Sonographic features of papillary thyroid microcarcinoma predicting high-volume central neck lymph node metastasis

Objective

To study the correlations between the sonographic features of papillary thyroid microcarcinoma (PTMC) and the presence of high-volume lymph node metastasis.

cN0甲状腺乳头状癌淋巴结转移的危险因素分析

背景与目的：术后病理证实的淋巴结转移在临床淋巴结转移阴性(clinical lymph node negative, cN0)的甲状腺乳头状癌中并不罕见,该研究旨在探讨cN0甲状腺乳头状癌淋巴结转移的危险因素,特别是大量淋巴结转移(>5个)、单侧单发癌灶对侧中央区转移的危险因素。方法：收集北京协和医院2008年—2014年由同一手术团队实施手术的cN0甲状腺乳头状癌患者350例(男性85例,女性265例;其中单侧单发癌灶212例)。分析患者的临床病理学特征,通过单因素、多因素分析寻找淋巴结转移的危险因素。结果：350例患者中共出现淋巴结转移138例(39.4%),大量淋巴结转移20例(5.7%),在单侧单发癌灶且行双侧腺体切除联合双侧中央区淋巴结清扫的169例患者中,24例出现对侧中央区淋巴结转移(14.2%)。淋巴结转移的危险因素的单因素分析中,肿物大小小于等于1 cm和大于1 cm(33.6%vs 58.5%,P<0.01)、超声肿物有钙化和无钙化者(31.7%vs 43.7%, P=0.03)淋巴结转移差异有统计学意义;多因素分析中,非微小癌是淋巴结转移的独立危险因素(OR=2.792, P<0.001)。出现大量淋巴结转移危险因素的单因素分析中,女性和男性(3.8%vs 11.8%,P=0.012)、年龄小于40岁和大于等于40岁(10.7%vs 3.4%,P=0.006)、肿物大小小于等于1 cm和大于1 cm(3.4%vs 13.4%,P=0.002)、超声肿物低回声和非低回声(13.9%vs 4.8%,P=0.026)者在有无大量淋巴结转移上差异有统计学意义;多因素分析中,男性(OR=5.152,P=0.002)、非微小癌(OR=5.712,P=0.001)、年龄小于40岁(OR=3.959,P=0.006)是大量淋巴结转移的独立危险因素。男性(OR=3.105,P=0.022)、非微小癌(OR=3.863,P=0.008)是单侧单发癌灶对侧中央区淋巴结转移的独立危险因素,其对侧中央区淋巴结转移率分别为26.5%、26.1%。结论：cN0甲状腺乳头状癌出现淋巴结转移的比例较高;对于其中非微小甲状腺乳头状癌应常规行中央区淋巴结清扫,对于男性、年龄小于40岁的微小甲状腺乳头状癌也应考虑采取积极的手术方式。     

Construction and validation of nomograms to reduce completion thyroidectomy by predicting lymph node metastasis in low-risk papillary thyroid carcinoma

ContextMore than 5 central lymph nodes metastases (CLNM) or lateral lymph node metastasis (LLNM) indicates a higher risk of recurrence in low-risk papillary thyroid carcinoma (PTC) and may lead to completion thyroidectomy (CTx) in patients initially undergoing lobectomy.ObjectiveTo screen potentially high-risk patients from low-risk patients by using preoperative and intraoperative clinicopathological features to predict lymph node status.MethodsA retrospective analysis of 8301 PTC patients in Wuhan Union Hospital database (2009–2021) was performed according to the 2015 American Thyroid Association (ATA) and 2021 National Comprehensive Cancer Network (NCCN) guidelines, respectively. Logistic regression and best subsets regression were used to identify risk factors. Nomograms were established and externally validated using the Differentiated Thyroid Cancer in China cohort.ResultsMore than 5 CLNM or LLNM was detected in 1648 (19.9%) patients. Two predictive models containing age, gender, maximum tumor size, free thyroxine (FT4) and palpable node (all p < 0.05) were established. The nomogram based on NCCN criteria showed better discriminative power and consistency with a specificity of 0.706 and a sensitivity of 0.725, and external validation indicated that 76% of potentially high-risk patients could achieve preoperative conversion of surgical strategy.ConclusionsModels based on large cohorts with good predictive performance were constructed and validated. Preoperative low-risk (T1-2N0M0) patients with age younger than 40 years, male gender, large tumor size, low FT4 and palpable nodes may be at high risk of LLNM or more than 5 CLNM, and they should receive more aggressive initial therapy to reduce CTx.     

术前血清甲状腺球蛋白检测对甲状腺乳头状癌颈部淋巴结转移的预测价值分析

目的 探讨术前血清甲状腺球蛋白(Preoperative serum thyroglobulin,PS-Tg)与甲状腺乳头状癌(Papillary carcinoma of thyroid,PTC)淋巴结转移(Lymph node metastasis,LNM)的关系。方法 本研究纳入2021年10月—2022年10月行甲状腺切除术并经术后病理证实的PTC患者,并收集其临床及病理资料283份。单因素、多因素logistic回归分析PS-Tg与PTC LNM的关系,绘制列线图将两者关系量化,通过ROC曲线确定最佳截断值。结果 PTC合并LNM组PS-Tg水平高于单纯PTC组(P＜0.05),单因素与多因素logistic回归分析发现PS-Tg水平升高可能是PTC发生LNM的独立危险因素,且PS-Tg水平升高可解释约15%的PTC LNM风险。结论 PS-Tg水平升高可能是PTC患者颈部LNM的危险因素,对术前LNM诊断有一定的预测价值。     

甲状腺乳头状癌中央区淋巴结转移评分系统的建立及验证

目的 构建甲状腺乳头状癌（papillary thyroid carcinoma,PTC）中央区淋巴结转移（central lymph node metastasis,CLNM）的评分系统,并评价和验证其工作效能。方法 选取2015年6月—2018年6月在甘肃省肿瘤医院行手术治疗的237例PTC患者为建模组,2018年7月—2019年6月符合相同条件的100例PTC患者为验证组。采用Logistic回归模型筛选CLNM的独立危险因素并构建评分系统,ROC曲线评估预测价值。结果 男性、肿瘤直径＞1 cm、多发癌灶、肿瘤位于腺体下极和包膜侵犯是预测PTC CLNM的独立危险因素（P<0.05）。建模组ROC曲线下面积为0.857,最佳诊断截点值为6分,诊断敏感性、特异性、阳性预测值和阴性预测值分别为81.9%、85.3%、78.6%和87.8%,验证组ROC曲线下面积为0.823。 结论 基于独立危险因素的评分系统对PTC患者CLNM有较好的预测价值,评分≥6分的患者CLNM发生风险较高,应积极行预防性中央区淋巴结清扫。     

甲状腺乳头状癌临床病理特征及中央区淋巴结清扫的临床分析

目的探讨甲状腺乳头状癌的临床病理特征和中央区淋巴结清扫的临床意义。方法选择2010年3月至2013年2月收治的80例甲状腺乳头状癌患者的临床病理特征,统计分析中央区淋巴结的转移情况并进行术后随访。结果中央区淋巴结转移个数与原发灶T分期有关(P<0.05),80例患者的临床病理特征和肿瘤大小差异较大。随访的结果显示,2例患者死亡,4例患者再次手术后存活。结论术前应明确诊断淋巴结转移,及时清扫淋巴结。临床诊断应结合多种病理特征做出正确的病理诊断,进而指导临床治疗和预后判断。     

hPF4 mRNA表达与甲状腺乳头癌血管生成、转移的关系

 目的 研究甲状腺乳头癌组织中人血小板第IV因子（human platelet factor 4 hPF4）表达与微血管密度（MVD）与淋巴结转移之间的关系。方法 对40例甲状腺乳头癌手术标本和10例癌旁正常组织标本采用逆转录多聚酶链反应（RT-PCR）检测hPF4 mRNA表达，并采用CD105单克隆抗体标记免疫组化法检测微血管密度。结果 正常组织hPF4 mRNA阳性率为80 %；癌组织hPF4阳性率为47.5 %，表达组MVD （25.4±11.7）低于不表达组（45.1±11.9），MVD存在显著性差异（t值为2.64，均P＜0.01），hPF4 mRNA阳性表达率在发生淋巴结转移的病例显著低于没发生转移的病例（χ2 = 9.42，P＜0.01）。结论 甲状腺乳头癌组织TSPmRNA表达可降低MVD和抑制淋巴结转移。     

A prediction model incorporating the BRAFV600E protein status for determining the risk of cervical lateral lymph node metastasis in papillary thyroid cancer patients with central lymph node metastasis

Background and objectivesCervical lateral lymph node metastasis (LLNM) is a predictor of poor prognosis for papillary thyroid carcinoma (PTC) patients. However, the risk factors for LLNM remain unclear. The purpose of the study was to examine the risk factors for LLNM and construct a prediction model.MethodsWith Ethics Committee approval, a total of 1198 PTC patients were retrospectively included in our study. Univariate and multivariate analyses were performed to explore the relationship between clinicopathological characteristics and LLNM. A nomogram for predicting LLNM in PTC patients with central lymph node metastasis (CLNM) was constructed and validated.ResultsThe negative BRAF^V600E protein expression was significantly correlated with positive LLNM status in PTC patients. In PTC patients with CLNM, the number of metastatic central lymph nodes (LNN) ≥ 3 and the ratio of metastatic central lymph nodes (LNR) ≥ 0.565 were found to be significantly associated with positive LLNM status. The nomogram for predicting LLNM risk in PTC patients with CLNM incorporated four risk factors: tumor size, the BRAF^V600E protein expression, LNN and LNR. The prediction model showed excellent discrimination, with a C-index of 0.714.ConclusionsThe negative BRAF^V600E protein expression was more likely to lead to LLNM. LNN ≥3 and LNR ≥0.565 were associated with LLNM risk in PTC patients with CLNM. Our nomogram might assist clinicians in developing individual suitable follow-up strategies for PTC patients with CLNM.     

Phosphorylated c-Jun NH2-terminal kinase is overexpressed in human papillary thyroid carcinomas and associates with lymph node metastasis

To evaluate the associations of phosphorylated c-Jun NH2-terminal kinase (p-JNK) expression with clinicopathological features in patients with papillary thyroid carcinoma, p-JNK expression were immunohistochemically measured in 121 thyroid samples. p-JNK was overexpressed in papillary thyroid carcinomas with respect to matched nontumorous tissues (P = 0.000), which was supported by western blot analysis. Increased p-JNK expression was significantly associated with the presence of lymph node metastases (P = 0.001) and advanced TNM stages (P = 0.02). Furthermore, p-JNK expression was positively correlated with osteopontin (OPN) expression (r = 0.58, P < 0.001). Activation of p-JNK may play a role in the carcinogenesis and lymph node metastasis of papillary thyroid carcinoma, and may be a molecular target for therapeutic intervention.     

Individual prediction of lateral neck metastasis risk in patients with unifocal papillary thyroid carcinoma

IntroductionMuch controversy exists over whether to perform lateral neck dissection (LND) on patients with papillary thyroid carcinoma (PTC). This study aimed to build predictive nomograms that could individually estimate lateral neck metastasis (LNM) risk and help determine follow up intensity.Patients and methodsUnifocal PTC patients who underwent LND between April 2012 and August 2014 were identified. Clinical and pathological variables were retrospectively evaluated using univariate and stepwise multivariate logistic regression analysis. Variables that had statistical significance in final multivariate logistic models were chosen to build nomograms, which were further corrected using the bootstrap resampling method.ResultsIn all, 505 PTC patients were eligible for analysis. Among these, 178 patients (35.2%) had lateral neck metastasis. Two nomograms were generated: nomogram (c) and nomogram (c + p). Nomogram (c) incorporated four clinical variables: age, tumor size, tumor site, and extrathyroidal extension (ETE). It had a good discriminative ability, with a C-index of 0.79 (bootstrap-corrected, 0.78). Nomogram (c + p) incorporated two clinical variables and two pathological variables: tumor size, tumor site, extranodal extension (ENE), and number of positive nodes in the central compartment. Nomogram (c + p) showed an excellent discriminative ability, with a C-index of 0.86 (bootstrap-corrected, 0.85).ConclusionTwo predictive nomograms were generated. Nomogram (c) is a clinical model, whereas nomogram (c + p) is a clinicopathological model. Each nomogram incorporates only four variables and can give an accurate estimate of LNM risk in unifocal PTC patients, which may assist clinicians in patient counseling and decision making regarding LND.     

微波消融治疗甲状腺乳头状癌术后淋巴结转移的临床研究和疗效观察

目的 为了提高对超声引导下经皮微波消融术治疗甲状腺乳头状癌术后颈部淋巴结转移癌的认识,并评价其疗效性和安全性。方法 选择84例甲状腺乳头状癌术后复发的患者,接受微波消融治疗后,通过超声造影增强检查,评估消融区内的肿瘤活性,在1、3、6个月以及12个月对患者进行肿瘤大小、体积和血清甲状腺球蛋白的测量临床评估。结果 103个颈部淋巴结转移癌全部成功接受了微波消融治疗,治疗后超声造影增强检查未检测到不完全消融,在最后一次随访中,平均最大直径从10.5±5.7mm减小到0.8±1.5mm(P＜0.05),平均体积从285.9±245.7mm³减小到4.0±8.0mm³(P＜0.05)。治疗后既未检测到已治疗的肿瘤发生进展,也没有新增可疑的淋巴结。结论 超声引导下经皮微波消融术可能成为某些不适合或拒绝进行手术治疗的甲状腺乳头状癌术后淋巴结转移患者的替代疗法,这种手术安全有效,并发症发生率低。     

甲状腺球蛋白预测甲状腺乳头状癌颈部淋巴结转移的增益价值

目的:探讨甲状腺球蛋白(thyroglobulin,Tg)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)颈部淋巴结转移预测中的临床价值。方法:回顾性分析甲状腺乳头状癌清甲结束后患者 218例,根据全身131I扫描结果分为无淋巴结转移组、一枚淋巴结转移组、两枚淋巴结转移组及多枚淋巴结转移组。分析各组患者组间Tg值的差异与相关性,采用ROC曲线计算达到最佳诊断效能时的Tg值。结果:无淋巴结转移组与淋巴结转移组之间Tg值有统计学差异(P＜0.05),不同数目淋巴结转移组之间Tg值无统计学差异(P＞0.05),且Tg值与淋巴结转移灶数目无相关性(P＞0.05)。当Tg值为1.5 ng/mL时诊断淋巴结转移的灵敏度68%,特异度80%,准确性72%,ROC曲线下面积达到最大值0.77。结论:尚不能依据Tg值判断甲状腺乳头状癌术后淋巴结转移数目及范围,但可以评估清甲治疗后淋巴结转移可能性,本研究建议的Tg截断值为1.5 ng/mL。     

pN1a甲状腺乳头状癌中央区淋巴结清扫数与临床转归的关系

背景与目的:甲状腺乳头状癌(papillary thyroid carcinoma,PTC)常发生颈部淋巴结转移,多见于颈部中央区.该研究旨在探讨转移淋巴结数小于等于5枚的pN1a PTC患者颈部中央区淋巴结清扫数与131I"清甲"治疗后临床转归的关系.方法:回顾性分析2012年2月—2014年12月北京协和医院收治的167例经术后病理证实存在1~5枚淋巴结转移的pN1a PTC患者的临床资料,均行全甲状腺切除或近全甲状腺切除联合中央区淋巴结清扫术.经过131I"清甲"治疗后中位随访26个月,将患者的临床转归根据美国甲状腺协会(American Thyroid Association,ATA)2015年发布的《成人甲状腺结节与分化型甲状腺癌诊治指南》分为:满意(excellent response,ER)、不确切(indeterminate response,IDR)、血清学反应欠佳(biochemical incomplete response,BIR)和影像学反应欠佳(structural incomplete response,SIR).计算不同淋巴结清扫数对应的累计ER率(以ERn表示,n为淋巴结清扫数,ERn为清扫数小于等于n枚淋巴结后达到ER的患者数占清扫数小于等于n枚淋巴结的总人数的百分比),分析中央区淋巴结清扫数与ERn的关系.结果:随着中央区淋巴结清扫数增多,ERn总体呈上升趋势,ER1、ER5、ER10和ER30分别为25.0%、66.7%、74.7%和79.1%,且n由1至10时ERn升高明显.n大于等于10的患者的满意率高于n小于10的患者,差异有统计学意义(85.7%vs 73.3%,P=0.05).多因素Logistic回归分析显示,中央区淋巴结清扫数大于等于10枚(OR=2.720,95%CI:1.052~7.033,P=0.039)、131I治疗前刺激性甲状腺球蛋白(stimulated thyroglobulin,sTg)水平(OR=0.955,95%CI:0.926~0.984,P=0.003)是影响ER的独立预后因素.结论:随着中央区淋巴结清扫数的增多,pN1a PTC患者131I"清甲"治疗后更易达到ER;对于淋巴结转移数小于等于5枚的pN1a PTC患者,中央区淋巴结清扫数大于等于10枚有助于其131I"清甲"治疗后达到ER.     

Risk factors for right paraesophageal lymph node metastasis in papillary thyroid carcinoma: A meta-analysis

ObjectiveProphylactic dissection of the right paraesophageal lymph node (RPELN) in thyroid cancer is controversial. We performed a meta-analysis to provide evidence for RPELN dissection in thyroid cancer.MethodsWe searched the PubMed and Science Citation Index Expanded (SCIE) databases for relevant studies published up to January 31, 2019. The patients involved all had a pathological diagnosis of papillary thyroid cancer (PTC) and had undergone total thyroidectomy or right lobectomy with central compartment lymph node dissection. The RPELNs had been kept aside during the operation.ResultsFourteen cohort studies involving 11,090 patients with PTC were included in the meta-analysis. There was RPELN metastases (RPELNM) in 1038 patients (9.36%). The factors related to RPELNM were: age <45 years, male sex, right lobe tumor, tumor >1 cm, extrathyroidal extension, capsular invasion, right paratracheal lymph node metastasis (RPTLNM), central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), and tumor multifocality. There was no association between RPELNM and Hashimoto's thyroiditis (HT) and inferior pole tumors or tumor in the middle of the gland. With superior pole tumors, there was even less RPELNM.ConclusionsThe clinical features related to RPELNM are age <45 years, male sex, tumor >1 cm, tumor diameter >2 cm, right lobe tumor, RPTLNM, extrathyroidal extension, capsular invasion, CLNM, CLNM ≥3, LLNM and multifocality, which should be considered when evaluating RPELN dissection.     

A retrospective study of papillary thyroid carcinoma: Hashimoto's thyroiditis as a protective biomarker for lymph node metastasis

PurposeThere is approximately 10%–50% of papillary thyroid carcinoma (PTC) patients with Hashimoto's thyroiditis (HT). In this research, we sought to better understand the role of HT in PTC progression as well as lymph node metastasis.MethodsIt is a retrospective and cross-sectional study, and 4131 PTC patients who underwent thyroidectomy were finally enrolled. Chi-square test, univariate and multivariate logistic regression analyses were employed to evaluate both the risk factors and the critical roles of HT during PTC metastasis.ResultIn this cohort, 1555 patients (37.6%) were diagnosed with HT. According to multivariate analysis, male sex, high levels of TG and TPOAb, tumor extrathyroidal extension, maximum diameter >1 cm, and multifocality were independent risk factors for both central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). In addition, age <55 years and smoking were risk factors for CLNM, while CLNM was one of the risk factors for LLNM. Furthermore, HT was suggested a valuable protective factor for both CLNM and LLNM. In patients with HT, the total number of central lymph nodes was higher, while the positive rate was lower. Compared with those without HT, age and sex did not predict CLNM and LLNM in patients with HT.ConclusionHT is considered a protective factor for both CLNM and LLNM in PTC. For patients with HT, surgeons should pay more attention to the preservation of parathyroid gland and the protection of recurrent laryngeal nerve due to less lymph node metastasis. Otherwise, radical operation is highly recommended.     

228例甲状腺微小乳头状癌临床特征及颈部淋巴结转移危险因素分析

背景与目的：甲状腺微小乳头状癌（papillary thyroid microcarcinoma,PTMC）的发病率不断增加,总体预后较好,但在临床诊治过程中存在争议。通过分析患者资料,总结PTMC的临床特征及危险因素,以指导临床精准治疗。方法：回顾性分析蚌埠医学院第一附属医院2015年1月—2017年12月间行手术治疗的PTMC患者的临床病理学资料。结果：在228例患者中,109例发生中央区淋巴结和（或）颈侧区淋巴结转移（47.81%）,单因素分析结果显示,患者性别、年龄、肿瘤最大径及原发灶数目与颈部淋巴结转移相关（P均＜0.05）;二元logistic多因素分析结果显示,男性患者、年龄＜45岁、肿瘤最大径>4 mm及多中心病灶是PTMC颈部淋巴结转移的独立危险因素（P均＜0.05）。结论：PTMC虽然肿瘤较小但不等同于淋巴结转移风险小,特别对于男性患者、年龄＜45岁、肿瘤最大径>4 mm及多中心病灶患者应积极进行外科手术干预。     

颈中央区域淋巴结清扫在临床颈淋巴结阴性甲状腺乳头状癌手术治疗中的应用

背景与目的:对临床已证实颈部淋巴结阳性(cN )甲状腺乳头状癌患者行联合根治术已无异议,但对临床颈淋巴结阴性(cN0)患者是否实行选择性颈淋巴结清扫,以及清扫范围、清扫时机等国内外均存在争议。本研究探讨cN0甲状腺乳头状癌患者手术颈部淋巴结处理的恰当方案。方法:2005年至2006年84例经术前常规B超、选择性颈部MRI检查确定为cN0甲状腺乳头状癌患者,随机分为A、B两组,各42例。A组行原发灶根治 常规同侧中央区域淋巴结清扫术;B组仅行原发灶根治术。术后均服甲状腺素内分泌治疗。结果:A组淋巴结检出率平均3枚/例,淋巴结转移率47.62%。两组在术后并发症发生率差异无统计学意义(P<0.05)。结论:原发灶根治 同侧中央区域淋巴结清扫是治疗cN0甲状腺乳头状癌的一种值得推荐的术式,在不造成额外损伤的基础上超越了单纯原发灶的治疗,具有前哨淋巴结活检的意义,还可避免再次颈淋巴结清扫时对喉返神经的损伤。     

甲状腺乳头状癌超声表现与侧颈区淋巴结转移间关系的研究

目的：研究甲状腺乳头状癌（ Papillary thyroid carcinoma ,PTC）高频超声表现与侧颈区淋巴结转移（ Lateral cervical lymph node metastasis ,LCLNM）间的关系。方法对449例患者的633个PTC结节进行分组。有LCLNM的为转移组,有91例患者共135个结节;无LCLNM的为无转移组,有358例患者共498个结节。所有结节的病理及有无LCLNM、颈中央区淋巴结转移（ Central cervical lymph nodule metasta-sis,CCLNM）均以术后病理诊断为金标准。用χ^2检验进行单因素分析,Logistic回归进行多因素分析。结果单因素分析显示男性、年龄＜45岁、多发、直径＞1 cm、微钙化多发（ d＜2 mm）、混合型血流（内部及边缘血流增多）、纵横比＜1、CCLNM、侵犯甲状腺包膜均与LCLNM相关（P＜0．05）,PTC位于上极易发生LCLNM（P＜0．017）。多因素分析显示微钙化多发、纵横比＜1、CCLNM、侵犯甲状腺包膜和结节位于甲状腺上极同时出现是LCLNM的危险因素（P＜0．005,OR＝1．626,2．644,0．479,2．579）。结论高频超声可精确描述甲状腺癌结节声像图表现,这些表现对术前提示侧颈区有无侧颈区颈部淋巴结转移具有重要价值,可为临床手术及治疗提供更多信息。