Detection rate and outcome of colonic serrated epithelial changes in patients with ulcerative colitis or Crohn's colitis.

BACKGROUND: Chronic ulcerative colitis (CUC) and colonic Crohn's disease (CD) increase colorectal neoplasia (CRN) risk. While sessile serrated polyp (SSP) is a known cancer precursor, serrated epithelial changes (SEC) are of uncertain prevalence and neoplastic risk. AIM: To assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single-centre cohort study. METHODS: Patients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006-12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan-Meier method. RESULTS: Between 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010-12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0-30%) and 30% (3-57%), respectively, in SEC patients compared to 4% (0-12%) and 9% (0-23%), respectively, in CUC or CD controls (P = 0.047, log-rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia (P = 0.09). CONCLUSIONS: Serrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn's disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship.

Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease.

BACKGROUND: Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal. AIM: To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN. METHODS: This investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD-CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. RESULTS: IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD-CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. CONCLUSION: These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.

Anti-Saccharomyces cerevisiae antibody (ASCA) positivity is associated with increased risk for early surgery in Crohn's disease.

BACKGROUND: Anti-Saccharomyces cerevisiae antibodies (ASCA) are a specific but only moderately sensitive diagnostic marker for Crohn's disease. We sought to explore the role of ASCA as a prognostic marker for aggressive disease phenotype in Crohn's disease. AIMS: To determine the role of ASCA status as a risk factor for early surgery in Crohn's disease. SUBJECTS: We performed a case control study in a cohort of patients, newly diagnosed with Crohn's disease, between 1991 and 1999. All patients were followed for at least three years. Case subjects (n = 35) included those who had major surgery for Crohn's disease within three years of diagnosis. Controls (n = 35) included patients matched to cases for age, sex, disease location, and smoking status, and who did not undergo major surgery for Crohn's disease within three years of diagnosis. METHODS: Blinded assays were performed on serum for ASCA (immunoglobulin (Ig)A and IgG). A paired analysis of cases-controls was performed to test for the association between ASCA status and risk of early surgery. RESULTS: ASCA IgA was strongly associated with early surgery (odds ratio (OR) 8.5 (95% confidence interval (CI) 2.0-75.9); p = 0.0013). ASCA IgG+ and ASCA IgG+/IgA+ patients were also at increased risk for early surgery (OR 5.5 (95% CI 1.2-51.1), p = 0.0265; and OR 5.0 (95% CI 1.1-46.9), p = 0.0433, respectively). The association between ASCA and early surgery was evident in patients requiring surgery for ileal or ileocolonic disease. CONCLUSIONS: Patients with Crohn's disease who are positive for ASCA IgA, IgG, or both, may define a subset of patients with Crohn's disease at increased risk for early surgery.