Apicobasal polarity and Ras/Raf/MEK/ERK signalling in cancer
Many glandular epithelia such as the GI tract are composed of a sheet of cells polarised along their apicobasal axes with the apical membrane facing the lumen of the tube and the basolateral membrane binding to neighbouring cells and the basal extracellular matrix (ECM). Generation of these two membrane domains with distinct cellular macromolecular contents (including proteins and lipids) provides the basic building blocks that support tissue architecture and their various functions.1 The apicobasal polarisation of epithelial cells is a complex and multistage programme controlled by a network of proteins and lipids. It is ...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Peng, J., Gassama-Diagne, A. Tags: Commentary Source Type: research

Putting the Wnt up colon cancer
If there is one cancer signalling pathway that Gut readers should be comfortable with, it is the Wnt pathway. Central to this pathway is the adenomatous polyposis coli (APC) gene responsible for familial adenomatous polyposis. Identification of the APC gene in 1991 heralded the start of an ongoing period of exponential growth in our understanding of the molecular basis of cancer, particularly of the large bowel. Clinicians can perhaps be forgiven for finding the ever-expanding list of genes and interacting pathways with their inaccessible names and acronyms daunting. For many, the paper in this issue by Elvira Bakker and c...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Hawinkels, L. J., Hardwick, J. C. Tags: Commentary Source Type: research

Telomere length and pancreatic cancer risk: breaking down the evidence
Telomeres, located at the ends of chromosomes and composed of a protein complex and tandem repeats of TTAGGG nucleotides, function to protect chromosomes from end-to-end fusions, breakage and degradation in dividing cells. Due to the inherent nature of DNA replication (‘the end replication problem’) and oxidative stress—telomeres gradually shorten with age. This has been demonstrated cross-sectionally in most tissues examined including the pancreas, and especially in cells with extensive proliferation (eg, leucocytes).1 2 Cells with critically short telomeres enter growth arrest, or senescence, and may re...
Source: Gut - May 12, 2017 Category: Gastroenterology Authors: Duell, E. J. Tags: Commentary Source Type: research

Assessment of faecal microbial transfer in irritable bowel syndrome with severe bloating
We read with interest the work by Halmos et al1 in which they describe the effects of dietary FODMAP (Fermentable Oligo-, Di- and Mono- saccharides And Polyols) restriction in patients with IBS on the intestinal microbiota. They showed that low FODMAP intake was associated with reduced total bacterial and lower relative abundance of butyrate-producing Clostridium cluster XIVa, changes that are generally considered unfavourable.2 Therefore, they discourage long-term dietary FODMAP restriction, a suggestion also supported by the recent work of McIntosh and colleagues who noticed unfavourable changes in both microbiota and me...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Holvoet, T., Joossens, M., Wang, J., Boelens, J., Verhasselt, B., Laukens, D., van Vlierberghe, H., Hindryckx, P., De Vos, M., De Looze, D., Raes, J. Tags: Open access PostScript Source Type: research

Proton pump inhibitor-responsive oesophageal eosinophilia: too early to change clinical practice
We read the article by Molina-Infante et al1 with great concern as it proposes a major change in the current practice guidelines for managing patients presenting for care by gastroenterologists worldwide. Proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE)1 is characterised by an eosinophilic infiltrate of the oesophageal epithelium that is responsive to PPI therapy alone. The authors suggest that endoscopies should be performed prior to a therapeutic trial of PPI, so as not to miss this subtype of eosinophilic oesophagitis (EoE). We maintain that these two entities not only have yet to be proven to be the ...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Muir, A. B., Wang, M.-L., Metz, D., Falk, G., Markowitz, J., Spergel, J. M., Liacouras, C. A. Tags: PostScript Source Type: research

Unique pathology of colonic spirochaetosis characterised by mucosal eosinophilia is linked to diarrhoea and IBS
We report here new observations on a colonic bacteria that, while traditionally considered a commensal, may be important in chronic diarrhoea and IBS. Colonisation of the colon by Brachyspira aalborgi and B. pilosicoli is characterised by the histological finding of extensive, densely packed, end-on attachment of spirochaetes to the mucosal wall, which is visible on H&E stain as a hazy mucosal border; bacterial colonisation is dramatically demonstrated by Warthin-Starry staining like Helicobacter pylori (figure 1).2 3 The significance of this finding and its role in human disease has been debated in the literature and ...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Goodsall, T. M., Talley, N. J., Rassam, L., Wood, N. K., Zala, A., Jones, M., Walker, M. M. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceDietary influences on the microbiota and microbial metacommunity  Griffin NW, Ahern PP, Cheng J, et al. Prior Dietary practices and connections to a human gut microbial metacommunity alter responses to diet interventions. Cell Host Microbe 2017;21:84–96. Westernisation is associated with a lower taxonomic and functional diversity, which can be partially restored by dietary interventions. Microbial communities of cohabitating individuals develop similarity, indicating that transfer of gut taxa occurs between people with close proximity. The relative strengths of selection and dispersal in influencing...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Dietary and pharmacological treatment of abdominal pain in IBS
The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1 Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors) Peppermint oil 5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron) Non-absorbed antibiotic (rifaximin) Secretagogues (lubiprostone, linaclotide) &...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Camilleri, M., Boeckxstaens, G. Tags: GUT Recent advances in clinical practice Source Type: research

Neoplastic gastrointestinal pathology: an illustrated guide
The title of this book would not have attracted my attention prior to being asked to review it. Neoplasia is covered in detail in existing GI pathology textbooks and there are also atlases of GI pathology. A quick glance at the contents, however, and I think the book should have been entitled ‘A Practical Guide (or Approach) to Neoplastic Gastrointestinal Pathology’. The introductory chapter covers terminology, grading, staging, reporting and screening, as well as a general approach to the biopsy specimen. There are numerous helpful tables as well as practical advice on distinguishing reactive atypia from dyspl...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Campbell, F. Tags: PostScript Source Type: research

Quantitative evaluation of human bone mesenchymal stem cells rescuing fulminant hepatic failure in pigs
Conclusions Our results delineated an integrated model of the multifaceted interactions between stem cells and recipients, which may open a new avenue to the discovery of single molecule-based therapeutics that simulate stem cell actions. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Shi, D., Zhang, J., Zhou, Q., Xin, J., Jiang, J., Jiang, L., Wu, T., Li, J., Ding, W., Li, J., Sun, S., Li, J., Zhou, N., Zhang, L., Jin, L., Hao, S., Chen, P., Cao, H., Li, M., Li, L., Chen, X., Li, J. Tags: Hepatology Source Type: research

BMP-9 interferes with liver regeneration and promotes liver fibrosis
Conclusions Constitutive expression of low levels of BMP-9 stabilises hepatocyte function in the healthy liver. Upon HSC activation, endogenous BMP-9 levels increase in vitro and in vivo and high levels of BMP-9 cause enhanced damage upon acute or chronic injury. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Breitkopf-Heinlein, K., Meyer, C., König, C., Gaitantzi, H., Addante, A., Thomas, M., Wiercinska, E., Cai, C., Li, Q., Wan, F., Hellerbrand, C., Valous, N. A., Hahnel, M., Ehlting, C., Bode, J. G., Müller-Bohl, S., Klingmüller, U., Tags: Editor's choice Hepatology Source Type: research

Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors
Conclusions We propose that high circulating IL-8 in human alcoholic hepatitis may cause pathogenic overzealous neutrophil activation, and therapeutic blockade via pepducins merits clinical study. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Wieser, V., Adolph, T. E., Enrich, B., Kuliopulos, A., Kaser, A., Tilg, H., Kaneider, N. C. Tags: Alcoholic liver disease, Hepatitis other, Open access Hepatology Source Type: research

Study of hepatitis E virus infection of genotype 1 and 3 in mice with humanised liver
Conclusions Human liver chimeric mice can be infected with HEV of different genotypes. This small animal model will be a valuable tool for the in vivo study of HEV infection and the evaluation of novel antiviral molecules. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Sayed, I. M., Verhoye, L., Cocquerel, L., Abravanel, F., Foquet, L., Montpellier, C., Debing, Y., Farhoudi, A., Wychowski, C., Dubuisson, J., Leroux-Roels, G., Neyts, J., Izopet, J., Michiels, T., Meuleman, P. Tags: Hepatitis other Hepatology Source Type: research

Hepatic overexpression of cAMP-responsive element modulator {alpha} induces a regulatory T-cell response in a murine model of chronic liver disease
Conclusions Our results demonstrate that overexpression of CREMα in T cells changes the inflammatory milieu, attenuating initiation and progression of CLD. Unexpectedly, our study indicates that CREMα transgenic T cells shift chronic inflammation in Nemohepa livers towards a protective Treg response. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Kuttkat, N., Mohs, A., Ohl, K., Hooiveld, G., Longerich, T., Tenbrock, K., Cubero, F. J., Trautwein, C. Tags: Open access Hepatology Source Type: research

Extracellular lipid-free apolipoprotein E inhibits HCV replication and induces ABCG1-dependent cholesterol efflux
Conclusions Our findings highlight a new mechanism in lipid metabolism regulation and interaction of the lipid metabolism with the HCV life cycle, which may be important for viral pathogenesis and might also be explored for antiviral therapy. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Crouchet, E., Lefevre, M., Verrier, E. R., Oudot, M. A., Baumert, T. F., Schuster, C. Tags: Open access, Hepatic cancer Hepatology Source Type: research

Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study
Background Accurate optical characterisation and removal of small adenomas (
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Rees, C. J., Rajasekhar, P. T., Wilson, A., Close, H., Rutter, M. D., Saunders, B. P., East, J. E., Maier, R., Moorghen, M., Muhammad, U., Hancock, H., Jayaprakash, A., MacDonald, C., Ramadas, A., Dhar, A., Mason, J. M., Neilson, Ahmed, Bevan, Bradburn, B Tags: Endoscopy, Open access, Colon cancer Source Type: research

Caecal ulceration in an asymptomatic man
A 66-year-old Caucasian man underwent bowel cancer screening colonoscopy. He was asymptomatic with no significant medical history and no family history of bowel cancer or IBD. Clinical examination was normal and routine blood tests including haematinics, renal function, electrolytes and liver function were normal. Colonoscopy revealed several shallow periappendiceal caecal ulcers (figure 1). CT revealed caecal thickening with a few small para-caecal lymph nodes. The liver, spleen, small intestine and remaining colon were normal (figure 2). Biopsies from the ulcer demonstrated acute inflammatory changes with a dense infiltr...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Wu, N., Freiman, J. S. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response
Conclusions We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Blasco-Baque, V., Garidou, L., Pomie, C., Escoula, Q., Loubieres, P., Le Gall-David, S., Lemaitre, M., Nicolas, S., Klopp, P., Waget, A., Azalbert, V., Colom, A., Bonnaure-Mallet, M., Kemoun, P., Serino, M., Burcelin, R. Tags: Open access Gut microbiota Source Type: research

Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD
Conclusions Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. Trial registration number clinicaltrial.gov (NCT01067547). (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Lee, T., Clavel, T., Smirnov, K., Schmidt, A., Lagkouvardos, I., Walker, A., Lucio, M., Michalke, B., Schmitt-Kopplin, P., Fedorak, R., Haller, D. Tags: Crohn's disease, Open access Inflammatory bowel disease Source Type: research

BVES regulates c-Myc stability via PP2A and suppresses colitis-induced tumourigenesis
Conclusion Loss of BVES promotes inflammatory tumourigenesis through dysregulation of Wnt signalling and the oncogene c-Myc. BVES promoter methylation status may serve as a CAC biomarker. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Parang, B., Kaz, A. M., Barrett, C. W., Short, S. P., Ning, W., Keating, C. E., Mittal, M. K., Naik, R. D., Washington, M. K., Revetta, F. L., Smith, J. J., Chen, X., Wilson, K. T., Brand, T., Bader, D. M., Tansey, W. P., Chen, R., Brentnall, T. A., Grady Tags: GI cancer Source Type: research

The safety of vedolizumab for ulcerative colitis and Crohn's disease
We report an integrated summary of the safety of vedolizumab. Design Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. Results In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infecti...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Colombel, J.-F., Sands, B. E., Rutgeerts, P., Sandborn, W., Danese, S., D'Haens, G., Panaccione, R., Loftus, E. V., Sankoh, S., Fox, I., Parikh, A., Milch, C., Abhyankar, B., Feagan, B. G. Tags: Crohn's disease, Ulcerative colitis, Open access Inflammatory bowel disease Source Type: research

IL-36R signalling activates intestinal epithelial cells and fibroblasts and promotes mucosal healing in vivo
Conclusions IL-36R signalling is activated upon intestinal damage, stimulates IECs and fibroblasts and drives mucosal healing. Modulation of the IL-36R pathway emerges as a potential therapeutic strategy for induction of mucosal healing in IBD. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Scheibe, K., Backert, I., Wirtz, S., Hueber, A., Schett, G., Vieth, M., Probst, H. C., Bopp, T., Neurath, M. F., Neufert, C. Tags: Inflammatory bowel disease Source Type: research

A microbial signature for Crohn's disease
Conclusions Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Pascal, V., Pozuelo, M., Borruel, N., Casellas, F., Campos, D., Santiago, A., Martinez, X., Varela, E., Sarrabayrouse, G., Machiels, K., Vermeire, S., Sokol, H., Guarner, F., Manichanh, C. Tags: Open access Inflammatory bowel disease Source Type: research

Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma
Conclusions PD-L1 is expressed on both tumour cells and in the immune stroma across all stages and histologies of G/GEJ. Surprisingly, we demonstrate that increasing CD8 infiltration is correlated with impaired PFS and OS. Patients with higher CD8+ T cell densities also have higher PD-L1 expression, indicating an adaptive immune resistance mechanism may be occurring. Further characterisation of the G/GEJ immune microenvironment may highlight targets for immune-based therapy. (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Thompson, E. D., Zahurak, M., Murphy, A., Cornish, T., Cuka, N., Abdelfatah, E., Yang, S., Duncan, M., Ahuja, N., Taube, J. M., Anders, R. A., Kelly, R. J. Tags: Pancreatic cancer Upper GI cancer Source Type: research

A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barretts neoplasia
Conclusions In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. Trial registration number NCT1871636 (Source: Gut)
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Terheggen, G., Horn, E. M., Vieth, M., Gabbert, H., Enderle, M., Neugebauer, A., Schumacher, B., Neuhaus, H. Tags: Open access, Oesophageal cancer Endoscopy Source Type: research

Updated guideline on the management of common bile duct stones (CBDS)
Common bile duct stones (CBDS) are estimated to be present in 10–20% of individuals with symptomatic gallstones. They can result in a number of health problems, including pain, jaundice, infection and acute pancreatitis. A variety of imaging modalities can be employed to identify the condition, while management of confirmed cases of CBDS may involve endoscopic retrograde cholangiopancreatography, surgery and radiological methods of stone extraction. Clinicians are therefore confronted with a number of potentially valid options to diagnose and treat individuals with suspected CBDS. The British Society of Gastroenterol...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Williams, E., Beckingham, I., El Sayed, G., Gurusamy, K., Sturgess, R., Webster, G., Young, T. Tags: Guidelines Source Type: research

Shall we blame CD4 T cells for everything?
Persistent inflammatory conditions in the liver promote chronic liver damage and liver fibrosis ultimately leading to hepatocellular carcinoma (HCC). Multiple cytokines have been investigated in the context of acute and chronic liver damage. Interleukin 17 (IL-17) is a proinflammatory cytokine produced by a subset of CD4 T cells (T helper 17 (Th17) cells). IL-17 recruits other immune cells such as monocytes and neutrophils to the site of inflammation in response to invasion by pathogens. It can promote inflammation and has been linked to various autoimmune disorders.1 In the liver, Th17 responses have been shown in non-alc...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Greten, T. F., Korangy, F. Tags: Commentary Source Type: research

NF-{kappa}B mediated transcription of DARPP-32 prevents Helicobacter pylori-induced cell death
Gastric cancer remains one of the leading neoplasms and currently ranks third in cancer mortality worldwide.1 Helicobacter pylori (H. pylori) infection, and the subsequent chronic inflammation that the organism induces, is a major risk factor for stomach cancer,2 along with smoking and a diet high in salt and nitrates (http://www.cancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-risk-factors). Within the past several years, the focus on aetiology has shifted from epidemiology to understanding the genomic landscape that occurs during gastric transformation. Specifically, the gastric cancer genome analysis demonst...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Merchant, J. L. Tags: Commentary Source Type: research

Helicobacter pylori-induced cell death is counteracted by NF-{kappa}B-mediated transcription of DARPP-32
Objective DARPP-32 is a frequently amplified and overexpressed gene that promotes several oncogenic functions in gastric cancer. Herein, we investigated the relationship between Helicobacter pylori infection, proinflammatory NF-B activation and regulation of DARPP-32. Design The study used in vivo and in vitro experiments. Luciferase reporter, quantitative real-time PCR, immunoblot, chromatin immunoprecipitation (ChIP), cell viability, H. pylori infection, tissue microarrays and immunohistochemical assays were used. Results Our results indicated that H. pylori infection increased the DARPP-32 mRNA and protein levels in g...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Zhu, S., Soutto, M., Chen, Z., Peng, D., Romero-Gallo, J., Krishna, U. S., Belkhiri, A., Washington, M. K., Peek, R., El-Rifai, W. Tags: Campylobacter, Salmonella, Shigella, Escherichia coli, Helicobacter pylori, Pancreatic cancer Upper GI cancer Source Type: research

Unravelling the multiple roles of apolipoprotein E in the hepatitis C virus life cycle
Worldwide, about 3% of the population is infected with HCV, and chronic infection is associated with a risk of serious progressive liver disease. The recent introduction of direct-acting antiviral agents (DAAs) has considerably improved the treatment of chronic HCV infection, and most patients are now cured without major side effects.1 However, subgroups of patients difficult-to-treat and requiring additional therapeutic approaches will probably emerge. Furthermore, DAAs are very expensive, limiting their use in some countries.1 Thus, in the absence of prophylactic vaccines, improvements to our understanding of the mechani...
Source: Gut - April 7, 2017 Category: Gastroenterology Authors: Roingeard, P., Dreneau, J., Meunier, J.-C. Tags: Commentary Source Type: research

A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency
Stool consistency and frequency patterns are complex traits that are often altered in GI disease, and recent studies published in Gut highlight the importance of stool frequency in relation to gut microbiota composition and the efficacy of pharmacological and dietary treatments in IBS.1–3 Despite reported heritability in invertebrates4 and similar evidence from open-field defaecation models in rats,5 the genetics of stool frequency has not been explored in humans. We undertook a genome-wide association study (GWAS) in two well-characterised population-based cohorts with genotype and defaecation data available: LifeLi...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Jankipersadsing, S. A., Hadizadeh, F., Bonder, M. J., Tigchelaar, E. F., Deelen, P., Fu, J., Andreasson, A., Agreus, L., Walter, S., Wijmenga, C., Hysi, P., D'Amato, M., Zhernakova, A. Tags: Open access PostScript Source Type: research

Response to 'Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis by Rühlemann et al
We read with great interest and enthusiasm the letter from Rühlemann et al1 regarding the possible diagnostic role of the faecal microbial profile in primary sclerosing cholangitis (PSC). In the study, 73 well-characterised patients with PSC were compared with 98 healthy control (HC) subjects and 88 subjects with UC in order to validate a diagnostic panel of microbial markers identified in our recent study of PSC.2 Out of 12 taxa included in a diagnostic panel, 10 were also identified in the German dataset. Using these 10 taxa, Rühlemann et al obtained the area under the curves (AUCs) of 0.86 and 0.79 for discriminatin...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Kummen, M., Hov, J. R. Tags: PostScript Source Type: research

Treatment strategy for video capsule retention by double-balloon enteroscopy
We read with great interest the recent endoscopy news reported by Gluck et al,1 presenting a novel prepless X-ray imaging capsule for colon cancer screening. The capsule emits low-dose X-rays that can penetrate the colon contents and identify polyps without the need for bowel preparation. However, one capsule retention occurred in 46 asymptomatic volunteers in a pilot study and it was retrieved by colonoscopy. Actually, capsule endoscopy retention is not rare even in patient without suspected Crohn's disease or bowel obstruction, with a retention rate of around 1.0%.2 3 Most retained capsules remain harmless but some can c...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Wang, Y., Liao, Z., Wang, P., Chen, J., Guo, J., Fu, H., Dong, Y., Li, Z., Du, Y. Tags: PostScript Source Type: research

Faecal microbiota profiles as diagnostic biomarkers in primary sclerosing cholangitis
Dear Sir, Primary sclerosing cholangitis (PSC) is a progressive disease of unknown aetiology. The presumed involvement of the gut–liver axis in disease pathogenesis1 has prompted investigations into mucosal2 and faecal intestinal microbiota composition, as has been reported by Kummen et al3 in this journal. Microbiota as diagnostic biomarkers of disease are of interest from the clinician’s point of view and Kummen et al3 have suggested a panel of taxa and even a single genus (Veillonella) with a reasonable diagnostic accuracy differentiating PSC and healthy controls (HCs). We here report on a cohort study from ...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Rühlemann, M. C., Heinsen, F.-A., Zenouzi, R., Lieb, W., Franke, A., Schramm, C. Tags: PostScript Source Type: research

Efficacy of vonoprazan-based second-line Helicobacter pylori eradication therapy in patients for whom vonoprazan-based first-line treatment failed
We read with great interest the article by Murakami et al,1 who performed a randomised, double-blinded study of vonoprazan-based Helicobacter pylori (H. pylori) eradication therapy. They showed high success rates for vonoprazan-based first-line and second-line H. pylori treatments, with eradication rates of 92.6% and 98%, respectively. However, the study populations of second-line therapy included patients for whom both lansoprazole-based and vonoprazan-based first-line treatments failed, and those for whom vonoprazan-based first-line therapy failed numbered only 14. In terms of second-line therapy, we think that the eradi...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Katayama, Y., Toyoda, K., Kusano, Y., Suda, T., Adachi, S., Terauchi, I., Oka, S., Takahashi, M., Tamano, M. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, the authors have dissected the role of a complex signalling network involving the Hippo, Notch and Wnt/β-catenin pathways on HCC formation and growth. Inactivation of liver Hippo signalling using transgenic mice deficient for mammalian sterile 20-like kinases (MST1 and MST2) resulted in augmentation of the activity of the transcription factors YAP and TAZ and the spontaneous development of HCC in 100% of mice. Hence, the authors confirmed a... (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Novel insight into the role of microbiota in colorectal surgery
Recent literature undeniably supports the idea that the microbiota has a strong influence on the healing process of an intestinal anastomosis. Understanding the mechanisms by which the bacterial community of the gut influences intestinal healing could open the door for new preventive and therapeutic approaches. Among the different mechanisms, data have shown that the production of specific reactive oxygen species (ROS) and the activation of specific formyl peptide receptors (FPRs) regulate intestinal wound healing. Evidence suggests that specific gut microbes such as Lactobacillus spp and Akkermansia muciniphila help to re...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Bachmann, R., Leonard, D., Delzenne, N., Kartheuser, A., Cani, P. D. Tags: GUT Recent advances in clinical practice Source Type: research

A tribute to Professor Shu Dong Xiao (1931-2016)
Great sadness and deep affection marked the recent passing of Professor and Dr Shu Dong Xiao, a renowned and respected gastroenterologist, the emeritus director of Shanghai Institute of Digestive Disease and the emeritus professor of Renji Hospital, School of Medicine, Shanghai Jiao Tong University, who had dedicated his whole life to the academic and clinical study of digestive diseases. Professor Xiao died from cardiopulmonary failure on 22 July 2016 at the age of 85. Professor Xiao was born in 1931 in Huangpi city, Hubei Province, China. He graduated from the Shanghai Second Medical College (currently known as Shanghai ...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Fang, J. Y. Tags: Obituary Source Type: research

Juan Rodes. A successful and extraordinary life of a visionary hepatologist
Dr Juan Rodés, architect of the Liver Unit of the Hospital Clinic of the University of Barcelona, an internationally renowned centre for research in liver disease, died in Barcelona on 10 January 2017, aged 78 years. He was one of the most inspiring and influential leaders in the field of clinical hepatology and the physician who changed modern medical practice in Spain. Juan graduated from the University of Barcelona School of Medicine, Barcelona, in 1962, and trained in Internal Medicine at the Hospital Clinic. The centre has had the privilege of having Dr Rodés as Head of Hepatology Professor of Medic...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Pares, A. Tags: Obituary Source Type: research

Rapid decrease in hepatitis C viremia by direct acting antivirals improves the natural killer cell response to IFN{alpha}
Conclusions IFN-responsiveness can be improved by inhibiting HCV replication and reducing the HCV-induced activation of the innate immune response. This may provide a rationale for clinical trials of a brief period of direct acting antiviral therapy followed by PegIFN/RBV therapy to reduce the overall treatment costs in low-income and middle-income countries. Trial registration numbers NCT01888900 and NCT00718172. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Serti, E., Park, H., Keane, M., O'Keefe, A. C., Rivera, E., Liang, T. J., Ghany, M., Rehermann, B. Tags: Hepatology Source Type: research

PGAM5-mediated programmed necrosis of hepatocytes drives acute liver injury
Conclusions Our data demonstrate for the first time that PGAM5 plays an indispensable role in the pathogenesis of ConA-induced liver injury. Downstream of PGAM5, Drp1-mediated mitochondrial fission is an obligatory step that drives the execution of hepatic necrosis and tissue damage. Our data highlight the PGAM5-Drp1 axis as a potential therapeutic target for acute immune-mediated liver injury. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: He, G.-W., Günther, C., Kremer, A. E., Thonn, V., Amann, K., Poremba, C., Neurath, M. F., Wirtz, S., Becker, C. Tags: Hepatitis other Hepatology Source Type: research

MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47phox-oxidative stress pathway in neutrophils
Conclusions miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Li, M., He, Y., Zhou, Z., Ramirez, T., Gao, Y., Gao, Y., Ross, R. A., Cao, H., Cai, Y., Xu, M., Feng, D., Zhang, P., Liangpunsakul, S., Gao, B. Tags: Alcoholic liver disease, Open access Hepatology Source Type: research

Global patterns and trends in colorectal cancer incidence and mortality
Conclusions Patterns and trends in CRC incidence and mortality correlate with present human development levels and their incremental changes might reflect the adoption of more western lifestyles. Targeted resource-dependent interventions, including primary prevention in low-income, supplemented with early detection in high-income settings, are needed to reduce the number of patients with CRC in future decades. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Arnold, M., Sierra, M. S., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F. Tags: Press releases, Colon cancer Source Type: research

ZEB1-induced tumourigenesis requires senescence inhibition via activation of DKK1/mutant p53/Mdm2/CtBP and repression of macroH2A1
Conclusions The tumourigenic capacity of ZEB1 depends on its inhibition of cancer cell senescence through the activation of a herein identified new molecular pathway. These results set ZEB1 as a potential target in therapeutic strategies aimed at inducing senescence. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: de Barrios, O., Gyorffy, B., Fernandez-Acenero, M. J., Sanchez-Tillo, E., Sanchez-Moral, L., Siles, L., Esteve-Arenys, A., Roue, G., Casal, J. I., Darling, D. S., Castells, A., Postigo, A. Tags: Colon Source Type: research

An unusual endoscopic ultrasound diagnosis in kidney-transplant patient
Clinical presentation A 29-year-old man who had undergone kidney transplantation in 1999 for chronic glomerular disease, on treatment with ciclosporin, azathioprine and steroids, was admitted for severe, diffuse abdominal pain. No fever or other symptoms were present. Multidetector CT (MDCT) scan showed several chest and abdominal lymphadenopathies and pericardial, pleural and abdominal effusions. A post-transplant lymphoproliferative disorder (PTLD) was suspected and, therefore, azathioprine and ciclosporin were suspended with resolution of serosal effusions. However, cytology and cytofluorimetry from ascites and pleural ...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Barresi, L., Tarantino, I., Ligresti, D., Curcio, G., Granata, A., Chiarello, G., Traina, M. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Circulating microRNA-203 predicts prognosis and metastasis in human colorectal cancer
Conclusions High levels of serum miR-203 associate with poor survival and metastasis, suggesting it to be a promising non-invasive prognostic and metastasis-predictive biomarker in patients with CRC. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Hur, K., Toiyama, Y., Okugawa, Y., Ide, S., Imaoka, H., Boland, C. R., Goel, A. Tags: Colon cancer, Hepatic cancer Source Type: research

Endoscopic mucosal resection for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions
Objective Endoscopic mucosal resection (EMR) is effective for large laterally spreading flat and sessile lesions (LSLs). Sessile serrated adenomas/polyps (SSA/Ps) are linked to the relative failure of colonoscopy to prevent proximal colorectal cancer. We aimed to examine the technical success, adverse events and recurrence following EMR for large SSA/Ps in comparison with large conventional adenomas. Design Over 74 months till August 2014, prospective multicentre data of LSLs ≥20 mm were analysed. A standardised dye-based conventional EMR technique followed by scheduled surveillance colonoscopy was used. Res...
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Pellise, M., Burgess, N. G., Tutticci, N., 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., Mahajan, H., McLeod, D., Bourke, M. J. Tags: Endoscopy, Colon cancer Source Type: research

Tumour-associated and non-tumour-associated microbiota in colorectal cancer
Conclusions CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Flemer, B., Lynch, D. B., Brown, J. M. R., Jeffery, I. B., Ryan, F. J., Claesson, M. J., O'Riordain, M., Shanahan, F., O'Toole, P. W. Tags: Open access, Colon cancer Gut microbiota Source Type: research

The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls
Objective Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease. Design We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Kummen, M., Holm, K., Anmarkrud, J. A., Nygard, S., Vesterhus, M., Hoivik, M. L., Troseid, M., Marschall, H.-U., Schrumpf, E., Moum, B., Rosjo, H., Aukrust, P., Karlsen, T. H., Hov, J. R. Tags: Ulcerative colitis, Pancreas and biliary tract Gut microbiota Source Type: research

Raf kinase inhibitor protein mediates intestinal epithelial cell apoptosis and promotes IBDs in humans and mice
Conclusions RKIP contributes to colitis development by promoting inflammation and mediating IEC apoptosis and might represent a therapeutic target of IBD. (Source: Gut)
Source: Gut - March 10, 2017 Category: Gastroenterology Authors: Lin, W., Ma, C., Su, F., Jiang, Y., Lai, R., Zhang, T., Sun, K., Fan, L., Cai, Z., Li, Z., Huang, H., Li, J., Wang, X. Tags: Colon cancer Inflammatory bowel disease Source Type: research