Comprehensive analysis of clinicopathologic and sonographic features in thyroid cancer with skip lymph node metastasis: establish and assessment of a prediction nomogram

Abstract Lateral Lymph Node Metastasis (LLNM) is common in Papillary Thyroid Carcinoma (PTC) and is associated with a poor prognosis. LLNM without central lymph node metastasis as skip metastasis is not common. We aimed to investigate clinicopathologic and sonographic risk factors for skip metastasis in PTC patients, and to establish a nomogram for predicting the possibility of skip metastasis in order to determine the therapeutic strategy. We retrospectively reviewed the data of 1037 PTC patients who underwent surgery from 2016 to 2020 at a single institution. Univariate and multivariate analyses were used to identify the clinicopathologic and preoperative sonographic risk factors of skip metastasis. A nomogram including the risk factors for predicting skip metastasis was further developed and validated. The incidence of skip metastasis was 10.7%. The univariate and multivariate analyses suggested that gender (p = 0.001), tumor location (p = 0.000), extrathyroidal extension (p = 0.000), and calcification (p = 0.000) were independent risk factors. For papillary thyroid microcarcinoma, tumor location (p = 0.000) and calcification (p = 0.001) were independent risk factors. A nomogram according to the clinicopathologic and sonographic predictors was developed. The receiver operating characteristic curve indicated that AUC was 0.824 and had an excellent consistency. The calibration plot analysis showed a good performance and clinical utility of the model. Decision curve analysis revealed it was clinically useful. A nomogram for predicting the probability of skip metastasis was developed, which exhibited a favorable predictive value and consistency. For the female PTC patient, tumor located at the upper pole is more likely to have skip metastasis. Surgeons and sonographers should pay close attention to the patients who have the risk factors. Evidence level: This article's evidence level is 3. Level 3 evidence is derived from nonrandomized, controlled clinical trials. In this study, patients who receive an intervention are compared to a control group. Authors may detect a statistically significant and clinically relevant outcome.

Predictive factors and risk analysis of recurrent laryngeal nerve invasion in papillary thyroid carcinoma ≤ 1 cm

ABSTRACT Objective: The recurrent laryngeal nerve (RLN) may be involved by papillary thyroid carcinoma ≤ 1 centimeter (PTC ≤ 1 cm). Current study investigated the predictive factors of RLN invasion in PTC ≤ 1 cm, the risk factors of disease recurrence in RLN invaded cases and the results of surgical management for RLN invasion. Materials and methods: Data of 374 PTC ≤ 1 cm patients were retrospectively collected. We performed univariate and multivariate analysis to identify predictive factors of RLN invasion and risk factors of disease recurrence. The abilities of factors in predicting RLN invasion were evaluated. Surgical outcomes and recurrence free survival (RFS) of patients were analyzed. Results: A total of 28 patients suffered RLN invasion, among which seven had disease recurrence. Preoperative vocal cord palsy (VCP), gross extrathyroidal extension, larger tumor size and tumor on the dorsal side of thyroid were verified as predictive factors of RLN invasion. RLN involved patients had poorer RFS, but better than those who also had upper-aerodigestive tract invasion. Upper-aerodigestive tract invasion, lateral neck lymph nodes metastasis (LNM) and BRAF V600E mutation were independent risk factors of disease recurrence in RLN invaded cases. Tumor shaving showed better RLN function preservation without increasing recurrent risk. Conclusions: Current study confirmed the rarity of RLN invasion in PTC ≤ 1 cm. Various aggressive features were verified as predictive factors of RLN invasion. Tumor shaving showed superiority in preserving nerve function without increasing recurrent risk. Special attentions should be paid for disease recurrence when RLN invasion accompanied by upper-aerodigestive tract invasion, lateral neck LNM or BRAF V600E mutation.

Comparison of prophylactic ipsilateral and bilateral central lymph node dissection in papillary thyroid carcinoma: a meta-analysis

Abstract Objective: The scope of surgical resection for paratracheal (level VI) lymph nodes in patients with Papillary Thyroid Carcinoma (PTC) remains debatable. The aim of our study was to evaluate the effectiveness and safety of prophylactic ipsilateral Central Neck lymph node Dissection (CND) versus bilateral CND at the time of total thyroidectomy for Clinically Node-negative (cN0) unilateral PTC. Methods: A systematic retrieval of electronic databases, including Pubmed, Web of Science, and the China Journal Net, was conducted from January 1990 to September 2021. Outcome data of interest included transient hypoparathyroidism, permanent hypoparathyroidism, transient Recurrent Laryngeal Nerve (RLN) injury, permanent RLN injury and local recurrence. We constructed the summary Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for every study with either fixed or random effect models. Results: A full total of 1792 patients from 6 studies were enrolled. Our meta-analysis showed that transient hypoparathyroidism was significantly more frequent in bilateral CND group (OR = 0.58; 95% CI 0.44-0.76). The prevalence of permanent hypoparathyroidism was significantly higher in bilateral CND group patients compared to those in ipsilateral CND group (OR = 0.26; 95% CI 0.15-0.45). On the other hand, our meta-analysis indicated that there were no significant differences in the incidence of transient RLN injury, permanent RLN injury and local recurrence. Conclusions: Compared with bilateral CND, the rate of temporary and permanent hypoparathyroidism in ipsilateral CND is lower, but the local recurrence is similar. It may be presumptuous to suggest that ipsilateral CND is an adequate treatment for cN0 unilateral PTC.

Correlation analysis of TPO antibody and thyroglobulin antibody with clinicopathological features of PTC / 中华内分泌外科杂志

Objective:To explore and analyze the correlation between thyroid peroxidase (TPO) and thyroglobulin (Tg) in patients with papillary thyroid carcinoma (papillary thyroid carcinoma, PTC) and to provide a more reasonable plan for the clinical diagnosis and treatment of patients.Methods:A retrospective analysis was made of 142 PTC patients who underwent surgical resection from Jun. 2019 to Jun. 2022 in the Oncology Department of Wenzhou Hospital of Traditional Chinese Medicine. 115 patients were selected, including 25 males (21.74%), and 90 females (78.26%), and the average age was (43.48±9.74) years old. The medical records, pathology reports, and demographic characteristics and pathological characteristics were collected. Immunohistochemical staining was used to detect the expression of TPO and Tg in PTC tissues, which were divided into positive and negative groups. Multifactorial Logistic regression analysis was used to analyze its relationship with clinicopathological characteristics and prognosis of patients.Results:The negative rate of TPO was 95.45% (105 cases). Univariate analysis showed that the tumor diameter ( t=5.746), lymph node metastasis, and the proportion of PT1 patients were significantly different between the two groups ( P<0.05), the TPO negative group was significantly higher than the positive group. Multivariate logistic regression analysis found that tumor diameter, lymph node metastasis, and proportion of PT1 patients were independent factors (95% CI=2.367-5.365, 1.101-2.738, 1.103-2.589, P<0.05). The positive rate of Tg was 77.41% (89 cases). Univariate analysis showed the proportion of people with BMI ≥ 25 ( χ2=11.180), tumor diameter ( t=2.117), and intracapsular invasion ( χ2=8.354), extrathyroidal invasion, lymph node metastasis ( χ2=27.740), and proportion of PT1 patients were significantly different between the two groups ( P<0.05). Multivariate logistic regression analysis found BMI≥25, intracapsular invasion, extrathyroidal invasion, lymph node metastasis, proportion of PT1 patients were independent factors affecting Tg in patients with PTC (95% CI=3.845-11.735, 1.485-2.983,1.171-2.762,4.083-16.526,1.003-2.174, P<0.05). There was a negative correlation between the expression of TPO and Tg in PTC ( r=-0.498, P<0.001) . Conclusion:TPO and Tg are highly correlated with tumor lymphatic metastasis, pathological grade, tumor diameter and tumor invasion range in patients with papillary thyroid carcinoma, and the expression of the two is negatively correlated, which can be used as effective indicators for evaluating the prognosis of patients.

Advances in diagnosis and treatment of medullary thyroid carcinoma complicated with papillary carcinoma / 中华内分泌外科杂志

Thyroid cancer is the most common malignant tumor of the endocrine system, and its incidence is increasing year by year showing younger trend. The pathological types of thyroid cancer are papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) are the two common types of thyroid cancer. Since MTC and PTC have different biological origins, invasiveness and prognosis. Therefore, the occurrence of both medullary carcinoma and papillary carcinoma is very rare and rarely reported in China and abroad and the treatment is challenging. In this paper, we review the pathogenesis, ancillary tests, diagnosis and treatment of this disease, with the aim of providing reference for clinical treatment of patients with medullary thyroid carcinoma complicated by papillary carcinoma.

Value of CT-based model in differential diagnosis of papillary thyroid carcinoma / 中华内分泌外科杂志

Objective:To evaluate the differential diagnosis of papillary thyroid carcinoma (PTC) based on CT signs.Methods:Retrospective analysis was performed on 156 patients with PTC confirmed by surgery and pathology in the Imaging Department of Jinhua Hospital Affiliated to Zhejiang University College of Medicine from Jan. 2017 to Jan. 2022 as PTC group, and 132 patients with nodular goiter (NG) as NG group. There were 112 females and 45 males in the PTC group. The age was (49.32±3.25) years. There were 104 females and 52 males in NG group. The age was (50.12±3.27) years. Preoperative plain and contrast-enhanced CT scans were performed to analyze the features of the images, and univariate analysis was performed on the morphologic features, high tension, plain "bite cake sign" , enhanced "bite cake sign" , microcalcification, blurred/reduced scope after enhancement, nodule density, and asymmetric diffuse enlargement of thyroid gland. Statistically significant factors were included in the multivariate Logistic regression analysis, and the differential model of PTC was established according to the selected risk factors. The value of the model in the differential diagnosis of PTC was evaluated by ROC curve.Results:The percentages of irregular shape, no high tension, plain scan "bite cake sign" , enhanced "bite cake sign" , microcalcification, enhanced blur/reduced scope, uniform nodule density, completely slightly low tissue density, no cystic degeneration, and asymmetric thyroid diffuse enlargement in PTC group were higher than those in NG group ( χ2=161.014, 3.387, 95.885, 151.331, 60) . 200, 18.104, 105.260, 16.855, 89.064, 16.913, P<0.05) , suggesting that the above CT signs had important diagnostic value in differentiating PTC and NG. Among the single CT signs, plain scan "bite cake sign" had the highest sensitivity, specificity and accuracy. The sensitivity of PTC diagnosis combined with other signs gradually decreased, while the specificity gradually increased. At the same time, plain scan "bite cake sign" and microcalcification signs had high specificity in PTC identification, and the specificity of PTC identification reached 100.00% when any 4 or more signs were present. Multivariate Logistic regression analysis. The results showed that irregular morphology ( OR=15.831, 95% CI: 7.444-33.670) , high tension ( OR=0.162, 95% CI: 0.108-0.242) , plain scan "bite cake sign" ( OR=5.601, 95% CI: 2.691-11.659) , microcalcification ( OR=4.031, 95% CI: 2.062-7.880) , edge blur/range reduction after enhancement ( OR=4.761, 95% CI: 3.126-7.260) , uniform density of nodules ( OR=4.778, 95% CI: 3.299-6.290) and increased asymmetric diffusion ( OR=3.758, 95% CI: 1.911-7.391) were important signs for distinguishing NG from PTC ( P<0.05) . The above factors were incorporated into the Logistic regression equation to construct the model, and then the ROC curve was drawn. The results showed that the area under the curve of the model established based on CT signs was 0.94 (0.925-0.983) , and the sensitivity and specificity were 90.37% and 91.45%, respectively. Conclusions:In CT signs, irregular shape, high tension, "biting cake sign" on plain scan, microcalcification, blurred edge/scope reduction signs after enhancement, and uniform nodule density are important signs for differentiating papillary thyroid carcinoma from nodular goiter. The constructed model has good predictive value for identifying papillary thyroid carcinoma.

Expression of HLA-G in the peripheral blood and cancerous tissues of patients with papillary thyroid cancer / 中华内分泌外科杂志

Objective:To examine the expression of human leukocyte antigen G (HLA-G) in the peripheral blood and cancerous tissues of patients with papillary thyroid carcinoma (PTC) .Methods:The expression of soluble HLA-G (sHLA-G) in the peripheral blood of 50 individuals with PTC (PTC group) , 25 patients with benign thyroid tumors (BTT group) from Department of Thyroid and Breast Surgery, Beilun branch of the First Affiliated Hospital of Zhejiang University and 20 healthy controls (healthy control group) from physical examination center was assessed by ELISA. Immunohistochemical examination of HLA-G levels was also performed on tissue specimens from patients in the PTC and BTT groups, and their correlation with clinicopathological features of thyroid cancer was analyzed. SPSS 19.0 was used for statistical analysis. The measurement data of normal distribution were tested by two independent samples t test. Chi square test was used to compare the rates between the two groups. Results:The sHLA-G expression in peripheral blood was 21.33 (±5.54) , 22.73 (±4.99) , and 18.29 (±4.43) ng/mL in the preoperative PTC, BTT, and healthy control groups, respectively. Compared to the healthy group, sHLA-G levels were considerably higher in the PTC and BTT groups, with statistically significant differences (totally P < 0.05) . There was no significant difference in statistically sHLA-G levels between the BTT and PTC groups ( P > 0.05) . The positive HLA-G expression rate in PTC tissues was 78% (39/50) . There was no evidence of HLA-G expression in common tissues adjacent to PTC. HLA-G was not expressed in benign tumors. HLA-G was linked with the PTC tumor diameter, and the rate of positive expression was considerably greater with tumor diameters >1 cm than with those ≤1 cm ( P<0.05) . The rate of HLA-G positive expression was not significantly correlated with sex, age, multiple foci, extra-glandular invasion, metastasis of lymph nodes, or the TNM stage in PTC individuals ( P > 0.05) . Conclusions:HLA-G is significantly expressed at high levels in PTC tissues, is correlated with the tumor diameter, and may probably have a significant role in this disease. Peripheral blood sHLA-G may be associated with thyroid tumorigenesis, and its value in PTC requires further verification.

Department of Clinicopathological analysis of papillary thyroid carcinoma with Hashimoto’s thyroiditis / 中华内分泌外科杂志

Objective:To discuss the effect of Hashimoto’s thyroiditis (HT) on papillary thyroid carcinoma (РТС) .Methods:The clinical features and pathological characteristics of 682 patients who underwent surgical treatment for the first time from Sep. 1st,2019 to May. 1st, 2021 in Department of Thyroid, Breast and Hernia Surgery, and confirmed by postoperative pathology as papillary thyroid carcinoma were retrospectively analyzed. There were 189 male patients, and 493 female patients, 529 patients < 55 years old and 153 patients ≥55 years old. 476 patients were classified as PTC group and 206 patients as PTC combined with HT group. Chi square test was used to compare the difference between two groups in gender, age, thyroglobulin antibody, thyroid stimulating hormone, thyroid peroxidase antibodies, thyroid peroxidase, number of lesions, metastasis lymph node in central region, thyroid stimulating hormone receptor antibody, carcinoembryonic antigen, whether microcarcinoma, vascular invasion, glandular outside violation, capsule and lateral transfer analysis, ultrasonic calcification, etc. At the same time, all patients were divided into the group without central lymph node metastasis (345 cases) and the group with central lymph node metastasis (337 cases) . The χ 2 test was used to compare the differences between the two groups in terms of sex, age, number of lesions, microcarcinoma, vascular invasion, extradular invasion, capsular invasion, lateral cervical lymph node metastasis, ultrasonic calcification and so on, so as to analyze the differences in clinical characteristics between the two groups. Results:There were 206 cases (30.21%) in PTC combined with HT group and 476 cases (69.79%) in PTC without HT group. There were significant differences in gender (12/194 vs 177/299) ( P=0.000) , age (175/31 vs 354/122) ( P=0.002) , TgAb (115/91 vs 455/21) ( P=0.000) ,TSH (13/175/18 vs 33/429/14) ( P=0.004) , TPOAb (90/116 vs 422/54) ( P=0.000) , number of lesions (114/92 vs 325/151) ( P=0.001) and lymph node metastasis in central area (87/119 vs 250/226) ( P=0.014) between the two groups ( P < 0.05) , but there were no significant differences in TRAb (196/10 vs 461/15) ( P=0.171) , CEA (205/1 vs 469/7) ( P=0.478) , microcarcinoma (136/70 vs 309/167) ( P=0.781) , vascular invasion (4/202 vs 16/460) ( P=0.446) , extraglandular invasion (52/154 vs 108/368) ( P=0.470) , capsule invasion (149/57 vs 358/118) ( P=0.429) , lateral neck lymph node metastasis (31/175 vs 72/404) ( P=0.979) or ultrasonic calcification (157/49 vs 392/84) ( P=0.063) . Compared with PTC group, PTC combined with HT group had the characteristics of more women, younger age, high TgAb, high TSH, high TPOAb, multiple lesions and high proportion of non central lymph node metastasis. There were 345 cases (50.59%) without central lymph node metastasis and 337 cases (49.41%) with central lymph node metastasis. Gender (71/274 vs 118/219) ( P=0.000) , age (246/99 vs 283/54) ( P=0.000) , exadular invasion (66/279 vs 94/243) ( P=0.007) , number of lesions (240/105 vs 199/138) ( P=0.004) , microcarcinoma (259/86 vs 186/151) ( P=0.000) , calcification on ultrasound (250/95 vs 299/38) ( P=0.000) , and HT (119/226 vs 87/250) ) ( P=0.014) had statistical significance ( P<0.05) but had no statistical significance in capsule invasion (250/95 vs 257/80) ( P=0.256) or vascular invasion (10/335 vs 10/327) ( P=0.958) . In addition, patients in the group with central lymph node metastasis were more male, younger, with multiple lesions, exadenocarcinoma, less microcarcinoma, and calcification on ultrasound without hashimoto. Univariate analysis showed that gender, age, number of lesions, extraglandular invasion, calcification, microcarcinoma and Hashimoto had significant effects on lymph node metastasis in the central region; Multivariate analysis showed that the presence of microcarcinoma, ultrasonic calcification, Hashimoto and the number of lesions were independent risk factors for central lymph node metastasis. Conclusion:HT may promote the occurrence of PTC, but at the same time inhibit its development, so that PC patients with HT have a better prognosis.

Preliminary study on excitation, detection and identification of parathyroid glands autofluorescence using fluorescence laparoscopic system / 中华内分泌外科杂志

Objective:To evaluate the excitation and identification of parathyroid autofluorescence in thyroid surgery by a fluorescence laparoscopic system.Methods:The clinical data of 6 patients with papillary thyroid carcinoma who underwent Laparoscopic thyroid surgery at the Second Affiliated Hospital of Guangxi Medical University from Mar. 2022 to Apr. 2022 were collected. The autofluorescence of the parathyroid glands was detected and identified by the OptoMedic fluorescence laparoscopic system during the operation. A rapid frozen sections pathological examination of possible parathyroid tissue with autofluorescence was performed to determine whether it was parathyroid tissue.Results:Parathyroid autofluorescence with different intensities was visualized intraoperatively in all 6 patients, and it was confirmed as parathyroid tissue by rapid frozen pathological section.Conclusions:The parathyroid gland has a unique autofluorescence feature. Using this feature to identify, locate and protect the parathyroid gland during surgery can help reduce the complications of parathyroid injury.

A nomograph model for prediction of central lymph node metastasis of papillary thyroid carcinoma / 预防医学

Objective@#To establish a nomograph model for prediction of cervical central lymph node metastasis (CLNM) among patients with thyroid papillary carcinoma (PTC), so as to provide the evidence for designing personalized treatment plans for PTC.@* Methods @#The data of patients that underwent thyroidectomy and were pathologically diagnosed with PTC post-surgery in the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from 2018 to 2021 were collected. Patients' data captured from 2018 to 2020 and from 2021 were used as the training set and the validation set, respectively. Predictive factors were screened using a multivariable logistic regression model, and the nomograph model for prediction of CLNM risk was established. The predictive value of the model was evaluated using the receiver operating characteristic (ROC) curve and the adjusted curve.@* Results@#Totally 1 820 PTC cases were included in the training set, including 458 cases with CLNM (25.16%), and 797 cases in the validation set, including 207 cases with CLNM (25.98%). The prediction model is p=ey/(1+ey), y=0.761 + 0.525 × sex + (-0.039) ×age + 0.351 × extrathyroid invasion + 0.368 × neck lymph node enlargement + 1.021×maximum tumor diameter + (-0.009) × TT4 + (-0.001) × anti-TPOAb. The area under the ROC curve was 0.732 for the training set and 0.731 for the validation set, and Hosmer-Lemeshow test showed a good fitting effect (P=0.936, 0.722).@*Conclusion@# The nomograph model constructed in this study has a high predictive value for CLNM among patients with PTC.

Comparison of somatic gene mutation between 114 cases with different subtypes of thyroid papillary carcinoma and the TCGA database / 预防医学

Objective@#To compare the difference in somatic gene mutation of PTC subtypes between 114 patients with papillary thyroid carcinoma (PTC) and The Cancer Genome Atlas (TCGA) database.@*Methods@#Totally 114 PTC patients admitted to The First Affiliated Hospital of Nanjing Medical University were recruited. The 18 hotspot genes associated with thyroid cancer were detected in thyroidectomy specimens were using next generation sequencing. PTC data were downloaded from the TCGA database in the cBioPortal website, and the difference in the somatic gene mutation was compared between 114 PTC patients and the TCGA database@*Results@#The 114 PTC patients included 73 women (64.04%) and had a mean age of (39.23±13.18) years. The prevalence of BRAF V600E (66.67% vs. 48.68%), TERTp (3.51% vs. 0.41%), PDGFRA (1.75% vs. 0%), PTEN (3.51% vs. 0.41%) and TP53 gene mutations (4.39% vs. 0.61%) was significantly higher among the 114 PCT patients than in the TCGA database (P<0.05). The prevalence of BRAF V600E (80.88% vs. 54.99%), TP53 (7.35% vs. 0.57%) and TSHR gene mutations (2.94% vs. 0%) was significantly higher in classical PTC(CPTC) patients than in the TCGA database, and the prevalence of BRAF V600E (36.84% vs.13.86%) and TERTp gene mutations (10.53% vs. 0%) was significantly higher in follicular variant PTC (FVPTC) patients than in the TCGA database. According to the American Thyroid Association Risk Stratification of Thyroid Cancer Recurrence, the prevalence of BRAF V600E and TP53 gene mutations was 77.14% and 8.57% among moderate-risk CPTC patients, the prevalence of BRAF V600E gene mutation was 27.27% among low-risk FVPTC patients, and the prevalence of TERTp gene mutation was 33.33% among moderate-risk FVPTC patients, which were all higher than in the TCGA database (55.10%, 0%, 3.28%, and 0%, respectively; P<0.05).@*Conclusion@#There are significant differences in the type and rate of somatic gene mutations between 114 PTC patients and the TCGA database.

circ_0092315 Promotes Proliferation and Invasion of Papillary Thyroid Carcinoma Cells via Regulating microRNA-1256/High Mobility Group A2 axis / 中国医学科学院学报

Objective To investigate the role and mechanism of circ_0092315 in the proliferation and invasion of papillary thyroid carcinoma cells. Methods The expression of circ_0092315 in papillary thyroid carcinoma cells was examined by real-time fluorescence quantitative PCR.The proliferation and invasion of TPC-1 cells was assessed by CCK-8 and Transwell assays.The protein level of high mobility group A2 (HMGA2) was determined by Western blotting.The regulatory relationship of circ_0092315,microRNA-1256 (miR-1256),and HMGA2 was explored by bioinformatics tools,dual-luciferase reporter assay,real-time fluorescence quantitative PCR,and Western blotting. ++++Results circ_0092315 was overexpressed in papillary thyroid carcinoma cells (all P<0.001).circ_0092315 promoted the proliferation and invasion of TPC-1 cells (all P<0.001).The transfection of si-circ_0092315 up-regulated the expression of miR-1256 (P<0.001),and miR-1256 inhibitor up-regulated the protein level of HMGA2 (P<0.001). ++++Conclusion circ_0092315 is overexpressed in TPC-1 cells and it promotes the proliferation and invasion of TPC-1 cells by regulating the miR-1256/HMGA2 axis.

Clinical significance of multigene assay in papillary thyroid carcinoma / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the clinical significance of multigene assay in papillary thyroid carcinoma（PTC）. Methods:Patients who underwent thyroidectomy in a tertiary hospital from August 2021 to May 2022 were enrolled. The eight-gene panel was used to detect the tumor tissue of patients, and the correlation between gene mutations and clinical features was analyzed. Results:Among 161 patients, mutation rate of BRAF V600E, RET/PTC1 and TERT promotor were 82.0%, 6.8% and 4.3%, respectively. BRAF V600E mutation was more common in male patients（P=0.023）. TERT promotor-mutated tumors had a large diameter（P=0.019）, a high proportion of multifocal lesions（P=0.050）, and a large number of lymph node metastases（P=0.031）. Among 89 patients who completed preoperative BRAF detection, there was a strong consistency between the preoperative aspiration test and postoperative panel（Cohen κ=0.694, 95%CI: 0.482-0.906, P<0.01）. In the hematoxylin-eosin sections obtained from 80 patients, BRAF V600E was still the main type of gene mutation, and the classical/follicular type was more distributed. TERT promotor and RET/PTC1 mutation were the main genetic events for tall-cell/columnar/hobnail type and diffuse sclerosing type, respectively. One-way ANOVA showed that there were differences in diagnosis age（P=0.029） and tumor size（P<0.01） among different pathological types. Conclusion:As a simple and feasible clinical detection method for PTC, the multigene assay can supplement the identification of important genetic events other than BRAF V600E, and provide more prognostic information and follow-up hints for postoperative patients.

Iodine nutritional status is not a direct factor in the prevalence of the BRAFV600E mutation in papillary thyroid cancer

ABSTRACT Objectives: Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. Of the iodine-metabolizing genes, BRAFV600E is a highly specific target for PTC and may have a reciprocal causative relationship with iodide-metabolizing genes. Materials and methods: In this study, we performed a data analysis of selected quantitative studies to determine the relationship between iodine nutritional status and the prevalence of the BRAF600E mutation in patients with PTC. Five studies were selected for meta-analysis based on the selection criteria. Results: A total of 2,068 patients were divided into three groups: low (urinary iodine concentration [UIC] < 100 μg/L), adequate (UIC 100-200 μg/L), and high (UIC ≥ 200 μg/L). The results were obtained using RevMan software, and the pooled odds ratios (ORs) were calculated using Mantel-Haenszel statistics with a 95% confidence interval (CI). The OR for the prevalence of the BRAFV600E mutation between the high and adequate groups was 1.25 (95% CI 0.64-2.43, p = 0.51), and the OR between the low and adequate groups was 0.98 (95% CI 0.42-2.31, p = 0.96). The BRAFV600E mutation risk did not change significantly at different levels of iodine nutrition (p = 0.33) in statistical analyses. Conclusion: We conducted preliminary research on dietary iodine intake and the BRAFV600E mutation in PTC. The results suggested that abnormal iodine intake might not directly influence the prevalence of the BRAFV600E mutation in these patients. Further research into the associations between dietary iodine intake and the BRAFV600E mutation in PTC, including the underlying mechanisms, is required.

Asociación entre tiroiditis linfocítica crónica y carcinoma papilar de tiroides: Revisión sistemática y metaanálisis de estudios en especímenes quirúrgicos / Association between chronic lymphocityc thyroiditis and papillary thyroid carcinoma: Systematic review and meta-analysis of studieson surgical specimens

Introducción. Existen resultados inconsistentes con relación al planteamiento de la hipótesis que sugiere una mayor probabilidad de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos con cambios compatibles con tiroiditis linfocítica crónica. En los metaanálisis existentes se han incluido estudios no comparables metodológicamente y no se proponen claras fuentes de sesgo, justificación para la realización del presente metaanálisis. Métodos. Se realizó una búsqueda bibliográfica en Pubmed y Embase. Fueron obtenidos estudios retrospectivos donde se comparaba la prevalencia de carcinoma papilar de tiroides en especímenes con y sin cambios por tiroiditis linfocítica crónica. La evidencia recolectada fue sintetizada estadísticamente. Resultados. Un total de 22 artículos fueron incluidos. La población estuvo conformada por 63.548 especímenes. El OR combinado fue 1,81 (IC95%: 1,51-2,21). Hubo heterogeneidad entre la distribución de las razones de oportunidad entre los estudios (I2= 91 %; p>0,00001). La forma del gráfico en embudo de los estudios incluidos en el análisis parece estar simétrica, lo que indica la ausencia del sesgo atribuible a los estudios pequeños. Conclusiones. La literatura actual sugiere que existe un mayor riesgo de documentar un carcinoma papilar de tiroides en especímenes quirúrgicos en los que se observan cambios compatibles con tiroiditis linfocítica crónica; sin embargo, existen fuentes de sesgo que no será posible controlar en estudios retrospectivos, por lo que recomendamos estudiar la hipótesis que sugiere una mayor probabilidad de diagnosticar un carcinoma papilar de tiroides en especímenes con cambios compatibles con tiroiditis linfocítica crónica mediante metodologías prospectivas

Introduction. Inconsistent results exist in the literature regarding the hypothesis statement suggesting an increased likelihood of documenting papillary thyroid carcinoma (PTC) in surgical specimens with changes compatible with chronic lymphocytic thyroiditis. Existing meta-analyses have included studies that are not methodologically comparable and do not propose clear sources of bias, thus, this is justification for the present meta-analysis. Methods. A literature search in Pubmed and Embase was performed from January 1, 1950 to December 31, 2020. Retrospective studies comparing the prevalence of papillary thyroid carcinoma in specimens with and without chronic lymphocytic thyroiditis changes were obtained. The collected evidence was statistically analyzed. Results. A total of 22 articles were included. The study population consisted of 63,548 surgical specimens. The pooled OR, based on the studies, was 1.81 (95% CI: 1.51-2.21). There was heterogeneity between the distribution of prevalence ratios and opportunity ratios across studies (I²= 91%; p>0.00001). The funnel plot shape of the studies included in the analysis appears to be symmetrical, indicating the absence of bias attributable to small studies. Conclusions. The current literature suggests that there is an increased risk of documenting papillary thyroid carcinoma in surgical specimens in which chronic lymphocytic thyroiditis-compatible changes are observed; however, there are sources of bias that will not be possible to control for in retrospective studies, so we recommend studying the hypothesis suggesting an increased likelihood of diagnosing PTC in specimens with chronic lymphocytic thyroiditis-compatible changes using prospective methodologies

Treatment strategies for low-risk papillary thyroid carcinoma: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Increasingly sensitive diagnostic methods, better understanding of molecular pathophysiology, and well-conducted prospective studies have changed the current approach to patients with thyroid cancer, requiring the implementation of individualized management. Most patients with papillary thyroid carcinoma (PTC) are currently considered to have a low risk of mortality and disease persistence/recurrence. Consequently, current treatment recommendations for these patients include less invasive or intensive therapies. We used the most recent evidence to prepare a position statement providing guidance for decisions regarding the management of patients with low-risk PTC (LRPTC). This document summarizes the criteria defining LRPTC (including considerations regarding changes in the TNM staging system), indications and contraindications for active surveillance, and recommendations for follow-up and surgery. Active surveillance may be an appropriate initial choice in selected patients, and the criteria to recommend this approach are detailed. A section is dedicated to the current evidence regarding lobectomy versus total thyroidectomy and the potential pitfalls of each approach, considering the challenges during long-term follow-up. Indications for radioiodine (RAI) therapy are also addressed, along with the benefits and risks associated with this treatment, patient preparation, and dosage. Finally, this statement presents the best follow-up strategies for LRPTC after lobectomy and total thyroidectomy with or without RAI.

Active surveillance for low-risk papillary thyroid microcarcinoma: A single center prospective observation study / 中华内分泌代谢杂志

Objective:To evaluate the feasibility, safety and effectiveness of the active surveillance as an alternative to surgery in patients with low-risk papillary thyroid microcarcinoma(PTMC); And to explore potential surgical indicators based on characteristics of patients and medical environment.Methods:A prospective cohort study was conducted in patients with low risk PTMC and received active surveillance management( n=98). Patient adherence, non-progression surgery rates were described, cumulative incidence of tumor growth≥3 mm and tumor volume increase≥50% under ultrasonic monitoring, as well as tumor doubling rate(TDR) were evaluated. Results:A total of 98 patients were enrolled in this prospective cohort. The median age was 39(30, 45) years, and the median baseline diameter of the index tumors was 5.0(3.8, 6.8) mm, with 63.3% of tumors being≤5 mm. After a median 22(12, 44) months follow-up, tumor size growth≥3 mm and tumor volume increase≥50% occurred in 11(11.2%) and 50(51.0%) patients, and no new lymph node metastasis, distant metastasis, and death occurred. Five cases(5.1%) required delayed surgery, and other five non-progression patients opted in surgery based on their own preferences. One patient lost to follow-up. The median post-tumor progression TDRs was significantly lower than that of pre-tumor progression TDRs [size growth per year: -0.09(-0.12, 0.48) vs 0.91(0.86, 1.25), P=0.014, n=8; volume increase per year: 0.29(-0.14, 0.70) vs 1.04(0.66, 2.17), P<0.001, n=39]. After tumor size and volume progression, 62.5% and 43.6% of tumors were remained stable or shrank, respectively. Conclusions:Actived surveillance can be considered as one of the management strategies for low-risk PTMC. Given the differences in population and clinical characteristics, it should be taken in to consideration in developing active surveillance management, such as candidate criteria, follow-up strategies, and intervention indications.

Bilateral renal metastases from papillary thyroid carcinoma: a case report / 中华泌尿外科杂志

Papillary thyroid carcinoma metastasizing to the kidney are extremely rare events, which may easily be misdiagnosed as renal cell carcinoma. The diagnosis needs to be based on immunohistochemical examination. We described a case of renal tumor to be proved renal metastatic carcinoma from thyroid origin by pathological examination. Computed tomography (CT) scan shows metastasis nodules in lungs. Following total thyroidectomy, he underwent iodine-131 ( 131Ⅰ), thyroid hormone and sorafenib to treat thyroid remnant tumor and metastases. Partial nephrectomy was conducted to remove the left renal metastatic carcinoma for preserving normal renal function. Follow-up revealed that partial pulmonary nodule gradually shrunk, and no new metastasis appeared.

Comparison between Ultrasonography and CT in Diagnosis of Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ2=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ 2=82.26,P<0.001;χ2=114.01,P<0.001;χ2=82.26,P<0.001) and accuracy (χ2=20.27,P<0.001;χ2=15.56,P<0.001;χ2=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ2=17.01,P<0.001;χ2=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.

Associations of arsenic and estrogen levels with the risk ofpapillary thyroid carcinoma / 预防医学

Objective@#To examine the associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma, so as to provide insights into prevention of papillary thyroid carcinoma.@*Methods@#Totally 57 patients with papillary thyroid carcinoma admitted to two tertiary hospitals in Urumqi, Xinjiang Uygur Autonomous Region in 2018 were selected as the case group, while 57 subjects with normal thyroid functions during the same period were selected as the control group. Subjects' gender, age, ethnicity, occupation and medical history of thyroid disease were collected using questionnaire surveys. Serum dimethyl arsenic acid (DMA) and monomethyl arsenic acid (MMA) were determined using high-performance liquid chromatography (HPLC) coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS), serum thyroid hormone (TSH) by radioimmunoassay, estradiol (E2) by enzyme-linked immunosorbent assay and estrogen receptor ERα and ERβ by western blotting. The associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma were evaluated using a multivariable logistic regression model.@*Results@#There were 16 males (28.07%) and 41 females (71.93%) in the case group, with a mean age of (42.63±11.01) years, and there were 21 males (36.84%) and 36 females (63.16%) in the control group, with a mean age of (40.89±11.30) years. There were no significant differences between the case and control groups in terms of age (χ2=0.373, P=0.542), gender (χ2=1.000, P=0.317) or ethnic composition (χ2=0.291, P=0.590). The serum levels of TSH [2.85 (1.61) vs. 2.45 (1.79) μmol/L], E2 [74.93 (120.44) vs. 61.60 (37.35) pmol/L], ERα [1.49 (1.13) vs. 0.70 (0.31)], ERβ [1.59 (0.55) vs. 0.72 (0.36)], DMA [116.02 (100.48) vs. 32.33 (56.06) μg/L] and MMA [56.92 (47.90) vs. 27.90 (24.99) μg/L] were all significantly higher in the case group than in the control group (Z=-2.414, -2.292, -4.923, -5.167, -5.448 and -4.019, all P<0.05). Multivariable logistic regression analysis showed DMA (OR=1.013, 95%CI: 1.003-1.024) and E2 levels (OR=1.020, 95%CI: 1.004-1.036) were associated with the risk of papillary thyroid carcinoma.@*Conclusion@#Increased arsenic load and elevated estradiol levels may be associated with the risk of papillary thyroid carcinoma.