Targeted depletion of an MDSC subset unmasks pancreatic ductal adenocarcinoma to adaptive immunity
Conclusions Neoplastic ductal cells of the pancreas induce distinct myeloid cell subsets that promote tumour cell survival and accumulation. Targeted depletion of a single myeloid subset, the Gr-MDSC, can unmask an endogenous T cell response, disclosing an unexpected latent immunity and invoking targeting of Gr-MDSC as a potential strategy to exploit for treating this highly lethal disease. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Stromnes, I. M., Brockenbrough, J. S., Izeradjene, K., Carlson, M. A., Cuevas, C., Simmons, R. M., Greenberg, P. D., Hingorani, S. R. Tags: Pancreas and biliary tract Source Type: research

Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid
Conclusions EPA-FFA therapy is safe and well tolerated in patients with advanced CRC undergoing liver surgery. EPA-FFA may have antiangiogenic properties. Remarkably, limited preoperative treatment may provide postoperative OS benefit. Phase III clinical evaluation of prolonged EPA-FFA treatment in CRCLM patients is warranted. Trial Identifier: ClinicalTrials.gov NCT01070355. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Cockbain, A. J., Volpato, M., Race, A. D., Munarini, A., Fazio, C., Belluzzi, A., Loadman, P. M., Toogood, G. J., Hull, M. A. Tags: Colon cancer, Hepatic cancer Source Type: research

The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial
Objective To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. Design A double-blinded, randomised, placebo-controlled multicentre clinical trial was conducted. Participants 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. Results The subje...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Ishikawa, H., Mutoh, M., Suzuki, S., Tokudome, S., Saida, Y., Abe, T., Okamura, S., Tajika, M., Joh, T., Tanaka, S., Kudo, S.-e., Matsuda, T., Iimuro, M., Yukawa, T., Takayama, T., Sato, Y., Lee, K., Kitamura, S., Mizuno, M., Sano, Y., Gondo, N., Sugimoto Tags: Colon cancer Source Type: research

An analysis of the learning curve to achieve competency at colonoscopy using the JETS database
Conclusions This is the largest study to date investigating the number of procedures required to achieve competency in colonoscopy. The current training certification benchmark in the UK of 200 procedures does not appear to be an inappropriate minimum requirement. The LC-Cusum chart provides real time feedback on individual learning curves for trainees. The association of training intensity and flexible sigmoidoscopy experience with colonoscopy completion could be exploited in training programmes. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Ward, S. T., Mohammed, M. A., Walt, R., Valori, R., Ismail, T., Dunckley, P. Tags: Endoscopy, Open access, Colon cancer Source Type: research

Faecal microbiota composition and host-microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome
Conclusions The faecal microbiota of patients with PI-IBS differs from that of healthy controls and resembles that of patients with IBS-D, suggesting a common pathophysiology. Moreover, our analysis suggests a variety of host–microbe associations that may underlie intestinal symptoms, initiated by gastroenteritis. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Jalanka-Tuovinen, J., Salojarvi, J., Salonen, A., Immonen, O., Garsed, K., Kelly, F. M., Zaitoun, A., Palva, A., Spiller, R. C., de Vos, W. M. Tags: Gastroenteritis, Irritable bowel syndrome Neurogastroenterology Source Type: research

Diarrhoea and duodenal disease
A 27-year-old Caucasian male presented with a one-month history of diarrhoea, severe abdominal cramping, heartburn and weight loss. The symptoms began right after breakfast in the morning and continued with 3–4 watery stools throughout the day, but none during the night. Spicy foods, alcoholic beverages and excessive water intake seemed to exacerbate the pain, but soda seemed to alleviate it. The patient denied use of antibiotics, antispasmodics, or antihypertensive drugs, and drank minimal milk. The patient denied any recent international travel or contact with diapers or ill persons but confirmed that the symptoms ...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Nielsen, J. A., Weber, J. J., Lager, D. J. Tags: GUT Snapshot Editor ' s quiz: Gi snapshot Source Type: research

IL-13R{alpha}2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis
Conclusions These studies show that UC lamina propria is replete with Type II NKT cells responsive to lyso-sulfatide glycolipid and bearing IL-13Rα2. Since lyso-sulfatide is a self-antigen, these data suggest that an autoimmune response is involved in UC pathogenesis. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Fuss, I. J., Joshi, B., Yang, Z., Degheidy, H., Fichtner-Feigl, S., de Souza, H., Rieder, F., Scaldaferri, F., Schirbel, A., Scarpa, M., West, G., Yi, C., Xu, L., Leland, P., Yao, M., Mannon, P., Puri, R. K., Fiocchi, C., Strober, W. Tags: Ulcerative colitis Inflammatory bowel disease Source Type: research

Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial
Conclusions Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher postinduction trough levels than patients without durable sustained response. Serum infliximab trough levels ≥3.5 µg/mL and ≥60% CRP decrease were significantly associated with durable sustained response. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Cornillie, F., Hanauer, S. B., Diamond, R. H., Wang, J., Tang, K. L., Xu, Z., Rutgeerts, P., Vermeire, S. Tags: Crohn's disease, Open access Inflammatory bowel disease Source Type: research

Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum
Conclusions Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Choi, E., Roland, J. T., Barlow, B. J., O'Neal, R., Rich, A. E., Nam, K. T., Shi, C., Goldenring, J. R. Tags: Editor's choice, Gastrointestinal hormones, Stomach and duodenum Source Type: research

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma
Conclusions Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival. (Source: Gut)
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Li, J., Chen, Z., Tian, L., Zhou, C., He, M. Y., Gao, Y., Wang, S., Zhou, F., Shi, S., Feng, X., Sun, N., Liu, Z., Skogerboe, G., Dong, J., Yao, R., Zhao, Y., Sun, J., Zhang, B., Yu, Y., Shi, X., Luo, M., Shao, K., Li, N., Qiu, B., Tan, F., Chen, R., He, Tags: Open access, Oesophageal cancer Oesophagus Source Type: research

Use of azathioprine in IBD: modern aspects of an old drug
Thiopurines have been considered the reference treatment for patients with steroid-dependent moderate to severe IBD for many years. This has been based on evidence describing the efficacy and safety of azathioprine and mercaptopurine in Crohn's disease (CD) and UC. In CD, efficacy has been established through controlled trials, meta-analyses, cohort studies and data on mucosal healing, as well as in withdrawal studies. A Cochrane meta-analysis concluded that azathioprine and mercaptopurine effectively maintained remission in CD with an OR between 2 and 3 compared to placebo.1 Mucosal healing was initially studied in patien...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Louis, E., Irving, P., Beaugerie, L. Tags: Crohn's disease Leading article Source Type: research

Osteopontin: a new player in regulating hepatic ductular reaction and hepatic progenitor cell responses during chronic liver injury
In recent years, an increasing number of reports have shown the involvement of osteopontin (OPN), a pleiotropic cytokine and an important component of the extracellular matrix (ECM), in the pathogenesis of liver injury and the development of fibrosis.1 2 OPN is also frequently overexpressed in hepatocellular carcinoma (HCC), where it modulates HCC growth, invasion and metastasis,2 and in cholangiocarcinoma, where its expression bears prognostic significance. Previous studies3 have shown that in injured livers OPN is expressed by hepatic stellate cells (HSC) and upregulates collagen I production. Interestingly, in HSC, OPN ...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Strazzabosco, M., Fabris, L., Albano, E. Tags: Commentary Source Type: research

Is aspirin for colorectal cancer prevention on the prime time yet?
Aspirin is the most widely studied drug for chemoprevention of colorectal cancer but there are limitations. First the risk-benefit issue has not been fully addressed. What is the risk of bleeding associated with prescribing aspirin to asymptomatic individuals versus the benefit of cancer protection one can obtain from this treatment? Second, the optimal dosing, frequency and duration of aspirin usage in average-risk subjects (ie, patients with non-cardiovascular disease and patients with non-familial polyposis) have not been settled. Third, the potential ethnic difference has not been studied. Up to now, almost all studies...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Sung, J. J. Tags: Commentary Source Type: research

Myeloid-derived suppressor cells in pancreatic cancer: more than a hidden barrier for antitumour immunity?
Myeloid-derived suppressor cells (MDSC) represent an immune cell subset with profound immune suppressor function. Initially described in 1978 as natural suppressor cells, this cell type has gained significant attention in recent years not only among tumour immunologists but also among medical oncologists interested both in developing new immune-based antitumour strategies and trying to understand how conventional non-immunological therapies affect antitumour immune responses.1 MDSC represent a mixture of immature cell types that accumulate in tumour-bearing mice and patients with cancer. Tumour-derived factors block the ma...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Greten, T. F. Tags: Commentary Source Type: research

The driving circuit of HBx and androgen receptor in HBV-related hepatocarcinogenesis
Hepatocellular carcinoma (HCC) is a global health concern. The sixth most common neoplasm, HCC yields a poor prognosis and high mortality rate, causing approximately 500 000 deaths per year. Chronic viral hepatitis—especially HBV and HCV—are major aetiologies of HCC, accounting for approximately 80% of HCC cases, particularly in endemic areas. Another clinical feature of HCC is that it disproportionately occurs in men, and the ratio of male to female patients ranges from 2 to 7:1.1 In large cohort studies, this predominance is only partly explained by gendered differences in environmental influences and be...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Wang, S.-H., Yeh, S.-H., Chen, P.-J. Tags: Commentary Source Type: research

Endoscopy training: time to stop counting procedures?
Until recently, training of endoscopists was largely up to the local environment, often unstructured and only sporadically supervised. Consequently, there were large variations in the performance of endoscopy, and the quality of the service was very often too poor.1 During recent years, some countries have made great efforts to formalise and structure endoscopist training, often within the framework of continual quality improvement initiatives. This has led to impressive and sustained improvement in the quality of endoscopy services, as recently shown for colonoscopies in the UK.2 The number of procedures performed during ...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Bretthauer, M., Brandrud, A. S. Tags: Commentary Source Type: research

IBS with intestinal microbial dysbiosis: a new and clinically relevant subgroup?
Symptoms compatible with IBS, that is, abdominal pain and discomfort, bloating, abdominal distention and an erratic bowel function, are very common reasons for GI consultations in primary care1 and patients with IBS are one of the most frequent patient categories in gastroenterology outpatient clinics.2 Despite being very common and in spite of considerable research effort during the last decades, the pathophysiology of IBS is still considered to be complex and incompletely understood3 4 and even though our understanding of this disabling condition arguably has increased tremendously, we still cannot use knowledge from pat...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Simren, M. Tags: Commentary Source Type: research

Chemokines and alcoholic hepatitis: are chemokines good therapeutic targets?
Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease that is associated with high mortality. Despite extensive research on AH over the last several decades, the pathogenesis of AH remains largely unknown, and there are no approved targeted therapies. Inflammation (neutrophil infiltration) is generally believed to play an important role in the pathogenesis of AH; however, the mechanisms underlying neutrophil infiltration in AH and the functions of neutrophils in AH are not fully understood.1 Despite its obscure role, inflammation has been actively investigated as a therapeutic target for the treatment of AH....
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Gao, B., Xu, M. Tags: Commentary Source Type: research

In Memoriam, Arlette Darfeuille-Michaud, PhD
Arlette Darfeuille-Michaud: Researcher, Lecturer, Leader, Mentor, and Friend It is with profound sadness that we note the loss, at age 59, of our dear friend and mentor Dr Arlette Darfeuille-Michaud on June 28, 2014, following a 15-month battle against cancer. Arlette was a Professor at Auvergne University, and director of an INSERM unit that investigates microbial-host interactions in intestinal inflammation, located in Clermont-Ferrand, France. Arlette advanced our understanding of intestinal diseases, and humanity in general, via pioneering research in gut microbiology, visionary leadership, energetic teaching, and exce...
Source: Gut - October 2, 2014 Category: Gastroenterology Authors: Raisch, J., Sivignon, A., Chassaing, B., Lapaquette, P., Miquel, S., Carvalho, F., Rolhion, N., Bringer, M.-A., Barnich, N., Boudeau, J., Di Martino, P. Tags: Obituary Source Type: research

The stomach: a biography
Stomachs are thought to have first evolved about 350 million years ago. At about the same time our vertebrate ancestors developed jaws that made possible the relatively rapid consumption of bulky meals. The evolution of acid secretion by the stomach therefore provided a novel solution to the problem of limiting the growth of ingested microorganisms while food is temporarily retained prior to delivery to the small intestine for breakdown and absorption. The evolutionary success of the stomach is attested by the fact that what is easily recognisable as the same organ is found in virtually all living vertebrates above the Agn...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Dockray, G. J. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, the authors set out to investigate the role that TH9 cells play in the pathogenesis of IBD by characterising interleukin 9 (IL-9) expression in patients with IBD and in mouse models of acute and... (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Moving towards personalised therapy in patients with hepatocellular carcinoma: the role of the microenvironment
The goal of personalised therapy based on hepatocellular carcinoma (HCC) molecular characteristics is still beyond our grasp. Systemic treatments show poor efficacy, mainly because of the great heterogeneity of the tumour. Indeed, differences in aetiology, disease stage and biochemical composition of the fibrotic liver make cirrhosis itself a highly dyshomogeneous disease. Cancer cells grow in a cirrhotic microenvironment, interacting with stromal cells and engaging matrix components that differ from patient to patient, hampering the development of drugs to treat all patients. Growing evidence suggests a role for the cross...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Giannelli, G., Rani, B., Dituri, F., Cao, Y., Palasciano, G. Tags: GUT Recent advances in basic science, Hepatic cancer Source Type: research

Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases
Conclusions PCLDs are associated with cholangiocyte MMP hyperactivity resulting from autocrine/paracrine stimulation by IL-6 and IL-8. Inhibition of this MMP hyperactivity with marimastat decreased hepatic cystogenesis in vitro and in an animal model of PCLD, offering a potential therapeutic tool. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Urribarri, A. D., Munoz-Garrido, P., Perugorria, M. J., Erice, O., Merino-Azpitarte, M., Arbelaiz, A., Lozano, E., Hijona, E., Jimenez-Aguero, R., Fernandez-Barrena, M. G., Jimeno, J. P., Marzioni, M., Marin, J. J. G., Masyuk, T. V., LaRusso, N. F., Priet Tags: Hepatology Source Type: research

Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma
Conclusions Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Liu, J., Yang, H.-I., Lee, M.-H., Lu, S.-N., Jen, C.-L., Batrla-Utermann, R., Wang, L.-Y., You, S.-L., Hsiao, C. K., Chen, P.-J., Chen, C.-J., Liaw, Chen, Chen, Hsieh, Lee, Yang, Chen, Chen, Huang, Jan, Chen, Sun, Wu, Chen, Chu, Ho, Lu, Wu, Ou, Lin, Shih, Tags: Cirrhosis, Hepatic cancer Hepatology Source Type: research

PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis
Conclusions These results establish the counteraction between PTEN and Tcl1 as a key mechanism that regulates the PPP and suggest that targeting the PTEN/Tcl1/hnRNPK/G6PD axis could open up possibilities for therapeutic intervention and improve the prognosis of patients with HCC. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Hong, X., Song, R., Song, H., Zheng, T., Wang, J., Liang, Y., Qi, S., Lu, Z., Song, X., Jiang, H., Liu, L., Zhang, Z. Tags: Hepatic cancer Hepatology Source Type: research

Fever and right upper quadrant pain in a 24-year-old male
Clinical presentation A 24-year-old male presented with a 4-week history of right upper quadrant pain, lethargy, pyrexia, night sweats, anorexia and weight loss. Past medical history included Coeliac disease (compliant with a gluten free diet) and liver cysts. On examination the patient had a temperature of 38.2°C and tender hepato-splenomegaly. Blood tests showed bilirubin 16 μmol/L (normal range 10–20 μmol/L), ALT 28 IU/L (normal range 10–50 IU/L), ALP 274 IU/L (normal range 40–129 IU/L), albumin 48 g/L (normal range 34–50 g/L), GGT 205 (normal ran...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Cheung, V. T. F., Joshi, D., Amin, Z., Webster, G. J. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN)
Objective Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation. Design mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudo...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Das, K. K., Xiao, H., Geng, X., Fernandez-del-Castillo, C., Morales-Oyarvide, V., Daglilar, E., Forcione, D. G., Bounds, B. C., Brugge, W. R., Pitman, M. B., Mino-Kenudson, M., Das, K. M. Tags: Pancreas and biliary tract Source Type: research

A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea
Background Irritable bowel syndrome with diarrhoea (IBS-D) is particularly debilitating due to urgency and episodic incontinence. Some 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (5-HT3RAs) have proven effective but have serious side effects. Ondansetron, also a 5-HT3RA, has been widely used as an antiemetic with an excellent safety record for over two decades. Our aim was to assess its effectiveness in IBS-D. Methods 120 patients meeting Rome III criteria for IBS-D entered a randomised, double-blind, placebo-controlled crossover study of 5 weeks of ondansetron 4 mg versus placebo with dose titration allo...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Garsed, K., Chernova, J., Hastings, M., Lam, C., Marciani, L., Singh, G., Henry, A., Hall, I., Whorwell, P., Spiller, R. Tags: Drugs: gastrointestinal system, Diarrhoea, Irritable bowel syndrome, Open access Neurogastroenterology Source Type: research

Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979-2011
Introduction Treatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a population-based cohort. Methods 48 967 individuals were diagnosed with IBD (Crohn's disease (CD), 13 185; ulcerative colitis (UC), 35 782) during 1979–2011. Cumulative probability of receiving 5-aminosalicylic acids (5-ASA), topical, oral corticosteroids, thiopurines, and tumour necrosis factor-α (TNF-α) blockers, and of first minor or major surgery according to period of diagnosis, was estim...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Rungoe, C., Langholz, E., Andersson, M., Basit, S., Nielsen, N. M., Wohlfahrt, J., Jess, T. Tags: Crohn's disease, Ulcerative colitis Inflammatory bowel disease Source Type: research

Detection of bacterial DNA in lymph nodes of Crohn's disease patients using high throughput sequencing
Conclusions It is unlikely that a single bacterium perpetuates inflammation in late stage CD; dysbiosis was common and we found no evidence of increased bacterial translocation. We believe that future studies should focus on early disease and viable bacteria in nodes, aphthous ulcers and granulomas, as they may be more relevant in the initiation of inflammation in CD. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: O'Brien, C. L., Pavli, P., Gordon, D. M., Allison, G. E. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

ClC-3 chloride channel/antiporter defect contributes to inflammatory bowel disease in humans and mice
Conclusions A defect in ClC-3 may contribute to the pathogenesis of IBD by promoting intestinal epithelial cell apoptosis and Paneth cell loss, suggesting that modulation of ClC-3 expression might be a new strategy for the treatment of IBD. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Huang, L.-Y., He, Q., Liang, S.-J., Su, Y.-X., Xiong, L.-X., Wu, Q.-Q., Wu, Q.-Y., Tao, J., Wang, J.-P., Tang, Y.-B., Lv, X.-F., Liu, J., Guan, Y.-Y., Pang, R.-P., Zhou, J.-G. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings
Objective Crohn's disease (CD) is associated with intestinal dysbiosis, altered blood T cell populations, elevated faecal calprotectin (FC) and increased intestinal permeability (IP). CD-associated features present in siblings (increased risk of CD) but not in healthy controls, provide insight into early CD pathogenesis. We aimed to (1) Delineate the genetic, immune and microbiological profile of patients with CD, their siblings and controls and (2) Determine which factors discriminate between groups. Design Faecal microbiology was analysed by quantitative PCR targeting 16S ribosomal RNA, FC by ELISA, blood T cell phenoty...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Hedin, C. R., McCarthy, N. E., Louis, P., Farquharson, F. M., McCartney, S., Taylor, K., Prescott, N. J., Murrells, T., Stagg, A. J., Whelan, K., Lindsay, J. O. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Bacterial protein signals are associated with Crohn's disease
Conclusions This study provides the first evidence that quantifiable bacterial protein signals are associated with CD, which can have a profound impact on future molecular diagnosis. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Juste, C., Kreil, D. P., Beauvallet, C., Guillot, A., Vaca, S., Carapito, C., Mondot, S., Sykacek, P., Sokol, H., Blon, F., Lepercq, P., Levenez, F., Valot, B., Carre, W., Loux, V., Pons, N., David, O., Schaeffer, B., Lepage, P., Martin, P., Monnet, V., S Tags: Pancreas and biliary tract, Open access Inflammatory bowel disease Source Type: research

Carbon dioxide insufflation improves the intubation depth and total enteroscopy rate in single-balloon enteroscopy: a randomised, controlled, double-blind trial
Objective The total enteroscopy rate of single-balloon enteroscopy (SBE) using air insufflation is not satisfactory, and whether carbon dioxide (CO2) insufflation increases the total enteroscopy rate of SBE is unknown. This randomised controlled trial aimed to determine whether CO2 insufflation facilitates the intubation depth and total enteroscopy rate of SBE. Design A total of 214 eligible patients referred for SBE were randomised to receive either air or CO2 insufflation, and included in the intention-to-test (ITT) analysis. In addition, 199 patients in whom enteroscopy was completed were included in the per-protocol (...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Li, X., Zhao, Y.-J., Dai, J., Li, X.-B., Xue, H.-B., Zhang, Y., Xiong, G.-S., Ohtsuka, K., Gao, Y.-J., Liu, Q., Song, Y., Fang, J.-Y., Ge, Z.-Z. Tags: Endoscopy Source Type: research

CCL20/CCR6-mediated migration of regulatory T cells to the Helicobacter pylori-infected human gastric mucosa
Conclusions As well as increasing Treg numbers, H pylori infection induces a change in their characteristics. Expression of CCR6, CXCR1 and CXCR2 probably enables their migration towards CCL20 and IL-8 in the infected gastric mucosa. Such qualitative changes may also explain how H pylori protects against some extragastric inflammatory disorders. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Cook, K. W., Letley, D. P., Ingram, R. J. M., Staples, E., Skjoldmose, H., Atherton, J. C., Robinson, K. Tags: Open access Helicobacter pylori Source Type: research

Use of proton pump inhibitors after antireflux surgery: a nationwide register-based follow-up study
Conclusions Risk of PPI use after ARS was higher than previously reported, and more than 50% of patients became long-term PPI users 10–15 years postsurgery. Patients should be made aware that long-term PPI therapy is often necessary after ARS. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Lodrup, A., Pottegard, A., Hallas, J., Bytzer, P. Tags: Open access Oesophagus Source Type: research

Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection
Conclusions Even after seemingly complete endoscopic resection, recurrence of BO is frequent and independent of additional thermal therapy. Due to the possibility of neoplasia recurrence even after long disease-free intervals, follow-up should be extended beyond 5 years. (Source: Gut)
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Anders, M., Bahr, C., El-Masry, M. A., Marx, A. H., Koch, M., Seewald, S., Schachschal, G., Adler, A., Soehendra, N., Izbicki, J., Neuhaus, P., Pohl, H., Rosch, T. Tags: Editor's choice, Oesophageal cancer Oesophagus Source Type: research

A novel twist in polycystic liver disease
Liver cysts are a frequent finding on radiological imaging. Prevalence rates depend on the technique, but with CT or MRI, simple hepatic cysts are seen in approximately one-fifth of the population.1 Usually no more than one or two small (
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Cnossen, W. R., Drenth, J. P. Tags: Commentary Source Type: research

Clearance of HBV markers and HCC risk: who is safe?
Despite highly effective antiviral treatment options, chronic hepatitis B and its complications remain a medical challenge worldwide. Hepatocellular carcinoma (HCC) is still the fifth most common cause of cancer death in men and albeit surveillance programmes can principally reduce morbidity and mortality from HCC, the effect is modest and implementation of surveillance programmes is still inadequate.1 Depending on geographic region, hepatitis B is implicated as a cause of HCC in 5%–80% of patients. While antiviral therapy with interferon-α and nucleos(t)id analogues may stop disease progression in chronic hepa...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Diepolder, H. M. Tags: Commentary Source Type: research

Revival of 5-HT3 antagonism as treatment of IBS-D?
While drug development for chronic constipation and IBS with constipation has moved ahead with the marketing of prucalopride and linaclotide in many countries, the development of agents for functional diarrhoea and IBS-D has been more troubled. With the limited availability of the serotonin (5-HT)3 antagonist alosetron, the global market of drugs for diarrhoeal disorders is still led by agents developed 40–60 years ago, including opioid receptor agonists (eg, loperamide), bile acid binders (eg, cholestyramine) and tricyclic antidepressants (eg, amitriptyline). Clearly, the development of new effective and safe d...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Barbara, G. Tags: Commentary Source Type: research

Are we improving disease outcomes in IBD? A view from the epidemiology side
Natural history studies provide invaluable data on the disease course. Rungoe et al1 report changes in medical treatment and surgery rates over the past three decades (1979–2011) using a large Danish population-based cohort of 48 467 patients with IBD issued from a Danish health administrative database. Interestingly, the authors found a decrease in surgery rates in both Crohn's disease (CD) and UC. Changes in surgery rates were accompanied by a significant decrease in the use of five aminosalicylic acids (5-ASA) and corticosteroids. The use of 5-ASA significantly decreased from 51% in 1995–2002 to 19% in ...
Source: Gut - September 2, 2014 Category: Gastroenterology Authors: Gower-Rousseau, C., Savoye, G., Colombel, J.-F., Peyrin-Biroulet, L. Tags: Commentary Source Type: research

Correction
V Mukhekat, I Ahmad, Y Merali, et al. PTU-078 The Application Of A Markov Model For Evauating Asa Therapy For Ulcerative Colitis. Gut 2014;63:Suppl 1 A73. The first author's name was published incorrectly. The correct name is Vinaykumar Mukhekar. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Tags: Correction Source Type: research

Helicobacter pylori infection in gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma: a re-evaluation
In 1991 Wotherspoon et al1 showed a close association between Helicobacter pylori infection and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) with the organism present in 92% of cases. Other studies have shown this association to be varying between 42% and 100%. In vitro studies at that time showed that lymphoma cell proliferation was associated with the presence of H. pylori mediated through specific tumour infiltrating T cells in a contact dependant manner. In the light of this finding Wotherspoon et al1 were able to demonstrate that eradication of H. pylori induced lymphoma regression. In a recent Gut ...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Sena Teixeira Mendes, L., D Attygalle, A., C Wotherspoon, A. Tags: PostScript Source Type: research

Defining HNPCC and Lynch syndrome: what's in a name?
Dear Sir, In June 2013, the Mallorca Group published revised guidelines for the clinical management of Lynch syndrome.1 In the title, HNPCC (Hereditary NonPolyposis Colorectal Cancer) is equated with Lynch syndrome, continuing a misuse of terms that has fuelled confusion for many years. The two terms describe different, although overlapping, diseases: the distinction is critical to an accurate understanding of hereditary colorectal cancer. HNPCC is defined clinically, usually as families satisfying Amsterdam I or II criteria.2 Lynch syndrome is defined genetically, by the presence of a germline mutation in DNA mismatch rep...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Kravochuck, S. E., Kalady, M. F., Burke, C. A., Heald, B., Church, J. M. Tags: PostScript Source Type: research

Better 5-year survival of fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: still too close to call
We read with great interest the letter by Eggert et al, in response to our recently published article which raised concerns about the better 5-year survival of fibrolamellar hepatocellular carcinoma (fHCC) compared with conventional hepatocellular carcinoma (HCC-NOS).1 2 In the letter, the authors pointed out that it cannot be concluded from our meta-analysis that ‘survival in fHCC is similar to conventional HCC in non-cirrhotic liver patients’, given the overlap in the CIs of the subgroup analyses (limited to non-cirrhotic liver patients) and the overall analysis of all cases. The authors further report findin...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Njei, B. Tags: PostScript Source Type: research

Response to fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: better 5-year survival or artefactual result of research methodology?
We are grateful for the opportunity to reply to Dr Njei's letter, which raised the question of whether a better 5-year survival for patients with fibrolamellar hepatocellular carcinoma (fHCC) versus patients with hepatocellular carcinoma (HCC) (that we recently reported), was real or an artefact of research methodology.1 In the letter, results of a meta-analysis were presented which were interpreted to show that the survival of fHCC and HCC do not differ in non-cirrhotic patients. We disagree with this interpretation of the results. In the meta-analysis, 11 studies were included in the overall analysis, while three of the ...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Eggert, T., McGlynn, K., Greten, T. F., Altekruse, S. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceNod2: —a key component of the microbial intestinal crypt interface  Nigro G, Rossi R, Commere P-H, et al. The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15, 792–8. Genetic factors play an important role in the pathogenesis of Crohn's disease (CD). The most significant of these implicates aberrant immune responses central to microbial sensing/signalling and mucosa-initiated effector responses. Nucleotide oligomerisation domain 2 (Nod2) is a member of the Nod-like receptor (NLR) family of intrace...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Microbiota and diabetes: an evolving relationship
The gut microbiota affects numerous biological functions throughout the body and its characterisation has become a major research area in biomedicine. Recent studies have suggested that gut bacteria play a fundamental role in diseases such as obesity, diabetes and cardiovascular disease. Data are accumulating in animal models and humans suggesting that obesity and type 2 diabetes (T2D) are associated with a profound dysbiosis. First human metagenome-wide association studies demonstrated highly significant correlations of specific intestinal bacteria, certain bacterial genes and respective metabolic pathways with T2D. Impor...
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Tilg, H., Moschen, A. R. Tags: GUT Recent advances in basic science Source Type: research

p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury
Conclusions We provide experimental evidence that p21 is required for sustained liver regeneration and tumour development in chronic liver injury indicating that p21 needs to be tightly regulated in order to balance liver regeneration and cancer risk. Moreover, we identify p21 as a negative prognostic marker in human HCC. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Marhenke, S., Buitrago-Molina, L. E., Endig, J., Orlik, J., Schweitzer, N., Klett, S., Longerich, T., Geffers, R., Sanchez Munoz, A., Dorrell, C., Katz, S.-F., Lechel, A., Weng, H., Krech, T., Lehmann, U., Dooley, S., Rudolph, K. L., Manns, M. P., Vogel, Tags: Hepatic cancer Hepatology Source Type: research

In vitro infection of primary human hepatocytes by HCV-positive sera: insights on a highly relevant model
Conclusions We identified critical factors leading to efficient PHH infection by HCV sera in vitro. Overall, we showed that this cellular model provides a useful tool for studying the mechanism of HCV infection in its natural host cell, selecting highly infectious isolates, and determining the potency of drugs towards various HCV strains. (Source: Gut)
Source: Gut - August 3, 2014 Category: Gastroenterology Authors: Gondeau, C., Briolotti, P., Razafy, F., Duret, C., Rubbo, P.-A., Helle, F., Reme, T., Ripault, M.-P., Ducos, J., Fabre, J.-M., Ramos, J., Pecheur, E.-I., Larrey, D., Maurel, P., Daujat-Chavanieu, M. Tags: Pancreas and biliary tract Hepatology Source Type: research