Thyroid Carcinoma Patients Research Articles

Risk stratification for central lymph node metastasis in mono-focal papillary thyroid carcinoma patients with encapsulated tumor as confirmed by preoperative ultrasound: a multi-center analysis.

Mono-focal papillary thyroid carcinoma (PTC) patients with encapsulated tumor have traditionally been considered as low central lymph node metastasis (CLNM) risk subgroup. The aim of the research was to quantitatively predict the probability of CLNM for mono-focal PTC patients with encapsulated tumor as confirmed by preoperative ultrasound based on pre- and post-operative indexes respectively to guide the selection of prophylactic central lymph node dissection (CLND) and follow-up strategies. A total of 1014 mono-focal PTC patients with encapsulated tumor as confirmed by preoperative ultrasound from three medical centers were retrospectively analyzed, with 534 patients served as Training group and 480 patients as Validation group. Multivariate analyses showed that age < 55 years old, male, clinical maximum tumor diameter (cMTD) > 0.5 cm, pathological maximum tumor diameter (pMTD) > 0.5 cm, and the presence of microscopic thyroid capsular invasion (mTCI) were independent CLNM risk factors. These were used to construct two nomograms that can effectively predict the central neck involvement in mono-focal PTC patients with encapsulated tumor. The first nomogram (pre-model) provides quantitative assessment on the necessity of prophylactic CLND, while the second nomogram (post-model) informs postoperative follow-up strategies. Meticulous and comprehensive stratification flow charts that quantitatively evaluate the risk of central lymph node metastasis both pre- and post-operatively were constructed for mono-focal PTC patients with encapsulated tumor as confirmed by preoperative ultrasound, which may benefit both clinical decision-making of prophylactic CLND and postoperative follow-up strategies for the management of neck regions.

Larotrectinib efficacy for liver metastases in papillary thyroid carcinoma patient harboring SQSTM1–NTRK1 fusion

BackgroundPooled data analysis from three phase I/II larotrectinib clinical trials revealed that larotrectinib demonstrated rapid and durable disease control and a favorable safety profile for patients with neurotrophic-tropomyosin receptor kinase (NTRK) fusion positive thyroid carcinoma. Herein, we report the case of a patient with papillary thyroid carcinoma (PTC) and liver metastases who demonstrated a durable response to treatment with larotrectinib.Case presentationA 50-year-old female with PTC was referred to our hospital for postoperative observation. Computed tomography (CT) scan was performed to screen for distant metastasis, since thyroglobulin concentration increased gradually, and revealed multiple distant metastases, including multiple liver metastases. Radioactive iodine was administered at a dose of 100 mCi. However, uptake was observed only in the thyroid bed, and distant metastases had no avidity. As liver metastases progressed, lenvatinib (24 mg/day) was initiated after confirmation of liver metastases by liver biopsy 9 years and 1 month after the initial referral to our hospital. Since the multiple metastases became refractory for lenvatinib, the OncoGuide™ NCC Oncopanel System was performed, and the SQSTM1–NTRK1 gene fusion was confirmed. Larotrectinib was subsequently administered at a dose of 200 mg/day. The CT before the initiation of larotrectinib showed multiple liver metastases with a maximum diameter of 48 mm. The first CT evaluation at 1 month after the initiation of larotrectinib treatment showed that the tumor volume was reduced by 28% in the RECIST 1.1 criteria. After 3 months of larotrectinib treatment, a 38% reduction in the tumor volume was achieved as the best clinical response. The only side effect was grade 1 myalgia. At 12 months after the initiation of larotrectinib treatment, none of the lesions had progressed.ConclusionsIn conclusion, larotrectinib demonstrated effective antitumor activity against liver metastases of PTC, a relatively rare site of distant metastasis. Furthermore, the efficacy of larotrectinib was maintained, even though the patient had a history of multi-tyrosine kinase inhibitor treatment and a relatively infrequent fusion gene, SQSTM1–NTRK1.

Ultrasound-guided percutaneous radiofrequency ablation versus surgery for solitary T1N0M0 papillary thyroid carcinoma in the danger triangle.

To compare the safety and efficiency of ultrasound-guided percutaneous radiofrequency ablation (RFA) and surgical resection (SR) for thyroid papillary carcinoma (PTC) in the danger triangle area. The clinical data of 298 patients who underwent either percutaneous RFA or SR for PTC in the thyroid danger triangle at our hospital between January 2018 and April 2020 were retrospectively analyzed. Propensity score matching is employed to regulate for confounding factors. All patients undergoing ablation were treated using a strategy that combined sufficient paratracheal fluid isolation with a low-power, short electrode. Disease progression was analyzed in patients with T1N0M0 PTC (T1a and T1b) employed in Kaplan‒Meier curves. Treatment parameters and the rates of local recurrence, distant metastasis, and complications are recorded and compared. Of 182 eligible patients who were included, 91 were in the RFA (age 44.84 ± 13.19; 71 females; 77 T1a) and 91 were in the SR (age 47.36 ± 11.05; 68 females; 69 T1a). The average treatment time, length of hospital stays, blood loss volume, and scar length are substantially less in the RFA than in the SR. Major complications as well as postoperative permanent recurrent laryngeal nerve injury and postoperative transient parathyroid dysfunction occurred only in the SR, with a substantial distinction between the two groups (p < 0.05). There is no substantial distinction in the disease progression between RFA and SR treatment of T1N0M0 PTC. RFA is as effective as surgery for PTC in the danger triangle area in the short term, with faster recovery and fewer complications. Radiofrequency ablation has a clinical efficacy comparable to surgery in the treatment of papillary thyroid carcinoma in the danger triangle area in the short term with the advantages of faster recovery and fewer complications when compared with surgery. Use of radiofrequency ablation (RFA) in the thyroid danger triangle is still controversial. RFA and surgery groups showed no difference in disease progressions, and no major complications occurred with RFA. Radiofrequency ablation offers a new option for papillary thyroid carcinoma patients in the danger triangle.

A nomogram for risk stratification of central cervical lymph node metastasis in patients with papillary thyroid carcinoma.

Whether to perform prophylactic central lymph node dissection for cN0 papillary thyroid carcinoma (PTC) patients is still controversial. This retrospective study aimed to develop and validate a nomogram based on ultrasound and dual-energy computed tomography (DECT) for the risk stratification of central lymph node metastasis (CLNM) in patients with PTC. A total of 525 patients from 2017 to 2019 [Tianjin First Central Hospital (Hospital A)] were retrospectively analyzed to form the training cohort and to conduct internal validation. Another group of 204 patients in 2020 (Hospital A) formed the temporal validation cohort. A total of 107 patients in 2020 [Binzhou Medical University Hospital (Hospital B)] formed the geographic validation cohort, which was a retrospective cohort study. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the performance of the nomogram. The locally weighted regression curve was used for risk stratification. Diameter, taller-than-wide, calcification, capsular invasion, and iodine concentration in the arterial and venous phases were independent risk predictors of CLNM. The AUC of the nomogram was 0.922 (95% confidence interval: 0.895-0.943) in the training cohort. Two external validation cohorts demonstrated the good performance of the nomogram in predicting CLNM, with AUCs of 0.912 and 0.861. The significantly improved net reclassification index and integrated discriminatory improvement index indicated that DECT was a powerful supplement to ultrasound for predicting CLNM. The risk stratification system divided all patients into low-risk (0-50 points), intermediate-risk (51-100 points), and high-risk groups (>100 points). The nomogram and risk stratification system estimated the utility of CLNM to guide individualized treatment of patients with PTC.

Incidence of Persistence and Recurrence of Differentiated Thyroid Cancer in Post-surgical Cases From a Tertiary Care Hospital in Dubai, United Arab Emirates.

Background Despite the excellent prognosis of differentiated thyroid carcinoma, recurrence remains a major concern. However, the persistence of thyroid cancer post-thyroidectomy is not uncommon. We aimed to characterise patients who underwent re-operative surgery for differentiated thyroid carcinoma and analyse the percentage of re-operations that truly were for "recurrent" disease versus the management of persistent disease. Methods We conducted a retrospective review of the hospital database, analysing patients who visited the nuclear medicine department at Mediclinic City Hospital, a tertiary care hospital in Dubai, United Arab Emirates, between 2015 and 2022. The study included patients with differentiated thyroid carcinoma who underwent re-operations after total thyroidectomy. Recurrence was defined as the development of disease after a patient had undetectable thyroglobulin and negative radiological scans within one year of the first surgery. Cases were categorised as "recurrent", "persistent", or "unable to classify" in the event of missing data. Results Out of 836 patients diagnosed with differentiated thyroid carcinoma who visited the nuclear medicine department, 71 underwent re-operations. The mean age of these patients was 44.4 years (CI 41.7-47.0), of whom 78.9% were females. Almost half (46.5%) underwent re-operations within the first year, and 98.6% were diagnosed with papillary thyroid carcinoma. We were able to classify 63.4% of cases (n=45) as persistent disease, while 24 cases were categorised as "unable to classify". Only two cases met the criteria for recurrent disease. Conclusion The majority of cases previously classified as "recurrent" in differentiated thyroid carcinoma were found to be a persistent disease, possibly indicating inadequate therapy. Further research may be required to explore the reasons behind this eye-opening rate of disease persistence. This highlights an area for improvement in the management and future outcomes of differentiated thyroid carcinoma patients.

Age Related Clinical Outcome After Radioiodine Ablation Therapy in Patients of Papillary Thyroid Carcinoma with Lymph Node Metastases

Age Related Clinical Outcome After Radioiodine Ablation Therapy in Patients of Papillary Thyroid Carcinoma with Lymph Node Metastases

Analysis of Association Between Basic and Clinicopathological Characteristics of Papillary Thyroid Carcinoma Patients with BRAF Mutation

Analysis of Association Between Basic and Clinicopathological Characteristics of Papillary Thyroid Carcinoma Patients with BRAF Mutation

Revolutionary multi-omics analysis revealing prognostic signature of thyroid cancer and subsequent in vitro validation of SNAI1 in mediating thyroid cancer progression through EMT

Thyroid carcinoma (TC), the most commonly diagnosed malignancy of the endocrine system, has witnessed a significant rise in incidence over the past few decades. The integration of scRNA-seq with other sequencing approaches offers researchers a distinct perspective to explore mechanisms underlying TC progression. Therefore, it is crucial to develop a prognostic model for TC patients by utilizing a multi-omics approach. We acquired and processed transcriptomic data from the TCGA-THCA dataset, including mRNA expression profiles, lncRNA expression profiles, miRNA expression profiles, methylation chip data, gene mutation data, and clinical data. We constructed a tumor-related risk model using machine learning methods and developed a consensus machine learning-driven signature (CMLS) for accurate and stable prediction of TC patient outcomes. 2 strains of undifferentiated TC cell lines and 1 strain of PTC cell line were utilized for in vitro validation. mRNA, protein levels of hub genes, epithelial-mesenchymal transition (EMT)-associated phenotypes were detected by a series of in vitro experiments. We identified 3 molecular subtypes of TC based on integrated multi-omics clustering algorithms, which were associated with overall survival and displayed distinct molecular features. We developed a CMLS based on 28 hub genes to predict patient outcomes, and demonstrated that CMLS outperformed other prognostic models. TC patients of relatively lower CMLS score had significantly higher levels of T cells, B cells, and macrophages, indicating an immune-activated state. Fibroblasts were predominantly enriched in the high CMLS group, along with markers associated with immune suppression and evasion. We identified several drugs that could be suitable for patients with high CMLS, including Staurosporine_1034, Rapamycin_1084, gemcitabine, and topotecan. SNAI1 was elevated in both undifferentiated TC cell lines, comparing to PTC cells. Knockdown of SNAI1 reduced the cell proliferation and EMT phenotypes of undifferentiated TC cells. Our findings highlight the importance of multi-omics analysis in understanding the molecular subtypes and immune characteristics of TC, and provide a novel prognostic model and potential therapeutic targets for this disease. Moreover, we identified SNAI1 in mediating TC progression through EMT in vitro.

The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents

IntroductionThe prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC.MethodsThis study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC.ResultsAmong the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455).ConclusionTumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Identification of disulfidptosis-associated genes and characterization of immune cell infiltration in thyroid carcinoma.

The primary objective of this study is to conduct a comprehensive screening and analysis of differentially expressed genes related to disulfidoptosis (DEDRGs) in thyroid carcinoma (THCA). This entails delving into the intricate characterization of immune cell infiltration within the THCA context and subsequently formulating and validating a novel prognostic model. To achieve our objectives, we first delineated two distinct subtypes of disulfidoptosis-related genes (DRGs) via consensus clustering methodology. Subsequently, employing the limma R package, we identified the DEDRGs critical for our investigation. These DEDRGs underwent meticulous validation across various databases, alongside an in-depth analysis of gene regulation. Employing functional enrichment techniques, we explored the potential molecular mechanisms underlying disulfidoptosis in THCA. Furthermore, we scrutinized the immune landscape within the two identified subtypes utilizing CIBERSORT and ESTIMATE algorithms. The construction of the prognostic model for THCA entailed intricate methodologies including univariate, multivariate Cox regression, and LASSO regression algorithms. The validity and efficacy of our prognostic model were corroborated through Kaplan-Meier survival curves and ROC curves. Additionally, a nomogram was meticulously formulated to facilitate the prediction of patient prognosis. To fortify our findings, we conducted a comprehensive Bayesian co-localization analysis coupled with rigorous in vitro experimentation, aimed at unequivocally establishing the validity of the identified DEDRGs. Our analyses unveiled Cluster C1, characterized by elevated expression levels of DEDRGs, as harboring a favorable prognosis accompanied by abundant immune cell infiltration. Correlation analyses underscored predominantly positive associations among the DEDRGs, further affirming their significance in THCA. Differential expression patterns of DEDRGs between tumor samples and normal tissues were evident across the GEPIA and HPA databases. Insights from the TIMER database underscored a robust correlation between DEDRGs and immune cell infiltration. KEGG analysis elucidated the enrichment of DEDRGs primarily in pivotal pathways including MAPK, PPAR signaling pathway, and Proteoglycans in cancer. Furthermore, analyses using CIBERSORT and ESTIMATE algorithms shed light on the crucial role played by DEDRGs in shaping the immune microenvironment. The prognostic model, anchored by five genes intricately associated with THCA prognosis, exhibited commendable predictive accuracy and was intricately linked to the tumor immune microenvironment. Notably, patients categorized with low-risk scores stood to potentially benefit more from immunotherapy. The validation of DEDRGs unequivocally underscores the protective role of INF2 in THCA. In summary, our study delineates two discernible subtypes intricately associated with DRGs, revealing profound disparities in immune infiltration and survival prognosis within the THCA milieu. The implications of our findings extend to potential treatment strategies for THCA patients, which could entail targeted interventions directed towards DEDRGs and prognostic genes, thereby influencing disulfidptosis and the immune microenvironment. Moreover, the robust predictive capability demonstrated by our prognostic model, based on the five genes (ANGPTL7, FIRRE, ODAPH, PROKR1, SFRP5), underscores its potential clinical utility in guiding personalized therapeutic approaches for THCA patients.

Efficacy of Empirical 131 I Radioiodine Therapy in Well-Differentiated Thyroid Carcinoma Patients With Thyroglobulin-Elevated Negative Iodine Scintigraphy Syndrome : A Systematic Review and Meta-analysis.

This study aimed to perform a systematic review and meta-analysis on the efficacy of empirical high-dose radioiodine therapy in treating differentiated thyroid cancer patients with thyroglobulin (Tg)-elevated negative iodine scintigraphy (TENIS) syndrome. We searched PubMed, EMBASE, and the Cochrane Library to identify relevant studies published until April 2022. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and registered in an international prospective register of systematic reviews (PROSPERO). Meta-analyses of proportions and odds ratios were performed to assess the beneficial effect of empirical high-dose radioiodine therapy in patients with TENIS syndrome. Subgroup analysis was also performed according to the presence of micrometastasis or macrometastasis. We identified 14 studies including 690 patients who received empirical high-dose radioiodine therapy for TENIS syndrome. Those who had micrometastasis exhibited additional lesions not previously observed on diagnostic whole-body scan (prop = 0.64, 95% confidence interval [CI], 0.51-0.77) and had reduced serum Tg levels (prop = 0.69; 95% CI, 0.52-0.84) after empirical radioiodine treatment. No such findings were observed among patients with macrometastasis. Moreover, we found that the empirical radioiodine treatment group had lower serum Tg levels than did controls (odds ratio = 0.27; 95% CI, 0.09-0.87), which suggests a lower risk of disease progression. Our findings indicate that empirical high-dose radioiodine therapy promoted beneficial effects and could be recommended for patients with TENIS syndrome, especially those with micrometastasis.

Assessing Krenning's score on 68 Ga-DOTATATE PET-CT and miPSMA score on 68 Ga-PSMA-11 PET-CT in TENIS: a comparison with FDG PET/CT and examining the feasibility of targeted radionuclide therapy.

The objective of this study was to assess receptor expression in metastatic differentiated thyroid carcinoma patients with progressive elevated thyroglobulin and negative iodine scintigraphy, we used 68 Ga-DOTATATE [Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)] (Krenning's score) and 68 Ga-PSMA-11 (Gallium-68 prostate-specific membrane antigen-11) PET-computed tomography (CT) [molecular imaging prostate-specific membrane antigen (miPSMA) score]. Patients with Krenning's score 3 and above and miPSMA score 2 and above were considered to determine the incidence of patients, who would qualify for treatment with 177 Lu-DOTATATE/PSMA [Lutetium-177 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)/prostate-specific membrane antigen]-based therapy. In addition, we compared 68 Ga-DOTATATE and 68 Ga-PSMA-11 PET-CT with 2-deoxy-2-[F-18]fluoroglucose ( 18 F-FDG) PET-CT (using maximum standardized uptake value). A total of 74 patients with histopathologically proven metastatic differentiated thyroid carcinoma with thyroglobulin elevation and negative iodine scintigraphy syndrome were studied retrospectively. They all had 18 F-FDG, 68 Ga-DOTATATE, and 68 Ga-PSMA-11 PET-CT scans available for undertaking this analysis. The lesions detected by 68 Ga-DOTATATE and 68 Ga-PSMA-11 were evaluated using Krenning's and miPSMA scores. In addition, quantitative comparisons of maximum standardized uptake values for 68 Ga-DOTATATE and 68 Ga-PSMA-11, as well as with 18 F-FDG, were conducted. Patient-wise analysis revealed positivity rates of 40.5% for 68 Ga-DOTATATE, 41.89% for 68 Ga-PSMA-11, and 75.67% for 18 F-FDG. Among the 74 patients, 14 (18.91%) were deemed eligible for 177 Lu-DOTATATE/PSMA-617 therapy based on Krenning's score of 3 and above both/either miPSMA score of 2 and above on 68 Ga-DOTATATE or 68 Ga-PSMA-11 PET-CT. Within this subgroup, seven out of 74 patients (9.45%) were eligible for 177 Lu-DOTATATE therapy, and nine out of 74 patients (12.16%) were eligible for 177 Lu-PSMA-targeted therapy. Four patients were eligible for both therapies. Among thyroglobulin elevation and negative iodine scintigraphy patient's subgroup, 9.45% could qualify for 177 Lu-DOTATATE and 12.16% for 177 Lu-PSMA-617. Four were eligible for both therapies. Given the lack of effective therapies, this subset of patients warrants consideration for radionuclide therapy exploration.

Increased risk for thyroid carcinoma in patients with Li-Fraumeni syndrome.

10612 Background: Patients with Li-Fraumeni syndrome (LFS) are predisposed to a 90% lifetime risk of cancer, thus undergoing extensive cancer surveillance. While thyroid cancer is not a core LFS-associated malignancy, increased incidence of thyroid carcinoma has been reported within the LFS tumor spectrum. In the general population, thyroid cancer incidence has soared mainly via incidental detection. We investigated the rate of thyroid carcinoma in relation to p53 mutational process and increased screening. Methods: A retrospective chart review was conducted for clinico-pathological features for adult carriers of confirmed germline TP53 variants at three tertiary cancer centers. Standardized incidence ratio (SIR) was calculated using age, sex, and year-specific expected incidence rates of thyroid cancer from Surveillance, Epidemiology, and End Results (SEER) 1975 – 2020 data. Results: Among 600 patients from 400 families with LFS, 39 (6.5%) patients from 36 (9%) families developed thyroid carcinoma at an average age of 42 years (median = 40, ranged from 23 to 70 years of age). The majority of LFS patients with thyroid carcinoma were female (N=30, 77%). Thyroid carcinoma was the presenting cancer diagnosis in 17 (44%) patients. Over 70% of thyroid carcinoma diagnoses (N=31) were detected incidentally either via LFS cancer screening (N=12, 39%) or via an imaging study unrelated to LFS screening (N=10, 32%). All 39 thyroid carcinomas were of follicular cell origin (non-medullary), most were multifocal (67% of N=32), and 30% had nodal metastasis (N=10 of 33). Of 35 tumors with histologic data, papillary carcinoma (papillary, follicular, and tall cell subtypes) was most common (N=29, 83%), followed by follicular carcinoma (N=4, 11%) and oncocytic carcinoma (N=2, 6%). LFS patients most often underwent a total thyroidectomy (N=27, 69%) compared to a hemithyroidectomy (N=10, 26%) or hemithyroidectomy with completion surgery within three months (N=2, 5%). Intermediate to high risk of recurrence based on tumor characteristics was noted in 17 patients (44%), warranting consideration of radioactive iodine (RAI) therapy, including tall cell subtype (N=3), oncocytic or follicular histology, incomplete resection (N=2), extrathyroidal extension (N = 6), and greater than five positive lymph nodes (N=6). Five (29%) of these 17 patients received RAI. The SIR for thyroid carcinoma in LFS compared to SEER was 13 (95% CI 9.2-17.8, p&lt;0.0001). The SIR was elevated for LFS patients diagnosed with thyroid carcinoma both prior to and after genetic testing (SIR 9.0, CI 5.3-14.2, p&lt;0.0001 and SIR 20, CI 12.2- 30.9, p&lt;0.0001, respectively). Conclusions: In this multi-institutional cohort, a 6-9% prevalence rate of thyroid carcinoma was observed in LFS patients and families, with &gt;70% of the tumors identified incidentally. The rate of thyroid carcinoma in LFS is significantly elevated over the general population.

Expression profiling and bioinformatics analysis of serum exosomal circular RNAs in lymph node metastasis of papillary thyroid carcinoma.

Most papillary thyroid carcinoma (PTC) patients have a good prognosis, but lymph node metastasis (LNM) is the most common progressive manifestation and often leads to a poor-prognosis. However, few studies focused on the underlying mechanisms of LNM. This study aimed to identity the potential role of exosomal circRNAs that contribute to LNM in PTC. We found that 9000 aberrantly expressed exosomal circRNAs in PTC patients with LNM, including 684 observably upregulation and 2193 notably downregulation. Functional enrichment analyses indicated that these aberrantly expressed circRNAs were mainly enriched in a variety of molecules and signaling pathways related to the progression and LNM of PTC. Bioinformatics analysis screened 14 circRNA-miRNA-mRNA networks associated with LNM-related signaling pathways in PTC. Moreover, circTACC2-miR-7-EGFR and circBIRC6-miR-24-3p-BCL2L11 axes were verified for potential involvement in PTC with LNM. Additionally, 4 upregulated circRNAs-related hub genes and 8 hub genes associated with downregulated circRNAs were screened, some of which were involved in LNM of PTC through verification. Collectively, our data provided a novel framework for in-depth investigation of the function of dysregulated exosomal circRNAs and their potential biomarkers in PTC patients with LNM.

Guidelines on the Release of Patients Treated with Iodine – 131 for Thyroid Cancer in Nuclear Medicine: Case of Madagascar

The most frequently used radiopharmaceutical for treatment of thyroid cancer is the radioactive iodine (RAI). Patients treated with RAI therapy cause risk of external radiation exposure to the public and family members. While the therapeutic use of iodine-131 for thyroid carcinoma patients offers enormous benefit to them, it contributes also significantly to the radiation exposure of individuals and population. Patients treated with radioiodine present a radiation hazard and precautions are necessary to limit radiation dose to the relatives and the members of the public. The study aims to develop guidelines for the release of thyroid cancer patients treated with I-131. For this purpose, simulations were performed for estimating suitable period of restriction during which close contact with the patient should be disallowed and limited. These simulations are based on the French working Group and the recommendations of the International Commission on Radiation Protection. The study was carried out at the Isotopes Laboratory (LRI), Department of Nuclear Medicine in Antananarivo, Madagascar. According to the current regulation in radiation protection in Madagascar, the dose limit for the members of the public is limited to 1 mSv. Guidelines for discharge from the hospital are as follows. Patients can travel using public transportation up to 15 minutes. Patients are suggested to sleep apart and restrict contact with partner for 4 days after leaving the hospital. Contact with children should be restricted according to their ages. Time to restrict contact with child ranging from 3 to 10 years is limited to 4 days, and up to 7 days for younger children. This guideline is based on the retained activity of 800 MBq or the external dose rate is less than 40 μSv/h at 1 m. For public transportation, the suggested travel times for thyroid cancer are similar to those recommended by the French group. The length of time for which patients are in contact with children in this study is widely less than recommendations by French Group.

Molecular characterization of circulating tumor cells (CTCs) in sporadic medullary thyroid carcinoma (spMTC) patients

Molecular characterization of circulating tumor cells (CTCs) in sporadic medullary thyroid carcinoma (spMTC) patients

Local treatment improves outcome of RAI - Refractory differentiated thyroid carcinoma (DTC) patients irrespectively of tyrosine kinase inhibitors (TKI) treatment: a single center experience

Local treatment improves outcome of RAI - Refractory differentiated thyroid carcinoma (DTC) patients irrespectively of tyrosine kinase inhibitors (TKI) treatment: a single center experience

Cervical lymph node metastasis prediction from papillary thyroid carcinoma US videos: a prospective multicenter study

BackgroundPrediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance.MethodsFrom September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity.ResultsIn total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P < 0.001) by using the AI model for assistance.ConclusionsThe AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists.Trial registrationWe registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.

Novel T cell exhaustion gene signature to predict prognosis and immunotherapy response in thyroid carcinoma from integrated RNA-sequencing analysis.

Exhausted CD8+ T lymphocytes and tumor-associated macrophages play critical roles in determining cancer prognosis and the efficacy of immunotherapy. Our study revealed a negative correlation between exhausted CD8+ T lymphocytes and prognosis in thyroid carcinoma (THCA). Consensus clustering divided patients into two subgroups of exhaustion with different prognoses, as defined by marker genes of exhausted CD8+ T cells. Subsequently, we constructed an eight-gene prognostic signature, and developed a risk score named the exhaustion-related gene score (ERGS) to forecast both prognosis and immunotherapy response in THCA. Bulk RNA sequencing analysis revealed a higher prevalence of M2 macrophages, indicative of an immunosuppressive tumor microenvironment (TME), in the high-ERGS group. Single-cell RNA sequencing showed that SPP1+ macrophages and CD14+ monocytes infiltrations were positively associated with higher ERGS. Functionally, it was determined that SPP1+ macrophages exert an immunosuppressive role, while CD14+ monocytes were implicated in promoting tumor progression and angiogenesis. Analysis of cell-cell interactions between SPP1+ macrophages and T cells highlighted the activation of the SPP1-CD44 and MIF-CD74 axes, both of which could foster an immunosuppressive TME. Therapeutic strategies that target SPP1+ macrophages, CD14+ monocytes, and the SPP1-CD44 and MIF-CD74 axes may potentially improve the prognosis and amplify the immunotherapy response in THCA patients.

Deep learning-based computer-aided diagnosis system for the automatic detection and classification of lateral cervical lymph nodes on original ultrasound images of papillary thyroid carcinoma: a prospective diagnostic study.

This study aims to develop a deep learning-based computer-aided diagnosis (CAD) system for the automatic detection and classification of lateral cervical lymph nodes (LNs) on original ultrasound images of papillary thyroid carcinoma (PTC) patients. A retrospective data set of 1801 cervical LN ultrasound images from 1675 patients with PTC and a prospective test set including 185 images from 160 patients were collected. Four different deep leaning models were trained and validated in the retrospective data set. The best model was selected for CAD system development and compared with three sonographers in the retrospective and prospective test sets. The Deformable Detection Transformer (DETR) model showed the highest diagnostic efficacy, with a mean average precision score of 86.3% in the retrospective test set, and was therefore used in constructing the CAD system. The detection performance of the CAD system was superior to the junior sonographer and intermediate sonographer with accuracies of 86.3% and 92.4% in the retrospective and prospective test sets, respectively. The classification performance of the CAD system was better than all sonographers with the areas under the curve (AUCs) of 94.4% and 95.2% in the retrospective and prospective test sets, respectively. This study developed a Deformable DETR model-based CAD system for automatically detecting and classifying lateral cervical LNs on original ultrasound images, which showed excellent diagnostic efficacy and clinical utility. It can be an important tool for assisting sonographers in the diagnosis process.