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Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis. Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research. Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field. The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis. Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.

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 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.

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.

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.

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.