LncRNA ZFAS1 promotes invasion of medullary thyroid carcinoma by enhancing EPAS1 expression via miR-214-3p/UCHL1 axis.

lncRNA ZFAS1 was identified to facilitate thyroid cancer, but its role in medullary thyroid carcinoma (MTC) remains unknown. This study aimed to unravel the potential function of this lncRNA in MTC by investigating the involvement of the lncRNA ZFAS1 in a ceRNA network that regulates MTC invasion. Proliferation, invasion, and migration of cells were evaluated using EdU staining and Transwell assays. Immunoprecipitation (IP) assays, dual-fluorescence reporter, and RNA IP assays were employed to examine the binding interaction among genes. Nude mice were used to explore the role of lncRNA ZFAS1 in MTC in vivo. ZFAS1 and EPAS1 were upregulated in MTC. Silencing ZFAS1 inhibited MTC cell proliferation and invasion under hypoxic conditions, which reduced EPAS1 protein levels. UCHL1 knockdown increased EPAS1 ubiquitination. ZFAS1 positively regulated UCHL1 expression by binding to miR-214-3p. Finally, silencing ZFAS1 significantly repressed tumor formation and metastasis in MTC. LncRNA ZFAS1 promotes invasion of MTC by upregulating EPAS1 expression via the miR-214-3p/UCHL1 axis.

Long-term response to MEK inhibitor monotherapy in a patient with papillary thyroid carcinoma harboring BRAF V600E mutation.

Solid tumors harboring mutations in the Braf gene (BRAF) are currently treated by combination Braf/MEK inhibitor therapy, and there is an extensive literature on patient response rates. Alternatively, few studies have documented the clinical response of BRAF mutation-positive solid tumors to MEK inhibitor monotherapy. We report the case of a 57-year-old female diagnosed with papillary thyroid carcinoma and progressive lung metastases initially treated by total thyroidectomy and subsequent thyroid-stimulating hormone suppression therapy. Next-generation sequencing revealed that the tumor harbored a BRAF V600E mutation, and the patient was enrolled in a clinical study of the oral MEK1/2 inhibitor binimetinib. Shortly after starting treatment, the patient experienced pneumothorax due to rapid regression of lung metastases, and computed tomography after 6 months of binimetinib treatment revealed a partial sustained response. One year later, the dose was reduced because of an acneiform rash. After 5 years of binimetinib treatment, lung metastases had regrown, and treatment was switched to the oral multikinase inhibitor lenvatinib. This case demonstrates the potential of MEK inhibitor monotherapy as an alternative treatment for BRAF mutation-positive papillary thyroid carcinoma.

Sonographic characteristics and clinical characteristics combined with nomogram for predicting the aggressiveness of papillary thyroid carcinoma coexisted with Hashimoto's thyroiditis.

OBJECTIVE: The association between Papillary Thyroid Carcinoma (PTC) and coexistent Hashimoto's Thyroiditis (HT) was controversial. The purpose of this study was to evaluate the presence of HT exerts any influence on the aggressiveness of PTC, and to establish a nomogram for predicting the possibility of aggressiveness in PTC. METHODS: 373 consecutive PTC patients with/without coexistent HT from January 2017 to December 2020 were retrospective reviewed. Patients' clinicopathologic and sonographic characteristics were collected for univariate and multivariate analyses. A nomogram was established based on the risk factors for aggressiveness in PTC. RESULTS: Male (p = 0.001), tumor size >1.0 cm (p = 0.046) and lymph node metastasis (p = 0.018) were negatively associated with PTC coexisted with HT, while it was significantly positively associated with the frequence of multifocality (p = 0.010). Univariate and multivariate analyses suggested that age ≥55 years (p = 0.000), male (p = 0.027), HT (p = 0.017), tumor size >1.0 cm (p = 0.015), multifocality (p = 0.041), distance to capsular ≤0 cm (p = 0.050) and blood flow (Grade I: p = 0.044) were independent risk factors for predicting the aggressiveness in PTC. A nomogram according to these predictors was further developed and validated. The receiver operating characteristic curve (AUC = 0.734 and 0.809 for training and validation cohorts, respectively) and decision curve analyses indicated that the nomogram model was clinically useful. The calibration curve revealed that the nomogram exhibited an excellent consistency. CONCLUSIONS: In this study, the coexistent HT might play a protective role in preventing the proliferation of PTC. Dispensable aggressive treatment may be reduced in PTC by pre-operative identification of sonographic and clinical characteristics and incorporating with the predicted nomogram model.

[Progress in Lymphangiogenesis and Lymphatic Metastasis of Thyroid Carcinoma].

Thyroid carcinoma is a common endocrine malignancy,with most cases being indolent.Lymphatic metastasis as a representative metastasis type defines the clinical stage and prognosis of thyroid carcinoma.The mechanism of lymphatic metastasis in malignancies has been a research hotspot for years,and certain progress being achieved.This article reviews the molecular markers of lymphatic vessels and their application in diagnosis and treatment of neoplasms,the mechanism and role of lymphangiogenesis in lymphatic metastasis,the tracing methods for sentinel lymph nodes by lymphatic drainage,and the use of ultrasound in cervical lymph node metastasis of thyroid carcinoma.Especially,this paper details the application of conventional ultrasound,transvenous contrast-enhanced ultrasound,and trans-lymphatic contrast-enhanced ultrasound in cervical lymph node metastasis of thyroid carcinoma.

Transoral endoscopic thyroidectomy submental vestibular approach for early-stage papillary thyroid carcinoma: a systematic review and meta-analysis.

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.

Analyzing the correlation between low proportion of hobnail features in papillary thyroid carcinoma and clinical aggressiveness risk.

PURPOSE: Hobnail features may enhance the clinical aggressiveness of papillary thyroid carcinoma (PTC). However, whether a low proportion (<30%) of these features contributes to increased PTC aggressiveness remains unclear. This study investigated whether PTC cases with a low proportion hobnail features (<30%) exhibit clinical invasiveness and pathological features of aggressiveness. METHODS: Pathological specimens from patients with postoperatively diagnosed PTC were retrospectively analyzed. Among them, 29 PTC cases with a low proportion of hobnail features (<30%) were compared with 173 consecutive classical PTC (cPTC) cases. Data regarding age at presentation, sex, tumor size, number of tumors, and histological characteristics were obtained by reviewing electronic medical records. Postoperative information was obtained during follow-up visits and telephone interviews. RESULTS: Twenty-nine patients with PTC with a low proportion of hobnail features (<30%) were identified, exhibiting a median age of 34 years. At a median follow-up of 31 (IQR, 23-37) months, two patients had recurrent disease in the PTC with a low proportion of hobnail features (<30%) group, whereas there was no recurrence in the cPTC group. No distant metastasis and postoperative mortality were observed in either group. Compared with the cPTC group, patients with PTC and a low proportion of hobnail features exhibited larger tumor volumes and higher susceptibility to capsular invasion and lymph node metastasis. Tumor size and hobnail features emerged as independent risk factors for lymph node metastasis. CONCLUSION: PTC with a low proportion hobnail features (<30%) and larger tumor volumes are associated with the occurrence of lymph node metastasis. A low proportion of hobnail features (<30%) in PTC may heighten invasiveness, elevating the risk of recurrence.

The Association of Pretreatment Systemic Immune Inflammatory Response Index (SII) and Neutrophil-to-Lymphocyte Ratio (NLR) with Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma.

Objective: 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.

Role of ultrasound in predicting telomerase reverse transcriptase (TERT) promoter mutation in follicular thyroid carcinoma.

Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. This study aimed to demonstrate the ultrasonographic (US) features of TERT promoter-mutated follicular thyroid cancer (FTC) and evaluate their predictive performance. A total of 63 patients with surgically confirmed FTC between August 1995 and April 2021 were included. All data were available for analysis of preoperative US findings and TERT promoter mutation results. Genomic DNA was extracted from the archived surgical specimens to identify TERT promoter mutations. Logistic regression analysis was performed to compare US findings between TERT promoter-mutated and wild-type FTCs. Of the 63 patients with FTC, 10 (15.9%) had TERT promoter mutations. TERT promoter-mutated FTCs demonstrated significantly different US suspicion categories compared to wild-type FTCs (Ps = 0.0054 for K-TIRADS and 0.0208 for ACR-TIRADS), with a trend toward an increasing prevalence of the high suspicion category (40.0% for both K-TIRADS and ACR-TIRADS; Ps for trend = 0.0030 for K-TIRADS and 0.0032 for ACR-TIRADS). Microlobulated margins and punctate echogenic foci were independent risk factors associated with TERT promoter mutation in FTC (odds ratio = 9.693, 95% confidence interval = 1.666-56.401, p = 0.0115 for margins; odds ratio = 8.033, 95% confidence interval = 1.424-45.309, p = 0.0182 for punctate echogenic foci). There were no significant differences in the composition and echogenicity of the TERT promoter-mutated and wild-type FTCs. TERT promoter-mutated FTCs were categorized more frequently as high suspicion by the K-TIRADS and ACR-TIRADS. Based on US findings, the independent risk factors for TERT promoter mutations in FTC are microlobulated margins and punctate echogenic foci.

Assessment of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS™) with modification of the management recommendations for pediatric thyroid nodules.

BACKGROUND: Thyroid nodules are unusual in children, but when present, they carry a higher risk for malignancy, as compared to adults. Several guidelines have been created to address the risk stratification for malignancy of thyroid nodules in adults, but none has been completely validated in children. A few authors have proposed lowering the size threshold to the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS™) management guidelines to decrease missed carcinomas at presentation in children; however, little information is known regarding their accuracy. OBJECTIVE: To assess the performance of proposed modifications of the ACR TI-RADS™ size criteria to guide management decisions in pediatric thyroid nodules and to assess the associated increase in number of fine needle aspiration (FNA) and follow-up exams. MATERIALS AND METHODS: This is a retrospective study of children under 18 years old who underwent ultrasound assessment of a thyroid nodule at a tertiary care pediatric institution between January 2006 and August 2021. The largest dimension, maximum ACR TI-RADS™ score, and final thyroid nodules' diagnoses were documented. The course of action based on the adult ACR TI-RADS™ and after modifying the size threshold for management recommendations was documented and compared. Statistics included descriptive analysis, weighted Kappa statistics, sensitivity, specificity, accuracy, and positive/negative predictive values of the ACR TI-RADS™ presented with 95% confidence intervals (CI) using either Clopper-Pearson or standard logit methods. RESULTS: Of 116 nodules, 18 (15.5%) were malignant. Most malignant nodules (94.4%, n = 17) were ACR TI-RADS™ 4 and ACR TI-RADS™ 5 categories. Based on the adult ACR TI-RADS™ criteria, 24 (24.5%) benign and 15 (83.3%) malignant nodules would have undergone FNA; 14 (14.3%) benign and 3 (16.7%) malignant nodules would have been followed up; and 60 (61.2%) benign and none of malignant nodules would have been dismissed. Three (16.7%) malignant nodules would not have been recommended FNA at presentation, delaying their diagnoses. By lowering the size-threshold criteria of the ACR TI-RADS™ guidelines, no malignancy would have been missed at presentation, but this also resulted in a higher number of FNA from 24 (24.5%) to 36 (36.7%) and follow-up ultrasound exams from 14 (14.3%) to 62 (63.3%). CONCLUSION: Applying potential modifications to the ACR TI-RADS™ guideline lowering the size threshold criteria of the thyroid nodule to guide management decisions for pediatric thyroid nodules can lead to early detection of malignant nodules in children, but at the cost of a significantly increased number of biopsies or ultrasound exams. Further tailoring of the guideline with larger multicentric studies is needed, before warranting its acceptance and general use in the pediatric population.

Comparison of unilateral versus bilateral central neck dissection for clinically invasive papillary thyroid carcinoma.

BACKGROUND: The American Thyroid Association guidelines primarily recommend central neck dissection for papillary thyroid carcinoma with advanced primary tumors or clinically positive neck nodes. However, the appropriate extent of dissection remains unclear. We aimed to compare the rate of locoregional recurrence between unilateral and bilateral central neck dissection in invasive papillary thyroid carcinoma. METHODS: Among 330 consecutive patients who underwent total thyroidectomy with central neck dissection for advanced papillary thyroid carcinoma, 212 underwent unilateral central neck dissection (UCND group) while 118 underwent bilateral central neck dissection (BCND group). We performed 1:1 propensity score matching, resulting in 99 matched pairs. Surgical outcomes and safety were compared between the two groups. Additionally, the impact of surgery on locoregional recurrence was compared using survival analysis. RESULTS: During a follow-up of 47.8 ± 20.4 months, 29 (8.8%) patients experienced locoregional recurrence within the entire study cohort. Following propensity score matching, no significant difference in recurrence-free survival was observed between the two groups (log-rank p = 0.516). Multivariate analysis revealed that only T4 staging was an independent risk factor for locoregional recurrence (p = 0.006). The mean number of total and metastatic central lymph nodes retrieved were significantly greater in BCND group (14.1 vs. 9.3, p < 0.001 and 6.8 vs. 4.6, p = 0.005, respectively). There was no significant difference in postoperative stimulated thyroglobulin levels between the two groups (0.79 ng/mL vs. 1.44 ng/mL, p = 0.389). CONCLUSION: The present study demonstrates no prognostic benefit in conducting bilateral central neck dissection. Unilateral central neck dissection may be the preferred choice for clinically invasive papillary thyroid carcinoma.

Ultrasound-guided percutaneous radiofrequency ablation versus surgery for solitary T1N0M0 papillary thyroid carcinoma in the danger triangle.

OBJECTIVES: To compare the safety and efficiency of ultrasound-guided percutaneous radiofrequency ablation (RFA) and surgical resection (SR) for thyroid papillary carcinoma (PTC) in the danger triangle area. METHODS: The clinical data of 298 patients who underwent either percutaneous RFA or SR for PTC in the thyroid danger triangle at our hospital between January 2018 and April 2020 were retrospectively analyzed. Propensity score matching is employed to regulate for confounding factors. All patients undergoing ablation were treated using a strategy that combined sufficient paratracheal fluid isolation with a low-power, short electrode. Disease progression was analyzed in patients with T1N0M0 PTC (T1a and T1b) employed in Kaplan‒Meier curves. Treatment parameters and the rates of local recurrence, distant metastasis, and complications are recorded and compared. RESULTS: Of 182 eligible patients who were included, 91 were in the RFA (age 44.84 ± 13.19; 71 females; 77 T1a) and 91 were in the SR (age 47.36 ± 11.05; 68 females; 69 T1a). The average treatment time, length of hospital stays, blood loss volume, and scar length are substantially less in the RFA than in the SR. Major complications as well as postoperative permanent recurrent laryngeal nerve injury and postoperative transient parathyroid dysfunction occurred only in the SR, with a substantial distinction between the two groups (p < 0.05). There is no substantial distinction in the disease progression between RFA and SR treatment of T1N0M0 PTC. CONCLUSION: RFA is as effective as surgery for PTC in the danger triangle area in the short term, with faster recovery and fewer complications. CLINICAL RELEVANCE STATEMENT: Radiofrequency ablation has a clinical efficacy comparable to surgery in the treatment of papillary thyroid carcinoma in the danger triangle area in the short term with the advantages of faster recovery and fewer complications when compared with surgery. KEY POINTS: Use of radiofrequency ablation (RFA) in the thyroid danger triangle is still controversial. RFA and surgery groups showed no difference in disease progressions, and no major complications occurred with RFA. Radiofrequency ablation offers a new option for papillary thyroid carcinoma patients in the danger triangle.

Transcriptomic Differences in Medullary Thyroid Carcinoma According to Grade.

Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3, EXO1, UBE2T, UBE2C, FOXM1, CENPA, DLL3, CCNA2, SOX2, KIF23, and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1, DLL3, and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival (p = 0.041) and overall survival (p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC.

Ultrasound-guided approach to surgery for nodal recurrence following lateral neck dissection for differentiated thyroid carcinoma. A single institution experience.

Introduction: Total thyroidectomy (TT) and central neck dissection (CND) had a significant effect on the reduction of local recurrence compared with TT alone. Lateral Neck Dissection (LND) was performed in all the cases with therapeutic intent. The suspicion of nodal recurrence is provided by the appearance of one or more enlarged nodes in the central and/or laterocervical compartment during the follow up period. Methods: From January 2018 to November 2023, 16 patients at the University General Surgery unit of the Polyclinic of Foggia underwent reoperation due to nodal recurrence after previously undergoing total thyroidectomy with central and lateral cervical dissection. Results: All surgical interventions were approached with intraoperative ultrasound performed by the operating surgeon. In all cases, ultrasound identification of the suspicious lymph node led to histological confirmation of malignancy. In only two cases it was necessary to carry out an extemporaneous intraoperative histological examination. No complications were recorded during the operations. Conclusions: Surgical reintervention in patients with nodal recurrence is challenging and requires an assessment by members of the interdisciplinary team. The ideal method should be economically convenient, easy to practice, with a quick learning curve, easily reproducible, and safe for patients. Intraoperative, ultrasound-guided, is a safe and effective technique. It facilitates tumor localization and removal, especially in patients requiring re-operative neck surgery.

Elevated Procalcitonin Levels can Occur in Bacterial Infections and also in Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a rare and challenging type of thyroid cancer originating from parafollicular cells (C cells) that produce calcitonin. Diagnosing and monitoring this carcinoma can be complex due to its unique biomarkers. Procalcitonin (PCT), a precursor of calcitonin, and carcinoembryonic antigen (CEA) are important markers for MTC. Elevated PCT levels, particularly when they remain high post-infection treatment, and elevated CEA levels are significant indicators for suspecting MTC. This report emphasises the diagnostic and prognostic importance of these biomarkers in MTC, highlighting their roles in detecting and monitoring disease progression. Integrating PCT and CEA measurements into routine clinical practice can enhance detection, provide understanding of therapeutic responses and aid in the effective management of MTC. LEARNING POINTS: Procalcitonin (PCT) is a more stable and reliable biomarker than calcitonin for diagnosing and monitoring medullary thyroid carcinoma (MTC).Elevated carcinoembryonic antigen (CEA) levels effectively monitor MTC progression, especially when calcitonin levels are inconsistent.Incorporating PCT and CEA measurements into routine practice enhances MTC management, providing reliable biomarkers for diagnosis and monitoring.

Development and validation of a clinical predictive model for high-volume lymph node metastasis of papillary thyroid carcinoma.

The central lymph node metastasis (CLNM) status in the cervical region serves as a pivotal determinant for the extent of surgical intervention and prognosis in papillary thyroid carcinoma (PTC). This paper seeks to devise and validate a predictive model based on clinical parameters for the early anticipation of high-volume CLNM (hv-CLNM, > 5 nodes) in high-risk patients. A retrospective analysis of the pathological and clinical data of patients with PTC who underwent surgical treatment at Medical Centers A and B was conducted. The data from Center A was randomly divided into training and validation sets in an 8:2 ratio, with those from Center B serving as the test set. Multifactor logistic regression was harnessed in the training set to select variables and construct a predictive model. The generalization ability of the model was assessed in the validation and test sets. The model was evaluated through the receiver operating characteristic area under the curve (AUC) to predict the efficiency of hv-CLNM. The goodness of fit of the model was examined via the Brier verification technique. The incidence of hv-CLNM in 5897 PTC patients attained 4.8%. The occurrence rates in males and females were 9.4% (128/1365) and 3.4% (156/4532), respectively. Multifactor logistic regression unraveled male gender (OR = 2.17, p < .001), multifocality (OR = 4.06, p < .001), and lesion size (OR = 1.08 per increase of 1 mm, p < .001) as risk factors, while age emerged as a protective factor (OR = 0.95 per an increase of 1 year, p < .001). The model constructed with four predictive variables within the training set exhibited an AUC of 0.847 ([95%CI] 0.815-0.878). In the validation and test sets, the AUCs were 0.831 (0.783-0.879) and 0.845 (0.789-0.901), respectively, with Brier scores of 0.037, 0.041, and 0.056. Subgroup analysis unveiled AUCs for the prediction model in PTC lesion size groups (≤ 10 mm and > 10 mm) as 0.803 (0.757-0.85) and 0.747 (0.709-0.785), age groups (≤ 31 years and > 31 years) as 0.778 (0.720-0.881) and 0.837 (0.806-0.867), multifocal and solitary cases as 0.803 (0.767-0.838) and 0.809 (0.769-0.849), and Hashimoto's thyroiditis (HT) and non-HT cases as 0.845 (0.793-0.897) and 0.845 (0.819-0.871). Male gender, multifocality, and larger lesion size are risk factors for hv-CLNM in PTC patients, whereas age serves as a protective factor. The clinical predictive model developed in this research facilitates the early identification of high-risk patients for hv-CLNM, thereby assisting physicians in more efficacious risk stratification management for PTC patients.

Selective anti-tumor activity of glutathione-responsive abasic site trapping agent in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death. Whether this strategy can be employed for ATC treatment is rarely investigated. The aim of this study is to exploit GSH-responsive AP site capture reagent (AP probe-net), which responses to the elevated glutathione (GSH) levels in the tumor micro-environment (TME), releasing reactive alkoxyamine to trap AP sites and block the APE1-mediated BER for targeted anti-tumor activity against ATC. In vitro experiments, including MTT andγ-H2AX assays, demonstrate their selective cytotoxicity towards ATC cells over normal thyroid cells. Flow cytometry analysis suggests that AP probe-net arrests the cell cycle in the G2/M phase and induces apoptosis. Western blotting (WB) results show that the expression of apoptotic protein increased with the increased concentration of AP probe-net. Further in vivo experiments reveal that the AP probe-net has a good therapeutic effect on subcutaneous tumors of the ATC cells. In conclusion, taking advantage of the elevated GSH in TME, our study affords a new strategy for targeted chemotherapy of ATC with high selectivity and reduced adverse effects.

OIP5-AS1/miR-455-3p/microfibril-associated protein 2 axis exacerbates the progression of thyroid carcinoma.

Background: The long non-coding RNA (lncRNA) Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) has been shown to participate in numerous biological and pathological processes, notably including oncogenesis. OIP5-AS1 modulates oncogenic or anti-tumor activities by controlling various microRNAs (miRs) in diverse cancer types. This study sought to examine the potential role of the lncRNA OIP5-AS1-mediated miR-455-3p/microfibril-associated protein 2 (MFAP2) axis and its influence on the progression of thyroid carcinoma. Methods: Cell proliferation, migration, and apoptosis were assessed through in vitro experimental measurements, which involved the use of Cell Counting Kit 8 (CCK8), transwell, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining techniques. The estimate algorithm was employed to examine the relationship between MFAP2 and the Stromal score, Immune score, and ESTIMATE score. Results: OIP5-AS1 expression was significantly more elevated in the thyroid carcinoma tissues and cell lines than the corresponding normal non-tumor tissues and cell lines. Following transfection with short-hairpin (sh)-OIP5-AS1, the CAL62 and SW1736 cells upregulated miR-455-3p and downregulated the MFAP2 expression levels. The downregulation of OIP5-AS1 expedited cellular apoptosis and hindered cellular proliferation and migration in the CAL62 and SW1736 cells. The in vitro experiments showed that both the suppression of MFAP2 and the increased expression of miR-455-3p exerted significant anti-cancer effects. In addition, the overexpression of MFAP2 counteracted the in vitro antineoplastic effects of the sh-OIP5-AS1 and miR-455-3p mimics. Conclusions: The results suggest that lncRNA OIP5-AS1 plays a crucial role in the advancement of thyroid carcinoma by inhibiting miR-455-3p to activate MFAP2.

Follicular Thyroid Carcinoma Arising from the Struma Ovarii Coexisting with Papillary Thyroid Carcinoma, Hashimoto's Thyroiditis and Polycystic Ovarian Syndrome-a Case Report and Literature Review.

Purpose: Struma ovarii is a highly specialized teratoma consisting primarily of mature thyroid tissue. However, malignant struma ovarii coexisting with thyroid carcinoma, not to mention autoimmune disease, is uncommon. Malignant struma ovarii complicated with papillary thyroid carcinoma, Hashimoto's thyroiditis and polycystic ovarian syndrome has never been reported in literature. Patients and Methods: A 32-year-old female was admitted to our hospital due to a history of abdominal distension and menolipsis over the past half a year. Physical examination touched a 6 × 6 cm mass with a clear boundary, normal movement, and no pressing pain in the right adnexal area, Imaging revealed a cystic solid mass of 6 × 7 cm in the right ovary and the level of tumor markers including CA125, CA199, CA153, CEA, AFP were normal, but with low TSH and increased TPOAb, TGAb, TRAb. Laparoscopic right ovary tumor resection was performed, followed by comprehensive staging surgery, as well as thyroidectomy after pathologic diagnosis. The patient was diagnosed with a combination of follicular thyroid cancer from struma ovarii, papillary thyroid carcinoma and Hashimoto's thyroiditis, along with polycystic ovarian syndrome. Immunohistochemical staining showed positivity for Ag, CK-pan, CK7, PAX8 and TTF-1 in the right ovarian mass, and the left thyroid was positive for the BRAF V600E mutation. Results: The patient underwent thyroxine suppression therapy and radioactive iodine 131I therapy after operation. Serum thyroglobulin was undetectable, and no signs of recurrence or metastasis were detected in the imaging examination at the 2-year follow-up. Conclusion: Malignant struma ovarii coexisting with thyroid carcinoma is rare. No report has been identified in literature review on the rare malignant struma ovarii coexisting with thyroid carcinoma, Hashimoto's thyroiditis and polycystic ovarian syndrome. Our case can offer experience of diagnosis and treatment to some extent for such rare case. Therefore, it is essential to consider the association between ovarian tumors and the endocrine system. This case is valuable in understanding the diagnosis and management of such an unusual complicated disease.

An age-and sex-matched postoperative therapy should be required in thyroid papillary carcinoma.

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.

Ultrasound-based nomogram to predict the recurrence in papillary thyroid carcinoma using machine learning.

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.