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不同类型胃恶性神经内分泌肿瘤与胃腺癌的临床病理特征和生存情况比较

张奔龙 高云鹤 鲁意迅 李力 梁文全 郗洪庆 王鑫鑫 张珂诚 陈凛

张奔龙, 高云鹤, 鲁意迅, 李力, 梁文全, 郗洪庆, 王鑫鑫, 张珂诚, 陈凛. 不同类型胃恶性神经内分泌肿瘤与胃腺癌的临床病理特征和生存情况比较[J]. 解放军医学院学报, 2023, 44(4): 324-332. doi: 10.3969/j.issn.2095-5227.2023.04.002
引用本文: 张奔龙, 高云鹤, 鲁意迅, 李力, 梁文全, 郗洪庆, 王鑫鑫, 张珂诚, 陈凛. 不同类型胃恶性神经内分泌肿瘤与胃腺癌的临床病理特征和生存情况比较[J]. 解放军医学院学报, 2023, 44(4): 324-332. doi: 10.3969/j.issn.2095-5227.2023.04.002
ZHANG Benlong, GAO Yunhe, LU Yixun, LI Li, LIANG Wenquan, XI Hongqing, WANG Xinxin, ZHANG Kecheng, CHEN Lin. Comparison of clinicopathological characteristics and overall survival between different types of gastric malignant neuroendocrine neoplasms and gastric adenocarcinoma[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(4): 324-332. doi: 10.3969/j.issn.2095-5227.2023.04.002
Citation: ZHANG Benlong, GAO Yunhe, LU Yixun, LI Li, LIANG Wenquan, XI Hongqing, WANG Xinxin, ZHANG Kecheng, CHEN Lin. Comparison of clinicopathological characteristics and overall survival between different types of gastric malignant neuroendocrine neoplasms and gastric adenocarcinoma[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(4): 324-332. doi: 10.3969/j.issn.2095-5227.2023.04.002

不同类型胃恶性神经内分泌肿瘤与胃腺癌的临床病理特征和生存情况比较

doi: 10.3969/j.issn.2095-5227.2023.04.002
基金项目: 国家自然科学基金项目(82103593;81972790);北京市自然科学基金项目(7214252);军委后勤保障部面上项目(20BJZ39)
详细信息
    作者简介:

    张奔龙,男,在读硕士。研究方向:胃部肿瘤发生、发展机制。Email: benlong970401@sina.com

    通讯作者:

    张珂诚,男,博士,副主任医师。Email: zhangkecheng@301hospital.com.cn

    陈凛,男,博士,主任医师。Email: chenlin@301hospital.com.cn

  • 中图分类号: R735

Comparison of clinicopathological characteristics and overall survival between different types of gastric malignant neuroendocrine neoplasms and gastric adenocarcinoma

More Information
  • 摘要:   背景  胃恶性神经内分泌肿瘤包括胃神经内分泌癌和含有神经内分泌癌成分的混合性神经内分泌-非神经内分泌肿瘤,混合性神经内分泌-非神经内分泌肿瘤绝大多数为腺-神经内分泌癌,因其罕见性,目前缺乏系统性的研究提高对其临床病理特征及预后的认识。   目的  以胃腺癌为参照,探究胃恶性神经内分泌肿瘤的临床病理特征和生存情况。   方法  采用回顾性病例对照研究的方法,收集2008年1月 - 2018年12月在解放军总医院第一医学中心行手术治疗的非cM1期胃恶性神经内分泌肿瘤及胃腺癌患者资料,分析、比较其临床病理特征。1:3倾向性评分匹配(PSM)调整胃恶性神经内分泌肿瘤和胃腺癌队列之间的混杂因素。Kaplan-Meier法绘制生存曲线,log-rank检验分析组间总生存率的差异,Cox回归模型分析患者预后的独立关联因素。   结果  共纳入5443例(96.0%)胃腺癌与226例(4.0%)胃恶性神经内分泌肿瘤,后者包括148例神经内分泌癌和78例腺-神经内分泌癌。胃恶性神经内分泌肿瘤与胃腺癌首诊年龄、性别、肿瘤大小、肿瘤部位、手术方法、胃切除方式、T分期、N分期、TNM分期的差异有统计学意义(P<0.05)。2875例胃腺癌和215例胃恶性神经内分泌肿瘤有完整的生存信息,倾向性匹配后进行生存分析,发现胃腺癌患者的总生存率显著优于胃恶性神经内分泌肿瘤患者(3年、5年生存率:67.3% vs 58.9%,59.8% vs 48.3%,P=0.002),亚组分析显示,胃腺癌患者的总生存率优于神经内分泌癌和腺-神经内分泌癌患者(3年、5年生存率:67.3% vs 57.5%和61.1%,59.8% vs 50.5%和44.9%,P均<0.05),但神经内分泌癌患者与腺-神经内分泌癌患者的总生存率无统计学差异(P=0.993)。对胃恶性神经内分泌肿瘤的分析显示,神经内分泌癌与腺-神经内分泌癌在首诊年龄、性别、肿瘤大小、肿瘤部位、手术方法、胃切除方式、T分期、N分期、TNM分期、免疫标记物表达上无统计学差异(P <0.05)。生存分析结果表明年龄(HR=1.945,95% CI:1.249 ~ 3.030)、肿瘤大小(HR=2.199,95% CI:1.029 ~ 4.701)、TNM分期[Ⅱ期 vs Ⅰ期(HR=1.669,95% CI:0.596 ~ 4.670),Ⅲ期 vs Ⅰ期(HR=5.710,95% CI:2.197 ~ 14.837)]与胃恶性神经内分泌肿瘤患者生存独立关联。  结论  胃恶性神经内分泌肿瘤与胃腺癌有着截然不同的临床病理特征,胃恶性神经内分泌肿瘤浸润能力更强,侵袭性更高,总生存率显著劣于胃腺癌,神经内分泌癌和腺-神经内分泌癌有着相似的临床病理特征及总生存率;年龄≥60岁、肿瘤≥3 cm、Ⅲ期多提示胃恶性神经内分泌肿瘤患者较差的预后。

     

  • 图  1  PSM前后,胃腺癌与恶性NEN患者OS的比较

    A:PSM前胃腺癌与恶性NEN患者OS的比较;B:PSM后胃腺癌与恶性NEN患者OS的比较

    Figure  1.  Comparison of OS between gastric AC and malignant NEN before and after PSM

    A: Comparison of OS between gastric AC and malignant NEN before PSM; B: Comparison of OS between gastric AC and malignant NEN after PSM

    图  2  NEC、MANEC、腺癌患者之间OS的比较

    A:NEC、腺癌患者之间OS的比较;B:MANEC、腺癌患者之间OS的比较;C:NEC、MANEC患者之间OS的比较

    Figure  2.  Comparison of OS among NEC, MANEC and AC patients

    A: Comparison of OS between NEC and AC patients; B: Comparison of OS between MANEC and AC patients; C: Comparison of OS between NEC and AC patients

    图  3  NEC和MANEC免疫组化结果

    A:NEC和MANEC中Syn、CgA和CD56表达的情况;B:CgA在NEC和MANEC中的表达情况;C:Syn在NEC和MANEC中的表达情况;D:CD56在NEC和MANEC中的表达情况

    Figure  3.  Illustrations of immunohistochemical staining patterns in NEC and MANEC

    A: An overview of the expression of Syn, CgA, and CD56 in NEC and MANEC; B: CgA expression in NEC and MANEC; C: Syn expression NEC and MANEC; D: CD56 expression in NEC and MANEC

    图  4  不同临床病理特征的恶性NEN患者OS的比较

    A:不同性别患者OS的比较;B:不同年龄患者OS的比较;C:不同手术方式患者OS的比较;D:不同胃切除方式患者OS的比较;E:不同肿瘤部位患者OS的比较;F:不同肿瘤大小患者OS的比较;G:不同TNM分期患者OS的比较

    Figure  4.  Comparison of OS in malignant NEN patients with different clinicopathological features

    A: Comparison of OS between male and female patients; B: Comparison of OS between different age groups; C: Comparison of OS between different operation approaches; D: Comparison of OS between different types of gastrectomy; E: Comparison of OS between different tumor locations; F: Comparison of OS between different tumor size groups; G: Comparison of OS between different tumor TNM stage

    表  1  胃恶性NEN与胃腺癌患者一般及临床病理特征比较(例,%)

    Table  1.   Comparison of characteristics of patients with gastric malignant NEN and AC (n, %)

    临床病理特征胃腺癌(n=5443)胃恶性NEN (n=226)P胃腺癌(n=645)胃恶性NEN (n=215)P
    年龄<0.001 0.653
     <60岁2564(47.1)77(34.1)239(37.1)76(35.3)
     ≥60岁2879(52.9)149(65.9)406(62.9)139(64.7)
    性别0.0100.731
     男性4119(75.7)193(85.4)558(86.5)184(85.6)
     女性1324(24.3)33(14.6)87(13.5)31(14.4)
    肿瘤位置<0.001 0.624
     胃上部1911(35.1)134(59.3)377(58.4)129(60.0)
     胃中部891(16.4)30(13.3)84(13.0)27(12.5)
     胃下部2514(46.2)56(24.8)174(27.0)53(24.7)
     弥漫型127(2.3)6(2.6)10(1.6)6(2.8)
    肿瘤直径<0.001 0.286
     <3 cm1654(30.4)41(18.1)100(15.5)40(18.6)
     ≥3 cm3789(69.6)185(81.9)545(84.5)175(81.4)
    胃切除方式<0.001 0.323
     近端胃切除1470(27.0)101(44.7)292(45.3)96(44.6)
     远端胃切除2578(47.4)57(25.2)191(29.6)55(25.6)
     全胃切除1395(25.6)68(30.1)162(25.1)64(29.8)
    手术路径0.0100.033
     开放手术3092(56.8)113(50.0)359(55.7)107(49.8)
     腹腔镜手术1941(35.7)102(45.1)232(36.0)97(45.1)
     机器人手术410(7.5)11(4.9)54(8.3)11(5.1)
    T分期<0.001 0.699
     T1 ~ T21985(36.5)43(19.0)137(21.2)43(20.0)
     T3 ~ T43458(63.5)183(81.0)508(78.8)172(80.0)
    N分期0.0130.637
     N0 ~ N13149(57.9)112(49.6)321(49.8)111(51.6)
     N2 ~ N32294(42.1)114(50.4)324(50.2)104(48.4)
    M分期--
     M05443(100)226(100.0)645(100)215(100)
     M10(0)0(0)0(0)0(0)
    TNM分期<0.001 0.822
     Ⅰ期1535(28.2)30(13.3)88(13.7)30(14.0)
     Ⅱ期1468(27.0)65(28.8)182(28.2)65(30.2)
     Ⅲ期2440(44.8)131(57.9)375(58.1)120(55.8)
    下载: 导出CSV

    表  2  神经内分泌癌与腺-神经内分泌癌患者一般及临床病理特征比较(例,%)

    Table  2.   Comparison of characteristics of patients with NEC and MANEC (n, %)

    临床病理特征胃恶性NENP
    NEC (n=148)MANEC (n=78)
    年龄0.191
     <60岁46(31.1)31(39.7)
     ≥60岁102(68.9)47(60.3)
    性别0.582
     男性125(84.5)68(87.2)
     女性23(15.5)10(12.8)
    肿瘤位置0.986
     胃上部88(59.5)46(59.0)
     胃中部19(12.8)11(14.1)
     胃下部37(25.0)19(24.4)
     弥漫型4(2.7)2(2.5)
    肿瘤直径0.502
     <3 cm25(16.9)16(20.5)
     ≥3 cm123(83.1)62(79.5)
    胃切除方式0.890
     近端胃切除66(44.6)35(44.9)
     远端胃切除36(24.3)21(26.9)
     全胃切除46(31.1)22(28.2)
    手术路径0.089
     开放手术81(54.7)32(41.0)
     腹腔镜手术62(41.9)40(51.3)
     机器人手术5(3.4)6(7.7)
    T分期0.066
     T1 ~ T223(15.5)20(25.6)
     T3 ~ T4125(84.5)58(74.4)
    N分期0.855
     N0 ~ N174(50.0)38(48.7)
     N2 ~ N374(50.0)40(51.3)
    M分期-
     M0148(100)78(100)
     M10(0)0(0)
    TNM分期0.068
     Ⅰ期14(9.5)16(20.5)
     Ⅱ期44(29.7)21(26.9)
     Ⅲ期90(60.8)41(52.6)
    下载: 导出CSV

    表  3  胃恶性NEN患者生存情况的单因素及多因素Cox回归分析

    Table  3.   Univariate and multivariate Cox regression analysis of overall survival in patients with gastric malignant NEN

    临床病理特征单因素分析多因素分析
    HR95% CIPHR95% CIP
    年龄0.0200.003
     ≥60岁 vs <60岁1.6071.079 ~ 2.3931.9451.249 ~ 3.030
    性别0.255
     女性 vs 男性0.7270.420 ~ 1.258
    病理分型0.993
     MANEC vs NEC1.0020.668 ~ 1.503
    肿瘤位置0.0030.099
     胃中部 vs 胃上部0.9390.518 ~ 1.7030.8361.2210.658 ~ 2.2630.527
     胃下部 vs 胃上部0.5300.311 ~ 0.9040.0200.5810.336 ~ 1.0050.052
     弥漫型 vs 胃上部3.5701.415 ~ 9.0120.0071.6540.623 ~ 4.3910.312
    肿瘤直径<0.001 0.042
     ≥3 cm vs <3 cm2.4031.516 ~ 3.8092.1991.029 ~ 4.701
    胃切除方式0.0090.194
     远端胃切除 vs 近端胃切除0.4580.260 ~ 0.8050.0070.6800.447 ~ 1.0320.070
     全胃切除 vs 近端胃切除1.1200.727 ~ 1.7260.6070.8360.318 ~ 2.1990.716
    手术路径0.080
     腹腔镜手术 vs 开放手术0.6270.417 ~ 0.9420.025
     机器人手术 vs 开放手术0.8350.334 ~ 2.0840.699
    TNM 分期<0.001 <0.001 
     Ⅱ期 vs Ⅰ期2.1060.785 ~ 5.6480.1391.6690.596 ~ 4.6700.329
     Ⅲ期 vs Ⅰ期7.6103.064 ~ 18.900<0.001 5.7102.197 ~ 14.837<0.001 
    下载: 导出CSV
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出版历程
  • 收稿日期:  2022-08-25
  • 网络出版日期:  2023-03-31
  • 刊出日期:  2023-04-28

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