Search Results (488)

Background/Objectives: The TOETVA and TORT have been successfully refined in recent years, with few complications and excellent results. In this study, we compared TORT and TOETVA in patients with papillary thyroid cancer. Methods: From September 2016 to January 2022, we retrospectively compared patient characteristics and clinical features from 100 TORT cases and 300 TOETVA cases, as well as their respective learning curves. Results: Median operation time of TORT was 80.4 min, similar to TOETVA (81.4 min, p = 0.719). Median docking time of TORT was 4.51 min and median console time was 27.72 min. The length of stay of TORT and TOETVA was 2.29 and 2.54 (p = 0.002). The median number of retrieved central lymph nodes for TOETVA and TORT were 2.89 and 2.99 (p = 0.746). Discussion: There was no significant difference with clinical features between TORT and TOETVA. Full article

Autosomal recessive familial partial lipodystrophy type 5 (FPLD5) due to a homozygous NP_001186481.1; p.E186* CIDEC variant has previously been reported in a 19-year-old female with diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Now, we report an 18-year-old Hispanic female who presented with FPL, along with hirsutism, acanthosis nigricans, and marked insulin resistance, and was found to have an extremely rare homozygous variant in CIDEC (NM_001199623.2:c.224G>T; NP_001186552.1; p.Ser75Ile) by whole exome sequencing. She also harbored a novel homozygous variant in WRN (NM_000553.4:c.1856T>G; NP_000544; p.Leu619Arg). Both serine 75 of the CIDEC protein and leucine 619 of the WRN protein were well conserved across species. She developed an invasive papillary thyroid carcinoma at the age of 17 years. Our report confirms the previously reported association of the biallelic CIDEC variant with the FPL phenotype and also highlights the extremely rare possibility of co-occurrence of FPLD5 with thyroid cancer, a clinical feature of Werner syndrome. Thus, our patient may not only need surveillance for the metabolic complications of FPLD5, such as diabetes, hypertriglyceridemia, and hepatic steatosis, but also for WRN-associated neoplasms and features of premature aging. Full article

Background/Objectives: The extent of initial surgical resection for low-risk papillary thyroid carcinoma (PTC) remains debated. Traditionally, total thyroidectomy (TT) has been the standard approach, although the 2015 American Thyroid Association (ATA) guidelines endorsed a more conservative strategy. The real-world adoption of these recommendations, however, is unclear. This study evaluated changes in the surgical management of low-risk PTC in a high-volume center following the implementation of the ATA guidelines and analyzed the impact on postoperative outcomes. Methods: We conducted a retrospective study of 1644 patients who underwent surgery for localized low-risk PTC < 4 cm between 2014 and 2023. Temporal trends in the initial surgical procedure (TT vs. thyroid lobectomy [TL]) were analyzed overall and by tumor size and patient demographics. The need for completion thyroidectomy after TL and postoperative outcomes were also assessed. Results: The use of TL increased from 0% in 2014 to 59.4% in 2023 (p < 0.001). For microcarcinomas, TL rose from 17.5% in 2016 to 78% in 2023, with similar but less pronounced trends for 1–2 cm tumors. TT remained predominant for nodules > 2 cm. The completion thyroidectomy rate declined from 32% in 2016 to 4% in 2022. Patients undergoing TT experienced higher rates of postoperative complications (12.4% vs. 3.0%), particularly transient hypoparathyroidism (8.9% vs. 0%), and permanent hypoparathyroidism (1.8% vs. 0%), as well as longer operative time and hospital stay (all p < 0.001). The incidence of hypoparathyroidism decreased over time as TL use increased. Conclusions: Adoption of the 2015 ATA guidelines has progressively increased the use of TL in the management of low-risk PTC. This shift in surgical practice is associated with a reduction in the overall postoperative complication burden at the population level, largely driven by decreased hypoparathyroidism. Although guideline uptake has been gradual, current trends suggest increasing acceptance of less aggressive surgical strategies in routine clinical practice. Full article

Background and Objectives: Mean platelet volume (MPV) is a routinely available blood marker that measures platelet size and activation, and it has been evaluated as a potential marker for thyroid malignancies. Platelets participate in tumor genesis through angiogenesis, immune evasion, and metastasis, making them plausible adjuncts for cancer risk evaluation. The objective is to systematically evaluate the role of MPV in thyroid cancers, with the main focus on diagnostic accuracy, prognostic value, and limitations, focusing on papillary thyroid carcinoma (PTC). Materials and Methods: A systematic search of PubMed was conducted from January 2015 to September 2025. Only free full-text studies on human subjects were included. Eligible studies included case–control, cohort, or observational designs reporting MPV or platelet indices in thyroid cancer compared with benign nodules or healthy controls. Data on diagnostic performance, associations with tumor stage, lymph node involvement, and recurrence were extracted and synthesized narratively. No formal risk-of-bias or study quality assessment tool was applied. The literature search was restricted to studies with freely available full-text articles, which may have introduced access-based selection bias. Results: Eleven studies met the inclusion criteria. Most of them reported high MPV values in papillary thyroid carcinoma (PTC), with limited evidence regarding other thyroid cancer subtypes. High values of MPC were reported in the majority of studies in PTC compared to benign nodules or healthy controls. The diagnostic performance of MPV alone was poor, but integration with inflammatory ratios such as the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), and with ultrasound systems (TI-RADS), improved accuracy. Regarding prognostic utility, some studies linked higher MPV with lymph node involvement or recurrence risk, while others did not find significant data. Thyroid function, autoimmune thyroid disease, and methodological variability in MPV measurement limited comparability across studies. Conclusions: MPV is a low-cost adjunct biomarker, especially when combined with other hematologic and imaging markers. However, MPV should not be used as a stand-alone diagnostic or prognostic tool. Larger, prospective studies are mandatory to clarify its clinical role. Full article

Over the past several decades, rapid advances in molecular genomics have transformed our understanding of thyroid malignancies and are increasingly integrated into international clinical guidelines. Mutational profiles and epigenetic events are now recognized not only as diagnostic and prognostic tools but also as predictors of therapeutic response. Papillary, follicular, oncocytic, medullary, and anaplastic thyroid carcinomas harbor distinct early driver mutations, such as BRAFV600E, RAS, and fusion events (RET, NTRK, and ALK), that cooperate with secondary alterations (TERT promoter, TP53, PIK3CA, and CDKN2A/B loss) to drive dedifferentiation, metastasis, and therapeutic resistance. Insights from The Cancer Genome Atlas (TCGA) and transcriptomic scoring systems (e.g., BRAF–RAS score) now link genotype to tumor morphology, metastatic tropism, and radioactive iodine refractoriness. These molecular insights have been incorporated into updated risk stratification frameworks, preoperative surgical planning, and treatment algorithms, informing the selection of kinase inhibitors, redifferentiation strategies, and enrollment in genotype-directed clinical trials for radioiodine-refractory disease. This review synthesizes recent evidence connecting genomic alterations to clinical behavior and highlights their translation into evolving approaches for thyroid cancer management. Full article

The thyroid cancer incidence has been continuously rising over the last decades. Recently, intelligent cancer detection software are gaining popularity, due to their high diagnostic accuracy and subsequent direct benefits in avoiding unnecessary surgical interventions. This study introduces a novel hybrid computer-aided diagnosis (CAD) system that combines convolutional neural networks (CNNs) and molecular data analysis to achieve comprehensive and reliable thyroid cancer diagnostics. The system consists of two key modules: The first is a CNN-based model leveraging transfer learning, processes ultrasound images to classify patients as either “healthy” or “with a thyroid nodule.” In cases where a nodule is detected, the second module utilizes molecular data to predict the malignancy risk, providing a probability score for clinical decision support. Different image augmentation techniques (traditional ones as well as novels) were carried out to enhance the robustness of the system. The combination of two independent modules makes it possible to use them decoupled, while used together they provide a powerful, in-depth diagnosis of thyroid cancer. The proposed system demonstrates strong performance: the ultrasound-based CNN module achieves an accuracy of 93.65%, with a sensitivity of 100% and a specificity of 69.23%. For the gene analysis component, the model achieves a training mean squared error (MSE) of 4.24 × 10⁻⁵ and a testing MSE 6.31 × 10⁻³. These results underscore the system’s competitive performance with existing thyroid cancer detection CAD systems in both diagnostic performance and the depth of insights provided, supporting clinicians in making informed, reliable decisions in thyroid cancer management. Full article

Background/Objectives: This study aimed to evaluate the prognostic significance of thyroid bed uptake on post-ablative whole-body scan (PAWBS) in predicting treatment response in intermediate-risk papillary thyroid carcinoma (PTC) patients undergoing high-dose radioactive iodine (RAI) therapy following total thyroidectomy. Methods: This retrospective study included 148 intermediate-risk PTC patients who underwent high-dose RAI therapy after total thyroidectomy. PAWBS was performed 7 days post-therapy, and thyroid bed uptake was visually graded. Treatment response was assessed using stimulated thyroglobulin (sTg) levels, imaging studies, and clinical follow-up. Responses were classified into excellent, indeterminate, biochemical incomplete, or structural incomplete categories. Logistic regression analyses were conducted to identify predictors of treatment response. Results: Among the 148 patients, 126 (85.1%) achieved an excellent response (ER), while 22 (14.9%) showed a non-excellent response (NER), which included indeterminate, biochemical incomplete, and structural incomplete responses. Patients with NER exhibited significantly higher thyroid bed uptake on PAWBS compared to ER patients (p = 0.001). Multivariate analysis revealed that higher thyroid bed uptake was an independent negative prognostic factor for achieving an excellent response (p < 0.001), along with sTg (p < 0.001). Conclusions: The intensity of thyroid bed uptake on PAWBS independently predicts treatment response in intermediate-risk PTC patients receiving high-dose RAI therapy, with higher uptake indicating a worse prognosis. Full article

Background: MicroRNAs (miRNAs) such as miR-155-5p and miR-221-3p are key regulators of gene expression in cancer. Although both have been implicated in colorectal cancer (CRC) and papillary thyroid carcinoma (PTC), data on their regional expression profiles and clinical associations remain scarce, particularly in the Middle East. This study assessed the expression patterns and clinical relevance of miR-155-5p and miR-221-3p in CRC and PTC patients from Sulaymaniyah Province, Iraq. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor and adjacent normal tissue samples were collected from 60 CRC patients and 50 PTC patients. miRNA expression levels were quantified using real-time quantitative PCR (RT-qPCR) and analyzed by the ΔΔCt method, adjusted for tumor cellularity. Statistical analyses were conducted to evaluate associations between miRNA expression and clinicopathological parameters. Results: miR-155-5p and miR-221-3p were frequently overexpressed in both CRC (65%) and PTC (72% and 68%, respectively). In CRC, miR-155-5p expression correlated significantly with histological grade, tumor location, and TNM stage (p < 0.05), while miR-221-3p did not show significant associations with clinicopathological features. In PTC, miR-155-5p exhibited a trend toward association with TNM stage (p = 0.02). No significant differences in expression levels of these miRNAs were observed between CRC and PTC samples. Conclusions: Overall, miR-155-5p and miR-221-3p are consistently overexpressed in CRC and PTC, indicating their potential as diagnostic biomarkers. miR-155-5p, in particular, shows promise as a marker of disease progression in CRC. These findings underscore the importance of region-specific studies in advancing our understanding of the molecular landscape of cancer. Full article

Background/objectives: The study aimed to present cases of malignant struma ovarii from seven centers in Türkiye and evaluate them within the context of the existing literature. Methods: We retrospectively analyzed clinical data from 17 patients treated at seven centers, focusing on clinical features, surgical management, pathology, thyroid function, adjuvant treatment, and outcomes. Additionally, a literature review including eight studies with 178 patients was conducted. Results: The mean age of patients was 44.7 years, with a mean tumor size of 9.2 cm. Elevated Ca 125 was found in 33.3% of patients, while thyroid function abnormalities and hyperthyroidism signs were rare. Pelvic pain and menstrual irregularities were common presenting symptoms. A total of 16 patients (94.1%) had unilateral tumors. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy were the most frequent surgical approaches. Histopathology predominantly showed classical papillary thyroid carcinoma (13 patients, 76%). All patients were FIGO stage I, with no metastasis. Thyroidectomy was performed in seven patients, identifying two concurrent thyroid cancers. Four patients received adjuvant radioactive iodine therapy. During a median follow-up of 43 months, no deaths and one recurrence were observed. The literature review showed a diagnosis age ranging 43–53 years and papillary thyroid carcinoma as the most common subtype. Thyroidectomy and RAI treatment were selectively applied. Among the reported studies, recurrence occurred in 7 of 76 patients (9.2%), while 5-year disease-free and overall survival rates exceeded 94% and 100%, respectively. BRAF mutations were uncommon. Conclusions: Malignant struma ovarii is a rare tumor with a favorable prognosis when diagnosed early and managed appropriately. Full article

Background/Objectives: To evaluate whether the interval between diagnosis and surgery is associated with aggressive histopathological features in papillary thyroid carcinoma (PTC) among patients treated at a tertiary hospitals in Saudi Arabia. Methods: This retrospective study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia, from November 2009 to November 2024. A total of 350 adult patients who underwent surgical intervention for PTC were included based on predefined inclusion and exclusion criteria. Data were collected from medical records and included demographic, clinical, and histopathological characteristics. The primary outcome was the presence of aggressive histopathological features, assessed through tumor subtype, tumor size, extrathyroidal extension (ETE), lymph-node involvement, extracapsular extension (ECE), multifocality, goitrous tumor, thyroiditis, perineural invasion, lymphovascular invasion, and margin status. Surgical timing was categorized into two groups: less than six months and six months or more from diagnosis. Results: Most patients were female (76.6%), with a mean age of 40.7 years, and 78.3% were classified as overweight or obese. The analysis showed no statistically significant differences in histopathological outcomes between the two surgical timing groups. A significant association was found between positive lymph-node involvement and surgery performed within the first six months of diagnosis (p = 0.004). Conclusions: This study showed that surgical timing does not significantly affect histopathological outcomes in papillary thyroid carcinoma, particularly in patients without aggressive disease features. The association between early surgery and positive lymph-node involvement may reflect the prioritization of patients with preoperative lymph-node disease for earlier surgical intervention, highlighting the importance of individualized treatment planning. Further research is needed to explore the long-term impact of surgical timing and potential subgroup differences. Full article

MicroRNA-221 (miR-221), a conserved small non-coding RNA, acts as a pivotal modulator of biological processes across multiple organ systems, the dysregulation of which is closely linked to the pathogenesis of various human diseases. This review systematically summarizes its multifaceted roles in cancer, cardiovascular diseases (CVDs), neurological disorders, digestive system diseases, respiratory conditions, and adipose-endocrine dysfunction. In cancer, miR-221 exerts context-dependent oncogenic/tumor-suppressive effects by targeting phosphatase and tensin homolog (PTEN), cyclin-dependent kinase inhibitor 1c (CDKN1C/p57), and BCL2 modifying factor (Bmf), thereby regulating cell proliferation, invasion, stemness, and resistance to cancer therapy; it also serves as a non-invasive biomarker for glioma, papillary thyroid carcinoma, and colorectal cancer. In the cardiovascular system, it balances antiviral defense in viral myocarditis, modulates ventricular fibrotic remodeling in heart failure, and regulates endothelial function in atherosclerosis, with cell-type/ventricle-specific effects. In neurological disorders, it protects dopaminergic neurons in Parkinson’s disease and modulates microglial activation in epilepsy. It also regulates hepatic pathogen defense and intestinal mucosal immunity. Mechanistically, miR-221 alters cellular phenotypes by targeting tumor suppressors or signaling components (e.g., PI3K/AKT, TGF-β/suppressor of mothers against decapentaplegic homolog(SMAD), Wnt/β-catenin). Therapeutically, miR-221-targeting strategies show preclinical promise in cancer and CVDs. Despite this progress, further studies are needed to resolve context-dependent functional discrepancies, validate biomarker utility, and develop cell-specific delivery systems. This review provides a framework to understand its pathophysiologcial roles and potential application as a biomarker and therapeutic target. Full article

Chronic inflammation plays a key role in cancer pathogenesis. Aggressive thyroid cancer is associated with immune infiltration and systemic inflammation. Long pentraxin 3 (PTX3) is an inflammatory protein implicated in tumor progression. This study evaluates PTX3 plasma levels in patients with non-medullary thyroid cancer (TC) compared to benign thyroid disease and investigates its tissue expression. We prospectively included 55 TC patients: 42 papillary, 3 follicular, 4 oncocytic, 4 anaplastic (ATC), and 2 poorly differentiated (PDTC). The control group consisted of 32 patients with benign thyroid disease. PTX3 plasma concentrations were measured by ELISA, and tissue expression of PTX3 and CD68 was analyzed using immunohistochemistry. PTX3 plasma levels did not significantly differ between TC and controls, but patients with PDTC and ATC had markedly higher concentrations. Tissue analysis showed strong PTX3 expression in three of four ATC cases in tumor and stromal cells, whereas benign and differentiated thyroid tissues exhibited minimal staining. CD68 expression was positive in ATC, indicating tumor-associated macrophage infiltration, but a few cells were double-positive for PTX3 and CD68. Our findings suggest a possible association between PTX3 and aggressive TC, particularly ATC. Further studies are needed to validate these findings and elucidate the cellular origin and functional role of PTX3. Full article

Background: Adolescents and young adults (AYA) with papillary thyroid carcinoma (PTC) often present with more extensive cervical lymph node metastasis (LNM) than older adults (AD). We aimed to identify age-associated molecular and immune features that might explain this phenotype and to explore potential translational implications for managing aggressive AYA PTC. Methods: We analyzed clinical and transcriptomic data from 501 PTC cases in The Cancer Genome Atlas (TCGA), stratified as AYA (<30 years, n = 64) and AD (≥30 years, n = 437). An institutional RNA-seq cohort (n = 13; 7 AYA, 6 AD) was used to screen for differentially expressed genes (DEGs). DEGs were defined by p ≤ 0.05 and |log2 fold change| ≥ 1. Intersection with invasion- and dissemination-related gene sets yielded a final age-related DEG list. Functional enrichment (GO/KEGG via DAVID), PPI network analysis (STRING, Cytoscape/cytoHubba), and immune deconvolution (CIBERSORT LM22) were performed. Protein-level validation was carried out by immunohistochemistry (IHC) in an independent cohort (n = 56; 28 AYA, 28 AD). Statistical comparisons used chi-square/Fisher’s exact tests for categorical variables, t-tests or nonparametric tests for continuous variables, and EdgeR with FDR correction for transcriptomic analyses. Results: In TCGA, LNM was more frequent in AYA than in AD (62.1% vs. 47.8%, p = 0.031). From intersected analyses, we identified 239 core DEGs distinguishing highly invasive, age-related tumors. Key upregulated genes in AYA included CXCR4, OPCML and S100A2; downregulated genes included ATP1A3, CHL1, HLA-DRA and IL-1β. Enriched pathways involved extracellular matrix organization, cell adhesion, calcium signaling and canonical oncogenic cascades (PI3K-Akt, MAPK, Wnt, Ras). Immune deconvolution showed reduced naïve B cells, M1 and M2 macrophages and resting mast cells and an increased proportion of M0 macrophages in AYA tumors. IHC validated differential protein expression for seven markers. Collectively, the data indicate an immune-suppressed, immune-excluded microenvironment in AYA PTC. Conclusions: AYA PTC exhibits distinct molecular and immune features that may underlie its propensity for lymphatic dissemination. These findings support evaluation of translational strategies, such as CXCR4 inhibition, restoration of antigen presentation, and macrophage reprogramming, to convert “cold” tumors into immune-permissive lesions. Validation in larger, prospective, multicenter cohorts is required. Full article

Objectives: The BRAF^V600E is the most common oncogene in thyroid cancer and is associated with the aggressiveness of papillary thyroid carcinoma (PTC). The aim of this study was to investigate the effectiveness of the arterial enhancement fraction (AEF) and dual-layer detector spectral computed tomography (DLCT) parameters for predicting the BRAF^V600E mutation in PTC. Methods: A total of 237 patients with PTC who underwent DLCT and BRAF^V600E mutation detection (mutant group: n = 187; wild group: n = 50) were retrospectively reviewed. The receiver operating characteristic curves evaluated the effectiveness of the prediction models based on the significantly different variables using logistic regression analysis. The nomogram of the prediction model with the highest AUC in the validation cohort was constructed. Results: The AUCs of the DLCT+ Hashimoto’s thyroiditis (HT) and AEF + DLCT + HT prediction models were 0.901 and 0.896, respectively, in the training cohort and 0.801 and 0.853 in the validation cohort. The calibration curve revealed the good agreement between the prediction results and the actual observations using the AEF + DLCT + HT model. The DCA demonstrated that the model can provide net benefit for all threshold probabilities. Conclusions: As an effective and visually noninvasive prediction tool, the AEF + DLCT + HT-based nomogram presented satisfactory effectiveness in preoperatively predicting the BRAF^V600E mutation in PTC. Full article

Objectives: Papillary thyroid carcinoma (PTC) frequently presents with cervical lymph node metastasis (CLNM), yet preoperative tools often encode BRAF V600E as a binary variable, potentially overlooking information contained in mutation abundance. We sought to quantify the dose–response relationship between BRAF V600E abundance and CLNM and to develop an interpretable model for preoperative risk stratification. Methods: We performed a single-center retrospective study of consecutive PTC patients who underwent preoperative BRAF V600E testing and surgery from 2019 to 2023. Patients were randomly split 70/30 into training and test sets. Candidate predictors included clinical and ultrasound features and BRAF V600E abundance. We used multivariable logistic regression and restricted cubic splines (RCS) to assess nonlinearity and compared six machine-learning algorithms (LR, KNN, SVM, XGB, LightGBM, and NN). Model performance was evaluated by F1, AUC, calibration, and decision-curve analyses; SHAP aided interpretation. Ethics approval: SYSKY-2024-169-01. Results: The cohort included 667 patients; CLNM occurred in 391 (58.6%). CLNM cases had higher BRAF abundance (median 23% vs. 17%) and characteristic clinical/sonographic differences. RCS revealed a nonlinear association between abundance and CLNM, with a steep risk rise of up to ~20.7% followed by a plateau. Among six algorithms, XGBoost showed the best validation performance (AUC 0.752; F1 0.73). SHAP indicated that maximum tumor diameter, BRAF abundance, age, and microcalcifications contributed most to predictions. Conclusions: Modeling BRAF V600E as a quantitative abundance—rather than a binary status—improves preoperative CLNM risk assessment in PTC. An interpretable XGBoost model integrating abundance with routine features demonstrates acceptable discrimination and potential clinical utility for individualized surgical planning and counseling. Full article