Utility of Random Biopsies in Inflammatory Bowel Disease

项目总结 长期患有炎症性肠病(IBD)的患者患结直肠癌的风险增加。 (CRC)是慢性炎症的结果。为了减少IBD相关CRC的发病率和死亡率， 建议从8-10年开始每隔1-3年用结肠镜监测癌前病变。 大多数IBD患者在确诊后数年。然而，进行异型增生最有效的方法是 监控还没有确定下来。IBD相关的癌前病变不典型增生可能 代表慢性炎症的视野效应，用标准清晰度白光很难看到 结肠镜检查。幸运的是，高清晰度白光结肠镜(HDWLC)的出现提高了我们的能力 以显示和移除癌前病变。尽管如此，收集四本书的历史实践 每隔10厘米在整个结肠进行一次无针对性的随机粘膜活组织检查继续被广泛应用于 IBD患者。其基本原理是随机活组织检查可能有助于发现这些难以发现的癌前病变。 损伤。然而，这种做法的建议是基于未加控制的观察和体外实验。 切除标本的研究。在一项测试随机活组织检查疗效的小型随机临床试验中， 在只接受靶向活检的患者中，异型增生的检测率在数字上更高。这有 导致了随机活组织检查的均衡。随机活检在炎症性肠病中的应用 疾病(URBI)试验将是一项多中心实用的随机临床试验，以最终评估 只获得8次随机活检并不比每隔1天获得4次随机活检的做法差 应用HDWLC监测IBD异型增生患者的结肠全长10 cm。 URBI试验还将为研究结肠炎相关发育不良的生物学提供一个机会。不典型增生是 分级为缺失、低级别(LGD)或高级别(HGD)。无限期发育不良(ID)用于以下情况 不确定是否存在LGD。更好地了解异常增殖症序列的生物学可能 改进病理分类，最大限度地减少对ID类别的需求。然而，几乎没有研究表明 用来了解炎症到异型增生的进展或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(成像质量细胞术 和空间转录)和综合分析方法，以告知生物进展从 炎症到HGD，包括ID的生物学。活检样本和相关临床数据收集在 URBI试验将为研究结肠炎相关性异型增生和ID的分子生物学提供理想的资源。 URBI试验将建立IBD异型增生监测的最佳实践，并增进我们对 结肠炎相关性异型增生的生物学。这笔U34赠款将用于建立所有必要的基础设施 以便在获得U01资金后快速启动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.