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The SUVmax is a measure of FDG uptake and is related with tumor aggressiveness in thyroid cancer, however, its association with molecular pathways is unclear. Here, we investigated the relationship between SUVmax and gene expression profiles in 80 papillary thyroid cancer (PTC) patients. We conducted an analysis of DEGs and enriched pathways in relation to SUVmax and tumor size. SUVmax showed a positive correlation with tumor size and correlated with glucose metabolic process. The genes that indicate thyroid differentiation, such as SLC5A5 and TPO, were negatively correlated with SUVmax. Unsupervised analysis revealed that SUVmax positively correlated with DNA replication(r = 0.29, p = 0.009), pyrimidine metabolism(r = 0.50, p

Objective: The unique metastatic pattern of skip lateral lymph node metastasis (SLLNM) in PTC patients may lead to missed diagnosis of lateral cervical metastatic lymph nodes. Therefore, many different SLLNM prediction models were constructed. In this study, partially eligible models (Hu 2020, Wang 2020, and Zhao 2023 nomograms) were selected for external validation, and then new variables were incorporated for model reconstruction to extend clinical applicability. Methods: 576 PTC patients from our center were selected to evaluate the performance of the three nomograms using the receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA). Three new variables were added to calibrate the model, including assessment of LN status on ultrasound (US-SLLNM), the distance from the tumor to the capsule (Capsular distance), and the number of central lymph node dissections (CLND number). Univariate and multivariate logistic regression analyses were used to screen independent predictors to reconstruct the model, and 1000 Bootstrap internal validations were performed. Results: SLLNM were present in 69/576 patients (12.0%). In external validation, the area under the ROC curves (AUCs) for Hu 2020, Wang 2020, and Zhao 2023 nomograms were 0.695 (95% CI:0.633-0.766), 0.792 (95% CI=0.73-0.845), and 0.769 (95% CI:0.713-0.824), respectively. The calibration curves for the three models were overall poorly fitted; DCA showed some net clinical benefit. Model differentiation and net clinical benefit improved by adding three new variables. Based on multivariate analysis, female, age, and maximum tumor diameter = 10 mm, located at the upper pole, Capsular distance < 0mm, US-SLLNM, CLND number = 5 were identified as independent predictors of SLLNM and were used to construct the new model. After 1000 Bootstrap internal validations, the mean AUC of the model was 0.870 (95% CI:0.839-0.901), the calibration curve was close to the ideal curve, and the net clinical benefit was significant. Conclusion: Overall, these nomograms were well differentiated and provided some net clinical benefit, but with varying degrees of underestimation or overestimation of the actual risk and high false-negative rates. New dynamic nomogram was constructed based on the addition of new variables and larger samples, showing better performance. [ABSTRACT FROM AUTHOR]

Objective: The association between autoimmunity-related tissue injury and thyroid cancer development remains an area of interest. Evidence suggests that patients with Graves disease (GD) may have an elevated risk for differentiated thyroid cancer. Multicenter studies are needed to gain insight into the correlates of papillary thyroid carcinoma (PTC) identified in this particular group of patients. This study aimed to investigate the prevalence of PTC and synchronous thyroid nodules in thyroidectomy specimens from GD patients in an endemic goiter region. Material and Methods: A retrospective review of institutional pathology records at two tertiary care centers identified 237 surgically treated patients with GD. Patients were categorized as having nodular Graves disease (N-GD) if synchronous nodular thyroid was identified by ultrasonography, while those without synchronous thyroid nodules were categorized as non-nodular or simple Graves disease (S-GD). The prevalence of PTC, histopathological correlates, and demographic characteristics were recorded and compared between groups N-GD and S-GD. Results: One hundred thirty-one and 106 patients were assigned to N-GD and S-GD, respectively. The mean age was significantly higher in N-GD (mean 45.52 years) compared to S-GD (mean 35.18 years) (p<0.001). The overall frequency of PTC was 36.3% (86/237) in the entire cohort. PTC was identified in 48.1% (63/131) of N-GD and 21.7% (23/106) of S-GD (p<0.001). Subcentimeter tumors constituted the majority of cases in both groups (76.2% in N-GD and 82.6% in S-GD) (p>0.05). The group of S-GD was enriched in BRAF-like PTCs, whereas N-GD had equal distribution for RAS- and BRAF-like tumors. Conclusion: This study underscores that the majority of PTCs encountered in GD were enriched in low-risk subcentimeter PTCs with a prevalence that varies depending on the presence of underlying nodular thyroid tissue. [ABSTRACT FROM AUTHOR]

Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1–4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC. [ABSTRACT FROM AUTHOR]

We herein present a patient initially suspected of multiple lytic skeletal metastasis of unknown primary on anatomical imaging. Metabolic imaging by [18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) detected focal [18F]FDG uptake in the right thyroid nodule, mild [18F]FDG uptake in soft tissue lesion in the left inferior parathyroid region, and multiple nonavid osteolytic skeletal lesions. Fine-needle aspiration cytology of the right thyroid nodule showed papillary thyroid carcinoma (PTC). The patient had raised serum parathyroid hormone and serum calcium levels, suggesting parathyroid disease. [18F]-sodium fluoride (NaF)-PET/CT showed a metabolic superscan pattern of hyperparathyroidism with brown tumors rather than metastatic lytic skeletal lesions. Patient underwent total thyroidectomy and bilateral central compartment clearance, along with soft tissue lesion resection in the left inferior parathyroid region. Finally, histopathology confirmed PTC classical variant with no aggressive histology features (pT1N0) for thyroid nodule and parathyroid adenoma for soft tissue lesion in the left inferior parathyroid region. The findings of the [18F]FDG and [18F]NaF-PET/CT imaging were helpful for making a final diagnosis of synchronous thyroid cancer and parathyroid adenoma, which in turn guided the appropriate treatment strategy. [ABSTRACT FROM AUTHOR]

It is crucial to preoperatively diagnose lateral cervical lymph node (LN) metastases (LNMs) in papillary thyroid carcinoma (PTC) patients. This study aims to develop deep-learning models for the automatic segmentation and classification of LNM on original ultrasound images. This study included 1000 lateral cervical LN ultrasound images (consisting of 512 benign and 558 metastatic LNs) collected from 728 patients at the Chongqing General Hospital between March 2022 and July 2023. Three instance segmentation models (MaskRCNN, SOLO and Mask2Former) were constructed to segment and classify ultrasound images of lateral cervical LNs by recognizing each object individually and in a pixel-by-pixel manner. The segmentation and classification results of the three models were compared with an experienced sonographer in the test set. Upon completion of a 200-epoch learning cycle, the loss among the three unique models became negligible. To evaluate the performance of the deep-learning models, the intersection over union threshold was set at 0.75. The mean average precision scores for MaskRCNN, SOLO and Mask2Former were 88.8%, 86.7% and 89.5%, respectively. The segmentation accuracies of the MaskRCNN, SOLO, Mask2Former models and sonographer were 85.6%, 88.0%, 89.5% and 82.3%, respectively. The classification AUCs of the MaskRCNN, SOLO, Mask2Former models and sonographer were 0.886, 0.869, 0.90.2 and 0.852 in the test set, respectively. The deep learning models could automatically segment and classify lateral cervical LNs with an AUC of 0.92. This approach may serve as a promising tool to assist sonographers in diagnosing lateral cervical LNMs among patients with PTC. • Accurate segmentation and classification of lateral lymph nodes are paramount for papillary thyroid carcinoma patients. • The segmentation performance of the deep-learning model was superior to the sonographer. • The deep-learning model showed the better diagnosis performance than the sonographer. [ABSTRACT FROM AUTHOR]

The function and mechanism of SYTL5 in papillary thyroid carcinoma (PTC) are still unclear. In this research, we found that SYTL5 was significantly overexpressed in PTC tissues compared with normal thyroid tissues. SYTL5 downregulation significantly weakened the proliferative, migratory, and invasive abilities of PTC cells. In addition, upregulated SYTL5 could promote cancer progression by activating the NF-κB signaling pathway. RAC1b expression is positively associated with SYTL5, and overexpressed RAC1b abrogated the antitumor effect after SYTL5 inhibition. In conclusion, our findings identify the oncogenic role of SYTL5 in PTC by activation of the NF-κB signaling pathway, thus facilitating PTC development and progression. [ABSTRACT FROM AUTHOR]

Objective: Papillary thyroid carcinoma (PTC) is a common malignancy whose incidence is three times greater in females than in males. The prognosis of ageing patients is poor. This research was designed to construct models to predict the overall survival of elderly female patients with PTC. Methods: We developed prediction models based on the random survival forest (RSF) algorithm and traditional Cox regression. The data of 4539 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Twelve variables were analysed to establish the models. The C-index and the Brier score were selected to evaluate the discriminatory ability of the models. Time-dependent receiver operating characteristic (ROC) curves were also drawn to evaluate the accuracy of the models. The clinical benefits of the two models were compared on the basis of the DCA curve. In addition, the Shapley Additive Explanations (SHAP) plot was used to visualize the contribution of the variables in the RSF model. Results: The C-index of the RSF model was 0.811, which was greater than that of the Cox model (0.781). According to the Brier score and the area under the ROC curve (AUC), the RSF model performed better than the Cox model. On the basis of the DCA curve, the RSF model demonstrated fair clinical benefit. The SHAP plot showed that age was the most important variable contributing to the outcome of PTC in elderly female patients. Conclusions: The RSF model we developed performed better than the Cox model and might be valuable for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Preoperative hematological parameters are predictors of pathological features and recurrence-free survival (RFS) in various malignancies. However, comprehensive studies of preoperative indicators associated with papillary thyroid carcinoma (PTC) are scarce. The present study investigated the association between preoperative indicators and RFS in patients with PTC. Accordingly, we explored the clinical impact of the prognostic nutritional index (PNI) on lymph node metastasis and RFS in patients with PTC. Methods: A total of 619 PTC patients were retrospectively reviewed between Jan 2013 and Dec 2017. Laboratory values were measured and calculated. Receiver operating characteristic curves were generated to calculate the cutoff value. Univariate and multivariate analyses using the COX proportional hazard model were performed for RFS. The effects of PNI and age on RFS were investigated by the Kaplan-Meier method. Clinical characteristics and PNI were tested with the chi-square test. Univariate and multivariate logistic analyses were conducted to evaluate the predictive value of PNI for lymph node metastasis. Results: In the multivariate Cox analysis, age, PNI and lymph node metastasis were independent prognostic indicators for RFS. The Kaplan-Meier method showed that the lower PNI group and age older than 55 years group displayed poor RFS. A low preoperative PNI was remarkably correlated with age, sex, extrathyroidal invasion, T stage, N stage and TNM stage. PNI was the only preoperative hematological indicator for lateral lymph node metastasis. Conclusions: Among the preoperative hematological indicators, PNI may serve as a promising and effective predictor for RFS and lateral lymph node metastasis in PTC patients. [ABSTRACT FROM AUTHOR]

Background: The presence of lymph node metastasis (LNM) is frequently observed in papillary thyroid carcinoma (PTC), and most clinical guidelines recommend total thyroidectomy. However, the impact of LNM on specific types of locoregional recurrence remains uncertain, particularly for stage T1 PTC. Methods: The present retrospective cohort study enrolled patients diagnosed with stage T1 PTC between 2008 and 2015. Propensity score matching was performed in patients with lobectomy accompanied by varying degrees of LNM. Logistic regression analysis was performed to compare the effect of LNM on relapse types, and Kaplan-Meier method was utilized to calculate recurrence-free survival. Results: The study cohort comprised 2,785 patients who were followed up for an average duration of 69 months. After controlling follow-up time and potential prognostic factors, we include a total of 362 patients in each group. Recurrence rates in the N0, N1a, and N1b groups were found to be 2.5%, 9.7%, and 10.2% respectively. Notably, group N1a versus group N0 (P=0.803), N1b group versus N0 group (P=0.465), and group N1b versus group N1a (P=0.344) had no difference in residual thyroid recurrence. However, when considering lymph node recurrence, both N1a(P=0.003) and N1b(P=0.009) groups showed a higher risk than N0 group. In addition, there was no difference in lymph node recurrence between N1b group and N1a group (P=0.364), but positive lymph node (PLN) and lymph node positive rate (LNPR) demonstrated a strong discriminatory effect (P<0.001). Conclusion: Lobectomy may be more appropriate for patients with unilateral stage T1 PTC in the low LNPR group. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma rarely undergoes anaplastic transformation. Some risk factors for anaplastic transformation of thyroid cancer are known, but such transformation is difficult to predict in practice. We report a case demonstrating elevations of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) over time as a precursor to anaplastic transformation of thyroid carcinoma. Case presentation: The patient was an 89 year-old woman with a history of chronic aortic dissection. She was referred to our department after her local doctor detected thyroid nodules. She had previously been found to have multinodular goiter and enlarged left cervical lymph nodes on computed tomography. Her chief complaint was cervical discomfort and hoarseness. Blood tests revealed: white blood cells (WBCs), 4900 /µL; CRP, 0.29 mg/dL; neutrophils, 64.4%; and lymphocytes, 25.4%. A 21 mm mass was identified in the upper left lobe. Left III (16 mm) and left VI (16 mm) lymph node were enlarged on ultrasonography. Fine-needle aspiration cytology diagnosed malignant papillary carcinoma. However, due to the advanced age and medical history of the patient, a non-surgical policy was implemented. The primary tumor grew to 4 cm in diameter by 9 months after diagnosis, and blood tests showed: WBC, 7700 /µL; CRP, 0.18 mg/dL; neutrophils, 65.3%; and lymphocytes, 22.3%. By 10 months after diagnosis, the tumor had increased rapidly in diameter to 8 cm, with blood tests showing: WBC, 6500 /µL; CRP, 1.01 mg/dL; neutrophils, 68.2%; and lymphocytes, 19.3%. Anaplastic transformation of papillary thyroid carcinoma was diagnosed, and the patient was placed on treatment under a policy of best supportive care. Multiple lung metastases appeared 11 months after diagnosis, and blood test results showed: WBC, 13,300 /μL; CRP, 11.28 mg/dL; neutrophils, 93.6%; and lymphocytes, 2.3%. Unfortunately, the patient died of disease progression 63 days after identification of undifferentiated metastasis. Conclusions: Chances to see the natural history of anaplastic transformation of thyroid cancer are rare. Elevations in NLR and CRP over time may be precursors to anaplastic transformation. [ABSTRACT FROM AUTHOR]

Objectives: To explore the impact of lymph node diameter on the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of cervical metastatic lymph nodes (CMLNs) from thyroid cancer. Methods: A total of 32 patients with 58 CMLNs from thyroid cancer underwent ultrasound-guided MWA and were included in the retrospective study. Patients were divided into three groups based on the mean largest diameter of the CMLNs: Group A (diameter =10mm), Group B (10mm < diameter =20mm), and Group C (diameter >20mm). The research involved comparing changes in cervical metastatic lymph nodes and serum thyroglobulin (sTg) levels, as well as the incidence of complications, before and after microwave ablation across three groups of patients. Results: The technical success rate of this study was 100% (32/32), and they showed no major complications. Compared with measurements taken before MWA, the mean largest diameter and volume of CMLNs, as well as the sTg level, showed significant reductions (p <0.05) at the last follow-up in all three patient groups. Group A and B exhibited higher lymph node volume reduction rates and complete disappearance rates compared to Group C. However, the recurrence rate in the three groups were in the following order: Group C > Group B > Group A. The occurrence rate of mild complications was Group A > Group C > Group B. Conclusion: MWA is a safe and effective method for treating CMLNs, with advantages for localized nodes but limitations for larger ones. Careful consideration and personalized plans are advised, based on comprehensive evidence assessment. [ABSTRACT FROM AUTHOR]

An association between high CD47 expression and poor cancer survival has been attributed to its function on malignant cells to inhibit phagocytic clearance. However, CD47 mRNA expression in some cancers lacks correlation or correlates with improved survival. IFT57 encodes an essential primary cilium component and is colinear with CD47 across amniote genomes, suggesting coregulation of these genes. Analysis of The Cancer Genome Atlas datasets identified IFT57 as a top coexpressed gene with CD47 among 1156 human cancer cell lines and in most tumor types. The primary cilium also regulates cancer pathogenesis, and correlations between IFT57 mRNA and survival paralleled those for CD47 in thyroid and lung carcinomas, melanoma, and glioma. CD47 ranked first for coexpression with IFT57 mRNA in papillary thyroid carcinomas, and higher expression of both genes correlated with significantly improved overall survival. CD47 and IFT57 mRNAs were coordinately regulated in thyroid carcinoma cell lines. Transcriptome analysis following knockdown of CD47 or IFT57 in thyroid carcinoma cells identified the cytoskeletal regulator CRACD as a specific target of IFT57. CRACD mRNA expression inversely correlated with IFT57 mRNA and with survival in low-grade gliomas, lung adenocarcinomas, and papillary thyroid carcinomas, suggesting that IFT57 rather than CD47 regulates survival in these cancers. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC), the predominant pathological type among thyroid malignancies, is responsible for the sharp increase in thyroid cancer. Although PTC is an indolent tumor with good prognosis, 60–70% of patients still have early cervical lymph node metastasis, typically in the central compartment. Whether there is central lymph node metastasis (CLNM) or not directly affects the formulation of preoperative surgical procedures, given that such metastases have been tied to compromised overall survival and local recurrence. However, detecting CLNM before operation can be challenging due to the limited sensitivity of preoperative approaches. Prophylactic central lymph node dissection (PCLND) in the absence of clinical evidence of CLNM poses additional surgical risks. This study aims to provide a comprehensive review of the risk factors related to CLNM in PTC patients. A key focus is on utilizing multimodal ultrasound (US) for accurate prognosis of preoperative CLNM and to highlight the distinctive role of US-based characteristics for predicting CLNM. [ABSTRACT FROM AUTHOR]

Objective: To conduct a comparative analysis of the efficacy, safety, and impact on quality of life outcomes between thermal ablation and surgical interventions in patients diagnosed with papillary thyroid carcinoma (PTC). Methods: A prospective study was undertaken, enrolling patients with PTC ≤5mm who underwent radiofrequency ablation (RFA), laser ablation (LA), or surgery, for analysis of efficacy and safety outcomes. The Thyroid Cancer-Specific Quality of Life questionnairewas administered to all patients before treatment and at 3, 6, and 12 months post-treatment. Results: A total of 162 eligible patients were included in the study. Major complications were not observed in the RFA and LA groups, while five cases were reported in the surgery group, although no statistically significant differences were observed. Minor complications were documented in two, three, and 14 patients in the RFA, LA, and surgery groups, respectively, with no significant variances noted. Surgical duration and hospitalization time were notably shorter in the thermal ablation groups. At the final follow-up, complete disappearance of nodules was seen in 71.4% of cases treated with RFA and 71.0% of cases managed with LA, with no significant disparities between the groups. Both RFA and LA exhibited similar effects on quality of life, with thermal ablation techniques showing better functional outcomes in comparison to surgery. Across all groups, adverse effects were most pronounced at the 3-month post-treatment mark but gradually reverted to baseline levels in the thermal ablation group, contrasting with the surgery group. Conclusions: For PTC ≤5mm, both RFA and LA exhibited similar cancer control outcomes and superior quality of life on par with surgery, while minimizing complications. These findings underscore the promise of RFA and LA as potential standard treatments for small PTCs, subject to further confirmation in future studies. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. Methods: The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. Results: In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. Conclusion: Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the diagnostic value of CEUS in atypical-enhanced PTC. METHODS: The clinical data, qualitative and quantitative parameters of CEUS in 177 Iso/hyper-enhanced thyroid nodules with definite pathological results were retrospectively analyzed in the Lanzhou University Second Hospital from June 2019 to January 2021. And the clinical value of CEUS in the diagnosis of atypical-enhanced PTC was assessed using univariate and multivariate analysis. RESULTS: Among the 177 thyroid nodules, 59 were benign and 118 were PTC. There were significant differences in age, enhancement border, ring enhancement, speed of wash in, speed of wash out, enhancement pattern, capsule interruption, time to peak, time to wash out, RT, TPH, and TTP (P < 0.05). Multivariate analysis showed unclear enhancement border and concentric enhancement were independent risk factors for the diagnosis of atypical-enhanced PTC by CEUS. The sensitivity, specificity, PPV, NPV, and accuracy of the model in diagnosing atypical-enhanced PTC were 88.1%, 71.2%, 86.0%, 75.0%, and 82.5%, respectively. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.910. CONCLUSION: The diagnosis of atypical-enhanced PTC can be better performed by enhancement characteristics and time intensity curve (TIC) of CEUS, which have a good clinical application value. [ABSTRACT FROM AUTHOR]

Though aetiology of lateral neck masses is complex, branchial cleft cyst is the second most common congenital lesions of the neck next only to thyroglossal duct cysts. Rarely ectopic thyroid tissue within a branchial cleft cyst may develop into primary papillary carcinoma, and even more rarely it may harbour metastases of primary thyroid papillary carcinoma. We report a rare case of lateral cystic neck mass in a 24-year-old female patient diagnosed as metastatic PTC. The patient was diagnosed after she underwent surgical excision of branchial cleft cyst. Later prospectively the patient underwent total thyroidectomy which revealed papillary thyroid micro invasive carcinoma. [ABSTRACT FROM AUTHOR]

Aim: To see whether prophylactic central compartment dissection is recommended for advanced papillary thyroid cancer or as part of selective neck node dissection. Central compartment dissection is a technically demanding surgical procedure and carries a higher incidence of complications. The present retrospective case-control study analysed the impact of prophylactic central compartment dissection on the long-term outcome of advanced (N0-T3/T4) papillary thyroid cancer. Materials and methods: Case records of patients operated on for papillary thyroid cancer from 2005 to 2010 were reviewed and patients with Tumour stage 3–4 and N0 nodal status were included in the study. The institutional protocol was to perform total thyroidectomy with central compartment dissection during the early phase of the study period (2005 to 2008) but this strategy was shifted to total thyroidectomy alone during the latter phase. Fifty-five patients were included in the study and 29 of the cohort had total thyroidectomy with prophylactic central compartment dissection as the primary surgery and the remaining 26 had a total thyroidectomy as the primary surgical procedure. Result: Patients were followed up for a median duration of 115 months and found to have no significant difference in the incidences of loco-regional recurrences between the groups. (n:4 (14%) Vs n: 3 (12%) p =.463). The disease-free survival and overall survival were not significantly different in the groups. There was a trend to an increase in the incidence of permanent hypoparathyroidism in patients who had central compartment dissection. Conclusion: Prophylactic central compartment dissection did not influence the 10-year outcome of advanced node-negative papillary thyroid cancers. [ABSTRACT FROM AUTHOR]

Cervical lymph node metastasis is one of the most common clinical presentations of papillary thyroid carcinoma (PTC). Occult thyroid carcinoma is described as absence of primary tumour or with presence of microcarcinoma in thyroid with cervical lymph node metastasis. Frequency of occult thyroid cancer has decreased due to developments in imaging and improved accuracy of histological examinations. 38 year old male presented to us with complaints of swelling over the left side of neck for the past 2 months. Ultrasonography was suggestive of multiple suspicious enlarged nodes in left level II, III, IV and V and fine needle aspiration cytology showed features of metastatic PTC. He was planned for total thyroidectomy with central compartment clearance and bilateral functional neck dissection. Final histopathology staging was pT0N1b. Radioactive iodine (RAI) screening showed residual functioning thyroid and later therapeutic RAI was administered. He has been on regular follow up and disease free for 1 year post treatment. Occult thyroid carcinoma is a rare diagnosis with multiple treatment plans. Few hypothesis for this entity includes tumor regression, ectopic thyroid carcinoma or missed pathological findings. [ABSTRACT FROM AUTHOR]

The incidence of lymph node metastasis in papillary thyroid carcinoma (PTC) is common and a significant risk factor for local recurrence; however, its impact on recurrence patterns among low-risk patients remains uncertain. We aimed to elucidate the effect of metastatic lymph node on recurrence type. The medical records of 1209 patients with stage T1 PTC who underwent unilateral thyroidectomy with ipsilateral central lymph node dissection were retrospectively analyzed. The study first identified risk factors for different types of recurrence and then categorized patients as high or low risk based on their lymph node positive ratio (LNPR). The diagnostic accuracy of LNPR in predicting recurrence was compared using receiver operating characteristic (ROC) curve analysis, while differences in recurrence-free survival were assessed using the Kaplan–Meier method. During follow-up, a total of 502 (41.5%) patients had central lymph node metastasis and 52 (4.3%) patients experienced recurrence. Notably, LNPR was significantly higher in relapsed patients compared to nonrelapsed patients, with mean values of 0.45 and 0.23, respectively (P <.001). The recurrence rate of residual thyroid did not differ significantly across different T stages (P =.679), N stages (P =.415), or LNPR risk groups (P =.175). However, the recurrence rate of lymph nodes showed a significant correlation with LNPR (P <.001). The area under the ROC curves for LNPR risk stratification at 5 and 10 years were approximately 0.691 and 0.634, respectively, both of which outperformed N stage. The findings underscore the significance of LNPR's reliability as a prognostic indicator for local lymph node recurrence in patients diagnosed with T1 stage PTC. [ABSTRACT FROM AUTHOR]

Background: Differentiated high‐grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high‐grade features while retaining the architectural and/or cytologic features of well‐differentiated follicular–cell‐derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management. Methods: The pathology archives of six institutions were searched for cases diagnosed on resection as "high‐grade thyroid carcinoma" using WHO criteria. The fine‐needle aspiration (FNA) cohort represents a 10‐year period (2013–2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features. Results: Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI‐RADS score of 4 or 5 (95.2%). Three main high‐grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p <.05); 68% of DHGTC cases were associated with high‐risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E. Conclusions: Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high‐grade thyroid carcinoma. Other findings include high‐risk molecular changes and clinicopathologic features such as older patient age and larger lesion size. A subset of thyroid FNAs of differentiated high‐grade thyroid carcinomas show marked nuclear atypia, mitotic activity, or necrosis together with high‐risk molecular alterations. [ABSTRACT FROM AUTHOR]

Background: Parathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience. Case presentation: We describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter. Conclusion: Parathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma. [ABSTRACT FROM AUTHOR]

Background: Pooled data analysis from three phase I/II larotrectinib clinical trials revealed that larotrectinib demonstrated rapid and durable disease control and a favorable safety profile for patients with neurotrophic-tropomyosin receptor kinase (NTRK) fusion positive thyroid carcinoma. Herein, we report the case of a patient with papillary thyroid carcinoma (PTC) and liver metastases who demonstrated a durable response to treatment with larotrectinib. Case presentation: A 50-year-old female with PTC was referred to our hospital for postoperative observation. Computed tomography (CT) scan was performed to screen for distant metastasis, since thyroglobulin concentration increased gradually, and revealed multiple distant metastases, including multiple liver metastases. Radioactive iodine was administered at a dose of 100 mCi. However, uptake was observed only in the thyroid bed, and distant metastases had no avidity. As liver metastases progressed, lenvatinib (24 mg/day) was initiated after confirmation of liver metastases by liver biopsy 9 years and 1 month after the initial referral to our hospital. Since the multiple metastases became refractory for lenvatinib, the OncoGuide™ NCC Oncopanel System was performed, and the SQSTM1–NTRK1 gene fusion was confirmed. Larotrectinib was subsequently administered at a dose of 200 mg/day. The CT before the initiation of larotrectinib showed multiple liver metastases with a maximum diameter of 48 mm. The first CT evaluation at 1 month after the initiation of larotrectinib treatment showed that the tumor volume was reduced by 28% in the RECIST 1.1 criteria. After 3 months of larotrectinib treatment, a 38% reduction in the tumor volume was achieved as the best clinical response. The only side effect was grade 1 myalgia. At 12 months after the initiation of larotrectinib treatment, none of the lesions had progressed. Conclusions: In conclusion, larotrectinib demonstrated effective antitumor activity against liver metastases of PTC, a relatively rare site of distant metastasis. Furthermore, the efficacy of larotrectinib was maintained, even though the patient had a history of multi-tyrosine kinase inhibitor treatment and a relatively infrequent fusion gene, SQSTM1–NTRK1. [ABSTRACT FROM AUTHOR]

Background: Isolated hypogonadotropic hypogonadism is a heterogeneous clinical entity. There is a growing list of molecular defects that are associated with hypogonadotropic hypogonadism (HH). TCF12, a recently identified molecular defect, causes craniosynostosis and is suggested to be used as a biomarker for prognosis in various cancer types. Recently, TCF12 variants were shown in a cohort with HH. Case presentation: A 15.3 years old female patient was referred to the endocrinology clinic for obesity. She had been gaining weight from midchildhood. She had her first epileptic seizure at the age of 15.1 years and mildly elevated thyroid autoantibodies were detected during evaluation for etiology of seizures. She had not experienced menarche yet. She was operated for left strabismus at the age of 7 years. School performance was poor and she was receiving special education. Tanner stage of breast was 1 and pubic hair was 3. The endocrine workup revealed hypogonadotropic hypogonadism. Also, the Sniffin' Sticks test detected anosmia. Thyroid ultrasonography was performed due to the mildly elevated thyroid autoantibodies, and thyroid nodules with punctate calcifications were detected. Total thyroidectomy and central lymph node dissection were performed regarding the cytological findings of the nodules and multicentric papillary thyroid carcinoma with no lymph node metastasis was detected on pathology specimens. Regarding the phenotypic features of the patients, whole exome sequencing was performed and heterozygous deletion of exon 1 and exon 6-8 in TCF12 was detected. Conclusion: Haploinsufficiency of TCF12 causes anosmic HH. Probably due to the incomplete penetrance and variable expressivity of the disease, patients could display variable phenotypic features such as intellectual disability, developmental delay, and craniosynostosis. Further description of new cases with TCF12 variations could enhance our understanding of craniosynostosis and its potential link to Kallmann syndrome associated with this gene. [ABSTRACT FROM AUTHOR]

Background: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. Methods: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. Results: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660–0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12–0.55), P < 0.001. Conclusion: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the role of shear wave elastography (SWE) and connective tissue growth factor (CTGF) in the assessment of papillary thyroid carcinoma (PTC) prognosis. Methods: CTGF expression was detected with immunohistochemistry. Clinical and pathological data were collected. Parameters of conventional ultrasound combined with SWE were also collected. The relationship among CTGF expression, ultrasound indicators, the elastic modulus and the clinicopathological parameters were analyzed. Results: Univariate analysis showed that patients with high risk of PTC were characterized with male, Uygur ethnicity, increased expression of CTGF, convex lesions, calcified, incomplete capsule, intranodular blood flow, rear echo attenuation, cervical lymph node metastasis, lesions larger than 1 cm, psammoma bodies, advanced clinical stage, increased TSH and high value in the shear modulus (P < 0.05). Multivariate analysis demonstrated that the risk factors of high expression of CTGF according to contribution size order were irregular shape, aspect ratio ≥ 1, and increased TSH. The logistic regression model equation was Logit (P) = 1.153 + 1.055 × 1 + 0.926 × 2 + 1.190 × 3 and the Area Under Curve value of the logistic regression was calculated to be 0.850, with a 95% confidence interval of 0.817 to 0.883. Conclusion: SWE and CTGF are of great value in the risk assessment of PTC. The degree of fibrosis of PTC is closely related to the prognosis. The hardness of PTC lesions and the expression level of CTGF are correlated with the main indexes of conventional ultrasound differentiating benign or malignant nodules. Irregular shape, aspect ratio ≥ 1, and increased TSH are independent factors of CTGF. [ABSTRACT FROM AUTHOR]

Background and aims: The recurrence of papillary thyroid carcinoma (PTC) is not unusual and associated with risk of death. This study is aimed to construct a nomogram that combines clinicopathological characteristics and ultrasound radiomics signatures to predict the recurrence in PTC. Methods: A total of 554 patients with PTC who underwent ultrasound imaging before total thyroidectomy were included. Among them, 79 experienced at least one recurrence. Then 388 were divided into the training cohort and 166 into the validation cohort. The radiomics features were extracted from the region of interest (ROI) we manually drew on the tumor image. The feature selection was conducted using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. And multivariate Cox regression analysis was used to build the combined nomogram using radiomics signatures and significant clinicopathological characteristics. The efficiency of the nomogram was evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to analyze the recurrence-free survival (RFS) in different radiomics scores (Rad-scores) and risk scores. Results: The combined nomogram demonstrated the best performance and achieved an area under the curve (AUC) of 0.851 (95% CI: 0.788 to 0.913) in comparison to that of the radiomics signature and the clinical model in the training cohort at 3 years. In the validation cohort, the combined nomogram (AUC = 0.885, 95% CI: 0.805 to 0.930) also performed better. The calibration curves and DCA verified the clinical usefulness of combined nomogram. And the Kaplan-Meier analysis showed that in the training cohort, the cumulative RFS in patients with higher Rad-score was significantly lower than that in patients with lower Rad-score (92.0% vs. 71.9%, log rank P < 0.001), and the cumulative RFS in patients with higher risk score was significantly lower than that in patients with lower risk score (97.5% vs. 73.5%, log rank P < 0.001). In the validation cohort, patients with a higher Rad-score and a higher risk score also had a significantly lower RFS. Conclusion: We proposed a nomogram combining clinicopathological variables and ultrasound radiomics signatures with excellent performance for recurrence prediction in PTC patients. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to compare the effectiveness and complications of the transoral endoscopic thyroidectomy submental vestibular approach (TOETSMVA) versus the transoral endoscopic thyroidectomy vestibular approach (TOETVA) or conventional open thyroidectomy (COT) in patients with early-stage papillary thyroid carcinoma (PTC). Methods: We searched online databases up to January 2024. The outcomes were analyzed using RevMan 5.4 and inverse variance. Results: Seven studies (two RCTs and five retrospective cohort studies) were included. We established higher significance differences for TOETSMVA in comparison with TOETVA in terms of all primary outcomes; operation time, hospital stay, number of resected lymph nodes [MD -21.05, 95% CI= -30.98, -11.12; p < 0.0001], [MD -1.76, 95% CI= -2.21, -1.32, p < 0.00001], [MD -2.99, 95% CI= -19.75, 13.76, p < 0.73], [MD -0.83, 95% CI = -1.19 to -0.47; p < 0.00001], respectively, except the drainage volume, it showed no difference [MD -2.99, 95% CI= -19.75, 13.76, p < 0.73]. In secondary outcomes, it was favored only in mandibular numbness and return to normal diet outcomes. Additionally, TOETSMVA compared with COT showed a significant difference in drainage volume, pain, cosmetic effect, and satisfaction score. Conclusions: TOETSMVA showed a significant improvement compared to the TOETVA in operation time, hospital stay, number of resected lymph nodes, mandibular numbness, and return to normal diet but did not show a difference in drainage volume. However, TOETSMVA was better in cosmetic effect, drainage volume, satisfaction, and pain scores compared with COT. Further RCTs with larger sample size, multicentral, and longer follow-up are necessary to evaluate the limitations. [ABSTRACT FROM AUTHOR]

Background and purpose: Thyroid papillary carcinoma (PTC) had a high possibility of recurrence after surgery, and thyroid stimulating hormone (TSH) suppression and radioactive iodine (131I) were used for postoperative therapy. This study explored the potential mechanism of lymph node metastasis (LNM) and aimed to develop differentiated treatments for PTC. Method: This study explored the risk factors of lymph node metastasis in PTC by analyzing the clinical information of 2073 cases. The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) and the Gene Expression Omnibus (GEO) databases of gene expression were analyzed to identify the interrelationships between gene expression to phenotype. Results: Analyzing clinical data, we found that male gender, younger age, larger tumor size, and extra-thyroidal extension (ETE) were risk significant risk factors for lymph node metastasis(P<0.05). Conversely, thyroid function parameters such as TSH, FT3, FT4, TSH/FT3, and TSH/FT4 didn't correlate with LNM (P>0.05), and TSH levels were observed to be higher in females(P<0.05). Gene expression analysis revealed that SLC5A5 was down-regulated in males, younger individuals, and those with lymph node metastasis, and a lower level of SLC5A5 was associated with a worse disease-free survival(P<0.05). Additionally, our examination of single-cell RNA sequencing (scRNA-seq) data indicated that SLC5A5 expression was reduced in tumors and lymph node metastasis samples, correlating positively with the expression of TSHR. Conclusion: The impact of TSH on PTC behavior remained unclear, while the capacity for absorbing 131I in dependence on SLC5A5 showed variations across different genders and ages. We conclude that postoperative treatment of PTC should take into account the differences caused by gender and age. [ABSTRACT FROM AUTHOR]

Objective: Various algorithms are currently used to evaluate patients with thyroid nodules. Thyroid fine needle aspiration biopsy (FNAB) is the most valuable method for assessment, but it yields 5-10% false negative results. Therefore, the McGill Thyroid Nodule Score (MTNS), which consists of 22 parameters, was developed for use in the preoperative period. In this study, we investigated the applicability of MTNS in patients with indeterminate FNAB results by comparing patients diagnosed with papillary thyroid cancer to those with benign outcomes according to the specimen result. Materials and Methods: Between January 2016 and August 2017, 382 patients who underwent thyroidectomy at our clinic were evaluated. A total of 140 patients categorized as Bethesda III- IV-V were included in the study. The MTNS was calculated and compared between the malignant and benign groups. Subsequently, patients were divided into four groups based on nodule diameter to evaluate their MTNS. Results: The median MTNS was 6 (range 1-16) in the benign group and 12 (range 3-23) in the malignant group. To determine the cut-off for MTNS, Receiver Operating Characteristic (ROC) analysis was conducted using the pathology result as the primary endpoint. The cut-off value was determined to be 8.5. Statistical analysis revealed that the sensitivity and specificity of MTNS were 83.0% and 85.5%, respectively. Conclusion: Ultrasonography (USG) and FNAB are currently preferred methods for approaching patients with thyroid nodules. In cases where FNAB results are inconclusive, MTNS can be safely applied clinically to identify high-risk patients. [ABSTRACT FROM AUTHOR]

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that accounts for 0.1%–0.15% of all thyroid cancers. More than half of the patients have tumor extension to adjacent organs, including the recurrent laryngeal nerve, trachea, and esophagus. The diagnosis of CASTLE is based on histology and immunohistochemistry. A 58-year-old female patient complained of hoarseness for one and half years. Right side vocal cord palsy was diagnosed by fiberscopy. Thyroid sonography revealed right thyroid tumors, which were reported to be papillary thyroid carcinoma through FNAC. Total thyroidectomy with central lymph node dissection was performed. Pathologist found 2 isolated malignancy tumors. One patient in the right thyroid lobe had papillary thyroid carcinoma features. The other extrathyroid tumor seemed to be separated from the first tumor and invaded the thyroid capsule. After multiple immunohistochemical studies, PTC synchronous CASTLE was the final diagnosis. Coexisting PTC and CASTLE is very rare. This is the first report to describe a case showing PTC at first, while subsequent pathologic examination revealed the presence of CASTLE in addition to PTC. Since the prognosis of CASTLE is favorable, the treatment is different from other aggressive thyroid cancers, such as poorly differentiated or anaplastic thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Aims: Tumour necrosis and/or increased mitoses define high‐grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut‐offs at five or more mitoses/2 mm2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non‐anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined. Methods: We analysed 50 consecutive PTC cases with distant metastases (DM‐PTC): 16 synchronous and 34 metachronous. A total of 108 non‐metastatic PTC (N‐DM‐PTC, 15.0‐year median follow‐up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut‐offs predictive of distant metastases. Results: Metastases correlated with necrosis (any extent = 43.8% all DM‐PTC, 53.1% metachronous DM‐PTC versus 5% N‐DM‐PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm2 was the best cut‐off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM‐PTC (AUC = 0.78), 18.8%/97.2% synchronous DM‐PTC (AUC = 0.63), 54.6%/97.2% metachronous DM‐PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut‐off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM‐PTC (AUC = 0.75), 25%/91.7% synchronous DM‐PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM‐PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM‐PTC. Conclusion: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM‐PTC. [ABSTRACT FROM AUTHOR]

Background: Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This study sought to delineate patterns of central and lateral neck involvement in unilateral papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). Methods: This was a retrospective correlative analysis of nodal patterns in surgical specimens from patients with unilateral PTC or MTC who had undergone thyroidectomy with at least ipsilateral central neck dissection between November 1994 and January 2024 at a tertiary referral center. Results: Included were 833 patients with unilateral PTC and 640 patients with unilateral MTC. Simultaneous presence or absence of node metastases was noted in ipsilateral central and lateral neck compartments in 76.6–78.1% of patients with PTC (both node positive in 27.0–54.7% and both node negative in 23.4–49.6%) and 77.3–80.0% of patients with MTC (both node positive in 26.6–33.2% and both node negative in 44.1–53.4%). Only one ipsilateral neck compartment was node positive in 21.9–23.4% of patients with PTC and 20.0–22.7% of patients with MTC. The ipsilateral central, but not the ipsilateral lateral compartment, was node positive in 8.8–16.9% with PTC and 8.6–8.8% of patients with MTC, whereas the ipsilateral lateral, but not the ipsilateral central compartment, was node positive in 6.5–13.1% with PTC and 11.3–14.1% with MTC. Ipsilateral lateral neck involvement sparing the ipsilateral central neck was 1.5–2 times more frequent in patients with node positive MTC than patients with node positive PTC (24.2–25.2% vs. 12.9–17.1%). Greater numbers of node metastases in the ipsilateral central neck compartment were associated with more frequent involvement of the ipsilateral lateral, contralateral central, and contralateral lateral neck compartments. Thyroid tumor diameter intensified nodal spread without changing nodal spread patterns. Conclusions: These histopathological findings, which need to be interpreted in light of the respective tumor biology, offer an unprecedented glimpse at the metastatic patterns of unilateral PTC and MTC. Customizing neck dissection to the patterns of nodal spread, considering operative status (initial vs. reoperative surgery) and experience with neck dissection, may require more frequent concomitant dissections of ipsilateral central and ipsilateral lateral neck compartments. [ABSTRACT FROM AUTHOR]

Background: During active surveillance (AS) of low-risk papillary thyroid carcinomas (PTCs), the majority remain stable, while some exhibit either an increase or a decrease in tumor diameter or tumor volume (TV). We aimed to evaluate the clinical outcomes and relevant parameters influencing tumor growth kinetics of low-risk PTCs. Methods: This retrospective cohort study evaluated clinical parameters of 402 patients with low-risk PTC sized <2 cm, with a follow-up duration over 3 years. Changes in maximum tumor diameter, TV, and initial TV doubling time (i-TVDT) calculated within 3 years were assessed. A significant change in TV was defined as a change of 75% or more. Results: Of the 402 patients with low-risk PTC, 93.3% (375/402) were diagnosed with papillary thyroid microcarcinoma. During a median follow-up of 5 years, 3.4% (14/402) of patients developed new cervical lymph node (LN) metastasis, and 8.2% (33/402) experienced a maximal diameter increase of ≥3 mm. The i-TVDT of <5 years emerged as an independent risk factor for both maximal diameter growth and new LN metastasis (p < 0.001 and p = 0.04, respectively). Based on TV changes and i-TVDT during AS, we identified four statistically significant tumor kinetic patterns (p < 0.001): Stable (±75% change in TV), Rapid growth (TV increase >75% and i-TVDT <5 years), Slow growth (TV increase >75% and i-TVDT ≥5 years), and Shrinkage (TV decrease >75%). Most of the PTCs remained stable (67.7%), but 17.2% were rapidly growing, with a median onset of growth of 2.0 years. Slowly growing PTCs, comprising 10.9%, grew at a median of 4.3 years. A minority, 4.2%, exhibited shrinkage. In total, 115 (28.6%) patients underwent delayed surgery >12 months after initiating AS. The reasons for delayed surgery included patient preference (51/115, 44.3%), disease progression (31/115, 27.0%), and suspected disease progression, which was referred to as tumor growth not meeting the criteria of an increase of ≥3 mm in maximal tumor diameter (17/115, 14.8%). Conclusion: An i-TVDT of <5 years serves as an important prognostic indicator for disease progression, including tumor growth and new LN metastasis. The four tumor kinetic patterns based on TV changes and i-TVDT assist in guiding personalized decisions early in AS. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma is the most common pathological type of thyroid cancer. Lymph node metastasis in patients with papillary thyroid carcinoma is common. We report a case of cervical lymph node metastasis of papillary thyroid carcinoma in a patient with maxillary gingival squamous cell carcinoma. A 77-year-old man presented with swelling and pain on the left side of the maxilla. Maxillary gingival squamous cell carcinoma without cervical lymph node metastasis was suspected from the CT images of the lesion in addition to panoramic radiography. A partial biopsy of the maxillary region was performed. Histopathological diagnosis was well to moderately differentiated squamous cell carcinoma. Chemoradiotherapy (CDDP: 400 mg and external radiation: 60 Gy) was performed for the maxillary tumor, and post-chemoradiotherapy outcomes were good for the maxillary tumor. However, contrast-enhanced CT taken 4 months after the primary treatment showed increase of the superior internal jugular node with heterogeneous enhancement and the mid internal jugular node with homogeneous enhancement and flecks of calcification on the left side of the neck. Cervical lymph node metastasis of the left maxillary gingival carcinoma after chemoradiotherapy was suspected from the CT images. Neck dissection was performed. Histopathological diagnosis was cervical lymph node metastasis of the left maxillary gingival squamous cell carcinoma and papillary carcinoma of the thyroid. [ABSTRACT FROM AUTHOR]

Background: Hypoparathyroidism is the most common complication for patients who undergo total thyroidectomy (TT) with bilateral central lymph node dissection (BCLND). The objective of this retrospective study was to investigate the relationship between parathyroid autotransplantation (PA) and postoperative hypoparathyroidism. Materials and Methods: Four hundred and sixty-five patients with papillary thyroid carcinoma (PTC) who underwent TT with BCLND (including prophylactic and therapeutic BCLND) by the same surgeon were enrolled in this retrospective study. They were divided into five groups based on the number of PAs. Group 0 was defined as no PA, while Group 1, 2, 3, and 4 were considered as 1, 2, 3, and 4 PAs during TT with BCLND, respectively. Results: Transient and permanent hypoparathyroidism occurred in 83 (17.8%) and 2 (0.4%) patients who underwent TT and BCLND, respectively. The incidence of transient hypoparathyroidism increased gradually with an increase in the number of PAs. Compared with the previous group, Groups 2 and 3 had significantly more cases of transient hypoparathyroidism (p=0.03 and p=0.04, respectively). All cases of permanent hypoparathyroidism occurred in the patients without PA. Compared with Group 0, there were more removed central lymph nodes (RCLNs) in patients with one PA. Furthermore, Group 2 had more metastatic central lymph nodes(MCLNs) and RCLNs than Group 1.The number of PAs was the only identified risk factor for transient hypoparathyroidism after the multivariate logistic regression analysis. The median parathyroid hormone level recovered to the normal range within 1 month after surgery. Conclusion: With an increasing number of PAs, the possibility of transient hypoparathyroidism also increases in patients with PTC who undergo TT and BCLND. Considering the rapid recovery of transient hypoparathyroidism in 1 month, two PAs during TT and BCLND could be a good choice, leading to an increase in the central lymph node yield and no permanent hypoparathyroidism. However, this conclusion should be validated in future multicenter prospective studies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Sex and age show a dimorphism role in the pathogenesis, lymph node metastasis, and prognostic outcomes of papillary thyroid carcinoma. This investigation endeavors to elucidate the mechanisms underlying these disparities. Methods: The clinicopathological characteristics and risk factors of lymph node metastasis were explored by analyzing the 2261 patients. The gene expression information of 497 samples from The Cancer Genome Atlas Thyroid Cancer database was used to explore the differentially expressed genes in different phenotypes. What's more, the single-cell RNA sequencing data obtained from the Gene Expression Omnibus database was used to explore the gene expression in specific cells. Results: Multivariate logistic regression analysis showed that in male patients, a larger tumor size, extrathyroidal extension, younger age, and the presence of calcification emerged as significant predictors for lymph node metastasis (LNM)(p < 0.05). Conversely, female patients exhibited a different profile, with larger tumor size, extrathyroidal extension, younger age, calcification, and bilateral tumors being identified as key risk factors (p < 0.05). Further stratification by age demonstrated distinct patterns: among the younger cohort, a larger tumor size, extrathyroidal extension, male gender, calcification, multifocality, and the presence of Hashimoto's thyroiditis held statistical significance (p < 0.05). In contrast, the older subgroup was characterized by a larger tumor size, extrathyroidal extension, male gender, calcification, bilateral tumors, and unclear margins as salient indicators of risk (p < 0.05). In the bulk gene analysis, there were two sex-age-related differentially expressed genes with a contrary trend in tissue sources and LNM status: TCL1A and CR2. The analysis of single-cell RNA sequencing showed that the infiltration of TCL1A- and CR2-related B cells varied in different clinical subtypes. Conclusion: Lymph node metastasis of papillary thyroid carcinoma in different sexes and ages may have distinct patterns, and the ages-sex-related B cell infiltration might explain the dimorphism biological behavior. [ABSTRACT FROM AUTHOR]

Immunoinflammatory response can participate in the development of cancer. To investigate the relationship between pretreatment systemic immune inflammatory response index (SII), systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and lymph node metastasis in patients with papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 547 PTC patients treated in Meizhou People's Hospital from January 2018 to December 2021. Clinicopathological data were collected, including gender, age, Hashimoto's thyroiditis, maximum tumor diameter, extra-membrane infiltration, disease stage, BRAF V600E mutation, pretreatment inflammatory index levels, and lymph node metastasis. The optimal cutoff values of SII, SIRI, NLR, PLR and LMR were calculated by receiver operating characteristic (ROC) curve, and the relationship between inflammatory indexes and other clinicopathological features and lymph node metastasis was analyzed. Results: There were 303 (55.4%) PTC patients with lymph node metastasis. The levels of SII, SIRI, NLR, and PLR in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis, while the levels of LMR were significantly lower than those in patients without lymph node metastasis (all p< 0.05). When lymph node metastasis was taken as the endpoint, the critical value of SII was 625.375, the SIRI cutoff value was 0.705, the NLR cutoff value was 1.915 (all area under the ROC curve > 0.6). The results of regression logistic analysis showed that age < 55 years old (OR: 1.626, 95% CI: 1.009– 2.623, p=0.046), maximum tumor diameter > 1cm (OR: 2.681, 95% CI: 1.819– 3.952, p< 0.001), BRAF V600E mutation (OR: 2.709, 95% CI: 1.542– 4.759, p=0.001), SII positive (≥ 625.375/< 625.375, OR: 2.663, 95% CI: 1.560– 4.546, p< 0.001), and NLR positive (≥ 1.915/< 1.915, OR: 1.808, 95% CI: 1.118– 2.923, p=0.016) were independent risk factors for lymph node metastasis of PTC. Conclusion: Age < 55 years old, maximum tumor diameter > 1cm, BRAF V600E mutation, SII positive, and NLR positive were independent risk factors for lymph node metastasis in PTC. [ABSTRACT FROM AUTHOR]

A 76-year-old female patient presented with an iodine-refractory papillary thyroid carcinoma (PTC), diagnosed eight years earlier, with several lymph node recurrences requiring successive surgeries. Fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging revealed a new unresectable loco-regional recurrence. The patient was diagnosed with a somatic BRAF V600E mutation. Therefore, dabrafenib and trametinib combination therapy was introduced and closely monitored by a dedicated multidisciplinary team, involving pharmaceutical consultations. As early as six weeks after treatment initiation, the patient reported multiple adverse events (AEs) to the clinical pharmacy team, who provided advice on resolving AEs or improving tolerance. Close interprofessional collaboration among healthcare workers involved in the care pathway allowed for the identification of the most opportune times for temporary suspension of treatment (four suspensions over seven months) or dose reduction (two reductions over 3.5 months). This resulted in a total treatment duration (one year) longer than the average times reported in the literature. The patient showed a rapid and excellent response to treatment immediately after initiation, culminating in a complete metabolic response assessed by [18F]FDG PET/CT imaging at nine months. Twenty-five months after treatment discontinuation, the disease remained controlled. Overall, dabrafenib and trametinib combination could offer excellent outcomes in selected patients with refractory BRAF-mutated PTC, with additional clinical pharmacy initiatives allowing for the optimized management of AEs and prolonged treatment periods. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer, the most common endocrine neoplasm, has a strong female predominance. There has been a steady increase in the incidence of thyroid cancer worldwide. This study aimed to investigate the prevalence of thyroid cancer and identify its predominant histological subtypes in the Aljuf region of Saudi Arabia. The study findings and new data obtained will contribute to advancing knowledge about thyroid cancer at the national level. Methods and Results: This retrospective, cross-sectional descriptive study was conducted in Sakaka, Aljouf region, Saudi Arabia. Data from thyroid specimens collected at King Abdul-Aziz Specialist Hospital and Prince Mutaib Hospital between January and December 2022 was analyzed. Among 3102 histopathological samples and 298 cytology samples received in both hospitals, 181 were thyroid specimens: histopathology samples [63(34.8%)] and fine-needle aspiration (FNA) samples for cytological diagnosis [118 (65.2%)]. The age of patients with thyroid disorders ranged from 17 to 69, with a mean age of 38.4 ± (SD)1.2 years. The highest percentage, 76(42%), were in the age group over 40. The majority of patients with thyroid disorders, 139 (76.8%), were women compared to 42(23.2%) men, giving a female-to-male ratio of 3.3: 1. 165(91.2%) of the study population were Saudi patients, while the non-Saudis represented only 16(8.8%) cases. Among 181 thyroid specimens, thyroid cancer was diagnosed in 33 patients (18.2%), benign tumors in 43 patients (23.8%) [follicular adenoma 39 (90.7%) and Hürthle cell adenoma 4 (9.3%)], goiter in 96 (53.0% cases), Hashimoto's thyroiditis in 6 cases (3.3%), and chronic lymphocytic thyroiditis in 3 cases (1.7%). The age of patients with thyroid cancer ranged from 20 to 57 years, with a mean age of 36.9 years. There were 25 (75.8%) females versus 8 (24.2%) males, with a ratio of 3.1:1. Papillary thyroid carcinoma was the most frequent histological subtype among patients with thyroid cancer, accounting for 75.8%, while follicular thyroid carcinoma represented 24.2%. Among 155 cancer cases, thyroid cancer ranked third (21.3%) after breast cancer (26.4%) and colon adenocarcinoma (23.9%). Conclusion: Thyroid pathology, including cancer, is notably prevalent among females and older age groups in the Al-Jouf region. Thyroid carcinoma is the third most diagnosed cancer type after breast carcinoma and colon adenocarcinoma in Al-Jouf in 2022. Papillary thyroid carcinoma is the most frequent histological subtype among Saudi patients with thyroid cancer.

Objective: The association between autoimmunity-related tissue injury and thyroid cancer development remains an area of interest. Evidence suggests that patients with Graves disease (GD) may have an elevated risk for differentiated thyroid cancer. Multicenter studies are needed to gain insight into the correlates of papillary thyroid carcinoma (PTC) identified in this particular group of patients. This study aimed to investigate the prevalence of PTC and synchronous thyroid nodules in thyroidectomy specimens from GD patients in an endemic goiter region. Material and Methods: A retrospective review of institutional pathology records at two tertiary care centers identified 237 surgically treated patients with GD. Patients were categorized as having nodular Graves disease (N-GD) if synchronous nodular thyroid was identified by ultrasonography, while those without synchronous thyroid nodules were categorized as non-nodular or simple Graves disease (S-GD). The prevalence of PTC, histopathological correlates, and demographic characteristics were recorded and compared between groups N-GD and S-GD. Results: One hundred thirty-one and 106 patients were assigned to N-GD and S-GD, respectively. The mean age was significantly higher in N-GD (mean 45.52 years) compared to S-GD (mean 35.18 years) (p0.05). The group of S-GD was enriched in BRAF-like PTCs, whereas N-GD had equal distribution for RAS- and BRAF-like tumors. Conclusion: This study underscores that the majority of PTCs encountered in GD were enriched in low-risk subcentimeter PTCs with a prevalence that varies depending on the presence of underlying nodular thyroid tissue.

Abstract Background Preoperative hematological parameters are predictors of pathological features and recurrence-free survival (RFS) in various malignancies. However, comprehensive studies of preoperative indicators associated with papillary thyroid carcinoma (PTC) are scarce. The present study investigated the association between preoperative indicators and RFS in patients with PTC. Accordingly, we explored the clinical impact of the prognostic nutritional index (PNI) on lymph node metastasis and RFS in patients with PTC. Methods A total of 619 PTC patients were retrospectively reviewed between Jan 2013 and Dec 2017. Laboratory values were measured and calculated. Receiver operating characteristic curves were generated to calculate the cutoff value. Univariate and multivariate analyses using the COX proportional hazard model were performed for RFS. The effects of PNI and age on RFS were investigated by the Kaplan-Meier method. Clinical characteristics and PNI were tested with the chi-square test. Univariate and multivariate logistic analyses were conducted to evaluate the predictive value of PNI for lymph node metastasis. Results In the multivariate Cox analysis, age, PNI and lymph node metastasis were independent prognostic indicators for RFS. The Kaplan-Meier method showed that the lower PNI group and age older than 55 years group displayed poor RFS. A low preoperative PNI was remarkably correlated with age, sex, extrathyroidal invasion, T stage, N stage and TNM stage. PNI was the only preoperative hematological indicator for lateral lymph node metastasis. Conclusions Among the preoperative hematological indicators, PNI may serve as a promising and effective predictor for RFS and lateral lymph node metastasis in PTC patients.

Abstract Background Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. Methods The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. Results In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC > 0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. Conclusion Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.

Abstract Background Mitochondrial DNA (mtDNA) copy number is associated with tumor activity and carcinogenesis. This study was undertaken to investigate mtDNA copy number in papillary thyroid cancer (PTC) tissues and to evaluate the risk of PTC development. The clinicopathological features of patients and mtDNA copy number were correlated. The value of mtDNA copy number was evaluated as a biomarker for PTC. Method DNA was extracted from 105 PTC tissues and 67 control thyroid tissues, and mtDNA copy number mtDNA oxidative damage were determined using qPCR techniques. Results Overall, the relative mtDNA copy number was significantly higher in PTC patients (p

Abstract Background Parathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience. Case presentation We describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter. Conclusion Parathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma.

Abstract Background Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. Methods In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the “Responder group”. Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. Results 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P