Robert Mead

Acetic Acid Spray Is an Effective Tool for the Endoscopic Detection of Neoplasia in Patients With Barrett's Esophagus

BACKGROUND & AIMS Diagnosis of Barretts neoplasia requires collection of large numbers of random biopsy samples; the process is time consuming and can miss early-stage cancers. We evaluated the role of acetic acid chromoendoscopy in identifying Barretts neoplasia. METHODS Data were collected from patients with Barretts esophagus examined at a tertiary referral center, between July 2005 and November 2008 using Fujinon gastroscopes and EPX 4400 processor (n = 190). All procedures were performed by a single experienced endoscopist. Patients were examined with white light gastroscopy and visible abnormalities were identified. Acetic acid (2.5%) dye spray was used to identify potentially neoplastic areas and biopsy samples were collected from these, followed by quadrantic biopsies at 2 cm intervals of the remaining Barretts mucosa. The chromoendoscopic diagnosis was compared with the ultimate histological diagnosis to evaluate the sensitivity of acetic acid chromoendoscopy. RESULTS Acetic acid chromoendoscopy had a sensitivity of 95.5% and specificity of 80% for the detection of neoplasia. There was a correlation between lesions predicted to be neoplasias by acetic acid and those diagnosed by histological analysis (r = 0.98). There was a significant improvement in the detection of neoplasia using acetic acid compared with white light endoscopy (P = .001). CONCLUSIONS Analysis of this large series showed that acetic acid-assisted evaluation of Barretts esophagus detects neoplasia better than white light endoscopy, with sensitivity and specificity equal to that of histological analysis.

Risk stratification system for evaluation of complex polyps can predict outcomes of endoscopic mucosal resection.

BACKGROUND: Apart from size, little is known about what makes a colonic polyp difficult to endoscopically remove. OBJECTIVE: The aim of this study was to evaluate polyp complexity by using a novel classification system and to assess how this affects success at endoscopic resection. DESIGN: This prospective cohort study was conducted at a tertiary referral center in the United Kingdom. INTERVENTIONS: Data were collected on patients referred for endoscopic resection of polyps >2 cm in size. Lesions were classified on the basis of size, morphology, site, and ease of access with the use of a novel scoring system (size/morphology/site/access). Endoscopic resection was performed to resect the lesions. Patients were followed up endoscopically to assess clinical outcomes. MAIN OUTCOME MEASURES: The primary outcomes measured were the endoscopic cure and complication rate by size/morphology/site/access grade and the cost savings of endoscopic resection over surgery. RESULTS: Endoscopic resection was performed on 220 patients (135 male) with 220 polyps, mean size of 43 mm (range, 20 mm–150 mm). Thirty-seven percent were classified as size/morphology/site/access 2 or 3; 63% were classified as the most challenging size/morphology/site/access level 4. Complete endoscopic clearance was achieved in 90% of cases with the first endoscopic resection attempt, improving to 96% with further endoscopic resection attempts. There were complications in 18 of 220 (8.1%) of cases. Complications were independent of lesion size and location but were affected by size/morphology/site/access grade (p = 0.018). Probability of clearance at first endoscopic resection attempt was affected by lesion complexity. Size/morphology/site/access 2 and 3 = 97.5 vs SMSA 4 = 87.5% (p = 0.009). Probability of cancer was not affected by size/morphology/site/access grade. For the whole cohort, endoscopic resection represented a cost saving of £726,288 (

Endoscopic mucosal resection of colonic polyps: a large prospective single centre series

1,123,858.05) over that of surgery. LIMITATIONS: The main limitation of this study is that it is a single-center, single-endoscopist series. CONCLUSIONS: The size/morphology/site/access scoring system is easy to use and provides valuable information on the lesion complexity and success and complication rates of endoscopic resection. This can be used for service planning, training endoscopists, and providing prognostic information for patients.

OC-055 A prospective study validating a novel and simple polyp classification and comparing the outcomes between a Japanese expert and Western expert in a UK setting: Abstract OC-055

Introduction The traditional approach to the management of large colonic polyps has been surgery. Endoscopic mucosal resection (EMR) is an emerging technique for the removal of large colorectal lesions. Most of the published literature comes from Japan, with limited data regarding safety, efficacy and outcome in the west. We aim to assess the feasibility and safety of EMR in the colon in a western setting. Methods A prospective review of patients undergoing EMR of colonic neoplasia >2 cm in size was performed. All patients were tertiary referrals from experienced consultants. The polyps were considered technically challenging due to size, difficult lesion access (peri-diverticular, peri-appendicular, touching the dentate line), or recurrences on previous EMR scars. They were referred to our service prior to surgical referral. Lesions were assessed using indigocarmine chromoendoscopy, and lesions with features suggestive of invasive malignancy were excluded. Completeness of resection was recorded by the endoscopist. Patients were followed up endoscopically where appropriate to assess for incomplete resection or recurrence. Results 214 patients with 214 polyps underwent EMR. The mean size was 43 mm (range 20–150). 180 were flat and 46 were on the right side of the colon. Primary reason for referral was the size in 91 cases, lesion access in 107 cases and a previous failed resection in 16 cases. Endoscopic clearance at first attempt was achieved in 92% of cases. Residual or recurrent disease was seen at the first endoscopic follow-up in 17% cases requiring further endoscopic resection. Overall endoscopic cure has been achieved in 95% of patients. Three patients went to surgery due to failed endoscopic resection. There were procedure related complications in 15/214 (7%) of cases. This consisted of delayed bleeding in nine patients, immediate bleeding in two cases and four post polypectomy syndrome. The risk of complications was independent of size or location. There were 13 cancers (7 > sm1 invasion) in flat polyps and 4 pedunculated polyp cancers (1 > Haggitt 2). 13 of these cases underwent surgery. Taking the cost of surgery as £12,000 and the cost of EMR as £561 this represents a potential cost saving of £2,231,946 for the cohort. Conclusion This is the largest UK series demonstrating that EMR is a safe and effective treatment for large difficult polyps with an overall complication rate of 7%. It avoided surgery in 93% of cases with substantial cost savings. We believe that EMR of large and difficult benign polyps should be the new standard of care.

PTU-164 Cost Effectiveness of an ER Dominant Approach in the Management of High Grade Intraepithelial Neoplasia and Mucosal Cancer in Barrett’S Oesophagus

Introduction Small hyperplastic Polyps have a very low malignant potential. However, they are currently being removed due to the lack of in-vivo histology techniques. Japanese endoscopists have published excellent results based on Kudos pit pattern. However, most of the published literature has used zoom endoscopy and vital stains, such as cresyl violet, and Kudos classification is difficult and inpractical to apply in a UK setting. Prospective validation of a new and easy mucosal pattern classification (NAC) Prospective comparison of the diagnostic accuracy of NAC classification when assessing colonic polyp using non-zoom endoscopes and indigo carmine dye spray. Methods NAC classification is based on three features: Mucosal patterns, vascular patterns and vascularity. Based on this polyps can be graded as N (non-neoplastic) A (adenoma) C (cancer). Fujinon non-zoom EC-590 colonoscopes with the EPX 4400 processor was used. Polyps were prospectively and independently assessed by a Japanese and a UK expert during screening colonoscopy, before and after indigo carmine dye spray. The lesions were subsequently removed to obtain the true diagnosis. MathCAD was used to process the statistics and chi2 test performed. Results A total of 121 polyps were evaluated. 60 polyp pictures from a prospective library for the validation exercise, and 61 polyps were prospectively examined during colonoscopy. Polyps evaluated during live endoscopy (61) showed the median polyp size was 7 mm (range 3–40 mm) (see Abstract 055). A chi2 test did not show any significant difference between the Japanese (Limb J) and UK (limb U) results (p=0.8). Abstract OC-055 Japan (J) UK (U) Histology Hyperplasitc (N) 18 20 15 Adenoma (A) 34 32 37 Cancer (C) 9 9 9 Sensitivity was 91% (J) and 87% (U). Specificity was 93% for J and U. Diagnostic accuracy was 92% (J) and 89% (U).

PWE-178 Feasibility, safety and efficacy of endoscopic resection of upper gastrointestinal submucosal lesions in a western setting

Introduction Endoscopic resection (ER) is an established effective treatment for high grade intraepithelial neoplasia (HGIN) and intramucosal cancer (IMC) arising in Barrett’s oesophagus. ER can lead to recurrence so it is suggested that all patients should undergo radiofrequency ablation (RFA) after ER as a complimentary treatment strategy. However no comparative study to support this concept has been performed. We aimed to compare the cost-effectiveness of an EMR-dominant approach vs an EMR-RFA approach for the treatment of HGIN and IMC in Barrett’s oesophagus. Methods All ER procedures between 2005 and 2012 were recorded in a prospective database which was analysed. Demographic data, histology, procedure success, long-term outcome and complications were assessed. Costs were calculated using NHS HRG codes plus equipment costs for ER and RFA. Results 92 patients were treated for dysplastic Barrett’s oesophagus or early Barrett’s cancer by ER. The mean age at first procedure was 69 years and 87% of the patients were male. 21 of 92 patients had advanced histological features on the initial ER specimen and were referred for surgical or oncological treatment. Of the remaining 71 cases, 63 have follow-up data with a mean duration of 4.3 years. 59 of 63 cases (94%) had successful eradication of HGIN/IMC by ER. The remaining 4 patients were referred for surgery for advanced disease (3) or extensive bulky disease not amenable to ER (1). ER was successful in a mean of 1.46 procedures per patient (range 1–3). Complication rate was 5.2% (4 bleeds, 1 microperforation, 2 strictures). Additional RFA was used in 11 cases. 12 (20%) of patients developed recurrence of HGIN/IMC during follow-up requiring further endoscopic therapy. 2 (3.4%) patients developed more advanced Barrett’s neoplasia during follow-up. The calculated cost per patient of an ER-dominant approach is £4125 compared to £8868 per patient for an RFA dominant approach. Conclusion ER acted as an accurate and safe staging procedure in up to 23% of cases found to have advanced histology. ER is an effective and safe treatment for HGIN/IMC within Barrett’s oesophagus without the need for routine RFA and can be performed successfully in a UK centre. However the recurrence of HGIN/IMC is not uncommon and therefore close follow-up is required to identify and treat it at an early stage. An ER-dominant approach may offer significant cost-savings compared to an RFA-dominant approach without compromising overall outcomes. Disclosure of Interest None Declared

OC-085 Circulating tumour markers can discriminate between patients with and without oesophageal neoplasia

Introduction Submucosal lesions are a relatively common finding at upper gastrointestinal endoscopy. Endoscopic resection (ER) may be warranted in larger lesions, those causing symptoms or those with malignant potential. However submucosal origin makes these lesions difficult to resect by an endoscopic approach. Advances in resection techniques have made this feasible. Methods Portsmouth Hospitals is a tertiary referral centre for advanced ER. All ER procedures between 2005 and 2011 were recorded in a prospective database. We analysed our database to identify all submucosal lesions removed by ER in the past 7 years. All procedures were carried out by a single skilled endoscopist. Demographic data, histology, procedure success, long-term outcome and complications were assessed. Results A total of 161 lesions were treated by UGI ER between 2005 and 2011. 14 of 161 were submucosal lesions. Nine of the 14 patients were female and the mean age was 54.3 years (range 34–69 years). Five lesions were located in the oesophagus, seven in the stomach and two in the duodenum. Histology revealed granular cell tumour (3), neuroendocrine tumour (5), inflammatory fibroid polyp (2), lipoma (2), gastrointestinal stromal tumour (1), Leiomyoma (1). All cases were successfully treated in a single ER session of which 6 cases were treated by conventional EMR, 9 by ESD techniques. The single complication was a microperforation during ESD of an oesophageal GIST which was endoscopically clipped. The patient was managed conservatively with intravenous antibiotics and was discharged after 3 days. There were no cases of significant bleeding and no patient required surgery. After a mean follow-up of 19.5 months all patients remain well and have no signs of recurrence. Conclusion The caseload of UGI ER for submucosal lesions in low with an average of two cases per year in a large UK specialist centre. The majority of cases required ESD skills and therefore these cases should be treated in specialist centres with expertise in this technique. Outcomes and complication rates were acceptable in this small series and major surgery was avoided in these patients reducing costs and bed occupancy.Abstract PWE-178 Table 1 Oesophagus Granular cell tumour 3 GIST 1 Leiomyoma 1 Gastric Neuroendocrine tumour 4 Lipoma 1 Inflammatory fibroid polyp 2 Duodenum Neuroendocrine tumour 1 Lipoma 1 Competing interests None declared.

Su1117 Prevalence, Management and Outcome of Submucosally Invasive Cancers in a Western Oesophagogastric EMR Population

Introduction Oesophageal cancer is the fastest rising cause of gastro-intestinal cancer in the UK, and associated with a poor prognosis. Early diagnosis represents the best opportunity for cure, but early disease is often asymptomatic. Current surveillance programs improve outcome, but rely on two yearly endoscopic screening of previously identified Barretts oesophagus patients. This has limited sensitivity and acceptability to patients. New endoscopic treatments for oesophageal dysplasia can avoid major surgery, but discriminating between patients with and without invasive disease can be challenging. A discriminating diagnostic blood test may offer improved patient outcome. Methods In this study, we optimised a series of promising diagnostic markers utilising circulating free DNA (cfDNA), with a preparation method allowing small DNA fragments to be purified. cfDNA was isolated from 115 patients including a “normal” population of 44 patients (Barretts oesophagus or normal endoscopic findings). Twenty-five patients had high grade dysplasia (HGD) or intra-mucosal cancer (IMC), and 46 patients had invasive cancer. In each case real time quantitative polymerase chain reaction (RT-PCR) was performed for Line 1 79 bp (quantitative total DNA marker), Line 1 300 bp, Alu 115 bp, Alu 247 bp and mitochondrial primers. Each marker was analysed for differences between normal, HGD and IMC, and invasive cancer populations using Mann–Whitney U tests and ROC curves. The best performing were analysed in combination by logistic regression. A Bonferroni correction was applied. Results The average age of the normal population group was 56.1 years, the HGD and IMC population group 70.0 years, and the cancer population group 68.9 years. The mean total DNA (ng/ml) was 10.8, 14.1, and 19.2 respectively. Mean DNA marker levels ng/ml. Analysing total DNA, mitochondrial DNA and Line 1 300bp fragment DNA levels, there were highly significant differences between the normal group vs all dysplastic and cancerous patients (p ≤ 0.003). Conclusion The combination DNA marker was able to discriminate the normal population from all dysplasia and cancer patients with a ROC curve of 0.778. This may offer the prospect of a simple blood test to stratify patients and improve surveillance for dysplasia and early cancer. The same model was able to discriminate the normal population from invasive cancer patients with a ROC curve of 0.847. This may help in the rapid identification of patients who require surgery.Abstract OC-085 Table 1 Mean DNA Total Mito 115 300 247 79/300 115/247 “Normal” 10.8 1.1 35.6 1.8 3.1 6.3 11.0 HGD + IMC 14.1 4.2 42.6 3.2 4.6 6.1 10.3 Inv. cancer 19.2 6.2 76.9 5.3 4.9 8.8 16.3 Competing interests None declared.

Upper gastrointestinal EMR service: long-term feasibility, safety, efficacy and cost effectiveness from a large UK centre

Introduction Risk of lymph node metastases depends on good or bad prognostic features of submucosally (SM) invasive cancer specimen following endoscopic resection (ER). Invasion limited to SM1 level, lack of lymphovascular invasion and well differentiated grade are good prognostic features and may indicate that radical resection is not required following ER. However, depth of SM invasion can be very difficult to assess in ER specimens and hence a “safe” strategy would be to offer radical surgery to all patients with SM invasive disease, irrespective of other features. This is the policy we follow. We aimed to evaluate the outcome of these cancers in an ER population. Methods All Upper Gastrointestinal ER procedures for the period 2005–2011 were recorded on a prospective database. All procedures were carried out by a single skilled endoscopist. Demographic data, histology, procedure success, long-term outcome and complications were assessed. Careful endoscopic assessment using chromoendoscopy, plus CT/EUS where appropriate, were performed prior to attempted endoscopic resection and afterwards if indicated. Results Cancer with submucosal invasion was detected in 26 of 123 (21.1%) cases of oesophagogastric neoplasia. 22 patients were male and the mean age was 75.2 years (range 54–84 years). Submucosal invasion was present in 16 of 74 (21.6%) lesions arising in Barrett9s oesophagus, 4 of 7 (57.1%) oesophageal squamous lesions and 6 of 39 (15.3%) gastric lesions. All patients were discussed at a multidisciplinary meeting and those patients who were fit were offered radical surgery or chemoradiotherapy. Six patients who were offered radical surgery opted for conservative management with endoscopic follow-up. 14 patients proceeded to radical surgery; six of these had no residual cancer in surgical specimen and eight had residual cancer present. 11 of the 14 are currently in disease free survival, two died of recurrence and one died of post-operative complications. Two patients received radical chemoradiotherapy; one is in disease free survival, the other died of advanced adenocarcinoma. One patient received radical radiotherapy and remains free of recurrence. Nine patients received conservative/endoscopic management; of these seven had disease free survival, two died of metastatic adenocarcinoma. Mean follow-up was 32 months. Conclusion Our results show that submucosal invasion is found in a significant proportion of patients undergoing upper gastrointestinal ER. Management of SM invasive cancer following ER remains challenging and our series shows a wide variation in management outcomes. Further research to guide the optimum management of this group of patients is required. Competing interests None declared.

PP-004 A prospective evaluation of acetic acid enhanced chromoendoscopy in the identification of dysplasia within Barrett's oesophagus

Introduction Endoscopic resection (ER) is an accepted treatment of early upper gastrointestinal neoplasia in Europe, but surgery remains the gold standard in the UK due to lack of data. We started an upper gastrointestinal ER service in 2005 and are reporting our 6 year outcome data. We serve six different regional cancer centres. Methods We analysed our database of all upper gastrointestinal (UGI) endoscopic resection procedures performed at our centre for the period 2005–2010. All procedures were carried out by a single skilled endoscopist. Demographic data, histology, procedure success, long-term outcome and complications were assessed. Results We have performed 160 UGI ER procedures (108 oesophageal (O), 29 gastric (G), 33 duodenal/ampullary (D)) in 127 patients (O=75, G=25, D=27). Mean age was 65.9 years (range 25–94). A mean of 1.32 UGI ER procedures were performed per patient (range 1–5). All neoplastic cases were diagnosed as high grade dysplasia or intramucosal cancer prior to EMR. Overall complication rate was 5.0%. Specific complications were four procedural bleeds and two delayed bleeds (all controlled endoscopically) one full thickness perforation clipped endoscopically and one episode of pancreatitis. There were no cases of procedure related mortality. 25 patients (19.7%) were upstaged, having been found to have sm1 invasion or deeper on histological examination of the initial ER specimen. This group were considered for radical treatment if fit, or conservative management if unfit or through patient choice. 16 patients (O=11, G=4, D=1) proceeded to radical surgery, of which 2 patients died of postoperative complications and 2 patients died of local recurrence; the other 12 remain well. 2 patients received chemo/radiotherapy; 1 died of advanced oesophageal cancer, the other remains well. Of the remaining 102 patients complete local remission was achieved in 79.4% of cases following a single ER procedure, and in 97.1% overall. After a mean 2.57 years follow-up; 4% of all patients are known to have recurrence or metachronous disease and are awaiting further ER. Development of our service has potentially led to a cost saving of £91 270 per year, plus 170 bed days saved per year through reduced requirement for radical surgery. Conclusion Our data demonstrates the long-term feasibility, efficacy and safety of an innovative ER service. It provides valuable information about the number and type of patients requiring this service helping inform future planning and commissioning. Our data demonstrates significant cost savings for the NHS.