to the evaluation of gastric precancerous conditions. Thirty-five years after its publication, we pay homage to Professor Morson's team by revisiting their positions in light of the dramatic advances of our understanding of gastric disease that have occurred during this ti...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Rugge, M., Genta, R. M., Graham, D. Y., Di Mario, F., Vaz Coelho, L. G., Kim, N., Malfertheiner, P., Sugano, K., Tsukanov, V., Correa, P. Tags: Open access, Stomach and duodenum, Pancreatic cancer Leading article Source Type: research

The {gamma}-glutamyl transpeptidase-to-platelet ratio as a predictor of liver fibrosis in patients co-infected with HBV and HIV
We read with great interest the recent article by Lemoine et al,1 whereby a novel biochemical-based score was able to accurately estimate liver fibrosis among patients chronically infected with HBV in West Africa. The -glutamyl transpeptidase (GGT)-to-platelet ratio (GPR) has several attractive features, including parameters that are easy to quantify, a straightforward calculation, and more importantly, much lower cost than other non-invasive methods. Yet as the authors conclude, the GPR needs further evaluation in other patient populations and one of utmost importance in resource-limited settings would be those co-infecte...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Boyd, A., Bottero, J., Lacombe, K. Tags: PostScript Source Type: research

High-dose vitamin D supplementation and liver histology in NASH
Dear Editor, We read with great interest the recent study by Beilfuss et al,1 which found vitamin D supplementation to ameliorate transforming growth factor-β-induced fibrogenesis in human hepatic stellate cells. Vitamin D is an important secosteroid hormone with pleiotropic effects that extend well beyond its established regulatory role in calcium and bone homeostasis. These include its recently described involvement in the regulation of immunomodulation, cell proliferation and differentiation, as well as anti-inflammatory and anti-fibrotic properties.2 Subjects with non-alcoholic fatty liver disease (NAFLD) have a l...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Kitson, M. T., Pham, A., Gordon, A., Kemp, W., Roberts, S. K. Tags: PostScript Source Type: research

Authors response: British Society of Gastroenterology guidelines on the diagnosis and management of coeliac disease
We were interested to read the reply to our letter1 by Kurien et al2 but consider that they have not made the case for performing a small bowel biopsy in all patients with coeliac disease (CD) to establish the diagnosis. Further support for our view that duodenal biopsy can be avoided in some patients was recently provided by Tortora et al.3 Kurien et al have also responded to that paper and their two responses suggest a fundamental misunderstanding of the data on which a ‘biopsy avoidance strategy’ is based. It is incorrect of them to assert that their 2008 study4 ‘clearly refutes’ our suggestion. ...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Austin, A. S., Forsyth, J. M., Hill, P. G., Holmes, G. K. T. Tags: PostScript Source Type: research

Safety and efficacy of TACE and gamma knife on hepatocellular carcinoma with portal vein invasion
We read with interest the article by Bruix et al1 in which Sorafenib was regarded as the standard treatment for hepatocellular carcinoma (HCC) patients with portal vein tumour thrombosis (PVTT). However, Sorafenib can only confer 2–3 months of overall survival (OS) benefit2 3 and is inapplicable to many patients due to extensive side effects and high price. Zhong et al4 proposed that liver resection might provide survival benefit to patients with HCC-PVTT with adequate liver function. However, this proposal was based on literature survey, lacked definite patient inclusion criteria and failed to provide informati...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Lu, X.-J., Dong, J., Ji, L.-J., Luo, J.-H., Cao, H.-M., Xiao, L.-X., Zhou, J., Ling, C.-Q. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceInfiltrating lymphocytes initiate necrotising enterocolitis Egan CE, Sodhi CP, Good M, et al. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis. J Clin Invest Published Online First: 21 Dec 2015. doi: 10.1172/JCI83356 Necrotising enterocolitis (NEC) is a severe inflammatory disease of the GI tract that occurs in premature infants and can result in death. The pathogenesis of NEC includes a perturbation of the intestinal barrier leading to an inflammatory infiltration into the intestinal mucosa of the host resulting in systemic sepsis. Most studies on the pathophysiology ...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

GLP-1 based therapies: clinical implications for gastroenterologists
The gut-derived incretin hormone, glucagon-like peptide 1 (GLP-1) lowers postprandial blood glucose levels by stimulating insulin and inhibiting glucagon secretion. Two novel antihyperglycaemic drug classes augment these effects; GLP-1 receptor agonists and inhibitors of the GLP-1 degrading enzyme dipeptidyl peptidase 4. These so called GLP-1 based or incretin based drugs are increasingly used to treat type 2 diabetes, because of a low risk of hypoglycaemia and favourable effect on body weight, blood pressure and lipid profiles. Besides glucose control, GLP-1 functions as an enterogastrone, causing a wide range of GI respo...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Smits, M. M., van Raalte, D. H., Tonneijck, L., Muskiet, M. H. A., Kramer, M. H. H., Cahen, D. L. Tags: GUT Recent advances in clinical practice, Pancreas and biliary tract, Editor's choice, Stomach and duodenum Source Type: research

Association between ultrasonography screening and mortality in patients with hepatocellular carcinoma: a nationwide cohort study
Objective Current guidelines recommend screening for hepatocellular carcinoma (HCC) in high-risk populations. However, the effectiveness of screening in reducing mortality has been challenged. In addition, it is unclear which subgroups benefit most from HCC screening. Design This nationwide cohort study identified a total of 52 823 newly diagnosed HCC patients between 1 January 2002 and 31 December 2007. These HCC patients were classified into the following cohorts according to the time intervals in which they received ultrasonography screening: 0–6 months (6M), 7–12 months (12M), 13–24&nb...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Wu, C.-Y., Hsu, Y.-C., Ho, H. J., Chen, Y.-J., Lee, T.-Y., Lin, J.-T. Tags: Hepatic cancer Hepatology Source Type: research

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches
Conclusions PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Michelotti, G. A., Tucker, A., Swiderska-Syn, M., Machado, M. V., Choi, S. S., Kruger, L., Soderblom, E., Thompson, J. W., Mayer-Salman, M., Himburg, H. A., Moylan, C. A., Guy, C. D., Garman, K. S., Premont, R. T., Chute, J. P., Diehl, A. M. Tags: Pancreas and biliary tract, Open access Hepatology Source Type: research

Ribavirin restores IFN{alpha} responsiveness in HCV-infected livers by epigenetic remodelling at interferon stimulated genes
Conclusions RBV-induced epigenetic changes, leading to decreased ISG expression, restore an IFN-responsive hepatic environment in patients with HCV, which may also prove useful in IFN-free regimens. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Testoni, B., Durantel, D., Lebosse, F., Fresquet, J., Helle, F., Negro, F., Donato, M. F., Levrero, M., Zoulim, F. Tags: Hepatology Source Type: research

Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen
Conclusions These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Zhang, T.-Y., Yuan, Q., Zhao, J.-H., Zhang, Y.-L., Yuan, L.-Z., Lan, Y., Lo, Y.-C., Sun, C.-P., Wu, C.-R., Zhang, J.-F., Zhang, Y., Cao, J.-L., Guo, X.-R., Liu, X., Mo, X.-B., Luo, W.-X., Cheng, T., Chen, Y.-X., Tao, M.-H., Shih, J. W., Zhao, Q.-J., Zhang Tags: Hepatitis B Hepatology Source Type: research

A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling
Conclusions These results advance our understanding of Mek/Erk-driven mTOR activation and its downstream targets in PDAC, and provide a mechanistic rationale for effective therapeutic matching for Aldh1a3-positive PDACs. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Kong, B., Wu, W., Cheng, T., Schlitter, A. M., Qian, C., Bruns, P., Jian, Z., Jäger, C., Regel, I., Raulefs, S., Behler, N., Irmler, M., Beckers, J., Friess, H., Erkan, M., Siveke, J. T., Tannapfel, A., Hahn, S. A., Theis, F. J., Esposito, I., Kle Tags: Pancreas and biliary tract Source Type: research

Increased expression of Solute carrier family 12 member 5 via gene amplification contributes to tumour progression and metastasis and associates with poor survival in colorectal cancer
Objective Using whole genome sequencing, we identified gene amplification of solute carrier family 12 member 5 (SLC12A5) located at 20q13.12 in colorectal cancer (CRC). We analysed its amplification, overexpression, biological effects and prognostic significance in CRC. Design SLC12A5 amplification status was evaluated by fluorescence in situ hybridisation (FISH). The effects of SLC12A5 re-expression or knockdown were determined in proliferation, apoptosis, invasion and metastasis assays. SLC12A5 target genes and related pathways were identified by reporter activity and cDNA microarray analyses. Clinical impact of SLC12A5...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Xu, L., Li, X., Cai, M., Chen, J., Li, X., Wu, W. K. K., Kang, W., Tong, J., To, K.-F., Guan, X.-Y., Sung, J. J. Y., Chan, F. K. L., Yu, J. Tags: Open access, Colon cancer Source Type: research

Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery
Conclusions We show that assessment of ctDNA is a non-invasive, exquisitely specific and highly sensitive approach for monitoring disease load, which has the potential to provide clinically relevant lead times compared with conventional methods. Furthermore, we provide a low-coverage protocol optimised for identifying SSVs with excellent correlation between SSVs identified in tumours and matched metastases. Application of ctDNA analysis has the potential to change clinical practice in the management of CRC. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Reinert, T., Scholer, L. V., Thomsen, R., Tobiasen, H., Vang, S., Nordentoft, I., Lamy, P., Kannerup, A.-S., Mortensen, F. V., Stribolt, K., Hamilton-Dutoit, S., Nielsen, H. J., Laurberg, S., Pallisgaard, N., Pedersen, J. S., Orntoft, T. F., Andersen, C. Tags: Colon cancer Source Type: research

Leadership training to improve adenoma detection rate in screening colonoscopy: a randomised trial
Objective Suboptimal adenoma detection rate (ADR) at colonoscopy is associated with increased risk of interval colorectal cancer. It is uncertain how ADR might be improved. We compared the effect of leadership training versus feedback only on colonoscopy quality in a countrywide randomised trial. Design 40 colonoscopy screening centres with suboptimal performance in the Polish screening programme (centre leader ADR ≤25% during preintervention phase January to December 2011) were randomised to either a Train-Colonoscopy-Leaders (TCLs) programme (assessment, hands-on training, post-training feedback) or feedback only (in...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Kaminski, M. F., Anderson, J., Valori, R., Kraszewska, E., Rupinski, M., Pachlewski, J., Wronska, E., Bretthauer, M., Thomas-Gibson, S., Kuipers, E. J., Regula, J. Tags: Endoscopy, Open access, Colon cancer Source Type: research

A 50-year-old woman with a recurrent oesophageal stricture
Clinical presentation A 50-year-old woman presented with a 4-month history of progressive dysphagia and associated weight loss. Her medical history was unremarkable, and she was not taking any medication. Gastroscopy revealed a tight impassable stricture at 30 cm (figure 1A) confirmed on barium swallow (figure 1B). Biopsies from the stricture were reported as consistent with reflux oesophagitis with no evidence of malignancy. The stricture was dilated revealing a short segment of normal distal oesophagus above a small hiatus hernia. She was started on a high-dose proton pump inhibitor. She re-presented 3 months l...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Akbar, T., Al Badri, A., Gordon, J. N. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Training and competence assessment in GI endoscopy: a systematic review
Conclusions The use of validated VR simulators in the early training setting accelerates the learning of practical skills. Learning curves are valuable for the continuous assessment of performance and are more relevant than threshold numbers. Future research will strengthen these conclusions by evaluating simulation-based as well as patient-based training in GI endoscopy. A complete curriculum with the assessment of competence throughout training needs to be developed for all GI endoscopy procedures. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Ekkelenkamp, V. E., Koch, A. D., de Man, R. A., Kuipers, E. J. Tags: Endoscopy, Colon cancer Source Type: research

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress
Conclusions SIRT1 is a master regulator of ER stress and severity of experimental colitis in case of MDD. It could deserve further interest as a therapeutic target of IBD. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Melhem, H., Hansmannel, F., Bressenot, A., Battaglia-Hsu, S.-F., Billioud, V., Alberto, J. M., Gueant, J. L., Peyrin-Biroulet, L. Tags: Inflammatory bowel disease Source Type: research

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease
Conclusions CD4+CD25+CD127loCD45RA+ Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Canavan, J. B., Scotta, C., Vossenkämper, A., Goldberg, R., Elder, M. J., Shoval, I., Marks, E., Stolarczyk, E., Lo, J. W., Powell, N., Fazekasova, H., Irving, P. M., Sanderson, J. D., Howard, J. K., Yagel, S., Afzali, B., MacDonald, T. T., Hernan Tags: Crohn's disease, Open access Inflammatory bowel disease Source Type: research

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia
Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Schuijt, T. J., Lankelma, J. M., Scicluna, B. P., de Sousa e Melo, F., Roelofs, J. J. T. H., de Boer, J. D., Hoogendijk, A. J., de Beer, R., de Vos, A., Belzer, C., de Vos, W. M., van der Poll, T., Wiersinga, W. J. Tags: Open access Gut microbiota Source Type: research

Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis
Conclusions Although not warranted for the general population, targeting high-risk smokers for serum pepsinogen screening may be a cost-effective strategy to reduce intestinal-type NCGA mortality. (Source: Gut)
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Yeh, J. M., Hur, C., Ward, Z., Schrag, D., Goldie, S. J. Tags: Pancreatic cancer Stomach Source Type: research

Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II)
Objective Focal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barrett's oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up. Herein, we report long-term outcomes of combined ER and RFA for BO (HGD and/or EC) from a single-arm multicentre interventional study. Design In 13 European centres, patients with BO≤12 cm with HGD and/or EC on 2 separate endoscopies were eligible for inclusion. Visible lesions (
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Phoa, K. N., Pouw, R. E., Bisschops, R., Pech, O., Ragunath, K., Weusten, B. L. A. M., Schumacher, B., Rembacken, B., Meining, A., Messmann, H., Schoon, E. J., Gossner, L., Mannath, J., Seldenrijk, C. A., Visser, M., Lerut, T., Seewald, S., ten Kate, F. J Tags: Oesophageal cancer Oesophagus Source Type: research

Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression
Objective Endoscopic surveillance for Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of evidence that it prevents advanced oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the impact of endoscopic BO surveillance on tumour stage and survival of patients with neoplastic progression. Design 783 patients with BO of at least 2 cm were included in a multicentre prospective cohort and followed during surveillance according to the American College of Gastroenterology guidelines. Cases of high-grade dysplasia and OAC were identified duri...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Kastelein, F., van Olphen, S. H., Steyerberg, E. W., Spaander, M. C. W., Bruno, M. J., on behalf of the ProBar-study group, Biermann, Geldof, van der Valk, Borg, Giard, Felt, Meijer, Alderliesten, Heinhuis, Borg, Arends, Kolkman, van Baarlen, Tan, den Har Tags: Oesophageal cancer Oesophagus Source Type: research

A unique monoclonal antibody for therapeutic use against chronic hepatitis B: not all antibodies are created equal
Even though current antiviral treatments based on pegylated interferon, or nucleos(t)ide analogues, in mono or combination therapies, have demonstrated clinical benefit to HBV-infected patients, chronic hepatitis B remains a difficult-to-cure disease. An absolute cure, defined as total elimination of HBV DNA, is currently not achievable, and a functional cure characterised by sustained virological response and HBV surface antigen (HBsAg) clearance off-treatment remains a challenge. Pegylated interferon treatment can lead to a sustained virological response and HBsAg clearance off-treatment in only 3–7% of patients,1 ...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Sureau, C. Tags: Commentary Source Type: research

Gut to lung
Over the last few years, microbiome-focused studies have propelled our understanding of the importance and contribution of several species of gut microbes to immunity and tissue homeostasis.1 Certain microbiota were discovered to essentially shape the intestinal immune system, and changes in the composition of the gut microbiome were found associated with a wide range of diseases, including IBD, metabolic diseases such as diabetes or even neurological disorders like autism.1 These studies laid the foundation for novel therapeutic interventions like microbiome-tailored treatments. As a first, seemingly simple but neverthele...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Knapp, S. Tags: Commentary Source Type: research

Screening for gastric cancer in Western countries
Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide.1 In 2013, 841 000 people worldwide died due to gastric cancer.2 Eastern Asia, Eastern Europe and some regions in Central and South America have the highest incidence of stomach cancer, whereas Western Europe and North America have lower rates. The majority of gastric malignancies are intestinal type adenocarcinomas.3 These cancers develop according to a multistep process, in strong association with Helicobacter pylori infection. This bacterium causes chronic gastritis, which can slowly progress via atrophy, intest...
Source: Gut - March 9, 2016 Category: Gastroenterology Authors: Lansdorp-Vogelaar, I., Kuipers, E. J. Tags: Commentary Source Type: research

Gut microbiota composition associated with stool consistency
Vandeputte et al1 recently reported a strong effect of stool consistency—as measured by the Bristol Stool Scale (BSS)—on the composition of the gut microbiota in 53 healthy females. This work potentially has a large impact on future microbiome studies as it suggests that such studies may need to be corrected for BSS scores. However, the generalisability of their study is not immediately evident as it did not include a replication cohort and was limited to females aged 20–55 years. We analysed gut microbiota in relation to BSS in LifeLines-DEEP, a large population-based cohort.2 From 1126 LifeLines-DE...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Tigchelaar, E. F., Bonder, M. J., Jankipersadsing, S. A., Fu, J., Wijmenga, C., Zhernakova, A. Tags: PostScript Source Type: research

Persistence of endoscopic rectal inflammation in UC treated with infliximab is not linked to ineffective TNF{alpha} downregulation
We reported herein our experience in assessing TNFα mucosal expression and mucosal healing (MH) in UC under treatment with infliximab (IFX). We revised the MH and TNFα expression before and after IFX treatment... (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Tursi, A., Principi, M., Picchio, M., Giorgio, F., Inchingolo, C. D., Piscitelli, D., Ierardi, E. Tags: PostScript Source Type: research

Lead time bias in estimating survival outcomes
We read with great interest the article by Govindarajan et al,1 whose aim was to compare the survival outcomes among patients with postcolonoscopy colon rectal cancer (PCCRC), patients with colonoscopy-detected cancers and those diagnosed with CRC with no prior colonoscopy. In this very well written paper, patients with PCCRC showed inferior survival time than colonoscopy-detected cancers, probably due to more advanced stages at diagnosis, while the worse outcomes were observed in those patients with no recent colonoscopy prior to diagnosis. Despite the undoubted interest, an important methodological issue should be consid...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Facciorusso, A., Ferrusquia, J., Muscatiello, N. Tags: PostScript Source Type: research

Ascitic fluid TREM-1 for the diagnosis of spontaneous bacterial peritonitis
We read with interest the study by Knoop et al1 who reported deleterious effects of antibiotics on the intestinal microflora. This observation should motivate the development of powerful tools for the diagnosis of infections to limit inappropriate antibiotic prescription. Spontaneous bacterial peritonitis (SBP) in patients with cirrhosis2 is a frequent life-threatening complication3 whose diagnosis is based on manual ascitic polymorphonuclear (PMN) count higher than 250 cells/μL.4 However, manual measurement of PMN count is operator dependent, makes quality control difficult and can delay the diagnosis.5 Recently, ...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Ichou, L., Carbonell, N., Rautou, P. E., Laurans, L., Bourcier, S., Pichereau, C., Baudel, J. L., Nousbaum, J. B., Renou, C., Anty, R., Tankovic, J., Maury, E., Guidet, B., Landraud, L., Ait-Oufella, H. Tags: PostScript Source Type: research

Tablet computer-based multimedia enhanced medical training improves performance in gastroenterology and endoscopy board style exam compared with traditional medical education
We read with interest the paper by Ekkelenkamp et al,1 who found that the early use of validated simulators during endoscopy training expedites the learning of procedural skills. Indeed, traditional teaching concepts do not take full advantage of advanced technology. We therefore prospectively investigated the impact of our self-developed custom wireless-enabled tablet PC-based multimedia training and test system on gastrointestinal endoscopy self-assessment program (GESAP®) exam performance. Control and the tablet groups were tested at the beginning and the end of their rotation by administration of all 200 random gen...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Baumgart, D. C., Wende, I., Grittner, U. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceThe role of interleukin-22 in epithelial barrier integrity Lindemans CA, Calafiore M, Mertelsmann AM, et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature 2015;528:560–4. Maintenance and regeneration of the epithelial barrier is critical in preventing infection and inflammation in the GI tract. Innate lymphoid cells (group 3, ILC3s) have immunoregulatory capacity in Crohn's disease by killing commensal stimulated pro-inflammatory T cells, but the role of ILC3s in barrier regeneration is unknown. ILC3s produce interleukin (IL) 17 and IL-22 in mucosal tissues. IL-22 ...
Source: Gut - February 12, 2016 Category: Gastroenterology Tags: JournalScan Source Type: research

Correction
Kong KL, Kwong DLW, Chan TH-M, et al. MicroRNA-375 inhibits tumour growth and metastasis in oesophageal squamous cell carcinoma through repressing insulin-like growth factor 1 receptor. Gut 2012;61:33–42. The representative image of lung (KYSE30-375+) in a SCID mouse in Figure 4 panel D was incorrect. The correct figure is shown below. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Tags: Correction Source Type: research

Proton pump inhibitor-responsive oesophageal eosinophilia: an entity challenging current diagnostic criteria for eosinophilic oesophagitis
Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ‘PPI-responsive oesophageal eosinophilia’ (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammati...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Molina-Infante, J., Bredenoord, A. J., Cheng, E., Dellon, E. S., Furuta, G. T., Gupta, S. K., Hirano, I., Katzka, D. A., Moawad, F. J., Rothenberg, M. E., Schoepfer, A., Spechler, S. J., Wen, T., Straumann, A., Lucendo, A. J., From the PPI-REE Task Force Tags: GUT Recent advances in clinical practice Source Type: research

Guts and Love
We need guts in life When we cry first time  Because birth is the first trial of pain We need guts at work When patients seek for health Because medicine may be a victory or a lie We need guts in the brain When our white coat is in the closet Because vulnerability of life is unveiled We need guts in the heart To love in one second and to feel it like infinity Because love can delete any pain, cure any disease and make us stronger, better than ever (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Danese, S. Tags: Poem Source Type: research

Chimeric antigen receptor (CAR)-engineered T cells redirected against hepatitis C virus (HCV) E2 glycoprotein
Conclusions Clearance of HCV-infected cells is a major therapeutic goal in chronic HCV infection, and adoptive transfer of anti-HCV/E2 CARs-grafted T cells represents a promising new therapeutic tool. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Sautto, G. A., Wisskirchen, K., Clementi, N., Castelli, M., Diotti, R. A., Graf, J., Clementi, M., Burioni, R., Protzer, U., Mancini, N. Tags: Open access Hepatology Source Type: research

Serum viral duplex-linear DNA proportion increases with the progression of liver disease in patients infected with HBV
Conclusions Using a novel PNA-mediated qPCR clamping assay, we first showed that serum dlDNA proportions progressively increased during the development of HBV-related liver diseases. The dlDNA proportion can be regulated by inflammatory cytokines, suggesting an association among inflammation, increased production of HBV dlDNA and development of HCC. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Zhao, X.-L., Yang, J.-R., Lin, S.-Z., Ma, H., Guo, F., Yang, R.-F., Zhang, H.-H., Han, J.-C., Wei, L., Pan, X.-B. Tags: Cirrhosis, Hepatitis B, Hepatic cancer Hepatology Source Type: research

TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro
Conclusions TGR5 is an important mediator of BA-induced cholangiocyte proliferation in vivo and in vitro. Furthermore, TGR5 protects cholangiocytes from death receptor-mediated apoptosis. These mechanisms may protect cholangiocytes from BA toxicity under cholestatic conditions, however, they may trigger proliferation and apoptosis resistance in malignantly transformed cholangiocytes, thus promoting CCA progression. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Reich, M., Deutschmann, K., Sommerfeld, A., Klindt, C., Kluge, S., Kubitz, R., Ullmer, C., Knoefel, W. T., Herebian, D., Mayatepek, E., Häussinger, D., Keitel, V. Tags: Pancreas and biliary tract, Hepatic cancer Hepatology Source Type: research

The acinar regulator Gata6 suppresses KrasG12V-driven pancreatic tumorigenesis in mice
Conclusions We propose that, in the pancreas, Gata6 acts as a tumour suppressor by enforcing acinar cell differentiation, by directly and indirectly repressing ectopic differentiation programmes, and by regulating crucial cancer-related gene expression pathways. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Martinelli, P., Madriles, F., Canamero, M., Pau, E. C.-d. S., Pozo, N. d., Guerra, C., Real, F. X. Tags: Pancreas and biliary tract Source Type: research

MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model
Conclusions Metabolic imaging with hyperpolarised [1-13C]pyruvate enables detection and monitoring of the progression of PCa precursor lesions. Translation of this MRI technique to the clinic has the potential to improve the management of patients at high risk of developing PCa. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Serrao, E. M., Kettunen, M. I., Rodrigues, T. B., Dzien, P., Wright, A. J., Gopinathan, A., Gallagher, F. A., Lewis, D. Y., Frese, K. K., Almeida, J., Howat, W. J., Tuveson, D. A., Brindle, K. M. Tags: Pancreas and biliary tract, Pancreatitis, Open access, Pancreatic cancer Source Type: research

The Thr300Ala variant in ATG16L1 is associated with improved survival in human colorectal cancer and enhanced production of type I interferon
Conclusions The CD-risk allele, Thr300Ala, in ATG16L1 is associated with improved overall survival in human CRC, generating a rationale to genotype ATG16L1 Thr300Ala in patients with CRC. We found that Thr300A alters production of MAVS-dependent type I IFN in CRC cells, providing a mechanism that may influence clinical outcomes. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Grimm, W. A., Messer, J. S., Murphy, S. F., Nero, T., Lodolce, J. P., Weber, C. R., Logsdon, M. F., Bartulis, S., Sylvester, B. E., Springer, A., Dougherty, U., Niewold, T. B., Kupfer, S. S., Ellis, N., Huo, D., Bissonnette, M., Boone, D. L. Tags: Crohn's disease, Open access, Colon cancer Source Type: research

Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation
Conclusions While the interpretation of AM patterns is reproducible, nearly 90% of HV have a pattern that is currently regarded as ‘abnormal’ by AM. Hence, AM is of limited utility for distinguishing between FC and HV. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Grossi, U., Carrington, E. V., Bharucha, A. E., Horrocks, E. J., Scott, S. M., Knowles, C. H. Tags: Constipation Neurogastroenterology Source Type: research

Clinical and endoscopic predictors of cytological dysplasia or cancer in a prospective multicentre study of large sessile serrated adenomas/polyps
Objective The serrated neoplasia pathway accounts for up to 30% of all sporadic colorectal cancers (CRCs). Sessile serrated adenomas/polyps (SSA/Ps) with cytological dysplasia (SSA/P-D) are a high-risk serrated CRC precursor with little existing data. We aimed to describe the clinical and endoscopic predictors of SSA/P-D and high grade dysplasia (HGD) or cancer. Design Prospective multicentre data of SSA/Ps ≥20 mm referred for treatment by endoscopic mucosal resection (September 2008–July 2013) were analysed. Imaging and lesion assessment was standardised. Histological findings were correlated with clinical ...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Burgess, N. G., Pellise, M., Nanda, K. S., Hourigan, L. F., Zanati, S. A., Brown, G. J., Singh, R., Williams, S. J., Raftopoulos, S. C., Ormonde, D., Moss, A., Byth, K., P'Ng, H., McLeod, D., Bourke, M. J., Mahajan, Bettington, Clouston, Dow, Bhathal, Pha Tags: Colon cancer Endoscopy Source Type: research

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology
Conclusions A. muciniphila is associated with a healthier metabolic status and better clinical outcomes after CR in overweight/obese adults. The interaction between gut microbiota ecology and A. muciniphila warrants further investigation. Trial registration number NCT01314690. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Dao, M. C., Everard, A., Aron-Wisnewsky, J., Sokolovska, N., Prifti, E., Verger, E. O., Kayser, B. D., Levenez, F., Chilloux, J., Hoyles, L., MICRO-Obes Consortium, Dumas, M.-E., Rizkalla, S. W., Dore, J., Cani, P. D., Clement, K. Tags: Editor's choice, Press releases Gut microbiota Source Type: research

Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohns disease
Conclusions A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-B pathway in intestinal epithelial cells and to prevent colitis in an animal model. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Quevrain, E., Maubert, M. A., Michon, C., Chain, F., Marquant, R., Tailhades, J., Miquel, S., Carlier, L., Bermudez-Humaran, L. G., Pigneur, B., Lequin, O., Kharrat, P., Thomas, G., Rainteau, D., Aubry, C., Breyner, N., Afonso, C., Lavielle, S., Grill, J. Tags: Inflammatory bowel disease Source Type: research

Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up
Conclusions Histological remission is a target distinct from endoscopic mucosal healing in UC and better predicts lower rates of corticosteroid use and acute severe colitis requiring hospitalisation, over a median of 6 years of follow-up. Our findings support the inclusion of histological indices in both UC clinical trials and practice, towards a target of ‘complete remission’. (Source: Gut)
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Bryant, R. V., Burger, D. C., Delo, J., Walsh, A. J., Thomas, S., von Herbay, A., Buchel, O. C., White, L., Brain, O., Keshav, S., Warren, B. F., Travis, S. P. L. Tags: Inflammatory bowel disease Source Type: research

Detection of precancerous gastric lesions and gastric cancer through exhaled breath
Objectives Timely detection of gastric cancer (GC) and the related precancerous lesions could provide a tool for decreasing both cancer mortality and incidence. Design 968 breath samples were collected from 484 patients (including 99 with GC) for two different analyses. The first sample was analysed by gas chromatography linked to mass spectrometry (GCMS) while applying t test with multiple corrections (p value
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Amal, H., Leja, M., Funka, K., Skapars, R., Sivins, A., Ancans, G., Liepniece-Karele, I., Kikuste, I., Lasina, I., Haick, H. Tags: Stomach and duodenum, Press releases, Pancreatic cancer Source Type: research

An unusual cause of odynophagia
Question A 45-year-old man presented with odynophagia, felt in the region of the upper chest. Upper GI endoscopy was normal and proton pump inhibitor therapy ineffective. Oesophageal function tests showed no reflux on 24 h pH monitoring; manometry revealed ineffective oesophageal motility (low-amplitude peristalsis) thought to explain his symptoms. He re-presented 6 years later with worsening odynophagia; repeat endoscopy showed a 1 cm nodule in the proximal oesophagus at 24 cm from the incisor teeth. Endoscopic biopsies showed features of low-grade adenocarcinoma of mucinous/tubular type. He was referr...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Moreman, C., Budihal, S., Ubhi, S., de Caestecker, J., Richards, C. J. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

A randomised, double-blind trial comparing budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis
Objective To investigate the efficacy and safety of two different budesonide formulations (effervescent tablet for orodispersible use (BET) and viscous suspension (BVS)) with different daily dosages for short-term treatment of eosinophilic oesophagitis (EoE). Design Adults with active EoE (n=76) randomly received 14 days’ treatment with either BET 2x1 mg/day (BET1, n=19) or BET 2x2 mg/day (BET2, n=19), or BVS 2x5 mL (0.4 mg/mL)/day (BVS, n=19) or placebo (n=19) in a double-blind, double-dummy fashion, with a 2-week follow-up. Primary end point was histological remission (mean of
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Miehlke, S., Hruz, P., Vieth, M., Bussmann, C., von Arnim, U., Bajbouj, M., Schlag, C., Madisch, A., Fibbe, C., Wittenburg, H., Allescher, H. D., Reinshagen, M., Schubert, S., Tack, J., Müller, M., Krummenerl, P., Arts, J., Mueller, R., Dilger, K. Tags: Open access Oesophagus Source Type: research

Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines
The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet...
Source: Gut - February 12, 2016 Category: Gastroenterology Authors: Veitch, A. M., Vanbiervliet, G., Gershlick, A. H., Boustiere, C., Baglin, T. P., Smith, L.-A., Radaelli, F., Knight, E., Gralnek, I. M., Hassan, C., Dumonceau, J.-M. Tags: Endoscopy, Open access Guidelines Source Type: research