More aggressive biological behavior in pediatric than in adult papillary thyroid carcinoma.

OBJECTIVE: Papillary thyroid carcinoma (PTC) remains a common malignancy of the endocrine system in children and adolescents. This study aimed to investigate the differences in clinical characteristics between children and adults with PTC. METHODS: A total of 360 patients [ 308 adults (≥20 years) and 52 children and adolescents (<20 years)] with PTC who underwent thyroid surgery in our center from 2017 to 2022 were retrospectively analyzed. Statistical analysis and comparisons of the clinicopathological data and tumor characteristics between children and adults were performed. RESULTS: Among all enrolled patients, the mean tumor diameter was 26.21 ± 12.72 mm in the pediatric group, while that in the adult group was 11.62 ± 10.21 mm, which was a significant difference (p < 0.001). Pediatric patients were more prone to central lymph node metastasis (90.38% vs. 49.35%, p<0.001), lateral lymph node metastasis (78.85% vs. 45.7%, p<0.001), capsular invasion (90.38% vs. 63.96%, p<0.001) and extrathyroidal extension (61.54% vs. 15.26%, p＜0.001) than adult patients. However, the pediatric group had a lower BRAFV600E mutation rate (54.76% vs. 87.7%, p < 0.001) and lower incidence of Hashimoto's thyroiditis (15.38% vs. 30.84%, p = 0.023) than the adult group. There were no significant differences in clinicopathological factors, such as sex, multifocality and hypothyroidism. CONCLUSIONS: Pediatric patients were more likely to present with advanced disease at diagnosis, including larger tumor volume, more lymph node metastasis, more extensive local invasion, and lower rates of BRAF mutation and concomitant Hashimoto's thyroiditis. Therefore, appropriate surgical management and comprehensive treatment decisions are needed for pediatric patients with PTC.

Advances in post-translational modifications of proteins and cancer immunotherapy.

Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular molecules. It involves the addition or removal of specific chemical groups on the amino acid residues of proteins. Its common forms include phosphorylation, ubiquitylation, methylation, and acetylation. Emerging research has highlighted lactylation, succinylation, and glycosylation. PTMs are involved in vital biological processes. The occurrence and development of diseases depends on protein abundance and is regulated by various PTMs. In addition, advancements in tumor immunotherapy have revealed that protein PTM is also involved in the proliferation, activation, and metabolic reprogramming of immune cells in tumor microenvironment. These PTMs play an important role in tumor immunotherapy. In this review, we comprehensively summarize the role of several types of PTMs in tumor immunotherapy. This review could provide new insights and future research directions for tumor immunotherapy.

Lymph node ratio independently associated with postoperative thyroglobulin levels in papillary thyroid cancer.

OBJECTIVES: To investigate the impact of the lymph node ratio (LNR) on postoperative thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: This was a retrospective, cohort study. The association between clinicopathological variables and postoperative unstimulated Tg (uTg) levels, preablative-stimulated Tg (sTg) levels, and postablative unstimulated Tg levels was analysed. RESULTS: A total of 300 patients with PTC were identified. Multivariate logistic analysis showed that M classification (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.62-3.34), and postoperative thyroid-stimulating hormone levels (OR, 1.01; 95% CI, 1.01-1.02) were independently associated with postoperative uTg levels. One hundred and sixteen patients underwent radioactive iodine (RAI) therapy. Multivariate analysis showed that LNR in the central neck (OR, 1.24; 95% CI, 1.02-1.51), LNR in the lateral neck (OR, 1.73; 95% CI, 1.09-2.77), RAI dose (OR, 1.43; 95% CI, 1.21-1.69), and M classification (OR, 1.79; 95% CI, 1.22-2.61) were independently associated with preablative sTg levels. Tumour size (OR, 1.01; 95% CI, 1.00-1.01), LNR in the central neck (OR, 1.28; 95% CI, 1.08-1.51), LNR in the lateral neck (OR, 1.66; 95% CI, 1.10-2.49), RAI dose (OR, 1.54; 95% CI, 1.34-1.79), and M classification (OR, 1.56; 95% CI, 1.12-2.19) were also independently associated with postablative uTg levels. CONCLUSION: LNR was independently associated with postoperative Tg levels in patients with PTC. Patients with high LNR were more likely to have incomplete biochemical responses after surgery.

Lymph node ratio as a tool to stratify patients with N1b papillary thyroid cancer.

BACKGROUND: The prognostic significance of lymph node ratio (LNR) in N1b papillary thyroid cancer is unclear. Therefore, the impact of LNR on disease-specific mortality (DSM) and overall survival (OS) in patients with N1b papillary thyroid cancer (PTC) needs to be defined. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database of patients who had undergone thyroidectomy and lymph node dissection. Factors associated with DSM and OS were analyzed and identified using univariate and multivariate Cox proportional risk models. X-tile software was used to find the best cutoff value of LNR. Kaplan-Meier estimates for DSM were plotted for LNR and were compared with the log-rank test. The ROC curve evaluated the validity of the model. RESULTS: A total of 3223 patients with N1b PTC were identified in the SEER database between 1975 and 2019. The best cutoff value for LNR was 0.6. The multivariate Cox proportional risk model showed that age, race, T3/T4 classification, distant metastasis, extent of surgery, number of metastatic lymph nodes, and LNR > 0.6 were independent risk factors for DSM (all p < 0.05). Age, sex, T4 classification, distant metastasis, extent of surgery, and LNR > 0.6 were independent risk factors for OS (all p < 0.05). The Kaplan-Meier method plotted a cumulative risk curve and showed that patients with LNR > 0.6 had a significantly higher risk of DSM than patients with LNR ≤ 0.6 (p = 0.002). CONCLUSION: LNR was a powerful predictor of DSM and OS in N1b PTC patients. LNR could be a useful tool for the stratification of PTC patients with lateral neck metastases.

Single BRAFV600E mutation is not associated with aggressive biological behavior in adolescent and pediatric papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma is more likely to show aggressive biological behaviors in the majority of pediatric patients than in adult patients. The aim of this study was to investigate the mutation rate of the BRAFV600E gene in adolescents and children with papillary thyroid carcinoma and to analyze the association between BRAFV600E gene mutation and tumor-aggressive pathological factors. METHODS: A total of 42 pediatric patients with papillary thyroid carcinoma who underwent thyroid surgery from 2017 to 2022 were studied retrospectively. Whether the BRAFV600E gene mutation in papillary thyroid carcinoma was related to aggressive biological behavior was analyzed. RESULTS: Among the 42 pediatric patients with papillary thyroid carcinoma, the median patient age was 15.71 ± 2.51 years (mean ± SD) and the median tumor diameter was 24.95 ± 12.29 mm (mean ± SD). Among all enrolled patients, the mutation rate of the BRAFV600E gene was 54.76% (23 of 42). There were 33 patients with classic papillary thyroid carcinoma, and 22 (66.67%) with classic subtypes were BRAFV600E positive. The BRAFV600E mutation was associated with lower distant metastasis (p = .013) and less Hashimoto's thyroiditis (p = .006). There was no significant difference in clinicopathological factors such as sex, age, tumor size, capsular invasion, multifocality, hypothyroidism, recurrence, lymph node metastasis, and extrathyroidal extension. CONCLUSIONS: The BRAFV600E mutation is not uncommon in pediatric papillary thyroid carcinoma but is not significantly associated with aggressive biological behavior. It is not possible to determine whether to adopt more active diagnosis and treatment measures on the basis of the mutation of a single BRAFV600E gene.

PGC-1α participates in tumor chemoresistance by regulating glucose metabolism and mitochondrial function.

Chemotherapy resistance is the main reason for the failure of cancer treatment. The mechanism of drug resistance is complex and diverse. In recent years, the role of glucose metabolism and mitochondrial function in cancer resistance has gathered considerable interest. The increase in metabolic plasticity of cancer cells' mitochondria and adaptive changes to the mitochondrial function are some of the mechanisms through which cancer cells resist chemotherapy. As a key molecule regulating the mitochondrial function and glucose metabolism, PGC-1α plays an indispensable role in cancer progression. However, the role of PGC-1α in chemotherapy resistance remains controversial. Here, we discuss the role of PGC-1α in glucose metabolism and mitochondrial function and present a comprehensive overview of PGC-1α in chemotherapy resistance.

Preoperative prediction of central neck metastasis in patients with clinical T1-2N0 papillary thyroid carcinoma.

BACKGROUND: Central neck metastasis (CNM) is common in patients with papillary thyroid carcinoma (PTC). However, the prediction of CNM risk remains poorly defined, especially for patients with clinically negative lymph nodes. We developed a preoperative clinical nomogram to predict CNM risk in patients with clinical T1-2N0 (cT1-2N0) PTC. METHODS: Data from 436 patients with unifocal cT1-2N0 PTC were available. We analyzed the association between preoperative variables and CNM using univariate and multivariate logistic regression and developed a clinical nomogram based on the multivariate regression model. The nomogram was validated externally using an independent dataset. RESULTS: The CNM rate was 25.5%. Three clinical variables were associated with CNM, including age, gender, and tumor size. We built a CNM nomogram integrating these three variables. It had a poor index of internal discrimination (C-index, 0.655; 95% CI 0.596-0.715) and a poor index of external discrimination (C-index, 0.690; 95% CI 0.611-0.769). CONCLUSIONS: We developed a preoperative nomogram to quantify the risk of CNM in unifocal cT1-2N0 PTC patients. However, our data showed that preoperative clinical parameters were not able to accurately predict the likelihood of CNM. Other variables need to be investigated to improve the prediction capability of this nomogram.

Design of new drugs for medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially curative therapeutic option to some MTC patients, most patients do not benefit from it due to the difficulty to access the tumors and tumor metastasis. The survival rate of MTC patients has improved with the recent advances in the research, which has improved our understanding of the molecular mechanism underlying MTC and enabled the development and approval of novel targeted drugs. In this article, we reviewed the molecular mechanisms related to MTC progression and the principle for the design of molecular targeted drugs, and proposed some future directions for prospective studies exploring targeted drugs for MTC.

Chimeric antigen receptor T-cell therapy for relapsed and refractory thyroid cancer.

The prognosis of most thyroid cancer patients is excellent, but for those with advanced or metastatic thyroid cancer, effective treatments are still lacking. Chimeric antigen receptor (CAR) T-cell therapy has gained remarkable achievements in hematologic malignancy but shown limited efficacy in solid tumors. In this report, we showed a relapsed and refractory thyroid cancer patient treated with TSHR + CD19 CAR-T, a combination of two 2nd generation CAR-T molecules targeting both TSHR and CD19. This patient finally achieved partial remission at 3 months and was tolerate well to the regimen. Our study suggested that the CAR-T therapy could be a feasible way in treating relapsed and refractory thyroid cancer.

Lymph node ratio in lateral neck is an independent risk factor for recurrence-free survival in papillary thyroid cancer patients with positive lymph nodes.

BACKGROUND: The purpose of this study was to explore the impact of the lymph node ratio on prognosis in papillary thyroid cancer patients with lymph node metastasis. METHODS: Data from papillary thyroid cancer patients with positive nodes who were initially treated at our institution during 2015-2016 were analysed. Univariate and multivariate Cox proportional hazard models were adopted to predict prognostic factors. A receiver operating characteristic (ROC) curve was used to find the best cut-off value of the lymph node ratio (LNR). Kaplan-Meier curves were used to show the relationship between the LNR in the lateral neck and recurrence-free survival. RESULTS: The median follow-up time was 64.6 months, and recurrence occurred in 16 of 662 patients (2.27%). Univariate analysis showed that male sex, primary tumour size (>17 mm), visible extrathyroidal extension, LNR in the central neck (>0.5), LNR in the lateral neck (>0.10), and visible extranodal extension were significantly correlated with recurrence-free survival (RFS) (p < 0.05). Multivariate analysis using the Cox proportional hazards model showed that the LNR in the lateral neck was an independent risk factor for RFS (p = 0.039; HR 14.76). CONCLUSION: The LNR in the lateral neck was an independent risk factor for recurrence-free survival. For patients with a high lymph node ratio in the lateral neck, more frequent follow-up might be needed.

Macroscopic extranodal extension is an independent predictor of lung metastasis in papillary thyroid cancer.

PURPOSE: Lymph node metastasis is common in patients with papillary thyroid cancer (PTC). Some metastatic lymph nodes may present extranodal extension (ENE). The clinical role of ENE in PTC has yet to be clearly identified. We evaluated macroscopic ENE as a potential prognostic indicator of lung metastasis in PTC. PATIENTS AND METHODS: We identified 1140 consecutive patients who had PTC initially resected at our cancer center. Clinical data and pathological results were reviewed. Univariate and multivariate logistic regression analyses were used to figure out the association between clinicopathological variables and lung metastasis. RESULTS: In this cohort, 51.7% of PTC patients had lymph node metastasis; 10.4% had macroscopic ENE positive nodes; 2.3% had lung metastasis. In patients with lymph node metastasis, the average number of positive nodes was 5.10 ± 4.91. Multivariable analysis of clinicopathological factors revealed that extrathyroidal extension (odds ratio [OR], 3.57; 95% CI, 1.41-9.04), macroscopic ENE (OR, 7.08; 95% CI, 2.54-19.74), and number of positive nodes were significantly associated with lung metastasis. Compared with 0-3 positive nodes, 7-9 positive nodes denoted a moderate risk of lung metastasis (OR, 4.53; 95% CI, 1.03-19.85). And 10 positive nodes or more indicated a high risk of lung metastasis (OR, 9.63; 95% CI, 2.65-35.02). CONCLUSION: Macroscopic ENE could serve as a strong independent prognostic factor of lungmetastasis in PTC. More attention should be paid to patients with ENE positive nodes duringfollow-up.

Extranodal extension is an independent predictor of extensive nodal metastasis in T1 papillary thyroid cancer.

PURPOSE: Extensive lymph node metastasis (ELM) can occur in some patients with T1 papillary thyroid cancer (PTC). However, the risk factors for ELM in patients with T1 PTC have not been fully explored. In this study, we aimed to examine the association between extranodal extension (ENE) and ELM in patients with T1 PTC. PATIENTS AND METHODS: We identified 645 consecutive patients who had T1 PTC initially resected at our centre. Clinical and pathological data were reviewed. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for ELM. RESULTS: ELM was identified in 3.9% of T1 PTC patients, and ENE was identified in 8.1% of patients. ENE was associated with male sex, large tumour size, more positive nodes, and comprehensive surgical treatment. In multivariate analysis, three variables were independently associated with ELM, including ENE (odds ratio [OR], 11.15; 95% confidence interval [CI], 4.54 to 27.30; P < 0.001), age (OR, 0.96; 95% CI, 0.93 to 0.99; P = 0.022), and tumour size (OR, 1.18; 95% CI, 1.06 to 1.31; P = 0.002). Bilateral multifocality and sex were not independently associated with ELM. CONCLUSION: ENE is a strong independent predictor of ELM in patients with T1 PTC. Patients with ENE-positive nodes might need extensive neck dissection.

Male patients with papillary thyroid cancer have a higher risk of extranodal extension.

BACKGROUND: There is a sex disparity in papillary thyroid cancer (PTC). Male sex is associated with a higher likelihood of advanced stage disease. This study aimed to examine the significance of sex for extranodal extension (ENE) in PTC. METHODS: We reviewed the data of PTC patients who had undergone initial surgical resection from July 2012 to December 2014 (N = 1531). The effects of sex and other clinicopathological factors on ENE were investigated. RESULTS: Of 1531 patients identified, 377 (24.6%) were male, 816 (53.3%) had positive nodes, and 256 (16.7%) had ENE. Compared with female patients, male patients had a higher risk of ENE (P < 0.001). Multivariable analysis of clinicopathological factors revealed that male sex (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.37-2.87; P < 0.001), age older than 60 years (OR, 1.93; 95% CI, 1.08-3.35; P = 0.023), extrathyroidal extension (OR, 3.52; 95% CI, 2.42-5.14; P < 0.001), bilateral multifocality (OR, 2.18; 95% CI, 1.53-3.13; P < 0.001), and more positive nodes were significantly associated with increased risk of ENE. Patients with 6-10 positive nodes were 16.45-fold higher to have ENE than patients with 5 positive nodes or less (95% CI, 11.07-24.68; P < 0.001). CONCLUSION: Male PTC patients had a higher risk of ENE than female. Sex was an independent predictor of ENE. The underlying mechanism needs to be investigated further.

Novel Anaplastic Thyroid Cancer PDXs and Cell Lines: Expanding Preclinical Models of Genetic Diversity.

CONTEXT: Anaplastic thyroid cancer (ATC) is a rare, aggressive, and deadly disease. Robust preclinical thyroid cancer models are needed to adequately develop and study novel therapeutic agents. Patient-derived xenograft (PDX) models may resemble patient tumors by recapitulating key genetic alterations and gene expression patterns, making them excellent preclinical models for drug response evaluation. OBJECTIVE: We developed distinct ATC PDX models concurrently with cell lines and characterized them in vitro and in vivo. METHODS: Fresh thyroid tumor from patients with a preoperative diagnosis of ATC was surgically collected and divided for concurrent cell line and PDX model development. Cell lines were created by generating single cells through enzymatic digestion. PDX models were developed following direct subcutaneous implantation of fresh tumor on the flank of immune compromised/athymic mice. RESULTS: Six ATC PDX models and 4 cell lines were developed with distinct genetic profiles. Mutational characterization showed one BRAF/TP53/CDKN2A, one BRAF/CDKN2A, one BRAF/TP53, one TP53 only, one TERT-promoter/HRAS, and one TERT-promoter/KRAS/TP53/NF2/NFE2L2 mutated phenotype. Hematoxylin-eosin staining comparing the PDX models to the original patient surgical specimens show remarkable resemblance, while immunohistochemistry stains for important biomarkers were in full concordance (cytokeratin, TTF-1, PAX8, BRAF). Short tandem repeats DNA fingerprinting analysis of all PDX models and cell lines showed strong concordance with the original tumor. PDX successful establishment rate was 32%. CONCLUSION: We have developed and characterized 6 novel ATC PDX models with 4 matching cell lines. Each PDX model harbors a distinct genetic profile, making them excellent tools for preclinical therapeutic trials.

The strap intermuscular approach can significantly increase the exposure rate of the external branch of the superior laryngeal nerve during thyroid surgery.

BACKGROUND: Avoiding injury to the external branch of the superior laryngeal nerve (EBSLN) is a major challenge during thyroid surgery. EBSLN injury can have an impact on the quality of life of patients. The aim of this study was to introduce the strap intermuscular approach, to dissect the EBSLN with two different approaches in thyroid surgery, to compare the differences between these two approaches, and to describe a way for surgeons to treat the upper thyroid gland to find the EBSLN. METHODS: A prospective study of hemithyroidectomy was performed. In total, 104 patients were included and randomly divided into two groups: one group used the traditional approach to expose and protect the EBSLN, and the other group used the strap intermuscular approach. We described the surgical procedure for the strap intermuscular approach and compared the differences in the rates of EBSLN exposure, injury, and classification to illustrate the advantages of the intermuscular approach in thyroid surgery. RESULTS: The exposure rate of the EBSLN was higher with the strap intermuscular approach than with the traditional approach (96.15% vs. 76.92%, p = 0.01), with an odds ratio (OR) and 95% confidence interval (CI) of 0.133 (0.028-0.630). The exposure rate of EBSLNs classified as type 1 was higher in the strap intermuscular approach than in the traditional approach (30.77% vs. 13.46%, p = 0.033), with an OR and 95% CI of 0.350 (0.130-0.942). CONCLUSIONS: The exposure rate of the EBSLN was significantly higher with the strap intermuscular approach method than with the traditional approach during thyroid surgery. This approach allows for better identification of the EBSLN during thyroidectomy.

Individual prediction of lateral neck metastasis risk in patients with unifocal papillary thyroid carcinoma.

INTRODUCTION: Much controversy exists over whether to perform lateral neck dissection (LND) on patients with papillary thyroid carcinoma (PTC). This study aimed to build predictive nomograms that could individually estimate lateral neck metastasis (LNM) risk and help determine follow up intensity. PATIENTS AND METHODS: Unifocal PTC patients who underwent LND between April 2012 and August 2014 were identified. Clinical and pathological variables were retrospectively evaluated using univariate and stepwise multivariate logistic regression analysis. Variables that had statistical significance in final multivariate logistic models were chosen to build nomograms, which were further corrected using the bootstrap resampling method. RESULTS: In all, 505 PTC patients were eligible for analysis. Among these, 178 patients (35.2%) had lateral neck metastasis. Two nomograms were generated: nomogram (c) and nomogram (c + p). Nomogram (c) incorporated four clinical variables: age, tumor size, tumor site, and extrathyroidal extension (ETE). It had a good discriminative ability, with a C-index of 0.79 (bootstrap-corrected, 0.78). Nomogram (c + p) incorporated two clinical variables and two pathological variables: tumor size, tumor site, extranodal extension (ENE), and number of positive nodes in the central compartment. Nomogram (c + p) showed an excellent discriminative ability, with a C-index of 0.86 (bootstrap-corrected, 0.85). CONCLUSION: Two predictive nomograms were generated. Nomogram (c) is a clinical model, whereas nomogram (c + p) is a clinicopathological model. Each nomogram incorporates only four variables and can give an accurate estimate of LNM risk in unifocal PTC patients, which may assist clinicians in patient counseling and decision making regarding LND.

A nomogram predicting contralateral central neck lymph node metastasis for papillary thyroid carcinoma.

BACKGROUND AND OBJECTIVES: Central compartment neck dissection (CCND) is recommended for patients with papillary thyroid carcinoma (PTC). However, whether to perform contralateral CCND remains unclear. An individualized estimation of the contralateral central neck metastasis (CNM) risk would assist in the tailoring of treatment for PTC patients. METHODS: Consecutive patients who underwent bilateral CCND for unilateral PTC between 2012 and 2014 in a tertiary center were identified. The clinicopathological data of 142 patients were analyzed retrospectively. The variables that had clinical significance in the final multivariate logistic regression model were built into a nomogram to assess the risk of metastasis of the contralateral central compartment. This model was internally validated using bootstrap resampling. RESULTS: This nomogram demonstrated good calibration and discrimination, with a concordance index of 0.834 (bootstrap corrected, 0.824). The variables with the greatest influence on the risk of contralateral CNM in this model included tumor size, the number of positive lymph nodes, and extranodal extension in the ipsilateral central neck. CONCLUSIONS: This nomogram integrates three variables to estimate an individualized risk of contralateral CNM in unilateral PTC patients. This model may assist in individual decision-making regarding contralateral CCND and help avoid the over- and under-treatment of PTC. J. Surg. Oncol. 2016;114:703-707. © 2016 Wiley Periodicals, Inc.

Intermittent intraoperative nerve monitoring in thyroid reoperations: Preliminary results of a randomized, single-surgeon study.

BACKGROUND: The purpose of this study was to evaluate whether intermittent intraoperative nerve monitoring (IONM) could reduce the incidence of recurrent laryngeal nerve (RLN) paralysis in thyroid reoperations. METHODS: Enrolled patients were randomly assigned into the nerve integrity monitor (NIM) group and the control group. RESULTS: The incidence of temporary RLN paralysis and permanent RLN paralysis was 12.2% and 4.9% in the NIM group compared with 7.0% and 2.3% in the control group (p = .658 and p = .966, respectively). The incidence of surgeon-related paralysis, tumor-related paralysis, and scar-related paralysis was 4.9%, 7.3%, and 4.9% in the NIM group compared with 4.7%, 2.3%, and 2.3% in the control group, respectively (p = 1, p = .575, and p = .966, respectively). CONCLUSION: Intermittent IONM could not provide additional benefits to reduce the incidence of temporary RLN paralysis and permanent RLN paralysis in thyroid reoperations. It could not reduce the incidence of paralysis caused by unintentional injuries. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1993-E1997, 2016.

Intermittent Intraoperative Neural Monitoring Technology in Minimally Invasive Video-Assisted Thyroidectomy: A Preliminary Study.

PURPOSE: Intraoperative neural monitoring (IONM) technology was applied in minimally invasive video-assisted thyroidectomy (MIVAT) to explore its safety and effectiveness. MATERIALS AND METHODS: Data were collected retrospectively from October 2009 to August 2011. Inclusion criteria included the following: (1) benign thyroid nodule with maximum diameter less than 4.0 cm by preoperative ultrasound evaluation; (2) no previous thyroid surgeries; (3) no cervical radiation history; (4) normal function of recurrent laryngeal nerve (RLN) examined by preoperative laryngoscopy; (5) patients who did not accept to take a "wait and see" follow-up strategy. Enrolled patients were randomly allocated into NIM group and control group. RESULTS: 46 patients were enrolled in NIM group, and 51 patients were enrolled in control group. All surgeries in NIM group were performed successfully, and majority of tracheal intubations were placed with one attempt. 47 RLNs in NIM group and 60 RLNs in control group were exposed. The time of RLN locating was 6.06 ± 1.48 min in NIM group and 6.92 ± 1.34 min in control group (p = .02). The time of RLN tracing and exposing was 28.96 ± 4.75 min in NIM group and 32.17 ± 5.56 min in control group (p = .02). 1 case of temporary RLN paralysis was observed in both groups, and no permanent RLN paralysis was reported. CONCLUSIONS: The application of intermittent IONM in MIVAT is feasible. Intermittent IONM can help reduce the time of RLN locating and the time of RLN tracing and exposing.

Association of TERT Promoter Mutation, But Not BRAF Mutation, With Increased Mortality in PTC.

CONTEXT: Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be associated with high recurrence and potentially increased mortality. PTC carrying the TERT promoter mutation has been associated with older age, recurrence, and aggressive disease. OBJECTIVE: The objective of this study was to determine the association of BRAF and TERT promoter gene alterations with recurrence and survival in a high-risk population. DESIGN: Genomic DNA was analyzed for the BRAF mutation from 256 persistent/recurrent PTC (p/rPTC; 202 new, 54 previously reported) and for the TERT promoter mutation and polymorphism (242 p/rPTC). Two-tailed Fisher exact tests or the Pearson χ(2) test were performed for the associations between mutations and other variables. Overall and disease-free survivals were compared by log rank tests on Kaplan-Meier plots and by Cox regression analysis. TERT promoter constructs were tested in PTC cell lines to determine their activities in these cells. RESULTS: BRAF V600E mutation was identified in 235 of 256 (91.8%), TERT promoter mutation at -124 was detected in 77 of 242 (31.8%), and TERT promoter polymorphism at -245 was found in 113 of 242 (46.7%) p/rPTC patients. A significant difference in survival was found in p/rPTC patients with the TERT promoter mutation, which also displayed increased activity in vitro as compared to the nonmutated promoter sequence. No association was noted between the BRAF mutation or TERT promoter polymorphism and recurrence or survival. A drawback of our study could be the limited number of patients with nonmutated BRAF (21 of 256 [8.2%]). CONCLUSIONS: Mutation in the TERT promoter, but not in BRAF, was associated with decreased survival in 19 (24.7%) p/rPTC patients who died of disease and in 38 (49.4%) p/rPTC patients who died at last contact. The presence or absence of the BRAF mutation and TERT promoter polymorphism, however, was not significantly correlated with survival.