Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer.

Importance: Interpatient variabilities in genomic variants may reflect differences in tumor statuses among individuals. Objectives: To delineate interpatient variabilities in RAS variants in thyroid tumors based on the fifth World Health Organization classification of thyroid neoplasms and assess their diagnostic significance in cancer detection among patients with thyroid nodules. Design, Setting, and Participants: This prospective diagnostic study analyzed surgically resected thyroid tumors obtained from February 2016 to April 2022 and residual thyroid fine-needle aspiration (FNA) biopsies obtained from January 2020 to March 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data were analyzed from June 20, 2022, to October 15, 2023. Exposures: Quantitative detection of interpatient disparities of RAS variants (ie, NRAS, HRAS, and KRAS) was performed along with assessment of BRAF V600E and TERT promoter variants (C228T and C250T) by detecting their variant allele fractions (VAFs) using digital polymerase chain reaction assays. Main Outcomes and Measures: Interpatient differences in RAS, BRAF V600E, and TERT promoter variants were analyzed and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values, and negative predictive values were calculated. Results: A total of 438 surgically resected thyroid tumor tissues and 249 thyroid nodule FNA biopsies were obtained from 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years). Median (IQR) follow-up for patients who underwent FNA biopsy analysis and subsequent resection was 88 (50-156) days. Of 438 tumors, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS. The interpatient differences in these variants were discriminated at VAF levels ranging from 0.15% to 51.53%. The mean (SD) VAF of RAS variants exhibited no significant differences among benign nodules (39.2% [11.2%]), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (25.4% [14.3%]), and malignant neoplasms (33.4% [13.8%]) (P = .28), although their distribution was found in 41.7% of NIFTPs and 50.7% of invasive encapsulated follicular variant papillary thyroid carcinomas (P < .001). RAS variants alone, regardless of a low or high VAF, were significantly associated with neoplasms at low risk of tumor recurrence (60.7% of RAS variants vs 26.9% of samples negative for RAS variants; P < .001). Compared with the sensitivity of 54.2% (95% CI, 48.8%-59.4%) and specificity of 100% (95% CI, 94.8%-100%) for BRAF V600E and TERT promoter variant assays, the inclusion of RAS variants into BRAF and TERT promoter variant assays improved sensitivity to 70.5% (95% CI, 65.4%-75.2%), albeit with a reduction in specificity to 88.8% (95% CI, 79.8%-94.1%) in distinguishing malignant neoplasms from benign and NIFTP tumors. Furthermore, interpatient differences in 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were discriminated in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 nondiagnostic FNAs (23.7%), and all tumors with follow-up surgical pathology confirmed malignancy. Conclusions and Relevance: This diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.

Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules.

Importance: Molecular testing of the presence of pathogenic genomic variants in a tumor without quantifying the variant allele fraction (VAF) does not differentiate the variation extent among tumors, often resulting in an inconclusive diagnosis because of interpatient variability. Objective: To examine the association between the quantification of VAFs of BRAF V600E and TERT promoter variants and a definitive cancer diagnosis of thyroid tumors. Design, Setting, and Participants: This diagnostic study analyzed a cohort of 378 surgically resected thyroid tumors with a maximum dimension of 1 cm or larger between March 15, 2016, and March 16, 2020, and a separate cohort of 217 residual thyroid fine-needle aspiration (FNA) biopsy specimens obtained from January 22, 2020, to March 2, 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data analysis was conducted between February 1, 2021, and February 1, 2023. Exposures: Quantitative VAF assays of BRAF V600E and TERT promoter variants (C228T and C250T) were performed by digital polymerase chain reaction molecular assays. Main Outcomes and Measures: The VAFs of BRAF V600E and TERT promoter variants were correlated with tumor histologic diagnoses and histopathologic features to delineate the association of VAF assays with tumor malignancy. The receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, negative predictive value, and logistic regression analysis based on follow-up histopathologic types were used to determine the diagnostic utility of the quantitative molecular assays. Results: A total of 595 specimens, including 378 surgically resected thyroid tumors and 217 thyroid nodule FNA biopsy specimens, were collected from 580 patients (436 [75.2%] female with a mean [SD] age of 50 [16] years and 144 [24.8%] male with a mean [SD] age of 55 [14] years). Sensitive VAF assays of 378 thyroid tumors revealed the presence of the BRAF V600E variant in 162 tumors (42.9%), with 26 (16.0%) at a low VAF of 1% or less and 136 (84.0%) at a high VAF of greater than 1%, and the presence of TERT promoter variants in 49 tumors (13.0%), including 45 C228T variants (91.8%), 15 (33.3%) of which were quantified as having a low VAF (≤1%) and 30 (66.7%) as having a high VAF (>1%), and 4 C250T variants (8.2%) with VAFs between 40.0% and 47.0%. All tumors detected with BRAF V600E and/or TERT promoter variants, whether at low or high VAFs, received a definitive cancer diagnosis. Further analysis delineated a significant association between high VAFs of either variant individually or different VAF levels for both variants in coexistence and aggressive histopathologic features of tumors. Excluding low VAFs assisted in identifying patients at an intermediate-to-high risk of recurrence (odds ratio, 5.3; 95% CI, 1.9-14.6; P = .001). The VAF assays on the residual FNA biopsy specimens showed a high agreement to those on surgical tissues (κ = 0.793, P < .001) and stratified malignancy in 40 of 183 indeterminate FNA cases (21.9%), with a sensitivity of 93.8% (95% CI, 67.7%-99.7%), specificity of 90.0% (95% CI, 75.4%-96.7%), positive predictive value of 78.9% (95% CI, 53.9%-93.0%), and negative predictive value of 97.3% (95% CI, 84.2%-99.9%). Conclusions and Relevance: This diagnostic study suggests that sensitive quantitative VAF assays of BRAF V600E and TERT promoter variants can elucidate the interpatient variability in tumors and facilitate a definitive cancer diagnosis of thyroid nodules by differentiating the variation extent of genomic variants, even at low VAFs.

The impact of surgical resection margins on outcomes for adults with head and neck osteosarcomas: A Canadian sarcoma research and Clinical Collaboration (CanSaRCC) study.

OBJECTIVE: The aim of the study is to describe the factors that influence outcome in adults with head and neck osteosarcoma (HNO) with a specific focus on the margin status. METHODS: Patients with a diagnosis of HNO between the years 1996-2021 were reviewed from the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) Database. Baseline characteristics, pathology, treatment, and outcomes were analyzed. Univariable (UVA) and multivariable (MVA) Cox regression models were performed. 5-year locoregional control rate and overall survival (OS) were estimated using Kaplan-Meier method and Log-Rank test. RESULTS: Of 50 patients with a median age of 40 years (range 16-80), 27 (54%) were male. HNO commonly involved the mandible (n = 21, 42%) followed by maxilla (n = 15, 30%). Thirteen (33.3%) had low-intermediate grade and 26 (66.6%) had high grade tumors. Three patients (6%) had negative resection margins (>5 mm), 24 (48%) had close margins (1-5 mm), 15 (30%) had positive margins (<1mm) and 7 (16%) had unknown margin status. In total, 39 (78%) received chemotherapy - 22 (44%) received neoadjuvant chemotherapy while 17 (34%) received adjuvant chemotherapy. A total of 12 (24%) patients received radiotherapy, of whom 8 (16%) had adjuvant and 3 (6%) had neo-adjuvant. Median follow-up time was 6.3 years (range 0.26-24.9). Disease recurred in 21 patients (42%), of whom 15 (30%) had local recurrence only, 4 (8%) had distant metastasis, and 2 (4%) had both local and distant recurrence. 5-year locoregional control rate and OS was 62% and 79.2% respectively. Resection margins <3 mm was associated with lower 5 years OS and locoregional control rate (Log-Rank p = 0.02, p = 0.01 respectively). CONCLUSION: Osteosarcomas of the head and neck are rare and local recurrence remains a concern. Surgical resection with negative resection margins may improve survival, and a 3 mm resection margin threshold may optimize survival. Radiotherapy and/or chemotherapy should be considered in a multidisciplinary setting based on risk-features.

Postoperative opioid use following head and neck endocrine surgery: A multi-center prospective study.

Background: Opioid abuse is widespread in North America and the over-prescription of opioids are a contributing factor. The goal of this prospective study was to quantify over-prescription rates, evaluate postoperative experiences of pain, and understand the impact of peri-operative factors such as adequate pain counseling and use of non-opioid analgesia. Methods: Consecutive recruitment of patients undergoing head and neck endocrine surgery was undertaken from January 1st 2020 to December 31st 2021 at four Canadian hospitals in Ontario and Nova Scotia. Postoperative tracking of pain levels and analgesic requirements were employed. Chart review and preoperative and postoperative surveys provided information on counseling, use of local anesthesia, and disposal plans. Results: A total of 125 adult patients were included in the final analysis. Total thyroidectomy was the most common procedure (40.8%). Median use of opioid tablets was 2 (IQR 0-4), with 79.5% of prescribed tablets unused. Patients who reported inadequate counseling (n = 35, 28.0%) were more likely to use opioids (57.2% vs. 37.8%, p < .05) and less likely to use non-opioid analgesia in the early postoperative course (42.9% vs. 63.3%, p < .05). Patients who received local anesthesia peri-operatively (46.4%, n = 58) reported less severe pain on average [2.86 (2.13) vs. 4.86 (2.19), p < .05] and used less analgesia on postoperative day one [0 MME (IQR 0-4) vs. 4 MME (IQR 0-8), p < .05]. Conclusion: Over-prescription of opioid analgesia following head and neck endocrine surgery is common. Patient counseling, use of non-opioid analgesia, and peri-operative local anesthesia were important factors in narcotic use reduction. Level of evidence: Level 3.

Association between the COVID-19 pandemic and first cancer treatment modality: a population-based cohort study.

BACKGROUND: Physicians were directed to prioritize using nonsurgical cancer treatment at the beginning of the COVID-19 pandemic. We sought to quantify the impact of this policy on the modality of first cancer treatment (surgery, chemotherapy, radiotherapy or no treatment). METHODS: In this population-based study using Ontario data from linked administrative databases, we identified adults diagnosed with cancer from January 2016 to November 2020 and their first cancer treatment received within 1 year postdiagnosis. Segmented Poisson regressions were applied to each modality to estimate the change in mean 1-year recipient volume per thousand patients (rate) at the start of the pandemic (the week of Mar. 15, 2020) and change in the weekly trend in rate during the pandemic (Mar. 15, 2020, to Nov. 7, 2020) relative to before the pandemic (Jan. 3, 2016, to Mar. 14, 2020). RESULTS: We included 321 535 people diagnosed with cancer. During the first week of the COVID-19 pandemic, the mean rate of receiving upfront surgery over the next year declined by 9% (rate ratio 0.91, 95% confidence interval [CI] 0.88-0.95), and chemotherapy and radiotherapy rates rose by 30% (rate ratio 1.30, 95% CI 1.23-1.36) and 13% (rate ratio 1.13, 95% CI 1.07-1.19), respectively. Subsequently, the 1-year rate of upfront surgery increased at 0.4% for each week (rate ratio 1.004, 95% CI 1.002-1.006), and chemotherapy and radiotherapy rates decreased by 0.9% (rate ratio 0.991, 95% CI 0.989-0.994) and 0.4% (rate ratio 0.996, 95% CI 0.994-0.998), respectively, per week. Rates of each modality resumed to prepandemic levels at 24-31 weeks into the pandemic. INTERPRETATION: An immediate and sustained increase in use of nonsurgical therapy as the first cancer treatment occurred during the first 8 months of the COVID-19 pandemic in Ontario. Further research is needed to understand the consequences.

Timeliness and Modality of Treatment for New Cancer Diagnoses During the COVID-19 Pandemic in Canada.

Importance: The impact of COVID-19 on the modality and timeliness of first-line cancer treatment is unclear yet critical to the planning of subsequent care. Objective: To explore the association of the COVID-19 pandemic with modalities of and wait times for first cancer treatment. Design, Setting, and Participants: This retrospective population-based cohort study using administrative data was conducted in Ontario, Canada, among adults newly diagnosed with cancer between January 3, 2016, and November 7, 2020. Participants were followed up from date of diagnosis for 1 year, until death, or until June 26, 2021, whichever occurred first, to ensure a minimum of 6-month follow-up time. Exposures: Receiving a cancer diagnosis in the pandemic vs prepandemic period, using March 15, 2020, the date when elective hospital procedures were halted. Main Outcomes and Measures: The main outcome was a time-to-event variable describing number of days from date of diagnosis to date of receiving first cancer treatment (surgery, chemotherapy, or radiation) or to being censored. For each treatment modality, a multivariable competing-risk regression model was used to assess the association between time to treatment and COVID-19 period. A secondary continuous outcome was defined for patients who were treated 6 months after diagnosis as the waiting time from date of diagnosis to date of treatment. Results: Among 313 499 patients, the mean (SD) age was 66.4 (14.1) years and 153 679 (49.0%) were male patients. Those who were diagnosed during the pandemic were less likely to receive surgery first (subdistribution hazard ratio [sHR], 0.97; 95% CI, 0.95-0.99) but were more likely to receive chemotherapy (sHR, 1.26; 95% CI, 1.23-1.30) or radiotherapy (sHR, 1.16; 95% CI, 1.13-1.20) first. Among patients who received treatment within 6 months from diagnosis (228 755 [73.0%]), their mean (SD) waiting time decreased from 35.1 (37.2) days to 29.5 (33.6) days for surgery, from 43.7 (34.1) days to 38.4 (30.6) days for chemotherapy, and from 55.8 (41.8) days to 49.0 (40.1) days for radiotherapy. Conclusions and Relevance: In this cohort study, the pandemic was significantly associated with greater use of nonsurgical therapy as initial cancer treatment. Wait times were shorter in the pandemic period for those treated within 6 months of diagnosis. Future work needs to examine how these changes may have affected patient outcomes to inform future pandemic guideline development.

Incident Cancer Detection During Multiple Waves of COVID-19: The Tsunami After the Earthquake.

No population-based study exists to demonstrate the full-spectrum impact of COVID-19 on hindering incident cancer detection in a large cancer system. Building upon our previous publication in JNCCN, we conducted an updated analysis using 12 months of new data accrued in the pandemic era (extending the study period from September 26, 2020, to October 2, 2021) to demonstrate how multiple COVID-19 waves affected the weekly cancer incidence volume in Ontario, Canada, and if we have fully cleared the backlog at the end of each wave.

Cancer Patients First Treated with Chemotherapy: Are They More Likely to Receive Surgery in the Pandemic?

Due to the ramping down of cancer surgery in early pandemic, many newly diagnosed patients received other treatments first. We aimed to quantify the pandemic-related shift in rate of surgery following chemotherapy. This is a retrospective population-based cohort study involving adults diagnosed with cancer between 3 January 2016 and 7 November 2020 in Ontario, Canada who received chemotherapy as first treatment within 6-months of diagnosis. Competing-risks regression models with interaction effects were used to quantify the association between COVID-19 period (receiving a cancer diagnosis before or on/after 15 March 2020) and receipt of surgical reSection 9-months after first chemotherapy. Among 51,653 patients, 8.5% (n = 19,558) of them ultimately underwent surgery 9-months after chemotherapy initiation. Receipt of surgery was higher during the pandemic than before (sHR 1.07, 95% CI 1.02-1.13). Material deprivation was independently associated with lower receipt of surgery (least vs. most deprived quintile: sHR 1.11, 95% CI 1.04-1.17), but did not change with the pandemic. The surgical rate increase was most pronounced for breast cancer (sHR 1.13, 95% CI 1.06-1.20). These pandemic-related shifts in cancer treatment requires further evaluations to understand the long-term consequences. Persistent material deprivation-related inequity in cancer surgical access needs to be addressed.

Discrimination, harassment, and intimidation amongst otolaryngology: head and neck surgeons in Canada.

BACKGROUND: Understanding mistreatment within medicine is an important first step in creating and maintaining a safe and inclusive work environment. The objective of this study was to quantify the prevalence of perceived workplace mistreatment amongst otolaryngology-head and neck surgery (OHNS) faculty and trainees in Canada. METHODS: This national cross-sectional survey was administered to practicing otolaryngologists and residents training in an otolaryngology program in Canada during the 2020-2021 academic year. The prevalence and sources of mistreatment (intimidation, harassment, and discrimination) were ascertained. The availability, awareness, and rate of utilization of institutional resources to address mistreatment were also studied. RESULTS: The survey was administered to 519 individuals and had an overall response rate of 39.1% (189/519). The respondents included faculty (n = 107; 56.6%) and trainees (n = 82; 43.4%). Mistreatment (intimidation, harassment, or discrimination) was reported in 47.6% of respondents. Of note, harassment was reported at a higher rate in female respondents (57.0%) and White/Caucasian faculty and trainees experienced less discrimination than their non-White colleagues (22.7% vs. 54.5%). The two most common sources of mistreatment were OHNS faculty and patients. Only 14.9% of those experiencing mistreatment sought assistance from institutional resources to address mistreatment. The low utilization rate was primarily attributed to concerns about retribution. INTERPRETATION: Mistreatment is prevalent amongst Canadian OHNS trainees and faculty. A concerning majority of respondents reporting mistreatment did not access resources due to fear of confidentiality and retribution. Understanding the source and prevalence of mistreatment is the first step to enabling goal-directed initiatives to address this issue and maintain a safe and inclusive working environment.

Development of a management protocol for internal carotid artery injury during endoscopic surgery: a modified Delphi method and single-center multidisciplinary working group.

BACKGROUND: Intra-operative internal carotid artery (ICA) injury during transnasal endoscopic surgery is a potentially catastrophic event. Such an injury is life-threatening in the immediate setting, with a reported peri-operative mortality rate of 10%. Nasal packing, muscle patches, direct vessel closure, and endovascular techniques have been described as useful strategies for managing ICA bleeds. The objective of this study was to develop a formalized management protocol for intra-operative ICA injury through engagement with a multi-disciplinary panel. METHODS: A modified Delphi method including literature review, iterative rounds of stakeholder feedback, and expert panel discussions was used to develop a management protocol for ICA injury during transnasal endoscopic surgery. The 10-person multi-disciplinary panel included otolaryngologists, neurosurgeons, interventional neuroradiologists, anesthesiologists, and operating room nursing staff. RESULTS: After three rounds of stakeholder engagement with the expert panel, consensus was reached on important elements to include within the protocol. The protocol was divided in three categories: Alert, Control, and Transfer. 'Alert' focusses on early communication with anesthesia and nursing staff. 'Control' focusses on techniques to expose the injury and obtain hemostasis or adequate tamponade. Lastly, 'Transfer' describes the process of contacting neuro-interventional radiology and safely transferring the patient. A one-page handout of the protocol was developed for placement in operating theatres. CONCLUSION: Due to the life-threatening nature of ICA injury, it is imperative that endoscopic sinus and skull base surgeons are prepared to manage this complication. Using a modified Delphi method with a multidisciplinary expert panel, a protocol for management of intra-operative ICA injury was developed.

Incident Cancer Detection During the COVID-19 Pandemic.

BACKGROUND: Resource restrictions were established in many jurisdictions to maintain health system capacity during the COVID-19 pandemic. Disrupted healthcare access likely impacted early cancer detection. The objective of this study was to assess the impact of the pandemic on weekly reported cancer incidence. PATIENTS AND METHODS: This was a population-based study involving individuals diagnosed with cancer from September 25, 2016, to September 26, 2020, in Ontario, Canada. Weekly cancer incidence counts were examined using segmented negative binomial regression models. The weekly estimated backlog during the pandemic was calculated by subtracting the observed volume from the projected/expected volume in that week. RESULTS: The cohort consisted of 358,487 adult patients with cancer. At the start of the pandemic, there was an immediate 34.3% decline in the estimated mean cancer incidence volume (relative rate, 0.66; 95% CI, 0.57-0.75), followed by a 1% increase in cancer incidence volume in each subsequent week (relative rate, 1.009; 95% CI, 1.001-1.017). Similar trends were found for both screening and nonscreening cancers. The largest immediate declines were seen for melanoma and cervical, endocrinologic, and prostate cancers. For hepatobiliary and lung cancers, there continued to be a weekly decline in incidence during the COVID-19 period. Between March 15 and September 26, 2020, 12,601 fewer individuals were diagnosed with cancer, with an estimated weekly backlog of 450. CONCLUSIONS: We estimate that there is a large volume of undetected cancer cases related to the COVID-19 pandemic. Incidence rates have not yet returned to prepandemic levels.

National Trends in Gender Diversity Among Trainees and Practicing Physicians in Otolaryngology-Head and Neck Surgery in Canada.

Importance: Monitoring the evolution of gender diversity within medicine is essential to understanding the medical workforce and anticipating its future. Objective: To evaluate gender distribution and trends among trainees and practicing physicians in the field of otolaryngology-head and neck surgery (OHNS) across Canada. Design, Setting, and Participants: This cross-sectional study collected demographic data on the Canadian population, medical students, resident physicians, fellows, practicing physicians, and full-time professors from the following publicly available databases: the Canadian Post-MD Education Registry, the Canadian Medical Education Statistics from the Association of Faculties of Medicine of Canada, the Canadian Medical Association Masterfile, the Canadian Resident Matching Service archives, and the Canadian Institute for Health Information from 2000 to 2019. Information about the gender distribution in leadership positions and fellowships was obtained through publicly available websites where gender was either listed or assigned by authors. Main Outcomes and Measures: The primary outcomes were the proportion of women in OHNS and the evolution of gender diversity over time. Results: In 2019, 65 of 155 of OHNS trainees were female (41.9%), whereas female representation among all surgical trainees combined was 1225 of 2496 (49.1%). Female OHNS trainees and practicing physicians are underrepresented despite a 13.3% increase in female trainees and a 14.3% increase in female staff physicians from 2000 to 2019. Proportionally fewer female graduates pursued a fellowship during a 10-year period compared with their male counterparts, with otology and neurotology having the lowest female representation (6 of 27 [22.2%]). A minimal increase occurred in the number of women holding academic leadership positions (eg, 4 of 13 residency training programs had a previous or current female director). Conclusions and Relevance: Despite the overall increase in the representation of women in the field of OHNS in Canada, these findings suggest that persistent gender gaps remain with respect to academic leadership positions and fellowship training. Continuous monitoring of the surgical workforce is important to highlight and address gender disparities within OHNS.

Regional Recurrences and Hyams Grade in Esthesioneuroblastoma.

Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% ( p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% ( p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [ p = 0.04], 49 vs. 91% [ p = 0.04], 44 vs. 92% [ p = 0.02], and 44 vs. 80% [ p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

Development of a Molecular Assay for Detection and Quantification of the BRAF Variation in Residual Tissue From Thyroid Nodule Fine-Needle Aspiration Biopsy Specimens.

Importance: Thyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics. Objective: To develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation. Design, Setting, and Participants: This diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021. Results: A total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/µL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy. Conclusions and Relevance: This diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.

Diagnostic Value of Galectin-3 in Distinguishing Invasive Encapsulated Carcinoma from Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features (NIFTP).

Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker test could provide useful insights into pre- and post-surgical management of the indeterminate thyroid nodule. Galectin-3 (Gal-3), a ß-galactosyl-binding molecule in the lectin group, is involved in different biological functions in well differentiated thyroid carcinomas. The aim of this study was to determine whether Gal-3 expression as a diagnostic marker could distinguish indolent NIFTP from invasive EFVPTC on tissue specimens from surgical thyroid nodules. Methods: immunohistochemical (IHC) analysis of cytoplasmic and nuclear Gal-3 expression was performed in formalin-fixed paraffin-embedded (FFPE) surgical tissues in four specific diagnostic subgroups- benign nodules, NIFTPs, EFVPTCs and lymphocytic/Hashimoto's thyroiditis (LTs). Results: cytoplasmic Gal-3 expression (mean ± SD) was significantly increased in invasive EFVPTCs (4.80 ± 1.60) compared to NIFTPs (2.75 ± 1.58, p < 0.001) and benign neoplasms (2.09 ± 1.19, p < 0.001) with no significant difference between NIFTPs and benign lesions (p = 0.064). The presence of LT enhanced cytoplasmic Gal-3 expression (3.80 ± 1.32) compared to NIFTPs (p = 0.016) and benign nodules (p < 0.001). Nuclear Gal-3 expression in invasive EFVPTCs (1.84 ± 1.30) was significantly higher than in NIFTPs (1.00 ± 0.72, p = 0.001), but similar to benign nodules (1.44 ± 1.77, p = 0.215), thereby obviating its potential clinical application. Conclusions: our observations have indicated that increased cytoplasmic Gal-3 expression shows diagnostic potential in distinguishing NIFTP among encapsulated follicular variant nodules thereby serving as a possible ancillary test to H&E histopathological diagnostic criteria when LT interference is absent, to assist in the detection of the invasive EFVPTC among such nodules.

Quality Indicators for the Diagnosis and Management of Menière's Disease.

OBJECTIVE: Menière's disease (MD) is a clinical disorder that often provides challenges in diagnosis and management. High-quality evidence to guide care providers is sparse, which can result in significant practice variations. Quality indicators (QIs) are one method that can be used to standardize and measure accepted care practices to improve healthcare quality and patient outcomes. Here, we developed practical, high-yield QIs that serve to measure and inform the quality of care provided to patients with MD. STUDY DESIGN: Modified RAND Corporation University of California, Los Angeles appropriateness methodology for QI development. SETTING: Multicenter nine-member expert panel. PATIENTS: NA. INTERVENTIONS: NA. MAIN OUTCOME MEASURE: Final QIs deemed appropriate measures of quality care with agreement by the expert panel. RESULTS: Twenty-seven candidate indicators were identified after literature review. After the first round of evaluations, the panel agreed on three candidate indicators as appropriate QIs. A subsequent expert panel meeting provided a platform to discuss disagreements. Two agreed-upon QIs were revised during this discussion before final evaluations. The expert panel ultimately agreed upon five QIs as appropriate measures of high-quality care after completing final evaluations and reviewing updated literature. The five quality indicators measure audiometric documentation, minimization of electrocochleography, use of intratympanic dexamethasone, use of intratympanic gentamycin, and rate of labyrinthectomy/vestibular neurectomy in refractory MD patient. CONCLUSIONS: This study proposes five QIs that cover key aspects of care for MD, such as accurate diagnosis and management options including initial destructive therapies. These QIs can serve multiple purposes, the most important of which is to galvanize quality improvement initiatives.

What is the optimal outcome after endoscopic sinus surgery in the treatment of chronic rhinosinusitis? A consultation of Canadian experts.

OBJECTIVES: Many experts feel that in the absence of well-defined goals for success, they have an easier time identifying failure. As success ought to not be defined only by absence of failure, we aimed to define optimal outcomes for endoscopic sinus surgery (ESS) in chronic rhinosinusitis (CRS) by obtaining expert surgeon perspectives. METHODS: A total of 12 surgeons participated in this targeted consultation. Face to face semi-structured interviews were performed with expert surgeons in the field of CRS and ESS. General impressions and personal definitions of acceptable operative success and optimal operative outcomes were compiled and summarized. RESULTS: According to an expert survey, patients' main objectives are an improvement in their chief complain, a general improvement in quality of life (QoL), and a better overall symptomatic control. The most important aspects of endoscopy for defining a successful intervention were an adequate mucus circulation, a healthy mucosa, minimal edema, and patency of all explored cavities or ostia. In the assessment of surgical outcomes, it was determined that both objective and patient reported data must be carefully examined, with more attention given to subjective outcomes. CONCLUSIONS: According to data gathered from a Canadian expert consultation, a definition of success must be based on both subjective data and nasal endoscopy. We propose to define an acceptable outcome as either a subjective improvement of at least the minimal clinically improvement difference of a validated patient reported outcome questionnaire, along with a satisfactory endoscopic result (1) or a complete subjective resolution with a sub-optimal endoscopy (2).

Quality Indicators for the Diagnosis and Management of Sudden Sensorineural Hearing Loss.

OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is an ideal entity for quality indicator (QI) development, providing treatment challenges resulting in variable or substandard care. The American Academy of Otolaryngology-Head and Neck Surgery recently updated their SSNHL guidelines. With SSNHL demonstrating a large burden of illness, this study sought to leverage the updated guidelines and develop QIs that support quality improvement initiatives at an individual, institutional, and systems level. METHODS: Candidate indicators (CIs) were extracted from high-quality SSNHL guidelines that were evaluated using the Appraisal of Guidelines for Research and Evaluation II tool. Each CI and its supporting evidence were summarized and reviewed by a nine-member expert panel based on validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND Corporation-University of California, Los Angeles appropriateness methodology. RESULTS: Fifteen CIs were identified after literature review. After the first round of evaluations, the panel agreed on 11 candidate indicators as appropriate QIs with 2 additional CIs suggested for consideration. An expert panel meeting provided a platform to discuss areas of disagreement before final evaluations. The expert panel subsequently agreed upon 11 final QIs as appropriate measures of high-quality care for SSNHL. CONCLUSION: The 11 proposed QIs from this study are supported by evidence and expert consensus, facilitating measurement across a wide breadth of quality domains. With the recently updated SSNHL guidelines, and a greater focus on quality improvement opportunities, these QIs may be used by healthcare providers for targeted quality improvement initiatives.

Outpatient versus inpatient superficial parotidectomy: clinical and pathological characteristics.

BACKGROUND: Superficial parotidectomy has a potential to be performed as an outpatient procedure. The objective of the study is to evaluate the safety and selection profile of outpatient superficial parotidectomy compared to inpatient parotidectomy. METHODS: A retrospective review of individuals who underwent superficial parotidectomy between 2006 and 2016 at a tertiary care center was conducted. Primary outcomes included surgical complications, including transient/permanent facial nerve palsy, wound infection, hematoma, seroma, and fistula formation, as well as medical complications in the postoperative period. Secondary outcome measures included unplanned emergency room visits and readmissions within 30 days of operation due to postoperative complications. RESULTS: There were 238 patients included (124 in outpatient and 114 in inpatient group). There was no significant difference between the groups in terms of gender, co-morbidities, tumor pathology or tumor size. There was a trend towards longer distance to the hospital from home address (111 Km in inpatient vs. 27 in outpatient, mean difference 83 km [95% CI,- 1 to 162 km], p = 0.053). The overall complication rates were comparable between the groups (24.2% in outpatient group vs. 21.1% in inpatient, p = 0.56). There was no difference in the rate of return to the emergency department (3.5% vs 5.6%, p = 0.433) or readmission within 30 days (0.9% vs 0.8%, p = 0.952). CONCLUSION: Superficial parotidectomy can be performed safely as an outpatient procedure without elevated risk of complications.