Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production
Conclusions Evidently, residence in globally distinct societies helps determine the composition of the gut microbiota that, in turn, influences the production of diet-dependent gut microbial metabolites. (Source: Gut)
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Wu, G. D., Compher, C., Chen, E. Z., Smith, S. A., Shah, R. D., Bittinger, K., Chehoud, C., Albenberg, L. G., Nessel, L., Gilroy, E., Star, J., Weljie, A. M., Flint, H. J., Metz, D. C., Bennett, M. J., Li, H., Bushman, F. D., Lewis, J. D. Tags: Gut microbiota Source Type: research

Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates
Conclusions The strength of the associations between stool consistency and species richness, enterotypes and community composition emphasises the crucial importance of stool consistency assessment in gut metagenome-wide association studies. (Source: Gut)
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Vandeputte, D., Falony, G., Vieira-Silva, S., Tito, R. Y., Joossens, M., Raes, J. Tags: Open access Gut microbiota Source Type: research

Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial
Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind ph...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Münch, A., Bohr, J., Miehlke, S., Benoni, C., Olesen, M., Öst, A., Strandberg, L., Hellström, P. M., Hertervig, E., Armerding, P., Stehlik, J., Lindberg, G., Björk, J., Lapidus, A., Löfberg, R., Bonderup, O., Avnstr Tags: Open access Inflammatory bowel disease Source Type: research

The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation
Conclusions HMOSs and 2'-FL directly inhibit LPS-mediated inflammation during ETEC invasion of T84 and H4 IECs through attenuation of CD14 induction. CD14 expression mediates LPS-TLR4 stimulation of portions of the ‘macrophage migration inhibitory factors’ inflammatory pathway via suppressors of cytokine signalling 2/signal transducer and activator of transcription 3/NF-B. HMOS direct inhibition of inflammation supports its functioning as an innate immune system whereby the mother protects her vulnerable neonate through her milk. 2'-FL, a principal HMOS, quenches inflammatory signalling. (Source: Gut)
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: He, Y., Liu, S., Kling, D. E., Leone, S., Lawlor, N. T., Huang, Y., Feinberg, S. B., Hill, D. R., Newburg, D. S. Tags: Intestinal inflammation Source Type: research

Seeing a cause for blindness in severe pancreatitis
During a holiday on a Mediterranean island, a 63-year old woman suffered a severe attack of pancreatitis secondary to gallstones. During the hospital stay, no sepsis was noted, but she was treated with prophylactic intravenous antibiotics, intravenous fluid and analgesia intensive care support was not required. After 22 days in hospital, she travelled back to the UK and presented to our department on advice to seek further help regarding ongoing symptoms of nausea and reduced appetite. A CT scan performed on admission demonstrated a developing 13x4.5 cm acute pancreatic collection with fat necrosis, splenic vein ...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Hopper, A. D., Gosling, D., Patwary, S., Partridge, D., Peterson, M. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

HNF4{alpha} is a therapeutic target that links AMPK to WNT signalling in early-stage gastric cancer
Conclusions Our results indicate that HNF4α is a targetable oncoprotein in GC, is regulated by AMPK signalling through AMPKα and resides upstream of WNT signalling. HNF4α may regulate ‘metabolic switch’ characteristic of a general malignant phenotype and its target WNT5A has potential prognostic values. The AMPKα-HNF4α-WNT5A signalling cascade represents a potentially targetable pathway for drug development. (Source: Gut)
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Chang, H. R., Nam, S., Kook, M.-C., Kim, K.-T., Liu, X., Yao, H., Jung, H. R., Lemos, R., Seo, H. H., Park, H. S., Gim, Y., Hong, D., Huh, I., Kim, Y.-W., Tan, D., Liu, C.-G., Powis, G., Park, T., Liang, H., Kim, Y. H. Tags: Open access, Pancreatic cancer Stomach Source Type: research

A large randomised controlled intervention trial to prevent gastric cancer by eradication of Helicobacter pylori in Linqu County, China: baseline results and factors affecting the eradication
Objective To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. Design A total of 184 786 residents aged 25–54 years were enrolled in this trial and received 13C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. Results The prevalence of H. pylori in trial participants was 57...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Pan, K.-f., Zhang, L., Gerhard, M., Ma, J.-l., Liu, W.-d., Ulm, K., Wang, J.-x., Zhang, L., Zhang, Y., Bajbouj, M., Zhang, L.-f., Li, M., Vieth, M., Liu, R.-y., Quante, M., Wang, L.-h., Suchanek, S., Zhou, T., Guan, W.-x., Schmid, R., Classen, M., You, W. Tags: Editor's choice, Stomach and duodenum, Pancreatic cancer Helicobacter pylori Source Type: research

EUS-guided gall bladder drainage with a lumen-apposing metal stent: a prospective long-term evaluation
Endoscopic ultrasound-guided gall bladder drainage (EUS-GBD) has been shown to be comparable with percutaneous gall bladder drainage (PTGBD) in terms of technical feasibility and clinical efficacy for the treatment of acute cholecystitis in high-risk surgical patients.1 However, a potential serious complication of this technique is air or bile leakage into the peritoneal cavity, since insertion of a drain or plastic stent requires a fistula tract with a diameter larger than the diameter of the inserted drain or stent. Therefore, a specifically designed lumen-apposing metal stents (LAMSs) has been developed for transenteric...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Walter, D., Teoh, A. Y., Itoi, T., Perez-Miranda, M., Larghi, A., Sanchez-Yague, A., Siersema, P. D., Vleggaar, F. P. Tags: Pancreas and biliary tract Endoscopy news Source Type: research

Hepatitis C: new clues to better vaccines?
HCV is a major public health problem in the USA and worldwide with the majority of acute infections progressing to chronicity in the absence of therapy. HCV infection is recognised as one of the major causes of liver disease, and is associated with the majority of liver transplantations in most countries. There have been tremendous advances in antiviral drug treatment for HCV over recent years, and current therapies can clear infections in the vast majority of people treated.1 However, treatment success can be limited by a range of factors, not least of which include the cost of therapy, which makes access to treatment cha...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Major, M. E. Tags: Commentary Source Type: research

In search for a disease-modifying treatment in irritable bowel syndrome
IBS continues to evade the efforts of medical science to translate knowledge of putative pathogenetic or pathophysiological mechanisms into successful pharmacological treatments. To some extent, laxatives and antidiarrhoeal medications are able to improve the erratic bowel habits associated with IBS, and recently linaclotides have been shown to relieve abdominal pain and constipation in IBS-C.1 Even so, in those experiencing treatment success this cannot be linked to a disease-modifying effect, since stopping the treatment leads to recurrence of symptoms. From this point of view, a hot topic during the past decades has bee...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Törnblom, H., Simren, M. Tags: Commentary Source Type: research

Stool consistency as a major confounding factor affecting microbiota composition: an ignored variable?
In this age of the microbiome, the one request most oft heard is ‘so what is the biomarker for this disease?’ In a world of ‘one-size-fits-all’ solutions, and a one pathogen-one disease framework of investigation, most doctors, clinical healthcare professionals, and healthcare industrialists just want the punchline—what is the bacterium that is causing that disease? The problem with this approach is that it remains a challenge to fully understand whether a given microbiome has any causative influence on a given condition, or whether identified associations have any relevance outside of a given...
Source: Gut - December 8, 2015 Category: Gastroenterology Authors: Gilbert, J. A., Alverdy, J. Tags: Commentary Source Type: research

GI highlights from the literature
In this study, Zhang and colleagues investigate how LRRK2 and Nod2 may act within... (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

The value of models in informing resource allocation in colorectal cancer screening: the case of the Netherlands
In May 2011, the Dutch government decided to implement a national programme for colorectal cancer (CRC) screening using biennial faecal immunochemical test screening between ages 55 and 75. Decision modelling played an important role in informing this decision, as well as in the planning and implementation of the programme afterwards. In this overview, we illustrate the value of models in informing resource allocation in CRC screening using the role that decision modelling has played in the Dutch CRC screening programme as an example. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: van Hees, F., Zauber, A. G., van Veldhuizen, H., Heijnen, M.-L. A., Penning, C., de Koning, H. J., van Ballegooijen, M., Lansdorp-Vogelaar, I. Tags: GUT Recent advances in clinical practice, Colon cancer Source Type: research

HBV cccDNA: viral persistence reservoir and key obstacle for a cure of chronic hepatitis B
At least 250 million people worldwide are chronically infected with HBV, a small hepatotropic DNA virus that replicates through reverse transcription. Chronic infection greatly increases the risk for terminal liver disease. Current therapies rarely achieve a cure due to the refractory nature of an intracellular viral replication intermediate termed covalently closed circular (ccc) DNA. Upon infection, cccDNA is generated as a plasmid-like episome in the host cell nucleus from the protein-linked relaxed circular (RC) DNA genome in incoming virions. Its fundamental role is that as template for all viral RNAs, and in conseque...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Nassal, M. Tags: GUT Recent advances in basic science Source Type: research

TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice
Conclusions Injection of TG1050 induced both splenic and intrahepatic functional T cells producing cytokines and displaying cytolytic activity in HBV-naìˆve and HBV-persistent mouse models together with significant reduction of circulating viral parameters. These results warrant clinical evaluation of TG1050 in the treatment of CHB. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Martin, P., Dubois, C., Jacquier, E., Dion, S., Mancini-Bourgine, M., Godon, O., Kratzer, R., Lelu-Santolaria, K., Evlachev, A., Meritet, J.-F., Schlesinger, Y., Villeval, D., Strub, J.-M., Van Dorsselaer, A., Marchand, J.-B., Geist, M., Brandely, R., Fin Tags: Hepatitis B, Open access Hepatology Source Type: research

Progenitor cell expansion and impaired hepatocyte regeneration in explanted livers from alcoholic hepatitis
Conclusions AH not responding to medical therapy is associated with lack of expression of cytokines involved in liver regeneration and profound mitochondrial damage along with lack of proliferative hepatocytes. Expansion of HPCs is inefficient to yield mature hepatocytes. Manoeuvres aimed at promoting differentiation of HPCs into mature hepatocytes should be tested in AH. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Dubuquoy, L., Louvet, A., Lassailly, G., Truant, S., Boleslawski, E., Artru, F., Maggiotto, F., Gantier, E., Buob, D., Leteurtre, E., Cannesson, A., Dharancy, S., Moreno, C., Pruvot, F.-R., Bataller, R., Mathurin, P. Tags: Hepatitis other Hepatology Source Type: research

The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cells
Conclusions Our findings therefore identify the miR-17-92 cluster as a functionally determining family of miRNAs in CSCs, and highlight the putative potential of developing modulators of this cluster to overcome drug resistance in pancreatic CSCs. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Cioffi, M., Trabulo, S. M., Sanchez-Ripoll, Y., Miranda-Lorenzo, I., Lonardo, E., Dorado, J., Reis Vieira, C., Ramirez, J. C., Hidalgo, M., Aicher, A., Hahn, S., Sainz, B., Heeschen, C. Tags: Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research

Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment
Conclusions Thus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Sainz, B., Alcala, S., Garcia, E., Sanchez-Ripoll, Y., Azevedo, M. M., Cioffi, M., Tatari, M., Miranda-Lorenzo, I., Hidalgo, M., Gomez-Lopez, G., Canamero, M., Erkan, M., Kleeff, J., Garcia-Silva, S., Sancho, P., Hermann, P. C., Heeschen, C. Tags: Pancreas and biliary tract Source Type: research

Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity
Conclusions Histone hyperacetylation in the spinal cord attenuates the pronociceptive effects of oestrogen on visceral sensitivity, suggesting that epigenetic regulation may be a potential approach to relieve visceral pain. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Cao, D.-Y., Bai, G., Ji, Y., Traub, R. J. Tags: Neurogastroenterology Source Type: research

Mesalazine and thymoquinone attenuate intestinal tumour development in Msh2loxP/loxP Villin-Cre mice
Objective Lynch syndrome is caused by germline mutations in DNA mismatch repair genes leading to microsatellite instability (MSI) and colorectal cancer. Mesalazine, commonly used for the treatment of UC, reduces MSI in vitro. Here, we tested natural compounds for such activity and applied mesalazine and thymoquinone in a Msh2loxP/loxP Villin-Cre mouse model for Lynch syndrome. Design Flow cytometry was used for quantitation of mutation rates at a CA13 microsatellite in human colon cancer (HCT116) cells that had been stably transfected with pIREShyg2-enhanced green fluorescent protein/CA13, a reporter for frameshift mutati...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Kortüm, B., Campregher, C., Lang, M., Khare, V., Pinter, M., Evstatiev, R., Schmid, G., Mittlböck, M., Scharl, T., Kucherlapati, M. H., Edelmann, W., Gasche, C. Tags: Open access, Editor's choice, Colon cancer GI cancer Source Type: research

Efficacy of oral methotrexate in paediatric Crohn's disease: a multicentre propensity score study
Conclusions In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Turner, D., Doveh, E., Cohen, A., Wilson, M. L., Grossman, A. B., Rosh, J. R., Lu, Y., Bousvaros, A., Deslandres, C., Noble, A., Baldassano, R. N., Levine, A., Lerner, A., Wilson, D. C., Griffiths, A. M. Tags: Inflammatory bowel disease Source Type: research

Early-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4
Conclusions Our results support the concept that variants in CTLA4 provide the basis for a novel Mendelian form of early-onset CD associated with systemic autoimmunity. Incomplete penetrance of autoimmunity further indicates the presence of other genetic and/or environmental modifiers. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Zeissig, S., Petersen, B.-S., Tomczak, M., Melum, E., Huc-Claustre, E., Dougan, S. K., Laerdahl, J. K., Stade, B., Forster, M., Schreiber, S., Weir, D., Leichtner, A. M., Franke, A., Blumberg, R. S. Tags: Inflammatory bowel disease Source Type: research

Global patterns of cardia and non-cardia gastric cancer incidence in 2012
Objective Globally, gastric cancer incidence shows remarkable international variation and demonstrates distinct characteristics by the two major topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global incidence estimates by subsite are lacking, we aimed to describe the worldwide incidence patterns of CGC and NCGC separately. Design Using Cancer Incidence in Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC by country, sex and age group (
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Colquhoun, A., Arnold, M., Ferlay, J., Goodman, K. J., Forman, D., Soerjomataram, I. Tags: Pancreatic cancer Stomach Source Type: research

Barrett's oesophagus length is established at the time of initial endoscopy and does not change over time: results from a large multicentre cohort
Conclusions There was no significant difference in BO length by age category in decades. In addition, the change in BO length from index to follow-up endoscopy was similar among patients>30 years. These findings suggest that a patient's BO segment length attains its full extent by the time of the initial endoscopic examination. (Source: Gut)
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Moawad, F. J., Young, P. E., Gaddam, S., Vennalaganti, P., Thota, P. N., Vargo, J., Cash, B. D., Falk, G. W., Sampliner, R. E., Lieberman, D., Sharma, P. Tags: Oesophageal cancer Oesophagus Source Type: research

British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps
These guidelines provide an evidence-based framework for the management of patients with large non-pedunculated colorectal polyps (LNPCPs), in addition to identifying key performance indicators (KPIs) that permit the audit of quality outcomes. These are areas not previously covered by British Society of Gastroenterology (BSG) Guidelines. A National Institute of Health and Care Excellence (NICE) compliant BSG guideline development process was used throughout and the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to structure the guideline development process. A systematic review of literature w...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Rutter, M. D., Chattree, A., Barbour, J. A., Thomas-Gibson, S., Bhandari, P., Saunders, B. P., Veitch, A. M., Anderson, J., Rembacken, B. J., Loughrey, M. B., Pullan, R., Garrett, W. V., Lewis, G., Dolwani, S. Tags: Open access, Intestinal cancer Guidelines Source Type: research

Weight loss in a man from West Africa
Clinical presentation A 71-year-old man was investigated for recent unintentional weight loss of approximately 15 kg (>20% total body mass) within the past 3 months. His past medical history included type 2 diabetes mellitus and hypertension, and he was an ex-smoker with a 40 pack-year history. Resident in the UK for 50 years, he was originally from Sierra Leone with no recent travel history. Examination revealed cachexia and lymphadenopathy. Admission blood tests demonstrated a white cell count of 12.1x109/L (with eosinophil level raised at 1.0x109/L), microcytic anaemia (haemoglobin of 109 g/L with...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Topan, R., James, S., Mullish, B. H., Zac-Varghese, S., Goldin, R. D., Thomas, R., Cox, J., Hoare, J. M. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

A new instrumental platform for Trans-Anal Submucosal Endoscopic Resection (TASER)
Message Existing trans-anal approaches for complete excision of large and complex rectal polyps (CRPs) remain suboptimal due to technical complexity and inflexibility leading to the risk of inadequate excision and need for proctectomy, especially when using a single-channel flexible endoscope. Trans-Anal Submucosal Endoscopic Resection (TASER) provides a flexible endo-surgical platform with enhanced visualisation and therapeutic options delivered via an endoscope assisted by simultaneous, dynamic trans-anal retraction devices (Figure 1). Preliminary results in 17 patients with complex and very large (>5 cm) as well...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Tsiamoulos, Z. P., Warusavitarne, J., Faiz, O., Castello-Cortes, A., Elliott, T., Peake, S. T., Bassett, P., Saunders, B. P. Tags: Endoscopy, Colon cancer, Intestinal cancer Endoscopy news Source Type: research

Emerging role of microRNAs to tackle drug resistance in pancreatic cancer
Despite the recent emergence of novel chemotherapy regimen such as nab-paclitaxel/gemcitabine and FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin), pancreatic ductal adenocarcinoma (PDA) is characterised by a poor response to chemotherapy and radiotherapy. Therefore, it remains a challenge for clinicians and scientists likewise to overcome resistance to treatment. PDA silently develops from preneoplastic lesions (PanINs I–III) to invasive cancer over a long period of time. A number of genetic mutations have been identified and well characterised during the evolution of PDA, such as the Kras oncogen...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Neesse, A., Gress, T. M. Tags: Commentary Source Type: research

When antimicrobial peptides hit the wrong target: a novel link between tumour macrophages and cancer stem cells
Understanding the interplay between tumour microenvironment and cancer cells is an active research area that holds many promises for identifying stroma-derived paracrine drivers of tumour growth or progression that may thus represent possible therapeutic targets. Pancreatic ductal adenocarcinoma (PDAC), the most common and almost invariably deadly pancreatic tumour, is characterised by a dense tumour stroma that contains a heterogeneous population of cells including stellate cells, fibroblasts, smooth muscle cells, endothelial cells, and a number of inflammatory and immune cells such as dendritic cells and macrophages.1 In...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Diaferia, G. R., Natoli, G. Tags: Commentary Source Type: research

Stimulating hepatocyte renewal: a new paradigm for the treatment of severe alcoholic hepatitis unresponsive to corticosteroids?
Patients with severe alcoholic hepatitis who are admitted to the hospital usually have evidence of decompensated cirrhosis with high serum bilirubin levels, low prothrombin time associated with dysfunction or failure of other organs/systems (kidney, brain, circulation).1 Spontaneous 1-month mortality is 35%.2 Pathophysiology of severe alcoholic hepatitis is incompletely understood.2–4 Alcohol consumption results in alterations of gut microbiome, increased intestinal permeability and subsequent translocation of Gram-negative bacteria. These bacteria may release pathogen-associated molecular patterns (PAMPs) such as li...
Source: Gut - November 8, 2015 Category: Gastroenterology Authors: Moreau, R. Tags: Commentary Source Type: research

Identification of a functional PRSS1 promoter variant in linkage disequilibrium with the chronic pancreatitis-protecting rs10273639
We read with interest the paper by Derikx et al1 replicating the association of the minor T allele of single nucleotide polymorphism rs10273639C/T, which is located 408 bp upstream of the translation initiation codon of the cationic trypsinogen (PRSS1) gene, with a protective effect against chronic pancreatitis.2 However, whether rs10273639 is the causal variant or not remains unknown. Resolving this issue is of intrinsic biological interest, and it may also have diagnostic and therapeutic value. During resequencing of the promoter region of PRSS1 in 287 French Caucasian individuals (see online supplementary material)...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Boulling, A., Sato, M., Masson, E., Genin, E., Chen, J.-M., Ferec, C. Tags: PostScript Source Type: research

Hypermethylation of ZNF545 is associated with poor prognosis in patients with early-stage hepatocellular carcinoma after thermal ablation
We read with interest the article by Wang et al1 on zinc-finger protein 545 (ZNF545) acting as a tumour suppressor gene (TSG) in gastric cancer by inhibiting rRNA transcription and its methylation as a prognostic factor for early stages of gastric cancer. Inactivation of TSGs through promoter hypermethylation also plays an important role in progression of hepatocellular carcinoma (HCC).2–4 We wish to report the results of the expression profile and epigenetic regulation of ZNF545 in HCC, and its methylation role on early-stage HCC progression after thermal ablation. Our results showed reduced or loss of ZNF545 expres...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Yu, J., Li, X., Tao, Q., Yu, X.-l., Cheng, Z.-g., Han, Z.-y., Guo, M., Liang, P. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceGenetic progression from Barrett's oesophagus to adenocarcinoma Stachler MD, Taylor-Weiner A, Peng S, et al. Paired exome analysis of Barrett's esophagus and adenocarcinoma. Nat Genet 2015;47:1047–55. While most patients with Barrett's oesophagus never progress to cancer, understanding the evolutionary processes in those that are at higher cancer risk and predicting their response to therapy is crucial. Here, the authors demonstrate with exome sequencing that patients with non-dysplastic Barrett's tissue surprisingly show a mutation rate comparable with prostate, breast and colon cancers. Furthermore, th...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Hepatitis C virus treatment in the real world: optimising treatment and access to therapies
Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has chang...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Zoulim, F., Liang, T. J., Gerbes, A. L., Aghemo, A., Deuffic-Burban, S., Dusheiko, G., Fried, M. W., Pol, S., Rockstroh, J. K., Terrault, N. A., Wiktor, S. Tags: GUT Recent advances in clinical practice, Editor's choice, Hepatic cancer Source Type: research

Emerging optical methods for surveillance of Barrett's oesophagus
The rapid rise in incidence of oesophageal adenocarcinoma has motivated the need for improved methods for surveillance of Barrett's oesophagus. Early neoplasia is flat in morphology and patchy in distribution and is difficult to detect with conventional white light endoscopy (WLE). Light offers numerous advantages for rapidly visualising the oesophagus, and advanced optical methods are being developed for wide-field and cross-sectional imaging to guide tissue biopsy and stage early neoplasia, respectively. We review key features of these promising methods and address their potential to improve detection of Barrett's neopla...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Sturm, M. B., Wang, T. D. Tags: GUT Recent advances in basic science, Oesophageal cancer Source Type: research

Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B
Conclusions 25% of women with chronic hepatitis B will demonstrate increased liver inflammation in the postpartum period. This is usually asymptomatic and resolves spontaneously. This is more likely if the woman is HBeAg-positive at baseline (2.56 times the risk), although flares also commonly occur in HBeAg-negative women. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Giles, M., Visvanathan, K., Lewin, S., Bowden, S., Locarnini, S., Spelman, T., Sasadeusz, J. Tags: Hepatitis B Hepatology Source Type: research

Strategies for the treatment of Hepatitis C in an era of interferon-free therapies: what public health outcomes do we value most?
Objective The expense of new therapies for HCV infection may force health systems to prioritise the treatment of certain patient groups over others. Our objective was to forecast the population impact of possible prioritisation strategies for the resource-rich setting of Scotland. Design We created a dynamic Markov simulation model to reflect the HCV-infected population in Scotland. We determined trends in key outcomes (e.g. incident cases of chronic infection and severe liver morbidity (SLM)) until the year 2030, according to treatment strategies involving prioritising, either: (A) persons with moderate/advanced fibrosis...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Innes, H., Goldberg, D., Dillon, J., Hutchinson, S. J. Tags: Hepatology Source Type: research

SOX9 regulates ERBB signalling in pancreatic cancer development
Conclusions By integrating data from patient samples and mouse models, we found that SOX9 regulates the ERBB pathway throughout pancreatic tumourigenesis. Our work opens perspectives for therapy targeting tumourigenic mechanisms. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Grimont, A., Pinho, A. V., Cowley, M. J., Augereau, C., Mawson, A., Giry-Laterriere, M., Van den Steen, G., Waddell, N., Pajic, M., Sempoux, C., Wu, J., Grimmond, S. M., Biankin, A. V., Lemaigre, F. P., Rooman, I., Jacquemin, P. Tags: Pancreas and biliary tract, Pancreatic cancer Source Type: research

Time to progression of pancreatic ductal adenocarcinoma from low-to-high tumour stages
Conclusions These results are consistent with the hypothesis that once pancreatic ductal adenocarcinomas become detectable clinically progression from low-stage to advanced-stage disease is rapid. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Yu, J., Blackford, A. L., dal Molin, M., Wolfgang, C. L., Goggins, M. Tags: Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research

Exploring the genetics of irritable bowel syndrome: a GWA study in the general population and replication in multinational case-control cohorts
Conclusions Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Ek, W. E., Reznichenko, A., Ripke, S., Niesler, B., Zucchelli, M., Rivera, N. V., Schmidt, P. T., Pedersen, N. L., Magnusson, P., Talley, N. J., Holliday, E. G., Houghton, L., Gazouli, M., Karamanolis, G., Rappold, G., Burwinkel, B., Surowy, H., Rafter, J Tags: Irritable bowel syndrome Neurogastroenterology Source Type: research

Two coincident cases of easily curable 'refractory sprue'
Clinical presentation On two consecutive days, two women, 82 and 76 years of age, were admitted with severe watery diarrhoea lasting for about 8 months. They presented with serious deconditioning and a weight loss of 16 and 20 kg, respectively. An extensive workup had yielded virtually identical results in both patients and led to the diagnosis of ‘refractory seronegative sprue’. There was no history of foreign travel or previous GI symptoms. Duodenal biopsy showed subtotal villous atrophy (VA) (figure 1) with an increased number of intraepithelial lymphocytes (figure 2). IgA and IgG tissue trans...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Schiller, D., Ziachehabi, A., Silye, R., Schofl, R. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Reproducibility of histological assessments of disease activity in UC
Conclusions Although ‘substantial’ to ‘almost perfect’ ICCs for intrarater agreement were found in the assessment of HA in UC, ICCs for inter-rater agreement were considerably lower. According to the consensus process results, standardisation of item definitions and modification of the existing indices is required to create an optimal UC histological instrument. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Mosli, M. H., Feagan, B. G., Zou, G., Sandborn, W. J., D'Haens, G., Khanna, R., Behling, C., Kaplan, K., Driman, D. K., Shackelton, L. M., Baker, K. A., MacDonald, J. K., Vandervoort, M. K., Samaan, M. A., Geboes, K., Valasek, M. A., Pai, R., Langner, C., Tags: Inflammatory bowel disease Source Type: research

miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD
Conclusions Our data indicate that miR-10a is decreased in the inflamed mucosa of IBD and downregulates mucosal inflammatory response through inhibition of IL-12/IL-23p40 and NOD2 expression, and blockade of Th1/Th17 cell immune responses. Thus, miR-10a could play a role in the pathogenesis and progression of IBD. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Wu, W., He, C., Liu, C., Cao, A. T., Xue, X., Evans-Marin, H. L., Sun, M., Fang, L., Yao, S., Pinchuk, I. V., Powell, D. W., Liu, Z., Cong, Y. Tags: Inflammatory bowel disease Source Type: research

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults
Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans. Trial registration number NCT00750438. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Chambers, E. S., Viardot, A., Psichas, A., Morrison, D. J., Murphy, K. G., Zac-Varghese, S. E. K., MacDougall, K., Preston, T., Tedford, C., Finlayson, G. S., Blundell, J. E., Bell, J. D., Thomas, E. L., Mt-Isa, S., Ashby, D., Gibson, G. R., Kolida, S., D Tags: Open access, Press releases Gut microbiota Source Type: research

Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks
Conclusions In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Morgun, A., Dzutsev, A., Dong, X., Greer, R. L., Sexton, D. J., Ravel, J., Schuster, M., Hsiao, W., Matzinger, P., Shulzhenko, N. Tags: Gut microbiota Source Type: research

Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas
Objective Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. Design We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatist...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Lin, S. J., Gagnon-Bartsch, J. A., Tan, I. B., Earle, S., Ruff, L., Pettinger, K., Ylstra, B., van Grieken, N., Rha, S. Y., Chung, H. C., Lee, J.-S., Cheong, J. H., Noh, S. H., Aoyama, T., Miyagi, Y., Tsuburaya, A., Yoshikawa, T., Ajani, J. A., Boussiouta Tags: Open access, Pancreatic cancer Stomach Source Type: research

Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy
Conclusions These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. Trial registration number NCT02175901. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Zhang, W., Chen, Q., Liang, X., Liu, W., Xiao, S., Graham, D. Y., Lu, H. Tags: Helicobacter pylori Source Type: research

In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity
Conclusions These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux. (Source: Gut)
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Derakhshan, M. H., Robertson, E. V., Yeh Lee, Y., Harvey, T., Ferrier, R. K., Wirz, A. A., Orange, C., Ballantyne, S. A., Hanvey, S. L., Going, J. J., McColl, K. E. Tags: Oesophagus Source Type: research

UK guidelines on the management of variceal haemorrhage in cirrhotic patients
These updated guidelines on the management of variceal haemorrhage have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines which this document supersedes were written in 2000 and have undergone extensive revision by 13 members of the Guidelines Development Group (GDG). The GDG comprises elected members of the BSG liver section, representation from British Association for the Study of the Liver (BASL) and Liver QuEST, a nursing representative and a patient representative. The qu...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Tripathi, D., Stanley, A. J., Hayes, P. C., Patch, D., Millson, C., Mehrzad, H., Austin, A., Ferguson, J. W., Olliff, S. P., Hudson, M., Christie, J. M., Lowsley-Williams, Guo Tags: Open access Guidelines Source Type: research

Magnetic compression for treatment of large oesophageal diverticula: a new endoscopic approach for a risky surgical disease?
Message Magnetic compression resulting in serosa-to-serosa apposition followed by pressure necrosis has been shown to be able to create solid anastomostic connections and has been reported in conditions such as oesophageal atresia, benign biliary strictures and malignant gastric outlet obstruction. This first series evaluated this technique for the management of large intrathoracic oesophageal diverticula by creating a communication between the bottom of the diverticulum and the distal oesophagus followed, in a second endoscopy session, by the transection of the proximal septum. Four patients underwent this procedure witho...
Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Bouchard, S., Huberty, V., Blero, D., Deviere, J. Tags: Endoscopy, Gastric emptying disorders, Stomach and duodenum Endoscopy news Source Type: research