GI highlights from the literature
Basic scienceCARD9, the microbiota and tryptophan in intestinal homeostasis Lamas B, Richard ML, Leducq V, et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med 2016;22:598–605. doi:10.1038/nm.4102 Genetics, environment and diet influence the composition of the gut microbiota. A change in any of these factors results in a dysbiosis, and this contributes to the pathogenesis of IBD. CARD9 is a susceptibility gene for IBD that is involved in immune responses against microorganisms. Card9 knockout mice (Card9–/–) are more susceptible t...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Erratum: A patient with acute pancreatitis and unusual vermiform stools
Hazen WL, Hayes DP, Pullens HJM. A patient with acute pancreatitis and unusual vermiform stools. Gut 2014;63:524. The answer section has already published in an earlier issue. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Tags: Correction Source Type: research

LT{beta}R signalling preferentially accelerates oncogenic AKT-initiated liver tumours
Conclusions Our findings link LTβR and oncogenic AKT signalling in the development of ICC. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Scarzello, A. J., Jiang, Q., Back, T., Dang, H., Hodge, D., Hanson, C., Subleski, J., Weiss, J. M., Stauffer, J. K., Chaisaingmongkol, J., Rabibhadana, S., Ruchirawat, M., Ortaldo, J., Wang, X. W., Norris, P. S., Ware, C. F., Wiltrout, R. H. Tags: Open access, Hepatic cancer Hepatology Source Type: research

A hepatic stellate cell gene expression signature associated with outcomes in hepatitis C cirrhosis and hepatocellular carcinoma after curative resection
Conclusions This work highlights the unique transcriptional niche of stellate cells, and identifies potential stellate cell targets for tracking, targeting and isolation. Hepatic stellate cell signature expression may identify patients with HCV cirrhosis or postresection HCC with poor prognosis. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Zhang, D. Y., Goossens, N., Guo, J., Tsai, M.-C., Chou, H.-I., Altunkaynak, C., Sangiovanni, A., Iavarone, M., Colombo, M., Kobayashi, M., Kumada, H., Villanueva, A., Llovet, J. M., Hoshida, Y., Friedman, S. L. Tags: Hepatic cancer Hepatology Source Type: research

Characterisation of liver pathogenesis, human immune responses and drug testing in a humanised mouse model of HCV infection
Conclusions The HIL mouse provides a model for the understanding of HCV-specific human immune responses and HCV-associated disease pathologies. It could also serve as a platform for antifibrosis and immune-modulatory drug testing. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Keng, C. T., Sze, C. W., Zheng, D., Zheng, Z., Yong, K. S. M., Tan, S. Q., Ong, J. J. Y., Tan, S. Y., Loh, E., Upadya, M. H., Kuick, C. H., Hotta, H., Lim, S. G., Tan, T. C., Chang, K. T. E., Hong, W., Chen, J., Tan, Y.-J., Chen, Q. Tags: Cirrhosis, Open access, Hepatic cancer Hepatology Source Type: research

In vivo evidence for ribavirin-induced mutagenesis of the hepatitis E virus genome
Conclusions In summary, this first investigation of intrahost HEV population evolution indicates that RBV causes HEV mutagenesis in treated patients and that an emergence of distinct mutants within the viral population occurs during RBV therapy. We also suggest that next-generation sequencing could be useful to guide personalised antiviral strategies. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Todt, D., Gisa, A., Radonic, A., Nitsche, A., Behrendt, P., Suneetha, P. V., Pischke, S., Bremer, B., Brown, R. J. P., Manns, M. P., Cornberg, M., Bock, C. T., Steinmann, E., Wedemeyer, H. Tags: Cirrhosis, Open access Hepatology Source Type: research

Opposite roles of cannabinoid receptors 1 and 2 in hepatocarcinogenesis
Conclusions Similar to their role in fibrogenesis, CB1 and CB2 exert opposite effects on hepatocarcinogenesis and may provide novel therapeutic targets. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Suk, K.-T., Mederacke, I., Gwak, G.-Y., Cho, S. W., Adeyemi, A., Friedman, R., Schwabe, R. F. Tags: Cirrhosis, Nonalcoholic steatosis, Editor's choice, Hepatic cancer Hepatology Source Type: research

Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy
Conclusions Overall, our data highlight TAMs as critical determinants of prognostic responsiveness to CTX and provide clinical and in vitro evidence that CTX overall directly re-educates TAMs to restrain tumour progression. These results suggest that the quantification of TAMs could be exploited to select patients more likely to respond to CTX and provide the basis for novel strategies aimed at re-educating macrophages in the context of CTX. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Di Caro, G., Cortese, N., Castino, G. F., Grizzi, F., Gavazzi, F., Ridolfi, C., Capretti, G., Mineri, R., Todoric, J., Zerbi, A., Allavena, P., Mantovani, A., Marchesi, F. Tags: Pancreas and biliary tract Source Type: research

Clinical profiles and outcomes in idiopathic duct-centric chronic pancreatitis (type 2 autoimmune pancreatitis): the Mayo Clinic experience
Conclusions The current diagnostic classification of probable IDCP and the inclusion of IBD as a supportive criterion appear valid, because patients have similar clinical profiles and disease-related outcomes to those with definitive IDCP. Concurrent IBD, especially in young patients, may suggest when IDCP is the underlying cause of recurrent acute pancreatitis, but additional studies are needed for validation. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Hart, P. A., Levy, M. J., Smyrk, T. C., Takahashi, N., Abu Dayyeh, B. K., Clain, J. E., Gleeson, F. C., Pearson, R. K., Petersen, B. T., Topazian, M. D., Vege, S. S., Zhang, L., Chari, S. T. Tags: Pancreas and biliary tract, Pancreatitis Source Type: research

New Wnt/{beta}-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals
Conclusions We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Qi, J., Yu, Y., Akilli Öztürk, O., Holland, J. D., Besser, D., Fritzmann, J., Wulf-Goldenberg, A., Eckert, K., Fichtner, I., Birchmeier, W. Tags: Colon cancer Source Type: research

Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD
Conclusions We here present the first report of PSC-associated faecal dysbiosis, independent from IBD signatures, suggesting the intestinal microbiota could be a contributing factor in PSC pathogenesis. Further studies are needed to confirm these findings and assess causality. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Sabino, J., Vieira-Silva, S., Machiels, K., Joossens, M., Falony, G., Ballet, V., Ferrante, M., Van Assche, G., Van der Merwe, S., Vermeire, S., Raes, J., Rymenans Tags: Crohn's disease, Pancreas and biliary tract, Open access Gut microbiota Source Type: research

Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease
Conclusions Reduced mucosal TSLP expression may contribute to intestinal damage in refractory and untreated CD. Further studies are needed to verify whether restoring TSLP might be therapeutically useful especially in refractory patients with CD. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Biancheri, P., Di Sabatino, A., Rescigno, M., Giuffrida, P., Fornasa, G., Tsilingiri, K., Pender, S. L. F., Papadia, C., Wood, E., Pasini, A., Ubezio, C., Vanoli, A., Forbes, A., MacDonald, T. T., Corazza, G. R. Tags: Crohn's disease, Open access, Coeliac disease Source Type: research

Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study
Objectives Severe sprue-like enteropathy associated with olmesartan has been reported, but there has been no demonstration of an increased risk by epidemiological studies. Aim To assess, in a nationwide patient cohort, the risk of hospitalisation for intestinal malabsorption associated with olmesartan compared with other angiotensin receptor blockers (ARB) and ACE inhibitors (ACEIs). Design From the French National Health Insurance claim database, all adult patients initiating ARB or ACEI between 1 January 2007 and 31 December 2012 with no prior hospitalisation for intestinal malabsorption, no serology testing for coelia...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Basson, M., Mezzarobba, M., Weill, A., Ricordeau, P., Allemand, H., Alla, F., Carbonnel, F. Tags: Coeliac disease, Gastrointestinal hormones Small bowel Source Type: research

Differential effects of {alpha}4{beta}7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo
Conclusions α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Fischer, A., Zundler, S., Atreya, R., Rath, T., Voskens, C., Hirschmann, S., Lopez-Posadas, R., Watson, A., Becker, C., Schuler, G., Neufert, C., Atreya, I., Neurath, M. F. Tags: Open access Inflammatory bowel disease Source Type: research

Tissue-infiltrating neutrophils represent the main source of IL-23 in the colon of patients with IBD
Conclusions This study provides the first evidence of CXCR1+CXCR2+IL-23-producing neutrophils that infiltrate and accumulate in inflamed colon tissue of patients with IBD. Thus, this novel source of IL-23 may play a key role in disease progression and will be important to take into consideration in the development of future strategies to monitor, treat and prevent IBD. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Kvedaraite, E., Lourda, M., Ideström, M., Chen, P., Olsson-Akefeldt, S., Forkel, M., Gavhed, D., Lindforss, U., Mjösberg, J., Henter, J.-I., Svensson, M. Tags: Inflammatory bowel disease Source Type: research

MDGA2 is a novel tumour suppressor cooperating with DMAP1 in gastric cancer and is associated with disease outcome
Background Using the promoter methylation assay, we have shown that MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) is preferentially methylated in gastric cancer. We analysed its biological effects and prognostic significance in gastric cancer. Methods MDGA2 methylation status was evaluated by combined bisulfite restriction analysis and bisulfite genomic sequencing. The effects of MDGA2 re-expression or knockdown on cell proliferation, apoptosis and the cell cycle were determined. MDGA2 interacting protein was identified by mass spectrometry and MDGA2-related cancer pathways by reporter activity and P...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Wang, K., Liang, Q., Li, X., Tsoi, H., Zhang, J., Wang, H., Go, M. Y. Y., Chiu, P. W. Y., Ng, E. K. W., Sung, J. J. Y., Yu, J. Tags: Open access, Pancreatic cancer Stomach Source Type: research

Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours
Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Hu, N., Wang, Z., Song, X., Wei, L., Kim, B. S., Freedman, N. D., Baek, J., Burdette, L., Chang, J., Chung, C., Dawsey, S. M., Ding, T., Gao, Y.-T., Giffen, C., Han, Y., Hong, M., Huang, J., Kim, H. S., Koh, W.-P., Liao, L. M., Mao, Y. M., Qiao, Y.-L., Sh Tags: Stomach and duodenum, Pancreatic cancer Source Type: research

Derivation of genetic biomarkers for cancer risk stratification in Barretts oesophagus: a prospective cohort study
Conclusions A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus. (Source: Gut)
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Timmer, M. R., Martinez, P., Lau, C. T., Westra, W. M., Calpe, S., Rygiel, A. M., Rosmolen, W. D., Meijer, S. L., ten Kate, F. J. W., Dijkgraaf, M. G. W., Mallant-Hent, R. C., Naber, A. H. J., van Oijen, A. H. A. M., Baak, L. C., Scholten, P., Böh Tags: Oesophageal cancer Oesophagus Source Type: research

Solving a disaster following coronary bypass operation
Clinical presentation A 72-year-old male patient underwent coronary bypass surgery and presented with atrial fibrillation upon completion of the operation. Intraoperative transesophageal echocardiography (TEE) was performed, followed by successful electric cardioversion. The initially stable patient developed a systemic inflammatory response syndrome on day 7 after the operation. The septic course progressed over the next days, necessitating reintubation and placement of a nasogastric feeding tube. Since the patient did not stabilise despite escalation of antibiotic therapy, he was referred to our department of general sur...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Neumann, P.-A., Laukoetter, M., Mennigen, R., Kebschull, L., Bettenworth, D., Lenze, F., Ullerich, H., Senninger, N., Vowinkel, T. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Guideline for obtaining valid consent for gastrointestinal endoscopy procedures
Much has changed since the last guideline of 2008, both in endoscopy and in the practice of obtaining informed consent, and it is vital that all endoscopists who are responsible for performing invasive and increasingly risky procedures are aware of the requirements for obtaining valid consent. This guideline is restricted to GI endoscopy but we cover elective and acute or emergency procedures. Few clinical trials have been carried out in relation to informed consent but most areas are informed by guidance from the General Medical Counsel (GMC) and/or are enshrined in legislation. Following an iterative voting process a ser...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Everett, S. M., Griffiths, H., Nandasoma, U., Ayres, K., Bell, G., Cohen, M., Thomas-Gibson, S., Thomson, M., Naylor, K. M. T. Tags: Endoscopy Guidelines Source Type: research

Treatment of chronic hepatitis E with ribavirin: lessons from deep sequencing
Much has been learned about hepatitis E virus (HEV) infection over the last years. We know today that hepatitis E of genotype 3 is a zoonotic infection in the Western world that can be transmitted through the consumption of raw or undercooked pork and game meat, with much higher than anticipated seroprevalence rates, a broad range of hepatic as well as extrahepatic manifestations, and a potential to persist and cause chronic hepatitis as well as cirrhosis in immunocompromised individuals, including transplant recipients as well as patients with haematologic malignancies or poorly controlled HIV infection.1 Fibrosis progres...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Gouttenoire, J., Szkolnicka, D., Moradpour, D. Tags: Commentary Source Type: research

Targeting cannabinoid receptors in hepatocellular carcinoma?
Hepatocellular carcinoma (HCC) represents a major health problem, accounting for 90% of primary liver cancer and the second cause of cancer-related death worldwide.1 The tumour predominantly occurs in cirrhotic livers following exposure to various risk factors, including hepatitis B and C virus infection, excessive alcohol intake and metabolic syndrome. The majority of patients are diagnosed at intermediate or advanced stages and are ineligible for curative treatment. Several mechanisms contribute to the initiation and progression of HCC, including chronic inflammation, DNA damage, epigenetic modifications, senescence, tel...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Mallat, A., Lotersztajn, S. Tags: Commentary Source Type: research

Primary sclerosing cholangitis: 50 years of a gut-liver relationship and still no love?
The relationship between the gut and the liver in primary sclerosing cholangitis (PSC) has puzzled researchers since the relationship was established almost 50 years ago.1 2 In Northern European populations, the prevalence of IBD in PSC ranges between 60% and 80%,3 and even in populations where the relationship is less apparent (eg, Asia) typical PSC patients (young males) show similar frequencies.4 It is by now reasonably well established that the type of IBD occurring in PSC differs from UC or Crohn's disease.5 From the clinical perspective, PSC-IBD is typically extensive yet quiescent, and shows a right-sided predo...
Source: Gut - September 7, 2016 Category: Gastroenterology Authors: Karlsen, T. H. Tags: Commentary Source Type: research

Diagnostic accuracy of the {gamma}-glutamyl transpeptidase to platelet ratio to predict liver fibrosis in Egyptian patients with HCV genotype 4
Given the high disease burden with viral hepatitis, and the advent of highly effective direct-acting antivirals against HCV infection, the WHO is now developing a global strategy to eliminate viral hepatitis by 2030.1 Increasing the uptake of HCV diagnosis and treatment will become a key intervention in achieving this goal. Although antiviral drugs should be considered for all persons with chronic HCV infection, those with significant liver fibrosis, and especially cirrhosis, should be prioritised for treatment, as they are at increased risk of hepatic complications. Current WHO guidelines for HCV recommend aspartate amino...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Shimakawa, Y., Bonnard, P., El Kassas, M., Abdel-Hamid, M., Esmat, G., Fontanet, A. Tags: PostScript Source Type: research

Human knockouts of PLA2G4A phenocopy NSAID-induced gastrointestinal and renal toxicity
We describe below a family with a different truncating mutation to further delineate the PLA2G4A-related phenotype. The family consists of healthy first cousin parents and 8-year-old triplets, two of whom had been treated for severe peptic ulcer disease since they were 2 years of age. The initial presentation was in the form of abdominal pain, anaemia and blood in stools, and multiple gastric and duodenal ulcers were diagnosed by endoscopy at 2 years of age. Gastrin and chromogranin levels were consistently normal. Response to proton pump inhibitor has been satisfactory, although a recent endoscopy revealed persi...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Maddirevula, S., Abanemai, M., Alkuraya, F. S. Tags: PostScript Source Type: research

High stability of faecal microbiome composition in guanidine thiocyanate solution at room temperature and robustness during colonoscopy
We read with interest the paper by Jalanka et al,1 who examined the influence of bowel preparation on intestinal microbiota by using phylogenetic microarray and quantitative PCR analyses of frozen samples. Conventionally, faecal samples are frozen on dry ice or in a deep-freezer (at –80°C) immediately after collection, as done by Jalanka et al, because bacterial taxa can change appreciably within 15 min at room temperature (RT).2 However, immediate deep-freezing is often inconvenient in routine clinical practice, and we wondered whether simple storage of faecal samples at RT in test tubes containing 4 M...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Nishimoto, Y., Mizutani, S., Nakajima, T., Hosoda, F., Watanabe, H., Saito, Y., Shibata, T., Yachida, S., Yamada, T. Tags: Open access PostScript Source Type: research

GI highlights from the literature
Basic scienceTargeting the Wnt pathway in colorectal tumorigenesis Valenta T, Degirmenca B, Moor AE, et al. Wnt Ligands secreted by subepithelial mesenchymal cells are essential for the survival of intestinal stem cells and gut homeostasis. Cell Reports 2016;15:911–18. Dysregulation of the Wnt signalling pathway is crucial for the development of intestinal tumorigenesis and stem cells require a precise concentration of available Wnt to maintain the intestinal epithelium. The authors of this manuscript suggest that targeting inappropriate Wnt signalling may be a strategy to prevent or to treat colorectal cancer. To in...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Erratum: Are we meeting the standards set for endoscopy? Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice
Williams EJ, Taylor S, Fairclough P, et al. Are we meeting the standards set for endoscopy? Results of a large-scale prospective survey of endoscopic retrograde cholangio-pancreatograph practice. Gut 2007;56:821–9. The 10th author's name has been corrected to Paula R Williamson. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Tags: Correction Source Type: research

Insulin resistance alters hepatic ethanol metabolism: studies in mice and children with non-alcoholic fatty liver disease
Conclusions Taken together, our data of animal experiments suggest that increased blood ethanol levels in patients with NAFLD may result from insulin-dependent impairments of ADH activity in liver tissue rather than from an increased endogenous ethanol synthesis. Trial registration number NCT01306396. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Engstler, A. J., Aumiller, T., Degen, C., Dürr, M., Weiss, E., Maier, I. B., Schattenberg, J. M., Jin, C. J., Sellmann, C., Bergheim, I. Tags: Nonalcoholic steatosis Hepatology Source Type: research

Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury
Conclusions In this pilot study in vitro testing using MH cells derived from patients with acute liver injury was able to identify patients with iDILI with an excellent sensitivity and a higher specificity than RUCAM, the most widely used current causality assessment score. Therefore, MH cells could be useful to identify the causative drugs even in polymedicated patients by adding objective data to causality assessment. Trial registration number : NCT02353455 (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Benesic, A., Leitl, A., Gerbes, A. L. Tags: Hepatology Source Type: research

Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study
Conclusions Using a novel human twin-study design, we demonstrate that discordancy in liver fat content between the twins can be explained by miRs, and that they are heritable. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Zarrinpar, A., Gupta, S., Maurya, M. R., Subramaniam, S., Loomba, R. Tags: Nonalcoholic steatosis Hepatology Source Type: research

Integrative microRNA profiling in alcoholic hepatitis reveals a role for microRNA-182 in liver injury and inflammation
Conclusions AH is characterised by a deregulated miRNA profile, including miR-182, which is associated with disease severity and liver injury. These results highlight the potential of miRNAs as therapeutic targets and biomarkers in AH. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Blaya, D., Coll, M., Rodrigo-Torres, D., Vila-Casadesus, M., Altamirano, J., Llopis, M., Graupera, I., Perea, L., Aguilar-Bravo, B., Diaz, A., Banales, J. M., Claria, J., Lozano, J. J., Bataller, R., Caballeria, J., Gines, P., Sancho-Bru, P. Tags: Hepatitis other, Pancreas and biliary tract Hepatology Source Type: research

The microtubule-associated protein PRC1 promotes early recurrence of hepatocellular carcinoma in association with the Wnt/{beta}-catenin signalling pathway
Conclusions We identified PRC1 as a novel Wnt target that functions in a positive feedback loop that reinforces Wnt signalling to promote early HCC recurrence. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Chen, J., Rajasekaran, M., Xia, H., Zhang, X., Kong, S. N., Sekar, K., Seshachalam, V. P., Deivasigamani, A., Goh, B. K. P., Ooi, L. L., Hong, W., Hui, K. M. Tags: Open access, Colon cancer, Hepatic cancer Hepatology Source Type: research

The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B
Objective The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB. Design The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression. Results In patients with CHB, the S267F variant was observe...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Hu, H.-H., Liu, J., Lin, Y.-L., Luo, W.-S., Chu, Y.-J., Chang, C.-L., Jen, C.-L., Lee, M.-H., Lu, S.-N., Wang, L.-Y., You, S.-L., Yang, H.-I., Chen, C.-J., for the REVEAL-HBV Study Group Tags: Hepatitis B, Hepatic cancer Hepatology Source Type: research

A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals
Conclusions EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Harinck, F., Konings, I. C. A. W., Kluijt, I., Poley, J. W., van Hooft, J. E., van Dullemen, H. M., Nio, C. Y., Krak, N. C., Hermans, J. J., Aalfs, C. M., Wagner, A., Sijmons, R. H., Biermann, K., van Eijck, C. H., Gouma, D. J., Dijkgraaf, M. G. W., Focke Tags: Pancreas and biliary tract, Pancreatic cancer Source Type: research

Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/{beta}-catenin signalling pathway via suppression of activator protein 2{alpha}
Conclusions Our results suggest that CCAL is a crucial oncogenic regulator involved in CRC tumorigenesis and progression. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Ma, Y., Yang, Y., Wang, F., Moyer, M.-P., Wei, Q., Zhang, P., Yang, Z., Liu, W., Zhang, H., Chen, N., Wang, H., Wang, H., Qin, H. Tags: Colon cancer Source Type: research

Carbonic anhydrase IV inhibits colon cancer development by inhibiting the Wnt signalling pathway through targeting the WTAP-WT1-TBL1 axis
Conclusions CA4 is a novel tumour suppressor in CRC through the inhibition of the Wnt signalling pathway by targeting the WTAP–WT1–TBL1 axis. CA4 methylation may serve as an independent biomarker for the recurrence of CRC. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Zhang, J., Tsoi, H., Li, X., Wang, H., Gao, J., Wang, K., Go, M. Y., Ng, S. C., Chan, F. K., Sung, J. J., Yu, J. Tags: Open access, Colon cancer Source Type: research

Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer
Conclusions These observations provide novel evidence for miR-21 blockade to be a key strategy in reducing CAC. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Shi, C., Yang, Y., Xia, Y., Okugawa, Y., Yang, J., Liang, Y., Chen, H., Zhang, P., Wang, F., Han, H., Wu, W., Gao, R., Gasche, C., Qin, H., Ma, Y., Goel, A. Tags: Colon cancer Source Type: research

Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms
Conclusions In primary care, undetectable FHb is a good ‘rule-out’ test for significant bowel disease and could guide who requires investigation. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Mowat, C., Digby, J., Strachan, J. A., Wilson, R., Carey, F. A., Fraser, C. G., Steele, R. J. C. Tags: Open access, Colon cancer Source Type: research

Improving safety of autologous haematopoietic stem cell transplantation in patients with Crohn's disease
Conclusions Autologous HSCT for patients with refractory CD is feasible, but extraordinary supportive measures need to be implemented. We suggest that this procedure should only be performed in highly experienced centres. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Jauregui-Amezaga, A., Rovira, M., Marin, P., Salas, A., Pino-Donnay, S., Feu, F., Elizalde, J. I., Fernandez-Aviles, F., Martinez, C., Gutierrez, G., Rosinol, L., Carreras, E., Urbano, A., Lozano, M., Cid, J., Suarez-Lledo, M., Mensa, J., Rimola, J., Rodr Tags: Crohn's disease Inflammatory bowel disease Source Type: research

IOIBD technical review on endoscopic indices for Crohn's disease clinical trials
Background Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. Methods In these re...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Vuitton, L., Marteau, P., Sandborn, W. J., Levesque, B. G., Feagan, B., Vermeire, S., Danese, S., D'Haens, G., Lowenberg, M., Khanna, R., Fiorino, G., Travis, S., Mary, J. Y., Peyrin-Biroulet, L. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study
The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Murakami, K., Sakurai, Y., Shiino, M., Funao, N., Nishimura, A., Asaka, M. Tags: Open access, Stomach and duodenum Helicobacter pylori Source Type: research

A rare cause of upper GI bleeding in a critically ill patient
See page 1438 for question Clinical presentation A 60-year-old woman presented with melaena at the intensive care unit 21 days after a complicated coronary artery bypass surgery with intraoperative cardiopulmonary resuscitation. The postoperative course was complicated by prolonged ventilator support and wound infections without signs of severe sepsis or multiorgan failure. She was haemodynamically stable with no significant drop in haemoglobin. Physical examination did not reveal abdominal tenderness, skin or mucosal lesions. Laboratory tests showed mild anaemia (92 g/l; normal range 120–180 g/l) and ...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Walker, C., Huber-Schumacher, S., Boettler, T., Thimme, R., Fischer, A. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

POU2F2-oriented network promotes human gastric cancer metastasis
Conclusions This study demonstrated that NF-B and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Wang, S.-M., Tie, J., Wang, W.-L., Hu, S.-J., Yin, J.-P., Yi, X.-F., Tian, Z.-H., Zhang, X.-Y., Li, M.-B., Li, Z.-S., Nie, Y.-Z., Wu, K.-C., Fan, D.-M. Tags: Open access, Pancreatic cancer Stomach Source Type: research

In oesophageal squamous cells, nitric oxide causes S-nitrosylation of Akt and blocks SOX2 (sex determining region Y-box 2) expression
Conclusions In oesophageal squamous cells, NO blocks SOX2 expression through Akt S-nitrosylation. NO also increases CDX2 and decreases p63 expression. By triggering molecular events preventing squamous differentiation while promoting intestinal differentiation, NO might contribute to Barrett's pathogenesis. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Asanuma, K., Huo, X., Agoston, A., Zhang, X., Yu, C., Cheng, E., Zhang, Q., Dunbar, K. B., Pham, T. H., Wang, D. H., Iijima, K., Shimosegawa, T., Odze, R. D., Spechler, S. J., Souza, R. F. Tags: Oesophageal cancer Oesophagus Source Type: research

Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus
Conclusions These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region. (Source: Gut)
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Fock, K. M., Talley, N., Goh, K. L., Sugano, K., Katelaris, P., Holtmann, G., Pandolfino, J. E., Sharma, P., Ang, T. L., Hongo, M., Wu, J., Chen, M., Choi, M.-G., Law, N. M., Sheu, B.-S., Zhang, J., Ho, K. Y., Sollano, J., Rani, A. A., Kositchaiwat, C., B Tags: Gastro-oesophageal reflux, Editor's choice, Oesophageal cancer Guidelines Source Type: research

MicroRNA in alcoholic hepatitis: implications for pathophysiology and treatment
Alcoholic hepatitis alcoholic hepatitis (AH) represents a necroinflammatory complication of alcoholic liver disease, which affects a relatively small but considerable fraction of heavy drinkers with various degrees of underlying alcoholic liver damage. The true incidence of alcoholic hepatitis (AH) is unclear, but is found in around 20% of those with available liver histology, and estimated in approximately 10%–35% of alcoholics hospitalised for decompensating liver disease.1 Severe alcoholic hepatitis (AH) severe alcoholic hepatitis (sAH) has a grave prognosis with a 1-month mortality rate of up to 50%, a figure ass...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Stickel, F., Dubuquoy, L. Tags: Commentary Source Type: research

MAPping the Wnt pathway to hepatocellular carcinoma recurrence
Introduction Early recurrence is a frequent cause of poor survival after hepatocellular carcinoma (HCC) resection. At the cell level, efforts to link HCC with the dysfunction of signalling pathways identified several alterations, especially in the Wnt/β-catenin pathway.1 Wnt signalling controls the balance between cell proliferation and differentiation and its regulation relies partly on subcellular compartmentalisation at the plasma membrane in late endosomes and/or on the cytoskeleton (see refs. 2 3 for reviews) (figure 1A). In this issue of Gut, Chen and collaborators4 identified the microtubule-associated Protein ...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Benoit, B., Poüs, C. Tags: Commentary Source Type: research

One small SNP for receptor virus entry, one giant leap for hepatitis B?
One small step for man, one giant leap for mankind: words that will be forever echoed in the annals of history from 1969 when Neil Armstrong set foot on the moon. Earlier that decade, another major landmark occurred in the field of hepatology with the discovery of hepatitis B (HBV) in 1967. The cure for HBV has since remained elusive; however, the recent discovery of sodium taurocholate contransporting polypeptide (NTCP), a key cell-surface transmembrane glycoprotein involved in HBV entry into hepatocytes1–3 marks a major opportunity for the development of novel therapeutic strategies. In this issue of Gut, Hu and co...
Source: Gut - August 8, 2016 Category: Gastroenterology Authors: Rajoriya, N., Feld, J. J. Tags: Commentary Source Type: research

Erratum: Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis
Angeli P, Rodríguez E, Piano S, et al. Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis. Gut 2015;64:1616–22. The funding statement has been updated to read: Part of the work reported in this study has been funded by the project PI12/00330, integrated in the Plan Nacional I+D+I and cofunded by ISCIII-Subdirección General de Evaluación and European Regional Development Fund (ERDF). (Source: Gut)
Source: Gut - July 7, 2016 Category: Gastroenterology Tags: Correction Source Type: research