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BACKGROUND Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. PATIENTS AND METHODS To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. RESULTS Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. CONCLUSIONS Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

Papillary thyroid cancer (PTC) is extremely rare in children. Herein, we present a case diagnosed with PTC at 15 months of age. We conducted a literature review of the published cases with PTC under five years of age. A 1.25-year-old male patient had initially presented with a complaint of progressively enlarging cervical mass that appeared four months earlier. On physical examination, a mass located in the anterior cervical region with the largest measurements of around 3x3 cm was detected. Cervical and thyroid ultrasonography showed a 50x27 mm solid mass in the right lateral neck. Excisional biopsy revealed a follicular variant of PTC with capsular invasion. Subsequently, he underwent a complementary total thyroidectomy. He was diagnosed with intermediate-risk (T3N0M0) PTC. He developed permanent hypoparathyroidism. In the first year of the operation, he was treated with radioiodine ablation (RAI) since basal and stimulated thyroglobulin (Tg) levels tended to increase. Whole-body scintigraphy was normal in the first year of RAI ablation. On levothyroxine sodium (LT4) treatment, levels of thyroid stimulating hormone (TSH) and Tg were adequately suppressed. He is now 8.5-years-old and disease-free on LT4 replacement therapy for seven years and three months. Pediatric PTC has different biological behavior and an excellent prognosis compared to adults. The optimal treatment strategy for pediatric TC is total thyroidectomy, followed by RAI ablation. Post-operative management should include regular follow-up, TSH suppression by adequate LT4 therapy, serial Tg evaluation, and radioiodine scanning when indicated.

BACKGROUND: Patients understandably have concerns about thyroidectomy scars. This study aimed to characterize patients’ perceptions of their thyroidectomy scar before and up to 1-year after surgery. METHODS: Patients with papillary thyroid cancer (n=83) completed semi-structured interviews before and at 2-weeks, 6-weeks, 6-months, and 1-year post-thyroidectomy. Interviews probed about scar concerns and appearance. Content analysis was used to identify themes. RESULTS: The majority of participants did not express concerns about scar appearance. When expressed, preoperative concerns often stemmed from previous surgery experiences or unease with neck incisions. Postoperatively, concerns about scar appearance decreased over time throughout the healing period with most patients being satisfied with their scar appearance by 6-months after surgery. CONCLUSIONS: Patients with papillary thyroid cancer express few concerns about scar thyroidectomy appearance. Surgeons can reassure patients who have preoperative concerns that most patients are satisfied with their scar appearance by 6-months after surgery.

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among the triggering receptors expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease-free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not in macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

Thyroid cancer (TC) is the eighth most frequently diagnosed cancer worldwide with a rising incidence in the past 20 years. Surgery is the primary strategy of therapy for patients with medullary TC (MTC) and differentiated TC (DTC). In DTC patients, radioactive iodine (RAI) is administered after thyroidectomy. Neck ultrasound, basal and thyroid-stimulating hormone-stimulated thyroglobulin are generally performed every three to six months for the first year, with subsequent intervals depending on initial risk assessment, for the detection of possible persistent/recurrent disease during the follow up. Distant metastases are present at the diagnosis in ∼5 % of DTC patients; up to 15 % of patients have recurrences during the follow up, with a survival reduction (70 %–50 %) at 10-year. During tumor progression, the iodide uptake capability of DTC cancer cells can be lost, making them refractory to RAI, with a negative impact on the prognosis. Significant advances have been done recently in our understanding of the molecular pathways implicated in the progression of TCs. Several drugs have been developed, which inhibit signaling kinases or oncogenic kinases (BRAFV600E, RET/PTC), such as those associated with Platelet-Derived Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor. Tyrosine kinase receptors are involved in cancer cell proliferation, angiogenesis, and lymphangiogenesis. Several tyrosine kinase inhibitors (TKIs) are emerging as new treatments for DTC, MTC and anaplastic TC (ATC), and can induce a clinical response and stabilize the disease. Lenvatinib and sorafenib reached the approval for RAI-refractory DTC, whereas cabozantinib and vandetanib for MTC. These TKIs extend median progression-free survival, but do not increase the overall survival. Severe side effects and drug resistance can develop in TC patients treated with TKIs. Additional studies are needed to identify a potential effective targeted therapy for aggressive TCs, according to their molecular characterization.

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

An ongoing debate exists over the optimal management of low-risk papillary thyroid cancer. The American Thyroid Association supports the concept of active surveillance to manage low-risk papillary thyroid cancer; however, the cost-effectiveness of active surveillance has not yet been established. We sought to perform a cost-effectiveness analysis comparing active surveillance versus surgical intervention for patients in the United States.A Markov decision tree model was developed to compare active surveillance and thyroid lobectomy. Our reference case is a 40-year-old female who was diagnosed with unifocal (15 mm), low-risk papillary thyroid cancer. Probabilistic outcomes, costs, and health utilities were determined using an extensive literature review. The willingness-to-pay threshold was set at $50,000/quality-adjusted life year gained. Sensitivity analyses were performed to account for uncertainty in the model's variables.Lobectomy provided a final effectiveness of 21.7/quality-adjusted life years, compared with 17.3/quality-adjusted life years for active surveillance. Furthermore, incremental cost effectiveness ratio for lobectomy versus active surveillance was $19,560/quality-adjusted life year (willing-to-pay threshold of $50,000/quality-adjusted life year), and thus surgical intervention proved to be cost-effective in patients between 40 and 69 years old. Further analysis revealed that, at the age of 69 years, active surveillance is more cost-effective than lobectomy, with a final effectiveness of 17.3/quality-adjusted life years. Compared to active surveillance, the incremental cost effectiveness ratio for lobectomy at the age of 69 was $27,235/quality-adjusted life year, which decreases quality-adjusted life years by 1.5.Lobectomy is a cost-effective strategy in middle-aged patients with low-risk papillary thyroid cancer. In contrast, active surveillance is cost-effective beginning at the age of 69. Identification of such nuances can help physicians and patients determine the best, most individualized long-term management strategy for low-risk papillary thyroid cancer.

Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied.Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables.A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P.01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P.001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004).For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine.

Introduction Multifocality is increasingly observed in papillary thyroid carcinoma (PTC) due to improvements in imaging and histopathological analysis. However, its significance in management, particularly as a sole risk-factor, remains controversial. This study aimed to investigate the prognostic value of multifocality in predicting recurrence following thyroid lobectomy in a contemporary group of PTC patients managed in the UK. Methods Patients with PTC in NHS Lothian (2009-19) and Guys and St Thomas NHS Foundation Trust (2012-19) were identified. Categorical variables were compared using Chi-squared or Fisher’s exact test. Five-year recurrence free survival (RFS) were analysed using Kaplan-Meier method and compared using log-rank. Results Of 828 patients; 492 (59%) had unifocal and 336 (41%) multifocal disease on final pathology. A higher rate of pathological nodal disease (22%v36%,p

In an assessment of risk for differentiated thyroid cancer (DTC) in individuals with human papillary thyroid cancer (PTC) and thyroid nodules a cohort prospective study was undertaken to establish the significance of preoperative thyroid-stimulating hormone (TSH) levels. Confirmed histologically PTC cases in one tertiary care center, and matched healthy individuals were tested for TSH, T3, T4 and T4 free total. The ORs and 95% confidence intervals have been calculated using conditional logistic regression models (CI). The blood TSH levels were related to the higher risk of PTC for men (OR,0,09; 95% Ci, 04–0,21, 95% CI and women) compared with the middle tertile of the TSH levels in the normal range (OR,0,07; 95 percent CI, 0,04–0,1). Over the normal range of TSH levels, an elevated PTC risks were connected amongst women (OR 0,09; 95% CI, 0,04–0,21) but not amongst men (OR,0,07; 95% CI, 0,04–0,1). With an increase in TSH level in the normal range between men and women, the risk for PTC reduced (Ptrend=0.041 and 0.0001). The risk of PTC related to TSH levels has been dramatically elevated above the normal range for men and TSH values below the normal range for women.

BACKGROUND Thyroglossal duct cysts (TDC) account for 7% of midline neck swellings. TDC carcinoma (TDCC) is rare, reported in 1% of all TDCs. We aimed to describe the incidence of TDCC, the accuracy of fine needle aspiration cytology (FNAC), and to identify suspicious, predictive ultrasound (USG) features. METHOD A cross sectional study of TDC patients in the Monash University Endocrine Surgery Database from 2001 to 2021. RESULTS Eighty-six patients had surgery for TDC, of median age 48 and a female preponderance (62%). Preoperative USG was used in 85% and FNAC in 57%. There were six cases (7%) of TDCC with papillary thyroid cancer (PTC). USG in five TDCC cases showed a solid nodule within the cyst wall. FNAC was undertaken in five TDCC cases from the solid nodule; malignant in one and suspicious for malignancy in two. Two TDCC patients had concurrent total thyroidectomy (TT), and three subsequently had a TT. Multifocal thyroid PTC was found in two patients. One patient had a recurrence in the lateral lymph nodes, nine years after excision of the TDCC and TT. All patients are alive and well with no distant metastases (median follow up 11 years). CONCLUSION The 7% incidence of TDCC is higher than the usually reported 1% in the literature. We recommend a preoperative USG to evaluate the TDC, thyroid gland and cervical lymph nodes, and an FNAC to target the solid component of the TDC, and favour total thyroidectomy for all patients with TDCC.

Context Thyroid cancer recurrence is associated with increased mortality and adverse outcomes. Recurrence risk is currently predicted using clinical tools, often restaging patients after treatment. Detailed understanding of recurrence risk at disease onset could lead to personalized and improved patient care. Objective We aimed to perform a comprehensive bioinformatic and experimental analysis of 3 levels of genetic change (mRNA, microRNA, and somatic mutation) apparent in recurrent tumors and construct a new combinatorial prognostic risk model. Methods We analyzed The Cancer Genome Atlas data (TCGA) to identify differentially expressed genes (mRNA/microRNA) in 46 recurrent vs 455 nonrecurrent thyroid tumors. Two exonic mutational pipelines were used to identify somatic mutations. Functional gene analysis was performed in cell-based assays in multiple thyroid cell lines. The prognostic value of genes was evaluated with TCGA datasets. Results We identified 128 new potential biomarkers associated with recurrence, including 40 mRNAs, 39 miRNAs, and 59 genetic variants. Among differentially expressed genes, modulation of FN1, ITGα3, and MET had a significant impact on thyroid cancer cell migration. Similarly, ablation of miR-486 and miR-1179 significantly increased migration of TPC-1 and SW1736 cells. We further utilized genes with a validated functional role and identified a 5-gene risk score classifier as an independent predictor of thyroid cancer recurrence. Conclusion Our newly proposed risk model based on combinatorial mRNA and microRNA expression has potential clinical utility as a prognostic indicator of recurrence. These findings should facilitate earlier prediction of recurrence with implications for improving patient outcome by tailoring treatment to disease risk and increasing posttreatment surveillance.

Long non-coding RNA LIFR-AS1 is low-expressed in many cancers, but its functions in papillary thyroid carcinoma (PTC) were not defined and require further study. The relationship between LIFR-AS1 expression and clinicopathological characteristics of patients with PTC was statistically analyzed. The downregulation of LIFR-AS1 in PTC tissues and cell lines was predicted by bioinformatics analysis and verified by qRT-PCR. After overexpressing or silencing LIFR-AS1, the regulatory role of LIFR-AS1 in PTC was examined by performing MTT, colony formation, wound healing, Transwell, ELISA, tube formation and xenograft tumor experiment. MiR-31-5p and SID1 transmembrane family member 2 (SIDT2) expressions in PTC tissues or cell lines were detected by qRT-PCR, Western blot, or in situ hybridization. The relationship between miR-31-5p and LIFR-AS1/SIDT2 was predicted by LncBase, TargetScan or Pearson correlation test and then verified by Dual-Luciferase Reporter assay, RNA pull-down assay and qRT-PCR. The regulatory effect of LIFR-AS1/miR-31-5p/SIDT2 axis on the biological behaviors of PTC cells was confirmed by functional experiments and rescue experiments mentioned above. The tumor size and lymphatic metastasis were correlated with LIFR-AS1 overexpression. Overexpressed LIFR-AS1 suppressed tumorigenesis in vivo. LIFR-AS1 and SIDT2 expressions were suppressed in PTC tissues, while that of miR-31-5p was elevated in PTC tissues. LIFR-AS1 was negatively correlated with miR-31-5p. LIFR-AS1 sponged miR-31-5p to upregulate SIDT2, thereby inhibiting the viability, proliferation, migration, invasion, and the secretion of vascular endothelial growth factor (VEGF) of PTC cells and angiogenesis of human umbilical vein endothelial cells (HUVECs). This paper demonstrates that LIFR-AS1/miR-31-5p/SIDT2 axis modulated the development of PTC.

Deubiquitinating enzyme OTU domain‐containing ubiquitin aldehyde‐binding proteins 1 (OTUB1) has been shown to have an essential role in multiple carcinomas. However, the function of OTUB1 in papillary thyroid cancer (PTC) and the underlying mechanisms regulating PTC cells proliferation remain poorly understood. In this study, OTUB1 was significantly upregulated in papillary thyroid carcinoma tissues and cells. Through in vitro and in vivo experiments, knockdown of OTUB1 suppressed PTC cells growth whereas OTUB1 overexpression enhanced the proliferation ability of PTC cells. Moreover, the eyes absent homologue 1 (EYA1) was recognized as a potential target of OTUB1 through mass spectrometry analysis, and we further verified that EYA1 protein level was positively correlated with OTUB1 expression in PTC cells and clinical samples. Mechanistically, OTUB1 could interact with EYA1 directly and deubiquitinate EYA1 to stabilize it. At last, EYA1 was found to play an essential role in OTUB1‐derived PTC cells growth. Overall, our investigation reveals that OTUB1 is a previously unrecognized oncogenic factor in PTC cells proliferation and suggests that OTUB1 might be a novel therapeutic target in PTC.

Background Chimeric antigen receptor T cells (CAR-Ts) have demonstrated remarkable efficacy in hematological cancers but have not yet translated in treating solid tumors. The significant hurdles limiting CAR-T therapy were from a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present TSH receptor (TSHR) as a putative target for CAR-T therapy of differentiated thyroid cancer (DTC). Methods We undertook a large-scale screen on thyroid cancer tissues and multiple internal organs through bioinformatical analysis and immunohistochemistry to date TSHR expression. Using 3 previously described monoclonal antibodies, we generated 3 third-generation CAR-Ts. We tested anti-TSHR CAR-T in vitro activity by T-cell function and killing assay. Then we tested preclinical therapeutical efficacy in a xenograft mouse model of DTC and analyzed mice’s physical conditions and histological abnormalities to evaluate anti-TSHR CAR-T’s safety. Results TSHR is highly and homogeneously expressed on 90.8% (138/152) of papillary thyroid cancer, 89.2% (33/37) of follicular thyroid cancer, 78.2% (18/23) of cervical lymph node metastases, and 86.7% of radioactive iodine resistance diseases. We developed 3 novel anti-TSHR CAR-Ts from monoclonal antibodies M22, K1-18, and K1-70; all 3 CAR-Ts mediate significant antitumor activity in vitro. Among these, we demonstrate that K1-70 CAR-T can have therapeutical efficacy in vivo, and no apparent toxicity has been observed. Conclusion TSHR is a latent target antigen of CAR-T therapy for DTC. Anti-TSHR CAR-T could represent a therapeutic option for patients with locoregional relapsed or distant metastases of thyroid cancer and should be tested in carefully designed clinical trials.

Background Metabolic syndrome (MetS) was a risk factor for papillary thyroid cancer (PTC). Whether MetS impacts the aggressiveness of PTC is still unclear. We carried out this study to clarify this issue. Methods We evaluated 745 consecutive PTC patients treated with surgery. Patients were divided into three groups based on their number of MetS components: patients without any MetS components, patients with 1–2 MetS components, and patients with 3–5 MetS components. The clinical features and histological aggressiveness of PTC at the time of diagnosis were evaluated. Results A total of 745 patients were included in this study. And, 145 patients had three or more metabolic components and were diagnosed as MetS. MetS was a risk factor for larger tumors (OR = 2.29, 95% CI: 1.31–4.03), more lymph node metastasis (OR = 1.97, 95% CI: 1.11–3.51), and later clinical stage (OR = 7.92, 95% CI: 1.59–39.34) after correction for age, sex, and thyroid-stimulating hormone (TSH) level and body mass index (BMI). Conclusion In our hospital-based cohort study MetS was associated with the aggressiveness of PTC. This association was still significant after adjusting for age, sex, TSH, and BMI.

Background A few researches evaluated the association of polymorphisms at SERPINA5 and fat mass and obesity-associated protein (FTO) genes with papillary thyroid cancer (PTC) globally. Here, we examined the presence of genetic variations within coding exon 3 of SERPINA5 gene and FTO rs9939609 polymorphism in Iranian PTC patients. Methods A total of 122 patients (42 cases for SERPINA5 and 80 cases for FTO gene) and 120 healthy subjects (40 subjects or SERPINA5 and 80 subjects for FTO gene) were recruited. The genetic variation within coding exon 3 of SERPINA5 gene was evaluated by reaction-single-strand conformation polymorphism (PCR-SSCP) and FTO rs9939609 polymorphism was evaluated by RFLP-PCR assay. Results The PCR-SSCP technique detected two rs6115G>A and rs6112T>C genetic variations within coding exon 3 of SERPINA5 gene and approved also by direct sequencing. For rs6112T>C polymorphism seven patients was heterozygous and for rs6115G>A seven PTC patients were heterozygous and two patients were homozygous. Conclusion This study indicated that SERPINA5 rs6115G>A and rs6112T>C polymorphisms might be a novel susceptibility locus for PTC in Iranian patients. However, our findings do not support an association between FTO rs9939609 polymorphism and PTC risk.

Introduction Papillary thyroid cancer corresponds to approximately 1% of all carcinomas; nevertheless, it is the most prevalent endocrine neoplasm in the world. Studies reveal that the BAX (−248 G > A) polymorphism may be associated with negative regulation of BAX gene transcription activity, causing a decrease in its protein expression. Objective The present study aimed to describe the genotype and allele frequencies of BAX single nucleotide polymorphisms (−248 G > A) (rs4645878) in the research patients, and to associate its presence with susceptibility to papillary thyroid cancer. Methods This case-control study was conducted with 30 patients with papillary thyroid cancer. For the evaluation of genetic polymorphisms, the polymerase chain reaction-restriction fragment length polymorphism technique was employed. Allele and genotype frequencies were estimated using the SPSS program, and significant associations were considered when p Results There was a significant genotypic difference between papillary thyroid cancer and the control group (p = 0.042). The GG genotype provided a protective factor for papillary thyroid cancer (p = 0.012, odds ratio (OR) = 0.313; confidence interval (CI) = 0.123–0.794). Likewise the G allele was a protective factor for papillary thyroid cancer (p = 0.009; OR = 0.360; CI = 0.163–0.793). The BAX gene polymorphism (−248 G > A) was associated with papillary thyroid cancer. Conclusion BAX (−248 G > A) GG genotype carriers, or at least one mutated allele, was associated with papillary thyroid cancer in the Brazilian population studied, and the G allele presence is considered a protective factor against papillary thyroid cancer occurrence.

BACKGROUND/AIM Thyroid lobectomy may cause post-lobectomy hypothyroidism. We investigated the difference in levothyroxine (LT4) supplementation and cessation between patients with benign disease and those with papillary thyroid carcinoma (PTC) and found that the rate of LT4 cessation could be decreased after thyroid-stimulating hormone (TSH) suppression in PTC. PATIENTS AND METHODS We retrospectively reviewed 88 patients with benign tumor and 463 patients with PTC and investigated the risk factors for LT4 supplementation after thyroid lobectomy. RESULTS During the median follow-up of 73.0 months, 207 (37.6%) patients maintained the euthyroid state, while 344 (62.4%) patients continued LT4 supplementation for LT4 replacement or TSH suppression. In patients with benign tumors, only high pre-TSH level (>1.98 mIU/l) was a significant risk factor (odds ratio [OR]=10.09). However, in patients with PTC, pre-TSH level ≥1.98 mIU/l (OR=3.28), pregnancy planning (OR=2.97), and age ≥42.5 years (OR=1.94) were significant risk factors. Moreover, the most potent risk factor was tumor aggressiveness (OR=4.00), which was found to be more significant than high pre-TSH. The overall rate of LT4 cessation in all patients was 37.6%; however, in the 303 patients who underwent the LT4-Off trial, there was no difference in the rate in the benign tumor, low-risk PTC, and intermediate-risk PTC groups (66.2%, 68.8%, and 70.8%, respectively; p=0.886). CONCLUSION When post-lobectomy TSH levels were adequate and the risk of recurrence was reduced, LT4 cessation in PTC could be achieved at the same rate as that in benign tumors, regardless of the duration of TSH suppression.

OBJECTIVE: To compare and evaluate diagnostic capabilities of preoperative ultrasonography (US) and magnetic resonance imaging (MRI) in the cervical lymph nodes of patients with papillary thyroid cancer. METHODS: A retrospective dataset involving 156 patients who had undergone thyroidectomy and preoperative US and MRI was assembled. Among these, 69 had cervical lymph node metastasis and 87 did not. At least four radiologists unilaterally and spontaneously investigated the US and MRI attributes of the cervical lymph nodes. The efficiency of diagnostic imaging for cervical lymph nodes, including their true-positive rate or sensitivity, true-negative rate or specificity, positive predictive value, negative predictive value, and predictive accuracy were analysed and assessed. RESULTS: In the assessment of cervical lymph node metastases of papillary thyroid cancer, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of diagnostic US vs. MRI were 58.0% vs. 79.7%, 69.0% vs. 83.9%, 59.7% vs. 79.7%, 67.4% vs. 83.9%, and 64.1% vs. 82.1%, respectively. The accuracy consistency of the two imaging modalities was 83.5%. CONCLUSIONS: MRI is more effective than US in diagnosing and assessing cervical lymph node metastases of papillary thyroid cancer.

OBJECTIVE We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that scrutinized the oncological benefits and postsurgical complications of total thyroidectomy (TT) plus prophylactic central neck dissection (pCND) versus TT alone among clinically node-negative (cN0) papillary thyroid cancer (PTC) patients. METHODS We screened five databases from inception to September 4, 2021 and evaluated the risk of bias of the eligible studies. We pooled dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI). RESULTS Overall, we included 5 RCTs with low risk of bias comprising 795 patients (TT plus pCND = 410 and TT alone = 385). With regard to efficacy endpoint, the rate of structural loco-regional recurrence did not significantly differ between both groups (n = 4 RCTs, RR = 0.49, 95% CI [0.19, 1.27], P = .14). With regard to safety endpoints, the rates of hypoparathyroidism (n = 5 RCTs, RR = 1.48, 95% CI [0.73, 2.97], P = .27), recurrent laryngeal nerve injury (n = 5 RCTs, RR = 1.34, 95% CI [0.59, 3.03], P = .48), and bleeding (n = 3 RCTs, RR = 1.75, 95% CI [0.42, 7.26], P = .44) did not significantly differ between both groups. CONCLUSION For cN0 PTC patients, there was no significant difference between TT plus pCND and TT alone with regard to the rate of structural loco-regional recurrence or frequency of postsurgical complications. Adaptation of pCND in cN0 PTC patients should be contemplated by taking into consideration the clinical oncological benefits and rate of postsurgical adverse events. LEVEL OF EVIDENCE 1 Laryngoscope, 2021.

As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its correlation with matched clinical information was performed using a 389 PTC patient cohort from the project of The Cancer Genome Atlas (TCGA). We identified 1,925 cancer-associated AS events (CASEs) by comparing paired tumors and neighboring healthy tissues. Parent genes with CASEs remarkably enriched in the pathways were linked with carcinogenesis, such as P53, KRAS, IL6-JAK-STAT3, apoptosis, and MYC signaling. The regulatory networks of AS implied an obvious correlation between the expression of splicing factor and CASE. We identified eight CASEs as predictors for overall survival (OS) and disease-free survival (DFS). The established risk score model based on DFS-associated CASEs successfully predicted the prognosis of PTC patients. From the unsupervised clustering analysis results, it is found that different clusters based on AS correlated with prognosis, molecular features, and immune characteristics. Taken together, the comprehensive genome-wide AS landscape analysis in PTC showed new AS events linked with tumorigenesis and prognosis, which provide new insights for clinical monitoring and therapy for PTC.

BackgroundBrown tumors are benign osteoclastic bone lesions encountered in patients with hyperparathyroidism. These tumors may demonstrate aggressive, destructive features in the skeleton and imitate metastatic bone lesions, particularly in patients with known primary neoplasm. In this case report of recurrent papillary thyroid cancer and ectopic parathyroid adenoma, we shed light on the importance of combining different nuclear medicine imaging modalities to differentiate brown tumors from metastatic bone lesions.Case presentationWe present a 39-year-old woman with a known history of papillary thyroid carcinoma classic type stage pT1N1b post-total thyroidectomy and radioactive iodine (I-131) therapy (RAI) presented with upper limb weakness and pain. An expansile lytic lesion involving the 6th cervical vertebra was seen in cervical spine MRI, which was suspicious for metastatic deposit. Therapeutic and diagnostic I-131 whole-body scans were negative for any I-13-avid lesions. Laboratory results revealed high calcium, parathyroid hormone, and alkaline phosphatase. A Technetium-99m-sestamibi (Tc-99m MIBI) scan was done with the standard protocol of spot views to the neck and upper chest area to localize any suspicious parathyroid adenoma. The scan demonstrated right supraclavicular and mediastinal Tc-99m MIBI-avid lesions suspicious for being ectopic parathyroid adenomas. Whole-body fluorine-18-2-fluoro-2-deoxy-d-glucose (18F-FDG), positron emission tomography/computed tomography (PET/CT) (18F-FDG PET/CT) was performed for further evaluation. It demonstrated multiple focal lytic skeletal lesions of abnormal increased FDG uptake as well as right supraclavicular FDG-avid lymph nodes. However, the superior mediastinal lesion was non-FDG-avid, suggesting the existence of two different entities: ectopic parathyroid adenoma with multiple brown tumors and metastatic right supraclavicular lymph nodes. The patient underwent right neck dissection and superior mediastinal mass excision. An intra-operative fresh serum parathyroid sample was sent, which dropped down to 100ng/ml from 863.7ng/ml. Later, histopathological results revealed that the right supraclavicular lymph nodes were metastatic papillary thyroid carcinoma. At the same time, the superior mediastinal mass proved to be parathyroid adenoma by histopathology, confirming the18F-FDG PET/CT findings.ConclusionsIn the case of papillary thyroid carcinoma, metastatic lymph nodes with hyperparathyroidism, and evidence of lytic bone lesions, careful interpretation of the different metabolic and functional imaging modalities are needed to exclude the concurrent parathyroid adenoma and facilitate the differentiation of brown tumors from bone metastases, leading to appropriate surgical and medical treatment plans.

INTRODUCTION: Papillary thyroid cancer (PTC) is the most common form of thyroid cancer. Although the survival rate is excellent, recurrence is as high as 20%. The mainstay of therapy is thyroidectomy and lymph node dissection based on risk factors. Data from other cancers suggest that surgical outcomes are most optimal at comprehensive cancer centers. We hypothesize that patients with PTC who had their initial operation at a comprehensive cancer center would have a better oncologic outcome. METHODS: We utilized an IRB-approved cancer care registry database of patients with thyroid cancer who were seen at our institution between 2000 and 2018. Patient records were updated with cancer-specific outcomes including recurrence and need for re-intervention. Clinical and surgical outcomes were then compared between patients who had their initial operation at a comprehensive cancer center (CCC group, n=503) versus those who did not (non-CCC group, n=72). RESULTS: Mean patient age was 49 ± 16 years and 70% were female. Average tumor size was 1.6 ± 1.6 cm. There was no difference in tumor size, age, gender or race between groups. Pre-operative ultrasound was more frequently performed at the CCC (89%) than at non-CCC’s (51%, p < 0.001). CCC patients were more likely to undergo initial total thyroidectomies compared to non-CCC patients (76% vs. 21%, p < 0.001). Positive surgical margins were more frequently found in patients at non-CCC’s (19%) than at the CCC (9.7%, p = 0.016). Finally, CCC patients had a significantly lower cancer recurrence rate (5.0% vs. 37.5%, p

Papillary thyroid cancer (PTC) usually has favorable prognosis; however, distant metastasis is a leading cause of death associated with PTC. MicroRNA-99a-3p (miR-99a-3p) is a member of the miR-99 family that is shown to be a tumor suppressor in various human cancers including the anaplastic thyroid cancer, another type of thyroid cancer. The Cancer Genome Atlas database and our previous study reported that miR-99a-3p is downregulated in human PTC tissues as well as human papillary thyroid carcinoma B-CPAP and TPC-1 cell lines. However, its pathological role in PTC remains unclear, especially its impact on PTC metastasis. In the present study, the role of miR-99a-3p in PTC metastasis was molecularly evaluated in in vitro and in vivo models. Our functional study revealed that overexpressing miR-99a-3p significantly suppresses epithelial-mesenchymal transition (EMT) and anoikis resistance as well as migration and invasion of B-CPAP and TPC-1 cells. The mechanical study indicated that glucose-regulated protein 94 (GRP94) is the direct target of miR-99a-3p. Moreover, GRP94 overexpression reverses the inhibitory effect of miR-99a-3p on PTC metastasis. In addition, the miR-99a-3p/GRP94 axis exerts its effect via inhibiting the expression and cytoplasmic relocation of integrin 2α (ITGA2). Furthermore, in vivo experiments confirmed that miR-99a-3p significantly inhibits tumor growth and lung metastasis in PTC xenograft mice. Overall, our findings suggested that the miR-99a-3p/GRP94/ITGA2 axis may be a novel therapeutic target for the prevention of PTC metastasis.

MicroRNA-519d-3p (miR-519d-3p) has emerged as a tumor suppressor in several human cancers. But whether miR-519d-3p is involved in papillary thyroid cancer (PTC) remains elusive. In this study, we investigated the potential relevance of miR-miR-519d-3p in PTC. A retrospective study of 119 PTCs was carried out. The RT-qPCR analysis was used to measure the expression of miR-519d-3p and FOXQ1 in PTC tissues and cells. Chi-square test, Kaplan–Meier curve analysis, and multivariate Cox regression analyses were performed to assess the clinical and prognostic value of miR-519d-3p in PTC. Then cellular experiments were used to explore its biological effects on PTC cells. Finally, the Pearson correlation coefficient, dual-luciferase reporter assay, and rescue experiments were used to analyze the association between miR-519d-3p and FOXQ1. miR-519d-3p was significantly downregulated in PTC tissues and cell lines. The decreased expression of miR-519d-3p was associated with reduced overall survival and progression-free survival of patients. The proliferative, migratory, and invasive abilities of cells were blocked or elevated after upregulation or downregulation of miR-519d-3p, while FOXQ1 reversed these cellular behaviors caused after upregulation or knockdown of miR-519d-3p. In conclusion, miR-519d-3p was downregulated in PTC and associated with OS and PFS of patients. MiR-519d-3p may be a tumor-inhibiting miRNA in PTC, and that miR-519d-3p/FOXQ1 axis mediated PTC tumor progression from cell proliferation, migration, and invasion in PTC cells.

Recent evidence revealed an inhibitory effect of circ-ITCH on the progression of papillary thyroid cancer via affecting the circ-ITCH/miR-22-3p/CBL axis. Rs4911154, an SNP located in circ-ITHC, was previously reported to be significantly associated with an increased risk of hepatocellular carcinoma. Ultrasound testing was used to evaluate the doubling time of thyroid nodules. 202 patients diagnosed with thyroid nodule disorders were divided into three groups according to their genotypes at rs4911154. We found that the A allele was correlated with a shortening doubling time of thyroid nodules. Moreover, the A allele contributed to reduced expression of circ-ITCH/CBL and increased expression of miR-22-3p. Besides, decreased tissue apoptosis was linked to the A allele. Luciferase assays indicated that miR-22-3p could effectively suppress the luciferase activities of CBL and circ-ITCH. Furthermore, manual up-regulation of miR-22-3p effectively suppressed the expression of CBL, while CBL siRNA apparently abolished circ-ITCH induced CBL upregulation, reduced proliferation and increased apoptosis of K1 and TPC-1 cells. A signaling pathway of circ-ITCH/miR-22-3p/CBL axis was established to explain the effect of SNP of circ-ITCH in thyroid tumor malignancy. Compared with the G allele, the A allele in rs4911154 contributed to the malignancy of thyroid nodules with decreased doubling time and down-regulated CBL expression.

Background Thyroglobulin measurement in fine-needle aspiration (FNA-Tg) is an additional diagnostic tool of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). However, its performance as a preoperative indicator of lateral neck LNM in PTC is unclear. We evaluated the use of FNA cytology and FNA-Tg to detect neck LNM presurgery using a simple methodology, and established a cut-off value for diagnosing LNM in PTC. Methods We performed a retrospective cohort study based on hospital records, including 299 FNA-Tg measurements from 228 patients with PTC. The cut-off value for FNA-Tg was obtained through a receiver operating characteristic (ROC) curve analysis. The relationships between various parameters and FNA-Tg were analyzed using Spearman’s correlation. Results Of 299 lymph nodes (LNs) from 228 patients following surgery, 151 were malignant and 148 were benign. The median FNA-Tg levels were 414.40 ng/mL and 6.36 ng/mL in the metastatic and benign LNs, respectively. An FNA-Tg cut-off value of 28.3 ng/mL had the best diagnostic performance (93.38% sensitivity, 70.27% specificity, area under the ROC curve [AUC] 0.868) in the whole cohort. The diagnostic value performed better in the lateral neck group (level II–V, n = 163) than in the central neck group (level VI, n = 136); in the lateral neck group, the sensitivity and specificity of the FNA-Tg cut-off (16.8 ng/mL) were 96.25% and 96.36%, respectively. Conclusions FNA-Tg is a useful technique for the diagnosis of LNM before surgery, especially in lateral neck dissection. Clinical trial registration number ChiCTR1900028547.

Background: Although the etiology of Hashimoto's thyroiditis (HT), a common autoimmune endocrine disease, is unknown, studies suggest a potential association with genetic factors and environmental conditions inducing excessive iodine intake. Additionally, HT patients have a high risk of papillary thyroid cancer (PTC), which is probably related to the chronic inflammation and autoimmune pathologic process occurring in HT, as it is thought to be associated with neoplastic transformation. Methods: Bioinformatics approaches can identify differentially expressed genes (DEGs) and analyze DEG functions in diseases. R software was used in this study to identify DEGs in HT and PTC using data in Gene Expression Omnibus (GEO). The online tools DAVID, Reactome, and AmiGO were employed for annotation, visualization, and integration of DEGs related to HT and PTC, and the STRING database and Cytoscape software were applied to predict and visualize protein-protein networks (PPIs) for DEG-encoded proteins. Coexpressed DEGs in HT and PTC were validated by reverse transcription PCR (RT-PCR). Results: In total, 326, 231, and 210 DEGs in HT specimens and samples of central PTC and PTC invasive areas, respectively, were detected. According to the PPI network, PTPN6, HLA-A, C3AR1, LCK and ITGB2 are hub genes among HT-DEGs, whereas FN1, CDH2, SERPINA1, and CYR61 are PTC-DEG hub genes. The shared DEGs LTF and CCL21 were validated by RT-PCR. Both bioinformatics and RT-PCR analyses showed LTF and CCL21 to be upregulated in HT tissues and downregulated in PTC tissues. Conclusions: We identified that expression of LTF and CCL21 are significantly different in HT and PTC, suggesting an underlying association between HT and PTC.

Background Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland. More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients' lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not sufficient in the treatment of ATC, so alternative therapies are needed. Methods and results The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, the effect of VPA on miRNAs affecting histone deacetylase was determined by Quantitative RT-PCR. In the SW1736 cell line, IC50 dose for VPA was found 1.6 mg/ml. In our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes including miR-323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101-5p increased significantly. Conclusions VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). However, further studies are required for more accurate results.

Background and aims Papillary thyroid microcarcinoma is defined as papillary thyroid cancer with a diameter of ≤1 cm. Despite its prevalence, there is wide variation in practice in the investigation and management of patients with papillary thyroid microcarcinoma throughout the UK and internationally. The primary aim of this paper is to describe the experience of investigation and management in a Scottish health board over the past 10 years. Methods and results Retrospective analysis of thyroidectomy and hemithyroidectomy resection samples from March 2009 to March 2020. 532 specimens were reviewed and 20 patients with PTMC were identified. 12 patients had an incidental finding of PTMC. Median U score- 3, Median Thy score- 2.5 for dominant or radiologically suspicious nodules. 8 specimens demonstrated aggressive histopathological features. 1 patient with positive nodal disease in the neck and 0 patients with positive nodal disease in the thorax on CT Neck and Chest. Conclusion Here we report the first UK Cohort describing the radiological investigation and management of papillary thyroid microcarcinoma. The results of our study are in accordance with a recent meta-analysis which found 4% nodal disease and 0.025% distant metastasis at time of presentation in patients with PTMC.

Background The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of all thyroid cancer patients. This is probably unnecessary, particularly for differentiated thyroid cancer (DTC) patients with an excellent response to treatment and places significant demand on health service resources. Design Single centre retrospective cohort analysis of patients diagnosed and treated at the Leeds Cancer Centre between 2001 and 2014. Patients A total of 756 patients were dynamically risk-stratified (DRS) as having 'excellent response to treatment' after total thyroidectomy and radioiodineremnant ablation (RRA) for DTC. Results Median follow-up was 11.2 (range: 6.5-18.5) years. Radiological recurrence occurred in 15/756 (2.0%) patients and was always preceded by a raised thyroglobulin or thyroglobulin antibody level. The vast majority of tumour recurrences (13/15, 85%) were identifiable within 5 years of diagnostic surgery. Patients classified as having high-risk disease as per American Thyroid Association (ATA) guidelines had an almost threefold higher recurrence rate (2/34 [5.9%] vs. 13/722 [1.8%]) than those with ATA low-risk or intermediate-risk disease. Tumour histology subtype was a significant contributing factor, with Hurthle cell cancer having a worse prognosis than papillary thyroid cancer (PTC) (5/68 [7.4%] vs. 9/582 [1.5%]; relative risk: 4.76 [95% confidence interval: 1.64-13.8]). Conclusions The recurrence rate of DRS patients with excellent response to treatment is low. It is reasonable to consider discharge of ATA low-risk or intermediate-risk patients with PTC who remain disease-free after 5 years of secondary care follow-up. Lifelong follow-up, however, currently remains the standard for subgroups at greater risk.

Background Endoscopic thyroidectomy is widely performed as it does not result in neck scar. However, there is a paucity of reports pertaining to completely endoscopic lateral neck dissection (LND). In this study, we introduce our step-wise approach for performing endoscopic selective LND via the chest–breast approach. We refer to this approach as Qin’s seven steps. Methods The Qin’s seven steps are: (1) establishment of working space range; (2) dissection of lymph nodes between the SCM and the sternohyoid muscle (level IV) and exposure of omohyoid; (3) dissection of lymph nodes at level IV; (4) dissection of lymph nodes at level III; (5) dissection of lymph nodes at carotid triangle (level III); (6) exposure of accessory nerve and dissection of lymph nodes at level II a; (7) dissection of lymph nodes at level II b. We reviewed the clinical data of 35 patients with papillary thyroid cancer (PTC) who were operated using the Qin’s seven steps. Results All 35 patients successfully underwent LND; bilateral LND was performed in 5 patients. The mean tumor size was 1.8 ± 1.0 cm; seven patients had multiple lesions. The mean number of retrieved lymph nodes in level II, III and IV were 8.8 ± 5.6, 6.1 ± 4.0 and 9.3 ± 5.1, respectively. As for complications, there were 3 cases of accessory nerve injury and 1 case of hypoglossal nerve injury. Internal jugular vein injury, cervical plexus injury and lymphatic leakage occurred in 2, 7, and 1 patients, respectively. Conclusion The Qin’s seven steps for performing endoscopic selective LND could be safely used in PTC patients with lateral lymph node metastasis. Satisfactory results were achieved in the short-term follow-up period. We recommend the use of Qin’s seven steps for PTC patients who are not desirous of neck scar.

BACKGROUND: The 2015 American Thyroid Association endorsed less aggressive management for low-risk papillary thyroid cancer (LR-PTC). We aimed to identify factors influencing physicians’ recommendations for LR-PTC. METHODS: We surveyed members of three professional societies and assessed respondents’ recommendations for managing LR-PTC using patient scenarios. Multivariable logistic regression models identified clinical and non-clinical factors associated with recommending total thyroidectomy (TT) and active surveillance (AS). RESULTS: The 345 respondents included 246 surgeons and 99 endocrinologists. Physicians’ preference for their own management if diagnosed with LR-PTC had the strongest association with their recommendation for TT and AS (TT: OR 12.3; AS: OR 7.5, p

To evaluate the diagnostic performance of computed tomography combined with ultrasound (CT/US) in metastatic central lymph nodes (CLNs) compared with US in patients with papillary thyroid cancer (PTC).Six-hundred patients with surgically proven PTC who underwent both US and CT examination before CLN dissection were evaluated retrospectively. All cases were divided into four subgroups according to the tumor size and number. Diagnostic performances of US, CT and CT/US were evaluated.Among 600 patients with CLN dissection, CT/US showed higher sensitivity (89.10%) and accuracy (83.00%) than US alone (76.06%, 76.50%). In the subgroup of solitary non-microcarcinomas, the AUC of CT/US was significantly higher than that for US alone (0.827 vs. 0.722, P 0.05). For the subgroup of solitary or multiple microcarcinomas, the performance efficiency of CT had no obvious advantage over that of US (0.698 vs. 0.740, 0.798 vs. 0.802, P 0.05). For the subgroup of multiple non-microcarcinomas, CT, US and US/CT had high diagnostic efficacy (AUC 0.8, Accuracy80%. P 0.05), and there was no significant difference between them.In the subgroup of solitary non-microcarcinoma, CT combined with US provided better diagnostic efficacy, and for those cases, complementary CT examination was recommended. In other subgroups, the diagnostic efficacy of US/CT was similar to that of US alone, and there was no significant benefit from additional CT examination.

The papillary thyroid cancers (PTCs) are the most common cancer of endocrine cancers. The primary treatment is surgery, and the prognosis is mostly well. In spite of many methods for the early diagnosis, the simpler and noninvasive methods are being sought. The aim of this study is to find out whether the value of thyroglobulin (Tg) is related with PTC.Prospectively; we measured the preoperative Tg value of 203 (159 females and 44 males) patients who underwent a total thyroidectomy with various indications in General Surgery Department of Gaziantep University. Tg values of 61 patients with benign lesions and 142 patients with PTC were compared.In the patients with PTC, the mean preoperative Tg value was 105.05 ng/ml and 76.80 ng/ml in the benign patients. According to receiver operating characteristic analysis, the cutoff point was determined 102 ng/ml. There was a statistically significant difference in preoperative Tg values between benign group and PTC (P0.05).Patients with a preoperative Tg values above 102 ng/mL may more likely to have PTC. It is thought that Tg levels may be accepted as a criterion for distinguish malignant/benign situations that should be supported with new studies.

Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (p < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.

BACKGROUND: Molecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory ((131)I-refractory) PTC. METHODS: PTC samples from 106 pediatric patients (age range: 4.3–19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983–March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison. RESULTS: We identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAF(V600E) in 41 patients, TERT(C228T) in 2 patients [1 of whom had a coexisting BRAF(V600E)], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAF(V600E) PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients

Objective: In 2015, American Thyroid Association (ATA) issued the first version of Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. The purpose of this study is to evaluate whether the ATA pediatric guidelines recommended surgical approach for the patient can be applied to surgical treatment of pediatric PTC in China. Method: From April 2012 to December 2020, clinical data of children (≤18 years) with PTC consecutively admitted and treated with initial surgery in the study’s department were retrospectively reviewed. Results: The authors found that the central lymph node metastasis (CLNM) rate was significantly higher than that in the lateral neck (83.33 % vs 62.96%, χ2 = 5.704, p = 0.017) .The lymph node metastasis rate was significantly lower in cN1b (-) patients than in cN1b (+) patient (55.00% vs 100.00%, χ2 = 15.263, p = 0.000); Meanwhile, the CLNM and LLNM rates of ipsilateral were significantly higher than those of contralateral central compartment (83.33༅vs 57.41༅%, χ2 = 8.704, p = 0.003). Lymph nodes of 51 lateral lymph node dissection (LND) were analyzed, which revealed the LNM rate of cN1b (-) patients was significantly lower than that of cN1b (+) patients (55.00% vs. 100.00%, χ2 = 15.263, p = 0.000). Conclusion: Children and adolescents have a higher rate of lymph node metastasis at the time of diagnosis. TT should be conducted in the majority of children with PTC. CND should be routinely performed; therapeutic LND is recommended for children with cN1b (+).