Faculty Bibliography

BACKGROUND:There are several options for primary surgical treatment of early-stage supraglottic squamous cell carcinoma (SCC), including transoral robotic surgery (TORS). The purpose of this study was to compare outcomes of TORS to open partial laryngectomy and transoral laser microsurgery (TLM). METHODS:Patients with clinical classification T1-2 supraglottic SCC diagnosed 2010-2019, treated with TORS, open partial laryngectomy, or TLM in the National Cancer Database were selected. RESULTS:One thousand six hundred three patients were included: 17% TORS, 26.5% TLM, 56.5% open. TORS patients had the lowest rates of adjuvant treatment (28.4% vs. TLM: 45.0%, open: 38.5%, p < 0.001), and lower positive margin rates than TLM (16.9% vs. 30.5%, p < 0.001). Thirty-day and ninety-day post-operative mortality did not differ between the approaches. Five-year survival was higher following TORS compared to open surgery (77.8% vs. 66.1%, p = 0.01); this difference persisted following matched-pair analysis. CONCLUSIONS:TORS may be a safe and effective surgical approach for early-stage supraglottic SCC in appropriate patients.

While motor cortical circuits contain information related to specific movement parameters¹, long-range inputs also have a critical role in action execution^2,3. Thalamic projections can shape premotor activity^2-6 and have been suggested⁷ to mediate the selection of short, stereotyped actions comprising more complex behaviours⁸. However, the mechanisms by which thalamus interacts with motor cortical circuits to execute such movement sequences remain unknown. Here we find that thalamic drive engages a specific subpopulation of premotor neurons within the zebra finch song nucleus HVC (proper name) and that these inputs are critical for the progression between vocal motor elements (that is, 'syllables'). In vivo two-photon imaging of thalamic axons in HVC showed robust song-related activity, and online perturbations of thalamic function caused song to be truncated at syllable boundaries. We used thalamic stimulation to identify a sparse set of thalamically driven neurons within HVC, representing ~15% of the premotor neurons within that network. Unexpectedly, this population of putative thalamorecipient neurons is robustly active immediately preceding syllable onset, leading to the possibility that thalamic input can initiate individual song components through selectively targeting these 'starter cells'. Our findings highlight the motor thalamus as a director of cortical dynamics in the context of an ethologically relevant behavioural sequence.

PURPOSE/UNASSIGNED:Fertility discussions are an integral part of comprehensive care for pediatric, adolescent, and young adult patients newly diagnosed with cancer and are supported by national guidelines. Current institutional practices are poorly understood. METHODS/UNASSIGNED:A cross-sectional survey was distributed to 220 Children's Oncology Group member institutions regarding fertility discussion practices. Descriptive statistics were calculated for all variables. The association between specific practices and selected outcomes on the basis of sex was examined via multivariable logistic regression. RESULTS/UNASSIGNED:< .001). Program characteristics associated with fertility discussions included reproductive endocrinology and infertility on site (females odds ratio [OR], 2.1; 95% CI, 1.0 to 4.3), discussion documentation mandate (females OR, 2.3; 95% CI, 1.0 to 5.5; males OR, 3.5; 95% CI, 1.4 to 8.7), and cumulative institution-based FP infrastructure (which included [1] routine practice of documentation, [2] template for documentation, [3] mandate for documentation, and [4] availability of FP navigation; females OR, 1.6; 95% CI, 1.1 to 2.3; males OR, 2.3; 95% CI, 1.6 to 3.4). Utilization of practices unsupported by guidelines included offering sperm banking after treatment initiation (39/135 programs; 28.9%), gonadotropin-releasing hormone analogs for ovarian suppression/FP (75/144 programs; 52.1%), ovarian tissue cryopreservation at diagnosis for patients with leukemia (19/64 programs; 29.7%), and testicular tissue cryopreservation (23/138 programs; 16.7%) not part of a clinical trial. CONCLUSION/UNASSIGNED:Despite recommended guidelines, fertility discussions with patients/families before treatment initiation are not routine at Children's Oncology Group institutions. Standard criteria to determine which options should be offered to patients are more common for males than females.

OBJECTIVES/OBJECTIVE:Hearing loss (HL) is associated with imbalance and increased fall risk. The mechanism underlying this relationship and differences across types of hearing loss remains unclear. Head mounted displays (HMD) can shed light on postural control mechanisms via an analysis of head sway. PURPOSE/OBJECTIVE:The purpose of this study was to evaluate head sway in response to sensory perturbations in individuals with bilateral (BHL) or unilateral hearing loss (UHL) and compare them to controls. MATERIALS AND METHODS/METHODS:We recruited 36 controls, 23 individuals with UHL and 14 with BHL. An HMD (HTC Vive) measured head sway while participants stood on the floor, hips-width apart. Stimuli included two levels of visuals and sound. Root Mean Square Velocity (RMSV) and Power Spectral Density (PSD) were used to quantify head sway. RESULTS:Adjusting for age, individuals with BHL had significantly higher anterior-posterior and medio-lateral RMSV than controls and individuals with UHL. Individuals with UHL demonstrated significantly lower response to visual perturbations in RMSV AP and in all 3 frequency segments of PSD compared to controls. Individuals with UHL showed significantly lower movements at high frequencies compared to controls. Sounds or severity of HL did not impact head sway. CONCLUSIONS:Individuals with BHL demonstrated increased sway with visual perturbations and should be clinically assessed for balance performance and fall risk. Individuals with UHL exhibited reduced responses to visual stimuli compared with controls, which may reflect conscious movement processing. Additional studies are needed to further understand the mechanistic relationship between hearing loss and imbalance.

OBJECTIVES/UNASSIGNED:To present a patient with the first case of NTM (nontuberculous mycobacteria) infection of the larynx extending to cervical trachea, and the first case of subglottic stenosis associated with an NTM infection. METHODS/UNASSIGNED:Case report and review of the literature. RESULTS/UNASSIGNED:laser incision, balloon dilation, and steroid injection of the subglottic stenosis. Patient remains disease free without further subglottic stenosis. CONCLUSION/UNASSIGNED:Laryngeal NTM infections are exceedingly rare. Failure to consider NTM infection in the differential diagnosis when presented with an ulcerative, exophytic mass in patients with increased risk factors (structural lung disease, Pseudomonas colonization, chronic steroid use, prior NTM positivity) may result in insufficient tissue evaluation, delayed diagnosis, and disease progression.

Epidemiological evidence suggests that kava (Piper methysticum Forst) drinks may reduce the risk of cancer in South Pacific Island smokers. However, little is known about the anti-carcinogenic effects of kava on tobacco smoking-related bladder cancer and its underlying mechanisms. Here we show that dietary feeding of kawain (a major active component in kava root extracts) to mice either before or after hydroxy butyl(butyl) nitrosamine (OH-BBN) carcinogen exposure slows down urinary bladder carcinogenesis and prolongs the survival of the OH-BBN-exposed mice. OH-BBN-induced bladder tumors exhibit significantly increased expression of lysine-specific demethylase 1 (LSD1), accompanied by decreased levels of H3K4 mono-methylation compared to normal bladder epithelium, whereas dietary kawain reverses the effects of OH-BBN on H3K4 mono-methylation. Human bladder cancer tumor tissues at different pathological grades also show significantly increased expression of LSD1 and decreased levels of H3K4 mono-methylation compared to normal urothelium. In addition, kava root extracts and the kavalactones kawain and methysticin all increase the levels of H3K4 mono- and di-methylation, leading to inhibitory effects on cell migration. Taken together, our results suggest that modification of histone lysine methylation may represent a new approach to bladder cancer prevention and treatment and that kavalactones may be promising agents for bladder cancer interception in both current and former smokers.

Background: Racial/ethnic (R/E) minorities with head and neck squamous cell carcinoma (HNSCC) have worse survival outcomes compared to White patients. While disparities in patient outcomes for R/E minorities have been well documented, the specific drivers of the inferior outcomes remain poorly understood. Patients and Methods: This was a population-based retrospective cohort study that analyzed HNSCC patients using the National Cancer Database (NCDB) from 2000"“2016. Patient outcomes were stratified by R/E groups including White, Black, Hispanic, Native American/Other, and Asian. The main outcome in this study was overall survival (OS). Univariate time-to-event survival analyses were performed using the Kaplan"“Meier product limit estimates and the log-rank test to evaluate the differences between strata. Results: There were 304,138 patients with HNSCC identified in this study, of which 262,762 (86.3%) were White, 32,528 (10.6%) were Black, 6191 were Asian (2.0%), and 2657 were Native American/Other (0.9%). Black R/E minorities were more likely to be uninsured (9% vs. 5%, p < 0.0001), have Medicaid insurance (22% vs. 8%, p < 0.0001), be in a lower income quartile (<30,000, 42% vs. 13%, p < 0.0001), have metastatic disease (5% vs. 2%, p < 0.001), and have a total treatment time 6 days longer than White patients (median 107 vs. 101 days, p < 0.001). The 5-year OS for White, Black, Native American/Other, and Asian patients was 50.8%, 38.6%, 51.1%, and 55.8%, respectively. Among the oropharynx HNSCC patients, the 5-year OS rates in p16+ White, Black, and Asian patients were 65.7%, 39.4%%, and 55%, respectively. After a multivariate analysis, Black race was still associated with an inferior OS (HR:1.09, 95% CI: 1.03"“1.15, p = 0.002). Conclusions: This large cohort study of HNSCC patients demonstrates that Black race is independently associated with worse OS, in part due to socioeconomic, clinical, and treatment-related factors.

OBJECTIVE:To evaluate the tolerance, overall experience, procedure discomfort, and patient anxiety using different routes in office-based laryngeal procedures. SUBJECTS AND METHODS/METHODS:We performed a retrospective analysis of patients undergoing office-based laryngeal procedures for the treatment or diagnosis of laryngeal lesions via transnasal, transoral, or percutaneous routes. Tolerability, overall experience, procedure discomfort, and patient's anxiety were evaluated and reported on a custom scale over 5. RESULTS:A total 178 procedures performed on 154 patients were reviewed. The video-recordings and data on 15 procedures were missing. A total of 163 procedures were included in this study. These were stratified as follows; 128 procedures via the transnasal fiberoptic approach, 16 procedures via the transoral fiberoptic approach, and 19 procedures via the percutaneous approach. There was no significant difference in the mean score of overall experience across the three different approaches (P= 0.926). The mean overall experience score for the transnasal approach was 1.85, vs 1.93 and 1.94 for the transoral and percutaneous approach, respectively. Similarly, there was no significant difference in the mean score of tolerability across the three different approaches. The mean tolerability score was 1.68 using the transnasal approach, compared to 1.6 using the transoral approach, and 1.84 using the percutaneous approach (P= 0.77). Anxiety scores, and procedure discomfort scores did not differ either among the three groups (P= 0.138 and P= 0.656, respectively). CONCLUSIONS:There was no significant difference in tolerability, anxiety, procedure discomfort, and overall experience regarding the different approaches employed.