Controversy on the time to progression of pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly aggressive and rapidly progressive disease by clinicians, which is one of the reasons why patients usually present at advanced stages of the disease and have a poor prognosis.1 In fact, this appears to be confirmed by the low number of small pancreatic cancers documented in population-based registries. Only 1.4% of 13 131 patients with pancreatic cancer in the SEER database (US National Cancer Institute's Surveillance, Epidemiology, and End Results) had tumours
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Gallmeier, E., Hernaez, R., Gress, T. M. Tags: Commentary Source Type: research

Changing the narrative on antibiotics
Campaigning for antibiotic conservation is a bit like the struggle against global warming. The polar ice melts while politicians, not known for long-range thinking, debate deadlines for others to meet. Similarly, new drug discovery diminishes as resistance to existing antibiotics increases. Public health officials and policy makers predict a bleak future and plead for reform of prescribing practices, but clinicians deal with individual patients, not populations, in the present. Perhaps, it is time to direct the educational narrative on antibiotics towards the consumer. Enthusiasm for antibiotic treatment, particularly for ...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Shanahan, F. Tags: Commentary Source Type: research

Cardiac mucosa: the heart of the problem
Traditional teaching holds that the normal stomach has three types of mucosae. The oxyntic mucosa of the gastric body and fundus has glands with parietal cells that secrete acid, and chief cells that secrete digestive enzymes. The mucosa of the antrum is comprised of mucus-secreting cells and endocrine cells that produce gastrin, which regulates acid production by the oxyntic mucosa. Finally, the most proximal portion of the stomach (the gastric cardia), a region with ill-defined borders, allegedly is lined by ‘cardiac mucosa’ comprised almost exclusively of mucus-secreting cells. Cardiac mucosa has been assume...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Spechler, S. J. Tags: Commentary Source Type: research

Changing nomenclature for PBC: from 'cirrhosis' to 'cholangitis'
The disease entity today widely called ‘primary biliary cirrhosis’ was first described by Addison and Gull in 18511 and Hanot in 1876.2 One hundred years after its first description, MacMahon and Thannhauser3 proposed the term ‘xanthomatous biliary cirrhosis’ for this disease based on the typical xanthoma formation with accumulation of cholesterol esters in the skin around the eyes in association with inflammatory destruction of small intrahepatic bile ductules leading to a biliary type cirrhosis. Xanthoma formation, however, is not a very common sign in this disorder. This may be the reason why the...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Beuers, U., Gershwin, M. E., Gish, R. G., Invernizzi, P., Jones, D. E. J., Lindor, K., Ma, X., Mackay, I. R., Pares, A., Tanaka, A., Vierling, J. M., Poupon, R. Tags: Pancreas and biliary tract Leading article Source Type: research

GI highlights from the literature
Basic scienceLactococcus lactis attenuates murine colitis by lowering oxidative stress Ballal SA, Veiga P, Fenn K, et al. Host lysozyme-mediated lysis of Lactococcus lactis facilitates delivery of colitis-attenuating superoxide dismutase to inflamed colons. Proc Natl Acad Sci 2015;112:7803–8. Oxidative stress contributes to chronic inflammation and dysbiosis in IBD. Finding ways to lessen oxidative stress may help to restore homeostasis in the intestine. Identifying microbes that target pathways such as oxidative stress provide stepping-stones towards new IBD therapies. Earlier work by Garrett's laboratory establishe...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

The stomach in health and disease
The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology an...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Hunt, R. H., Camilleri, M., Crowe, S. E., El-Omar, E. M., Fox, J. G., Kuipers, E. J., Malfertheiner, P., McColl, K. E. L., Pritchard, D. M., Rugge, M., Sonnenberg, A., Sugano, K., Tack, J. Tags: Ulcer, Campylobacter, Salmonella, Shigella, Escherichia coli, Helicobacter pylori, GUT Recent advances in clinical practice, Dyspepsia, Gastric emptying disorders, Stomach and duodenum, Pancreatic cancer Source Type: research

Colorectal cancer screening: a global overview of existing programmes
Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers worldwide, with wide geographical variation in incidence and mortality across the world. Despite proof that screening can decrease CRC incidence and mortality, CRC screening is only offered to a small proportion of the target population worldwide. Throughout the world there are widespread differences in CRC screening implementation status and strategy. Differences can be attributed to geographical variation in CRC incidence, economic resources, healthcare structure and infrastructure to support screening such as the ability to identify the target...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Schreuders, E. H., Ruco, A., Rabeneck, L., Schoen, R. E., Sung, J. J. Y., Young, G. P., Kuipers, E. J. Tags: GUT Recent advances in clinical practice, Colon cancer Source Type: research

Genetic architecture of colorectal cancer
Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3–5%) of cases arise from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well defined genes. In contrast, CRC is predominantly a late onset ‘sporadic’ disease, developing in individuals with no obvious hereditary syndrome. In recent years, genome wide association studies have discovered that over 40 genetic regions are associated with weak effects on sporadic CRC, and it has been estimated that increasingly large geno...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Peters, U., Bien, S., Zubair, N. Tags: GUT Recent advances in basic science, Colon cancer Source Type: research

Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis
This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF, ACLF grades 1, 2 and 3) with that of acute kidney injury (AKI) classification (no AKI, AKI stages 1, 2 and 3). Design The study was performed in 510 patients with an acute decompensation of cirrhosis previously included in the European Association for the Study of the Liver–Chronic Liver Failure consortium CANONIC study. ACLF was evaluated at enrolment and 48 h after enrolment, and AKI was evaluated at 48 h according to Acute Kidney Injury Network c...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Angeli, P., Rodriguez, E., Piano, S., Ariza, X., Morando, F., Sola, E., Romano, A., Garcia, E., Pavesi, M., Risso, A., Gerbes, A., Willars, C., Bernardi, M., Arroyo, V., Gines, P., for the CANONIC Study Investigators of the EASL-CLIF Consortium Tags: Hepatology Source Type: research

Impact of common risk factors of fibrosis progression in chronic hepatitis C
Conclusions Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Rueger, S., Bochud, P.-Y., Dufour, J.-F., Mullhaupt, B., Semela, D., Heim, M. H., Moradpour, D., Cerny, A., Malinverni, R., Booth, D. R., Suppiah, V., George, J., Argiro, L., Halfon, P., Bourliere, M., Talal, A. H., Jacobson, I. M., Patin, E., Nalpas, B., Tags: Hepatitis C Hepatology Source Type: research

Tim-3 fosters HCC development by enhancing TGF-{beta}-mediated alternative activation of macrophages
Conclusions Tim-3 displays critical roles in microenvironment-induced activation and protumoral effects of TAMs in HCC. Interference of Tim-3 might be great potential in HCC therapy. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Yan, W., Liu, X., Ma, H., Zhang, H., Song, X., Gao, L., Liang, X., Ma, C. Tags: Hepatic cancer Hepatology Source Type: research

Adherence to surveillance guidelines after removal of colorectal adenomas: a large, community-based study
Objective To determine adherence to recommended surveillance intervals in clinical practice. Design 2997 successive patients with a first adenoma diagnosis (57% male, mean age 59 years) from 10 hospitals, who underwent colonoscopy between 1998 and 2002, were identified via Pathologisch Anatomisch Landelijk Geautomatiseerd Archief: Dutch Pathology Registry. Their medical records were reviewed until 1 December 2008. Time to and findings at first surveillance colonoscopy were assessed. A surveillance colonoscopy occurring within ±3 months of a 1-year recommended interval and ±6 months of a recomm...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: van Heijningen, E.-M. B., Lansdorp-Vogelaar, I., Steyerberg, E. W., Goede, S. L., Dekker, E., Lesterhuis, W., ter Borg, F., Vecht, J., Spoelstra, P., Engels, L., Bolwerk, C. J. M., Timmer, R., Kleibeuker, J. H., Koornstra, J. J., de Koning, H. J., Kuipers Tags: Endoscopy, Open access, Colon cancer Source Type: research

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy
Conclusions The prevalence of small-bowel neoplasia in asymptomatic patients with LS was 1.5%. All neoplastic lesions were located in the duodenum and within reach of conventional gastroduodenoscopy. Although VCE has the potential to detect these neoplastic lesions, small-bowel neoplasia may be missed. Trial registration number NCT00898768. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Haanstra, J. F., Al-Toma, A., Dekker, E., Vanhoutvin, S. A. L. W., Nagengast, F. M., Mathus-Vliegen, E. M., van Leerdam, M. E., de Vos tot Nederveen Cappel, W. H., Sanduleanu, S., Veenendaal, R. A., Cats, A., Vasen, H. F. A., Kleibeuker, J. H., Koornstra, Tags: Endoscopy, Colon cancer, Intestinal cancer Source Type: research

Real-time optical diagnosis for diminutive colorectal polyps using narrow-band imaging: the VALID randomised clinical trial
Background Diminutive (≤5 mm) colorectal polyps are common, and overwhelmingly benign. Routinely, after polypectomy, they are examined pathologically to determine the surveillance intervals. Advances in equipment and techniques, such as narrow-band imaging (NBI) colonoscopy, now permit reliable real-time optical diagnosis. Methods We conducted a randomised single-masked study involving three institutions to determine whether optical diagnosis of diminutive colorectal polyps meets clinical practice standards and reduces the need for histopathology. We randomly assigned eligible patients undergoing routine high-defi...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Kaltenbach, T., Rastogi, A., Rouse, R. V., McQuaid, K. R., Sato, T., Bansal, A., Kosek, J. C., Soetikno, R. Tags: Endoscopy, Colon cancer, Intestinal cancer Source Type: research

Effects of bowel cleansing on the intestinal microbiota
Conclusions Our results suggest that the bowel cleansing using two separate dosages introduces fewer alterations to the intestinal microbiota than a single dose and hence may be preferred in clinical practice. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Jalanka, J., Salonen, A., Salojarvi, J., Ritari, J., Immonen, O., Marciani, L., Gowland, P., Hoad, C., Garsed, K., Lam, C., Palva, A., Spiller, R. C., de Vos, W. M. Tags: Drugs: gastrointestinal system, Endoscopy, Editor's choice, Colon cancer Gut microbiota Source Type: research

Spatial variation of the colonic microbiota in patients with ulcerative colitis and control volunteers
Conclusions Our study demonstrates a conserved spatial structure to the colonic microbiota, differentiating the luminal and mucosal communities, within the context of marked interpersonal variability. While elements of this structure overlap between UC and control volunteers, there are differences between the two groups, both in terms of the overall taxonomic composition and how spatial structure is ascribable to distinct taxa. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Lavelle, A., Lennon, G., O'Sullivan, O., Docherty, N., Balfe, A., Maguire, A., Mulcahy, H. E., Doherty, G., O'Donoghue, D., Hyland, J., Ross, R. P., Coffey, J. C., Sheahan, K., Cotter, P. D., Shanahan, F., Winter, D. C., O'Connell, P. R. Tags: Endoscopy, Ulcerative colitis, Open access, Colon cancer Gut microbiota Source Type: research

The ATG16L1-T300A allele impairs clearance of pathosymbionts in the inflamed ileal mucosa of Crohn's disease patients
Conclusions CD patients homozygous for the ATG16L1–T300A risk allele show impaired clearance of pathosymbionts in ileal inflammation indicating that ATG16L1 is essential for effective elimination of pathosymbionts upon inflammation. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Sadaghian Sadabad, M., Regeling, A., de Goffau, M. C., Blokzijl, T., Weersma, R. K., Penders, J., Faber, K. N., Harmsen, H. J. M., Dijkstra, G. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease
Objective Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab. Design In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most dis...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Vande Casteele, N., Khanna, R., Levesque, B. G., Stitt, L., Zou, G. Y., Singh, S., Lockton, S., Hauenstein, S., Ohrmund, L., Greenberg, G. R., Rutgeerts, P. J., Gils, A., Sandborn, W. J., Vermeire, S., Feagan, B. G. Tags: Crohn's disease, Open access Inflammatory bowel disease Source Type: research

A 28-year-old woman with hypertrophic right leg and haematochezia
A 28-year-old woman presented to our hospital because of daily haematochezia and weakness. Physical examination showed pale conjunctivae and several capillary malformations consisting of port-wine stain on the surface of the right lower limb. The right leg was also hypertrophic and thicker than the left leg. Laboratory tests showed haemoglobin level of 8.8 g/dL. The platelet count and coagulation parameters were normal. Oesophagogastroduodenoscopy did not reveal any bleeding lesion. At colonoscopy, several vascular malformations were detected extending from the caecum to the rectum, with ectasia and congestion of the ...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Gizzi, G., Fabbri, C., Fuccio, L. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice
Conclusions These findings suggest that specific enhancement of the pFlux for small organic solutes across the claudin-based TJs initiates colonic inflammation. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Tanaka, H., Takechi, M., Kiyonari, H., Shioi, G., Tamura, A., Tsukita, S. Tags: Inflammatory bowel disease Source Type: research

Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria
Conclusions Different risk factors exist among FD subgroups based on the Rome III criteria, indicating distinct aetiopathogenesis of the subdivisions that may necessitate different therapeutic strategies. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Fang, Y.-J., Liou, J.-M., Chen, C.-C., Lee, J.-Y., Hsu, Y.-C., Chen, M.-J., Tseng, P.-H., Chen, C.-C., Chang, C.-Y., Yang, T.-H., Chang, W.-H., Wu, J.-Y., Wang, H.-P., Luo, J.-C., Lin, J.-T., Shun, C.-T., Wu, M.-S., for the Taiwan Gastrointestinal Disease Tags: Dyspepsia, Open access, Pancreatic cancer Stomach Source Type: research

APR-246 potently inhibits tumour growth and overcomes chemoresistance in preclinical models of oesophageal adenocarcinoma
Conclusions APR-246 has significant antitumour activity in OAC. Given that APR-246 is safe at therapeutic levels our study strongly suggests that APR-246 can be translated into improving the clinical outcomes for OAC patients. (Source: Gut)
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Liu, D. S. H., Read, M., Cullinane, C., Azar, W. J., Fennell, C. M., Montgomery, K. G., Haupt, S., Haupt, Y., Wiman, K. G., Duong, C. P., Clemons, N. J., Phillips, W. A. Tags: Oesophageal cancer Oesophagus Source Type: research

Bowel preparation for colonoscopy: relevant for the gut's microbiota?
Potential contributions of the host-associated gut microbiota to human physiology continue to receive extensive research interest. While various lines of evidence support a role of the microbiota in maintaining human health, perturbations in normal microbiota composition have been correlated with various dietary changes and disease states,1 particularly diarrhoea.2 We have long known that close interactions between microbiota and the host’s immune system occur in the distal small intestine and that microbes are highly metabolically active in the proximal large intestine. Recent global efforts have accumulated a wealt...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Mai, V., Stine, O. C. Tags: Commentary Source Type: research

Tim-3 expression in tumour-associated macrophages: a new player in HCC progression
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide due to its emergence based on chronic liver disease. Thus, HCC can ultimately be caused by multiple factors, including chronic viral infection, alcohol abuse or obesity. Nevertheless, only a few therapeutic options are available, especially for patients in later stages of disease.1 Accordingly, prognosis of patients is often poor and HCC contributes disproportionately to cancer-related deaths worldwide. Thus, further research into HCC is required to inform the development of novel therapies as well as improvements to existing regimens. An importan...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Flecken, T., Sarobe, P. Tags: Commentary Source Type: research

Claudins and barrier dysfunction in intestinal inflammation: cause or consequence?
The intestinal epithelium forms a barrier between the body and the external environment facilitating the selective uptake of water, ions and nutrients while excluding bacteria, antigens and toxins. This raises the question whether breaches in this barrier can be a primary cause of intestinal inflammation or whether barrier loss is merely the inevitable consequence of inflammation causing epithelial damage, without barrier loss itself playing a pathogenic role. This question has puzzled investigators for decades and is of some importance, as the answer will determine whether restoring barrier loss is a plausible target for ...
Source: Gut - September 8, 2015 Category: Gastroenterology Authors: Watson, A. J. M. Tags: Commentary Source Type: research

Anti-angiogenic effect of metformin in human liver carcinogenesis related to metabolic syndrome
Dear Editor, We read with interest the work by Chen et al1 who reported the decreased risk for developing hepatocellular carcinoma (HCC) in patients treated with metformin in a dose-dependent and time-dependent manner. Indeed, the metabolic syndrome (MS) is becoming one of the leading risk factors for liver carcinogenesis, mainly through the presence of diabetes.2 3 In addition to clinical data confirming previous studies,4 Chen et al1 were the first to highlight experimental antitumoral effects of metformin both on hepatoma cell lines and on murine models through cell-cycle arrest via AMPK activation. However, whether the...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Cauchy, F., Mebarki, M., Albuquerque, M., Laouirem, S., Rautou, P. E., Soubrane, O., Raymond, E., Bedossa, P., Paradis, V. Tags: PostScript Source Type: research

Pancreatic epithelial fluid and bicarbonate secretion is significantly elevated in the absence of peripheral serotonin
We read the manuscript by Sonda et al1 recently published in Gut with great interest. The authors elegantly demonstrated that lack of peripheral serotonin (5-HT) in tryptophan hydroxylase 1 knockout (TPH1–/–) mice remarkably limited pancreatic damage and leucocyte infiltration during the early phase of cerulein-induced acute pancreatitis (AP) and identified 5-HT as an important regulator of zymogen secretion in acinar cells. Although the study was very comprehensive, the ductal function of TPH1–/– mice was not investigated, which might be another key player in this protection. Notably, 5-HT was show...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Maleth, J., Madacsy, T., Pallagi, P., Balazs, A., Venglovecz, V., Rakonczay, Z., Hegyi, P. Tags: PostScript Source Type: research

Gi highlights from the literature
Basic scienceUnderstanding the pathogenesis of pouchitis Morgan XC, Kabakchiev B, Waldron L, et al. Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol 2015:16:67. doi:10.1186/s13059-015-0637-x Approximately 10%–35% of patients with UC will require colectomy with pouch reconstruction, and half of these patients will develop pouchitis. In addition, one-fifth will ultimately suffer pouch failure. Therefore, defining the basis of pouchitis is clearly of utmost importance. Similar to IBD, both host genetics an...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Molecular markers for colorectal cancer screening
Colorectal cancer (CRC), although a significant cause of morbidity and mortality worldwide, has seen a declining incidence and mortality in countries with programmatic screening. Faecal occult blood testing and endoscopic approaches are the predominant screening methods currently. The discovery of the adenoma–carcinoma sequence and a greater understanding of the genetic and epigenetic changes that drive the formation of CRC have contributed to innovative research to identify molecular markers for highly accurate, non-invasive screening tests for CRC. DNA, proteins, messenger RNA and micro-RNA have all been evaluated....
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Dickinson, B. T., Kisiel, J., Ahlquist, D. A., Grady, W. M. Tags: GUT Recent advances in clinical practice, Colon cancer Source Type: research

Stromal biology and therapy in pancreatic cancer: a changing paradigm
Pancreatic ductal adenocarcinoma (PDA) exhibits one of the poorest prognosis of all solid tumours and poses an unsolved problem in cancer medicine. Despite the recent success of two combination chemotherapies for palliative patients, the modest survival benefits are often traded against significant side effects and a compromised quality of life. Although the molecular events underlying the initiation and progression of PDA have been intensively studied and are increasingly understood, the reasons for the poor therapeutic response are hardly apprehended. One leading hypothesis over the last few years has been that the prono...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Neesse, A., Algul, H., Tuveson, D. A., Gress, T. M. Tags: GUT Recent advances in basic science, Pancreas and biliary tract, Pancreatic cancer Source Type: research

IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells
Conclusions This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Miot, C., Beaumont, E., Duluc, D., Le Guillou-Guillemette, H., Preisser, L., Garo, E., Blanchard, S., Hubert Fouchard, I., Creminon, C., Lamourette, P., Fremaux, I., Cales, P., Lunel-Fabiani, F., Boursier, J., Braum, O., Fickenscher, H., Roingeard, P., De Tags: Hepatic cancer Hepatology Source Type: research

Correction
Genua M, D'Alessio S, Cibella J, et al. The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation. Gut 2015;64:589–600. The representative endoscopic image of Figure 3 panel C group WT (DSS) was incorrect. The correct figure is shown below. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Tags: Correction Source Type: research

The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma
Conclusions ERK5 regulates the biology of HCC cells and modulates tumour development and growth in vivo. This pathway should be investigated as a possible therapeutic target in HCC. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Rovida, E., Di Maira, G., Tusa, I., Cannito, S., Paternostro, C., Navari, N., Vivoli, E., Deng, X., Gray, N. S., Esparis-Ogando, A., David, E., Pandiella, A., Dello Sbarba, P., Parola, M., Marra, F. Tags: Hepatic cancer Hepatology Source Type: research

Control of hepatocyte proliferation and survival by Fgf receptors is essential for liver regeneration in mice
Conclusions These results demonstrate that Fgfr signalling in hepatocytes is essential for liver regeneration and suggest activation of Fgfr signalling as a promising approach for the improvement of the liver's regenerative capacity. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Padrissa-Altes, S., Bachofner, M., Bogorad, R. L., Pohlmeier, L., Rossolini, T., Bohm, F., Liebisch, G., Hellerbrand, C., Koteliansky, V., Speicher, T., Werner, S. Tags: Hepatology Source Type: research

KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins
Conclusions Exogenous hepatic KLF2 upregulation improves liver fibrosis, endothelial dysfunction and portal hypertension in cirrhosis. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Marrone, G., Maeso-Diaz, R., Garcia-Cardena, G., Abraldes, J. G., Garcia-Pagan, J. C., Bosch, J., Gracia-Sancho, J. Tags: Cirrhosis Hepatology Source Type: research

Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study
Conclusions The single-nucleotide polymorphisms rs10273639 at the PRSS1–PRSS2 locus and rs7057398 and rs12688220 at the CLDN2–MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Derikx, M. H., Kovacs, P., Scholz, M., Masson, E., Chen, J.-M., Ruffert, C., Lichtner, P., te Morsche, R. H. M., Cavestro, G. M., PanEuropean Working group on Alcoholic Chronic Pancreatitis members and collaborators, Ferec, C., Drenth, J. P. H., Witt, H., Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis
Conclusions These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Li, P., Wu, H., Zhang, H., Shi, Y., Xu, J., Ye, Y., Xia, D., Yang, J., Cai, J., Wu, Y. Tags: Colon cancer Source Type: research

Comparing histological activity indexes in UC
Conclusions Correlation between indexes is strong. Intraobserver reproducibility and interobserver agreement for all indexes is very good. Histological items that showed the best interobserver agreement are ‘erosion/ulceration’ and ‘acute inflammatory cells infiltrate/neutrophils in lamina propria’. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Bressenot, A., Salleron, J., Bastien, C., Danese, S., Boulagnon-Rombi, C., Peyrin-Biroulet, L. Tags: Inflammatory bowel disease Source Type: research

An uncommon presentation of a common pathogen
Question A 70-year-old woman presented with severe spasmodic abdominal pain, nausea, recurrent vomiting and mild diarrhoea. Two months earlier she underwent autologous stem cell transplantation for stage 2A follicular lymphoma. Her medical history was otherwise unremarkable. Physical examination revealed mild epigastric tenderness. Blood tests showed an elevated lactate dehydrogenase (325 IU/L; normal range 135–214 IU/L) and elevated transaminases (alanine transaminase 126 IU/L; aspartate transaminase 90 IU/L; normal range 10–35 IU/L). Blood cell counts were within the normal range. Ult...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Boettler, T., Lutz, L., Schmidt, N., Thimme, R., Neumann-Haefelin, C. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Predictors and risks for death in a population-based study of persons with IBD in Manitoba
Conclusions There is a significantly increased risk of mortality in CD compared with controls while in UC an increased risk for death was only evident in the first year from diagnosis. Surgery poses an increased risk for death in both CD and UC lasting up to 1 year. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Bernstein, C. N., Nugent, Z., Targownik, L. E., Singh, H., Lix, L. M. Tags: Crohn's disease, Colon cancer Inflammatory bowel disease Source Type: research

Value of endoscopy and MRI for predicting intestinal surgery in patients with Crohn's disease in the era of biologics
Objective Severe endoscopic lesions (SEL) in patients with colonic Crohn's disease (CD) have been linked to higher risk of colectomy. The aims of this study were to reassess the predictive value of colonoscopy compared against MRI for requirement of resection surgery in patients with CD and determine the influence of current therapeutic options. Design In this single-centre, observational, prospective, longitudinal study, patients with an established diagnosis of CD and suspected activity were included. After baseline assessment, including colonoscopy and MRI, patients were followed until resection surgery or the end of s...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Jauregui-Amezaga, A., Rimola, J., Ordas, I., Rodriguez, S., Ramirez-Morros, A., Gallego, M., Masamunt, M. C., Llach, J., Gonzalez-Suarez, B., Ricart, E., Panes, J. Tags: Endoscopy, Crohn's disease, Colon cancer Inflammatory bowel disease Source Type: research

Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)
Conclusions The quality of colonoscopy was affected by patient-related, endoscopist-related and centre-related characteristics. Policies addressing organisational issues should improve the quality of colonoscopy in our programme and similar programmes. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Zorzi, M., Senore, C., Da Re, F., Barca, A., Bonelli, L. A., Cannizzaro, R., Fasoli, R., Di Furia, L., Di Giulio, E., Mantellini, P., Naldoni, C., Sassatelli, R., Rex, D., Hassan, C., Zappa, M., the Equipe Working Group, the Equipe Working Group, Campari, Tags: Endoscopy, Colon cancer Source Type: research

Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations
This study evaluated the role of humoral activity in IBS-D. Methods A single mucosal jejunal biopsy, luminal content and blood were obtained from healthy volunteers (H; n=30) and IBS-D (n=49; Rome III criteria) participants. Intraepithelial lymphocytes, mast cells, B lymphocytes and plasma cells were studied by imaging techniques. Differential gene expression and pathway analysis were assessed by microarray and PCR techniques. Blood and luminal immunoglobulins (Igs) were quantified. Gastrointestinal symptoms, respiratory atopy and stress and depression were also recorded. Results Patients with IBS-D showed a higher numbe...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Vicario, M., Gonzalez-Castro, A. M., Martinez, C., Lobo, B., Pigrau, M., Guilarte, M., de Torres, I., Mosquera, J. L., Fortea, M., Sevillano-Aguilera, C., Salvo-Romero, E., Alonso, C., Rodino-Janeiro, B. K., Soderholm, J. D., Azpiroz, F., Santos, J. Tags: Irritable bowel syndrome Neurogastroenterology Source Type: research

A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis
Conclusions This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Zhuang, Y., Cheng, P., Liu, X.-f., Peng, L.-s., Li, B.-s., Wang, T.-t., Chen, N., Li, W.-h., Shi, Y., Chen, W., Pang, K. C., Zeng, M., Mao, X.-h., Yang, S.-m., Guo, H., Guo, G., Liu, T., Zuo, Q.-f., Yang, H.-j., Yang, L.-y., Mao, F.-y., Lv, Y.-p., Zou, Q. Tags: Open access, Stomach and duodenum Helicobacter pylori Source Type: research

Kyoto global consensus report on Helicobacter pylori gastritis
Conclusions A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. (Source: Gut)
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Sugano, K., Tack, J., Kuipers, E. J., Graham, D. Y., El-Omar, E. M., Miura, S., Haruma, K., Asaka, M., Uemura, N., Malfertheiner, P., on behalf of faculty members of Kyoto Global Consensus Conference, on behalf of faculty members of Kyoto Global Consensus Tags: Dyspepsia, Open access, Editor's choice, Stomach and duodenum, Pancreatic cancer Guidelines Source Type: research

Bile acids and FGF receptors: orchestrators of optimal liver regeneration
Because it fosters our dreams of immortality, regeneration has been for centuries a matter of fascination for countless biologists and clinicians. While in mammals regeneration is obviously less spectacular than in hydra, newt or zebrafish, it allows, in any case, repairing intestine, skin or liver. The latter organ is seen as a paradigmatic regeneration model because, as for an amputated fin's zebrafish or newt's forelimb, it is indeed possible to follow the complete restoration of a rodent liver mass after a 2/3 partial hepatectomy (PH) within a few days. The caveat is that most of our knowledge about liver regeneration ...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Gilgenkrantz, H., Tordjmann, T. Tags: Commentary Source Type: research

Statins, Rho GTPases and KLF2: new mechanistic insight into liver fibrosis and portal hypertension
Statins, standard of care drugs used in metabolic syndrome and cardiovascular diseases, seem to be safe for chronic liver disease.1 2 Beyond their cholesterol-lowering effect by inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), statins exert multiple pleiotropic effects.3 These pleiotropic effects make statins cheap and also well-investigated drugs in terms of tolerability and safety. Therefore, statins offer possibilities not only to test new hypotheses, and reveal novel pathomechanisms and targets, as shown by Marrone et al in this issue,4 but also for therapeutic approaches. Indeed, use of sta...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Trebicka, J., Schierwagen, R. Tags: Commentary Source Type: research

Predicting future disease course in Crohn's disease by colonoscopy or magnetic resonance: which is the crystal ball?
Crohn's disease (CD) is a chronic and progressive condition leading to cumulative bowel damage overtime, mainly related to stricturing or penetrating lesions. About half of patients with CD require surgical intestinal resection 10 years after diagnosis.1 Importantly, the development of disease complications (stricture, fistula and/or abscess) is known to be the main indication for surgery in these patients.1 The identification of factors associated with a higher need for surgery for CD is a prerequisite to the development of therapeutic strategies potentially altering disease course, with the final aim of preventing u...
Source: Gut - August 7, 2015 Category: Gastroenterology Authors: Danese, S., Peyrin-Biroulet, L., Fiorino, G. Tags: Commentary Source Type: research

Common variants at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with chronic pancreatitis in Japan
To the Editor, We read with great interest the article by Derikx et al1 reporting a replication study of the association between common variants at the PRSS1–PRSS2 and CLDN2–MORC4 loci and chronic pancreatitis (CP). In agreement with the results originally reported by Whitcomb et al,2 they showed that the rs10273639 T allele at the PRSS1–PRSS2 locus protected against CP, whereas the rs7057398 C allele in RIPPLY1 and rs12688220 T allele in MORC4 at the CLDN2–MORC4 locus increased disease susceptibility.1 It has been recognised that geographical differences exist in the genetics of pancreatitis.3 Beca...
Source: Gut - July 9, 2015 Category: Gastroenterology Authors: Masamune, A., Nakano, E., Hamada, S., Kakuta, Y., Kume, K., Shimosegawa, T. Tags: PostScript Source Type: research

Immunogenicity to infliximab is associated with HLA-DRB1
Dear Editor, We read with great interest the manuscript by Ungar and colleagues describing the temporal evolution of antibodies to infliximab (ATI) in patients with IBD treated with infliximab (IFX).1 By prospectively following 125 patients with IBD, they showed that ATI formation is a dynamic process. Clinically relevant ATI were typically formed within the first 12 months but transient ATI, which are of little clinical significance, can be formed at any time during treatment. They furthermore demonstrated that the evolution of ATI correlates with clinical loss of response and that concomitant immunomodulator use pro...
Source: Gut - July 9, 2015 Category: Gastroenterology Authors: Billiet, T., Vande Casteele, N., Van Stappen, T., Princen, F., Singh, S., Gils, A., Ferrante, M., Van Assche, G., Cleynen, I., Vermeire, S. Tags: PostScript Source Type: research