A Predictive Model for Lateral Cervical Lymph Node Metastasis in Thyroid Cancer

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126–0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.

Background:The 2015 American Thyroid Association guidelines recommend total thyroidectomy (TT) followed by radioactive iodine (RAI) therapy as the primary treatment modality for intermediate-risk papillary thyroid carcinoma (PTC) patients with lateral lymph node metastasis (LLNM). However, the supporting evidence remains insufficient. The clinical superiority of TT versus lobectomy (LT) in this patient population remains unclear, and the optimal surgical approach for intermediate-risk PTC with LLNM continues to be debated.Aim:This meta-analysis examined the clinical superiority of TT versus LT for intermediate-risk PTC with unilateral LLNM.Methods:This PRISMA/AMSTAR-compliant meta-analysis (PROSPERO: CRD42023410775) evaluated recurrence-free survival (RFS) in intermediate-risk PTC with unilateral LLNM. Systematic searches of PubMed, Web of Science, and Cochrane Library (2004–2024) combined Medical Subject Heading terms and title/abstract: (“papillary thyroid carcinoma” OR “papillary thyroid cancer” OR “PTC”) AND (“lateral cervical lymph node metastasis” OR “lateral neck lymph node metastasis” OR “lateral lymph node metastasis” OR “lateral cervical nodal metastasis” OR “N1b”) AND (“thyroidectomy” OR “total thyroidectomy” OR “lobectomy”). Two investigators independently extracted data on surgical outcomes, adjuvant RAI therapy, and RFS metrics, with quality assessed via Newcastle–Ottawa Scale. Prespecified subgroup analyses examined RAI utilization and surgical extent impacts. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Review Manager 5.3, prioritizing adjusted HR. Heterogeneity was assessed via I2 statistics.Results:Among 609 initially identified references, 8 studies met the inclusion and exclusion criteria, comprising 2462 intermediate-risk PTC patients with unilateral LLNM. Of these, 53.3% (1313/2462) underwent TT, and 46.7% (1149/2462) underwent LT. Compared with the TT group, LT showed no statistically significant difference on RFS (HR = 1.08, 95% CI 0.83–1.40, P = 0.56). In subgroup analyses: Compared with TT + RAI, LT showed no significant difference in RFS (HR = 0.66, 95% CI 0.40–1.08, P = 0.10); Compared with TT + RAI, LT or TT alone showed no significant difference in RFS (HR = 0.65, 95% CI 0.41–1.03, P = 0.07); Compared with TT alone, LT showed no significant difference in RFS (HR = 1.16, 95% CI 0.63–2.12, P = 0.64); Compared with TT + RAI, TT alone showed no significant difference in RFS (HR = 0.87, 95% CI 0.42–1.81, P = 0.37).Conclusion:For intermediate-risk PTC patients with isolated unilateral LLNM, TT, and LT demonstrate comparable oncological outcomes in terms of RFS. Unilateral LLNM alone should not constitute an absolute indication for TT. When no additional high-risk features are present, LT may serve as a preferable alternative to optimize quality of life while maintaining oncological safety.

The aim of this study was to evaluate the number of central cervical lymph node metastasis (CCLNM) in predicting lateral cervical lymph node metastasis (LCLNM) in patients with papillary thyroid carcinoma (PTC). From January 2005 to October 2010, a total of 133 patients diagnosed as PTC underwent central and lateral cervical lymph node dissection were enrolled in this study. Quantitative analysis was performed to explore the correlation between the number of CCLNM and LCLNM. The sensitivity of central cervical node metastasis to predict lateral cervical node metastasis was 84.7%(61/72), and the positive predictive value (PPV) was 66.3% (61/92). The incidence of lateral cervical LNM was correlated with the number of CCLNM (r=0.911, P=0.004). The LCLNM rates in patients with number of CCLNM <2 and ≥ 2 were 54.5% (12/22) and 70.0% (49/70), respectively, with a non-significant difference (P=0.181). The LCLNM rates in patients with number of CCLNM < 3 and ≥ 3 were 50.0% (19/38) and 77.8% (42/54), showing a significant difference (P=0.006). The LCLNM rates in patients with number of CCLNM <4 and ≥ 4 were 55.1% (27/49) and 79.1% (34/43), with a significant difference (P=0.015). The LCLNM rates in patients with number of CCLNM <5 and ≥ 5 with the LLNM rate were 57.6% (34/59) and 81.8% (27/33), showing a significant difference (P=0.019). The LCLNM rates in patients with number of CCLNM <6 and ≥ 6 were 60.0% (39/65) and 81.5% (22/27), showing a significant difference (P=0.047). CCLNM has a significant association with LCLNM in patients with papillary thyroid carcinoma. LCLNM is mainly observed in patients with ≥ 3 CCLNM. Therefore, the number of CLNM ≥ 3 may be a valuable predictor of lateral cervical lymph node metastasis, and lateral cervical lymph node dissection should be considered.

Currently, there is a lack of evidence-based risk factors for the lateral cervical lymph node metastasis of papillary thyroid carcinoma (PTC). Thus, the risk factors and recurrence rate of lateral cervical lymph node metastasis were investigated in the present study for patients with PTC who underwent initial radical surgery. The data of 274 patients with PTC who underwent initial radical surgery over a 10-year period from January, 2009 to December, 2018 were retrospectively analyzed. By applying univariate analysis, lymphovascular invasion, venous invasion, extrathyroidal infiltration, paratracheal lymph node metastasis and tumor size were designated as significant risk factors for lateral cervical lymph node metastasis. As regards multivariate analysis, paratracheal lymph node metastasis and tumor size were identified as independent risk factors. The recurrence rate was higher in patients presenting with lateral cervical lymph node metastasis, and the disease-free survival rate was significantly lower in the patient group presenting with lateral cervical lymph node metastasis. On the whole, the present study demonstrated that paratracheal lymph node metastasis and tumor size were independent risk factors for lateral cervical lymph node metastasis.

Objective: To investigate the correlation between cervical lymph node skip metastasis with ultrasonographic characteristics of papillary thyroid micro- carcinoma (PTMC). Methods: We reviewed ultrasonographic features of 385 primary PTMC and cervical lymph node metastasis, confirmed by pathology in Tianjin Medical University Cancer Institute and Hospital, to evaluate the efficacy of ultrasonography in the diagnosis of cervical lymph node metastasis of PTMC patients. The relationship between ultrasonographic features of primary lesions and skip metastasis of cervical lymph nodes was analyzed by χ(2) test and multiple factor Cox regression. Results: Among the 385 cases of PTMC patients with cervical lymph node metastasis, 231 cases were central lymph node metastasis alone, 31 cases were lateral cervical lymph node metastasis alone, 123 cases were both central and lateral cervical lymph node metastasis. Among the 354 cases without skip metastasis of cervical lymph nodes, 48 cases were level Ⅱ, 92 cases were level Ⅲ, 83 cases were level Ⅳ, 9 cases were level Ⅴ, 354 cases were level Ⅵ. Among the 31 cases with skipping metastasis of cervical lymph nodes, 12 cases were level Ⅱ, 14 cases were level Ⅲ, 14 cases were level Ⅳ, 1 case was level Ⅴ. The sensitivity and specificity of preoperative ultrasonography in the diagnosis of central cervical lymph node metastasis were 46.3% and 66.7%, respectively, and those of lateral cervical lymph node were 91.0% and 87.8%, respectively. Univariate analysis showed that the abutment/perimeter, diameter and location of PTMC were significantly associated with skip metastasis (P<0.05), multivariate analysis showed that abutment/perimeter and location of PTMC were significantly associated with skip metastasis (P<0.05). Conclusions: The sensitivity and specificity of preoperative ultrasound diagnosis for lateral cervical lymph node metastasis of PTMC is higher than that of central metastasis. PTMC with abutment/perimeter ≥1/4 and upper portion location are prone to skip metastasis.

To analyse the clinical features and treatment strategies of papillary thyroid carcinoma(PTC) coexistent with lymphocytic thyroiditis (LT). A total of 292 patients including 25 males and 267 females with LT and thyroid nodules treated in the department of head and neck surgery between Sep 2011 and Sep 2014 was analysed retrospectively and divided into two groups according to pathological results, of them 262 patients, with a median age of 47 years old, were LT with PTC and 30 patients, with a median age of 54 years old, were LT with benign nodules. Among 262 patients having LT with PTC, 259 were diagnosed as having malignant or suspicious malignant nodules and 3 having benign nodules with ultrasound before surgery, 98 cases were considered multifocal malignant nodules by preoperative ultrasound, and 112 cases were positive in cervical lymph nodes, including bilateral positive in 37 cases. Of 30 patients having LT with benign nodules, 14 were diagnosed malignant or suspicious malignant nodules and 16 benign nodules. The mean age in 262 patients with PTC was less significantly than that in 30 patients with benign nodules (P<0.05). Ultrasound showed a high proportion of calcification and microcalcification in patients with PTC (34%) compared to patients with benign nodules(13%)(P<0.05). There were not significant differences in the mean levels of serum thyroid stimulating hormone(TSH) (2.80 vs 2.99 mU/L, P=0.233), thyroglobulin(TG) (27.14 vs 18.60 μg/L, P=0.747), and anti-thyroglobulin antibodies(ATG)(417.3 vs 378.7 U/ml, P=0.834) between patients with PTC and those with benign nodules. In patients with PTC, multifocal tumor accounted for 42%. The central and lateral lymph node metastasis rates were respectively 50% and 24%, and the occult metastasis rate of lateral neck lymph node was 16%. Univariate analysis showed that age less than 45 years old, multifocal tumor, tumor diameter more than or equal to 2cm and extrathyroidal extension were associated with central lymph node metastasis (P<0.05), but not with lateral neck metastasis. Multivariate analysis showed a closed correlation only between the lymph node metastases in central and lateral neck levels (P<0.05). Calcification and microcalcification have the same importance in the ultrasonic diagnosis for PTC in patients with LT. Total thyroidectomy and prophylactic central lymph node should be a choice for LT with PTC. Lymph node metastasis in level Ⅵ indicates the possibility of lateral cervical lymph node metastasis in the patients having LT with PTC.

Lateral lymph node metastasis (LLNM) is very common in medullary thyroid carcinoma (MTC), but there is still controversy about how to manage cervical lateral lymph nodes, especially for clinically negative MTC. The aim of this study is to develop and validate a nomogram for predicting LLNM risk in MTC. A total of 234 patients from two hospitals were retrospectively enrolled in this study and divided into LLNM positive group and LLNM negative group based on the pathology. The correlation between LLNM and preoperative clinical and ultrasound variables were evaluated by univariable and multivariable logistic regression analysis. A nomogram was generated to predict the risk of the LLNM of MTC patients, validated by external dataset, and evaluated in terms of discrimination, calibration, and clinical usefulness. The training, internal, and external validation datasets included 152, 51, and 31 MTC patients, respectively. According to the multivariable logistic regression analysis, gender (male), relationship to thyroid capsule and serum calcitonin were independently associated with LLNM in the training dataset. The predictive nomogram model developed with the aforementioned variables showed favorable performance in estimating risk of LLNM, with the area under the ROC curve (AUC) of 0.826 in the training dataset, 0.816 in the internal validation dataset, and 0.846 in the external validation dataset. We developed and validated a model named MTC nomogram, utilizing available preoperative variables to predict the probability of LLNM in patients with MTC. This nomogram will be of great value for guiding the clinical diagnosis and treatment process of MTC patients.

Papillary thyroid cancer (PTC) metastasizes to central lymph node (CLN). CLN metastasis is associated with high risk of locoregional recurrence and distant metastasis. The significance of the number of metastatic CLN has not been addressed. This study was designed to evaluate the clinical implication of the number of metastatic CLN in PTC. We reviewed the patients who underwent total thyroidectomy and CLN dissection with or without lateral neck dissection due to PTC, from March 2008 to June 2009. The relationships between the number of CLN and risk factors, including age, gender, tumor size, extrathyroidal extension, and lateral lymph node metastasis, were assessed. Patients were divided into three groups according to the number of CLN: group A=0; group B=1-2; and group C=≥3. Of 258 patients enrolled in this study, 113 were in group A, 73 in group B, and 72 in group C. Extrathyroidal extension and lateral neck lymph node metastasis were related to increased rate of CLN metastasis (P<0.05). Tumor size increased as the number of CLN increased; group C had the largest tumor size (P<0.05). When evaluating the distribution of patients with extrathyroidal extension, group C had a significant odds ratio (4.213, P<0.05). When evaluating the distribution of lateral neck lymph node metastasis, groups B and C had significant odds ratio (14.353, 75.403, respectively, P<0.05). The number of CLN metastasis correlated with the negative prognostic factors, including tumor size, extrathyroidal extension, and lateral neck lymph node metastasis. This suggests that the number of CLN has prognostic implication.

BackgroundPapillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer and lymph node metastasis (LNM) significantly impacts patient prognosis. Preoperatively identifying lateral lymph node metastasis (LLNM) presents significant challenges, as current diagnostic techniques, such as ultrasonography, have limited sensitivity and precision. This study aimed to develop and validate a predictive model for LLNM in patients with PTC, using data from the Surveillance, Epidemiology, and End Results (SEER) database and external validation cohorts.MethodsData from 18,342 patients with PTC diagnosed from 2016 to 2020 were retrieved from the SEER database. The patients were arbitrarily categorized into training (n=12,839) and validation (n=5,503) cohorts. Both univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors for LLNM. A predictive nomogram was developed based on these factors, and its accuracy was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).ResultsFive independent predictors of LLNM were identified: sex, age, race, tumor (T) stage, and metastasis (M) stage. The nomogram demonstrated strong predictive performance, with an area under the curve (AUC) of 0.715 [95% confidence interval (CI): 0.706–0.724] in the training cohort and 0.707 (95% CI: 0.693–0.720) in the validation cohort. The calibration curves indicated good agreement between the predicted and actual outcomes, while DCA confirmed the clinical applicability of the model across various risk thresholds.ConclusionsThis study successfully developed a predictive model for LLNM in patients with PTC by integrating demographic and clinicopathological indicators. This model demonstrates significant predictive precision and practical clinical use, assisting medical professionals in identifying high-risk patients and optimizing surgical choices. Further studies incorporating more variables are warranted to improve the diagnostic accuracy of the model.

BackgroundAt present, preoperative diagnosis of lateral cervical lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) mostly depends on the training and expertise of ultrasound doctors. A machine-learning model for predicting LLNM accurately before PTC surgery may help to determine the scope of surgery and reduce unnecessary surgical trauma.MethodsThe data of patients with primary PTC who underwent thyroidectomy with lateral cervical lymph node surgery at Beijing Tongren Hospital between July 2009 and June 2021 were retrospectively analyzed. All patients had complete ultrasonic examination, clinical data, and definite pathology diagnosis of lymph nodes. LLNM was confirmed by postoperative pathology. The patients were randomly divided into a training set (155 cases) and a test set (98 cases) at a ratio of 6:4. Eleven parameters, including patient demographics, ultrasound results, and tumor-related conditions, were collected, and a prediction model was established using the support vector machine (SVM) algorithm. Several other machine-learning algorithms were also used to establish models for comparison. The accuracy, precision, recall, F1-score, sensitivity, specificity, Cohen’s kappa value, and area under the receiver operating characteristic curve (AUC) were used to evaluate model performance.ResultsA total of 87 males and 156 females were included in the study, aged 14–80 years. One hundred and four patients of them had LLNM and 139 did not have LLNM. The pandas Python library was used for the statistical analysis, and the Spearman coefficient was used to analyze the correlation between each parameter and the prediction index. The SVM model performed the best among all the models. Its accuracy, precision, recall, F1-score, sensitivity, specificity, Cohen’s kappa value, and AUC were 90.8%, 91.0%, 90.8%, 90.8%, 87.5%, 94.0%, 81.6%, and 91.0%, respectively.ConclusionsThis model can enable surgeons to improve the accuracy of ultrasonography in predicting LLNM without additional examination, thus avoiding missing positive lateral cervical lymph nodes and reducing the sequelae caused by unnecessary lateral neck dissection.

Lateral lymph node (LLN) metastasis sometimes occurs in patients with early rectal cancer that has invaded the submucosa (SM) and muscularis propria (MP). This study aims to identify the risk factor(s) for LLN metastasis in such patients. We retrospectively analyzed 65 patients with pathological SM or MP lower rectal adenocarcinoma, for whom radical resection had been performed at a single institution. We performed LLN dissection in 52 (80%) patients. The LLN dissection rates in the case of pathological SM and MP tumors were 65.6% and 94.4%, respectively, and the corresponding LLN metastasis rates were 6.9% and 11.1%. Severe tumor budding was found to be a risk factor for LLN metastasis (P = 0.002). Further, of six patients with LLN metastasis, four did not have coincident mesenteric lymph node metastasis. In rectal cancer that has pathologically invaded SM and MP, LLN metastasis is not negligible. LLN dissection could lower the local recurrence rate of SM and MP rectal cancer. In case LLN dissection is not performed, patients with a high tumor budding grade should be administered adjuvant therapy.

PurposeThe aim of this study was to find useful metabolites to predict lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC) through a metabolomics approach and investigate the potential role of metabolites as a novel prognostic marker.Materials and methodsFifty-two consecutive patients (median age: 41.5 years, range 15–74 years) were enrolled who underwent total thyroidectomy and central LN dissection with or without lateral LN dissection in Severance Hospital between October 2013 and July 2015. The study specimens were provided by the Severance Hospital Gene Bank, and consisted of PTC from each patient. The specimens were prepared for proton nuclear magnetic resonance (1H-NMR) spectroscopy. Spectral data by 1H-NMR spectroscopy were acquired, processed, and analyzed. Patients were grouped in three ways, according to the presence of LN metastasis, central LN metastasis and lateral LN metastasis. Chi-square test and the student t-test were used to analyze categorical variables and continuous variables, respectively. The Mann-Whitney U test was used for univariate analysis of metabolites. Orthogonal projections to latent structure discriminant analysis (OPLS-DA) was used for multivariate analysis to discriminate metabolic differences between the two groups.ResultsAmong 52 patients, 32 had central LN metastasis and 19 had lateral LN metastasis. No clinical or histopathological characteristic was significantly different for all comparisons. On univariate analysis, no metabolite showed significant difference for all comparisons. On multivariate analysis, OPLS-DA did not discriminate the presence and absence of LN metastasis. Lactate was found to be the most promising metabolite.ConclusionsNo metabolite could discriminate the presence of LN metastasis. However, lactate was found to be the most promising metabolite for discrimination. Further studies with larger sample sizes are needed to elucidate significant metabolites which can indicate the presence of LN metastasis in patients with PTC.

BackgroundThere is a lack of large studies focusing on the prognostic significance of lateral lymph node (LLN) metastasis following LLN dissection (LLND) in rectal cancer. The aim of this study was to evaluate the prognostic impact of LLN metastases on survival of patients with advanced low rectal cancer.MethodsConsecutive patients with locally advanced, but not metastatic, extraperitoneal rectal cancer treated with neoadjuvant (chemo)radiotherapy plus total mesorectal excision between 2004 and 2015 were included in the study. LLND was performed when pretreatment imaging documented enlarged LLNs (7 mm or greater in size). Localization of nodal metastases and long‐term outcomes were analysed. Kaplan–Meier analysis was used to compare the survival of patients with ypN0 disease with that of patients with mesorectal ypN+/LLN− status and patients with positive LLNs. The Cox proportional hazards model was used to evaluate predictors of disease‐free survival (DFS) and local recurrence.ResultsA total of 613 patients were included in the study; LLND was performed in 212 patients (34·6 per cent) and 57 (9·3 per cent) had LLN metastasis. Patients with LLN metastasis had improved DFS and local recurrence cumulative incidence rates compared with patients with mesorectal ypN2+/LLN− disease (DFS: P = 0·014; local recurrence: P = 0·006). Although the DFS rate of patients with LLN metastasis was worse than that of patients with ypN0 disease (P < 0·001), the cumulative incidence of local recurrence was similar (P = 0·491). In multivariable analysis, residual LLN metastasis was not an independent predictor of worse DFS or local recurrence.ConclusionLLN metastasis is not an independent predictor of local recurrence or survival. Survival of patients presenting with LLN metastasis after (chemo)radiotherapy was intermediate between that of patients with ypN0 status and those with mesorectal ypN2 positivity.

Objective: To explore the risk factors for contralateral central lymph nodes (Cont-CLNs) metastasis of unilateral papillary thyroid carcinoma (PTC) and to guide the decision-making of clinical surgical scope. Methods: The data of 362 patients who underwent total thyroidectomy and bilateral central lymph node dissection at the Sichuan Cancer Hospital from September 2020 to April 2022 and were confirmed as unilateral PTC by postoperative pathology were retrospectively analyzed. Among them, 87 were male and 275 were female, aged from 11 to 76 years. According to whether presence of Cont-CLNs metastasis, they were divided into the metastasis group (115 cases) and the non-metastasis group (247 cases). The relationship between the demographic characteristics, clinicopathological characteristics and other indicators of the two groups of patients and their metastases of Cont-CLNs was analyzed. Univariate analysis, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to screen the risk factors for Cont-CLNs metastasis. Postoperative follow up was performed in the patients. Results: Univariate analysis showed that age, gender, combined Hashimoto's thyroiditis, extranodal invasion, pretracheal and prelaryngeal lymph node metastasis, ipsilateral central lymph nodes (Ipsi-CLNs) metastasis on the affected side, lateral cervical lymph node metastasis on the affected side, lesion location, and tumor diameter were associated with Cont-CLNs metastasis (all P values<0.05). Multivariate revealed that: each of male gender, Ipsi-CLNs metastasis, pretracheal and prelaryngeal lymph node metastasis, cancer focus location in the isthmus, and unilateral glandular lobe combined with isthmus was an independent risk factor for Cont-CLNs metastasis. For predicting the metastasis risk of Cont-CLNs, the optimal critical value of the number of metastasized Ipsi-CLNs was 2.5, and the area under the ROC curve (AUC) was 0.700; the optimal cut-off value of the number of metastasized pretracheal and prelaryngeal lymph nodes was 1, with an AUC of 0.681. The AUC of gender was 0.630, and the AUC of the cancer lesion location was 0.545. Multivariate ROC curve analysis for Cont-CLNs metastasis based on gender, the number of metastasized Ipsi-CLNs, the number of metastasized pretracheal and prelaryngeal lymph nodes, and the location of cancer foci showed an AUC of 0.794. The patients were followed up until January 2025. Excluding 3 cases with hoarseness caused by recurrent laryngeal nerve invasion before the operation and 3 cases with resection and reconstruction of invaded recurrent laryngeal nerves discovered during the operation, there were no patients with permanent recurrent laryngeal nerve palsy after the operation. There were 3 cases with postoperative permanent hypoparathyroidism. There no patients with postoperative recurrence. Conclusion: Risk factors for Cont-CLNs metastasis include male sex, Ipsi-CLNs metastasis, pretracheal and prelaryngeal lymph nodes metastasis, and tumor location in the isthmus or unilateral lobe plus isthmus. In unilateral PTC with the risk factors, Cont-CLNs dissection may be considered.

To investigate the ability of matrix metalloproteinase (MMP)-2 and CD44 variant 6 (CD44v6) protein levels to diagnose papillary thyroid cancer (PTC), compared with routine diagnostic methods using tissue sections; to explore the relationship between MMP-2 and CD44v6 protein levels and lymph node metastases (LNM) in PTC. Archival PTC specimens from patients with PTC, with or without lateral cervical LNM, were included in this retrospective immunohistochemical study. MMP-2 and CD44v6 protein levels were analysed immunohistochemically using routinely prepared tissue sections. Specimens from 66 patients with PTC were reviewed retrospectively (35 patients with lateral cervical LNM; 31 patients without LNM). The percentages of samples with cells that demonstrated positive protein staining differed significantly between PTC specimens, benign thyroid nodules and adjacent normal follicular epithelium (MMP-2: 86.4%, 60.0%, and 25.7%, respectively; CD44v6: 80.3%, 37.1% and 22.9%, respectively). The level of CD44v6 protein staining was found to be significantly and positively correlated with the level of MMP-2 protein staining in PTC specimens. Both MMP-2 and CD44v6 might be useful tumour markers for predicting risk of lateral cervical LNM in patients with PTC.