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Papillary thyroid cancer (PTC) is the most common type of primary thyroid cancer. Despite the low malignancy and relatively good prognosis, some PTC cases are highly aggressive and even develop refractory cancer in the thyroid. Growing evidence suggested that microenvironment in tumor affected PTC biological behavior due to different immune states. Different interconnected components in the immune system influence and participate in tumor invasion, and are closely related to PTC metastasis. Immune cells and molecules are widely distributed in PTC tissues. Their quantity and proportion vary with the host's immune status, which suggests that immunotherapy may be a very promising therapeutic modality for PTC. In this paper, we review the role of immune cells and immune checkpoints in PTC immune microenvironment based on the characteristics of the PTC tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) and lymphocytic thyroiditis (LT) co-occur with a prevalence of about 30%. PTC harboring BRAFV600E (PTC-BRAF) confers a worse prognosis, but it is unclear if LT alters prognostic features and recurrence of PTC. Objective: We compared the prevalence of PTC-BRAF with and without LT. The risk of adverse pathological features in (i) PTC in the presence and absence of BRAF mutation, irrespective of LT status, was compared to (ii) PTC in the presence and absence of LT, irrespective of BRAF status. Methods: We searched PubMed, Embase, and Web of Science Core Collection for observational studies published from 2010 to June 2023 on adult patients with PTC. The search strategy yielded 47 studies with relevant data. Data of baseline characteristics, clinicopathological features, and the quality assessment tool were extracted by two reviewers. The study was registered with PROSPERO (CRD42023437492). Results: Of the 47 studies, 39 studies with a total cohort of 28 143, demonstrated that the odds of PTC-BRAF were significantly lower in the presence of LT compared to its absence (odds ratio [OR] 0.53, 95% confidence interval [CI]: 0.48–0.58, p < 0.00001). In PTC-BRAF patients, there was a positive association of central neck nodal disease (CNND), PTC > 1 cm, extra-thyroidal extension, American Joint Committee on Cancer (AJCC) Stage 3–4, and multifocality with pooled ORs of 1.54 (95% CI: 1.16–2.04), 1.14 (95% CI: 0.82–1.58), 1.66 (95% CI: 1.40–1.97), 1.53 (95% CI: 1.35–1.75), and 1.24 (95% CI: 1.11–1.40) respectively, compared to wild-type PTC, irrespective of LT status. In the same studies, PTC with LT patients had lower pooled ORs of 0.64 (95% CI: 0.51–0.81) for CNND, 0.83 (95% CI: 0.73–0.95) for PTC > 1 cm, 0.71 (95% CI: 0.58–0.86) for ETE, 0.84 (95% CI: 0.75–0.94) for AJCC Stage 3–4 compared to PTC without LT, irrespective of BRAF status. PTC recurrence was not affected by BRAF or LT, with pooled ORs of 1.12 (95% CI: 0.66–1.90, p = 0.67) and 0.60 (95% CI: 0.28–1.30, p = 0.20) respectively. Similar results were seen with recurrence expressed as hazard ratio in this limited data-set. Conclusion: The odds of PTC-BRAF are significantly lower in the presence of LT than without. PTC with LT, irrespective of BRAF status, was significantly associated with better prognostic factors. Further studies are required to evaluate if LT inhibits PTC-BRAF, and whether this is relevant to the role of immunotherapy in advanced thyroid cancer. [ABSTRACT FROM AUTHOR]

Objective: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/ recurrence. Methods: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. Results: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031]. Conclusion: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC. [ABSTRACT FROM AUTHOR]

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice. [ABSTRACT FROM AUTHOR]

Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed. [ABSTRACT FROM AUTHOR]

Purpose: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown. Patients and methods: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC. Results: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes. Conclusion: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: The prevalence of papillary thyroid cancer is gradually increasing and the trend of youthfulness is obvious. Some patients may not be able to undergo surgery, which is the mainstay of treatment, due to physical or financial reasons. Therefore, the prediction of cancer-specific survival (CSS) in patients with non-operated papillary thyroid cancer is necessary. Methods: Patients’ demographic and clinical information was extracted from the Surveillance, Epidemiology, and End Results database. SPSS software was used to perform Cox regression analyses as well as propensity score matching analyses. R software was used to construct and validate the nomogram. X-tile software was used to select the best cutoff point for patient risk stratification. Results: A total of 1319 patients were included in this retrospective study. After Cox regression analysis, age, grade, T stage, M stage, radiotherapy, and chemotherapy were used to construct the nomogram. C-index, calibration curves, and receiver operating characteristic curves all verified the high predictive accuracy of the nomogram. The decision curve analysis demonstrated that patients could gain clinical benefit from this predictive model. Survival curve analysis after propensity score matching demonstrated the positive effects of radiotherapy on CSS in non-operated patients. Conclusion: Our retrospective study successfully established a nomogram that accurately predicts CSS in patients with non-operated papillary thyroid cancer and demonstrated that radiotherapy for operated patients can still help improve prognosis. These findings can help clinicians make better choices. [ABSTRACT FROM AUTHOR]

Background: The presence of lateral lymph node metastases (LNM) in paediatric patients with papillary thyroid cancer (PTC) is an independent risk factor for recurrence. We aimed to identify risk factors and establish a prediction model for lateral LNM before surgery in children and adolescents with PTC. Methods: We developed a prediction model based on data obtained from 63 minors with PTC between January 2014 and June 2023. We collected and analysed clinical factors, ultrasound (US) features of the primary tumour, and pathology records of the patients. Multivariate logistic regression analysis was used to determine independent predictors and build a prediction model. We evaluated the predictive performance of risk factors and the prediction model using the area under the receiver operating characteristic (ROC) curve. We assessed the clinical usefulness of the predicting model using decision curve analysis. Results: Among the minors with PTC, 21 had lateral LNM (33.3%). Logistic regression revealed that independent risk factors for lateral LNM were multifocality, tumour size, sex, and age. The area under the ROC curve for multifocality, tumour size, sex, and age was 0.62 (p = 0.049), 0.61 (p = 0.023), 0.66 (p = 0.003), and 0.58 (p = 0.013), respectively. Compared to a single risk factor, the combined predictors had a significantly higher area under the ROC curve (0.842), with a sensitivity and specificity of 71.4% and 81.0%, respectively (cutoff value = 0.524). Decision curve analysis showed that the prediction model was clinically useful, with threshold probabilities between 2% and 99%. Conclusions: The independent risk factors for lateral LNM in paediatric PTC patients were multifocality and tumour size on US imaging, as well as sex and age. Our model outperformed US imaging and clinical features alone in predicting the status of lateral LNM. [ABSTRACT FROM AUTHOR]

Background: The mechanism and impact of Hashimoto's disease (HT) in patients with papillary thyroid carcinoma (PTC) remains a subject of ongoing debate. The optimal extent of thyroid resection is also controversial in cases of low-risk PTC. Objective: To investigate the clinical outcomes and prognoses associated with different extents of surgical resection in patients diagnosed with PTC coexisting with HT. Methods: We retrospectively analyzed data on the clinical features and treatment outcomes of patients with PTC concomitant with HT who underwent lobectomy with isthmusectomy and those who underwent total thyroidectomy at Peking University International Hospital between December 2014 and August 2023. Results: Twenty-one patients in group A underwent lobectomy with isthmusectomy and prophylactic central neck dissection, whereas twenty patients in group B underwent total thyroidectomy with prophylactic central lymph node (LN) dissection, except one who did not undergo LN dissection. Group A demonstrated shorter surgery time (105.75 min ± 29.35 vs. 158.81 min ± 42.01, p = 0.000), higher parathyroid hormone (PTH) levels on postoperative day 1 [26.96 pg/ml (20.25, 35.45) vs. 9.01 pg/ml (2.48, 10.93), p = 0.000] and a shorter postoperative hospital stay [2.95 d (2.0, 4.0) vs. 4.02 d (3.0, 5.0), p = 0.008] than those of group B, with statistically significant differences. Both groups exhibited similar recovery patterns in terms of PTH [32.10 pg/ml (22.05, 46.50) vs. 20.47 pg/ml (9.43, 34.03), p = 0.192] and serum calcium (2.37 mmol/L ± 0.06 vs. 2.29 mmol/L ± 0.19, p = 0.409) after 1 month following the surgery. According to the Kaplan-Meier curves, no significant difference in the 5-year disease-free survival rates were observed between patients in group A (100%) and group B (97.1%) (Log rank test: p = 0.420, Breslow test: p = 0.420). Conclusion: Lobectomy with isthmusectomy and prophylactic central neck dissection is a safe and feasible treatment option for patients with low-risk PTC coexisting with HT. [ABSTRACT FROM AUTHOR]

Objective: A non-invasive method using plasma microRNAs provides new insights into thyroid cancer diagnosis. The objective of this study was to discover potential circulating biomarkers of papillary thyroid carcinoma (PTC) through the analysis of plasma miRNAs using next-generation sequencing (NGS). Methods: Plasma miRNAs were isolated from peripheral blood samples collected from healthy individuals, patients diagnosed with PTC, and those with benign thyroid nodules. The Illumina NovaSeq 6000 platform was employed to establish the miRNA expression profiles. Candidate miRNAs for diagnostic purposes were identified utilizing the Random Forest (RF) algorithm. The selected miRNAs were subsequently validated in an independent validation set using RT-qPCR. Results: NGS results revealed consistent plasma miRNA expression patterns among healthy individuals and patients with benign thyroid nodules in the discovery set (6 healthy cases, 17 benign cases), while differing significantly from those observed in the PTC group (17 PTC cases). Seven miRNAs exhibiting significant expression differences were identified and utilized to construct an RF classifier. Receiver operating characteristic (ROC) analysis for PTC diagnosis, and the area under the curve (AUC) was 0.978. Subsequent KEGG and GO analyses of the target genes associated with these 7 miRNAs highlighted pathways relevant to tumors and the cell cycle. Independent validation through RT-qPCR in a separate cohort (15 CONTROL, 15 PTC groups) underscored hsa- miR-301a-3p and hsa-miR-195-5p as promising candidates for PTC diagnosis. Conclusion: In conclusion, our study established a seven-miRNA panel in plasma by Random Forest algorithm with significant performance in discriminating PTC from healthy or benign group. hsa-miR-301a-3p, hsa-miR-195-5p in plasma have potential for further study in the diagnosis of PTC in Asian ethnic. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the expression of microRNAs (miRNAs) -146b-3p, -221-5p, -222-3p, and -21a-3p and the methylation pattern of the thyroid-stimulating hormone receptor (TSHR) gene in blood plasma samples from papillary thyroid cancer (PTC) patients before and after thyroidectomy compared to healthy controls (HCs). This study included 103 participants, 46 PTC patients and 57 HCs, matched for gender and age. Significantly higher preoperative expression levels of miRNAs and TSHR methylation were determined in the PTC patients compared to HCs. Post-surgery, there was a notable decrease in these biomarkers. Elevated TSHR methylation was linked to larger tumor sizes and lymphovascular invasion, while increased miRNA-222-3p levels correlated with multifocality. Receiver operating characteristic (ROC) analysis showed AUCs below 0.8 for all candidate biomarkers. However, significant changes in the expression of all analyzed miRNAs and TSHR methylation levels indicate their potential to differentiate PTC patients from healthy individuals. These findings suggest that miRNAs and TSHR methylation levels may serve as candidate biomarkers for early diagnosis and monitoring of PTC, with the potential to distinguish PTC patients from healthy individuals. Further research is needed to validate these biomarkers for clinical application. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is the most frequent endocrine cancer. Aberrant expression of miRNAs can increase the risk of thyroid cancer. We aimed to investigate the miR-126-3p and miR-146a-5p plasma levels in patients with thyroid nodules and to identify their associations with clinicopathological characteristics, and progression of PTC. Methods: We enrolled forty healthy control and forty patients with thyroid nodules; benign thyroid nodules (BTN), (n=30), and PTC(n=10). We analyzed miR-126-3p and miR-146a-5p levels by using real-time PCR. Results: miR-126-3p expression level was downregulated in PTC patients (0.40±0.11) compared with BTN (0.58±0.12) and healthy subjects (0.87±0.31), P<0.001*. Regarding miR-146a-5p, its level was upregulated in PTC patients (4.59±1.61) compared with BTN (3.77±0.96) and healthy subjects (0.99±0.41), Additionally, miR-126-3p and miR-146b-5p levels were significantly associated with tumor progression, lymph node metastasis, TNM staging, and thyroid function tests. The diagnostic power of miR-126-3p in the prediction of PTC, the AUC was 0.860 with a sensitivity of 60 % and specificity of 87.3% at cutoff values =0.49. miR-146a-5p level in the prediction of PTC, the AUC was 0.742 with a sensitivity of 80 % and specificity of 74.3% at cutoff values =3.4. Conclusions: miR-146a-5p and miR-126-3p levels were dysregulated in patients with PTC compared to patients with BTN and the control group. The dysregulated miRNAs were associated with clinicopathological features of PTC. [ABSTRACT FROM AUTHOR]

[Display omitted] • The suspicious ultrasonography features are related to immune response in thyroid cancer. • The features were also related to epithelial to mesenchymal transition (EMT). • Immune response and EMT were related to aggressive clinical behaviors. • Immune response and EMT reflected in the decision by radiologists and convolutional neural networks. Ultrasonography (US) features of papillary thyroid cancers (PTCs) are used to select nodules for biopsy due to their association with tumor behavior. However, the molecular biological mechanisms that lead to the characteristic US features of PTCs are largely unknown. This study aimed to investigate the molecular biological mechanisms behind US features assessed by radiologists and three convolutional neural networks (CNN) through transcriptome analysis. Transcriptome data from 273 PTC tissue samples were generated and differentially expressed genes (DEGs) were identified according to US feature. Pathway enrichment analyses were also conducted by gene set enrichment analysis (GSEA) and ClusterProfiler according to assessments made by radiologists and three CNNs - CNN1 (ResNet50), CNN2 (ResNet101) and CNN3 (VGG16). Signature gene scores for PTCs were calculated by single-sample GSEA (ssGSEA). Individual suspicious US features consistently suggested an upregulation of genes related to immune response and epithelial-mesenchymal transition (EMT). Likewise, PTCs assessed as positive by radiologists and three CNNs showed the coordinate enrichment of similar gene sets with abundant immune and stromal components. However, PTCs assessed as positive by radiologists had the highest number of DEGs, and those assessed as positive by CNN3 had more diverse DEGs and gene sets compared to CNN1 or CNN2. The percentage of PTCs assessed as positive or negative concordantly by radiologists and three CNNs was 85.6% (231/273) and 7.1% (3/273), respectively. US features assessed by radiologists and CNNs revealed molecular biologic features and tumor microenvironment in PTCs. [ABSTRACT FROM AUTHOR]

Context Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined. Objective This work aimed to examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4 cm in diameter. Methods A retrospective review was conducted of all consecutive patients who underwent nonoperative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001 to 2021. We included patients with an initial ultrasound–fine-needle aspiration confirming either (a) Bethesda 5 or 6 cytology or (b) a "suspicious" Afirma molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth. Results Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules 2 cm or larger. No patients were found to develop new-incident occurrence of lymph node or distant metastasis. One patient, however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start of nonoperative selection. A total of 21% of patients had an increase in maximum diameter more than 3 mm, while volume increase of 50% or greater was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth. Conclusion These data expand consideration of active surveillance of PTC in select patients with intrathyroidal suspected malignancy greater than 1 cm in diameter. Rescue surgery, if required at a later time point, appears effective. [ABSTRACT FROM AUTHOR]

Background: Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking. Objectives: This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice. Methods: A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes. Results: MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation. Conclusions: MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making. [ABSTRACT FROM AUTHOR]

Objective: To assess the risk factors of cervical lymph node metastasis in elderly patients aged 65 years and older diagnosed with papillary thyroid cancer (PTC). Design and method: In this retrospective analysis, we included a total of 328 elderly patients aged 65 years and older diagnosed with PTC. We thoroughly examined clinical features from these patients. Utilizing univariate and multivariate logistic regression analyses, we aimed to identify factors contributing to the risk of central and lateral lymph node metastasis (CLNM/LLNM) in this specific population of PTC patients aged 65 years and older. Results: In the univariate analysis, CLNM was significantly associated with tumor size, multifocality, bilaterality, and microcalcification, while only tumor size = 1cm (OR = 0.530, P = 0.019, 95% CI = 0.311 - 0.900) and multifocality (OR = 0.291, P < 0.001, 95% CI = 0.148 - 0.574) remained as risk factors in the multivariate analysis. LLNM was confirmed to be associated with male (OR = 0.454, P < 0.020, 95% CI = 0.233 - 0.884), tumor size = 1cm (OR = 0.471, P = 0.030, 95% CI = 0.239 - 0.928), age = 70 (OR = 0.489, P = 0.032, 95% CI = 0.254 - 0.941), and microcalcification (OR = 0.384, P = 0.008, 95% CI = 0.189 - 0.781) in the multivariate analysis. In elderly PTC patients with CLNM, male gender (OR = 0.350, P = 0.021, 95% CI = 0.143 - 0.855), age = 70 (OR = 0.339, P = 0.015, 95% CI = 0.142 - 0.810), and bilaterality (OR = 0.320, P = 0.012, 95% CI = 0.131 - 0.779) were closely associated with concomitant LLNM in both univariate and multivariate analyses. Conclusion: For elderly PTC patients aged 65 and older, tumor size = 1cm and multifocality are significant risk factors for CLNM. Meanwhile, male, tumor size = 1cm, age = 70, and microcalcification are crucial predictors for LLNM. In patients already diagnosed with CLNM, male, age = 70, and bilaterality increase the risk of LLNM. [ABSTRACT FROM AUTHOR]

Background: The diffuse sclerosing variant (DSV) is among the aggressive variants of papillary thyroid carcinoma (PTC) and is more prevalent in pediatric patients than in adult patients. Few studies have assessed its characteristics owing to its low incidence. We aimed to evaluate the relationship between recurrence and age in the DSV of PTC. Methods: We retrospectively reviewed patients diagnosed with the DSV or conventional PTC (cPTC) after surgery at a medical center between May 1988 and January 2019. We compared the clinico-pathological characteristics and surgical outcomes of the DSV and cPTC groups and between adult and pediatric patients with DSV. Results: Among the 24,626 patients, 202 had the DSV, and 24,424 were diagnosed with cPTC. The recurrence rate was significantly higher in the DSV group than in the cPTC group. In the DSV group, the recurrence rate was significantly higher in the pediatric patient group than in the adult patient group. Moreover, the association between recurrence and age group showed different patterns between the DSV and cPTC groups with restricted cubic splines (RCS). While both RCS curves showed a U-shaped distribution, the RCS curve tended to be located within the younger age group. Conclusions: This study demonstrated that pediatric patients with DSV are at a greater risk for recurrence compared with adult patients; moreover, the pattern of recurrence risk according to age is different from that of cPTC. [ABSTRACT FROM AUTHOR]

Purpose: Multifocal disease in PTC is associated with an increased recurrence rate. Multifocal disease (MD) is underdiagnosed with the current gold standard of pre-operative ultrasound staging. Here, we evaluate the use of EMI-137 targeted molecular fluorescence-guided imaging (MFGI) and spectroscopy as a tool for the intra-operative detection of uni- and multifocal papillary thyroid cancer (PTC) aiming to improve disease staging and treatment selection. Methods: A phase-1 study (NCT03470259) with EMI-137 was conducted to evaluate the possibility of detecting PTC using MFGI and quantitative fiber-optic spectroscopy. Results: Fourteen patients underwent hemi- or total thyroidectomy (TTX) after administration of 0.09 mg/kg (n = 1), 0.13 mg/kg (n = 8), or 0.18 mg/kg (n = 5) EMI-137. Both MFGI and spectroscopy could differentiate PTC from healthy thyroid tissue after administration of EMI-137, which binds selectively to MET in PTC. 0.13 mg/kg was the lowest dosage EMI-137 that allowed for differentiation between PTC and healthy thyroid tissue. The smallest PTC focus detected by MFGI was 1.4 mm. MFGI restaged 80% of patients from unifocal to multifocal PTC compared to ultrasound. Conclusion: EMI-137-guided MFGI and spectroscopy can be used to detect multifocal PTC. This may improve disease staging and treatment selection between hemi- and total thyroidectomy by better differentiation between unifocal and multifocal disease. Trial registration: NCT03470259 [ABSTRACT FROM AUTHOR]

The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease. A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations. Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features. A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases. [ABSTRACT FROM AUTHOR]

Background: Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. Materials and methods: Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. Results: The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01). Conclusion: These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). Methods: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. Results: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p >.05), and significantly outperformed the radiomics model (p <.05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. Conclusion: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC. [ABSTRACT FROM AUTHOR]

The association of clinical, pathological, and immunohistochemical characteristics of papillary thyroid cancer with cause-specific mortality was analyzed in a case-control study within a cohort of patients from the Altai Regional Oncology Center. According to multivariate analysis, the independent predictors of fatal outcome within 10 years after surgery in patients living in Altai region are nuclear pattern of Hsp70 expression, thyroid capsular invasion, Ki-67 expression index >7%, and patient's age >45 years for men and >50 years for women. The prognostic model based on these features contributes to a significant improvement in the individual prognostic performance for papillary thyroid cancer in the modeling sample. The model has high statistical significance (χ2=64.73; p<0.001) and discriminative power (AUC=0.950, prediction accuracy 88.5%). [ABSTRACT FROM AUTHOR]

Context Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and prognosis. Objective This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity, total antioxidant capacity [TAC], and sortilin), as potential indicators of angioinvasion in PTC. Design A cross-sectional study involving 50 angioinvasive patients with PTC (study group) and 30 patients with PTC with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion. Setting Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context. Patients or Other Participants Participants included patients with PTC, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded. Intervention(s) Serum biomarkers were measured to evaluate their association with PTC angioinvasion. Main Outcome Measure(s) Primary outcome measures included serum levels of 8-OHdG, total oxidative capacity, TAC, and sortilin. Results Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, whereas TAC showed a notable decrease (all P <.01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high area under the curve value (0.963) for angioinvasion discernment. Conclusion Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results. [ABSTRACT FROM AUTHOR]

Purpose: Risk stratification based on somatic mutations in TERT promoter and BRAF/RAS has been well established for papillary thyroid cancer (PTC), and there is emerging evidence showed that TERT promoter methylation was frequently observed in thyroid cancer patients with adverse features. This study was aimed to comprehensive explore the prognostic value of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation in PTC. Methods: The relationships of BRAF/RAS mutations, TERT promoter mutations, and TERT promoter methylation with clinical characteristics and outcomes of PTC were analyzed in 382 patients with PTC. Results: TERT promoter mutation and hypermethylation were collectively observed in 52 (13.6%) samples and associated with BRAF/RAS mutation, aggressive clinical characteristics, and poor clinical outcomes of PTC. Coexistence of BRAF/RAS and TERT alterations was found in 45 of 382 (11.8%) PTC patients and strongly associated with old patient age, extrathyroidal extension, advanced pathologic T stage and metastasis. Importantly, patients with both BRAF/RAS and TERT alterations had higher rates of tumor recurrence (13.6% vs 1.5%, P = 0.042) and disease progression (24.4% vs 3.3%, P < 0.001) than patients without any alterations, and cox regression analysis revealed that the coexistence of BRAF/RAS and TERT alterations, but not BRAF/RAS or TERT alterations alone, increased the risk of progression-free interval with an adjusted HR of 10.35 (95% CI: 1.79–59.81, P = 0.009). Conclusions: This study suggested that comprehensively analysis of BRAF/RAS mutations, TERT promoter mutation and methylation is an effective strategy to identify high-risk patients with PTC. [ABSTRACT FROM AUTHOR]

Purpose: The four and a half LIM domain protein 1 (FHL1) has been found to act as a tumor suppressor in several cancers. However, the clinical and functional significance, as well as underlying molecular mechanisms of FHL1 in papillary thyroid cancer (PTC) are largely unknown. Methods: Bioinformatics analyses, qRT-PCR and Western blotting were used to investigate the expression of FHL1 in PTC. Cell proliferation was measured using CCK8, Edu, colony formation, and flow cytometry assays. Cell migration and invasion were examined by wound healing and Transwell assays. qRT-PCR, Western blot, immunofluorescence and Top/Fop reporter assays were performed to assess the underlying mechanisms. Results: FHL1 expression was significantly downregulated in PTC. FHL1 downregulation negatively correlated with stage, T classification, and N classification of the patients. The downregulation of FHL1 is associated with poor prognosis. Overexpression of FHL1 inhibited PTC cells' proliferation, invasion, migration and Wnt/β-catenin pathway activity. LiCl partially restored the inhibitory effects of FHL1 on aggressive phenotypes and Wnt/β-catenin pathway activity of PTC cells. Conclusion: FHL1 is downregulated in PTC and its expression is associated with better clinical outcomes for patients with the disease. FHL1 acts as a tumor suppressor via, at least partially, suppressing Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Background: Thyroid disorders, relatively common diseases of the endocrine system, have risen gradually in recent years. Early detection and accurate diagnosis of thyroid cancer hold exceptional importance. This study aimed to determine the efficacy of a modified TI-RADS and BRAFV600E mutation testing for thyroid cancer (PTC) diagnosis. Methods: Ninety five thyroid nodules (48 benign and 47 malignant) from 81 patients were examined using Kwak Thyroid Imaging Reporting and Data System (TI-RADS) were subjected to shear wave elasticity (SWE), BRAFV600E genotyping and fine needle aspiration (FNA) cytology. Results: The modified TI-RADS exhibited superior diagnostic accuracy compared to TI-RADS in differentiating benign nodules from malignant thyroid nodules. Moreover, the AUC of modified TI-RADS in conjunction with BRAFV600E was the highest at 95% CI (0.898– 0.992, p=0.003), surpassing other diagnostic methods in enhanced sensitivity and maintaining high specificity. Conclusion: The diagnostic efficiency of this combination surpassed that of individual diagnostic methods. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence. METHODS: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated. RESULTS: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031]. DISCUSSION AND CONCLUSION: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.

Abstract Background Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

Abstract Purpose Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown. Patients and methods We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC. Results In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes. Conclusion Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis.

Abstract Background The presence of lateral lymph node metastases (LNM) in paediatric patients with papillary thyroid cancer (PTC) is an independent risk factor for recurrence. We aimed to identify risk factors and establish a prediction model for lateral LNM before surgery in children and adolescents with PTC. Methods We developed a prediction model based on data obtained from 63 minors with PTC between January 2014 and June 2023. We collected and analysed clinical factors, ultrasound (US) features of the primary tumour, and pathology records of the patients. Multivariate logistic regression analysis was used to determine independent predictors and build a prediction model. We evaluated the predictive performance of risk factors and the prediction model using the area under the receiver operating characteristic (ROC) curve. We assessed the clinical usefulness of the predicting model using decision curve analysis. Results Among the minors with PTC, 21 had lateral LNM (33.3%). Logistic regression revealed that independent risk factors for lateral LNM were multifocality, tumour size, sex, and age. The area under the ROC curve for multifocality, tumour size, sex, and age was 0.62 (p = 0.049), 0.61 (p = 0.023), 0.66 (p = 0.003), and 0.58 (p = 0.013), respectively. Compared to a single risk factor, the combined predictors had a significantly higher area under the ROC curve (0.842), with a sensitivity and specificity of 71.4% and 81.0%, respectively (cutoff value = 0.524). Decision curve analysis showed that the prediction model was clinically useful, with threshold probabilities between 2% and 99%. Conclusions The independent risk factors for lateral LNM in paediatric PTC patients were multifocality and tumour size on US imaging, as well as sex and age. Our model outperformed US imaging and clinical features alone in predicting the status of lateral LNM.

Mingyan Wang,1– 3,&ast; Siyuan Yang,1– 3,&ast; Linxin Yang,1– 3 Ning Lin1– 3 1Ultrasound Department of Shengli Clinical Medical College of Fujian Medical University, Fuzhou City, Fujian Province, 350001, People’s Republic of China; 2Ultrasound Department of Fujian Provincial Hospital, Fuzhou City, Fujian Province, 350001, People’s Republic of China; 3Ultrasound Department of Fuzhou University Affiliated Provincial Hospital, Fuzhou City, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Lin, Ultrasound Department of Fujian Provincial Hospital, 134 East Street, Fuzhou City, 350001, Fujian Province, People’s Republic of China, Tel +86 0591-87557768, Email NingLin2413@163.comAim: The study aimed to compare the diagnostic performance of AI-SONICTM Thyroid System (AI-SONICTM) with six thyroid nodule ultrasound risk stratification systems, as well as the interobserver agreement among different-year ultrasound examiners using the same diagnostic approach.Methods: This retrospective study included patients who underwent thyroid ultrasound examination and surgery between 2010 and 2022. Three ultrasound examiners with 2, 5, and 10 years of experience, respectively, used AI-SONICTM and six guidelines to risk-stratify the nodules. The diagnostic performance and interobserver agreement were assessed.Results: A total of 370 thyroid nodules were included, including 195 papillary thyroid carcinomas (PTC) and 175 benign nodules. For physicians of varying seniority from low to high, AI-SONICTM had a moderate sensitivities of 82.56%, 83.08%, 84.62%, respectively, while AACE/ACE/AME had the highest diagnostic sensitivities (96.41%, 95.38%, 96.41%, respectively); And relatively higher specificities were 85.14%, 85.71%, 85.71% for KSThR, while moderate specificities with values of 84.0%, 85.14%, and 85.71%, respectively were found for AI-SONICTM; The accuracy was highest for ATA (excluding non-classifiable nodules), with values of 87.26%, 87.93%, and 88.82%, respectively, while the accuracy for AI-SONICTM were 83.24%, 84.05%, and 85.14%, respectively. The Kendall’s tau coefficient indicated strong or moderate interobserver agreement among all examiners using different diagnostic methods (Kendall’s tau coefficient > 0.6, P< 0.001). AI-SONICTM showed the highest interobserver agreement (Kendall’s tau coefficient=0.995, P< 0.001). A binary probit regression analysis showed that nodules with cystic components had a significantly higher regression coefficient value of 0.983 (P=0.002), indicating that AI-SONICTM may have higher accuracy for nodules with cystic components.Conclusion: AI-SONICTM and the six thyroid nodule ultrasound risk stratification systems showed high diagnostic performance for papillary thyroid carcinoma. All examiners showed strong or moderate interobserver agreement when using different diagnostic methods. AI-SONICTM may have higher accuracy for nodules with cystic components.Keywords: AI-SONICTM thyroid system, six thyroid risk stratification guidelines, papillary thyroid cancer

Introduction: Ultrasonography (US) features of papillary thyroid cancers (PTCs) are used to select nodules for biopsy due to their association with tumor behavior. However, the molecular biological mechanisms that lead to the characteristic US features of PTCs are largely unknown. Objectives: This study aimed to investigate the molecular biological mechanisms behind US features assessed by radiologists and three convolutional neural networks (CNN) through transcriptome analysis. Methods: Transcriptome data from 273 PTC tissue samples were generated and differentially expressed genes (DEGs) were identified according to US feature. Pathway enrichment analyses were also conducted by gene set enrichment analysis (GSEA) and ClusterProfiler according to assessments made by radiologists and three CNNs - CNN1 (ResNet50), CNN2 (ResNet101) and CNN3 (VGG16). Signature gene scores for PTCs were calculated by single-sample GSEA (ssGSEA). Results: Individual suspicious US features consistently suggested an upregulation of genes related to immune response and epithelial-mesenchymal transition (EMT). Likewise, PTCs assessed as positive by radiologists and three CNNs showed the coordinate enrichment of similar gene sets with abundant immune and stromal components. However, PTCs assessed as positive by radiologists had the highest number of DEGs, and those assessed as positive by CNN3 had more diverse DEGs and gene sets compared to CNN1 or CNN2. The percentage of PTCs assessed as positive or negative concordantly by radiologists and three CNNs was 85.6% (231/273) and 7.1% (3/273), respectively. Conclusion: US features assessed by radiologists and CNNs revealed molecular biologic features and tumor microenvironment in PTCs.

Abstract Background Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. Materials and methods Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. Results The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p