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Re: Cumulative burden of inflammation predicts colorectal neoplasia risk in ulcerative colitis: a large single-centre study
Gut ( IF 24.5 ) Pub Date : 2018-03-13 , DOI: 10.1136/gutjnl-2018-316205
Yoshinaga Okugawa 1, 2, 3 , Yuji Toiyama 1, 2, 3 , Masato Kusunoki 3 , Ajay Goel 1, 2
Affiliation  

In a recent issue of the journal, Choi and colleagues have assessed cumulative inflammatory burden (CIB) using endoscopic and histological findings from surveillance colonoscopy, and for the first time have revealed that CIB was significantly associated with the development of colorectal neoplasia (CRN) in patients with UC. This study is an elegant article and very meaningful from a clinical standpoint because the mean severity of microscopic inflammation derived from all surveillance procedures performed in the last decade has suggested it to be an important predictive biomarker for risk stratification of CRN in patients with UC. However, we would like to draw attention to a few important issues related to this very interesting article. First, the authors evaluated endoscopic and histological inflammatory scores from the most extreme degree of documented inflammatory regions present within any segment of the colorectum in this study. In this context, we have recently assessed DNA methylation levels of five specific microRNAs (miRNAs) in different parts within the colorectum (caecum, transverse colon and rectum) from patients with UC, and demonstrated that the methylation levels in rectal mucosa were significantly higher compared with transverse colon or caecum. Methylation levels of all miRNAs in non-dysplastic rectal mucosa from patients with UC-CRN were significantly higher than those without. Furthermore, combination analysis using methylation levels of all five miRNAs in rectal mucosa successfully identified patients harbouring UC-CRN with remarkably high area under the curve (AUC) values (AUC: 0.81, 95% CI 0.71 to 0.88). In contrast, Watanabe and coworkers conducted a randomised controlled trial to compare detection rates of neoplasia by analysing targeted versus random biopsies in 247 patients with UC, and demonstrated that detection rates of patients with UC-CRN were similar in both surveillance methodologies. Interestingly, these researchers strongly recommended obtaining an additional random biopsy from the rectum, because neoplasia is frequently located even in the endoscopically non-inflamed rectum in patients with UC. Based on this evidence, it would be more valuable for patients with UC if their CIB score in non-neoplastic rectal mucosa could identify patients with risk for UC-CRN, compared with invasive and extensive colonoscopic evaluations. Second, as we know, various types of blood markers have been developed to assess systemic inflammatory severity in several diseases, including C reactive protein (CRP), Glasgow Prognostic Score and neutrophil lymphocyte ratio. Shen and colleagues assessed the cumulative average of repeated measures of inflammatory markers (erythrocyte sedimentation rate and CRP) in patients with psoriatic arthritis and revealed that the cumulative average of their inflammatory markers was significantly associated with increased arterial stiffness. These data highlight that a non-invasive approach that can measure cumulative scores using bloodbased inflammatory markers might also have the potential to reflect accumulation of inflammation and to predict patients who are at risk for developing UC-CRN. It would be more interesting to note if the cumulative scores using blood-based inflammatory markers would have any predictive value in assessing risk for the development of UC-CRN. Finally, Choi et al assessed the potential of CIB for risk stratification in UC-CRN, which includes dysplasia and cancer. Even more importantly, from a predictive perspective, identification of patients with high risk for dysplasia is also feasible in clinical use. If CIB increases stepwise in each step of dysplasia-carcinoma sequence, optimal cut-off value of CIB could differentiate patients with risk of UC-dysplasia.

中文翻译:

回复:炎症的累积负担可预测溃疡性结肠炎的结直肠肿瘤风险:一项大型单中心研究

在最近一期的期刊中,Choi 及其同事使用结肠镜检查的内窥镜和组织学发现评估了累积炎症负荷 (CIB),并首次发现 CIB 与结肠直肠肿瘤 (CRN) 的发展显着相关。 UC 患者。这项研究是一篇优雅的文章,从临床角度来看非常有意义,因为从过去十年中执行的所有监测程序得出的微观炎症的平均严重程度表明,它是 UC 患者 CRN 风险分层的重要预测生物标志物。但是,我们想提请注意与这篇非常有趣的文章相关的一些重要问题。第一的,作者评估了本研究中结肠直肠任何节段中存在的最极端程度的炎症区域的内窥镜和组织学炎症评分。在这种情况下,我们最近评估了 UC 患者结肠直肠内不同部位(盲肠、横结肠和直肠)中五种特定 microRNA (miRNA) 的 DNA 甲基化水平,并证明直肠粘膜中的甲基化水平显着高于带有横结肠或盲肠。UC-CRN 患者非发育不良直肠黏膜中所有 miRNA 的甲基化水平显着高于非发育不良患者。此外,使用直肠粘膜中所有 5 种 miRNA 的甲基化水平进行组合分析,成功识别出具有曲线下面积 (AUC) 值(AUC:0.81,95% CI 0.71 至 0.88)的患者。相比之下,Watanabe 及其同事进行了一项随机对照试验,通过分析 247 名 UC 患者的靶向活检与随机活检来比较瘤形成的检出率,并证明两种监测方法中 UC-CRN 患者的检出率相似。有趣的是,这些研究人员强烈建议从直肠中进行额外的随机活检,因为即使是内窥镜下未发炎的 UC 患者,肿瘤也经常位于直肠中。根据这个证据,与侵入性和广泛的结肠镜评估相比,如果他们在非肿瘤性直肠黏膜的 CIB 评分可以识别有 UC-CRN 风险的患者,那么对于 UC 患者将更有价值。其次,正如我们所知,已经开发了各种类型的血液标志物来评估多种疾病的全身炎症严重程度,包括 C 反应蛋白 (CRP)、格拉斯哥预后评分和中性粒细胞淋巴细胞比率。沉及其同事评估了银屑病关节炎患者炎症标志物(红细胞沉降率和 CRP)重复测量的累积平均值,并发现其炎症标志物的累积平均值与动脉僵硬度增加显着相关。这些数据强调,可以使用基于血液的炎症标志物测量累积分数的非侵入性方法也可能有可能反映炎症的积累并预测有发展为 UC-CRN 风险的患者。更有趣的是,使用基于血液的炎症标志物的累积评分是否在评估 UC-CRN 发展风险方面具有任何预测价值。最后,Choi 等人评估了 CIB 在 UC-CRN 风险分层中的潜力,其中包括发育不良和癌症。更重要的是,从预测的角度来看,在临床使用中识别出发育不良的高风险患者也是可行的。如果 CIB 在异型增生-癌序列的每一步中逐步增加,
更新日期:2018-03-13
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