The prognostic value of lymph node dissection in patients with parathyroid carcinoma.

Background: Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Methods: Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer-specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. Results: The 5- and 10-year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). Conclusions: PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

Circulating small extracellular vesicle-based miRNA classifier for follicular thyroid carcinoma: a diagnostic study.

BACKGROUND: The diagnosis of follicular thyroid carcinoma (FTC) prior to surgery remains a major challenge in the clinic. METHODS: This multicentre diagnostic study involved 41 and 150 age- and sex-matched patients in the training cohort and validation cohort, respectively. The diagnostic properties of circulating small extracellular vesicle (sEV)-associated and cell-free RNAs were compared by RNA sequencing in the training cohort. Subsequently, using a quantitative real-time polymerase chain reaction (qRT‒PCR) assay, high-quality candidates were identified to construct an RNA classifier for FTC and verified in the validation cohort. The parallel expression, stability and influence of the RNA classifier on surgical strategy were also investigated. RESULTS: The diagnostic properties of sEV long RNAs, cell-free long RNAs and sEV microRNAs (miRNAs) were comparable and superior to those of cell-free miRNAs in RNA sequencing. Given the clinical application, the circulating sEV miRNA (CirsEV-miR) classifier was developed from five miRNAs based on qRT‒PCR data, which could well identify FTC patients (area under curve [AUC] of 0.924 in the training cohort and 0.844 in the multicentre validation cohort). Further tests revealed that the CirsEV-miR score was significantly correlated with the tumour burden, and the levels of sEV miRNAs were also higher in sEVs from the FTC cell line, organoid and tissue. Additionally, circulating sEV miRNAs remained constant after different treatments, and the addition of the CirsEV-miR classifier as a biomarker improves the current surgical strategy. CONCLUSIONS: The CirsEV-miR classifier could serve as a noninvasive, convenient, specific and stable auxiliary test to help diagnose FTC following ultrasonography.

Exosome-mediated delivery of miR-519e-5p promotes malignant tumor phenotype and CD8+ T-cell exhaustion in metastatic PTC.

CONTEXT: Distant metastases are the primary cause of therapy failure and mortality in patients with papillary thyroid carcinomas (PTCs). However, the underlying mechanism responsible for the initiation of tumor cell dissemination and metastasis in PTCs has rarely been investigated. OBJECTIVE: The aim of this study was to investigate effects and underlying molecular mechanisms of circulating exosomal microRNAs (miRNAs) in distant metastatic PTCs. METHODS: The most relevant circulating exosomal miRNA to distant metastatic PTCs were verified between distant metastatic PTCs and nondistant metastatic PTCs by miRNA microarray, quantitative real-time polymerase chain reaction (qRT‒PCR) assays and receiver operating characteristic (ROC) curves. The parental and recipient cells of that circulating exosomal miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of circulating exosomal miRNAs that contribute to the development of distant metastases. RESULTS: We identified that PTC-derived exosomal miR-519e-5p was significantly upregulated in the circulatory system in distant metastatic PTCs. Further tests demonstrated that PTC cells can acquire a more malignant phenotype via hnRNPA2B1 mediated sorting of tumor suppressor miR-519e-5p into exosomes to activate Wnt signaling pathway via upregulating PLAGL2. Furthermore, miR-519e-5p included in PTC-derived exosomes can be transferred to recipient CD8+ T cells and aid in tumor immune escape in distant organs through inhibiting Notch signaling pathway by downregulating NOTCH2. CONCLUSION: Our findings highlighted the dual role of PTC-derived exosomal miR-519e-5p in distant metastasis, which may improve our understanding of exosome-mediated distant metastatic mechanisms.

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.

Identification of Circulating Exosomal microRNAs Associated with Radioiodine Refractory in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) has a favorable prognosis, but a fraction of cases show progressive behaviors, becoming radioiodine refractory (RAIR) PTC. To explore circulating exosomal microRNAs (miRNAs) associated with RAIR PTC, the miRNA profiles in exosomes from parental and induced RAIR cell lines were firstly identified with a next-generation sequencing technique. The Na+/I- symporter (NIS) related miRNAs were then validated by quantitative real-time PCR (qRT-PCR) in plasma of PTC patients with non-131I-avid metastases and those with 131I-avid metastases. The regulation of exosomal miRNAs on NIS were also verified. We identified that miR-1296-5p, upregulation in exosomes from RAIR cell lines, and the plasma of patients with RAIR PTC achieved the largest areas under the curve (AUC) of 0.911 and that it is an independent risk factor for RAIR PTC. In addition, miR-1296-5p was abundantly detected in the tissue of RAIR PTC and can directly target downstream gene of NIS. Taken together, our findings suggested that circulating exosomal miRNAs, particularly miR-1296-5p, may be involved in the pathogenesis of RAIR PTC by directly targeting NIS.

Clinicopathologic Characteristics and Outcomes of Massive Multinodular Goiter: A Retrospective Cohort Study.

Background: Thyroidectomy for massive goiters is challenging because of the increased risk of tracheomalacia, combined sternotomy, postoperative morbidity, and mortality, whereas studies investigating the clinicopathologic characteristics, postoperative morbidities, and surgical outcomes of massive goiters are limited. Methods: Patients with goiters undergoing thyroid surgery between 2009 and 2019 were retrospectively reviewed. A total of 227 patients were enrolled and divided into massive goiter group and large goiter group according to the weight of the goiter. Clinicopathologic characteristics, postoperative morbidities, and surgical outcomes were compared between the two groups. Results: Seventy-four patients (32.6%) had a goiter weighing more than 250 g and 153 patients (67.4%) were categorized in the large goiter group. Compared to large goiter patients, massive goiter patients had higher rates of retrosternal extension (82.4% vs. 30.7%), combined sternotomy (12.2% vs. 1.3%), intensive care unit admission (25.7% vs. 7.2%), transient hypoparathyroidism (41.9% vs. 25.5%), and transient recurrent laryngeal nerve palsy (10.8% vs. 3.3%) as well as prolonged length of hospital stay (P < 0.05). Conclusions: Massive goiter patients were at increased risk of combined sternotomy, intensive care unit admission, postoperative morbidities as well as prolonged length of hospital stay after thyroidectomy compared to large goiter patients, but most of them can be treated through a cervical approach with a favorable outcome.

Risk stratification in patients with anaplastic thyroid carcinoma: role of age.

BACKGROUND: Thyroid carcinoma is the only cancer that regards age as an important predictor of thyroid cancer-specific survival (CSS). While the 8th American Joint Committee on Cancer (AJCC) staging system raised the age cutoff from 45 to 55 years for differentiated thyroid carcinoma (DTC) to more accurately predict the prognosis, there is no new information regarding the role of age in the prognosis of anaplastic thyroid carcinoma (ATC). The aim of this study was to determine the optimal age cutoff values for mortality risk stratification in ATC patients. Furthermore, a nomogram to predict ATC CSS was developed in each age group. METHODS: Patients diagnosed with ATC between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. After applying inclusion and exclusion criteria, a total of 1140 patients were enrolled as cohort 1 to describe the characteristics of ATC, while a total of 556 patients were included as cohort 2 to determine age cutoff values for risk stratification by X-tile program. Training set and testing set were randomly generated to develop and validate a predictive nomogram of CSS in each age group. RESULTS: The 6-month, 1-year, and 2-year survival was 27.6%, 15.1%, and 6.2%, respectively, in cohort 1. X-tile program results showed that the optimal age cutoff values for mortality risk stratification were 65 and 85 years old (p < 0.001). Distant metastasis was independently associated with CSS in patients younger than 85 years old, and these patients benefited more from complete resection of the tumor and radiotherapy/chemotherapy. However, no predictors of CSS were identified in patients over 85 years old, and interventions (surgery, radiotherapy, and chemotherapy) targeting ATC had little role in disease control in these patients. The nomogram was developed and validated based on the independent CSS predictors in each age group. The C-index values of the training set and testing set were 0.735 [95% CI, 0.696-0.774] and 0.733 [95% CI, 0.663-0.804] for CSS in patients of ≤64 years old, while the values were 0.767 [95% CI, 0.730-0.804] and 0.783 [95% CI, 0.718-0.848] in patients of 65-84 years old. All of the C-index values were larger than 0.7, which showed acceptable prediction performance of the nomograms. CONCLUSIONS: Age can be used as an auxiliary stratification factor of prognosis in ATC patients. The survival may be improved in patients younger than 85 years old if combination therapy (surgery, radiotherapy, and chemotherapy) was indicated and applicable, while no optimal therapeutic strategy was determined in patients older than 85 years old. The established nomograms can provide good prediction of CSS according to age group.

Distant metastasis in medullary thyroid carcinoma: Clinical outcomes and implications of T stage.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer tumour, node, and metastasis staging system did not take T stage into consideration when evaluating Stage IV C medullary thyroid carcinoma (MTC) patients. The aim of this study is to investigate the clinical outcomes and implications of T stage in this population. METHODS: Eligible patients from the Surveillance, Epidemiology, and End Results database and the Department of Thyroid Surgery in West China Hospital of Sichuan University and who were diagnosed with Stage IV C MTC were included in this study. The overall survival (OS), the cancer-specific survival (CSS), and the precise cause of MTC-induced death were analysed. The potential risk factors, including the T stage, in the OS and CSS were evaluated by univariate and multivariate Cox regression models. RESULTS: This retrospective study enroled 204 Stage IV C MTC patients. The 5- and 10-year OS rates were 31.8% and 17.1%, respectively, and the 5- and 10-year CSS rates were 40.4% and 22.5%, respectively. More importantly, the rates of MTC-induced death between primary or distant metastatic lesions in Stage IV C MTC patients were comparable in our institution. Additionally, the univariate and multivariate analyses demonstrated that the presence of an advanced T stage was an independent prognostic factor for both the OS (T4 vs. T1-T3, hazard ratio [HR]: 1.714, 95% confidence interval [CI]: 1.175-2.500, p = .005) and the CSS (T4 vs. T1-T3, HR: 1.848, 95% CI: 1.229-2.780, p = .003). CONCLUSION: To achieve a better risk stratification, further classification of Stage IV C MTC patients by the T stage may be preferable.

Case Report: A New Entity: Multiple Differentiated Variant of Papillary Thyroid Carcinoma With Advanced Clinical Behavior.

There are many histological morphological types of papillary thyroid carcinoma (PTC), but the most frequently seen types are conventional. A single PTC commonly has a conventional and/or a variant morphological pattern. PTC with multiple (more than two) well-differentiated morphological patterns are extremely rare. We herein report the rare case of a 48-year-old male with initial diaphragmatic, pancreatic, and liver tumors from PTC. Then, the PTC was discovered following resection of these tumors, an ultrasound-guided fine-needle aspiration (US-FNA) cytology of a huge mass in the thyroid's left lobe revealed a PTC. After postoperative recovery, physical and ultrasound examinations identified an irregular large nodule in the thyroid's isthmus and left lobe, several swollen lymph nodes in the left neck, a mass in the left gluteus maximus, and several masses in both the bilateral parotid and salivary regions. The US-FNA's pathological examination confirmed metastatic PTCs in the left gluteus maximus and bilaterally in the parotid and salivary glands. An 18-fluorodeoxyglucose positron-emission tomography and computed tomography scan revealed abnormal uptakes in numerous locations (e.g., thyroid's isthmus and left lobe, bilateral parotid gland, and subcutaneous tissues). The patient underwent palliative therapy-including total thyroidectomy, bilateral central neck dissection, left lateral neck dissection, and excision of the bilateral parotid and salivary glands. A whole-body scan post-therapeutic radioactive iodine ablation revealed exclusive thyroid bed uptake. The patient subsequently underwent thyroid stimulating hormone (TSH) repression therapy and chemotherapy with lenvatinib, and thereafter achieved stable clinical conditions. Further histopathological analysis of the PTC revealed multiple differentiated morphological patterns in the single tumor located in the isthmus and left lobe of the thyroid, and in some metastatic lesions. Different metastatic lesions also presented different morphological patterns of PTC. In conclusions, we identified a new entity of PTC as a multiple differentiated variant of PTC (MDV-PTC) with an aggressive clinical nature.

Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. METHODS: Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. RESULTS: The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. CONCLUSIONS: This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

Pseudomonas aeruginosa injection decreases drainage in lateral neck dissection for metastatic thyroid cancer.

BACKGROUND: Pseudomonas aeruginosa injection (PAI) has been proven effective against chylous fistula but not in decreasing drainage after lateral neck dissection (LND). To verify the safety of spraying PAI onto the surface of the traumatic cavity after total thyroidectomy with LND and to evaluate whether its application can reduce the drainage volume. METHODS: A total of 85 patients with metastatic papillary thyroid cancer (PTC) who agreed to total thyroidectomy with unilateral LND were recruited from March 2016 to September 2017. During the operation, PAI was applied in 44 patients, while 41 remaining patients served as the control group. The thyroid function and parathyroid function, drainage volume, hospital stay, and incidence of complications were compared between the two groups. RESULTS: The groups had few differences in age, gender, BMI, thyroid function, parathyroid function, diameter of tumor, and the number of the harvested lymph nodes. The median total drainage volume was significantly smaller and the mean hospital stay was obviously shorter in the PAI group compared to the non-PAI group. But the median volumes of peak 24-hour drainage which appeared during the first day after operation had few differences in the two groups. Postoperative fever in the PAI group was higher than in the non-PAI group. None of the patients had permanent recurrent laryngeal nerve paralysis and tumor recurrence on the 12th month after operation. CONCLUSIONS: The application of PAI to the wound cavity after LND is safe and effective for reducing the drainage volume and hospital stay.

A miRNA-clinicopathological nomogram for the prediction of central lymph node metastasis in papillary thyroid carcinoma-analysis from TCGA database.

It is of significance to evaluate central lymph node status in patients with papillary thyroid carcinoma (PTC), because it can decrease postoperative complications resulting from unnecessary prophylactic central lymph node dissection (CLND). Due to the low sensitivity and specificity of neck ultrasonography in the evaluation of central lymph node metastasis (CLNM), it is urgently required to find alternative biomarkers to predict CLNM in PTC patients, which is the main purpose of this study.RNA-sequencing datasets and clinical data of 506 patients with thyroid carcinoma from the Cancer Genome Atlas (TCGA) database were downloaded and analyzed to identify differentially expressed miRNAs (DEMs), which can independently predict CLNM in PTC. A nomogram predictive of CLNM was developed based on clinical characteristics and the identified miRNAs. Receiver operating characteristics curves were drawn to evaluate the predictive performance of the nomogram. Bioinformatics analyses, including target genes identification, functional enrichment analysis, and protein-protein interaction network, were performed to explore the potential roles of the identified DEMs related to CLNM in PTC.A total of 316 PTC patients were included to identify DEMs. Two hundred thirty-seven (75%) PTC patients were randomly selected from the 316 patients as a training set, while the remaining 79 (25%) patients were regarded as a testing set for validation. Two DEMs, miRNA-146b-3p (HR: 1.327, 95% CI = 1.135-1.551, P = .000) and miRNA-363-3p (HR: 0.714, 95% CI = 0.528-0.966, P = .029), were significantly associated with CLNM. A risk score based on these 2 DEMs and calculating from multivariate logistic regression analysis, was significantly lower in N0 group over N1a group in both training (N0 vs N1a: 2.04 ±â€Š1.01 vs 2.73 ±â€Š0.61, P = .000) and testing (N0 vs N1a: 2.20 ±â€Š0.93 vs 2.79 ±â€Š0.68, P = .003) sets. The nomogram including risk score, age, and extrathyroidal extension (ETE) was constructed in the training set and was then validated in the testing set, which showed better prediction value than the other three predictors (risk score, age, and ETE) in terms of CLNM identification. Bioinformatics analyses revealed that 5 hub genes, SLC6A1, SYT1, COL19A1, RIMS2, and COL1A2, might involve in pathways including extracellular matrix organization, ion transmembrane transporter activity, axon guidance, and ABC transporters.On the basis of this study, the nomogram including risk score, age, and ETE showed good prediction of CLNM in PTC, which has a potential to facilitate individualized decision for surgical plans.

Diagnostic and prognostic value of preoperative systemic inflammatory markers in anaplastic thyroid cancer.

BACKGROUND: Easily accessible, generalized, and inexpensive methods are expected to differentiate anaplastic thyroid carcinoma (ATC) from advanced differentiated thyroid cancer (aDTC). We aimed to explore potential diagnostic and prognostic value of systematic inflammatory markers (SIMs) in ATC and aDTC. METHODS: About 22 ATC, 101 aDTC, and 100 matched early DTC patients were analyzed retrospectively. SIMs included the comprehensive index, neutrophil-monocyte-platelet-to-lymphocyte ratio (NMPLR) and the previously reported ones. Receiver operating characteristic, Kaplan-Meier, and COX regression analyses were mainly conducted. RESULTS: NMPLR exhibited the highest area under the curve value 0.806 (P < .0001) to diagnose ATC from aDTC. NMPLR was identified as an independent risk factor for overall survival (OS) (hazard ratio [HR]: 47.821, 95% confidence interval [CI], 2.863-798.765, P = .007) in ATC, as well as for OS (HR: 7.360, 95% CI, 1.620-33.430, P = .010) and recurrence-free survival (HR: 4.172, 95% CI, 1.139-15.286, P = .031) in aDTC. Taken both refractory types (ATC and aDTC) together, NMPLR could independently predict OS (HR: 6.470; 95% CI, 2.134-19.616; P = .001). CONCLUSION: NMPLR is a generalized index. It showed excellent potential in differential diagnosis and survival prediction in refractory thyroid cancer. However, it needs to be validated in larger cohort and clinical practice.

A Nomogram to Predict Hungry Bone Syndrome After Parathyroidectomy in Patients With Secondary Hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTX) has been demonstrated as an effective treatment for patients with secondary hyperparathyroidism (SHPT) of renal origin. However, severe hypocalcemia, called hungry bone syndrome (HBS), is a common complication following PTX in these patients and can lead to poor clinical outcomes, even death. Therefore, exploring risk factors for HBS and establishing a prediction nomogram allow intensive monitoring and prompt treating this postoperative complication, which is the main purpose of this study. METHODS: From October 2016 to October 2018, PTX with autotransplantation (PTX + AT) procedures were performed in 131 patients with SHPT of renal origin by a surgeon and his team in the Thyroid and Parathyroid Surgery Center, West China Hospital, Sichuan University, China. After applying the inclusion and exclusion criteria, a total of 114 patients were enrolled for analyses in this study. Comprehensive data including preoperative, intraoperative, and postoperative variables were prospectively collected and retrospectively analyzed. The univariate and multivariate logistic regression analyses with internal validation by bootstrapping were used to confirm independent risk factors for postoperative HBS. The nomogram was developed based on the statistical analysis results. Receiver operator characteristic (ROC) curves were drawn to compare the prediction performance among different predictors. RESULTS: The occurrence of postoperative HBS was 76.3% (87 out of 114 patients) in this study. Univariate analysis showed that preoperative intact parathyroid hormone (iPTH), serum alkaline phosphatase, bone-specific alkaline phosphatase (bone-ALP) were significantly higher in HBS group than those in non-HBS group, while preoperative corrected serum calcium and albumin were significantly lower in HBS group than those in non-HBS group. Total weight of resected parathyroid glands was significantly heavier in HBS group versus non-HBS group. Multivariate logistic regression analysis with internal validation by bootstrapping demonstrated preoperative iPTH, bone-ALP, preoperative corrected serum calcium, and total weight of resected parathyroid glands were independently associated with postoperative HBS. The nomogram including the abovementioned four independent predictors was constructed and showed better prediction performance than the other four predictors in terms of postoperative HBS. CONCLUSIONS: On the basis of this study, we found higher preoperative iPTH level, higher bone-ALP level, heavier total weight of resected parathyroid glands, and lower preoperative corrected serum calcium level were independent predictors of postoperative HBS in patients with SHPT of renal origin. The nomogram can expediently, accurately, and objectively predict the risk of postoperative HBS in individual patient with SHPT of renal origin.

Association of the Preoperative Inflammation-Based Scores with TNM Stage and Recurrence in Patients with Papillary Thyroid Carcinoma: A Retrospective, Multicenter Analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) have been reported to be prognostic biomarkers in various cancers. Our study evaluated whether the preoperative NLR, PLR and PNI predicted tumor-node-metastasis (TNM) stage and recurrence in papillary thyroid carcinoma (PTC) patients. METHODS: A total of 1873 patients with PTC from 9 centers in mainland China were retrospectively assessed. Receiver operating characteristic (ROC) curves were generated, and Kaplan-Meier analyses were performed to evaluate the prognostic value of inflammation-based scores. Univariate and multivariate analyses were conducted to identify risk factors for recurrence. RESULTS: A decreased PNI and an increased PLR were predictive of TNM stage (p=0.005 and p=0.030, respectively), while a decreased NLR was predictive of recurrence (p=0.040). Univariate and multivariate analyses indicated that N1 status (odds ratio (OR), 1.898; 95% confidence interval (CI), 1.253-2.874; p=0.002), NLR≤1.6 (OR, 1.596; 95% CI, 1.207-2.111; p=0.001) and PNI≤53.1 (OR, 1.511; 95% CI, 1.136-2.009; p=0.005) were independent factors that predicted recurrence. CONCLUSION: The NLR, PLR and PNI have predictive value for TNM stage and recurrence in patients with PTC, but their predictive efficiency is limited. Caution should be used when considering clinical applications of inflammation-based scores.

Plasma Exosomal miR-146b-5p and miR-222-3p are Potential Biomarkers for Lymph Node Metastasis in Papillary Thyroid Carcinomas.

BACKGROUND: Lymph node metastasis (LNM) is associated with increased risk of recurrence and poor prognosis in papillary thyroid cancer (PTC). Novel non-invasive biomarkers for the prediction of LNM in PTC patients are still urgently needed. In this study, the relationship between the expression of plasma exosomal microRNAs (miRNAs) and LNM was analyzed. Further, we aimed to explore if exosomal miRNAs can serve as indicators of LNM in PTC patients. METHODS: A total of 64 PTC patients who underwent total thyroidectomy and neck dissection from June 2018 to July 2018 in West China Hospital were enrolled in this study. Plasma exosomes were isolated by exoRNeasy Serum/Plasma Maxi Kit. The levels of selected exosomal miRNAs were detected by real-time quantitative PCR (qRT-PCR). Cox proportional hazard analyses and receiver operating characteristic (ROC) curves were conducted to evaluate the predictive efficiency. Furthermore, PTC cell lines with transfection of miRNA mimics/inhibitors were used to verify the functions of exosomal miRNAs. RESULTS: 49 PTC patients with LNM and 15 without LNM were included in the present study. Exosomal miR-146b-5p and miR-222-3p were both significantly upregulated in patients with LNM (P values were 0.008 and 0.015, respectively). ROC analyses revealed that the areas under the curves (AUCs) of miR-146b-5p and miR-222-3p for LNM prediction were 0.811 and 0.834, respectively. Moreover, the AUC increased to 0.895 when the two miRNAs used together. Wound healing assays and transwell assays showed that miR-146b-5p and miR-222-3p significantly enhanced the migration and invasion ability of PTC cells in vitro. CONCLUSION: Plasma exosomal miR-146b-5p and miR-222-3p could serve as potential biomarkers for LNM in PTC.

Pseudomonas aeruginosa-mannose sensitive hemagglutinin injection therapy for the treatment of chyle fistula following neck dissection.

BACKGROUND: The efficacy of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) injection therapy in the treatment of chyle fistula following neck dissection is unclear. METHODS: This prospective study enrolled 26 patients who developed chyle fistula after neck dissection. Patients were divided into high-output (>500 mL) and low-output groups (≤500 mL) and were initially treated conservatively for 5 days in the high-output group or 7 days in the low-output group. When conservative treatment failed, topical PA-MSHA therapy was applied. RESULTS: Twelve of 26 patients were cured with conservative treatment, and the remaining 14 patients were all successfully resolved by PA-MSHA therapy. Chyle fistula got resolved in the low-output and high-output groups after the initiation of therapy were at a median 1 days and 6 days, respectively. Among them, 12 (85.7%) patients experienced fever and 11 (78.6%) patients experienced neck pain. CONCLUSIONS: Topical PA-MSHA injection therapy could effectively manage chyle fistula following neck dissection.

Implications of Extrathyroidal Extension Invading Only the Strap Muscles in Papillary Thyroid Carcinomas.

Background: Based on the new TNM classification, differentiated thyroid carcinomas with extrathyroidal extension (ETE) into the strap muscles are designated as T3b. The current study analyzed the clinical significance of this new stage in patients with papillary thyroid cancer (PTC). Subjects and Methods: This retrospective cohort study included 4045 eligible PTC patients. The patients were divided into four groups according to the extent of ETE: no ETE, ETE into perithyroidal tissue, T3b (ETE into the strap muscles), and ETE beyond the strap muscles. Differences in the clinical characteristics and prognosis of the four groups were assessed. Results: Of these 4045 patients, 2300 (56.9%) had no ETE, 1004 (24.8%) had ETE into perithyroidal tissue, 371 (9.2%) had ETE into the strap muscles, and 370 (9.1%) had ETE beyond the strap muscles. Tumor size, multifocality, lymph node metastasis (LNM), distant metastasis (DM), recurrence, and recurrence-free survival (RFS) between patients with ETE into perithyroidal tissue and patients without ETE did not show differences, but significant differences were observed between patients with T3b and patients without ETE, and only patients with ETE beyond the strap muscles had significantly worse overall survival (OS) than the other three groups. However, T3b did not independently predict worse RFS in univariable and multivariable analyses. Conclusions: T3b, distinguished from minimal ETE, may be related to larger tumor size, higher prevalence of multifocality, LNM, DM, recurrence, and worse RFS than no ETE, but it may not affect OS and may not independently predict recurrence in PTC patients.

Association between TERT promoter mutations and clinical behaviors in differentiated thyroid carcinoma: a systematic review and meta-analysis.

BACKGROUND: The association between telomerase reverse transcriptase (TERT) promoter mutations and some clinical behaviors in thyroid cancer remains controversial and requires additional investigation. This study aimed to evaluate the association between TERT promoter mutations and clinical behaviors (including clinicopathological features and prognosis) in differentiated thyroid carcinomas (DTC). METHODS: We performed an up-to-date systematic review and current comprehensive meta-analysis. We searched three electronic databases for relevant studies. We used fixed- or random-effect models to calculate pooled estimated odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs). RESULTS: We included 51 eligible studies incorporating 11,382 cases. Average frequencies of TERT promoter mutations in DTC, papillary (PTC), and follicular (FTC) thyroid carcinomas were 10.9%, 10.6%, and 15.1%, respectively. In DTC and PTC, TERT promoter mutations were significantly associated with sex, age, tumor size, vascular invasion, extrathyroidal extension, lymph node and distant metastases, advanced tumor, nodes, and metastasis (TNM) stage, persistence/recurrence, and disease-specific mortality. In FTC, TERT promoter mutations were significantly associated with age, distant metastases, advanced TNM stage, persistence/recurrence, and disease-specific mortality. CONCLUSIONS: TERT promoter mutations could be considered as biomarkers assisting in risk stratification, prognostic prediction, and individualizing therapeutic options for DTC (PTC and FTC).

Large-Scale Comparative Analysis Reveals A Simple Model To Predict The Prevalence Of Thyroid Nodules.

BACKGROUND: The frequency of thyroid nodules (TNs) has increased rapidly in recent decades. We established a simple, effective model to predict TN occurrence by a large-scale comparative analysis of the Chinese population. SUBJECTS AND METHODS: A total of 13,307 subjects were included to screen risk factors between the case group (TN+) and the control group (TN-) by univariate and multivariate analyses. A simple prediction model formed by a subset of five factors was established. The optimal index points for predicting the prevalence of TNs, the model discriminatory power and the association of the model with the size of TNs were assessed. RESULTS: Age at diagnosis ≥45 years, female sex, body mass index (BMI) ≥24 kg/m2, hypertension, antithyroglobulin antibody (TGAB) ≥16.5 IU/mL were independently related to an increased risk of TNs. The cutoff value of 4 points was found to be the best prediction for the prevalence of TNs in the current study, and the model had better discriminatory power than other single independent predictors. In addition, a positive correlation was also found between the index points and the diameter of TNs. CONCLUSION: Based on our prediction model, thyroid high-resolution ultrasound and associated laboratory tests may be necessary for patients with index points ≥4 due to a higher prevalence of thyroid nodules.