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Objectives: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma., Materials and Methods: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R 2 ., Results: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (<20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R 2 indices when compared to current N-classification., Conclusion: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed., (Copyright © 2020. Published by Elsevier Ltd.)

Evidence from observational studies suggest a positive association between serum thyroid-stimulating hormone (TSH) levels and differentiated thyroid carcinoma. However, the cause-effect relationship is poorly understood and these studies are susceptible to bias and confounding. This study aimed to investigate the causal role of TSH in both benign thyroid nodules and thyroid cancer in up to 451,025 UK Biobank participants, using a genetic technique, known as Mendelian randomization (MR). Hospital Episode Statistics and Cancer Registry databases were used to identify 462 patients with differentiated thyroid carcinoma and 2031 patients with benign nodular thyroid disease. MR methods using genetic variants associated with serum TSH were used to test causal relationships between TSH and the two disease outcomes. Mendelian randomization provided evidence of a causal link between TSH and both thyroid cancer and benign nodular thyroid disease. Two-sample MR suggested that a 1 s.d. higher genetically instrumented TSH (approximately 0.8 mIU/L) resulted in 4.96-fold higher odds of benign nodular disease (95% CI 2.46-9.99) and 2.00-fold higher odds of thyroid cancer (95% CI 1.09-3.70). Our results thus support a causal role for TSH in both benign nodular thyroid disease and thyroid cancer.

Introduction: Warthin's tumor (WT) is a common benign salivary gland neoplasm with a negligible risk of malignant transformation. However, there is a risk of malignant tumors being misdiagnosed as WT on cytology and inappropriately managed conservatively., Methods: Patients from nine centers in Italy and the United Kingdom undergoing parotid surgery for cytologically diagnosed WT were included in this multicenter retrospective series. Definitive histology was compared with preoperative cytological diagnoses. Surgical complications were recorded., Results: A total of 496 tumors were identified. In 88.9%, the final histological diagnosis was WT. In 21 cases (4.2%) a malignant neoplasm was diagnosed, which had been incorrectly labeled as WT on cytology., Conclusions: The risk of undiagnosed malignancy should be balanced against surgical risks when considering the management of WT. Although nonsurgical management remains an appropriate option, there may be a rationale for serial clinical or radiological evaluation if surgical excision is not performed., (© 2019 Wiley Periodicals, Inc.)

Background: Cell-free DNA (cfDNA) can be detected in the circulation of healthy individuals, but is found in higher concentrations in cancer patients. Furthermore, mutations in tumor cells can be identified in circulating DNA fragments. This has been the subject of significant interest in the field of cancer research, but little has been published in thyroid cancer., Objectives: To assess all available evidence on the use of circulating cfDNA in the diagnosis, management and surveillance of patients with differentiated thyroid cancer, and collate it into a systematic review to guide future research., Methods: A comprehensive literature search on the measurement of cfDNA in thyroid cancer was undertaken, and results from relevant studies collated into a systematic review., Results: Nine studies were identified, with varying methodologies and findings. Key techniques and findings are summarized., Conclusion: There is limited but promising evidence that somatic mutations in thyroid cancer can be detected in circulating cfDNA and are associated with more advanced disease. Further research is required to develop a clinically useful tool based on cfDNA to improve the management of thyroid cancers.

External beam radiotherapy (EBRT) is not a first line treatment in differentiated thyroid carcinoma (DTC), but is recommended as an adjuvant treatment in certain cases. The evidence for EBRT in DTC is limited. A comprehensive literature search was performed. Data on patient demographics, disease stage, treatment characteristics, and outcomes were collected from included articles after quality appraisal. Sixteen articles met the inclusion criteria, with a pooled population of 5114. Only 1 study was prospective and there were no randomized controlled trials. Most of the evidence suggests that EBRT improves locoregional control in patients at high risk of locoregional recurrence. This was corroborated by analysis of pooled patient data. Available evidence suggests an improvement in locoregional control when EBRT is used in patients over the age of 45 at high risk for locoregional recurrence. However, there is a need for long-term prospective multicenter research on the subject. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2297-E2305, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Split-thickness skin graft vaginoplasty is one of many methods for vaginal reconstruction. In its 130-year history it has been modified by numerous authors in attempts to improve graft viability and neovaginal function. We describe a modern approach that aims to improve outcomes and reduce complications., Cases: Two cases of split-thickness skin graft vaginoplasty are presented in which the traditional Abbé-McIndoe technique was supplemented by the combined use of vacuum-assisted closure and fibrin tissue sealant. In both cases 100% graft survival and normal neovaginal function were observed, with no recipient site complications. Both patients mobilized on postoperative day 3, and both were sexually active 4 months postoperatively., Conclusion: This approach has not been described previously in the literature. The impressive results seen in these cases suggest that the use of vacuum-assisted closure and fibrin tissue sealant in combination may improve graft survival and resulting neovaginal function.