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Objective. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, represents the most prevalent autoimmune thyroid disorder globally. The potential influence of HT on the clinical and pathological attributes, as well as the clinical outcomes of differentiated thyroid carcinoma (DTC), remains a point of ongoing debate within the medical community. The central focus of this study was to analyze the influence of HT on clinico‐pathological characteristics and its prognostic impact in a large cohort of DTC from Middle Eastern ethnicity. Design, Patients, Measurements. An extensive analysis involving 1822 DTC patients was conducted to determine the association with clinico‐pathological characteristics as well as prognosis, using Chi‐square tests and Kaplan‐Meier curves. Results. 23.9% (435/1822) of DTC patients were diagnosed with HT. Univariate analysis revealed a positive correlation between presence of HT and clinico‐pathological factors such as female gender, younger age, and early stage tumor. In contrast, HT demonstrated a negative association with several aggressive clinical features, including extrathyroidal extension, distant metastasis, recurrent/persistent disease and high‐risk categorization by the American Thyroid Association (ATA) guidelines. Despite HT being associated with favorable clinico‐pathological features in Middle Eastern DTC patient, our study found no significant influence on overall survival or recurrence‐free survival. Conclusion. The finding of an association between HT and favorable clinico‐pathological characteristics, but lack of impact on prognosis, underscores the complexity of HT‐DTC relationship, necessitating further comprehensive research to fully understand these interactions. [ABSTRACT FROM AUTHOR]

Background: The European Thyroid Association Thyroid Imaging Data and Reporting Systems (EU-TIRADS) is widely used in the risk stratification of thyroid nodule malignancy. However, data on the subject in Sub-Saharan Africa are limited. The objective of this study is to evaluate the clinical, sonographic and histopathological concordance of thyroid nodules in the diagnosis of thyroid cancer. Methods: This was an analytical cross-sectional study that examined the clinical, ultrasound and pathological data of 61 patients from 4 hospitals in the city province of Kinshasa over a period of 24 months, from June 01, 2020 to May 31, 2022. Results: Of the 61 patients, their mean age was 47.38 ± 8.8 years. The mean clinical score of the patients was 3.4 ± 0.84 with the extremes ranging from 1 to 5. The majority of the patients were classified as having an intermediate risk, ie 85.2% of the cases. It was noted that 41% of the nodules had a high risk according to the EU-TIRADS score and 8.2% of the nodules were malignant after histopathological analysis. The ROC curves reported at the diagnosis of malignancy show an area under the curve of 0.709 with 95% CI (0.486–0.931), a Youden index of 0.769 for the clinical score, and an area under the curve of 0.830 with 95% CI (0.605–0.995), a Youden index of 0.772 for the EU-TIRADS score. Conclusion: In a low-income country, a well-performed thyroid ultrasound and the well-applied clinical score could be an important tool in the selection of thyroid nodules suspected of malignancy and requiring histopathological examination to avoid excessive acts in the patient. [ABSTRACT FROM AUTHOR]

Simple Summary: Total thyroidectomy and dissection of cervical lymph node compartments, depending on serum calcitonin levels and ultrasound findings, is standard treatment for patients with medullary thyroid cancer. The aim of this study was to evaluate whether pre-operative calcitonin and CEA levels can be useful as biomarkers of the extent of lymph node metastases at diagnosis. Results indicate that pre-operative serum calcitonin and CEA levels can predict presence, number, and site of lymph node metastases and, more specifically, values of 90 pg/mL for calcitonin and 17 ng/mL for CEA accurately indicate the N1b status. Since surgery is the only curative treatment for medullary thyroid cancer and there is not a strong indication regarding the extent of lymphadenectomy, these findings may help in the choice of the extent of neck dissection. Background: In medullary thyroid cancer (MTC), lymph node metastases are often present at diagnosis and the extent of surgery is usually based upon pre-operative calcitonin and CEA levels as well as ultrasound findings. The aim of this study was to evaluate the role of pre-operative calcitonin and CEA levels as predictive markers of the burden of lymph node metastases at diagnosis. Methods: we conducted a retrospective study analyzing 87 MTC patients. Results: The median levels of calcitonin and CEA were 88.4 pg/mL and 7.0 ng/mL, respectively, in patients with no lymph nodes metastases; 108.0 pg/mL and 9.6 ng/mL, respectively, in patients with metastases to 1–5 lymph nodes; 520.5 pg/mL and 43.2 ng/mL, respectively, in patients with metastases to >5 lymph nodes. There were no significant differences in pre-operative calcitonin and CEA values between N0 and N1a patients, whereas they were significantly higher in N1b patients. Pre-operative cut-off levels distinguishing N0/N1a from N1b patients were 90 pg/mL for calcitonin (sensitivity 100%, specificity 59.3%, AUC = 0.82) and 17 ng/mL for CEA (sensitivity 100%, specificity 75%, AUC = 0.89). Conclusions: in patients with MTC, pre-operative serum calcitonin and CEA levels may drive the decision-making process to better define the extent of surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of radioactive iodine (RAI) for the treatment of patients with thyroid cancer at intermediate risk of recurrence is controversial. Evidence to date has not conclusively proven that there are benefits of this strategy to survival or recurrence after surgery for thyroid cancer. We describe key elements that can help clinicians decide when to prescribe RAI to this group of patients. These include a thorough discussion of the purpose of RAI therapy, better prediction of recurrence risk, the use of tumor markers after surgery, the use of the genetic profile of the tumor when available, and a detailed evaluation of the adverse effects of RAI, patient medical problems, and patient preferences. Integration of these variables will ensure a more comprehensive assessment of the risks and benefits of RAI treatment with the ultimate goal of avoiding overtreatment and reducing harm. The use of radioactive iodine (RAI) after total thyroidectomy for patients at the American Thyroid Association (ATA) who are at intermediate risk of recurrence is controversial. This is due to the lack of prospective randomized trials proving a benefit to recurrence or survival of RAI therapy in this group. In the absence of such evidence, clinicians struggle to recommend for or against this therapeutic approach which frequently results in overtreatment. This review describes key elements in the decision-making process that help clinicians more comprehensively evaluate the need for RAI therapy in patients with thyroid cancer at intermediate risk of recurrence. A clear definition of the purpose of RAI therapy should be conveyed to patients. In this sense, adjuvant RAI therapy intends to decrease recurrence, and ablation therapy is used to facilitate surveillance. Better stratification of the intermediate risk category into a low–intermediate subgroup and an intermediate–high-risk subgroup results in less heterogeneity and a more precise prediction of recurrence risk. The evaluation of post-operative thyroglobulin levels may prevent the overtreatment of low–intermediate-risk patients when their thyroglobulin level is <2.5 ng/mL. the integration of tumor genomics (when available) alongside pathologic features can enhance the ability of the clinician to predict iodine concentration in thyroid cancer cells. Finally, a detailed consideration of the adverse effects of RAI, patients' comorbidities, and patient preferences will result in a patient-centered personalized approach. Systematic examination of these variables will ultimately provide a framework for making more educated decisions on the use of RAI in patients at intermediate risk of recurrence that will prevent overtreatment and minimize harm. [ABSTRACT FROM AUTHOR]

Dyshormonogenesis (DG) is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin (TG) gene are a cause of DG, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up for congenital hypothyroidism (CH) since the neonatal period, and she had normal TSH levels on replacement therapy. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in the TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on fine needle aspiration biopsy (FNAB) and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm, well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/mm2 and 10%, respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less commonly reported in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of CH, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and possible mortality. [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]

Early onset medullary thyroid carcinoma, later pheochromocytomas, and nonspecific extra-endocrine features (hypermobility and persistent constipation) are part of the clinical phenotype of Multiple Endocrine Neoplasia type 2B (MEN2B). A de novo pathogenic M918T variant in the rearranged during transfection proto-oncogene is usually identified. Affected children are often seen by multiple clinicians over a long period before consideration of a diagnosis of MEN2B, with metastatic medullary thyroid carcinoma often the precipitator. We describe the clinical presentation and course of 5 children ultimately diagnosed with MEN2B in New South Wales and the Australian Capital Territory, Australia between 1989 and 2021. All cases had intestinal ganglioneuromatosis that could have prompted an earlier diagnosis. Population wide newborn genomic screening for rare diseases is on the horizon. We propose that MEN2B genomic screening should be included in newborn screening programs and that careful exclusion of intestinal ganglioneuromatosis would allow earlier identification leading to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Medullary thyroid carcinoma constitutes 5% to 10% of all thyroid cancers. Metastatic adenopathies may pose challenges in intricate anatomical locations, such as the parapharyngeal space. A rare case of metastatic medullary thyroid carcinoma in the parapharyngeal space has been treated in our unit using combined trans-cervical trans-oral robotic surgery. Our objective was to provide a detailed description of the surgery performed on this patient. Method: We reported a singular case report worth of interest. Result: A 42-year-old woman was addressed in our unit for the management of a medullary thyroid carcinoma adenopathy located in the right parapharyngeal space. A parapharyngeal 40.0 mm × 25.0 mm × 12.0 mm adenopathy was removed using a combined trans-cervical and trans-oral robotic approach without sacrifice or injury of vascular or nervous structure. Neither the tracheostomy nor the feeding tube was implemented. Feeding was resumed on postoperative day 1 and hospitalization spanned 7 days. Conclusion: An innovative combined trans-cervical and trans-oral robotic surgery approach was conducted to address a metastatic medullary thyroid carcinoma in the parapharyngeal space. This surgical technique allowed us to circumvent the need for a trans-mandibular approach, tracheostomy, and feeding tube and enabling successful tumor removal without fragmentation. Postoperative care was significantly eased. The sole complication observed was dysphonia, likely resulting from intra-operative stretching of the vagus nerve during the dissection of the carotid artery. [ABSTRACT FROM AUTHOR]

Objective: Although many studies have shown the relationship between type 1 diabetes mellitus (T1DM) and autoimmune thyroid diseases, few studies have conducted a morphological evaluation of the thyroid gland in T1DM without thyroid disease. This study aimed to compare thyroid ultrasonography findings of the healthy control group with the T1DM group without thyroid disease and examine the relationship between β-cell autoantibodies and the presence of thyroid nodules. Methods: This cross-sectional study included 119 patients with T1DM and 105 healthy controls. Thyroid function tests, thyroid volume, and presence of thyroid nodules were compared between the two groups. Patients with T1DM were divided into two groups according to the presence of thyroid nodules, and risk factors that may affect the development of thyroid nodules were tried to be determined. Results: No significant difference was found between the control group and the T1DM group in terms of thyroid function tests, thyroid volume, and presence of thyroid nodules. In the T1DM group, the number of female patients and the islet cell antibody (ICA) positivity rate were higher in the presence of thyroid nodules. As a result of regression analysis, ICA positivity in the T1DM group increased threefold the risk of having thyroid nodules. Conclusion: A relationship was observed between ICA positivity and thyroid nodules in T1DM. Thus, cases with ICA positivity may have a higher probability of nodules in the thyroid gland, and neck examinations should be performed more frequently. [ABSTRACT FROM AUTHOR]

Context.--Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. Objective.--To examine the clinicopathologic features of a series of 32 follicular cell-derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. Design.--Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. Results.--The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyper- plastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. Conclusions.--Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Squamous cell carcinomas (SCC) account for over 90% of oral cancers. Over the last few decades, there has been a significant increase in the number of cases. Metastasis of oral cancer to the thyroid is extremely rare. Rarer still are tumours metastasizing from the tongue to the thyroid. We present a case of a patient who presented to her dentist with a tongue SCC. Despite radical curative treatment, the tumour metastasized to the thyroid and the patient succumbed to the metastatic disease. We, additionally, highlight the importance of thorough lymph node and neck examination in the dental setting to help identify pathology in patients. CPD/Clinical Relevance: The importance of a thorough lymph node and neck examination at routine dental check-ups is highlighted. [ABSTRACT FROM AUTHOR]

Background The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Notably, there is evidence suggesting an association between tissue stiffness and the aggressiveness of the disease. We therefore aimed to explore the effect of tissue stiffness on LNM-related invasiveness in PTC patients. Method A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on their pathological results. The effects of interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell) on the LNM-related recurrence rate and mortality in each patient with PTC subgroup were analyzed. The activation of cancer-associated fibroblasts (CAFs) and extracellular matrix component type 1 collagen (COL-I) in the lesion were compared and analyzed across different subgroups. The underlying biological basis of differences in each subgroup was identified using RNA sequencing (RNA-seq) data. Results The Eshell value and Eshell/E in the LNM group were significantly higher than those in the non-LNM group of patients with PTC (Eshell: 72.72 ± 5.63 vs 66.05 ± 4.46; Eshell/E: 1.20 ± 1.72 vs 1.09 ± 1.10, P  < .001). When Eshell/E > 1.412 and LNM were both present, the recurrence rate and mortality were significantly increased compared to those of group of patients with LNM (91.67% and 7.29%, respectively). The CAF activation and COL-I content in the Eshell/E+ group were significantly higher than those in the Eshell/E− group (all P  < .001), and the RNA-seq results revealed significant extracellular matrix (ECM) remodeling in the LNM-Eshell/E+ group. Conclusions Stiff peri-cancerous tissue induced CAF activation, COL-I deposition, and ECM remodeling, resulting in a poor prognosis for PTC patients with LNM. [ABSTRACT FROM AUTHOR]

Objective Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC; RAIR-DTC) have a poor prognosis. The aim of this study was to provide new insights and possibilities for the diagnosis and treatment of RAIR-DTC. Methods The metabolomics of 24 RAIR-DTC and 18 non-radioiodine-refractory (NonRAIR) DTC patients samples were analyzed by liquid chromatograph-mass spectrometry. Cellular radioiodine uptake was detected with γ counter. Sodium iodide symporter (NIS) expression and thyroid stimulating hormone receptor (TSHR) were measured by Western blot analysis. CCK8 and colony formation assays were used to measure cellular proliferation. Scratch and transwell assays were performed to assess cell migration and invasion. Annexin V/PI staining was used to detect cell apoptosis. Cell growth in vivo was evaluated by a tumor xenograft model. The acetoacetate (AcAc) level was measured by ELISA. Pathological changes, Ki67, NIS, and TSHR expression were investigated by immunohistochemistry. Results The metabolite profiles of RAIR could be distinguished from those of NonRAIR, with AcAc significantly lower in RAIR. The significantly different metabolic pathway was ketone body metabolism. AcAc increased NIS and TSHR expression and improved radioiodine uptake. AcAc inhibited cell proliferation, migration, and invasion, and as well promoted cell apoptosis. Ketogenic diet (KD) elevated AcAc levels and significantly suppressed tumor growth, as well as improved NIS and TSHR expression. Conclusion Significant metabolic differences were observed between RAIR and NonRAIR, and ketone body metabolism might play an important role in RAIR-DTC. AcAc improved cellular iodine uptake and had antitumor effects for thyroid carcinoma. KD might be a new therapeutic strategy for RAIR-DTC. [ABSTRACT FROM AUTHOR]

Background: Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor that originates from the parafollicular C cells of thyroid gland. Understanding the fundamental pathophysiology of MTC is essential for clinical management. Single-cell RNA sequencing (scRNA-seq) technology is a powerful tool for identifying distinct cell types, offering a new biological foundation for comprehending the MTC ecosystem and developing precise treatment. Methods: Formalin fixed and paraffin-embedded (FFPE) samples of primary and adjacent non-cancerous tissues of three MTC cases were collected, and single-cell transcriptome data of MTC were obtained by using scRNA-seq technology. Annotated cell subpopulations were categorized and functionally enriched by principal component analysis, differential gene expression, and cell clustering analysis, to explore the biological process of tumor evolution that may be involved in each cell subpopulation. The copy number variation (CNV) profile was used to distinguish the malignancy of parafollicular thyroid cells, and the evolutionary trajectories of normal cells and tumor cells were revealed by the proposed time series analysis. The highly expressed genes in each cell subpopulation were analyzed by the FindAllMarker function of Seurat software, and verified by immunohistochemistry and fluorescence in situ hybridization. The prognostic value of specific cell subtypes was validated using large-scale public datasets. Results: A total of 32,544 cells were obtained from the MTC tissue samples and 11,751 cells from the adjacent non-cancerous samples, which were classified into 7 heterogenous subpopulations by using R package of Seurat module. Copy number variations (CNVs) were significantly higher in tumor tissues than in adjacent non-tumor samples, predominantly enriched in subtypes C2 and C4. In addition, the pseudo-time for trajectory analysis suggested that the evolution of MTC tumor cells might begin with the C2 subtype, then transition to the early cancer subgroup C3, and further differentiate into four major malignant cell subpopulations C0, C1, C5 and C6. Survival analysis of a thyroid cancer cohort using the TCGA dataset revealed that high expression of genes linked to the C0 subcluster was correlated with poorer overall survival compared to low expression. Immunohistochemical staining showed that MAP3K4 was highly expressed in MTC tissues compared to adjacent non-cancerous tissues. Fluorescence in situ hybridization also confirmed the amplification of these two genes in MTC samples. Conclusions: By conducting scRNA-seq on FFPE samples, we mapped the single-cell transcriptome of MTC, uncovering the tumor heterogeneity and unique biological features of each cellular subpopulation. The biological roles of identified tumor cell subpopulations such as C0 and C3 subtypes of parafollicular cells suggested the potential to discover new therapeutic targets and biomarkers for MTC, providing valuable insights for future translational and clinical research. [ABSTRACT FROM AUTHOR]

Objective: The accurate diagnosis of thyroid nodules is crucial for effective management and the detection of malignancy. Fine-needle aspiration biopsy (FNAB) and fine-needle non-aspiration biopsy (FNNAB) are widely used techniques for evaluating thyroid nodules. In this study, we aimed to investigate the impact of anthropometric parameters and sonographic characteristics on the choice between FNAB and FNNAB in terms of diagnostic yield. Material and Methods: This retrospective and cross-sectional analysis involved 188 cases with a total of 225 thyroid nodules. Each nodule initially underwent either FNAB or FNNAB and if the initial biopsy did not yield a diagnostic result, the nodule was re-biopsied using the alternate technique. Ultrasound was used to evaluate the nodules, with a focus on echogenicity, calcifications, size, vascularity, and the presence of a halo sign. Both FNAB and FNNAB were performed using a 25-gauge needle, with the only difference being the application of suction. Results: FNAB demonstrated a higher diagnostic rate for nodules with a taller-than-wide shape (anteroposteriorto-transverse ratio ≥1), nodules sized 10–40 mm, nodules with volumes <0.5 cc, and hypoechoic nodules (P < 0.001 for all). FNAB also outperformed FNNAB in the assessment of the right-sided, inferior, and posterior nodules (P < 0.001), nodules with and without calcification (P = 0.041 and P = 0.020, respectively), and nodules with type 1 and type 2 vascularity patterns (P = 0.006 and P = 0.017, respectively). FNAB was effective in obese individuals (Body mass index ≥40 kg/m2), males with a waist circumference of <94 cm, females with a waist circumference of ≥80 cm, and females with a neck circumference of ≥34 cm (P = 0.011, P = 0.044, P = 0.029, and P = 0.008, respectively). Conclusion: Anthropometric parameters and sonographic characteristics influenced the diagnostic yield of FNAB and FNNAB, with FNAB generally demonstrating superior results. Given the importance of obtaining an accurate diagnostic result from fine-needle biopsy, clinicians should consider both the sonographic features of the nodule and the anthropometric measurements of the patient when selecting a biopsy technique. [ABSTRACT FROM AUTHOR]

Simple Summary: The study analyzed income disparities in 5-year survival rates (5YSR) among cancer patients in South Korea from 2002 to 2018. Overall, 5YSR improved from 2002–2006 to 2014–2018, particularly for lung, liver, and stomach cancers. The Slope Index of Inequality (SII) indicated significant income-related disparities, with higher survival rates associated with higher incomes, notably for lung and liver cancers. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. The findings highlight persistent income-related gaps in cancer survival despite overall improvements, emphasizing the need for targeted interventions to address socioeconomic inequalities in cancer care outcomes. Background: The overall survival rates among cancer patients have been improving. However, the increase in survival is not uniform across socioeconomic status. Thus, we investigated income disparities in the 5-year survival rate (5YSR) in cancer patients and the temporal trends. Methods: This study used a national cancer cohort from 2002 to 2018 that was established by linking the Korea Central Cancer Registry and the National Health Insurance Service (NHIS) claim database to calculate the cancer survival rate by income level in the Republic of Korea. Survival data were available from 2002 onward, and the analysis was based on the actuarial method. We compared the survival of the earliest available 5-year period of 2002–2006 and the latest available 5-year period of 2014–2018, observing until 31 December 2021. Income level was classified into six categories: Medical Aid beneficiaries and five NHIS subtypes according to insurance premium. The slope index of inequality (SII) and relative index of inequality were used to measure absolute and relative differences in 5YSR by income, respectively. Results: The 5YSR between the 2002–2006 and 2014–2018 periods for all cancers improved. A significant improvement in 5-year survival rates (5YSR) over the study period was observed in lung, liver, and stomach cancer. The SII of survival rates for lung (17.5, 95% confidence interval (CI) 7.0–28.1), liver (15.1, 95% CI 10.9–19.2), stomach (13.9, 95% CI 3.2–24.7), colorectal (11.4, 95% CI 0.9–22.0), and prostate (10.7, 95% CI 2.5–18.8) cancer was significantly higher, implying higher survival rates as income levels increased. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. Conclusions: Although substantial improvement in the 5YSR was observed across cancer types and income levels from 2002 to 2018, this increase was not uniformly distributed across income levels. Our study revealed persistent income disparities in the survival of cancer patients, particularly for lung and liver cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy, but the literature still lacks clear risk and protective factors. This study aimed to evaluate and compare the risk factors for post-surgical HypoPTH in a large series of patients at a tertiary academic high-volume center undergoing total thyroidectomy for both benign and malignant diseases. It also focused on identifying risk and protective factors for persistent HypoPTH. Background: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy. Several risk factors have been identified, but data on postoperative follow-up are scarce. Methods: The study focused on 1965 patients undergoing surgery for benign and malignant thyroid diseases at a tertiary-level academic center. Anamnestic, biochemical, surgical, pathological, and follow-up data were evaluated. HypoPTH was defined by a serum concentration of PTH < 10 pg/mL on the first or the second post-operative day. Persistent HypoPTH was defined by the need for calcium/active vitamin D treatment > 12 months after surgery. Results: Postoperative HypoPTH occurred in 542 patients. Multivariate analysis identified the association of central lymph-nodal dissection, reduced preoperative PTH levels, a lower rate of parathyroid glands preserved in situ, and longer duration of surgery as independent risk factors. At a median follow-up of 47 months, HypoPTH regressed in 443 patients (more than 6 months after surgery in 7%) and persisted in 53 patients. Patients receiving a lower dose of calcium/active vitamin D treatment at discharge (HR 0.559; p < 0.001) or undergoing prolonged, tailored, and direct follow-up by the operating endocrine surgeon team had a significantly lower risk of persistent HypoPTH (2.4% compared to 32.8% for other specialists) (HR 2.563; p < 0.001). Conclusions: Various patient, disease, and surgeon-related risk factors may predict postoperative HypoPTH. Lower postoperative calcium/active vitamin D treatment and prolonged, tailored follow-up directly performed by operating endocrine surgeons may significantly reduce the rate of persistent HypoPTH. [ABSTRACT FROM AUTHOR]

Background and objective: The prevalence of thyroid cancer (TC) has exhibited an upward trajectory in recent years. An accelerating amount of evidence shows a significant association between Hashimoto's thyroiditis (HT) and TC. The present study encompasses a meticulously designed systematic review and meta-analysis with the aim of scrutinizing the risk of TC and clarifying sex disparities in HT. Methods: A comprehensive search was conducted across reputable online databases, including PubMed, Cochrane Library, EMBASE, and Web of Science. English-language publications on the correlation between HT and TC were examined without temporal restrictions. Two authors independently screened the articles and extracted pertinent data. The collected data underwent statistical analysis using the STATA software, enabling the calculation of the pooled Odds Ratio (OR) and 95% confidence intervals (CI). Additionally, a supplementary analysis was conducted on studies incorporating sex-specific data to determine the OR (female vs. male) and the sex-based prevalence of TC in HT. Results: A total of 2,845 records were obtained, and 26 retrospective studies were included in this meta-analysis. The results indicated a significant role for HT in TC (OR: 2.22, 95% CI: 1.85–2.67). Supplementary analysis indicated that the prevalence of TC in HT patients was lower in women (0.31, 95% CI: 0.17–0.45) than in men (0.37, 95% CI: 0.21–0.53). However, the result was not statistically significant. Conclusion: This systematic review and meta-analysis provide evidence that HT is associated with increasing odds of TC. Regular review of HT patients holds positive clinical significance. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the effectiveness of ultrasound criteria, TI-RADS score, and elastography in distinguishing benign thyroid nodules from malignant ones, as a substitute for invasive diagnostic procedures. Although the minority of thyroid nodules is malignant, invasive diagnostic procedures are often necessary. Methods: In this prospective study, a total of 104 thyroid nodules were assessed using fine-needle aspiration cytology. The euthyroid state of the patients was ensured. Conventional ultrasound and shear wave elastography (SWE) were performed by a single experienced operator. Final postoperative histopathologic findings were compared to conventional ultrasound and elastography findings. Results: SWE elasticity indices (EIs) were found to be significantly higher in malignant nodules than benign ones (p < 0.05). Combined results of both TI-RADS and SWE increased the sensitivity of detection of malignant nodules. Conclusion: Combined SWE and TI-RADS could enhance the diagnostic accuracy in differentiating thyroid nodules by leveraging their complementary strengths. [ABSTRACT FROM AUTHOR]

Background: In recent years, the incidence of thyroid nodules has increased significantly. There are various ways to treat thyroid nodules, and ablation therapy is one of the important ways to treat thyroid nodules. However, there are many complications and deficiencies in the current ablation treatment of thyroid nodules, especially the incomplete ablation of thyroid cancer nodules, which limits the further application of ablation technology. Case Summary: In this paper, we report two cases of incomplete ablation of thyroid nodules, one of which underwent surgical treatment due to anxiety after ablation, and the postoperative pathology confirmed that there was still residual papillary thyroid carcinoma, and the other patient underwent an operation after ablation, but visited our medical institution again due to cervical lymph node metastasis in a short period of time, and after radical cervical lymph node dissection, pathology confirmed multiple cervical lymph node metastasis. Radionuclide therapy was performed after surgery, and two patients are currently receiving endocrine suppression therapy, and their condition is stable with no signs of recurrence. Conclusion: The incomplete ablation of thyroid cancer nodules limits the development of ablation therapy, making ablation treatment a double-edged sword. Guidelines and expert consensus can guide their development, but they need to evolve with the times, and a multidisciplinary diagnostic team can help screen the most suitable patients. Only by using this technology more standardly, using the most appropriate technology, and treating the most suitable patients, can benefit more and more patients. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated changes in psychological and physiological indices in cancer survivors who participated in a forest therapy camp in Korea. Methods: A total of 37 cancer survivors (19 and 18 in the experimental and control groups, respectively) participated in this study. Over a 2-night and 3-day period, the participants in the experimental group took part in a forest therapy camp that included activities such as gymnastics, walking, five-senses experiences, and meditation. Both groups completed self-report questionnaires that measured their stress levels and profile of mood states, both before and after the forest therapy camp. Blood samples were collected to measure the levels of cortisol, serotonin, and natural killer (NK) cells. Results: After the forest therapy camp, the experimental group exhibited reduced stress levels (p = .031) and a significant improvement in total mood disturbance (p = . 047) when compared with the control group. The level of serotonin also significantly increased (p < .001). However, in contrast to the prediction, a significant increase in cortisol was noted in the experimental group relative to the control group (p = .016). Moreover, no significant difference in NK cells was noted between the two groups. Conclusion: Forest therapy can be easily applied to cancer survivors. The positive psychological effects of the forest therapy camp were confirmed by improvements in stress and mood states and the increased level of serotonin in forest therapy camp participants. However, there is a need for a follow-up evaluation of cortisol and NK cells due to the absence of significant between-group differences. [ABSTRACT FROM AUTHOR]

Introduction: Hashimoto's thyroiditis (HT) is one of the most common autoimmune endocrine disorders in the pediatric age group. In this study, it was aimed to retrospectively examine our cases, who were children and adolescents diagnosed with HT. Materials and Methods: We retrospectively examined 119 patients between the ages of 1 and 18, who were diagnosed with HT. In all of the cases, physical examination findings, thyroid function tests, anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (Anti-Tg) antibodies, thyroid ultrasonographies and accompanying autoimmune diseases were evaluated. Results: The female/male ratio was 3.5/1. In our cases, the median age at the time of diagnosis was 12.29 years and 10 (8.4%) of the cases were under the age of five. At the time of diagnosis, 37% of the cases were euthyroid, 21.8% had overt hypothyroidism, 34.5% had subclinical hypothyroidism, 2.5% had subclinical hyperthyroidism and 4.2% had overt hyperthyroidism. At the time of diagnosis, 102 cases (85.7%) had anti-TPO and 82 cases (68.9%) had anti-Tg positivity. The Anti-TPO levels at the time of admission were found to be significantly higher in the hypothyroid group compared to the euthyroid group. Conclusion: Thyroid function test results of patients with Hashimoto's thyroiditis may vary in the follow-up period. Even though most cases with euthyroidism remain euthyroid, some might progress to hypothyroidism. Although Hashimoto's thyroiditis is most frequently seen in adolescents, approximately 10% of the cases are under the age of five. Therefore, autoimmune thyroiditis should be considered in hypothyroidism occurring in the early stages of life. [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid cancer in the United States has risen dramatically since the 1970s, driven by an increase in the diagnosis of small tumors. There is a paucity of published New Mexico (NM) specific data regarding thyroid cancer. We hypothesized that due to New Mexico's unique geographic and cultural makeup, the incidence of thyroid cancer and tumor size at diagnosis in this state would differ from that demonstrated on a national level. Methods: The New Mexico Tumor Registry (NMTR) was queried to include all NM residents diagnosed with thyroid cancer between 1992 and 2019. For 2010 to 2019, age-adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate and tumor size by race/ethnicity and residence (metropolitan vs non-metropolitan) were assessed with rate ratios between groups. For 1992 to 2019, temporal trends in age-adjusted incidence rates for major race/ethnic groups in NM [Non-Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software. Results: Our study included 3,161 patients for the time period 2010 to 2019, including NHW (1518), Hispanic (1425), and AI (218) cases. The overall incidence rates for NM AIs were lower than those for Hispanics and NHWs because of a decreased incidence of very small tumors (<1.1 cm). The incidence rates for large tumors (>5.1 cm) was equivalent among groups. In the early 2000s, Hispanics also had lower rates of small tumors when compared to NHWs but this trend disappeared over time. Conclusion: AIs in New Mexico have been left out of the nationwide increase in incidental diagnosis of small thyroid tumors. This same pattern was noted for Hispanics in the early 2000s but changed over time to mirror incidence rates for NHWs. These data are illustrative of the health care disparities that exist among New Mexico's population and how these disparities have changed over time. [ABSTRACT FROM AUTHOR]

Background: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. Methods: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan–Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. Results: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24–143 months). The mean VRR was 81% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA (n = 33) or surgery (n = 4) or left under observation (n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared with nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183–4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms (n = 4) or newly detected thyroid tumors (n = 22), one benign and 21 malignant. The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. Conclusion: RFA is safe and effective for treating benign thyroid nodules, with a high VRR at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients. [ABSTRACT FROM AUTHOR]

The oral multikinase inhibitors sorafenib and lenvatinib are currently available as first-line treatment for patients with unresectable or metastatic thyroid cancer. However, treatment options for patients who are refractory to these multikinase inhibitors are limited. This study aimed to evaluate the safety and efficacy of rechallenged lenvatinib after failure of both lenvatinib and sorafenib in patients with metastatic thyroid cancer in the real-world clinical practice. We retrospectively reviewed the data of consecutive 16 patients with metastatic thyroid cancer who received lenvatinib as a rechallenge after failure of initial lenvatinib and sorafenib treatment at Shizuoka Cancer Center between 2016 and 2023. Of these, the initial lenvatinib was discontinued in 12 patients owing to progressive disease, in 3 patients owing to adverse events, and in 1 patient owing to both. The overall response rate was 6.7%, and disease control was achieved by rechallenge with lenvatinib in all patients with the target lesions. The median progression free survival after rechallenging with lenvatinib was 15.0 months. No new signs of toxicity were observed after rechallenging with lenvatinib. Our findings suggest that rechallenge with lenvatinib after failure of both lenvatinib and sorafenib showed manageable safety and modest efficacy in patients with metastatic thyroid cancer in clinical practice. The strategy of lenvatinib rechallenge may provide an alternative option for patients with no targetable driver genes or when selective kinase inhibitors are not indicated. [ABSTRACT FROM AUTHOR]

Background: The advent and increased use of high-resolution ultrasonography has resulted in improved detection of thyroid nodules. Even with the use of various Thyroid Imaging–Reporting and Data System, accurate imaging diagnosis of malignant thyroid nodules has been suboptimal, which necessitated use of newer modalities like contrast-enhanced ultrasonography alone and in combination for this purpose. Although the combined use of various Thyroid Imaging–Reporting and Data System and contrast-enhanced ultrasonography has turned out to be accurate in many studies, the ideal way to integrate contrast-enhanced ultrasonography into the Thyroid Imaging–Reporting and Data System algorithm is under-investigated. Purpose: To estimate and compare the diagnostic accuracy of American College of Radiology Thyroid Imaging–Reporting and Data System and contrast-enhanced ultrasonography in differentiating benign and malignant nodules alone and in combination. To estimate the diagnostic accuracy of contrast-enhanced ultrasonography in re-categorisation of Thyroid Imaging–Reporting and Data System 3 and Thyroid Imaging–Reporting and Data System 4 thyroid nodules. Materials and methods: This was a prospective cohort study performed in a tertiary care university–based hospital for 3 years. Adult patients with clinical or previous sonographic diagnosis of thyroid nodules were selected. Each of the nodules were assessed using ultrasonography and categorised using American College of Radiology Thyroid Imaging–Reporting and Data System criteria. The lesion was then assessed for contrast-enhanced ultrasonography features. The final diagnosis of the nodules was made using fine needle aspiration cytology. The diagnostic accuracy in diagnosis of malignant thyroid nodules for each of the American College of Radiology Thyroid Imaging–Reporting and Data System and contrast-enhanced ultrasonography alone and in combination was assessed. The diagnostic accuracy of contrast-enhanced ultrasonography in diagnosis of malignant thyroid nodules categorised as Thyroid Imaging–Reporting and Data System 3 and Thyroid Imaging–Reporting and Data System 4 was also assessed. Results: American College of Radiology Thyroid Imaging–Reporting and Data System had a sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 86.6%, 54.5%, 17.4%, 97.3% and 57.7%, respectively, in diagnosis of malignant thyroid nodules. Contrast-enhanced ultrasonography had a sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 86.6%, 95.4%, 67.9%, 98.4% and 94.4%, respectively, in diagnosis of malignant thyroid nodules. Contrast-enhanced ultrasonography had sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of 93.3%, 100.0%, 100.0%, 99.2% and 99.3%, respectively, in re-categorisation of Thyroid Imaging–Reporting and Data System 3 and Thyroid Imaging–Reporting and Data System 4 nodules. Conclusion: Contrast-enhanced ultrasonography can play a key role in diagnosis of malignant thyroid nodules which are categorised as indeterminate on grey-scale ultrasound. [ABSTRACT FROM AUTHOR]

Background: Primary squamous cell carcinoma (SCC) of the thyroid and anaplastic thyroid carcinoma (ATC) show significant clinical and histologic overlap. Their biological behaviors are so similar that the fifthWHO updates SCC as a morphologic pattern of ATC rather than a separate entity. However, molecular genomic evidence that determines them as the same histologic type is limited. We aimed to explore whether they belong to the same classification from a molecular-typing perspective. Methods: A cohort enrolled 15 SCCs and 15 ATCs was collected. Whole exome sequencing (WES) and RNA-sequencing were performed to analyze molecular genetic and gene-expression profiles. Results: Significantly differential-mutant genes were BRAF, DPCR1, PCYOX1L, BRSK2, NRG1, PRR14L, TET1, VAMP4 suggesting differences in mutation level, as well as differences in highfrequency mutated genes, and SCC had a much lower tumor mutation burden than ATC. Mutational co-occurrence and mutual exclusion were less frequent in SCC than in ATC. 2047 differentialexpress genes were screened, indicating differences in gene expression were extremely strong. In principal component analysis, ATC and SCC could be notably clustered together, respectively, meanwhile they could be explicitly distinguished. Unsupervised clustering analysis validated they can indeed be clearly separated from each other which demonstrated that they may be two distinctive entities. Conclusions: It is controversial yet SCC is classified as a morphologic pattern of ATC. We revealed that SCC exhibited molecular genetic characteristics distinct from ATC. Although the fifth WHO categorizes them together, this study may provide strong molecular genetic evidence for the next edition of WHO classification that may allow for the separation of thyroid SCC from ATC. [ABSTRACT FROM AUTHOR]

Diagnosing encapsulated follicular-patterned thyroid tumors like Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma (IEFVPTC), Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP), and Well-Differentiated Tumor of Uncertain Malignant Potential (WDT-UMP) remains challenging due to their morphological and molecular similarities. This study aimed to investigate the protein distinctions among these three thyroid tumors and discover biological tumorigenesis through proteomic analysis. We employed total shotgun proteome analysis allowing to discover the quantitative expression of over 1398 proteins from 12 normal thyroid tissues, 13 IEFVPTC, 11 NIFTP, and 10 WDT-UMP. Principal component analysis revealed a distinct separation of IEFVPTC and normal tissue samples, distinguishing them from the low-risk tumor group (NIFTP and WDT-UMP). IEFVPTC exhibited the highest number of differentially expressed proteins (DEPs) compared to the other tumors. No discriminatory proteins between NIFTP and WDT-UMP were identified. Moreover, DEPs in IEFVPTC were significantly associated with thyroid tumor progression pathways. Certain hub genes linked to the response of immune checkpoint inhibitor therapy, revealing the potential predictor of prognosis. In conclusion, the proteomic profile of IEFVPTC differs from that of low-risk tumors. These findings may provide valuable insights into tumor biology and offer a basis for developing novel therapeutic strategies for follicular-patterned thyroid neoplasms. [ABSTRACT FROM AUTHOR]

Background: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. Methods: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. Results: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660–0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12–0.55), P < 0.001. Conclusion: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Serum TSH suppression in the management of PTC patients will inevitably cause iatrogenic thyrotoxicosis. Our study challenges, for the first time, the role of human recombinant thyrotropin (rh-TSH) as a mitogen on PTC cell lines. For this study, both K1 and TPC-1 cells were treated with clinically relevant rh-TSH under various conditions. The expression levels of TSHR and thyroglobulin (Tg) were determined and, subsequently, the proliferation and migration were assessed. Additionally, cells were engineered to overexpress TSHR in order to multiply TSH signal transduction. Under the conditions employed, rh-TSH was inadequate for inducing either the proliferation or the migration rate of both transformed and non-transformed cells, while Tg expression was increased. We report that, clinically speaking, rh-TSH doses cannot induce proliferation and migration in PTC cell lines, thus questioning TSH suppression in PTC patients. Further research is warranted to dissect the underlying mechanisms. These results could translate into better PTC patient management. Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the impact of tumor size on T3b differentiated thyroid cancer prognosis. No significant difference was found in the prognosis of small T3b tumors compared to the T1 tumors. Disease-specific survival, disease-free survival, and overall survival were significantly lower only in large T3b tumors compared to T2 and T3a. If T3b tumors are 2 cm or smaller, downstaging may be considered. The modified T category, reclassifying T3b (≤2 cm) as T1, showed better staging performance than the existing category. Adopting this modified T category could improve the prognostic accuracy of the AJCC/TNM staging. The prognostic significance of tumor size in T3b differentiated thyroid cancer (DTC) remains debated and underexplored. This study aimed to examine the varying impact of T3b based on tumor size, analyzing disease-specific survival, disease-free survival, and overall survival. A retrospective review of 6282 DTC patients who underwent thyroid surgery at Seoul St. Mary's Hospital from September 2000 to December 2017 was conducted. T3b was classified into three subcategories, T3b-1 (≤2 cm), T3b-2 (2–4 cm), and T3b-3 (>4 cm), using the same size criteria for T1, T2, and T3a. T3b-1 showed no significant difference in disease specific survival compared to T1, and both disease-free and disease-specific survival curves were sequentially ranked as T1, T3b-1, T2, T3a, T3b-2, and T3b-3. The modified T category, reclassifying T3b-1 as T1, demonstrated superior staging performance compared to the classic T category (c-index: 0.8961 vs. 0.8959 and AUC: 0.8573 vs. 0.8518). Tumors measuring 2 cm or less within the T3b category may require downstaging, and a modified T category could improve the precision of prognostic staging compared to the current T category. [ABSTRACT FROM AUTHOR]

Background: Thyroid nodules (TN) are more frequent in the iodine-deficient region and the proportion of benign nodules is higher compared to areas with sufficient iodine intake. Objective: The aim of this study was to assess factors associated with malignant TN specially the EU-TIRADS ultrasound score in a Moroccan population with a high prevalence of iodine deficiency. Methods: In a prospective cross-sectional study, we enrolled outpatients referred for TN with fine needle aspiration biopsy (FNAB) according to EU-TIRADS 2017 classification. Malignancy of TN was defined by histological results indicating a thyroid malignancy on thyroid micro-biopsy or after surgical resection if indicated. Results: 225 participants with TN were enrolled. The median age was 54 (42.5 to 62) years-old. The prevalence of malignant TN was 8.9%. Malignant TN were significantly smaller than non-malignant ones (p = 0.008) and sub-centimetric TN were more frequent in malignant TN (25% vs 1.5%; p < 0.001). On multivariate analysis, male gender (OR : 9.33 ; 95% CI [2.02 ; 43.01]; p = 0,004) and EU-TIRADS score of 5 (OR : 55.6 ; 95% CI [9.34 ; 327.91] ; p < 0.001) were independent factors associated with malignant TN. The EU-TIRADS score of 4 was not associated to malignant TN. Conclusion: Our data suggest a trend of over-diagnosing indolent thyroid cancer. The EU-TIRADS score of 4 was not associated with TN malignancy. Considering clinical, accessory sonographic features, and size threshold for FNAB in EU-TIRADS 4 score TN may refine the diagnosis performance of this score in our population [ABSTRACT FROM AUTHOR]

The article reviews the development and purpose of the Great Britain Multidisciplinary Head and Neck Cancer Guidelines, highlighting their role in standardizing care and improving outcomes through a multidisciplinary approach. It also discusses the nature of head and neck cancers, the impact of HPV on cancer incidence, and the organization of head and neck cancer services and patient management.

Metastatic renal cell carcinoma to the thyroid is a rare yet aggressive histopathologic diagnosis, which may often be omitted from the initial clinical differential. This is in part due to the long latency period between the initial renal primary and appearance of metastatic disease, coupled with the diagnostic limitations of fine-needle aspiration biopsies. We herein present an interesting case of a metastatic clear-cell renal-cell carcinoma mimicking an aggressive primary thyroid neoplasm, 10 years after a nephrectomy for a renal primary, highlighting key diagnostic and management considerations. [ABSTRACT FROM AUTHOR]

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that accounts for 0.1%–0.15% of all thyroid cancers. More than half of the patients have tumor extension to adjacent organs, including the recurrent laryngeal nerve, trachea, and esophagus. The diagnosis of CASTLE is based on histology and immunohistochemistry. A 58-year-old female patient complained of hoarseness for one and half years. Right side vocal cord palsy was diagnosed by fiberscopy. Thyroid sonography revealed right thyroid tumors, which were reported to be papillary thyroid carcinoma through FNAC. Total thyroidectomy with central lymph node dissection was performed. Pathologist found 2 isolated malignancy tumors. One patient in the right thyroid lobe had papillary thyroid carcinoma features. The other extrathyroid tumor seemed to be separated from the first tumor and invaded the thyroid capsule. After multiple immunohistochemical studies, PTC synchronous CASTLE was the final diagnosis. Coexisting PTC and CASTLE is very rare. This is the first report to describe a case showing PTC at first, while subsequent pathologic examination revealed the presence of CASTLE in addition to PTC. Since the prognosis of CASTLE is favorable, the treatment is different from other aggressive thyroid cancers, such as poorly differentiated or anaplastic thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Objective: Chronic hypothyroidism is associated with significant neurocognitive deficits. However, present data about the effect of acute hypothyroidism on cognitive functions are limited. This study aimed to investigate the cognitive functions of patients with differentiated thyroid carcinoma (DTC) in acute hypothyroidism caused by l-thyroxine withdrawal (THW) using auditory event-related potentials (AERPs). Methods: Twenty-three patients with DTC and fifteen healthy subjects (group 1) were involved in the study. AERPs were recorded using the standard auditory "Oddball" paradigm from the Fz, Cz, Pz, and Oz regions. P300 waves were analyzed. The first records were obtained from group 1 and DTC patients under thyroxine treatment (group 2a). In the patient group, AERP recordings of the patients were repeated approximately 1 month after the withdrawal of thyroid hormone (THW) when the patients became hypothyroid (Group 2b). Results: P300 latencies were found to be significantly longer in group 2a in the Cz (P < .01), Pz (P < .001), and Oz (P < .001) regions compared to group 1, except for Fz. Group 2b P300 latencies were also longer than group 1 Cz (P < .009), Pz (P < .001), and Oz (P < .001) regions, except Fz. When comparing group 2a and group 2b, the P300 latency of group 2b was longer in the Pz region (P < .05). Conclusion: In this study, it was shown that cognitive functions in patients with DTC had a slower cognitive function in the state of acute hypothyroidism induced by 1-month THW than in both healthy individuals and during l-thyroxine treatment. [ABSTRACT FROM AUTHOR]

The incidence of thyroid tumors has been increasing yearly over the past decade, making it the fourth highest tumor in women. This places various biological burdens on those affected. Currently, thyroid tumors are primarily diagnosed using percutaneous fine needle aspiration and ultrasound. However, these methods are complex, expensive, and less accurate, and they may fail to detect some thyroid nodules. As an alternative, researchers are focusing on blood‐based biomarkers in addition to the traditional diagnostic methods, assisted predominantly by nanomaterials. Early identification of thyroid cancer is crucial as it is highly treatable. Various sensing systems have been developed using nanomaterial‐mediated approaches to enhance the detection system. Nanomaterials are effectively applied in biosensors for surface functionalization and are conjugated with biomolecules to improve the interaction with the target analyte. This review discusses nanomaterial‐assisted thyroid tumor detection, with a special focus on nanomaterial‐based biosensors. [ABSTRACT FROM AUTHOR]

Background: Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This study sought to delineate patterns of central and lateral neck involvement in unilateral papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). Methods: This was a retrospective correlative analysis of nodal patterns in surgical specimens from patients with unilateral PTC or MTC who had undergone thyroidectomy with at least ipsilateral central neck dissection between November 1994 and January 2024 at a tertiary referral center. Results: Included were 833 patients with unilateral PTC and 640 patients with unilateral MTC. Simultaneous presence or absence of node metastases was noted in ipsilateral central and lateral neck compartments in 76.6–78.1% of patients with PTC (both node positive in 27.0–54.7% and both node negative in 23.4–49.6%) and 77.3–80.0% of patients with MTC (both node positive in 26.6–33.2% and both node negative in 44.1–53.4%). Only one ipsilateral neck compartment was node positive in 21.9–23.4% of patients with PTC and 20.0–22.7% of patients with MTC. The ipsilateral central, but not the ipsilateral lateral compartment, was node positive in 8.8–16.9% with PTC and 8.6–8.8% of patients with MTC, whereas the ipsilateral lateral, but not the ipsilateral central compartment, was node positive in 6.5–13.1% with PTC and 11.3–14.1% with MTC. Ipsilateral lateral neck involvement sparing the ipsilateral central neck was 1.5–2 times more frequent in patients with node positive MTC than patients with node positive PTC (24.2–25.2% vs. 12.9–17.1%). Greater numbers of node metastases in the ipsilateral central neck compartment were associated with more frequent involvement of the ipsilateral lateral, contralateral central, and contralateral lateral neck compartments. Thyroid tumor diameter intensified nodal spread without changing nodal spread patterns. Conclusions: These histopathological findings, which need to be interpreted in light of the respective tumor biology, offer an unprecedented glimpse at the metastatic patterns of unilateral PTC and MTC. Customizing neck dissection to the patterns of nodal spread, considering operative status (initial vs. reoperative surgery) and experience with neck dissection, may require more frequent concomitant dissections of ipsilateral central and ipsilateral lateral neck compartments. [ABSTRACT FROM AUTHOR]

Background: Ki-67 immunostaining is commonly used in neuroendocrine tumors to estimate the proliferative index and for grading. This study investigates its association with the invasiveness of follicular-derived thyroid carcinomas (TCs). Methods: A retrospective analysis of patients with TC at three McGill University teaching hospitals between January 2018 and November 2023 was conducted. The inclusion criteria included patients with malignant thyroid tumors and accessible Ki-67 LI data from final pathology specimens. The data collected included patient demographics, Ki-67 LI values, and different invasiveness attributes, such as molecular mutations, the histological subtype, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive lymph nodes (LNs). Results: In total, 212 patients met the inclusion criteria, of which 80.7% were females and 19.3% were males. The Ki-67 LI ranged from 1% to 30%, with the majority of the cases within the range of 1–15%. A significant association was observed between higher Ki-67 LI and high-risk histological subtypes of thyroid carcinoma (p < 0.001). Similarly, Ki-67 LI was significantly associated with LVI and positive LN metastasis (p < 0.001 and p = 0.036, respectively). However, no significant association was found between the Ki-67 LI and gene mutations or ETE (p = 0.133 and p = 0.190, respectively). Using percentiles to establish a cutoff, patients with a Ki-67 LI higher than 6.7 showed a higher likelihood of being associated with invasive features. Conclusion: Elevated Ki-67 LI can serve as an indicator of aggressiveness in follicular-derived TC, especially when associated with distinct histological subtypes, LVI and positive LNs. [ABSTRACT FROM AUTHOR]

Background: The high doses of radioiodine‐131 (131I) and, subsequently, the high radioactive burden for dog and environment warrants optimization of 131I therapy in dogs with thyroid carcinoma (TC). Hypothesis/Objectives: To evaluate the effect of a revised protocol with recombinant human thyroid stimulating hormone (rhTSH) on tumor radioactive iodine uptake (RAIU) in dogs with TC. Animals: Nine client‐owned dogs diagnosed with TC. Methods: A prospective cross‐over study in which tumor RAIU was calculated and compared at 8 hours (8h‐RAIU) and 24 hours (24h‐RAIU) after injection of radioactive iodine‐123 (123I), once with and once without rhTSH (ie, 250 μg, IM, 24 and 12 hours before 123I) in each dog. Simultaneously, serum total thyroxine (TT4) and TSH were measured at baseline (T0), and 6 (T6), 12 (T12), 24 (T24), and 48 hours (T48) after the first rhTSH administration. Results: Tumor RAIU was significantly higher at 24 hours with rhTSH compared to no rhTSH (mean difference = 8.85%, 95% CI of [1.56; 16.14]; P =.03), while this was non‐significant at 8 hours (mean difference = 4.54%, 95% CI of [0.35; 8.73]; P =.05). A significant change of serum TT4 (median difference T24 − T0 = 35.86 nmol/L, interquartile range [IQR] = 15.74 nmol/L) and TSH (median difference T24 − T0 = 1.20 ng/mL, IQR = 1.55 ng/mL) concentrations occurred after administration of rhTSH (P <.001). Conclusions and Clinical Importance: Recombinant human TSH could optimize 131I treatment in dogs with TC by increasing tumor RAIU and thus 131I treatment efficacy. [ABSTRACT FROM AUTHOR]

Simple Summary: By synthesizing the latest research and clinical data, this review underscores the transformative potential of robotic surgery in thyroid cancer management and identifies key areas for further research to optimize patient outcomes. Our aim is to enhance the discourse on improving surgical care for thyroid cancer patients and to pave the way for future innovations in the field. Thyroid cancer is among the most common endocrine malignancies, necessitating effective surgical interventions. Traditional open cervicotomy has long been the standard approach for thyroidectomy. However, the advent of robotic surgery has introduced new possibilities for minimally invasive procedures with benefits in terms of cosmetic outcomes, enhanced precision, comparable complication rates, and reduced recovery time. This study mainly reviewed the most widely used and well-known robotic thyroidectomy approaches: the transaxillary approach, the bilateral axillo–breast approach, and the transoral approach. This review examines the current status and future potential of robotic surgery in thyroid cancer treatment, comparing its efficacy, safety, and outcomes with those of conventional open cervicotomy. Challenges such as a longer operative time and higher costs exist. Future directions include technological advancements, tele-surgery, single-port surgery, and the integration of artificial intelligence. Robotic surgery holds promise in optimizing patient outcomes in thyroid cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: STING is a key element in the cGAS/STING cytosolic sensing pathway and several STING agonists are currently being evaluated as anticancer drugs in the field of cancer immunotherapy. This study provides a unique catalog of STING expressions in tumor cells as well as its clinical relevance and association with PD-L1 expression in tumor and inflammatory cells in more than 130 different tumor entities. Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry. STING-positive tumor cells were found in 130 (93.5%) of 139 tumor entities. The highest STING positivity rates occurred in squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%–95.7%); adenocarcinoma of the pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); and serous high-grade ovarian cancer (86.0%). High STING expression was linked to adverse phenotypes in breast cancer, clear cell renal cell carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and papillary carcinoma of the thyroid (p < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma (p = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells (p < 0.0001 each) but was unrelated to the density of CD8+ lymphocytes. STING expression is variable across tumor types and may be related to aggressive tumor phenotype and PD-L1 positivity. The lack of relationship with tumor-infiltrating CD8+ lymphocytes argues against a significant IFN production by STING positive tumor cells. [ABSTRACT FROM AUTHOR]

Simple Summary: In the following study, we aimed to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases (BMs) from thyroid cancer. To achieve this, from a total of 4320 thyroid cancer patients recorded in our institutional database over a 30-year period, data on 20 patients with brain metastases were retrospectively collected and analyzed. While thyroid cancer patients generally have a favorable prognosis, those with BMs often face a poorer outlook, marked by shorter survival times. Patients who experienced a longer interval (more than 24 months) between the diagnosis of thyroid cancer and the appearance of BMs had significantly better overall survival (OS). Surgical resection, combined with multidisciplinary adjuvant treatment, is essential for managing patients with BMs from thyroid cancer. Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable owing to lower survival rates among such patients compared to those without intracranial involvement. Many questions about their management remain unclear. The aim of the present study was to analyze the characteristics, treatment modalities, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, the data of 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of primary thyroid cancer and brain metastasis, and survival were analyzed. Among our patient cohort, the mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis, the mean age was found to be 64.8 ± 14.9 years. The histological types of primary thyroid cancer were identified as papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range: 0–180 months). Ten patients were identified as having a single intracranial lesion, and ten patients were found to have multiple lesions. Surgical resection was primarily performed in fifteen patients, and whole-brain radiotherapy, radiotherapy, or tyrosine kinase inhibitors were applied in the remaining five patients. The overall median survival time was 15 months after the diagnosis of BMs from TC (range: 1–252 months). Patients with thyroid cancer can develop brain metastasis even many years after the diagnosis of the primary tumor. The results of our study demonstrate increased overall survival in patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary carcinoma and those with follicular thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of multiple primary cancers (MPCs) among 96,174 cancer patients at the Korea Cancer Center Hospital (KCCH) from 2003 to 2022 was 2.3%. Breast cancer (15.7%) was the most common primary cancer, with lung cancer (15.2%) being the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years, decreasing for third and fourth primary cancers (2.1 years and 1.6 years, respectively). Lymphoma had the highest relative risk (2.1) for developing MPCs. Specific primary cancers showed significant associations with subsequent cancers, informing future research and management strategies. Rising cancer survival rates have led to an increased risk of multiple primary cancers (MPCs). Data on MPCs in South Korea are limited. This study aimed to address incidence and clinical characteristics of MPCs in a single cancer center in Korea during a 20-year period. We retrospectively analyzed 96,174 cancer patients at the Korea Cancer Center Hospital between 2003 and 2022, identifying 2167 patients with metachronous MPCs based on Surveillance, Epidemiology, and End Results SEER criteria. We categorized patients by cancer type (15 major solid cancer groups and 3 major hematologic cancer groups), including pathological diagnosis, assessed latency periods, and relative risks (RRs) for developing MPCs. The overall MPC incidence was 2.3%. Breast cancer (15.7%) was the most common primary cancer, and lung cancer (15.2%) was the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years. Decreasing latency periods for third and fourth primary cancers were observed (2.1 years and 1.6 years, respectively). Most cancers maintained their dominant pathological type despite notable changes in the prevalence of specific pathologies for certain types of second primaries. Lymphoma showed the highest RR (2.1) for developing MPCs. Significant associations were found between specific primary and subsequent cancers, including breast–ovary, thyroid–breast, stomach–pancreas, colorectal–head and neck, lung–prostate, and lymphoma–myeloid neoplasms. These findings contribute to a better understanding of MPC occurrence. They can inform future research on their etiology and development of improved management strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Medullary thyroid carcinoma (MTC) is driven by a small number of pathogenic genetic variants and tumours usually exhibit a correspondingly low tumour mutational burden. This reduces tumour visibility to the immune system and impacts the immune cell profile of the tumour microenvironment. In the last decade targeted pathway inhibitors have revolutionized the therapeutic landscape for patients with advanced disease, with increasing options for systemic therapy tailored to the molecular signature of the tumour. Therefore, understanding the molecular basis of disease, pathogenesis of immune evasion and mechanisms of escape of pathway inhibition is of paramount importance. Here, we summarize genetic and molecular drivers of MTC and their relevance to tumour immunogenicity, the cellular milieu of the tumour microenvironment, and response to targeted therapy. In this review, we explore the underlying molecular biology of medullary thyroid carcinoma (MTC) and its interplay with the host immune system. MTC is consistently driven by a small number of specific pathogenic variants, beyond which few additional genetic events are required for tumorigenesis. This explains the exceedingly low tumour mutational burden seen in most MTC, in contrast to other cancers. However, because of the low tumour mutational burden (TMB), there is a correspondingly low level of tumour-associated neoantigens that are presented to the host immune system. This reduces tumour visibility and vigour of the anti-tumour immune response and suggests the efficacy of immunotherapy in MTC is likely to be poor, acknowledging this inference is largely based on the extrapolation of data from other tumour types. The dominance of specific RET (REarranged during Transfection) pathogenic variants in MTC tumorigenesis rationalizes the observed efficacy of the targeted RET-specific tyrosine kinase inhibitors (TKIs) in comparison to multi-kinase inhibitors (MKIs). Therapeutic durability of pathway inhibitors is an ongoing research focus. It may be limited by the selection pressure TKI treatment creates, promoting survival of resistant tumour cell clones that can escape pathway inhibition through binding-site mutations, activation of alternate pathways, and modulation of the cellular and cytokine milieu of the tumour microenvironment (TME). [ABSTRACT FROM AUTHOR]

BACKGROUND: The functioning of the thyroid gland is a multi-component process that in some conditions may undergo alterations. The thyroid gland is part of the endocrine system that produces the iodine-containing hormones thyroxine and triiodothyronine. Thyroid hormones, control metabolism and energy, growth processes, maturation of tissues and organs, regulation of blood flow, and, therefore, providing vital functions of the body. The role of thyroid hormones in the regulation of blood flow is determined by the intensity of their production and the quantity in the blood. Presumably, in case of oncological and non-oncological diseases of the thyroid gland, the fluidity of the blood, which depends on the rheological properties, will be different. OBJECTIVE: Our aim was investigating rheological characteristics for studying of changes of rheology in patients with thyrotoxicosis, with benign tumor pathology of the thyroid gland, with thyroid cancer and finding possible diagnostic markers for differentiating benign and malignant thyroid tumors METHODS: In this regard, we examined, using modern methods accepted in clinical practice, a standard list of recommended diagnostic tests in the group of patients (thyrotoxicosis: n = 25; benign tumor: n = 47), thyroid cancer: n = 35) and control group (n = 15), and with new original methods, parameters that describe the rheological properties of the blood, such as blood rheological index, volume, thickness, surface area of erythrocytes, erythrocyte aggregation index, deformation index, plasma viscosity, hematocrits. RESULTS: Against the background of relative changes in the studied values, it is necessary to pay attention to the fact that erythrocyte aggregation in patients with a benign form and control, as well as in patients with a malignant form and control, differ significantly from each other, in addition, there is a significant difference between aggregation in the group of patients with benign and control aggregation. malignant forms of the disease. It is significant that aggregability differs in patients with thyrotoxicosis and in controls. This indicates that erythrocyte aggregation is particularly informative. The blood rheological index most clearly demonstrated the difference between benign and malignant forms of the disease. Significantly changed compared to control in various forms of thyroid diseases. CONCLUSION: Additional diagnostic markers for differentiating benign and malignant thyroid tumors may be consideredeerythrocyte aggregation index and blood rheological index. [ABSTRACT FROM AUTHOR]

Background Nonmedullary thyroid cancer (NMTC) comprises approximately 90% of all thyroid cancers, and about 3% to 9% of NMTC cases have a familial origin. Familial NMTC (FNMTC) in the absence of a documented familial cancer syndrome such as Cowden syndrome is characterized by the occurrence of thyroid cancer of follicular cell origin in 2 or more first-degree relatives. Methods Whole-exome sequencing (WES) was used to identify pathogenic genetic variants in 2 Persian families with FNMTC. The purpose of this work is to assess the pathogenic status of these variants as well as the cosegregation status of the variants observed in the examined families. Results By analyzing WES data in the first family, SRGAP1 : NM_020762: exon16: c.C1849T was identified as a pathogenic variant. This variant was confirmed by Sanger sequencing. In the second family, the variant FOXE1 : NM_004473: exon1: c.531_532insCGCGA was identified but was not confirmed by Sanger sequencing. Conclusion Based on the data, SRGAP1 can be a potential candidate gene for susceptibility to FNMTC in the first family. However, additional analyses like whole genome sequencing and copy number variations are required to ascertain the disease status in second family. [ABSTRACT FROM AUTHOR]

BACKGROUND: About 75% of medullary thyroid cancers (MTCs) are sporadic with 45% to 70% being driven by a RET mutation. Selpercatinib is an approved treatment for RET-mutated (mutRET) MTC; however, treatments are needed for wild-type RET MTC (wtRET). Genomic alterations and transcriptomic signatures of wtRET MTC may reveal new therapeutic insights. STUDY DESIGN: We did a retrospective analysis of MTC samples submitted for DNA/RNA sequencing and programmed cell death ligand 1 expression using immunohistochemistry at a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified laboratory. Tumor microenvironment immune cell fractions were estimated using RNA deconvolution (quanTIseq). Transcriptomic signatures of inflammation and MAP kinase pathway activation scores were calculated. Mann-Whitney U, chi-square, and Fisher's exact tests were applied (p values adjusted for multiple comparisons). RESULTS: The 160-patient cohort included 108 mutRET and 52 wtRET MTC samples. wtRET tumors frequently harbored mitogen-activated protein kinase (MAPK) pathway mutations, including HRAS (42.31%), KRAS (15.7%), NF1 (6.7%), and BRAF (2%), whereas only 1 MAPK pathway mutation (NF1) was identified among mutRET MTC. Recurrent mutations seen in wtRET MTC included MGA, VHL, APC, STK11, and NFE2L2. Increased transcriptional activation of the MAPK pathway was observed in patients with wtRET harboring mutations in MAPK genes. Although the frequency of programmed cell death ligand 1 expression was similar in wtRET and mutRET (10.2% vs 7%, p = 0.531), wtRET tumors were more often tumor mutational burden high (7.7% vs 0%, p = 0.011), and wtRET MTC exhibited higher expression of immune checkpoint genes. CONCLUSIONS: We identified molecular alterations and immune-related features that distinguish wtRET from mutRET MTC. Although RET mutation drives MTC in the absence of other alterations, we showed that wtRET MTC frequently harbors MAPK pathway mutations. These findings may indicate a potential basis for MAPK-targeted therapy, possibly in combination with immunooncology agents for selected patients with wtRET MTC. [ABSTRACT FROM AUTHOR]

Aim: Evidence shows that 20%–30% of patients who aspirate do so silently. Research to date has not demonstrated clear evidence to indicate which patients are at higher risk of silent aspiration. Our aim was to use univariate logistic regression analysis of retrospective case review to determine potential patterns of silent aspiration. Materials and methods: We conducted a retrospective analysis of 455 fiberoptic endoscopic evaluation of swallowing (FEES) reports. The patients were divided into four groups: G1 – neurological diseases (n = 93), G2 – head and neck surgery (n = 200), G3 – gastroenterological diseases (n = 94) and G4 – other patients (n = 68). Data included the occurrence or absence of saliva penetration or aspiration, of silent fluid/solid food penetration or aspiration, type of penetration or aspiration, occurrence of cranial nerve paresis, radiotherapy and tracheostomy. Univariate logistic regression was used to evaluate independent risk factors of silent aspiration in the study population. Three models with different independent variables were considered. Results: There is a statistically significant difference in the frequency of occurrence of silent penetration and aspiration within the groups (p < 0.001), with intraglutative being most frequent. Fluid and food penetration and aspiration correlated with saliva penetration and aspiration in all groups (p < 0.001). Cranial nerve paresis (IX and X), radiotherapy and tracheostomy correlate with saliva penetration and aspiration (p = 0.020 for cranial nerve paresis; p = 0.004 for radiotherapy; p < 0.001 for tracheostomy). One hundred and fifteen patients (45.81%) in the subgroup of patients with intraglutative aspiration had cranial nerve paresis (IX, X or IX–X). Conclusions: Patients who should be prioritised or considered to be at a higher need of instrumental swallowing evaluation are those with IX and X cranial nerve paresis, tracheostomy and those who have had radiotherapy, with saliva swallowing problems, especially after paraganglioma, thyroid and parathyroid glands and middle and posterior fossa tumour surgery. WHAT THIS PAPER ADDS: What is already known on the subject: Clinical signs of penetration or aspiration include coughing, throat clearing and voice changes, while silent penetration or aspiration patients aspirate without demonstrating any clinical symptoms. The most common consequences of silent aspiration include aspiration pneumonia, recurrent lower respiratory tract infections and respiratory failure. Additionally, malnutrition and dehydration can be indicators of silent aspiration. Patients may unknowingly reduce their oral intake and lose weight. Retrospective studies have shown that 20%–30% of patients aspirate silently (e.g. patients after stroke, acquired brain injury, head and neck cancer treatment, prolonged intubation). Clinical examination of swallowing can miss up to 50% of cases of silent aspiration. What this paper adds to existing knowledge: Currently, silent aspiration is often discussed in neurological literature, but its applications to head and neck surgery are limited. In this study, we identify head and neck surgery patients who should be prioritised or considered to be in higher need of instrumental swallowing evaluation due to a higher risk of silent aspiration. What are the potential or actual clinical implications of this work?: Post‐treatment structural changes can result in lower cranial nerve paresis (IX, X, XII) and face injury, in which vagus and glossopharyngeal nerves are injured. After tracheostomy and radiotherapy, patients with problems swallowing saliva need careful clinical examination, particularly cranial nerve examination. [ABSTRACT FROM AUTHOR]