Trends and projections of the global burden of thyroid cancer from 1990 to 2030.

Background: We aimed to explore the burden of thyroid cancer worldwide from 1990 to 2019 and to project its future trends from 2020 to 2030. Methods: Based on annual data on thyroid cancer cases from 1990 to 2019 available in the Global Burden of Disease (GBD) database, we calculated the age-standardised incidence, death, and disability-adjusted life year (DALY) rates for thyroid cancer. We used the estimated annual percentage change (EPAC) to quantify the temporal trends in these age-standardised rates from 1990 to 2019 and applied generalised additive models to project the disease burden from 2020 to 2030. Results: The global age-standardised incidence rate (ASIR) of thyroid cancer increased from 1990 to 2019, with a higher overall disease burden in women than in men at both study time points. The male-to-female ratios for the ASIR increased from 0.41 in 1990 to 0.51 in 2019, while the ratio for the age-standardised death rate (ASDR) increased from 0.60 to 0.82. The models predicted the United Arab Emirates would have the fastest rising trend in both the ASIR (estimated annual percentage changes (EAPC) = 4.19) and age-standardised DALY rate (EAPC = 4.36) in 2020-30, while Saint Kitts and Nevis will have the fastest rising trend in the ASDR (EAPC = 2.29). Meanwhile, the growth trends for the ASDR and age-standardised DALY rate are projected to increase across countries in this period. A correlation analysis of the global burden of thyroid cancer between 1990-2019 and 2020-30 showed a significant positive correlation between the increase in the ASIR and socio-demographic index (SDI) in low-SDI and low-middle-SDI countries. Conclusions: The global burden of thyroid cancer is increasing, especially in the female population and in low-middle-SDI regions, underscoring a need to target them for effective prevention, diagnosis, and treatment.

Application of Carbon Nanoparticles in Transoral Endoscopic Thyroidectomy Vestibular Approach for Unilateral Papillary Thyroid Cancer.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied technology. Carbon nanoparticles (CNs) are novel lymph node tracers that have been widely used in China to help remove central lymph nodes (CLNs) and protect the parathyroid glands (PGs) in open thyroid cancer surgery. This study is to evaluate the effectiveness and safety of CNs in TOETVA. MATERIALS AND METHODS: A total of 158 patients who underwent TOETVA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The participants were divided into a CNs group (n=88) and a control group (n=70), based on whether they received a intraoperative injection of CNs or not. Meanwhile, the CNs group were additionally divided into 2 subgroups, leakage subgroup (n=26) and standard subgroup (n=62). The 2 groups and subgroups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: All common metrics had no significant differences were found between the CNs group and the control group ( P >0.05). The standard subgroup of CNs group had advantage over the control group on PGs identification (59/62 vs. 59/70 for superior PG, 56/62 vs. 52/70 for inferior PG, P <0.05). Moreover, the standard subgroup harvested more CLNs than the control group (8.97±2.96 vs. 7.47±2.93, P <0.05). More operation time was spent on the leakage subgroup of CNs group than the control group (160.00±17.61 vs. 140.00±13.32, P <0.05). Meanwhile, the leakage subgroup had disadvantage on intraoperative hemorrhage (26.15±10.80 vs. 21.21±7.09, P <0.05) and hospital durations (4.96±0.72 vs. 4.57±0.69, P <0.05). Furthermore, the leakage group identified fewer inferior PG than the control group (7/26 vs. 52/70, P <0.05). Contrary to the standard subgroup, the CLNs of the leakage subgroup was also unsatisfactory compared with the control group (4.96±1.84 vs. 7.47±2.93, P <0.05). CONCLUSIONS: The application of CNs suspension tracing technology has a definite effect in TOETVA. It can improve the thoroughness of lymph node dissection in the central region and enhance recognition of the PG. However, refined extracapsular anatomy is indispensable to prevent CN leakage. Leaked CNs will also be counterproductive to the operation.

The diagnostic potential of two exosome-derived circRNAs for papillary thyroid cancer.

BACKGROUND: As a critical component of exosomes, circular RNAs (circRNAs) have shown great value in cancer diagnosis. This study aimed to identify circRNAs in exosomes for the diagnosis of PTC (papillary thyroid carcinoma). METHODS: We selected hsa_circ_0082002 and hsa_circ_0003863 based on circRNA microarray. The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 in the sera of healthy control (n = 68), benign thyroid tumors (n = 60), and PTC without and with Hashimoto's thyroiditis (n = 164) were quantified by qPCR (quantitative polymerase chain reaction). Receiver operating characteristic analyses were conducted to evaluate the diagnostic sensitivity and specificity. Bioinformatics databases were used to predict the microRNAs and proteins binding with hsa_circ_0082002 and hsa_circ_0003863. RESULTS: The levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively associated and statistically increased in PTC compared to healthy and benign thyroid tumors. Intriguingly, higher levels of exosomal hsa_circ_0082002 and hsa_circ_0003863 were positively correlated with lymph node metastasis and vascular invasion in PTC. Further stability tests show that exosomal hsa_circ_0082002 and hsa_circ_0003863 could exist stably in sera treated by several freeze-thaw cycles at -20 °C and with a storage time shorter than 24 h at 4 °C. Furthermore, hsa_circ_0082002 and hsa_circ_0003863 were predicted to interact with microRNAs and proteins, suggesting that hsa_circ_0082002 and hsa_circ_0003863 might contribute to the occurrence and progression of PTC through interacting with microRNAs and RNA binding proteins. CONCLUSION: Collectively, we identified two PTC-related circRNAs incorporated in exosomes and uncovered their potential as tumor markers to diagnose PTC, in particular, more aggressive PTC.

circAGTPBP1 promotes the progression of papillary thyroid cancer through the notch pathway via the miR-34a-5p/notch1 axis.

The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq. We conducted in vitro and in vivo experiments to investigate the biological functions of circAGTPBP1 in PTC progression. We found that circAGTPBP1 was upregulated in PTC tissues and cell lines, and its expression was positively correlated with tumor size, lymph node metastasis, and clinical stage. Using RNA-seq and bioinformatic analysis, we identified miR-34a-5p and NOTCH1 as downstream targets of circAGTPBP1. Functionally, circAGTPBP1 knockdown significantly inhibited the migration, invasion, and metastasis of PTC cell lines in vitro, while the miR-34a-5p inhibitor reversed these effects. Additionally, circAGTPBP1 knockdown inhibited tumor growth in vivo. Our findings suggest that circAGTPBP1 may act as a tumor promoter and could be a potential therapeutic target for PTC.

Transoral Endoscopic Thyroidectomy Vestibular Approach Versus Gasless Transaxillary Endoscopic Thyroidectomy for Patients With Unilateral Papillary Thyroid Carcinoma: A Retrospective Study.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) and gasless transaxillary endoscopic thyroidectomy (GTET) are 2 newly applied technologies. This study is to compare the 2 approaches from the aspects of effectiveness and safety. MATERIALS AND METHODS: A total of 339 patients who underwent TOETVA or GTET with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The 2 groups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: The operative time of the TOETVA group was significantly longer than the GTET group (141.39±16.11 vs. 98.45±12.24, P <0.05). The TOETVA group had advantages over GTET group when the reduction of parathyroid hormone was compared (19.18±17.43 vs. 23.07±15.72, P <0.05). Meanwhile, more parathyroids were detected in central neck specimens in GTET group (40/181 vs. 21/158, P <0.05). TOETVA had an advantage on total number of central lymph nodes over GTET (7.65±3.11 vs. 4.99±2.45, P <0.05), whereas the number of positive central lymph nodes was similar ( P >0.05). No differences were found between the 2 groups on other data. CONCLUSIONS: TOETVA and GTET are both safe and effective for unilateral papillary thyroid carcinomas. TOETVA has advantage on protection of inferior parathyroid glands and harvest of central lymph node dissection. Meanwhile, GTET can save more time compared with TOETVA. Surgeons and patients should freely choose the approaches based on their demands.

Management of papillary thyroid cancer with tracheal invasion and lung cancer: A case report.

The present study reports the case of a 64-year-old patient with papillary thyroid cancer (PTC) and tracheal invasion, along with primary lung cancer. Firstly, the patient received tumor electrocautery under tracheoscopy to enlarge the space for tracheal intubation. Next, the patient received one-stage radical thyroidectomy, with window resection of the trachea and thoracoscopic radical resection of the lung cancer. The patient was discharged safely after several days of therapy. To the best of our knowledge, this case is the first reported case of a one-stage radical thyroidectomy with a window resection of the trachea and thoracoscopic radical resection of the lung cancer in the literature. Simultaneous surgery for PTC with tracheal invasion and lung cancer is a great challenge for the patient and the surgeon. Appropriate surgical management of the tracheal invasion is of great importance to the operation and prognosis. This case may provide reference for surgeons in similar situations.

A nomogram for predicting overall survival in patients with follicular thyroid cancer after thyroidectomy: a SEER database analysis.

Background: A good predictive model requires patient participation in prognostic counseling and subsequent clinical follow-up. We aimed to construct and validate a nomogram for predicting overall survival (OS) in patients with follicular thyroid cancer (FTC) after thyroidectomy. Methods: This was a retrospective observational study. We screened 802 patients with initially diagnosed FTC from the Surveillance Epidemiology and End Results (SEER) database between 2010 and 2015. Then the patients were all divided into the training set and validation set randomly at a ratio of 7:3. Univariate and multivariate Cox proportional hazard models were used to analyze the influence of different variables on OS. The concordance index (C-index) and calibration curves were used to evaluate the precision of the nomogram. Results: Univariate and multivariate analyses demonstrated that four factors, namely age, grade, race, and M stage (all P<0.05), were independent predictors of OS in FTC patients. Based on these factors, a predictive model was established by using the training cohort and validated by the validation cohort. A good consistency between the actual OS and predicted OS was showed by the calibration curves. Moreover, compared with the traditional tumor-node-metastasis (TNM) staging system, the nomogram had better predictive ability for the survival of patients with FTC. The C-index of the nomogram in the training set and validation set had high consistency in evaluating the survival rate of patients with FTC [training set: C-index =0.904, 95% confidence interval (CI): 0.883-0.925; validation set: C-index =0.835, 95% CI: 0.772-0.898; TNM: C-index =0.775, 95% CI: 0.732-0.818]. Conclusions: Based on several clinical variables, we established the first predictive model of FTC after thyroidectomy by using Cox multivariate analysis which provide a basis for each patient with prognosis and postoperative follow-up.

MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.

BACKGROUND: Papillary thyroid carcinoma (PTC) grows slowly but has a great risk of metastasis. MicroRNAs are well known as vital tumor-related gene regulators. In PTC, the role of miR-203a-3p and the underlying mechanisms remain not completely understood. METHODS: We conducted CCK8 assay, wound healing assay, transwell experiment and flow cytometry analyses to investigate the function of miRNA-203a-3p. The interaction of miRNA-203a-3p with its gene MAP3K1 was characterized by quantitative real-time polymerase chain reaction, western blotting and luciferase assay. RESULTS: We found that the levels of miRNA-203a-3p were statistically decreased in PTC tissues. When mimics were delivered to TPC-1 and KTC-1 cells to upregulate miR-203a-3p, it was observed that cell proliferation, metastatic abilities and cell cycle process were prevented but cell apoptosis was enhanced. Furthermore, we proved the interaction between MAP3K1 and miR-203a-3p. Intriguingly, similar to miR-203a-3p mimics, siMAP3K1 showed a tumor-suppressive effect, and this effect could be reversed when miR-203a-3p was simultaneously inhibited. Finally, selected autophagy-linked proteins such as LC3 Beclin-1 were detected and found to be increased when miR-203a-3p was upregulated or MAP3K1 was inhibited. CONCLUSION: Overall, miR-203a-3p inhibits the oncogenic characteristics of TPC-1 and KTC-1 cells via suppressing MAP3K1 and activating autophagy. Our findings might enrich the understanding and the therapeutic strategies of PTC.

A nomogram for predicting overall-specific survival in thyroid cancer patients with total thyroidectomy: a SEER database analysis.

BACKGROUND: A good predictive model requires patients to attend consultations for prognosis and subsequent clinical follow up. The aim of the present study was to build a nomogram chart with independent prognostic factors for thyroid cancer (TC) patients with total thyroidectomy. METHODS: This was a retrospective, observational study. Data were collected from the Surveillance, Epidemiology, End Results (SEER) database and approved by the institutional review board of our institution. In total, 11,614 patients with TC after thyroidectomy were selected from 2010 to 2015. We divided the selected patients into a modeling group and a verification group at a ratio of 7:3. The effective factors were selected to establish the nomogram model through Cox analysis. Finally, internal verification was carried out through the testing group. RESULTS: Chi-squared analysis of various factors in the modeling group and the testing group had no significant statistical significance, indicating that random grouping was meaningful. Most of the TC patients were female patients. The following variables were selected through univariate and multivariate Cox analysis for overall-specific survival: age, histological type, grade, tumor size, stage TMN, and sex. These variables were used to establish predictions of 3- and 5-year survival rates using a nomogram. Both the modeling group and the verification group had good predictive ability with their C-index all greater than 0.8. CONCLUSIONS: We established the first postoperative prediction model of TC with total thyroidectomy through the variables selected via the Cox multivariate analysis, which laid the foundation for the prognostic prediction and postoperative follow up of each patient.

Transoral Endoscopic Thyroidectomy Vestibular Approach Versus Endoscopic Thyroidectomy Via Areola Approach for Patients With Unilateral Papillary Thyroid Carcinoma: A Retrospective Study.

BACKGROUND: Endoscopic thyroidectomy via areola approach (ETA) has been widely used in thyroidectomy for many years as it can effectively avoid a scar in the neck. Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied and has gained popularity quickly. This study is to compare the safety and effectiveness of TOETVA and ETA. MATERIALS AND METHODS: A total of 95 patients who underwent TOETVA or ETA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2020. The basic information (such as gender, age), intraoperative hemorrhage, postoperative drainage volume, hospital durations, intraoperative and postoperative complications, operative time, central lymph node dissection time, total number of central lymph nodes, and number of metastatic central lymph nodes were compared. RESULTS: The operative time of the TOETVA group was significantly longer than the ETA group (148.11±19.78 vs. 135.90±12.77 min, P<0.05). However, the result was opposite when central lymph node dissection time was compared (10.31±2.93 vs. 12.48±3.55, P<0.05). TOETVA had an advantage on total number of central lymph nodes over ETA (7.82±3.35 vs. 5.26±2.45, P<0.05). No differences were found between the 2 groups on other data. CONCLUSION: TOETVA and ETA have the similarity on surgical safety and effectiveness. TOETVA has its advantage on central lymph node dissection and might be a reasonable alternative for ETA and open surgery in the future.

Overexpression of microRNA-203 can downregulate survivin and function as a potential therapeutic target in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common type of thyroid carcinoma. PTC has a considerably high five-year survival rate; however, the possibility of recurrence is also high. Therefore, there is a requirement to clarify the molecular mechanism of PTC to promote understanding regarding the development of the disease and further improve prognosis. A number of studies have demonstrated that microRNAs (miRNAs or miRs) contribute to the progression of PTC. The present study revealed that the expression level of miR-203 was significantly lower in PTC tissues and cell lines compared with in the normal controls. In addition, inhibition of miR-203 was identified to be associated with an overexpression of survivin, which was observed in PTC samples. miR-203 regulates the expression of Bcl-2 via its downstream regulator survivin. Furthermore, the present study identified that inhibition of miR-203 histone acetylation was associated with high expression levels of miR-203 in PTC tissue samples. In summary, the results indicate that miR-203 functions as a biomarker and may serve as a candidate target for the development of novel therapeutic strategies to treat PTC.

Shenmai injection improves the postoperative immune function of papillary thyroid carcinoma patients by inhibiting differentiation into Treg cells via miR-103/GPER1 axis.

Shenmai injection (SMI) is increasingly used in tumor combination therapy, devoting to enhancing anti-tumor effects and reducing the toxicity of chemotherapy drugs. This study aimed to explore the role of SMI in papillary thyroid carcinoma (PTC) treatment. Flow cytometry was used to examine Treg cells percentage in CD4 + T cells. The expression of RNA and protein was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Inducers were used to stimulate CD4 + T cells to differentiate into Treg cells. The interaction between miR-103 and G protein-coupled estrogen receptor 1 (GPER1) was confirmed with the dual luciferase assays. Cell transfection and recombinant plasmids were used to achieve endogenous expression. Compared with patients not treated with 131 I, the Treg cells percentage and Foxp3 expression were clearly increased in patients with 131 I radiotherapy, just the opposite in SMI combination therapy. SMI inhibited the differentiation of CD4 + T cells into Treg cells. Aberrant expression of miR-103 and GPER1 induced by 131 I was reversed by SMI and 131 I combination therapy. GPER1 was negatively regulated by miR-103 and SMI inhibits the differentiation of CD4 + T cells into Treg cells via miR-103/GPER1 axis, which improves the postoperative immunological function of PTC patients with 131 I radiotherapy.

Level V Metastasis, a Novel Predicative Factor for Recurrence in N1b Papillary Thyroid Carcinoma.

BACKGROUND: Lymph nodal (LN) metastasis, classified as pN1b, is considered as an independent poor prognostic factor for Papillary thyroid carcinoma (PTC) patients. However, whether LN metastasis can serve as a predictive factor for recurrence or disease-free survival of N1b PTC is still plagued by controversy. METHODS: The N1b PTC patients who underwent total thyroidectomy and unilateral modified radical neck dissection (MRND) by the same surgical team in Ningbo NO.2 Hospital from March, 1998 to March, 2015 were included in this study. The clinical and pathological characteristics of each patient were recorded in detail. Univariate and multivariate Cox proportional hazards regression models were performed to analyze the associations between clinicopathological characteristics with recurrence. Kaplan-Meier analysis and log-rank test were used for the analysis of overall RFS and level V metastasis. RESULTS: A total of 214 patients were eligible for the final analyses. Of the 214 finally included patients with N1b PTC, 39 patients were classified with recurrence and 175 without recurrence. The final univariate and multiple Cox proportional hazards analysis only suggested level V metastasis as the independent predictive factor of N1b PTC recurrence (HR: 4.11; 95% CI:1.22-11.05, P=0.028). The patients with level V metastasis showed a significantly lower 10-year RFS rate (P=0.031) as illustrated by Kaplan-Meier analysis and log-rank test. CONCLUSION: Level V metastasis is a novel indicator for tumor recurrence and 10-year RFS in patients with N1b PTC.

MiR-221, a potential prognostic biomarker for recurrence in papillary thyroid cancer.

BACKGROUND: Many studies have reported several transcriptionally deregulated microRNAs (miRNAs) in papillary thyroid cancer (PTC) tissue in comparison with benign thyroid nodules and normal thyroid tissues. However, the correlation between miRNA expressions and PTC recurrence still remains unclear. METHODS: The PTC patients who scheduled to undergo total thyroidectomy by the same surgical team in Ningbo NO.2 Hospital from March 1998 to March 2008 were enrolled in this study. The clinical and pathological characteristics of each patient were recorded in detail. The selected miRNA expressions were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Potential predictive factors for cancer recurrence were evaluated by univariate and multivariate Cox proportional hazard analysis. RESULTS: A total of 78 patients were enrolled with 49 females at a mean age of 45.8 years. Enrolled patients were divided into two groups: nonrecurrent group (n = 54) and recurrent group (n = 24). The results from the univariate Cox proportional hazard analysis revealed that primary tumor size, TNM stage, extrathyroid extension, miR-221, and miR-222 expressions were significantly associated with PTC recurrence (P < 0.05). The tissue expression of miR-221 was the only independent risk factor for PTC recurrence (HR 1.41; 95%CI 1.14-1.95, P = 0.007) by multiple Cox proportional hazard analysis. CONCLUSIONS: This study identified the potential role of miR-221 as a prognostic biomarker for the recurrence in PTC.