Increasing detection rates for diminutive adenomas: are we on the right track?
Van Doorn et al recently reported that Endocuff, an endoscopic cap with plastic projections fitted onto the distal end of the colonoscope increases adenoma detection rates (ADRs).1 While the study is of impeccable design and the device demonstrates to be safe and helpful to improve the inspection of colonic folds, there remain open questions concerning the Endocuff as well as for similar novel ADR enhancing modalities currently emerging on the market. Do they merely improve ADR as a function of improved detection of diminutive adenomas, and if so does such an ‘enhanced’ ADR actually contribute to colorectal can...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: von Renteln, D., Barkun, A. N. Tags: PostScript Source Type: research

Digging deeper into the intronic sequences of the SPINK1 gene
We read with great interest the recent paper by Beer and Sahin-Tóth1 addressing the ‘missing heritability’ observed in approximately 60% of German cases of chronic pancreatitis.2 These authors opined that ‘discovery studies tend to focus on exons and exon–intron boundaries and may thus miss many intronic variants’.1 This premise seems eminently reasonable, given the generally much larger size of intronic sequences as compared with the coding sequences of protein-coding genes. However, there is a trade-off here. On the one hand, larger sequence size means larger target size for mutation,...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Zou, W.-B., Masson, E., Boulling, A., Cooper, D. N., Li, Z.-S., Liao, Z., Ferec, C., Chen, J.-M. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceRho-A prenylation—a new key player in IBD pathogenesis? López-Posadas R, Becker C, Gùˆnther C, et al. Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation. J Clin Invest 2016;126:611–26. doi:10.1172/JCI80997 Intestinal epithelial cells (IECs) serve as a barrier against pathogens, toxins and antigens. In vivo studies have revealed that disruption of the IEC layer plays a significant role in the pathogenesis of IBD, but the specific intrinsic mechanisms responsible for barrier function loss remain unclear. Rho GTPases are signalling molecules that take part i...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial
Objective Little clinical data are available regarding the optimal treatment of patients who harbour adefovir-resistant HBV. Design In this multicentre trial, patients who had adefovir-resistant HBV with serum HBV DNA levels>60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=50) or TDF and entecavir (ETV, 1 mg/day) combination therapy (TDF/ETV, n=52) for 48 weeks. All who completed 48 weeks in either group received TDF monotherapy for 48 additional weeks. Results Baseline characteristics were comparable between groups, including HBV DNA levels (m...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Lim, Y.-S., Yoo, B. C., Byun, K. S., Kwon, S. Y., Kim, Y. J., An, J., Lee, H. C., Lee, Y. S. Tags: Hepatology Source Type: research

Liver transplantation for hepatocellular carcinoma beyond the Milan criteria
This study collectively reviewed 6012 patients of hepatocellular carcinoma from the China Liver Transplant Registry. Expanded criteria were evaluated to characterise an optimised expansion with acceptable outcomes beyond the Milan criteria. Results Compared with the Milan criteria, Valencia, University of California, San Francisco, University Clinic of Navarra and Hangzhou criteria provided an expansion of 12.4%, 16.3%, 19.6%, and 51.5%, respectively. The post-transplant survivals of patients fulfilling the expanded criteria were comparable to that of the Milan criteria. The analysis of net reclassification improvement an...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Xu, X., Lu, D., Ling, Q., Wei, X., Wu, J., Zhou, L., Yan, S., Wu, L., Geng, L., Ke, Q., Gao, F., Tu, Z., Wang, W., Zhang, M., Shen, Y., Xie, H., Jiang, W., Wang, H., Zheng, S. Tags: Open access, Hepatic cancer Hepatology Source Type: research

Antitumour activity of an inhibitor of miR-34a in liver cancer with {beta}-catenin-mutations
Conclusions This work demonstrates the key oncogenic role of miR-34a in liver tumours with β-catenin gene mutations. We suggest that patients diagnosed with HCC with β-catenin mutations could be treated with an inhibitor of miR-34a. The potential value of this strategy lies in the modulation of the tumour suppressor HNF-4α, which targets cyclin D1, and the induction of a proapoptotic programme. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Gougelet, A., Sartor, C., Bachelot, L., Godard, C., Marchiol, C., Renault, G., Tores, F., Nitschke, P., Cavard, C., Terris, B., Perret, C., Colnot, S. Tags: Colon cancer, Hepatic cancer Hepatology Source Type: research

Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators
Conclusions Although no single mediator may account for this effect, serum shortly post-OLT enhances HCV infection. FGF-2 is a novel endogenous driver of HCV replication and a potential therapeutic target. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Van, N. D., Falk, C. S., Sandmann, L., Vondran, F. W. R., Helfritz, F., Wedemeyer, H., Manns, M. P., Ciesek, S., von Hahn, T. Tags: Open access Hepatology Source Type: research

Activated Schwann cells in pancreatic cancer are linked to analgesia via suppression of spinal astroglia and microglia
Conclusions Activated SC in PCa recapitulate the hallmarks of ‘reactive gliosis’ and contribute to analgesia due to suppression of spinal glia. Our findings propose a mechanism for how cancer might remain pain-free via the SC–central glia interplay during cancer progression. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Demir, I. E., Tieftrunk, E., Schorn, S., Saricaoglu, O. C., Pfitzinger, P. L., Teller, S., Wang, K., Waldbaur, C., Kurkowski, M. U., Wörmann, S. M., Shaw, V. E., Kehl, T., Laschinger, M., Costello, E., Algül, H., Friess, H., Ceyhan, G. O. Tags: Pancreas and biliary tract, Editor's choice, Pancreatic cancer Source Type: research

Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer
Conclusions Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Hamm, A., Prenen, H., Van Delm, W., Di Matteo, M., Wenes, M., Delamarre, E., Schmidt, T., Weitz, J., Sarmiento, R., Dezi, A., Gasparini, G., Rothe, F., Schmitz, R., D'Hoore, A., Iserentant, H., Hendlisz, A., Mazzone, M. Tags: Colon cancer Source Type: research

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis
Objective MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. Design We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by quantitative real-time PCR (qRT-PCR). We tested metastatic activity of selected miRNAs and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analysed in six sets of CRC cases (n=449), including The Cancer Genome Atla...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Ling, H., Pickard, K., Ivan, C., Isella, C., Ikuo, M., Mitter, R., Spizzo, R., Bullock, M. D., Braicu, C., Pileczki, V., Vincent, K., Pichler, M., Stiegelbauer, V., Hoefler, G., Almeida, M. I., Hsiao, A., Zhang, X., Primrose, J. N., Packham, G. K., Liu, K Tags: Colon cancer Source Type: research

Population-based assessment of the outcomes in patients with postcolonoscopy colorectal cancers
The objective of this study was to assess the outcomes of patients diagnosed with postcolonoscopy colorectal cancers (PCCRCs). Design We conducted a population-based retrospective cohort study, including all patients diagnosed with colorectal cancer (CRC) in Ontario, Canada from 2003 to 2009. Patients were categorised into three groups: DETECTED (diagnosed within 6 months of first colonoscopy), PCCRC (diagnosed 6–36 months after first colonoscopy) or NOSCOPE (no colonoscopy within 36 months of diagnosis). Univariate and multivariable analyses were conducted to study overall survival, surgical treatmen...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Govindarajan, A., Rabeneck, L., Yun, L., Tinmouth, J., Paszat, L. F., Baxter, N. N. Tags: Endoscopy, Colon cancer Source Type: research

Development and validation of the WASP classification system for optical diagnosis of adenomas, hyperplastic polyps and sessile serrated adenomas/polyps
Objective Accurate endoscopic differentiation would enable to resect and discard small and diminutive colonic lesions, thereby increasing cost-efficiency. Current classification systems based on narrow band imaging (NBI), however, do not include neoplastic sessile serrated adenomas/polyps (SSA/Ps). We aimed to develop and validate a new classification system for endoscopic differentiation of adenomas, hyperplastic polyps and SSA/Ps
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: IJspeert, J. E. G., Bastiaansen, B. A. J., van Leerdam, M. E., Meijer, G. A., van Eeden, S., Sanduleanu, S., Schoon, E. J., Bisseling, T. M., Spaander, M. C., van Lelyveld, N., Bargeman, M., Wang, J., Dekker, E., Dutch Workgroup serrAted polypS & Polyposi Tags: Endoscopy Source Type: research

Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery
Conclusions ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Mondot, S., Lepage, P., Seksik, P., Allez, M., Treton, X., Bouhnik, Y., Colombel, J. F., Leclerc, M., Pochart, P., Dore, J., Marteau, P., the GETAID Tags: Crohn's disease, Open access Gut microbiota Source Type: research

Siblings of patients with Crohns disease exhibit a biologically relevant dysbiosis in mucosal microbial metacommunities
Conclusions Individuals with elevated CD-risk display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii. This dysbiosis in healthy people at risk of CD implicates microbiological processes in CD pathogenesis. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Hedin, C., van der Gast, C. J., Rogers, G. B., Cuthbertson, L., McCartney, S., Stagg, A. J., Lindsay, J. O., Whelan, K. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

TLR-independent anti-inflammatory function of intestinal epithelial TRAF6 signalling prevents DSS-induced colitis in mice
Conclusions Intestinal epithelial TRAF6-dependent but MyD88/TRIF-independent and, thus, TLR-independent signalling pathways are critical for preventing propagation of DSS-induced colon inflammation by the gut microbiota. Moreover, our experiments using mice with dual MyD88/TRIF deletion in IECs unequivocally show that the gut microbiota trigger non-epithelial TLRs rather than epithelial TLRs to restrict DSS colitis severity. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Vlantis, K., Polykratis, A., Welz, P.-S., van Loo, G., Pasparakis, M., Wullaert, A. Tags: Open access Experimental colitis Source Type: research

Gastric tumour-derived ANGPT2 regulation by DARPP-32 promotes angiogenesis
Conclusions Our novel findings establish the role of DARPP-32-STAT3 axis in regulating ANGPT2 in cancer cells to promote angiogenesis and tumorigenesis. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Chen, Z., Zhu, S., Hong, J., Soutto, M., Peng, D., Belkhiri, A., Xu, Z., El-Rifai, W. Tags: Pancreatic cancer Stomach Source Type: research

miR-30-HNF4{gamma} and miR-194-NR2F2 regulatory networks contribute to the upregulation of metaplasia markers in the stomach
Conclusions The interplay of the two transcription factors HNF4 and NR2F2 and their coordinate regulation by miR-30 and miR-194, respectively, represent a miRNA to transcription factor network responsible for the expression of intestinal transcripts in stomach cell lineages during the development of intestinal metaplasia. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Sousa, J. F., Nam, K. T., Petersen, C. P., Lee, H.-J., Yang, H.-K., Kim, W. H., Goldenring, J. R. Tags: Stomach and duodenum, Pancreatic cancer Source Type: research

A bleeding umbilical mass
Question A 57-year-old man with a 3-year history of diabetes was referred to our surgical department for evaluation of a bleeding lesion in the umbilicus (figure 1). The patient reported having been evaluated 4 months before and scheduled for umbilical hernia repair. At presentation, the patient reported vague back pain, whereas he denied fever, nausea or vomiting. Upon physical examination, the abdomen was soft, with normal bowel sounds. There was an obvious, ulcerated umbilical mass measuring about 4 cm in diameter. It was hard in consistency, with serosanguinous discharge. The surrounding skin did not appear r...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Guerra, F., Pulighe, F., Sacchetti, R., Serra, S., De Nisco, C. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus
Conclusion Our data demonstrate the premalignant potential of metaplastic columnar epithelium without goblet cells in the context of Barrett's oesophagus. (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Lavery, D. L., Martinez, P., Gay, L. J., Cereser, B., Novelli, M. R., Rodriguez-Justo, M., Meijer, S. L., Graham, T. A., McDonald, S. A. C., Wright, N. A., Jansen, M. Tags: Open access, Oesophageal cancer Oesophagus Source Type: research

Clinical response to peroral endoscopic myotomy in patients with idiopathic achalasia at a minimum follow-up of 2 years
Conclusions In this multicentre retrospective analysis, a high initial success rate of POEM is followed by a mid-term recurrence rate of 18%. Reflux oesophagitis, albeit mild, is frequent and should probably be treated by regular low-dose PPI therapy. Trial registration number NCT 01405417 (UKE study). (Source: Gut)
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Werner, Y. B., Costamagna, G., Swanström, L. L., von Renteln, D., Familiari, P., Sharata, A. M., Noder, T., Schachschal, G., Kersten, J. F., Rösch, T. Tags: Oesophagus Source Type: research

Sleeping in on pancreatic cancer pain: Schwann cell secreted IL-6 pushes snooze on the pain alarm
Pain is an essential signal of danger and provides motivation to seek treatment, facilitating early diagnosis of disease. Pancreatic cancer is particularly lethal and has a 5-year survival rate below 5%. This is mainly due to delayed perception of visceral pain resulting in late diagnosis, by which time the tumour has metastasised.1 This sobering statistic highlights the need for rapid detection and the importance of understanding pain mechanisms in pancreatic cancer. Patients with pancreatic cancer who report more intense pain have shorter survival times, indicating pain intensity is prognostic for disease progression.2 F...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Hughes, P. A. Tags: Commentary Source Type: research

Microbiome-based companion diagnostics: no longer science fiction?
In the last decade, our knowledge on the role of the gut microbiome in health and disease has greatly increased, accompanied by an unseen hype around both its diagnostic and therapeutic potential. Yet, one application area of the microbiome has thus far remained understudied: its role as guidance for therapeutic decisions, treatment monitoring and prediction of response. In this issue of Gut, Mondot et al1 investigate to what extent the microbiome can both inform us on as well as contribute to treatment outcome in resection surgery for Crohn's disease (CD). Although often the only resort next to dilatation,2 this intervent...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Raes, J. Tags: Open access Commentary Source Type: research

Not All Mice Are the Same: Standardization of Animal Research Data Presentation
As the editors of several journals, we have joined forces to highlight the importance of providing essential details related to animal experiments, particularly for studies that include mouse work. This is a critical issue that partially underlies the problem of irreproducible results that is attracting international attention1 as well as the attention of funding agencies such as the National Institutes of Health.2 For mouse studies, this can be a daunting problem given that many manuscripts do not provide sufficient details regarding the number of animals used for a given experiment, the sex of the animals, their age, and...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Omary, M. B., Cohen, D. E., El-Omar, E., Jalan, R., Low, M., Nathanson, M., Peek, R., Turner, J. Tags: Commentary Source Type: research

The continuing uncertainty about cancer risk in inflammatory bowel disease
Introduction An increased risk of colorectal cancer (CRC) among individuals with IBD was suggested in the 1920s and later supported by epidemiologic studies.1 The association between IBD and CRC is not thought to arise from shared risk factors,2 but rather from a causal effect of IBD on CRC through chronic inflammation and other mechanisms that promote malignant transformation of the colonic mucosa.3 As a result, patients with IBD are considered at high risk of CRC and therefore receive anti-inflammatory treatment, colonoscopic surveillance with biopsies and prophylactic colectomy. Multiple reviews and meta-analyses have t...
Source: Gut - May 9, 2016 Category: Gastroenterology Authors: Adami, H.-O., Bretthauer, M., Emilsson, L., Hernan, M. A., Kalager, M., Ludvigsson, J. F., Ekbom, A. Tags: Endoscopy, Crohn's disease, Ulcerative colitis, Pancreas and biliary tract, Colon cancer Leading article Source Type: research

Real-world risk score for hepatocellular carcinoma (RWS-HCC): a clinically practical risk predictor for HCC in chronic hepatitis B
We read with great interest the recent paper by Abu-Amara et al1 showing that hepatocellular carcinoma (HCC) risk scores derived from Asian cohorts with chronic hepatitis B (CHB) were applicable to a heterogeneous North American patient population as well. They reported that the scoring systems were especially accurate in identifying low-risk patients and as such it is reasonable to use them to guide HCC surveillance recommendations. Out of the five risk scores evaluated, the Chinese University (CU)-HCC and Guide with Age, Gender, HBV DNA, Core promoter mutations and Cirrhosis (GAG-HCC) performed the best.2 3 However, HBV ...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Poh, Z., Shen, L., Yang, H.-I., Seto, W.-K., Wong, V. W., Lin, C. Y., Goh, B.-B. G., Chang, P.-E. J., Chan, H. L.-Y., Yuen, M.-F., Chen, C.-J., Tan, C.-K. Tags: PostScript Source Type: research

A retrospective study of anaemia in neonates exposed to thiopurines in utero
Thiopurines, including azathioprine and mercaptopurine, have a good safety record in pregnancy.1–3 Meta-analysis shows that maternal thiopurine use is not associated with either congenital abnormality or low birth weight.1 A positive association with preterm delivery has been attributed to the severity of the underlying condition for which thiopurine use acts as a surrogate marker.1 However, Jharap et al suggest that all infants exposed to thiopurines in pregnancy should be routinely tested for anaemia. This conclusion is based on a subgroup analysis of only 16 infants, a median ‘anaemic’ haemoglobin of 1...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Wiles, K., Chandiramani, M., Jiwani, S., Nelson-Piercy, C. Tags: PostScript Source Type: research

Clarifying the clinical relevance of SPINK1 intronic variants in chronic pancreatitis
Recently, we reported the identification of a functional PRSS1 promoter variant in perfect linkage disequilibrium (LD) with the chronic pancreatitis (CP)-‘protective’ rs10273639.1 This, together with several other recent papers published in Gut,2–4 underscored the importance of functional analysis for improving our understanding of the underlying pathophysiological mechanisms and also more fundamentally for establishing the clinical relevance or otherwise of CP-associated variants from the outset. In many diseases, in vitro functional analysis often represents the only practical means to determine the pat...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Zou, W.-B., Boulling, A., Masson, E., Cooper, D. N., Liao, Z., Li, Z.-S., Ferec, C., Chen, J.-M. Tags: PostScript Source Type: research

The gamma-glutamyl transpeptidase to platelet ratio (GPR) shows poor correlation with transient elastography measurements of liver fibrosis in HIV-positive patients with chronic hepatitis B in West Africa. Response to: 'The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa by Lemoine et al
Lemoine et al's excellent article from the Gambia reported on non-invasive markers of liver fibrosis in patients with chronic HBV infection.1 They propose a novel biomarker—the gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR)—as a routinely available test that could identify patients with fibrosis or cirrhosis in resource-limited settings, thereby informing prognosis and guiding monitoring. Notably, the study excluded patients with conditions that might predispose to altered GGT or platelet counts, including pregnancy, significant alcohol consumption, use of antiviral therapy, acute malaria and hepat...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Stockdale, A. J., Phillips, R. O., Geretti, A. M., On behalf of the HEPIK Study Group, On behalf of the HEPIK Study Group, Appiah, Ruggiero, Villa, Chadwick, Bhagani, Bonnett, Sarfo, Dusheiko, Owusu, Beloukas, Harrison, Foster, Smith, Ambrose, Adjei-Asant Tags: Open access PostScript Source Type: research

The presence of the anti-inflammatory protein MAM, from Faecalibacterium prausnitzii, in the intestinal ecosystem
We recently reported in your journal the discovery of an anti-inflammatory protein produced by Faecalibacterium prausnitzii, a commensal bacterium involved in Crohn's disease (CD) dysbiosis.1 We wish to highlight and complete these recent data. The involvement of the intestinal microbiota in the pathogenesis of CD is well recognised. It has been shown that dysbiosis (an imbalance in the composition of the intestinal microbiota) could participate in chronic and inappropriate activation of the intestinal immune system and lead to inflammation. Dysbiosis is characterised by a deficiency of certain bacteria, such as Faecalibac...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Quevrain, E., Maubert, M.-A., Sokol, H., Devreese, B., Seksik, P. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceExploring anti-stem cell therapy in colorectal cancer  Storm EE, Durinck S, de Sousa e Melo F, et al. Targeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem cell function. Nature 2016;529:97–100. Adenomatous polyposis coli mutations resulting in activation of the WNT pathway are thought to be a founder event in the majority of human colorectal cancers (CRCs), yet targeting the WNT pathway has not yielded any effective therapies. There is a subset of CRCs that express recurrent gene fusions of members of the R-spondin (RSPO, WNT agonists) that exhibit WNT activation through tra...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Role of bismuth in improving Helicobacter pylori eradication with triple therapy
In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for Helicobacter pylori eradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (ie, 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%–40% to the success with resistant in...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Dore, M. P., Lu, H., Graham, D. Y. Tags: GUT Recent advances in clinical practice Source Type: research

Neoangiogenesis-related genes are hallmarks of fast-growing hepatocellular carcinomas and worst survival. Results from a prospective study
Objective The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. We translate the results of a genome-wide high-throughput analysis into a tool that accurately predicts at presentation tumour growth and survival of patients with HCC. Design Ultrasound surveillance identified HCC in 78 (training set) and 54 (validation set) consecutive patients with cirrhosis. Patients underwent two CT scans 6 weeks apart (no treatment in-between) to determine tumour volumes (V0 and V1) and calculate HCC doubling time. Baseline-paired HCC and surrounding tissue biopsies for microarray study (Agilent ...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Villa, E., Critelli, R., Lei, B., Marzocchi, G., Camma, C., Giannelli, G., Pontisso, P., Cabibbo, G., Enea, M., Colopi, S., Caporali, C., Pollicino, T., Milosa, F., Karampatou, A., Todesca, P., Bertolini, E., Maccio, L., Martinez-Chantar, M. L., Turola, E Tags: Hepatic cancer Hepatology Source Type: research

Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial
Conclusions TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV. Trial registration number ClinicalTrials.gov ID NCT01639092. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Lim, Y.-S., Byun, K. S., Yoo, B. C., Kwon, S. Y., Kim, Y. J., An, J., Lee, H. C., Lee, Y. S. Tags: Hepatology Source Type: research

Kinase analysis in alcoholic hepatitis identifies p90RSK as a potential mediator of liver fibrogenesis
Conclusions p90RSK is upregulated in patients with chronic liver disease and mediates liver fibrogenesis in vivo and in vitro. These results suggest that the p90RSK pathway could be a new therapeutic approach for liver diseases characterised by advanced fibrosis. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Morales-Ibanez, O., Affo, S., Rodrigo-Torres, D., Blaya, D., Millan, C., Coll, M., Perea, L., Odena, G., Knorpp, T., Templin, M. F., Moreno, M., Altamirano, J., Miquel, R., Arroyo, V., Gines, P., Caballeria, J., Sancho-Bru, P., Bataller, R. Tags: Cirrhosis, Hepatitis other Hepatology Source Type: research

Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease
Conclusions Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Llopis, M., Cassard, A. M., Wrzosek, L., Boschat, L., Bruneau, A., Ferrere, G., Puchois, V., Martin, J. C., Lepage, P., Le Roy, T., Lefevre, L., Langelier, B., Cailleux, F., Gonzalez-Castro, A. M., Rabot, S., Gaudin, F., Agostini, H., Prevot, S., Berrebi, Tags: Alcoholic liver disease, Hepatitis other Hepatology Source Type: research

Carcinoembryonic Antigen Cell Adhesion Molecule 1 long isoform modulates malignancy of poorly differentiated colon cancer cells
Conclusions CC1-L regulates inflammation and STAT3 signalling and contributes to the maintenance of a less-invasive CRC metastatic phenotype of poorly differentiated carcinomas. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Arabzadeh, A., Dupaul-Chicoine, J., Breton, V., Haftchenary, S., Yumeen, S., Turbide, C., Saleh, M., McGregor, K., Greenwood, C. M. T., Akavia, U. D., Blumberg, R. S., Gunning, P. T., Beauchemin, N. Tags: Colon cancer, Hepatic cancer Source Type: research

Efficacy and safety of endoscopic resection of large colorectal polyps: a systematic review and meta-analysis
Conclusions Endoscopic resection of large polyps appeared to be an extremely effective and safe intervention. However, an adequate endoscopic surveillance is necessary for its long-term efficacy. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Hassan, C., Repici, A., Sharma, P., Correale, L., Zullo, A., Bretthauer, M., Senore, C., Spada, C., Bellisario, C., Bhandari, P., Rex, D. K. Tags: Intestinal cancer Endoscopy Source Type: research

Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1
Conclusions Decreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Zhou, Q., Yang, L., Larson, S., Basra, S., Merwat, S., Tan, A., Croce, C., Verne, G. N. Tags: Endoscopy, Irritable bowel syndrome, Open access, Colon cancer Neurogastroenterology Source Type: research

Deep resequencing of 131 Crohn's disease associated genes in pooled DNA confirmed three reported variants and identified eight novel variants
Objective Genome wide association studies (GWAS) and meta-analyses for Crohn's disease (CD) have not fully explained the heritability of CD, suggesting that additional loci are yet to be found and that the known loci may contain high effect rare risk variants that have thus far gone undetected by GWAS. While the cost of deep sequencing remains too high to analyse many samples, targeted sequencing of pooled DNA samples allows the efficient and cost effective capture of all variations in a target region. Design We performed pooled sequencing in 500 Korean CD cases and 1000 controls to evaluate the coding exon and 5' and 3' ...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Hong, S. N., Park, C., Park, S. J., Lee, C. K., Ye, B. D., Kim, Y. S., Lee, S., Chae, J., Kim, J.-I., Kim, Y.-H., IBD Study Group of the Korean Association for the Study of Intestinal Diseases (KASID) Tags: Crohn's disease Inflammatory bowel disease Source Type: research

A rare cause of upper GI bleeding and wasting disease
Clinical presentation A 74-year-old Turkish woman was admitted with loss of appetite, weight loss and progressive anaemia. Her medical history included rheumatoid arthritis, type 2 diabetes and end-stage renal disease with nephrotic syndrome diagnosed 2 years ago. Endoscopy of the upper GI tract revealed a distinct intramural gastric haematoma with diffuse, seeping haemorrhage and large gastric intraluminal blood clots (figure 1A, B; online supplementary films 1 and 2). The mucosa appeared partly necrotic, and the gastric wall showed a sponge-like consistence and marked vulnerability. An abdominal CT scan was performe...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: van Erp, R. J., Schröppel, B., Barth, T. F., Seufferlein, T., Schmidt, S. A., Meining, A., Kleger, A. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation
Conclusions LMIR3-deficient colonic mast cells were pivotal in the exacerbation of DSS-induced colitis in LMIR3–/– mice. Ceramide liposomes attenuated DSS-induced colitis by inhibiting ATP-mediated activation of colonic mast cells through ceraimide–LMIR3 binding. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Matsukawa, T., Izawa, K., Isobe, M., Takahashi, M., Maehara, A., Yamanishi, Y., Kaitani, A., Okumura, K., Teshima, T., Kitamura, T., Kitaura, J. Tags: Open access Inflammatory bowel disease Source Type: research

Live birth and adverse birth outcomes in women with ulcerative colitis and Crohn's disease receiving assisted reproduction: a 20-year nationwide cohort study
Conclusions Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Norgard, B. M., Larsen, P. V., Fedder, J., de Silva, P. S., Larsen, M. D., Friedman, S. Tags: Crohn's disease, Ulcerative colitis, Editor's choice Inflammatory bowel disease Source Type: research

Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction
Background Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut. Objective To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation. Design Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expr...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Tulic, M. K., Vivinus-Nebot, M., Rekima, A., Rabelo Medeiros, S., Bonnart, C., Shi, H., Walker, A., Dainese, R., Boyer, J., Vergnolle, N., Piche, T., Verhasselt, V. Tags: Mucosal immunity Source Type: research

Proton pump inhibitors alter the composition of the gut microbiota
Conclusions Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences. (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Jackson, M. A., Goodrich, J. K., Maxan, M.-E., Freedberg, D. E., Abrams, J. A., Poole, A. C., Sutter, J. L., Welter, D., Ley, R. E., Bell, J. T., Spector, T. D., Steves, C. J. Tags: Ulcer, Gastro-oesophageal reflux, Open access Gut microbiota Source Type: research

Proton pump inhibitors affect the gut microbiome
In this study, we investigated the influence of PPI use on the gut microbiome. Methods The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis. Results 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon's diversity and with changes in 20% of the bacterial taxa (false discovery rate
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., Dijkstra, G., Franke, L., Xavier, R. J., Jonkers, D., Wijmenga, C., Weersma, R. K., Zhernakova, A. Tags: Clostridium difficile, Open access Gut microbiota Source Type: research

Long-term results of the European achalasia trial: a multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy
Conclusions After at least 5 years of follow-up, PD and LHM have a comparable success rate with no differences in oesophageal function and emptying. However, 25% of PD patients require redilation during follow-up. Based on these data, we conclude that either treatment can be proposed as initial treatment for achalasia. Trial registration numbers Netherlands trial register (NTR37) and Current Controlled Trials registry (ISRCTN56304564). (Source: Gut)
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Moonen, A., Annese, V., Belmans, A., Bredenoord, A. J., Bruley des Varannes, S., Costantini, M., Dousset, B., Elizalde, J. I., Fumagalli, U., Gaudric, M., Merla, A., Smout, A. J., Tack, J., Zaninotto, G., Busch, O. R., Boeckxstaens, G. E. Tags: Oesophagus Source Type: research

The impact of three-dimensional imaging on polyp detection during colonoscopy: a proof of concept study
Message Failures in lesion detection at colonoscopy deliver imperfect protection against colorectal cancer. Minimally elevated lesions are more likely to contain high-grade dysplasia or invasive carcinoma, but are frequently undetected during conventional two-dimensional (2D) colonoscopy. We performed a randomised, complete, across-subjects counterbalanced study of 3D versus 2D imaging for lesion detection during simulated colonoscopy in a simulation laboratory. Thirty-six gastroenterology fellows, comprising 50% of the nationwide pool in Australia, were tested on their ability to detect a 1 mm lesion that was similar...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Sakata, S., Grove, P. M., Stevenson, A. R. L., Hewett, D. G. Tags: Endoscopy, Colon cancer Endoscopy news Source Type: research

Altered intestinal microbiota as a major driving force in alcoholic steatohepatitis
Alcoholic hepatitis (AH) covers a spectrum of disease severities from subclinical liver inflammation to acute liver failure. Among the histological features of alcoholic liver disease (ALD), AH is associated with the highest risk of fibrosis progression, leading to development of cirrhosis in 40% of cases. Patients hospitalised for severe forms of AH show 1-month mortality rates of 40–50%.1 Patients with AH form a heterogeneous population, in severity, and probably in disease pathogenesis. This diverse clinical picture might be caused by various factors including host factors, immunity and as recently suggested, inte...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Tilg, H., Mathurin, P. Tags: Commentary Source Type: research

House dust mite: a new player in intestinal inflammation?
Over the past decades, incidence rates of immune-mediated inflammatory diseases including asthma and IBDs have been rising steadily in both Western and low/middle-income countries.1 The cause of this increase has been a topic of intense investigation, and a variety of factors such as diet, hygiene and pollution have been implicated. One of the most clear correlations between disease and environment is that between exposure to house dust mite (HDM) and asthma exacerbations.2 HDM contains several antigens, including Der p1, a cysteine protease that damages the airway epithelium thus allowing antigens to pass into the pulmona...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Wildenberg, M. E., van den Brink, G. R. Tags: Commentary Source Type: research

Treating achalasia; more than just flipping a coin
Even as the preferred treatment of achalasia migrates towards per-oral endoscopic myotomy (POEM), the relative merits of pneumatic dilation (PD) and laparoscopic Heller myotomy (LHM) continue to be argued. In this issue of Gut, the long-term results of the European achalasia trial comparing 201 patients randomised to PD or LHM are presented,1 reporting similar outcomes between therapies. After a minimum follow-up of 5 years, 82% of patients with PD and 84% of patients with LHM had a sustained good response when analysed by intention to treat (or 91% of patients with PD and 82% of patients with LHM when analysed per pr...
Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Kahrilas, P. J. Tags: Commentary Source Type: research