Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.
目的： 对比中低位直肠癌经肛全直肠系膜切除术（taTME）与腹腔镜全直肠系膜切除术（laTME）的近期手术安全性和远期预后。 方法： 本研究为回顾性队列研究。首先纳入北京协和医院基本外科结直肠专业组前瞻性登记数据库2014年7月至2020年6月连续登记的接受全直肠系膜切除术的直肠癌患者，分为taTME和laTME两组，进行疗效对比研究。提取数据库中患者人口学资料、肿瘤学一般资料、新辅助治疗情况、术中情况及术后并发症、病理资料及随访数据。主要结局指标为吻合口漏发生率，次要结局指标为3年无病生存率（DFS）和3年局部复发率。正态分布的计量资料组间比较采用独立t检验；偏态分布的计量资料用M（范围）表示。分类变量组间比较采用χ(2)或Fisher精确概率法检验。在进行疗效对比时，对性别、体质指数、术前核磁评估分期、核磁测量的肿瘤距肛缘的距离、新辅助放化疗与否5个变量进行倾向性评分匹配（PSM）以调整混杂因素。采用Kaplan-Meier曲线及Log-rank检验比较两组的DFS，并应用Cox比例风险模型分析影响中低位直肠癌患者DFS的独立危险因素。另外，收集上述数据库中自2017年2月至2021年3月连续登记的经肛操作由同一医师主刀完成的taTME手术病例，采用多维累积和（CUSUM）控制图绘制学习曲线。比较渡过学习曲线后taTME组与laTME组的疗效并分析这部分"成熟"病例DFS的独立危险因素。 结果： 入组243例患者，182例接受laTME，61例接受taTME。PSM后laTME组和taTME组分别为52例，这两组在性别、年龄、体质指数、肿瘤临床分期、肿瘤距肛缘的距离、核磁评估的环周切缘及壁外血管侵犯、新辅助治疗方面差异无统计学意义（均P>0.05）。PSM后，与laTME组比较，taTME组手术时间更长[（198.4±58.3）min比（147.9±47.3）min，t=-4.321，P<0.001]，出血超过100 ml的比例更高[17.3%（9/52）比0，P=0.003]。taTME组术后吻合口漏[26.9%（14/52）比3.8%（2/52），χ(2)=10.636，P=0.001]及总并发症发生率[55.8%（29/52）比19.2%（10/52），χ(2)=14.810，P<0.001]均显著高于laTME组；差异均具有统计学意义（均P<0.05）。两组获取淋巴结数目及病理环周切缘阳性比例差异均无统计学意义（均P>0.05）。全组中位随访24（1~72）个月，4例失访，随访率为98.4%（239/243）。laTME组3年DFS明显优于taTME组（83.9%比73.0%，P=0.019），差异有统计学意义；两组3年局部复发率差异无统计学意义（1.7%比3.6%，P=0.420）。多因素分析结果显示，taTME手术（HR=3.202，95%CI：1.592~6.441，P=0.001）及术后病理分期Ⅱ期（HR=13.862，95%CI：1.810~106.150，P=0.011）、Ⅲ期（HR=8.705，95%CI：1.104~68.670，P=0.040）为影响中低位直肠癌患者DFS的独立危险因素（均P<0.05）。学习曲线分析显示：taTME手术在第28例跨越学习曲线。跨越学习曲线后的taTME病例与laTME病例PSM后显示，两组吻合口漏[6.7%（1/15）比5.3%（2/38），P=1.000]及术后总并发症[33.3%（5/15）比26.3%（10/38），P=0.737]发生率比较，差异均无统计学意义（均P>0.05）。对跨越学习曲线后的"成熟"病例进行分析，taTME手术仍为影响中低位直肠癌患者DFS的独立危险因素（HR=5.351,95%CI：1.666~17.192，P=0.005）。跨越学习曲线与否并不是taTME术后中低位直肠癌患者DFS的独立影响因素（HR=0.954,95%CI：0.227~4.017，P=0.949）。 结论： taTME手术可能较传统laTME手术增加术后吻合口漏的风险且肿瘤学预后可能劣于传统手术。在学习曲线内行taTME手术更容易增加术后吻合口漏的风险。.
Keywords: Anastomotic leak; Laparoscopic total mesorectal excision; Prognosis; Rectal neoplasms, mid-low; Transanal total mesorectal excision.