regulator, phospholipase C-gamma1 (PLC γ 1), had a marked impact on cellular migration and adhesion of pancreatic cancer cells, key functions observed with MLN64 in cancer cells. Conclusions MLN64/StARD3, one of the key regulators of cancer cells, has an aberrant expression in human pancreatic cancer which is linked to the clinical outcome. With its role in cancer cells and discovery of inhibitory means to MLN64/ StARD3, the molecule presents a good target for therapeutic considerations in pancreatic cancer.

Abstract Background Due to the Covid-19 pandemic there has been unprecedented pressure on endoscopy services. Faecal immunochemical tests (FIT) are designed to detect small amounts of blood in stool samples using antibodies specific to human haemoglobin. This test is highly specific and sensitive for colorectal cancer (CRC) and has been shown to detect mucosal healing in ulcerative colitis(1). FIT was utilised at our hospital to prioritise urgency of colonoscopy referrals. We aimed to determine whether this caused a delay in the diagnosis of inflammatory bowel disease (IBD) in this cohort. Methods Consecutive colonoscopy referrals (urgent, semi-urgent and routine) from September 2020 to April 2021 were prioritised by FIT result. Any patient with a FIT>/=10mcg were deemed category 1 (colonoscopy within 30 days) and FIT<10mcg were deemed category 2 (colonoscopy within 90 days). Demographic data were collected along with procedure result and histology. Results One hundred and twelve patients (52% female) had a FIT test and a subsequent diagnostic test (96 had a colonoscopy, 12 had a flexible sigmoidoscopy, 3 had a CT colonography and 1 patient declined a colonoscopy but later had a CT abdomen and pelvis. Patients who did not go on to have a diagnostic test were excluded. Sixty four patients had a FIT<10 (mean age 61), 35 had a FIT 10–400 (mean age 64) and 13 patients had a FIT>400 (mean age 52). Median number of days from FIT result to diagnostic test was 56 (range -9–163) in the group with FIT<10, 44 (-28–93) in the group with FIT 10–400 and 44 (10–89) in the group with FIT>400. There were no cancer diagnoses in the FIT<10 group. No patients in this group had colonic inflammation. Of the patients with FIT 10–400; 4 had colonic or ileocaecal valve inflammation, 12 had polyps and 2 had a CRC. Of the patients with inflammation one had mild right sided inflammation (FIT 228), one had colitis (FIT 367), one had proctitis (FIT 87) and one had ileitis of the ileocaecal valve (FIT 119). Of the patients with FIT>400; 4/13 had a colorectal malignancy (one of which was a polyp cancer), 4/13 had colonic polyps and 3/13 had active colonic inflammation. Of the patients with inflammation one had right sided inflammation, likely crohns disease, one had severely active ulcerative colitis (UC) and one had mild proctitis, likely UC. Conclusion In this cohort there were no CRC or IBD diagnoses in the patients with FIT<10. Therefore there was no delay in investigation of any patient subsequently diagnosed with IBD. This suggests that FIT may be safely used to stratify the priority of referrals for colonoscopy in symptomatic patients. Further work is required to confirm this.

Introduction The management of chronic pancreatitis is complex. In Manchester, a multi-disciplinary approach to care has been in place since 1999. Patients are assessed by specialist pancreatologists, surgeons, and dietitians with a consensus approach toward endoscopic intervention as a first step. This study reports the outcome of surgery in patients managed by this approach. Methods A retrospective database searches to identify all patients having pancreatic surgery for chronic pancreatitis (CP) in the Manchester Royal Infirmary) over a 20-year period from 1999-2019. Patients were excluded from the study if final histology revealed cancer. Results 20 patients were identified; mean (range) age in years 49 (18-80). Sixteen (80%) were male. Alcohol was the cause in 10, 3 were idiopathic with the remainder including genetic, auto-immune, and pancreas divisum. Nineteen had undergone prior endoscopic intervention. Ten patients underwent Whipple pancreatoduodenectomy, nine underwent longitudinal pancreatojejunostomy with partial head resection and there was one distal pancreatectomy. Hospital stay ranged from 6 to 32 days with a mean of 15 days. There was no operative mortality. Pancreatic exocrine insufficiency was documented in 60% before surgery and in 85% after. Diabetes was present in 55% before surgery and in 65% after. Conclusion Multidisciplinary assessment is the key to the selection of patients to undergo surgery for chronic pancreatitis. In this selected population, surgery can be undertaken safely with low mortality.

Introduction Chronic pancreatitis is defined as a spectrum of inflammatory disorders of the exocrine pancreas that typically result in loss of function and pain. It often results in weight loss due to the progressive loss of endocrine and exocrine function. Surgical interventions for chronic pancreatitis are the last resort option and normally saved for patients with intractable pain however the impact of surgery on weight gain has not been previously studied. Aim To examine the impact of surgery on weight gain in patients with chronic pancreatitis. Methods A retrospective database search to identify all patients having pancreatic surgery indicated for CP in a tertiary center (Manchester Royal Infirmary) over a 20-year period from 1999-2019. Patients were excluded from the study if histology showing pancreatic carcinoma was identified. Pre-op weights were taken from nutritional screening at the time of admission for surgery. Post-op weights were taken from follow-up clinic appointments on average six months postoperatively. Results On studying patient weights pre-and post-op it was found that 40% of patients had a steady weight gain, 25% had a weight drop, 30% had no documented weights for comparison and 5% had stable weights. Conclusion This study has shown that over half of the cohort of patients with recorded pre and post op weights had either gained weight or kept their weight steady after surgery. This supports the hypothesis that surgical intervention in patients with chronic pancreatitis does not compromise patient weights and merits further study.

Introduction Chronic pancreatitis is defined as a spectrum of inflammatory disorders of the exocrine pancreas that typically result in loss of function and pain. The main indication for operating on patients with chronic pancreatitis is managing intractable pain or treating complications, however surgical intervention is usually the last resort after conservative measures have failed. Evidence from previous studies stated that early surgery has a more favorable outcome on the treatment of intractable pain compared to endoscopic management. Aim To compare the analgesic requirements of patients who underwent surgical intervention for chronic pancreatitis pre-and post-operatively. Methods A retrospective database search to identify all patients having pancreatic surgery indicated for CP in a tertiary center (Manchester Royal Infirmary) over a 20-year period from 1999-2019. Patients were excluded from the study if histology showing pancreatic carcinoma was identified. Results Analgesia was scored as a 1 for simple painkillers, 2 for PRN opiates, and 3 for regular opiates with pre- and post-op cumulative scores compared. The cumulative pain score pre-operatively was 46 (5 people scoring 1, 1 scoring 2, 13 scoring 3, and one patient not taking any painkillers). Post-operatively pain score breakdown was 5 scoring 1,3 scoring 2 and 12 scoring 3, however, 4 patients that remained on regular opiates were found to be on a reduced dose compared to pre-operatively. A reduction of 0.5 was used to denote patients that remained on regular opiates but had a reduction in their dosage. Therefore the cumulative pain score was 45. The one patient whose analgesia requirements increased postoperatively developed a complication (pancreatic leak) post-operatively. This is believed to be the reason for the increased dependence. Excluding this patient gives a pre-operative cumulative pain score of 46 and a post-operative cumulative pain score of 42. Conclusion From our patient cohort, we can demonstrate a reduction in total analgesic requirements postoperatively. Whilst this remains an uncommon indication for surgical intervention it appears to hold potential benefits and merits study on a larger scale.

Drug-induced liver injury (DILI) in IBD patients is mostly attributed to thiopurines and methotrexate. Less has been reported about biologics-related DILI in IBD patients with existing data restricted to case reports. We retrospectively collected data on a multi-centre cohort of IBD patients with DILI attributed to biologics. This was a part of the European Crohn`s and Colitis Organisation (ECCO) initiated CONFER (Collaborative Network for Exceptionally Rare case reports) project. A call was made to all ECCO members to report DILI following initiation of biologics. Data were recorded on a standardised case report form and analysed with descriptive statistics. Eighteen patients with DILI attributed to biologics have so far been reported in this cohort (M: F −10:8, CD: UC- 10:8, Median age 33 years). DILI was attributed to infliximab in 15 patients, vedolizumab in 2 and adalimumab in 1. Seven patients were on concomitant immunomodulators (5 thiopurines, 2 methotrexate). Coexistent axial or peripheral arthropathy was recorded in 6 patients. Patients had a median of 3 doses (range 1–22) prior to development of DILI. Median time to DILI following last exposure to biologics was 51 days (range 12–84 days). Predominant hepatocellular pattern of liver function tests was noted in 9 patients, predominant cholestatic in 2 and mixed picture in the remaining 7. Antinuclear antibodies were present in 11/18 (3 of these anti smooth also muscle Ab positive) with elevated IgG in 9 patients. Liver biopsy was performed in 9 patients with 6 suggesting drug toxicity, 2 showing additional features of autoimmune liver disease and one showing co-existent steatohepatitis. The biologic was discontinued in all but 2 patients. Six patients had steroids following liver injury. Complete recovery of liver function was seen in 13, and partial in 3 patients following discontinuation of biologics in a median time of 35 days. Alternative biologics were started for IBD in 13 patients (10 switched from infliximab to vedolizumab, 2 from infliximab to adalimumab, and one from infliximab to ustekinemab),) with no recurrence of DILI. In a median follow-up of 17 months, 2 patients were formally diagnosed to have autoimmune liver disease requiring additional immunosuppression. DILI is reported in patients receiving biologics for IBD predominantly with Infliximab with development of autoimmunity in a subset of patients. Majority recover on stopping the offending agenda with no recurrence on switching the biologics. Results should be interpreted with caution as causality could not be certain given the retrospective nature of the study. A larger cohort is required to study DILI related to biologics in IBD.

Introduction Very few data are available about the clinical course of chronic pancreatitis caused by Cystic Fibrosis Transmembrane Conductance Regulator (CFTR-Panc) gene mutations, when compared with non-CFTR causes of chronic pancreatitis, alcohol being the commonest cause. Methods To study the clinical presentation and course of pancreatitis in patients with Cystic Fibrosis gene carrier status, compared with larger cohort of other causes of pancreatitis. A retrospective analysis of all the patients in Manchester Foundation Trust Specialist Pancreatology Unit with Chronic pancreatitis and CFTR gene carrier status between 1999 to 2018, compared with the published literature for other causes of chronic pancreatitis. Results A total number of 41 patients were heterozygous for CFTR gene mutations 29 male, Average age at presentation was 34.6 (range 11–65). Presentation varied: recurrent attacks of pancreatitis: 30 (73%); solitary attack of pancreatitis: 10 (24.3%) 1 (2.4%) patient presented with unexplained weight loss. Complications of pancreatitis occurred in (68.2%) Conclusion We report a different course and complication rate of chronic pancreatitis in CFTR carrier patients when compared to other causes of pancreatitis in the literature. In this retrospective cohort analysis, when compared with the published literature, patients with chronic pancreatitis caused by a mutation in one CFTR gene appear to have a lower incidence of diabetes, which took longer to develop. Other complications of pancreatitis - pseudocysts, pancreatic strictures and necrosis, were also less frequent in our cohort when compared to the literature, suggesting a less aggressive disease course. However, we noted no difference in the pattern of exocrine insufficiency between the two groups. Based on these findings, a larger prospective study is now required. References Ammann, et al.. Gastroenterology. 1996 Jul;111(1):224–31. Hao, et al. PLoS One. 2018 Jun 8;13(6):e0198365. doi: 10.1371/journal.pone.0198365. eCollection 2018. Lévy et al Gastroenterol Clin Biol. 2006 Jun-Jul;30(6–7):838–44.Malka et al Gastroenterology 2000; 119: 1324–1332.

Introduction 20% of patients with acute pancreatitis develop necrosis, which has a poor prognosis and significant mortality rate. Endoscopic necrosectomy is the primary intervention in the management of walled-off pancreatic necrosis (WOPN)1. After insertion of a lumen-apposing self-expanding metal stent (LASEMS), necrosis is removed using tools such as snares and forceps. Multiple procedures are often required, with repeated insertion of the endoscope into the cavity causing patient discomfort. EndoRotor® is a through-the-scope catheter with a rotating blade, cutting tissue which is then drawn into the catheter via suction. We present the first UK case series of EndoRotor® use for endoscopic necrosectomy. We aimed to evaluate the feasibility, safety and efficacy of its use in clearing WOPN. Methods All procedures were performed under conscious sedation by endoscopists experienced in necrosectomy. A 54 year old female developed a 19 cm x 8 cm area of WOPN as a consequence of acute pancreatitis. A LASEMS was inserted and EndoRotor® necrosectomy was performed five days later. Most of the necrotic tissue was cleared and the procedure was well tolerated. Final clearance was completed with a further snare necrosectomy 6 days later. Imaging confirmed a significant reduction in the cavity size (8cm x 2cm) and the patient was discharged. A 56 year old female was admitted with acute pancreatitis and discharged home after 12 days. She was later admitted for elective cholecystectomy but became unwell. A CT found a 28cm x 9cm area of WOPN. A LASEMS was inserted and a necrosectomy was performed two days later. All visible necrosis was removed using EndoRotor® four days later. Later examination showed some residual necrosis within a well healing cavity, requiring no further intervention. A 48 year old male was admitted with acute severe pancreatitis, developing multiorgan failure requiring ICU care. A CT confirmed an 18cm x 12cm pancreatic collection and a LASEMS was inserted. The patient had four necrosectomies before having an EndoRotor® necrosectomy with good result. Two further necrosectomies were required before LASEMS removal. Results All patients underwent EndoRotor® necrosectomy without complication. To achieve complete removal of WOPN the median number of procedures (including with EndoRotor®) was three (range 2–7). Conclusions As EndoRotor® draws necrosis in by suction, repeated insertion of the endoscope into the cavity is not needed, allowing greater tolerability and improved clearance of necrosis. Initial experience suggests that EndoRotor® is a safe and efficient tool for clearing WOPN. Reference Bakker OJ, et al. Dutch Pancreatitis Study Group. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA. 2012;307(10):1053–61

Background and study aims Pancreatic fluid collection (PFC) is a common complication of pancreatitis for which endoscopic ultrasound-guided drainage is first-line treatment. A new single-device, lumen-apposing, covered self-expanding metal stent (LAMS) has been licensed for PFC drainage. We therefore present our multicenter experience with the LAMS for PFC drainage in a multicenter prospective case series to assess success and complication rates. Patients and methods All adult patients from 11 tertiary centers who had LAMS placement for PFC from July 2015 to July 2016 were included. Data including indications, technical success, clinical success, collection resolution, stent removal, early and late adverse events (AEs), mortality and recurrence at 6 months were collected. Results 116 patients, median age 52.5 years (range 16 – 80) and 67 % male, were treated with a single LAMS in each case. The indication was walled off necrosis (WON) in 70 and pseudocyst in 46. Median size of the PFC was 11 cm (5 – 21 cm) and the estimated median necrotic volume in WON was 30 % (5 % – 90 %). Stent insertion was technically successful in 115 (99.1 %) and clinically successful in 109 (94 %). Early serious AEs (SAEs): n = 7 sepsis, n = 1 stent blockage with food, n = 1 stent migration requiring laparotomy, n = 1 stent dislodgement and n = 1 bleeding requiring emboliZation. Late AEs: n = 1 buried stent and n = 1 esophageal fistula. Non-procedure-related deaths: n = 3 (2.5 %). Conclusion This multicenter case series demonstrates that use of the new LAMS is feasible, effective and relatively safe in draining PFC with a technical success rate of 99 % and cumulative SAE rate of 11.2 %.

Introduction Needleknife assisted cannulation has been shown to be effective in ERCPs where standard techniques have failed. Concerns regarding risk of complication, particularly pancreatitis and perforation, have led to it being used only as a last resort. We evaluated the current practice and safety profile in a regional tertiary referral centre. Methods We performed a prospective observational study of ERCP outcomes in patients with intact ampullae. Experienced endoscopists with HPB expertise performed all ERCPs, and were asked to follow their standard practice. We used three ampulla classifications; non-prominent, prominent and distorted by tumour. The number of attempts at cannulation was recorded, as were the techniques used. Primary outcome measures were cannulation success and complication rates. Results Over a period of 8 months, 222 procedures were performed on patients who had not had previous ERCP. Successful cannulation in this group was achieved in 91.7%. Needleknife assisted cannulation was performed in 37 cases (17%). All needleknife cuts were started at the ampullary orifice. Needleknife use varied between different ampulla types (p = 0.44). Needleknife cannulation was most frequently attempted in ampullae involving tumour (33% attempted) but often unsuccessful (60% failure), compared to non-distorted (16.7% attempted, 22% failure rate). There was a wide range in the number of cannulation attempts made in both the needleknife and non needleknife groups (range 1–25) but there was a significant difference between the number of cannulation attempts in the standard cannulation and needleknife groups (p < 0.001). Despite this, there was no difference in the complication rate between standard cannulation and needleknife groups 5.6% v 7.3% (p = 0.522). Conclusion Needleknife assisted cannulation is more likely to be used where the ampulla is involved with tumour and where ERCP is indicated for malignant disease. However, in this context, needleknife assisted cannulation is more likely to fail. Reassuringly despite being used after failed attempts at cannulation using standard techniques, the complication rate for needleknife-assisted cannulation is not statistically different. The likelihood of progression to needleknife use may be predicted by ERCP indication and ampullary characteristics. This may facilitate consideration of an early conversion to needleknife-assisted cannulation, but also early abandonment of procedure for alternative methods (percutaneous or surgical) in these groups. Disclosure of Interest None Declared

Introduction ERCP training and service provision has been an area of intense interest internationally. Recent papers have highlighted discrepancies in practice and performance between individuals, units and countries. At present, there is no consensus as to how to best select and train individuals, or how to assess competency at the completion of training. This survey aimed to identify the selection processes for entry to ERCP training in use in the UK, alongside the entry characteristics of current trainees and their training and career aspirations. Methods A nationwide electronic survey of UK gastroenterology trainees. Results Responses were received from 15 of 20 deaneries, with 104 individual replies, of which 67 are currently training in ERCP. 3 deaneries have competitive selection in place comprising a combination of interview, portfolio review and endoscopic skills assessment. One deanery demands attainment of competency in both gastroscopy and colonoscopy prior to ERCP training. 91.4% are competent in OGD prior to ERCP training, whilst most intend to train in colonoscopy alongside ERCP 46.3% would like to simultaneously train in hepatology while 53.6% intend to combine with training in EUS 52.9% would expect to perform 200–500 ERCPs prior to certification of competence, but 76.5% have encountered difficulty in obtaining training-time commitments, others training or list suitability. 57.9% expect to attend less than 4 lists each month. Only 17.7% expect to be adequately trained at CCT and 79.4% intend to undertake fellowship. Conclusion Most deaneries have no formal selection process prior to beginning ERCP training. Those with competitive selection use differing criteria. There is dissatisfaction with the availability of training and acceptance that competency is unlikely to be achieved prior to CCT. The majority expect to undertake a post-CCT fellowship. Despite this, there is still interest in undertaking more subspecialty training, particularly EUS but also hepatology. The BSG working party has made suggestions regarding the structure of high quality training. This includes limiting training numbers by formalised selection to allow maximisation of training opportunity. It also makes recommendation of minimum list frequency and annual procedure numbers. These levels are not currently being achieved. Service commitment, other training needs and trainee competition are commonly cited as reasons for this. Most trainees lack confidence that ERCP competency will be attained during speciality training, in keeping with BSG working party expectation that post CCT fellowships will become standard. Current ERCP training cannot confidently produce independent endoscopists. This needs to be reflected in pre- and post-CCT training organisation and in new consultant job planning. Reference 1 With thanks to the BSG trainee committee for their assistance. Disclosure of Interest None Declared

Introduction ERCP is a technically demanding procedure, with significant risk of complications. Cannulation success is widely regarded as a key performance indicator of high- quality ERCP practice (1). Multiple factors affecting the complexity of a complete ERCP procedure have been suggested as a way of adding relevance to success rates and complication incidence. We propose a novel concept where complexity stratification is used to predict outcome based on ampullary characteristics. Methods 200 ERCPs performed on a virgin ampulla were prospectively recorded. We classified ampulla as non-prominent, prominent or distorted by tumour. Cannulation method and number of ampullary contacts were recorded. Cannulation success and incidence of complications were the primary outcome measures. Results The most common indication was biliary duct stones (54%). Ampullae were classified as non-prominent in 107 cases, prominent in 78 and involving tumour in 15. Overall deep cannulation was successful in 189 cases (94%), with significant variation between ampullary groups. Non-prominent and prominent ampullae were more likely to be cannulated successfully, (95.3%, 94.9% respectively), than those involving tumour (80%) (p = 0.004). Fewest contacts prior to cannulation were made on the non-prominent ampullae and most on those involving tumour (p < 0.001). Needleknife assisted cannulation was used most frequently on ampullae involving tumours and least often on non-prominent ampullae (p = 0.044). The presence of a peri-ampullary diverticulum or a covering mucosal fold, did not reduce cannulation success. 15 patients had complications (7.5%) - pancreatitis (10), perforation (3), infection (1) and bleeding (1). 12 complications occurred in the non-prominent group, with increased incidence of perforation, pancreatitis and bleeding (p = 0.04). Complications were more likely in younger patients (p = 0.03). Complication rate was not affected by patient gender, cannulation outcome, number of ampullary contacts or trainee involvement. Neither presence of diverticulae nor covering folds increased complication rate. Conclusion The assessment of ampullary characteristics may prove to be a novel means of predicting cannulation difficulty and anticipating risk of complication. Non-prominent ampullae appear to be easier to cannulate, with fewer ampullary contacts and less use of needleknife fistulotomy, but complication rates appear highest. Statistical significance is limited by the sample size and low incidence of cannulation failure and complications, so further study is required. These findings may have implication for case selection in ERCP training, and may add validity to key outcome quality indicators in practice. Reference 1 ASGE. Quality Indicators for ERCP. 2015. Disclosure of Interest None Declared

Introduction Pancreatic fluid collections (PFC) are a common local complication of pancreatitis with incidences of 5–16% and 20–40% in acute and chronic pancreatitis, respectively.1 Classification of PFC includes acute peripancreatic fluid collection, pancreatic pseudocyst, acute necrotic collection and walled-off necrosis (WON). A new lumen-apposing, covered self-expanding metal stent on a catheter-based delivery system (Hot AXIOS, Boston Scientific) may have higher technical success rates, easier deployment and lower migration than plastic stents. We present the first multicentre prospective case series from the UK and Ireland to assess success and complication rates associated with Hot AXIOS stent for the drainage of PFC. Methods All adult patients who had Hot AXIOS stent placement for PFC from July 2015-February 2016 were included. Eight centres participated (London, Glasgow, Edinburgh, Newcastle, Cambridge, Manchester, Dublin and Leeds). All patients had CT of the PFC prior to placement. Data including technical success, resolution of collection, complications and stent migration were collected. Results Forty patients were treated with a single Hot AXIOS stent in each case. The median age was 57 years (range 31–78). 25 were male and 15 female. Indications were WON (24), pseudocyst (15) and abscess.1 The median size of the PFC was 11 cm (4–20 cm). Thirty-eight patients (95%) had trans-gastric stents, 1 had trans-duodenal and 1 had a trans-oesophageal stent. Procedures were technically successful in all patients. Of 22 patients with available follow-up data to date, the collection resolved in 19 (86%) and reduced in size in 3 (14%). The median time to resolution was 36 (7–208) days. Twelve patients (30%) had 33 necrosectomies and/or endoscopic lavage following stent insertion. Stents migrated out in 2 patients and was displaced during necrosectomy in 1. Serious adverse events occurred in 1/40 (2.5%): a small bowel obstruction resulting from stent migration, managed surgically. There was no procedure related or 30 day mortality (data available in 27 patients). Conclusion This multicentre case series demonstrates that the Hot AXIOS system is safe and effective in draining PFC with a technical success rate of 100% and low serious adverse event rate. Reference 1 Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: Revision of the Atlanta classification and definitions by international consensus. Gut 2013. Disclosure of Interest None Declared

ERCP is a technically demanding procedure, with significant risk of complications. Cannulation success is widely regarded as a key performance indicator of high-quality ERCP practice1, 2. Multiple factors have been suggested as a way of adding relevance to success rates and complication incidence. We propose a novel concept where ampullary characteristics are used to predict outcome.