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S1171 Polyp Growth With Increase in Age in Patients Undergoing Colonoscopy Screening
S1171
AGA Abstracts
Polyp Growth With Increase in Age in Patients Undergoing Colonoscopy Screening Albert B. Lowenfels, Jennifer L. Holub, David A. Lieberman, Patrick Maisonneuve, Luke Williams AIM: Colonic polyps are causally related to the nearly 150,000 yearly incident cases of colon cancer in the USA. The study aim was to identify and quantitate variables that affect polyp size in a large sample of patients undergoing CS for indications of routine screening or family history of colorectal cancer. METHODS: 93,110 adult patients from 67 GI practices in 25 states undergoing CS who had colorectal polyps on exam were identified in the Clinical Outcomes Research Initiative (CORI) database. Polyp size of the largest polyp was the outcome variable; patient age, race, gender, type of practice, anatomic location, and indication for procedure were independent variables. Ten-year age bands were used to stratify patient age; the size of the largest polyp in each patient was stratified into four ordinal groups (05 mm, 5.1-9, 9.1-15, >15 mm). Ordinal logistic regression was used to obtain multivariateadjusted estimates of polyp size in relation to patient age. RESULTS: For patients <50 years, the respective mean polyp size (mm) in males and females were 5.8 + 4.15 and 5.7 + 4.16. Size increased to 7.3 + 6.02 and 6.9 + 5.52 mm for patients >80 years. After multivariate adjustment, odds of having a larger polyp increased with each increasing age group, compared to those under 50 years (see Table). The odds ratio for polyp size in the oldest age group versus youngest age group was 1.61 (95% CI = 1.46-1.77, p = <0.0001). Other factors with multivariate-adjusted significant odds ratios were gender (males vs females 1.18, P = <0.0001), race (blacks versus whites 1.33, P = <0.0001), practice type (community vs academic 1.26, P = <0.0001), and polyp location (distal vs proximal colon 0.89, P = <0.0001). CONCLUSION: Size of the largest polyp detected at CS increases significantly with age, and among variables included in a multivariate model, age has the strongest association with polyp size.
S1173 Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Crohn's Disease Grace Gathungu, John P. Ferguson, Mark S. Silverberg, Bruce Trapnell, Lee Denson, Judy H. Cho, Graham L. Radford-Smith Background/Aims: The pathogenesis of Inflammatory Bowel Disease (IBD) is defined as a dysregulated mucosal immunity to commensal bacteria in genetically susceptible individuals {Cho et al, Nat Immun Rev 2008}. A recent meta-analysis reported 32 risk loci, estimated to explain 10% of the overall variance in CD risk {Barrett et al, Nat Gen 2008}. Neutralizing antibodies to cytokines are proposed as risk factors. Antibodies against granulocyte macrophage colony-stimulating factor (GM-CSF Ab) were elevated in adult and pediatric CD patients and associated with ileal location. CD patients with high GMCSF Ab had reduced neutrophil phagocytic capacity and NOD2 deficient mice given neutralizing ab to GM-CSF developed a transmural ileitis {Han et al, Gastro 2009}. We investigated GM-CSF Ab levels in a cohort of adult IBD patients from the NIDDK IBD genetics consortium. We plan to investigate these and other anti-cytokine antibodies along with host genotype, environmental factors (smoking) and clinical variables (immunosuppressive therapy). Methods: Serum samples from 303 adult IBD patients were analyzed for GM-CSF Ab and IBD markers (Table2). Levels of GM-CSF Ab were compared with clinical variables including disease location, age at diagnosis, smoking status at diagnosis, and exposure to IBD medication (immunosuppressants and biologics). Results: Median GM-CSF Ab levels were 1.14 ug/mL in UC serum samples and 4.14 ug/mL in CD serum samples and were associated with ileal involvement (P = .004). Ileal location and increased GM-CSF Ab levels were associated with stricturing/ penetrating behavior and smokers had over all decreased GMCSF Ab levels. Conclusions: We confirm a previous finding of elevated GM-CSF Ab levels in adult patients with CD. Carriage of risk alleles for ATG16L1 and a high GM-CSF Ab level were predictive of Ileal location. Exposure to Immunosuppressants decreased risk of stricturing or penetrating disease behavior although not significant. Finally, CD smokers and ex-smokers had lower expression GM-CSF Ab levels than non-smokers. GM-CSF Ab expression by IBD diagnosis
S1172 Genetic Markers Associated With the Development of Denovo Crohn's Disease After Ileal Pouch-Anal Anastomosis Diana Cheng-Robles, Dermot P. McGovern, Gil Y. Melmed, Dror Berel, Eric A. Vasiliauskas, Marla Dubinsky, Andrew Ippoliti, David Shih, Stephan R. Targan, Phillip Fleshner Background: Of patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) or inflammatory bowel disease unclassified (IBDU), up to 10% will develop denovo Crohn's disease (CD). An association between family history and the development of denovo CD after IPAA has been reported (Melmed et al, Shen et al), suggesting the importance of genetic background. The aim of this study was to determine the association between known CD susceptibility genes in the development of denovo CD in UC or IBDU patients undergoing IPAA. Methods: UC or IBDU patients undergoing IPAA by a single surgeon were enrolled into a prospective database. SNPs with known association with CD were chosen for the analyses. Denovo CD after IPAA was diagnosed by inflammation, pouch fistula, or perianal complication. Allelic associations analyzed using Fishers exact test and Cox proportional hazards methods. Results: 43 out of 256 pts (16%) developed denovo CD; afferent limb inflammation (n=33), pouch fistula (n=6) or perianal disease (n=4). Median time developing denovo CD was 21 months (range 1-42). 3 out of 86 SNPs were associated with denovo CD; RHOU (p=0.001), SCN3A (p=0.007), and PTPN2 (p=0.013) and borderline association seen with PUS10 (p=0.056). CD free survival after IPAA can be seen by Kaplan Meier graph (Figure 1). Having two risk alleles showed a significantly higher rate of denovo CD (p<0.00001). Conclusions: We demonstrated 3 SNPs associated with CD susceptibility that are related to the development of CD in UC or IBDU patients after IPAA. Further investigation is needed but this study suggests the importance of genetic factors in the pathogenesis of denovo CD after IPAA.
Odds Ratio Estimates from Logistic Regression
dataset for NOD2 SNPs incomplete S1174 UC Patients With High Level Antibody Responses to CD-Associated Microbial Antigens Exhibit Aberrant IFNG DNA Methylation Patterns Rivkah Gonsky, Richard L. Deem, Brian Ko, Dror Berel, Carrie Derkowski, Dermot P. McGovern, Carol J. Landers, Stephan R. Targan BACKGROUND: Dysregulated mucosal immune response to enteric bacterial flora in genetically susceptible individuals is believed to trigger IBD. High antibody responses toward multiple microbial antigens is associated with more aggressive disease and risk for surgery in CD. Enhanced Th1 cytokine expression, particularly IFN-γ, is commonly associated with
AGA Abstracts
S-196
AGA Abstracts
Polyp Growth With Increase in Age in Patients Undergoing Colonoscopy Screening Albert B. Lowenfels, Jennifer L. Holub, David A. Lieberman, Patrick Maisonneuve, Luke Williams AIM: Colonic polyps are causally related to the nearly 150,000 yearly incident cases of colon cancer in the USA. The study aim was to identify and quantitate variables that affect polyp size in a large sample of patients undergoing CS for indications of routine screening or family history of colorectal cancer. METHODS: 93,110 adult patients from 67 GI practices in 25 states undergoing CS who had colorectal polyps on exam were identified in the Clinical Outcomes Research Initiative (CORI) database. Polyp size of the largest polyp was the outcome variable; patient age, race, gender, type of practice, anatomic location, and indication for procedure were independent variables. Ten-year age bands were used to stratify patient age; the size of the largest polyp in each patient was stratified into four ordinal groups (05 mm, 5.1-9, 9.1-15, >15 mm). Ordinal logistic regression was used to obtain multivariateadjusted estimates of polyp size in relation to patient age. RESULTS: For patients <50 years, the respective mean polyp size (mm) in males and females were 5.8 + 4.15 and 5.7 + 4.16. Size increased to 7.3 + 6.02 and 6.9 + 5.52 mm for patients >80 years. After multivariate adjustment, odds of having a larger polyp increased with each increasing age group, compared to those under 50 years (see Table). The odds ratio for polyp size in the oldest age group versus youngest age group was 1.61 (95% CI = 1.46-1.77, p = <0.0001). Other factors with multivariate-adjusted significant odds ratios were gender (males vs females 1.18, P = <0.0001), race (blacks versus whites 1.33, P = <0.0001), practice type (community vs academic 1.26, P = <0.0001), and polyp location (distal vs proximal colon 0.89, P = <0.0001). CONCLUSION: Size of the largest polyp detected at CS increases significantly with age, and among variables included in a multivariate model, age has the strongest association with polyp size.
S1173 Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in Crohn's Disease Grace Gathungu, John P. Ferguson, Mark S. Silverberg, Bruce Trapnell, Lee Denson, Judy H. Cho, Graham L. Radford-Smith Background/Aims: The pathogenesis of Inflammatory Bowel Disease (IBD) is defined as a dysregulated mucosal immunity to commensal bacteria in genetically susceptible individuals {Cho et al, Nat Immun Rev 2008}. A recent meta-analysis reported 32 risk loci, estimated to explain 10% of the overall variance in CD risk {Barrett et al, Nat Gen 2008}. Neutralizing antibodies to cytokines are proposed as risk factors. Antibodies against granulocyte macrophage colony-stimulating factor (GM-CSF Ab) were elevated in adult and pediatric CD patients and associated with ileal location. CD patients with high GMCSF Ab had reduced neutrophil phagocytic capacity and NOD2 deficient mice given neutralizing ab to GM-CSF developed a transmural ileitis {Han et al, Gastro 2009}. We investigated GM-CSF Ab levels in a cohort of adult IBD patients from the NIDDK IBD genetics consortium. We plan to investigate these and other anti-cytokine antibodies along with host genotype, environmental factors (smoking) and clinical variables (immunosuppressive therapy). Methods: Serum samples from 303 adult IBD patients were analyzed for GM-CSF Ab and IBD markers (Table2). Levels of GM-CSF Ab were compared with clinical variables including disease location, age at diagnosis, smoking status at diagnosis, and exposure to IBD medication (immunosuppressants and biologics). Results: Median GM-CSF Ab levels were 1.14 ug/mL in UC serum samples and 4.14 ug/mL in CD serum samples and were associated with ileal involvement (P = .004). Ileal location and increased GM-CSF Ab levels were associated with stricturing/ penetrating behavior and smokers had over all decreased GMCSF Ab levels. Conclusions: We confirm a previous finding of elevated GM-CSF Ab levels in adult patients with CD. Carriage of risk alleles for ATG16L1 and a high GM-CSF Ab level were predictive of Ileal location. Exposure to Immunosuppressants decreased risk of stricturing or penetrating disease behavior although not significant. Finally, CD smokers and ex-smokers had lower expression GM-CSF Ab levels than non-smokers. GM-CSF Ab expression by IBD diagnosis
S1172 Genetic Markers Associated With the Development of Denovo Crohn's Disease After Ileal Pouch-Anal Anastomosis Diana Cheng-Robles, Dermot P. McGovern, Gil Y. Melmed, Dror Berel, Eric A. Vasiliauskas, Marla Dubinsky, Andrew Ippoliti, David Shih, Stephan R. Targan, Phillip Fleshner Background: Of patients undergoing ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) or inflammatory bowel disease unclassified (IBDU), up to 10% will develop denovo Crohn's disease (CD). An association between family history and the development of denovo CD after IPAA has been reported (Melmed et al, Shen et al), suggesting the importance of genetic background. The aim of this study was to determine the association between known CD susceptibility genes in the development of denovo CD in UC or IBDU patients undergoing IPAA. Methods: UC or IBDU patients undergoing IPAA by a single surgeon were enrolled into a prospective database. SNPs with known association with CD were chosen for the analyses. Denovo CD after IPAA was diagnosed by inflammation, pouch fistula, or perianal complication. Allelic associations analyzed using Fishers exact test and Cox proportional hazards methods. Results: 43 out of 256 pts (16%) developed denovo CD; afferent limb inflammation (n=33), pouch fistula (n=6) or perianal disease (n=4). Median time developing denovo CD was 21 months (range 1-42). 3 out of 86 SNPs were associated with denovo CD; RHOU (p=0.001), SCN3A (p=0.007), and PTPN2 (p=0.013) and borderline association seen with PUS10 (p=0.056). CD free survival after IPAA can be seen by Kaplan Meier graph (Figure 1). Having two risk alleles showed a significantly higher rate of denovo CD (p<0.00001). Conclusions: We demonstrated 3 SNPs associated with CD susceptibility that are related to the development of CD in UC or IBDU patients after IPAA. Further investigation is needed but this study suggests the importance of genetic factors in the pathogenesis of denovo CD after IPAA.
Odds Ratio Estimates from Logistic Regression
dataset for NOD2 SNPs incomplete S1174 UC Patients With High Level Antibody Responses to CD-Associated Microbial Antigens Exhibit Aberrant IFNG DNA Methylation Patterns Rivkah Gonsky, Richard L. Deem, Brian Ko, Dror Berel, Carrie Derkowski, Dermot P. McGovern, Carol J. Landers, Stephan R. Targan BACKGROUND: Dysregulated mucosal immune response to enteric bacterial flora in genetically susceptible individuals is believed to trigger IBD. High antibody responses toward multiple microbial antigens is associated with more aggressive disease and risk for surgery in CD. Enhanced Th1 cytokine expression, particularly IFN-γ, is commonly associated with
AGA Abstracts
S-196