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Abstract Objective To evaluate sanitary techniques for radical thyroid cancer surgery via the transaxillary approach without inflation single-port endoscopic surgery (TAWISES) and the conventional open anterior cervical approach (COACAS) in a controlled manner. Methods This work was a retrospective analysis of the clinical data of 60 patients admitted to our hospital for unilateral radical thyroid cancer surgery between 01/2021 and 12/2022. The control group underwent COACAS (30 patients), and the experimental group underwent TAWISES (30 patients). The patients’ operative time, intraoperative bleeding volume, 24-h postoperative pain index, drainage tube carrying time, hospitalization duration and complication rate were compared and analyzed. The patients were followed up for 3, 6 and 12 months postoperatively and evaluated based on numbness, muscular tightness, pain and other discomfort in the neck, as well as satisfaction with social adaptation and cosmetic incisions. The recurrence status was assessed for 1 year in both groups of patients. A questionnaire survey was conducted to assess patient acceptance of the two surgical approaches. The economic characteristics (cost-effectiveness and cost-utility) of the different approaches in our region were evaluated comprehensively. Results The length of the incision, drainage tube carrying time and hospitalization duration were greater in the experimental group than in the control group (P 0.05). Neck discomfort was greater in the control group, and the difference was statistically significant at the 3-month postoperative follow-up (P 0.05). However, mild discomfort was significantly more common in the experimental group (63.33% > 36.67%, 80% > 53.33%, P

Background: Filamin A (FLNA) is a member of the filamin family and has been found to be critical for the progression of several cancers. However, its biological function in papillary thyroid cancer (PTC) remains largely unexplored. Methods: Data from The Cancer Genome Atlas (TCGA) databases were utilized to analyze the FLNA expression level and its influence on the clinical implications of patients with PTC. Gene Expression Omnibus (GEO) and qRT-PCR was used to verify the expression levels of FLNA in PTC. Kaplan–Meier survival analysis was conducted to evaluate the prognostic value of FLNA in PTC. Transwell assays and wound healing were performed to examine the biological function of FLNA knockdown in PTC cells. Gene set enrichment analysis (GSEA) and Western blotting were conducted to investigate the potential mechanisms underlying the role of FLNA in PTC progression. In addition, the relationship between FLNA expression and the tumor immune microenvironment (TME) in PTC was explored. Results: FLNA was significantly upregulated in PTC tissues. High expression levels of FLNA was correlated with advanced TNM stage, T stage, and N stage, as well as poor disease-free interval (DFI) and progression-free interval (PFI) time in PTC patients. Moreover, we found that FLNA knockdown inhibited the migration and invasion of PTC cells. Mechanistically, FLNA knockdown inhibited epithelial–mesenchymal transition (EMT) in PTC and affected the activation of the FAK/AKT signaling pathway. In addition, FLNA expression was associated with TME in PTC. Conclusion: FLNA may be regarded as a new therapeutic target for PTC patients.

Background: Mönckeberg sclerosis is a form of calcification of the tunica media of small and medium size arteries. It occurs more often in the peripheral arteries of the lower limbs and it has been associated with diabetes and renal disease. Although there are a few reports of Mönckeberg sclerosis in thyroid vessels, there are no data regarding its significance in thyroid disease. Objective: The aim was to investigate the possible prognostic value of Mönckeberg sclerosis in thyroid vessels of patients with diagnosed thyroid cancer. Methods: We retrospectively studied patients with papillary thyroid cancer treated at the Theagenio Hospital of Thessaloniki from 2005 to 2021. The patients were divided into two groups based on the presence, or absence, of histopathological findings of Mönckeberg sclerosis in the thyroid vessels along with papillary thyroid cancer. Patient characteristics, histopathological details, personal history of thyroid disease, and metabolic parameters were compared between the two groups. Results: Thirty-three patients with papillary thyroid carcinoma and Mönckeberg sclerosis were identified and matched to 33 controls with papillary thyroid cancer, without evidence of Mönckeberg sclerosis. The metabolic profile of patients with Mönckeberg sclerosis was not significantly different from those who did not have Mönckeberg sclerosis. Moreover, the comparison between the two groups did not reveal any remarkable differences in terms of the aggressiveness of the disease. Conclusion: The presence of Mönckeberg sclerosis does not seem to impact on histological characteristics of patients with papillary thyroid cancer.

Abstract E3 ubiquitin ligase synoviolin (SYVN1) has been reported to participate in many human cancers. This study aimed to investigate SYVN1’s roles and molecular pathways in papillary thyroid cancer (PTC). The functions of SYVN1 in PTC were further analyzed using gain- and loss-of-function methods and numerous investigations in cellular function and molecular biology. The findings demonstrated that the overexpression of SYVN1 markedly suppressed the proliferation, migration, and invasion of PTC cell lines (NPA87 and TPC-1). We found that SYVN1 interacted with HMGB1 and promoted its ubiquitination and degradation. In addition, SYVN1 effectively impairs cell proliferation, migration, invasion, and the formation of tumor xenografts in mice models. However, this effect may be partly reversed by overexpressing HMGB1. Thus, SYVN1 may inhibit the proliferation, migration, and invasion of PTC cells by disrupting HMGB1. Consequently, SYVN1 might be considered a promising therapeutic target for PTC.

Abstract Background Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear. Methods In the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2’-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC. Results The data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis. Conclusion Taken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis.

Rui Zhang,1,&ast; Zhengwei Gui,2,&ast; Jianguo Zhao,1 Lu Zhao2 1Department of Thyroid and Breast Surgery, Wuhan No. 1 Hospital, Wuhan, 430030, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Zhao, Department of Thyroid and Breast Surgery, Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology, No. 1095 of Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email luzhao268@outlook.comPurpose: B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, contributed to tumor progression and metastasis in various tumors, whereas, the role of BCL9 in papillary thyroid cancer (PTC) has not been investigated.Methods: We acquired PTC gene expression data from The Cancer Genome Atlas (TCGA) database. Fifty-nine PTC tissues were applied to validate the clinical significance of BCL9. Cell experiments were applied to investigate the role of BCL9. Bioinformatics analysis was employed to investigate the biological functions of BCL9.Results: We found that BCL9 was higher expressed (P < 0.05) and an independent risk factor for lymph node metastasis (OR = 3.770, P = 0.025), as well as associated with poorer progression-free survival (PFS) (P = 0.049) in PTC. BCL9 knockdown inhibited proliferation and invasion of PTC cells. BCL9 was positively associated with the key genes of Wnt/β-catenin and MAPK pathway by co-expression analysis. GO, KEGG and GSEA analysis showed BCL9 might participated in PPAR, cAMP, and focal adhesion pathway. CIBERSORT analysis found BCL9 was negatively associated with CD8+ T cells and NK cell infiltration and positively with PD-L1 expression.Conclusion: Therefore, BCL9 was associated with lymph node metastasis and shorter PFS of PTC, due to promotion of PTC cell proliferation and invasion, activation of Wnt/β-catenin and MAPK pathway, inhibition of CD8+ T and NK cell infiltration, and promotion of PD-L1 expression.Keywords: BCL9, papillary thyroid cancer, lymph node metastasis, tumor immune microenvironment, tumor-infiltrating immune cells

Abstract Background Although papillary thyroid cancer (PTC) patients are known to have an excellent prognosis, up to 30% of patients experience disease recurrence after initial treatment. Accurately predicting disease prognosis remains a challenge given that the predictive value of several predictors remains controversial. Thus, we investigated whether machine learning (ML) approaches based on comprehensive predictors can predict the risk of structural recurrence for PTC patients. Methods A total of 2244 patients treated with thyroid surgery and radioiodine were included. Twenty-nine perioperative variables consisting of four dimensions (demographic characteristics and comorbidities, tumor-related variables, lymph node (LN)-related variables, and metabolic and inflammatory markers) were analyzed. We applied five ML algorithms—logistic regression (LR), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and neural network (NN)—to develop the models. The area under the receiver operating characteristic (AUC-ROC) curve, calibration curve, and variable importance were used to evaluate the models’ performance. Results During a median follow-up of 45.5 months, 179 patients (8.0%) experienced structural recurrence. The non-stimulated thyroglobulin, LN dissection, number of LNs dissected, lymph node metastasis ratio, N stage, comorbidity of hypertension, comorbidity of diabetes, body mass index, and low-density lipoprotein were used to develop the models. All models showed a greater AUC (AUC = 0.738 to 0.767) than did the ATA risk stratification (AUC = 0.620, DeLong test: P

Abstract Background Total thyroidectomy is the main line of treatment for papillary thyroid cancer. Central lymph node dissection (CLND) is still debatable. In this study, we aimed to correlate the central lymph node status with the age of patients. Methods This is a retrospective study including patients with papillary thyroid cancer (PTC) who underwent total thyroidectomy and CLND at a tertiary cancer center during the period from January 2012 to September 2022. Patients were subdivided into 3groups: patients younger than 20 years old, patients between 20 and 40 years old, and patients older than 40 years old. Correlation between central lymph node status, lateral lymph node status, and harvest count with each other and between age groups was done. Results 315 patients were included. The younger the age group the higher the possibility of harboring positive central nodes, however, the positivity of lateral nodes was similar. Neither central nodal harvest nor positive central node count significantly differed between groups. The lateral nodal harvest was significantly higher in the

Introduction: Mutations of CHEK2 are usually inherited and have been implicated in breast cancers, colorectal cancers, thyroid cancers, kidney cancers, and prostate cancers. The CHEK2 gene codes for checkpoint kinase 2 protein which is an effector in the ATM-CHEK2-p53 pathway and responds to DNA double-strand breaks. Case Presentation: We describe a unique case of a 29-year-old Canadian female who presented with synchronous papillary thyroid carcinoma and rectal adenocarcinoma who was subsequently found to have a sporadic CHEK2 (checkpoint kinase 2) mutation. She presented with an 8-month history of bright red blood per rectum and saw two different physicians who diagnosed hemorrhoids and possible rectal ulcers, respectively. When the symptoms continued, the patient pursued a colonoscopy exam which found a large rectal tumor. Subsequent clinical staging diagnosed a rectal adenocarcinoma and a synchronous papillary thyroid carcinoma. Due to her synchronous tumors, a genetic panel was performed, which revealed a low-risk CHEK2 mutation. Our patient had a full response to neoadjuvant brachytherapy of the rectum and surgical treatment of her cancers. Conclusion: This is the first case report, to our knowledge, of a patient with a CHEK2 mutation who presented with synchronous papillary thyroid carcinoma and invasive colonic adenocarcinoma. The incidence of colorectal cancers and papillary thyroid cancers in those under 30 with no family history is very low, which signifies the rarity of their simultaneous occurrence at such a young age.

Objective: To evaluate sanitary techniques for radical thyroid cancer surgery via the transaxillary approach without inflation single-port endoscopic surgery (TAWISES) and the conventional open anterior cervical approach (COACAS) in a controlled manner. Methods: This work was a retrospective analysis of the clinical data of 60 patients admitted to our hospital for unilateral radical thyroid cancer surgery between 01/2021 and 12/2022. The control group underwent COACAS (30 patients), and the experimental group underwent TAWISES (30 patients). The patients' operative time, intraoperative bleeding volume, 24-h postoperative pain index, drainage tube carrying time, hospitalization duration and complication rate were compared and analyzed. The patients were followed up for 3, 6 and 12 months postoperatively and evaluated based on numbness, muscular tightness, pain and other discomfort in the neck, as well as satisfaction with social adaptation and cosmetic incisions. The recurrence status was assessed for 1 year in both groups of patients. A questionnaire survey was conducted to assess patient acceptance of the two surgical approaches. The economic characteristics (cost-effectiveness and cost-utility) of the different approaches in our region were evaluated comprehensively. Results: The length of the incision, drainage tube carrying time and hospitalization duration were greater in the experimental group than in the control group (P < 0.05). The differences in complication rate, intraoperative bleeding volume, 24-h postoperative pain index and recurrence rate were not statistically significant between the two groups (P > 0.05). Neck discomfort was greater in the control group, and the difference was statistically significant at the 3-month postoperative follow-up (P < 0.05). The differences at the 6- and 12-month postoperative follow-ups were not statistically significant (P > 0.05). However, mild discomfort was significantly more common in the experimental group (63.33% > 36.67%, 80% > 53.33%, P < 0.05). The experimental group had better social adaptability, greater total medical costs, and better overall patient medical satisfaction than did the control group (P < 0.05). The acceptance of TAWISL was greater than that of COACAS (P < 0.05). Conclusion: Compared with COACLAS, TAWISES is safe and effective and better meets the cosmetic, psychological and social adaptation needs of patients. TAWISES is also more cost effective and can be better utilized for the population in our region, filling the gap in surgical modalities for thyroid cancer in in our region. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. 10% to 15% of individuals show familial clustering with three or more affected members, but the factors underlying this risk are unknown. In a group of recently studied individuals with POT1 pathogenic variants and ultra-long telomere length, PTC was the second most common solid tumor. We tested whether variants in POT1 and four other telomere-maintenance genes associated with familial cancer underlie PTC susceptibility. Among 470 individuals, we identified pathogenic or likely pathogenic variants in three genes encoding telomere-binding proteins: POT1 , TINF2 , and ACD. They were found in 4.5% and 1.5% of familial and unselected cases, respectively. Individuals harboring these variants had ultra-long telomere length, and 15 of 18 (83%) developed other cancers, of which melanoma, lymphoma, and sarcoma were most common. Among individuals with PTC and melanoma, 22% carried a deleterious germline variant, suggesting that a long telomere syndrome might be clinically recognizable. Successive generations had longer telomere length than their parents and, at times, developed more cancers at younger ages. Tumor sequencing identified a single oncogenic driver, BRAF p.Val600Glu, in 10 of 10 tumors studied, but no telomere-maintenance mechanism, including at the TERT promoter. These data identify a syndromic subset of PTCs with locus heterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations. DeBoy et al. identify telomere-lengthening variants in genes encoding three telomere-binding proteins as monogenic risk factors for papillary thyroid cancers, the most common of endocrine malignancies. Eighty-three percent of individuals had second cancers, of which melanoma, sarcoma, and lymphoid malignancies were most common. [ABSTRACT FROM AUTHOR]

The synchronous malignant melanoma of the neck and papillary thyroid cancer is rare but severe condition. Here, we describe the case of a patient with papillary thyroid cancer and melanoma invasivum cutis. A 49-year-old man had a change on the neck at the last 3–4 months that he accidentally noticed. He had hoarse voice, was afebrile, did not sweat more than usual and feel exhausted, without rash or itching. MR examination of the neck and upper mediastinum before the surgery indicated a hyperintense focal change in the left thyroid gland which dimensions was 19·15mm and several hyperintense inhomogeneous lymph glands of the jugular chain, on the both sides, with different sizes. On the basis of the conducted analyzes, in addition to total thyroidectomy, two-sided functional dissection of the lymph nodes of the neck was performed. The pathohistological diagnosis of the left lobus was: Carcinoma papillary glandulae thyreoideae invasivum (G-I, nG-I, pT2, Lx, Vo). CT of head, neck and thorax were made, where it was noticed that the CT of the head and lungs were normal. PET/CT findings indicated that there was no rest or recurrence of the tumor. The message from this case report is that when diagnosing and treating thyroid cancer, the observed changes in the neck lymph nodes also indicate cancers of non-thyroid pathology such as malignant melanoma. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. Objectives: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). Methods: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. Results: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method Conclusion: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers. [ABSTRACT FROM AUTHOR]

The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject. [ABSTRACT FROM AUTHOR]

Purpose: Circular RNAs (circRNAs) are increasingly recognized for their important roles in various cancers, including papillary thyroid cancer (PTC). The specific mechanisms by which the circLIF receptor subunit alpha (circLIFR, hsa_circ_0072309) influences PTC progression remain largely unknown. Methods: In our study, CircLIFR, miR-429, and TIMP2 levels were assessed using reverse transcription-quantitative PCR. The roles of circLIFR and miR-429 in PTC cells were determined using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. Western blotting was utilized to examine the levels of TIMP2. The direct interaction between circLIFR, TIMP2, and miR-429 was confirmed using dual-luciferase reporter, RNA immunoprecipitation, and fluorescence in situ hybridization assays. Results: In PTC tissues and cells, a decrease in circLIFR and TIMP2 levels, accompanied by an increase in miR-429 levels, was observed. Overexpression of circLIFR or downregulation of miR-429 effectively suppressed the proliferation and migration of PTC cells. Conversely, the knockdown of circLIFR or overexpression of miR-429 had the opposite effect. Furthermore, circLIFR overexpression suppressed tumor growth in vivo. Mechanistically, circLIFR modulated TIMP2 expression by serving as a sponge for miR-429. Rescue experiments indicated that the antitumor effect of circLIFR could be reversed by miR-429. Conclusion: This study confirmed circLIFR as a novel tumor suppressor delayed PTC progression through the miR-429/TIMP2 axis. These findings suggested that circLIFR held promise as a potential therapeutic target for PTC. [ABSTRACT FROM AUTHOR]

Metastasis poses a significant challenge in combating tumors. Even in papillary thyroid cancer (PTC), which typically exhibits a favorable prognosis, high recurrence rates are attributed to metastasis. Cytoplasmic linker protein 170 (CLIP170) functions as a classical microtubule plus-end tracking protein (+TIP) and has shown close association with cell migration. Nevertheless, the specific impact of CLIP170 on PTC cells remains to be elucidated. Our analysis of the GEO and TCGA databases unveiled an association between CLIP170 and the progression of PTC. To explore the impact of CLIP170 on PTC cells, we conducted various assays. We evaluated its effects through CCK-8, wound healing assay, and transwell assay after knocking down CLIP170. Additionally, the influence of CLIP170 on the cellular actin structure was examined via immunofluorescence; we further investigated the molecular expressions of epithelial-mesenchymal transition (EMT) and the transforming growth factor-β (TGF-β) signaling pathways through Western blotting and RT-qPCR. These findings were substantiated through an in vivo nude mouse model of lung metastasis. We observed a decreased expression of CLIP170 in PTC in contrast to normal thyroid tissue. Functionally, the knockdown of CLIP170 (CLIP170KD) notably enhanced the metastatic potential and EMT of PTC cells, both in vitro and in vivo. Mechanistically, CLIP170KD triggered the activation of the TGF-β pathway, subsequently promoting tumor cell migration, invasion, and EMT. Remarkably, the TGF-β inhibitor LY2157299 effectively countered TGF-β activity and significantly reversed tumor metastasis and EMT induced by CLIP170 knockdown. In summary, these findings collectively propose CLIP170 as a promising therapeutic target to mitigate metastatic tendencies in PTC. [ABSTRACT FROM AUTHOR]

It is stated that Hashimoto's Thyroiditis (HT) is a risk factor for the development of Papillary Thyroid Cancer (PTC). However, the effect of HT on the coexistence of HT and PTC is still controversial. In this study, our aim is to investigate the effect of the presence of HT on clinicopathological data in patients with PTC. All 356 patients whose pathology was reported as PTC who were operated between 2015 and 2023 were included in the study. PTC patients were divided into 2 groups as those with and without HT. The effect of HT association on clinicopathological features was investigated. In 356 PTC patients, the rate of HT was 31.2%. PTC patients with HT had less multifocality (p < 0.05), more lymph node metastases (LNM) (p < 0.01) compared to PTC patients without HT. The presence of HT did not affect the bilaterality of the tumor, tumor diameter, lymphovascular invasion, or capsule invasion. While multifocality was observed less frequently in PTC patients with HT, lymph node metastasis rates were higher. [ABSTRACT FROM AUTHOR]

Preserving the integrity of parathyroid glands is crucial in papillary thyroid cancer (PTC) surgery to avoid hypoparathyroidism. In recent years, two novel dyes, activated carbon nanoparticles (CNP) and indocyanine green (ICG), have been utilized to assist in parathyroid gland identification. However, the use of CNP or ICG alone can result in extravasation of dye or excessive fluorescence of non-parathyroid tissue, which can affect the accuracy of surgical outcomes by yielding false negative or false positive results. Therefore, it is important to further optimize the application of these two dyes in surgery. We analyzed case files of 124 PTC patients who underwent routine total or near-total thyroidectomy with bilateral lymph node dissection in the central region at the Affiliated People's Hospital of Ningbo University from January to November 2022. The patients were randomly divided into three groups based on the type of intraoperative dye used. The CNP group (n = 38) received an intra-thyroidal injection of CNP dye. The ICG group (n = 42) used the ICG near-infrared fluorescence endoscopy system to show parathyroid fluorescence. The group that received a combined approach of ICG and CNP (n = 44) leveraged the advantages of both methods that allow for positive development of ICG and negative development of CNP to identify and preserve the parathyroid gland during operation. The parathyroid hormone detection reagent (PTH test method) was employed to verify the highly suspected parathyroid tissue in all three groups. We analyzed intraoperative data pertaining to intraoperative parathyroid identification, misexcision, number of autotransplantation, and postoperative hypoparathyroidism among the three groups. Compared with the ICG group and the CNP group, the combined group demonstrated more prominent advantages in identifying average the number of lower parathyroid glands (1.93 ± 0.26, p = 0.015), reducing the average numberrate of misexcision (0.45 ± 0.5, p = 0.004), and reducing the incidence of postoperative temporary hypothyroidism (3/44, p = 0.015). The combined use of ICG and CNP dual-dye with PTH test method appears to be more effective in both identifying and protecting parathyroid glands during PTC surgery. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) progresses slowly and has a good prognosis, while the prognosis is worse if combined with central neck lymph node metastasis at an early stage. The different endoscope approaches may affect the thoroughness of lymph node dissection. This study aimed to compare the clinical efficacy and safety of prophylactic central lymph node dissection (CLND) for cN0 PTC performed via breast and transoral approach versus via breast approach alone. Materials and methods: A retrospective analysis of the surgical data of 136 patients with stage cN0 PTC was performed from August 2020 to December 2022. Among them, 64 underwent the breast and transoral approach (combined approach group), and 72 underwent the breast approach alone (breast approach group). The relevant indexes of surgery, the number of lymph nodes dissected, the occurrence of postoperative complications, and the cosmetic satisfaction of incision were statistically compared between the two groups. Results: The operation time of the combined approach group was 156.4 ± 29.8 min, significantly longer than that of the breast approach group, 119.6 ± 55.9 min, and the difference was statistically significant (P<0.05). The two groups of patients were compared in terms of intraoperative bleeding, postoperative drainage, hospitalization time, incision cosmetic satisfaction, and the occurrence of postoperative complications, and the differences were not statistically significant (P>0.05). The total number of lymph nodes retrieved in the central area (10.6 ± 7.1) and the number of positive lymph nodes (4.6 ± 4.9) in the combined approach group were significantly more than those in the breast approach group (7.4 ± 4.8, 1.6 ± 2.7), and the difference was statistically significant (P<0.05). The difference between the two groups in terms of the number of negative lymph nodes was not statistically significant (P>0.05). Conclusions: The study demonstrated that choosing the breast combined transoral approach for prophylactic CLND of cN0 PTC could more thoroughly clear the central area lymph nodes, especially the positive lymph nodes, which could help in the evaluation of the disease and the guidance of the treatment, while not increasing the postoperative complications. It provides a reference for clinicians to choose the appropriate surgical approach and also provides new ideas and methods for prophylactic CLND in patients with cN0 PTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Thyroid cancer is the most diagnosed endocrine cancer. There are several types of thyroid cancer, which vary in aggressiveness and survival rate. Well-differentiated thyroid cancers, such as papillary and follicular thyroid cancer, are therapeutic-responsive, with high survival rates. Anaplastic thyroid cancer is undifferentiated, represents <2% of thyroid cancer cases, and is completely unresponsive to therapy, with a grim 5-year survival rate of <4%. Varying gene expression between non-cancerous and cancerous tissue may help define similarities and differences between these thyroid cancer types and, thus, help with the development of more effective therapeutic and diagnostic strategies. Long non-coding RNA molecules are identified as important cell regulators that can alter cell behavior at several different levels. The roles of several long-noncoding RNAs have been identified to characterize thyroid cancer. This review covers several long non-coding RNAs identified for their pathologic expression patterns and functions as cancer-promoting molecules. Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations. [ABSTRACT FROM AUTHOR]

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3–18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery. [ABSTRACT FROM AUTHOR]

Background: While males present with more adverse clinicopathologic features in papillary thyroid carcinoma (PTC), younger age has previously been shown to be a favorable prognostic factor. We examined the combined effect of male sex and young age on PTC outcomes. Methods: We conducted a retrospective analysis of a prospectively maintained database of thyroid cancer surgery patients (2000–2020) at a single quaternary care institution. We included papillary thyroid carcinoma cases and excluded those with prior cancer‐related thyroid surgery. We examined demographics, cancer stage, surgical outcomes, and complications by age and sex, analyzing groups below and above the age of 40 years. Results: A total of 680 patients with PTC were included. Females constituted 68% (age ≥40 years: 44% and <40 years: 24%) and males 32% (≥40 years: 24% and <40 years: 8%). A significant difference (p < 0.001) of N1 disease distribution was found between the groups. N1a metastasis was greater in patients younger than 40 regardless of sex ((M < 40 (15%), F < 40 (15%), M ≥ 40 (12%), and F ≥ 40 (9%)). While, M < 40 had greater N1b metastasis (36%) than all other groups (M ≥ 40 (28%), F < 40 (22%), and F ≥ 40 (10%)). There was no significant difference in the distribution of T stages between groups. Groups showed no differences in 30‐day outcomes, recurrence at 1 year, reoperation, mortality, nerve injury, or hypocalcemia. Conclusions: Young males with PTC face increased occurrence of nodal metastasis yet experience similar recurrence rates as their female and older counterparts. Subgroup analysis underscores the predictive role of sex and age in advanced PTC cases. [ABSTRACT FROM AUTHOR]

Background Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases. Methods A total of 1042 lymph node metastases, derived from 129 PTC patients, were reexamined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications, and the proportion of the lymph node taken up by tumor cells. Predictors for a failure to achieve a complete biochemical and structural response to treatment were determined. Results The presence of more than 5 lymph node metastases was the only independent predictor for a failure to achieve a complete response to treatment (odds ratio [OR] 3.39 [95% CI, 1.57-7.33], P <.05). Diameter nor any of the other evaluated lymph node features were significantly associated with the response to treatment. Conclusions Detailed reexamination of lymph nodes revealed that only the presence of more than 5 lymph node metastases was an independent predictor of failure to achieve a complete response to treatment. No predictive value was found for other histopathological features, including the diameter of the lymph node metastases. These findings have the potential to improve risk stratification in patients with PTC and clinically evident lymph node metastases. [ABSTRACT FROM AUTHOR]

CircRNAs have been found to participate in the progression of various tumors. In the present study, we aimed to clarify the role of hsa_circ_0092355 in papillary thyroid cancer (PTC) cell development. RT-qPCR was used to determine the expression of hsa_circ_0092355, miR-543, and PDE5A. PTC cell proliferation was ascertained via a cell colony formation assay and the CCK-8 test. Western blotting was performed to examine the expression levels of PDE5A and apoptosis-associated proteins (Bcl-2 and Bax) in PTC cells. A scratch wound assay was performed to measure the migration of PTC cells. A mouse xenograft test was performed to assess the effects of hsa_circ_0092355 in vivo. RIP and dual-luciferase reporter assays confirmed the association between miR-543 and hsa_circ_0092355 or PDE5A. Associations between miR-543, hsa_circ_0092355, and PDE5A were evaluated using Pearson's correlation coefficient. Upregulation of hsa_circ_0092355 was observed in PTC tissues. The hsa_circ_0092355 knockdown blocked the proliferation and migration of PTC cells and induced apoptosis. Moreover, hsa_circ_0092355 knockdown blocked PTC xenograft tumor growth in vivo. The miR-543 inhibitor could reverse the changes induced by hsa_circ_0092355 knockdown by hsa_circ_0092355 targeting miR-543. Furthermore, miR-543 suppresses PTC progression by downregulating PDE5A expression. Our findings suggest that the PTC tumor promoter hsa_circ_0092355 may promote carcinogenesis by controlling the miR-543/PDE5A pathway. [ABSTRACT FROM AUTHOR]

Context Obesity is a risk factor for the development of papillary thyroid cancer (PTC). However, the molecular mechanisms by which obesity promotes PTC are unclear. Objective This study aims to identify adipokines that are linked to PTC progression. Methods An adipokine antibody array was used to determine the serum levels of 40 adipokines in normal-weight and obese PTC patients. Enzyme-linked immunosorbent assay was used to determine the serum levels of adiponectin. Recombinant human adiponectin was produced by human adipose-derived stem cells and used to treat PTC cells. Cell proliferation and migration were evaluated using the CCK8 and Transwell assays. Bioinformatics analysis was used to predict mechanisms by which adiponectin affects PTC. Results Adipokines differentially expressed between normal-weight and obese patients showed a gender-dependent pattern. Obese PTC patients had a significantly lower serum adiponectin level than normal-weight patients, especially in female individuals. Adiponectin levels were negatively correlated with aggressive features of PTC, including tumor diameter > 1 cm, extrathyroidal extension, and lymph node metastasis. Recombinant human adiponectin inhibited the proliferation and migration of human PTC cells in vitro. Bioinformatics analysis identified adiponectin receptor 2 (ADIPOR2) and the autophagy pathway as possible mediators of adiponectin function in TC. In vitro experiments confirmed that adiponectin activated autophagy in PTC cells. These findings shed new lights into the role and mechanisms of adiponectin in TC pathogenesis. Conclusion Adiponectin is involved in development of obesity-related PTC. Adiponectin can directly inhibit thyroid cancer growth and metastasis through the autophagy pathway. [ABSTRACT FROM AUTHOR]

Purpose: Radioiodine (RAI) therapy remains the gold-standard approach for distant metastatic differentiated thyroid cancer (TC). The main objective of our work was to identify the clinical and molecular markers that may help to predict RAI avidity and RAI therapy response of metastatic lesions in a cohort of papillary thyroid cancer (PTC) patients. Methods: We performed a retrospective analysis of 122 PTC patients submitted to RAI therapy due to distant metastatic disease. We also analysed, through next-generation sequencing, a custom panel of 78 genes and rearrangements, in a smaller cohort of 31 metastatic PTC, with complete follow-up, available RAI therapy data, and existing tumour sample at our centre. Results: The most frequent outcome after RAI therapy was progression of disease in 59.0% of cases (n = 71), with median estimate progression-free survival of 30 months. RAI avidity was associated with PTC subtype, age and stimulated thyroglobulin at first RAI therapy for metastatic disease. The most frequently altered genes in the cohort of 31 PTC patients' primary tumours were RAS isoforms (54.8%) and TERT promoter (TERTp) (51.6%). The presence of BRAF p.V600E or RET/PTC alterations was associated with lower avidity (p = 0.012). TERTp mutations were not associated with avidity (p = 1.000) but portended a tendency for a higher rate of progression (p = 0.063); similar results were obtained when RAS and TERTp mutations coexisted (p = 1.000 and p = 0.073, respectively). Conclusions: Early identification of molecular markers in primary tumours may help to predict RAI therapy avidity, the response of metastatic lesions and to select the patients that may benefit the most from other systemic therapies. [ABSTRACT FROM AUTHOR]

E3 ubiquitin ligase synoviolin (SYVN1) has been reported to participate in many human cancers. This study aimed to investigate SYVN1's roles and molecular pathways in papillary thyroid cancer (PTC). The functions of SYVN1 in PTC were further analyzed using gain- and loss-of-function methods and numerous investigations in cellular function and molecular biology. The findings demonstrated that the overexpression of SYVN1 markedly suppressed the proliferation, migration, and invasion of PTC cell lines (NPA87 and TPC-1). We found that SYVN1 interacted with HMGB1 and promoted its ubiquitination and degradation. In addition, SYVN1 effectively impairs cell proliferation, migration, invasion, and the formation of tumor xenografts in mice models. However, this effect may be partly reversed by overexpressing HMGB1. Thus, SYVN1 may inhibit the proliferation, migration, and invasion of PTC cells by disrupting HMGB1. Consequently, SYVN1 might be considered a promising therapeutic target for PTC. [ABSTRACT FROM AUTHOR]

Background: Although papillary thyroid carcinoma (PTC) has a favorable prognosis, it could affect patient life quality and become a serious threat because of invasion and metastasis. Many investigations have suggested that circular RNAs (circRNAs) are involved in different cancer regulations. Nevertheless, circRNAs role in invasive PTC remains unclear. Methods: In the present investigation, next-generation sequencing was applied to explore abnormal circRNA expression. The expression of circRNA phosphoglycerate dehydrogenase (circPHGDH) in PTC cell lines and tissues were examined. Then, we investigated regulatory mechanism and circPHGDH downstream targets using bioinformatics analysis and luciferase reporting analysis. Then transwell migration, Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used for cells migration and proliferation analysis. In vivo metastasis and tumorigenesis assays were also employed to evaluate the circPHGDH role in PTC. Results: The data showcased that circPHGDH expression increased in both PTC cell lines and tissues, which suggested that circPHGDH functions in PTC progression. circPHGDH downregulation suppressed PTC invasion and proliferation in both in vivo and in vitro experiments. Bioinformatics and luciferase reporter results confirmed that both microRNA (miR)-122-5p and pyruvate kinase M2 subtype (PKM2) were downstream targets of circPHGDH. PKM2 overexpression or miR-122-5p suppression reversed PTC cell invasion and proliferation post silencing circPHGDH by restoring aerobic glycolysis. Conclusion: Taken together, our research found that circPHGDH downregulation reduced PTC progression via miR-122-5p/PKM2 axis regulation mediated by aerobic glycolysis. [ABSTRACT FROM AUTHOR]

Objective: There is still controversy about whether cervical lymph node dissection should be performed in surgical treatment of PTC. Based on the data of thyroid cancer patients from Liaocheng People's Hospital from 2015 to 2018, this study focused on appropriate indications for cervical lymph node dissection surgery. Methods: The clinical and pathological data of patients with initial treatment of PTC in thyroid surgery department from 2015 to 2018 were collected. In all cases, 1001 patients underwent total thyroidectomy + central lymph node dissection, and 1107 patients underwent total thyroidectomy + central + cervical lymph node dissection. Results: The average metastasis rate of all cases was 57.23%, and even the metastasis rate of PTMC was as high as 48.97%. The total metastasis rate of central and lateral cervical lymph nodes was 74.44%, and the cervical lymph nodes were present in 49.32% of the metastatic cases. In 55.56% of the cases, the tumor diameter was more than 1 cm, and the metastasis rate of cervical lateral area was 56%. With the increase of tumor diameter, the cervical metastasis rate increased from 22.54% to 73.33%. Conclusion: The metastasis rate of PTC is more than 50%, and nearly half of them have cervical metastasis, especially in patients with high risk factors. We observed that PTC 1 cm or greater has significant rates of metastasis. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between contrast-enhanced ultrasound (CEUS) features of PTC and central lymph node metastasis (CLNM) and to develop a predictive model for the preoperative identification of CLNM. Methods: This retrospective study evaluated 750 consecutive patients with PTC from August 2020 to April 2023. Conventional ultrasound and qualitative CEUS features were analyzed for the PTC with or without CLNM using univariate and multivariate logistic regression analysis. A nomogram integrating the predictors was constructed to identify CLNM in PTC. The predictive nomogram was validated using a validation cohort. Results: A total of 684 patients were enrolled. The 495 patients in training cohort were divided into two groups according to whether they had CLNM (pCLNM, n= 191) or not (nCLNM, n= 304). There were significant differences in terms of tumor size, shape, echogenic foci, enhancement direction, peak intensity, and score based on CEUS TI-RADS between the two groups. Independent predictive US features included irregular shape, larger tumor size (≥ 1.0cm), and score. Nomogram integrating these predictive features showed good discrimination and calibration in both training and validation cohort with an AUC of 0.72 (95% CI: 0.68, 0.77) and 0.79 (95% CI: 0.72, 0.85), respectively. In the subgroup with larger tumor size, age ≤ 35 years, irregular shape, and score > 6 were independent risk factors for CLNM. Conclusion: The score based on preoperative CEUS features of PTC may help to identify CLNM. The nomogram developed in this study provides a convenient and effective tool for clinicians to determine an optimal treatment regimen for patients with PTC. [ABSTRACT FROM AUTHOR]

Background: Although papillary thyroid cancer (PTC) patients are known to have an excellent prognosis, up to 30% of patients experience disease recurrence after initial treatment. Accurately predicting disease prognosis remains a challenge given that the predictive value of several predictors remains controversial. Thus, we investigated whether machine learning (ML) approaches based on comprehensive predictors can predict the risk of structural recurrence for PTC patients. Methods: A total of 2244 patients treated with thyroid surgery and radioiodine were included. Twenty-nine perioperative variables consisting of four dimensions (demographic characteristics and comorbidities, tumor-related variables, lymph node (LN)-related variables, and metabolic and inflammatory markers) were analyzed. We applied five ML algorithms—logistic regression (LR), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), and neural network (NN)—to develop the models. The area under the receiver operating characteristic (AUC-ROC) curve, calibration curve, and variable importance were used to evaluate the models’ performance. Results: During a median follow-up of 45.5 months, 179 patients (8.0%) experienced structural recurrence. The non-stimulated thyroglobulin, LN dissection, number of LNs dissected, lymph node metastasis ratio, N stage, comorbidity of hypertension, comorbidity of diabetes, body mass index, and low-density lipoprotein were used to develop the models. All models showed a greater AUC (AUC = 0.738 to 0.767) than did the ATA risk stratification (AUC = 0.620, DeLong test: P < 0.01). The SVM, XGBoost, and RF model showed greater sensitivity (0.568, 0.595, 0.676), specificity (0.903, 0.857, 0.784), accuracy (0.875, 0.835, 0.775), positive predictive value (PPV) (0.344, 0.272, 0.219), negative predictive value (NPV) (0.959, 0.959, 0.964), and F1 score (0.429, 0.373, 0.331) than did the ATA risk stratification (sensitivity = 0.432, specificity = 0.770, accuracy = 0.742, PPV = 0.144, NPV = 0.938, F1 score = 0.216). The RF model had generally consistent calibration compared with the other models. The Tg and the LNR were the top 2 important variables in all the models, the N stage was the top 5 important variables in all the models. Conclusions: The RF model achieved the expected prediction performance with generally good discrimination, calibration and interpretability in this study. This study sheds light on the potential of ML approaches for improving the accuracy of risk stratification for PTC patients. Trial registration: Retrospectively registered at (trial registration number: ChiCTR2300075574, date of registration: 2023-09-08). [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is prevalent among younger populations and has a favorable survival rate. However, a significant number of patients experience psychosocial stress and a reduced quality of life (QoL) after surgical treatment. Therefore, comprehensive evaluations of the patients are essential to improve their recovery. Methods: The present study enrolled 512 young and middle-aged patients diagnosed with PTC who underwent surgery at our institution between September 2020 and August 2021. Each participant completed a series of questionnaires: Generalized Anxiety Disorder 7 (GAD-7), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Thyroid Cancer-Specific Quality of Life Questionnaire (THYCA-QoL), and Readiness to Return-to-Work Scale (RRTW). Results: GAD-7 data showed that almost half of the study subjects were experiencing anxiety. Regarding health-related quality of life (HRQoL), participants reported the highest levels of fatigue, insomnia, voice problems, and scarring, with patients in anxious states reporting worse symptoms. Based on RRTW, more than half of the subjects had returned to work and had better HRQoL compared to the others who were evaluating a possible return to work. Age, gender, BMI, education, diet, residence, health insurance, months since surgery, monthly income, and caregiver status were significantly correlated with return to work. Additionally, having a caregiver, higher monthly income, more time since surgery, and living in a city or village were positively associated with return to work. Conclusion: Young and middle-aged patients with PTC commonly experience a range of health-related issues and disease-specific symptoms following surgery, accompanied by inferior psychological well-being, HRQoL, and work readiness. It is crucial to prioritize timely interventions targeting postoperative psychological support, HRQoL improvement, and the restoration of working ability in PTC patients. [ABSTRACT FROM AUTHOR]

Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAFV600E-mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4–19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2–75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ≥1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4–5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer. Clinical Trial Registration number: Japan Registry of Clinical Trials: jRCT2011200018 [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to investigate the suggested association between body mass index and aggressive histopathological subtypes of thyroid cancer. Thus, we studied 3868 patients who underwent thyroidectomy from 2020 to 2022 at four European centres. We found that overweight and obese patients with papillary thyroid carcinoma had higher rates of aggressive histopathological subtypes, bilateral, multifocal tumours, and larger nodal metastases. These findings suggest that people with higher body mass index may be at an increased risk of developing more aggressive features of thyroid cancer. Obesity's role in thyroid cancer development is still debated, as well as its association with aggressive histopathological subtypes (AHSs). To clarify the link between Body Mass Index (BMI) and AHS of differentiated thyroid carcinoma (DTC), we evaluated patients who underwent thyroidectomy for DTC from 2020 to 2022 at four European referral centres for endocrine surgery. Based on BMI, patients were classified as normal-underweight, overweight, or obese. AHSs were defined according to 2022 WHO guidelines. Among 3868 patients included, 34.5% were overweight and 19.6% obese. Histological diagnoses were: 93.6% papillary (PTC), 4.8% follicular (FTC), and 1.6% Hürthle cell (HCC) thyroid carcinoma. Obese and overweight patients with PTC had a higher rate of AHSs (p = 0.03), bilateral, multifocal tumours (p = 0.014, 0.049), and larger nodal metastases (p = 0.017). In a multivariate analysis, BMI was an independent predictor of AHS of PTC, irrespective of gender (p = 0.028). In younger patients (<55 years old) with PTC > 1 cm, BMI predicted a higher ATA risk class (p = 0.036). Overweight and obese patients with FTC had larger tumours (p = 0.036). No difference was found in terms of AHS of FTC and HCC based on BMI category. Overweight and obese patients with PTC appear to be at an increased risk for AHS and aggressive clinico-pathological characteristics. [ABSTRACT FROM AUTHOR]

To investigate the function of ten-eleven translocation 1 (TET1) and its underlying mechanism in papillary thyroid cancer (PTC). Using the RNA-Seq data based on GDC TCGA, we analyzed the gene expression pattern of TET1 in PTC. Immunohistochemistry was carried out to assess the TET1 protein level. Then, its diagnostic and prognostic functions were determined by various bioinformatics approaches. Enrichment analysis was performed to explore the potential pathways in which TET1 is mainly involved. Finally, the immune cell infiltration analysis was conducted and the association of TET1 mRNA expression with the expression levels of immune checkpoints, tumor mutation burden (TMB) score, microsatellite instability (MSI) score, and cancer stem cells (CSC) score was examined. TET1 expression was lower in PTC tissues compared with that in normal tissues (P < 0.01). Besides, TET1 had a certain value in diagnosing PTC, and low-TET1 mRNA expression led to favorable disease-specific survival (DSS) (P < 0.01). The enrichment analysis revealed autoimmune thyroid disease and cytokine-cytokine receptor interaction were the consistent pathways in which TET1 participated. TET1 was negatively correlated with the Stromal score and Immune score. The different proportions of immune cell subtypes were observed between high- and low-TET1 expression groups. Interestingly, TET1 mRNA expression was inversely related to the expression levels of immune checkpoints, and TMB, MSI, and CSC scores. TET1 might be a robust diagnostic and prognostic biomarker for PTC. TET1 affected the DSS of PTC patients possibly through the regulation of immune-related pathways and tumor immunity. [ABSTRACT FROM AUTHOR]

Purpose: Sex hormones are thought to be responsible for the unique gender differences in papillary thyroid cancer(PTC). Most previous studies on these have focused on the expression of estrogen receptors, or have been limited to animal studies. The aim of our study was to explore the relationship between serum sex hormones and the pathological features of PTC in the clinical setting, as further evidence of the role of sex hormones in PTC. Methods: Retrospective data analysis of patients who underwent thyroid surgery at the Department of Thyroid Surgery, Nanjing Drum Tower Hospital from January 2022 to September 2022 Correlation between serum sex hormone and pathological features was analyzed in male patients and in menopausal female patients. Serum sex hormones include luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), total testosterone(TT), progesterone(P), and prolactin(PRL). Tumor pathological characteristics include the number and size of tumor, presence of extrathyroidal extension(ETE), presence of lymph node metastasis(LNM). Results: Preoperative serum E2 in male patients was positively correlated with tumor size in PTC, LH was negatively correlated with LNM, while TT and P were negatively correlated with ETE. Similar findings were not observed in menopausal female patients. Conclusion: We observed that serum sex hormones correlate with the pathological features of PTC in male patients, for the first time in a clinical study. High serum estrogens may be a risk factor for PTC, while androgens are the opposite. This somewhat corroborates previous research and provides new variables for future PTC prediction models. [ABSTRACT FROM AUTHOR]

Purpose: Telomerase reverse transcriptase (TERT) has been reported in papillary thyroid carcinoma (PTC). This study aimed to investigate the correlation of TERT promoter mutations with clinical and ultrasound (US) features in PTC and to develop a model to predict TERT promoter mutations. Methods: Preoperative US images, postoperative pathological features, and TERT promoter mutation information were evaluated in 365 PTC patients confirmed by surgery. Univariate and multivariate factor analyses were performed to identify risk factors for TERT promoter mutations. A predictive model was established to assess the clinical predictive value. Results: Of the 365 patients with PTC (498 nodules), the number of those with TERT promoter mutations was 67 cases (75 nodules), and the number of those without mutations was 298 cases (423 nodules). The median age was 40 years in the wild-type group and 60 years in the mutant group. Male patients made up 35.82% of the mutant group and 22.82% of the wild-type group. Multivariate analysis revealed that the independent risk factors associated with the occurrence of TERT promoter mutation in PTC were as follows: older age (odds ratio (OR) = 1.07; p = 0.002), maximum diameter of ≥ 10 mm (OR = 3.94; p < 0.0001), unilateral (OR = 4.15; p < 0.0001), multifocal (OR = 7.69; p < 0.0001), adjacent to the thyroid capsule (OR = 1.94; p = 0.044), and accompanied by other benign nodules (OR = 1.94, p = 0.039). A predictive model was established, and the area under the curve (AUC) of the receiver operating characteristic was 0.839. TERT promoter mutations were associated with high-risk US and clinical features compared with the wildtype group. Conclusion: TERT promoter mutations were associated with older ages. They were also found to be multifocal, with a maximum diameter of ≥ 10 mm, unilateral, adjacent to the thyroid capsule, and accompanied by other benign nodules. The predictive model was of high diagnostic value. [ABSTRACT FROM AUTHOR]

Background: In previous studies, we demonstrated the downregulation of several miRNAs from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region, the individual contribution of these molecules to PTC development and progression remains unclear. Objective: In this study, we aimed to clarify the contribution of DLK1-DIO3-derived miRNAs to PTC. Methods: We used different computational approaches and in vitro resources to assess the biological processes and signaling pathways potentially modulated by these miRNAs. Results: Our analysis suggests that, out of more than 100 mature miRNAs originated from the DLK1-DIO3 region, a set of 12 miRNAs accounts for most of the impact on PTC development and progression, cooperating to modulate distinct cancer-relevant biological processes, such as cell migration, extracellular matrix remodeling, and signal transduction. The restoration of the expression of one of these miRNAs (miR-485–5p) in a BRAFT199A-positive PTC cell line impaired proliferation and migration, suppressing the expression of GAB2 and RAC1, validated miR-485–5p targets. Conclusions: Overall, our results shed light on the role of the DLK1-DIO3 region, which harbors promising tumor suppressor miRNAs in thyroid cancer, and open prospects for the functional exploration of these miRNAs as therapeutic targets for PTC.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The incidence of PTC has increased annually worldwide. Thus, PTC diagnosis and treatment attract more attention. Noncoding RNAs (lncRNAs) play crucial roles in PTC progression and act as prognostic biomarkers. Moreover, microRNAs (miRNAs) and epithelial-mesenchymal transition (EMT)-associated proteins have potential biomarkers for diagnosing and treating PTC. However, the correlation of lncRNAs with miRNAs and EMT-associated proteins needs further clarification. The present review highlights the recent advances of lncRNAs in PTC. We significantly summarized the two molecular regulatory mechanisms in PTC progress, including lncRNAs-miRNAs-protein signaling axes and lncRNAs-EMT pathways. This review will help our understanding of the association between lncRNAs and PTC and may assist us in evaluating the prognosis for PTC patients. Taken together, targeting the lncRNAs regulatory network has promising applications in diagnosing and treating PTC.

OBJECTIVES: To evaluate the influence of facility case-volume on survival in patients with locally advanced papillary thyroid cancer (PTC), and to identify prognostic case-volume thresholds for facilities managing this patient population. STUDY DESIGN: Retrospective database study. METHODS: The 2004-2017 National Cancer Database was queried for patients receiving definitive surgery for locally advanced PTC. Using K-means clustering and multivariable Cox proportional-hazards (CPH) regression, two groups with distinct spectrums of facility case-volumes were generated. Multivariable CPH regression and Kaplan-Meier analysis assessed for the influence of facility case-volume and the prognostic value of its stratification on overall survival (OS). RESULTS: Of 48,899 patients treated at 1304 facilities, there were 34,312 (70.2%) females and the mean age was 48.0 ± 16.0 years. Increased facility volume was significantly associated with reduced all-cause mortality (HR 0.996; 95% CI, 0.992-0.999; p = 0.008). Five facility clusters were generated, from which two distinct cohorts were identified: low (LVF;

Abstract Background Mutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of hypodontia, and identified several genes, including AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9, that are directly associated with dental agenesis and carcinogenesis. The objective of this study was to investigate the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women diagnosed with papillary thyroid cancer (PTC), compared to a control group of women without any malignancy or thyroid disease. Materials and methods This case–control study was carried at the Department of Orthodontics, School of Dental Medicine University of Zagreb, and Department of Oncology and Nuclear Medicine Sestre Milosrdnice University Hospital Centre. The study involved a clinical examination and evaluation of dental status, panoramic X-ray analysis, and assessment of medical and family history of 116 female patients aged 20–40 with PTC, as well as 424 females in the control group who were of similar age. Results The prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3% in the experimental group and 3.5% in the control group. The experimental group showed a higher occurrence of missing upper lateral incisors, lower left central incisors, and all the third molars (except the upper left) compared to the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3.5%, 0.7%, p = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia occurs 7.7 times more frequently in women with PTC. Conclusion Our study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.

Abstract Background The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. Methods This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. Results There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.