Clinical and Genetic Factors Associated With Complications After Crohn’s Ileocolectomy

Abstract

BACKGROUND: Ileocolectomy is the most common surgery performed for Crohn’s disease, and postoperative complications occur frequently. There has been minimal evaluation of complications after ileocolectomy as a function of both clinical and genetic factors. OBJECTIVE: The purpose of this study was to evaluate both genetic and clinical factors associated with complications after Crohn’s ileocolectomy. DESIGN: This was a retrospective clinical and genetic cohort study. SETTINGS: This study was conducted at a high-volume tertiary care center. PATIENTS: We identified 269 patients with Crohn’s disease who had undergone 287 ileocolectomies at our institution between July 2008 and October 2018. MAIN OUTCOME MEASURES: We measured the association of complications with a combination of clinical factors and 6 Crohn’s-associated single nucleotide polymorphisms in NOD2 (rs2076756, rs2066844, and rs2066845), IRGM (rs4958847 and rs13361189), and ATG16L1 (rs2241880). RESULTS: There were 86 ileocolectomies of 287 (30%) with complications requiring intervention. The single nucleotide polymorphism rs13361189 in the gene IRGM was significantly associated with complications on univariate and multivariate analysis. There were 61 patients with a variant at the rs13361189 single nucleotide polymorphism and 26 of them had complications, although only 55 of the 208 wild-type patients had complications (43% vs 26%; OR = 2.1; p = 0.02). Other significant factors associated with complication after ileocolectomy were open surgery, placement of a proximal ileostomy, and a greater perioperative decrease in hematocrit. LIMITATIONS: This study was limited by its retrospective design and inherent selection bias. CONCLUSIONS: In addition to clinical risk factors, the rs13361189 single nucleotide polymorphism in the IRGM gene was independently associated with complications after ileocolectomy for Crohn’s disease. The use of such genetic determinants may identify patients at increased risk for surgical complications after ileocolectomy. See Video Abstract at http://links.lww.com/DCR/B124. FACTORES CLÍNICOS Y GENÉTICOS ASOCIADOS CON COMPLICACIONES DESPUÉS DE LA ILEOCOLECTOMÍA DE CROHN ANTECEDENTES: La ileocolectomía es la cirugía más común realizada para la enfermedad de Crohn y con frecuencia ocurren complicaciones postoperatorias. Ha habido una evaluación mínima de complicaciones después de la ileocolectomía, en función de factores clínicos y genéticos. OBJETIVO: Evaluar factores genéticos y clínicos asociados con complicaciones, después de la ileocolectomía por Crohn. DISEÑO: Estudio retrospectivo de cohorte clínico y genético. AJUSTES: Este estudio se realizó en un centro de atención terciaria de alto volumen. PACIENTES: Identificamos a 269 pacientes con enfermedad de Crohn, sometidos a 287 ileocolectomías en nuestra institución, entre julio de 2008 y octubre de 2018. PRINCIPALES MEDIDAS DE RESULTADO: La asociación de complicaciones con una combinación de factores clínicos y seis polimorfismos de un solo nucleótido asociados a Crohn en NOD2 (rs2076756, rs2066844 y rs2066845), IRGM (rs4958847 y rs13361189) y ATG16L1 (rs2241880). RESULTADOS: Hubieron 86 ileocolectomías en 287 (30%) pacientes con complicaciones que requirieron intervención. El polimorfismo de un solo nucleótido rs13361189 en el gen IRGM se asoció significativamente con complicaciones en el análisis univariado y multivariado. Hubieron 61 pacientes con una variante en el polimorfismo de un solo nucleótido rs13361189 y 26 de ellos tuvieron complicaciones, mientras que solo 55 de los 208 pacientes de tipo salvaje (WT) tuvieron complicaciones (43% vs 26%, OR 2.1, p = 0.02). Otros factores significativos asociados con las complicaciones después de la ileocolectomía fueron, la cirugía abierta, la colocación de una ileostomía proximal y una mayor disminución perioperatoria del hematocrito. LIMITACIONES: Este estudio estuvo limitado por su diseño retrospectivo y sesgo de selección inherente. CONCLUSIONES: Además de los factores de riesgo clínicos, el polimorfismo de un solo nucleótido rs13361189 en el gen IRGM se asoció independientemente con complicaciones después de la ileocolectomía, para la enfermedad de Crohn. El uso de tales determinantes genéticos puede identificar a los pacientes con mayor riesgo de complicaciones quirúrgicas, después de la ileocolectomía. Consulte Video Resumen en http://links.lww.com/DCR/B124.

It is not NOD2 — genetic and clinical risk factors for postoperative complications following ileocolic resection in Crohn’s disease

“…One study by Giudici et al also investigating NOD2 polymorphisms rs2066844, rs2066845, and rs2066847 in CD patients undergoing abdominal surgery in general could not identify homozygosity as risk factor for postoperative complications but a longer time period for disease onset in the p.Leu1007fsX1008 (rs2066847) cohort [19], whereas a study by Geramain et al found the NOD2 SNP rs5743289 to be an independent risk factor for postoperative abdominal septic complications [20]. A third study by Kline et al assessed the impact of NOD2 SNPs rs2076756, Arg702Trp (rs2066844), and p.Gly908Arg (rs2066845) [21]. In our cohort, rs2076756 was not assessed and the others were quite rare with only one homozygote Arg702Trp (rs2066844) and one p.Gly908Arg (rs2066845), respectively, but Kline et al also did not find one of the NOD2 SNPs to be associated with postoperative complications after ileocecal resection [21].…”

“…A third study by Kline et al assessed the impact of NOD2 SNPs rs2076756, Arg702Trp (rs2066844), and p.Gly908Arg (rs2066845) [21]. In our cohort, rs2076756 was not assessed and the others were quite rare with only one homozygote Arg702Trp (rs2066844) and one p.Gly908Arg (rs2066845), respectively, but Kline et al also did not find one of the NOD2 SNPs to be associated with postoperative complications after ileocecal resection [21]. In our follow-up data, we could not detect significant differences in the need for further surgical therapy or increased need for immunosuppressive or immune-modulatory therapy over time regarding the risk factors identified by others [18][19][20]: homozygous NOD2 variant, smoking, or fistulating disease.…”

Influence of nutritional status in the postoperative period of patients with inflammatory bowel disease

“…In IBD, surgery is indicated for clinical intractability, complications, and neoplasms, and is considered an option in CD patients with isolated ileal disease[ 4 ]. Postoperative complications are frequent in IBD, especially intra-abdominal sepsis, surgical site infection (SSI), and adynamic ileum[ 5 - 9 ]. Increased understanding of the effects of nutritional status on surgical outcomes and the patient characteristics that are predictive of surgery-associated complications are essential for prompt implementation of adequate nutritional interventions[ 10 ].…”

Creating a Surgical Biobank: The Hershey Medical Center Experience

“…Over 100 original clinical and scientific research articles have been published using these specimens. These publications have been the result of work with more than 30 collaborating scientists and relate to the genetics and pathophysiology diverticulitis, 31,32 the genetic basis of IBD, 33,34 disease phenotype/ genotype correlations, [35][36][37] mucus defense, 38,39 bowel permeability and myofibroblast function in IBD, [40][41][42][43] and colorectal cancer. 44,45…”