Benjamin J. Colleypriest

Does rectal diclofenac reduce post-ERCP pancreatitis? A district general hospital experience

Introduction There is controversy in the literature recently regarding the efficacy of rectal non-steroidal anti-inflammatory drugs (NSAID) to prevent post-ERCP pancreatitis (PEP). The aim of this study was to compare the incidence of PEP in three distinct groups of patients at the Royal United Hospital, Bath: no use of rectal diclofenac, selective use and blanket use without contraindication. Method Readmission data, blood results, radiology reports and discharge summaries were used to identify patients with PEP from August 2010 to December 2015. The administration of rectal diclofenac postprocedure was recorded from the endoscopy reporting system. Results 1318 endoscopic retrograde cholangiopancreatographies (ERCP) were performed by four endoscopists during the study period with 66 (5.0%) cases of pancreatitis. 445 ERCPs were performed prior to the introduction of NSAID use during which time, with an incidence of 35 (7.9%) episodes of PEP. During the selective period of NSAID use (high-risk patients) 539 ERCPs were performed and 72 (13.4%) patients received NSAIDs. 17 (3.2%) developed PEP. 334 ERCPs were performed when NSAIDs were given to all patients without contraindication. 289 (86.5%) of patients received rectal diclofenac and 13 (3.9%) developed pancreatitis. There is a statistically significant decrease in PEP comparing the groups of patients receiving NSAIDs selectively (p=0.0009) or routinely (p=0.0172) when compared with none. There is no difference between the selective and routine group (p=0.571). Conclusion Our data demonstrate that the introduction of a selective or routine use of NSAIDs for PEP in a District General Hospital (DGH) significantly decreases the risk of pancreatitis (risk reduction 43.7%).

PTU-027 Prophylaxis of Post ERCP Pancreatitis in the UK. have the Esge Created Consensus?

Introduction Post ERCP pancreatitis (PEP) occurs in 3.5% of unselected cases 10% of which are severe. PEP is significantly higher in certain patient groups, for example patients with Sphincter of Oddi dysfunction or with a pre-cut sphincterotomy. The 2010 European Society for Gastrointestinal Endoscopy (ESGE) guidelines on PEP prophylaxis recommend routine use of rectal NSAIDs and the insertion of pancreatic stents (PS) in high risk patients1. This study surveys UK practise of PEP prophylaxis in view of ESGE guidelines. Methods 220 ERCPists were invited to complete an online survey concerning their awareness of ESGE guidelines, patient selection for PEP, and use of rectal NSAIDs and insertion of PS. 67 responses from 53 UK hospitals were received (response rate = 30.4%). Results 79% of respondents were aware of ESGE guidelines, of which 47% had subsequently changed their practise. Only 9% of respondents used PEP for all patients as recommended by the ESGE. The majority (66%) used PEP in selected patients, whilst 25% never used PEP. Choice of PEP is demonstrated in the below table. Concerns relating to ESGE guidelines were expressed in a free text comments sections Abstract PTU-027 Table Form of PEP used by survey respondents Rectal NSAID 16.4% Pancreatic Stent 23.8% Both (NSAID/PS) 34.3% Never use PEP 25.4% Conclusion If this study is representative of wider practise it would suggest there is widespread variation in the administration of PEP in the UK. Only a minority of respondents were adherent to ESGE guidelines, although the majority had considered them. A significant number of departments were in the process of developing separate local guidelines. Stenting otherwise uncannulated pancreatic ducts and NSAID nephrotoxicity were commonly raised reasons for not adopting ESGE guidelines. Given there are currently no UK guidelines for PEP, this may be an opportunistic time for collaboration. A coordinated strategy of national guidelines or research may contribute to creating a consensus in practise across the UK and ultimately reduce the incidence of PEP. Disclosure of Interest None Declared Reference European Society of Gastrointestinal Endoscopy (ESGE) Guideline: Prophylaxis of post-ERCP pancreatitis. Dumonceau, J.M., Andriulli, A., Deviere, J., Mariani, A., Rigaux, J., Baron, T.H. & Testoni, P.A. Endoscopy 2010; 42: 503–515.

PWE-098 Is methane testing a useful adjunct to hydrogen breath testing?

Introduction Hydrogen breath testing (BT) is a useful non-invasive test for diagnosing small intestinal bacterial overgrowth (SIBO) and carbohydrate maldigestion. In a proportion of patients methane is produced at the expense of hydrogen leading to false negative results. This retrospective study evaluated the diagnostic yield of methane testing in addition to hydrogen. Methods Electronic records were interrogated for the results of all glucose and lactose BT performed for SIBO and lactose intolerance respectively between 22/05/2015 and 03/01/2018 using the GastroCH4ECK® machine, Bedfont® Scientific Ltd. Results During the study interval 569 patients (age range 16–86 y, 66% female) were referred for BT with glucose (48.5%) or lactose challenge (51.5%). Hydrogen and methane production was positive in 10.1% (71.4% female) and 4.7% (61.5% female) of patients undergoing glucose BT for SIBO. Two patients were hydrogen/methane co-producers. Hence 28.2% of patients with SIBO solely produced methane and would have been missed with only hydrogen assessment. Hydrogen and methane production was positive in 25.6% (80.0% female) and 5.1% (68% female) of patients undergoing lactose BT for lactose malabsorption respectively. Two patients were hydrogen/methane co-producers. 14.8% of patients with positive lactose BT only produced methane and would have been missed with hydrogen mono-testing. Overall 18.9% of all patients with a positive BT (n=24, 75% female) were sole methane-producers that would have been misdiagnosed if hydrogen mono-testing was conducted. Conclusions In this study we have demonstrated that combined hydrogen/methane BT helps optimise diagnosis in patients with suspected SIBO or lactose intolerance. An extra 28.2% of positive breath tests for patients with SIBO and 14.8% for lactose malabsorption were identified with the addition of methane to hydrogen testing. Interestingly the proportion of patients producing methane was higher in SIBO than lactose malabsorption. Compared with the overall study population, a greater proportion of males tested positive for methane on glucose challenge. In comparison a greater proportion of females were methane positive on lactose BT. Currently only the minority of centres offer methane testing and our results suggest that a significant number of patients with possible SIBO or lactose malabsorption may be missed. Methane BT should be considered particularly for male patients with suspected SIBO.

PTH-019 Does Rectal Diclofenac Reduce Post ERCP Pancreatitis in The UK?

Introduction Post ERCP pancreatitis(PEP) occurs in up to 10% of unselected cases and carries significant morbidity. PEP is significantly higher in certain patient groups, for example females, young age, Sphincter of Oddi dysfunction, previous pancreatitis and following pancreatic duct cannulation. There is a growing body of evidence that NSAIDS should be used in PEP prophylaxis but use is still uncommon in the UK. The 2010 European Society for Gastrointestinal Endoscopy Guidelines on PEP recommends routine use of rectal NSAIDs in all patients. There is only one published RCT from the UK demonstrating the efficacy of NSAIDS in reducing PEP. Rectal diclofenac was introduced into ERCP practice at the RUH in two phases. Firstly, a selective use in patients determined to be at high risk as determined by criteria above. Secondly diclofenac was used routinely in all patients without contraindication. Methods A retrospective analysis of 5 years ERCP data was performed using readmission data, blood results, radiology reports and discharge summaries to identify patients with PEP from August 2010 – December 2015. The administration of rectal diclofenac post procedure was recorded from the endoscopy reporting system. Fisher’s exact test was used to statistically analyse categorical data. Results 1318 ERCPs were performed by 4 endoscopists during the study period with 66 (5.0%) cases of pancreatitis. 445 ERCPs were performed prior to the introduction of NSAID use during which time there were 35 (7.9%) episodes of PEP. During the selective period of NSAID use (only used if patient deemed high risk by endoscopist) 539 ERCPs were performed and 72 (13.4%) patients received NSAIDS. 17 (3.2%) developed PEP. 334 ERCPs were performed when NSAIDS were given to all patients without contraindication. 289 (86.5%) of patients received rectal diclofenac and 13 (3.9%) developed pancreatitis. There is a statistically significant decrease in PEP comparing the groups of patients receiving NSAIDS selectively (p = 0.0009) or routinely (p = 0.0172) when compared with none. There is no difference between the selective and routine group (p = 0.571). Conclusion The use of rectal diclofenac post ERCP decreases the rate of PEP when used in a selective or routine protocol. Despite a growing body of evidence for NSAIDS use routine administration is used by the minority of endoscopists in the UK. The evidence for use of NSAIDS in PEP is heterogeneous a number of factors including diagnostic criteria for pancreatitis, type and route of NSAID and selective high risk or routine use. We believe that this heterogeneity and lack of UK evidence accounts for the slow uptake of NSAIDS for PEP. Our data demonstrates that the introduction of a selective or routine use of NSAIDS for PEP in a DGH significantly decreases the risk of pancreatitis (RR 43.7%). Disclosure of Interest None Declared

Sa1368 Generation of a Human Oesophageal Tissue Culture Model From Forceps Biopsies

Introduction Barrett’s oesophagus is the condition whereby the normal stratified squamous epithelium at the lower oesophagus is replaced with simple columnar epithelium in the context of gastro-oesophageal reflux disease. This increases the risk of oesophageal adenocarcinoma (OA) ten-fold, and the majority of people diagnosed with OA do not survive for 12 months. Our understanding of the molecular and cellular mechanisms underlying Barrett’s oesophagus is hindered due to lack of at a suitable model. We set out to develop a model from explant tissue biopsies of adult human oesophagus, as opposed to murine models (mice have a keratinised oesophageal epithelium and do not get Barrett’s oesophagus) or the use of cell lines (which do not recapitulate the normal tissue). Method We devised a study protocol and secured ethical approval (REC reference number 13/YH/0197) to obtain forceps biopsy specimens from consenting adults attending for routine diagnostic gastroscopies at the Royal United Hospital Bath. Specimens were then transported to the University of Bath where we have tested multiple culture conditions. These include choice of culture media, substrate (eg glass, plastic – coated or uncoated, semi-permeable membrane at air/liquid interface), cell adhesion factors (eg collagen I, collagen IV, fibronectin, Matrigel®), choice of tissue preparation (enzyme treatment with dispase in the absence or presence of trypsin, dissection with scissors or minced with a blade), plating density, media volume and use of a cell feeder layer. Results We have recruited 42 participants to date and attempted tissue culture on 36 of these. (Biopsies from 6 patients have been processed for RNA analysis.) Over time we have gradually optimised culture conditions. Of the most recent 6 participants, 5 have cultured successfully with cell survival for at least 14 days. Explant colony growth had been particularly vigorous (>12 mm) when plated on Matrigel® and a feeder layer cell line (mitomycin C-inactivated mouse embryonic fibroblast (iMEF) cell line 3T3-Swiss albino, ATCC® CCL-92™) on plastic coverslips. Explants have also adhered and cultured successfully on collagen IV-coated (sc-29010, Santa Cruz Biotech) plastic coverslips without a feeder layer. Explant colonies were fixed/permeabalised before immunofluorescent staining was performed for cytokeratin 14 (K14), smooth muscle actin (SMA), p63, E-cadherin and SLUG antigens. iMEFs are clearly delineated with SMA staining and the explant outgrowths are positive for K14, p63, E-cadherin and SLUG. Conclusion It is possible to culture adult human oesophageal tissue in vitro from standard pinch-biopsy forceps specimens at gastroscopy and we are in the final stages of optimising conditions, confirming characterisation by repeating experiments and devising a protocol. Disclosure of interest None Declared.

PTU-156 Hepatocyte Nuclear Factor 4 Alpha (hnf4a) Is Demonstrated In Barrett’s Metaplasia, But Not In Normal Human Oesophagus

Introduction Barrett’s metaplasia (BM) is the main risk factor for oesophageal adenocarcinoma, a cancer which carries a mortality of >50% at 12 months. Refluxate containing gastric and bile acids seems to be causative for inflammation at the lower oesophagus, but it is not known how this induces replacement of stratified squamous epithelium (SSQE) with columnar epithelium at a molecular level.There is likely to be a progenitor cell population replacing denuded epithelium, although the origin of these cells has not been proven. Genes that play a role in gut tissue patterning during embryogenesis have received attention. One such ‘master switch’ our laboratory is investigating encodes the hepatocyte nuclear factor 4 alpha (HNF4α) transcription factor. Methods We optimised an immunohistochemistry protocol for demonstrating HFN4α on formalin-fixed paraffin-embedded slides of human tissue. This protocol was applied to forceps biopsy specimens of normal oesophagus, gastro-oesophageal junction (GOJ), stomach, ileum, colon and BM (UK REC reference: 13/YH/0197). Tissues were examined from at least 3 different patients per anatomical site. Results In healthy tissues, nuclear HNF4α positive immunostaining was demonstrated in stomach, ileum and colonic epithelium, but not in normal SSQE in the oesophagus. At the GOJ, there was clear delineation between HNF4α positive nuclei in the columnar gastric cardia mucosa, and negative HNF4α staining of SSQE. In contrast, the columnar epithelial nuclei in BM were consistently positive. Abstract PTU-156 Figure 1 Conclusion HNF4α transcription factor is demonstrable in BM, but not SSQE. We are not aware that this HNF4α gastrointestinal distribution has been previously published. HNF4α is likely to be a key transcription factor in the pathogenesis of BM. Previous work in our laboratory with a mouse explant tissue culture model has shown that another candidate transcription factor responsible for BM (Cdx2) was insufficient to induce an intestinal phenotype, whereas HNF4α induced villin, K18, trefoil factor 3 and mucin 5AC. We propose a 2-hit hypothesis for the development of BM: induction of HNF4α (which initially converts the oesophageal SSQE to columnar epithelium) and Cdx2 (which causes intestinalisation of the columnar epithelium). Demonstration of HNF4α in BM but not SSQE is supportive of this theory. Disclosure of Interest None Declared.

PTU-032 Would you like a Trainee to Perform your Colonoscopy?

Introduction Quality assurance in colonoscopy is underpinned by a framework of nationally agreed quality indicators and auditable outcomes to maintain minimum standards. High quality colonoscopy training is a vital part of ensuring these standards and is important that quality is assured during training lists so these patients receive the same standard of care. It is understandable that patients may be concerned if a trainee is performing their procedure and vital that evidence based consent is obtained to address concerns. This study aimed to compare quality delivered on training and non-training colonoscopy lists in order to inform patients. Methods A 12 month period (Jan 2012 to Jan 2013) of data from the endoscopy reporting system was retrospectively analysed. Caecal intubation rates, procedure duration, endoscopist reported pain score, sedation usage and polyp detection rates were analysed for seven training endoscopists. Data was compared for seven training endoscopists between training and non-training lists. Statistical analyses used χ testing and linear regression in Stata 11. Results Complete data were available for 422 training lists and 936 Service colonoscopies (300 BCSP) Mean(SD) age was similar in service and trainee groups; 61.0(12.3) and 60.6(14.2) years respectively, p = 0.657. There was no difference in caecal intubation rates between groups (trainees 93.8% and service 94.4%, p-0.657). Polyp detection was similar amongst trainees 119(28.2%) as non-BCSP service procedures 186(29.3%), p = 0.71. Midazolam was used less frequently during service lists(737 [78.7%]) vs (367 [87.0%]) (p < 0.001). A statistically but not clinically significantly larger average doses was used 2.3 (0.7) and 2.2(0.7) mg, p = 0.001 during service lists. Interestingly mean doses of fentanyl were similar 59.5(23.2) and 57.7(22.2) mcg, p = 0.46, but lower mean doses of pethidine 36.8 (12.5) and 43.2 (12.2) mg, p = 0.001 were used during training lists. Endoscopist reported pain scores were greater on service lists, with 223 (52.8%) trainees and 332 (35.5%) trainers reporting no symptoms, 431 (46.1%) and 143 (33.9%) mild, 149 (15.9%) and 53 (12.6%) moderate, and 24 (2.6%) and 3 (0.7%) severe symptoms respectively (p < 0.001). As expected, procedure duration was longer on training procedures; 30.6 (12.3) vs. 46.6 (14.2) minutes, p < 0.001. Conclusion In conclusion, colonoscopy is delivered at a similar high quality when performed by trainees compared with trained endoscopists. Although trainees took longer, caecal intubation rates and polyp detection were similar to those of trained endoscopists. Interestingly, patient discomfort reported by endocopist was lower during training colonoscopies and could possibly relate to longer procedure time. These conclusions will be used for patient information and monitored as quality assurance. Disclosure of Interest None Declared