Background: Although the current gold standard for diagnosing thyroid nodule malignancy is ultrasound-guided fine-needle aspiration (FNA) cytology, about 20–25% of cytological evaluations are considered indeterminate for malignancy. This limitation has led to the emergence of next-generation sequencing panels, for example, ThyroSeq v3 (TSv3), which recognize highly diagnostic genetic mutations of common thyroid carcinomas in FNA samples and classify them as test-negative or test-positive, helping optimize treatment for indeterminate thyroid nodules (ITNs). Our goals were to evaluate the benign call rate (BCR) of TSv3 and assess its diagnostic performance and clinical utility while highlighting the points of consideration for a public Canadian institution. Methods: This is a single-center study conducted at the Royal Victoria Hospital (McGill University Health Centre) in Montreal, Canada, between January and February 2019. Patients were offered TSv3 following the McGill algorithm for ITN workup, a novel protocol developed at our institution to select only diagnostic surgery candidates to minimize waste of public resources, considering the single-payer health care system. Patient demographics, cytopathology results, TSv3 data, treatment plan, and final histopathology result were reviewed. Results: A total of 50 ITNs underwent TSv3 testing; molecular analysis yielded 20 (40%) “positive” results and 24 (48%) “negative” results. Six (12%) results were classified as “currently negative” or “negative but limited.” “Currently negative” results indicate a low-risk mutation that alone is insufficient for development of a malignant lesion. “Negative but limited” results indicate a sample that is nondiagnostic for malignancy due to low cell count. BCR was calculated as (“negative” and “currently negative”)/total, resulting in a BCR of 58%. Twenty-three (46%) patients were scheduled for surgery and 27 (54%) patients continued with surveillance. Ninety-one percent (20 of 22) of the resected target nodules were malignant on final pathology. Conclusions: TSv3 proved beneficial in classifying ITNs as positive or negative, avoiding surgery in the latter cases. We found a lower reduction rate in surgery and BCR than the previously published studies, which is attributable to the criteria of the McGill algorithm. In the Canadian public health care system, preventing unnecessary surgery represents significant cost savings for the provincial government while also improving patient quality of life.

Background: Systematic elective paratracheal dissection for papillary thyroid carcinoma is controversial. Objective: This study aims to analyze the pattern of locoregional recurrence (LRR) to determine the potential benefit of elective paratracheal dissection and to identify prognostic factors influencing locoregional control and disease specific survival. Methods: A cohort of 342 patients who underwent a total thyroidectomy with or without neck dissection for a papillary thyroid carcinoma was retrospectively reviewed. Clinicopathological variables predicting for survival and control were examined. Results: All patients underwent total thyroidectomy and 84 underwent neck dissection as primary treatment. Sixty-six patients underwent a central compartment neck dissection. Twenty-eight (8.2%) patients developed LRR, of which 12 did not undergo neck dissection at initial surgery. The majority of neck recurrences were found in the lateral neck. Two patients (0.7%) without a paratracheal dissection done initially recurred only in the central compartment. On univariable analysis significant pathological predictors of locoregional control included tumor size, extrathyroidal extension (ETE), lymphovascular invasion and pathological lymph node status. Only ETE was a significant adverse prognostic variable for disease specific survival. On regression analysis, ETE and lymphovascular invasion were the only significant independent predictors of LRR. Paratracheal dissection did neither influence LRR nor central compartment control when adjusted for the effect of other variables. Conclusions: Strong conclusions are difficult to draw without a comparable group, but these results suggest that the absolute benefit of elective paratracheal dissection is small.

Background: Molecular testing has been used for cytologically indeterminate thyroid nodules (Bethesda III and IV), where the risk of malignancy is 10–40%. However, to date, the role of molecular testing in cytologically suspicious or positive for malignancy (Bethesda V and VI) thyroid nodules has been controversial. The aim of this study was to determine whether patients who had molecular testing in Bethesda V and VI thyroid nodules had the optimal extent of surgery performed more often than patients who did not have molecular testing performed. Methods: A retrospective chart review of 122 cases was performed: 101 patients from the McGill University teaching hospitals and 21 patients from the Hillel Yaffe Medical center, Technion University. Patients included in the study were those with Bethesda V or VI thyroid nodules who underwent molecular testing (ThyGenext® or ThyroseqV3®) (McGill n = 72, Hillel Yaffe n = 14). Patients with Bethesda V or VI thyroid nodules who did not undergo molecular testing were used as controls (McGill n = 29, Hillel Yaffe n = 7). Each case was reviewed in order to determine whether the patient had optimal surgery. This was defined as total thyroidectomy in the presence of either a positive lymph node, extrathyroidal extension, or an aggressive pathological variant of papillary thyroid carcinoma (tall cell, hobnail, columnar cell, diffuse sclerosing, and solid/trabecular) documented on the final pathology report. In all other cases, a lobectomy/hemi/subtotal thyroidectomy was considered as optimal surgery. Chi-squared testing was performed to compare groups. Results: When molecular testing was done, 91.86% (79/86) of surgeries in the molecular testing group were optimal, compared to 61.11% (22/36) in the control group. At McGill University teaching hospitals and at Hillel Yaffe, 91.67% (66/72) and 92.86% (13/14) of surgeries in the intervention group were considered as optimal, respectively. This compares to 58.62% (17/29) at McGill and 71.43% (5/7) at Hillel Yaffe when molecular testing was not performed ( p = .001, p = .186). Conclusions: In this study, molecular testing in Bethesda V and VI thyroid tumors significantly improved the likelihood of optimal surgery. Therefore, molecular testing may have an important role in optimizing surgical procedures performed in the setting of Bethesda V and VI thyroid nodules. Prospective studies with larger sample sizes are required to further investigate this finding. Graphical

Background: The aim of this study is to prospectively review the role of sentinel lymph node (SLN) biopsy in the management of well differentiated thyroid carcinoma (WDTC), and to determine the efficacy of intraoperative frozen section analysis at detecting SLN metastasis and central compartment involvement. Methods: The SLN biopsy protocol using 1% methylene blue was performed in 300 patients undergoing thyroidectomy for WDTC. A limited pretracheal central compartment neck dissection (CCND) was performed on all patients. Lymph nodes staining blue were considered as SLN's. Both frozen and permanent section analyses were performed. Results: SLN's with metastasis were found in 14.3% (43/300) of cases. Of this, 11% (33/300) were positive on intraoperative frozen section analysis. Frozen section results failed in predicting central compartment involvement in 15 cases (5%) whereas central neck compartment involvement was missed in 5 cases (1.7%) when based on permanent section results. On frozen section analysis, the sensitivity, specificity, positive predictive value and negative predictive value (95% CI) of our SLN biopsy technique aiming to remove all disease from the central compartment was 68.8% (53.6-80.9), 100% (98.1-100), 100% (87.0-100) and 94.4% (90.7-96.7) respectively with P < 0.0001. On permanent section analysis, the values were 89.6% (76.6-96.1), 100% (98.1-100), 100% (89.8-100), and 98.1% (95.3-99.3) with P < 0.0001. Conclusion: This data series demonstrates that patients with WDTC have positive SLN's in 14.3% of cases. Moreover, when the SLN's are negative for metastasis on frozen section, the central compartment was disease-free in 94.4% of cases. Finally, this study shows that 23.3% of positive SLN's were false negatives on intraoperative frozen section. According to this data, SLN involvement is an accurate predictor of central compartment metastasis, however surgeons should use caution when relying on intraoperative frozen section to determine whether to perform a CCND.

Background: We sought to determine the ability of the endoscopic Mueller maneuver (MM) to predict the severity of OSAS based on upper airway (UA) collapse. Methods: This chart review retrospectively analyzed the results of endoscopic Mueller maneuvers examining the UA on 506 patients suspected of having OSAS. There were 3 areas of UA collapse that were evaluated: velopharynx (VP), base of tongue (BOT), and lateral pharyngeal walls (LPW). A sleep study was done after the examination to assess the severity of OSAS based on the apnea-hypopnea index (AHI). Results: A total of 506 patients met criteria for OSAS, with 194 mild cases (5 ≤ AHI < 15), 163 moderate cases (15 ≤ AHI < 30) and 149 severe cases (30 ≤ AHI). At the VP, 30 patients had minimal collapse (mean AHI = 17); 41 patients had moderate VP collapse (mean AHI = 25); 392 patients had severe VP collapse (mean AHI = 27). At the BOT, 144 patients had minimal collapse (mean AHI = 19); 187 patients had moderate BOT collapse (mean AHI = 24); 175 patients had severe BOT collapse (mean AHI = 33). At the LPW, 158 patients had minimal collapse (mean AHI = 20); 109 patients had moderate LPW collapse (mean AHI = 25); 120 patients had severe LPW collapse (mean AHI =33). The correlations found between VP collapse, BOT collapse, and LPW collapse and OSAS severity were: r = 0.069 (95 % CI; −0.022, 0.16), r = 0.26 (95 % CI; 0.18, 0.34) and r = 0.22 (95 % CI; 0.12, 0.31), respectively. Conclusions: In this study, the degree of collapse of the UA at all levels, especially at the BOT and LPW levels, correlate significantly with the severity of OSAS. The Mueller maneuver helped identify patients with severe sleep apnea based on UA collapse. The MM cannot be used to diagnose OSAS, but can be a valuable tool to help the physician estimate the severity of sleep apnea and the urgency to obtain a sleep study.

Background: The 2016 American Thyroid Association guidelines indicate that patients with Graves’ disease who undergo a thyroidectomy should be rendered euthyroid through the use of antithyroid drugs (ATD) prior to surgery to avoid complications such as a thyroid storm. At times, the use of ATDs can have limited efficacy and therefore some patients will inevitably remain biochemically hyperthyroid at the time of surgery. The aim of this study is to assess if hyperthyroid patients undergoing a thyroidectomy are at an increased risk of developing a thyroid storm in comparison to euthyroid patients. Furthermore, this study seeks to establish a correlation between thyroid storm identified by the levels of thyroid hormones (T3 and T4) and the level of thyroid stimulating hormone (TSH). Methods: A retrospective cohort study was conducted at two Canadian centers, one in Montreal and the other in Nova Scotia. Sixty-seven patients undergoing thyroidectomy for Graves’ disease from January 2006 to December 2016 were evaluated. Results: The study comprised 67 participants with a mean age of 46 years (range16–78 years). A total of 78% of patients were on methimazole, 34% on beta-blockers, 27% on potassium iodine solution, 10% on propylthiouracil and 7% on steroids. At the time of surgery 21% were in an overt hyperthyroid state and 33% were in a subclinical hyperthyroid state. The average TSH level of 0.03 mIUL/L (range 0.01–0.23 mIUL/L). Sixteen percent of patients had a TSH level less than 0.01 mIUL/L. The average free T4 level was 29.58 pmol/L (range 11.5–95.2 pmol/L). The average total T3 level was 11.52 nmol/L (range 4.5–29.1 nmol/L) and free T3 level was 6.35 pmol/L (range 6.1–6.6 pmol/L). No patient developed thyroid storm. Conclusions: In our study, biochemically hyperthyroid patients undergoing thyroidectomy did not develop thyroid storm. Additional studies with larger sample sizes are needed to better understand the risk of thyroid storm in hyperthyroid patients.