Comparative efficacy of water & indigo carmine vs water or air method

描述(由申请人提供)： 结直肠腺瘤的检测和切除是预防结直肠癌(CRC)的推荐方法。在单独的研究中，我们报告了用注水代替空气注气(水法)提供的总体腺瘤发现率(ADR)和近端微小ADR明显高于在插入镜时使用的通常的空气注气方法。当在水法中加入吲哚红时，与仅用水法或传统空气法检查的历史队列相比，染料突出了微小的结肠病变，总体ADR显著增加，与单独使用水法相比，近端较小的ADR显著增加。这项建议解决的问题是，在随机对照试验中，水法(使用或不使用吲哚红)是否会导致与仅使用空气方法相比有显著更高的近端微小不良反应。最初的假设认为，与水法或空气法相比，随机采用水+吲哚红方法的患者中至少有一个近端小腺瘤(ADR)的比例更高。在萨克拉门托VAMC接受结肠镜检查的无症状退伍军人将被考虑参加结直肠癌筛查。在两年半的招募期间，共有330名经过同意的退伍军人将被随机分组，以确认在水与空气的比较中，水组的近端矮小不良反应有20%(34%-14%)的差异；在吲哚红+水与水的比较中，有30%(%-34%)的差异支持吲哚红+水的方法。同意包括同意以随机方法接受结肠镜检查，回答结肠镜检查前后的问卷，并允许以不确定的方式记录检查以进行数据分析。PI在所有三种方法中都有经验，将检查所有入选的患者。为了确保高质量的表现，所有组的男性受试者和女性受试者的推荐总体ADR应分别保持在25%和15%。将遵循适用的人体受试者保护和不良事件监测程序。结果数据将被前瞻性地收集和监测，并由相关的数据安全措施守卫。将使用Logistic回归和方差分析进行适当的评估。人群研究表明，传统的空气结肠镜检查未能消除筛查后结肠镜检查后的癌症或近端结肠的癌症死亡率。即使是微小的腺瘤也有明显的不典型增生。一种简单、廉价、易于学习的方法，即在水法中加入吲哚红，可能会增加近端微小腺瘤的产量。较高的ADR可减少漏诊的腺瘤，从而将间歇性结直肠癌的负担降至最低。长期目标是进行进一步的研究，以确定是否可以通过新的方法在退伍军人中减少筛查后结肠镜检查后的间歇性癌症和近端结肠的癌症死亡率。

DESCRIPTION (provided by applicant): Project Summary/Abstract Detection and removal of colorectal adenomas is the recommended approach to the prevention of colorectal cancers (CRC). In separate studies we reported that water infusion in lieu of air insufflation (water method) provided a significantly higher overall adenoma detection rate (ADR) and proximal diminutive ADR than the usual method of air insufflation used during scope insertion. When indigocarmine was added to the water method, the dye highlighted small colonic lesions and significantly increased the overall ADR compared with historical cohorts examined by the water method alone or the conventional air method, as well as proximal diminutive ADR when compared with the water method alone. This proposal addresses the question of whether the water method (with or without indigocarmine) will result in a significantly higher proximal diminutive ADR compared with the air method alone in a RCT. The primary hypothesis asserts that a higher proportion with at least one proximal diminutive adenoma (ADR) will be found in the group randomized to the water + indigocarmine method compared with those randomized to the water method alone or the air method. Asymptomatic veterans referred for sedated colonoscopy for CRC screening at the Sacramento VAMC will be considered for enrollment. Over a 2.5 year recruitment period a total of 330 consented veterans will be randomized to confirm a 20% (34% - 14%) difference in proximal diminutive ADR in favor of the water group in the water vs. air comparison; and a 30% (64% - 34%) difference in favor of the indigocarmine + water method in the indigocarmine + water vs. water comparison. Consent covers agreement to undergo colonoscopy by the randomized methods, respond to pre- and post-colonoscopy questionnaires and allow the examination to be recorded for data analysis in a de-identified fashion. The PI, experienced in all three methods, will examine all enrolled patients. To ensure quality performance, all groups are expected to maintain the recommended overall ADR of 25% in male subjects and 15% in female subjects. Applicable human subject protection and adverse event monitoring procedures will be followed. Outcome data will be gathered and monitored prospectively and guarded by relevant data security measures. Appropriate evaluation with logistic regression and analysis of variance will be employed. Population studies showed that traditional air colonoscopy failed to eliminate post screening colonoscopy cancers or cancer mortality in the proximal colon. Even diminutive adenomas harbor significant dysplasia. A simple, inexpensive, easy-to-learn method of adding indigocarmine to the water method may increase the yield of proximal diminutive adenomas. A higher ADR may minimize the burden of interval CRC by decreasing missed adenomas. The long term goal is to perform further studies to determine if post screening colonoscopy interval cancers and cancer mortality in the proximal colon can be attenuated among the veteran population by the novel methods.