A history of luminal gastroenterology in Britain: the inside guide
Residing recently in the Sheila Sherlock room in the refurbished accommodations at the William Harvey house at the College of Physicians in London, I was reminded that it was she who first told me (at one of my unsuccessful Consultant interviews) that "Gastroenterologists help people to get square meals through round holes". I have been at that task ever since, often with an endoscope in hand, as recounted in a recent memoir called The Tunnel at the End of the Light (www.peterbcotton.com). I approached Peter Down's majestic history of the British contributions to ‘luminal gastroenterology’ with some t...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Cotton, P. Tags: PostScript Source Type: research

Quality of life after restorative proctocolectomy in Muslim patients
Dear Editor, Current guidelines from the British Society of Gastroenterology concerning the management of IBD in adults1 highlight that surgery remains necessary in up to 30% of patients with UC. First described by Parks and Nicholls,2 restorative proctocolectomy with ileal pouch–anal anastomosis (RPC) has become the established operation for patients with therapy-resistant UC, indeterminate colitis, familial adenomatous polyposis and for some patients with UC-related neoplasia.3 4 Ethnic variations in the incidence and prevalence of IBD in the UK are diminishing.5 IBD has increased dramatically in British South Asia...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Iqbal, F., Zaman, S., Bowley, D. M., Vaizey, C. J. Tags: PostScript Source Type: research

GI highlights from the literature
Basic scienceThe complexities of host–microbiota interaction Gevers D, Kugathasan S, Denson LA, et al. The treatment-naïve microbiome in new-onset Crohn's Disease. Cell Host Microbe 2014;15:382–92. Crohn's disease is a complex disorder in which genetics and environmental factors establish and contribute to disease pathogenesis. Genetic studies implicate an underlying role for aberrant immune responses central to microbial sensing/signalling and mucosa-initiated effector responses. It is now well recognised that the gut microbiome plays an important role in disease pathogenesis but many current studies are ...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

Synchronous superficial spreading lesions of the stomach
Clinical presentation An asymptomatic 61-year-old man with a medical history of successful Helicobacter pylori eradication therapy 7 years earlier underwent a screening oesophagogastroduodenoscopy (OGD). Laboratory investigations, including serum carcinoembryonic antigen and cancer antigen 19-9, showed no significant abnormalities. The OGD showed an irregular nodulated lesion in the lesser curvature of the gastric antrum (figure 1) and an aggregated lesion consisting of small nodules and hypertrophic gastric folds in the greater curvature of the lower gastric body (figure 2). Barium meal examination showed a filling d...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Namikawa, T., Kobayashi, M., Hanazaki, K. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Symptomatic reflux disease: the present, the past and the future
The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oeso...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Boeckxstaens, G., El-Serag, H. B., Smout, A. J. P. M., Kahrilas, P. J. Tags: GUT Recent advances in clinical practice, Gastro-oesophageal reflux, Open access, Oesophageal cancer Source Type: research

Tracing PAKs from GI inflammation to cancer
P-21 activated kinases (PAKs) are effectors of Rac1/Cdc42 which coordinate signals from the cell membrane to the nucleus. Activation of PAKs drive important signalling pathways including mitogen activated protein kinase, phospoinositide 3-kinase (PI3K/AKT), NF-B and Wnt/β-catenin. Intestinal PAK1 expression increases with inflammation and malignant transformation, although the biological relevance of PAKs in the development and progression of GI disease is only incompletely understood. This review highlights the importance of altered PAK activation within GI inflammation, emphasises its effect on oncogenic signalling ...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Dammann, K., Khare, V., Gasche, C. Tags: GUT Recent advances in basic science Source Type: research

Jnk1 in murine hepatic stellate cells is a crucial mediator of liver fibrogenesis
Conclusions Jnk1 in HSCs, but not in hepatocytes, significantly contribute to liver fibrosis development, identifying Jnk1 in HSCs as a profibrotic kinase and a promising cell-directed target for liver fibrosis. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Zhao, G., Hatting, M., Nevzorova, Y. A., Peng, J., Hu, W., Boekschoten, M. V., Roskams, T., Muller, M., Gassler, N., Liedtke, C., Davis, R. J., Cubero, F. J., Trautwein, C. Tags: Cirrhosis, Pancreas and biliary tract Hepatology Source Type: research

Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C
Conclusions In compensated patients with advanced fibrosis due to HCV-1, triple therapy with TVR led to satisfactory rates of safety, tolerability and on-treatment virological response with adequate managements of AEs. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Colombo, M., Fernandez, I., Abdurakhmanov, D., Ferreira, P. A., Strasser, S. I., Urbanek, P., Moreno, C., Streinu-Cercel, A., Verheyen, A., Iraqi, W., DeMasi, R., Hill, A., Lauffer, J. M., Lonjon-Domanec, I., Wedemeyer, H. Tags: Cirrhosis, Open access Hepatology Source Type: research

Turmeric curcumin inhibits entry of all hepatitis C virus genotypes into human liver cells
Conclusions Turmeric curcumin inhibits HCV entry independently of the genotype and in primary human hepatocytes by affecting membrane fluidity thereby impairing virus binding and fusion. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Anggakusuma, , Colpitts, C. C., Schang, L. M., Rachmawati, H., Frentzen, A., Pfaender, S., Behrendt, P., Brown, R. J. P., Bankwitz, D., Steinmann, J., Ott, M., Meuleman, P., Rice, C. M., Ploss, A., Pietschmann, T., Steinmann, E. Tags: Hepatic cancer Hepatology Source Type: research

A validated tool to predict colorectal neoplasia and inform screening choice for asymptomatic subjects
Conclusions The scoring system based on age, gender, smoking, family history, Body Mass Index and self-reported diabetes is useful in predicting the risk of colorectal neoplasia. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Wong, M. C. S., Lam, T. Y. T., Tsoi, K. K. F., Hirai, H. W., Chan, V. C. W., Ching, J. Y. L., Chan, F. K. L., Sung, J. J. Y. Tags: Endoscopy, Colon cancer Source Type: research

Chloride channel inhibition by a red wine extract and a synthetic small molecule prevents rotaviral secretory diarrhoea in neonatal mice
Conclusions Our results support a pathogenic role for enterocyte CaCCs in rotaviral diarrhoea and demonstrate the antidiarrhoeal action of CaCC inhibition by an alcohol-free, red wine extract and by a synthetic small molecule. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Ko, E.-A., Jin, B.-J., Namkung, W., Ma, T., Thiagarajah, J. R., Verkman, A. S. Tags: Pancreas and biliary tract, Diarrhoea Colon Source Type: research

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy
This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficie...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Kaminski, M. F., Polkowski, M., Kraszewska, E., Rupinski, M., Butruk, E., Regula, J. Tags: Endoscopy, Open access, Colon cancer Source Type: research

Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome
Objective The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS. Design 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with Puncorrected
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Wouters, M. M., Lambrechts, D., Knapp, M., Cleynen, I., Whorwell, P., Agreus, L., Dlugosz, A., Schmidt, P. T., Halfvarson, J., Simren, M., Ohlsson, B., Karling, P., Van Wanrooy, S., Mondelaers, S., Vermeire, S., Lindberg, G., Spiller, R., Dukes, G., D'Ama Tags: Constipation, Diarrhoea, Irritable bowel syndrome Neurogastroenterology Source Type: research

Development and validation of a rapid, generic measure of disease control from the patient's perspective: the IBD-Control questionnaire
Introduction The use of patient reported outcome measures to support routine inflammatory bowel disease (IBD) care is not widespread and suggests that existing questionnaires lack relevance to day-to-day decisions or are too cumbersome to administer. We developed a simple, generic tool for capturing disease control from the patient's perspective to address these barriers. Methods Development based on literature review, patient focus groups/interviews and a steering group, defining a limited set of generic questions. The ‘IBD-Control’ questionnaire comprises 13 items plus a visual analogue scale (VAS) (0–...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Bodger, K., Ormerod, C., Shackcloth, D., Harrison, M., on behalf of the IBD Control Collaborative, Ahmed, Bowering, Brown, Hurst, Gledhill Tags: Crohn's disease, Ulcerative colitis, Open access Inflammatory bowel disease Source Type: research

Genomic ATG16L1 risk allele-restricted Paneth cell ER stress in quiescent Crohn's disease
Conclusions The ATG16L1 T300A polymorphism defines a specific subtype of patients with CD, characterised by Paneth cell ER stress even during quiescent disease. Paneth cell ER stress correlates with bacterial persistence, and is thus likely to modulate antimicrobial functionality of this cell type in patients with CD. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Deuring, J. J., Fuhler, G. M., Konstantinov, S. R., Peppelenbosch, M. P., Kuipers, E. J., de Haar, C., van der Woude, C. J. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

AIEC pathobiont instigates chronic colitis in susceptible hosts by altering microbiota composition
Conclusions AIEC, and perhaps other pathobionts, may instigate chronic inflammation in susceptible hosts by altering the gut microbiota composition so as to give it an inherently greater ability to activate innate immunity/pro-inflammatory gene expression. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Chassaing, B., Koren, O., Carvalho, F. A., Ley, R. E., Gewirtz, A. T. Tags: Editor's choice Inflammatory bowel disease Source Type: research

Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study
Objectives To evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia. Methods In this prospective, randomised, double-blind, placebo-controlled trial conducted in Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for cardiovascular protection (81–324 mg/day) were randomised to esomeprazole 20 mg/day or placebo for ≤72 weeks. All patients received concomitant mucosal protection (gefarnate 100 mg/day). The primary endpoint was time t...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Sugano, K., Choi, M.-G., Lin, J.-T., Goto, S., Okada, Y., Kinoshita, Y., Miwa, H., Chiang, C.-E., Chiba, T., Hori, M., Fukushima, Y., Kim, H.-S., Chang, C.-Y., Date, M., on behalf of the LAVENDER Study Group Tags: Ulcer Stomach Source Type: research

Waist belt and central obesity cause partial hiatus hernia and short-segment acid reflux in asymptomatic volunteers
We report the effects of waist belt and increased waist circumference (WC) on the physiology of the GOJ in asymptomatic volunteers. Design 12 subjects with normal and 12 with increased WC, matched for age and gender were examined fasted and following a meal and with waist belts on and off. A magnet was clipped to the squamo-columnar junction (SCJ). Combined assembly of magnet-locator probe, 12-channel pH catheter and 36-channel manometer was passed. Results The waist belt and increased WC were each associated with proximal displacement of SCJ within the diaphragmatic hiatus (relative to upper border of lower oesophageal ...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Lee, Y. Y., Wirz, A. A., Whiting, J. G. H., Robertson, E. V., Smith, D., Weir, A., Kelman, A. W., Derakhshan, M. H., McColl, K. E. L. Tags: Oesophagus Source Type: research

In oesophageal squamous cells exposed to acidic bile salt medium, omeprazole inhibits IL-8 expression through effects on nuclear factor-{kappa}B and activator protein-1
Conclusions In oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-B and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognised PPI effects might contribute to the healing of reflux oesophagitis. (Source: Gut)
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Huo, X., Zhang, X., Yu, C., Zhang, Q., Cheng, E., Wang, D. H., Pham, T. H., Spechler, S. J., Souza, R. F. Tags: Gastro-oesophageal reflux Oesophagus Source Type: research

Molecular targets for antifibrotic therapy in liver disease: using magic bullets for crossfire rather than a one-sided shotgun attack
The c-Jun-N-terminal kinase (JNK) is a member of the mitogen-activated protein kinase (MAPK) family. Upon activation, JNK regulates various cellular responses, such as differentiation, proliferation, migration, the immune reaction and cell death.1 JNK activation is also involved in multiple pathways in liver physiology and disease pathogenesis.2 There are three isoforms of JNK in mammals. Whereas JNK3 is mainly expressed in the brain, heart and testis, JNK1 and JNK2 are expressed in most cells, including hepatic parenchymal and non-parenchymal cells. JNK1 and JNK2 have typically been considered to have overlapping or redun...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Hellerbrand, C. Tags: Commentary Source Type: research

ATG16L1 Crohn's disease risk stresses the endoplasmic reticulum of Paneth cells
With 163 genetic loci identified to date, genome wide association studies have revealed the significant genetic complexity associated with risk for IBD.1 Autophagy, pinpointed through the discovery of risk variants in ATG16L12 and other autophagy genes,1 remains one of the most interesting disease-specific revelations of Crohn’s disease genetics. Around a fifth of the overall genetic risk yet known for Crohn's disease may lie in genes that are directly involved in autophagy,1 including NOD2, which has recently been exposed as an autophagy inducer,3 a decade after it was reported as the first Crohn's disease risk gene...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Kaser, A., Blumberg, R. S. Tags: Commentary Source Type: research

Curcumin against hepatitis C virus infection: spicing up antiviral therapies with 'nutraceuticals'?
Infection with the HCV is one of the major causes of chronic liver disease with an estimated 184 million persons worldwide positive for HCV antibodies1 and 3–4 million newly infected each year. The situation is worrying in emerging countries of Central and Southeast Asia, North Africa and Middle East with seroprevalence around 3%–5%. Central Africa and Egypt remain regions of very high endemicity with a 25% prevalence in the latter. Hepatitis C is therefore a global health problem with striking inequalities in the access to healthcare and implementation of treatments between world regions. HCV is an enveloped R...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Pecheur, E.-I. Tags: Commentary Source Type: research

An intestinal arsonist: pathobiont ignites IBD and flees the scene
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions characterised by recurrent episodes of intestinal inflammation. It is widely accepted that genetic predisposition and environmental factors contribute to the onset and the development of IBD. Many host factors that influence the onset of IBD have been identified and mainly include genes that are involved in microbial recognition, like NOD2, or in the immune response to infection, like interleukin-23. By contrast, the search for a microbial cause of IBD has not led to definitive answers. Trillions of microbe...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Jellbauer, S., Raffatellu, M. Tags: Commentary Source Type: research

Beyond phase 3 registration trials: defining safety for triple therapy with protease inhibitors in cirrhosis
Clinical trials are the standard method for evaluating a new drug for treatment of disease in humans. The phase 3 trial is designed to evaluate a new agent's clinical benefit and possible side effects; as such, it is considered to be the definitive test of the agent's usefulness. While there is no substitute for well-designed phase 3 trials, one should be aware of their limitations.1 Usually, the protocols use very strict selection criteria, creating ‘ideal’ patients, not necessarily reflecting the patient population seen by treating physicians. Good examples were the phase 3 studies for treatment of chronic he...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: Ferenci, P., Dusheiko, G. Tags: Commentary Source Type: research

Highlights from this issue
LUMINALNovel insight into the effect of PPIs on the oesophagus It is well appreciated that gastric acid can induce oesophagitis and that proton pump inhibitors (PPIs) promote the healing of gastro-oesophageal reflux disease (GORD) through inhibiting gastric acid secretion. More recently, it has been shown that some of the direct, caustic effects of refluxed acid on oesophageal epithelial cells are secondary to chemokines such as interleukin (IL)-8 produced by those cells. It has also been shown that PPIs have a number of potential anti-inflammatory actions independent of their effects on gastric acid secretion, including t...
Source: Gut - June 6, 2014 Category: Gastroenterology Authors: El-Omar, E., Gerbes, A., Grady, W., Rosch, T. Tags: Digest Source Type: research

XIAP deficiency is a mendelian cause of late-onset IBD
Sir, We read with interest the review by Holm Uhlig on monogenic diseases associated with intestinal inflammation.1 XIAP deficiency, caused by X-linked inherited mutations in BIRC4, is highlighted as a mendelian cause of very early onset IBD. Consistently with the observation of Crohn's disease (CD) in XIAP deficiency, the RING activity of XIAP was recently shown to be required for NOD2-dependent immune responses.2 In his review Dr Uhlig suggests to consider monogenetic diseases as causes for IBD particularly in patients younger than 6 years of age. In addition to the reviewed literature, our group has recently report...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Speckmann, C., Ehl, S. Tags: PostScript Source Type: research

Crohn's disease and the 'white plague': a hypothesis
The article by Yang et al1 contributes to the emerging evidence that genetic predisposition to Crohn's Disease (CD) has an ethnicity-specific variation.s1–s4 The genetic architecture of autoimmune and inflammatory diseases has been subject to recent positive selection in human history, probably driven by the historical exposure to pathogens.2 s5–s7 Thus, the differing genetic susceptibilities in East Asians (Koreans and Japanese) vis-à-vis the Caucasoid Euro-Americans might reflect the differences in their historical exposure to predominant pathogens occurring during the historical migrations of anatomic...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Das, K. Tags: Postscript Source Type: research

Reduced white matter microstructural integrity correlates with cognitive deficits in minimal hepatic encephalopathy
We read with interest the article by Goldbecker et al1 comparing the accuracy for the diagnosis of hepatic encephalopathy (HE) of the three most commonly used batteries of psychometric test and critical flicker frequency. They conclude that the Psychometric Hepatic Encephalopathy Score (PHES) battery2 is the most robust method for diagnosis of HE. As mentioned by Goldbecker et al,1 there is a wide agreement that HE needs to be diagnosed and treated and an increasing body of evidence shows that patients benefit from early treatment of overt and minimal HE (MHE). However, the diagnosis of MHE and lower stages of overt HE str...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Montoliu, C., Urios, A., Forn, C., Garcia-Panach, J., Avila, C., Gimenez-Garzo, C., Wassel, A., Serra, M. A., Giner-Duran, R., Gonzalez, O., Aliaga, R., Belloch, V., Felipo, V. Tags: PostScript Source Type: research

GI highlights from the literature
In this study, the authors investigate the role of IL-22 in the gut of mice during Salmonella infection. IL-22–/– mice orally infected with Salmonella were colonised less by this bacteria than infected wild-type (WT) mice, and this was rescued by injecting infected IL-22–/– mice with IL-22. The differences in levels of pathogen colonisation were not... (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: McLean, M. H. Tags: JournalScan Source Type: research

A rare cause of weight loss
Clinical presentation A 36-year-old man of Eastern European origin presented with a 4-week history of odynophagia, dysphagia, 10 kg weight loss and night sweats. There was no significant past medical history, he was on no regular medications but the travel history was notable with several years spent working in Africa. Clinical examination revealed loss of subcutaneous fat, muscle wasting, extensive lymphadenopathy and oral candidiasis. Initial blood tests revealed Hb 9.0 g/dL (13.0–16.7), white cell count 6.2x109/L (3.5–11), erythrocyte sedimentation rate 44 mm/h, C reactive protein 113 mg/L (
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Flanagan, P. K., Coupland, S. E., Arumainathan, A., Probert, C. S. J. Tags: GUT Snapshot Editor ' s quiz: GI snapshot Source Type: research

Management of gastrointestinal and liver diseases during pregnancy
In the majority of patients with chronic gastrointestinal and liver diseases, maintenance therapy is required during pregnancy to control the disease, and disease follow-up or disease control might necessitate endoscopy. Evidence on the safety of drugs and imaging techniques during pregnancy is scarce and sometimes difficult to interpret. In this review we summarise existing literature with the aim of optimising counselling of patients with common chronic gastrointestinal and liver diseases who want to conceive. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: van der Woude, C. J., Metselaar, H. J., Danese, S. Tags: GUT Recent advances in clinical practice Source Type: research

Reduced fibrosis in recurrent HCV with tacrolimus, azathioprine and steroids versus tacrolimus: randomised trial long term outcomes
Conclusions Long term immunosuppression with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis assessed by Ishak stage and CPA, less portal hypertension and decompensation, compared with tacrolimus alone. ISRCTN94834276 —Randomised study for immunosuppression regimen in liver transplantation. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Manousou, P., Cholongitas, E., Samonakis, D., Tsochatzis, E., Corbani, A., Dhillon, A. P., Davidson, J., Rodriguez-Peralvarez, M., Patch, D., O'Beirne, J., Thorburn, D., Luong, T., Rolles, K., Davidson, B., McCormick, P. A., Hayes, P., Burroughs, A. K. Tags: Open access Hepatology Source Type: research

Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir in Asian patients with chronic hepatitis B
Conclusions At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant side effect of besifovir was L-carnitine depletion, requiring carnitine supplementation. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Lai, C.-L., Ahn, S. H., Lee, K. S., Um, S. H., Cho, M., Yoon, S. K., Lee, J.-W., Park, N. H., Kweon, Y.-O., Sohn, J. H., Lee, J., Kim, J.-A., Han, K.-H., Yuen, M.-F. Tags: Hepatitis B, Editor's choice Hepatology Source Type: research

Genetic inactivation of Nupr1 acts as a dominant suppressor event in a two-hit model of pancreatic carcinogenesis
Conclusions According to Nupr1 status, KIC mice develop tumours that phenocopy human classical or QM-PDAC, respectively, and present differential drug sensitivity, thus becoming attractive models for preclinical drug trials. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Cano, C. E., Hamidi, T., Garcia, M. N., Grasso, D., Loncle, C., Garcia, S., Calvo, E., Lomberk, G., Dusetti, N., Bartholin, L., Urrutia, R., Iovanna, J. L. Tags: Pancreas and biliary tract, Pancreatic cancer Source Type: research

SPARC independent drug delivery and antitumour effects of nab-paclitaxel in genetically engineered mice
Conclusions nab-Paclitaxel accumulates and acts in a dose-dependent manner. The interaction of plasma SPARC and albumin-bound drugs is observed at low doses of nab-paclitaxel but is saturated at therapeutic doses in murine tumours. Thus, this study provides important information for future preclinical and clinical trials in PDA using nab-paclitaxel in combination with novel experimental and targeted agents. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Neesse, A., Frese, K. K., Chan, D. S., Bapiro, T. E., Howat, W. J., Richards, F. M., Ellenrieder, V., Jodrell, D. I., Tuveson, D. A. Tags: Pancreas and biliary tract, Open access Pancreatic cancer Source Type: research

Use of CT colonography in the English Bowel Cancer Screening Programme
Conclusions In the BCSP, detection rates after positive gFOBt are lower for CTC than colonoscopy, although populations undergoing the two tests are different. Centres with more experienced radiologists have higher detection and accuracy. Rigorous quality assurance of BCSP radiology is needed. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Plumb, A. A., Halligan, S., Nickerson, C., Bassett, P., Goddard, A. F., Taylor, S. A., Patnick, J., Burling, D. Tags: Endoscopy, Open access, Colon cancer Colorectal cancer Source Type: research

Postcolonoscopy colorectal cancers are preventable: a population-based study
Conclusions In our experience, 86.4% of all PCCRCs could be explained by procedural factors, especially missed lesions. Quality improvements in performance of colonoscopy, with special attention to the detection and resection of proximally located flat precursors, have the potential to prevent PCCRCs. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: le Clercq, C. M. C., Bouwens, M. W. E., Rondagh, E. J. A., Bakker, C. M., Keulen, E. T. P., de Ridder, R. J., Winkens, B., Masclee, A. A. M., Sanduleanu, S. Tags: Endoscopy, Colon cancer Colorectal cancer Source Type: research

Colorectal cancers soon after colonoscopy: a pooled multicohort analysis
Conclusions Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Robertson, D. J., Lieberman, D. A., Winawer, S. J., Ahnen, D. J., Baron, J. A., Schatzkin, A., Cross, A. J., Zauber, A. G., Church, T. R., Lance, P., Greenberg, E. R., Martinez, M. E. Tags: Endoscopy, Colon cancer Source Type: research

A distinct vagal anti-inflammatory pathway modulates intestinal muscularis resident macrophages independent of the spleen
The cholinergic anti-inflammatory pathway (CAIP) has been proposed as a key mechanism by which the brain, through the vagus nerve, modulates the immune system in the spleen. Vagus nerve stimulation (VNS) reduces intestinal inflammation and improves postoperative ileus. We investigated the neural pathway involved and the cells mediating the anti-inflammatory effect of VNS in the gut. The effect of VNS on intestinal inflammation and transit was investigated in wild-type, splenic denervated and Rag-1 knockout mice. To define the possible role of α7 nicotinic acetylcholine receptor (α7nAChR), we used knockout and b...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Matteoli, G., Gomez-Pinilla, P. J., Nemethova, A., Di Giovangiulio, M., Cailotto, C., van Bree, S. H., Michel, K., Tracey, K. J., Schemann, M., Boesmans, W., Vanden Berghe, P., Boeckxstaens, G. E. Tags: GUT Recent advances in basic science Neurogastroenterology Source Type: research

Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine
Conclusions Observations suggest that that peripheral TPH inhibitors uncouple the positive linkage of enterochromaffin cell-derived 5-HT to intestinal inflammation. Because peripheral TPH inhibitors evidently do not enter the murine ENS, they lack deleterious effects on constitutive intestinal motility in mice. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Margolis, K. G., Stevanovic, K., Li, Z., Yang, Q. M., Oravecz, T., Zambrowicz, B., Jhaver, K. G., Diacou, A., Gershon, M. D. Tags: Neurogastroenterology Source Type: research

Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial
This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure. Design Randomised, controlled, single-blind, multicentre study. 69 patients with secondary IFX failure were randomised to IFX dose intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co-primary end points at week 12 were proportion of patients responding (Crohn's Disease Activity Index (CDAI) decrease ≥70, or ≥50% reduction in active fistulas) and accumulat...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Steenholdt, C., Brynskov, J., Thomsen, O. O., Munck, L. K., Fallingborg, J., Christensen, L. A., Pedersen, G., Kjeldsen, J., Jacobsen, B. A., Oxholm, A. S., Kjellberg, J., Bendtzen, K., Ainsworth, M. A. Tags: Crohn's disease Inflammatory bowel disease Source Type: research

Fatigue management in patients with IBD: a randomised controlled trial
Objective To assess the effectiveness of solution-focused therapy (SFT) on fatigue and quality of life (QoL) in patients with fatigued inflammatory bowel disease (IBD). Design Randomised controlled trial in two Dutch hospitals. Patients with IBD with quiescent IBD and with a Checklist Individual Strength—Fatigue (CIS—fatigue) score of ≥35 were enrolled. Patients were 1:1 randomised to receive SFT or care as usual (CAU) for 3 months. Patients were followed for a further 6 months after the SFT. Primary endpoint was defined as changes in fatigue and QoL during follow-up. Secondary endpoints included ...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Vogelaar, L., van't Spijker, A., Timman, R., van Tilburg, A. J. P., Bac, D., Vogelaar, T., Kuipers, E. J., van Busschbach, J. J. V., van der Woude, C. J. Tags: Inflammatory bowel disease Source Type: research

Mouse Paneth cell antimicrobial function is independent of Nod2
Conclusions Our data reveal that Nod2 does not directly regulate PC antimicrobial activity in B6 mice. Moreover, we demonstrate that previously reported Nod2-dependent influences on gut microbial composition may be overcome by environmental factors, such as cohousing with WT littermates. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Shanahan, M. T., Carroll, I. M., Grossniklaus, E., White, A., von Furstenberg, R. J., Barner, R., Fodor, A. A., Henning, S. J., Sartor, R. B., Gulati, A. S. Tags: Crohn's disease, Open access Inflammatory bowel disease Source Type: research

Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding
Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour. (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Scholtz, S., Miras, A. D., Chhina, N., Prechtl, C. G., Sleeth, M. L., Daud, N. M., Ismail, N. A., Durighel, G., Ahmed, A. R., Olbers, T., Vincent, R. P., Alaghband-Zadeh, J., Ghatei, M. A., Waldman, A. D., Frost, G. S., Bell, J. D., le Roux, C. W., Goldst Tags: Open access Stomach Source Type: research

Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells
Objectives Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of oesophageal adenocarcinoma (EAC) and its progression. Design lncRNAs that are abnormally upregulated in EACs were identified by RNA-sequencing analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 25 EAC patients. Cell biological assays in combination with small interfering RNA-mediated knockdown were performed in order to probe the functional relevance of the...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Yang, X., Song, J. H., Cheng, Y., Wu, W., Bhagat, T., Yu, Y., Abraham, J. M., Ibrahim, S., Ravich, W., Roland, B. C., Khashab, M., Singh, V. K., Shin, E. J., Yang, X., Verma, A. K., Meltzer, S. J., Mori, Y. Tags: Oesophageal cancer Oesophagus Source Type: research

Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review
Objective To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). Design PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include ≥200 individuals, to have response rates ≥50% and recall periods
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: El-Serag, H. B., Sweet, S., Winchester, C. C., Dent, J. Tags: Gastro-oesophageal reflux Oesophagus Source Type: research

Oral antiviral therapy for hepatitis B: the case of besifovir, a new kid on the block with a long way to go
In the last 5 years, the landscape of HBV antiviral treatment has changed significantly to such an extent that most of the clinical problems have been solved for countries where third-generation nucleo s(t)ide analogues (NUC), such as entecavir (ETV) and tenofovir (TDF) are routinely available.1–3 Indeed, because of the high potency and high genetic barrier of these products, 5–6 years administration of ETV or TDF suppresses viral replication in>95% of the cases, with increasing rates of HBeAg seroconversion (up to 50%) and HBsAg seroconversion (up to 10%). In patients with long-lasting viral suppr...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Lampertico, P. Tags: Commentary Source Type: research

Does the gut-brain axis control anticipatory food reward? Novel insights from bariatric surgery
This study adds significantly to an emerging... (Source: Gut)
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Van Oudenhove, L., Weltens Tags: Commentary Source Type: research

Selective inhibition of mucosal serotonin as treatment for IBD?
Serotonin (5-HT) has extensively been studied in the central and enteric nervous system. Altered levels of 5-HT play a role in many central nervous system (CNS) disorders and can be treated with specific 5-HT receptor agonists and antagonists. Interestingly, 95% of the bodies 5-HT is located outside central neuronal regions and in the intestine. The discovery of 5-HT secreting cells in the intestinal epithelium has resulted in a fruitful area of research that is focused on the function of intestinal epithelium-derived 5-HT.1 The subsequent discovery that 5-HT may play an important role in driving intestinal inflammation ha...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Levin, A. D., van den Brink, G. R. Tags: Commentary Source Type: research

Interval cancer: nightmare of colonoscopists
Colonoscopy has become the number one gastrointestinal endoscopic procedure in the world and is considered the gold standard for detecting colorectal cancer (CRC) and its precursors. For a long time, it was thought to be close to perfect in preventing CRC, implying that the disease does virtually not occur soon after colonoscopy has been performed. However, an increasing body of epidemiological evidence questions this and demonstrates the occurrence of these so-called postcolonoscopy CRCs (PCCRCs) as a kind of interval cancers. The term interval cancer is taken from screening and describes the occurrence of cancer in the t...
Source: Gut - May 5, 2014 Category: Gastroenterology Authors: Haug, U., Regula, J. Tags: Commentary Source Type: research