Correlation between surgical position and neck pain in patients undergoing thyroidectomy: a prospective observational study.

BACKGROUND: Thyroid diseases are one of the most common health problems worldwide. Although they represent a necessary step in order to perform thyroidectomy, hyperextension of the neck can potentially increase postoperative pain. The aim of this study is to determine a correlation between the degree of neck hyperextension on the operative table and the postoperative pain in patients undergoing open thyroidectomy. METHODS: Patients were prospectively enrolled from the cohort of patients operated at the Endocrine Surgery Unit of the University Hospital of Pisa, between May and July 2021. Both of patients who underwent total thyroidectomy or hemi-thyroidectomy were recruited. The following data were analysed in order to find a correlation with postoperative pain at 24 h: age, gender, type of surgery, BMI, operative time, and degree of neck extension. RESULTS: Overall, 195 patients were enrolled. A direct, statistically significant correlation emerged between the degree of neck hyperextension and the postoperative pain 24 h after surgery, regardless of the pain of the surgical wound (p < 0.001; beta 0.270). CONCLUSIONS: A direct correlation emerges between neck tilt angle and postoperative neck pain. Moreover, total thyroidectomy (TT) predisposes more to postoperative neck pain, considering the type of surgery.

A novel deep machine learning algorithm with dimensionality and size reduction approaches for feature elimination: thyroid cancer diagnoses with randomly missing data.

Thyroid cancer incidences endure to increase even though a large number of inspection tools have been developed recently. Since there is no standard and certain procedure to follow for the thyroid cancer diagnoses, clinicians require conducting various tests. This scrutiny process yields multi-dimensional big data and lack of a common approach leads to randomly distributed missing (sparse) data, which are both formidable challenges for the machine learning algorithms. This paper aims to develop an accurate and computationally efficient deep learning algorithm to diagnose the thyroid cancer. In this respect, randomly distributed missing data stemmed singularity in learning problems is treated and dimensionality reduction with inner and target similarity approaches are developed to select the most informative input datasets. In addition, size reduction with the hierarchical clustering algorithm is performed to eliminate the considerably similar data samples. Four machine learning algorithms are trained and also tested with the unseen data to validate their generalization and robustness abilities. The results yield 100% training and 83% testing preciseness for the unseen data. Computational time efficiencies of the algorithms are also examined under the equal conditions.

Thermal ablation for the treatment of malignant thyroid nodules: present and future.

As the utilization of high-resolution imaging modalities, such as ultrasound, becomes increasingly prevalent, there has been a swift rise in the detection rates of malignant thyroid nodules (MTC). Surgery remains the cornerstone of standard treatment for these nodules. However, the advent and evolution of thermal ablation (TA) techniques, encompassing radiofrequency ablation, laser ablation, and microwave ablation, have emerged as a novel therapeutic avenue for patients with MTC, particularly for those deemed unsuitable for surgery due to high risks or for those who refuse surgery. Presently, TA has been validated as an efficacious and safe intervention for both benign thyroid nodules and a subset of MTC. An expanding body of research has been dedicated to broadening the applicability of TA, initially from recurrent thyroid cancer and lymph nodes to now encompass isolated papillary thyroid microcarcinomas (PTMC) alongside a comprehensive exploration into the expanded parameters such as size, number, and location of PTMC, and its applicability in other types of thyroid cancer. This review provides a detailed synthesis of the clinical evidence about the use of TA in the management of MTC, as endorsed by current guidelines. It further delves into the ongoing research efforts aimed at extending its indications and discusses the prospective implications and challenges of integrating TA into the clinical management paradigms for MTC.

Safety and cosmesis of gasless endoscopic thyroidectomy: a retrospective study.

Despite growing interest in gasless endoscopic unilateral thyroid lobectomy via the axillary approach, there are a lack of sufficient data on its safety and cosmetic outcomes. This retrospective study analysed the clinical outcomes and postoperative complications of 161 patients who underwent this surgery for thyroid cancer and nodules, with particular attention given to complications and patient satisfaction with cosmetic outcomes. All 161 patients (143 females, 18 males) successfully underwent the operation without conversion to open surgery. Temporary vocal cord paralysis occurred in five patients, with no other serious complications observed. The cosmetic outcomes were generally good, with no recurrences or tumour implantations observed during follow-up. For carefully selected patients, gasless endoscopic unilateral thyroid lobectomy via the axillary approach is not only safe but also provides excellent cosmetic results.

PRDM1 promotes the ferroptosis and immune escape of thyroid cancer by regulating USP15-mediated SELENBP1 deubiquitination.

BACKGROUND: The deubiquitinating enzyme Ubiquitin-specific peptidase 15 (USP15) is upregulated in various cancers and promotes tumor progression by increasing the expression of several oncogenes. This project is designed to explore the role and mechanism of USP15 in thyroid cancer (TC) progression. METHODS: Selenium-binding protein 1 (SELENBP1), USP15, CCL2/5, CXCL10/11, IL-4, and TGF-ß1 mRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). SELENBP1, USP15, GPX4, IL-10, Arg-1, Granzyme B, TNF-α, and PR domain zinc finger protein 1 (PRDM1) protein levels were examined by western blot assay. Fe+ level, malondialdehyde (MDA), and lipid-ROS levels were determined using special kits. The proportion of CD11b+CD206+ positive cells was detected using a flow cytometry assay. The role of SELENBP1 on TC cell growth was examined using a xenograft tumor model in vivo. After GeneMANIA prediction, the interaction between USP15 and SELENBP1 was verified using Co-immunoprecipitation (CoIP) assay. The binding between PRDM1 and USP15 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: SELENBP1 was increased in TC subjects and cell lines, and its knockdown repressed TC cell proliferation, migration, invasion, immune escape, and induced ferroptosis in vitro, as well as blocked tumor growth in vivo. In mechanism, USP15 interacted with SELENBP1 and maintained its stabilization by removing ubiquitin. Meanwhile, the upregulation of USP15 was induced by the transcription factor PRDM1. CONCLUSION: USP15 transcriptionally mediated by PRDM1 might boost TC cell malignant behaviors through deubiquitinating SELENBP1, providing a promising therapeutic target for TC treatment.

Shotgun proteomics of thyroid carcinoma exosomes - Insight into the role of exosomal proteins in carcinogenesis and thyroid homeostasis.

BACKGROUND: Transport of molecules via exosomes is one of the factors involved in thyroid cancer development, and transported molecules may serve as cancer biomarkers. The aim of the study was to characterize protein content of thyroid-derived exosomes and their functional effect exerted on recipient cells. METHODS: LC-MS/MS proteomics of exosomes released by FTC and 8305C thyroid carcinoma cell lines, and Nthy-ori 3-1 normal thyroid follicular cells was performed, followed by bioinformatic analysis and functional tests (wound healing and Alamar Blue assays). RESULTS: Exosomes from Nthy-ori 3-1 cells had the highest number of 1504 proteins, while in exosomes from thyroid carcinoma FTC and 8305C cells 730 and 1304 proteins were identified, respectively. For proteins uniquely found in FTC- and 8305C-derived exosomes, enriched cancer-related gene ontology categories included cell adhesion, positive regulation of cell migration, N-glycosylation, drug resistance, and response to NK/T cell cytotoxicity. Furthermore, through label-free quantification (that identified differentially expressed proteins) and comparison with The Human Protein Atlas database several potential diagnostic and/or prognostic biomarkers were indicated. Finally, exosomes from FTC and 8305C cells displayed ability to stimulate migratory properties of recipient Nthy-ori 3-1 cells. Additionally, 8305C-derived exosomes increased recipient cell viability. CONCLUSIONS: Multiple proteins identified in thyroid cancer-derived exosomes have a direct link to thyroid cancer progression. Also, in functional tests exosomes enhanced growth and dissemination of non-transformed thyroid cells. GENERAL SIGNIFICANCE: The obtained results expands the knowledge concerning the role of exosomal proteins in thyroid cancer and indicate potential biomarkers for further evaluation in clinical settings.

Improving the diagnostic performance of inexperienced readers for thyroid nodules through digital self-learning and artificial intelligence assistance.

Background: Data-driven digital learning could improve the diagnostic performance of novice students for thyroid nodules. Objective: To evaluate the efficacy of digital self-learning and artificial intelligence-based computer-assisted diagnosis (AI-CAD) for inexperienced readers to diagnose thyroid nodules. Methods: Between February and August 2023, a total of 26 readers (less than 1 year of experience in thyroid US from various departments) from 6 hospitals participated in this study. Readers completed an online learning session comprising 3,000 thyroid nodules annotated as benign or malignant independently. They were asked to assess a test set consisting of 120 thyroid nodules with known surgical pathology before and after a learning session. Then, they referred to AI-CAD and made their final decisions on the thyroid nodules. Diagnostic performances before and after self-training and with AI-CAD assistance were evaluated and compared between radiology residents and readers from different specialties. Results: AUC (area under the receiver operating characteristic curve) improved after the self-learning session, and it improved further after radiologists referred to AI-CAD (0.679 vs 0.713 vs 0.758, p<0.05). Although the 18 radiology residents showed improved AUC (0.7 to 0.743, p=0.016) and accuracy (69.9% to 74.2%, p=0.013) after self-learning, the readers from other departments did not. With AI-CAD assistance, sensitivity (radiology 70.3% to 74.9%, others 67.9% to 82.3%, all p<0.05) and accuracy (radiology 74.2% to 77.1%, others 64.4% to 72.8%, all p <0.05) improved in all readers. Conclusion: While AI-CAD assistance helps improve the diagnostic performance of all inexperienced readers for thyroid nodules, self-learning was only effective for radiology residents with more background knowledge of ultrasonography. Clinical Impact: Online self-learning, along with AI-CAD assistance, can effectively enhance the diagnostic performance of radiology residents in thyroid cancer.

Central lymph node ratio is an important recurrence prognostic factor for pediatric differentiated thyroid cancer.

Background: The current risk stratification methods for Pediatric Differentiated Thyroid Carcinoma (DTC) are deemed inadequate due to the high recurrence rates observed in this demographic. This study investigates alternative clinicopathological factors, specifically the Central Lymph Node Ratio (CLNR), for improved risk stratification in pediatric DTC. Methods: A retrospective review of 100 pediatric DTC patients, aged 19 or younger, treated between December 2012 and January 2021 at the First Affiliated Hospital of Guangxi Medical University was conducted. Clinicopathological variables were extracted, and univariate logistic regression identified factors correlated with recurrence. Kaplan-Meier (KM) survival analysis and subsequent statistical tests were used to assess the significance of these factors. Results: The CLNR, with a cutoff value of 77.78%, emerged as a significant predictor of recurrence. Patients with a CLNR above this threshold had a 5.467 times higher risk of recurrence. The high CLNR group showed a higher proportion of male patients, clinically lymph node positivity (cN1), and extrathyroidal extension (ETE) compared to the low-risk group (p<0.05). Conclusion: CLNR is a valuable predictor for recurrence in pediatric DTC and aids in stratifying patients based on Recurrence-Free Survival (RFS). For patients with a high CLNR, aggressive iodine-131 therapy, stringent TSH suppression, and proactive postoperative surveillance are recommended to mitigate recurrence risk and facilitate timely detection of recurrent lesions.

A novel minimally invasive endoscopic approach of thyroid surgery-endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach.

Background: Since the endoscopic thyroidectomy was firstly reported by Hüscher in 1997, there has been an ongoing debate regarding whether mainstream endoscopic thyroidectomy can be classified as minimally invasive surgery. In this study, we innovatively proposed the endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach (ETSPIA), a novel minimally invasive surgical technique, and compared its efficacy with the well-established transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: We retrospectively analyzed 50 patients who underwent ETSPIA and 50 patients who underwent TOETVA at Beijing Tongren Hospital, comparing their clinical characteristics, operative duration, blood loss, postoperative alterations in parathyroid hormone (PTH) and serum calcium, recovery post-surgery, complications, and follow-up data. Results: The ETSPIA group had a shorter operation time compared to the TOETVA group (243.40±58.67 vs. 278.08±78.50 min; P=0.01). The ETSPIA group also had less intraoperative blood loss than the TOETVA group (20.60±10.58 vs. 33.00±11.11 mL; P<0.001). More central lymph nodes were dissected in the ETSPIA group compared to the TOETVA group (5.90±4.72 vs. 3.36±2.80; P=0.002). However, the difference in the number of positive central lymph nodes dissected was not statistically significant (1.38±2.33 for ETSPIA vs. 0.94±1.39 for TOETVA; P=0.26). The ETSPIA group had a shorter length of stay (LOS) compared to the TOETVA group (6.82±2.02 vs. 8.26±2.72 days; P=0.003). The alteration in PTH levels 1 day after surgery was less pronounced in the ETSPIA group compared to the TOETVA group (-26.38%±18.43% vs. -35.75%±22.95%; P=0.04). At the 1-month postoperative mark, the ETSPIA group showed a marginal increase in PTH levels, whereas the TOETVA group exhibited a slight decrease (10.12%±35.43% vs. -11.53%±29.51%; P=0.03). Regarding the average percentage change in serum calcium level 1 day after surgery, the ETSPIA group showed a smaller change, though this difference was not statistically significant (-4.79%±5.47% vs. -5.66%±3.90%; P=0.40). Furthermore, the incidence of hoarseness attributable to transient recurrent laryngeal nerve (RLN) injury in postoperative patients was lower in the ETSPIA group compared to the TOETVA group, but this difference did not reach statistical significance (0% vs. 4%; P=0.15). Conclusions: Overall, compared to TOETVA, the ETSPIA is characterized by a shorter operative route, enhanced protection of the parathyroid glands, reduced trauma, and expedited postoperative recovery.

Nomogram for predicting the risk of central lymph node metastasis in papillary thyroid microcarcinoma: a combination of sonographic findings and clinical factors.

Background: A considerable controversy over performing thyroidectomy and central lymph node dissection in patients with papillary thyroid microcarcinoma (PTMC) remained. However, accurate prediction of central lymph node metastasis (CLNM) is crucial for surgical extent and proper management. The aim of this study was to develop and validate a practical nomogram for predicting CLNM in patients with PTMC. Methods: A total of 1,029 patients with PTMC who underwent thyroidectomy and central lymph node dissection at Tangdu Hospital (the Second Affiliated Hospital of Air Force Medical University) and Xijing Hospital (the First Affiliated Hospital of Air Force Medical University) were selected. Seven hundred and nine patients were assigned to the training set and 320 patients to the validation set. Data encompassing demographic characteristics, ultrasonography results, and biochemical indicators were obtained. Stepwise backward selection and multiple logistic regression were used to screen the variables and establish the nomogram. Concordance index (C-index), receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were employed to evaluate the nomogram's distinguishability, accuracy, and clinical utility. Results: Young age, multifocality, bigger tumor, presence of microcalcification, aspect ratio (height divided by width) ≥1, loss of fatty hilum, high free thyroxine (FT4), and lower anti-thyroid peroxidase antibody (TPOAb) were significantly associated with CLNM. The nomogram showed strong predictive capacity, with a C-index and accuracy of 0.784 and 0.713 in the training set and 0.779 and 0.703 in the external validation set, respectively. DCA indicated that the nomogram demonstrated strong clinical applicability. Conclusions: We established a reliable, cost-effective, reproducible, and noninvasive nomogram for predicting CLNM in patients with PTMC. This tool could be a valuable guidance for deciding on management in PTMC.

Survey of clinician perspective on management of papillary thyroid microcarcinoma in Australia and New Zealand.

Background: The incidence of thyroid cancer has been rapidly increasing in recent years largely due to improved diagnostic methods. There is evidence to suggest that in papillary thyroid microcarcinoma (PTMC), active surveillance (AS) is comparable in effectiveness compared to immediate surgery (IM). We conducted a survey of Clinicians and Surgeons from Australia and New Zealand to assess the role of AS in the management of PTMC. Methods: A short electronic survey was created on the platform Survey Monkey, separate links containing the survey were sent to various medical societies to be distributed to its members. The list of medical societies included: General Surgeons Australia, Endocrine Society of Australia, Australian and New Zealand Endocrine Surgeons, Australian and New Zealand Head and Neck Cancer Society and New Zealand Association of General Surgery. Results: We received 110 complete responses, which demonstrated that 63% of clinicians will discuss AS with patients diagnosed with PTMC. Surgeons are more likely to discuss AS compared to endocrinologists (P=0.03). Forty-eight percent of respondents report managing patients with AS in the past year, those who are able to perform thyroid ultrasounds are more likely to utilise AS (P=0.03). Common perceived barriers to AS include patient anxiety, lack of access to regular follow-up and lack of patient compliance. Conclusions: Our survey shows that Australian and New Zealand clinicians are generally aware of AS as a treatment option for PTMC, but there remain considerable barriers for common implementation.

Thyroid cancer and pregnancy: a systematic ten-year-review.

Background: Thyroid cancer is the second most common malignancy during pregnancy, especially the well-differentiated thyroid cancer (well-DTC). Therefore, complex medical and social dilemmas arise, dealing with which requires deep knowledge of the nature and characteristics of the disease and pregnancy as a whole. The purpose of this review is to present the diagnostic and therapeutic strategies of thyroid cancer during pregnancy and the postpartum period. Methods: Extended review of the literature [2011-2023] was performed. Two hundred ninety-six articles were found, from which 225 were excluded due to irrelevant subjects. Seventy-one articles were assessed for eligibility, from which 33 articles were cohort studies and case reports and were included in the review. Results: From the 33 included studies, 18 were retrospective cohort studies, 1 was cohort study, 2 were case control studies, 1 was meta-analysis and 11 were case reports. The primary endpoints of these studies refer to the progression and recurrence of DTC during pregnancy, the prevalence of thyroid cancer in pregnancy and the most appropriate time for surgical intervention. Conclusions: The majority of the studies agree that well-differentiated tumors with mild clinical and imaging characteristics do not require immediate surgical treatment, but mere monitoring. Surgery can be delayed after childbirth. In contrast, tumors with aggressive behavior as well as non-differentiated ones, require immediate surgery because delay under these circumstances can dramatically reduce survival rates. Finally, a history of thyroid cancer does not seem to affect future deliveries, on condition that no residual disease exists at the onset of pregnancy.

Efficacy and safety of multikinase inhibitors for patients with refractory thyroid cancer: Systematic review and network meta-analysis.

CONTEXT: Multikinase inhibitors (MKIs) improve the treatment of refractory thyroid cancer, included radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and advanced medullary thyroid carcinoma (aMTC). OBJECTIVE: This study aims to compare the efficacy of MKIs in improving survival outcomes and safety. DATA SOURCES: Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2023. STUDY SELECTION: Three independent authors selected these studies. Randomised-controlled trials that compared the use of a MKI to other MKIs or placebo were included. DATA EXTRACTION AND SYNTHESIS: This review followed PRISMA guidelines. Risk of bias was analyzed using the Cochrane RoB 2 tool. Bayesian network meta-analysis was performed. Treatments were grouped into common nodes based on the type of MKI. MAIN OUTCOMES AND MEASURES: Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate, disease control rate, clinical benefit rate, and adverse events. RESULTS: Cabozantinib 60 mg/d (CAB60) was associated with the highest prolonged PFS in RAIR-DTC patients, followed by lentivatinib 18 or 24 mg/d (LEN18 or LEN24), and apatinib. PFS was also improved in in aMTC patients received CAB 140 mg/d (CAB140), CAB60, or anlotinib. A significantly greater improvement on the performance of OS was seen in CAB60, LEN24, anlotinib, and sorafenib in RAIR-DTC patients, but which in aMTC patients were lack of statistical differences. Compared with the low-dose of MKIs, high-dose of MKIs such as CAB, LEN, and vandetanib increased the incidence of adverse events. CONCLUSION: CAB60, LEN, and apatinib are promising topical MKIs with statistically significant primary outcomes in RAIR-DTC patients, while CAB and anlotinib are effective in prolonging PFS in aMTC patients.

Paraplegic Patient with Metastatic Papillary Thyroid Cancer: A Multidisciplinary Approach to Radioactive Iodine Therapy Safety and Efficacy Strategy.

High-activity radioactive iodine (RAI) therapy for metastatic thyroid cancer (TC) requires isolation to minimize radiation exposure to third parties, thus posing challenges for patients needing hands-on care. There are limited data on the approach to high-activity RAI treatment in paraplegic patients. We report a state-of-the-art multidisciplinary approach to the management of bedbound patients, covering necessary radiation safety measures that lead to radiation exposure levels as low as reasonably achievable. Given the limited literature resources on standardized approaches, we provide a practical example of the safe and successful treatment of a woman with BRAFV600E-mutant tall-cell-variant papillary TC and pulmonary metastases, who underwent dabrafenib redifferentiation before RAI therapy. The patient was 69 y old and had become paraplegic because of a motor-vehicle accident. Since caring for a paraplegic patient with neurogenic bowel and bladder dysfunction poses radiation safety challenges, a multidisciplinary team comprising endocrinologists, nuclear medicine physicians, radiation safety specialists, and the nursing department developed a radiation mitigation strategy to ensure patient and staff safety during RAI therapy. The proposed standardized approach includes thorough monitoring of radiation levels in the workplace, providing additional protective equipment for workers who handle radioactive materials or are in direct patient contact, and implementing strict guidelines for safely disposing of radioactive waste such as urine collected in lead-lined containers. This approach requires enhanced training, role preparation, and practice; use of physical therapy equipment to increase the exposure distance; and estimation of the safe exposure time for caregivers based on dosimetry. The effective and safe treatment of metastatic TC in paraplegic patients can be successfully implemented with a comprehensive radiation mitigation strategy and thorough surveying of personnel for contamination.

Risk factors for cervical lymph node metastasis of papillary thyroid cancer in elderly patients aged 65 and older.

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

Improving the Risk Prediction of the 2015 ATA Recurrence Risk Stratification in Papillary Thyroid Cancer.

BACKGROUND: Various prognostic factors are expected to refine the American Thyroid Association (ATA) recurrence risk stratification for patients with papillary thyroid cancer (PTC). However, it remains unclear to what extent integrating these factors improves patient treatment decision-making. METHODS: We developed two predictive models for structural incomplete response (SIR) at the one-year follow-up visit, based on comprehensive clinical data from a retrospective cohort of 2539 patients. Model 1 included the recurrence risk stratification and lymph node features (i.e., number and ratio of metastatic lymph nodes, N stage). Model 2 further incorporated preablation stimulated thyroglobulin (s-Tg). An independent cohort of 746 patients was used for validation analysis. We assessed the models' predictive performance compared to the recurrence risk stratification using the integrated discrimination improvement (IDI) and the continuous net reclassification improvement (NRI). The clinical utility of the models was evaluated using decision curve analysis. RESULTS: Both Model 1 and Model 2 outperformed the recurrence risk stratification in predicting SIR, with improved correct classification rates (Model 1: IDI=0.02, event NRI=42.31%; Model 2: IDI=0.07, event NRI=53.54%). The decision curves indicated that both models provided greater benefits over the risk stratification system in clinical decision-making. In the validation set, Model 2 maintained similar performance while Model 1 did not significantly improve correct reclassification. CONCLUSION: The inclusion of lymph node features and s-Tg showed potential to enhance the predictive accuracy and clinical utility of the existing risk stratification system for PTC patients.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Medullary Thyroid Cancer: Molecular Drivers and Immune Cellular Milieu of the Tumour Microenvironment-Implications for Systemic Treatment.

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).

Brain Metastases from Thyroid Carcinoma: Prognostic Factors and Outcomes.

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.

Pre-operative thyroglobulin measurement for thyroid cancer risk of recurrence and response to therapy.

BACKGROUND: Thyroid cancer has an overall favorable prognosis, but no pre-operative biochemical marker has been shown to distinguish between low and high-risk disease or predict response to therapy. METHODS: We retrospectively reviewed 162 patients that underwent thyroid surgery for thyroid cancer between 2006 and 2022 in whom a pre-operative thyroglobulin level (Tg) was measured. We subdivided patients into low, intermediate and high-risk thyroid cancer and based on their response to therapy per ATA guidelines. RESULTS: We showed that as pre-operative Tg level increased, patients were more likely to have high-risk disease (p â€‹< â€‹0.01). We found a linear association between the primary tumor size and high-risk histology with pre-operative Tg (p â€‹< â€‹0.01). Pre-operative Tg level was significantly associated with response to therapy following initial surgical management. Specifically, as pre-operative Tg increases, patients were less likely to achieve an excellent response (p â€‹< â€‹0.01). CONCLUSIONS: Our retrospective analysis demonstrated that pre-operative Tg is significantly associated with ATA structural risk of recurrence and response to therapy and may have the potential to guide initial therapy and follow-up management.