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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (6): 730-740    DOI: 10.3724/zdxbyxb-2021-0210
    
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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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 wordsMedullary thyroid carcinoma      Lateral cervical lymph node metastasis      Meta-analysis      Clinical characteristics      Ultrasonic tomography      Risk factor     
Received: 26 July 2021      Published: 22 March 2022
CLC:  R736.1  
Corresponding Authors: LUO Dingcun     E-mail: ldc65@163.com
Cite this article:

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.

URL:

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


甲状腺髓样癌患者颈外侧淋巴结转移危险因素分析

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 
Figure 1 Flowchart of screening process of literature related to risk factors of lateral cervical lymph node metastasis in medullary thyroid carcinoma

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

Table 1 Basic characteristics of 15 involved studies
Figure 2 Forest plots for the meta analysis of the effects of clinical and ultrasound factors on lateral cervical lymph node metastasis in patients with medullary thyroid carcinoma
Figure 3 Sensitivity analysis results of central lymph node metastasis, elevated preoperative calcitonin and elevated carcinoembryonic antigen
Figure 4 The funnel plots for the meta-analysis of the association between gender and lateral cervical lymph node metastasis in medullary thyroid carcinoma

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

Table 2 Rating quality of evidence and strength of recommendations
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