The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC. OBJECTIVE: In this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors. METHODS: A series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC. RESULTS: HF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-ß-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway. CONCLUSION: This study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review.

Gambogenic acid is a derivative of gambogic acid, a polyprenylated xanthone isolated from Garcinia hanburyi. Compared with the more widely studied gambogic acid, gambogenic acid has demonstrated advantages such as a more potent antitumor effect and less systemic toxicity than gambogic acid according to early investigations. Therefore, the present review summarizes the effectiveness and mechanisms of gambogenic acid in different cancers and highlights the mechanisms of action. In addition, drug delivery systems to improve the bioavailability of gambogenic acid and its pharmacokinetic profile are included. Gambogenic acid has been applied to treat a wide range of cancers, such as lung, liver, colorectal, breast, gastric, bladder, and prostate cancers. Gambogenic acid exerts its antitumor effects as a novel class of enhancer of zeste homolog 2 inhibitors. It prevents cancer cell proliferation by inducing apoptosis, ferroptosis, and necroptosis and controlling the cell cycle as well as autophagy. Gambogenic acid also hinders tumor cell invasion and metastasis by downregulating metastasis-related proteins. Moreover, gambogenic acid increases the sensitivity of cancer cells to chemotherapy and has shown effects on multidrug resistance in malignancy. This review adds insights for the prevention and treatment of cancers using gambogenic acid.

Diagnostic performance of shear wave elastography in thyroid nodules with indeterminate cytology: A systematic review and meta-analysis.

Purpose: Thyroid nodules classified as indeterminate in previous fine-needle aspiration cytology often necessitate additional evaluation to determine their histology, while shear wave elastography (SWE) offers an alternative option in this regard. The objective of this study was to assess the diagnostic effectiveness of SWE in evaluating indeterminate nodules. Methods: The PubMed, EMBASE, and Web of Science databases were searched from 1st January 1970 to 1st March 2023. The studies were reviewed and the data was extracted by two separate reviewers. A Bayesian bivariate model was utilized to quantitatively synthesize the diagnostic accuracy and yield of the studies in R. Results: A total of seven studies, involving indeterminate thyroid nodules undergoing SWE were included, and the overall malignancy rate was 34.1% (307/900). The summarized estimates of sensitivity and specificity were 0.792 (95% credible interval [CI], 0.727-0.850) and 0.845 (95% CI, 0.797-0.887), respectively. The summarized estimate for the diagnostic odds ratio (DOR) was 17.8 (95% CI, 14.0-22.6). Summarized receiver operating characteristic (SROC) plots indicated a trade-off between sensitivity and specificity, and the estimate of AUC was 0.866 (95% CI, 0.834-0.895). The summary estimates for positive and negative likelihood ratios were 4.67 (95% CI, 3.98-5.85) and 0.26 (95% CI, 0.23-0.28), respectively. Conclusions: The overall accuracy of SWE remains satisfactory in indeterminate thyroid nodules. However, it should be noted that the available data are still extremely limited, and more studies or guidelines are required to provide further insights.

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.

Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA's significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA's action represents a crucial research direction to pursue in the future.

The value of total tumor diameter in unilateral multifocal papillary thyroid carcinoma: a propensity score matching analysis.

Background: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma. Methods: Retrospective data analysis was done on 1936 individuals who underwent complete thyroidectomy for PTC. Patients were classified into subgroups according to unilateral multifocality, central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The relationships of clinicopathological features among these groups were analyzed. Results: Unilateral multifocality was observed in 117 patients. The clinicopathological features of the unilateral multifocal PTC were similar to the unifocal PTC with approximate TTD. The unilateral multifocality played no independent role in CLNM and LLNM. Moreover, the efficiency of TTD in predicting CLNM and LLNM was significantly higher than that of MTD. Conclusion: In the case of unilateral multifocal PTC, TTD is a more accurate indicator of the biological characteristics of the tumor than MTD.

Diagnostic performance of ultrasound risk stratification systems on thyroid nodules cytologically classified as indeterminate: a systematic review and meta-analysis.

PURPOSE: Ultrasound (US) risk stratification systems (RSSs) are increasingly being utilized for the optimal management of thyroid nodules, including those with indeterminate cytology. The goal of this study was to evaluate the category-based diagnostic performance of US RSSs in identifying malignancy in indeterminate nodules. METHODS: This systematic review and meta-analysis was registered on PROSPERO (CRD42021266195). PubMed, EMBASE, and Web of Science were searched through December 1, 2022. Original articles reporting data on the performance of US RSSs for indeterminate nodules were included. The numbers of nodules classified as true negative, true positive, false negative, and false positive were extracted. RESULTS: Thirty-three studies evaluating 7,225 indeterminate thyroid nodules were included. The diagnostic accuracy was quantitatively synthesized using a Bayesian bivariate model based on the integrated nested Laplace approximation in R. For the intermediate- to high-risk category, the sensitivity levels of the American College of Radiology, the American Thyroid Association, the European Thyroid Association, the Korean Thyroid Association/Korean Society of Thyroid Radiology, and Kwak et al. were found to be 0.80, 0.72, 0.76, 0.96, and 0.97, respectively. The corresponding specificity measurements were 0.36, 0.50, 0.49, 0.28, and 0.17. Furthermore, for the high-risk category, the sensitivity values were 0.40, 0.46, 0.55, 0.47, and 0.10, while the specificity levels were 0.91, 0.90, 0.71, 0.91, and 0.99, respectively. CONCLUSION: The overall diagnostic performance of the US RSSs was moderate in the differentiation of indeterminate nodules.

Mitochondrial dysfunction-targeting therapeutics of natural products in Parkinson's disease.

Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, often occurs in middle-aged and elderly individuals. The pathogenesis of PD is complex and includes mitochondrial dysfunction, and oxidative stress. Recently, natural products with multiple structures and their bioactive components have become one of the most important resources for small molecule PD drug research targeting mitochondrial dysfunction. Multiple lines of studies have proven that natural products display ameliorative benefits in PD treatment by regulating mitochondrial dysfunction. Therefore, a comprehensive search of recent published articles between 2012 and 2022 in PubMed, Web of Science, Elesvier, Wliey and Springer was carried out, focusing on original publications related to natural products against PD by restoring mitochondrial dysfunction. This paper presented the mechanisms of various kinds of natural products on PD-related mitochondrial dysfunction regulation and provided evidence that natural products are promising to be developed as drugs for PD therapeutics.

Diagnostic performance of adult-based ultrasound risk stratification systems in pediatric thyroid nodules: a systematic review and meta-analysis.

Purpose: Ultrasound (US) is the first choice in the detection of thyroid nodules in pediatric and adult patients. The purpose of this study was to evaluate the diagnostic performance of adult-based US risk stratification systems (RSSs) when applied to the pediatric population. Methods: Medline, Embase, and Cochrane Library (CENTRAL) were searched up to 5 March 2023 for studies about the diagnostic performance of adult-based US RSS in pediatric patients. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were also analyzed. Results: The sensitivity was highest in American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS) category 4-5 and American Thyroid Association RSS high-intermediate risk (ATA), which was 0.84 [0.79, 0.88] and 0.84 [0.75, 0.90], respectively. The specificity was highest in ACR-TIRADS category 5 and Europe-TIRADS (EU-TIRADS) category 5, which was 0.93 [0.83, 0.97] and 0.93 [0.88, 0.98], respectively. The ACR-TIRADS, ATA, and EU-TIRADS showed moderate diagnostic performance in pediatric thyroid nodule patients. For Korea-TIRADS (K-TRADS) category 5, the summary sensitivity and specificity with a 95% CI were 0.64 [0.40, 0.83] and 0.84 [0.38, 0.99], respectively. Conclusions: In conclusion, the ACR-TIRADS, ATA, and EU-TIRADS have moderate diagnostic performance in pediatric thyroid nodule patients. The diagnostic efficacy of the K-TIRADS was not as high as expected. However, the diagnostic performance of Kwak-TIRADS was uncertain because of the small sample size and small number of studies included. More studies are needed to evaluate these adult-based RSSs in pediatric patients with thyroid nodules. RSSs specific for pediatric thyroid nodules and thyroid malignancies were necessary.

Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica.

Cancer is currently the most important problem endangering human health. As antitumor drugs have always been the most common methods for treating cancers, searching for new antitumor agents is of great significance. Brusatol, a quassinoid from the seeds of Brucea javanica, exhibits a potent tumor-suppressing effect with improved disease outcome. Studies have shown that brusatol not only shows potential tumor inhibition through multiple pharmacological effects, such as promoting apoptosis and inhibiting metastasis but also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents and overcoming chemical resistance in a wide range of cancer types. In this paper, the antitumor effects and mechanisms of brusatol were reviewed to provide evidence that brusatol has the exact antitumor efficacy of chemotherapeutic agents and show the potential of brusatol to be developed as a promising antitumor drug.

Surgical treatment and prognosis values of extranodal extension to recurrent laryngeal nerve in papillary thyroid carcinoma.

PURPOSE: Recurrent laryngeal nerve (RLN) invasion by extranodal extension (ENE) is a rare condition that may occur in papillary thyroid cancer (PTC), and it has never been characterised in the literature.Our research aims to investigate the clinical significance of ENE to RLN including its effect on vocal cord function, relationship with the aggressive behaviour of PTC, and optimal surgical methods. METHODS: A total of 3119 patients, including 2868 patients without RLN invasion, 251 patients with RLN invasion [categorised into the ENE invasion group (n = 55) and extrathyroidal extension (ETE) invasion group (n = 196)] were analyzed retrospectively. Data on clinicopathological characteristics, vocal cord paralysis (VCP), postoperative complications, surgical methods, rates of recurrence and metastasis were collected. Predictive disease-free survival (DFS) was analysed using the Kaplan-Meier method. RESULTS: The ENE invasion group showed a similar rate of VCP and DFS compared with the ETE invasion group (P = 0.15, P = 0.38, respectively). Sharp separation applied on the invaded nerves preserves the visual integrity of the RLN without significantly reducing the DFS (P > 0.05). ETE or ENE to RLN, lymph nodes metastasis (LNM), and T4 stage were independent factors for total recurrence [P = 0.04, hazard ratio (HR), 1.97 (1.04-3.75); P = 0.00, HR, 4.63 (2.24-9.54); P = 0.00, HR, 3.63 (1.94-6.77); P = 0.00, HR, 6.1 (3.24-11.50)]. RLN invasion, both by ETE or ENE, was significantly associated with reduced DFS (P = 0.00; P = 0.00, respectively). CONCLUSIONS: ENE to RLN, while rare, has not previously been well-studied. Our interesting premise and important findings including ENE to RLN has the same poor prognostic impact on recurrence as does invasion of the RLN by ETE and surgical management for the invaded RLN that preserves its visual integrity without compromising DFS. Those novel findings indicate that ENE to RLN could be considered as an additional factor beyond post-operative disease status and risk stratification, and it would be a valuable addition to further individualise treatment/surveillance for PTC.

The Effects of Radioiodine Therapy on the Recovery of Parathyroid Function in Patients with Protracted Hypoparathyroidism after Total Thyroidectomy for Papillary Thyroid Carcinoma.

BACKGROUND: To determine the effect of 131I treatment on postoperative parathyroid function and the timing of recovery of parathyroid function (RPF) in patients with protracted hypoPT. METHODS: 260 patients with papillary thyroid cancer (PTC) were retrospectively analyzed, including 166 patients treated with radioactive iodine-131 (131I) classified into the 131I group and 94 patients without 131I treatment classified into the control group. Data on clinicopathological characteristics, demographics, dose and interval time of 131I treatment, number of parathyroid glands remaining in situ (PGRIS), occurrence of hypoPT, duration of RPF, preoperative and postoperative levels of Ca and PTH were collected. RESULTS: The patients in the 131I group showed a higher persistent hypoPT rate than those in the control group (p = 0). The PGRIS and total number of PG were significantly higher in patients who recovered from protracted HypoPT (p = 0.02; p = 0.03). PGRIS and 131I treatment [1 ∼ 2 VS 0, p = 0.03, OR 3.19; 3 ∼ 4 VS 0, p = 0.02, OR3.62; p = 0.02, OR 1.98, respectively] were independent factors influencing postoperative persistent hypoPT. The timing of RPF differed significantly for patients in the control group compared to those in the 131I group [p = 0.00]. CONCLUSIONS: We found that 131I treatment significantly prolonged the RPF of patients with protracted hypoPT and caused late RPF (even beyond 12 months). The diagnosis of "permanent" hypoPT should be cautiously made at least 12 months after surgery, especially in patients who receive 131I treatment.

Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review.

Classical Hodgkin lymphoma (cHL) is the most common type of HL that occurs mainly in people aged between 15-30 and over 55 years. Although its general prognosis is favorable, 10%-30% of patients with cHL will ultimately develop relapsed or refractory disease (r/r cHL). Improving the cure rate of r/r cHL has proven to be challenging. Some novel agents, such as brentuximab vedotin and immune checkpoint inhibitors, which have been used in conventional regimens for patients with r/r cHL in the past decade, have been shown to have good curative effects. This paper reviews the conventional regimens for patients with r/r cHL and focuses on the newest clinical trials and treatment measures to prolong prognosis and reduce adverse events. The evaluation of prognosis plays a vital role in analyzing the risk of relapse or disease progression; thus, finding new predictive strategies may help treat patients with r/r cHL more efficaciously.

Targeted therapy and drug resistance in thyroid cancer.

Thyroid cancer is the most common endocrine malignancy, the incidence of which has increased significantly over the past decades. Advanced thyroid cancers, especially locally advanced or metastatic poorly differentiated thyroid cancer and anaplastic thyroid cancer, also show increased incidence and mortality rate. The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer. However, the drug efficacy in those patients is not satisfying owing to primary and secondary drug resistance. Hence, a full comprehension of the underlying mechanisms is worth discussing. In this review, we introduce the clinical application of existing kinase inhibitors that are recommended for patients with advanced thyroid cancer and discuss several significant resistance mechanisms, including key signaling pathway regulation, the tumor microenvironment, ABC transporters, epithelial-to-mesenchymal transition and cancer stem-like cells, apoptosis, autophagy, and aerobic glycolysis. Understanding the molecular basis of drug resistance in thyroid cancer will be helpful for the enhancement of drug combination therapy and promoting the development of new drugs against advanced thyroid cancer.

Diagnostic value of supersonic shear impulse elastography for malignant cervical lymph nodes: a Bayesian analysis.

PURPOSE: This study aimed to assess the diagnostic performance of supersonic impulse (SSI) elastography in differentiating malignant and benign cervical lymph nodes. METHODS: The Medline, Embase, and Cochrane Central databases were searched until December 1, 2020. Two different reviewers checked the studies and extracted the data. The diagnostic yields were quantitatively synthesized using a Bayesian bivariate model with an integrated nested Laplace approximation in R. RESULTS: In total, 590 patients with 892 cervical lymph nodes who underwent SSI elastography were included. The total prevalence of malignancy was 33.7% (301/892), and the four elastic modulus values (mean, maximum, minimum, and standard deviation) were significantly different between malignant and benign lymph nodes. For the mean elastic modulus, the summary estimates for sensitivity and specificity were 0.720 (95% credible interval [CrI], 0.592 to 0.824) and 0.877 (95% CrI, 0.727 to 0.969), respectively. The estimated area under the curve (AUC) was 0.845 (95% CrI, 0.672 to 0.914). For the maximum elastic modulus, the sensitivity and specificity were estimated to be 0.809 (95% CrI, 0.698 to 0.899) and 0.816 (95% CrI, 0.643 to 0.924), respectively. The estimated AUC was 0.834 (95% CrI, 0.579 to 0.938). The minimum and standard deviation of the elastic modulus and the outcomes of the positive and negative likelihood ratio, diagnostic odds ratio, and risk difference were also calculated. CONCLUSION: SSI elastography is an acceptable imaging technique for diagnosing malignant cervical lymph nodes, and it can play a complementary role today. Both maximum and mean elastic modulus values should be taken into consideration to make a clinical judgment.

Ultrasound-guided thermal ablation for cervical lymph node metastasis from thyroid carcinoma: a meta-analysis of clinical efficacy and safety.

To evaluate the efficacy and safety of thermal ablation (radiofrequency, microwave, and laser) for treating lymph node metastasis from papillary thyroid carcinoma. A literature search was performed in the Medline, Embase, and Cochrane Library databases. Thirteen studies focusing on the efficacy and safety of thermal ablation for treating lymph node metastasis were eligible. The assessed outcomes were primarily pooled using a random- or fixed-effects model based on the results of the heterogeneity test. A total of 235 patients with 445 metastatic lymph nodes were included. Laser, microwave, and radiofrequency ablation all showed a significant reduction in maximum diameter and volume of metastatic lymph nodes (P < 0.0001). Microwave ablation had a higher volume reduction rate (99%; 95% CI, 98-100%) comparing to the other two techniques (P = 0.0057). For all ablations, the pooled completely disappear rate was 70% (95% CI, 45-87%) and the recurrent rate was 3% (95% CI, 2-5%). Thyroglobulin levels significantly decreased (P < 0.0001). No major complications were encountered; the pooled proportion of voice change was low to 4% (95% CI, 2-7%). Thermal ablation is acceptable treatments to manage lymph nodes metastasis from papillary thyroid carcinoma in terms of efficacy and safety for non-surgical candidates.

Does the number of autotransplanted parathyroid glands affect postoperative hypoparathyroidism and serum parathyroid hormone levels?

BACKGROUND: To investigate how number of autotransplanted parathyroid glands (PGs) affects the incidence of postoperative hypoparathyroidism and the recovery of parathyroid function. METHODS: A systematic search was performed in the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. The evaluated indices included the incidence of postoperative transient and permanent hypoparathyroidism and parathyroid hormone (PTH) levels during follow-up. RESULTS: Twenty articles with 7291 patients were included. A higher incidence of transient hypoparathyroidism was found in the PG autotransplantation group than in the preservation group (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.90, 2.96). However, there was no significant difference between the two groups regarding permanent hypoparathyroidism (OR: 1.17; 95% CI: 0.71, 1.91). Parathyroid hormone (PTH) levels in the PG autotransplantation group changed significantly more than the preservation group at postoperative 1-day and 1-month, but became similar at the 6-month, 1-year and 2-year follow-up. Autotransplantation of 2 and 3 PGs demonstrated a higher incidence of transient hypoparathyroidism than 1 PG (OR: 2.09; 95% CI: 1.41, 3.11 and OR: 9.70; 95% CI: 2.11, 44.39, respectively), but no significant difference was observed between the autotransplantation of 3 and 2 PGs (OR: 0.99; 95% CI: 0.03, 29.06). Additionally, the incidence of permanent hypoparathyroidism was not significantly different when different number of PGs was autotransplanted. CONCLUSIONS: PG autotransplantation is an effective mid- and long-term strategy for the preservation of parathyroid function. Although transient hypoparathyroidism was positively correlated with the number of autotransplanted PGs, no remarkable correlation was observed for permanent hypoparathyroidism.

Correlation between Pre-Operative 25-Hydroxyvitamin D Levels and Poor Prognostic Factors for Papillary Thyroid Cancer.

PURPOSE: To evaluate the relationship between pre-operative 25-hydroxyvitamin D (25 (OH) D) levels and poor prognostic factors for papillary thyroid cancer (PTC). METHODS: A total of 1161 patients diagnosed with PTC were analyzed retrospectively. The patients were categorized .based on their pre-operative 25 (OH) D levels into three groups: the severe vitamin D deficiency (VDD) group (25 (OH) D < 10 ng/mL), moderate VDD group (20 ng/mL > 25 (OH) D ≥ 10 ng/mL), and control group (25(OH)D ≥ 20 ng/mL) Differences in the demographic and clinicopathological characteristics among the three groups were analyzed. Linear and logistic regression analyses were also performed to determine the effect of 25 (OH) D levels on the established poor prognostic factors for PTC. RESULTS: We observed a negative correlation between 25 (OH) D levels and tumor size (r = -0.067, P = 0.049). Severe VDD and moderate VDD were independently associated with lymph node metastasis and distant metastasis diagnosed during surgery (P = 0.00, odds ratio (OR) = 4.11; P = 0.00, OR = 3.33, respectively). After adjusting parameters such as sex, age, body mass index, and thyroid-stimulating hormone (TSH) levels, severe VDD and moderate VDD were found to be closely associated with advanced cancer stage (stage III or IV) (P = 0.018, OR = 3.02; P = 0.041, OR = 3.60, respectively). Additionally, a significant correlation (P = 0.007) was observed between the pre-operative 25 (OH) D and TSH levels. CONCLUSION: 25 (OH) D levels were significantly associated with certain poor prognostic factors for PTC, including larger tumor diameter and the occurrence of lymph node metastasis. More prospective studies are needed to evaluate whether the assessment and supplementation of vitamin D contributes to the pre-operative management of patients with PTC.

Role of the 2018 American Thyroid Association statement on postoperative hypoparathyroidism: a 5-year retrospective study.

BACKGROUND: Definitions of postoperative hypoparathyroidism (hypoPT) have never reached consent until the American Thyroid Association (ATA) statement was released, with new characteristics and challenges. METHODS: Patients with papillary thyroid carcinoma who underwent primary total thyroidectomy between January 2013 and June 2018 were retrospectively enrolled. Symptoms of hypocalcemia and their frequency were stringently followed. Patients were divided into groups according to the ATA statement. Incidence of postoperative hypoPT and serum parathyroid hormone levels accompanied by calcium levels, from 1-day to at least 24-month follow-up. RESULTS: A total of 1749 patients were included: 458 (26.2%) had transient and 63 (3.6%) had permanent hypoPT. Transient hypoPT was found in 363 (20.7%) patients with biochemical hypoPT, 72 (4.1%) with clinical hypoPT, and 23 (1.3%) with relative hypoPT; permanent hypoPT was detected in 8 (0.5%) patients with biochemical hypoPT, 55 (3.1%) with clinical hypoPT, and none with relative hypoPT. Female sex, age ≥ 55 years, unintentional parathyroid gland resection, and autotransplantation of ≥ 2 parathyroid glands were independent risk factors for transient biochemical hypoPT. Age ≥ 55 years, bilateral central neck dissection, and isthmus tumor location were independent risk factors for transient clinical hypoPT. A postoperative 1-day percentage of parathyroid hormone (PTH) reduction of > 51.1% was an independent risk factor for relative hypoPT (odds ratio, 4.892; 95% confidence interval, 1.653-14.480; P = 0.004). No independent risk factor for permanent hypoPT was found. CONCLUSION: ATA diagnostic criteria for postoperative hypoPT are of great value in differentiating patients by hypocalcemia symptoms and choosing corresponding clinical assistance; however, they may underestimate the actual incidence.

Selective Parathyroid Autotransplantation During Total Thyroidectomy for Papillary Thyroid Carcinoma: A Cohort Study.

Purpose: The relationship between the selective parathyroid gland (PG) autotransplantation and hypoparathyroidism is still not completely clear. The aim was to ascertain whether the number of autotransplanted PGs affected the incidence of hypoparathyroidism and recovery of parathyroid function in the long-term for patients with papillary thyroid carcinoma (PTC). Methods: A retrospective cohort study included all patients with PTC who had underwent primary total thyroidectomy with central neck dissection between January 2013 and December 2017. The patients were divided into three groups (0, 1, and 2 PGs autotransplanted, respectively). Results: Of the 2,477 patients, 634 (25.6%) received no PG autotransplantation, 1,078 (43.5%) and 765 (30.9%) were autotransplanted 1 and 2 PGs, respectively, and the incidence of permanent hypoparathyroidism (>1 year) was 1.7%, 0.7%, and 0.4% (P = 0.0228). Both 1 or 2 PGs autotransplanted increased the incidence of transient biochemical hypoparathyroidism (odds ratio [OR], 1.567; 95% confidence interval [CI], 1.258-1.953; P < 0.0001; OR, 2.983; 95% CI, 2.336-3.810; P < 0.0001, respectively) but reduced the incidence of permanent hypoparathyroidism (OR, 0.373; 95% CI, 0.145-0.958; P = 0.0404; OR, 0.144; 95% CI, 0.037-0.560; P = 0.0052, respectively). Both 1 or 2 PGs autotransplanted did not independently influence the occurrence of hypocalcemia symptoms. Conclusion: Selective parathyroid autotransplantation is less likely to lead to post-operative symptomatic hypocalcemia, although it could lead to a transient decrease in parathyroid hormone. However, in the long run, it is still an effective strategy to preserve parathyroid function.