Risk factors for lateral cervical lymph node metastasis in medullary thyroid carcinoma

doi:10.3724/zdxbyxb-2021-0210

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 Dingcun^2,*(

)

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 words： Medullary 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

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	WU Fan
	ZHOU Tianhan
	LU Kaining
	PAN Ting
	NI Yeqin
	ZHAO Lingqian
	JIANG Kecheng
	ZHANG Yu
	LUO Dingcun

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.

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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

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

Table 2 Rating quality of evidence and strength of recommendations


[1]	MOHAMMADI M, HEDAYATI M. A brief review on the molecular basis of medullary thyroid carcinoma[J]. Cell J, 18(4): 485-492

[2]	SIEGELR L, MILLERK D, JEMALA. Cancer statistics, 2018[J]CA-Cancer J Clin, 2018, 68( 1): 7-30. doi: 10.3322/caac.21442

[3]	SCOLLOC, BAUDINE, TRAVAGLIJ P, et al.Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer[J]J Clin Endocrinol Metab, 2003, 88( 5): 2070-2075. doi: 10.1210/jc.2002-021713

[4]	WELLS JR.S A, ASAS L, DRALLEH, et al.Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma[J]Thyroid, 2015, 25( 6): 567-610. doi: 10.1089/thy.2014.0335

[5]	MITCHELLA L, GANDHIA, SCOTT-COOMBESD, et al.Management of thyroid cancer: united kingdom national multidisciplinary guidelines[J]J Laryngol Otol, 2016, 130( S2): S150-S160. doi: 10.1017/S0022215116000578

[6]	MAIA A L, SIQUEIRA D R, KULCSAR M A V, et al. Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism[J]. Arq Bras Endocrinol Metabol, 2014, 58(7): 667-700

[7]	KONSTANTINIDISA, STANGM, ROMANS A, et al.Surgical management of medullary thyroid carcinoma[J]Updates Surg, 2017, 69( 2): 151-160. doi: 10.1007/s13304-017-0443-y

[8]	LUOD, WANX, LIUJ, et al.Optimally estimating the sample mean from the sample size, median, mid-range, and/or mid-quartile range[J]Stat Methods Med Res, 2018, 27( 6): 1785-1805. doi: 10.1177/0962280216669183

[9]	SHIJ, LUOD, WENGH, et al.Optimally estimating the sample standard deviation from the five‐number summary[J]Res Syn Meth, 2020, 11( 5): jrsm.1429. doi: 10.1002/jrsm.1429

[10]	WANX, WANGW, LIUJ, et al.Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range[J]BMC Med Res Methodol, 2014, 14( 1): 135. doi: 10.1186/1471-2288-14-135

[11]	逯翘楚, 付利军, 李利文, 等. 甲状腺髓样癌临床特征及颈部淋巴结转移风险因素讨论[J]. 中华内分泌外科杂志, 2019, 13(2): 139-143 LU Qiaochu, FU Lijun, LI Liwen, et al. Clinical analysis of medullary thyroid carcinoma and risk factors of cervical lymph node metastasis[J]. Chinese Journal of Endocrine Surgery, 2019, 13(2): 139-143. (in Chinese)

[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 LI Shuling, HOU Xiukun, DONG Julai, et al. Prediction of lateral cervical lymph node metastasis in patients with sporadic medullary thyroid carcinoma using preoperative clinical and ultrasonographic features[J].Chinese Journal of Clinical Oncology, 2019, 46(20): 1031-1035. (in Chinese)

[13]	刘鑫, 朱乔丹, 邵智颖, 等. 颈外侧部淋巴结转移与甲状腺髓样癌超声特征的相关因素分析[J]. 影像研究与医学应用, 2020, 4(17): 64-66 LIU Xin, ZHU Qiaodan, SHAO Zhiying, et al. Analysis of correlation factors between lateral cervical lymph node metastasis and ultrasound characteristics of medullary thyroid carcinoma[J]. Journal of Imaging Research and Medical Application, 2020, 4(17): 64-66. (in Chinese)

[14]	史亚飞, 张颖超, 樊友本, 等. 甲状腺髓样癌手术切除范围的研究[J]. 中华普通外科杂志, 2020, 35(11): 856-861 SHI Yafei, ZHANG Yingchao, FAN Youben, et al. A study on resection extent for medullary thyroid carcinoma[J]. Chinese Journal of General Surgery, 2020, 35(11): 856-861. (in Chinese)

[15]	MACHENSA, HOLZHAUSENH J, DRALLEH. Skip metastases in thyroid cancer leaping the central lymph node compartment[J]Arch Surg, 2004, 139( 1): 43-45. doi: 10.1001/archsurg.139.1.43

[16]	CHANDEZEM M, NOULLETS, FARONM, et al.Can we predict the lateral compartment lymph node involvement in ret-negative patients with medullary thyroid carcinoma?[J]Ann Surg Oncol, 2016, 23( 11): 3653-3659. doi: 10.1245/s10434-016-5292-2

[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. doi: 10.1089/thy.2017.0514

[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. doi: 10.1002/hed.24969

[19]	FANW, XIAOC, WUF. Analysis of risk factors for cervical lymph node metastases in patients with sporadic medullary thyroid carcinoma[J]J Int Med Res, 2018, 46( 5): 1982-1989. doi: 10.1177/0300060518762684

[20]	ITOY, MIYAUCHIA, KIHARAM, et al.Static prognostic factors and appropriate surgical designs for patients with medullary thyroid carcinoma: the second report from a single-institution study in Japan[J]World J Surg, 2018, 42( 12): 3954-3966. doi: 10.1007/s00268-018-4738-z

[21]	OPSAHLE M, AKSLENL A, SCHLICHTINGE, et al.The role of calcitonin in predicting the extent of surgery in medullary thyroid carcinoma: a nationwide population-based study in norway[J]Eur Thyroid J, 2019, 8( 3): 159-166. doi: 10.1159/000499018

[22]	YEL, ZHOUX, LUJ, et al.Combining serum calcitonin, carcinoembryonic antigen, and neuron‐specific enolase to predict lateral lymph node metastasis in medullary thyroid carcinoma[J/OL]J Clin Lab Anal, 2020, 34( 7): e23278. doi: 10.1002/jcla.23278

[23]	PARKH, PARKJ, CHOIM S, et al.Preoperative serum calcitonin and its correlation with extent of lymph node metastasis in medullary thyroid carcinoma[J]Cancers, 2020, 12( 10): 2894. doi: 10.3390/cancers12102894

[24]	WUX, LIB, ZHENGC, et al.Risk factors for lateral lymph node metastases in patients with sporadic medullary thyroid carcinoma[J]Technol Cancer Res Treat, 2020, 153303382096208. doi: 10.1177/1533033820962089

[25]	SPANHEIMERP M, GANLYI, CHOUJ F, et al.Prophylactic lateral neck dissection for medullary thyroid carcinoma is not associated with improved survival[J]Ann Surg Oncol, 2021, 28( 11): 6572-6579. doi: 10.1245/s10434-021-09683-8

[26]	HAUGENB R, ALEXANDERE K, BIBLEK C, et al.2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer[J]Thyroid, 2016, 26( 1): 1-133. doi: 10.1089/thy.2015.0020

[27]	金玲爽. 45例甲状腺髓样癌患者颈部淋巴结转移规律及术式探讨[J]. 临床耳鼻咽喉头颈外科杂志，2018, 32（19）: 1504-1506 JIN Lingshuang. The patterns of cervical lymph node metastasis and the surgical treatment for untreated medullary thyroid carcinoma[J]. Journal of Clinical Otorhinolaryngology Head and Neck Surgery, 2018, 32(19): 1504-1506. (in Chinese)

[28]	XUES, HANZ, LUQ, et al.Clinical and ultrasonic risk factors for lateral lymph node metastasis in papillary thyroid microcarcinoma: a systematic review and meta-analysis[J]Front Oncol, 2020, 436. doi: 10.3389/fonc.2020.00436

[29]	WEI X, WANG M, WANG X, et al. Prediction of cervical lymph node metastases in papillary thyroid microcarcinoma by sonographic features of the primary site [J]. Cancer Biol Med, 2019, 16(3): 587-594

[30]	SCOPSIL, SAMPIETROG, BORACCHIP, et al.Multivariate analysis of prognostic factors in sporadic medullary carcinoma of the thyroid: a retrospective study of 109 consecutive patients[J]Cancer, 1996, 78( 10): 2173-2183. doi: 10.1002/(SICI)1097-0142(19961115)78:10<2173::AID-CNCR20>3.0.CO;2-V

[31]	SAADM F, ORDONEZN G, RASHIDR K, et al.Medullary carcinoma of the thyroid[J]Medicine, 1984, 63( 6): 319-342. doi: 10.1097/00005792-198411000-00001

[32]	HADDADR I, NASRC, BISCHOFFL, et al.NCCN guidelines insights: thyroid carcinoma, version 2.2018[J]J Natl Compr Canc Netw, 2018, 16( 12): 1429-1440. doi: 10.6004/jnccn.2018.0089

[33]	KIMJ H, PYOJ S, CHOW J. Clinicopathological significance and prognosis of medullary thyroid microcarcinoma: a meta-analysis[J]World J Surg, 2017, 41( 10): 2551-2558. doi: 10.1007/s00268-017-4031-6

[34]	MACHENSA, DRALLEH. Biomarker-based risk stratification for previously untreated medullary thyroid cancer[J]J Clin Endocrinol Metab, 2010, 95( 6): 2655-2663. doi: 10.1210/jc.2009-2368

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