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浙江大学学报(医学版)  2021, Vol. 50 Issue (6): 730-740    DOI: 10.3724/zdxbyxb-2021-0210
专题报道     
甲状腺髓样癌患者颈外侧淋巴结转移危险因素分析
吴凡1,周天晗1,陆凯宁2,潘婷1,倪烨钦2,赵玲倩1,姜可成1,张煜2,罗定存2,*()
1.浙江中医药大学第四临床医学院,浙江 杭州 310053
2.浙江大学医学院附属杭州市第一人民医院肿瘤外科,浙江 杭州 310003
Risk factors for lateral cervical lymph node metastasis in medullary thyroid carcinoma
WU Fan1,ZHOU Tianhan1,LU Kaining2,PAN Ting1,NI Yeqin2,ZHAO Lingqian1,JIANG Kecheng1,ZHANG Yu2,LUO Dingcun2,*()
1. The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou 310053, China;
2. Department of Surgical Oncology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
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摘要:

目的:探讨影响甲状腺髓样癌(MTC)患者颈外侧转移性淋巴结的临床及超声影像危险因素。方法:检索PubMed、Web of Science、Embase、Cochrane、万方数据和中国知网等数据库收录的关于MTC患者颈外侧转移性淋巴结危险因素的相关文献,按照纳入和排除标准筛选文献,经质量评价后采用Stata?14.0软件进行meta分析。根据样本量、范围、中位数和四分位数间距估计均值和标准差,利用固定效应模型或随机效应模型计算各变量比值比(OR)或标准化均数差(SMD)及两者95%置信区间(CI),采用Egger法和Begg法评估文献发表偏倚。研究已在PROSPERO注册(CRD42021254955)。结果:最终纳入15篇文献,共有患者1424例,发生颈外侧淋巴结转移543例(38.13%)。Meta分析结果显示,男性(OR=1.64,95%CI:1.29~2.09,Z=4.06,P<0.01),肿瘤直径不小于1?cm(OR=5.09,95%CI:2.43~10.67,Z=4.31,P<0.01),肿瘤多灶性(OR=2.55,95%CI:1.79~3.61,Z=5.22,P<0.01),肿瘤被膜侵犯(OR=7.80,95%CI:4.84~12.55,Z=8.46,P<0.01),肿瘤腺外侵犯(OR=9.46,95%CI:5.66~15.81,Z=8.58,P<0.01),转移性颈部中央淋巴结(简称中央淋巴结)(OR=23.58,95%CI:9.44~58.87,Z=6.77,P<0.01),术前降钙素水平升高(SMD=1.17,95%CI:0.67~1.67,Z=4.56,P<0.01),超声下病灶边缘不光整(OR=4.32,95%CI:2.43~7.68,Z=4.99,P<0.01)及超声下病灶形态不规则(OR=6.81,95%CI:3.64~12.73,Z=6.01,P<0.01)是MTC患者发生颈外侧淋巴结转移的危险因素,而年龄不小于45岁(OR=1.22,95%CI:0.65~2.29,Z=0.62,P>0.05),术前癌胚抗原水平升高(SMD=0.95,95%CI:–0.48~2.38,Z=1.30,P>0.05)以及超声下钙化(OR=1.28,95%CI:0.75~2.18,Z=0.92,P>0.05)与MTC患者颈外侧转移性淋巴结无明显相关性。结论:男性、肿瘤直径不小于1?cm、肿瘤多灶性、肿瘤被膜侵犯、肿瘤腺外侵犯、转移性中央淋巴结、术前降钙素水平升高、超声下病灶边缘不光整以及超声下病灶形态不规则的MTC患者发生颈外侧淋巴结转移的风险较高,建议行颈外侧淋巴结清扫。

关键词: 甲状腺髓样癌颈外侧淋巴结转移meta分析临床特征超声影像危险因素    
Abstract:

Objective: To investigate risk factors of lateral cervical lymph node metastasis (LLNM) in patients with medullary thyroid carcinoma (MTC). Methods: Published studies regarding clinicopathological factors of LLNM in MTC were searched in PubMed, Web of Science, Embase, Cochrane library, Wanfang date and CNKI. Statistical analysis was performed using Stata 14.0 software. The mean and standard deviation from the sample size, range, median, and interquartile range was estimated. Odds ratio (OR) or standard mean difference (SMD) with 95% confidence interval (CI) of related factors were analyzed by fixed/random-effects models. Egger’s test and Begg’s test were applied to assess the publication bias of the literature. This study was registered with PROSPERO (CRD42021254955). Results: Fifteen studies involving 1424 patients were included in the analysis, among whom 543 cases had LLNM (38.13%). Meta-analysis revealed that an increased risk of LLNM was associated with male gender (OR=1.64, 95%CI: 1.29–2.09, Z=4.06, P<0.01), tumor diameter≥1cm (OR=5.09, 95%CI: 2.43–10.67, Z=4.31, P<0.01), multifocality (OR=2.55, 95%CI: 1.79–3.61, Z=5.22, P<0.01), capsule invasion (OR=7.80, 95%CI: 4.84–12.55, Z=8.46, P<0.01), extracapsular extension (OR=9.46, 95%CI: 5.66–15.81, Z=8.58, P<0.01), cervical central lymph node metastasis (OR=23.58, 95%CI: 9.44–58.87, Z=6.77, P<0.01), elevated preoperative calcitonin (SMD=1.17,95%CI: 0.67–1.67, Z=4.56, P<0.01), spiculated margin on ultrasonography (OR=4.32, 95%CI: 2.43–7.68, Z=4.99, P<0.01), irregular shape on ultrasonography (OR=6.81, 95%CI: 3.64–12.73, Z=6.01, P<0.01); while age ≥ 45 years (OR=1.22, 95%CI: 0.65–2.29, Z=0.62, P>0.05), elevated preoperative carcinoembryonic antigen (SMD=0.95, 95%CI: –0.48–2.38, Z=1.30, P>0.05) and calcification on ultrasonography (OR=1.28, 95%CI: 0.75–2.18, Z=0.92, P>0.05) were not associated with LLNM.Conclusion: Male gender, tumor diameter≥1?cm, multifocality, capsule invasion, extracapsular extension, central lymph node metastasis, elevated preoperative calcitonin, spiculated margin and irregular shape on ultrasonography are risk factors for LLNM in MTC, when these clinical and ultrasonic features are present, lateral neck lymph node dissection is recommended.

Key words: Medullary thyroid carcinoma    Lateral cervical lymph node metastasis    Meta-analysis    Clinical characteristics    Ultrasonic tomography    Risk factor
收稿日期: 2021-07-26 出版日期: 2022-03-22
CLC:  R736.1  
基金资助: 浙江省基础公益研究计划(LGF22H160082,LGF22H070008);杭州市医药卫生科技计划(A20200432)
通讯作者: 罗定存     E-mail: ldc65@163.com
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引用本文:

吴凡,周天晗,陆凯宁,潘婷,倪烨钦,赵玲倩,姜可成,张煜,罗定存. 甲状腺髓样癌患者颈外侧淋巴结转移危险因素分析[J]. 浙江大学学报(医学版), 2021, 50(6): 730-740.

WU Fan,ZHOU Tianhan,LU Kaining,PAN Ting,NI Yeqin,ZHAO Lingqian,JIANG Kecheng,ZHANG Yu,LUO Dingcun. Risk factors for lateral cervical lymph node metastasis in medullary thyroid carcinoma. J Zhejiang Univ (Med Sci), 2021, 50(6): 730-740.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0210        https://www.zjujournals.com/med/CN/Y2021/V50/I6/730

图 1  甲状腺髓样癌患者颈外侧淋巴结转移的临床及超声影像危险因素相关文献筛选流程图

第一作者[文献序号]

年份

国家

研究类型

总例数

颈外侧淋巴结转移例数

危险因素

NOS评分

Machens[15]

2004

德国

回顾性研究

141

30

7

Chandeze[16]

2016

法国

回顾性研究

97

31

①④⑥⑦⑧⑨

7

Oh[17]

2017

韩国

回顾性研究

73

26

①⑩??

8

Pena[18]

2017

美国

回顾性研究

66

22

①⑧⑨

8

Fan[19]

2018

中国

回顾性研究

65

26

①②③④⑤

8

Ito[20]

2018

日本

回顾性研究

164

55

①④

7

Opsahl[21]

2019

挪威

回顾性研究

58

12

①⑥⑧

8

逯翘楚[11]

2019

中国

回顾性研究

84

39

①②③④⑤

8

李树岭[12]

2020

中国

回顾性研究

94

53

①⑩??

7

Ye[22]

2020

中国

回顾性研究

74

36

⑧⑨

7

Park[23]

2020

韩国

回顾性研究

170

62

①⑥⑦⑧

7

Wu[24]

2020

中国

回顾性研究

125

49

①④⑤⑥⑦

8

刘鑫[13]

2020

中国

回顾性研究

85

40

④⑤⑩??

8

史亚飞[14]

2020

中国

回顾性研究

39

17

①②③④⑤⑥⑧

8

Spanheimer[25]

2021

美国

回顾性研究

89

45

8

表 1  15篇纳入文献的基线资料
图 2  各项临床和超声因素对甲状腺髓样癌患者颈外侧转移性淋巴结影响的meta分析森林图
图 3  转移性中央淋巴结、术前降钙素水平升高和术前癌胚抗原水平升高的敏感性分析结果
图 4  甲状腺髓样癌患者性别与颈外侧转移性淋巴结的meta分析漏斗图

研究指标

证据质量评价

证据等级

推荐强度

研究类型

偏倚风险

不一致性

间接性

精确性

发表偏倚

大效应量

混杂因素

剂量效应关系

男性

回顾性研究

无严重间接性

无严重不精确性

肿瘤直径不小于1?cm

回顾性研究

无严重间接性

无严重不精确性

*

中等

肿瘤多灶性

回顾性研究

无严重间接性

无严重不精确性

*

中等

肿瘤被膜侵犯

回顾性研究

无严重间接性

无严重不精确性

*

中等

肿瘤腺外侵犯

回顾性研究

无严重间接性

无严重不精确性

*

中等

转移性中央淋巴结

回顾性研究

异质性较高

无严重间接性

无严重不精确性

*

术前降钙素水平升高

回顾性研究

异质性较高

无严重间接性

无严重不精确性

较低

超声下边缘不光整

回顾性研究

无严重间接性

无严重不精确性

*

中等

超声下形态不规则

回顾性研究

无严重间接性

无严重不精确性

*

中等

表 2  证据质量评价及推荐强度
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12 李树岭, 候秀坤, 董居来, 等. 术前临床及原发肿瘤超声影像学特征对散发性甲状腺髓样癌颈外侧淋巴结转移预测分析[J]. 中国肿瘤临床, 2019, 46(20): 1031-1035
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17 OHH S, KWONH, SONGE, et al.Preoperative clinical and sonographic predictors for lateral cervical lymph node metastases in sporadic medullary thyroid carcinoma[J]Thyroid, 2018, 28( 3): 362-368.
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18 PENAI, CLAYMANG L, GRUBBSE G, et al.Management of the lateral neck compartment in patients with sporadic medullary thyroid cancer[J]Head Neck, 2018, 40( 1): 79-85.
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