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This paper presents the integration of a Monte-Carlo solver inside SYRTHES, an open-source thermal code, originally based on finite elements method. Insensitive to both the geometric complexity of the model and the fineness of its discretization, this stochastic method is a good complementary option to simulate large configurations with specific locations of interest. Radiation, conduction and convection can be combined to solve thermal problems in complex geometries. The Monte-Carlo method is described before showing its integration in the code SYRTHES. Comparisons against results obtained thanks to finite elements and Monte-Carlo approaches or analytical solutions are presented. Finally, industrial cases illustrate the advantages of using these two complementary approaches.

Background: Thyroid cancer is the most common endocrine malignancy, and accurate diagnosis is crucial for effective management. Fine needle aspiration cytology, guided by the Bethesda System for Reporting Thyroid Cytopathology, categorizes thyroid nodules into six categories, with Bethesda III and IV representing indeterminate diagnoses that pose significant challenges for clinical decision-making. Understanding the molecular profiles of these categories may enhance diagnostic accuracy and guide treatment strategies. Methods: This study retrospectively analyzed data from 217 patients with Bethesda III and IV thyroid nodules who underwent ThyroSeq v3 molecular testing followed by thyroid surgery at McGill University teaching hospitals. The analysis focused on the presence of specific molecular mutations, copy number alterations (CNAs), and gene expression profiles (GEPs) within these nodules. The relationship between these molecular findings and the clinico-pathological features of the patients was also examined. Results: This study identified notable differences in the molecular landscape of Bethesda III and IV thyroid nodules. Bethesda IV nodules exhibited a higher prevalence of CNAs and distinct GEPs compared to Bethesda III nodules. Interestingly, the BRAFV600E mutation was found exclusively in Bethesda III nodules, which correlated with more aggressive malignant behavior. These findings underscore the potential of molecular profiling to differentiate between the clinical behaviors of these indeterminate nodule categories. Conclusions: Molecular profiling, including the assessment of CNAs, GEPs, and specific mutations like BRAFV600E, provides valuable insights into the nature of Bethesda III and IV thyroid nodules. The distinct molecular characteristics observed between these categories suggest that such profiling could be instrumental in improving diagnostic accuracy and tailoring treatment approaches, ultimately enhancing patient outcomes in thyroid cancer management.

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase ( TERTp ) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis >3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp -positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination ( n = 13, 43.3%), followed by TERTp alone ( n = 8, 26.7%) and TERTp/RAS ( n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations ( n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk ( p = 0.006) and were more frequently associated with aggressive histologic subtypes ( p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

Background: Molecular testing can reduce the need for diagnostic thyroidectomy in cytologically indeterminate thyroid nodules. However, the health-related quality of life in patients managed with molecular testing is not well studied., Objective: The objective of this scoping review was to identify and analyze the health-related quality of life outcomes in patients with indeterminate thyroid nodules who are expected to undergo or have undergone surgery or molecular testing., Methods: A comprehensive search was conducted on PubMed, Scopus, PsychINFO, and Embase to identify relevant studies. The search terms included "thyroid neoplasms" or "thyroid nodule" and "molecular testing" or "surgery" and "quality of life". The included articles were analyzed for their main study objective, study design, participant characteristics, and main results., Results: Eight studies were included in this scoping review. Four evaluated the quality-adjusted life years for patients with indeterminate thyroid nodules. Three of these studies found that molecular testing slightly improved quality-adjusted life years compared to surgery, while one study found no difference. Two studies assessed surgical health-related quality of life outcomes and reported that patients with indeterminate thyroid nodules who were expected to undergo surgery favored surgical procedures, while those who underwent surgery experienced impaired health-related quality of life. Two studies evaluated molecular testing in patients with indeterminate thyroid nodules and found that the final molecular test result significantly impacted health-related quality of life outcomes. Patients with suspicious/positive molecular test results had worse symptoms of goiter, anxiety, and depression, while those with benign results had preserved health-related quality of life scores. Patients with benign results from molecular testing experience better health-related quality of life within the first year compared to those with benign surgical outcomes., Conclusions: This scoping review highlights the importance of considering health-related quality of life outcomes in the management of patients with indeterminate thyroid nodules. Benign molecular testing results yield better quality of life than benign surgical outcomes within the first year, suggesting molecular testing as a preferable option. Further research comparing the impact of surgery and molecular testing on health-related quality of life is needed to improve shared decision-making and patient outcomes.

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing., Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis., Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) ( p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs ( p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) ( p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations ( CNAs ) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%)., Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

Background: Ki-67 immunostaining is commonly used in neuroendocrine tumors to estimate the proliferative index and for grading. This study investigates its association with the invasiveness of follicular-derived thyroid carcinomas (TCs)., Methods: A retrospective analysis of patients with TC at three McGill University teaching hospitals between January 2018 and November 2023 was conducted. The inclusion criteria included patients with malignant thyroid tumors and accessible Ki-67 LI data from final pathology specimens. The data collected included patient demographics, Ki-67 LI values, and different invasiveness attributes, such as molecular mutations, the histological subtype, lymphovascular invasion (LVI), extrathyroidal extension (ETE), and positive lymph nodes (LNs)., Results: In total, 212 patients met the inclusion criteria, of which 80.7% were females and 19.3% were males. The Ki-67 LI ranged from 1% to 30%, with the majority of the cases within the range of 1-15%. A significant association was observed between higher Ki-67 LI and high-risk histological subtypes of thyroid carcinoma ( p < 0.001). Similarly, Ki-67 LI was significantly associated with LVI and positive LN metastasis ( p < 0.001 and p = 0.036, respectively). However, no significant association was found between the Ki-67 LI and gene mutations or ETE ( p = 0.133 and p = 0.190, respectively). Using percentiles to establish a cutoff, patients with a Ki-67 LI higher than 6.7 showed a higher likelihood of being associated with invasive features., Conclusion: Elevated Ki-67 LI can serve as an indicator of aggressiveness in follicular-derived TC, especially when associated with distinct histological subtypes, LVI and positive LNs.

Background: Minimally invasive parathyroidectomy (MIP) in patients with a parathyroid adenoma (PA) requires imaging modalities for precise localization. Parathyroid hormone assay on ultrasound-guided fine-needle aspiration washout, or PTH washout, can be used for this purpose. It is unclear whether PTH washout complements traditional PA localization techniques such as a sestamibi (MIBI) scan or diminishes its need. This study aims to determine whether a positive PTH washout obviates the need for an MIBI scan in the preoperative localization of a PA., Method: A multi-center retrospective, comparative review comprised adult patients who underwent MIP at 2 McGill University teaching hospitals between 2018 and 2022. Patients who had both PTH washout and MIBI scan for preoperative localization of PA, final histopathology reports available, and preoperative/postoperative results recorded were included in the final analysis., Results: Of the 193 patients' charts reviewed, 87 were included in this study. Of these 87 patients, 74.7% (65/87) had a positive PTH washout result. Among those, MIBI correctly detected 90.8% (59/65) of the PAs. The MIBI scan did not contribute meaningful information for any of the 65 patients who had positive PTH washout results., Conclusion: These findings strongly support the use of preoperative dedicated ultrasound as the initial standard procedure. When a PA candidate on ultrasound is found, a PTH washout should be performed. If positive, it could suffice as the sole localization method for MIP surgery. When a PA was identified on ultrasound and confirmed with PTH washout, the MIBI scan did not add more information. Benefits include fewer patient tests, less exposure to ionizing radiation, and reduced healthcare expenses., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: While ultrasound-guided fine-needle aspiration cell block (FNACB) is a cost-effective, expeditious, and reliable procedure used routinely in the initial evaluation of head and neck masses, it has limited efficacy in diagnosing lymphoproliferative disorders such as non-Hodgkin lymphoma (NHL). Flow cytometry performed on an fine-needle aspiration (FNA) sample [ultrasound-guided fine-needle aspirate flow cytometry or flow cytometry performed on an FNA sample (FNAFC)], has been shown to be a valuable adjunct to FNACB in the diagnosis of lymphoproliferative disorders of the spleen, kidney, and thyroid. The objective of this study was to appraise FNAFC's utility as an ancillary tool to detect NHL arising in the head and neck region in adult patients., Methods: This is a retrospective study involving 52 adult patients with head and neck lymphadenopathies and masses suspicious for lymphoproliferative disorders, who underwent ultrasound-guided FNACB and ultrasound-guided FNAFC between January 2017 and November 2022. Patient demographics, FNACB histopathological and immunophenotypic results, postoperative histopathology results (when available), and follow-up information until May 2023 were reviewed., Results: Of the 52 FNACB samples, 23 samples (44.2%) yielded a diagnosis negative for carcinoma, 20 samples (38.5%) were nondiagnostic on account of scant cellularity, 8 samples (15.4%) were suspicious for malignancy, and a single sample (1.9%) was compatible with malignancy. Regarding FNAFC samples, 37 samples (71.2%) were diagnosed as showing no evidence for a lymphoproliferative disorder, 4 samples (7.7%) as nondiagnostic because of insufficient cell count, 4 samples (7.7%) as suspicious for a lymphoproliferative neoplasm, and 7 samples (13.5%) as compatible with a lymphoproliferative neoplasm, most frequently a B-cell lymphoma. 7 of the 11 patients (63.6%) with a suspicious/positive FNAFC result underwent excisional biopsy for additional work up. Postoperative histopathology reports corroborated FNAFC's findings in 6 patients (85.7%), while the remaining patient's (14.3%) suspicious FNAFC result was discordant with postoperative histopathology results. The other 4 patients (36.4%) did not require excisional biopsy as the hemato-oncologist deemed the information provided by the FNAFC as sufficient for the diagnosis and treatment of an NHL in the specific clinical contexts of those patients. All patients with nondiagnostic (due to insufficient cell count), inconclusive, or negative FNAFC (ie, nondiagnostic of a lymphoproliferative disorder) were followed up for a mean follow-up period of 11.9 months (range: 61.2 months; SD: 10.2 months), during which no new lymphadenopathies/masses nor progression was observed., Conclusions: FNAFC is a useful and practical supplementary tool in the diagnosis of lymphoproliferative disorders in the head and neck region, principally B-cell lymphoma. While conventional FNACB offers a valuable insight into the initial work up of head and neck masses, FNAFC can routinely detect small abnormal cell populations. Furthermore, in specific clinical contexts, it can reliably diagnose NHL, thereby averting the need for an excisional biopsy in a subset of patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A BRAF V600E mutation in papillary thyroid cancer (PTC) has been shown to be associated with aggressive behavior. Nevertheless, not all BRAF V600E PTCs behave aggressively. Allele frequency (AF) is the number of mutated molecules divided by the total number of wild-type molecules at a specific location in the genome. The relationship between BRAF V600E AF and the histopathological features of thyroid malignancies is not well understood. We hypothesized that the BRAF V600E AF will correlate directly with aggressive histopathological behavior. The aim of this study was to examine this relationship., Methods: A retrospective chart review was performed for patients treated for BRAF V600E thyroid malignancies from 2019 to 2022 at McGill University tertiary care hospitals ( n = 317). Patients with BRAF V600E -positive malignancies that included information on AF were included ( n = 44). The correlation between AF and tumor histopathological features was analyzed., Results: Out of the 44 nodules with a BRAF V600E mutation, those with aggressive features of PTC had a mean AF of 25.8%, which was significantly higher than the non-aggressive group with a mean AF of 10.25% ( p = 0.020). Additionally, there was a statistically significant difference in mean AF between patients with a positive sentinel LN (29%) and those with a negative sentinel LN (17.8%) ( p = 0.021). Classical PTC was present in 29.5% (13/44) of nodules, with a mean AF of 15.6%. The tall cell subtype was found in 64% (28/44) of nodules, with a mean AF of 23%. Solid and hobnail subtypes were less common in this study, and there was no statistically significant relationship between AF and histopathological subtypes ( p = 0.107). Nodules smaller than 1cm had a mean AF of 13.3%, while nodules ranging from 1 2cm had a mean AF of 20.6%, and those larger than 2cm had a mean AF of 27.7%. However, no statistical difference was observed between AF and nodule size ( p = 0.160)., Conclusion: In this study, BRAF V600E mutations in conjunction with AF help to determine whether thyroid malignancies will display aggressive behavior. This pre-operative finding can help thyroid specialists to determine the extent of thyroidectomy and whether lymph node dissection is required.

Background: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions, RET/PTC and THADA/IGF2BP3 , that have been described as oncogenic events in thyroid neoplasms., Methods: We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either RET/PTC or THADA/IGF2BP3 gene fusion., Results: This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the RET/PTC fusion and seven had the THADA/IGF2BP3 fusion. Of the five nodules in the RET/PTC group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven THADA/IGF2BP3 nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the THADA/IGF2BP3 fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions., Conclusions: RET/PTC nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas THADA/IGF2BP3 nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment.

While some studies suggest that PTEN mutations correlate with a low-risk phenotype in pediatric thyroid nodules, the relationship between the mutation and malignancy in the adult populations is abstruse. This study investigated whether PTEN mutations result in thyroid malignancy, and whether these malignancies are aggressive. This multicenter study involved 316 patients who underwent preoperative molecular testing, and subsequent lobectomy or total thyroidectomy at two quaternary care hospitals. A four-year retrospective review was performed on the 16 charts of patients that opted for surgery following a positive PTEN mutation on molecular testing results from January 2018 to December 2021. Of the total 16 patients, 37.5% ( n = 6) had malignant tumours, 18.75% ( n = 3) had non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and 43.75% ( n = 7) had benign disease. Aggressive features were detected in 33.33% of the malignant tumours. Malignant tumours were found to have a statistically significant higher allele frequency (AF). The aggressive nodules were all poorly differentiated thyroid carcinomas (PDTCs) with copy number alterations (CNAs) and the highest AFs.

Objective: To examine various factors associated with an increased risk of reoperation for persistent or recurrent malignant thyroid cancers., Study Design: Retrospective cohort study., Setting: Tertiary academic hospital centers., Methods: Patients undergoing surgery for thyroid cancer at 2 tertiary academic institutions from 2006 to 2020 were included. Those who underwent a reoperative procedure were compared with patients only requiring 1 procedure. The Pearson chi-square and independent t test were used to compare group data accordingly. Furthermore, a binomial logistic regression was performed, while machine learning models were used to construct a predictive algorithm., Results: This study included 2266 patients with surgically managed thyroid malignancy, of which 54 (2.4%) necessitated reoperations. Those requiring a second surgical procedure were more likely to be male (40.7% vs 20.9%, P < .001), undergo bilateral (24.1% vs 3.3%, P < .001) and lateral (16.7% vs 1.8%, P < .001) neck dissections, and have a greater number of metastatic lymph nodes (mean, 9.1 vs 3.5; P < .001) and a larger tumor size (mean, 3.0 vs 2.0 cm; P < .001). According to the binomial logistic regression model, lateral neck dissection, greater number of metastatic lymph nodes, and larger tumor size significantly increased the odds of necessitating a second procedure by 7.8 (95% CI, 2.523-24.083), 1.1 (95% CI, 1.032-1.152), and 1.3 (95% CI, 1.064-1.559), respectively. Last, machine learning models could not significantly predict the occurrence of reoperation., Conclusion: This study identified patient- and cancer-related characteristics associated with an increased risk of requiring reoperation for thyroid malignancies., (© 2022 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Genomic testing has enhanced pre-surgical decision making for cytologically indeterminate thyroid nodules, but there remains uncertainty regarding RAS mutations. The addition of extra genetic alterations to previous driver mutation panels has been shown to improve predictive value. This study aims to evaluate the relationship between the mutant allele frequency (AF) and likelihood of malignancy in thyroid nodules with RAS mutations., Methods: A retrospective cohort review was performed evaluating patients with indeterminate cytology (Bethesda categories III, IV and V) and ThyroSeq® v3 testing demonstrating a RAS mutation, who underwent surgery. Univariate and multivariate regression analyses were used to evaluate relationships between AF, other genetic alterations, and malignancy., Results: Thirty-nine patients met criteria, 77% of the thyroid nodules (30/39) were found to be malignant. None demonstrated aggressive pathology. On univariate regression, there was no relationship between AF and likelihood of malignancy. There was, however, a significant correlation between AF and the rate of an additional genetic alteration. Multivariate analysis found a trend between RAS, a second genetic alteration and malignancy, but it did not reach statistical significance., Conclusions: There was no direct relationship between the level of allelic frequency in thyroid nodules expressing RAS mutations and the likelihood of malignancy. There was a statistically significant relationship between increasing AF and the presence of a second genetic abnormality, suggesting a possible progression from initial driver mutation and then a second genetic alteration prior to malignant transformation., (© 2023. The Author(s).)

Background: This study aims to develop and validate, a clinically useful modified index of fragility (mIFG) to identify patients at risk of fragility and to predict postoperative adverse events., Method: An observational study was performed using the American College of Surgeons National Surgical Quality Improvement Program database, from 2006 to 2018. All patients undergoing nonemergency head and neck cancer surgery were included. A seven-item index (mIFG) was developed using variables associated with frailty, cachexia, and sarcopenia, drawn from the literature (weight loss, low body mass index, dyspnea, diabetes, serum albumin, hematocrit, and creatinine). Multivariable logistic regression was used to model the association between mIFG, postoperative adverse events and death. A validation cohort was then used to ascertain the diagnostic accuracy of the mIFG., Results: A total of 23,438 cases were included (16,407 in the derivation group and 7031 in the validation group). There was a total of 4273 postoperative major adverse events (AE) and deaths, 1023 postoperative pulmonary complications and 1721 wound complications. Using the derivation cohort, the 7-item mIFG was independently associated with death, major AEs, pulmonary and wound complications, when controlling for significant covariates. The mIFG predicted death and major adverse events using the validation cohort with an accuracy of 0.70 (95% CI: 0.63-0.76) and 0.64 (95% CI: 0.63-0.66), respectively. The mIFG outperformed the modified Frailty index., Conclusion: The modified index of fragility is a reliable and easily accessible tool to predict risk of postoperative adverse events and death in patients undergoing head and neck cancer surgery., (© 2023. The Author(s).)

This study aimed to examine whether concurrent mutations with a TERT promoter mutation are associated with a greater likelihood of more aggressive disease than a TERT promoter mutation alone. The medical records of 1477 patients who underwent thyroid surgery at two tertiary hospitals between 2017 and 2022 were reviewed. Twenty-four patients had TERT promoter mutations based on molecular profile testing. Clinicodemographic data, mutational profiles, and histopathological features were assessed. Descriptive analysis, Fisher's exact test, and binary logistic regression were performed. Seven patients had single-gene TERT promoter mutations, and 17 had concurrent mutations, including BRAF V600E , HRAS , NRAS , PIK3CA , and EIF1AX . The overall prevalence of malignancy was 95.8%, of which 78.3% were aggressive thyroid cancers. There was a statistically significant association between concurrent mutations and disease aggressiveness. The odds of having aggressive disease were 10 times higher in patients with a TERT promoter mutation and a concurrent molecular alteration than in those with a TERT promoter mutation alone. This is an important finding for thyroid specialists to consider when counseling patients concerning risk stratification and management options.

ThyroSeq V3 (TsV3) tests for various genetic alterations, including gene expression alterations (GEAs), to improve diagnostic accuracy and clinical decision-making for indeterminate thyroid nodules. This study aimed to clarify the clinico-pathological features and outcomes of GEA-positive thyroid nodules, which have not yet been well-described in the literature. A retrospective chart review was performed whereby patients were included if they underwent thyroid surgery between January 2018 and May 2022 at two McGill University teaching hospitals and their surgery was preceded by pre-operative molecular TsV3 testing. In total, 75 of the 328 patients with thyroid nodules (22.9%) who underwent molecular testing and surgery were GEA-positive. On surgical pathology, GEA-positive nodules showed a significantly higher malignancy rate compared to their GEA-negative counterparts (90.7% vs. 77.7%, respectively, p = 0.011). Among those that were malignant, 48.5% had at least one aggressive pathological feature, including histological subtype, extra-thyroidal extension, or lymph node metastasis. BRAF V600E mutation had a significantly greater association with aggressive malignant GEA-positive nodules compared to non-aggressive ones (p < 0.001). This study demonstrates that GEA may be an effective diagnostic and prognostic tool for thyroid nodule management. However, further investigation is needed to characterize the clinico-pathological features of GEA in isolation and in association with other gene alterations.

Molecular mutations and alterations play a role in thyroid tumorigenesis. Different alterations are associated with different clinical and pathological characteristics. Copy number alterations (CNAs) are known to be present in some thyroid tumors; however, their idiosyncratic clinicopathological implications are not yet well elucidated. A retrospective chart review was performed to identify patients with CNAs on pre-operative molecular testing results who subsequently underwent surgical treatment between January 2016 and April 2022 at McGill University teaching hospitals. Of the 316 patients with thyroid nodules who opted for molecular testing with ThyroSeqV3 followed by surgery, 67 (21.2%) nodules were positive for CNAs, including 23 Bethesda III, 31 Bethesda IV, 12 Bethesda V and 1 Bethesda VI nodules. On surgical pathology, 29.9% were benign and 70.1% were malignant or non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Among those that were malignant/NIFTP, 17.02% were considered to be aggressive cancers. The presence of other molecular alterations was found to be an independent predictor of malignancy in multivariate analysis (OR = 5.087, 95% C.I. = 1.12-23.04, p = 0.035). No unique factor was correlated with aggressiveness; however, CNA-positive thyroid nodules that were associated with high-risk mutations such as BRAF V600E , TP53 , NTRK1/3 fusion, or PTEN mutation with high allele frequency (AF) ended up being aggressive cancers. Most of the CNA-positive thyroid nodules resulted in follicular patterned tumors in 41 (65.2%) cases and oncocytic tumors in 20 (29.9%) cases. This study demonstrates that 70.1% of surgically resected thyroid nodules with CNAs were malignant/NIFTP. Most CNA-positive thyroid nodules were either oncocytic patterned tumors or follicular patterned tumors. Furthermore, CNA-positive thyroid nodules were more likely to be malignant if they were associated with other molecular alterations or mutations.

The risk of malignancy (ROM) of EIF1AX -mutated thyroid nodules has been theorized to be contingent on the position of the mutation within the gene and the presence of co-existing mutations. However, due to EIF1AX 's low mutation frequency, sample sizes currently reported in the literature are too diminutive to appraise the clinical utility of molecular diagnostic testing. The objective of this study was to elucidate prognostic indicators of EIF1AX -mutated thyroid tumors and cancer aggressiveness by examining a large cohort of cytologically indeterminate thyroid nodules (CITNs) that underwent molecular testing and subsequent surgical resection. This is a multicenter study involving 764 subtotal and total thyroidectomy patients that underwent preoperative molecular testing at two quaternary care hospitals. A five-year retrospective review was performed on the 42 charts of patients that opted for surgery following a positive EIF1AX mutation on ThyroseqV3 results from January 2018 to May 2022. Patient demographics, cytopathology results, molecular testing results, and postoperative histopathology were reviewed. Of the 42 surgically resected nodules that harbored an EIF1AX mutation, 16 (38.1%) were benign, six (14.3%) were non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) or well-differentiated thyroid neoplasms of uncertain malignant potential (WDT-UMPs), and 20 (47.6%) were malignant. An isolated EIF1AX mutation conferred a ROM of 47.6%, whereas the ROM for nodules with at least one additional molecular alteration was 72.7%. The ROM increased to 100% for nodules with at least one additional molecular alteration and the A113&#95;splice site mutation. Six malignant nodules were aggressive, with five having variegated components of poorly differentiated thyroid carcinoma (PDTC). EIF1AX -mutated thyroid nodules are more susceptible to malignancy in the presence of the A113&#95;splice site mutation and when co-mutated with RAS and/or TP53 . This deleterious amalgam is associated with aggressive disease and renders these nodules PDTC. A preoperative molecular test finding of an EIF1AX mutation can be a useful tool for thyroid specialists to optimize clinical management.

Background: The EIF1AX mutation has been identified in various benign and malignant thyroid lesions, with a higher prevalence in poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma, especially when combined with RAS or TP53 mutation. However, data and clinical significance of EIF1AX mutations in thyroid nodules is still limited. We investigated the prevalence of EIF1AX mutations and co-mutations in cytologically indeterminate thyroid nodules at our institution., Methods: A 5-year retrospective analysis was performed on surgically resected thyroid nodules with identified EIF1AX mutations on molecular testing with ThyroseqV3 ® . Mutation type and presence of co-mutations were correlated with histopathologic diagnosis and clinical characteristics. Histopathology diagnoses were subsequently categorized as benign, borderline, malignant or aggressive malignant (≥ 10% PDTC component). Chi-square test was used to compare the malignancy associations of the: 1) A113&#95;splice mutation compared to non-A113&#95;splice mutations 2) singular A113&#95;splice mutations compared to singular non-A113&#95;splice mutations. Fisher's Exact Test was used to determine the association of A113&#95;splice mutation with aggressive malignancies compared to non-A113&#95;splice mutations. A p value of 0.05 or less was considered statistically significant., Results: Out of 1583 patients who underwent FNA, 621 had further molecular testing. 31 cases (5%) harbored EIF1AX mutations. Of these cases, 12 (38.7%) were malignant, 2 (6.5%) were borderline, and 17 (55%) were benign. 4/31 cases (13%) were aggressive malignant (≥ 10% PDTC component). The most prevalent mutation was the A113&#95;splice mutation at the junction of intron 5 and exon 6 (48%). All other mutations, except one, were located at the N-terminal in exon 2. 7/31 cases (22.6%) harbored ≥ 1 co-mutation(s), including 4 RAS, 3 TP53, 1 TERT and 1 PIK3CA, with 86% of them being malignant. All 4 nodules with RAS co-mutations were malignant including one PDTC., Conclusion: Our study reports the largest cohort of EIF1AX mutations in Bethesda III/IV FNA samples with surgical follow-up to our knowledge. The presence of the EIF1AX mutation confers a 45.2% risk of malignancy (ROM) or borderline after surgery. However, the coexistence of EIF1AX mutations with other driver mutations such as RAS, TERT or TP53 conferred an 86% ROM. While 55% of thyroid nodules were benign at the time of surgery, the possible malignant transformation of these nodules, had they not been resected, is unknown. Finally, 13% of the nodules with EIF1AX mutations were aggressive with a significant PDTC component. These findings can further aid in clinical decisions for patients with thyroid nodules., (© 2022. The Author(s).)

In the past few decades, molecular characterization of thyroid cancer has made significant progress and is able to identify thyroid-cancer-related molecular markers that can then be applied clinically for improved decision making. The aim of this review is to provide a general overview about the molecular markers (mutations and alterations) of thyroid cancers, present several molecular tests, and discuss the clinical applications of identifying these markers supported by the clinical experience of several high-volume thyroid cancer specialists at the McGill university hospitals in Montreal, Canada. Our group experience showed that molecular testing can reclassify more than half of the patients with indeterminate thyroid nodules (Bethesda III and IV) into benign and spare these patients from unnecessary diagnostic surgery. Furthermore, it can help optimize the initial management in thyroid cancers with no evidence of high risk of recurrence of disease preoperatively. While routine molecular testing is not firmly established for thyroid FNA specimens that are suspicious or positive for malignancy (Bethesda V and VI), knowledge of a thyroid nodule's molecular risk group profile in such cases, together with its clinical and radiologic features, can help select the optimal surgical options (lobectomy versus upfront total thyroidectomy and central neck dissection), as demonstrated by our studies.

Objective: Major postoperative adverse events (MPAEs) following head and neck surgery are not infrequent and lead to significant morbidity. The objective of this study was to ascertain which factors are most predictive of MPAEs in patients undergoing head and neck surgery., Methods: A cohort study was carried out based on data from patients registered in the National Surgical Quality Improvement Program (NSQIP) from 2006 to 2018. All patients undergoing non-ambulatory head and neck surgery based on Current Procedural Terminology codes were included. Perioperative factors were evaluated to predict MPAEs within 30-days of surgery. Age was classified as both a continuous and categorical variable. Retained factors were classified by attributable fraction and C-statistic. Multivariate regression and supervised machine learning models were used to quantify the contribution of age as a predictor of MPAEs., Results: A total of 43 701 operations were analyzed with 5106 (11.7%) MPAEs. The results of supervised machine learning indicated that prolonged surgeries, anemia, free tissue transfer, weight loss, wound classification, hypoalbuminemia, wound infection, tracheotomy (concurrent with index head and neck surgery), American Society of Anesthesia (ASA) class, and sex as most predictive of MPAEs. On multivariate regression, ASA class (21.3%), hypertension on medication (15.8%), prolonged operative time (15.3%), sex (13.1%), preoperative anemia (12.8%), and free tissue transfer (9%) had the largest attributable fractions associated with MPAEs. Age was independently associated with MPAEs with an attributable fraction ranging from 0.6% to 4.3% with poor predictive ability (C-statistic 0.60)., Conclusion: Surgical, comorbid, and frailty-related factors were most predictive of short-term MPAEs following head and neck surgery. Age alone contributed a small attributable fraction and poor prediction of MPAEs., Level of Evidence: 3.

Patients with head and neck cancer report high unmet psychosocial needs as they undergo lifesaving treatments that can significantly alter their appearance and cause functional impairments. This qualitative analysis of recordings of 88 pre- and post-surgical consultations involving 20 patients respond to the need for empirical studies of patient-provider conversations about body image concerns. It indicates that the emphasis on concerns about survival, cure, and physical recovery during clinical consultations may leave concerns about the impacts of surgery on appearance and function unexplored and even silenced. The interviews with patients and medical team members that complement the analysis of the recordings suggest that an emphasis on survival, cure, and physical recovery can respond to the need for reassurance in the context of serious illness. However, it can also be problematic as it contributes to the silencing of patients' concerns and to a potential lack of preparedness for the consequences of surgery. The results of this study can contribute to raising surgeons' awareness of the interactional dynamics during clinical consultations. Moreover, the results highlight the unique role that surgeons can play in validating patients' psychosocial concerns to support patients' rehabilitation in both physical and psychosocial domains.

Objective: Examine the association of Graves' disease with the development of postoperative neck hematoma., Design: A cohort of patients participating in the Thyroid Procedure-Targeted Database of the National Surgical Quality Improvement Program from January 1, 2016 to December 31, 2018., Setting: A North American surgical cohort study., Methods: 17 906 patients who underwent thyroidectomy were included. Propensity score matching was performed to adjust for differences in baseline covariates. Multivariate logistic regression was used to ascertain the association between thyroidectomy for Graves' disease and risk of postoperative adverse events within 30 days of surgery. The primary outcome was postoperative hematoma. Secondary outcomes were postoperative hypocalcemia and recurrent laryngeal nerve injury., Results: One-to-three propensity score matching yielded 1207 patients with mean age (SD) of 42.6 (14.9) years and 1017 (84.3%) female in the group with Graves' disease and 3621 patients with mean age (SD) of 46.7 (15.0%) years and 2998 (82.8%) female in the group with indications other than Graves' disease for thyroidectomy. The cumulative 30-day incidence of postoperative hematoma was 3.1% (38/1207) in the Graves' disease group and 1.9% (70/3621) in other patients. The matched cohort showed that Graves' disease was associated with higher odds of postoperative hematoma (OR 1.65, 95% CI 1.10-2.46) and hypocalcemia (OR 2.04, 95% CI 1.66-2.50) compared with other indications for thyroid surgery. There was no difference in recurrent laryngeal nerve injury among the 2 groups., Conclusions: Patients with Graves' disease undergoing thyroidectomy are more likely to suffer from postoperative hematoma and hypocalcemia compared to patients undergoing surgery for other indications.

Background: In clinical practice, thyroid tumor size plays a critical role in the staging of thyroid malignancies and in the selection of nodules that should undergo ultrasound-guided fine-needle aspiration. Thyroid tumor size is influenced by the elapsed time since the beginning of oncogenesis and by the presence of somatic mutations driving growth, such as BRAF V600E mutations, associated with aggressive phenotypes, and RAS-like mutations, associated with more indolent behavior. Although large nodules are often considered to be more alarming, the true impact of tumor size on prognosis remains controversial. The aim of this study was to assess the relationship between mutational status, tumor size and aggressiveness, with emphasis on BRAF V600E and RAS-like mutations., Method: We conducted a multicentric retrospective chart review in Montréal, Canada, of all patients who underwent thyroid surgery between January 2016 and December 2020, with well-differentiated thyroid cancer on final pathology, and who had undergone molecular testing revealing the presence of BRAF V600E mutations or RAS-like mutations (NRAS, HRAS or KRAS)., Results: We included 214 cases. There were 117 (54.7%) cases of BRAF V600E and 97 (45.3%) cases of RAS-like mutations. The BRAF V600E group was statistically associated with a smaller mean tumor size when compared with the RAS group of 1.55 cm and 2.04 cm, respectively. In a multivariate model, tumors with BRAF V600E mutations were also more likely to display aggressive pathological features, including extra-thyroidal extension, lymph node metastasis, columnar cell features, tall cell histology, or hobnail histology (OR 26.69; 95% CI 11.15-70.81). In contrast, tumor size was not associated with pathologic aggressive features on multivariate analysis (OR 0.81; 95% CI 0.54-1.22)., Conclusion: This study demonstrates that thyroid tumors expressing BRAF V600E mutations correlate with aggressive pathologic features more than tumors expressing RAS-like mutations. When comparing tumors with BRAF V600E and RAS-like mutations, the former were found to be smaller. As a result of this finding, this study suggests that molecular alterations may better predict aggressive pathologic features than the size of the tumor., (© 2022. The Author(s).)

Importance: Patient education and engagement is a pivotal component of surgical recovery. Ensuring proper patient education involves a thorough understanding of one's diagnosis and recovery plan, while reducing language and learning barriers to help patients make informed decisions and improve their hospital experience., Objective: To assess whether using an animated surgical guide will help patients who are undergoing head and neck surgery feel more satisfied with their surgery and recovery process., Design, Setting, and Participants: A randomized clinical trial was conducted between January and August 2020 at a single tertiary care academic center in Montreal, Canada. A consecutive sample of individuals who were undergoing any of the following surgical procedures was recruited: head and neck cancer resection with or without reconstruction, parotidectomy, thyroidectomy, parathyroidectomy, laryngectomy, or transoral robotic resection. The treating team was masked to group allocation, while study participants in the nonintervention group were unaware of the multimedia platform to avoid introducing bias in their survey responses., Interventions: Patients were randomly allocated to either the treatment arm, in which they obtained access to a multimedia patient education platform, or the control arm, in which they received traditional patient education methods via clinical visits., Main Outcomes and Measures: Primary analysis compared patient satisfaction scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire INFO 25, a validated questionnaire on the perceived quality of information received by patients with cancer (possible scores ranging from 20 to 80)., Results: A total of 100 patients (50 in each arm; 63 women [63%]; 6 African American [6%, 12 Hispanic/Latino [12%], 11 Middle Eastern [11%], and 78 White [78%] individuals) completed the preintervention and postintervention questionnaires. In those who received access to the patient education platform, there was an 11.3-point (Cohen d = 1.02; control group score, 61.1 of 80; treatment group score, 72.4 of 80) difference of greater postoperative satisfaction scores at 1 month. While both groups felt that they received an adequate amount of information concerning their disease process, patients in the treatment arm had significantly better satisfaction with information concerning their medical tests, treatments, and other services., Conclusions and Relevance: This randomized clinical trial of patients undergoing head and neck cancer treatment demonstrates that multimedia patient education platforms may enhance current traditional methods, providing complementary information on patients' treatment plans and recovery process, mental health, family life, and supplementary services. Further research is currently underway to confirm whether this platform will lead to decreased hospital stay, shorter complication rates, and long-term effects., Trial Registration: ClinicalTrials.gov Identifier: NCT04048538.

Objectives: The aim of this study was to ascertain the relationship between Bethesda category and molecular mutation of thyroid nodules in patients undergoing thyroidectomy., Design: A retrospective cohort of patients who underwent thyroidectomy following needle biopsy and molecular profile testing was performed., Setting: Two tertiary care academic hospitals., Participants: Consecutive patients with a dominant thyroid nodule who underwent both USFNA and molecular profile testing followed by thyroidectomy were included in the study., Main Outcome and Measures: The main outcome was postoperative diagnosis of thyroid cancer and aggressivity of disease based on histopathological variants, nodal metastasis or extra-thyroidal extension. Associations between Bethesda category, molecular mutation and postoperative pathology was assessed using descriptive analysis and chi-square testing., Results: Four hundred fifty-one patients were included. 95.9% (93/97) of patients with a BRAFV600E mutation had a Bethesda category V or VI (p < .001), and all had confirmed thyroid cancer on postoperative pathology. Those with H, K or N RAS or EIF1AX mutations, gene expression profiling (GEP) or copy number alterations showed an association with Bethesda categories III and IV (p ≤ .01). Those with no identified molecular mutation had a lower incidence of aggressive thyroid cancer compared to those with an identified mutation (12.6% vs. 44.3%, p < .01)., Conclusion: BRAFV600E mutations were associated with thyroid cancer subtypes known to be more aggressive whereas RAS and EIF1AX mutations, copy number alterations, and GEP were related to Bethesda categories III and IV. These findings may help thyroid specialists better identify aggressive thyroid nodules associated with indeterminate Bethesda categories., (© 2021 John Wiley & Sons Ltd.)

Background: While some studies suggest that the BRAF V600E mutation correlates with a high-risk phenotype in papillary thyroid microcarcinoma (PTMC), more evidence is necessary before this mutation can be used to help guide decision making in the management of small thyroid nodules. This study investigated whether BRAF V600E mutation is associated with aggressive features in PTMC (≤ 1 cm) and small PTC (1-1.5 cm)., Methods: Retrospective chart review was performed on 121 patient cases. Patients who underwent thyroid surgery for PTMC (≤ 1 cm) or small PTC (1-1.5 cm) were included if molecular testing was done for BRAF V600E mutation. Two study groups were created based on tumour size: PTMC (n = 55) and small PTC (n = 66). The groups were analysed for the presence of a BRAF V600E mutation and aggressive features, including macroscopic extrathyroidal extension (ETE), lymph node metastasis (LNM), and high-risk histological features (tall cell, columnar cell, hobnail, solid/trabecular, and diffuse sclerosing). The Fischer exact test was used to calculate statistical significance., Results: BRAF V600E mutations were detected in 43.6% of PTMC and 42.4% of small PTC. Of the mutated PTMC nodules, 54.1% demonstrated aggressive characteristics as compared to 19.4% of the non-mutated PTMCs (p = 0.010). Of the mutated small PTC tumours, 82.1% had aggressive features. In contrast, 28.9% of the non-mutated small PTCs showed aggressive features (p < 0.001)., Conclusions: Our findings demonstrate an association between a BRAF V600E mutation and aggressive features in PTMC (≤ 1 cm) and small PTC (1-1.5 cm). Therefore, determining the molecular status of these thyroid nodules for the presence of BRAF V600E can help guide patient management., (© 2021. The Author(s).)

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.

The Bethesda classification system for thyroid fine needle aspirate (FNA) is used to predict the risk of malignancy and to guide the management of thyroid nodules. We postulated that thyroid malignancies characterized as Bethesda III on FNA have more aggressive features than those classified as Bethesda IV. A retrospective chart review was performed to identify those who underwent thyroid surgery at a single tertiary hospital setting between 2015 and 2020. Associations between Bethesda category, molecular genetic test results, and histopathologic findings were examined. Out of 628 surgeries that were performed, 199 (54.2%) Bethesda III nodules and 216 (82.8%) Bethesda IV nodules were malignant. Of those that were malignant, 37 (18.6%) and 22 (10.2%) Bethesda III and Bethesda IV nodules showed aggressive features, respectively ( p value = 0.014). There was a proportionally increased number of aggressive features in extra-thyroidal extension, lymph nodes metastasis, and all aggressive subtypes of papillary thyroid cancer in the Bethesda III category. Although Bethesda IV nodules are much more likely to be malignant ( p value = 0.002), our study suggests that Bethesda III nodules that are resected are more likely to have aggressive features than Bethesda IV nodules, with a statistically significant increase in the solid variant of papillary thyroid cancer and lymph node metastasis.

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.

Importance: Frailty represents a multidimensional syndrome that is increasingly being used to stratify risk in surgical patients. Current frailty risk models are limited among those undergoing thyroid or parathyroid surgery., Objective: To develop and compare preoperative risk indices to determine factors associated with short-term major postoperative adverse events in patients undergoing thyroid or parathyroid surgery., Design, Setting, and Participants: This cohort study evaluated 154 895 patients in the American College of Surgeons National Surgical Quality Improvement Program who underwent thyroid or parathyroid surgery from January 1, 2007, to December 31, 2016., Exposures: Preoperative frailty-related and surgical factors from a derivation cohort were evaluated using simple and multiple logistic regression. Variables potentially associated with postoperative adverse events were subsequently combined into a personalized preoperative Cervical Endocrine Surgery Risk Index (CESRI) and compared with existing risk models using the validation cohort., Main Outcomes and Measures: Composite variable of any major postoperative adverse event, including death, within 30 days of surgery., Results: Of the 154 895 operations reviewed, 3318 patients (2.1%; 2296 women and 1022 men; mean [SD] age, 56.1 [15.6] years) experienced a major postoperative adverse event, with 163 deaths (0.1%). Older age (age, ≥80 years: odds ratio [OR], 2.35; 95% CI, 1.74-3.13), inpatient status (OR, 3.55; 95% CI, 3.08-4.11), male sex (OR, 1.49; 95% CI, 1.29-1.71), current tobacco smoking (OR, 1.25; 95% CI, 1.05-1.48), dyspnea (OR, 1.58; 95% CI, 1.29-1.91), recent weight loss (OR, 1.88; 95% CI, 1.23-2.78), functional dependence (OR, 2.77; 95% CI, 2.05-3.69), obesity (OR, 1.33; 95% CI, 1.10-1.60), anemia (OR, 2.14; 95% CI, 1.82-2.52), leukocytosis (OR, 1.73; 95% CI, 1.38-2.14), hypoalbuminemia (OR, 1.87; 95% CI, 1.56-2.23), use of anticoagulation (OR, 2.16; 95% CI, 1.64-2.81), and length of surgery (>4 hours: OR, 2.92; 95% CI, 2.37-3.59) were independently associated with major adverse events or death on multiple regression analysis (C statistic, 0.77; 95% CI, 0.76-0.78). The area under the curve of the CESRI to determine major adverse events, including death, using the validation cohort was 0.63 (95% CI, 0.61-0.64), with a sensitivity of 0.66 (95% CI, 0.64-0.68) and specificity of 0.66 (95% CI, 0.65-0.66). The CESRI outperformed other risk models for determining adverse events (CESRI vs 5-Factor Modified Frailty Index: delta C index, 0.11; 95% CI, 0.09-0.13; CESRI vs American Society of Anesthesiologists Physical Status Classification System: delta C index, 0.05; 95% CI, 0.03-0.07; CESRI vs American College of Surgeons Risk Calculator: delta C index, 0.02; 95% CI, 0.01-0.03; and CESRI vs Head and Neck Surgery Risk Index: delta C index, 0.04; 95% CI, 0.03-0.06)., Conclusions and Relevance: This study suggests that the CESRI is able to determine major postoperative adverse events in patients undergoing thyroid or parathyroid surgery.

Background: Molecular testing of thyroid nodules is a diagnostic tool used to better understand the nature of thyroid nodules. The aim of this study is to better comprehend the relationship between specific mutations and aggressive behavior of the tumour as demonstrated on postoperative pathological analysis., Methods: A retrospective chart review of 103 cases was performed. Included were patients who had undergone molecular testing using a panel that tests for 9 mutations (ThyGenX®) and were found to have malignant tumours. The following gene alterations were found pre-operatively in the nodules: BRAF V600E (n = 32), BRAF K601E (n = 4), NRAS (n = 11), HRAS (n = 4), KRAS (n = 3), RET/PTC1 rearrangement (n = 1), TERT promoter (n = 2), PAX8-PPARγ rearrangement (n = 1), and 45 cases where no mutation was detected. Aggressive behavior was defined by extra-thyroidal extension (ETE), lymph node metastasis (LN+), and the following variants of papillary thyroid carcinoma: tall cell, solid, diffuse sclerosing, columnar cell and hobnail. Chi-squared testing was performed to compare groups., Results: The group with BRAF V600E, RET/PTC1 rearrangement, and TERT promoter mutations was associated with ETE 37.1%, and LN+ 45.7% of the time compared to 4.3 and 13.0% in the group with other mutations, and 4.4 and 4.4% in the group with no mutations (p-value 0.02, p-value < 0.001, p-value 0.006). In addition, the BRAF V600E, RET/PTC1 rearrangement, and TERT mutations group demonstrated tall cell variants (17.1%), columnar cell variants (5.7%), and hobnail variants (3%). The other mutations group demonstrated columnar cell variants (4.3%), and the no mutations group demonstrated solid variants (2.2%)., Conclusions: In this study, BRAF V600E, RET/PTC1 rearrangement, and TERT mutations were associated with aggressive behaving thyroid malignancies as defined above. Molecular testing may be a useful method to anticipate aggressive tumour types and therefore assist in planning the extent and timing of surgery.

Background: We ascertain the association of postoperative infection on survival in patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC)., Methods: A retrospective study of patients with stage III/IVA OCSCC undergoing curative-intent surgery was performed. Postoperative infection was considered within 30 days after surgery. Kaplan-Meier survival curves were used to compare overall survival (OS) in patients with postoperative infection. Cox regression and propensity-score matching were used to adjust for confounders., Results: Fifty-four of 114 patients had a postoperative infection. The 5-year OS in patients with a postoperative infection (24.1%) was lower than those without (65.2%; P < .0001). Postoperative infection was a negative predictor of OS after adjusting for patient, antibiotic, pathologic, and operative factors; the adjusted hazard ratio for OS was 2.54 (95% confidence interval, 1.27-5.09)., Conclusion: Postoperative infection is a strong negative predictor of OS in patients with OCSCC undergoing ablative surgery., (© 2019 Wiley Periodicals, Inc.)

Background: Reported rates of thyroid cancer in Graves' disease (GD) vary widely. The aim of this study was to evaluate the prevalence of papillary thyroid carcinoma (PTC), including aggressive forms, in GD compared to matched controls undergoing thyroidectomy. Furthermore, it seeks to elucidate any patient- or tumour-associated factors predictive of malignancy or an aggressive course., Methods: We performed a matched cohort study of GD patients undergoing thyroidectomy at our institution between 2006 to 2018. Clinicodemographic factors, preoperative characteristics, surgical factors, final histopathology as well postoperative course were collected. Aggressive PTC was defined as evidence of lymph node metastasis, extrathyroidal extension, gross vascular invasion and/or aggressive histologic variants. Prevalence of PTC was compared with sex, age and nodule size-matched euthyroid patients that underwent thyroidectomy in the same time period., Results: A total of 132 patients were included in the study with a mean age of 46 (±14) years. Malignancy was identified in 36/66 (55%) patients with GD; 20/66 (30%) were incidental carcinomas and 9/66 (14%) were associated with aggressive pathologic features. In the aggressive group, lymph node metastasis to the central compartment was present in 8 (12%) cases, extrathyroidal extension in 4 (6%) cases and one (1.5%) patient had a diffuse sclerosing tumor variant. No significant differences in outcome were found between the two groups. GD patients were more likely to have incidental carcinomas (p = 0.035). Adjusting for baseline patient characteristics, GD patients demonstrated an increased likelihood of harbouring a malignancy (odds ratio (OR) = 2.67; 95% confidence interval (CI) 1.00-7.18) compared to controls., Conclusion: More than half of patients with GD undergoing thyroidectomy had concurrent thyroid malignancy with aggressive features present in 14% of patients. GD may confer a heightened risk of thyroid cancer; thyroid nodules should therefore be carefully investigated.

Importance: Patients 65 years or older are the most frequent users of operative resources and are also the most vulnerable to postoperative adverse events (AEs). Frailty indices are increasingly being used for preoperative risk stratification within head and neck cancer surgery, but most models lack a multifactorial basis and cannot be directly applied to clinical practice. A practical risk index is needed for clinicians to gauge risk factors preoperatively., Objective: To develop a preoperative risk index of short-term major postoperative AEs for patients undergoing head and neck cancer surgery., Design: Cohort analysis of patients from multiple medical centers undergoing inpatient ablative or reconstructive head and neck cancer surgery and registered in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) from 2006 to 2016., Exposures: Inpatient ablative or reconstructive head and neck cancer surgery., Main Outcomes and Measures: Sociodemographic, frailty-related, and surgical factors in the derivation cohort were evaluated using simple and multiple logistic regression. Risk factors were subsequently integrated into a preoperative head and neck surgery risk index (HNSRI) and compared with existing models using the validation cohort. A composite variable of major postoperative AEs was used, including death within 30 days of surgery., Results: A total of 43 968 operations were found using the ACS NSQIP database. Of these, 12 569 cases were excluded as non-head and neck cancer or emergency surgery. Of the included 31 399 operations reviewed, the mean (SD) patient age was 56.9 (15.4) years, and 16 994 of the patients were women (54.1%). A total of 4556 (14.5%) patients had a major postoperative AE, and 209 (0.7%) died. Older age, male sex, smoking, anticoagulation, recent weight loss, functional dependence, free-tissue transfer, tracheotomy, duration of surgery, wound classification, anemia, leukocytosis, and hypoalbuminemia were independently associated with major AEs or death on multiple regression analysis (C statistic, 0.83). The area under the curve of the HNSRI to predict major AEs including death using the validation cohort (n = 15 699) was 0.84 (95% CI, 0.83-0.85) with a sensitivity of 80.1% (95% CI, 79.4%-80.8%) and specificity, 72.3% (95% CI, 70.3%-74.2%). The HNSRI outperformed existing risk models for prediction of AEs: delta C index of the HNSRI to the modified frailty index 11, 0.23 (95% CI, 0.22-0.25); the American Society of Anesthesiologists classification, 0.14 (95% CI, 0.13-0.16); and the ACS risk calculator, 0.02 (95% CI, 0.01-0.03)., Conclusions and Relevance: The proposed HNSRI demonstrated a high sensitivity and specificity for major postoperative AEs and death in the studied population. This risk index can be used to counsel patients awaiting head and neck cancer surgery.

Background: Medullary thyroid cancer (MTC) cells are capable of secreting various tumor markers including calcitonin and carcinoembyronic antigen (CEA). The purpose of this study is to determine whether abnormal CEA levels may be used as a tumor marker to predict the severity of disease in MTC., Methods: A retrospective analysis was completed for 33 patients with MTC who had preoperative serum CEA levels. Univariate and multivariate analyses were used to quantify the relationship between serum CEA levels and tumor stage and prognosis., Results: On multivariate analysis, elevated preoperative CEA levels were significantly associated with the size and stage of tumor, distant metastasis, decreased biochemical cure, and mortality. There was a significant association between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml). There was also a positive correlation with increased cancer stage (> 377 ng/ml), distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml, patient mortality was 67%., Conclusion: In this study, both pre-operative calcitonin and CEA levels were significantly correlated with the extent of disease in MTC. While calcitonin has a linear relationship with disease progression, abnormal CEA levels were a better indicator of advanced disease. CEA levels > 271 ng/ml are significant for advanced tumor size and staging, metastasis to the central compartment, and decreased chance of biochemical cure. CEA levels greater than 500 ng/ml are associated with significant patient mortality.

Background: The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic biopsy be based on ultrasound findings (i.e. size and nodule characteristics). The overall effect of these changes results in fewer nodules requiring biopsy. This study was conducted to determine if the changes to the guidelines will result in overlooked thyroid cancers, specifically malignancies with aggressive characteristics measuring between 1 and 1.49 cm., Methods: Patients (n = 2083) with thyroid nodules who underwent total or subtotal/hemi thyroidectomy with or without neck dissection by a single surgeon between 2006 and 2016 were retrospectively enrolled. Demographic information and nodule characteristics were collected for all patients. Ultrasonography and final pathology reports were reviewed for patients with thyroid nodules between the sizes of 1-1.49 cm (n = 155)., Results: 45% (n = 70) of patients with nodules between 1 and 1.49 cm were "low suspicion" nodules according to ultrasound. 47 of these nodules contained malignancies on final histopathological examination, 100% of which were of the papillary subtype. 21% (n = 10) of these malignant nodules demonstrated extrathyroidal extension and 34% (n = 16) were associated with regional metastases., Conclusions: Reliance on sonographic patterns alone could result in missed cancer diagnoses in patients with thyroid nodules measuring between 1 and 1.49 cm. Moreover, a portion of these malignancies may be associated with aggressive features. The effect of this finding on long-term outcomes is unclear.

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.

Objective: Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy originating from parafollicular C-cells with the potential for aggressive behavior. The extent of lymph node (LN) dissection at the time of surgery is controversial, with different schools of thought prevailing. Some systematically perform LN dissections, whereas others base their decision on radiologic evidence of disease and some with the assistance of pre-operative calcitonin (CT) levels., Methods: We retrospectively assessed the correlation between pre-operative CT levels and clinico-pathologic factors among 42 patients with MTC between 1994 and 2015. Furthermore, we refined the use of pre-operative serum CT levels and explored for the first time a test called the Calcitonin Secretory Index (CSI, ng/mL/mm)., Results: Pre-operative CT levels correlated independently with tumor size ( P<.0001), number of metastatic LNs ( P<.01), and increased rates of distant metastasis. The CSI better predicted early LN disease ( P<.045). Patients with early LN metastasis had a CSI >30 ng/mL/mm, a representative threshold above which the surgical cure declines considerably., Conclusion: In our experience, pre-operative CT levels and now the CSI appear as sensitive and specific risk stratification markers for MTC. Despite negative findings on dedicated pre-operative neck imaging in addition to total thyroidectomy, a CSI >30 ng/mL/mm would prompt bilateral central node dissection. Due to the small sample size, our study provides preliminary evidence of the value of CSI in clinical practice., Abbreviations: ANOVA = analysis of variance; ATA = American Thyroid Association; CSI = Calcitonin Secretory Index; CT = calcitonin; LN = lymph node; MTC = medullary thyroid carcinoma; ROC = receiver operating characteristic.

Objective: Determine if anatomic dimensions of airway structures are associated with airway obstruction in obstructive sleep apnea (OSA) patients., Methods: Twenty-eight subjects with ( n  = 14) and without ( n  = 14) OSA as determined by clinical symptoms and sleep studies; volunteer sample. Skeletal and soft tissue dimensions were measured from radiocephalometry and magnetic resonance imaging. The soft palate thickness, mandibular plane-hyoid (MP-H) distance, posterior airway space (PAS) diameters and area, and tongue volume were calculated., Results: Compared to controls, the OSA group demonstrated a significantly longer MP-H distance ( P  = 0.009) and shorter nasal PAS diameter ( P  = 0.02). The PAS area was smaller ( P  = 0.002) and tongue volume larger in the OSA group ( P  = 0.004). The MP-H distance, PAS measurements, and tongue volume are of clinical relevance in OSA patients., Conclusions: A long MP-H distance, and small PAS diameters and area are significant anatomic measures in OSA; however the most substantial parameter found was a large tongue volume.

Background: The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid disease. This study set out to understand the relationship between the levels of fT4 and fT3 and differentiated thyroid cancer., Methods: A case-control study was conducted with 142 cases and 86 controls from the McGill University Teaching Hospitals. All patients underwent thyroid surgery. Cases were defined as patients with malignant nodules confirmed on final pathology and controls were defined as patients with benign nodules. The serological levels of TSH, fT4 and fT3 were measured preoperatively. Odds ratios were determined for each parameter and logistic regressions were calculated between markers and probability of malignancy. Additionally, fT4 values were divided by fT3 values (fT4/fT3 quotient) for each patient and an odds ratio was calculated., Results: Amongst cases, the mean TSH was 2.25 ± 0.360U/mL, fT4 was 14.8 ± 0.689pmol/L, and fT3 was 4.65 ± 0.463pmol/L. Amongst controls, the mean TSH was 2.36 ± 1.68U/mL, fT4 was 14.3 ± 1.71pmol/L, and fT3 was 5.27 ± 0.957pmol/L. Patients in the control group were more likely to have low TSH, while patients in the case group would have high fT4 and patients in the control group were more likely to have a low fT4. The OR for patients with TSH >4.4U/mL was 2.13 (0.97, 4.65), and for patients with TSH <0.4U/mL was 0.46 (0.22, 0.95). The OR for patients with fT4 > 16pmol/L was 2.10 (1.09, 4.06), and for patients with fT4 < 10pmol/L was 0.45 (0.20, 0.98). The OR for patients with fT3 > 5.5pmol/L was 0.39 (0.14, 1.28). The OR for patients with fT3 < 3pmol/L was 1.83 (0.25, 13.69). The average fT4/fT3 was 3.39 ± 0.206 for cases and 2.93 ± 0.467 for controls. The fT4/fT3 quotient was considered high if it was >3.3 (OR =6.00 (2.94, 12.25))., Conclusion: In this study, a direct relationship between high levels of fT4 and malignancy was uncovered. Furthermore, low levels of TSH and fT4 increased the likelihood that a nodule was benign. In this study a fT4/fT3 ratio >3.3 increased the risk of malignancy by 3.6 times (p-value =0.0013).

Background: Thyroid nodules are common and often benign, although prove to be malignant upon surgical pathology in 5-15% of cases. When assessed with ultrasound-guided fine-needle aspiration (USFNA), 15-30% of the nodules yield an indeterminate result. The Afirma® gene expression classifier (AGEC) was developed to improve management of indeterminate thyroid nodules (ITNs) by classifying them as "benign" or "suspicious." Objectives were (1) to assess the performance of the AGEC in two Canadian academic medical centres (2), to search for inter-institutional variation and (3) to compare AGEC performance in Canadian versus American institutions., Methods: We undertook a retrospective cohort study of patients with indeterminate cytopathology (Bethesda Class III or IV) as per USFNA who underwent AGEC testing. We reviewed patient demographics, cytopathological results, AGEC data and, if the patient underwent surgery, results from their final pathology., Results: In total, we included 172 patients with Bethesda Class III or IV thyroid nodules underwent AGEC testing, 109 in Montreal, Quebec and 63 in St. John's, Newfoundland, in this study. Among the nodules sent for testing, 55% (60/109) in Montreal and 46% (29/63) in St. John's returned as "benign." None of these patients underwent surgery. On the other hand, 45% (49/109) nodules in Montreal and 54% (34/63) in St. John's were found to be "suspicious," for a total of 83 specimens. Seventy seven of these patients underwent surgery. Both in Montreal and St. John's, the final pathology yielded malignant thyroid disease in approximately 50% of the specimens categorized as "suspicious." Since 2013, no patient diagnosed with a benign nodule as per AGEC testing was found to harbor a malignant thyroid nodule on follow-up., Conclusions: Molecular analysis is increasingly used in the management of indeterminate thyroid nodules. This study highlights the experience of two Canadian centres with AGEC testing. We found inter-institutional variability in the rate of nodules returning as "benign," however we found similar rates of confirmed malignancy in nodules returning as "suspicious." According the literature, results for AGEC testing in two Canadian institutions align with results reported in American centres.

Background: Management decisions are not straightforward when the Ultrasound Guided Fine Needle Aspiration (USFNA) demonstrates a Bethesda score of either category III or IV, and a diagnostic hemi-thyroidectomy or a repeat USFNA (r-USFNA) could be performed. The aim of this study is to assess the effectiveness of r-USFNA in the management of indeterminate thyroid nodules by evaluating the likelihood of obtaining a definite diagnosis., Methods: We reviewed the medical records of all patients with thyroid nodules between 2011 and 2015 at the Jewish General Hospital (Montreal, Canada). Three hundred fifty-one patients who had undergone a surgical procedure (hemi or total thyroidectomy) and a diagnosis of B3 or B4 on the primary USFNA (p-USFNA) were included in the study. Ninety-six of the included patients also had a repeat USFNA prior to the surgery. Demographic data, type of procedure, and McGill Thyroid Nodule Score (MTNS) were obtained from the medical records. Malignancy rates were calculated based on the final surgical histopathology report., Results: Upon r-USFNA, an average 76 % of patients did not change Bethesda categories, 7.4 % downgraded to a benign category. The results showed that, on an average 17.3 % of patients with p-USFNA of B3 and 20 % of patients with p-USFNA of B4, upgraded to a malignant or suspicious for malignancy category, thus changing the clinical management to total thyroidectomy. Our data demonstrates that r-USFNA facilitates choosing the correct surgery of total thyroidectomy in about 20 % of nodules that have upgraded from B3/B4 to a more definite malignant category., Conclusions: r-USFNA in patients with indeterminate diagnoses (B3 or B4) increases categorization into more definite categories. Approximately 20 % of patients are found to have malignant thyroid nodules and suspicious for malignancy thyroid nodules upon repeating the biopsy, hence a diagnostic hemi-thyroidectomy was avoided and a more definitive surgery could be performed. Furthermore, repeat USFNA results in a fewer number of hemi-thyroidectomy and completion thyroidectomy procedures.

Background: It has been reported that thyroglobulin antibody are more frequently elevated in patients with thyroid cancercompared to general population. This study aims at evaluating whether preoperative thyroglobulin antibody (TgAb) levels increase the likelihood that a thyroid nodule is malignant., Methods: A retrospective review of 586 patients who underwent thyroidectomy was conducted. Demographic data, TgAb levels, and final histopathology were recorded. Patients were divided into two groups: TgAb positive (defined as TgAb ≥ 30 IU/ml) and TgAb low/negative (defined as TgAb < 30)., Results: Preoperative TgAb levels were available in 405 patients. There were 353 (87 %) patients in the TgAblow/negative group (malignancy rate: 50.42 %) and 52 (13 %) patients in the TgAb positive group (malignancy rate: 65.38 %). The sensitivity, specificity, positive predictive value and negative predictive value of TgAb ≥ 30 IU/ml for thyroid malignancy were 16.04 %, 90.67 %, 65.38 % and 49.58 %, respectively. The relative risk of having a malignant thyroid nodule when the TgAb titers were≥30 IU/ml was 1.30 (CI1.04-1.62) and the odds ratio was 1.86 (CI 1.01-3.41). Both the Pearson chi-square test (p = 0.024) and Fisher's exact test (p = 0.017) yielded statistical significance between the two groups., Conclusions: In this study, patients with preoperative TgAb ≥ 30 IU/ml had a higher rate of malignancy when compared topatients with TgAb < 30 IU/ml. This suggests that an elevated TgAb level may indicate that a thyroid nodule is at an increased risk for malignancy.

Background: Ultrasound guided fine needle aspiration (USFNA) biopsies of thyroid nodules sometimes create a decision-making dilemma for surgeons as they may yield falsely benign results. The McGill Thyroid Nodule Score + (MTNS+) was developed to aid in clinical guidance regarding the management of patients with these USFNA results. The aim of this study was to assess the MTNS+ as a clinical tool in patients with benign preoperative thyroid nodule USFNAs and to analyze the relationship between nodule size and malignancy in these patients., Methods: We conducted a retrospective chart review of 1312 patients who underwent thyroidectomies between 2010 and 2015 at the McGill University Teaching Hospitals. Patients with Bethesda II (benign) USFNA results, calculated MTNS+, and nodule size evaluated on ultrasound were included in the study. The false-negative rate was calculated, and MTNS+ and nodule size were each compared to final pathology results. Binary logistic regression was used for statistical analysis., Results: Of the 1312 patients, 101 met the inclusion criteria and together had an average MTNS+ score of 6.83, which corresponds to a predicted malignancy rate between 25 and 33 %. Final pathology revealed malignancy in 16 (15.8 %) subjects. The average MTNS+ of patients with malignant nodules on surgical pathology was 8.25, while that of patients with benign nodules was 6.56. Patients with nodule size 1-1.9 cm (a) and 2-2.9 cm (b) each had an equal rate of malignancy of 2.97 % (n = 3), nodule size 3-3.9 cm (c) had a rate of 1.98 % (n = 2), and nodule size ≥4 cm (d) a rate of 7.92 % (n = 8)., Conclusion: The rate of malignancy (15.8 %) is higher than expected when reviewing the risk of malignancy in nodules considered as Bethesda class 2. On the other hand, the rate is lower than the 25-33 % predicted by the MTNS+. We also found a higher malignancy rate for nodules above 4 cm in size, but size was a poor predictor of malignancy when used alone. Therefore, while the MTNS+ may be helpful at helping to identify USFNAs that are incorrectly classified as benign, the percentage risk of malignancy is lower than expected.

Objective: Hypocalcemia following thyroidectomy often prolongs hospital stay and is potentially life-threatening. The objective of this study is to determine whether the season when thyroidectomy is performed is associated with postoperative hypocalcemia., Study Design: Retrospective case series of patients undergoing thyroid surgery from 2009 to 2015., Setting: Tertiary care academic institution in Montreal, Canada., Subjects and Methods: A consecutive sample of 823 patients undergoing thyroidectomy by a single high-volume otolaryngologist for a suspected or confirmed thyroid malignancy. Patient demographics, procedure type, calcium and vitamin D supplementation, and seasonal rate of hypocalcemia postthyroidectomy were calculated and compared., Results: Average seasonal rates of postthyroidectomy hypocalcemia in the winter, spring, summer, and autumn were, respectively, 8.3% (8 of 216), 7.3% (12 of 165), 1.5% (3 of 201), and 3.5% (8 of 228; P < .005). Patients operated in the winter were 5.6 times more likely to develop hypocalcemia as compared with those in the summer (P < .01; 95% confidence interval: 1.7-18.7). In a multiple regression analysis factoring in season when surgery was performed, procedure type, and preoperative vitamin D/calcium supplementation, surgery occurring in the winter predicted a hypocalcemia event (correlation coefficient [SE]: 0.72 [0.024], P = .026; 0.006 [0.025], P = .81; 0.004 [0.019], P = .82, respectively)., Conclusion: In this study, patients undergoing thyroidectomy in the winter months were more likely to develop postoperative hypocalcemia when compared with those operated in the summer. Further studies are needed to understand the role of vitamin D in the observed seasonal difference in hypocalcemia rates., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Background: Vocal cord paralysis (VCP) is found in both benign and malignant thyroid disease. This study was performed to determine if the presence of preoperative VCP predicts malignancy., Methods: A retrospective analysis was performed on a cohort of 1923 consecutive patients undergoing thyroid surgery. The incidence of preoperative VCP was recorded. Patient and nodule characteristics were correlated with final pathology., Results: 1.3% of our cohort was found to have preoperative VCP. Malignant pathology was discovered in 76% of patients with preoperative VCP. Among these patients, 72% had a left sided paralysis. 10.5% of patients with preoperative VCP had perineural invasion (PNI) on final pathology, compared to 1.1% of patients with normal VC function., Conclusion: Preoperative VCP appears to be a strong, though not an absolute, indicator of malignancy. Most VCP were on the left side. Assessing for preoperative VCP is crucial in all patients who need thyroid surgery, as even benign nodules can be accompanied by preoperative vocal cord paralysis.