P Phull

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

Background:Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy.Methods:Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations.Results:We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin.Conclusions:In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma.

British Society of Gastroenterology position statement on serrated polyps in the colon and rectum

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations—serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

Familial collagenous colitis involving a 6-year old child

Collagenous colitis is a recognised cause of persistent, non-bloody, watery diarrhoea. There are few cases of collagenous colitis reported in children or occurring within families. To our knowledge, no familial cases under 14 years of age have been reported previously; we describe a case of familial collagenous colitis affecting a 6-year old girl and her mother. The relevant published literature is reviewed and management is discussed. Colonic mucosal biopsies should be considered in both adults and children presenting with persistent watery diarrhoea even in the absence of any macroscopic abnormality at colonoscopy.

Variation in caecal intubation rates between screening and symptomatic patients

Background The caecal intubation rate (CIR) is an important quality standard for endoscopists, as well as for national bowel cancer screening programmes; however, individuals undergoing colonoscopy for bowel screening and symptomatic patients represent different groups, and their characteristics may affect colonoscopy performance. Objective To compare colonoscopists’ performance, as assessed by the CIR, in symptomatic patients compared to individuals undergoing colonoscopy for bowel cancer screening. Methods Retrospective audit of CIRs for all patients undergoing colonoscopy at our institution during the year 2008. We retrieved the data from an endoscopy reporting software database and from the local bowel cancer screening programme database. Demographic data was extracted, as well as details of known factors that may affect completion of colonoscopy, such as poor bowel preparation, presence of diverticular disease, polyps, tumour and strictures. The unadjusted CIRs for colonoscopists participating in the screening programme were compared between the bowel screening and the symptomatic patient groups. Results Five screening colonoscopists performed 1056 colonoscopies, of which 488 were bowel screening procedures. The overall CIR was significantly lower in the symptomatic, compared to the screening, individuals (88.5% versus 93%, P < 0.02). No significant differences were observed between the two groups for risk factors that could impair the CIR. The CIR was <90% for two of the five colonoscopists in symptomatic patients, and just under 90% for one colonoscopist in screening individuals. Multivariate analysis revealed that non-screening colonoscopy was an independent predictor for an incomplete procedure (OR 1.8; 95% CI 1.2–2.8). Conclusions The CIR, a key quality performance indicator for colonoscopy, is lower in symptomatic patients compared to individuals undergoing colorectal cancer screening. These results suggested that CIR should be monitored independently in screening and non-screening colonoscopies.

PTU-151 Predicting 30-Day Mortality and Re-Stenting Following Self Expanding Metal Stent (SEMS) Insertion for The Palliation of Dysphagia in Patients with Oesophageal Cancer

Introduction Management of dysphagia due to malignant obstruction of the oesophagus can be challenging. Endoscopically placed self-expanding metal stents (SEMS) remain an important tool and have been performed under direct vision in our institution since 2004. A previous audit suggested a significant morbidity and mortality rate and therefore the aim of this study was to identify risk factors for 30 day mortality and re-intervention. Methods A retrospective review of all patients undergoing oesophageal SEMS insertion was performed over the period 2004–2014. Data collected included patient demographics, tumour stage/position, stent type inserted, survival following SEMS insertion, bioprofile and other therapies. Univariate analysis was performed and was followed by multivariate logistic regression to identify independent variables associated with 30 day mortality and re-stenting. Results 396 patients (median age 74 years, 252 males) had 514 stents were inserted over the study period and were included in the study. Regarding 30 day mortality, univariate analysis showed association with distal tumours (OR 1.6), stent length >10 cm (OR 3.0), oncological treatment (OR 0.4), raised CRP (OR 6.1), raised white cell count (OR 6.0), anaemia (OR 2.8) and low albumin (OR 4.9). Multivariate analysis showed white cell count (OR 8.1, 2.0–21.9, p < 0.001, albumin <35 g/l (OR 6.9, 2.6–18.8, p < 0.001) and oncological treatment (OR 0.3, 0.1–0.8, p = 0.013) were independent predictors of 30 day mortality. Regarding re-intervention, univariate analysis showed association with age > 70 (OR 0.6), junctional tumours (OR 0.5), stent length >10 cm (OR 0.6), raised CRP (OR 0.5) and raised white cell count (OR 0.4). Multivariate analysis showed age > 70 (OR 0.5, 0.3–0.9, p = 0.032) and raised white cell count (OR 0.4, 0.2–0.8, p = 0.009) were independent predictors of re-intervention. Conclusion Raised inflammatory markers were associated with poorer outcomes following oesophageal SEMS insertion and oncological treatment was protective. Longer survival appears to be associated with re-intervention following initial stent insertion. This data may provide a framework for the creation of a prognostic scoring system prior to SEMS insertion. Disclosure of Interest None Declared

Initial experience of direct-to-test endoscopic ultrasonography for suspected choledocholithiasis

Background and aims Endoscopic ultrasound has become an invaluable tool in the investigation of patients with suspected pancreatobiliary disease. We set out to determine whether a “direct-to-test” endoscopic ultrasound procedure could be offered to selected patients with suspected choledocholithiasis. Methods and results We included patients referred to our general gastroenterology service with clinical history, symptomatology and/or laboratory results compatible with choledocholithiais. Almost all patients had already had a transabdominal ultrasound performed at the request of their general practitioner. All patients underwent direct-to-test day-case endoscopic ultrasound under conscious sedation. Procedures were performed by a single practitioner using an oblique-viewing radial echoendoscope. The diagnostic yield and frequencies of discharge, onward referral and follow-up were determined. Overall diagnostic yield of direct-to-test endoscopic ultrasound was 61%. The most common diagnoses were cholelithiasis (18%) and choledocholithiasis (11%); one periampullary cancer was also detected. A definitive outcome (discharge or referral for a therapeutic procedure) occurred in 14 of 28 patients (50%). The remaining 14 patients underwent further out-patient evaluation. Eventual diagnoses in this group included autoimmune hepatitis, primary biliary cirrhosis and drug-induced hepatitis. Conclusions For patients with suspected biliary disease, direct-to-test endoscopic ultrasound has a high diagnostic yield, and may be an appropriate mode of investigation.

PWE-018 Trends in endoscopic stenting and clinical outcome for oesophageal malignancy over the last decade in north east scotland

Introduction Management of dysphagia due to oesophageal cancer can be challenging and self-expanding metal stents (SEMS) have an important role in this. SEMS have been placed under direct vision in our institution since 2004 and a previous audit showed a significant rise in numbers particularly repeat stenting. A new referral protocol was implemented from 2011 to better aid assessment and appropriate insertion of SEMS and so the aim of this study was to assess changes in trends of SEMS insertion following this. Method Retrospective analysis of all oesophageal SEMS inserted in our institution from 2004 to 2014 was performed. Patient demographics, tumour pathology and location, repeat stenting and 30 day mortality were recorded. Emerging trends were analysed by examining changes on a yearly basis and proportional analysis before and after the change in referral protocol. Results 393 patients with a mean age 72.9 years (242 males) were included with 510 SEMS being inserted overall (117 repeat stents) and Figure 1shows this graphically. Median age was 77 in 2004 which dropped steadily over the decade to 71 in 2010 and then remained between 73–75. SEMS insertion increased significantly from 6 in 2004 to 74 in 2011 and then dropped to 52 over the next 3 years. Repeat stenting rose until 2012 (1 in 2004 to 18 in 2011) and then fell following the change in protocol. The majority of tumours were adenocarcinomas (>60%) and were in the distal oesophagus or gastro-oesophageal junction. 30 day mortality peaked in 2010 and then steadily declined following the change in protocol but has increased again in the last year.Abstract PWE-018 Figure 1 Conclusion There has been a significant increase in the number of SEMS inserted in our institution over the last decade. The previous audit revealed that patients were likely being stented too soon and the change in protocol has reduced overall numbers but more importantly repeated stenting. The recent rise in mortality may represent SEMS being inserted closer to the end of a patients life and therefore a true palliative intervention. Disclosure of interest None Declared.

PTU-254 Incidence, presentation and outcomes for patients with ischaemic colitis admitted to an open-access gi bleeding unit

Introduction Ischaemic colitis (IC) is the most common form of gastrointestinal ischaemia; an acute impairment of perfusion of the colon leads to mucosal injury resulting in inflammation, ulceration and occasionally full-thickness necrosis. A recent meta-analysis has suggested that ∼20% of patients require surgery, and the mortality rate is almost 13%.1The aim of this study was to determine the incidence, presentation and outcomes for patients with ischaemic colitis. Method Retrospective audit of prospectively collected data for the open-access GI Bleeding Unit (GIBU) at our institution between January 1995 and December 2004. Data was extracted from the GIBU database for all patients coded as IC or ‘other colonic’ diagnoses. The diagnosis of IC was validated by cross-checking with the hospital endoscopy and pathology software systems. Results Over the 10 year period studied, there were 1885 admissions with lower GI bleeding of which 108 (5.7%) had an endoscopically and/or histologically confirmed diagnosis of IC. The number of cases of IC increased over time; the incidence of bleeding from ischaemic colitis increased from 0.24 per 100,000 in 1995 to 5.06 per 100,000 of the adult population in 2004. The mean age of the patients was 69 (range 35–91) years, with 93 (86.1%) being >55 yrs; 83 (76.9%) were female. Presentation was with rectal bleeding in 103 (95.4%) cases, diarrhoea in 52 (48.1%) and vomiting in 38 (35.2%). Regular medication included aspirin in 39 (36.1%) of patients, NSAIDS in 19 (17.6%), and anti-coagulants in 12 (11.1%). Of the 108 admissions, 107 (99.1%) underwent lower GI endoscopy and 96 of these (89.7%) had biopsies taken for histology. One patient proceeded directly to surgical resection without prior endoscopic examination. Analysis of outcomes revealed rebleeding in 3 (2.8%) cases, with 5 (4.6%) patients requiring surgical resection; 30 day mortality was 3.7%. Readmission with IC was seen in 2 (1.9%) cases during the period studied. Conclusion The incidence of IC appears to be rising, with the majority of patients being female and over 55 years of age. However, the surgery and mortality rates are lower than previously reported, and recurrence is rare. Disclosure of interest None Declared. Reference O’Neill S, Yalamarthi S. Systematic review of the management of ischaemic colitis. Colorectal Dis. 2012;14:e751–e763

PWE-342 Evaluation of fobt-positive individuals not undergoing colonoscopy in the bowel screening programme

Introduction In the UK, population based colorectal cancer (CRC) screening is conducted based on biennial faecal occult blood testing (FOBT), with follow-up colonoscopy for positive results. However, a proportion of FOBT-positive subjects do not undergo colonoscopy, due to individual choice, comorbidity or current/recent colonic investigations for symptoms. The aim of this study was to evaluate this group of FOBT screen-positive subjects who do not undergo a screening colonoscopy. Method Retrospective audit of prospectively collected data within the North East Scotland bowel screening database, between 1/06/2007 to 31/05/2013. Data was collected for reasons why colonoscopy was not performed, as well as the performance and results of further alternative imaging. Results During the 6 year period of the audit, 4975 screening colonoscopy referrals were received for 4704 individuals (253 subjects had presented through 2 rounds and 18 through 3 rounds of the screening programme). Overall, 1081 (21.73%) referrals did not have a colonoscopy performed; 492 (45.5%) declined, a clinical decision was made in 525 (48.6%), 46 (4.3%) were under surveillance, 14 (1.3%) did not attend the appointment, 2 (0.01%) individuals died and no reason was identified in 2 cases. Of the 492 subjects that declined colonoscopy, 36 (7.3%) had the procedure performed in the private sector, other reasons were recorded in 34 (6.9%) cases and no reason was recorded for the remaining subjects. Of the 525 cases in whom a clinical decision was made not to perform colonoscopy, the reasons were recorded as significant co-morbidity in 159 (30.3%) with 25 (4.8%) cases of cancer, 151 (28.8%) subjects had colonic imaging within the previous 12 months, 26 (5%) had active IBD, 118 (22.5%) were in the symptomatic service with a colonoscopy appointment already arranged, 12 (2.3%) individuals had previous failed colonoscopies on >1 occasion, and other/no reason was recorded in 59 (11.2%) subjects. Radiological colonic imaging (as an alternative to colonoscopy) was performed in 109 subjects: 38 CT colonography, 32 barium enema and 41 minimal-preparation CT scan abdomen/pelvis. Twelve cases of colorectal cancer were diagnosed in this group. Conclusion The major reasons for screening colonoscopy not being performed are individuals declining or a clinical decision, with co-morbidity a major factor. Radiological imaging in selected cases has a significant yield for colorectal cancer. Disclosure of interest None Declared.

PTU-295 Endoscopic ultrasound: changing trends over a decade

Introduction Endoscopic Ultrasound (EUS) is a well established modality, in particular, fine needle aspiration (FNA) is used to sample suspicious lesions. The uptake in EUS is not well documented with the number of procedures performed and their indication unknown. Understanding demand for a procedure is essential for allocating resources in an endoscopy service. Our primary aim was to examine the trends in EUS in our unit and to examine EUS-FNA sensitivity and specificity in pancreatic and non-pancreatic lesions. Method Retrospective review of all EUS procedures from 2002 until 2013 was performed. Data collected included patient demographics, indication for EUS procedure (oesophago-gastric (OG) or pancreatobiliary (PB)) and obtained FNA samples. Pathology results of FNA specimens from 2011–2013 (n = 143) were analysed further with reference to number of passes into any lesion sampled. Sensitivity and specificity rates of FNA were calculated for pancreatic and non-pancreatic lesions respectively. Results The number of EUS procedures rose from 54 in 2002 to 287 in 2013. EUS FNA started in 2006 with the purchase of a linear echoendoscope which was associated with increasing number of EUS. There was a further increase in numbers in 2011 with the appointment of an additional consultant with an interest in EUS. There was a dip in total numbers 2008–2009 due to technical issues. Overall, there was a significant increase in the number of PB EUS comparing 2002 with 2013 (9/54 vs. 207/287, p < 0.0001). There was a significant increase in the number of FNA performed comparing 2002 with 2013 (0/54 vs 48/287, p = 0.0006). EUS-FNA sensitivity for solid pancreatic lesions was 61.5%, for non-pancreatic lesions it was 66% but specificity was 100% in both groups of lesions. In solid pancreatic masses, diagnostic cytology was associated with increased numbers of passes into the lesion compared to non-diagnotic cytology (median 4 passes vs. median 2 passes, p = 0.001). There was no difference number of passes for non-pancreatic lesions with respect to diagnostic cytology rates. Conclusion There has been a significant increase in the utility of EUS in our unit, particularly PB EUS. Our current EUS FNA sensitivity is not good enough but will change practice to have a minimum number of passes for each lesion type. Reassessment of this service will then be conducted to determine whether any other improvements are required. Disclosure of interest None Declared.Abstract PTU-295 Figure 1