Recovery of Recurrent Laryngeal Nerve Function With Neoadjuvant Treatment: Neural Characterization.

OBJECTIVES: Neoadjuvant targeted therapy has emerged as a promising treatment strategy for locally aggressive thyroid cancer. Its impact on tumor and adjacent tissues remains a nascent area of study. Here we report on a series of six subjects with locally advanced thyroid cancer and recurrent laryngeal nerve (RLN) paralysis who experienced recovery of RLN function with neoadjuvant treatment and describe the morphologic and electrophysiologic characteristics of these recovered nerves. METHODS: This is a multicenter retrospective review. Descriptive analysis was conducted to examine the following parameters for recovered nerves: (1) nerve morphology, characterized as Type A (involving epineurium only) versus Type B (extending beyond epineurium); (2) proximal stimulability (normal vs. abnormal vs. absent); and (3) surgical management (resection vs. preservation). RESULTS: Six subjects with unilateral VFP were identified. Median time to return of VF mobility was 3 months (range 2-13.5). All nerves (100%) were noted to have Type A morphology at surgery. Proximal stimulability was normal in four subjects (66.7%), abnormal in one (16.7%), and absent in one (16.7%). Nerves that had improvement of function through neoadjuvant therapy were able to be surgically preserved in five subjects (83.3%). CONCLUSIONS: This represents the first characterization of RLNs that have recovered function with neoadjuvant treatment of locally advanced thyroid cancer. Although much remains unknown, our findings indicate carcinomatous neural invasion is a reversible process and recovered nerves may demonstrate normal morphology and electrophysiologic activity. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3415-3419, 2024.

Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid Surgery: A Review From the American Head and Neck Society Endocrine Surgery Section.

Importance: Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery. Observation: This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)-both label free and in combination with indocyanine green-based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery. Conclusions and Relevance: Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

Recurrent Laryngeal Nerve Invasion by Thyroid Cancer: Laryngeal Function and Survival Outcomes.

BACKGROUND: Recurrent laryngeal nerve (RLN) invasion by thyroid carcinoma represents an advanced disease status with potentially significant co-morbidity. METHODS: In a retrospective single-center study, we included patients with invaded RLNs operated on while using nerve monitoring techniques. We studied pre-, intra-, and postoperative parameters associated with postoperative vocal cord paralysis (VCP); 5-year recurrence-free survival (RFS); and 5-year overall survival (OS) in addition to two subgroup analyses of postoperative VCP in patients without preoperative VCP and based on source of RLN invasion. RESULTS: Of 65 patients with 66 nerves-at-risk, 39.3% reported preoperative voice complaints. Preoperative VCP was documented in 43.5%. The RLN was invaded by primary tumor in 59.3% and nodal metastasis in 30.5%. Papillary thyroid carcinoma was the most common pathologic subtype (80%). After 6 months, 81.8% had VCP. Complete tumor resection of the RLN was not associated with 5-year RFS (p = 0.24) or 5-year OS (p = 0.9). Resecting the RLN did not offer statistically significant benefit on 5-year RFS (p = 0.5) or 5-year OS (p = 0.38). Radioactive Iodine (RAI) administration was associated with improvement in 5-year RFS (p = 0.006) and 5-year OS (p = 0.004). Patients without preoperative VCP had higher IONM amplitude compared with patients with VCP. After a mean follow-up of 65.8 months, 35.9% of patients had distant metastases, whereas 36.4% had recurrence. CONCLUSION: Preoperative VCP accompanies less than half of patients with RLN invasion. Invaded RLNs may have existent electrophysiologic stimulability. Complete tumor resection and RLN resection were not associated with better 5-year RFS or OS, but postoperative RAI was. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2285-2292, 2022.

Pediatric intraoperative nerve monitoring during thyroid surgery: A review from the American Head and Neck Society Endocrine Surgery Section and the International Neural Monitoring Study Group.

Children are more likely to experience recurrent laryngeal nerve (RLN) injury during thyroid surgery. Intraoperative nerve monitoring (IONM) may assist in nerve identification and surgical decision making. A literature review of pediatric IONM was performed and used to inform a monitoring technique guide and expert opinion statements. Pediatric IONM is achieved using a variety of methods. When age-appropriate endotracheal tubes with integrated surface electrodes are not available, an alternative method should be used. Patient age and surgeon experience with laryngoscopy influence technique selection; four techniques are described in detail. Surgeons must be familiar with the nuances of monitoring technique and interpretation; opinion statements address optimizing this technology in children. Adult IONM guidelines may offer strategies for surgical decision making in children. In some cases, delay of second-sided surgery may reduce bilateral RLN injury risk.

Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association.

BACKGROUND: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.

Benign Intratracheal Thyroid: A Systematic Review of 43 Cases With Five New Case Reports.

OBJECTIVE/HYPOTHESIS: To examine the clinical features of benign intratracheal thyroid (ITT) and their management strategies and outcomes. STUDY DESIGN: Case series study. METHODS: This systemic review was conducted in two international academic centers. This review includes 43 patients: one new case from the Massachusetts Eye and Ear Infirmary, four new cases from Beijing Tongren Hospital, and 38 previously published cases. We analyzed these 43 cases and summarized the patients' epidemiological data, clinical features, and treatment regimens. RESULTS: ITTs were less common in men than in women (male:female ratio of 3:10). ITT was observed in patients as young as neonates and as old as 85 years. Orthotopic thyroid nodules were present in 55.8% of the patients with ITT. Malignancy was incidentally found in 4.6% of all ITTs. Imaging examinations showed that the ITTs were typically attached to the posterolateral/lateral tracheal wall of the first, second, or third tracheal rings. Tissue attachment between the ITT and normal thyroid lobes was seen in 59.5% of the patients. Thirty-seven patients underwent surgery: 30 underwent open surgery, and seven underwent endoscopic debulking resections. One neonate received thyroid suppression therapy. One patient with ITT and papillary thyroid cancer was treated with radiotherapy and ultimately died after recurrence. CONCLUSIONS: Surgical resection is an effective treatment for benign ITT. We hypothesized that abnormalities during the embryonic development of Berry's ligament might play a role in ITT pathogenesis. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2609-E2617, 2021.

Intraoperative nerve monitoring in thyroid surgery: Analysis of recurrent laryngeal nerve identification and operative time.

OBJECTIVE: To evaluate the clinical value of intraoperative nerve monitoring (IONM) by comparing the procedure times for thyroidectomies performed with and without IONM. METHODS: A prospective, randomized, controlled study was conducted on 32 patients (representing 41 nerves at risk) undergoing thyroidectomies carried out by two experienced head and neck surgeons (CC & WP). Sixteen thyroidectomies were performed without IONM (the "non-IONM group"), while 16 thyroidectomies were performed with IONM (the "IONM group"). The measured datapoints were setup time, time to visual identification of the recurrent laryngeal nerve (RLN), time to confirm the RLN electrophysiologically, dissection time, and total operative time. RESULTS: With both surgeons, the IONM group had shorter visual times to RLN identification than the non-IONM group (CC: 3.7 minutes vs 5.3 minutes; WP: 3.4 minutes vs 9.7 minutes). Additionally, the electrophysiological identification time for the IONM group was shorter than the visual identification time for the non-IONM group. The setup times, dissection times, and total operative times of the 2 groups did not significantly differ (P > .05). No RLN injuries were observed. CONCLUSIONS: IONM reduces the time needed for RLN identification in thyroidectomies. Functional RLN confirmation can reassure surgeons of the operative results. Moreover, use of IONM does not significantly impact setup and total operative times. LEVEL OF EVIDENCE: 2.

Superior Laryngeal Nerve Signal Attenuation Influences Voice Outcomes in Thyroid Surgery.

OBJECTIVES/HYPOTHESIS: The objective was to identify whether injury of the external branch of the superior laryngeal nerve (EBSLN) or changes in EBSLN parameters after dissection during thyroidectomies correlate with changes in voice quality postoperatively. STUDY DESIGN: Prospective multicenter case series. METHODS: A prospective multicenter study was conducted on patients undergoing thyroidectomies with intraoperative nerve monitoring. Electromyography waveforms of EBSLN stimulation before (S1) and after superior pole dissection (S2) were evaluated using endotracheal tube (ETT) and cricothyroid intramuscular (CTM) electrodes. Voice outcomes were assessed using Voice-Related Quality of Life Surveys and Voice Handicap Index. RESULTS: A total of 131 at-risk EBSLNs were evaluated in 80 patients. Two nerves showed loss of CTM twitch coupled with an absent S2 signal response. Complete EBSLN loss of signal was more likely with: 1) Cernea EBSLN anatomic classification Type 2B; 2) with a longer distance from the sternothyroid muscle insertion site; and 3) with larger lobar volumes (P < .05). Patients who experienced a more than 50% decrement in CTM amplitudes of S2 (n = 7) by CTM electrodes had a statistically significant decline in their voice outcomes compared to those who did not (n = 69) (P < .05). CONCLUSIONS: Patients experienced worse voice outcomes when at least one EBSLN response amplitude decreased by more than 50% after dissection when measured by CTM needle electrodes. CTM needle electrodes have an ability to measure finer amplitude changes compared to ETT electrodes, may represent a safe method to deduce subtle EBSLN injuries, and may serve to optimize voice outcomes during thyroidectomy. CTM needle electrodes are safe and tolerated well. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1436-1442, 2021.

Surgical impact of a dedicated endocrine surgeon on an academic otolaryngology department.

OBJECTIVES: Endocrine surgery is emerging as a dedicated subspecialty in otolaryngology. We assess the impact of an endocrine surgeon on an academic otolaryngology department's thyroid and parathyroid surgery volume. METHODS: A retrospective study of overall endocrine caseloads and resident case logs at a single academic center in the Midwest was performed. All thyroid and parathyroid cases performed by the otolaryngology department at an academic center from 2011 to 2017 were reviewed. In September 2012, an otolaryngologist who had completed an American Head and Neck Society endocrine surgery fellowship joined the faculty. The volume of endocrine surgery performed by the residents was also analyzed. Comparison of means and linear regression models were performed. RESULTS: From 2011 to 2012, the department performed a mean of 77 thyroid and 11.5 parathyroid surgeries annually. After the endocrine surgeon joined the department, this increased to an average of 212.8 thyroidectomies (P < 0.01) and 72.4 parathyroidectomies (P < 0.01) a year. The head and neck surgeons and generalists still performed an average of 42.4 thyroidectomies and 2.6 parathyroidectomies a year. For graduating residents, the average number of thyroid/parathyroid cases increased from 42.5 in 2012 to 151 in 2016. CONCLUSION: The addition of a fellowship-trained endocrine surgeon substantially increased the thyroid and parathyroid surgical volume of the otolaryngology department. Importantly, generalists and head and neck surgeons in the department continued to perform a significant number of these cases. Departments seeking similar surgical growth and expanded resident experience may consider the value of engaging a dedicated endocrine surgeon. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:832-835, 2020.

A faster parathyroidectomy: Techniques to shorten non-surgical operating room time.

OBJECTIVE: To assess the capacity of different techniques to reduce non-operative times during parathyroid surgery. The impact of monitored anesthesia care (MAC) instead of general anesthesia, and the pre-operative placement of a second peripheral intravenous catheter (PIV) were analyzed. METHODS: A retrospective case series at an academic medical center was performed to study patients undergoing parathyroidectomy by a single surgeon between November 2013 and October 2016. Three operating room (OR) time measurements were compared: pre-incision time, post-closure time, and total OR time. RESULTS: Surgeries performed under MAC (n = 21) had statistically shorter pre-incision (33.2 min vs. 39.7 min, p < .001), post-closure (10.1 min vs. 16.2 min, p = .002), and total operative times (113.0 min vs. 151.5 min, p < .001) compared to those in which general anesthesia (n = 169) was used. Of the 169 patients who underwent general anesthesia, 25 had a second PIV placed preoperatively and 144 had only a single PIV. All 3 time periods were statistically shorter in patients who had a second PIV versus those who had only a single PIV (pre-incision 32.2 min vs. 41.0 min, p < .001; post-closure 12.2 min vs. 16.9 min, p < .001; total 117.9 min vs. 157.4 min, p < .001). CONCLUSIONS: In patients undergoing parathyroid surgery in which ioPTH levels will be used, the placement of a second PIV in the pre-operative holding area and performance of surgery under MAC can significantly shorten non-operative and total OR time.

Flexible model for patient engagement: Achieving quality outcomes and building a research agenda for head and neck cancer.

BACKGROUND: This article describes the benefits of patient-driven research in the field of head and neck oncology, reviews lessons learned from establishing partnerships with patients and caregivers, and serves as a model for further patient-driven research endeavors. METHODS: Head and neck cancer survivors underwent training including that of effective communication and the basics of research methodology. They then drove the agendas for monthly meetings that included a multidisciplinary team of providers, facilitated by a physician champion (S.S.C.). RESULTS: The advisors reported concrete areas for improvement of the clinical flow, including the formation of a dental oncology clinic and a post-treatment survivorship clinic. They also refined research topics of interest, such as treatment regret. The advisors have also driven efforts to increase public awareness and have participated in cancer symposiums and local presentations. CONCLUSION: Patient-driven research improves the relevance and implementation of head and neck oncology research and clinical processes.

INCIDENTAL THYROID NODULES: RACE/ETHNICITY DISPARITIES AND OUTCOMES.

OBJECTIVE: Black patients have a significantly lower incidence of well-differentiated thyroid cancer (WDTC) compared to all other race/ethnic groups, while white patients appear to be at greater risk. This study examines incidental thyroid nodules (ITNs) to assess whether racial disparities in WDTC arise from a differential discovery of ITNs-perhaps due to socioeconomic disparities-or reflect true differences in thyroid cancer rates. METHODS: A retrospective review was performed of all patients who underwent fine-needle aspiration (FNA) of thyroid nodules by our academic medical center's endocrinology division between January 2006 and December 2010. Medical records were reviewed to identify whether the biopsied thyroid nodule was discovered incidentally through nonthyroid-related imaging or identified by palpation. RESULTS: FNAs were performed on 1,369 total thyroid nodules in 1,141 study patients; 547 (48%) were classified as white, and 593 (52%) were classified as nonwhite. Among this cohort, 36.6% of patients underwent biopsy for an ITN. White patients were 1.6 times more likely to have undergone a biopsy for a nodule that was incidentally identified compared to nonwhites ( P<.0001). Indicators of socioeconomic status (SES) did not have a significant association with ITNs. Within the ITN cohort, 4.9% of nonwhite patients were found to have a thyroid malignancy compared to 12.9% of white patients ( P<.01). CONCLUSION: The higher incidence of thyroid cancer in white patients appears to be not only due to diagnostic bias, but also to a true difference in cancer prevalence. ABBREVIATIONS: FNA = fine-needle aspiration; ITN = incidental thyroid nodule; SEER = Surveillance Epidemiology and End Results; SES = socioeconomic status; WDTC = well-differentiated thyroid cancer.

Comparison of incidental versus palpable thyroid nodules presenting for fine-needle aspiration biopsy.

BACKGROUND: Many attribute the rise in incidence of thyroid cancer to a deluge of radiologically identified incidental thyroid nodules. The clinical implications are unclear. METHODS: A review was performed of all patients who underwent fine-needle aspirations of thyroid nodules by our academic medical center's Endocrinology Division between 2006 and 2010. Medical records were reviewed to identify whether the thyroid nodule was discovered incidentally or by palpation. RESULTS: Of 1153 patients, 37.4% underwent a biopsy because of an incidental thyroid nodule. These patients were significantly more likely to be >45 years old, men, white race, and with a body mass index >30 kg/m2 . Of the 17.2% of incidentalomas that led to surgery, 8.5% were found to be thyroid cancer. CONCLUSION: Thyroid nodules discovered incidentally are increasing the diagnosis of subclinical thyroid cancers. Not investigated previously, our study found that the mode of detection was not related to malignancy or surgery.

Socioeconomic disparities and comorbidities, not race, affect salivary gland malignancy survival outcomes.

OBJECTIVES/HYPOTHESIS: This study sought to determine whether comorbidities, race, and socioeconomic factors affect 5- and 10-year survival outcomes for patients with salivary gland malignancies treated at a single large academic institution with a large African American population. STUDY DESIGN: A retrospective cohort study was performed of all patients with salivary gland malignancies, from 1990 to 2015, at a large academic medical center. METHODS: Standard statistical analysis was performed using Kaplan-Meier survival curve analysis and Cox proportional hazard models. RESULTS: The overall 5- and 10-year survival rates decreased with age ≥ 60 years (P < .001), stage 3 or 4 (P < .001), clinical T stage 3 or 4 (P < .001), and clinical N stage 1, 2, or 3 (P < .001). Living in a ZIP code with an increasing proportion of residents with a high school degree or less (P < .05), being male (P < .05), increasing age at the time of diagnosis (P < .001), and increasing Charlson comorbidity index (P < .05) detrimentally impacted survival at 5 and 10 years. Race was associated with socioeconomic variables, but race was not a prognostic indicator of survival. CONCLUSIONS: Socioeconomic factors and comorbidities, not race, were negative prognostic indicators of survival of patients with salivary gland malignancies. Using race as a marker for socioeconomic status should be used with caution. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2545-2550, 2017.

Bony cochlear nerve canal stenosis and speech discrimination in pediatric unilateral hearing loss.

OBJECTIVES/HYPOTHESIS: To examine the relationship between bony cochlear nerve canal (BCNC) width, degree of hearing loss, and speech discrimination in children with unilateral sensorineural hearing loss (USNHL). STUDY DESIGN: Retrospective chart review (case-control study). METHODS: Audiometric database was cross-referenced with radiologic database at pediatric tertiary care facility to identify children with USNHL and temporal bone computed tomography. BCNC widths were measured independently by two radiologists blinded to affected ear. Regression analyses investigated associations among variables. RESULTS: One hundred and sixty children with USNHL had temporal bone imaging. Mean BCNC width was significantly smaller in affected ears, P = 0.0001. Narrower width was associated with more severe hearing loss, P = 0.01. Among children who had narrower cochlear nerve canals in affected ears compared to unaffected ears, smaller width was associated with lower speech discrimination score, P = 0.03. Increasing asymmetry in BCNC width between affected and unaffected ears was associated with poorer discrimination scores, P = 0.02. Among ears with asymmetrically smaller cochlear nerve canals, a 1-mm reduction in cochlear canal width between the normal and affected ear was associated with 30.4% lower word recognition score percentage in the affected ear, P = < 0.001. CONCLUSION: There is a significant association between BCNC stenosis and impaired speech discrimination, independent of degree of hearing loss. Further investigation is needed to determine whether BCNC stenosis is a poor prognostic factor for auditory rehabilitation.

Resistance to noise-induced hearing loss in 129S6 and MOLF mice: identification of independent, overlapping, and interacting chromosomal regions.

Noise-induced hearing loss (NIHL) is a prevalent health risk. Inbred mouse strains 129S6/SvEvTac (129S6) and MOLF/EiJ (MOLF) show strong NIHL resistance (NR) relative to CBA/CaJ (CBACa). In this study, we developed quantitative trait locus (QTL) maps for NR. We generated F1 animals by intercrossing (129S6 × CBACa) and (MOLF × CBACa). In each intercross, NR was recessive. N2 animals were produced by backcrossing F1s to their respective parental strain. The 232 N2-129S6 and 225 N2-MOLF progenies were evaluated for NR using auditory brainstem response. In 129S6, five QTL were identified on chromosomes (Chr) 17, 18, 14, 11, and 4, referred to as loci nr1, nr2, nr3, nr4, and nr5, respectively. In MOLF, four QTL were found on Chr 4, 17, 6, and 12, referred to as nr7, nr8, nr9, and nr10, respectively. Given that NR QTL were discovered on Chr 4 and 17 in both the N2-129S6 and N2-MOLF cross, we generated two consomic strains by separately transferring 129S6-derived Chr 4 and 17 into an otherwise CBACa background and a double-consomic strain by crossing the two strains. Phenotypic analysis of the consomic strains indicated that whole 129S6 Chr 4 contributes strongly to mid-frequency NR, while whole 129S6 Chr 17 contributes markedly to high-frequency NR. Therefore, we anticipated that the double-consomic strain containing Chr 4 and 17 would demonstrate NR across the mid- and high-frequency range. However, whole 129S6 Chr 17 masks the expression of mid-frequency NR from whole 129S6 Chr 4. To further dissect NR on 129S6 Chr 4 and 17, CBACa.129S6 congenic strains were generated for each chromosome. Phenotypic analysis of the Chr 17 CBACa.129S6 congenic strains further defined the NR region on proximal Chr 17, uncovered another NR locus (nr6) on distal Chr 17, and revealed an epistatic interaction between proximal and distal 129S6 Chr 17.