B Hayee

Fecal M2-Pyruvate Kinase (M2-PK): A Novel Marker of Intestinal Inflammation

Background: Surrogate markers of bowel inflammation are increasingly being recognized as important, not only as markers of disease activity in inflammatory bowel disease (IBD) but also to differentiate irritable bowel syndrome (IBS) from IBD. The dimeric M2‐isoform of pyruvate kinase (M2‐PK) has been reported to be elevated in fecal specimens from colorectal cancer (CA) patients, but its role in IBD is unknown. This study investigated the usefulness of fecal M2‐PK in cohorts of patients with IBD, IBS, and CA. Methods: Stool samples were obtained for calprotectin and M2‐PK measurements in patients with previously diagnosed IBD or new patients being investigated for lower gastrointestinal (GI) symptoms in a UK university hospital. Other investigations were performed as directed by the investigating physician and patients with known IBD were assessed for disease activity by a physician global assessment, Harvey–Bradshaw index (HBI), or endoscopic grading. Results: Fecal M2‐PK and calprotectin measurements were obtained for 148 patients: 50 with ulcerative colitis (UC); 31 with Crohns disease (CD), 43 with irritable bowel syndrome/functional bowel disorders (IBS); 7 with colorectal CA, and 17 with miscellaneous conditions (excluded from the analysis). Median M2‐PK values (U/mL) were significantly elevated in UC: 20.0 (95% confidence interval [CI] 5.4–69.0, P < 0.0001), CD: 24.3 (95% CI 6.4–44.0, P < 0.0001), and CA: 7.0 (95% CI 4.3–88.0, P < 0.0006) compared to IBS: 0.1 (95% CI 0.0–3.2). There was a strong linear correlation of M2‐PK with calprotectin levels. A predetermined cutoff level of 3.7 U/mL for a normal M2‐PK test produced a sensitivity, specificity, and positive predictive value (PPV) of 73%, 74%, and 89%, respectively, for organic disease. Furthermore, M2‐PK levels were significantly elevated in active, compared to inactive, disease for CD (30 versus 0.55 U/mL, P < 0.005) and UC (40 versus 1.2 U/mL, P = 0.006), respectively. Conclusions: Fecal M2‐PK is elevated in IBD as well as in CA patients and is a sensitive and relatively specific marker for organic GI pathology, with a PPV of 89%. Furthermore, it appears to be a potentially valuable, noninvasive marker of disease activity in IBD.

Vedolizumab in Inflammatory Bowel Disease Associated with Autoimmune Liver Disease Pre- and Postliver Transplantation: A Case Series.

To the Editor: Inflammatory bowel disease (IBD) associated with primary and autoimmune sclerosing cholangitis seems to represent a distinct clinical entity in comparison with “classical” ulcerative colitis and Crohn’s disease. Antitumor necrosis factor (TNF) therapy can be efficacious, but systemic complications remain a real concern, especially after liver transplantation (LT), whereas evidence for other therapeutic interventions is limited to preclinical models and small case series. Vedolizumab (VDZ), a humanized monoclonal antibody directed against the a4b7 integrin, is indicated for induction and maintenance of remission of moderate to severe IBD, either naive or refractory to anti-TNF agents. In this letter, we report our experience of VDZ for 10 patients with primary sclerosing cholangitis/autoimmune sclerosing cholangitis–IBD preand post-LT (n 1⁄4 5, respectively). Table 1 summarizes the disease characteristics and outcomes. Overall, a clinical response was seen in 4/10 patients (40%), 1 of whom achieved clinical remission (sustained to last follow-up). Surgery was required for 1 patient during induction because of acute severe colitis. The median duration of VDZ therapy in the 9 patients who received maintenance was 7.4 (1.4–12.5) months. In responders, a drop in fecal calprotectin (mg/g; median 708 [60–2696] versus 90 [32–960], P 1⁄4 0.03 by Wilcoxon test) and an improvement in quality of life scores were observed (5 [0, 13] versus 13 [8, 16], P 1⁄4 0.03). Abnormalities in liver biochemistry were seen in 2 postLT patients, but both had recurrence of their liver disease before VDZ initiation. No infective complications were attributed to VDZ use. There were no malignancies identified during the follow-up period. This is the first case series of VDZ use in primary sclerosing cholangitis/autoimmune sclerosing cholangitis–IBD patients preand post-LT. Therapy has been well tolerated by all patients, and no safety signals have been identified during the follow-up period despite concomitant immunosuppressants. Even in the context of anti-TNF failure, a good response rate has been documented with improvement in symptoms, objective markers of intestinal inflammation, and quality of life. Followup in this cohort is too short so far to comment on whether VDZ therapy influences the expected rate of pre-LT flares or postLT recurrence of liver disease, but to date, no such events have been recorded. As experience increases, taking into account its potential beneficial effects for autoimmune liver disease and the infectious complications associated with antiTNF use, it seems likely that VDZ will become the treatment of choice for IBD in this group of patients.

Letter: vedolizumab for autoimmune liver disease associated inflammatory bowel disease

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PTH-044 Risk of stenosis and outcomes following endoscopic resection of large colorectal lesions involving more than 75% of the luminal circumference

Introduction Little is known about the risk of stenosis and outcomes following endoscopic resection of colorectal lesions which leave extensive mucosal defects. A limited number of studies suggest significant stenosis rates, although reported outcomes and suggested management are conflicting. We determined the risk of stenosis and outcomes of endoscopic resection leaving mucosal defects≥75% of the circumference. Method Patients who underwent endoscopic resection using endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and hybrid techniques of colorectal lesions≥2 cm were included. Patients were grouped according to circumferential extent of the mucosal defect. Surveillance colonoscopy was performed at 3 and 12 months. Clinicopathological characteristics and outcomes were compared between groups. Results 435 lesions≥2 cm were resected using EMR (n=342), ESD (n=45) or hybrid techniques (n=48). Circumferential extent of the mucosal defect was ≥75% in 41 patients. 8 were fully circumferential: 1 caecal lesion and the rest in the recto-sigmoid and rectum. 3 circumferential lesions contained deeply invasive adenocarcinoma and 1 benign lesion ultimately required surgery. 41 lesions with a mucosal defect ≥75% of the circumference had a mean size of 100.5 mm vs 49.0 mm for other lesions (p<0.001). These patients had significantly more complications (16.7% vs 4.7%, p<0.001), including a higher rate of perforation (8.3% vs 2.3%, p=0.02), although none required surgery, and a significantly higher rate of recurrence (44.8% vs 9.2%, p<0.001). 79% of patients without cancer were free from recurrence and had avoided surgery at last follow up compared to 97% with mucosal defects<75% (p<0.001). Stenosis occurred in 7 patients: 4 lesions extensively involving the rectum and recto-sigmoid and 2 lesions involving the sigmoid extending to the rectosigmoid. 1 of these involved a mucosal defect of only 50% of the circumference and 3 were fully circumferential. 1 patient had a symptomatic anorectal stenosis requiring dilatation under anaesthesia, 1 patient was asymptomatic but underwent early dilatation after the first surveillance endoscopy. The remaining patients were asymptomatic and managed expectantly. In all these latter cases spontaneous improvement in the stricture was noted at the subsequent surveillance colonoscopy. Conclusion The majority of patients with these extensive complex lesions can successfully be treated with endoscopic resection and avoid surgery. However, these patients have a significantly greater risk of complications and recurrence and should be managed in a tertiary institution. Although there is a significant risk of stenosis, it appears that most cases are asymptomatic and spontaneously improve with expectant management. Disclosure of Interest None Declared

PTH-042 Outcomes of endoscopic resection of recurrent colorectal lesions treated at a uk tertiary referral centre

Introduction Endoscopic resection of large colorectal lesions, especially by piecemeal EMR, carries a significant risk of recurrence. Although several series examine the outcomes and risk of recurrence following endoscopic resection, few focus on the outcomes of patients being treated for recurrence after initial expert resection, and these mostly focus on one technique to deal with recurrence. We evaluated the outcomes after recurrence of colorectal lesions after apparent successful endoscopic resection in a specialised UK tertiary institution employing a range of resection techniques. Method Consecutive patients who underwent endoscopic resection of colorectal lesions≥2 cm were included. All lesions were assessed with magnification chromoendoscopy supplemented by colonoscopic ultrasound in selected cases. A lesion specific approach was used to decide on resection technique. Outcomes were evaluated for patients treated for recurrent lesions. Results Of 396 colorectal lesions≥2 cm successfully resected at our institution, recurrence occurred in 50. 36% of these patients had already had a mean of 1.6 previous failed attempts at resection prior to referral to our institution, and 66% had had either a failed attempt at resection or extensive sampling involving ≥6 biopsies or tattoo placed under the lesion. 69% of patients were successfully treated with further endoscopic resection and avoided surgery. 27 patients had endoscopic resection of a recurrence larger than 20 mm, with a mean lesion size of 48.3+/-19.1 mm. Techniques used were EMR (n=16), ESD (n=2), Hybrid ESD and EMR (n=9). The remaining lesions<2 cm were resected using EMR. A mean of 1.4+/-0.75 procedures were required to achieve successful endoscopic treatment of recurrence. 24 patients who were ultimately successfully treated with endoscopic resection required a single further endoscopic resection after recurrence, 10 patients required 2 or more further resections. 8 patients required surgery, 4 as a result of developing invasive adenocarcinoma with the recurrence. There were no perforations as a result of endoscopic resection of recurrent lesions and only 1 patient was readmitted with post-procedural bleeding which was managed conservatively. Conclusion These data demonstrate the challenges of an advanced endoscopic resection service in much of western practice where patients with recurrent lesions represent a particularly complex cohort, most of whom have already had extensive prior manipulation or attempts at resection. Familiarity with a range of resection techniques and appropriate equipment is essential to successfully treat recurrent lesions in this group with endoscopic resection, which can be achieved in the majority of patients without significant complications. Disclosure of Interest None Declared

PTH-008 Endoscopic Resection of Large Colorectal Polyps in A UK Tertiary Referral Unit

Introduction Whilst the extensive experience of endoscopic resection of large colorectal polyps in Japan has resulted in clear and consistent indications for various techniques depending on polyp size and morphology, practise in western Europe is less well defined. We report the results of a prospective series of endoscopic resections using a variety of techniques from one of only a few tertiary referral centres in the UK providing advanced interventional endoscopy. The patients in this series present some unique challenges, for example the high proportion of patients referred with deeply scarred lesions after previous failed attempts at resection, and the large mean polyp size. Methods A prospective series of colorectal endoscopic resections form a tertiary referral centre in the UK. Surveillance endoscopy was performed at 3 months and 12 months after resection. Results 363 polyps with a mean size of 56 mm were resected in 326 patients who had a mean age of 71 years: 309 by EMR, 38 by ESD and 16 by hybrid procedures involving ESD. The mean follow up was 12.2 months. Almost all patients were referred after their polyps were at least biopsied and 38% of polyps were deeply scarred from previous intervention. Despite this, adenoma recurrence occurred in only 9.7% of patients, 17% of which were diminutive. 6 patients with recurrence required surgery, 2 right hemicolectomies, 1 TEMS and 1 anterior resection and 2 declined surgery. 67% of patients with recurrence were treated successfully endoscopically with no further recurrence. Of those patients without invasive cancer at their first endoscopic resection, 95% were free from recurrence and had avoided surgery at last follow up. There was only one clinically significant perforation. 2 patients were admitted with post-procedure bleeding, 1 managed conservatively and 1 with endoscopic clips. Conclusion These data demonstrate the effectiveness of a tertiary interventional endoscopy unit in a western setting in treating large and complex colorectal polyps, with low recurrence rates and very few significant complications. In contrast to practise in the east, more education is required to prevent multiple attempted interventions before referral to a highly specialised unit. Disclosure of Interest None Declared

PTU-062 Vedolizumab: Early Experience and Medium-Term Follow up Data from Two UK Tertiary IBD Centres

Introduction Vedolizumab was recently granted NICE approval for moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC). Novel pathways agreed by our CCG meant that patients at Guy’s & St. Thomas’ and King’s College Hospitals had early access to vedolizumab. Methods Records of patients commencing vedolizumab between Nov 2014–15 were screened. Those completing at least 14 weeks of treatment were included. Clinical activity was assessed using Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) at baseline, 14 and 30 weeks. Response: HBI/SCCAI reduction ≥3. Remission: HBI < 5 or SCCAI <3. Continuous data are summarised as medians (range). Pre- and post-induction values were compared using Wilcoxon signed-rank test. Results 60 patients (CD: 32, 53%, UC 25, 42%, IBD-U 3, 5%) commenced vedolizumab (m:f 29:31, age: 39 (18–74), follow-up: 5 months (1–13)). 19 were excluded from our analysis (3 IBD-U, 5 stomas, 11 treated for <14 weeks). Clinical data from the remaining 41 was analysed. Of 32 patients with active disease at baseline, 17 (53%) responded and 11 (34%) achieved remission by week 14. The response and remission rates for CD were 8/15 (53%) and 6/15 (40%). In UC they were 9/17 (53%) and 5/17 (29%). Response and remission rates in anti-TNF experienced patients were 12/26 (46%) and 6/36 (35%) compared to 5/6 (83%) and 5/6 (83%) in anti-TNF naïve patients, respectively. 7/11 (64%) with active disease at baseline who completed 30 weeks of treatment responded and achieved remission. Faecal calprotectin fell significantly (pre-induction: 1076 (90–4800), post-induction: 478 (10–3184), p = 0.029 for n = 14) and CRP remained stable (pre-induction: 4 (1–70), post-induction: 4 (1–72), p = 0.28 for n = 40). Rates of steroid use at each time point: 19/41 (46%) at baseline, 11/41 (21%) at week 14 and 3/15 (20%) at week 30. Surgery was required in 4/41 (10%, CD:3 and UC:1). Conclusion Our experience mirrors a previously reported real-world cohort1 and demonstrates similar efficacy to the GEMINI trials. This data demonstrates a meaningful reduction in clinical and biochemical disease activity as well as a steroid-sparing effect in patients with complex and previously refractory disease. We did not see a significant difference in efficacy between patients with UC and CD. Reference 1 Christensen B. et al. Post-marketing experience of vedolizumab for IBD: The University of Chicago experience. ECCO; Barcelona, 2015. Disclosure of Interest None Declared

PTU-004 Safe and Effective Day Case Endoscopic Resection of Giant Colorectal Adenomas Greater than 8CM is Achievable in a Tertiary Referral Unit

Introduction There are few reports on the management of very large sessile colorectal polyps in western practice. Endoscopic resection of these lesions can be technically challenging and they have traditionally been subjected to surgical resection in western centres. Our aim was to determine the safety and effectiveness of endoscopic resection of giant colorectal polyps in a tertiary referral interventional endoscopy unit. Methods All lesions were assessed with magnification chromoendoscopy. Patients with colorectal polyps greater than or equal to 8 cm deemed suitable for endoscopic resection were included. Several techniques were employed including piecemeal endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and hybrid techniques involving EMR, ESD, transanal resection or transanal endoscopic microsurgery (TEMS). All patients underwent surveillance magnification chromoendoscopy at 3 and 12 months. Results 88 lesions greater than or equal to 8 cm were resected with a median size of 10 cm (range 8 cm-16cm). Mean age was 74 years. 49 lesions were in the rectum or rectosigmoid, 13 in the right colon and 27 in the descending and sigmoid colon. There were 6 tubular adenomas, 73 tubulovillous adenomas, 7 adenocarcinomas and 1 sessile serrated adenoma. The recurrence rate was 17%, 64% detected at the first surveillance endoscopy and 36% later recurrences. Of these, 2 patients required surgery in the form of TEMS and a right hemicolectomy, 1 died of unrelated causes, and the rest were managed with a repeat endoscopic resection and were free from recurrence at last surveillance. There were no clinically significant perforations. 3 perforations were closed with endoscopic clips and managed conservatively without complications. There were 2 unplanned admissions for bleeding which did not require further intervention. The recurrence and complication rate were significantly higher than for adenomas smaller than 8 cm. 72% were successfully completed as day cases. Of those patients without invasive cancer at their initial resection and alive at last follow up, 93% avoided surgery and were free from recurrence. Conclusion Successful endoscopic resection of giant colorectal adenomas is achievable in a western setting with a low risk of complications. In our series, none of 49 patients with rectal or rectosigmoid lesions, who would have traditionally required an anterior resection or abdominoperineal excision, required a major surgical resection. Almost all patients with benign polyps were successfully treated endoscopically and avoided surgery. Nonetheless, it is associated with a higher risk of complications and recurrence compared with lesions less than 8 cm and therefore should be considered in specialist units. Disclosure of Interest None Declared

PWE-024 Early Change in Faecal Calprotectin Predicts Primary Non- Response to Anti-TNFΑ Therapy in Inflammatory Bowel Disease

Introduction The early identification of primary non-response to anti-TNFα therapy facilitates the timely management of patients with inflammatory bowel disease (IBD). A recent, pilot study to detect prognostic markers of early response to anti-TNFα therapy identified the two genes coding for the calprotectin subunits (S100A8, S100A9) to be among the most highly expressed gene transcripts in non-responders. This study tests the hypothesis that measurements of faecal calprotectin (FCAL) pre- and post- anti-TNFα induction can predict primary non-response in both Crohn’s disease (CD) and ulcerative colitis (UC) Methods Retrospective study of 32 CD and 18 UC patients treated over a two-year period. Outcomes were assessed using Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI) (response: drop in HBI/SCCAI >3, remission: HBI < 5, SCCAI <3, steroid free) at 6 months. ΔFCAL was calculated as (FCALpost induction – FCALpre induction)*100/FCAL pre induction. Results At 6 months, 23 (72%) CD and 10 (56%) UC patients had responded. In remission were 17 (53%) and 5 (28%) respectively. Comparing non-responders to combined response and remission groups, the area under the curve of ΔFCAL to predict outcomes at 6 months was 0.97 for CD and 0.96 for UC. Using ROC analysis, a decrease of 70% returned a sensitivity and specificity of 99% and 96%, respectively (likelihood ratio, LR = 23) in CD. For UC a a decrease of 70% had a sensitivity and specificity of 88% and 86%, respectively (LR = 6). Conclusion A drop in FCAL < 70% after induction predicts primary non-response to anti-TNFα in both CD and UC. Disclosure of Interest None Declared

PTH-041 Per Oral Endoscopic Myotomy: First UK Experience

Introduction Per-oral endoscopic myotomy (POEM) has been adopted as a minimally invasive treatment option for achalasia. The first case of POEM was performed at King’s College Hospital in late 2013. Here we present our initial case series with video demonstration of technique. Methods Prospective data was collected for consecutive patients undergoing POEM including demographics, procedure technique, the use of Endoluminal Functional Lumen Imaging Probe (EndoFLIP) and adverse events. Follow up data at 3 months and 12–24 months post-POEM including Eckardt scores and lower oesophageal sphincter integrated resting pressure (IRP-4s) were compared with pre-POEM findings. Post-POEM Gastro-oesophageal Reflux Health-Related Quality of Life scale (GORD-HQL) was recorded. Statistical analysis was achieved using Wilcoxon matched-pairs signed rank test. Results POEM was performed in 33 patients (12 F, age 49.5±13.25 years). Pre-operative high-resoloution manometry confirmed type II achalasia in all patients. 19 patients had previous treatment (Botulinum n = 8, Pneumatic dilatation n = 10, Heller myotomy n = 5, POEM n = 1, >1 treatment n = 2). Median pre-POEM Eckardt Score 8, range 3–12. Median gastric and oesophageal myotomy was 3 cm (range 2–4) and 12 cm (range 5–16) respectively with a selective circular myotomy in all cases and a posterior approach in n = 5. There was significant reduction in post-operative Eckardt score at 3 months Median 0, range 0–6 (p < 0.0001) and IRP-4s (p = 0.0078, figs. 1 and 2). Sustained improvement in Eckardt score was observed at 12–24 months post-POEM (p = 0.0005). One patient required revision of POEM at 6 months. EndoFLIP Intra-operative EndoFLIP measurements before and after myotomy have been implemented to aid confirmation of adequate myotomy (Figure 3).Abstract PTH-041 Figure 1 Adverse Events One patient underwent single clip displacement and was replaced at gastroscopy day 1 post POEM. There were no cases of perforation, infection or major bleeding. Gastro-oesophageal reflux Post-POEM GORD-HQL score was collected in 26 patients with a median score of 2.5, range 0–31. Two cases of reflux (positive 24 hr pH at 3 months) were identified and successfully managed with maintenance proton pump inhibitor. Conclusion POEM was performed successfully in 33 patients in whom 57.5% had prior endoscopic or surgical treatment representing a potentially more challenging patient population. This study is in line with international consortia and ASGE findings1 that POEM is a safe and efficacious procedure for the treatment of achalasia for both short term and sustained symptomatic benefit. Reference 1 Stavropoulos S, Desilets D, Fuchs KH et al; Per-oral endoscopic myotomy white paper summary; Gastrointestinal Endoscopy. 2014;1:1–15. Disclosure of Interest None Declared