Clinical and Genetic Factors Impact Time to Surgical Recurrence After Ileocolectomy for Crohn's Disease

Abstract

Objective:The aim of this study was to evaluate factors associated with time to surgical recurrence after Crohn's ileocolectomy.Summary Background Data:The most common surgery performed for Crohn's disease is ileocolectomy. Identifying patients at high risk for surgical recurrence may assist with medical and surgical decision-making.Methods:Data were obtained from 409 patients with Crohn's disease (CD) who had undergone ≥1 ileocolectomies at Penn State Hershey Medical Center. Six single-nucleotide polymorphisms (SNPs) associated with CD were evaluated in these patients: rs2076756, rs2066844, and rs2066845 in NOD2, rs4958847 and rs13361189 in IRGM, and rs2241880 in ATG16L1. Genotype and clinical factors were analyzed to determine associations with time to recurrent ileocolectomy. A subgroup analysis was performed on 241 patients naïve to biologics before initial ileocolectomy to assess the effect of biologic therapy on time to recurrent surgery.Results:There were 286 patients who underwent a single ileocolectomy, whereas 123 required multiple ileocolectomies. Ileocolonic involvement [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.21–3.00, P = 0.006] and rs2066844 in NOD2 (HR 1.8, 95% CI 1.17–2.77, P = 0.007) were associated with decreased time to surgical recurrence by multivariate analysis. In patients naïve to preoperative biologics, the initiation of postoperative biologics was associated with a 40% decreased incidence of surgical recurrence (HR 0.60, CI 0.39–0.93, P = 0.02) over time.Conclusions:Ileocolonic distribution of disease and the rs2066844 SNP in NOD2 are associated with shorter time to recurrent ileocolectomy. The initiation of postoperative biologics in naïve patients was associated with a reduced incidence of recurrence over time.

Creating a Surgical Biobank: The Hershey Medical Center Experience

“…These include identifying patients at risk for earlier recurrence of Crohn's disease after ileocecectomy or correlating allele variants with a more severe overall course, including surgical complications. 37,50 Decades ago, such studies required complicated and expensive methods of investigation, but newer techniques of specimen study, such as next-generation sequencing, RNA sequencing, rapid 16S microbiome analysis, and bioinformatic processing, have led to a deluge of candidate biomarkers that can potentially assist the surgeon in clinical assessment and care of the surgical patient. As assay platforms have become more affordable and easier to use, whole genome and exome sequencing can be readily performed, as is evidenced by these platforms now being commercially available to the lay public for relatively low prices.…”

The Role of Inflammation in Crohn’s Disease Recurrence after Surgical Treatment

“…While its role in CD pathogenesis is certain, its implication in recurrence, although reason-able, is less definite and a meta-analysis [17] has failed to demonstrate a significant association [18]. A more recent study has identified instead, at multivariable analysis, an independent association between recurrence and a particular NOD2 polymorphism, rs2066844, which was not previously investigated [19]. Another gene, SMAD3, has never been linked to CD pathogenesis but was found to be an independent predictor of recurrence after ileocolic resection [20].…”

Perforating and nonperforating indications in repeated surgeries for Crohn’s disease

“…Several studies have assessed the risk factors for postoperative CD recurrence. Reported risk factors for postoperative recurrence include a smoking habit, family history, young age at diagnosis, ileocolonic disease, perianal disease, preoperative duration and perforating lesions[ 7 - 10 ].…”