甲状腺髓样癌患者颈外侧淋巴结转移危险因素分析

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

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。

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≥1 cm(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.