内镜黏膜下剥离术与经肛门内镜显微手术对直肠神经内分泌肿瘤的疗效对比分析

Efficacy analysis of endoscopic submucosal dissection and transanal endoscopic microsurgery in the treatment of rectal neuroendocrine tumors

目的比较内镜黏膜下剥离术(ESD)与经肛门内镜显微手术(TEM)对肿瘤最大径≤20 mm直肠神经内分泌肿瘤(NET)的近期、远期疗效和安全性。方法回顾性收集2014年1月1日至2022年6月30日在北京大学人民医院经ESD或TEM治疗的111例肿瘤最大径≤20 mm直肠NET患者的临床资料。根据治疗方式,将111例患者分为ESD组(76例)和TEM组(35例)。比较肿瘤最大径<10 mm与10~20 mm患者、ESD与TEM组患者的临床病理特征(年龄、距肛缘距离、浸润深度等),以及ESD与TEM组的临床疗效和预后。随访时间为41个月(16个月,76个月)。采用倾向评分匹配(PSM)方法平衡ESD与TEM组临床特征的差异。采用独立样本t检验、Wilcoxon秩和检验、卡方检验进行统计学分析,单因素和多因素二元logistic回归分析淋巴结或远处转移的危险因素。结果111例直肠NET患者的肿瘤最大径(范围)为(6.6±0.3)mm(2~20 mm)。肿瘤最大径<10 mm患者85例(76.6%),肿瘤最大径为10~20 mm患者26例(23.4%)。肿瘤最大径<10 mm与肿瘤最大径为10~20 mm患者的年龄、距肛缘距离、黏膜下层浸润发生率比较[(49.8±11.6)岁比(56.8±13.8)岁、5.0 cm(4.0 cm,8.0 cm)比8.0 cm(5.0 cm,8.0 cm)、69.4%(59/85)比96.2%(25/26)],差异均有统计学意义(t=2.58、Z=-2.23、χ^(2)=6.35,P=0.011、0.026、0.012)。ESD和TEM治疗直肠NET的整块切除率为100.0%(111/111),完全切除率为93.7%(104/111),术后出血发生率为2.7%(3/111),无术后穿孔和其他重大并发症。随访期间,无局部复发病例,异时性复发率为0.9%(1/111),3.6%(4/111)的患者出现淋巴结或远处转移,无死亡病例。肿瘤最大径为10~20 mm的患者与肿瘤最大径<10 mm的患者相比,更多选择TEM[57.7%(15/26)比23.5%(20/85)],差异有统计学意义(χ^(2)=10.76,P=0.001)。PSM前,ESD组共7例患者术后垂直切缘阳性,随访期21个月(15个月,48个月)内2例发生淋巴结或远处转移的患者接受了外科直肠根治手术。TEM组患者肿瘤最大径为10~20 mm、黏膜下层浸润的占比均高于ESD组[42.9%(15/35)比14.5%(11/76)、88.6%(31/35)比69.7%(53/76)],差异均有统计学意义(χ^(2)=10.76、3.65,P=0.001、0.032)。PSM后,ESD组与TEM组完全切除率、术后出血率、异时性复发率、淋巴结或远处转移率比较[89.3%(25/28)比100.0%(28/28)、3.6%(1/28)比0(0/28)、3.6%(1/28)比0(0/28)、0(0/28)比3.6%(1/28)],差异均无统计学意义(均P>0.05),但ESD组手术时间和住院时间均短于TEM组[27.0 min(25.0 min,30.0 min)比39.0 min(32.0 min,45.0 min)、5.0 d(4.0 d,5.0 d)比6.0 d(3.0 d,9.0 d)],差异均有统计学意义(Z=-3.38、-2.23,P=0.001、0.021)。结论ESD与TEM对肿瘤最大径≤20 mm的直肠NET的治疗效果相当,但ESD具有手术时间、住院时间均更短的优势。

Objective To compare the short-and long-term efficacy and safety of endoscopic submucosal dissection(ESD)and transanal endoscopic microsurgery(TEM)in the treatment of rectal neuroendocrine tumor(NET)with maximum diameter≤20 mm.Methods From January 1,2014 to June 30,2022,the clinical data of 111 patients with rectal NET with maximum diameter≤20 mm treated by ESD or TEM at Peking University People′s Hospital were retrospectively analyzed.According to the treatment of ESD or TEM,111 patients with rectal NET were divided into ESD group(76 cases)and TEM group(35 cases).The clinicopathological characteristics(age,distance from anal margin,depth of invasion,etc.)were compared between patients with tumor maximum diameter<10 mm and 10 to 20 mm,and between ESD group patients and TEM group patients.The clinical efficacy and prognosis were also compared between ESD group and TEM group.The follow-up time was 41 months(16 months,76 months).The propensity score matching(PSM)method was used to balance the differences of clinical characteristics between ESD and TEM groups.Independent sample t test,Wilcoxon rank-sum and chi-square test were used for statistical analysis.The risk factors of lymph node or distant metastasis were analyzed by univariate and multivariate binary logistic regression.Results The maximum tumor diameter of 111 patients with rectal NET was(6.6±0.3)mm(ranged from 2 to 20 mm).The maximum tumor diameter of 85 cases(76.6%)was<10 mm and that of 26 cases(23.4%)was between 10 mm and 20 mm.There were statistically significant differences in age,distance from the anal margin and incidence of submucosal infiltration between patients with tumor maximum diameter<10 mm and patients with tumor maximum diameter 10 to 20 mm((49.8±11.6)years old vs.(56.8±13.8)years old;5.0 cm(4.0 cm,8.0 cm)vs.8.0 cm(5.0 cm,8.0 cm);69.4%,59/85 vs.96.2%,25/26;t=2.58,Z=-2.23,χ^(2)=6.35,P=0.011,0.026 and 0.012).The en block resection rate of rectal NET treated with ESD or TEM was 100.0%(111/111),the complete resection rate was 93.7%(104/111),and the postoperative bleeding rate was 2.7%(3/111).There were no postoperative perforation or other major complications.During the follow-up period,there was no local recurrence.The metachronous recurrent rate was 0.9%(1/111),3.6%(4/111)patients had lymph node or distant metastasis,and there was no death.Compared with patients with tumor maximum diameter<10 mm,more patients with tumor maximum diameter of 10 to 20 mm selected TEM(57.7%,15/26 vs.23.5%,20/85),and the difference was statistically significant(χ^(2)=10.76,P=0.001).Before PSM,a total of 7 patients in the ESD group had positive vertical margins,and during the follow-up of 21 months(15 months,48 months),2 patients had lymph node or distant metastasis and received surgery.The proportion of patients with tumor maximum diameter of 10 to 20 mm and submucosal invasion in TEM group were both higher than those in ESD group(42.9%,15/35 vs.14.5%,11/76;88.6%,31/35 vs.69.7%,53/76),and the differences were statistically significant(χ^(2)=10.76 and 3.65,P=0.001 and 0.032).After PSM,there were no statistically significant differences in the complete resection rate,postoperative bleeding rate,metachronous recurrence rate,lymph node or distant metastasis rate between ESD group and TEM group(89.3%,25/28 vs.100.0%,28/28;3.6%,1/28 vs.0,0/28;3.6%,1/28 vs.0,0/28;0,0/28 vs.3.6%,1/28;all P>0.05).However,the operation time and hospital stay of the ESD group were both shorter than those of the TEM group(27.0 min(25.0 min,30.0 min)vs.39.0 min(32.0 min,45.0 min);5.0 d(4.0 d,5.0 d)vs.6.0 d(3.0 d,9.0 d)),and the differences were statistically significant(Z=-3.38 and-2.23,P=0.001 and 0.021).Conclusion The efficacy of ESD and TEM in rectal NET with maximum diameter≤20 mm is equal,however,ESD has the advantage of shorter procedure time and hospital stay.