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Su1341 Systematic Analysis of Factors Associated With Progression and Regression of Ulcerative Colitis in the Swiss IBD Cohort Study
in vascular microstructure. In inflamed villi, there is a definite increase in density of vessels which became curvilinear and spiral. Mucosal healing is demonstrated by reduction or disappearance of the ulcers. We followed the ileal inflammation with sequential examinations. In one patient, marked inflammation of the terminal ileum with numerous ulcerations and prolapse of the ileal mucosa was treated with infliximab. 4 months later, colonoscopic examination revealed marked improvement in the mucosal lesions, healing of the aphthoid ulcers and reduction of villous inflammation.1.5 years later, the mucosal lesions disappeared. Infliximab was stopped. there was recurrence of inflammation and terminal ileal mucosal prolapse. Gradual increase in the mucosal inflammation was observed in subsequent endoscopies. The mucosal lesions included: inflammation of individual villi with bleeding into the intestinal cavity; inflammation of villi arranging in a circle around Peyer's patches with early formation of aphthoid ulcers. In another patient thalidomide therapy was initiated and six months after treatment the intestinal ulcers have nearly disappeared. Discussion It is generally believed that the earliest lesion of Crohn's disease begins as an aphthous ulcer. In this study we sequentially follow our patients who have CD or aphthoid ulcers and observe the changes under treatment. We were able to characterize regression of inflammation and aphthoid ulcers upon treatment with biologics, and the genesis of new lesions after cessation of the drug. Our study provides a clue as to the appearance of early lesions hence an opportunity for early treatment, and a direction towards research into pathogenesis.
CRC, colorectal cancer; HGD, high-grade dysplasia, LGD, low-grade dysplasia Su1341 Systematic Analysis of Factors Associated With Progression and Regression of Ulcerative Colitis in the Swiss IBD Cohort Study Ekaterina Safroneeva, Stephan R. Vavricka, Nicolas Fournier, Frank Seibold, Christian Mottet, Alex Straumann, Gerhard Rogler, Alain Schoepfer Background: There is a lack of studies having systematically assessed in a large cohort of patients with ulcerative colitis (UC) the disease location over time as well as risk factors associated with progression or regression of disease extent. Aim: to assess disease location over time and to evaluate associated risk factors. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). Disease locations over time were analyzed and risk factor analysis for a change in disease location was performed using logistic regression modeling. Non parametric data are illustrated as median and interquartile range [IQR]. Results: A total of 1,016 UC patients (45.6% females, median age at diagnosis 31 [23.340.5] years) were included. At diagnosis, UC patients presented with the following disease locations: 199 (19.6%) proctitis, 338 (33.3%) left sided colitis, 381 (37.5%) extensive colitis/ pancolitis, and 98 (9.6%) unknown. During a median of 9 [5-16] years disease duration, a disease progression was documented in 145/1016 (14.3%) of patients, a regression in 176/1016 (17.3%) of patients, whereas 624/1016 (61.4%) of patients had a stable disease location (7% of patients with unknown evolution of disease location over time). Logistic regression modeling identified the following factors associated with disease progression in UC patients presenting with proctitis or left-sided UC at diagnosis: treatment with systemic steroids (OR 2.077, 95%-CI 1.359-3.174, p = 0.001), treatment with immunomodulators (azathioprine, 6-MP, methotrexate) (OR 1.647, 95%-CI 1.119-2.424, p=0.011), treatment with TNF-antagonist(s) (OR 1.668, 95%-CI 1.077-2.581, p = 0.022), and treatment with calcineurin-inhibitors (OR 3.159, 95%-CI 1.679-5.943, p < 0.001). Neither gender, age at UC diagnosis, body mass index, presence of extraintestinal manifestations, smoking status at diagnosis, positive UC family history, nor 5-ASA treatment were associated with disease progression. No specific factors were found to be associated with regression in UC patients with extensive colitis/pancolitis or left-sided colitis at diagnosis. Conclusion: Over a median of 9 years disease duration about two thirds of UC patients maintained the initial disease location whereas one third either had a progression or a regression of the initial disease location. Treatment with systemic steroids, immunomodulators, TNF-antagonists, or calcineurin-inhibitors was significantly associated with disease progression.
A typical ileal ulcer shown with spectral enhancement. The villi surrounding the ulcer became globular and adherent to the underlying structures. Bleeding into the lamina propria of inflamed villi could be seen. Blood vessels in these villi are increased and curved.
Confocal laser endomicroscopic image of inflamed villus. Layer of enterocyte has increased permeability to fluorescein. The blood vessels of the villi are increased and curved. Angiogenesis is an early feature of inflamation of the villus in Crohn's disease.
Su1342 Early Lesions in Small Intestinal Crohn's Disease (CD): An Endoscopic and Confocal Laser Endomicroscopic (CLE) Appraisal Ying Kit Leung, Ying Huang
Su1343 Fibrosis Does Not Increase With Disease Duration in Ulcerative Colitis Jessica R. de Bruyn, Sybren L. Meijer, Manon E. Wildenberg, Gijs R. van den Brink, Geert R. D'Haens
INTRODUCTION Direct observation of the intestinal microstructure has been made possible with the advent of high-resolution endoscopes with zoom, and CLE. In this study, we are able to characterize: 1. changes in the villus structure that surround an aphthoid ulcer; 2. demonstration of mucosal healing while on biologics; 3. identification of early lesions when the disease recurs. MATERIAL AND METHODS A total of 26 patients with CD or ileal ulcers are enrolled. In twelve patients more than one colonoscopies were performed (10 - 51 years). The patients with abdominal pain and aphthoid ulcers were treated with mesalamine & budesonide, and for severe Crohn's disease, infliximab and or thalidomide. Repeat colonoscopies were performed at intervals that varied from 4 months to 2 years to observe the result of the therapy. CLE was used in two patients. Results Acute inflammation of villi surrounding an aphthoid ulcer presents as a rosette of villi surrounding a central ulcer. In the severely inflamed villi, extravasation of blood into the lamina propria is seen. The blood vessels of the villi become tortuous and more numerous in number. CLE demonstrated the changes
Introduction Intestinal fibrosis in Crohn's disease is a process stimulated by chronic inflammation leading to an increased presence of myofibroblasts in all layers of the intestinal wall. Ulcerative colitis (UC) is classically considered to be a purely mucosal disease although rarely transmural complications such as strictures and stenosis develop. Fibrogenesis in UC has not been studied systematically yet and may be a neglected phenomenon. We therefore investigated whether there is a different fibrotic load in acute vs longstanding UC and whether the degree of fibrosis in UC correlates with the severity of inflammation. Methods Colectomy specimens from all UC patients operated in our academic hospital between 20072012 were reviewed. Specimens from patients with recent onset refractory therapy UC (diagnosis < 2 years) and longstanding UC with dysplasia (> 10 years) were selected. Patients
S-441
AGA Abstracts
AGA Abstracts
CRC, 18 advanced adenomas and 18 normal colon samples were sequenced by RRBS; the top 20 candidates were tested by MSP in independent samples including 18 IBD-CRC and 13 IBD-controls. Three novel markers (PDGFD, CHST2, SFMBT2) were selected for comparison to BMP3 and NDRG4; all were assayed by QuARTS in stool samples from 33 IBD-CRN cases (8 CRC, 8 HGD, 8 LGD ≥ 1cm, 10 LGD <1cm) and 50 IBD controls. Four controls were excluded for insufficient β-actin. Median IBD disease duration was 23 years (interquartile range [IQR] 9-35) in cases and 13 (8-20) years in controls (p=0.0009). No other significant differences were seen when comparing age, sex, inflammation severity, IBD extent or co-morbid primary sclerosing cholangitis. Marker levels were not influenced by disease duration after stratification by case and control status. Detection rates at 90% specificity are reported (table). Conclusions: Accurate and novel methylation markers of IBD-CRN were identified by RRBS and validated in both tissues and stools of IBD-CRN patients and IBD controls. Non-optimized novel marker assays were comparable to established candidates. Results were minimally influenced by conventional IBD-CRN risk factors; however, a sensitive test for small polyps, such as chromoendoscopy, may be needed to clear diminutive polyps after positive sDNA. Detection of IBD-associated Colorectal Neoplasms by Methylated Stool DNA at 90% Specificity
CRC, colorectal cancer; HGD, high-grade dysplasia, LGD, low-grade dysplasia Su1341 Systematic Analysis of Factors Associated With Progression and Regression of Ulcerative Colitis in the Swiss IBD Cohort Study Ekaterina Safroneeva, Stephan R. Vavricka, Nicolas Fournier, Frank Seibold, Christian Mottet, Alex Straumann, Gerhard Rogler, Alain Schoepfer Background: There is a lack of studies having systematically assessed in a large cohort of patients with ulcerative colitis (UC) the disease location over time as well as risk factors associated with progression or regression of disease extent. Aim: to assess disease location over time and to evaluate associated risk factors. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). Disease locations over time were analyzed and risk factor analysis for a change in disease location was performed using logistic regression modeling. Non parametric data are illustrated as median and interquartile range [IQR]. Results: A total of 1,016 UC patients (45.6% females, median age at diagnosis 31 [23.340.5] years) were included. At diagnosis, UC patients presented with the following disease locations: 199 (19.6%) proctitis, 338 (33.3%) left sided colitis, 381 (37.5%) extensive colitis/ pancolitis, and 98 (9.6%) unknown. During a median of 9 [5-16] years disease duration, a disease progression was documented in 145/1016 (14.3%) of patients, a regression in 176/1016 (17.3%) of patients, whereas 624/1016 (61.4%) of patients had a stable disease location (7% of patients with unknown evolution of disease location over time). Logistic regression modeling identified the following factors associated with disease progression in UC patients presenting with proctitis or left-sided UC at diagnosis: treatment with systemic steroids (OR 2.077, 95%-CI 1.359-3.174, p = 0.001), treatment with immunomodulators (azathioprine, 6-MP, methotrexate) (OR 1.647, 95%-CI 1.119-2.424, p=0.011), treatment with TNF-antagonist(s) (OR 1.668, 95%-CI 1.077-2.581, p = 0.022), and treatment with calcineurin-inhibitors (OR 3.159, 95%-CI 1.679-5.943, p < 0.001). Neither gender, age at UC diagnosis, body mass index, presence of extraintestinal manifestations, smoking status at diagnosis, positive UC family history, nor 5-ASA treatment were associated with disease progression. No specific factors were found to be associated with regression in UC patients with extensive colitis/pancolitis or left-sided colitis at diagnosis. Conclusion: Over a median of 9 years disease duration about two thirds of UC patients maintained the initial disease location whereas one third either had a progression or a regression of the initial disease location. Treatment with systemic steroids, immunomodulators, TNF-antagonists, or calcineurin-inhibitors was significantly associated with disease progression.
A typical ileal ulcer shown with spectral enhancement. The villi surrounding the ulcer became globular and adherent to the underlying structures. Bleeding into the lamina propria of inflamed villi could be seen. Blood vessels in these villi are increased and curved.
Confocal laser endomicroscopic image of inflamed villus. Layer of enterocyte has increased permeability to fluorescein. The blood vessels of the villi are increased and curved. Angiogenesis is an early feature of inflamation of the villus in Crohn's disease.
Su1342 Early Lesions in Small Intestinal Crohn's Disease (CD): An Endoscopic and Confocal Laser Endomicroscopic (CLE) Appraisal Ying Kit Leung, Ying Huang
Su1343 Fibrosis Does Not Increase With Disease Duration in Ulcerative Colitis Jessica R. de Bruyn, Sybren L. Meijer, Manon E. Wildenberg, Gijs R. van den Brink, Geert R. D'Haens
INTRODUCTION Direct observation of the intestinal microstructure has been made possible with the advent of high-resolution endoscopes with zoom, and CLE. In this study, we are able to characterize: 1. changes in the villus structure that surround an aphthoid ulcer; 2. demonstration of mucosal healing while on biologics; 3. identification of early lesions when the disease recurs. MATERIAL AND METHODS A total of 26 patients with CD or ileal ulcers are enrolled. In twelve patients more than one colonoscopies were performed (10 - 51 years). The patients with abdominal pain and aphthoid ulcers were treated with mesalamine & budesonide, and for severe Crohn's disease, infliximab and or thalidomide. Repeat colonoscopies were performed at intervals that varied from 4 months to 2 years to observe the result of the therapy. CLE was used in two patients. Results Acute inflammation of villi surrounding an aphthoid ulcer presents as a rosette of villi surrounding a central ulcer. In the severely inflamed villi, extravasation of blood into the lamina propria is seen. The blood vessels of the villi become tortuous and more numerous in number. CLE demonstrated the changes
Introduction Intestinal fibrosis in Crohn's disease is a process stimulated by chronic inflammation leading to an increased presence of myofibroblasts in all layers of the intestinal wall. Ulcerative colitis (UC) is classically considered to be a purely mucosal disease although rarely transmural complications such as strictures and stenosis develop. Fibrogenesis in UC has not been studied systematically yet and may be a neglected phenomenon. We therefore investigated whether there is a different fibrotic load in acute vs longstanding UC and whether the degree of fibrosis in UC correlates with the severity of inflammation. Methods Colectomy specimens from all UC patients operated in our academic hospital between 20072012 were reviewed. Specimens from patients with recent onset refractory therapy UC (diagnosis < 2 years) and longstanding UC with dysplasia (> 10 years) were selected. Patients
S-441
AGA Abstracts
AGA Abstracts
CRC, 18 advanced adenomas and 18 normal colon samples were sequenced by RRBS; the top 20 candidates were tested by MSP in independent samples including 18 IBD-CRC and 13 IBD-controls. Three novel markers (PDGFD, CHST2, SFMBT2) were selected for comparison to BMP3 and NDRG4; all were assayed by QuARTS in stool samples from 33 IBD-CRN cases (8 CRC, 8 HGD, 8 LGD ≥ 1cm, 10 LGD <1cm) and 50 IBD controls. Four controls were excluded for insufficient β-actin. Median IBD disease duration was 23 years (interquartile range [IQR] 9-35) in cases and 13 (8-20) years in controls (p=0.0009). No other significant differences were seen when comparing age, sex, inflammation severity, IBD extent or co-morbid primary sclerosing cholangitis. Marker levels were not influenced by disease duration after stratification by case and control status. Detection rates at 90% specificity are reported (table). Conclusions: Accurate and novel methylation markers of IBD-CRN were identified by RRBS and validated in both tissues and stools of IBD-CRN patients and IBD controls. Non-optimized novel marker assays were comparable to established candidates. Results were minimally influenced by conventional IBD-CRN risk factors; however, a sensitive test for small polyps, such as chromoendoscopy, may be needed to clear diminutive polyps after positive sDNA. Detection of IBD-associated Colorectal Neoplasms by Methylated Stool DNA at 90% Specificity