1Department of Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 2Sanford R. Weiss, M.D., Center for Hereditary Colorectal Neoplasia, Cleveland Clinic, Cleveland, Ohio 3Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Dis Colon Rectum. 2014 Jan;57(1):39-46. doi: 10.1097/01.dcr.0000437690.18709.76.
BACKGROUND: Right-sided serrated polyps are precursors to sporadic microsatellite unstable colon cancers via the methylator pathway and have a high rate of synchronous and metachronous lesions. Serrated polyps also occur in Lynch syndrome, where right-sided microsatellite unstable cancers arise from germline mutations in mismatch repair genes. OBJECTIVE: The aim of this study was to compare serrated neoplasia in patients with sporadic and hereditary microsatellite unstable colon cancer and to examine the effect of right colectomy on the risk of metachronous polyps and cancers. DESIGN: This is a retrospective, descriptive, cohort study from database and chart review. SETTING: This study was conducted at a tertiary care hospital with a center for hereditary colorectal cancer. PATIENTS: Patients who had colon cancers with a high degree of microsatellite instability, methylator cancers, and Lynch syndrome cancers, were included. INTERVENTIONS: Interventions included colectomy, surveillance colonoscopy, and polypectomy. MAIN OUTCOME MEASURES: The primary outcomes measured were the incidence and location of metachronous polyps and cancers. RESULTS: Eighty-five patients were included: 47 with methylator cancers and 38 with Lynch syndrome. Median ages at surgery were 75 years (range, 41-90) and 48 years (range, 27-77), p < 0.0001. Forty-six (98%) patients with methylator cancers and 17 (45%) patients with Lynch syndrome underwent a right colectomy, p < 0.0001. Metachronous cancers occurred in 19/60 (32%) of patients with Lynch syndrome and no patients with methylator cancers, p < 0.0001. Thirty-four patients with methylator cancers had colonoscopic follow-up, with a median of 2 colonoscopies per patient over a 32-month follow-up (range, 1-136). Sixty-three percent of patients with Lynch syndrome had colonoscopic follow-up, median of 4 colonoscopies per patient over 102 months (range, 1-462), p < 0.0001. Four (9%) patients with methylator cancers each had 1 metachronous serrated polyp, compared with 10/37 (27%) patients with Lynch syndrome (p = 0.049), whose median number of polyps was 2 (range, 1-8). Characteristics of other associated polyps were similar between cohorts. LIMITATIONS: This study is somewhat limited by potential inherent bias from its retrospective design. Also, a high number of deaths in the CIMP+ cohort could have contributed to the low number of serrated polyps detected on colonoscopy surveillance, but given current understanding of serrated polyp growth, this may truly represent the left colon's tendency not to develop serrated polyps. CONCLUSIONS: Cancers with a high degree of microsatellite instability arise through 2 different molecular mechanisms. Metachronous serrated neoplasia, benign and malignant, following right colectomy in patients with the CpG-island methylator phenotype of colorectal cancer is uncommon. However, the colons of patients with Lynch syndrome are at high risk after segmental colectomy.
背景：右侧锯齿状息肉是通过甲基化途径成为散发性微卫星不稳定结直肠癌的前体，并且具有很高的同步和异时性病变发生率。锯齿状息肉也发生在林奇综合征中，其中右侧微卫星不稳定癌症是由错配修复基因种系突变引起的。 目的：本研究旨在比较散发性和遗传性微卫星不稳定结直肠癌患者的锯齿状肿瘤，并研究右结肠切除术对异时性息肉和癌症风险的影响。 设计：这是一项回顾性、描述性队列研究，来自数据库和图表回顾。 地点：本研究在一家拥有遗传性结直肠癌中心的三级保健医院进行。 患者：包括患有高度微卫星不稳定、甲基化癌症和林奇综合征癌症的结肠癌患者。 干预措施：干预措施包括结肠切除术、监测结肠镜检查和息肉切除术。 主要观察指标：主要观察指标是异时性息肉和癌症的发生率和位置。 结果：共纳入 85 例患者：47 例为甲基化癌症患者，38 例为林奇综合征患者。手术时的中位年龄分别为 75 岁（范围 41-90 岁）和 48 岁（范围 27-77 岁），p <0.0001。46 例（98%）甲基化癌症患者和 17 例（45%）林奇综合征患者接受了右结肠切除术，p <0.0001。19/60 例（32%）林奇综合征患者发生异时性癌症，而无甲基化癌症患者发生，p <0.0001。34 例甲基化癌症患者接受了结肠镜随访，中位随访时间为每例患者 2 次结肠镜检查，随访时间为 32 个月（范围为 1-136 个月）。63%的林奇综合征患者接受了结肠镜随访，中位随访时间为每例患者 4 次结肠镜检查，随访时间为 102 个月（范围为 1-462 个月），p <0.0001。4 例（9%）甲基化癌症患者各有 1 个异时性锯齿状息肉，而 37 例（27%）林奇综合征患者中有 10 例（p=0.049），其息肉中位数为 2 个（范围为 1-8 个）。两组患者的其他相关息肉特征相似。 局限性：由于回顾性设计的固有潜在偏差，本研究存在一定的局限性。此外，CIMP+队列中的大量死亡可能导致结肠镜监测中发现的锯齿状息肉数量较少，但考虑到目前对锯齿状息肉生长的了解，这可能确实代表了左结肠不易发生锯齿状息肉的倾向。 结论：具有高度微卫星不稳定性的癌症通过 2 种不同的分子机制发生。在结直肠癌 CpG 岛甲基化表型的患者中，右结肠切除术后，异时性锯齿状肿瘤，良性和恶性，很少见。然而，林奇综合征患者的结肠在节段性结肠切除术后风险很高。
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