Thyroid Cancer Research Articles

Cancer-related Fear and Worry in Patients with Low-Risk Thyroid Cancer: A Longitudinal Cohort Study.

Little is known about how patients' emotions impact the choice between hemi- and total thyroidectomy (TT) for low-risk thyroid cancer (LR-TC) and how these emotions change after treatment. To investigate thyroid cancer-specific fear and worry both before and after treatment of LR-TC with hemi- or TT. This prospective cohort study enrolled adults with confirmed or likely LR-TC at 15 institutions. Participants completed measures of thyroid cancer-related fear and worry at the time of their treatment decision and 9-months later. Participants were categorized as having low, medium, or high levels of fear and worry in accordance with the literature. Those choosing hemi-thyroidectomy were compared to those choosing TT. Of 177eligible patients, 125 (70.6%) enrolled and 114 completed both surveys (91.2% retention). Overall, 41 (36.0%) participants chose hemi-thyroidectomy and 73 (64.0%) chose TT. Across all participants, thyroid cancer-related fear and worry both decreased significantly after surgery (fear 25.8±6.4 to 23.1±7.4; worry 8.2±2.4 to 5.4±2.1, p<0.001). The proportion of participants with high fear decreased from 64.9% to 50.9%, while the proportion with high worry decreased from 75.4% to 41.2% (p<0.001 for both). At both time points, no differences existed between those choosing hemi- and TT in levels of worry or fear. Patients with LR-TC report lower levels of fear and worry 9-months after surgery regardless of the extent of surgery, suggesting that both surgeries provide an emotional benefit to some patients. Thyroid cancer-related fear and worry do not appear to influence patients' decisions to undergo hemi- or TT.

Identification of potential biomarkers of papillary thyroid carcinoma.

This study aimed to identify candidate biomarkers for papillary thyroid carcinoma using an integrative analysis of bioinformatics and machine learning (ML). The PTC datasets GSE6004, GSE3467, and GSE33630 (species: Homo sapiens) were downloaded from NCBI and analyzed using the limma package to obtain DEGs. Once DEGs were identified, GO and KEGG enrichment analyses were performed as the first step in the bioinformatics process. Subsequently, a protein-protein interaction (PPI) network was constructed according to the common genes in bioinformatics and machine learning using STRING to elucidate the important genes involved in PTC pathogenesis. In machine learning, finding genes entails feature selection to identify the key genes that distinguish biological states. Hybrid feature selection will be used for this. In the second step, the original data sets were preprocessed to detect and correct missing and noisy data; after that, all data were merged. Following performing Linear and Discriminative Hybrid Feature Selection (LDHFS) on the processed dataset, machine learning algorithms such as Random Forest (RF), Naive Bayes (NB), and Support Vector Machines (SVM) are utilized. Bioinformatics and machine learning analyses indicate that the genes RXRG, CDH2, ETV5, QPCT, LRP4, FN1, and LPAR5 are integral to the progression of thyroid cancer. This study attained the highest accuracy utilizing the RF algorithm, achieving an accuracy rate of 94.62%, a Kappa value of 91.36%, and an AUC value of 96.13%. These results offer additional evidence and confirmation for the genetic alterations of these genes. These findings may accelerate the development of prospective therapeutic and diagnostic methods in future research. Bioinformatics and machine learning techniques identified the common genes "RXRG, CDH2, ETV5, QPCT, LRP4, FN1, and LPAR5" as PTC biomarkers, providing novel reference markers for the diagnosis and treatment of PTC patients. The model is anticipated to possess significant predictive value and assist in the early diagnosis and screening of clinical PTC. These insights enhance the field of PTC management and offer guidance for future research.

Breast cancer and neoplasms of the thyroid gland: a bidirectional two-sample Mendelian randomization study.

With the rising incidence of breast cancer (BC) and neoplasms of the thyroid gland, a potential link between the two has drawn increasing attention. However, the causal relationship remains unclear due to various confounding factors. This study aims to investigate the causality between BC and thyroid tumors using Mendelian Randomization (MR) analysis. We conducted a bidirectional two-sample MR analysis, utilizing breast cancer-associated single nucleotide polymorphisms (SNPs) from the Breast Cancer Association Consortium (BCAC) and thyroid tumor-related SNPs from the FinnGen (https://www.finngen.fi/) database. First, we performed univariable MR (UVMR) to assess the causal relationship between BC and both malignant and benign thyroid tumors, followed by reverse causality analysis. To account for potential confounders, we applied multivariable MR (MVMR). The inverse-variance weighted (IVW) method was primarily used, with secondary analyses performed using the weighted median and MR-Egger regression approaches. UVMR analysis revealed a significant positive causal relationship between BC and malignant thyroid tumors (odds ratio [OR] and 95% confidence interval [CI]: 1.291, 1.143-1.458, P = 3.90×10-5). No causal relationship was found between BC and benign thyroid tumors. The MVMR analysis, adjusting for confounding factors such as smoking, drinking, and body mass index (BMI), confirmed the robustness of the results. This study provides genetic evidence supporting a causal relationship between BC and malignant thyroid tumors. These findings highlight the importance of thyroid cancer screening in BC patients. However, further MR studies or randomized controlled trials (RCTs) are necessary to assess small effects accurately.

Consideration of Early Dynamic Risk Stratification to Guide Discharge from Oncologic Follow-Up in Patients with Differentiated Thyroid Cancer.

Background: The current dogma is a life-long follow-up for patients treated for follicular-derived differentiated thyroid cancers (DTC). Our primary objective was to determine the time to recurrence in a series of DTC patients with an excellent response to therapy 6 months after total thyroidectomy and radioiodine therapy. The secondary objectives were to determine the time to suspicion of recurrence and to identify factors associated with recurrence. Methods: This retrospective cohort study included patients treated for DTC between 2008 and 2012 and in remission 6 months after total thyroidectomy and radioiodine treatment. The criteria for remission were negative imaging and suppressed thyroglobulin (Tg) <0.2 ng/mL or rh-TSH-(recombinant human TSH) stimulated Tg <1 ng/mL according to the 2015 ATA (American Thyroid Association) guidelines. Recurrence was defined by cytologically and/or histologically proven cervical lymph node metastasis or the administration of a second radioiodine treatment. Results: Among 721 patients treated for DTC, 158 were excluded because of persistent disease at 6 months, 71 because of missing follow-up data, and 492 were included. The mean and median follow-up time were 7.0 and 7.9 years (interquartile range IQR [2.1-11.3]). Recurrence occurred for 7 patients (1.4%), 1 initially classified as high recurrence risk, 3 as intermediate, and 3 as low risk according to the 2015 ATA guidelines. All relapses occurred within 10 years after initial management (4 within the first 5 years). For patients with recurrence, rise in Tg and/or suspicious lymph nodes were detected in six out of seven cases in the first 8 years and for the last case 10 years after initial surgery. Conclusion: Low and intermediate recurrence risk DTC patients with excellent response 6 months after total thyroidectomy and radioiodine and in remission 10 years later have an extremely low recurrence risk. Follow-up might be undertaken by primary care providers from this time point. These discharge recommendations should be confirmed by further prospective studies.

Holomics and Artificial Intelligence-Driven Precision Oncology for Medullary Thyroid Carcinoma: Addressing Challenges of a Rare and Aggressive Disease.

Background/Objective: Medullary thyroid carcinoma (MTC) is a rare yet aggressive form of thyroid cancer comprising a disproportionate share of thyroid cancer-related mortalities, despite its low prevalence. MTC differs from other differentiated thyroid malignancies due to its heterogeneous nature, presenting complexities in both hereditary and sporadic cases. Traditional management guidelines, which are designed primarily for papillary thyroid carcinoma (PTC), fall short in providing the individualized care required for patients with MTC. In recent years, the sheer volume of data generated from clinical evaluations, radiological imaging, pathological assessments, genetic mutations, and immunological profiles has made it humanly impossible for clinicians to simultaneously analyze and integrate these diverse data streams effectively. This data deluge necessitates the adoption of advanced technologies to assist in decision-making processes. Holomics, which is an integrated approach that combines various omics technologies, along with artificial intelligence (AI), emerges as a powerful solution to address these challenges. Methods: This article reviews how AI-driven precision oncology can enhance the diagnostic workup, staging, risk stratification, management, and follow-up care of patients with MTC by processing vast amounts of complex data quickly and accurately. Articles published in English language and indexed in Pubmed were searched. Results: AI algorithms can identify patterns and correlations that may not be apparent to human clinicians, thereby improving the precision of personalized treatment plans. Moreover, the implementation of AI in the management of MTC enables the collation and synthesis of clinical experiences from across the globe, facilitating a more comprehensive understanding of the disease and its treatment outcomes. Conclusions: The integration of holomics and AI in the management of patients with MTC represents a significant advancement in precision oncology. This innovative approach not only addresses the complexities of a rare and aggressive disease but also paves the way for global collaboration and equitable healthcare solutions, ultimately transforming the landscape of treatment and care of patients with MTC. By leveraging AI and holomics, we can strive toward making personalized healthcare accessible to every individual, regardless of their economic status, thereby improving overall survival rates and quality of life for MTC patients worldwide. This global approach aligns with the United Nations Sustainable Development Goal 3, which aims to ensure healthy lives and promote well-being at all ages.

Targetable treatment resistance in thyroid cancer with clonal hematopoiesis.

Anaplastic thyroid cancer (ATC) is a clinically aggressive malignancy with a dismal prognosis. Combined BRAF/MEK inhibition offers significant therapeutic benefit in patients with BRAF V600E -mutant ATCs. However, relapses are common and overall survival remains poor. Compared with differentiated thyroid cancer, a hallmark of ATCs is significant infiltration with myeloid cells, particularly macrophages. ATCs are most common in the aging population, which also has an increased incidence of TET2 -mutant clonal hematopoiesis (CH). CH-mutant macrophages have been shown to accelerate CH-associated pathophysiology including atherosclerosis. However, the clinical and mechanistic contribution of CH-mutant clones to solid tumour biology, prognosis and therapeutic response has not been elucidated. Here we show that TET2 -mutant CH is enriched in the tumour microenvironment of patients with solid tumours and associated with adverse prognosis in ATC patients. We find that Tet2 -mutant macrophages selectively infiltrate mouse Braf V600E -mutant ATC and that their overexpression of Tgfβ-family ligands mediates resistance to BRAF/MEK inhibition. Importantly, inhibition of Tgfβ signaling restores sensitivity to MAPK pathway inhibition, opening a path for synergistic strategies to improve outcomes of patients with ATCs and concurrent CH.

Clinical and Histopathological Features of Thyroid Cancer with TERT Promoter Molecular Alterations in Isolation Versus with Concurrent Molecular Alterations: A Multicenter Retrospective Study

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis &gt;3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp-positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination (n = 13, 43.3%), followed by TERTp alone (n = 8, 26.7%) and TERTp/RAS (n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations (n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk (p = 0.006) and were more frequently associated with aggressive histologic subtypes (p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

Evaluation of the relationship between thyroid cancer and the concurrent detection of thyroid nodules on the background of primary hyperparathyroidism

Introduction: Primary Hyperparathyroidism (PHPT) is commonly caused by a benign parathyroid adenoma that results in overactivity of the gland and subsequent hypercalcemia due to elevated parathyroid hormone (PTH). This endocrine pathology is associated with thyroid cancer, specifically Papillary Thyroid Cancer (PTC). However, the explanation for their synchronous presentation is unknown. Moreover, it causes diagnostic and treatment challenges that impact patient outcomes. Aims and Objectives: To critically analyze published research to address the relationship between PHPT and thyroid cancer, the role of ultrasound imaging in detecting sinister thyroid nodules in PHPT patients and the features of PHPT that predispose the risk of thyroid malignancy. Study Design: Literature Review Methodology: Electronic database searches of PubMed and CINAHL Plus through EBSCOhost were conducted using the keywords "primary hyperparathyroidism", "thyroid nodules" and "thyroid cancer". Following application of filters and removal of duplicates, 627 relevant results remained. Articles were screened for eligibility based on predetermined selection criteria. Following a review of titles and abstracts, 10 peer-reviewed articles were chosen for further analysis. The studies included were critically appraised using the EBL Critical Appraisal Checklist. Results: 10 articles were examined, 2 were prospective cohort studies and 8 were retrospective cohort studies. All studies involved exhaustive medical chart reviews of patients with PHPT, to investigate the concomitance of thyroid malignancy. Six studies established cervical ultrasound as the optimal method of recognition and preoperative localization of thyroid and parathyroid lesions. Overall, the incidence of thyroid cancer among PHPT patients ranged between 2.9% to 32.9%. Four studies established age, gender and PTH levels as risk factors. Conclusion: The existing literature is consistent with previous studies and purports that individuals with a background fo PHPT are at an increased risk of thyroid cancer. Furthermore the highest likelihood of identifying thyroid cancer is through preoperative localization of parathyroid adenomas by cervical ultrasound, in female patients over the age of 50. Key Findings: Further research is needed to understand the underlying pathogenesis and genetic mechanisms that encompass the relationship between PHPT and thyroid cancer.

Thyroid Cancer Incidence During 2020 to 2021 COVID-19 Variant Waves

How rates of thyroid cancer diagnosis were affected by the emergence of COVID-19 variants during the 2020 to 2021 era of the pandemic has not been described. To estimate the total number of undiagnosed cases of thyroid cancer, by histologic type, during the first 2 years of the COVID-19 pandemic (2020 and 2021) by comparing observed to expected incidence and to test for changes in size of cancer at incidence during the same period compared to prior years. This longitudinal study analyzed trends in thyroid cancer diagnoses from 2016 to 2021 among US adults using data from the Surveillance, Epidemiology, and End Results 22 (SEER-22) program database. Data analyses were performed in April to May 2024. Age-adjusted incidence rate per 100 000 US adults, changes in incidence, estimated number of undiagnosed cases, and mean cancer size. Absolute rates of overall thyroid cancer incidence in the first quarter of 2016 and of 2019 were 21.0 and 18.8 per 100 000, respectively. From 2020 through 2021, the quarterly rates were 17.3, 11.1, 17.2, 17.9, 17.4, 19.0, 17.1, and 17.3 per 100 000, respectively. The observed incidence of thyroid cancers decreased by 11% for papillary cancers 2 cm or smaller (risk ratio [RR], 0.89; 95% CI, 0.83-0.95), 14% for papillary cancers larger than 2 cm (RR, 0.86; 95% CI, 0.79-0.93), 8% for follicular cancers (RR, 0.92; 95% CI, 0.82-0.92), 10% for medullary cancers (RR, 0.90; 95% CI, 0.78-1.04), and 15% for anaplastic cancers (RR, 0.85; 95% CI, 0.68-1.07) from March 2020 to December 2021. Oncocytic cancers declined in incidence early in the pandemic, but rates returned to baseline or above through 2021 (RR, 1.15; 95% CI, 0.97-1.37). Extrapolated to the general US population, the total estimated number of thyroid cancer cases not diagnosed (expected minus observed) from March 2020 to December 2021 was approximately 10 200: 5400 papillary cancers 2 cm or smaller (95% CI, 2380-8530), 3700 papillary cancers larger than 2 cm (95% CI, 1660-5810), 600 follicular cancers (95% CI, -260 to 1550), 300 medullary cancers (95% CI, -110 to 720), and 190 anaplastic cancers (95% CI, -75 to 530). Mean size at diagnosis did not change significantly between 2016 and 2021 for any histologic type. This longitudinal study found that by the end of 2021, many thyroid cancers remained undiagnosed. These were predominantly small papillary cancers but also affected all histologic types except oncocytic. These deficits in diagnosis could produce a temporary increase in the rate of patients presenting with larger or more advanced stage cancers in the future, and consequently, temporary increases in population morbidity and mortality.

Australian males and females have similar rates of presentation for symptomatic and advanced thyroid cancer: Retrospective analysis of the Australian New Zealand Thyroid Cancer Registry.

Thyroid cancer is more commonly diagnosed in females, however recent research has challenged whether this finding is due to a true difference in biology or rates of diagnosis, with concerns that over-diagnosis may be a factor in differences. The rates of symptomatic versus incidental diagnosis by males and females is not well known. This study used the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) to explore whether symptomatic presentation varies between sexes. Retrospective analysis on ANZTCR data between 2017 and 2022 was performed. Symptomatic cases were those with thyroid compressing symptoms, toxic goiter, Graves' disease, or abnormal laryngoscopy. Cases with asymptomatic goiter or surgeries for a thyroid nodule were classified as incidental. Among 1082 patients with differentiated thyroid cancer, 32% of males and 38% of females presented with symptomatic thyroid disease (p=0.06). A similar rate of presentation of advanced thyroid cancer (T3/4) was seen with male and female patients (n=70, 47% vs. n=79, 53%). Females exhibited a higher prevalence of low-risk relapse cancers according to American Thyroid Association stratification (66.3% vs. 50.4%), whereas males exhibited a higher prevalence of high-risk relapse cancers compared to females (27.3% vs. 15.3%, p<0.001). Regression showed symptoms were associated with more advanced T stage (OR=1.62, p=0.02). Symptomatic presentation was similar between males and females, but symptomatic presentation was associated with larger cancers. This study highlights comparable rates of symptomatic detection between males and females with DTCs and symptomatic presentations were responsible for less than 40% of presentations.

MAPK pathway and NIS in B-CPAP human papillary thyroid carcinoma cells treated with resveratrol

BackgroundResveratrol, a herbal phytoalexin, is known to have anti-tumor effects in several tumors including thyroid cancer cells. AimThe aim of this study was to determine the effects of resveratrol on the expression of BRAF, ERK and NIS mRNA levels and protein expression in B-CPAP human thyroid papillary cancer cell line. MethodsB-CPAP cells were treated with resveratrol at concentrations of 10–100 μM for 24–48–72 h. Cell viability was assessed by XTT Cell Proliferation Assay. BRAF, ERK and NIS mRNA levels were evaluated by rt-PCR method. Protein expressions were evaluated by Western Blot method. ResultsResveratrol was found to inhibit cell proliferation in a time and dose dependent manner. The IC50 values of resveratrol were 18.7 μM and 56.8 μM after 48 h and 72 h respectively. Resveratrol treatment of B-CPAP cells resulted in up to 1.5-fold reduction in BRAF mRNA and up to 5.5 fold reduction in ERK mRNA levels. NIS mRNA levels showed up to 3-fold increase. Western Blot studies confirmed the rt- PCR results with a decrease in BRAF and ERK, and increase in NIS protein expressions. ConclusionThis study demonstrated that resveratrol inhibits thyroid papillary carcinoma cell proliferation and reduces poor prognostic BRAF and ERK mRNA and protein expressions, while increasing NIS mRNA and protein expression suggesting a redifferentiating effect. More studies are needed to evaluate resveratrol as a novel therapeutic agent in the treatment of papillary thyroid cancer.

TERT promoter mutations contribute to adverse clinical outcomes and poor prognosis in radioiodine refractory differentiated thyroid cancer

Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp’s role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAFV600E (9/143, 6.3%) than those with both BRAFV600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAFV600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAFV600E alone (33.3%, 3/9). Only one patient with both BRAFV600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAFV600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAFV600E alone (p < 0.01). Our findings suggest that molecular testing for TERTp and other mutations like BRAFV600E may inform early diagnosis, prognosis, and treatment strategies before progression to RAIR-DTC.

Pregnancy-related hormonal changes and thyroid growth: do they have an impact on the higher incidence of differentiated thyroid cancer in women?

To analyze whether pregnancy could play a role in the higher prevalence of differentiated thyroid carcinoma (DTC) in women. Estrogens strongly modify thyroid economy by increasing iodine clearance, thyroid hormone requirement and production. Human chorionic gonadotropin (hCG) contributes to the increased thyroid hormone synthesis. Both estrogens and hCG can interfere with the regulation of thyroid volume and with thyroid nodule development and progression. The potential effect of hCG is exclusively related to its weak agonistic activity on TSH receptor. Estrogen implication on normal and nodule-derived thyrocyte growth has been demonstrated in vitro and in animal models. Furthermore, there is solid clinical evidence showing a promoting effect of pregnancy on thyroid volume and nodule development. Two metanalysis, one including retrospective and another prospective observational studies, failed to show an association between pregnancy and DTC. A large pooled prospective analysis using multivariable-adjusted Cox proportional hazard models did not demonstrate an association between DTC and parity. Similarly, no association between PTC occurrence and parity was observed in a prospective cohort analysis by linkage to the statewide Surveillance, Epidemiology, and End Results (SEER). The presently available evidence does not support an involvement of pregnancy in DTC etiology.

Lower Thyroid Cancer Incidence During the COVID-19 Pandemic—Should We Be Concerned?

Lower Thyroid Cancer Incidence During the COVID-19 Pandemic—Should We Be Concerned?

Prevalence of cancer survivors diagnosed during adolescence and young adulthood in the United States.

Adolescent and young adult (AYA) cancer incidence rates are rising, and survivors are at risk for numerous cancer- and treatment-related consequences. Despite growing attention to this population, prevalence estimates are lacking. To estimate the number of individuals living in the United States with a history of cancer diagnosed during the AYA period. Prevalence of cancer survivors diagnosed between the ages of 15 and 39 years was estimated using data from the Surveillance, Epidemiology, and End Results (SEER) program as of January 1, 2020. Limited duration prevalence data were also used to generate complete prevalence by sex, years since diagnosis (0-<1, 1-<5, 5-<10, 10-<15, 15-<20, 20+), and attained age (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70+) for the 15 most common AYA cancer sites. There were an estimated 2,111,838 survivors of AYA cancers in the United States as of January 1, 2020. More survivors were female (66%) and long-term (>5 years from diagnosis, 83%) or very long-term survivors (>10 years from diagnosis, 68.8%). A large percentage (44%) were more than 20 years from diagnosis. The most common cancer sites among females were breast (24%) and thyroid cancers (23%) and, among males, testicular cancer (31%). Across the population, the highest percentage of survivors of AYA cancers were 40- to 49-years of age (25.3%). There are over 2.1 million cancer survivors diagnosed in the AYA period who are living in the United States; most are more than 10 years from diagnosis.

Therapeutic efficacies of remnant ablation and radioiodine adjuvant therapy in differentiated thyroid cancer.

Successful ablation in 131I therapy for differentiated thyroid cancer (DTC) includes both remnant ablation (RA) and radioiodine adjuvant therapy (RAT). This study aimed to differentiate between the therapeutic efficacies of RA and RAT, investigate the factors associated with their effectiveness, and assess their impact on prognosis. This retrospective study included patients with DTC who underwent initial 131I therapy at our tertiary center. The successful RA (SRA) and successful RAT (SRAT) was determined based on the 131I-diagnostic whole-body scan (Dx-WBS), TSH-stimulated thyroglobulin (sTg) levels, and neck ultrasound at the 6th month after 131I therapy. The patients were divided into complete response and persistent/recurrent disease groups during the follow-up period. A total of 232 patients were included, 91.8% (213/232) of patients achieved SRA, only 8.1% (19/232) failed RA (FRA). Among the 213 patients in the SRA group, 70.4% (150/213) achieved SRAT and 29.6% (63/213) failed RAT (FRAT). Only pre-ablation sTg >10 ng/mL (OR = 46.968, 95% CI 9.731-226.699, P < 0.001) was an independent risk factor predicting the failure of RAT. The prognostic analysis included 215 patients, and 6.1% (13/215) were classified as persistent/recurrent disease at the last follow-up. Both pre-ablation sTg >10 ng/mL (HR = 4.765, 95% CI 1.371-16.566, P = 0.014) and FRAT (HR = 10.104, 95% CI 1.071-95.304, P = 0.043) independently predicted persistent/recurrent disease. RA is easy to achieve successfully, whereas RAT evaluation provides greater value than RA for prognosis prediction. For patients with low Tg levels and no imaging evidence of disease, routine Dx-WBS during follow-up has minimal significance.

Patient satisfaction and operator proficiency in gasless transaxillary endoscopic thyroidectomy under IONM: a retrospective cohort study.

This study aims to evaluate the surgical safety and effectiveness of gasless transaxillary endoscopic thyroidectomy (GTET), assess patients' short-term perceptions and long-term outcomes, and delineate the learning curve and key surgical techniques of the operators. Clinicopathological and postoperative follow-up data from patients with unilateral thyroid cancer in the same period were collected. These patients were divided into the GTET group and the traditional open surgery group to compare and analyze the differences and explore the factors affecting the learning curve of GTET. Patients who chose GTET had better general health and thyroid conditions than those in the open group, and the quality of postoperative life was better in the GTET group than in the open group, with the main differences between the two groups being appearance and neck and shoulder function. The GTET learning curve in this study peaked at 19 cases, with slight differences between left and right, and a larger sample size is still needed to explore the factors affecting the learning curve. GTET has a reliable safety and efficacy profile for patients with unilateral thyroid cancer. Intraoperative nerve monitoring (IONM) techniques require some adaptation in GTET. In some respects, patients' postoperative experience and quality of life are superior to those of conventional open surgery. There is a learning curve for GTET, but large samples are still needed to explore its true significance.

[18F]TFB PET/CT misses intense [124I]iodine-avid metastases after redifferentiation therapy in metastatic thyroid cancer

BackgroundFluorine 18-labelled tetrafluoroborate ([18F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [18F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [18F]TFB and compare its properties to [124I]IodinePET/CT in patients with metastatic thyroid cancer.MethodsFive patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [18F]TFB and were given 230 ± 9 MBq [124I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [124I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [18F]TFB and [124I]Iodine were calculated.ResultsThree patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [18F]TFB and 30 (91%) on [124I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [124I]Iodine PET/CT with a median SUVmax of 3.3 (range, 0.4–285.0). All of these lesions were [18F]TFB-negative.Conclusion[18F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer.Trial registration numberNCT03196518, registered on June 22, 2017.

FTO/IGF2BP2-mediated N6 methyladenosine modification in invasion and metastasis of thyroid carcinoma via CDH12.

Epigenetic reprogramming plays a critical role in cancer progression of cancer, and N6-methyladenosine (m6A) is the most common RNA modification in eukaryotes. The purpose of this study was to explore the related modification mode of m6A regulator construction and evaluate the invasion and migration of thyroid cancer. Our results showed that m6A levels were significantly increased in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) samples, which may have been induced by the down-regulation of demethylase fat mass and obesity-associated gene (FTO). Moreover, FTO inhibited PTC and ATC invasion and metastasis through the epithelial-to-mesenchymal transition (EMT) pathway in vivo and in vitro. Mechanistically, an m6A-mRNA epitranscriptomic microarray showed that Cadherin 12 (CDH12) is the key target gene mediated by FTO in an m6A-dependent manner. CDH12 promotes invasion and metastasis through the EMT pathway in thyroid cancer, both in vivo and in vitro. Furthermore, we found that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an important m6A reading protein, that regulates the stability of CDH12 mRNA and mediates EMT progression, thereby promoting the invasion and metastasis of PTC and ATC. Thus, FTO, IGF2BP2 and CDH12 may be effective therapeutic targets for PTC and ATC with significant invasion or distant metastasis. Schematic summary of FTO-IGF2BP2 axis in modulation of CDH12 mRNA m6A and upregulation of CDH12 expression in the invasion and metastasis of thyroid carcinoma.

Association of pre-op TSH levels with Thyroid Carcinoma in a Tertiary Care Setup in Karachi, Pakistan

Objectives: This study aimed to explore the relationship between pre-operative TSH levels and the presence of thyroid cancer in patients with nodular thyroid disease in the Pakistani population, using data gathered from patients treated at Dr. Ruth K. M. Pfau Civil Hospital Karachi. Study Design &amp; Setting: A cross-sectional study was conducted at the Dow University of Health Sciences and Dr. Ruth K. M. Pfau Civil Hospital Karachi from January 2022 to December 2022. Methodology: Patients with thyroid swellings (presenting with either solitary nodules or with multinodular goiter), both benign as well as suspected/confirmed malignancy based on FNAC results were recruited in the study. Preoperative TSH levels, along with other clinical data, were collected. Thyroidectomy was carried out in patients fulfilling the criteria for surgery, with specimens sent for histopathology. An independent t-test was used to compare TSH levels between malignant and benign nodules. Results: A total of 82 patients were enrolled. Malignancy was confirmed in 41.5% (25 papillary carcinoma, 9 follicular carcinoma). Significantly higher mean TSH levels were observed in patients with malignant nodules (4.76 IU/mL) compared to those with benign nodules (2.48 IU/mL) (p &lt; 0.001). Conclusion: This study suggests a potential association between elevated pre-operative TSH levels and thyroid cancer in the Pakistani population. These findings warrant further investigation to explore causality and potential underlying mechanisms. The study highlights the value of TSH monitoring, particularly in resource-constrained settings.