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胰腺导管腺癌行腹腔镜下胰十二指肠切除术后早期复发的列线图模型及其预测价值分析

刘舜 谢诚 刘亚辉

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胰腺导管腺癌行腹腔镜下胰十二指肠切除术后早期复发的列线图模型及其预测价值分析

DOI: 10.12449/JCH240123
伦理学声明:本研究方案于2023年11月30日经由吉林大学第一医院伦理委员会审批,批号:(2023年)临审第(2023-708)号。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:刘舜负责设计研究框架、数据收集、统计学分析、起草论文;谢诚负责数据收集、统计学分析、绘制图表;刘亚辉负责拟定写作思路,论文修改,指导撰写文章并最后定稿。
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    通信作者:

    刘亚辉, yahui@jlu.edu.cn (ORCID: 0000-0003-3081-8156)

Value of a nomogram model in early recurrence of pancreatic ductal adenocarcinoma after laparoscopic pancreaticoduodenectomy

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    Corresponding author: LIU Yahui, yahui@jlu.edu.cn (ORCID: 0000-0003-3081-8156)
  • 摘要:   目的  探究胰腺导管腺癌(PDAC)患者行腹腔镜胰十二指肠切除术(LPD)后肿瘤早期复发的危险因素并建立预测模型。  方法  回顾性分析2016年4月—2022年7月于吉林大学第一医院行LPD的240例PDAC患者的临床资料,以术后肿瘤早期复发(复发时间≤12个月)为研究结局。按照7∶3比例,随机将患者分为训练组(n=168)与验证组(n=72)。训练组术后早期复发70例(41.67%),非早期复发98例(58.33%)。验证组术后早期复发32例(44.44%),非早期复发40例(55.56%)。计数资料组间比较采用χ2检验或Fisher精确概率法。Logistic回归分析影响术后早期复发的危险因素。采用受试者工作特征曲线下面积(AUC)评估模型的区分度,AUC>0.75为该模型有足够的区分度。用Bootstrap重采样法随机抽样1 000次验证,并用验证组再次验证。使用校准曲线和Hosmer-Lemeshow拟合优度检验评估校准度,决策曲线评估临床实用性。  结果  单因素、多因素分析结果显示:术前CA19-9水平≥37 U/mL、肿瘤最大直径>3 cm、肿瘤低分化、有淋巴结转移、术后未行辅助化疗是影响PDAC行LPD术后早期复发的独立危险因素[OR(95%CI)分别为6.265(1.938~20.249)、10.878(4.090~28.932)、3.679(1.435~9.433)、0.209(0.080~0.551)、0.167(0.058~0.480),P值均<0.05]。以此为基础构建列线图模型,AUC=0.895(95%CI:0.846~0.943,P<0.001),校准曲线Hosmer-Lemeshow检验表明模型具有良好的校准度(P=0.173)。决策曲线显示列线图具有良好的临床应用价值。  结论  术前CA19-9水平≥37 U/mL、肿瘤最大直径>3 cm、肿瘤低分化、有淋巴结转移、术后未行辅助化疗是影响PDAC LPD术后早期复发的独立危险因素,以此为依据构建列线图模型可有效预测术后早期复发。

     

  • 图  1  预测 PDAC患者行LPD术后早期复发的列线图

    Figure  1.  A nomogram predicting early recurrence after radical LPD with resectable PDAC

    图  2  列线图预测 PDAC患者行LPD术后早期复发的ROC曲线(训练组)

    Figure  2.  The nomogram predicts the ROC curve of early recurrence after radical LPD with resectable PDAC (Training group)

    图  3  列线图预测 PDAC患者行LPD术后早期复发的ROC曲线(验证组)

    Figure  3.  The nomogram predicts the ROC curve of early recurrence after radical LPD with resectable PDAC (Validation group)

    图  4  PDAC患者行LPD术后早期复发的校准曲线(训练组)

    Figure  4.  Calibration curve for early postoperative recurrence of radical LPD with resectable PDAC (Training group)

    图  5  PDAC患者行LPD术后早期复发的校准曲线(验证组)

    Figure  5.  Calibration curve for early postoperative recurrence of radical LPD with resectable PDAC (Validation group)

    图  6  PDAC患者行LPD术后早期复发的决策曲线(训练组)

    Figure  6.  Decision curve for early postoperative recurrence of radical LPD with resectable PDAC (Training group)

    图  7  PDAC患者行LPD术后早期复发的决策曲线(验证组)

    Figure  7.  Decision curve for early postoperative recurrence of radical LPD with resectable PDAC (Validation group)

    表  1  训练组和验证组基线数据特征比较

    Table  1.   Comparison of baseline data characteristics between training group and verification group

    项目 训练组(n=168) 验证组(n=72) χ² P
    <60岁/≥60岁(例) 88/80 35/37 0.287 0.592
    男/女(例) 92/76 42/30 0.261 0.610
    BMI[例(%)] 0.008 0.928
    <24.0 kg/m3 113(67.26) 48(66.67)
    ≥24.0 kg/m3 55(32.74) 24(33.33)
    高血压[例(%)] 29(17.26) 12(16.67) 0.013 0.911
    糖尿病[例(%)] 37(22.02) 12(16.67) 0.890 0.345
    上腹部手术史[例(%)] 17(10.12) 10(13.89) 0.717 0.397
    术前CA19-9[例(%)] 0.512 0.474
    <37 U/mL 46(27.38) 23(31.94)
    ≥37 U/mL 122(72.62) 49(68.06)
    术前CA125[例(%)] 0.540 0.463
    <35 U/mL 146(86.90) 65(90.28)
    ≥35 U/mL 22(13.10) 7(9.72)
    术前总胆红素[例(%)] 0.003 0.953
    ≤170 μmol /L 109(64.88) 47(65.28)
    >170 μmol /L 59(35.12) 25(34.72)
    术前胆道引流[例(%)] 73(43.45) 25(34.72) 1.590 0.207
    ASA[例(%)] 0.224 0.636
    1+2 144(85.71) 60(83.33)
    3+4 24(14.29) 12(16.67)
    术中失血量[例(%)] 0.025 0.874
    ≤400 mL 122(72.62) 53(73.61)
    >400 mL 46(27.38) 19(26.39)
    术中输血[例(%)] 40(23.80) 18(25.00) 0.039 0.843
    胰腺质地[例(%)] 0.167 0.682
    63(37.50) 25(34.72)
    105(62.50) 47(65.28)
    胰管直径[例(%)] 0.185 0.667
    ≤3 mm 49(29.17) 23(31.94)
    >3 mm 119(70.83) 49(68.06)
    胰瘘[例(%)] 15(8.93) 7(9.72) 0.038 0.845
    胆瘘[例(%)] 4(2.38) 5(6.94) 2.908 0.088
    延迟性胃瘫 [例(%)] 7(4.17) 3(4.17) 0.222 0.637
    腹腔感染[例(%)] 10(5.95) 4(5.56) 0.085 0.771
    肺部感染[例(%)] 3(1.79) 2(2.78) 0.6381)
    术后出血[例(%)] 3(1.79) 5(6.94) 4.163 0.055
    肿瘤最大直径[例(%)] 0.067 0.796
    ≤3cm 67(39.88) 30(41.67)
    >3cm 101(60.12) 42(58.33)
    肿瘤分化程度[例(%)] 0.013 0.909
    低分化 97(57.74) 41(56.94)
    中分化或高分化 71(42.26) 31(43.06)
    淋巴结转移[例(%)] 109(64.88) 49(68.06) 0.226 0.635
    神经浸润[例(%)] 142(84.52) 61(84.72) 0.002 0.969
    脉管浸润[例(%)] 108(64.29) 45(62.50) 0.070 0.792
    术后辅助化疗[例(%)] 49(29.17) 24(33.33) 0.413 0.520
    注:1)为Fisher精确概率法。
    下载: 导出CSV

    表  2  PDAC患者行LPD术后早期复发单因素分析

    Table  2.   Univariate analysis of early recurrence after radical LPD in PDAC patients

    项目 训练组(n=168) 验证组(n=72) χ² P
    <60岁/≥60岁(例) 47/51 41/29 1.844 0.175
    男/女(例) 58/40 34/36 1.856 0.173
    BMI[例(%)] 2.874 0.090
    <24.0 kg/m3 71(72.45) 42(60.00)
    ≥24.0 kg/m3 27(27.55) 28(40.00)
    高血压[例(%)] 18(18.37) 11(15.71) 0.201 0.654
    糖尿病[例(%)] 20(20.41) 17(24.29) 0.357 0.550
    上腹部手术史[例(%)] 12(12.24) 5(7.14) 1.169 0.280
    术前总胆红素[例(%)] 0.269 0.604
    ≤170 μmol /L 62(63.27) 47(67.14)
    >170 μmol /L 36(36.73) 23(32.86)
    术前胆道引流[例(%)] 46(46.94) 27(38.57) 1.163 0.281
    ASA[例(%)] 0.200 0.655
    1+2 83(84.69) 61(87.14)
    3+4 15(15.31) 9(12.86)
    术前CA19-9[例(%)] 24.718 <0.001
    <37 U/mL 41(41.84) 5(7.14)
    ≥37 U/mL 57(58.16) 65(92.86)
    术前CA125[例(%)] 0.149 0.699
    <35 U/mL 86(87.76) 60(85.71)
    ≥35 U/mL 12(12.24) 10(14.29)
    术中失血量[例(%)] 0.168 0.682
    ≤400 mL 70(71.43) 52(74.29)
    >400 mL 28(28.57) 18(25.71)
    术中是否输血[例(%)] 23(23.47) 17(24.29) 0.015 0.903
    胰腺质地[例(%)] 0.059 0.808
    36(36.73) 27(38.57)
    62(63.27) 43(61.43)
    胰管直径[例(%)] 0.297 0.586
    ≤3 mm 27(27.55) 22(31.43)
    >3 mm 71(72.45) 48(68.57)
    胰瘘[例(%)] 7(7.14) 8(11.43) 0.922 0.337
    胆瘘[例(%)] 5(2.04) 2(2.86) 1.0001)
    延迟性胃瘫[例(%)] 2(2.04) 5(7.14) 0.1291)
    术后腹腔感染[例(%)] 5(5.10) 5(7.14) 0.304 0.743
    术后肺部感染[例(%)] 2(2.04) 1(1.43) 1.0001)
    术后出血[例(%)] 2(2.04) 1(1.43) 1.0001)
    肿瘤最大直径[例(%)] 32.789 <0.001
    ≤3 cm 57(58.16) 10(14.29)
    >3 cm 41(41.84) 60(85.71)
    肿瘤分化程度[例(%)] 15.892 <0.001
    低分化 44(44.90) 53(75.71)
    中分化或高分化[例(%)] 54(55.10) 17(24.29)
    淋巴结转移[例(%)] 49(50.00) 60(85.71) 22.858 <0.001
    神经浸润[例(%)] 83(84.69) 59(84.29) 0.005 0.943
    脉管浸润[例(%)] 64(65.31) 44(62.86) 0.107 0.744
    术后辅助化疗[例(%)] 36(36.73) 13(18.57) 6.520 0.011
    注:1)为Fisher精确概率法。
    下载: 导出CSV

    表  3  PDAC患者行LPD术后早期复发的多因素Logistic回归分析

    Table  3.   Multivariate Logistic regression analysis of early recurrence after radical LPD in PDAC patients

    相关因素 偏回归系数 标准误差 Wald值 P OR 95%CI
    术前CA19-9 1.835 0.599 9.398 0.002 6.265 1.938~20.249
    肿瘤最大直径 2.387 0.499 22.869 <0.001 10.878 4.090~28.932
    淋巴结转移 1.303 0.480 7.356 0.007 3.679 1.435~9.433
    肿瘤分化程度 -1.563 0.493 10.037 0.002 0.209 0.080~0.551
    术后辅助化疗 -1.791 0.539 11.035 0.001 0.167 0.058~0.480
    常量 -3.167 0.721 19.279 <0.001 0.042
    下载: 导出CSV
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  • 收稿日期:  2023-09-25
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