Targeting mTOR dependency in pancreatic cancer
Conclusions KRAS PTEN tumours are uniquely responsive to mTOR inhibition. Targeted anti-mTOR therapies may offer clinical benefit in subsets of human PDAC selected based on genotype, that are dependent on mTOR signalling. Thus, the genetic signatures of human tumours could be used to direct pancreatic cancer treatment in the future. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Morran, D. C., Wu, J., Jamieson, N. B., Mrowinska, A., Kalna, G., Karim, S. A., Au, A. Y. M., Scarlett, C. J., Chang, D. K., Pajak, M. Z., Australian Pancreatic Cancer Genome Initiative (APGI), Oien, K. A., McKay, C. J., Carter, C. R., Gillen, G., Champio Tags: Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research

Effect of magnesium supplementation and depletion on the onset and course of acute experimental pancreatitis
Background and objective High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis. Methods Pancreatic acini were incubated with up to 10 mM magnesium; [Ca2+]i (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Schick, V., Scheiber, J. A., Mooren, F. C., Turi, S., Ceyhan, G. O., Schnekenburger, J., Sendler, M., Schwaiger, T., Omercevic, A., Brandt, C. v. d., Fluhr, G., Domschke, W., Kruger, B., Mayerle, J., Lerch, M. M. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Gene expression profiling-derived immunohistochemistry signature with high prognostic value in colorectal carcinoma
Conclusions Our immunohistochemistry signature may be clinically practical for personalised prediction of CRC prognosis. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Chang, W., Gao, X., Han, Y., Du, Y., Liu, Q., Wang, L., Tan, X., Zhang, Q., Liu, Y., Zhu, Y., Yu, Y., Fan, X., Zhang, H., Zhou, W., Wang, J., Fu, C., Cao, G. Tags: Colon cancer Source Type: research

Source of dietary fibre and diverticular disease incidence: a prospective study of UK women
Background Previous prospective studies have found the incidence of intestinal diverticular disease decreased with increasing intakes of dietary fibre, but associations by the fibre source are less well characterised. We assessed these associations in a large UK prospective study of middle-aged women. Methods and findings During 6 (SD 1) years follow-up of 690 075 women without known diverticular disease who had not changed their diet in the last 5 years, 17 325 were admitted to hospital or died with diverticular disease. Dietary fibre intake was assessed using a validated 40-item food questionnaire and rem...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Crowe, F. L., Balkwill, A., Cairns, B. J., Appleby, P. N., Green, J., Reeves, G. K., Key, T. J., Beral, V., Abbott, Armstrong, Benson, Black, Brown, Bull, Callaghan, Canoy, Chadwick, Chivenga, Crossley, Ewart, Ewart, Fletcher, Floud, Gathani, Gerrard, Goo Tags: Open access Colon Source Type: research

Interaction between preprandial and postprandial rectal sensory and motor abnormalities in IBS
Conclusions Meal intake affects rectal sensorimotor function in IBS and health. Importantly, the rectal tone responses to a high-caloric meal are different between patients with IBS and controls, as well as between hypersensitive and normosensitive patients with IBS. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Tornblom, H., Van Oudenhove, L., Tack, J., Simren, M. Tags: Neurogastroenterology Source Type: research

{beta}7 integrins are required to give rise to intestinal mononuclear phagocytes with tolerogenic potential
Conclusions Mice lacking β7 integrins in the innate immune compartment are more susceptible to intestinal inflammation, which is correlated with a requirement of β7 integrins to reconstitute gut mononuclear phagocytes with tolerogenic potential. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Villablanca, E. J., De Calisto, J., Torregrosa Paredes, P., Cassani, B., Nguyen, D. D., Gabrielsson, S., Mora, J. R. Tags: Gut immunity Source Type: research

Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation
Conclusions A 24-month treatment course with risedronate 35 mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: van Bodegraven, A. A., Bravenboer, N., Witte, B. I., Dijkstra, G., van der Woude, C. J., Stokkers, P. C. M., Russel, M. G., Oldenburg, B., Pierik, M., Roos, J. C., van Hogezand, R. A., Dik, V. K., Oostlander, A. E., Netelenbos, J. C., van de Langerijt, L. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer
Conclusions Patients with IBD with a history of cancer are at increased risk of developing any (new or recurrent) cancer, with a predominant incidence of new cancers. Treatment with immunosuppressants has no overall major impact per se on this risk. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Beaugerie, L., Carrat, F., Colombel, J.-F., Bouvier, A.-M., Sokol, H., Babouri, A., Carbonnel, F., Laharie, D., Faucheron, J.-L., Simon, T., de Gramont, A., Peyrin-Biroulet, L., for the CESAME Study Group Tags: Inflammatory bowel disease Source Type: research

Ten day sequential versus 10 day modified bismuth quadruple therapy as empirical firstline and secondline treatment for Helicobacter pylori in Chinese patients: an open label, randomised, crossover trial
Conclusions Ten day sequential and modified bismuth quadruple therapies are both highly effective as empirical firstline therapies for H pylori in Chinese patients. ClinicalTrials.gov NCT 01760824 (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Liu, K. S. H., Hung, I. F. N., Seto, W. K. W., Tong, T., Hsu, A. S. J., Lam, F. Y. F., But, D. Y. K., Wong, S. Y., Leung, W. K. Tags: Helicobacter pylori Source Type: research

Genetic variation in the lymphotoxin-{alpha} (LTA)/tumour necrosis factor-{alpha} (TNF{alpha}) locus as a risk factor for idiopathic achalasia
Conclusions Our study provides evidence for rs1799724 at the LTA/TNFα locus as a susceptibility factor for idiopathic achalasia. Additional studies are needed to dissect which genetic variants in the LTA/TNFα locus are disease-causing and confirm other variants as potential susceptibility factors for achalasia. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Wouters, M. M., Lambrechts, D., Becker, J., Cleynen, I., Tack, J., Vigo, A. G., Ruiz de Leon, A., Urcelay, E., Perez de la Serna, J., Rohof, W., Annese, V., Latiano, A., Palmieri, O., Mattheisen, M., Mueller, M., Lang, H., Fumagalli, U., Laghi, L., Zanino Tags: Oesophagus Source Type: research

A rare cause of dysphagia in a young Caucasian man
Clinical presentation A 23-years-old Caucasian man was admitted to our institution for progressive weight loss and dysphagia. His past medical history was apparently unremarkable, including his laboratory tests, except for the presence of uninvestigated episodes of dysphagia he had since childhood. The patient performed a barium oesophagogram which showed oesophageal dysmotility (figure 1A) followed by an oesophagogastroduodenoscopy, demonstrating the presence of multiple tubular duplications of the middle and distal third of the oesophagus, with a contextual stricture of the lumen crossable only with ultrathin endoscope (...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Cecinato, P., Zecchini, R., Cavina, M., Ragazzi, M., Sassatelli, R. Tags: Editor ' s quiz: GI snapshot Source Type: research

Hospital and surgeon volume in relation to long-term survival after oesophagectomy: systematic review and meta-analysis
Conclusions This meta-analysis demonstrated better long-term survival (even after excluding early deaths) after oesophagectomy with high-volume surgery, and surgeon volume might be more important than hospital volume. These findings support centralisation with fewer surgeons working at large centres. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Brusselaers, N., Mattsson, F., Lagergren, J. Tags: Oesophageal cancer Oesophagus Source Type: research

A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease
Conclusions Based on a multidisciplinary approach, items relevant for fistula management were identified and algorithms on diagnosis and treatment of pCD were developed. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Gecse, K. B., Bemelman, W., Kamm, M. A., Stoker, J., Khanna, R., Ng, S. C., Panes, J., van Assche, G., Liu, Z., Hart, A., Levesque, B. G., D'Haens, G., Bouguen, Sturm, Laharie, Feagan, Sandborn, Sands, Colombel, for the World Gastroenterology Organization Tags: Crohn's disease, Editor's choice Guidelines Source Type: research

Use of a preclinical model of pancreas cancer to identify potential candidates for rapalogue therapy
The oft-repeated statistics are dismal: pancreatic ductal adenocarcinoma (PDA) has only a 6% 5-year survival rate that has not changed significantly in 30 years and the vast majority of PDA patients perish within 6 months of diagnosis. Several possible reasons contribute to these grim results. PDA is difficult to detect, it is recalcitrant to most targeted treatments and conventional therapies only have a modest effect on survival. Compared with other cancers, PDA was revealed to be remarkably genetically homogenous with 95% or more of PDA harbouring oncogenic mutations in the Kras gene,1 generating hope that fin...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Takeuchi, K. K., Crawford, H. C. Tags: Commentary Source Type: research

{alpha}4{beta}7 integrin: beyond T cell trafficking
Integrins and chemokines are critical for immune cell recruitment to tissue under homeostatic and pathological conditions.1 The heterodimeric integrin α4β7, expressed on T cells, specifies the recruitment of T cells to the intestinal mucosa upon its interaction with its ligand MAdCAM-1.1 Intestinal specificity is imprinted in T cells via upregulation of α4β7 integrin upon their interaction with CD103 dendritic cells (DCs) in the mesenteric lymph node when their cognate antigen is being presented by the major histocompatibility complex.2 The vitamin A metabolite retinoic acid (RA), produced by CD103 DC...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Kempster, S. L., Kaser, A. Tags: Commentary Source Type: research

In sero veritas: what serum markers teach us about HCV infection of primary human hepatocytes
HCV has chronically infected an estimated number of 160 million individuals worldwide.1 In the course of 10–20 years of persistent infection, approximately 20% of these patients are at risk of developing severe liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma.2 Besides the ability to establish chronic infection, the pronounced genetic variability of HCV and the diverse course of chronic infection ranging from relatively benign to exacerbating liver disease are hallmarks of hepatitis C. Moreover, response to classical antiviral treatment based on pegylated interferon alpha (PEG-IFN-&alpha...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Pietschmann, T. Tags: Commentary Source Type: research

Fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: better 5-year survival or artifactual result of research methodology?
Among the primary hepatic malignant tumours, hepatocellular carcinoma (HCC) is the most common, while fibrolamellar carcinoma is a rare variant of HCC. In a recent article by Eggert et al examining the epidemiology of fibrolamellar hepatocellular carcinoma (fHCC) in the USA from 2000 to 2010,1 the authors reported better 5-year survival for fHCC compared with conventional HCC similar to previous studies.2–7 Even though several previous studies have advocated that fHCC is less aggressive than conventional HCC, some recent studies have failed to confirm the observation of a better outcome in fHCC.8–11 Cirrhosis i...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Njei, B. Tags: Commentary Source Type: research

p21Waf1/Cip1 revisited: oncogenic function in hepatocellular carcinoma
p21Waf1/Cip1 was originally identified as a crucial p53-regulated factor that controls cyclin-dependent kinase 1/2 (CDK1/CDK2) activities and sequesters proliferating cell nuclear antigen. The physical interaction with CDKs prevents binding and phosphorylation of retinoblastoma proteins which is required for the release of E2F transcription factors important for S-phase progression. Consequently, p21Waf1/Cip1 was classified as a tumour suppressor that interferes with cell cycle progression and DNA synthesis.1 2 Meanwhile, it has been realised that p21Waf1/Cip1 has a plethora of alternative functions in apoptosis, different...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Goldenberg, D., Eferl, R. Tags: Commentary Source Type: research

New insights into intestinal secretion
Apart from malabsorption and intestinal barrier dysfunction (via a ‘leak-flux’ mechanism), diarrhoea may reflect active ion secretion in the small intestine and/or colon. In recent years, our understanding about intestinal secretory mechanisms has increased enormously. Important new findings are (1) chloride, bicarbonate and potassium may be secreted simultaneously, but via independent transport processes and (2) movement of a specific ion across cell membranes may occur via several types of channels selective for that ion, but differing in their molecular structure and intrinsic biophysical properties. Additio...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Schulzke, J. D., Siegmund, B., Gunzel, D. Tags: Commentary Source Type: research

What is the role for bisphosphonates in IBD?
IBD has been associated with an increased risk of osteoporosis and fracture.1 Current guidelines suggest using dual energy x-ray absorptiometry (DXA) to identify IBD patients with osteoporosis as candidates for possible therapy, but focus on IBD patients with established risk factors (ie, postmenopausal women, hypogonadal men or long term (≥3 month) users of glucocorticoids). While the exact role and timing for DXA in IBD is not fully defined, it is even more controversial to consider when therapeutic intervention is indicated. Among the possible choices, bisphosphonates remain the most commonly prescribed pharmaco...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Bernstein, C. N., Targownik, L. E., Leslie, W. D. Tags: Commentary Source Type: research

Highlights from this issue
LuminalA global consensus report on fistulising peri-anal Crohn's disease The World Congress of Gastroenterology 2013, held in Shanghai, called for the development of state-of-the-art, evidence based views for designated areas of gastroenterology. An expert consensus group was formed and developed a consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease (pCD), based on best available evidence (see page 1381). The group carried out a systematic literature review; statements were formed, discussed and approved in multiple rounds. Consensus was defined as at least 80...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: El-Omar, E., Gerbes, A., Grady, W. Tags: Digest Source Type: research

Correction
This article is now Open Access, under CC-BY NC license. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Tags: Corrections Source Type: research

Correction
Schernhammer ES, Giovannucci E, Kawasaki T, et al. Dietary folate, alcohol and B vitamins in relation to LINE-1 hypomethylation in colon cancer. Gut 2010;59:794–9. In table 3, the correct unit for energy-adjusted daily vitamin B12 intake was "mg per day", but not "g per day". This error did not alter the results (other than unit), interpretation of the data or the authors' conclusions. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Tags: Corrections Source Type: research

Mevalonate kinase deficiency and IBD: shared genetic background
Dear editor, We read with interest the article entitled ‘Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease’ written by Uhlig1 and published by Gut. The study, describing the very early onset of intestinal inflammation in several orphan monogenic diseases, aimed at determining the presence of a link between the IBD-like phenotype shown by these rare diseases and the intestinal inflammation seen in typical IBD. The IBD aetiology is multifactorial: at present, genome-wide association studies have identified 163 susceptibility loci associate...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Bianco, A. M., Girardelli, M., Vozzi, D., Crovella, S., Kleiner, G., Marcuzzi, A. Tags: Open access PostScript Source Type: research

Beyond scoring: a modern histological assessment of chronic hepatitis should include tissue angiogenesis
We read with great interest the leading article by Rosselli et al1 which offers a contemporary perspective to the clinical issue of interpreting progression (and regression) of chronic liver diseases (CLDs). We fully agree with the view that the histological scoring of fibrosis is a reductive approach to the assessment of CLDs, as it does not fully reflect the complex events involved in the progression to cirrhosis. As suggested by Rosselli et al, a more insightful morphological analysis of liver biopsy should consider other important factors contributing to disease progression/regression, and possibly to cancer developmen...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Guido, M., Pizzi, M., Sacerdoti, D., Giacomelli, L., Rugge, M., Bolognesi, M. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, nlrp6–/– mice were less able to clear infection by Citrobacter rodentium, although they did display the same robust mucosal immune response as wild-type mice, including expression of inflammasome-related cytokines... (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Update on basic and clinical aspects of eosinophilic oesophagitis
This article focuses exclusively on basic and clinical insights of EoE gathered during the last few years. Regarding aetiopathogenesis it has become clear that EoE is a food-triggered disease with milk and wheat as the dominant culprit food categories. However, it is still debated whether a disturbed mucosal integrity allowing allergens to cross the mucosal barrier, or changes in wheat and milk manufacturing might induce these inflammatory responses. Furthermore, basic science and clinical studies have accordingly confirmed that a chronic eosinophilic inflammation leads to a remodelling of the oesophagus with micro- and ma...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Straumann, A., Schoepfer, A. Tags: GUT Recent advances in clinical practice, Editor's choice Source Type: research

Ex vivo culture of the intestinal epithelium: strategies and applications
Limited pools of resident adult stem cells are critical effectors of epithelial renewal in the intestine throughout life. Recently, significant progress has been made regarding the isolation and in vitro propagation of fetal and adult intestinal stem cells in mammals. It is now possible to generate ever-expanding, three-dimensional epithelial structures in culture that closely parallel the in vivo epithelium of the intestine. Growing such organotypic epithelium ex vivo facilitates a detailed description of endogenous niche factors or stem-cell characteristics, as they can be monitored in real time. Accordingly, this techno...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Leushacke, M., Barker, N. Tags: Drugs: gastrointestinal system, GUT Recent advances in basic science Source Type: research

Atypical gastric bleeding in a 55-year-old man, beyond the scope of treatment?
Clinical presentation A 55-year-old man was admitted with a 3-week history of haematemesis with abdominal and back pain. He had a background of severe alcohol related pancreatitis 5 years previously and possible gastric varices. At presentation he was shocked (pulse 127, blood pressure 94/68, lactate 7.1 mM). Haemoglobin 8.0 g/L, platelet count 447 000/µL, liver function tests and coagulation were normal. After resuscitation and antibiotics he underwent oesophagogastroduodenoscopy in the Intensive Care Unit. Fresh blood was seen in the stomach, with thrombus adherent to an ulcer on a raised area o...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Bird, T. G., Harrison, E. M., Ireland, H. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy
Conclusions Hh signalling promotes transition of quiescent hepatic stellate cells to fibrogenic MF, some of which become progenitors that regenerate the liver epithelial compartment after PH. Hence, scarring is a component of successful liver regeneration. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Swiderska-Syn, M., Syn, W. K., Xie, G., Kruger, L., Machado, M. V., Karaca, G., Michelotti, G. A., Choi, S. S., Premont, R. T., Diehl, A. M. Tags: Hepatology Source Type: research

HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability
Objective Little is known about the long-term clinical outcome and durability of HBsAg seroclearance following nucleos(t)ide analogue (NUC) therapy in patients with chronic hepatitis B (CHB). Design During a median follow-up period of 6 years (33 567 patient-years) of 5409 CHB patients who were initially treated with lamivudine or entecavir, a total of 110 achieved HBsAg seroclearance (0.33% annual seroclearance rate) and were included in this study. Results Baseline alanine aminotransferase (ALT) level>5 times of upper limit of normal was associated with higher probability of HBsAg seroclearance (HR 1.80, p
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Kim, G.-A., Lim, Y.-S., An, J., Lee, D., Shim, J. H., Kim, K. M., Lee, H. C., Chung, Y.-H., Lee, Y. S., Suh, D. J. Tags: Hepatitis B, Hepatic cancer Hepatology Source Type: research

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis
Conclusions A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Huang, W., Booth, D. M., Cane, M. C., Chvanov, M., Javed, M. A., Elliott, V. L., Armstrong, J. A., Dingsdale, H., Cash, N., Li, Y., Greenhalf, W., Mukherjee, R., Kaphalia, B. S., Jaffar, M., Petersen, O. H., Tepikin, A. V., Sutton, R., Criddle, D. N. Tags: Pancreas and biliary tract, Pancreatitis, Open access Source Type: research

Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-{alpha} activation
Conclusions Because of its lack of toxicity, its ability in reducing inflammation and its selective PPARα action, PEA might be an innovative molecule to broaden pharmacological strategies against UC. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Esposito, G., Capoccia, E., Turco, F., Palumbo, I., Lu, J., Steardo, A., Cuomo, R., Sarnelli, G., Steardo, L. Tags: Ulcerative colitis Colon Source Type: research

Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism
Objective Intestinal permeability and psychological stress have been implicated in the pathophysiology of IBD and IBS. Studies in animals suggest that stress increases permeability via corticotropin-releasing hormone (CRH)-mediated mast cell activation. Our aim was to investigate the effect of stress on intestinal permeability in humans and its underlying mechanisms. Design Small intestinal permeability was quantified by a 2 h lactulose–mannitol urinary excretion test. In a first study, 23 healthy volunteers were subjected to four different conditions: control; indomethacin; public speech and anticipation of el...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Vanuytsel, T., van Wanrooy, S., Vanheel, H., Vanormelingen, C., Verschueren, S., Houben, E., Salim Rasoel, S., Toth, J., Holvoet, L., Farre, R., Van Oudenhove, L., Boeckxstaens, G., Verbeke, K., Tack, J. Tags: Neurogastroenterology Source Type: research

A novel urine peptide biomarker-based algorithm for the prognosis of necrotising enterocolitis in human infants
Conclusions Ensemble modelling combining clinical parameters with biomarker analysis dramatically improves our ability to identify the population at risk for developing progressive NEC. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Sylvester, K. G., Ling, X. B., Liu, G. Y., Kastenberg, Z. J., Ji, J., Hu, Z., Peng, S., Lau, K., Abdullah, F., Brandt, M. L., Ehrenkranz, R. A., Harris, M. C., Lee, T. C., Simpson, J., Bowers, C., Moss, R. L. Tags: Necrotizing enterocolitis Source Type: research

A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis
Objective Bacteria play an important role in the onset and perpetuation of intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's disease (CD), in which dysbiosis has been better characterised, in ulcerative colitis (UC), only small cohorts have been studied and showed conflicting data. Therefore, we evaluated in a large cohort if the microbial signature described in CD is also present in UC, and if we could characterise predominant dysbiosis in UC. To assess the functional impact of dysbiosis, we quantified the bacterial metabolites. Design The predominant microbiota from 127 UC patients and 87 ag...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., Ballet, V., Claes, K., Van Immerseel, F., Verbeke, K., Ferrante, M., Verhaegen, J., Rutgeerts, P., Vermeire, S. Tags: Crohn's disease, Ulcerative colitis Inflammatory bowel disease Source Type: research

Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease
Conclusions Our results reveal the UPS, and CYLD specifically, as an important contributor to IBD pathogenesis, which is favoured by both genetic and microbial factors. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Cleynen, I., Vazeille, E., Artieda, M., Verspaget, H. W., Szczypiorska, M., Bringer, M.-A., Lakatos, P. L., Seibold, F., Parnell, K., Weersma, R. K., Mahachie John, J. M., Morgan-Walsh, R., Staelens, D., Arijs, I., De Hertogh, G., Muller, S., Tordai, A., Tags: Crohn's disease Inflammatory bowel disease Source Type: research

The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab
Objective To characterise the temporal evolution of antibodies to infliximab (ATI). Design Prospective observational study of infliximab-treated patients with inflammatory bowel disease between 2009 and 2012. Interventions Trough levels of infliximab and ATI were measured before each infusion by anti- ELISA. Patients were monitored for disease activity by clinical activity indexes and for dose-intensification or infliximab cessation. The occurrence of transient ATI disappearing spontaneously without intervention was recorded separately. Results 125 patients were included (98 Crohn's disease, 27 ulcerative colitis, media...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Ungar, B., Chowers, Y., Yavzori, M., Picard, O., Fudim, E., Har-Noy, O., Kopylov, U., Eliakim, R., Ben-Horin, S., on behalf of ABIRISK consortium Tags: Crohn's disease, Ulcerative colitis Inflammatory bowel disease Source Type: research

miR-141 Regulates colonic leukocytic trafficking by targeting CXCL12{beta} during murine colitis and human Crohn's disease
Conclusions This study showed that the pathway of miR-141 targeting CXCL12β is a possible mechanism underlying inflammatory cell trafficking during colonic inflammation process. Inhibiting colonic CXCL12β expression and blocking colonic immune cell recruitment by using miRNA precursors represents a promising approach that may be valuable for CD treatment. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Huang, Z., Shi, T., Zhou, Q., Shi, S., Zhao, R., Shi, H., Dong, L., Zhang, C., Zeng, K., Chen, J., Zhang, J. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia
Conclusions Our preclinical results validate DES as a promising therapeutic approach to diabetes and obesity, which offers reversibility, low risk, low invasiveness and triple benefits including fat mass loss, glucose and lipid metabolism improvement which mechanistically may involve increased villus growth in the upper gut. (Source: Gut)
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Habegger, K. M., Al-Massadi, O., Heppner, K. M., Myronovych, A., Holland, J., Berger, J., Yi, C.-X., Gao, Y., Lehti, M., Ottaway, N., Amburgy, S., Raver, C., Muller, T. D., Pfluger, P. T., Kohli, R., Perez-Tilve, D., Seeley, R. J., Tschop, M. H. Tags: Small bowel Source Type: research

Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis
Background and aims Acid-suppressive medications, particularly proton pump inhibitors (PPIs), may decrease the risk of oesophageal adenocarcinoma (OAC) in patients with Barrett's oesophagus (BO). We performed a systematic review with meta-analysis of studies evaluating the association between acid-suppressive medications (PPIs and histamine receptor antagonists (H2RAs)) and risk of OAC or high-grade dysplasia (BO-HGD) in patients with BO. Methods We performed a systematic search of multiple electronic databases and conference proceedings up to June 2013 to identify studies reporting the association between use of acid-sup...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Singh, S., Garg, S. K., Singh, P. P., Iyer, P. G., El-Serag, H. B. Tags: Gastrointestinal hormones, Oesophageal cancer Oesophagus Source Type: research

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology
A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; qual...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Ludvigsson, J. F., Bai, J. C., Biagi, F., Card, T. R., Ciacci, C., Ciclitira, P. J., Green, P. H. R., Hadjivassiliou, M., Holdoway, A., van Heel, D. A., Kaukinen, K., Leffler, D. A., Leonard, J. N., Lundin, K. E. A., McGough, N., Davidson, M., Murray, J. Tags: Open access, Coeliac disease Guidelines Source Type: research

HBsAg seroclearance with NUCs: rare but important
A major breakthrough in the treatment of chronic hepatitis B virus (HBV) infection had been the approval of nucleoside and nucleotide analogues (NUCs), which inhibit the reverse transcriptase and, thereby, dramatically suppress HBV DNA. To date, five NUCs are approved for the treatment of hepatitis B, with tenofovir and entecavir considered as first-line therapy.1 Treatment with tenofovir or entecavir leads to viral suppression below the limit of detection in almost 100% of adherent patients.1 This is associated with regression of fibrosis or even cirrhosis.2 3 Furthermore, some studies suggest a lowered incidence of hepat...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Cornberg, M., Honer zu Siederdissen, C. Tags: Commentary Source Type: research

An apPEAling new therapeutic for ulcerative colitis?
IBD includes Crohn's Disease and ulcerative colitis (UC), which are multifaceted chronic inflammatory conditions. Their aetiology is thought to involve the interaction of genetic, immunological and environmental factors. Current therapeutics have not succeeded in eliminating the burden of these diseases. Some are associated with side effects, which themselves can cause discomfort for the patient, leading to a decrease in compliance and a return to the status quo prior to medication. In addition, the cost of current therapeutics is very high.1 All of these considerations require the development of less toxic, better tolerat...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: McKernan, D. P., Finn, D. P. Tags: Commentary Source Type: research

More than a gut feeling: predicting surgical necrotising enterocolitis
Despite recent advances in neonatal practice, necrotising enterocolitis (NEC) remains the most common and devastating gastrointestinal emergency in premature infants. In fact, as more extremely premature infants survive, the incidence appears to be increasing worldwide.1 Severe NEC is characterised by coagulative necrosis of the distal ileum and proximal colon with clinical presentation ranging from abdominal distension, pneumatosis intestinalis, frank blood in stools, intestinal gangrene, bowel perforation, sepsis and shock. Approximately 9000 infants develop NEC in the USA each year and mortality rates range from 10%&nda...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Weitkamp, J.-H. Tags: Commentary Source Type: research

Roseburia hominis: a novel guilty player in ulcerative colitis pathogenesis?
Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) or ulcerative colitis (UC) comprise the two most common forms of intestinal inflammation characterised by a chronic relapsing disease course. The aetiology of both disorders has still not yet been identified. Whereas it has been elegantly demonstrated in many studies in the last years that genetic factors are crucially involved, other so-called environmental factors are much less well defined.1 In recent years evidence was accumulating that the gut microbiota and its manipulation might constitute one of those relevant ‘environmental’ factors. ...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Tilg, H., Danese, S. Tags: Commentary Source Type: research

Chemokines in colitis: microRNA control
Huang et al1 identified and tested the role of a specific microRNA (miRNA) in the pathogenesis of IBD. The study of microRNAs is a burgeoning field within epigenetics. These small non-coding RNAs mediate translation-level repression of protein expression by binding to the 3' -untranslated region of specific messenger RNA transcripts. In the innate and adaptive immune response, miRNAs play an important role in negative regulation of inflammatory conditions in the intestine. Inflammatory regulators such as IL-6, tumor necrosis factor (TNF) and toll-like receptors have been shown to induce miRNA expression in both acute and c...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Roy, I., Veldkamp, C. T., Volkman, B. F., Dwinell, M. B. Tags: Commentary Source Type: research

Duodenal exclusion devices: promising tools in treating obesity and type 2 diabetes
The prevalence of obesity and type 2 diabetes is increasing worldwide at an alarming rate. As of 2008, the worldwide prevalence of type 2 diabetes was estimated to be approximately 9% of the global adult population.1 While pharmacotherapeutic options for the treatment of type 2 diabetes are expanding, patients suffering from type 2 diabetes continue to experience a significantly higher risk of developing comorbidities such as cardiovascular disease, kidney disease and cancer.2 Therefore, the development of new therapeutic modalities for the treatment of obesity and type 2 diabetes is crucial. Bariatric surgery is currently...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: Cummings, B. P. Tags: Commentary Source Type: research

Highlights from this issue
Acid suppression and Barrett's oesophagus: what do we really know? Although widely believed, the data supporting the premise that suppression of hydrochloric acid exposure to the oesophagus decreases the risk of oesophageal adenocarcinoma is inconsistent at best. In addition, it is known that bile acids may play a role in the formation of Barrett's oesophagus and oesophageal cancer, which would mean medicines like proton pump inhibitors (PPI) may not affect cancer formation in the oesophagus. This led Singh and colleagues to perform a systematic review with meta-analysis of studies evaluating the association between acid-s...
Source: Gut - July 8, 2014 Category: Gastroenterology Authors: El-Omar, E., Gerbes, A., Grady, W., Rosch, T. Tags: Digest Source Type: research

Increased {kappa}-opioid receptor expression and function during chronic visceral hypersensitivity
In a recent article in Gut, Hughes et al1 identified distinct patterns of immune dysfunction in IBS patients compared with healthy subjects. In particular, they showed that peripheral blood mononuclear cell (PBMC) supernatants from healthy subjects inhibited colonic afferents in a μ-opioid receptor (MOR)-mediated manner. These findings correlated with β-endorphin from T lymphocytes providing an important MOR-mediated antinociceptive influence in the healthy gut.2 Intriguingly, these inhibitory effects were lost with PBMC supernatants from constipation-predominant IBS patients suggesting a loss of MOR-mediated inhib...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Hughes, P. A., Castro, J., Harrington, A. M., Isaacs, N., Moretta, M., Hicks, G. A., Urso, D. M., Brierley, S. M. Tags: PostScript Source Type: research