Objective:To investigate the clinical risk factors of large volume lymph node metastasis (LV-LNM) in the central region of papillary thyroid cancer (PTC) .Methods:The clinical data of 1367 PTC patients admitted to the Department of Oncological Surgery, Hangzhou First People’s Hospital, Affiliated to Zhejiang University School of Medicine from Jan. 2016 to Jan. 2019 were retrospectively analyzed. There were 310 males and 1057 females. A total of 1644 cases of central region were included in the study.According to the number of lymph node metastasis in the central area, they were classified into small-volume lymph node metastasis (SV-LNM) group and LV-LNM group.71 cases of LV-LNM, 1573 cases of SV-LNM.The correlation between CLNM and LV-LNM and various clinicopathological features such as the sex, age, tumor size and so on of PTC patients was analyzed by chi-square test and Logistic regression analysis.Results:The proportion of CLNM in the affected side was 35.28% (580/1 644) , and the incidence of LV-LNM in the central area of the affected side was 4.32% (71/1644) . Univariate analysis showed that the LV-LNM in the central region of the affected side was closely correlated with gender, age, bilateral lesions, multiple lesions, size of lesions, membranous invasion and lateral cervical lymph node metastasis on the affected side were closely related ( P<0.05) . Multivariate regression analysis showed that male (OR=2.115, P=0.006) , age < 38 years old (OR=0.586, P=0.004) , multiple lesions on the affected side (OR=2.837, P=0.004) , lesions >7mm on the affected side (OR=1.762, P=0.002) and cervical lymph node metastasis on the affected side (OR=7.023, P<0.001) were independent predictors of LV-LNM in the central region of the affected side ( P<0.001) . The receiver operating characteristic curve (ROC) , sensitivity and specificity of LV-LNM predicted by the model were 0.839, 81.69% and 78.39%. The incidence of ipsilateral cervical lymph node metastasis in the affected central region of LV-LNM was 11.57 times higher than that of SV-LNM. Conclusion:PTC with male, age < 38 years old, multiple lesions on the affected side, lesion >7 mm and lateral cervical lymph node metastasis are prone to LV-LNM in the affected central region.

Objective To investigate the diagnostic value of lymph node size and distribution in ipsilateral central lymph node metastasis (ICLNM) of single papillary thyroid carcinoma (PTC) in CT examination.Method The CT data of 278 single PTC with diameter ＞ 1.0 cm confirmed by operation and pathology were retrospectively analyzed.According to the ipsilateral central lymph node diameter,these cases were divided into ＜ 0.2 cm group,0.2-0.4 cm group and ≥0.4 cm group,and the distribution difference of ICLNM positive and negative between the three groups were analyzed.Then according to the lymph node distribution,0.2 to 0.4 cm group were divided into turbidity group (≥ 3) and non-turbidity group (1-2),and ≥0.4 cm group were divided into cluster group (≥ 3) and non-cluster group (1-2).The differences betweeen turbidity group and non-turbidity group,cluster group and non-cluster group were analyzed.Results In 278 PTC,the proportion of ICLNM positive and negative was 65.8％(183/278) and 34.2％(95/278),respectively.ICLNM positive in ＜0.2 cm group,0.2-0.4 cm group and ≥0.4 cm group accounted for 37.3％ (31/83),68％ (66/97) and 87.8％ (86/98),respectively.x2 value and P value in between groups and within groups were 51.082 and 0,16.956 and 0,49.955 and 0,11.022 and 0.001,respectively.ICLNM positive in turbidity group and non-turbidity group accounted for 74.0％ (57/77) and 45％ (9/20),respectively.x2 value and P value were 6.151 and 0.013,respectively.ICLNM positive in cluster group and and non-cluster group accounted for 92.6％(50/54) and 82％(36/44),respectively.x2 value and P value were 2.619 and 0.106,respectively.Conclusions Among CT examination of patients with PTC,with the increase of the diameter and number of lymph nodes in central group,the positive proportion of ICLNM positive increases.For the 0.2-0.4 cm group,the turbidity phenomenon suggests that the possibility of metastasis is greater.The accurate identification of these signs can help surgeons take a more thorough surgical treatment and have great significance to reduce postoperative recurrence.

Objective To investigate the relationship between Hashimoto thyroiditis (HT) and thyroid papillary carcinoma (PTC) by analyzing the expression of BRAF V600E mutation and (N-,H-,K-) RAS codons 12,13 and 61 mutants in cases of multifocal PTC with HT.Methods 80 tumor samples in 37 multifocal PTC with HT cases,were analyzed for the genotypic changes of BRAF V600E,as well as the (N-,H-,K-)RAS codons 12,13 and 61 mutants by DNA sequencing assay and amplification refractory mutation system (ARMS).Results BRAF V600E mutation was detected in 51 samples and RAS gene mutations was found in 3 samples (N-RAS codon 61 mutant in 2 samples and H-RAS codon 61 mutant in 1 sample).Different clonal origin was present in 20 cases of multifocal PTC with HT (54.1％,20/37).There was no statistical significance (P ＞ 0.05) in the incidence of the difference in the origin of tumor cells,compared with the results (61.7％,37/60) of multifocal PTC without HT in the related literature.Conclusion In more than half of multifocal PTC with HT cases,the tumor cells originate from different clones.Our results do not support the opinion that HT predisposes patients to develop PTC,because HT does not have a significant effect on expression of BRAF and RAS gene mutation in PTC,accordingly HT is more likely to be a part of the host tumor immune response system.

OBJECTIVE To investigate the clinical value of the lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN, right VI-2) dissection in papillary thyroid carcinoma (PTC). METHODS We studied the relationships between LN-prRLN metastasis and the clinicopathological characteristics in 408 patients with right or bilateral PTC who underwent LN-prRLN dissection. RESULTS Right VI-2 lymph node metastasis was 16.67％. Single factor analysis showed that there were statistically significant correlations between right VI-2 metastasis and gender, age, size and number of right thyroid lobe tumor, capsular invasion, right VI-1 lymph node metastasis and their size, and also metastatic lymph node in the right cervical lateral compartment. Multivariate Logistic regression analysis showed that Right VI-2 lymph node metastasis was related to right tumor size, capsular invasion, the right VI-1 metastasis and right lateral lymph node metastasis(P＜0.05). The receiver-operator characteristic (ROC) analysis showed that the risk factors of LN-prRLN: age ＜35.5 years, right tumor size ＞0.85 cm, lymph node (right VI-1) number ＞1.5, metastatic lymph node (right VI-1) size ＞0.45 cm, lymph node number in the right cervical lateral compartment ＞0.5 and the areas under the ROC curves were 0.585, 0.787, 0.788, 0.725, 0.719. CONCLUSION The dissection of LN-prRLN should be considered when patient with the risk factors such as male, age ＜35.5 years, right tumor size ＞0.85 cm, capsular invasion, lymph node (right VI-1) number ＞1.5, metastatic lymph node (right VI-1) size ＞0.45 cm, lymph node number in the right cervical lateral compartment ＞0.5.

Objective To analyze long noncoding RNAs (lncRNAs) expression profiles in papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (PTC-HT,group A) and PTC only (PTC,group B).Methods 55 cases of thyroid species were collected.High-throughput microarray lncRNh was used to detect the expression difference of lncRNAs between group A and group B.Real-time quantitative PCR (QRT-PCR) was used to verify.Results 1031 lncRNAs and 1338 mRNAs were detected abnormally expressed in tissue samples of group A compared to B.GO and Pathway analysis of mRNAs suggested some biological processes changed obviously,such as immune system and immune reaction.QRT-PCR showed that the expression of uc002stn.1,ENST00000452578 and uc002sti.1 in group A and group B was significantly different.Conclusion IncRNAs expression was significantly different in PTC with or without HT,which may play important roles in the pathogenesis of PTC with HT.

Objective To investigate the diagnostic value of computed tomography (CT) histogram analysis for thyroid malignant solitary coarse calcification nodules (MSCN).Methods A total of 89 thyroid solitary coarse calcification nodules (coarse calcification ≥5 mm,no definite soft tissue around calcification) confirmed either by surgery or histopathological examination in 86 patients enrolled in this study from Jan.2009 to Dec.2015 were evaluated,including 33 MSCN from 32 patients and 56 benign solitary coarse calcification nodules (BSCN) from 56 patients.Overall,27 cut-off values were calculated by N (4 ≤ N ≤ 30) times of 50 Hounsfield units (HU) in the range of 200 HU to 1500 HU,and each cut-off value and the differences in the corresponding area percentages in the CT histogram were recorded for MSCN and BSCN.The optimal cut-off value and the corresponding area percentage were established by receiver operating characteristic (ROC) curve analysis.Results In the 24 groups with an ROC area under the curve (AUC) of more than 0.7,at a cut-off value of 1150 HU and at an area percentage of no less than 98.4％,the ROC AUC reached a maximum of 0.86,and the accuracy,sensitivity,and specificity were 70.8％,93.9％,and 57.1％,respectively.At a cut-off value of 450 HU and at an area percentage of no less than 46.3％,the accuracy,sensitivity,and specificity were 76.4％,48.5％,and 92.9％,respectively.At a cut-off value of 550 HU and at an area percentage of no less than 81.5％,the accuracy,sensitivity,and specificity were 75.3％,33.3％,and 100％,respectively.Conclusions In comparison with the cut-off value of 1150 HU with an area percentage of no less than 98.4％,the sensitivities for the cut-off value of 450 HU with an area percentage of no less than 46.3％ and for the cut-off value of 550 HU with an area percentage of no less than 81.5％ were lower;however,the specificities increased significantly,providing an important basis for reducing the misdiagnosis of MSCN.

OBJECTIVE The aim of the study was to evaluated the difference and consistency in tumor size measured by sonographic and pathological examination in papillary thyroid carcinoma(PTC).METHODS A total of 114 patients with PTC, including 122 malignant nodules, was collected from Hangzhou First People's Hospital between Jun 2012 and Jun 2014. The tumor sizes were measured by preoperative sonographic and postoperative pathologic evaluation. Pearson correlation analysis, paired t-test, and Bland-Altman plot were used to evaluate the correlation and consistency in tumor size measured by the two methods.RESULTS Pearson correlation analysis showed that the largest tumor size measured by sonography were positively correlated with pathologic size (r=0.957, P=0.000). Paired t-test showed that there were statistically difference between sonographic size and pathological size (8.24±5.06) mmvs (7.79±4.75) mm,P=0.001. The absolute difference value of the largest tumor size measured by the two methods was from zero to 6.5 mm, with the average of (1.03±1.14) mm. Bland-Altman analysis showed that the limits of agreement (LoA) of difference was from -2.41 mm to 3.33 mm, with the 95% confidence interval from -2.87 mm to 3.78 mm.Within the limit of the consistency, the maximum moduli was 2.9 mm.CONCLUSION There is a significant discrepancy between the preoperative sonographic and the pathologic size of the papillary thyroid carcinoma, which should be taken into account in clinical practice.

OBJECTIVE To investigate the expression of serum miR-222-3p in papillary thyroid carcinoma and its clinical significance.METHODS Total RNA in serum was extracted from 121 patients of papillary thyroid carcinoma and benign thyroid diseases.The reverse transcription quantitative real-time polymerase chain reaction(qRT-PCR) method was used to detect the expression of miR-222-3p,and then the potential correlation between serum miR-222-3p and clinical pathological characteristics of papillary thyroid carcinoma was analyzed.The receiver operating characteristic area under the curve(ROCAUC) and their index for diagnosis evaluation were also calculated.RESULTS The median expression level of serum miR-222-3p in papillary thyroid carcinoma patients was significantly higher than that of control group (2.2188 vs 0.7022,P=0.002).Although the expressions of serum miR-222-3p was not associated with the gender,age,capsule invasion,TNM stage,but it was positively correlated with tumor size,bilateral involvement,lesion quantity and lymph node status.ROC curve analysis showed that the specificity and sensitivity of the miR-222-3p diagnosis of papillary thyroid cancer were 79.75％ and 61.90％,respectively,while the ROC-AUC was 0.717.CONCLUSION The serum miR-222-3p is over expressed in papillary thyroid carcinoma and its expression is significantly correlated with tumor progression.It will be helpful for PTC diagnosis.

OBJECTIVE To explore the feasibility of detection for mutated BRAF V600E gene based on amplification refractory mutation system(ARMS),and to evaluate its clinical significance of BRAF V600E gene mutation in thyroid nodules.METHODS The method of ARMS was used to detect BRAF V600E mutation status in 179 patients with PTC and 115 patients with benign lesions.The diagnosis index of BRAF V600E mutation status for identifying the nature of the thyroid nodule was calculated.The potential correlation between BRAF V600E mutation and PTC clinicpathological characteristics was also analyzed.RESULTS Detection of BRAF V600E mutation status in thyroid lesions based on ARMS was feasible and believable.The positive rate of mutated BRAF V600E gene in PTC was 82.68％,whereas the rate in benign lesions was only 1.74％,indicating statistical differences between the two groups(x2=183.568,P＜0.01).The diagnostic sensitivity of BRAF V600E mutation was 82.68％,specificity was 98.26％,accuracy was 88.76％,and Youden index was 0.8094.There was no associations between the BRAF V600E mutation status and PTC clinicpathological characteristics(eg.gender,age,tumor size,numbers of lesions,bilateral lesions,extrathyroidal extension and lymph node metastasis).CONCLUSION Detection of BRAF V600E mutation based on ARMS has higher sensitivity and specificity in distinguishing PTC from benign lesions,indicating BRAF V600E gene is an ideal marker of PTC for clinical early diagnosis.

Objective To assess the value of CT in identification and diagnosis of benign and malignant calcified thyroid nodules.Methods Retrospective analysis was performed on the CT data of 313 surgically and pathologically confirmed cases with 378 calcified nodules.Based on the size,morphology,and number,calcification was divided into microcalcification (d≤2 mm and axis displayed in only one cross-section),coarse calcification (d＞2 mm or displayed in two or more cross-sections),annular calcification (arc or annular),and multiple microcalcifications (solitary multiple microcalcification without a soft tissue lump);a distribution of microcalcification,coarse calcification,and annular calcification as well as a clearer enhanced periphery or internal calcification than nonenhanced data in benign and malignant thyroid nodules were observed.Results The 378 nodules consisted of 259 benign nodules (68.5％) (all were nodular goiters) and 119 malignant nodules (31.5％) (including 111 papillary thyroid carcinomas,4 follicular carcinomas,3 medullary thyroid carcinomas and 1 lymphoma).Microcalcification was more common in malignant nodules (MNs) than in benign nodules (BNs),with a rate of 43.6％ vs 12.4％,respectively (P≤0.05),and its sensitivity,specificity,positive predicted value,and negative predicted value were 42.9％,87.6％,61.4％ and 76.9％,respectively.Coarse calcification,annular calcification,and clearer enhanced periphery or internal calcification than nonenhanced data were more common in BNs than in MNs,with rates of 52.9％ vs 20.2％ (P≤0.05),66.0％ vs 42.0％ (P≤0.05) and 43.2％ vs 19.3％ (P≤0.05),respectively,whose sensitivity,specificity,positive predicted value and negative predicted value were 66.0％ vs 22.4％ vs 43.2％,58.0％ vs 86.6％ vs 80.7％,77.4％ vs 78.4％ vs 83％,and 43.9％ vs 33.9％ vs 39.8％,respectively.Two multiple microcalcifications without a soft tissue lump were MNs (papillary thyroid carcinoma).Conclusions Microcalcification and multiple calcifications are conducive to the diagnosis of MNs,whereas coarse calcification,annular calcification,and clearer enhanced periphery or internal calcification than nonenhanced data benefit the diagnosis of BNs,but the low specificity and high false positive rate suggest that the judgment of BNs or MNs should not depend on coarse calcification alone.