Alistair Makin

Antioxidant Therapy Does Not Reduce Pain in Patients With Chronic Pancreatitis: The ANTICIPATE Study

BACKGROUND & AIMS We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. METHODS We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed for 6 months while receiving either antioxidant therapy (Antox version 1.2, Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/day). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative assessments of clinical and diary pain scores, scores on quality-of-life tests (the European Organization for Research and Treatment of Cancer [EORTC-QLQ-C30], Quality of Life Questionnaire-Pancreatic modification [QLQ-PAN28], European Quality of Life questionnaire [EuroQOL EQ-5D], and European Quality of Life questionnaire - Visual Analog Score [EQ-VAS]), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively defined by protocol. RESULTS After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (-0.36; 95% confidence interval [CI], -1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group and 2.93 for the antioxidant group, a difference of 0.11; 95% CI, 1.05-0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, β-carotene, and selenium were increased significantly in the antioxidant group. CONCLUSIONS Administration of antioxidants to patients with painful chronic pancreatitis of predominantly alcoholic origin does not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants.

The use of thrombin injections in the management of bleeding gastric varices: a single-center experience

BACKGROUND There is a relative dearth of literature on the definitive endoscopic management of bleeding gastric varices. Variceal ligation with bands and detachable snares, sclerosants, cyanoacrylate glue, and thrombin injections have been used with variable success. OBJECTIVE To report our experience with bovine thrombin injection for the treatment of bleeding gastric varices. DESIGN A retrospective review. SETTING Tertiary-referral hospital. PATIENTS Forty-two cases of gastric varices were identified from our endoscopy database between July 1998 and July 2003. Thirteen patients had thrombin injection. INTERVENTION Thrombin injection therapy for bleeding gastric varices. MAIN OUTCOME MEASUREMENTS Control of hemorrhage, risk of rebleeding, and mortality. RESULTS Of the 13 patients who underwent thrombin injections, hemostasis in the acute setting was successful in 92% of cases. Patients received 1 to 4 sessions of thrombin, with a mean total dose of 10.8 mL for variceal eradication. One patient continued to bleed and needed a transjugular intrahepatic portosystemic shunt as a rescue procedure. The patient with hepatocellular carcinoma died within 30 days, and 4 more patients died after a median follow-up of 22 months; none died because of bleeding. There was no rebleeding in the remaining patients at a median follow-up of 25 months. LIMITATIONS The retrospective nature and small number. CONCLUSIONS In our series, injection with thrombin proved to be an effective endoscopic treatment in the majority of patients with bleeding gastric varices. The overall mortality, after controlling bleeding, was 38% (5/13), subsequent to a median follow-up of 22 months.

Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn's disease.

BACKGROUND/OBJECTIVE Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohns disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed. METHODS British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively. RESULTS In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively). CONCLUSION The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population.

T1259 Serum Metabolite Profiles Differentiate Crohn's Disease From Ulcerative Colitis and From Healthy Controls

Introduction Metabolomics is a powerful scientific strategy which identifies low molecular weight (bio)chemicals (metabolites) present in the metabolome of a cell, tissue or organism. The aim of this study was to undertake a two-stage metabolomic study of circulatory serum from patients with ulcerative colitis (UC) and Crohn9s disease (CD) and matched healthy controls, to determine if we could establish a characteristic metabolic signature for each of these diseases. Methods Patients were selected from a cohort of 332 IBD patients, comprising 134 males and 198 females during November 2007–March 2009. The base study comprised 30 CD, 30 UC and 29 control patients, all white male Results After quality assurance, 4289 peaks were consistently detected by the UPLC-MS analysis of the base study samples. After univariate screening (p Conclusion This study illustrates, for the first time, that serum metabolomics is effective at distinguishing IBD patients from normal subjects, and to a lesser extent CD from UC. It demonstrates the potential of metabolomics to differentiate disease phenotypes and may give new insights into the aetiology of IBD.

PWE-008 Clinical outcomes of ustekinumab in resistant crohn’s disease: UK IBD tertiary referral centre ‘real-world’ experience

Introduction Ustekinumab (UST) binds to the p40 subunit of IL12 and IL23 to prevent IL12RB1 cell-surface receptor activation and thus inhibits downstream inflammatory signalling. It is approved for moderately to severely active Crohn’s disease (NICE TA456). We assessed the clinical outcomes and safety of UST in a ‘real-world’ cohort of refractory Crohn’s disease patients treated at a single UK centre. Methods We retrospectively collected data from the electronic records of Crohn’s disease patients treated with UST at a single UK IBD tertiary referral centre. Patient demographics and adverse events were recorded. Clinical response to UST was evaluated at baseline and follow up using Harvey-Bradshaw Index (HBI) scores, C reactive protein (CRP), and faecal calprotectin (FC). Paired Student’s T Tests were used to determine statistical significance. Results 26 patients (mean age 36 years; age 18–62 years; M:F ratio=1:1.6) with a variety of Crohn’s disease phenotypes (L1=8; L2=6; L3=12) were treated with UST. 9 patients (35%) had stricturing disease and 5 patients (19%) penetrating disease. All patients had failed at least one anti-TNF agent. 15 patients (58%) had failed two anti-TNF agents, and 11 (42%) had failed an anti-TNF and subsequent vedolizumab therapy. 7 patients (27%) received immunomodulatory co-therapy (AZA=5; MTX=2), and 11 (42%) received bridging steroids. 12 week data was available for 20 patients. At 12 weeks, mean HBI significantly improved (5 vs 9; p<0.05). There was reduction in mean FC (763 vs 1026; ns), but no change in mean CRP (14 vs 11; ns). 10 patients (50%) demonstrated subjective and objective (FC +/-CRP +/- endoscopic) response to therapy. 6 of these patients received bridging steroids, of which all had reduced and 4 had completed their steroid course. Of all treated patients 2 discontinued UST (recurrence of a transitional cell carcinoma; primary non-response to therapy requiring surgery), and side effects were reported in 2 patients (Bell’s Palsy; lower respiratory tract infection). Conclusions UST appears clinically effective and safe in this cohort of treatment-refractory Crohn’s disease patients after 12 weeks of therapy. Future work to combine ‘real world’ data and to assess longer term outcomes will help us to better understand and place the use of UST in the management of Crohn’s disease.

PTU-022 Needleknife Assisted Cannulation in a UK Tertiary Referral Centre – Utilisation and Complications in Standard Practice

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

PTH-029 Ampullary Characteristics as A Novel Means of Predicting ERCP Complexity

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

Gastric amyloidosis presenting with severe weight loss.

A previously well 59-year-old lady with 70 kg weight loss and chronic diarrhoea over a 28-month period presented following collapse and subsequent diagnosis of pulmonary embolism. Previous investigations for this weight loss included normal gastroscopy and colonoscopy, CT and MRI abdomen, barium follow through and octreotide scan. She underwent echocardiogram which revealed myocardial speckling and asymmetrical left ventricular hypertrophy. Repeat oesophago-gastro-duodenoscopy and colonoscopy for rectal bleeding was performed. Colonoscopy revealed intramucosal haematomas and electron microscopy (EM) of the gastric biopsies confirmed amyloid deposition. Amyloidosis of the gastrointestinal (GI) tract and heart were confirmed on serum amyloid protein scan. GI amyloid is rare and symptoms include weight loss, diarrhoea, GI bleeding and gut dysmotility.1 GI amyloidosis should be considered as a diagnosis and sought when other common causes have been excluded. The greatest yield is by Congo red staining or EM of rectal specimens.