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.

Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Total thyroidectomy versus less-than-total thyroidectomy for papillary thyroid carcinoma of isthmus: a systematic review and meta-analysis.

Background: Papillary thyroid carcinoma of isthmus (PTCI) has a more aggressive nature, a higher rate of lymph node metastasis and tumor recurrence. Clinicians have different preferences for the surgical approach to PTCI, but there are no definitive guidelines. The purpose of this article is to compare the oncologic outcomes and complications of total thyroidectomy and less-than-total thyroidectomy for PTCI using meta-analysis. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for articles that met the inclusion criteria, with an unlimited start date and an end date of February 19, 2023. Exclusion criteria were applied to filter out articles for further analysis. Ultimately, seven articles were used for analysis, all of which were retrospective studies. The MINORS scale was adopted to evaluate the quality of the included literature, and Review Manager 5.4 was used for data analysis. Results: A total of 814 patients were included in the seven articles, including 401 in the less-than-total thyroidectomy group (trial group) and 413 in the total thyroidectomy group (control group). The results of the meta-analysis showed that there was no significant difference in the tumor recurrence rate between the two groups after total thyroidectomy or less-than-thyroidectomy for PTCI (odds ratio, 1.51; 95% confidence interval: 0.49, 4.65; P=0.47), and there was no statistical difference in the incidence of all postoperative complications between the two groups. Conclusions: There may be some limitations in this analysis, such as publication bias and the fact that the included articles were all retrospective studies with a certain degree of heterogeneity. PTCI patients with early staging and no significant lymph node metastases may be able to choose a more conservative surgical approach, which is less-than-total thyroidectomy. Patients with relatively late staging and significant preoperative lymph node metastases or extra thyroidal extension may opt for total thyroidectomy plus lymph node dissection in the central region and, if necessary, lymph node dissection in the lateral cervical region.

Trends, Influence Factors, and Doctor-Patient Perspectives of Web-Based Visits for Thyroid Surgery Clinical Care: Cross-Sectional Study.

BACKGROUND: In recent years, the new generation of telecommunication technologies has profoundly changed the traditional medical industry. To alleviate the medical difficulties faced by patients with thyroid diseases, hospitals have opened web-based visits and actively combined online-to-offline outpatient services. OBJECTIVE: This study aims to explore differences between office and web-based outpatient services from doctors' and patients' perspectives, illustrate the effect of the COVID-19 pandemic on outpatient services, and provide clues for improving the online-to-offline mode of care for patients with thyroid diseases. METHODS: We collected the complete web-based and office outpatient records of the Thyroid Surgery Center of West China Hospital. A total of 300,884 completed patient encounters occurred (201,840 office visits and 99,044 web-based visits) from January 1, 2019, to May 31, 2022. We performed logistic regression to evaluate the association between the chosen visit type and patients' sociodemographic characteristics. RESULTS: The number of web-based visits rapidly increased since March 2020 and reached 45.1% (4752/10,531) of all encounters in December 2021. The COVID-19 pandemic dramatically accelerated the development of web-based visits. Web-based visits were preferred by patients 18-45 years old (odds ratio [OR] 2.043, 95% CI 1.635-2.552, P<.001), patients with relatively high-paying jobs (technical staff: OR 1.278, 95% CI 1.088-1.479, P=.003; office clerk: OR 1.25, 95% CI 1.07-1.461, P=.005; national public servant: OR:1.248, 95% CI 1.042-1.494, P=.02), and patients living in Sichuan Province (excluding Chengdu; OR 1.167, 95% CI 1.107-1.23, P<.001). The medicine cost (P<.001) and examination cost (P<.001) of office visits were significantly higher than those of web-based visits. CONCLUSIONS: Web-based outpatient visits have increased rapidly in recent years, and the COVID-19 pandemic has boosted their development. The preference for web-based visits was influenced by the socioeconomic and demographic characteristics of both patients and doctors.

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.

Transoral Endoscopic Thyroidectomy Vestibular Approach for Thyroid Lobectomy.

The manuscript describes the transoral endoscopic thyroidectomy vestibular approach (TOETVA) for thyroid lobectomy. The patient is placed in the supine position with extension and fixation of the neck. One 20 mm transverse incision and two 5 mm incisions are made through the mucosa of the oral vestibule for camera and instrument placement after disinfection of the skin and oral cavity. The workspace is established and maintained by the skin suspension device, which is made of unabsorbable string (3-0) and rubber bands, and the CO2 insufflation pressure. Lobectomy using a medial-to-lateral technique and prophylactic ipsilateral central neck dissection is performed simultaneously on patients with papillary thyroid cancer (PTC). The specimen is extracted through the 20 mm incision. The parathyroid gland is immediately searched for in the specimen and auto-transplanted to the left brachioradialis. A drainage tube is inserted through the retractor hole into the bed of the thyroid gland, and absorbable sutures are used to close the mucosal incisions in the oral vestibule and the linea alba cervicalis. Prophylactics administered intravenously are recommended for the first 24 h after surgery, and oral antibiotics are used for 7 days postoperatively.

Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model.

In recent years, Hashimoto's thyroiditis (HT) has become the most common autoimmune thyroid disease. It is characterized by lymphocyte infiltration and the detection of specific serum autoantibodies. Although the potential mechanism is still not clear, the risk of Hashimoto's thyroiditis is related to genetic and environmental factors. At present, there are several types of models of autoimmune thyroiditis, including experimental autoimmune thyroiditis (EAT) and spontaneous autoimmune thyroiditis (SAT). EAT in mice is a common model for HT, which is immunized with lipopolysaccharide (LPS) combined with thyroglobulin (Tg) or supplemented with complete Freund's adjuvant (CFA). The EAT mouse model is widely established in many types of mice. However, the disease progression is more likely associated with the Tg antibody response, which may vary in different experiments. SAT is also widely used in the study of HT in the NOD.H-2h4 mouse. The NOD.H2h4 mouse is a new strain obtained from the cross of the nonobese diabetic (NOD) mouse with the B10.A(4R), which is significantly induced for HT with or without feeding iodine. During the induction, the NOD.H-2h4 mouse has a high level of TgAb accompanied by lymphocyte infiltration in the thyroid follicular tissue. However, for this type of mouse model, there are few studies to comprehensively evaluate the pathological process during the induction of iodine. A SAT mouse model for HT research is established in this study, and the pathologic changing process is evaluated after a long period of iodine induction. Through this model, researchers can better understand the pathological development of HT and screen new treatment methods for HT.

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.

Production of 5-aminolevulinic acid from hydrolysates of cassava residue and fish waste by engineered Bacillus cereus PT1.

The economical production of 5-aminolevulinic acid (ALA) has recently received increasing attention for its extensive use in agriculture. In this study, a strain of Bacillus cereus PT1 could initially produce ALA at a titre of 251.72 mg/L by using a hydrolysate mixture of low-cost cassava residue and fish waste. The integration of endogenous hemA encoding glutamyl-tRNA reductase led to a 39.30% increase in ALA production. Moreover, improving cell permeability by deletion of the LytR-CpsA-Psr (LCP) family gene tagU led to a further increase of 59.73% in ALA production. Finally, the engineered strain B. cereus PT1-hemA-ΔtagU produced 2.62 g/L of ALA from the previously mentioned hydrolysate mixture in a 7-L bioreactor. In a pot experiment, foliar spray of the ALA produced by B. cereus PT1-hemA-ΔtagU from the hydrolysates increased salt tolerance of cucumber by improving chlorophyll content and catalase activity, while decreasing malondialdehyde content. Overall, this study demonstrated an economic way to produce ALA using a microbial platform and evidenced the potential of ALA in agricultural application.

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.

Pretracheal Lymph Node Subdivision in Predicting Contralateral Central Lymph Node Metastasis for Unilateral Papillary Thyroid Carcinoma: Preliminary Results.

Background: The aims of this study were to assess the clinical value of pretracheal lymph node subdivision in identifying patients with contralateral central lymph node metastasis (CLNM) and risk factors for occult contralateral CLNM in unilateral PTC. Methods: A total of 139 unilateral PTC patients with a clinically node-negative neck (cN0) who underwent bilateral central neck dissection (CND) were prospectively enrolled. Intraoperatively, the pretracheal region was further divided into ipsilateral and contralateral subregions. Ipsilateral and contralateral pretracheal lymph nodes (LNs) as well as other CLNs (prelaryngeal, ipsilateral paratracheal and contralateral paratracheal) were labeled separately and sent for pathological examination. Demographic and clinicopathologic variables were analyzed to identify factors predictive of contralateral CLNM. Results: Of 139 patients, bilateral CLNM was present in 37 (26.6%) patients. Contralateral pretracheal LNM was significantly associated with contralateral CLNM. In multivariate analysis, prelaryngeal LNM (P = 0.004, odds ratio = 3.457) and contralateral pretracheal LNM (P = 0.006, odds ratio = 3.362) were identified as risk factors for contralateral CLNM. Neither neck recurrence nor distant metastasis was observed within the mean follow-up duration of 9.1 ± 1.8 months. Conclusions: In most unilateral cN0 PTCs, performing ipsilateral CND is appropriate, while patients presenting with evident nodal disease intraoperatively or preoperatively in the contralateral central neck should undergo bilateral CND. Intraoperative re-evaluation of prelaryngeal and contralateral pretracheal LNs may be helpful in determining the extent of CND.

Non-Linear Correlation Between Tumor Size and Survival Outcomes for Parathyroid Carcinoma: A SEER Population-Based Cohort Study.

Background: Parathyroid carcinoma (PC) is a rare malignancy without a commonly acknowledged prognostic assessment and treatment system. This study captures how independent prognostic factors and tumor size correlate with outcomes in patients with PC. Methods: The Surveillance, Epidemiology, and End Results database was used to perform a retrospective analysis on PC patients from 2000 to 2018. Univariate and multivariable survival analyses were performed to evaluate cancer-specific survival (CSS) and overall survival (OS), to identify independent prognostic factors in the PC patient population. A generalized additive model was applied to conduct smooth curve fitting and to examine the association between tumor size and relative risk of death. Results: A total of 590 patients were included. The 5- and 10-year OS were 80.8% and 67.1%, respectively. 5- and 10-year CSS was estimated to be 93.6% and 92.1%, respectively. The association between tumor size and relative risk of death can be generalized as a U-shaped curve. The mortality risk reaches its lowest point when tumor diameter approaches 2cm. At a tumor diameter cutoff of 3cm for CSS and 4cm for OS, there is an abrupt drop in survival rates. Multivariate Cox analysis revealed age, no surgery, and debulking surgery as consistent predictors of lower OS and CSS. Conclusions: A non-linear correlation between tumor size and death risk has been identified in patients with PC, along with an accurate size threshold at which survival rates sharply decrease. Further investigation is needed to determine if these trends are seen in other malignancies with promising prognoses.