Utility of Random Biopsies in Inflammatory Bowel Disease

项目摘要 长期炎症性肠病（IBD）患者患结直肠癌的风险增加 (CRC)是慢性炎症的结果为了降低IBD相关CRC的发病率和死亡率， 建议从8-10岁开始，每1-3年进行一次结肠镜检查，以监测癌前异型增生 对于大多数IBD患者来说，然而，最有效的方法来执行发育不良 监督尚未确定。IBD相关的癌前发育不良病变可能 并且难以用标准清晰度白色光看到 结肠镜检查幸运的是，高清晰度白色结肠镜（HDWLC）的出现提高了我们的能力， 来观察和切除癌前发育不良病变。尽管如此，收集四个的历史实践 在整个结肠中每10 cm进行非靶向随机粘膜活检继续被广泛用于 IBD患者基本原理是随机活检可能有助于发现这些很难看到的癌前病变 病变然而，这种做法的建议是基于不受控制的观察和离体的 切除标本的研究。在一项小型随机临床试验中，测试了随机活检的有效性， 仅接受靶向活检的患者的异型增生检出率在数值上更高。这 导致了随机活检的平衡。随机活检在炎症性肠道中的拟议效用 疾病（URBI）试验将是一项多中心实用随机临床试验，以明确评估是否 仅获得八个随机活检并不劣于每隔一个周期获得四个随机活检的实践 在接受HDWLC异型增生监测的IBD患者中，整个结肠> 10 cm。 URBI试验也将提供一个研究结肠炎相关发育不良生物学的机会。发育不良是 分级为不存在、低等级（LGD）或高等级（HGD）。不确定性发育不良（ID）用于当有 不确定是否存在LGD。更好地理解发育异常序列的生物学可以 改善病理分类，并最大限度地减少对ID类别的需求。然而，很少有研究 这样做是为了了解炎症进展到发育不良或ID的分子特征， 现代组学技术。我们将利用新的空间分子成像技术（成像质谱细胞术 和空间转录组学）和综合分析方法，以告知生物学进展， 炎症对HGD的影响，包括ID的生物学。 URBI试验将为结肠炎相关异型增生和ID的分子生物学研究提供理想的资源。 URBI试验将建立IBD发育不良监测的最佳实践，并促进我们对以下方面的理解： 结肠炎相关发育不良的生物学这笔U34赠款将用于建立所有必要的基础设施 一旦U 01资金到位，就可以迅速启动URBI试验。

PROJECT SUMMARY Patients with long standing inflammatory bowel diseases (IBD) have an increased risk of colorectal cancer (CRC) as a consequence of chronic inflammation. To reduce morbidity and mortality from IBD-related CRC, surveillance for precancerous dysplasia with colonoscopy is recommended every 1-3 years beginning 8-10 years after diagnosis for most patients with IBD. However, the most effective way to perform dysplasia surveillance has not been definitively established. IBD-associated precancerous dysplastic lesions may represent a field effect from chronic inflammation and are difficult to see with standard definition white light colonoscopy. Fortunately, the advent of high-definition white light colonoscopy (HDWLC) improved our ability to visualize and remove precancerous dysplastic lesions. Nonetheless, the historical practice of collecting four untargeted random mucosal biopsies every 10 cm throughout the colon continues to be widely employed for patients with IBD. The rationale is that random biopsies may help detect these difficult to see precancerous lesions. However, the recommendations for this practice are based on uncontrolled observations and ex-vivo studies of resected specimen. In the one small randomized clinical trial to test the efficacy of random biopsies, the rate of dysplasia detection was numerically higher in the patients only getting targeted biopsies. This has led to equipoise regarding random biopsies. The proposed Utility of Random Biopsies in Inflammatory Bowel Disease (URBI) trial will be a multicenter pragmatic randomized clinical trial to definitively assess whether obtaining only eight random biopsies is non-inferior to the practice of obtaining four random biopsies every 10cm throughout the colon among patients with IBD undergoing dysplasia surveillance with HDWLC. The URBI trial will also present an opportunity to study the biology of colitis-associated dysplasia. Dysplasia is graded as absent, low-grade (LGD) or high-grade (HGD). Indefinite dysplasia (ID) is used when there is uncertainty whether or not there is LGD. Better understanding the biology of the dysplasia sequence could improve pathologic classification and minimizing the need for the ID category. Yet, little research has been done to understand the progression of inflammation to dysplasia or the molecular characteristics of ID using modern omics technologies. We will utilize new spatial molecular imaging techniques (imaging mass cytometry and spatial transcriptomics) and an integrative analytic approach to inform the biologic progression from inflammation to HGD, including the biology of ID. The biopsy samples and linked clinical data collected in the URBI trial will provide an ideal resource to study the molecular biology of colitis-associated dysplasia and ID. The URBI trial will establish best practices for IBD dysplasia surveillance and advance our understanding of the biology of colitis-associated dysplasia. This U34 grant will be used to establish all necessary infrastructure to allow for a rapid launch of the URBI trial once U01 funding is secured.