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Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease.

ABSTRACT: Serrated epithelial change (SEC) is a histologic finding in longstanding colitis that may be associated with dysplasia. Our primary aim was to determine the incidence of dysplasia and colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with SEC. Secondary aims were to determine the rate of location concordance between SEC and dysplasia/CRC and to identify other risk factors associated with dysplasia in IBD patients with SEC.A retrospective, descriptive, observational study was performed by searching the Pathology Data System at a single tertiary referral center for a histologic finding of "serrated epithelial change." The patient's first pathology specimen with SEC was designated the index SEC. All subsequent pathology reports were evaluated for the occurrence and location of dysplasia or CRC. Univariable and multivariable logistic regression were performed to identify predictors of dysplasia.There were 187 patients with confirmed IBD and 1 or more histologic findings of SEC without prior dysplasia. Mean IBD duration was 16 years, and median follow-up time was 28 months. The rate of high-grade dysplasia or CRC was 17 per 1000 patient-years. Thirty-nine of 187 patients (21%) had synchronous or metachronous dysplasia or CRC. Location concordance was 68%. Multivariable analysis found SEC on follow-up examinations, older age at IBD diagnosis, male gender, and a first-degree relative with CRC were associated with dysplasia in IBD patients with SEC.This uncontrolled study describes a high frequency of dysplasia in patients with a histologic finding of SEC. SEC seen on successive endoscopic examinations further increased the risk of dysplasia. Further controlled studies are needed to determine if SEC is a precancerous lesion in IBD patients and if SEC can be endoscopically identified.

SUBMITTER: Parian A

PROVIDER: S-EPMC5555397 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease.

Parian Alyssa A Koh Joyce J Limketkai Berkeley N BN Eluri Swathi S Rubin David T DT Brant Steven R SR Ha Christina Y CY Bayless Theodore M TM Giardiello Francis F Hart John J Montgomery Elizabeth E Lazarev Mark G MG

Gastrointestinal endoscopy 20151218 1

<h4>Background and aims</h4>Serrated epithelial change (SEC) is a histologic finding in longstanding colitis that may be associated with dysplasia. Our primary aim was to determine the incidence of dysplasia and colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with SEC. Secondary aims were to determine the rate of location concordance between SEC and dysplasia/CRC and to identify other risk factors associated with dysplasia in IBD patients with SEC.<h4>Methods</h4>A retrospec ...[more]

PMID: 26709112

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Project description:BackgroundChromoendoscopy is preferred over high-definition white light endoscopy (HDWLE) for dysplasia surveillance in inflammatory bowel disease (IBD) patients, but is more time-consuming to perform and real-world evidence is limited. The prevalence of sessile serrated lesions (SSLs) in IBD patients is also unknown.ObjectiveTo determine the yield of polypoid and non-polypoid dysplasia and SSLs in IBD patients undergoing dysplasia surveillance and the associations for these lesions.DesignA retrospective cohort study from a tertiary IBD centre.MethodsA keyword search of the colonoscopy reporting system was performed. IBD patients with colonic disease that underwent colonoscopy for surveillance between 1 February 2015 and 1 February 2018 were included. Clinical, endoscopic and histopathological outcomes were extracted for the analysis.ResultsOf 2114 patients identified, 276 eligible colonoscopies in 126 patients were analysed. The median age at colonoscopy was 51 years (interquartile range: 42-58 years). 71/126 (56%) of colonoscopies were performed in male patients, with 57/126 (45%) having ulcerative colitis, 68/126 (54%) Crohn's colitis and 1/126 (0.79%) IBD-unspecified. The prevalence for any neoplasia was 75/276 (27%). The prevalence for all serrated lesions was 43/276 (16%). Increased age was a risk factor for finding a neoplastic lesion on both univariate and multivariate analyses. Chromoendoscopy was associated with twice the odds of finding a neoplastic lesion (odds ratio: 1.99, 95% confidence interval: 1.13-3.51, p = 0.02), on multivariate analysis. No factor was associated with an increased risk of finding a serrated lesion.ConclusionSignificant neoplastic lesions and serrated lesions were detected in 27% and 16% of colonoscopies performed in IBD patients, respectively, with the highest yield in older patients. Chromoendoscopy significantly increased neoplasia yield compared to HDWLE and still has a robust utility in this pragmatic real-world study.

Project description:Background & aimsLittle is known about the clinical significance of indefinite dysplasia (IND) in patients with inflammatory bowel diseases (IBD) undergoing colonoscopic surveillance for colorectal neoplasia.MethodsWe conducted a retrospective cohort analysis of 492 patients with colonic IBD for 8 or more years or concomitant primary sclerosing cholangitis, with no history of advanced colorectal neoplasia (high-grade dysplasia or colorectal cancer) or colectomy, undergoing colorectal neoplasia surveillance at a tertiary IBD referral center from 2001 through 2017. Subjects received consistent histopathologic grading of dysplasia. We collected data on time to development of (advanced) colorectal neoplasia or colectomy using Kaplan Meier methods. We identified factors independently associated with (advanced) colorectal neoplasia with multivariable Cox regression analysis.ResultsAfter 2149 person-years of follow-up, 53 patients (10.8%) received a diagnosis of IND without prior or synchronous low-grade dysplasia (LGD). Compared to patients without dysplasia, patients with IND had a significantly higher risk of advanced colorectal neoplasia (adjusted hazard ratio, 6.85; 95% CI, 1.78-26.4) and colorectal neoplasia (adjusted hazard ratio, 3.25; 95% CI, 1.50-7.05), but not colectomy (P = .78). Compared to IND, LGD was associated with a significantly higher risk of advanced colorectal neoplasia (P = .05). Following a diagnosis of no dysplasia, IND only, or LGD, the incidence rates of advanced colorectal neoplasia were 0.4% per patient-year, 3.1% per patient-year, and 8.4% per patient-year, respectively.ConclusionsIn a retrospective analysis of patients with IBD undergoing colorectal neoplasia surveillance with consistent histopathologic grading of dysplasia, IND was independently associated with a significant increase in risk of advanced colorectal neoplasia. These findings require validation and if confirmed, a reappraisal of the colorectal neoplasia surveillance guidelines.

Project description:BACKGROUND & AIMS:Patients with inflammatory bowel diseases who have postinflammatory polyps (PIPs) have an increased risk of colorectal neoplasia (CRN). European guidelines propose that patients with PIPs receive more frequent surveillance colonoscopies, despite limited evidence of this increased risk. We aimed to define the risk of CRN and colectomy in patients with inflammatory bowel diseases and PIPs. METHODS:We conducted a multicenter retrospective cohort study of patients with inflammatory bowel diseases who underwent colonoscopic surveillance for CRN, from January 1997 through January 2017, at 5 academic hospitals and 2 large nonacademic hospitals in New York or the Netherlands. Eligible patients had confirmed colonic disease with duration of at least 8 years (or any duration, if they also had primary sclerosing cholangitis) and no history of advanced CRN (high-grade dysplasia or colorectal cancer) or colectomy. The primary outcome was occurrence of advanced CRN according to PIP status; secondary outcomes were occurrence of CRN (inclusive of low-grade dysplasia) and colectomy. RESULTS:Of 1582 eligible patients, 462 (29.2%) had PIPs. PIPs were associated with more severe inflammation (adjusted odds ratio 1.32; 95% confidence interval [CI] 1.13-1.55), greater disease extent (adjusted odds ratio 1.92; 95% CI 1.34-2.74), and lower likelihood of primary sclerosing cholangitis (adjusted odds ratio 0.38; 95% CI 0.26-0.55). During a median follow-up period of 4.8 years, the time until development of advanced CRN did not differ significantly between patients with and those without PIPs. PIPs did not independently increase the risk of advanced CRN (adjusted hazard ratio 1.17; 95% CI 0.59-2.31). The colectomy rate was significantly higher in patients with PIPs (P = .01). CONCLUSIONS:In a retrospective analysis of data from 2 large independent surveillance cohorts, PIPs were associated with greater severity and extent of colon inflammation and higher rates of colectomy, but were not associated with development of any degree of CRN. Therefore, intervals for surveillance should not be shortened based solely on the presence of PIPs.

Project description:BackgroundMyeloid cells, including monocytes, macrophages, microglia, dendritic cells and neutrophils are a part of innate immunity, playing a major role in orchestrating innate and adaptive immune responses. Microglia are the resident myeloid cells of the central nervous system, and many Alzheimer's disease (AD) risk loci are found in or near genes that are highly or sometimes uniquely expressed in myeloid cells. Similarly, inflammatory bowel disease (IBD) loci are also enriched for genes expressed by myeloid cells. However, the extent to which there is overlap between the effects of AD and IBD susceptibility loci in myeloid cells remains poorly described, and the substantial IBD genetic maps may help to accelerate AD research.MethodsHere, we leveraged summary statistics from large-scale genome-wide association studies (GWAS) to investigate the causal effect of IBD (including ulcerative colitis and Crohn's disease) variants on AD and AD endophenotypes. Microglia and monocyte expression Quantitative Trait Locus (eQTLs) were used to examine the functional consequences of IBD and AD risk variants enrichment in two different myeloid cell subtypes.ResultsOur results showed that, while PTK2B is implicated in both diseases and both sets of risk loci are enriched for myeloid genes, AD and IBD susceptibility loci largely implicate distinct sets of genes and pathways. AD loci are significantly more enriched for microglial eQTLs than IBD. We also found that genetically determined IBD is associated with a lower risk of AD, which may driven by a negative effect on the accumulation of neurofibrillary tangles (beta=-1.04, p=0.013). In addition, IBD displayed a significant positive genetic correlation with psychiatric disorders and multiple sclerosis, while AD showed a significant positive genetic correlation with amyotrophic lateral sclerosis.ConclusionTo our knowledge, this is the first study to systematically contrast the genetic association between IBD and AD, our findings highlight a possible genetically protective effect of IBD on AD even if the majority of effects on myeloid cell gene expression by the two sets of disease variants are distinct. Thus, IBD myeloid studies may not help to accelerate AD functional studies, but our observation reinforces the role of myeloid cells in the accumulation of tau proteinopathy and provides a new avenue for discovering a protective factor.

Dataset Information

Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease.

Publications

Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease.

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