Kahi Charles J
Department of Medicine, Indiana University School of Medicine, Richard L. Roudebush VA Medical Center, Indianapolis, IN, USA.
Clin Endosc. 2019 May;52(3):235-238. doi: 10.5946/ce.2018.112. Epub 2019 Jan 8.
Conventional adenomas have historically been considered to be the only screening-relevant colorectal cancer (CRC) precursor lesion. The prevailing paradigm was that most CRCs arise along the chromosomal instability pathway, where adenomas accumulate incremental genetic alterations over time, leading eventually to malignancy. However, it is now recognized that this "conventional" pathway accounts for only about two-thirds of CRCs. The serrated pathway is responsible for most of the remainder, and is a disproportionate contributor to postcolonoscopy CRC. Hallmarks of the serrated pathway are mutations in the BRAF gene, high levels of methylation of promoter CpG islands, and the sessile serrated polyp (SSP). Accumulating evidence shows that SSPs can be considered adenoma-equivalent from the standpoint of CRC screening. SSPs have a higher prevalence than previously thought, and appear to have a relatively long dwell time similar to that of conventional adenomas. In addition, SSPs, whether sporadic or as part of the serrated polyposis syndrome, are associated with increased risk of synchronous and metachronous neoplasia. These features collectively support that SSPs are highly relevant to CRC prevention.
传统腺瘤一直以来都被认为是唯一与筛查相关的结直肠癌(CRC)前驱病变。普遍的范式是,大多数结直肠癌沿着染色体不稳定途径发生,在此过程中腺瘤随着时间推移积累渐进性基因改变,最终导致恶性肿瘤。然而,现在人们认识到,这种“传统”途径仅占结直肠癌的约三分之二。锯齿状途径则导致了其余大部分病例,并且在结肠镜检查后发生的结直肠癌中占比过高。锯齿状途径的特征包括BRAF基因突变、启动子CpG岛的高度甲基化以及无蒂锯齿状息肉(SSP)。越来越多的证据表明,从结直肠癌筛查的角度来看,SSP可被视为等同于腺瘤。SSP的患病率比之前认为的更高,并且似乎具有与传统腺瘤相似的相对较长的存在时间。此外,SSP无论是散发性的还是作为锯齿状息肉病综合征的一部分,都与同步和异时性肿瘤形成风险增加相关。这些特征共同支持SSP与结直肠癌预防高度相关。