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.     

Predictive value of the Delphian lymph node in cervical lymph node metastasis of papillary thyroid carcinoma

IntroductionDelphian lymph node metastasis (DLNM) has proven to be a risk factor for a poor prognosis in head and neck malignancies. This study aimed to reveal the clinical features and evaluate the predictive value of the Delphian lymph node (DLN) in papillary thyroid carcinoma (PTC) to guide the extent of surgery.MethodsTianjin Medical University Cancer Institute and Hospital pathology database was reviewed from 2017 to 2020, and 516 PTC patients with DLN detection were enrolled. Retrospective analysis was performed, while multivariate analysis was performed to identify the risk factors for DLNM.ResultsAmong the 516 PTC patients with DLN detection, the DLN metastasis rate was 25.39% (131/516). Tumor size >1 cm, location in the upper 1/3, central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM) and lymphovascular invasion were independent risk factors for DLNM. Patients with DLNM had a higher incidence of ipsilateral CLNM, contralateral CLNM (CCLNM) and LLNM, and larger numbers and size of metastatic CLNs than those without DLNM. The incidence of CLNM among cN0 patients with DLNM was higher than that among those without DLNM. The incidence of CCLNM among unilateral cN + patients with DLNM was similarly higher than that among patients without DLNM.ConclusionsDLNM indicates a high likelihood and large number of cervical lymph nodes metastases in PTC patients. Surgeons are strongly recommended to detect DLN status during operation by means of frozen pathology, so as to evaluate the possibility of cervical nodal metastasis and decide the appropriate extent of surgery.     

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.     

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.     

甲状腺乳头状癌伴桥本甲状腺炎患者中央区淋巴结转移预测模型的构建与验证

目的:评估HT合并PTC患者中央淋巴结转移（central lymph node metastasis,CLNM）的预测因素。建立列线图预测PTC伴HT患者发生CLNM的可能性。方法:回顾性收集了2018年1月至2021年12月在我院接受甲状腺手术的4 171例PTC患者的资料。最后,共纳入671例PTC合并HT患者。其中,468例患者组成训练组,其余203例患者组成了验证组,以验证模型的性能。预测因子选择采用LASSO回归模型,并采用多因素logistic回归分析建立预测模型,建立了预测CLNM的列线图,并进行了内部验证。结果:LASSO回归模型显示,有17个变量可能是影响CLNM发生的因素（P<0.05）。随后,多因素逻辑回归分析显示,年龄较低、结节性高回声、肿瘤大直径、肿瘤多灶性、甲状腺外扩张（extrathyroidal extension,ETE）、颈部淋巴结肿大、癌胚抗原（carcino-embryonic antigen,CEA）是发生中央区淋巴结转移（CLNM）的独立预测因素。基于独立预测因素构建PTC合并HT患者发生CLNM列线图,并进行内部验证。通过建立预测模型,训练组发生CLNM的ROC曲线下面积（AUC）为0.774（95%CI,0.725~0.824）,验证组发生CLNM的ROC曲线下面积（AUC）为0.781（95%CI,0.712~0.850）。列线图对训练队列和验证队列以及合并数据集均显示出良好的校准和鉴别能力。结论:本研究构建的列线图预测模型对甲状腺乳头状癌伴桥本甲状腺炎患者发生中央区淋巴结转移（CLNM）有良好的预测作用。为临床治疗方案提供合理的参考,帮助临床医生为患者制定个性化的治疗方案。     

Preoperative prediction of central lymph node metastasis in cN0T1/T2 papillary thyroid carcinoma: A nomogram based on clinical and ultrasound characteristics

BackgroundPreoperative status of central lymph nodes is a key determinant of the initial surgical extent for papillary thyroid carcinoma (PTC). We aimed to develop and validate a nomogram based on preoperative clinical characteristics and ultrasound features to predict central lymph node status in patients with clinically lymph node-negative (cN0) T1/T2 PTC.MethodsThis retrospective study included 729 patients with cN0T1/T2 PTC who were treated between January 2015 and March 2020. Based on the ratio of 6:4, 431 patients who underwent surgeries relatively earlier comprised the training set to develop the nomogram, while the other 298 who underwent surgeries relatively later comprised validation set to validate the performance of nomogram. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to identify predictors of central lymph node metastasis (CLNM). These variables were used to construct a nomogram for predicting the risk of CLNM. The predictive performance, discriminative ability, calibration, and clinical utility of the nomogram model were evaluated in both sets.ResultsA total of 313 (42.9%) PTC patients were identified with CLNM. On multivariate logistic regression analyses, malegender, younger age, larger maximum diameter, multifocality, capsular invasion, infiltrative margins, intra-nodular vascularity, and aspect ratio >1 were independent risk factors for CLNM. Nomogram integrating these 8 factors showed excellent discrimination in the training [area under the curve (AUC): 0.788] and validation (AUC: 0.829) sets, and obtained well-fitted calibration curves. The cut-off value of this nomogram was 0.410 (～245 points). Decision curve analysis confirmed the clinical utility of the nomogram.ConclusionThe CLNM-predicting nomogram can facilitate stratification of cN0T1/T2 PTC patients. Prophylactic central neck lymph node dissection can be considered for those with high nomogram scores.     

Shear wave elastography combined with gray-scale ultrasound for predicting central lymph node metastasis of papillary thyroid carcinoma

ObjectiveTo investigate the relationship between shear wave elastography (SWE) elasticity indices of papillary thyroid carcinoma (PTC) and central lymph node metastasis (CLNM) and to evaluate the value of SWE combined with gray-scale ultrasound (US) for predicting preoperative CLNM.MethodThis study included 172 patients with a pathology diagnosis of PTC who underwent preoperative gray-scale US and SWE evaluation. Patients were divided into CLNM-positive and CLNM-negative groups. We analyzed the association between SWE elasticity indices (Emax, Emean and Emin) and CLNM, compared the diagnostic efficacy of gray-scale US alone versus SWE combined with gray-scale US for predicting CLNM, and analyzed the influence of Hashimoto's thyroiditis (HT) on the diagnostic efficacy of CLNM.ResultsSWE elasticity values Emax, Emean and Emin were significantly higher in CLNM-positive patients (P=0.000, 0.000 and 0.003, respectively). The AUC of Emax was higher than that of other SWE indices for predicting CLNM (AUC = 0.749; 95% CI = 0.676–0.822). In multivariate analysis, microcalcification (OR = 5.254; 95% CI = 2.496–11.061), extrathyroidal extension (OR = 4.210; 95% CI = 1.423–12.456), multifocality (OR = 3.084; 95% CI = 1.190–7.991) and Emax >59.0 kpa (OR = 4.934; 95% CI = 2.318–10.500) were independent risk factors for predicting CLNM. The AUC of SWE combined with gray-scale US for predicting CLNM (AUC = 0.825; 95% CI = 0.760–0.879) was significantly higher (P = 0.011) than that for gray-scale US alone (AUC = 0.774; 95% CI = 0.704–0.834). There was no significant difference in AUC between the HT and non-HT subgroups in predicting CLNM (0.798 vs. 0.833, P = 0.640).ConclusionsSWE can be used to predict CLNM in PTC patients. SWE combined with gray-scale US can improve the prediction of CLNM.     

High-risk factors for lymph node metastasis in contralateral central compartment in unilateral papillary thyroid carcinoma（cT1N0）

ObjectiveThe incidence of papillary thyroid carcinoma (PTC) increases yearly. Central lymph node metastasis (CLNM) is common in PTC. Many studies have addressed ipsilateral CLNM; however, few studies have evaluated contralateral CLNM. The purpose of this study is to investigate the high-risk factors of lymph node metastasis in the contralateral central compartment of cT1 stage in PTC.MethodsIn total, 369 unilateral PTC (cT1N0) patients who underwent total-thyroidectomy with bilateral central lymph node dissection (CLND) between 2013 and 2016 in our hospital were retrospectively enrolled. Univariate and multivariate analyses identified the high-risk factors for contralateral CLNM of PTC.ResultsThe total metastasis rate of the ipsilateral central neck compartment was 31.71% (117/369). The total metastasis rate of the contralateral central neck compartment was 8.13% (30/369). The multivariate analysis showed that multifocality (p = 0.009), ipsilateral CLNM (p＜0.001), number of ipsilateral CLNM ＞2 (p = 0.006), tumor located at the inferior pole (p = 0.032) and tumor diameter ＞ 1 cm (p = 0.029) were independent risk factors for contralateral CLNM at cT1 stage in PTC, with odds ratios (ORs) of,4.132 (95% confidence intervals (CI): 1.430–11.936) ，8.591 (95% CI: 3.200–23.061) ，0.174 (95% CI: 0.050–0.601) ，0.353 (95% CI: 0.136–0.917)and 0.235 (95% CI: 0.064–0863), respectively.ConclusionThe combinational use of these risk factors will help surgeons devise an appropriate surgical plan preoperatively. This information could provide reference for the readers who are interested and help to determine the optimal extent of CLND in patients with PTC, especially for cT1b patients.     

甲状腺乳头状微小癌颈部淋巴结转移的影响因素分析

目的:探讨甲状腺乳头状微小癌（PTMC）发生淋巴结转移（LNM）的影响因素。方法:收集535例行甲状腺切除术且病理证实为PTMC患者的临床资料,比较PTMC患者中有和无淋巴结转移、不同转移区域、不同肿瘤直径组间临床病理特征,分析淋巴结转移与临床病理特征的相关性。结果:PTMC合并淋巴结转移组192例（35.89%）,非淋巴结转移组343例（64.11%）,两组比较,淋巴结转移组年龄<55岁、男性、癌灶多发、双侧分布、直径>0.5 cm、合并桥本氏甲状腺炎（HT）、中/高危复发危险分层比例显著升高,差异均有统计学意义（均P＜0.05）;中央区淋巴结转移（CLNM）组147例（76.56%）,颈侧区淋巴结转移（LLNM）组45例（23.44%）,与CLNM组比较:LLNM组癌灶多发、双侧分布、合并HT比例升高,BRAF基因突变率比例降低,差异均有统计学意义（均P＜0.05）;肿瘤直径≤0.5 cm组187例（34.95%）,直径>0.5 cm组348例（65.05%）,与直径≤0.5 cm组比较:直径>0.5 cm组癌灶多发、双侧分布、合并LNM、包膜外侵犯、中/高危复发危险分层比例升高,差异均有统计学意义（均P＜0.05）;多因素Logistics回归分析显示年龄<55岁、男性、癌灶多发、直径>0.5 cm、合并HT是LNM的独立危险因素（均P＜0.05）。结论:年龄<55岁、男性、癌灶多发、直径>0.5 cm、合并HT是PTMC淋巴结转移的独立危险因素,颈部淋巴结转移增加PTMC复发风险。     

A Nomogram for Predicting Lateral Lymph Node Metastasis in Cases of Papillary Thyroid Micro-Carcinoma with Suspected Lymph Node Metastasis

The elevation for lateral lymph node metastasis (LLNM) plays an important role in therapeutic decision-making for thyroid carcinoma. A reliable forecasting model for LLNM in patients with papillary thyroid micro-carcinoma (PTMC) is needed, using clinicopathological characteristics. A total of 576 PTMC patients with suspicious lateral cervical lymph node (II, III, IV or V region) metastasis and known clinicopathological variables were randomly collected at Shenzhen Second People’s Hospital. Cervical lymph node status of every patient was assessed by ultrasonography (US). The patients in this cohort study underwent thyroidectomy and lateral neck lymph node dissection. Univariate analysis and logistic regression analysis were performed to screen out the predictive variables associated with LLNM, and a nomogram was constructed by integrating clinicopathological features collected in our study. The overall LLNM rate was 23.0% (133/576). After statistical analysis, central lymph node metastasis (CLNM), prelaryngeal lymph node metastasis (PLNM), bilateral lesions, tumor location in thyroid (upper or lower), and gross extrathyroidal extension (ETE) were found to be independent predictive factors for LLNM (P < 0.01). The nomogram built to predict LLNM in PTMC patients passed the calibration step and the area under the receiver operating characteristic curve was 0.967, which showed that the nomogram we used had a good predictive effect. The nomogram constructed in this study has a good predictive value for LLNM, which will help thyroid surgeons to make a more accurate surgical plan for patients with PTMC. A strict preoperative evaluation and total thyroidectomy and lateral neck dissection may be indicated when patients with PTMC have a high score.     

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。     

Patient's age with papillary thyroid cancer: Is it a key factor for cervical lymph node metastasis?

BackgroundAge is one of the important prognostic indicators of papillary thyroid cancer (PTC). However, the distinct metastatic patterns and prognosis of age-related lymph node metastasis (LNM) are unclear. This study aims to investigate the impact of age on LNM.MethodsWe conducted two independent cohort studies to assess age–nodal disease association using logistic regression analysis and a restricted cubic splines model. A multivariable Cox regression model was utilized to test the impact of nodal disease on cancer-specific survival (CSS) after age stratification.ResultsFor this study, we included 7572 and 36,793 patients with PTC in Xiangya and SEER cohorts, respectively. After adjustment, advanced age was linearly associated with decreasing risk of central LNM. Patients of age ≤18 years (OR = 4.41, P < 0.001) and 19–45 years (OR = 1.97, P = 0.002) had a higher risk of developing lateral LNM than patients of age >60 years in both cohorts. Furthermore, CSS is significantly reduced in N1b disease (P < 0.001), not N1a disease, regardless of age. The incidence of high-volume LNM (HV-LNM) was significantly higher in patients of age ≤18 years and 19–45 years than in those of age >60 years (P < 0.001), in both cohorts. In addition, CSS was compromised in patients with PTC of age 46–60 years (HR = 1.61, P = 0.022) and those of age >60 (HR = 1.40, P = 0.021) after developing HV-LNM.ConclusionsPatient age is significantly associated with LNM and HV-LNM. Patients with N1b disease or patients with HV-LNM of age >45 years have significantly shorter CSS. Age can, thus, be a useful guide for determining treatment strategies in PTC.     

甲状腺乳头状癌颈淋巴结转移特点及危险因素分析

目的:探讨甲状腺乳头状癌颈淋巴结转移特点及相关危险因素在颈部不同区域淋巴结转移中的意义.方法:回顾性分析北京世纪坛医院2010年1月至2014年12月术后病理证实为甲状腺癌的404例患者的临床资料,就年龄、性别、术前TSH水平、肿瘤最大径、多灶病变、被膜侵犯、合并桥本甲状腺炎、合并结节性甲状腺肿等因素与颈部不同区域淋巴结转移之间的关系进行分析.结果:甲状腺癌发生淋巴结转移时,多数转移至中央区,其次为颈侧区,颈侧区淋巴结转移中Ⅲ区和Ⅳ区转移率相当,且明显高于Ⅱ区.单因素分析结果显示,性别、肿瘤最大径、多灶病变、被膜侵犯、合并结节性甲状腺肿与中央区、颈侧区淋巴结转移均有关(P＜0.05),而年龄和中央区淋巴结转移有相关性(P＜0.05),合并桥本甲状腺炎与颈侧区淋巴结转移有相关性(P＜0.05);多因素Logistic回归分析结果显示,男性患者、年龄＜45岁、肿瘤最大径＞1cm、多灶病变是中央区淋巴结转移的独立危险因素(P＜0.05),而多灶病变、被膜侵犯、合并桥本甲状腺炎是颈侧区淋巴结转移的独立危险因素(P＜0.05).结论:甲状腺乳头状癌中年龄＜45岁的男性患者、肿瘤最大径＞1cm、多灶病变可增加中央区淋巴结转移的风险.而表现为多灶病变、被膜侵犯、合并桥本甲状腺炎、可疑跳跃性转移及中央区淋巴结转移阳性的患者,颈侧区淋巴结转移风险性增加.     

多模态超声及术前BRAF基因预测甲状腺微小乳头状癌颈部淋巴结转移的价值

目的:分析甲状腺微小乳头状癌（papillary thyroid microcarcinoma,PTMC）多模态超声特征,结合临床资料及术前BRAF V600E基因检测,探讨PTMC患者颈部淋巴结转移（cervical lymph node metastasis,CLNM）的高危因素及其预测价值。方法:回顾性分析烟台毓璜顶医院2021年7月至2022年8月经手术病理证实的106例PTMC患者（114个病灶）,术前均行常规超声、CEUS、SWE检查及BRAF V600E基因检测。根据术后病理分为颈部淋巴结未转移组和转移组,应用单因素及多因素分析PTMC患者CLNM的危险因素。结果:单因素分析显示,患者性别、病灶内钙化类型、病灶增强水平、峰值强度（PI）及弹性模量平均值(Eavg)在两组间差异具有统计学意义（P＜0.05）,BRAF基因突变差异无统计学意义（P=0.855）。多因素分析显示,男性患者、病灶内微钙化、超声造影呈等或高增强,CLNM风险更高（P＜0.05）,三者联合诊断的灵敏度(92.3%)及准确度(73.9%)均高于单一诊断,差异有统计学意义（P＜0.05）。结论:男性、微钙化、CEUS呈等或高增强可以独立预测CLNM,而术前BRAF基因突变结果并不能作为预测CLNM的危险因素。基于临床资料和多模态超声特征联合构建的临床预测模型在术前评估PTMC患者CLNM方面具有较高的灵敏度和预测效能,能为诊疗方案的制定提供有价值的参考。     

Lymph node metastasis in suprasternal space in pathological node–positive papillary thyroid carcinoma

BackgroundThe objective of the current study was to investigate the clinical significance of the suprasternal space lymph node (SSLN) in pathological node-positive (pN+) papillary thyroid carcinoma (PTC) patients.MethodOne hundred and forty patients with pN + PTC who underwent neck dissection were enrolled into this study. SSLN was resected and used as a specimen to investigate the relationship of SSLN with several clinicopathological parameters.ResultsThe metastasis rate of SSLN was 20.7%. On univariate analysis, we found that SSLN metastasis was significantly associated with primary cancer site (inferior portion), strap muscle invasion, level III metastasis, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles. On multivariate analysis, primary cancer site (inferior portion), strap muscle invasion, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles were independent risk factors for SSLN metastasis of PTC.ConclusionFor pN + PTC patients, special attention should be paid to the issue of SSLN metastasis.     

Nomogram for predicting lymph node metastasis rate of submucosal gastric cancer by analyzing clinicopathological characteristics associated with lymph node metastasis

Background

To combine clinicopathological characteristics associated with lymph node metastasis for submucosal gastric cancer into a nomogram.

Methods

We retrospectively analyzed 262 patients with submucosal gastric cancer who underwent D2 gastrectomy between 1996 and 2012. The relationship between lymph node metastasis and clinicopathological features was statistically analyzed. With multivariate logistic regression analysis, we made a nomogram to predict the possibility of lymph node metastasis. Receiver operating characteristic (ROC) analysis was also performed to assess the predictive value of the model. Discrimination and calibration were performed using internal validation.

Results

A total number of 48 (18.3%) patients with submucosal gastric cancer have pathologically lymph node metastasis. For submucosal gastric carcinoma, lymph node metastasis was associated with age, tumor location, macroscopic type, size, differentiation, histology, the existence of ulcer and lymphovascular invasion in univariate analysis (all P<0.05). The multivariate logistic regression analysis identified that age ≤50 years old, macroscopic type III or mixed, undifferentiated type, and presence of lymphovascular invasion were independent risk factors of lymph node metastasis in submucosal gastric cancer (all P<0.05). We constructed a predicting nomogram with all these factors for lymph node metastasis in submucosal gastric cancer with good discrimination [area under the curve (AUC) =0.844]. Internal validation demonstrated a good discrimination power that the actual probability corresponds closely with the predicted probability.

Conclusions

We developed a nomogram to predict the rate of lymph node metastasis for submucosal gastric cancer. With good discrimination and internal validation, the nomogram improved individualized predictions for assisting clinicians to make appropriated treatment decision for submucosal gastric cancer patients.     

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.     

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。     

The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis

BACKGROUND:

The effects of the BRAF^V600E mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta‐analysis to assess the strength of associations between these conditions and the BRAF^V600E mutation.

METHODS:

The authors identified the clinical studies that examined the association of the BRAF^V600E mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty‐one relevant studies were hand‐searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model.

RESULTS:

The average prevalence rate of the BRAF^V600E mutation was 49.4%. In 26 studies, compared with the patients who had the wild‐type BRAF genes, the PTC patients with the BRAF^V600E mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68‐2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21‐1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61‐2.49). In 8 studies, patients with the mutation had 2.14‐fold increased risk of recurrent and persistent disease (95% CI, 1.67‐2.74). The associations were generally consistent across the different study populations.

CONCLUSIONS:

This meta‐analysis demonstrates that the BRAF^V600E mutation is closely related to the high‐risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAF^V600E mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients. Cancer 2012;. © 2011 American Cancer Society.     

Nomogram for the prediction of lymph node metastasis and survival outcomes in rectal neuroendocrine tumour patients undergoing resection

BackgroundThe current study analysed rectal neuroendocrine tumour (RNET) patients undergoing resection to identify predictive factors and construct nomograms for lymph node metastasis, cancer-specific survival (CSS) and overall survival (OS).MethodsRNET patients registered in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Multivariable logistic regression analysis was used to investigate the relationships between clinicopathological factors and lymph node metastasis. A multivariate competing risk model was applied to investigate factors independently associated with CSS. Through the Cox regression model, a multivariable analysis of OS was performed. Nomograms were established based on independent predictive factors. Calibration plots, receiver operating characteristic (ROC) curves and Brier scores were used to evaluate the predictive accuracy of the nomograms.ResultsIn this study, 1,253 RNET patients were included for further analysis. Tumour size ≥12 mm (P<0.001), T3/T4 stage (P<0.001) and M1 stage (P=0.001) were independently associated with lymph node metastasis. The performance of the nomogram was acceptable for predicting lymph node metastasis, with an area under the ROC curve (AUC) of 0.937 [95% confidence interval (CI): 0.874–1.000]. Calibration curves and the Hosmer-Lemeshow test revealed desirable model calibration (P=0.99996). The multivariate competing risk model analysis showed that grade II (P=0.017), tumour size ≥12 mm (P=0.007), AJCC TNM stage II (P=0.002), stage III (P<0.001) and stage IV (P<0.001) were significantly associated with worse CSS. In the competing risk nomogram model, the time-dependent AUC revealed good discriminatory ability of the model (time from 1 to 107 months, AUC >0.900), and the Brier score showed good accuracy of the nomogram, which was greater than that of the AJCC TNM stage. Multivariate Cox analysis showed that age >60 years (P=0.002), median income ≥$65,000 (P=0.013), AJCC TNM stage III (P=0.038) and AJCC TNM stage IV (P<0.001) were independently associated with worse OS. In the nomogram for the prediction of OS, the C-statistic was 0.703 (95% CI: 0.615–0.792), which was significantly better than that of the AJCC TNM stage (0.703 vs. 0.607, P=0.009). A calibration plot for the probability of survival demonstrated good calibration.ConclusionsThe present study is the first to establish nomograms with great discrimination and accuracy for the prediction of lymph node metastases, CSS and OS in RNET patients, which can be used to guide treatment decision-making and surveillance.