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A82 A GENE VARIANT IS ASSOCIATED WITH POST-OPERATIVE RECURRENCE OF CROHN’S DISEASE.

ABSTRACT: AbstractBackgroundCrohn’s disease often requires intestinal resection, which is not considered curative. Repeat surgical intervention is necessary in over half of the patients following their initial operation. Although many genetic loci are implicated in Crohn’s disease, few have been associated with post-resection recurrence.AimsTo identify genetic factors that predict recurrence of CD following intestinal resection.MethodsA cohort of Crohn’s disease subjects who underwent intestinal resection was analyzed to determine genetic and clinical factors associated with post-resection recurrence. Genotype was assessed at eight loci associated with adaptive immunity (, and ). Univariate and multivariate survival analyses were performed using a log-rank test and Cox-proportional hazard model, respectively.Results191 Crohn’s disease subjects with 11.2 years mean post-operative follow-up were included. 46% experienced a surgical recurrence. Factors associated with increased incidence of recurrence included male gender(p=0.05), and shortened time to first intestinal surgery(5.0 vs 7.3years p=0.03), while inflammatory disease behaviour was associated with a lower chance of repeat surgery(p<0.01). Of the loci assessed on multivariate analysis, homozygosity for a risk allele at (rs1847472) was significantly associated with disease recurrence(HR-1.24 CI-1.00–1.54 p<0.05).ConclusionsWe identify as a susceptibility locus for post-operative recurrence of Crohn’s disease in our cohort. is critical in the differentiation and function of T-cells, as a regulator of B-cell activity, and is associated with several dysregulated immunologic phenomena. Its identification as a risk locus in post-operative Crohn’s disease recurrence suggests a potential role for regulatory T cells, effector T cells, humoral immunity, and immunologic memory in the development of this disease process.Funding AgenciesCIHR

SUBMITTER: Laffin M

PROVIDER: S-EPMC6508141 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Project description:BackgroundVenous thromboembolism (VTE) is the most common preventable cause of 30-day post-operative mortality, with many events occurring after hospital discharge. High-level evidence supports post-discharge VTE chemoprophylaxis following abdominal/pelvic cancer resection; however, some studies support a more tailored approach. Our objectives were to (1) identify risk factors associated with post-discharge VTE in a large cohort of patients undergoing colorectal cancer resection and (2) develop a post-discharge VTE risk calculator.MethodsPatients who underwent colorectal cancer resection from 2012 to 2016 were identified from ACS NSQIP colectomy and proctectomy procedure-targeted modules. Multivariable logistic regression was used to identify factors associated with post-discharge VTE. Incorporating pre-operative, intra-operative, and post-operative variables, a post-discharge VTE risk calculator was constructed and validated.ResultsOf 51,139 patients, 387 (0.76%) developed post-discharge VTE. Pre-operative factors associated with post-discharge VTE included BMI (e.g., morbidly obese OR 2.27, 95% CI 1.65-3.12 vs. normal BMI), and thrombocytosis (OR 1.41, 95% CI 1.03-1.92). Intra-operative factors included operative time (4-6 h OR 1.56, 95% CI 1.12-2.17; > 6 h, OR 1.85, 95% CI 1.21-2.84, vs. < 2 h), and type of operation (e.g., open partial colectomy OR 1.67, 95% CI 1.30-2.16 vs. laparoscopic partial colectomy). Post-operative factors included anastomotic leak (OR 2.05, 95% CI 1.31-3.21) and post-operative ileus (OR 1.39, 95% CI 1.07-1.79). Using the risk calculator, the predicted probability of post-discharge VTE ranged from 0.04 to 10.29%. On a 10-fold cross validation, the calculator's mean C-Statistic was 0.65.ConclusionsPatient-specific factors are associated with varying rates of post-discharge VTE. We present the first post-discharge VTE risk calculator designed for use at the time of discharge following colorectal cancer resection.

Project description:BackgroundAlthough surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical therapy in preventing recurrence of endometriosis following surgery.Objective and rationaleWe performed a review of prospective observational studies and randomised controlled trials (RCTs) to evaluate the risk of endometriosis recurrence in patients undergoing post-operative hormonal suppression, compared to placebo/expectant management.Search methodsThe following databases were searched from inception to March 2020 for RCTs and prospective observational cohort studies: MEDLINE, Embase, Cochrane CENTRAL and Web of Science. We included English language full-text articles of pre-menopausal women undergoing conservative surgery (conserving at least one ovary) and initiating hormonal suppression within 6 weeks post-operatively with either combined hormonal contraceptives (CHC), progestins, androgens, levonorgesterel-releasing intra-uterine system (LNG-IUS) or GnRH agonist or antagonist. We excluded from the final analysis studies with <12 months of follow-up, interventions of diagnostic laparoscopy, experimental/non-hormonal treatments or combined hormonal therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies.OutcomesWe included 17 studies (13 RCTs and 4 cohort studies), with 2137 patients (1189 receiving post-operative suppression and 948 controls), which evaluated various agents: CHC (6 studies, n = 869), progestin (3 studies, n = 183), LNG-IUS (2 studies, n = 94) and GnRH agonist (9 studies, n = 1237). The primary outcome was post-operative endometriosis recurrence, determined by imaging or recurrence of symptoms, at least 12 months post-operatively. The secondary outcome was change in endometriosis-related pain. Mean follow up of included studies ranged from 12 to 36 months, and outcomes were assessed at a median of 18 months. There was a significantly decreased risk of endometriosis recurrence in patients receiving post-operative hormonal suppression compared to expectant management/placebo (relative risk (RR) 0.41, 95% CI: 0.26 to 0.65), 14 studies, 1766 patients, I2 = 68%, random effects model). Subgroup analysis on patients treated with CHC and LNG-IUS as well as sensitivity analyses limited to RCTs and high-quality studies showed a consistent decreased risk of endometriosis recurrence. Additionally, the patients receiving post-operative hormonal suppression had significantly lower pain scores compared to controls (SMD -0.49, 95% CI: -0.91 to -0.07, 7 studies, 652 patients, I2 = 68%).Wider implicationsHormonal suppression should be considered for patients not seeking pregnancy immediately after endometriosis surgery in order to reduce disease recurrence and pain. Various hormonal agents have been shown to be effective, and the exact treatment choice should be individualised according to each woman's needs.

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A82 A GENE VARIANT IS ASSOCIATED WITH POST-OPERATIVE RECURRENCE OF CROHN’S DISEASE.

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