The association between pre-colectomy thiopurine use and risk of neoplasia after ileal pouch anal anastomosis in patients with ulcerative colitis or indeterminate colitis: a propensity score analysis

溃疡性结肠炎或未定型结肠炎患者行回肠储袋肛门吻合术后,术前使用硫嘌呤类药物与肿瘤发生风险之间的关联:倾向评分分析

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Abstract

BACKGROUND: The risk of neoplasia of the pouch or residual rectum in patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is incompletely investigated. Thiopurine use is associated with a reduced risk of colorectal neoplasia in patients with UC. We tested the hypothesis that thiopurine use prior to TPC may be associated with a reduced risk of primary neoplasia after IPAA. METHODS: We conducted a retrospective cohort analysis of patients from a tertiary referral center from January 2008 to December 2017. Eligible patients with UC or IC underwent TPC with IPAA and had at least two pouchoscopies with biopsies ≥ 6 months after surgery. Propensity score analysis was conducted to match thiopurine exposed vs unexposed groups based on clinical covariates. Multivariable Cox regression analysis estimated the risk of neoplasia. RESULTS: A total of 284 patients with UC or IC (57.4% male, median age 35.6 years) were analyzed. Ninety-seven patients (34.2%) were confirmed to have thiopurine exposure ≥ 12 weeks immediately prior to TPC ("exposed") and 187 (65.8%) were confirmed to have no thiopurine exposure for at least 365 days prior to TPC ("non-exposed"). Compared to non-exposed patients, patients with thiopurine exposure less often had dysplasia (7.2% vs 23.0%, p = 0.001) and had lower grades of dysplasia before colectomy. After IPAA, patients with neoplasia were older (44.0 vs 34.8 years, p = 0.03), more likely to have had dysplasia as colectomy indication (44.4% vs 15.4%, p = 0.007), and more likely to require pouch excision (55.6% vs 10.2%, p < 0.0001), compared to patients without neoplasia. On propensity-matched cohort analysis, no factors were significantly associated with risk of primary neoplasia. CONCLUSION: Thiopurine exposure for at least the 12 weeks prior to TPC in patients with UC or IC does not appear to be independently associated with risk of primary neoplasia following IPAA.

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