Timothy R. Elliott

Compartment-specific immunity in the human gut: properties and functions of dendritic cells in the colon versus the ileum

Objective Dendritic cells (DC) mediate intestinal immune tolerance. Despite striking differences between the colon and the ileum both in function and bacterial load, few studies distinguish between properties of immune cells in these compartments. Furthermore, information of gut DC in humans is scarce. We aimed to characterise human colonic versus ileal DC. Design Human DC from paired colonic and ileal samples were characterised by flow cytometry, electron microscopy or used to stimulate T cell responses in a mixed leucocyte reaction. Results A lower proportion of colonic DC produced pro-inflammatory cytokines (tumour necrosis factor-α and interleukin (IL)-1β) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4+FoxP3+IL-10+ (regulatory) T cells. There were enhanced proportions of CD103+Sirpα− DC in the colon, with increased proportions of CD103+Sirpα+ DC in the ileum. A greater proportion of colonic DC subsets analysed expressed the lymph-node-homing marker CCR7, alongside enhanced endocytic capacity, which was most striking in CD103+Sirpα+ DC. Expression of the inhibitory receptor ILT3 was enhanced on colonic DC. Interestingly, endocytic capacity was associated with CD103+ DC, in particular CD103+Sirpα+ DC. However, expression of ILT3 was associated with CD103− DC. Colonic and ileal DC differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, and this corresponded to their ability to imprint these homing markers on T cells. Conclusions The regulatory properties of colonic DC may represent an evolutionary adaptation to the greater bacterial load in the colon. The colon and the ileum should be regarded as separate entities, each comprising DC with distinct roles in mucosal immunity and imprinting.

Resolution of norfloxacin-induced acute liver failure after N-acetylcysteine therapy: further support for the use of NAC in drug-induced ALF?

Liver injury due to idiosyncratic drug reactions can be difficult to diagnose and may lead to acute liver failure (ALF), which has a high mortality rate. N-acetylcysteine (NAC) is effective treatment for paracetamol toxicity, but its role in non-paracetamol drug-induced ALF is controversial. We report on the use of a validated bedside tool to establish causality for drug-induced liver injury (DILI) and describe the first case of resolution of norfloxacin-induced ALF after NAC therapy. NAC is easy to administer and generally has a good safety profile. We discuss the evidence to support the use of NAC in ALF secondary to DILI and possibilities for further clinical research in this field.

PWE-067 Does Endocuff-vision Improve Adenoma Detection

Introduction Although colonoscopy is considered the optimal procedure for bowel cancer screening, it remains an imperfect tool for cancer prevention, due to missed adenomas and early cancers. Optimal imaging modalities, innovative scopes and accessories (cap-assisted colonoscopy) have attempted to decrease the adenoma miss rate. Adenoma detection rates (ADR) have been shown to be a key performance indicator Methods Endocuff-vision is a simple accessory mounted at the end of the scope with a proximal row of 6mm length soft plastic, finger-like projections. During scope insertion, these projections invert towards the shaft of the tube and during withdrawal they evert to hold back the colonic folds augmenting the forward endoscopic views. ADRs were recorded and evaluated for screening colonoscopy procedures before and after introduction of Endocuff-vision. Results To date, four screening endoscopists (BPS, STG, CF, AH) have used the Endocuff-vision as part of a clinical evaluation process form August 2013 until November 2013. From our local Bowel Cancer Screening Program database, the figures of caecal intubation rate (CIR) and the ADRs of the screening endoscopists during April 2013 to July 2013 before Endo-cuff were retrieved: BPS: CIR-100%/ADR-62.72%, STG: CIR-95.84%/ADR-40.03%, CF: CIR-93%/ADR-36.76%, AH: CIR-96.25%/ADR- 55.35%. Prior to the introduction of the Endocuff-vision, the cumulative CIR was 96.27% and ADR was calculated to be 48.71%. The total number of procedures where Endocuff-vision has been mounted was in 30 occasions (BPS-10, STG-11, CF-3, AH-6) with similar CIR rates but increased cumulative ADR of 65.5%. On 3 patients the Endocuff-vision was electively removed from the scope due to insertion difficulties through fixed sigmoid colonic segments secondary to severe diverticular disease. There were no adverse events reported during the trial evaluation period. Conclusion In this small pilot study, use of the Endocuff appeared to improve the ADR by 17%. There were no complications from the use of the cuff although it was electively removed in 3 cases with severe sigmoid colon diverticulosis. Further randomised evaluation of this simple novel device is warranted. Disclosure of Interest None Declared.

Severe perianal shingles during azathioprine and budesonide treatment for Crohn's disease—preventable with zoster vaccine?

Patients with inflammatory bowel disease (IBD), particularly those on immunosuppressive medications, suffer a high incidence of, and worse clinical outcomes relating to, herpes zoster (HZ) reactivation. We report on the presentation and management of a patient with Crohns disease who developed severe perianal HZ after starting azathioprine and oral budesonide treatment. The zoster vaccine may prevent such zoster reactivation in patients with IBD. The zoster vaccine is effective in decreasing the risk of HZ in older adults but its role in younger adults and those with IBD has not been tested prospectively. A review of the potential risks and benefits of this live vaccine in patients with IBD and an approach to further determining its role in this patient population is discussed.

PWE-377 Pitfalls in piecemeal resection of complex colorectal polyps

Introduction The role of piecemeal endoscopic mucosal resection (p-EMR) for sessile/flat colonic polyps previously destined for surgery is expanding. However, surgery remains appropriate in some cases. The objectives of this study were to determine the primary reasons in this decision-making, and factors associated with polyp non-excision, and the presence of submucosal invasive cancer (SMIC). Method A prospective observational cohort study of all polyps referred for consideration of p-EMR to our tertiary centre between January 2010 and August 2012 was performed. For each case, a detailed endoscopic evaluation of the polyp was performed prior to the polyp being excised or not excised. The primary reason for polyp non-excision was documented. Univariable and multivariable analyses were performed to determine factors associated with (i) non-excision and (ii) submucosal invasive cancer (SMIC). Results Seventy-one of 419 (17%) polyps were not excised (p-EMR not attempted in 52/71 and abandoned in 19/71 cases). The primary reasons for non-excision were; suspected SMIC (36/71), polyp size +/- location, poor polyp access and patient comorbidities. On multivariate analysis, factors associated with polyp non-excision were increasing polyp size (p < 0.001), site (caecum and sigmoid colon, p < 0.001), surface features suggestive of SMIC (Paris IIc, Kudo V and NICE III, all p < 0.001) and female gender (p = 0.04). SMIC was present in 9% of polyps >2cm and was more prevalent in the rectum to the descending colon than in the transverse colon to caecum (p = 0.04). Although surface features were associated with SMIC on univariable analysis and the positive predictive values are relatively high (Paris IIc 80%, Kudo V 86% and NICE III 86%)., the sensitivity of these features for a diagnosis of SMIC were relatively low (Paris IIc 11%, Kudo V 49% and NICE III 51%). Conclusion A percentage of polyps referred to a tertiary institution were not suitable for p-EMR, most commonly because of suspicion of SMIC. Specific surface features of malignancy may be present but the physician’s overall endoscopic evaluation was also useful in predicting suitability of polyps for p-EMR. Disclosure of interest None Declared.

PTH-041 Large (<4 cm) and giant (≥4 cm) colorectal polyps: comparison of piecemeal resection outcomes

Introduction Piecemeal Endoscopic Mucosal Resection (p-EMR) is a standard and safe endoscopic technique for resection of large colorectal polyps (>2 cm). Limited data are available regarding p-EMR of giant polyps (>4 cm). Method A prospective study recording short and long-term outcomes after p-EMR for colorectal polyps > 2 cm between Jan 2010 and August 2012 was conducted. We compared two cohorts of patients: group-A with large polyps (2 to <4 cm) vs group-B with giant (≥4 cm) polyps. Chi-square/Fischer’s tests were performed between categorical variables including patient demographics/polyp features/techniques applied {p-EMR with spiral snare and hybrid p-EMR). Our primary outcome was to compare the safety, efficacy and complication rate between the two groups. Results Group-B patients were older than group-A patients (mean 70.6 vs. 67.8 yrs, p = 0.01) and were more likely to have come from a tertiary referral source (p = 0.05). Large polyp referrals were almost twice as frequent as giant polyp referrals (218 vs. 123, p < 0.001). Median polyp size was 2.5cm in group-A and 5cm in group-B. Giant polyps were most commonly found in the recto-sigmoid segment (26% rectum and 28% sigmoid, p < 0.001), whilst large polyps were more evenly distributed throughout the colon. No significant difference in cancer prevalence was recorded between the groups. Endoscopic excision was complete in 89% in large (median time 18min) and in 70% in giant groups (median time 38min). All large polyps were excised in one session, whilst 4% of giant polyps required more than one session. Incomplete submucosal lift (46% vs 63%, p = 0.002) and difficult polyp position (45% vs 63%, p < 0.001) were more common in giant polyps. Spiral snare EMR (6% vs 28%, p < 0.001) and hybrid (0% vs 7%, p < 0.001) techniques were more commonly used in giant than in large polyps. Procedural bleeding occurred more frequently in giant polyps (5% vs 17%, p < 0.001). Delayed bleeding was also significantly higher in giant polyps (15% vs 34%, p < 0.001), but hospitalisation or further intervention did not vary significantly by polyp size. The overall long-term recurrence at 24 months was 17% (11% vs 28%, p = 0.02). The follow up occurrence was more frequent for giant polyps at 3 month (43% vs 72%, p < 0.001) and 9 month (14% vs 26%, p = 0.007) intervals. Benign recurrence requiring surgery and the cancer prevalence did not vary between polyp size group. Conclusion Piecemeal resection is a safe and efficacious modality for the resection of colorectal polyps >4 cm. However, these giant polyps more often require spiral snare or hybrid resection techniques and their higher adenoma recurrence rate post p-EMR may dictate shorter surveillance intervals. Disclosure of interest None Declared.

OC-047 A multi disciplinary team (mdt) approach for complex benign colo rectal polyps: a tertiary referral centre experience

Introduction Multi-disciplinary team (MDT) working is an established part of cancer care. Limited data is available on their impact for benign complex colorectal polyps. Increased numbers of these polyps are referred to our tertiary centre for further management. Method Polyp MDT comprising of gastroenterologists, colorectal surgeons and histopathologists was established in January 2013 to discuss the management of complex polyps (large or recurrent polyps or those where endoscopic access was difficult). Cases that were referred to individual consultants and had a provisional management plan made were then discussed at the MDT and a consensus management plan was agreed. The impact of MDT management plan was then evaluated. Results 96 cases were discussed between January 2013 and October 2014. Of those 75 (78%) were tertiary referrals. The reasons for polyp complexity included large polyps 53 (55%), those with difficult access 52 (54%) and previous failed attempt 35 (36%). Majority of the polyps were in recto sigmoid, 49 (51%) or in caecum, 32 (32%). In 38 cases (40%) provisional management plan was changed after MDT discussion. This plan was then followed in 80/96 (82%) cases. Combined surgical-endoscopic approaches were proposed in 68 cases (65%). 25/96 patients had polypectomy during a single hospital visit. The remaining cases (71/96) needed further assessment before attempted polypectomy. Complete polypectomy was achieved in 85/96 (89%) of patients: endoscopically in 75/96 cases (78%): 38 by endoscopic excision alone and 37 by combined endo-surgical approaches. Ten polyps were resected surgically. Of the remaining 11 patients no polyps were found in 2 of those referred, 2 patients were referred back their local hospital for surgery, 5 were not fit for a polypectomy and are under surveillance, 1 had metastatic colorectal cancer and 1 declined any intervention. Cancer was found in 7/96 polyps and 6/7 had surgical resection (the remaining patient had metastatic disease). Conclusion The polyp MDT consensus management plan led to a change in the proposed management in almost half of the patients. This resulted in complete polypectomy for a large majority of patients referred to our service. Disclosure of interest None Declared.

PTU-010 Trans-anal submucosal endoscopic resection – taser compilation

Introduction Current surgical/trans-anal and endoscopic techniques for resection of very large (>5 cm)/complex rectal polyps (CRP’s) remain problematic due to technical complexity, inadequate excision and safety issues. Method Four patients with complex benign rectal polyps, two circumferential lesions and two with severe submucosal scarring due to multiple previous resection attempts were resected utilising the TASER approach. Prior to referral, all patients were being considered for proctectomy due to failed conventional endoscopic therapy. Trans-Anal-Submucosal-Endoscopic-Resection (TASER) involves placing the Gelport-Path platform across the anus to facilitate three air-tight rectal access ports. An endoscope through one port was then used to provide vision, gas insufflation and carry resection knives, snares and haemostatic devices while the two remaining ports were used for laparoscopic retractors, suturing or cutting devices. The purpose of this case series is to demonstrate the feasibility of this new hybrid, endo-surgery approach. Results Four TASER procedures were employed in 4 patients (mean age 63 years, 2 males/2 females) with 4 CRPs (mean size 75 mm/range, 50–130 mm). Complete excision was achieved in all polyps. Mean procedure time was 185 min/range, 65–480 min. TASER-aided resection was performed utilising Endoscopic Submucosal Dissection/ESD in 1/4, ESD+Piecemeal-Endoscopic-Mucosal-Resection/P-EMR in 2/4 and ESD + Trans-Anal-Minimally Invasive Surgery/TAMIS in 1/4. In the two cases of severe submucosal fibrosis, dissection resulted in small full-thickness, extra-peritoneal defects that were easily repaired with suturing and clips. No episodes of bacteremia or delayed bleeding occurred. All patients had an uneventful recovery and were discharged within 24 hrs. First follow up colonoscopy showed slight luminal narrowing without structuring and no recurrence in 2 patients and first follow up is pending in the other two cases. Conclusion TASER appears to be a safe and effective endo-surgical approach providing a flexible platform for the minimally-invasive management of extensive/recurrent rectal polyps, previously destined for surgery. Disclosure of interest None Declared.

OC-048 Trans-anal Submucosal Endoscopic Resection (taser): A New Endo-surgical Approach To The Resection Of Giant Rectal Lesions

Introduction Trans-anal surgical (TEMS/TAMIS) and advanced endoscopic resection (ESD, P-EMR) procedures have the potential to provide complete and successful eradication of giant rectal polyps. Both approaches however have limitations in terms of practicality and safety. We describe a new endo-surgery technique called Trans-Anal Submucosal Endoscopic Resection (TASER) which combines the advantages of both the endoscopic and transanal surgical approach. Methods The GelPoint Path trans-anal access port allows simultaneous passage of an endoscope and two laparoscopic retractors. Working with the endoscopic image the laparoscopic retractors (Johen 33 mm forceps) allow dynamic tissue retraction to facilitate endoscopic dissection (Flush knife–BT) or snare placement (Olympus snare master/spiral snare). All procedures were performed under general anaesthesia and with patients in the lithotomy position. Results Eleven patients (mean age 55 years, 3 male/8 female) underwent TASER for 11 lesions, distributed from the lower rectum to the recto-sigmoid junction and with a median size of 85 mm, range 40–180 mm. Polyp morphology was (3/11 flat (Paris 2a), 4/11 sessile (Paris 1s) and 4/11 mixed type (Paris 2a+1s). In all cases a circumferential mucosal incision was made and histology confirmed free lateral margins in all cases. 10/11 rectal polyps were adenomatous and one had a small focus of moderate differentiated adenocarcinoma (incomplete local excision). Complete endoscopic excision in a single session was achieved in 10/11 cases (91%). Median completion time of the procedure was 215 min, range 120–480 min. Tissue retraction was used in every case and resection was completed by ESD alone (4/11), ESD + EMR (4/11) ESD + EMR + trans-anal surgical excision (3/11). Intra-procedural bleeding occurred in 8 cases, controlled with hemostatic clips and Coagrasper (Olympus); surgical suturing was required in one case (1/8). Prophylactic clips (2/11) and surgical sutures (1/11) were placed to treat deep muscle injury. There were no perforations and no delayed bleeding episodes. Patients were discharged the day following TASER in all cases. Surveillance at 3–6 months revealed no recurrence in 6 cases, whereas in four cases the follow up procedure is still pending. The malignant polyp case was referred to surgery with a good clinical outcome (T3, N0, M0). Conclusion TASER appears to be a safe and efficient approach providing an optimal platform for resection of large rectal lesions. In our experience it provides the optimal platform for the minimally-invasive management of these high risk lesions. Disclosure of Interest None Declared.

PWE-068 Endoscopic Resection Of Complex Colonic Polyps – Where Do The Boundaries Lie?

Introduction The role of endoscopic resection for colonic polyps previously destined for surgery is expanding. However, surgery remains appropriate in some cases. The aim of this study was to examine tertiary polyp referrals that did not undergo endoscopic polypectomy. The objectives were to determine (i) the proportion of polyps referred for polypectomy that were not endoscopically resected, (ii) the primary reason in this decision-making and (iii) factors associated with polyps that were not endoscopically resected. Methods A prospective observational study of all polyps referred for endoscopic resection (ER) to a tertiary centre between January 2010 and August 2012 was performed. For each case, ER was either completed, abandoned or not attempted. The primary reason for abandoning or not attempting ER was documented. Demographics, polyp characteristics and histology were recorded and a comparative analysis (using chi-square test and independent-samples T test) was made between patients in whom ER was abandoned or not attempted with those in whom ER was completed. Results ER was either abandoned (n/29) or not attempted (n/55) in 84 of 423 polyp referrals. This was most commonly because of suspected invasive cancer (45/84). Of these 45 polyps, 12 had characteristic macroscopic features of cancer on inspection. In 24/45, invasive cancer was suspected after advanced endoscopic examination (including surface morphology (Paris/NICE/Kudo) classification and forceps palpation). In 9/45, invasive cancer was only suspected during attempted ER, which was then abandoned. The remaining 41/84 polyps for which ER was abandoned or not attempted appeared benign. The positive and negative predictive values of endoscopic evaluation for the diagnosis of invasive cancer were 86% and 96% respectively. The benign-appearing polyps were not endoscopically resected because of (i) a high risk location (ie. overlying the appendix, IC valve or a diverticulum), n = 12; (ii) difficult access, n = 12; (iii) size ≥ 5 cm combined with other factors, n = 8; (iv) age/comorbidities, n = 4 or (v) poor tolerance of colonoscopy, n = 2. Forty-six percent of these benign polyps were in the caecum. In comparison with patients who underwent complete ER, those in whom ER was abandoned or not attempted were more likely to be female (56 vs. 37%, P < 0.001), had larger mean polyp size (4.7 cm vs 3.7 cm P < 0.001), and had a higher incidence of polyp cancer on histology (47 vs. 2.7% P < 0.001). Conclusion Twenty percent of polyps referred to a tertiary institution for polypectomy may not be suitable for endoscopic resection. This is most commonly due to the presence of invasive cancer which can usually be recognised by endoscopic examination. Disclosure of Interest None Declared.