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Article(id=1203033498182447554, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203033494428541350, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.05.0510, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1672675200000, receivedDateStr=2023-01-03, revisedDate=null, revisedDateStr=null, acceptedDate=1681056000000, acceptedDateStr=2023-04-10, onlineDate=1764755137247, onlineDateStr=2025-12-03, pubDate=1685203200000, pubDateStr=2023-05-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764755137247, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764755137247, creator=13701087609, updateTime=1764755137247, updator=13701087609, issue=Issue{id=1203033494428541350, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='5', pageStart='489', pageEnd='626', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764755136353, creator=13701087609, updateTime=1764756085669, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203037476202967229, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203033494428541350, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203037476202967230, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203033494428541350, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=510, endPage=515, ext={EN=ArticleExt(id=1203033499101000138, articleId=1203033498182447554, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Analysis of risk factors for cervical lymph node metastasis in papillary thyroid carcinoma: a single-center retrospective study, columnId=1203033497192591798, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Special Issue on Risk Factors Related to Thyroid Malignant Nodules, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the risk factors of lymph node metastasis in papillary thyroid carcinoma (PTC)patients who had thyroid nodule operation. Methods The clinical data of 4742 patients, who had surgical treatment for thyroid nodule from January 2016 to December 2020 in the First Medical Center of Chinese PLA General Hospital, were collected for retrospective study. The pathologic specimens of thyroid and lymph nodes of all the patients were retained during surgery. The patients were divided into metastasis group (n=2407) and non-metastasis group (n=2335) according to lymph node metastasis. The differences of age, sex, body mass index, thyroid stimulating hormone (TSH) value, tumor diameter, capsule invasion, and range of glandular lobe involvement were analyzed between the two groups. The independent risk factors for lymph node metastasis of papillary thyroid carcinoma were evaluated by logistic regression, and multivariate regression analysis were performed based on tumor diameter dividing into subgroups of small and non-small cancers. Results In 4742 patients with PTC, the incidence of cervical lymph node metastasis was 50.8% (2407 cases). Multivariate analysis showed that male, age <45 years, increased tumor diameter, external thyroid extension (ETE), and multiple tumors were independent risk factors for cervical lymph node metastasis(P<0.001). BMI (P=0.369), TSH level (P=0.246) and Hashimoto thyroiditis were not associated risk factors. Subgroup analysis showed that unilateral multiple foci was an independent risk factor for lymph node metastasis in non-microcarcinomas (OR=1.67, 95%CI 1.20-2.31, P=0.002), and ETE in microcarcinomas was also a risk factor for lymph node metastasis (OR=1.58, 95%CI 1.27-1.96, P<0.001). Conclusion Male, <45 years old, tumor size ≥9.5 mm, ETE and multiple tumors are independent risk factors for cervical lymph node metastasis in PTC patients.

, correspAuthors=Zhao-Hui Lv, authorNote=null, correspAuthorsNote=
* E-mail:
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目的 探讨甲状腺乳头状癌（PTC）发生颈部淋巴结转移的危险因素。方法 收集2016年1月－2020年12月于解放军总医院第一医学中心因甲状腺结节接受手术并行颈部淋巴结清扫、术后经病理证实为乳头状癌的4742例患者的临床资料进行回顾性分析，根据有无颈部淋巴结转移将患者分为转移组（n=2407）与无转移组（n=2335）。比较两组年龄、性别、体重指数（BMI）、促甲状腺激素（TSH）水平、肿瘤直径、被膜侵犯和腺叶累及范围等方面的差异，采用多因素logistic回归分析评估PTC发生颈部淋巴结转移的独立危险因素，并按照肿瘤直径分为微小癌与非微小癌亚组进行多因素回归分析。结果 4742例PTC患者中2407例发生颈部淋巴结转移，发生率为50.8%。多因素logistic回归分析结果显示，男性、年龄<45岁、肿瘤直径增大、甲状腺外浸润（ETE）、肿瘤多灶为PTC患者颈部淋巴结转移的独立危险因素（P<0.001），而BMI（P=0.369）、TSH水平（P=0.246）和合并桥本甲状腺炎不是危险因素。亚组分析显示，非微小癌中单侧多灶为发生颈部淋巴结转移的独立危险因素（OR=1.67，95%CI 1.20～2.31，P=0.002），而微小癌中ETE是发生颈部淋巴结转移的独立危险因素（OR=1.58，95%CI 1.27～1.96，P<0.001）。结论 男性、年龄<45岁、肿瘤大小≥9.5 mm、ETE和肿瘤多灶为PTC发生颈部淋巴结转移的独立危险因素。

, correspAuthors=吕朝晖, authorNote=null, correspAuthorsNote=
吕朝晖，E-mail：
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康韶洋，硕士研究生，主要从事内分泌代谢疾病方面的研究

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康韶洋，硕士研究生，主要从事内分泌代谢疾病方面的研究

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康韶洋，硕士研究生，主要从事内分泌代谢疾病方面的研究

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Risk factors of central lymph node metastasis in cN0 papillary thyroid carcinoma: a study of 529 patients[J]. Med Sci Monit, 2014, 20: 807-811., articleTitle=Risk factors of central lymph node metastasis in cN0 papillary thyroid carcinoma: a study of 529 patients, refAbstract=null), Reference(id=1203033509016335358, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, doi=null, pmid=null, pmcid=null, year=2014, volume=24, issue=1, pageStart=27, pageEnd=34, url=null, language=null, rfNumber=[12], rfOrder=14, authorNames=Ito Y, Miyauchi A, Kihara M, journalName=Thyroid, refType=null, unstructuredReference=Ito Y, Miyauchi A, Kihara M, et al. Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation[J]. 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Different clonal origin of bilateral papillary thyroid carcinoma, with a review of the literature[J].Endocr Pathol, 2012, 23(2): 101-107., articleTitle=Different clonal origin of bilateral papillary thyroid carcinoma, with a review of the literature, refAbstract=null), Reference(id=1203033509209272330, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, doi=null, pmid=null, pmcid=null, year=2021, volume=12, issue=null, pageStart=640565, pageEnd=null, url=null, language=null, rfNumber=[14], rfOrder=16, authorNames=Huang Y, Yin Y, Zhou W, journalName=Front Endocrinol (Lausanne), refType=null, unstructuredReference=Huang Y, Yin Y, Zhou W. Risk factors for central and lateral lymph node metastases in patients with papillary thyroid micro-carcinoma: retrospective analysis on 484 cases[J]. 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J Endocrinol Invest, 2018, 41(9): 1029-1035., articleTitle=Small papillary thyroid carcinoma with minimal extrathyroidal extension should be managed as ATA low-risk tumor, refAbstract=null), Reference(id=1203033509473513497, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, doi=null, pmid=null, pmcid=null, year=2021, volume=62, issue=12, pageStart=1702, pageEnd=1709, url=null, language=null, rfNumber=[17], rfOrder=19, authorNames=Seifert R, Schäfers MA, Heitplatz B, journalName=J Nucl Med, refType=null, unstructuredReference=Seifert R, Schäfers MA, Heitplatz B, et al. Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases[J]. J Nucl Med, 2021, 62(12): 1702-1709., articleTitle=Minimal extrathyroid extension in papillary micro carcinoma of the thyroid is an independent risk factor for relapse through lymph node and distant metastases, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1203033499977609702, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, xref=1, ext=[AuthorCompanyExt(id=1203033499985998311, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, companyId=1203033499977609702, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China), AuthorCompanyExt(id=1203033499998581224, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, companyId=1203033499977609702, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1解放军总医院第一医学中心内分泌科，北京 100853)]), AuthorCompany(id=1203033500103438829, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, xref=2, ext=[AuthorCompanyExt(id=1203033500111827438, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, companyId=1203033500103438829, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2School of Medicine, Nankai University, Tianjin 300071, China), AuthorCompanyExt(id=1203033500120216047, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, companyId=1203033500103438829, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2南开大学医学院，天津 300071)])], figs=[ArticleFig(id=1203033505249850176, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=EN, label=Fig. 1, caption=ROC curve for predicting lymph node metastasis based on the diameter of tumors, figureFileSmall=EMSlM3rnlkAGXrMp7qfXVQ==, figureFileBig=DwRYMNI4MgirzTjDToKa1A==, tableContent=null), ArticleFig(id=1203033505333736265, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=CN, label=图1, caption=肿瘤直径预测淋巴结转移的ROC曲线

ROC. 受试者工作特征；AUC. 曲线下面积

, figureFileSmall=EMSlM3rnlkAGXrMp7qfXVQ==, figureFileBig=DwRYMNI4MgirzTjDToKa1A==, tableContent=null), ArticleFig(id=1203033505530868570, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=EN, label=Tab. 1, caption=

Comparison of general characteristics between two groups of PTC patients

, figureFileSmall=null, figureFileBig=null, tableContent=
项目转移组(n=2407)无转移组(n=2335)χ2/tP
性别[例(%)]  104.68<0.001
 男848(35.2)509(21.8)
 女1559(64.8)1826(78.2)
年龄(岁，$\bar{x}±s$)41.6±11.246.8±10.5274.32<0.001
BMI(kg/m2, $\bar{x}±s$)24.9±2.925.0±3.40.810.369
TSH[mU/L,M(Q1,Q3)]2.0(1.3,2.9)2.0(1.3,3.0)1.350.246
HT[例(%)]  2.030.154
 有503(20.9)528(22.6)
 无1903(79.1)1807(77.4)
肿瘤最大径(mm, $\bar{x}±s$)14.5±9.69.7±6.3419.90<0.001
肿瘤特征[例(%)]  43.782<0.001
 单灶998(41.5)1191(51)
 单侧多灶368(15.3)285(12.2)
 双侧多灶1039(43.2)858(36.8)
ETE[例(%)]  53.31<0.001
 是644(27.5)418(18.4)
 否1700(72.5)1851(81.6)  
), ArticleFig(id=1203033505639920485, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=CN, label=表1, caption=

两组PTC患者一般特征比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目转移组(n=2407)无转移组(n=2335)χ2/tP
性别[例(%)]  104.68<0.001
 男848(35.2)509(21.8)
 女1559(64.8)1826(78.2)
年龄(岁，$\bar{x}±s$)41.6±11.246.8±10.5274.32<0.001
BMI(kg/m2, $\bar{x}±s$)24.9±2.925.0±3.40.810.369
TSH[mU/L,M(Q1,Q3)]2.0(1.3,2.9)2.0(1.3,3.0)1.350.246
HT[例(%)]  2.030.154
 有503(20.9)528(22.6)
 无1903(79.1)1807(77.4)
肿瘤最大径(mm, $\bar{x}±s$)14.5±9.69.7±6.3419.90<0.001
肿瘤特征[例(%)]  43.782<0.001
 单灶998(41.5)1191(51)
 单侧多灶368(15.3)285(12.2)
 双侧多灶1039(43.2)858(36.8)
ETE[例(%)]  53.31<0.001
 是644(27.5)418(18.4)
 否1700(72.5)1851(81.6)  
), ArticleFig(id=1203033505774138219, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=EN, label=Tab. 2, caption=

Comparison of clinical data of PTC patients with different tumor diameters

, figureFileSmall=null, figureFileBig=null, tableContent=
项目肿瘤直径P
<0.5 cm (n=838)0.5～1.0 cm (n=1866)1.0～1.5 cm (n=1068)≥1.5 cm (n=970)
性别[例(%)]    <0.001
 女631(75.3)1358(72.8)772(72.3)(1)624(64.3)(1)(2)
 男207(24.7)508(27.2)296(27.7)(1)346(35.7)(1)(2)
年龄(岁，$\bar{x}±s$)45.4±10.144.4±10.743.9±11.3(1)42.9±12.5(1)(2)<0.001
BMI(kg/m2, $\bar{x}±s$)24.5±3.324.9±3.624.8±3.725.5±4.0(1)(2)<0.001
TSH[mU/L,M(Q1,Q3)]1.9(1.3,3.0)2.0(1.3,3.0)2.0(1.3,2.9)2.0(1.3,3.1)0.951
ETE[例(%)]    <0.001
 有79(9.7)358(19.7)(1)283(27.1)(1)(2)342(36.2)(1)(2)(3)
 无732(90.3)1455(80.3)(1)761(72.9)(1)(2)603(63.8)(1)(2)(3)
淋巴结转移[例(%)]    <0.001
 无603(71.9)1035(55.4)(1)438(41.0)(1)(2)260(26.8)(1)(2)(3)
 有236(28.2)831(44.5)(1)630(59.0)(1)(2)710(73.2)(1)(2)(3) 
), ArticleFig(id=1203033505883190132, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=CN, label=表2, caption=

不同肿瘤直径的PTC患者临床资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目肿瘤直径P
<0.5 cm (n=838)0.5～1.0 cm (n=1866)1.0～1.5 cm (n=1068)≥1.5 cm (n=970)
性别[例(%)]    <0.001
 女631(75.3)1358(72.8)772(72.3)(1)624(64.3)(1)(2)
 男207(24.7)508(27.2)296(27.7)(1)346(35.7)(1)(2)
年龄(岁，$\bar{x}±s$)45.4±10.144.4±10.743.9±11.3(1)42.9±12.5(1)(2)<0.001
BMI(kg/m2, $\bar{x}±s$)24.5±3.324.9±3.624.8±3.725.5±4.0(1)(2)<0.001
TSH[mU/L,M(Q1,Q3)]1.9(1.3,3.0)2.0(1.3,3.0)2.0(1.3,2.9)2.0(1.3,3.1)0.951
ETE[例(%)]    <0.001
 有79(9.7)358(19.7)(1)283(27.1)(1)(2)342(36.2)(1)(2)(3)
 无732(90.3)1455(80.3)(1)761(72.9)(1)(2)603(63.8)(1)(2)(3)
淋巴结转移[例(%)]    <0.001
 无603(71.9)1035(55.4)(1)438(41.0)(1)(2)260(26.8)(1)(2)(3)
 有236(28.2)831(44.5)(1)630(59.0)(1)(2)710(73.2)(1)(2)(3) 
), ArticleFig(id=1203033505979659133, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=EN, label=Tab. 3, caption=

Multivariate logistic regression analysis of cervical lymph node metastasis in PTC patients

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因素βWald χ2OR(95%CI)P
男性0.55158.9791.734(1.507～1.996)<0.001
年龄<45岁0.879185.8832.408(2.122～2.732)<0.001
肿瘤直径
 <0.5 cm(参考值)
 0.5～1.0 cm0.44522.1771.591(1.312～1.931)<0.001
 1.0～1.5 cm1.11971.7993.062(2.363～3.966)<0.001
 ≥1.5 cm1.746170.8755.730(4.410～7.444)<0.001
ETE0.26311.3431.301(1.116～1.516)<0.001
累及情况
 单灶(参考值)
 单侧多灶0.46522.1771.591(1.312～1.931)<0.001
 双侧多灶0.30118.8101.351(1.179～1.548)<0.001
), ArticleFig(id=1203033506084516739, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=CN, label=表3, caption=

PTC患者颈部淋巴结转移的多因素logistic回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
因素βWald χ2OR(95%CI)P
男性0.55158.9791.734(1.507～1.996)<0.001
年龄<45岁0.879185.8832.408(2.122～2.732)<0.001
肿瘤直径
 <0.5 cm(参考值)
 0.5～1.0 cm0.44522.1771.591(1.312～1.931)<0.001
 1.0～1.5 cm1.11971.7993.062(2.363～3.966)<0.001
 ≥1.5 cm1.746170.8755.730(4.410～7.444)<0.001
ETE0.26311.3431.301(1.116～1.516)<0.001
累及情况
 单灶(参考值)
 单侧多灶0.46522.1771.591(1.312～1.931)<0.001
 双侧多灶0.30118.8101.351(1.179～1.548)<0.001
), ArticleFig(id=1203033506201957260, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=EN, label=Tab. 4, caption=

Subgroup analysis of the correlation between PTMC and non-PTMC lymph node metastasis

, figureFileSmall=null, figureFileBig=null, tableContent=
组别临床病理特征未调整调整后
OR(95%CI)POR(95%CI)P
PTMC单灶1(参考值) 1(参考值)
单侧多灶1.56(1.24～1.97)<0.0011.54(1.21～1.96)a<0.001
双侧多灶1.54(1.30～1.82)<0.0011.52(1.27～1.81)a<0.001
非PTMC单灶1(参考值) 1(参考值)
单侧多灶1.68(1.23～2.29)0.0011.67(1.20～2.31)a0.002
双侧多灶1.17(0.97～1.43)0.1081.20(0.97～1.47)a0.087
PTMC无ETE1(参考值) 1(参考值)
有ETE1.60(1.30～1.96)<0.0011.58(1.27～1.96)b<0.001
非PTMC无ETE1(参考值) 1(参考值)
有ETE1.21(0.99～1.48)0.0621.28(1.03～1.59)b0.023
), ArticleFig(id=1203033506340369303, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033498182447554, language=CN, label=表4, caption=

PTMC与非PTMC淋巴结转移相关性的亚组分析

, figureFileSmall=null, figureFileBig=null, tableContent=
组别临床病理特征未调整调整后
OR(95%CI)POR(95%CI)P
PTMC单灶1(参考值) 1(参考值)
单侧多灶1.56(1.24～1.97)<0.0011.54(1.21～1.96)a<0.001
双侧多灶1.54(1.30～1.82)<0.0011.52(1.27～1.81)a<0.001
非PTMC单灶1(参考值) 1(参考值)
单侧多灶1.68(1.23～2.29)0.0011.67(1.20～2.31)a0.002
双侧多灶1.17(0.97～1.43)0.1081.20(0.97～1.47)a0.087
PTMC无ETE1(参考值) 1(参考值)
有ETE1.60(1.30～1.96)<0.0011.58(1.27～1.96)b<0.001
非PTMC无ETE1(参考值) 1(参考值)
有ETE1.21(0.99～1.48)0.0621.28(1.03～1.59)b0.023
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甲状腺乳头状癌颈部淋巴结转移的危险因素分析——单中心回顾性研究
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康韶洋 1 , 胡晓东 1 , 聂智梅 1 , 许怀瑾 1, 2 , 李洁菲 1, 2 , 赵思童 1 , 柳洪宙 1 , 王玉寒 1 , 王安宁 1 , 吕朝晖 1, 2, *
解放军医学杂志 | 甲状腺恶性结节相关危险因素专题研究 2023,48(5): 510-515
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解放军医学杂志 | 甲状腺恶性结节相关危险因素专题研究 2023, 48(5): 510-515
甲状腺乳头状癌颈部淋巴结转移的危险因素分析——单中心回顾性研究
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康韶洋1, 胡晓东1, 聂智梅1, 许怀瑾1, 2, 李洁菲1, 2, 赵思童1, 柳洪宙1, 王玉寒1, 王安宁1, 吕朝晖1, 2, *
作者信息
  • 1解放军总医院第一医学中心内分泌科，北京 100853
  • 2南开大学医学院，天津 300071

    • 康韶洋，硕士研究生，主要从事内分泌代谢疾病方面的研究

通讯作者:

吕朝晖，E-mail：
Analysis of risk factors for cervical lymph node metastasis in papillary thyroid carcinoma: a single-center retrospective study
Shao-Yang Kang1, Xiao-Dong Hu1, Zhi-Mei Nie1, Huai-Jin Xu1, 2, Jie-Fei Li1, 2, Si-Tong Zhao1, Hong-Zhou Liu1, Yu-Han Wang1, An-Ning Wang1, Zhao-Hui Lv1, 2, *
Affiliations
  • 1Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
  • 2School of Medicine, Nankai University, Tianjin 300071, China
出版时间: 2023-05-28 doi: 10.11855/j.issn.0577-7402.2023.05.0510
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摘要
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目的 探讨甲状腺乳头状癌（PTC）发生颈部淋巴结转移的危险因素。方法 收集2016年1月－2020年12月于解放军总医院第一医学中心因甲状腺结节接受手术并行颈部淋巴结清扫、术后经病理证实为乳头状癌的4742例患者的临床资料进行回顾性分析，根据有无颈部淋巴结转移将患者分为转移组（n=2407）与无转移组（n=2335）。比较两组年龄、性别、体重指数（BMI）、促甲状腺激素（TSH）水平、肿瘤直径、被膜侵犯和腺叶累及范围等方面的差异，采用多因素logistic回归分析评估PTC发生颈部淋巴结转移的独立危险因素，并按照肿瘤直径分为微小癌与非微小癌亚组进行多因素回归分析。结果 4742例PTC患者中2407例发生颈部淋巴结转移，发生率为50.8%。多因素logistic回归分析结果显示，男性、年龄<45岁、肿瘤直径增大、甲状腺外浸润（ETE）、肿瘤多灶为PTC患者颈部淋巴结转移的独立危险因素（P<0.001），而BMI（P=0.369）、TSH水平（P=0.246）和合并桥本甲状腺炎不是危险因素。亚组分析显示，非微小癌中单侧多灶为发生颈部淋巴结转移的独立危险因素（OR=1.67，95%CI 1.20～2.31，P=0.002），而微小癌中ETE是发生颈部淋巴结转移的独立危险因素（OR=1.58，95%CI 1.27～1.96，P<0.001）。结论 男性、年龄<45岁、肿瘤大小≥9.5 mm、ETE和肿瘤多灶为PTC发生颈部淋巴结转移的独立危险因素。

甲状腺乳头状癌  /  淋巴结转移  /  危险因素

Objective To investigate the risk factors of lymph node metastasis in papillary thyroid carcinoma (PTC)patients who had thyroid nodule operation. Methods The clinical data of 4742 patients, who had surgical treatment for thyroid nodule from January 2016 to December 2020 in the First Medical Center of Chinese PLA General Hospital, were collected for retrospective study. The pathologic specimens of thyroid and lymph nodes of all the patients were retained during surgery. The patients were divided into metastasis group (n=2407) and non-metastasis group (n=2335) according to lymph node metastasis. The differences of age, sex, body mass index, thyroid stimulating hormone (TSH) value, tumor diameter, capsule invasion, and range of glandular lobe involvement were analyzed between the two groups. The independent risk factors for lymph node metastasis of papillary thyroid carcinoma were evaluated by logistic regression, and multivariate regression analysis were performed based on tumor diameter dividing into subgroups of small and non-small cancers. Results In 4742 patients with PTC, the incidence of cervical lymph node metastasis was 50.8% (2407 cases). Multivariate analysis showed that male, age <45 years, increased tumor diameter, external thyroid extension (ETE), and multiple tumors were independent risk factors for cervical lymph node metastasis(P<0.001). BMI (P=0.369), TSH level (P=0.246) and Hashimoto thyroiditis were not associated risk factors. Subgroup analysis showed that unilateral multiple foci was an independent risk factor for lymph node metastasis in non-microcarcinomas (OR=1.67, 95%CI 1.20-2.31, P=0.002), and ETE in microcarcinomas was also a risk factor for lymph node metastasis (OR=1.58, 95%CI 1.27-1.96, P<0.001). Conclusion Male, <45 years old, tumor size ≥9.5 mm, ETE and multiple tumors are independent risk factors for cervical lymph node metastasis in PTC patients.

papillary thyroid carcinoma  /  lymph node metastasis  /  risk factor
康韶洋, 胡晓东, 聂智梅, 许怀瑾, 李洁菲, 赵思童, 柳洪宙, 王玉寒, 王安宁, 吕朝晖. 甲状腺乳头状癌颈部淋巴结转移的危险因素分析——单中心回顾性研究. 解放军医学杂志, 2023 , 48 (5) : 510 -515 . DOI: 10.11855/j.issn.0577-7402.2023.05.0510
Shao-Yang Kang, Xiao-Dong Hu, Zhi-Mei Nie, Huai-Jin Xu, Jie-Fei Li, Si-Tong Zhao, Hong-Zhou Liu, Yu-Han Wang, An-Ning Wang, Zhao-Hui Lv. Analysis of risk factors for cervical lymph node metastasis in papillary thyroid carcinoma: a single-center retrospective study[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (5) : 510 -515 . DOI: 10.11855/j.issn.0577-7402.2023.05.0510
正文
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甲状腺乳头状癌(papillary thyroid carcinoma，PTC)是甲状腺恶性肿瘤中最常见的病理类型[1]，如果发生颈部淋巴结转移意味着其侵袭性和复发风险增加[2]，而研究显示PTC颈部淋巴结转移率可达40%～90%[3-4]。颈部中央区解剖结构深在，常被周围组织遮挡，超声探查对于淋巴结转移的敏感性仅为30%左右[5]，预防性颈部淋巴结清扫的收益仍存在争议。因此，对于可能存在淋巴结转移的PTC患者早期进行有效识别尤为重要。本研究回顾性分析行PTC手术及颈部淋巴结清扫患者的临床资料，探讨PTC发生颈部淋巴结转移的危险因素，旨在为临床早期有效识别可能存在的淋巴结转移提供参考。
1 资料与方法
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1.1 研究对象
收集2016年1月－2020年12月就诊于解放军总医院第一医学中心行甲状腺切除术的6811例患者的临床资料，最终纳入4742例进行回顾性分析。所有患者均行中央区和侧颈部淋巴结清扫，且病理均证实为PTC。纳入标准：(1)行甲状腺切除术及淋巴结清扫术并对切除组织进行病理分析的患者；(2)术后病理证实为PTC；(3)手术时年龄≥18岁。排除标准：(1)既往曾行甲状腺切除术或射频消融术；(2)既往有儿童期颈部放射线照射史；(3)相关化验指标、病理结果缺失。本研究已获解放军总医院第一医学中心伦理委员会审批(伦审第S2022-0115-01号)。
1.2 指标收集、定义及分组
收集手术患者住院记录中的性别、年龄、身高、体重等人口学资料；记录术后病理报告中的相关特征(肿瘤数目、大小、所在腺叶位置、是否合并桥本甲状腺炎和腺外浸润情况)及肿瘤直径。桥本甲状腺炎(Hashimoto thyroiditis，HT)是指镜下可见的甲状腺实质弥漫性淋巴细胞或浆细胞浸润，伴有淋巴滤泡生发中心形成和结缔组织增生；甲状腺外浸润(extra thyroidal extension，ETE)定义为甲状腺癌细胞侵犯邻近组织，如周围脂肪组织、带状肌、气管、食管、喉返神经、椎前筋膜、颈总动脉等；肿瘤直径为孤立病灶中的最大直径，或者多病灶病例中最大肿瘤的最大直径；微小乳头状癌(papillary thyroid microcarcinoma，PTMC)是指最大直径≤1 cm的乳头状癌。所有患者根据是否存在淋巴结转移分为转移组(n=2407)与无转移组(n=2335)；根据肿瘤的个数和累及腺叶的情况分为单灶组(n=2189)、单侧多灶组(n=653)和双侧多灶组(n=1897)；以0.5 cm为间隔，按肿瘤最大直径分为4组，包括最大直径<0.5 cm组(n=838)，最大直径0.5～1.0 cm组(n=1866)，最大直径1.0～1.5 cm组(n=1068)，最大直径≥1.5 cm组(n=970)。此外，按照肿瘤直径大小将患者分为PTMC亚组(n=2704)和非PTMC亚组(n=2038)。所有患者均在术前常规行甲状腺激素水平检测。其中血清促甲状腺激素(thyroid stimulating hormone，TSH)水平检测使用德国西门子公司TSH免疫分析试剂盒完成。
1.3 指标分析
比较转移组与无转移组患者的临床资料，筛选人口学资料及病理报告中的指标进行单因素分析，将单因素分析中P<0.05的变量纳入多因素logistic分析，确定PTC患者颈部淋巴结转移的独立危险因素。为进一步探究肿瘤直径与淋巴结转移的关系，依照肿瘤直径分组，比较不同直径组临床病例特征的差异，并以肿瘤直径作为检验变量，以淋巴结转移率为状态变量，绘制受试者工作特征(receiver operator characteristic，ROC)曲线。在寻找到最佳截断值后，进一步对PTMC与非PTMC进行亚组分析。
1.4 统计学处理
采用SPSS软件26.0(SPSS Inc.，Chicago，IL，USA)和R软件(http://www.R-project.org，The R Foundation)进行统计分析。采用Q-Q图和直方图判断计量资料是否符合正态分布，正态分布资料以$\bar{x}±s$表示，两组间比较采用t检验，多组间比较采用单因素方差分析；非正态分布资料以M(Q1，Q3)表示，两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis检验；计数资料以例(%)表示，组间比较采用χ2检验或Fisher精确检验，两两比较采用Bonferroni校正法；将单因素分析中P<0.05的变量纳入多因素logistic回归分析，探讨PTC发生颈部淋巴结转移的影响因素，结果以优势比(OR)及95%可信区间(CI)表示。所有检验均为双侧检验，P<0.05为差异有统计学意义。
2 结果
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2.1 PTC患者一般资料
所有PTC患者中，发生颈部淋巴结转移者2407例(50.8%)，未发生转移者2335例(49.3%)。与无转移组比较，转移组男性更多见(35.2% vs. 21.8%)、年龄更小[(41.6±11.2)岁vs. (46.8±10.5)岁，P<0.001]，从肿瘤特征角度看，转移组的多灶肿瘤(58.5% vs. 49%)、累及双侧腺叶(76.6% vs. 72.5%)和ETE(27.5% vs. 18.4%)者占比更高，且肿瘤直径更大[(14.5±9.6) mm vs.(9.7±6.3) mm]，组间比较差异均有统计学意义(P<0.001)，但两组间BM I、血清TSH水平和桥本甲状腺炎发生率差异无统计学意义(表1)。
2.2 不同直径PTC亚组患者的临床资料比较
与肿瘤直径<0.5 cm比较，肿瘤直径≥1.0 cm的患者年龄更小、男性占比更高，肿瘤直径≥1.5 cm组患者BM I更高；随着肿瘤直径增大，ETE及淋巴结转移者逐渐增多(P<0.001)(表2)。
2.3 肿瘤最大径预测颈部淋巴结转移的ROC曲线
ROC曲线分析显示，肿瘤直径预测淋巴结转移的曲线下面积(AUC)为0.679(95%C I 0.664～0.694)，根据约登指数找到最佳截断值为9.5 mm(图1)。
2.4 颈部淋巴结转移危险因素的多因素logistic回归分析
多因素logistic回归分析显示，男性、年龄<45岁、肿瘤直径增大、ETE和多灶肿瘤为PTC患者颈部淋巴结转移的独立危险因素(P<0.001，表3)。
2.5 PTM C与非PTM C淋巴结转移的相关性亚组分析
在PTM C组与非PTM C组之间，以淋巴结转移作为因变量进行logistic亚组回归分析，模型纳入年龄、性别、肿瘤直径、有无ETE、肿瘤多灶性作为变量，结果显示，与单灶肿瘤相比，单侧多灶和双侧多灶均可增加PTM C患者淋巴结转移的发生风险。然而，在非PTMC患者中仅单侧多灶与淋巴结转移发生风险相关(OR=1.67，95%CI 1.20～2.31)。ETE的发生与淋巴结转移密切相关，且在PTM C中更为显著(OR=1.58，95%CI 1.27～1.96，P<0.001，表4)。
3 讨论
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颈部淋巴结转移在PTC患者中较为常见，且与不良预后密切相关[6]。本研究PTC的颈部淋巴结转移发生率为50.8%，与先前文献报道接近[7]。因PTC复发行二次颈部淋巴结清扫可增加喉返神经损伤及甲状旁腺功能减退的可能性[8]。因此，探讨PTC患者颈部淋巴结转移的特征及危险因素，可为更早地判定高风险人群以及制定个体化的治疗方案提供参考。
PTC在女性中的发病率远高于男性，本研究患者中女性与男性的比例约为3:1，但男性发生淋巴结转移的比例为62.4%，明显高于女性(46.0%)，多因素分析结果证实男性为PTC患者颈部淋巴结转移的独立危险因素。此外，本研究发现，年龄也是颈部淋巴结转移的独立危险因素，年龄<45岁者发生颈部淋巴结转移的风险为年龄≥45岁者的2.2倍，与周瑾[9]等的研究结果一致。
肿瘤直径在肿瘤分期诊断中具有重要价值，直径较大预示着可能具有更高的侵袭性。然而，关于肿瘤直径与淋巴结转移相关的临界值，不同研究的结论并不一致。王文栋等[10]认为PTC直径>0.5 cm是发生颈部淋巴结转移的独立预测因素，Liang等[11]则认为肿瘤直径>2.0 cm为颈部淋巴结转移的独立危险因素。本研究按肿瘤直径将患者分为<0.5 cm组、0.5～1.0 cm组、1.0～1.5 cm组和≥1.5 cm组，结果显示，随着肿瘤直径增加，淋巴结转移率逐渐增高，不同直径组间淋巴结转移发生率差异均有统计学意义。将肿瘤直径单独作为评估颈部淋巴结转移的指标，绘制ROC曲线，结果显示其评估淋巴结转移风险的最佳临界值为9.5 mm。该临界值与1 cm接近，从侧面论证了Ito等[12]报道的PTMC具有惰性生长特性及大多数情况下较少出现肿瘤相关疾病进展的结论，提示监测肿瘤直径变化对淋巴结转移具有较高的预测价值。
本研究还对肿瘤的多灶性及腺叶累及情况进行分析，结果发现，在PTMC患者中，与单灶PTMC相比，无论是否累及双侧腺叶，多灶PTMC发生淋巴结转移风险均增高；然而在较大直径的非PTMC患者中，与单灶患者比较，双侧多灶并非淋巴结转移的独立危险因素(P=0.087)，提示在非PTMC患者中，单侧多灶而非双侧多灶为淋巴结转移的危险因素。其原因可能与同侧病灶的肿瘤更大概率具有相同的克隆来源相关，代表了一种腺体内肿瘤细胞播散，而对侧病灶则往往来源于不同的生发中心，因此，相比较于单发病灶，双侧多灶没有表现出更高的侵袭特性[13]。有研究发现，在PTMC中，双侧病灶具有更高的淋巴结转移风险[14]，然而，在本研究的PTMC患者中，双侧多灶并未表现出更高的淋巴结转移风险，PTMC与较大直径的PTC拥有不同淋巴结侵袭特性的机制还有待进一步研究。总之，在临床工作中，建议对单侧多灶的非PTMC患者行预防性颈部淋巴结清扫，以去除可能存在的隐匿性淋巴结转移。
ETE在乳头状癌中的意义仍存在争议。有研究报道ETE与分化型甲状腺癌中较高的颈部淋巴结转移发生率、远处转移或病死率均无关[15]，Castagna等[16]发现，癌组织的微小浸润(指仅侵犯周围脂肪组织和带状肌的浸润灶)仅在直径>1.5 cm的PTC中才是颈部淋巴结转移的危险因素。然而，本研究表明，存在ETE的PTMC患者具有更高的颈部淋巴结转移风险(OR=1.58，95%CI 1.27～1.96，P<0.001)，与Seifert等[17]的研究结果一致，提示存在ETE的微小癌在生物学上更具有侵袭性，在术前选择观察策略及术后选择放射治疗时需格外关注甲状腺腺外肿瘤的浸润情况。
综上所述，本研究发现，肿瘤直径与PTC淋巴结转移的相关性最高(OR=5.730，95%CI 4.410～7.444)，肿瘤直径每增加5 mm，PTC发生淋巴结转移的风险即明显上升。对于男性、年龄<45岁、肿瘤直径≥9.5 mm的单侧多发病灶患者行甲状腺癌手术治疗时，建议进行更加细致的颈部淋巴结探查清扫，以避免临床工作中因隐匿淋巴结转移的存在而造成二次手术。此外，PTMC中出现ETE也是淋巴结转移的强相关因素，尽管美国癌症协会的最新分期指南降低了未侵及带状肌以外组织ETE患者的肿瘤分期，但在临床实践中更应警惕微小癌中ETE阳性患者淋巴结转移高风险的存在。本研究仍存在一定的局限性，如未对中央区淋巴结转移个数进行调查，为回顾性研究等，因此，本研究结果是否具有普遍性仍有待更多前瞻性、多中心对照研究进一步验证。
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2023年第48卷第5期
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doi: 10.11855/j.issn.0577-7402.2023.05.0510
  • 接收时间：2023-01-03
  • 首发时间：2025-12-03
  • 出版时间：2023-05-28
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  • 收稿日期：2023-01-03
  • 录用日期：2023-04-10
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    1解放军总医院第一医学中心内分泌科，北京 100853
    2南开大学医学院，天津 300071

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