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    • Comparison of the Recent Efficacy of Robot-assisted and Thoracic Laparoscopic Minimally Invasive Mckeown Radical Resection of Esophageal Cancer based on Propensity Score Matching

    • ZHANG Tianci

      ,  

      YUAN Ligong

      ,  

      TIAN Jieyong

      ,  

      LI Xinhao

      ,  

      HUANG Zhining

      ,  

      WU Xianning

      ,  
    • Journal of Sun Yat-sen University(Medical Sciences)   Vol. 45, Issue 2, Pages: 310-318(2024)
    • DOI:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240312.003    

      CLC: R655.4
    • Published:20 March 2024

      Received:16 November 2023

      Accepted:21 February 2024

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  • ZHANG Tianci,YUAN Ligong,TIAN Jieyong,et al.Comparison of the Recent Efficacy of Robot-assisted and Thoracic Laparoscopic Minimally Invasive Mckeown Radical Resection of Esophageal Cancer based on Propensity Score Matching[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(02):310-318. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20240312.003.

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    Abstract

    Objective

    To explore the safety and efficacy of robot-assisted minimally invasive esophagectomy (robot-assisted minimally invasive esophagectomy, RAMIE) and thoracic laparoscopy combined with minimally invasive esophageal resection (minimal invasive esophagectomy, MIE).

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    Methods

    The data of 188 patients treated with Da Vinci robot assisted minimally invasive esophageal resection (RAMIE) from April 2021 to December 2022 were analyzed. In the RAMIE group, 69 patients, 49 males and 20 female, age (67.2 ± 7.2); 119 in the MIME group, respectively, 89 males and 30 female, age (69.1 ± 7.0). At 1 ∶ 1, including 58 patients in the RAMIE group and 58 patients in the MIE group. The t-test, Wilcoxon rank-sum test, χ2 test, and so on.

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    Results

    After PSM treatment, the clinical data between the two groups. There was no significant difference in operation time, postoperative tube days, and total number of lymph node dissection between the RAMIE and MIE groups (P <0.05); the RAMIE group was better in terms of intraoperative bleeding and the MIE group, statistically significant (P <0.05); the MIE group was better in drainage flow and lymph node dissection for three days (P <0.05). In terms of postoperative complications, there was no statistical difference between RAMIE and MIE groups (P>0.05).

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    Conclusion

    The recent efficacy of robot-assisted minimally invasive esophagectomy is comparable to that of thoracic laparoscopy and minimally invasive Mckeown esophagectomy; robotic-assisted minimally invasive esophagectomy can reduce intraoperative bleeding and have more advantages in left recurrent laryngeal nerve lymph node dissection.

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    Keywords

    esophageal cancer; Da Vinci machine system; minimally invasive esophageal cancer surgery; tendency matching score; minimal invasive esophagectomy

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    食管癌发生率在全球恶性肿瘤排行榜排第七,死亡率第六

    1。每年约有一半的新发病例发生在中国,其中男性的发病率高于女性,在中国男性中食管癌的发病率和死亡率分别排在第五和第四位2。食管癌治疗整体疗效仍然不理想,根据最新证据指南推荐其主要治疗模式是以手术为主的综合治疗模式,对于早期可切除的胸段食管癌首选手术治疗,对于中晚期食管癌,经过积极的新辅助治疗,大大提高了手术成功率3。经过数十年微创技术的发展,微创食管癌切除术成为主流术式,胸腹腔镜联合微创食管癌切除术(minimal invasive esophagectomy,MIE)避免了开放手术创伤大,并发症多和恢复慢等缺点4。随着达芬奇机器人系统的不断发展,机器人辅助微创食管癌切除术(robot-assisted minimally invasive esophagectomy,RAMIE)成为食管癌微创治疗的另一个选择5-7。国内一项Meta分析纳入了纳入1 073文章,提示RAMIE相比于MIE手术有临床优势8。近年来,关于RAMIE治疗食管癌近、远期疗效的研究获得关注9-12,但由于目前国内开展RAMIE的单位相对较少,作为安徽地区开展RAMIE例数最多的中心,对单中心RAMIE数据和MIE进行对比仍有重要意义。本研究旨在比较RAMIE和MIE的近期疗效和并发症发生率,以探讨 RAMIE的安全性和有效性。
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    1 材料与方法

    1.1 一般资料

    回顾性分析中国科学技术大学第一附属医院胸外科 2021年 4月至 2022年 12月收治的食管癌手术患者临床资料。所有患者术前行胸部+上腹部增强CT扫描、上消化道造影、胃镜及病理检查、心电图、肺功能,心脏彩超检查,有脑血管病史的加做头颅磁共振检查,经济条件允许的术前可行PET-CT检查,根据美国麻醉医师协会ASA分级进行术前麻醉风险评估。术后采用AJCC第8版食管癌分期系统进行肿瘤分期。本研究符合《赫尔辛基宣言》的要求,数据使用通过我院伦理委员会审核伦理审核, 编号:2024-RE-8。豁免患者知情同意。

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    纳入标准:术前临床分期为 cT1~3N0~ 1M0 期可手术治疗额食管癌患者;术前病理学检查证实为食管癌;接受 RAMIE 或 MIE ;手术采用右胸、上腹、左颈三切口手术;吻合方式为经左颈端-侧吻合。

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    排除标准:临床资料不完整。患者合并严重心肺功能不全,不适合麻醉及手术治疗。既往有胸、腹部手术史不适合微创手术者。

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    此期间共收治符合纳入标准的食管癌患者198例,排除临床资料不完整 7 例,有腹部手术史未进行全腔镜手术3例,共 188 例纳入本研究(附图)。手术前由科室讨论决定手术指征。

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    1.2 手术方法

    1.2.1 RAMIE

    患者采用单腔气管插管,封堵右侧主支气管,麻醉满意后取左侧卧位,常规消毒铺巾后取右侧腋中线第7肋间8 mm切口为观察孔,右侧腋前线第4肋间、腋后线第9肋间8 mm切口为机器人操作孔,腋前线第5肋间1 cm切口为辅助操作孔(图1A)。建立人工气胸,压力8 mmHg,对接机器人机械臂,由上至下依次清扫右喉返神经旁淋巴结(图1B),左喉返神经旁淋巴结(图1C),隆突下淋巴结,食管旁淋巴结。完成食管游离。改平卧位,于脐下偏左侧1 cm处做一8 mm切口为腹腔镜观察孔。选择右肋缘下8 mm及左侧脐水平腹直肌旁取8 mm切口为机器人操作孔,右侧脐水平腹直肌外侧缘1 cm切口为助手操作孔(图1D)。对接机器人机械臂,由小弯侧游离小网膜囊,清扫胃左、肝总、脾动脉旁淋巴结,离断胃左血管,由大弯侧游离胃大网膜,上至食管裂孔,下至幽门并清扫胃周淋巴结。剑突下做5 cm切口,于食管下段离断食管,将胃牵至体外制作管胃,宽度约3 cm。胃底留置牵引线于食管相连。经左侧胸锁乳突肌内缘切口游离颈段食管,将管胃牵拉至颈部后使用圆形吻合器做端侧吻合。吻合完毕后手辅助放置鼻-胃管、鼻-十二指肠营养管后关闭腹部切口,颈部切口常规留置引流管。

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    图1  RAMIE组体位及淋巴结清扫

    Fig. 1  Body position and lymph node dissectionin the RAMIE group

    A: Chest position and incision in the RAMIE group; B: Dissected the adjacent lymph nodes of the right recurrent laryngeal nerve in the RAMIE group; C: Dissected the adjacent lymph nodes of the left recurrent laryngeal nerve in the RAMIE group; D: Abdominal position and incision in the RAMIE group. LRLN: left recurrent laryngeal nerve; RRLN: right recurrent laryngeal nerve.

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    1.2.2 MIE

    麻醉与体位与RAMIE相同,选右腋前线第4肋间长2.0 cm切口为主操作孔,腋中线第7肋间长1.0 cm切口为镜孔,腋后线与肩胛线之间第8肋间长1.5 cm 切口为辅助操作孔(图2A),使用超声刀和电钩完成胸段食管游离,常规探查并清扫双侧喉返神经旁(图2BC)、食管旁、隆突下等处淋巴结。完成食管游离后改平卧位,腹腔取剑突下.右侧锁骨中线与肋缘交点,左锁骨中线与肋缘交点下3 cm处做辅助切口(5 mm),脐下做镜孔(1 cm),镜孔与右侧辅助切口中点做主操作孔(1 cm)(图2D),腹腔由小弯侧游离小网膜囊,清扫胃左、肝总、脾动脉旁淋巴结(图2E),其余游离顺序及颈部吻合与RAMIE相同。

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    图2  MIE组体位及淋巴结清扫

    Fig. 2  Body position and lymph node dissectionin the MIE group

    A: Chest position and incision in the MIE group; B:Dissected the adjacent lymph nodes of the left recurrent laryngeal nerve in the MIE group; C: Dissected the adjacent lymph nodes of the right recurrent laryngeal nerve in the MIE group; D:Abdominal position and incision in the MIE group; E: Dissected the abdominal lymph nodes in the MIE group. LRLN: left recurrent laryngeal nerve; RRLN: right recurrent laryngeal nerve; LGA: left gastric artery ; SA: splenic artery; HA: hepatic artery.

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    1.3 统计学方法

    记录一般资料包括性别、年龄、肿瘤大小、术前合并症、术前ASA分级等。围手术期资料包括手术时间、术中出血量、术后引流管带管时间、术后住院时间。手术中由手术医师将切除的淋巴结标本组并记录淋巴结清扫范围及数目。由床位医生观察并记录术后并发症严重程度及处理等情况。倾向性评分匹配:选择性别、年龄、pTNM 分期、肿瘤部位、病理类型、分化程度和ASA分级为协变量;以手术方式为因变量,各协变量为自变量。通过 Logistic 回归计算倾向性评分值,采用SPSS26.0软件将RAMIE组和MIE组按1∶1最邻近匹配法进行匹配,卡钳值取 0.2,共计有 58例匹配成功。

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    采用SPSS 26.0统计学软件对数据进行分析。定性资料分类资料的比较,用皮尔逊卡方检验、校正的卡方检验、Fisher’s精确检验;定量资料比较采用t检验。P<0.05为差异有统计学意义。

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    2 结 果

    2.1 RAMIE组和MIE组一般临床资料比较

    本研究共纳入研究样本198例,经筛选最后入组188例样本,其中RAMIE组69例,男性49例,女性20例,年龄(67.2±7.2)岁;MIE组119例,男性 89例,女性30例,年龄(69.1±7.0)岁。采用倾向性评分匹配法对两组患者进行 1∶1匹配,匹配后 RAMIE组 58例,其中男性44例,女性14例,年龄(67.00±6.79)MIE组 58例,其中男性43例,女性13例,年龄(67.33±7.84;表1)。

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    表1  RAMIE组和MIE组一般临床资料PSM前、后比较
    Table 1  Comparison of General clinical data between RAMIE and MIE group before and after PSM
    VariablesPre-PSMPost-PSM

    RAMIE

    n=69)

    MIE

    n=119)

    t/χ2P

    RAMIE

    n=58)

    MIE

    n=58)

    t/χ2P
    Sex 0.319 0.572 0.046 0.830
    Male 49 89 44 43
    Female 20 30 14 15
    Age 67.26±7.29 69.19±7.04 1.791 0.075 67.00±6.79 67.33±7.84 0.241 0.810
    Height 163.32±8.40 164.71±7.53 1.173 0.242 163.64±8.66 163.41±8.11 0.144 0.886
    Weight 58.81±10.01 60.64±9.61 1.240 0.216 59.586±9.57 58.733±10.15 0.466 0.642
    BMI 22.210±3.69 22.577±3.83 1.131 0.522 22.478±3.69 22.036±3.08 0.699 0.486
    Tumor diameter 3.348±1.59 3.239±1.34 0.501 0.617 3.190±1.41 3.328±1.28 0.551 0.583
    Tumor site 3.734 0.155 0.378 0.828
    Up 7 14 6 6
    Middle 44 59 35 32
    Lower 18 46 17 20
    Degrre of differentiation 2.637 0.268 1.199 0.549
    High 9 22 8 12
    Middle 42 58 37 32
    Low 18 39 13 14
    Psthology type 5.258 0.022 - -
    Squamous carcinoma 66 119 58 58
    Other 3 0 0 0
    Preoperative ASA classification 0.002 0.961 0.340 0.560
    2 41 72 36 39
    3 27 47 22 19
    Tumor stage 3.600 0.308 1.016 0.797
    1 15 27 14 14
    2 37 63 31 32
    3 15 29 12 12
    4 2 0 1 0
    Preoperative complications
    Hypertension 19 31 0.049 0.824 14 15 0.046 0.83
    Diabetes 3 9 0.756 0.385 3 4 0.152 0.697
    Cerebrovascular disease 13 14 1.778 0.182 13 5 4.209 0.04
    Coronary heart disease 4 4 0.636 0.425 3 3 0 1
    Arhythmia 6 24 4.286 0.038 6 12 2.367 0.124

    PSM: propensity score-matched; RAMIE: robot-assisted minimally invasive esophagectomy;MIE: minimal invasive esophagectomy.

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    2.2 RAMIE组和MIE组围术期资料比较

    RAMIE组和MIE组在手术时间[(275.72±84.14)vs(272.22±183.32)P>0.05];术后带管时间[(7.40±3.48)vs(7.74±3.38) P>0.05];术后住院天数[(10.43±4.32)vs(9.69±4.27) P>0.05];右喉返[(2.03±2.17)vs(2.12±2.87)P>0.05];淋巴结清扫总数[(20.78±6.85)vs(20.05±9.48) P>0.05];差异无统计学意义。RAMIE组和MIE组在术中出血[(73.10±52.29)vs(106.03±44.99)P<0.05];总住院天数[(13.29±5.40)vs(15.36±5.27)P<0.05];左喉返[(2.97±2.47)vs(1.90±2.14)P<0.05];淋巴结清扫总组数[(5.88±2.44)vs(5.09±1.26)P<0.05]差异有统计学意义(表2)。

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    表2  RAMIE组和MIE组患者围术期资料对比
    Table 2  Comparison of perioperative data of patients between RAMIE and MIE group
    VariablesRAMIE(n=58)MIE(n=58)tP
    Operation time/min 275.72±84.14 272.22±183.32 0.132 0.895
    Intraoperative bleeding /mL 73.10±52.29 106.03±44.99 3.636 <0.001
    Postoperative tube time /d 7.40±3.48 7.74±3.38 0.541 0.589
    Hospitalization days/d 13.29±5.40 15.36±5.27 2.088 0.039
    Dumber of days in hospital after surgery /d 10.43±4.32 9.69±4.27 0.929 0.355
    Lymph nodes of the right recurrent laryngeal nerve/n 2.03±2.17 2.12±2.87 2.490 0.856
    Lymph nodes of the left recurrent laryngeal nerve/n 2.97±2.47 1.90±2.14 0.182 0.014
    Total groups number of lymph node dissection 5.88±2.44 5.09±1.26 2.197 0.03
    Total number of lymph node dissection 20.78±6.85 20.05±9.48 0.471 0.638

    RAMIE: robot-assisted minimally invasive esophagectomy; MIE: minimal invasive esophagectomy.

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    2.3 RAMIE组和MIE组并发症比较

    RAMIE和MIE组在术后肺部感染、声音嘶哑、吻合口瘘等相关并发症方面存在差异,差异无统计学意义(P>0.05;表3)。

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    表3  RAMIE组和MIE组患者术后并发症对比
    Table 3  Comparison of postoperative complications of patients between RAMIE and MIE group
    VariablesRAMIE(n=58)MIE(n=58)χ2P
    Pulmonary air leakage 0.176 0.675
    Yes 4 2
    No 54 56
    Pulmonary infection 0.058 0.809
    Yes 11 10
    No 47 48
    Severe pulmonary infection 1.574 0.21
    Yes 7 12
    No 51 55
    Hoarseness 1.369 0.242
    Yes 3 0
    No 55 58
    Stomal leak 0.259 0.611
    Yes 3 1
    No 55 57
    Chylothorax 0.500
    Yes 1 0
    No 57 58

    RAMIE: robot-assisted minimally invasive esophagectomy; MIE: minimal invasive esophagectomy.

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    3 讨 论

    本研究比较达芬奇机器人辅助微创食管癌切除术和胸腹腔镜联合微创Mckeown食管癌切除术的短期治疗效果。PSM分析拥有减少两组病例间的选择性偏倚,使筛选出来的研究对象在临床特征(潜在的混杂因素)上具有可比性,使研究结果更接近于随机对照研究的作用。结果表明,经过PSM处理后,两组患者临床基本信息无明显差异性表现,术前合并症无明显差异。围手术期相关因素分析:RAMIE组和MIE组关于手术时间、术后带管时间、术后住院天数、右喉返淋巴结清扫数、淋巴结清扫总数方面差异无统计学意义(P>0.05)。同时RAMIE组在术中出血、总住院天数、左喉返淋巴结清扫数和淋巴结清扫总组数方面优于MIE组(P<0.05)。RAMIE组术后三天引流量较MIME组更多(P<0.05)。在围术期并发症方面,RAMIE组和MIE组在术后肺漏气,肺部感染,吻合口瘘,声音嘶哑等方面无明显差异(P>0.05)。

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    本研究中我们观察RAMIE组和MIE组两组患者围手术期的数据比较中我们可以看到,在手术时长、术后带管时间、术后住院天数和淋巴结清扫总数这些评估手术质量的主要指标上面,两组资料无明显统计学差异(P>0.05),说明达芬奇手术能达到传统胸腹腔镜手术相同的手术效果。4篇

    13-16同样采用McKeown 手术的meta分析结果表明:接受 RAMIE 的手术与 MIE 手术相比,术中的胸部手术时间差异无统计学意义17-18。因为我们中心 RAMIE组和MIE组均采用McKeown 手术方式,颈部吻合方法均为器械吻合,手术步骤固定,同时术者均有数百例的手术经验,手术熟练度均较高,RAMIE组和MIE组两组患者相关围手术期的数据比较无明显差异表明RAMIE这种手术是一种容易被术者掌握的手术方式。
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    两组患者在术中出血、总住院天数、左喉返神经淋巴结清扫及淋巴结清扫总组数方面RAMIE组优于MIE组。Nakanoko等

    19在对于左喉返神经旁淋巴结清扫的针对研究结果显示机器人辅助食管癌根治手术不但可以清扫左喉返神经旁淋巴结同时也可以减少神经的损伤。Betzler等20对机器人辅助食管癌根治术与胸腔镜食管癌根治术的围手术期疗效进行了比较显示机器人手术不但可以降低手术相关并发症,还可以降低术后平均住院日。Tagkalos等21一项纳入了112例行RAMIE或开胸食管癌根治术(open transthoracic esophagectomy, OTE)研究显示RAMIE相较于开胸食管癌手术可以减少手术出血量以及肺部相关并发症发生率。这反应可RAMIE手术的优势,RAMIE手术可以借助灵活的机械臂、3D的手术视野以及稳定的机械臂,得以在狭小空间内完成精确操作,这在手术操作中带来显著优势,弥补了腹腔镜2D视角和腔镜器械在狭小空间内完成精细操作困难的劣势22-23
    transl

    本研究中我们观察到RAMIE组相较于MIE组术后并发症包括:肺部漏气,肺部感染、吻合口瘘、声音嘶哑、乳糜胸等术后并发症无明显差异。Betzler等

    20对机器人辅助食管癌根治术与胸腔镜食管癌根治术的围手术期疗效进行了比较,结果显示,机器人手术患者术后并发症发生率、吻合口瘘发生率、ICU停留时间都低于胸腔镜手术患者。李刚等17研究表明RAMIE手术不但能够更多的清扫左喉返神经淋巴结同时还能降低患者声音嘶哑的发生概率Tagkalos等21的研究结果显示RAMIE组术后并发症发生率显著低于OTE组。同时,RAMIE组术中出血量,肺部并发症发生率,心律失常发生率,疼痛程度均显著低于OTE组。RAMIE组患者出院时生活质量评分及出院后6周生活质量评分显著高于OTE组。以上研究结果与本研究存在差异,可能跟RAMIE手术需要较长学习曲线相关,本研究采用的RAMIE组数据是本中心自采用达芬奇机器人手术以来的所有手术患者数据,Han 等24研究发现,机器人食管癌手术学习曲线为51例,另外有研究显示达芬奇机器人手术学习曲线为20台手术25-26。Van Der 等27研究显示在无任何机器人手术经验的前提下,其机器人食管癌根治术学习曲线为70例。而术者在作为助手进行20例机器人食管癌手术后,其机器人食管癌根治术学习曲线为24例。在学习曲线初段可能会出现副损伤以及手术相关并发症,在度过学习曲线后总手术时间显著缩短、主要并发症发生率显著降低。因本研究数据包含学习曲线内患者资料,因此在术后相关并发症比较中未体现出RAMIE的优势。
    transl

    综上所述,本研究显示RAMIE可以在不但可以相同时间内完成食管癌根治手术还能更大范围的完成淋巴结清扫,同时还能使手术更加精细,患者更快速地康复。因此RAMIE是一种更加安全更加有效的手术方式,值得推广使用。

    transl

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