P109 Use of faecal calprotectin as predictor of relapse in patients under maintenance treatment with infliximab

S52 actions. We addressed whether the action of LCAP depends on CGRP induction. Methods: An HLA-B27 transgenic rat model of chronic colitis was treated with three weekly sessions of LCAP (LCAP column or a sham column). The effects of LCAP on clinical and endoscopic disease activity, bone marrow cell induction, and colonic blood flow were then examined. The tissue mRNA levels of CGRP and its receptors, RAMP1 and CRLR, were also determined using real time-PCR. Changes in these LCAP effects after the intravenous administration of a CGRP antagonist (CGRP8 37, 100 mg/kg) were also observed. In a second experiment, the effect of the intravenous administration of CGRP (400 mg/mL/day) or saline on disease activity, bone marrow cell induction, and colonic blood flow were investigated in a colitis rat model. Results: Treatment with the LCAP column, but not the sham column, significantly improved the clinical disease activity (P = 0.049) and the endoscopic disease activity (P = 0.034), induced the bone marrow cells (P = 0.032), and enhanced the colonic blood flow (P = 0.015) in association with an increase in the CGRP mRNA levels (P = 0.029). In contrast, the mRNA levels of the CGRP receptors, RAMP1 and CRLR, were not affected by LCAP. These LCAP actions were abolished by pretreatment with a CGRP antagonist, suggesting that LCAP activity depends on CGRP induction. Similar to the LCAP effect, the administration of CGRP, but not a control administration, improved the clinical disease activity (P = 0.009) and the endoscopic disease activity (P = 0.009), induced the bone marrow cells (P = 0.004), and enhanced the colonic blood flow (P = 0.032). Conclusions: The tissue repair and anti-inflammatory actions of LCAP are associated with its induction of CGRP. CGRP is an attractive, novel therapeutic target for the treatment of UC patients. P108 FAM5C, a possible causal molecule in ulcerative colitis revealed through a transcriptomic analysis of the bowel mucosa P.J. Smith1 *, A.P. Levine1 , G.W. Sewell1 , N.R. O’Shea1 , M. Rodriguez-Justo2 , M. Novelli2 , R. Vega3 , S.L. Bloom3 , A.M. Smith1 , A.W. Segal1 . 1 University College London, Division of Medicine, London, United Kingdom, 2 University College London Hospitals NHS Foundation Trust, Department of Histopathology, London, United Kingdom, 3 University College London Hospitals NHS Foundation Trust, Department of Gastroenterology, London, United Kingdom Background: Abnormalities of the colonic mucosa have been implicated in the pathogenesis of ulcerative colitis (UC). We investigated mRNA profiles of macroscopically non-inflamed mucosal biopsies from the colon in patients with UC, Crohn’s disease (CD) and control subjects without gastrointestinal disease (HC), to identify genes that might be involved in the aetiology of the disease. Methods: Paired biopsies were taken for histology and mRNA extraction from macroscopically non-inflamed mucosa in the ascending and descending colon, and the rectum, from 24 patients with UC, 14 with CD and 27 HCs undergoing routine colonoscopy. Patients were in complete clinical remission and were either on no treatment or on 5-aminosalicylates +/ azathioprine. cRNA was hybridised to Illumina HumanHT-12 v4 Expression Beadchips. Array expression data were log transformed and normalised. Only probes with a detection p-value <0.01 were analysed. Differential gene expression analysis between groups (using p < 0.05 FDR correction) and outlier analysis (p < 0.005, fold change (FC) 1.5) were performed at each location using customised software. Results were verified by qPCR and candidate molecules were examined in an independent cohort of UC patients. Results: In group comparisons, of the 26,261 expressed probes, Family with Sequence Similarity 5, member C (FAM5C) was the

Poster presentations only gene to be significantly under-expressed in UC, both in the rectum (FC = 1.58, p = 0.0008) and the descending colon (FC = 1.64, p = 0.0011). Outlier analysis showed that FAM5C was also grossly under-expressed in the ascending colon in 37.5% of UC patients, demonstrating that its expression is abnormal throughout the colon in a significant proportion of individuals. Expression levels were not abnormal in CD. Expression of FAM5C in UC did not correlate with the known markers of inflammation, IL-8, S100A8, DEFA5 and DEFA6, or with treatment. The under-expression of FAM5C in UC was confirmed in biopsies of non-inflamed rectal mucosa from an independent cohort of patients (FC = 1.68, p = 0.0073) and by qPCR (p < 0.001). Conclusions: This is the first description of the underexpression of FAM5C in UC. As these observations were made in non-inflamed mucosa, low levels of this protein might be involved in the pathogenesis of the disease. Indications that FAM5C may function as tumour suppressor [1], could link to the observed predisposition to colonic malignancy in UC. Reference(s) [1] Kuriowa T et al., (2009), Expression of the FAM5C in tongue squamous cell carcinoma., Oncol Rep, 22 (5), 1005 11.

Clinical: Diagnosis and outcome P109 Use of faecal calprotectin as predictor of relapse in patients under maintenance treatment with infliximab R. Ferreiro1 *, M. Barreiro-de Acosta1 , M. Otero2 , A. Lorenzo1 , C. Alonso2 , J.E. Dominguez-Munoz1 . 1 University Hospital, Gastroenterology, Santiago, Spain, 2 Department of Laboratory Medicine, Santiago, Spain Background: In inflammatory bowel disease (IBD), predicting relapse by measuring non-invasive biomarkers could allow early changes to treatment. Data is scarce regarding the usefulness of close monitoring with calprotectin to predict relapse. The aim of the study was to evaluate the predictive value of a faecal calprotectine test checking for flares in patients with IBD under maintenance treatment with Infliximab. Methods: A prospective study was designed. Inclusion criteria were IBD patients (Crohn’s disease [CD] and ulcerative colitis [UC]) in clinical remission under a continuous 5 mg/kg Infliximab therapy. Fresh faecal calprotectin was measured using a rapid test on the day of the drug infusion. Clinical examination was performed two months after infusion. Relapse was defined as a Harvey Bradshaw score >4 in CD patients and as a Mayo score >2 in UC patients. The U-Mann Whitney test and the ROC analysis were performed in SPSS. Results: 53 patients were included; mean age 46±2 years; 28 (52.8%) being female, 62.3% having CD and 37.7% UC. After two months, 41 (77.4%) patients remained in clinical remission and 12 (22.6%) presented a relapse. For patients in remission mean calprotectin levels were 110 mg/kg of faeces. Patients who flared had significantly higher calprotectin levels than patients in remission (p < 0.005). The calprotectin levels in patients with relapse had a mean of 332 mg/kg. A further ROC analysis (flare vs remission) suggested that a calprotectin level of 110.5 mg/kg was the best cut-off point showing high sensitivity (100%) and high specificity (73.2%) to confirm the flare. The area under the curve was 0.88 with good accuracy (p < 0.005). Conclusions: In IBD patients under infliximab maintenance therapy, calprotectin levels highly correlate with a predictor of relapse. Remission is associated with low calprotectine levels. More studies and an increased number of patients should

Clinical: Diagnosis and outcome

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confirm the usefulness of calprotectin to modulate therapy during medical checks. P110 Surveillance for colorectal cancer in colitis patients: effect of the implementation of new British and American guidelines on neoplasia yield 1

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E. Mooiweer *, A.E. van der Meulen , A.A. van Bodegraven , J.M. Jansen4 , N. Mahmmod5 , J. Nijsten1 , M.G. van Oijen1 , P.D. Siersema1 , B. Oldenburg1 . 1 University Medical Centre Utrecht, Department of Gastroenterology and Hepatology, Utrecht, Netherlands, 2 Leiden University Medical Centre, Department of Gastroenterology and Hepatology, Leiden, Netherlands, 3 VU University Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, Netherlands, 4 OLVG, Department of Gastroenterology and Hepatology, Amsterdam, Netherlands, 5 Antonius Hospital, Department of Gastroenterology and Hepatology, Nieuwegein, Netherlands Background: Ulcerative colitis and Crohn’s colitis are associated with an increased risk of colorectal cancer (CRC). Therefore, recently updated American Gastroenterological Association (AGA) and British Society of Gastroenterology (BSG) guidelines recommend endoscopic surveillance. As surveillance intervals differ significantly between guidelines, we assessed the difference in neoplasia yield and colonoscopic workload when either the new AGA or BSG guidelines were employed. Methods: All IBD patients enrolled in the colonoscopic surveillance program were identified in five hospitals using the patients’ medical records. Patients were stratified according to the new BSG and AGA guidelines based on risk factors present at the last surveillance colonoscopy and colonoscopic workload was calculated based on the associated intervals. Cumulative incidence of colitis-associated neoplasia (CAN), defined as low-grade dysplasia (LGD) in flat mucosa or a nonadenoma like mass, high-grade dysplasia (HGD) or CRC was compared between risk groups of either guideline using Log rank testing. Results: A total of 1018 patients were identified that were enrolled in the surveillance program. Employing the new BSG intervals, 204 patients would be assigned to annual surveillance (20%), 393 patients to surveillance every three years (39%) and 421 patients to surveillance every five years (41%), resulting in an average of 420 colonoscopies/year. When the new AGA intervals would be applied, 64 patients (6%) would undergo annual and 954 patients (94%) biannual surveillance, resulting in an average of 541 colonoscopies/year. Thus, implementation of the new BSG guidelines could reduce the colonoscopic workload by 22% compared to the new AGA guidelines. Yield of CAN would be 22/204 (11%) in the high risk group (12 LGD, 6 HGD, 4 CRC) and 27/393 (7%) in the intermediate risk group (7%) (21 LGD, 0 HGD, 6 CRC) and 15/421 (4%) in the low risk group (14 LGD, 0 HGD, 1 CRC) if BSG guidelines had been applied (p = 0.26). If AGA guidelines had been applied, the yield of CAN would be 13/64 (20%) in high risk group (8 LGD, 4 HGD, 1 CRC) and 51/954 (5%) in the low risk group (39 LGD, 2 HGD, 10 CRC) (p = 0.02). Conclusions: Implementation of risk stratification-based intervals as recommended by the new BSG guidelines reduces the colonoscopic workload substantially compared to the AGA guidelines. However, risk stratification as recommended by the AGA seems to be more effective in discriminating between high and low risk patients than the BSG guidelines.

P111 Pulmonary involvement in Crohn’s disease patients M. Di Girolamo1 *, A. Scarcelli1 , A. Bertani1 , A. Sartini1 , A. Merighi1 , C. Ruggiero1 , U. Morandi1 , E. Villa1 . 1 Policlinico Modena, Italy Background: Crohn’s Disease (CD) is associated with extraintestinal manifestations. Pulmonary lesions (PLs) are still poorly characterized, even if there are growing number of reports about drug-induced PLs (ASA) and incidentalomas (screening Rx/CT scan) in symptomatic and asymptomatic patients, respectively. PLs are clinically chronic bronchitis and bronchiolitis, and histologically nonnectrotizing granulomatous inflammation. Biopsy or a surgical intervention and microbiological tests are needed to make differential diagnosis. Therapy consists generally in surgical removal, but some cases of marked improvement during anti-TNFa therapy exist. Methods: We report our experience of 2 asymptomatic pts with pulmonary nodules. A 47 year-old woman with ileal CD, affected by thalassemic trait, systemic sclerosis, Raynaud, in therapy with ASA and prostaglandins, p-ANCA positive; due to lymphadenopathy ultrasound evidence, she performed a CT scan, which showed a consolidative parenchymal area in the middle lobe, with circumscribed consolidation focal area in the lingula and nodulariform thickening in the right lower lobe. PET-CT scan showed glucose hypermetabolism. She underwent to surgery, with the diagnosis of outbreaks of chronic nonnecrotizing giant cell granulomatous inflammation, pleural and septal organized fibrosis, coexisting aspects of organizing pneumonia, chronic pleurisy with follicular bronchiolitis; no evidence of malignancy. Typical and atypical mycobacterial infection tests were negative. A 69 year-old man with ileum-colic CD and evidence of a lower right pulmonary lobe incidentaloma during a screening Rx, confirmed by PETCT scan, without altered glucose metabolism. He therefore underwent an atypical lower right pulmonary lobe resection, with diagnosis of outbreaks of chronic giant cell granulomatous peri-bronchiolar inflammation with some vascultic aspetcs and concomitant organized pneumonia. Typical and atypical mycobacterial infections tests were negative. Results: Excluding infectious and malignancy, in our opinion they could be pulmonary involvement of CD, expression of its autoimmune aetiology. Conclusions: Pulmonary involvement is not a rare extraintestinal manifestation of CD. The majority of PLs reported were diffuse interstitial pneumonitis, with non-caseating granulomas. It is necessary to make a diagnosis, excluding infectious and malignancy, and treat with appropriated surgical therapy. P112 iSCAN-High definition colonoscopy correlates with white light endoscopy and histology assessment in mucosal healing for ulcerative colitis M. Iacucci1 *, M. Fort Gasia1 , X. Gui2 , R. Panaccione1 , G. Kaplan1 , J. Love1 , S. Ghosh1 . 1 University of Calgary, Gastroenterology, Calgary, Canada, 2 University of Calgary, Pathology, Calgary, Canada Background: White light (WL) colonoscopy is used to assess the endoscopic appearance in ulcerative colitis (UC). High definition iSCAN offers the potential to better characterize the mucosa in patients with UC and may provide information about both inflammation and mucosal healing. Our aim was to assess high definition iSCAN in patients with UC and compare findings to WL endoscopy and histopathology. Methods: 45 patients (21 female, median age = 41, range = 19 90 years) with UC were recruited and assessed by both high definition-iSCAN colonoscopy (Pentax, Tokyo) and WL colonoscopy. Mayo endoscopy subscores were assigned to