Mh Chapman

Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicentre study

Background Characteristic pancreatic duct changes on endoscopic retrograde pancreatography (ERP) have been described in autoimmune pancreatitis (AIP). The performance characteristics of ERP to diagnose AIP were determined. Methods The study was done in two phases. In phase I, 21 physicians from four centres in Asia, Europe and the USA, unaware of the clinical data or diagnoses, reviewed 40 preselected ERPs of patients with AIP (n=20), chronic pancreatitis (n=10) and pancreatic cancer (n=10). Physicians noted the presence or absence of key pancreatographic features and ranked the diagnostic possibilities. For phase II, a teaching module was created based on features found most useful in the diagnosis of AIP by the four best performing physicians in phase I. After a washout period of 3 months, all physicians reviewed the teaching module and reanalysed the same set of ERPs, unaware of their performance in phase I. Results In phase I the sensitivity, specificity and interobserver agreement of ERP alone to diagnose AIP were 44, 92 and 0.23, respectively. The four key features of AIP identified in phase I were (i) long (>1/3 the length of the pancreatic duct) stricture; (ii) lack of upstream dilatation from the stricture (<5 mm); (iii) multiple strictures; and (iv) side branches arising from a strictured segment. In phase II the sensitivity (71%) of ERP significantly improved (p<0.05) without a significant decline in specificity (83%) (p>0.05); the interobserver agreement was fair (0.40). Conclusions The ability to diagnose AIP based on ERP features alone is limited but can be improved with knowledge of some key features.

PWE-055 Characterisation of serum proteins in biliary tract cancer, primary sclerosing cholangitis and immunoglobulin G4-associated cholangitis using 2-dimensional difference gel electrophoresis and tandem mass spectrometry

Introduction Distinguishing biliary tract cancer (BTC: cholangiocarcinoma and gallbladder carcinoma) from benign biliary disease such as pre-malignant primary sclerosing cholangitis (PSC) or immunoglobulin G4-associated cholangitis (IAC) can be difficult. Serum markers such as CA19.9 and immunoglobulin G4 lack sensitivity and specificity. There is a need for better biomarkers to differentiate these clinically similar diseases. We aimed to perform serum immunoaffinity depletion, 2-dimensional difference gel electrophoresis (2-DIGE) and liquid chromatography tandem mass spectrometry to identify differential biomarkers in benign and malignant biliary disease and healthy volunteers. Methods Blood was prospectively collected from 37 patients with BTC, 11 with PSC, 7 with IAC and 30 healthy volunteers. Serum was pooled into the four clinical groups and immunoaffinity depleted via fast protein liquid chromatography to remove highly abundant proteins. Following 2-DIGE using minimal labelling Cy-dyes, gels were scanned then analysed with DeCyder software. Protein spots with a >2-fold differential expression (p<0.01, Student t test) were picked, trypsin digested and subjected to nanoflow reversed-phase liquid chromatography coupled to electrospray ionisation tandem mass spectrometry for protein identification. Results The median age of BTC, PSC, IAC and healthy groups were similar at 68 (range 27–93), 47 (range 22–76), 63 (range 43–71) and 64 (range 40–79) years, respectively. The median serum bilirubin in the BTC, PSC and IAC groups was 40 (range 8–616), 20 (range 7–457) and 12 (range 5–40) μmol/l, respectively. 30/37 BTC, 4/11 PSC and 1/4 IAC patients, had elevated (>37 IU/ml) CA 19.9 levels. 61 protein spots were picked, of which 34 were upregulated and 13 downregulated in BTC vs healthy, 32 upregulated and 9 downregulated in BTC vs PSC, and 7 upregulated and 12 downregulated in PSC vs IAC. Leucine-rich glycoprotein, apolipoprotein A-IV and E, MASP2, CLEC3B, RAD1 and vimentin were upregulated and Hsp90, C4BPA and SERPIND1 downregulated in BTC vs PSC. Carbonic anhydrase 1, lumican and twinfilin-2 were upregulated and IgG4 chain C region and MASP2 were downregulated in PSC vs IAC, respectively. Serum validation of putative markers is underway. Conclusion Differentially expressed serum proteins in benign and malignant biliary disease were identified using this proteomic approach. These putative markers may be useful in monitoring patients with PSC who are at increased risk of BTC.

PWE-035 Early experience of pancreatoscopy-directed electrohydraulic lithotripsy for pancreatic ductal stones in painful chronic pancreatitis

Introduction Painful chronic pancreatitis is often associated with main duct obstruction due to stones. Approaches to management are challenging, including surgery, extracorporeal shock wave lithotripsy (ESWL), or endoscopic approaches. All have their limitations. Electrohydraulic lithotripsy (EHL) using Spyglass™ directed visualisation is highly effective for treating difficult bile duct stones, and is increasingly used in the UK. Here we report our early experience of Spyglass ™ pancreatoscopy and EHL for pancreatic duct stones. Method We retrospectively audited our unit’s use of Spyglass™EHL in the period February 2013–February 2015, with a focus on those patients undergoing pancreatic EHL. Indication, procedural details, and clinical outcome were assessed. Results Eighty-five procedures for Spyglass™and EHL for stones were performed, of which 5 (6%) were carried out for pancreatic stones in 4 patients (3 female, mean age 46 years ±16 years). All patients had painful chronic pancreatitis, with radiological evidence of a dilated pancreatic duct, and main duct stone disease within 2 cm of the ampulla. Surgical options had been considered in all cases. Prior to EHL all patients had undergone pancreatic sphincterotomy and pancreatic duct stenting. Stone fragmentation and duct decompression was achieved in 75% (3/4) of cases. One patient required two EHL procedures to achieve clearance. In the patient with failed clearance, pancreatoscopy revealed that the stone was not in the main duct, but in the adjacent parenchyme. There were no procedure related complications. All patients with successful EHL had pain relief/marked improvement at clinical review (mean follow up - 6.8 ± 5 months).Abstract PWE-035 Table 1 Patient Aetiology of Chronic Pancreatitis Age (years) Sedation Main duct stone location Stone Size (cm) Number of EHL sessions Success Follow up (months) Previous ERCPs 1 Idiopathic 57 Conscious Head 1.2 2 Yes 13.5 4x 2 Spink1-mutation 43 Propofol Head 1.5 1 Yes 5.9 1x 3 Spink1-mutation 19 Propofol Head and tail 2.2 1 Yes 1.2 1x 4 Biliary 53 Conscious Head 1.0 1 No - 1x Conclusion Pancreatoscopy with EHL may have a valuable role in treating obstructing pancreatic duct stones, possibly avoiding the need for surgery in some patients. However, careful patient selection is mandatory, and more studies are needed to better define treatment approaches. Disclosure of interest None Declared.

OC-108 Improving the diagnosis of pancreaticobiliary malignancy by the detection of minichromosome maintenance protein 5 in biliary brushings

Introduction Biliary brush cytology is the standard method of evaluating a biliary stricture but has a low sensitivity for the detection of malignancy. Minichromosome maintenance (Mcm) replication proteins (Mcm 2–7) are raised in a number of cancers, where the active cycling of malignant cells results in the expression of these licensing proteins on the epithelial surface of the tumour. In pancreaticobiliary malignancies Mcm proteins are dysregulated in the epithelial lining of the bile ducts and in bile samples taken from patients with malignant pancreaticobiliary disease. The aim of this study was to evaluate an automated immunoflurometric assay of Mcm5 as a marker of malignancy in patients with indeterminate biliary strictures. Method Biliary brush samples were collected prospectively at endoscopic retrograde cholangiopancreatography from patients with an indeterminate biliary stricture. Following sampling the brush was placed in a buffer solution, agitated and frozen to –80oC. On defrosting the sample was placed in a microtitre plate strip of 8 wells coated with a purified mouse monoclonal antibody to Mcm5 and incubated for 2 h. The colour intensity was measured using a plate reader and a cut-off of 1.2 was used to indicate a positive result. Patients also underwent brush cytology and/or biliary biopsy as part of standard practice. Results 75 patients were included in the study; median age was 65 years (range 20–94) and 68% (51/75) were male. Mcm5 levels in biliary brush samples were significantly more sensitive than brush cytology (89% vs.18%; P= < 0.05) for the detection of malignancy in patients with an indeterminate stricture. The specificity, PPV and NPV of the Mcm5 assay were 96%, 98% and 84% respectively. Conclusion Mcm5 from biliary brush cytology determined by a simple automated test is a more sensitive indicator of pancreaticobiliary malignancy than routine brush cytology. Disclosure of interest None Declared.

PTH-121 The Burden Of Poor Nutrition In Chronic Pancreatitis: What Are The Impact Of Behavioural And Socioeconomic Factors?

Introduction Nutrition centred research in pancreatitis has largely focused on acute pancreatitis. There is limited nutritional data in patients with Chronic Pancreatitis (CP), a condition that predisposes to endocrine and exocrine failure, fat-soluble vitamin deficiency and osteoporosis, which may worsen a patient’s quality of life and long-term outcome. We aim to determine the prevalence of malnutrition (using the Malnutrition Universal Screening Tool -MUST), active alcohol consumption and cigarette smoking in patients with CP. Methods Prospective study of consecutive patients with CP attending a tertiary clinic between October and December 2013. They were invited to participate in a face-to-face questionnaire study. Behavioural and socioeconomic data were collated. Results A cohort of 86 patients identified were predominantly male (67%), White British (62%), median age 58 years (range 18–90), of socio-economic class (SEC) 8 (21% never worked/long-term unemployed) with educational level (EL) 1 (29% degree or equivalent). Aetiologies included alcohol (29%), idiopathic (25%), autoimmune (22%) and gallstones (11%). The aetiology in 6% was actively under investigation. Median follow up was 27.5 months (range 0 – 151) from index appointment. Active alcohol exposure was noted in 33% (28/86) with excessive amounts (m >21 u, f >14 u/week) in 8% (7/86). The majority of patients (> 70%) with ongoing exposure to alcohol had primary aetiologies other than alcohol. Active cigarette smoking was noted in 34%. MUST scores ≥ 1 were noted in 38% (33/86) conferring “medium to high risk of malnutrition”. Multiple linear regression analysis of age, gender, ethnicity, SEC, EL, aetiology, alcohol exposure and smoking did not show any statistically significant variables that predicted MUST score. 27% (9/33) patients “at risk of malnutrition” had been referred to or had been seen by a dietitian within the previous 12 months. The remaining 73% (24/33) “at risk” patients all claimed to have received nil or suboptimal nutritional advice with regards to CP within the previous 24 months. Conclusion Patients with CP attending our tertiary clinic are at significant risk of malnutrition, which may be under-recognised. Behavioural and socioeconomic factors do not allow reliable prediction of risk of malnutrition to be made, in this cohort. This data emphasises the need for an algorithmic approach to improve recognition of malnutrition in CP and for implementation of specialist dietetic, alcohol liaison and smoking cessation services within the outpatient environment. Disclosure of Interest None Declared.

OC-068 The Impact Of Endoscopic Therapy On Patient-perceived Outcome And Quality Of Life In Sphincter Of Oddi Dysfunction

Introduction Biliary Sphincter of Oddi dysfunction (SOD) is a benign but often debilitating condition. Significant improvement in pain following endoscopic sphincterotomy or sphincteroplasty (ES) in patients with Type 1 SOD, is excellent. Symptomatic improvement in patients with type 2 or 3 SOD is less favourable (reported 50–70% and 30–50% respectively). We aim to determine the impact of ES, on pain symptoms and global quality of life (QOL) in these groups, which has not previously been well defined. Methods An ERCP database and electronic clinic lists (from September 2011 to 2013) were analysed to identify all cases of suspected SOD. Patients underwent a telephone questionnaire. The Glasgow Benefit Inventory (GBI), which assesses multiple physical, emotional and social parameters, was used to quantify global post-interventional QOL benefit. Total GBI scores can range from -100 (maximal negative benefit) to +100 (maximal positive benefit). Results 163 new patients with suspected biliary SOD were identified of whom 89 underwent ERCP. 3 patients were excluded due to an alternative diagnosis at ERCP. The remaining cohort was predominantly Female (87%) and White British (86%) with median age 37 years (range 18–69). 88% had undergone prior cholecystectomy. Patients were attributed with the following pre-test diagnoses – 20/86 (23%) SOD1, 53/86 (62%) SOD2, 13/86 (15%) SOD3. Median post-ERCP follow up was 12 months (range 2–27). In patients who underwent endotherapy and completed questionnaires: 93% (14/15) SOD1, 76% (36/48) SOD2 and 83% (10/12) SOD3 subjectively reported pain improvement post-ERCP (within median 1 month). Sustained response (median 6 months) was noted in 60, 30 and 46% of SOD 1/2/3 respectively. Median total GBI scores in the patients who had sustained improvement were +44 (SOD1), +31 (SOD2) and +29 (SOD3). There was a clear correlation between subjective response to ES and GBI scores (see table). Negative total scores were recorded across all SOD subtypes in patients who had no symptom improvement whatsoever following ES. Total GBI scores in all categories were higher in SOD1 than SOD2 than SOD3. Abstract OC-068 Table 1 Median GBI Scores (Post- ES) Response to ESF SOD subtype SOD1 SOD2 SOD3 No improvement –19.4 –31 –63 Initial response then relapse 8.3 8.3 –19 Sustained response 44 31 29 Conclusion ES for SOD1 appears to provide sustained benefit in symptoms and QOL above that achieved in SOD2/3. QOL measured by GBI is strongly correlated to symptomatic response to ES despite pain response being only a minor contributor to the GBI rating. Therefore, GBI may be helpful to determine clinical, emotional and social factors that could help to predict those patients who will respond to ES. Disclosure of Interest None Declared.

A 25 year single centre experience in 128 patients with primary sclerosing cholangitis

Introduction Dominant biliary strictures (DS) occur commonly in patients with primary sclerosing cholangitis (PSC), who have an increased risk of developing cholangiocarcinoma (CCA). The natural history and optimal management of dominant strictures remains controversial with most reports suggesting that endoscopic interventions improve outcome. Methods The authors describe a 25 year experience of endoscopic retrograde cholangiopancreatography (ERCP) in patients with PSC at a single tertiary referral centre in London. Patients were identified through case note review, endoscopy and pathology database searches and through a specific PSC database. Results During a mean follow-up of 6 years (0.1–23.6 years), 128 patients with PSC (81 M, 47 F; median age 49 years) had a median of 2 ERCPs (range 1–24). 70 patients with dominant biliary strictures had a median of 3 (range 0–34) interventions, compared to 1 (0–7) in the 58 without dominant strictures. Endoscopic interventions included: (1) stenting alone (51%), (2) dilatation alone (19%) or (3) dilatation and stenting (16%), while 14% had no or failed interventions, most of whom required percutaneous transhepatic drainage. There were no procedure-related deaths. The survival of those with dominant strictures was worse than those without, even after exclusion of those who developed CCA. Use of ursodeoxycholic acid was not significantly different between groups. CCA developed in 20/128 patients (16%), only in those with dominant strictures (20 of 70, 29%, compared to 0 of 58). Jaundice was the presenting feature in 15 (75%) of those with CCA, which developed a median of 3 years (0–21 years) after the diagnosis of PSC, with 8/20 (40%) presenting within the first year. Mean time from diagnosis of CCA to death was 7 months (1–23 months). Conclusion Repeated endoscopic therapy in patients with PSC appears to be safe. However, this data highlights the poor prognosis in the subgroup with dominant strictures, even after exclusion of those who developed CCA. In this series, CCA only occurred in patients with dominant bile duct strictures.

Achieving a pathological diagnosis in biliary tract cancer

Introduction Diagnosing BTC is challenging because of a lack of reliable tumour markers and radiological similarities with benign hepatobiliary disease. Current guidelines advise confirmatory histology and/or cytology should be sought for the diagnosis of biliary tract cancer (BTC) (Khan et al, Gut 2002;51(Suppl VI)). However, tissue sampling for pathological diagnosis is hampered by tumour site and morphology limiting access to diagnostic tissue, with success rates of only 60–70% (Connor S et al, 2005;9:476; Witzigmann et al, 2006;244:230). Methods All patients (n=256) with a final clinical diagnosis of BTC (229 cholangiocarcinoma, 27 gallbladder cancer) between January 2003 and September 2010 were included (135M, 121F; mean age 70 years, range 23–107 years). All cytology and tissue biopsy data, including number and technique, for each patient were recorded. Results 59/256 patients (23%) were referred with a tissue diagnosis. Of the 197/256 patients (77%) without a prior tissue diagnosis, 196 had attempted tissue sampling (median 1 procedure, range 1–6) at our hospital. Out of a total of 341 tissue samples, 127 were taken for biliary cytology and 54 for other cytology (pleural and ascitic fluid n=38; endoscopic ultrasound-guided fine needle aspiration (FNA) n=15; bile n=1), of which 43/127 (34%) and 11/54 (20%), respectively, were positive for cancer. 124 percutaneous and 36 endobiliary biopsies were taken, of which 70% and 44% respectively, were positive. 45 (13%) samples were reported as suspicious for malignancy and a further 15 (4%) had suboptimal specimens unsuitable for pathological diagnosis; all were classified negative for malignancy. Overall, 161/197 (82%) had a pathological confirmation of cancer at our hospital, giving a total positivity rate of 220/256 (86%). A clinical diagnosis of BTC, based on multidisciplinary review and evidence of disease progression, was made in the remaining 36 (14%) patients. Conclusion A pathological diagnosis of BTC can be achieved in 86% of patients, exceeding previous best published data. The sensitivity of biliary cytology in routine clinical practice is low, but a pathological diagnosis can be obtained with a combination of other endoscopic and percutaneous approaches, allowing alternative diagnoses to be excluded and appropriate treatment given.