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Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.

ABSTRACT: Background:Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity. Methods:Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards. Demographic and clinical data were obtained from the electronic medical record. RNA extraction and human transcriptome microarray were performed on noninflamed ileal margins from operative specimens. Clinical data and random forest were analyzed in R. Principal components analysis, hierarchical clustering, and pathway enrichment were performed in Partek. Results:Sixty-five patients completed the study, and 5 were excluded from analysis due to extreme variability on whole transcriptome analysis. Unsupervised hierarchical clustering revealed that patients with an i0 Rutgeerts score generally segregated from all others. In anti-TNF-naïve patients, unsupervised hierarchical clustering revealed complete segregation of patients with an i0 score. Reduced escalation in therapy and continued mucosal remission, consistent with indolent disease, were seen in the 4 years following surgery. Random forest identified 30 transcripts differentiating i0 patients from the other groups. Pathway enrichment highlighted toll-like receptor, NOD-like receptor, and TNF signaling. This transcriptome signature did not identify i0 anti-TNF-exposed patients. However, anti-TNF-exposed patients with indolent postoperative courses were found to have a transcriptome signature distinct from those with aggressive disease. Conclusions:Anti-TNF-naïve and -exposed patients have unique expression profiles at the time of surgery, which may offer predictive value in assessing the risk of nonrecurrence. 10.1093/ibd/izy228_video1izy228.video15804852517001.

SUBMITTER: Cushing KC

PROVIDER: S-EPMC6354560 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.

Cushing Kelly C KC Mclean Richard R McDonald Keely G KG Gustafsson Jenny K JK Knoop Kathryn A KA Kulkarni Devesha H DH Sartor R Balfour RB Newberry Rodney D RD

Inflammatory bowel diseases 20190101 1

<h4>Background</h4>Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity.<h4>Methods</h4>Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards. Demographic and clinical data were obtained from the elect ...[more]

PMID: 29982468

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Project description:BackgroundMany patients with Crohn's disease will develop complications that require surgery. Recurrence after surgery is common.AimTo assess racial differences in postoperative recurrence between African-Americans and Caucasians.MethodsMedical records of Crohn's disease patients who underwent surgery (ileal, colonic, or ileocolonic resection) between June 2014 and June 2016 were reviewed. The primary endpoints were clinical and endoscopic remission at 6-12 months after a Crohn's disease surgery. Secondary outcomes included biological and histologic remission. Risks of recurrence were assessed by univariate, multivariate, and propensity score-matched analysis.ResultsThirty-six African-American and 167 Caucasian patients with Crohn's disease were included for analysis. There was no difference in disease location, disease behaviour, type of surgery performed, and pre- or postoperative medication use between the two groups. The rate of endoscopic remission did not differ between African-American and Caucasian patients (50% vs 42%, P = 0.76), and race did not influence the risk of endoscopic recurrence on univariate, multivariate, or propensity score-matched analysis. The rate of clinical remission was significantly lower in African-American patients compared to Caucasian patients (36% vs. 63%, P = 0.008). African-American race was significantly associated with clinical recurrence on univariate (odds ratio (OR) 6.76, 95% CI 1.50-30.40; P = 0.01), multivariate (OR 5.02, 95% CI 1.60-15.80; P = 0.006), and propensity-matched analysis (68% vs. 32% in Caucasians, P = 0.005). Rates of biologic and histologic remission were similar between the two groups on all analyses.ConclusionsWe found that African-American patients with Crohn's disease have a similar degree of objective measures of mucosal inflammation after surgery including endoscopic recurrence as compared to Caucasian patients. However, African-American race was significantly associated with clinical recurrence, suggesting the presence of ethnic variation in postoperative presentation in Crohn's disease.

Dataset Information

Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.

Publications

Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.

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