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Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary of background data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

ObjectivesHelicobacter pylori infection is a common cause of chronic gastritis worldwide and an established risk factor for developing gastric malignancy. The endoscopic appearances predicting H. pylori status are an ongoing area of research, as are their diagnostic accuracies. This study aimed to establish the diagnostic accuracy of several mucosal features predictive of H. pylori negative status and formulate a simple prediction model for use at the time of endoscopy.DesignPatients undergoing high-definition upper gastrointestinal (GI) endoscopy without magnification were recruited prospectively. During the endoscopy, the presence or absence of specific endoscopic findings was noted. Sydney protocol biopsies were used as the diagnostic reference standard, and urease test if taken. The results informed a logistic regression model used to produce a simple diagnostic approach. This model was subsequently validated using a further cohort of 30 patients.Results153 patients were recruited and completed the study protocol. The prevalence of active H. pylori infection was 18.3% (28/153). The overall diagnostic accuracy of the simple prediction model was 80.0%, and 100% of patients with active H. pylori infection were correctly classified. The presence of regular arrangement of collecting venules (RAC) showed a positive predictive value for H. pylori naïve status of 90.7%, rising to 93.6% for patients under the age of 60.ConclusionA simple endoscopic model may be accurate for predicting H. pylori status of a patient, and the need for biopsy-based tests. The presence of RAC in the stomach is an accurate predictor of H. pylori negative status, particularly in patients under the age of 60.Trial registration numberThe study was registered with ClinicalTrials.gov, No. NCT02385045.

Background & aims: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs). Methods: Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m 2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group. Results: Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group. Conclusion: One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation. Trial registration: ClinicalTrials.gov Identifier NCT02459561.

Background A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease. Methods A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. Results Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p p = 0.001), (4) healthy controls and inactive Crohn’s (SMD = 1.265 95% CI: 0.845 to 1.686, p p p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. Conclusion The use of gut permeability measurements in screening and monitoring of coeliac and Crohn’s disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.

Introduction Trimethylamine N-oxide (TMAO) is formed in the liver from trimethylamine, and is exclusively generated by gut microbiota from the metabolism of dietary carnitine and choline. Elevated plasma levels have been implicated in the pathogenesis of Type 2 Diabetes and cardiovascular disease. The Endobarrier is an endoscopically implanted duodenal jejunal bypass liner (DJBL) designed to mimic the effects of bariatric surgery leading to significant weight loss and improvements in glycaemic control and we present novel data of its effects on the plasma metabolic profile of these patients. Methods The Endobarrier Trial (NCT02459561) is a large multicentre, randomised, controlled trial across two sites in the UK which recruited 170 patients with Type 2 Diabetes and BMI 30–50 kg/m2. Participants were randomised to receive the DJBL (n=85) for one year or conventional medical therapy, diet and exercise (n=85). Plasma samples were collected from all participants at baseline, 6 months and 1 year and analysed using 1H NMR spectroscopy and multivariate statistical analysis to identify key metabolic perturbations between both patient cohorts. Results A total of 112 patients were followed up for one year. 309 plasma samples were processed and then analysed. A typical 1H NMR plasma spectrum is shown in figure 1. Reduction in plasma concentrations of trimethylamine N-oxide (TMAO) were found in the DJBL group at 6 months and 1 year compared with the control group. Conclusions Raised levels of Plasma TMAO have been associated with the development of diabetes and in this study were found to reduce following 6 months and 1 year of DJBL therapy compared with controls. This is the first study of its kind to explore alterations in the metabolic profiles of patients receiving the DJBL by utilising high field 1H nuclear magnetic resonance (NMR) spectroscopy technique. These results may provide a possible insight into the mechanisms of how this device may elicit its effect on weight loss and glycaemic improvement, by reducing plasma TMAO and potentially altering the gut microbial metabolic function.

BackgroundThe EndoBarrier®(GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months.ResultsThere was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98;p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47;p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0;p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48;p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated.ConclusionsThe results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss.Trial registrationCurrent Controlled Trials ISRCTN30845205.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.

BACKGROUND AND AIMS: Obesity associated with diabetes mellitus is a significant worldwide problem associated with considerable health care costs. Whilst surgical intervention is effective, it is invasive, costly and associated with complications. This study aims to evaluate the safety and efficacy of the EndoBarrier®, a duodenal-jejunal sleeve bypass as an alternative treatment of diabetes mellitus in obese patients. MATERIALS AND METHODS: This was a multi-centre, non-randomised trial recruiting obese patients with type 2 diabetes from three sites in the UK. Eligible participants had a BMI of 30-50 kg/m2and HbA1c levels of 7.5-10%. The study comprised a 12-month period with the EndoBarrier® inserted and a 6-month follow-up period after it had been explanted. The primary study outcomes were weight, BMI, HbA1c levels and fasting insulin and glucose levels. RESULTS: Forty-five patients were recruited and 31 patients (69%) completed the 12-month study period. Significant reductions in weight (95%CI 0.62-29.38; p

Purpose of Review Obesity is increasing at an alarming rate and now poses a global threat to humankind. In recent years, we have seen the emergence of medical devices to combat the obesity epidemic. These therapeutic strategies are discussed in this review dividing them into gastric and duodenal therapies. Recent Findings Traditionally, medical devices for obesity such as the intragastric balloon have focused on reducing gastric size, but more recently there has been a shift towards developing devices that modulate neural and hormonal responses to induce early satiety thus reducing oral intake. Summary Medical devices for obesity treatment may have a role in those patients who are struggling to control their weight despite significant lifestyle modifications such as diet and exercise and who decline or are unfit for bariatric surgery. For the wider adoption and integration of these devices in the obesity treatment paradigm, more long-term efficacy and safety data from randomised controlled trials are required.

IntroductionImmune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce.MethodsWe conducted a multicenter (six cancer centers), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with Common Terminology Criteria for Adverse Events (CTCAE) grade 0 for diarrhea at 12 weeks after IFX initiation. We also assessed cancer outcomes at 1 year using RECIST V1.1 criteria.Results127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhea CTCAE grade >2 and 115 (90.6%) required hospitalization for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistic regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04 to 0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13 to 8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared with patients with IFX-responsive enterocolitis (37.5%; p=0.013).ConclusionThis is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Using predefined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI therapy.

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Uncertainty exists about risk:benefit of proximal intestinal exclusion with Endobarrier (EB), a novel endoscopic duodenal jejunal liner device for obesity, both with and without diabetes. In view of this, during 2017, an independent, secure, on-line registry was established under the auspices of the Association of British Clinical Diabetologists, for the collection of safety and efficacy data worldwide. As of December 2017, data had been entered on 403 patients {age 51.3 ± 11.8 year, 62% male, 89% europid, 74% diabetes, BMI 42.6 ± 10.2 kg/m2} from 13 centres in 4 countries: Australia, Austria, Czech Republic and United Kingdom. EB led to many benefits, including: in those with both baseline and explant data, mean ± SD weight fell by 14.5 ± 10.3 kg from 125.3 ± 26.7 to 110.8 ± 26.4 kg (n = 265 p Disclosure R.E.J. Ryder: Other Relationship; Self; AstraZeneca. Speaker's Bureau; Self; Bioquest, Janssen Pharmaceuticals, Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk A/S. L. Munro: None. J.J. McMaster: None. J. Bessell: None. J.M. Bascomb: None. J.E. Collins: None. L. Kow: None. J. Chisholm: None. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc.. P.N. Pferschy: None. J.P. Teare: Research Support; Self; GI Dynamics Inc.. J.C. Mason: None. J.P. Byrne: None. M.C. Wyres: None. M.L. Cull: None. W. Burbridge: Other Relationship; Self; Menarini Group. S.P. Irwin: None. M. Yadagiri: None. E. Fogden: None. M. Anderson: None. P. Sen Gupta: None. M. Benes: None.

Introduction Obesity is a modern pandemic. One of the major complications of obesity is the development of diabetes which leads to considerable mortality, morbidity and enormous health care costs. 1 The EndoBarrier is an endoscopically implantable duodenal-jejunal sleeve bypass (DJSB); anchored in the duodenum, preventing ingested food from coming into contact with the proximal intestine and induces weight loss and improvement in glycaemic control. The aim of this prospective study was to assess the safety and efficacy of the EndoBarrier in obese patients with type 2 diabetes. Method This was a non-randomised study conducted at three investigational sites (Southampton, London, and Manchester) over an 18 month period with clinical and biochemical assessments carried out at 3 monthly intervals. The device was implanted for 12 months with 6 months follow up. All patients were obese with poorly controlled diabetes. Adverse events were recorded and statistical analysis was performed. Results A total of 45 subjects were enrolled into the study At 12 months following implant: 1) HbA1c significantly reduced from baseline at 0.8% below the mean at baseline (95% CI 0.1–1.6; p 2) Mean weight loss was 15 kg (95% CI 0.62–29.38; p 3) BMI was reduced by 4.9kg/m 2 (95% CI 1.1–8.7; p 14 patients withdrew from the study, 6 required premature EndoBarrier removal. Of these, only 2 patients presented with device related complications (device migration and gastrointestinal bleeding), the others withdrew due to unrelated medical adverse events. Conclusion The EndoBarrier appears to be a safe and effective treatment strategy in those who are overweight and have poor glycaemic control despite medical therapy, or in those who are eligible but decline bariatric surgery. Larger randomised controlled trials with longer follow-up periods post-explant of the device need to be performed to investigate the device’s effects on long term glycaemic control and weight. Reference Control C. f. D. & Prevention. Prevalence of overweight and obesity among adults with diagnosed diabetes-United States, 1988–1994 and 1999–2002. MMWR. Morbidity and mortality weekly report2004;53:1066. Disclosure of Interest None Declared

Objective: The endoscopic findings associated with Helicobacter pylori–naïve status, current infection or past infection are an area of ongoing interest. Previous studies have investigated parameters with a potential diagnostic value. The aim of this study was to perform meta-analysis of the available literature to validate the diagnostic accuracy of mucosal features proposed in the Kyoto classification. Data sources: The databases of MEDLINE and Embase, clinicalTrials.gov and the Cochrane Library were systematically searched for relevant studies from October 1999 to October 2019. Methods: A bivariate random effects model was used to produce pooled diagnostic accuracy calculations for each of the studied endoscopic findings. Diagnostic odds ratios and sensitivity and specificity characteristics were calculated to identify significant predictors of H pylori status. Results: Meta-analysis included 4380 patients in 15 studies. The most significant predictor of an H pylori-naïve status was a regular arrangement of collecting venules (diagnostic odds ratio 55.0, sensitivity 78.3%, specificity 93.8%). Predictors of active H pylori infection were mucosal oedema (18.1, 63.7%, 91.1%) and diffuse redness (14.4, 66.5%, 89.0%). Map-like redness had high specificity for previous H pylori eradication (99.0%), but poor specificity (13.0%). Conclusion: The regular arrangement of collecting venules, mucosal oedema, diffuse redness and map-like redness are important endoscopic findings for determining H pylori status. This meta-analysis provides a tentative basis for developing future endoscopic classification systems.

Introduction The colorectal cancer (CRC) microbiome is niche specific and individualised. Several putative driver organisms enriched on CRCs have been identified from human studies, but few data exist which properly account for important clinical variables in CRC. In this study, we used a meta-taxonomic approach to demonstrate how the CRC microbiome varies with disease stage, histological markers of prognosis and host molecular phenotypes. Method A prospective study was performed on patients undergoing colonoscopy and elective surgery for CRC at three hospitals in UK and Czech Republic. Tissue was sampled from tumours, adenomas, adjacent normal mucosa and mucosa from healthy colon controls. The V1-2 regions of the 16S rRNA gene were sequenced (Illumina MiSeq); data were processed in Mothur and analysed in Stamp and R. Species assignment was performed with NCBI BLAST for microbial genomes. False discovery rate p value correction accounted for multiple testing. Histological analysis and tumour molecular phenotyping were performed according to Royal College of Pathology guidelines. Results One hundred and ninety six patients were recruited: 158 CRC patients, 24 adenoma patients and 14 normal colon controls (median age 70; range 35–90). Tumours were staged as 6 T0, 4 T1, 23 T2, 97 T3, 27 T4; 99 N0, 40 N1, 27 N2; 6 M1. No significant differences were seen in diversity or taxonomy between the UK and Czech cohorts. Adenoma and healthy colon control samples were taxonomically indistinct. However, CRCs were characterised by reduced Shannon diversity (p Conclusion This large prospective analysis demonstrates that the CRC microbiome is stage-specific and appears to evolve with disease progression. We conclude that oral pathobionts which colonise advanced stage disease relate to markers of tumour prognosis, raising the possibility that they may be directly influencing tumour invasion. Disclosure of Interest None Declared

OBJECTIVES: Distinguishing between the inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) is important for both management and prognostic reasons. Discrimination using noninvasive techniques could be an adjunct to conventional diagnostics. Differences have been shown between the intestinal microbiota of CD and UC patients and controls; the gut bacteria influence specific urinary metabolites that are quantifiable using proton high-resolution nuclear magnetic resonance (NMR) spectroscopy. This study tested the hypothesis that such metabolites differ between IBD and control cohorts, and that using multivariate pattern-recognition analysis, the cohorts could be distinguished by urine NMR spectroscopy. METHODS: NMR spectra were acquired from urine samples of 206 Caucasian subjects (86 CD patients, 60 UC patients, and 60 healthy controls). Longitudinal samples were collected from 75 individuals. NMR resonances specific for metabolites influenced by the gut microbes were studied, including hippurate, formate, and 4-cresol sulfate. Multivariate analysis of all urinary metabolites involved principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA). RESULTS: Hippurate levels were lowest in CD patients and differed significantly between the three cohorts (P

Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management.To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD.The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls.A total of 3907 patients with IBD (Crohn's disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria.For women with IBD, there was a 1.87-fold increase in incidence of prematurity (37 weeks gestation; 95% CI 1.52 to 2.31; p0.001) compared with controls. The incidence of low birth weight (2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p0.001).The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.

The risk of cancer in patients with Crohn’s disease is not well defined. Using meta-analytical techniques, the present study was designed to quantify the risk of intestinal, extraintestinal, and hemopoietic malignancies in such patients. A literature search identified 34 studies of 60,122 patients with Crohn’s disease. The incidence and relative risk of cancer were calculated for patients with Crohn’s disease and compared with the baseline population of patients without Crohn’s disease. Overall pooled estimates, with 95 percent confidence intervals, were obtained, using a random-effects model. The relative risk of small bowel, colorectal, extraintestinal cancer, and lymphoma compared with the baseline population was 28.4 (95 percent confidence interval, 14.46–55.66), 2.4 (95 percent confidence interval, 1.56–4.36), 1.27 (95 percent confidence interval, 1.1–1.47), and 1.42 (95 percent confidence interval, 1.16–1.73), respectively. On subgroup analysis, patients with Crohn’s disease had an increased risk of colon cancer (relative risk, 2.59; 95 percent confidence interval, 1.54–4.36) but not of rectal cancer (relative risk, 1.46; 95 percent confidence interval, 0.8–2.55). There was significant association between the anatomic location of the diseased bowel and the risk of cancer in that segment. The risk of small bowel cancer and colorectal cancer was found to be higher in North America and the United Kingdom than in Scandinavian countries with no evidence of temporal changes in the cancer incidence. The present meta-analysis demonstrated an increased risk of small bowel, colon, extraintestinal cancers, and lymphoma in patients with Crohn’s disease. Patients with extensive colonic disease that has been present from a young age should be candidates for endoscopic surveillance; however, further data are required to evaluate the risk of neoplasia over time.

In a placebo-controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n = 16), super evening primrose oil (n = 19), or olive oil as placebo (n = 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red-cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three-fold and at 6 months by four-fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red-cell membrane concentrations of dihomogamma-linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell-membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.

Background and aims Celiac disease remains underdiagnosed at endoscopy. We aimed to assess the utility of I-Scan (virtual chromo-endoscopy) to improve sensitivity of endoscopy to detect markers of villous atrophy in this condition. Methods Patients from 2 UK hospitals were studied in 3 groups. Group 1: standard high definition, white light endoscopy (WLE); Group 2: WLE plus I-Scan; Group 3: non-high definition control group. The presence of endoscopic markers was recorded. At least 4 duodenal biopsies were taken from all patients. Serology was performed concurrently and observations were compared with histology. Results 758 patients (62% female, mean age 52) were recruited (Group 1: 230; Group 2: 228; Group 3: 300). 135 (17.8%) new diagnoses of coeliac disease were made (21 Group 1; 24 Group 2; 89 Group 3). The sensitivity for detection of endoscopic markers of villous atrophy was significantly higher in both Group 1 (85.7%, p = 0.0004) and Group 2 (75%, p = 0.005) compared to non-high definition controls (41.6%). There was no significant difference between high definition only and I-Scan groups (p = 0.47). In non-high definition endoscopy a missed diagnosis was associated with lesser degrees of villous atrophy (p = 0.019) and low tTG titre (p = 0.007). Conclusions High definition endoscopy with or without I-Scan increases the detection of celiac disease during routine endoscopy.

Background Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. Methods This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. Findings 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. Interpretation CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. Funding NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

The ability of erythrocytes to resist lipid peroxidation may be a useful marker of antioxidant status in alcoholic patients, in whom depletion of dietary antioxidants may combine with increased production of free radicals to produce liver damage. There are conflicting reports, however, on the resistance of erythrocytes from alcoholic patients to lipid peroxidation. This study examined the relation between the degree of alcohol induced liver disease and the resistance of erythrocytes to chemically induced lipid peroxidation, measuring lipid peroxidation as malondialdehyde production. Erythrocytes from alcoholic patients with Child's C cirrhosis had significantly increased resistance to lipid peroxidation compared with both controls (p < 0.001) and alcoholic patients with moderate liver disease (p < 0.001). There was no difference between alcoholic patients with moderate liver disease and controls. Increased resistance to free radical initiated lipid peroxidation in alcoholic patients is related to liver damage rather than to alcohol abuse alone. This could arise from changes in the lipid composition of the erythrocyte membranes resulting from abnormal liver function. Tests of antioxidant status based upon the resistance of erythrocytes to free radical stress in vitro may therefore be flawed when such changes in membrane lipid composition can occur.

Chronic alcohol consumption induces cytochrome P450IIE1, enabling habitual abusers to consume far greater quantities of alcohol than normal subjects. This pathway of metabolism leads to the production of free radical species, which cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats of equal male: female ratio (n = 24) were fed alcohol by gavage twice daily to achieve a dosage of 15 g/kg body weight. Mean peak blood alcohol concentrations of 186 mg% were produced in males and 156 mg% in females. The animals were allowed free access to standard laboratory chow and water. Control animals were pair-fed to the alcoholic group and fed isocaloric glucose by gavage. Groups of animals were killed between 9 and 11 am on consecutive mornings, after nocturnal feeding, since it has previously been shown that fasting rapidly depletes hepatic glutathione concentrations. Hepatic glutathione was measured by a spectrophotometric enzymatic recycling procedure. As a marker of lipid peroxidation hepatic malonaldehyde (MDA) was measured by high performance liquid chromatography. Hepatic MDA was increased in the alcoholic group (p < 0.001), as was total hepatic glutathione (p < 0.0001). Plasma concentrations of alpha-tocopherol were increased in the alcoholic group, but ascorbic acid and superoxide dismutase values were not affected. No sex differences were detected. The increased MDA production in the alcohol group is strong evidence that lipid peroxidation is a mechanism of alcoholic tissue damage. The rise in hepatic glutathione may be an adaptive response to free radical production that protects the rat against tissue damage.

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing throughout Asia. Since the 1950s, there has been substantial migration from South Asia (India, Pakistan, and Bangladesh) to the United Kingdom. The aim of this study was to define the clinical phenotype of IBD in UK South Asians living in North West London, and to compare the results with a white Northern European IBD cohort.The phenotypic details of 367 South Asian IBD patients (273 ulcerative colitis (UC) and 94 Crohn's disease (CD)), undergoing active follow-up in five North West London hospitals, were compared with those of 403 consecutively collected white Northern European IBD patients (188 UC and 215 CD).The phenotype of IBD differed significantly between the two populations. 63.0% of South Asian UC patients had extensive colitis compared with 42.5% of the Northern European cohort (P0.0001). Proctitis was uncommon in South Asian UC patients (9.9 vs. 26.1% in Northern European patients, P0.0001). In the South Asian CD cohort, disease location was predominantly colonic (46.8%). CD behavior differed significantly between the groups, with less penetrating disease compared with Northern Europeans (P=0.01) and a reduced need for surgery (P=0.003).The phenotype of IBD in South Asians living in North West London is significantly different from that of a white Northern European IBD cohort. Knowledge of ethnic variations in disease phenotype may help to identify key genetic, environmental, and behavioral factors contributing to the development of IBD.

In early hepatic fibrosis, increased amounts of type III collagen are deposited. Persistently high serum concentrations of aminoterminal type III procollagen propeptide (PIIIP) correlate with the activity of the fibrogenic process. Another index for the detection of fibrosis, the PGA index, combines the prothrombin time, gamma-glutamyl transpeptidase activity, and serum apolipoprotein A1 concentration (the latter falls with progressive fibrosis). We compared PIIIP measurements and PGA index in patients with various histological forms of alcoholic liver disease (104), primary biliary cirrhosis (38), and chronic B virus hepatitis (27), and in healthy age-matched controls (30). The ability of each test to identify correctly patients with fibrosis or cirrhosis was assessed with receiver operating curves. The PGA index was much higher in all groups of patients with alcoholic liver disease than in controls (p < 0.0001). PIIIP concentrations were also substantially higher than in controls (p < 0.05 for fatty liver, p < 0.0001 for all other groups), especially in the group with alcoholic hepatitis and cirrhosis. For the detection of cirrhosis the PGA was 91% sensitive and 81% specific and the PIIIP concentration was 94% sensitive and 81% specific. The two tests combined had 85% sensitivity, but 93% specificity. Among patients with primary biliary cirrhosis, both PGA index and PIIIP concentration correlated well with the severity of the disease, determined by the Mayo score (r = 0.72 and 0.66 respectively). The combined tests were 96% sensitive for the detection of fibrosis. All patients with chronic B virus hepatitis had raised PGA and PIIIP values in comparison with controls (p < 0.0001) but there were no differences between subgroups. Substantially raised PIIIP concentrations thus identify the subgroup of alcoholic patients with both hepatitis and cirrhosis. The combination of PGA index and PIIIP concentration may be useful for targeting treatment with antifibrotic drugs and to reduce the need for liver biopsy.

At low concentrations ethanol is metabolized largely by alcohol dehydrogenase to acetaldehyde, while at higher concentrations a microsomal ethanol oxidising system (MEOS) is involved, namely cytochrome P450 IIE1, which also probably generates free radical species. In hyperthyroidism hepatic glutathione stores are depleted and net superoxide anion production occurs. In contrast, in hypothyroidism hepatic glutathione may be increased and thus renders the liver less sensitive to alcohol generated free radical production. Steroid hormones inhibit lipid peroxidation. Sixty male Wistar rats either underwent thyroidectomy, adrenalectomy, or sham procedures. Twenty control animals were pair fed with thyroidectomized animals, whilst another twenty fed ad libitum. An intraperitoneal injection of alcohol (75 mmol/kg) was given 2.5 h prior to sacrifice to half the animals in each group, the remainder receiving saline. The total hepatic glutathione contents of the pair fed and the ad libitum groups were not different, but were significantly increased by thyroidectomy (p = < 0.001). This effect was significantly reduced by alcohol (p < 0.01). The sham procedures and dietary restrictions had no effect. The ethanol alone reduced total hepatic glutathione, but this only reached statistical significance in the thyroidectomized and sham-adrenalectomized groups. Hepatic malonaldehyde (MDA) levels were significantly reduced in the thyroidectomy group but alcohol had no effect on them. We conclude that hypothyroidism increased hepatic glutathione status, presumably by reducing radical production by enzyme systems, which would otherwise consume this important scavenger. Long term exposure to ethanol with induction of MEOS is probably required for it to generate toxic levels of free radical species.

We have determined the extent to which acute ethanol administration perturbs the synthesis of ventricular contractile and non-contractile proteins in vivo. Male Wistar rats were treated with a standard dose of ethanol (75 mmol kg-1 body weight; i.p.). Controls were treated with isovolumetric amounts of saline (0.15 mol l-1 NaCl). Two metabolic inhibitors of ethanol metabolism were also used namely 4-methylpyrazole (alcohol dehydrogenase inhibitor) and cyanamide (acetaldehyde dehydrogenase inhibitor) which in ethanol-dosed rats have been shown to either decrease or increase acetaldehyde formation, respectively. After 2.5 h, fractional rates of protein synthesis (i.e. the percentage of tissue protein renewed each day) were measured with a large (i.e. 'flooding') dose of L-[4-3H]phenylalanine (150 mumol (100 g)-1 body weight into a lateral vein). This dose of phenylalanine effectively floods all endogenous free amino acid pools so that the specific radioactivity of the free amino acid at the site of protein synthesis (i.e. the amino acyl tRNA) is reflected by the specific radioactivity of the free amino acid in acid-soluble portions of cardiac homogenates. The results showed that ethanol alone and ethanol plus 4-methylpyrazole decreased the fractional rates of mixed, myofibrillar (contractile) and sarcoplasmic (non-contractile) protein synthesis to the same extent (by approx. 25 per cent). Profound inhibition (i.e. 80 per cent) in the fractional rates of mixed, myofibrillar and sarcoplasmic protein synthesis occurred when cyanamide was used to increase acetaldehyde formation. There was also a significant decrease in cardiac DNA content. The results suggest that acute ethanol-induced cardiac injury in the rat may be mediated by both acetaldehyde and ethanol.

Several environmental and genetic factors have been implicated to date in the development of Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to provide a quantification of the risk of oral contraceptive pill (OCP) use in the etiology of inflammatory bowel disease.A literature search was performed to identify comparative studies reporting on the association of oral contraceptive use in the etiology of UC and CD between 1983 and 2007. A random-effect meta-analysis was used to compare the incidence of UC or CD between the patients exposed to the OCP and nonexposed patients. The results were adjusted for smoking.A total of 75,815 patients were reported on by 14 studies, with 36,797 exposed to OCP and 39,018 nonexposed women. The pooled relative risk (RR) for CD for women currently taking the OCP was 1.51 (95% confidence interval [CI] 1.17-1.96, P= 0.002), and 1.46 (95% CI 1.26-1.70, P0.001), adjusted for smoking. The RR for UC in women currently taking the OCP was 1.53 (95% CI 1.21-1.94, P= 0.001), and 1.28 (95% CI 1.06-1.54, P= 0.011), adjusted for smoking. The RR for CD increased with the length of exposure to OCP. Moreover, although the RR did not reduce once the OCP was stopped, it was no longer significant once the OCP was stopped (CI contains 1), both for CD and for UC.This study provides evidence of an association between the use of oral contraceptive agents and development of IBD, in particular CD. The study also suggests that the risk for patients who stop using the OCP reverts to that of the nonexposed population.

Fecal calprotectin (FC) is a relatively new marker of intraluminal intestinal inflammation. Using meta-analytical techniques, the study aimed to evaluate the diagnostic precision of FC for inflammatory bowel disease (IBD) and colorectal cancer (CRC) in adults and children.Quantitative meta-analysis was performed on prospective studies, comparing FC levels against the histological diagnosis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for each study. Summary receiver-operating characteristic (sROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated.Thirty studies of 5,983 patients were included. FC levels in patients with IBD were higher by 219.2 micrograms per gram (microg/g) compared with normal patients (P0.001). sROC curve analysis showed a sensitivity of 0.95 (95% CI 0.93-0.97), specificity of 0.91 (95% CI 0.86-0.91), and an area under the curve (AUC) of 0.95 for the diagnosis of IBD. Patients with colorectal neoplasia had nonsignificantly higher FC levels by 132.2 microg/g compared with noncancer controls (P= 0.18). Sensitivity and specificity of FC for the diagnosis of CRC were 0.36 and 0.71, respectively, with an AUC of 0.66. The diagnostic precision of FC for IBD was higher in children than adults with better accuracy at a cutoff level of 100 microg/g versus 50 microg/g. Sensitivity analysis and metaregression analysis did not significantly alter the results.FC cannot be recommended as a screening test for CRC in the general population. FC appeared to offer a good diagnostic precision in distinguishing IBD from non-IBD diagnoses, with higher precision at a cutoff of 100 microg/g.

Background & Aims Symptoms suggestive of colorectal cancer may originate outside the colorectum. Computed tomographic colonography (CTC) is used to examine the colorectum and abdominopelvic organs simultaneously. We performed a prospective randomized controlled trial to quantify the frequency, nature, and consequences of extracolonic findings. Methods We studied 5384 patients from 21 UK National Health Service hospitals referred by their family doctor for the investigation of colorectal cancer symptoms from March 2004 through December 2007. The patients were assigned randomly to groups that received the requested test (barium enema or colonoscopy, n = 3574) or CTC (n = 1810). We determined the frequency and nature of extracolonic findings, subsequent investigations, ultimate diagnosis, and extracolonic cancer diagnoses 1 and 3 years after testing patients without colorectal cancer. Results Extracolonic pathologies were detected in 959 patients by CTC (58.7%), in 42 patients by barium enema analysis (1.9%), and in no patients by colonoscopy. Extracolonic findings were investigated in 142 patients (14.2%) and a diagnosis was made for 126 patients (88.1%). Symptoms were explained by extracolonic findings in 4 patients analyzed by barium enema (0.2%) and in 33 patients analyzed by CTC (2.8%). CTC identified 72 extracolonic neoplasms, however, barium enema analysis found only 3 (colonoscopy found none). Overall, CTC diagnosed extracolonic neoplasms in 72 of 1634 patients (4.4%); 26 of these were malignant (1.6%). There were significantly more extracolonic malignancies detected than expected 1 year after examination, but these did not differ between patients evaluated by CTC (22.2/1000 person-years), barium enema (26.5/1000 person-years; P = .43), or colonoscopy (32.0/1000 person-years; P = .88). Conclusions More than half of the patients with symptoms of colorectal cancer are found to have extracolonic pathologies by CTC analysis. However, the proportion of patients found to have extracolonic malignancies after 1 year of CTC examination is not significantly greater than after barium enema or colonoscopy examinations. International Standard Randomised Controlled Trials no: 95152621.isrctn.com.

Introduction Coeliac disease (CD) remains underdiagnosed. Many patients with CD have undergone a previous endoscopy where the opportunity to make a diagnosis was missed. Clinicians may rely on endoscopic markers of CD to guide biopsy but they lack sensitivity. A routine duodenal biopsy approach may solve this problem but it is expensive. Methods to improve the detection of CD at endoscopy to guide biopsy would seem advantageous. I-Scan, a digital enhancement technique, has shown promising results. However, only one, single centre study has been performed. This was an uncontrolled, unblinded trial in high prevalence population (35% CD). We aimed to assess the utility of I-Scan in a lower prevalence population in a randomised controlled trial Method Patients from 2 UK hospitals (Royal Hallamshire Hospital, Sheffield and St. Mary’s Hospital, London) were randomised into 2 groups: Group 1 standard HD white light endoscopy (WLE) and Group 2 WLE plus I-Scan. Patients were compared to a standard non-HD WLE control group, Group 3. All patients received at least 4 duodenal biopsies. Coeliac serology was performed concurrently. The presence of endoscopic markers of CD, scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vascularity was noted and compared to VA on histology as the gold standard Results 700 patients (63% female, mean age 51.7) were recruited (201 into Group 1, 199 in Group 2 and 300 into Group 3). In total 130 (18.5%) new diagnoses of CD were made (19 in Group 1, 22 in Group 2 and 89 in Group 3). In new CD cases, endoscopic markers of CD were seen in 80.5% in the HD groups compared to 41.6% in Group 3 (p Conclusion HD endoscopy significantly increases the detection of the endoscopic markers of CD (p Disclosure of interest None Declared.

The incidence of adenocarcinoma of the oesophagus is increasing; this type of carcinoma commonly arises on Barrett's oesophagus. We report a case of in-situ adenocarcinoma of the lower oesophagus arising in submucosal oesophageal mucous glands without intestinal metaplasia. We describe the histological findings, discuss the difficulties of differentiating this from invasive disease and review the current literature regarding this rare condition.

Although hepatobiliary involvement is common in the acquired immunodeficiency syndrome, it infrequently leads to biliary tract abnormalities. We describe a 39-year-old man with human immunodeficiency virus infection and no previous acquired immunodefiency syndrome-defining illnesses, who presented with malaise, right upper quandrant pain, lymphadenopathy and cholestasis. An endoscopic retrograde cholangiopancreatography demonstrated sclerosing cholangitis due to disseminated B-cell non-Hodgkin's lymphoma. Following chemotherapy, his symptoms and signs rapidly improved, so that 1 month later his endoscopic retrograde cholangiopancreatography has returned entirely to normal.

Omeprazole causes irreversible inhibition of the hydrogen/potassium adenosine triphosphatase enzyme, leading to a marked reduction in both acid secretion and volume of gastric juice. Reported side-effects include nausea, vomiting, diarrhoea, constipation, and headache. We report the development of dry mouth during omeprazole therapy.We have identified six patients taking omeprazole for more than 6 weeks who complained of a dry mouth. Salivary production was measured as whole salivary flow produced over a 10-min period spat into a collecting vessel and as 5% citric acid-stimulated parotid salivary flow collected with a Lashley cup device placed over the parotid duct. Flow rates were evaluated both during and after cessation of treatment. Saliva produced was then cultured for microbes.Four of the six had subnormal parotid or whole salivary flow rates on treatment that recovered after stopping treatment. The increase after treatment was marked in four. Significant amounts of Candida albicans grew from the saliva of the three patients with the lowest salivary flows; one saliva also grew Staphylococcus aureus.Salivary flow is reduced in some patients treated with omeprazole, returning to normal after cessation of treatment. This reduction may predispose to opportunistic infection, particularly in the edentulous.

Introduction Colonoscopy is frequently performed in patients presenting with melaena who have a negative upper gastrointestinal endoscopy (UGIE). Published literature suggests a diagnostic yield of 8%–30%, the most common pathologies being colonic angiodysplasia and right-sided tumours. However these conditions often give rise to occult haemorrhage and a microcytic profile before patients present with overt bleeding. In patients presenting de novo with melaena a raised urea is known to be predictive of upper GI haemorrhage before any endoscopic assessment. Our aim was to examine the value of colonoscopy in the subgroup of patients with a negative UGIE, and to assess whether the absence of a raised blood urea and/or the presence of a microcytic erythrocyte profile at presentation are predictors of positive colonoscopy. Methods Our reporting software was interrogated for the interval November 2007–October 2011. All cases of colonoscopy where melaena was the main indication, and which were preceded by a negative UGIE were analysed. In addition, we collected data on the admission blood urea and mean corpuscular volume (MCV). Patients for whom altered/fresh rectal bleeding were included in the indications in addition to melaena were excluded. Results 724 patients had a total of 829 endoscopic evaluations of melena, and of these 62 patients (53% female) with a median age of 69 year (range 27–91) met our inclusion criteria. 6 of 62 (9.6%) had a cause for the melena identified on colonoscopy: cecal angiodysplasia in 2/6, right-sided malignancies in 2/6 and right-sided diverticular bleeds in 2/6. The admission urea was not significantly lower in patients with a positive colonoscopy (median 11.5 mmol/l, range 5.1–14.7) compared to those with a negative colonoscopy (median 7.2 mmol/l, range 1.4–33.6) (p=0.43). Admission MCV however was significantly lower in patients with a colonic haemorrhage (median 77 fL, range 64–89) compared to patients with a negative colonoscopy (median 90 fL, range 66–116) (p=0.012), with 3/6 (50%) having a low MCV compared to 5/56 (8.9%) of those with a negative colonoscopy (normal = 84–99 fL). Conclusion The diagnostic yield of colonoscopy in patients with melaena and a non-contributory UGIE in our centre was low (9.6%). A normal/low blood urea on admission did not predict a positive diagnosis for the haemorrhage at colonoscopy in our cohort. However, patients with a colonic source of bleeding had a significantly lower MCV, suggesting a chronic natural history for such right sided colonic haemorrhages. Competing interests None declared. References 1. Tedesco FJ. Gastrointest Endosc 1981. 2. Ibach MB . Dig Dis Sci 1995. 3. Blatchford O . Lancet 2000.

Introduction The Global Rating Scale (GRS) and Joint Advisory Group on GI Endoscopy (JAG) auditable outcome standards have been used to improve quality and define minimum standards for colonoscopy across the UK. 1 JAG also provides a clear competency based framework to assess trainee performance; however, there is reluctance in some units to allow independent senior registrars, who have passed JAG assessment, to practise independently. At our teaching centre we encourage appropriately trained registrars to perform their own lists. Supervision is available if needed and departmental protocols define limits of therapy to be undertaken independently (eg, large polypectomies). Attendance at training lists to continue development is also actively encouraged. Our aim was to evaluate whether this provided a quality of service comparable to national standards. Methods We used data collected retrospectively from endoscopy reporting software (Ascribe-Scorpio) on the caecal intubation rate, polyp detection rate, sedation usage and complication rate, to evaluate the performance of senior gastroenterology trainees between 2007 and 2011, against the JAG auditable outcomes for colonoscopy. Results Over a 4-year period, 17 senior gastroenterology registrars performed a total of 2917 colonoscopies. 2221 (76.1%) procedures were unsupervised and 696 (23.9%) were supervised. An uncorrected caecal intubation rate of 94.9% was achieved during unsupervised procedures, 96.6% with supervision (p=0.93, X 2 ). Polyp (all type) detection rate was 30%. Average sedation dose for patients aged >70 years, was pethidine 30 mg and midazolam 1.96 mg; aged Conclusion Our findings show that given appropriate training and support, independently practising senior UK gastroenterology registrars contribute significantly to service delivery, providing high quality colonoscopy, meeting JAG auditable outcome standards. Competing interests None declared. Reference 1. Roland V . BSG Quality and Safety Indicators for Endoscopy (JAG) . 2007.

To date there have been no published studies which have reliably compared the general protein synthesis rates of the three major salivary glands either between themselves or with reference to other exocrine tissues. The main shortcoming of previous work has been the failure of the experimentalists to recognize the need to define the specific radioactivity of the precursor pool at the site of protein synthesis i.e. aminoacyl-tRNA [l]. By flooding the intracellular pool of phenylalanine with tritiated amino-add we have accurately measured the fractional rates of protein synthesis in the salivary glands and compared data with that from liver in this study. Mde wstar rats weighing approximately 150 g were purchased from B. and K. Universal Ltd (Hull, UK) and housed in a temperature controlled. humidified animal houseon a 12 hour light: 12 hour dark cycle. The rats were maintained on a commercial peileted chow and water ad libitum. On attaining 200-220 g body weight the rats were divided into 3 groups. Food, but not water, was withdrawn from al the animals a14 pm the day before the experiment. On the day of the experimentation rats were either injected i.p. with 10 ml/ kg ethanol (Ethanol-treated Group) or saline (Control Group) or allowed to refeed (Refed Group) in a darkened room.Two and a half hours later the rates of protein synthesis were measured by the 'flooding dose' technique as described by Garlidc et d 121. At 2 min and 10 min afler an i.v. dose of L-[4 3H]-phenylalanine the rats were decapitated and salivary glands and livers rapidly dissected out and plunged into liquid nitrogen. Processing of tissues for phenylalanine specific radioactivities was as described previously [2] and modified later to include the addition of protease inhibitors during the initial processing steps [3]. The fractional rate of protein synthesis, k, , was defined as the percentage of the protein pool renewed each day, and is calculated from the formula

Introduction Gastro-oesophageal reflux disease (GORD) is a common condition with a prevalence of about 20% in Western countries.1 In some patients GORD symptoms are associated with oesophageal mucosal injury, yet in others there is no macroscopic evidence of erosive disease. We sought to assess the natural history of patients with GORD symptoms with respect to the persistence or emergence of erosive disease over time, as well as the development of complications, including oesophageal strictures, Barrett9s epithelium (BE) and oesophageal cancer. Methods We analysed a database of over 50 000 oesophagogastroduodenoscopies (OGDs) performed at our unit between 1985 and 2006. From this database, we identified all patients undergoing OGD for GORD symptoms, who had subsequently undergone at least one further OGD at least 6 months after the index OGD. At the index OGD patients were categorised as having erosive oesophagitis (EE) or non-erosive reflux disease (NERD) based upon the presence or absence of mucosal injury. Changes or persistence of the index phenotype (EE or NERD) during follow-up OGDs were defined, as were the development of strictures, BE or oesophageal cancer. Results We identified 394 patients undergoing at least two OGDs for GORD symptoms. EE was present at the index endoscopy in 38% of patients (50% male, mean age 54 years) and NERD in 62% (53% male, mean age 54 years). Mean follow-up time was 4.8 years for EE and 5.2 years in NERD patients. Results of follow-up OGDs are shown in Abstract 062. Conclusion Patients with symptomatic GORD who undergo repeat OGD, even over extended time periods (mean follow-up 5 years) have a stable phenotype with respect to the persistence of EE or NERD, although NERD is significantly more likely to persist as a phenotype than EE. Patients with EE are significantly more prone to GORD complications.