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Background In inflammatory bowel disease (IBD), many scenarios call for fecal diversion, leaving behind defunctionalized bowel. The theoretical risk of colorectal cancer (CRC) in this segment is frequently cited as a reason for resection. To date, no studies have characterized the incidence of neoplasia in the diverted colorectal segments of IBD patients. Methods A retrospective cohort analysis was conducted for IBD patients identified through a tertiary care center pathology database. Patients that had undergone colorectal diversion and were diverted for ≥ 1 year were included. Incidence of diverted dysplasia/CRC was calculated for Crohn’s disease (CD) and ulcerative colitis (UC) with respect to diverted patient-years (dpy) and patient-years of disease (pyd). Results In total, 154 patients comprising 754 dpy and 1984 pyd were analyzed. Only 2 cases of diverted colorectal dysplasia (CD 1, UC 1) and 1 case of diverted CRC (UC) were observed. In the UC cohort (n = 75), the rate of diversion-associated CRC was 4.5 cases/1000 dpy (95% CI 0.11–25/1000) or 1.5 cases/1000 pyd (95% CI 0.04–8.2/1000). In the CD cohort (n = 79), no patients developed CRC, although a dysplasia rate of 1.9 cases/1000 dpy (95% CI 0.05–11/1000) or 0.77 cases/1000 pyd (95% CI 0.02–4.3/1000) was observed. All patients developing neoplasia had disease duration > 10 years and microscopic inflammation. Conclusions Diverted dysplasia occurred infrequently with rates overlapping those reported in registries for IBD-based rectal cancers. Neoplasia was undetected in patients with < 10 pyd, regardless of diversion duration, suggesting low yield for endoscopic surveillance before this time.

Background: Crohn's disease (CD) and ulcerative colitis (UC) result from pathophysiologically distinct dysregulated immune responses, as evidenced by the preponderance of differing immune cell mediators and circulating cytokine expression profiles. MicroRNAs (miRNAs) are small, noncoding RNAs that act as negative regulators of gene expression and have an increasingly recognized role in immune regulation. We hypothesized that differences in circulating immune cells in CD and UC patients are reflected by altered miRNA expression and that miRNA expression patterns can distinguish CD and UC from normal healthy individuals. Methods: Peripheral blood was obtained from patients with active CD, inactive CD, active UC, inactive UC, and normal healthy adults. Total RNA was isolated and miRNA expression assessed using miRNA microarray and validated by mature miRNA quantitative reverse-transcription polymerase chain reaction. Results: Five miRNAs were significantly increased and two miRNAs (149* and miRplus-F1065) were significantly decreased in the blood of active CD patients as compared to healthy controls. Twelve miRNAs were significantly increased and miRNA-505* was significantly decreased in the blood of active UC patients as compared to healthy controls. Ten miRNAs were significantly increased and one miRNA was significantly decreased in the blood of active UC patients as compared to active CD patients. Conclusions: Peripheral blood miRNAs can be used to distinguish active CD and UC from healthy controls. The data support the evidence that CD and UC are associated with different circulating immune cells types and that the differential expression of peripheral blood miRNAs may form the basis of future diagnostic tests for inflammatory bowel disease. (Inflamm Bowel Dis 2011;)

Background: Anti-glycan antibody serologic markers may serve as a useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and the need for surgery in IBD. Methods: The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery). Results: Fourteen studies were included in the systemic review and nine in the meta-analysis. Individually, anti-Saccharomyces cervisiae antibodies (ASCA) had the highest DOR for differentiating IBD from healthy (DOR 21.1; 1.8–247.3; two studies), and CD from UC (DOR 10.2; CI 7.7–13.7; seven studies). For combination of ≥2 markers, the DOR was 2.8 (CI 2.2–3.6; two studies) for CD-related surgery, higher than any individual marker, while the DOR for differentiating CD from UC was 10.2 (CI 5.6–18.5; three studies) and for complication was 2.8 (CI 2.2–3.7; two studies), similar to individual markers. Conclusions: ASCA had the highest diagnostic value among individual anti-glycan markers. While anti-chitobioside carbohydrate antibody (ACCA) had the highest association with complications, ASCA and ACCA associated equally with the need for surgery. Although in most individual studies the combination of ≥2 markers had a better diagnostic value as well as higher association with complications and need for surgery, we found the combination performing slightly better than any individual marker in our meta-analysis. (Inflamm Bowel Dis 2012)

Background: CpG island (CGI) hypermethylation at discrete loci is a prevalent cancer-promoting abnormality in sporadic colorectal carcinomas (S-CRCs). We investigated genome-wide CGI methylation in inflammatory bowel disease (IBD)-associated CRCs (IBD-CRCs). Methods: Methylation microarray analyses were conducted on seven IBD-CRCs, 17 S-CRCs, and eight normal control colonic tissues from patients without CRC or IBD. CGI methylator phenotype (CIMP), a surrogate marker for widespread cancer-specific CGI hypermethylation, was examined in 30 IBD-CRCs and 43 S-CRCs. Results: The genome-wide CGI methylation pattern of IBD-CRCs was CIMP status-dependent. Based on methylation array data profiling of all autosomal loci, CIMP+ IBD-CRCs grouped together with S-CRCs, while CIMP− IBD-CRCs grouped together with control tissues. CIMP− IBD-CRCs demonstrated less methylation than did age-matched CIMP− S-CRCs at autosomal CGIs (z-score −0.17 vs. 0.09, P = 3 × 10−3) and CRC-associated hypermethylation target CGIs (z-score −0.43 vs. 0.68, P = 1 × 10−4). Age-associated hypermethylation target CGIs were significantly overrepresented in CGIs that were hypermethylated in S-CRCs (P = 1 × 10−192), but not in CGIs that were hypermethylated in IBD-CRCs (P = 0.11). In contrast, KRAS mutation prevalence was similar between IBD-CRCs and S-CRCs. Notably, CIMP+ prevalence was significantly higher in older than in younger IBD-CRC cases (50.0 vs. 4.2, P = 0.02), but not in S-CRC cases (9.7 vs. 16.7, P = 0.92). Conclusions: Cancer-specific CGI hypermethylation and age-associated CGI hypermethylation are diminished in IBD-CRCs relative to S-CRCs, while the KRAS mutation rate is comparable between these cancers. CGI hypermethylation appears to play only a minor role in IBD-associated carcinogenesis. We speculate that aging, rather than inflammation per se, promotes CIMP+ CRCs in IBD patients. (Inflamm Bowel Dis 2011;)