Establishment Of A Risk Factor Model For Postoperative Recurrence Of Crohn's Disease And The Effect Of Drug Therapy On Reoperation Rate

Background and ObjectiveCrohn's disease(CD)is a chronic,disabling and immune-related disease,and over 80%of patients undergo surgical treatment during their natural course.Numerous studies showed that approximately 35%patients are still at risk for reoperation 10 years after the primary surgery.The purpose of this study was to investigate the cumulative clinical,endoscopic,imaging recurrence rate and cumulative reoperation rate respectively,and to explore independent risk factors for reoperation as well as establish a prediction model in order to provide a reference model for clinical evaluation of reoperation risk.Meanwhile,we try to stratify the patients based on the risk factors in our model and those reported by other studies,and explore the influence of postoperative medication on the reoperation rate,in order to provide reference for reducing reoperation in patients with Crohn's disease.and reduced the occurrence of reoperation.MethodsPart one:Retrospective analysis was performed on 159 patients with CD who visited Peking Union Medical College Hospital during January 1,2000 to March 29,2021 and with a history of intestinal surgery and a pathological diagnosis.The general demographic data,clinical data,endoscopic data,imaging data and surgical data of the patients were collected,and Kaplan-Meier method was used to analyze the cumulative surgical recurrence rate.Non-parametric test,chi-square test or Fisher's exact test was used for univariate analysis.Logistic analysis was performed to identify independent risk factors for postoperative recurrence.The risk prediction model for postoperative reoperation was established based on Logistic regression model,and the model was verified by the leave-one-out cross validation.Part two:The effect of postoperative drug therapies(including 5-aminosalicylic acid,immunosuppressants and biological agents)on the reoperation rate were compared respectively according to the risk stratification of reoperation.Kaplan-Meier method was used to calculate the effect of postoperative drug therapies on cumulative reoperation rate of patients with different risk stratification,and log-rank test was used to compare the survival curves of patients in the two groups,P<0.05 was considered statistically significant.Fisher's exact test was used to compare the effects of different drugs on reoperation rate.ResultsPart one:The cumulative clinical recurrence rates of CD patients at 1,3,5 and 10 years were 23.3%,52.9%,73.6%and 88.5%,respectively.The cumulative endoscopic recurrence rates at 1 and 3 years were 22.6%and 73.6%,respectively.The cumulative reoperation rates at 1,3 5 and 10 years were 5.5%,10.8%,20.4%and 42.0%,respectively.And the cumulative imaging recurrence rates were 12.9%,46.4%and 73.2%at 1,3 and 5 years,respectively.Smoking history,perforation-type lesions(B3),short interval from the onset of gastrointestinal symptoms to the initial operation,and the absence of postoperative drug therapies were independent risk factors for reoperation.Finally,a prediction model was established based on three variables:smoking history,perforating lesions(B3)and the time between the occurrence gastrointestinal symptoms to the first operation.Patients with the total score greater than 1.5 points were considered at high risk for reoperation.The area under the ROC curve of the prediction model(95%CI)was 0.774(0.690-0.859).And the area under the ROC curve(95%CI)was 0.656(0.548-0.764)for the model verified by the leave-one-out cross validation.Part two:Based on both the prediction model of this study and the risk factors in the literature,the difference between reoperation rate was not statistically significant in the low risk group with or without postoperative drug therapies While in the high-risk group,the cumulative reoperation rate in patients receiving postoperative drug therapies was lower than that in patients without drug therapy[(based on this study)the cumulative reoperation rate 1 year after the primary surgery was 1.9%vs.23.8%,the cumulative reoperation rate 5 years after the primary surgery was 27.2%vs.54.5%,the cumulative reoperation rate 10 years after the primary surgery was 44.6%vs.90.0%(P<0.001);(based on the literature)the cumulative reoperation rate 1,5 and 10years after the primary surgery were 1.7%vs.23.8%,20.5%vs.50.6%and 34.3%vs.90.1%(P<0.001)].And the rate of reoperation was higher in patients who did not receive postoperative drug therapies than those who received immunosuppressants or biologics;Patients treated with aminosalicylic acid alone after surgery had a higher rate of reoperation than those treated with immunosuppressants or biologics.There was no significant difference in the reoperation rate between the patients treated with immunosuppressants and those treated with biologic.ConclusionsThe recurrence rate of CD is high and the clinical symptomatic recurrence of some small bowel CD is atypical.The independent risk factors for reoperation of CD are smoking history,B3,the short interval between onset of gastrointestinal symptoms and initial surgery.The prediction model of this study can be used to stratify the reoperation risk for CD.In the group with high-risk of CD reoperation,the postoperative drug therapies can reduce the cumulative reoperation rate.Immunosuppressant and TNF-ainhibitors have a preventive effect on reoperation,while aminosalicylic acid have a limited preventive effect.