Abstract：
BACKGROUND: The optimal interval of colonoscopy (CS) surveillance in cases with Lynch syndrome (LS), and stratification according to the causative mismatch repair gene mutation, has received much attention. To verify a feasible and effective CS surveillance strategy, we investigated the colorectal cancer (CRC) incidence at different intervals and the characteristics of precancerous colorectal lesions of LS cases.
METHODS: This retrospective multicenter study was conducted in Japan. CRCs and advanced adenomas (AAs) in 316 LS cases with germline pathogenic variants (path_) were analyzed according to the data of 1,756 registered CS.
RESULTS: The mean time interval for advanced CRCs (ACs) detected via CS surveillance was 28.7 months (95% confidence interval: 13.8-43.5). The rate of AC detection within (2.1%) and beyond 2 years (8.7%) differed significantly (p = 0.0003). AAs accounted for 43%, 46%, and 41% of lesions < 10 mm in size in the MLH1-, MSH2-, and MSH6-groups, respectively. The lifetime incidence of metachronous CRCs requiring intestinal resection for path_MLH1, path_MSH2, and path_MSH6 cases was 34%, 23%, and 14% in these cases, respectively. The cumulative CRC incidence showed a trend towards a 10-year delay for path_MSH6 cases as compared with that for path_MLH1 and path_MSH2 cases.
CONCLUSIONS: In cases with path_MLH1, path_MSH2, and path_MSH6, maintaining an appropriate CS surveillance interval of within 2 years is advisable to detect of the colorectal lesion amenable to endoscopic treatment. path_MSH6 cases could be stratified with path_MLH1 and MSH2 cases in terms of risk of metachronous CRC and age of onset.
METHODS: This retrospective multicenter study was conducted in Japan. CRCs and advanced adenomas (AAs) in 316 LS cases with germline pathogenic variants (path_) were analyzed according to the data of 1,756 registered CS.
RESULTS: The mean time interval for advanced CRCs (ACs) detected via CS surveillance was 28.7 months (95% confidence interval: 13.8-43.5). The rate of AC detection within (2.1%) and beyond 2 years (8.7%) differed significantly (p = 0.0003). AAs accounted for 43%, 46%, and 41% of lesions < 10 mm in size in the MLH1-, MSH2-, and MSH6-groups, respectively. The lifetime incidence of metachronous CRCs requiring intestinal resection for path_MLH1, path_MSH2, and path_MSH6 cases was 34%, 23%, and 14% in these cases, respectively. The cumulative CRC incidence showed a trend towards a 10-year delay for path_MSH6 cases as compared with that for path_MLH1 and path_MSH2 cases.
CONCLUSIONS: In cases with path_MLH1, path_MSH2, and path_MSH6, maintaining an appropriate CS surveillance interval of within 2 years is advisable to detect of the colorectal lesion amenable to endoscopic treatment. path_MSH6 cases could be stratified with path_MLH1 and MSH2 cases in terms of risk of metachronous CRC and age of onset.
摘要：
背景：Lynch综合征（LS）患者的结肠镜检查（CS）监测的最佳间隔，根据致病的错配修复基因突变进行分层，受到了很多关注。验证了一种可行有效的CS监测策略,我们调查了LS例结直肠癌（CRC）在不同时间间隔的发生率和癌前病变的特征。
方法：这项回顾性多中心研究在日本进行。根据1,756例注册CS的数据分析了316例具有种系致病性变异（path_）的LS患者的CRC和晚期腺瘤（AAs）。
结果：通过CS监测检测到的晚期CRC（AC）的平均时间间隔为28.7个月（95％置信区间：13.8-43.5）。在2年内（2.1％）和超过2年（8.7％）的AC检测率存在显着差异（p=0.0003）。AA占43%，46%,在MLH1-中，41%的病变大小<10毫米，MSH2-,和MSH6组，分别。路径_MLH1，路径_MSH2和路径_MSH6病例需要肠切除的异时CRC的终生发生率为34％，23%,在这些情况下，有14%的人，分别。与path_MLH1和path_MSH2病例相比，path_MSH6病例的累积CRC发生率显示出延迟10年的趋势。
结论：对于path_MLH1、path_MSH2和path_MSH6的病例，建议在2年内保持适当的CS监测间隔，以检测适合内镜治疗的结直肠病变。path_MSH6病例可与path_MLH1和MSH2病例在异时CRC风险和发病年龄方面进行分层。
方法：这项回顾性多中心研究在日本进行。根据1,756例注册CS的数据分析了316例具有种系致病性变异（path_）的LS患者的CRC和晚期腺瘤（AAs）。
结果：通过CS监测检测到的晚期CRC（AC）的平均时间间隔为28.7个月（95％置信区间：13.8-43.5）。在2年内（2.1％）和超过2年（8.7％）的AC检测率存在显着差异（p=0.0003）。AA占43%，46%,在MLH1-中，41%的病变大小<10毫米，MSH2-,和MSH6组，分别。路径_MLH1，路径_MSH2和路径_MSH6病例需要肠切除的异时CRC的终生发生率为34％，23%,在这些情况下，有14%的人，分别。与path_MLH1和path_MSH2病例相比，path_MSH6病例的累积CRC发生率显示出延迟10年的趋势。
结论：对于path_MLH1、path_MSH2和path_MSH6的病例，建议在2年内保持适当的CS监测间隔，以检测适合内镜治疗的结直肠病变。path_MSH6病例可与path_MLH1和MSH2病例在异时CRC风险和发病年龄方面进行分层。
