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Introduction The frequency and severity of abdominal pain after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs) of ≥ 20 mm is unknown, as are the risk factors to predict its occurrence. We aimed to prospectively characterize pain after colonic EMR , determine the rapidity and frequency of its resolution after analgesia, and estimate the frequency of needing further intervention. Methods Procedural and lesion data on consecutive patients with LSLs who underwent EMR at a single tertiary referral center were prospectively collected. If pain after colonic EMR, graded using a visual analogue scale (VAS), lasted > 5 minutes, 1 g of paracetamol was administered. Pain lasting > 30 minutes lead to clinical review and upgrade to opiate analgesics. Investigations and interventions for pain were recorded. Results 67/336 patients (19.9 %, 95 %CI 16.0 %–24.5 %) experienced pain after colonic EMR (median VAS 5, interquartile range 3–7). Multivariable predictors of pain were: lesion size ≥ 40 mm, odds ratio [OR] 2.15 (95 %CI 1.22–3.80); female sex, OR 1.99 (95 %CI 1.14–3.48); and intraprocedural bleeding requiring endoscopic control, OR 1.77 (95 %CI 0.99–3.16). Of 67 patients with pain, 51 (76.1 %, 95 %CI 64.7 %–84.7 %) had resolution of their “mild pain” after paracetamol and were discharged without sequelae. The remaining 16 (23.9 %) required opiate analgesia (fentanyl), after which 11/16 patients (68.8 %; “moderate pain”) could be discharged. The 5/67 patients (7.5 %) with “severe pain” had no resolution despite fentanyl; all settled during hospital admission (median duration 2 days), intravenous analgesia, and antibiotics. Conclusion Pain after colonic EMR occurs in approximately 20 % of patients and resolves rapidly and completely in the majority with administration of intravenous paracetamol. Pain despite opiates heralds a more serious scenario and further investigation should be considered.

Obscure gastrointestinal (GI) bleeding (OGIB) is defined as small bowel bleeding of unknown etiology after negative endoscopic evaluation including esophagogastroduodenoscopy and colonoscopy with endoscopic evaluation of the terminal ileum. The presentation of OGIB may be either overt or occult. The former refers to persistent or recurrent visible GI bleeding (eg, melena and / or hematochezia, and rarely hematemesis), while the latter indicates the presence of persistently positive results of fecal oc-cult blood testing, iron deficiency anemia, or both, without evidence of visible GI bleeding. This review focuses exclusively on obscure‑overt GI bleeding and presents entities that should be considered as part of the differential diagnosis in patients with this type of bleeding, as well as details the role of endoscopic and radiographic techniques in the evaluation and treatment.

Background and Aims Although sporadic duodenal and/or ampullary adenomas (DAs) are uncommon, they are increasingly diagnosed during upper endoscopy. These patients have a 3- to 7-fold increased risk of colonic neoplasia compared with the normal population. It is unknown, however, whether they also have an increased risk of additional small-bowel (SB) polyps. Our aim was to establish the prevalence of SB polyps in patients with DA. Methods In a single-center, prospective study, we used video capsule endoscopy (VCE) to investigate the prevalence of SB polyps in patients with a DA compared with patients undergoing VCE for obscure GI bleeding or iron deficiency anemia. Results Over 25 months, 201 patients were enrolled in the study; the mean age was 65 years and 47% were male. There were 101 control patients and 100 cases of DA cases (mean size, 30 mm (range, 10-80 mm)). We did not identify any SB polyps in either group. Colonic polyps were found more frequently in the DA group compared with controls (61% versus 37%, respectively (P =.002)). Advanced colonic adenoma (high-grade dysplasia, >10 mm, villous histology) were found in 18% of the DA group and 5% of the control group (P =.018). Conclusion Our data suggest that patients with a DA are not at risk for additional SB polyps and hence do not support screening with VCE. However, colonoscopy is mandatory due to the significantly higher risk of colonic polyps including advanced adenomas. (Clinical trial registration number: NCT02470416.)

To assess the clinical significance of antibodies to infliximab (ATI) formation in patients with inflammatory bowel disease (IBD).Infliximab therapy in patients with IBD is highly effective though up to 50% of patients lose response to infliximab. ATI formation occurs in 6% to 60% of patients on scheduled infliximab maintenance therapy.Infliximab trough levels and ATI at trough were prospectively determined in patients with IBD on maintenance infliximab therapy. Patients on infliximab maintenance therapy with at least 3 ATI measurements were included. Patients were divided into 2 groups: sustained negative (1 µg/mL) ATI levels, and fluctuating ATI levels (at least 1 sample with ATI1 and at least one1 µg/mL).Forty-eight patients with IBD with available clinical data and serum samples were included. 25 patients had sustained low ATI levels and 23 patients had fluctuating ATI levels. Both groups were similar in IBD subtype distribution (Crohn's disease in 73.9% and 60%), mean serum albumin levels (4.2 vs. 3.9 g/dL), and mean trough serum infliximab levels (3.3 vs. 4.6 µg/mL) in fluctuating ATI and low ATI groups, respectively. There were no significant differences in the rate of clinical response (64% vs. 76%) and mean serum C-reactive protein levels (9.4 vs. 8.5 mg/dL, ULN=5) in the fluctuating ATI and low ATI groups. Similar rates of clinical response in the fluctuating ATI and low ATI groups were observed in ulcerative colitis (33% vs. 40%) and Crohn's disease (76% vs. 100%).The fluctuating pattern of appearance of ATI in patients with IBD was not associated with loss of clinical response or a rise in C-reactive protein. The authors suggest that in clinical decision making, only sustained appearance of ATI should be considered as an adverse therapeutic factor.

Achalasia is not uncommonly diagnosed in elderly patients and its incidence and prevalence are growing in this population. However, a scarcity of studies has assessed the typical pathophysiological and clinical features of the disease as well as the effectiveness and safety of the various therapeutic options in elderly populations. Botulinum toxin injection has been used for achalasia treatment since 1994 and is traditionally considered the preferred treatment for fragile elder patients. However, recently more evidence has become available regarding the safety and effectiveness of pneumatic balloon dilation (BD), laparoscopic Heller myotomy (LHM) and per-oral endoscopic myotomy (POEM) in elderly patients with achalasia. In the current review we present the current literature on this topic with a focus on the clinical presentation of achalasia in the elderly and manometric features thereof, as well as summarize the effectiveness and safety of the various therapeutic options. Furthermore, we propose a practical management algorithm as a means to guide the treatment of future cases. We recommend that a conservative/BTI approach should be adopted in the fragile unfit patient. In the elderly fit patient, the treatment decision should be based on the achalasia type, patient preference and the available expertise, similar to the approach adopted for the non-elderly population.

Background and Aims Clinically significant post-EMR bleeding (CSPEB) is the most-frequent serious adverse event after EMR of large laterally spreading colonic lesions (LSLs). There is no proven prophylactic therapy, and it remains a significant drawback of EMR. We aimed to systematically describe and evaluate the features of the post-EMR mucosal defect (PED) and their relationship to CSPEB. Methods A prospective study of LSLs referred for EMR at a tertiary center was performed. PEDs without visible features were recorded as bland blue. Nonbland blue (NBB) PED features included size, number, and herniation of submucosal vessels and presence of submucosal hemorrhage, fibrosis, fat, and exposed muscle. NBB PEDs were analyzed for association with CSPEB, defined as bleeding occurring after completion of the procedure necessitating readmission or reintervention. Results From April 2012 to May 2017, 501 lesions in 501 patients were eligible for analysis. The frequency of CSPEB was 30 of 501 (6.0%). More than or equal to 3 visible vessels was a significant predictor of CSPEB (P = .016). None of the following showed a significant correlation with CSPEB: presence of visible vessels, their diameter, herniation, or other nonvascular PED features. Submucosal vessels were more common in the left-sided colon segment (88.6% vs 78.3%, P = .004) and were significantly larger (20.8% vs 12.1% ≥1 mm, P = .037), more numerous (median 4 vessels [interquartile range, 2-7] vs 2 vessels [interquartile range, 1-4], P Conclusions More than or equal to 3 visible vessels within the PED may be predictive for CSPEB and may define a target group for real-time prophylactic intervention. No other endoscopically visible features of the PEDs were predictive of CSPEB. (Clinical trial registration number: NCT03117400 .)

Background and study aims Large series suggest endoscopic mucosal resection is safe and effective for the removal of large (≥ 10 mm) sessile serrated polyps (SSPs), but it exposes the patient to the risks of electrocautery, including delayed bleeding. We examined the feasibility and safety of piecemeal cold snare polypectomy (pCSP) for the resection of large SSPs. Methods Sequential large SSPs (10 – 35 mm) without endoscopic evidence of dysplasia referred over 12 months to a tertiary endoscopy center were considered for pCSP. A thin-wire snare was used in all cases. Submucosal injection was not performed. High definition imaging of the defect margin was used to ensure the absence of residual serrated tissue. Adverse events were assessed at 2 weeks and surveillance was planned for between 6 and 12 months. Results 41 SSPs were completely removed by pCSP in 34 patients. The median SSP size was 15 mm (interquartile range [IQR] 14.5 – 20 mm; range 10 – 35 mm). The median procedure duration was 4.5 minutes (IQR 1.4 – 6.3 minutes). There was no evidence of perforation or significant intraprocedural bleeding. At 2-week follow-up, there were no significant adverse events, including delayed bleeding and post polypectomy syndrome. First follow-up has been undertaken for 15 /41 lesions at a median of 6 months with no evidence of recurrence. Conclusions There is potential for pCSP to become the standard of care for non-dysplastic large SSPs. This could reduce the burden of removing SSPs on patients and healthcare systems, particularly by avoidance of delayed bleeding.

BACKGROUND Imatinib is generally well tolerated in the treatment of advanced gastrointestinal stromal tumors (GIST). Gastrointestinal vascular ectasia (GIVE) and gastric antral vascular ectasia (GAVE), while rare, are significant under-reported complications of imatinib therapy. CASE REPORT We present one patient with GIVE complicating imatinib therapy with a literature review of this rare side-effect. RESULTS A 68-year-old woman was diagnosed with advanced GIST, wild-type CKIT. After 3 months of treatment with imatinib, she had partial response. However, she was diagnosed with GAVE and, later, also with GIVE. During her 3-year imatinib treatment, she suffered from severe anemia and required blood transfusions. Conservative treatments were not helpful and the ectatic lesions resolved only with cessation of imatinib. CONCLUSION This confirms a causal relationship between GIVE and imatinib. GIVE and GAVE should be considered possible causes of anemia and upper gastrointestinal bleeding in patients receiving imatinib therapy.

Background and Aims Endoscopic submucosal dissection (ESD) is an effective, minimally invasive, surgery-sparing technique for the treatment of early gastric cancer (EGC). It is not well established whether EGC within the Japanese expanded criteria can be safely and effectively treated using ESD in the West. We describe the outcomes of ESD for endoscopically suspected, biopsy specimen–confirmed EGC and its adenomatous precursor lesions (pEGC) using the Vienna classification of dysplasia in a Western cohort. Methods Prospective data were collected on all pEGCs undergoing ESD at a single expert endoscopy center. Outcomes were compared among pEGC, satisfying the Japanese absolute and expanded criteria, those outside criteria, and those specimens that contained low-grade dysplasia (LGD) only. Specialist GI pathologists reviewed and classified all ESD specimens. Patients were followed up at 6 and 12 months. Results Over 71 months, 135 pEGCs in 121 patients (mean age, 72.0 years; 61.2% men) underwent ESD. Median pEGC size was 20 mm (interquartile range, 15-30), and 62 (45.9%) satisfied the expanded clinical criteria. Perforation occurred in 1.5% and postprocedural bleeding in 5.2%. Forty-two pEGCs (31.1%) contained LGD only. Rates of en bloc and R0 resection were 94.8% and 86.7%, respectively. One hundred seven pEGCs (79.2%) met the absolute or expanded criteria for endoscopic cure. Two pEGCs recurred during follow-up. Ten of 26 patients with pEGC (38.5%) outside criteria for cure underwent surgery after ESD with residual tumor detected in 3 specimens. Fifteen patients with outside criteria for pEGCs did not undergo surgery because of frailty or their expressed wish. Eleven of 15 patients have so far undergone first surveillance with 1 of 11 experiencing endoscopic and histologic recurrence. Conclusions ESD is a safe and effective treatment for pEGCs in a Western context. Patients who either decline or are too frail for surgery, with outside criteria resections, may benefit from ESD for local disease control. Large Western studies of ESD for pEGCs are required to define long-term patient outcomes and surveillance guidelines, particularly where pathology shows LGD or high-grade dysplasia only. (Clinical trial registration number: NCT02306707.)

Background Sessile serrated polyps (SSPs) are important precursors of colorectal carcinoma and interval cancer. Large SSPs (≥ 20 mm) outside the definition of serrated polyposis syndrome (SPS) have not been studied in comparison with SPS. We aimed to describe the characteristics of patients with large SSPs in this context. Methods Patients with at least one SSP (≥ 20 mm) were eligible. Data from three consecutive colonoscopies were used to compare clinical and endoscopic characteristics in three patient groups: SPS, a solitary large SSP, and patients with at least two SSPs without fulfilling the criteria for SPS (oligo-SSP). Data on the diagnostic colonoscopy were collected retrospectively, whereas the remaining data was collected prospectively. Results 67/146 patients (45.9 %) had SPS, 53/146 (36.3 %) had a solitary SSP, and 26/146 (17.8 %) were categorized as oligo-SSP. Personal (16.4 %, 9.4 %, and 11.5 %, respectively) and family (17.9 %, 17.0 %, and 23.1 %, respectively) history of colorectal carcinoma did not differ significantly between groups. Polyp burden was greater in SPS compared with solitary SSP but was not different from oligo-SSP (advanced adenomas: SPS 32.8 % vs. solitary SSP 9.4 % [P = 0.002] vs. oligo-SSP 34.6 % [P = 0.87]; ≥ 10 conventional adenomas: 11.9 % vs. 0 % [P = 0.01] vs. 3.8 % [P = 0.44], respectively). Dysplasia in large SSPs was frequent in all groups (41.1 % overall). SPS was recognized by referring endoscopists in only 9.0 % of cases. Conclusion Patients with oligo-SSPs have similar synchronous polyp burden and clinical characteristics as patients with SPS and may require similar surveillance. Modification of the criteria for the diagnosis of SPS to include this group seems warranted. Patients with a solitary SSP have a lower risk of synchronous polyps, including advanced adenomas. Larger studies are warranted to determine whether these patients may return to standard surveillance following complete examination and clearance of the colon.

Background and aims: Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). Methods: Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. Results: Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8±15.4 years and duration of follow-up was 7.93±6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC–IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3±1.4 years and mean transplant-free survival was 23.5±1.6 years. Cox proportional-hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 ( p = 0.004) and 2.58 ( p = 0.046), respectively]. Conclusions: Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD. * Abbreviations: : PSC : primary sclerosing cholangitis; IBD : inflammatory bowel disease; CCA : cholangiocarcinoma; LT : liver transplantation; UC : ulcerative colitis; ERCP : endoscopic retrograde cholangiopancreatography; UDCA, ursodeoxycholic acid; MRCP : magnetic resonance cholangiopancreatography; CD : Crohn’s disease.

There are few therapeutic options for patients with inflammatory bowel disease who lose response to infliximab because they produced antibodies against the drug. We performed a retrospective analysis to investigate whether administration of immune modulators to 5 patients who developed antibodies to infliximab (ATI) restored response to this drug; 3 patients were given azathioprine/6-mercaptopurine and 2 patients were given methotrexate. Concentrations of infliximab and ATIs, and antitumor necrosis factor (TNF) activity, were analyzed using enzyme-linked immunosorbent assay-based competition assays of serum samples collected before and after patients were given the immunomodulator. In all patients, levels of ATIs gradually decreased and trough levels of infliximab increased; clinical responses were restored to all patients. In competition assays, immunomodulator-induced elimination of ATIs was associated with increased anti-TNF activity in serum. The addition of immunomodulators to therapy might be helpful to patients who have lost response to anti-TNF agents owing to formation of antidrug antibodies.

EMR of sessile periappendiceal laterally spreading lesions (PA-LSLs) is technically demanding because of poor endoscopic access to the appendiceal lumen and the thin colonic wall at the base of the cecum. We aimed to assess the feasibility and safety of EMR for PA-LSLs.Consecutive LSLs ≥20 mm and PA-LSLs ≥10 mm detected at 3 academic endoscopy centers from September 2008 until January 2017 were eligible. Prospective patient, procedural, and lesion data were collected. PA-LSLs were compared with LSLs in other colonic locations.Thirty-eight PA-LSLs were compared with 1721 LSLs. Referral for surgery without an attempt at EMR was more likely with PA-LSLs (28.9% vs 5.1%, P .001), and those that involved a greater percentage of the appendiceal orifice (AO) were less likely to be attempted (P = .038). Most PA-LSLs (10/11) were not attempted because of deep extension into the appendiceal lumen; 2 of 11 of these surgical specimens contained invasive cancer. Once attempted, complete clearance of visible adenoma (92.6% PA-LSLs vs 97.6% LSLs, P = .14), adverse events, and rates of adenoma recurrence did not vary significantly between PA-LSLs and LSLs. All 7 patients with prior appendicectomy achieved complete adenoma clearance. There were no cases of post-EMR appendicitis. Twenty of 22 PA-LSLs (91%) eligible for surveillance avoided surgery to longest follow-up.EMR is a safe, effective, and durable treatment for PA-LSLs when specific criteria are fulfilled. If the distal margin of the PA-LSL within the AO cannot be visualized or if more than 50% of the circumference of the orifice is involved, surgery should be considered. (Clinical trial registration number: NTC01368289.).

diminutive polyps if the prediction for surveillance intervals is accurate in R90%, because the prevalence of advanced adenomas in diminutive polyps was very low (approximately 1%) in previous studies. However, NICE classification cannot distinguish between advanced and non-advanced lesions. Methods: In this study we assessed prevalence of advanced adenomas in small (5-10 mm) and diminutive (!0.5 mm) polyps within 110.405 screening colonoscopies performed within a nationwide quality assurance program in Austria between November 2007 and June 2013. Results: 68.6% (nZ23.097) of polpys ! 10mm (nZ33.674) were diminutive and 31.4% (nZ10.577) were small polyps. 39.2% (nZ9.060) of the diminutive lesions were located in the proximal colon and 60.8% (nZ14.037) in the distal colon. Small polyps were in 49.6% (nZ5.245) located in the proximal and in 50.4% (nZ5.332) in the distal colon. In the proximal colon diminutive respectively small polyps were in 5.7% and 14.8% advanced adenomas, in 49.1% and 57.6% adenomas, in 43.5% and 34.5% hyperplastic and in 0.9% and 1.6% serrated lesions. In the distal colon diminutive respectively small polyps were in 4.1% and 15.4% advanced adenomas, in 27.3% and 51.2% adenomas, in 67.4% and 41.3% hyperplastic and in 0.4% and 0.6% serrated lesions. Conclusion: Data of our study showed a higher prevalence of advanced adenomas in diminutive and small lesions than reported in previous studies. Approximately every second polyp in the proximal and 67% of polyps in the distal colon were hyperplastic. Every 18th polyp in the proximal and every 24th polyp in the distal colon had advanced features. Since recommendations for resect and discard strategy is based on prevalence of histological features, this issue has to be addressed especially in large screening cohorts before establishing resect and discard in everyday clinical practice since advanced lesions in small and diminutive polyps might be underestimated.

P511 Epstein-Barr Virus in inflammatory bowel disease correlation with different therapeutic regimens F. Magro1 *, J. Santos-Antunes1, A. Albuquerque1, F. Vilas-Boas1, G.N. Macedo2, N. Nazareth2, S. Lopes1, J. Sobrinho-Simoes3, S. Teixeira3, C. Camila-Dias4, J. Cabral5, A. Sarmento2, G. Macedo1. 1Centro Hospitalar S. Joao, Gastroenterology, Porto, Portugal, 2CEBIMED Biomedicine Research Center, Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal, 3Centro Hospitalar S. Joao, Clinical Pathology Department, Porto, Portugal, 4Faculty of Medicine, University of Porto, CIDES Department of Health Information and Decision Sciences, Porto, Portugal, 5Faculty of Medicine, University of Porto, Institute of Pharmacology and Therapeutics, Porto, Portugal