International Expert Consensus on US Lexicon for Thyroid Nodules.

Multiple US-based systems for risk stratification of thyroid nodules are in use worldwide. Unfortunately, the malignancy probability assigned to a nodule varies, and terms and definitions are not consistent, leading to confusion and making it challenging to compare study results and craft revisions. Consistent application of these systems is further hampered by interobserver variability in identifying the sonographic features on which they are founded. In 2018, an international multidisciplinary group of 19 physicians with expertise in thyroid sonography (termed the International Thyroid Nodule Ultrasound Working Group) was convened with the goal of developing an international system, tentatively called the International Thyroid Imaging Reporting and Data System, or I-TIRADS, in two phases: (phase I) creation of a lexicon and atlas of US descriptors of thyroid nodules and (phase II) development of a system that estimates the malignancy risk of a thyroid nodule. This article presents the methods and results of phase I. The purpose herein is to show what has been accomplished thus far, as well as generate interest in and support for this effort in the global thyroid community.

Preoperative Evaluation of Thyroid Cancer: A Review of Current Best Practices.

OBJECTIVE: The incidence of thyroid cancer has significantly increased in recent decades. Although most thyroid cancers are small and carry an excellent prognosis, a subset of patients present with advanced thyroid cancer, which is associated with increased rates of morbidity and mortality. The management of thyroid cancer requires a thoughtful individualized approach to optimize oncologic outcomes and minimize morbidity associated with treatment. Because endocrinologists usually play a key role in the initial diagnosis and evaluation of thyroid cancers, a thorough understanding of the critical components of the preoperative evaluation facilitates the development of a timely and comprehensive management plan. The following review outlines considerations in the preoperative evaluation of patients with thyroid cancer. METHODS: A clinical review based on current literature was generated by a multidisciplinary author panel. RESULTS: A review of considerations in the preoperative evaluation of thyroid cancer is provided. The topic areas include initial clinical evaluation, imaging modalities, cytologic evaluation, and the evolving role of mutational testing. Special considerations in the management of advanced thyroid cancer are discussed. CONCLUSION: Thorough and thoughtful preoperative evaluation is critical for formulating an appropriate treatment strategy in the management of thyroid cancer.

Ultrasonography of the thyroid, parathyroids, and beyond.

BACKGROUND: Ultrasonography has become an essential tool for the evaluation and management of thyroid and parathyroid diseases. Its applications extend beyond neck endocrine conditions to a multitude of pathologies within the head and neck region. OBJECTIVES: Our study aimed to: (1) provide a broad review of neck ultrasonography and key findings in neck endocrine diseases; (2) support skilled performance office-based diagnostic ultrasonography and its varied applications. MATERIALS AND METHODS: A review of the current literature was supplemented with clinical examples of key ultrasonographic findings. RESULTS: Current applications and key findings of ultrasonography in the diagnosis and management of neck endocrine conditions are reviewed. CONCLUSION: Ultrasonography is a fundamental component in the evaluation and management of neck endocrine diseases. The reader is encouraged to use this review to enhance office-based performance and application of ultrasonography.

Pre-Operative Antithyroid Antibodies in Differentiated Thyroid Cancer.

OBJECTIVE: To evaluate the significance of antithyroglobulin and antithyroid peroxidase antibody levels associated with locoregional metastatic disease in patients with well-differentiated thyroid cancer. METHODS: Patients underwent initial treatment for well-differentiated thyroid cancer at our institution between 2014 and 2018. The following variables were collected: age, sex, pre-operative thyroid-stimulating hormone, thyroglobulin, antithyroglobulin antibody (TgAb), antithyroid peroxidase antibody (TPOAb), the extent of surgery, T-stage, N-stage, extrathyroidal extension (ETE), extranodal extension (ENE), lymphovascular invasion, and multifocal disease. The relationships between disease status and pre-operative TPOAb, TgAb, thyroglobulin, and thyroid-stimulating hormone were analyzed. RESULTS: A total of 405 patients (mean age, 52 years) were included in the study, of which 66.4% were women. Elevated TgAb was associated with the presence of lymph node metastases (LNM) in both the central and lateral neck (P < .01), with a stronger correlation to N1b versus N1a disease (P = .03). The presence of ETE was inversely related to the TgAb titer (P = .03). TPOAb was associated with a lower T-stage (P = .04), fewer LNM (P = .04), and a lower likelihood of ETE (P = .02). From multivariable analysis, TgAb ≥40 IU/mL was an independent predictive factor for a higher N-stage (P < .01 for N0 vs N1; P = .01 for N1a vs N1b), and ENE (P < .01). TPOAb ≥60 IU/mL was associated with a lower T-stage (P = .04 for T <3) and absence of ETE (P = .01). CONCLUSION: Elevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T- and N-stage. Pre-operative antithyroid antibody titers may be useful to inform the disease extent and features.

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-µm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

Current Experience of Ultrasound Training in Otolaryngology Residency Programs.

OBJECTIVES: The applications of using ultrasound for the evaluation and management of otolaryngologic diagnoses are expanding. The purpose of this study was to evaluate the current experience of ultrasound training in otolaryngology residency programs. METHODS: All allopathic and osteopathic otolaryngology residency programs in the United States were surveyed online via an e-mailed survey link to the resident representatives of the Section for Residents and Fellows in Training of the American Academy of Otolaryngology-Head and Neck Surgery. We present a descriptive analysis of the survey results. RESULTS: A total of 110 responses were obtained from resident representatives at MD and DO otolaryngology residency programs, representing a response rate of 94.8%. Forty-four percent of residents reported that they would not feel comfortable with performing ultrasound-guided procedures after residency; 43% reported that they do not perform ultrasound procedures as a part of their residency training; and 60% of those trainees performing ultrasound procedures do not log the procedures. Twenty-three percent of residents did not have access to an ultrasound machine. Most respondents (71%) desired more exposure to diagnostic and/or interventional ultrasound training during residency. CONCLUSIONS: Although current experience is variable, there is a strong interest in increasing resident skill acquisition in ultrasound training among otolaryngology residents. Some barriers to these goals may be a lack of trained faculty members using ultrasound and insufficient recording mechanisms for residents performing ultrasound procedures.

Thyroid cancer mortality is higher in Filipinos in the United States: An analysis using national mortality records from 2003 through 2012.

BACKGROUND: Well-differentiated thyroid carcinoma has a favorable prognosis, but patients with multiple recurrences have drastically lower survival. Filipinos in the United States are known to have high rates of thyroid cancer incidence and disease recurrence. To the authors' knowledge, it is unknown whether Filipinos also have higher thyroid cancer mortality rates. METHODS: The authors studied thyroid cancer mortality in Filipino, non-Filipino Asian (NFA), and non-Hispanic white (NHW) adults using US death records (2003-2012) and US Census data. Age-adjusted mortality rates and proportional mortality ratios (PMRs) were calculated. Sex, nativity status, age at death, and educational attainment also were examined. RESULTS: The authors examined 19,940,952 deaths. The age-adjusted mortality rates due to thyroid cancer were highest in Filipinos (1.72 deaths per 100,000 population; 95% confidence interval [95% CI], 1.51-1.95) compared with NFAs (1.03 per 100,000 population; 95% CI, 0.95-1.12) and NHWs (1.17 per 100,000 population; 95% CI, 1.16-1.18). Compared with NHWs, higher proportionate mortality was observed in Filipino women (3-5 times higher) across all age groups, and among Filipino men, the PMR was 2 to 3 times higher in the subgroup aged >55 years. Filipinos who completed a higher educational level had a notably higher PMR (5.0) compared with their counterparts who had not (3.5). CONCLUSIONS: Negative prognostic factors for thyroid cancer traditionally include age >45 years and male sex. The results of the current study demonstrate that Filipinos die of thyroid cancer at higher rates than NFA and NHW individuals of similar ages. Highly educated Filipinos and Filipino women may be especially at risk of poor thyroid cancer outcomes. Filipino ethnicity should be factored into clinical decision making in the management of patients with thyroid cancer. Cancer 2017;123:4860-7. © 2017 American Cancer Society.

ACTIVE SURVEILLANCE FOR PAPILLARY THYROID MICROCARCINOMA: NEW CHALLENGES AND OPPORTUNITIES FOR THE HEALTH CARE SYSTEM.

OBJECTIVE: The dramatic increase in papillary thyroid carcinoma (PTC) is primarily a result of early diagnosis of small cancers. Active surveillance is a promising management strategy for papillary thyroid microcarcinomas (PTMCs). However, as this management strategy gains traction in the U.S., it is imperative that patients and clinicians be properly educated, patients be followed for life, and appropriate tools be identified to implement the strategy. METHODS: We review previous active surveillance studies and the parameters used to identify patients who are good candidates for active surveillance. We also review some of the challenges to implementing active surveillance protocols in the U.S. and discuss how these might be addressed. RESULTS: Trials of active surveillance support nonsurgical management as a viable and safe management strategy. However, numerous challenges exist, including the need for adherence to protocols, education of patients and physicians, and awareness of the impact of this strategy on patient psychology and quality of life. The Thyroid Cancer Care Collaborative (TCCC) is a portable record keeping system that can manage a mobile patient population undergoing active surveillance. CONCLUSION: With proper patient selection, organization, and patient support, active surveillance has the potential to be a long-term management strategy for select patients with PTMC. In order to address the challenges and opportunities for this approach to be successfully implemented in the U.S., it will be necessary to consider psychological and quality of life, cultural differences, and the patient's clinical status.

Redefining "Value" in Surgery: Development of a Comprehensive Value Score for Outpatient Endocrine Surgery.

OBJECTIVE: The value-based healthcare model aims to improve the quality of care and lower health care costs. The standard value equation (ie, Value = Quality/Cost), while conceptually useful, is grossly oversimplified and lacks clinical relevance. This study introduces a more detailed value equation that generates disease-specific value scores and incorporates real-world clinical and cost data to demonstrate its use. STUDY DESIGN: Prospective observational study. SETTING: Tertiary institution. METHODS: A comprehensive new health care value equation was developed that includes 23 unique inputs. Sixteen inputs represent quality (numerator) and 7 inputs represent cost (denominator). Patients undergoing thyroid or parathyroid surgery were enrolled, and data were entered into the new equation to generate surgery-specific value scores for each patient. A subanalysis was performed for telehealth visits. RESULTS: Ten patients were enrolled (60% female) with an average age of 62 years. The average total monetary cost per patient was $41,884 ($27,885 direct). Across all patients, the average total quality score was 0.99, and the cost score was 6.1, resulting in a final value score of 0.19. A subanalysis showed that changing a postoperative visit from in-person to telehealth would increase the value score by 0.66%. CONCLUSION: This analysis creates a comprehensive value equation for surgical services that incorporates the complexity of modern surgical care. The new equation includes objective and subjective outcomes and health equity, quantitatively compares the value of different surgical interventions and health care services, illustrates how specific interventions can lead to the higher value of care, and can serve as the framework for future value equations.

Parathyroid Adenoma Orientation for Gland Embryologic Origin on Ultrasonography.

Importance: Accurate preoperative localization is critical to success in targeted parathyroidectomy for primary hyperparathyroidism. Objective: To determine if the association between the long axis of a parathyroid adenoma (PTA) candidate and strap musculature on sagittal ultrasonography (US) can be used to predict the embryologic origin of the gland. Design, Setting, and Participants: This diagnostic study was performed using the Stanford Research Repository. Patients 18 years or older with primary hyperparathyroidism who underwent parathyroidectomy between January 2009 and October 2021 were considered. Additional inclusion criteria were having clear sagittal view of the adenoma candidate on US, confirmation of the gland of origin intraoperatively, and confirmation of hypercellular parathyroid on final pathology. Data were analyzed from October 2021 to June 2022. Exposures: B-mode US and surgical parathyroidectomy. Main Outcomes and Measures: The index test was using US to measure the angle between the long axis of an adenoma candidate and the strap musculature in the sagittal plane. This angle was used to test whether inferior and superior PTAs could be accurately assigned. The hypothesis was formulated prior to data collection. Results: A total of 426 patients (mean [range] age, 61.1 [20-96] years; 316 [74.2%] female) with 442 adenomas met inclusion criteria. Of the 442 adenomas, 314 (71.0%) had measurable angles, of which 204 (46.2%) were assigned a superior origin, 238 (53.8%) were assigned an inferior origin, and 128 (29%) were indeterminate. Of the surgically identified superior PTAs, 144 (70.6%) had a definable angle, and of the surgically identified inferior PTAs, 170 (71.4%) had a definable angle. The receiver operating characteristic analysis found 94° as the optimized angle for differentiating true negatives from true positives, with an overall sensitivity of 74% and specificity of 72%. This supported using 90° as a break point for US review. True positives were considered superior adenomas with an angle greater than 90°; true negatives were inferior adenomas with an angle less than 90°. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of angulation analysis for determining PTA origin were 72.2% (95% CI, 64.9%-79.5%), 73.5% (95% CI, 66.9%-80.1%), 69.8% (95% CI, 62.5%-77.1%), 75.8% (95% CI, 69.3%-82.3%), and 72.9%, respectively. A subgroup analysis of 426 adenomas using the posterior carotid artery border on transverse US as a surrogate for predicting gland origin showed the following for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy: 49.5% (95% CI, 42.6%-56.4%), 82.3% (95% CI, 77.3%-87.3%), 71.4% (95% CI, 63.9%-78.9%), 64.6% (95% CI, 59.1%-70.1%), and 66.9%, respectively. Conclusions and Relevance: This diagnostic study showed that PTA angulation on sagittal plane US can be used to predict gland of origin and guide surgery. The relationship between adenoma and posterior carotid artery border on transverse US can also be used to predict gland origin. These easy-to-apply US-based tests can be used in conjunction with other imaging modalities to guide targeted parathyroidectomy.

Thyroid Nodule Rupture Following Radiofrequency Ablation for Benign Thyroid Nodules.

Importance: Nodule rupture is a rare but serious complication of thyroid radiofrequency ablation (RFA). With growing adoption of thyroid RFA across the US, an understanding of thyroid nodule rupture (TNR) is crucial for recognition, management, and, ultimately, prevention. Objective: To determine procedural and patient factors that may contribute to TNR and describe experiences in managing TNR while synthesizing existing literature. Design, Setting, and Participants: This retrospective case series examined all RFA procedures for benign thyroid nodules performed by 2 attending physicians at a single academic referral center between December 2019 and January 2024. A total of 298 consecutive patients underwent RFA for benign thyroid nodules. Criteria for offering RFA included nodules with 2 benign fine-needle aspirations, no suspicious ultrasonography features, a greatest dimension of 2 cm or greater, compressive or cosmetic concerns, and accessibility to a straight needle. Exposures: All RFAs were performed using ultrasonography guidance using the moving-shot technique and a 7-mm or 10-mm active tip. Main Outcomes and Measures: The primary outcome was TNR, and measures were procedure, nodule, and patient characteristics that may have contributed to its pathogenesis. Secondary outcomes were nodule volume reduction, thyroid function, and management and sequelae of TNR. The hypothesis on the pathogenesis of TNR was formed before data collection. Results: Six of 298 patients (2%; 4 women [67%]) with a mean age of 48.5 years (range, 34-65 years) experienced TNR for a mean of 36 days postprocedure (range, 19-54 days). The mean (SD) initial nodule volume among patients with TNR was 31.45 (16.52) mL, and 3 of 6 patients (50%) underwent prior lobectomy. All ruptures were anterior. All patients were treated conservatively, and none required surgery. Five patients recovered completely; the sixth and most recent patient was healing as of last follow-up. Conclusions and Relevance: There are limited data on the etiology and optimal management of TNR. These 6 cases of anterior rupture suggest that a potential contributor to TNR is thermal and mechanical trauma exerted at the fulcrum point during the moving-shot technique. The use of a smaller active tip (eg, 7 mm) and cessation of energy delivery before this point may help avoid TNR. More robust reporting of this complication may clarify risk factors for and enhance prevention of TNR.

Obesity Promotes Marrow-Derived Myeloid Cell Accumulation while Exercise Reduces Proliferative Signaling in Colon Cancer.

PURPOSE: Obesity increases colon cancer risk that has been previously linked to marrow-derived myeloid cells. We previously demonstrated that exercise training (EX) prevents colon cancer initiation, potentially through reduced myelopoiesis. However, it remains unknown whether early myeloid cell accumulation and inflammation in the colon precedes carcinogenesis with high-fat diet (HFD)-induced obesity, and if EX can attenuate these effects. We hypothesized that obesity would promote colon carcinogenesis that was preceded by myeloid cell accumulation and inflammation that would be attenuated by EX. METHODS: C57BL/6 mice were randomized to a HFD or control (CON) diet for 8 weeks. The HFD mice switched to CON diet and all mice were given intraperitoneal injections of azoxymethane (AOM) to induce colon cancer and randomized into EX or sedentary (SED) conditions. RESULTS: HFD mice developed more aberrant crypt foci (ACF), a marker for early carcinogenesis, compared to CON (p < 0.01), and EX developed fewer ACF compared to SED (p < 0.0001). Marrow-derived (p < 0.001) CD206+ macrophages were elevated in HFD compared to CON at study week 16 (p < 0.01). Marrow-derived CD206- macrophages (p < 0.05) and marrow-derived (p < 0.05) CD206+ macrophages were more abundant in HFD compared to CON at study week 42. EX did not alter colon immune cell populations. ß-Catenin protein was higher in HFD compared to CON at study week 42 (p < 0.05), and STAT3 protein content was lower at study week 28 with EX compared to SED (p < 0.05). CONCLUSIONS: The results suggest that obesity promotes colon ACF formation, potentially through early inflammatory myeloid cell accumulation. Despite attenuating ACF, EX did not alter myeloid cell accumulation in the colon, suggesting that EX inhibits ACF formation through alternative mechanisms which may include reduced ß-Catenin and STAT3 signaling.

Feasibility of a Novel 3D Ultrasound Imaging Technique for Intraoperative Margin Assessment during Tongue Cancer Surgery.

Squamous cell carcinoma (SCC) of the tongue is the most prevalent form of oral cavity cancer, with surgical intervention as the preferred method of treatment. Achieving negative or free resection margins of at least 5 mm is associated with improved local control and prolonged survival. Nonetheless, margins that are close (1-5 mm) or positive (less than 1 mm) are often observed in practice, especially for the deep margins. Ultrasound is a promising tool for assessing the depth of invasion, providing non-invasive, real-time imaging for accurate evaluation. We conducted a clinical trial using a novel portable 3D ultrasound imaging technique to assess ex vivo surgical margin assessment in the operating room. During the operation, resected surgical specimens underwent 3D ultrasound scanning. Four head and neck surgeons measured the surgical margins (deep, medial, and lateral) and tumor area on the 3D ultrasound volume. These results were then compared with the histopathology findings evaluated by two head and neck pathologists. Six patients diagnosed with tongue SCC (three T1 stage and three T2 stage) were enrolled for a consecutive cohort. The margin status was correctly categorized as free by 3D ultrasound in five cases, and one case with a "free" margin status was incorrectly categorized by 3D ultrasound as a "close" margin. The Pearson correlation between ultrasound and histopathology was 0.7 (p < 0.001), 0.6 (p < 0.001), and 0.3 (p < 0.05) for deep, medial, and lateral margin measurements, respectively. Bland-Altman analysis compared the mean difference and 95% limits of agreement (LOA) for deep margin measurement by 3D ultrasound and histopathology, with a mean difference of 0.7 mm (SD 1.15 mm). This clinical trial found that 3D ultrasound is accurate in deep margin measurements. The implementation of intraoperative 3D ultrasound imaging of surgical specimens may improve the number of free margins after tongue cancer treatment.

Radiofrequency ablation of benign thyroid nodules: A prospective, multi-institutional North American experience.

BACKGROUND: Radiofrequency ablation for benign thyroid nodules aims to achieve a volume reduction rate of ≥50%. However, factors that predict treatment success have not been defined in a large-scale study. METHODS: A prospective cohort study of biopsy-proven benign thyroid nodules treated with radiofrequency ablation at 3 institutions was performed. Patient demographics, nodule sonographic features, procedural data, and nodule volume reduction were evaluated. Binary logistic regression analysis was performed to identify features associated with treatment response. RESULTS: A total of 620 nodules were analyzed. The pooled median volume reduction rate at 12 months was 70.9% (interquartile range 52.9-86.6). At 1 year follow-up, 78.4% of nodules reached treatment success with a volume reduction rate ≥50%. The overall complication rate was 3.2% and included temporary voice changes (n = 14), vasovagal episodes (n = 5), nodule rupture (n = 3), and lightheadedness (n = 2). No permanent voice changes occurred. Four patients developed postprocedural hypothyroidism. Large baseline nodule volume (>20 mL) was associated with a lower rate of successful volume reduction (odds ratio 0.60 [0.37-0.976]). Large nodules achieved treatment success by 12-month follow-up at a rate of 64.5%, compared with 81.4% for small nodules and 87.2% for medium nodules. CONCLUSION: To our knowledge, this is the largest North American cohort of patients with benign thyroid nodules treated with radiofrequency ablation. Overall, radiofrequency ablation was an effective treatment option with a low risk of procedural complications. Large volume nodules (>20 mL) may be associated with a lower rate of successful reduction with radiofrequency ablation treatment.

Comorbid Depression in Patients With Head and Neck Cancer Compared With Other Cancers.

Importance: Depression is more prevalent among individuals with cancer than in the general population and is correlated with increased mortality in patients with head and neck cancer (HNC) in particular. Objective: To compare the prevalence of depression between patients with HNC and patients with other cancers. Design, Setting, and Participants: This retrospective cohort study used population-level data on patients aged 18 years or older with cancer who participated in the 2019 National Health Interview Survey and had completed the Personal Health Questionnaire-8 (PHQ-8). The analysis was performed between August 7, 2023, and April 5, 2024. Exposure: Any cancer diagnosis. Main Outcomes and Measures: The main outcome was prevalence and severity of depression based on the PHQ-8. The magnitude of the difference in baseline characteristics was measured between patients with HNC and those with other cancer types, and 95% CIs were used to measure the precision of these estimates. Multivariable logistic regressions were used to evaluate the association of demographic, socioeconomic, anxiety, and clinical variables with depression. Results: From a weighted cohort of 23 496 725 adult patients with cancer, 377 080 were diagnosed with HNC (87.5% aged 51-84 years; 77.9% male). The prevalence of any depression on the PHQ-8 (mild, moderate, or severe) was 40.1% in patients with HNC vs 22.3% in patients with other cancers. Compared with patients with other cancers, patients with HNC were equally likely to screen positive for anxiety (23.6% vs 16.0%; difference, 7.6%; 95% CI, -5.9% to 21.1%), take medication for depression (10.1% vs 13.9%; difference, -3.8%; 95% CI, -11.9% to 4.4%), and state that they never feel depressed (59.7% vs 53.7%; difference, 6.0%; 95% CI, -9.1% to 21.0%). On multivariable logistic regression analysis, having HNC was associated with an increased likelihood of depression (odds ratio [OR], 2.94; 95% CI, 1.39-6.22). Other factors associated with depression were being unmarried or not living with a partner (OR, 1.94; 95% CI, 1.55-2.43) and having anxiety (OR, 23.14; 95% CI, 17.62-30.37). Conclusions and Relevance: This cohort study found that patients with HNC were twice as likely to screen positive for depression on a validated survey than those with other cancers, despite having similar rates of self-reported depression and depression medication use. These findings suggest that self-reporting of depression may result in underreporting and undertreatment in this population and, thus, a need for further work in developing interventions to improve identification of and optimize treatment for patients with HNC and comorbid depression.

Proposal for standardized ultrasound analysis of the salivary glands: Part 1 submandibular gland.

Objectives: The Salivary Gland Committee of the American Academy of Otolaryngology-Head and Neck Surgery seeks to standardize terminology and technique for ultrasonograpy used in the evaluation and treatment of salivary gland disorders. Methods: Development of expert opinion obtained through interaction with international practitioners representing multiple specialties. This committee work includes a comprehensive literature review with presentation of case examples to propose a standardized protocol for the language used in ultrasound salivary gland assessment. Results: A multiple segment proposal is initiated with this focus on the submandibular gland. We provide a concise rationale for recommended descriptive language highlighted by a more extensive supplement that includes an extensive literature review with additional case examples. Conclusion: Recommendations are provided to improve consistency both in performing and reporting submandibular gland ultrasound.

Genotype-dependent cooperation of ionizing radiation with BRAF inhibition in BRAF V600E-mutated carcinomas.

BACKGROUND: A substantial proportion of solid tumors carry the BRAF V600E mutation, which causes activation of the MEK/MAPK pathway and is a poor prognostic indicator. Patients with locally advanced human cancers are often treated with external beam radiation therapy. Given the association of Raf overactivation with radioresistance, we hypothesized that, in BRAF V600E-mutated carcinomas, there would be combinatorial activity between radiation and PLX4720, a specific BRAF V600E-inhibitor. METHODS: Two BRAF V600E-mutated cancer cell lines and one BRAF-V600E wildtype (WT) cancer cell line were obtained. We performed cell viability assays and clonogenic assays using combinations of radiation and PLX4720. We assessed MEK and MAPK phosphorylation at different PLX4720 concentrations with western blotting, and cell cycle progression was evaluated by flow cytometry. RESULTS: Our results show combinatorial, additive activity between radiation and PLX4720 in BRAF V600E-mutated cell lines, but not in the BRAF WT line. In BRAF V600E-mutated cells, there was a PLX4720 concentration-dependent decrease in MEK and MAPK phosphorylation. In cells with BRAF V600E mutations, PLX4720 caused cell cycle arrest at G1, and, when combined with radiation, caused a combined G1 and G2 cell cycle arrest; this pattern of cell cycle effects was not seen in the BRAF WT cell line. CONCLUSIONS: These data suggest additive, combinatorial activity between radiation and PLX4720 in cancers carrying BRAF V600E mutations. Our data has potential for translation into the multimodality treatment of BRAF V600E-mutated cancers.

History of Thyroid Surgery in the Last Century.

Before the 20th century, thyroid surgery was regarded as "horrid butchery" such that no honest and sensible surgeon would ever engage in it. Yet, by the mid-20th century, thyroidectomy had become a respected, life-saving, safe, and increasingly practiced operation. From Kocher to Wells and onward into the 21st century, the evolution of thyroid surgery has continued, enhanced by the integration of endocrinology, genetics, immunology, physiology, technology, training, and multidisciplinary care. The ability to personalize and optimize the care of thyroid disorders has been progressively achieved through shared insights and discoveries, highlights of which are described herein.

Hyperthyroidism Due to Graves Disease After Radiofrequency Ablation.

Management options for benign, autonomously functioning, and malignant thyroid nodules were limited to surgery or targeting by radioactive iodine before the availability of radiofrequency ablation (RFA). Despite being a relatively new technique, RFA may be favored for patients of high surgical risk, and for those who wish to avoid hypothyroidism. Although insurance coverage for the procedure can be a significant barrier, several groups of investigators have shown improved quality of life for RFA compared to surgery, due to the less invasive nature and favorable risk profile. Hyperthyroidism due to transient thyroiditis is a known risk of RFA, secondary to direct trauma and subsequent thyroid hormone release. Here we present a case of an adult with large, symptomatic, multinodular goiter, with no prior history of thyroid autoimmunity, who underwent RFA with successful volume reduction of two nodules, but who developed acute hyperthyroidism due to Graves disease eight weeks after RFA. Larger studies evaluating the risks of RFA should evaluate for incident hyperthyroidism, specifically for Graves disease/thyroid autoimmunity, as this could represent an additional risk of the procedure.

Prognostication of papillary thyroid microcarcinoma based on preoperative ultrasound.

Background: Diagnosis of papillary thyroid microcarcinoma, defined as papillary thyroid carcinoma measuring 1cm or less in greatest diameter, has increased with improvements in ultrasound technology and widespread familiarity and utilization. Given the indolent course of papillary thyroid carcinoma, active surveillance is considered an acceptable alternative to surgical resection for select patients. Candidacy for active surveillance is determined by a number of patient and tumor characteristics. Specifically, the location of the tumor within the thyroid gland plays one of the key roles in decision making. Here we evaluate characteristics of the primary tumor and distance to the thyroid capsule in association with locoregional metastases to help guide risk assessment. Methods: Retrospective chart review of all thyroid surgeries performed by two surgeons at one medical center from 2014-2021 to evaluate characteristics of papillary thyroid microcarcinoma on preoperative ultrasound that are associated with locoregional metastatic disease. Results: Our data show a sensitivity of 65% and specificity of 95% for identifying regional metastases in papillary thyroid microcarcinoma using preoperative ultrasound. We found no correlation between regional metastasis and size of tumor, distance to thyroid capsule or trachea, tumor contour, or presence of autoimmune thyroiditis. Nodules in the superior or midpole were associated with central or lateral neck metastases, whereas nodules in the isthmus or inferior pole were only associated with central neck metastases. Conclusions: Active surveillance may be a reasonable option for even those papillary thyroid microcarcinomas adjacent to the thyroid capsule.