ß-Catenin is required for radial cell patterning and identity in the developing mouse cochlea.

Development of multicellular organs requires the coordination of cell differentiation and patterning. Critical for sound detection, the mammalian organ of Corti contains functional units arranged tonotopically along the cochlear turns. Each unit consists of sensory hair cells intercalated by nonsensory supporting cells, both specified and radially patterned with exquisite precision during embryonic development. However, how cell identity and radial patterning are jointly controlled is poorly understood. Here we show that ß-catenin is required for specification of hair cell and supporting cell subtypes and radial patterning of the cochlea in vivo. In 2 mouse models of conditional ß-catenin deletion, early specification of Myosin7-expressing hair cells and Prox1-positive supporting cells was preserved. While ß-catenin-deficient cochleae expressed FGF8 and FGFR3, both of which are essential for pillar cell specification, the radial patterning of organ of Corti was disrupted, revealed by aberrant expression of cadherins and the pillar cell markers P75 and Lgr6. Moreover, ß-catenin ablation caused duplication of FGF8-positive inner hair cells and reduction of outer hair cells without affecting the overall hair cell density. In contrast, in another transgenic model with suppressed transcriptional activity of ß-catenin but preserved cell adhesion function, both specification and radial patterning of the organ of Corti were intact. Our study reveals specific functions of ß-catenin in governing cell identity and patterning mediated through cell adhesion in the developing cochlea.

Unusual presentation of HPV-positive squamous cell carcinoma of the nasolacrimal duct as carcinoma of unknown primary.

Most human papillomavirus (HPV)-positive carcinomas of unknown primary (CUP) in the cervical lymph nodes are ultimately found to arise from the oropharynx, which has by far the highest prevalence of HPV-positivity among head and neck tumors. However, HPV is also detected in a subset of tumors from other sites. In this case report, we describe the first reported instance of a lacrimal sac carcinoma presenting as an HPV-positive CUP. A 64-year-old male presented with isolated right-sided neck swelling, found on core biopsy to be HPV-positive squamous cell carcinoma (SCC). Initial diagnostic workup did not reveal a primary site, and he was treated for T0N1M0 oropharyngeal SCC with chemoradiation. Shortly afterwards he developed epiphora and was found to have an FDG-avid lesion along his inferior right orbit. Biopsy revealed HPV-positive SCC, presumed to be the true primary site of his previously diagnosed CUP. He was treated with surgical resection, proton-beam radiation, and carboplatin-paclitaxel. He had an excellent outcome with no evidence of disease 18 months following treatment completion. This case underscores the importance of continued vigilance and thorough investigation for a primary tumor site even when cervical nodal metastases are HPV-positive. While the vast majority of HPV-positive head and neck tumors arise in the oropharynx, other anatomical sites may also harbor HPV-positive malignancies.

Opioid prescribing practices in academic otolaryngology: A single institutional survey.

OBJECTIVES: Opioids are highly addictive medications and otolaryngologists have a responsibility to practice opioid stewardship. We investigated postoperative opioid prescribing patterns among resident and attending physicians as an educational platform to underscore the importance of conscientious opioid prescribing. METHODS: This quality improvement study was designed as a cross-sectional electronic survey. Residents and attending clinical faculty members at a single academic institution were queried from February through April 2020. An electronic survey was distributed to capture postoperative opioid prescribing patterns after common procedures. At the conclusion of the study, results were sent to all faculty and residents. RESULTS: A total of 29 attending otolaryngologists and 22 residents completed the survey. Resident physicians prescribed on average fewer postoperative opioid pills than attendings. Among attendings, the largest number of opioids were prescribed following tonsillectomy (dose varied by patient age), neck dissection (12.6 pills), brow lift (13.3 pills), facelift (13.3 pills), and open reduction of facial trauma (10.7 pills). For residents, surgeries with the most postoperatively prescribed opioids were for tonsillectomy (varied by patient age), neck dissection (13.4 pills), open reduction of facial trauma (10.5 pills), parotidectomy (10.0 pills), and thyroid/parathyroidectomy (9.0 pills). The largest volume of postoperative opioids for both groups was prescribed following tonsillectomy. Attendings prescribed significantly more opioids after facelift and brow lift than did residents (p = 0.01 and p = 0.003, respectively). CONCLUSION: There was good concordance between resident and attending prescribers. Improvement in opioid prescribing and pain management should be an essential component of otolaryngology residency education and attending continuing medical education. LEVEL OF EVIDENCE: 4.

Nasal and paranasal sinus mucosal melanoma: Long-term survival outcomes and prognostic factors.

OBJECTIVE: To determine prognostic factors and survival patterns for different treatment modalities for nasal cavity (NC) and paranasal sinus (PS) mucosal melanoma (MM). METHODS: Patients from 1973 to 2013 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and multivariable cox proportional hazard modeling were used for survival analyses. RESULTS: Of 928 cases of mucosal melanoma (NC = 632, PS = 302), increasing age (Hazard Ratio [HR]:1.05/year, p < 0.001), T4 tumors (HR: 1.81, p = 0.02), N1 status (HR: 6.61, p < 0.001), and PS disease (HR: 1.50, p < 0.001) were associated with worse survival. Median survival length was lower for PS versus NC (16 versus 26 months, p < 0.001). Surgery and surgery + radiation therapy (RT) improved survival over non-treatment or RT alone (p < 0.001). Adding RT to surgery did not yield a survival difference compared with surgery alone (p = 0.43). Five-year survival rates for surgery and surgery + RT were similar, at 27.7% and 25.1% (p = 0.43). CONCLUSION: Surgery increased survival significantly over RT alone. RT following surgical resection did not improve survival.

Pediatric Postoperative Pulse Oximetry Monitoring During Transport to the Postanesthesia Care Unit Reduces Frequency of Hypoxemia.

BACKGROUND: The standard use of pulse oximetry during the transport of postoperative patients from the operating room (OR) to the postanesthesia care unit (PACU) is not routinely practiced. A study was conducted to determine if the frequency of hypoxemia on admission to the PACU decreased after implementation of routine use of transport pulse oximeters for postoperative patients being transferred to the PACU. METHODS: In this prospective cohort study, which was conducted at an academic pediatric hospital, the primary outcome measure was the frequency of hypoxemic events on arrival to the PACU. RESULTS: A total of 506 patients in the preintervention phase and 597 in the postintervention phase met the inclusion criteria. Six hypoxemic events on arrival to the PACU were identified in preintervention phase versus zero in the postintervention period, p = 0.009. Use of oxygen monitors during transport from the OR to the PACU increased from 0% to 100%, p < 0.0001, in the postintervention phase. The median duration of unmonitored time during transport decreased from 272 seconds to 13 seconds, p < 0.0001. Of the 605 patients who met the inclusion criteria for sustainment audits-conducted 18 months after the postimplementation evaluation-99.8% were transported to the PACU with a pulse oximeter, and there were zero reported hypoxemic patients on PACU admission. CONCLUSION: The routine use of portable oxygen monitoring when transferring patients from the OR to the PACU is a low-cost, noninvasive safety measure that should be considered at any institution performing pediatric general anesthesia.

Robotic Thyroidectomy via Posterior Neck Approach Using the Da Vinci Single Port System.

We describe a remote access thyroidectomy technique: robotic thyroidectomy via posterior neck approach using the Da Vinci single port (Sp) robotic system. This approach is feasible and safe in the Western population. Laryngoscope, 2023.

A Contemporary Review of Molecular Therapeutic Targets for Adenoid Cystic Carcinoma.

ACC is a rare malignant tumor of the salivary glands. In this contemporary review, we explore advances in identification of targetable alterations and clinical trials testing these druggable targets. A search of relevant articles and abstracts from national meetings and three databases, including PubMed, Medline, and Web of Science, was performed. Following keyword search analysis and double peer review of abstracts to ensure appropriate fit, a total of 55 manuscripts were included in this review detailing advances in molecular targets for ACC. The most researched pathway associated with ACC is the MYB-NFIB translocation, found to lead to dysregulation of critical cellular pathways and thought to be a fundamental driver in a subset of ACC disease pathogenesis. Other notable molecular targets that have been studied include the cKIT receptor, the EGFR pathway, and NOTCH1, all with limited efficacy in clinical trials. The ongoing investigation of molecular abnormalities underpinning ACC that may be responsible for carcinogenesis is critical to identifying and developing novel targeted therapies.

Feeding Tube Placement Following Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To identify factors that may predict the need for feeding tubes in patients undergoing transoral robotic surgery (TORS) in the perioperative setting. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary center. METHODS: A retrospective series of patients undergoing TORS for oropharyngeal squamous cell carcinoma (OPSCC) was identified between October 2016 and November 2019 at a single tertiary academic center. Patient data were gathered, such as frailty information, tumor characteristics, and treatment, including need for adjuvant therapy. Multiple logistic regression was performed to identify factors associated with feeding tube placement following TORS. RESULTS: A total of 138 patients were included in the study. The mean age was 60.2 years (range, 37-88 years) and 81.9% were male. Overall 82.9% of patients had human papilloma virus-associated tumors, while 28.3% were current or former smokers with a smoking history ≥10 pack-years. Eleven patients (8.0%) had a nasogastric or gastrostomy tube placed at some point during their treatment. Five patients (3.6%) had feeding tubes placed perioperatively (<4 weeks after TORS), of which 3 were nasogastric tubes. Six patients (4.3%) had feeding tubes placed in the periadjuvant treatment setting for multifactorial reasons; 5 of which were gastrostomy tubes. Only 1 patient (0.7%) was gastrostomy dependent 1 year after surgery. Multiple logistic regression did not demonstrate any significant predictive variables affecting perioperative feeding tube placement following TORS for OPSCC. CONCLUSIONS: Feeding tubes are seldom required after TORS for early-stage OPSCC. With appropriate multidisciplinary planning and care, patients may reliably avoid the need for feeding tube placement following TORS for OPSCC.

Eosinophilic Granulomatosis With Polyangiitis: An Unusual Case of Pediatric Subglottic Stenosis.

Systemic disease is an uncommon cause of subglottic stenosis (SGS). We report a case of severe SGS due to underlying eosinophilic granulomatosis with polyangiitis (EGPA) in a child presenting with isolated stridor. EGPA is a rare systemic vasculitis with very limited cases reported in the pediatric population. While surgical intervention was required given the degree of stenosis in this case, medical management of the underlying systemic disease process is critical when there is clinical suspicion of SGS in the context of systemic vasculitis. Laryngoscope, 131:656-659, 2021.

Opioid Usage and Prescribing Predictors Following Transoral Robotic Surgery for Oropharyngeal Cancer.

OBJECTIVE/HYPOTHESIS: Pain management following transoral robotic surgery (TORS) varies widely. We aim to quantify opioid usage following TORS for oropharyngeal squamous cell carcinoma (OPSCC) and identify prescribing predictors. STUDY DESIGN: Retrospective cohort study. METHODS: A consecutive series of 138 patients undergoing TORS for OPSCC were reviewed from 2016 to 2019. Opioid usage (standardized to morphine milligram equivalents [MME]) was gathered for 12 months post-surgery via prescribing record cross-check with the Massachusetts Prescription Awareness Tool. RESULTS: Of 138 OPSCC TORS patients, 92.8% were human papillomavirus (HPV) positive. Adjuvant therapy included radiation (XRT;67.4%) and chemoradiation (cXRT;6.5%). Total MME usage from start of treatment averaged 1395.7 MMEs with 76.4% receiving three prescriptions or less. Categorical analysis showed age <65, male sex, overweight BMI, lower frailty, former smokers, HPV+, higher T stage, and BOT subsite to be associated with increased MMEs. Adjuvant therapy significantly increased MMEs (TORS+XRT:1646.2; TORS+cXRT:2385.0; TORS alone:554.7 [P < .001]) and 12-month opioid prescription totals (TORS+XRT:3.2; TORS+cXRT:5.5; TORS alone:1.6 [P < .001]). Adjuvant therapy increased time to taper (total MME in TORS alone versus TORS+XRT/cXRT: 0 to 3 months:428.2 versus 845.5, 4 to 6 months:46.8 versus 541.8, 7 to 9 months:12.4 versus 178.6, 10 to 12 months:11.0 versus 4.4,[P < .001]). Positive predictors of opioid prescribing at the 4- to 6-month and 4- to 12-month intervals included adjuvant therapy (odds ratio [OR]:5.56 and 4.51) and mFI-5 score ≥3 (OR:36.67 and 31.94). Following TORS at 6-, 9-, and 12-month, 15.7%, 6.6%, and 4.1% were still using opioids. CONCLUSIONS: In OPSCC treated with TORS, opioid use tapers faster for surgery alone versus with adjuvant therapy. Opioid prescribing risks include adjuvant therapy and higher frailty index. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1888-E1894, 2021.

Impact of surgical margins on local control in patients undergoing single-modality transoral robotic surgery for HPV-related oropharyngeal squamous cell carcinoma.

BACKGROUND: The impact of close surgical margins on oncologic outcomes in HPV-related oropharyngeal squamous cell carcinoma (HPV + OPSCC) is unclear. METHODS: Retrospective case series including patients undergoing single modality transoral robotic surgery (TORS) for HPV + OPSCC at three academic medical centers from 2010 to 2019. Outcomes were compared between patients with close surgical margins (<1 mm or requiring re-resection) and clear margins using the Kaplan-Meier method. RESULTS: Ninety-nine patients were included (median follow-up 21 months, range 6-121). Final margins were close in 22 (22.2%) patients, clear in 75 (75.8%), and positive in two (2.0%). Eight patients (8.1%) recurred, including two local recurrences (2.0%). Four patients died during the study period (4.0%). Local control (p = 0.470), disease-free survival (p = 0.513), and overall survival (p = 0.064) did not differ between patients with close and clear margins. CONCLUSIONS: Patients with close surgical margins after TORS for HPV + OPSCC without concurrent indications for adjuvant therapy may be considered for observation alone.

A Preliminary Study of Vocal Health Among Collegiate A Cappella Singers.

OBJECTIVE: Collegiate a cappella groups have grown significantly in popularity and prominence; however, there have been few studies that evaluate the vocal health of this subgroup of young singers. The objective of this preliminary study was to conduct a multiparametric evaluation of the vocal health characteristics of a sample of collegiate a cappella singers. We further tested whether differences in vocal health assessments exist between a cappella singers with and without vocal training and trained collegiate singers who do not participate in a cappella groups. STUDY DESIGN: Point prevalence study. METHODS: Forty-one collegiate singers participated in this study. Participants were divided into the following three groups: trained singers (TS), trained a cappella singers (ATS), and untrained a cappella singers (AUS). Participants were administered a set of surveys to assess self-perception of singing voice health and perceived access and attitudes toward voice-related health care. Acoustic and laryngoscopic assessments of participant's speaking and singing voice was performed and validated vocal health questionnaires administered as a means to objectively evaluate for the presence of voice problems. RESULTS: Overall, 87.5% of the ATS and 60% of the AUS groups reported experiencing problems with their singing voice. However, no vocal abnormalities were detected during laryngoscopic and acoustic assessments. Furthermore, minimal differences between any of the measured vocal health parameters were observed between the TS, ATS, and AUS groups. CONCLUSION: Collectively, a high percentage of collegiate a cappella singers with and without vocal training report singing voice problems. However, our sample of a cappella singers did not have increased singing voice problems as compared to vocally trained collegiate singers not in a cappella groups. We did find that a cappella singers may be more inclined to seek information about maintaining a healthy singing voice from their fellow musicians as opposed to singing teachers or other voice health professionals. Singing teachers, otolaryngologists, and speech-language pathologists may need to play a more active role in educating a cappella singers regarding maintaining good vocal health.

Congenital Hearing Loss Is Associated With a High Incidence of Central Nervous System Abnormalities.

OBJECTIVE(S): To assess the incidence of central nervous system abnormalities in pediatric subjects with sensorineural hearing loss (SNHL). METHODS: One hundred forty-three pediatric subjects evaluated for SNHL at a single academic center from 2007 to 2014 were included and divided into eight diagnosis groups based on etiology of SNHL. One hundred forty-three age- and gender-matched control subjects with no known brain-related pathology or history of hearing loss were included as healthy controls for comparison. Two neuroradiologists independently evaluated magnetic resonance imaging (MRI) and computed tomography (CT) scans for each subject. Comparison of abnormal cerebral development was performed using an ordinal logistic regression model. Concordance between CT and MRI of the temporal bone was assessed using the kappa statistic. RESULTS: The etiologies of hearing loss in our cohort were 37.8% genetic, 12.6% infectious, 1.4% ototoxin-induced, and 48.3% idiopathic. Brain MRI revealed cerebral developmental abnormalities in defined regions in >30% of the SNHL cohort, significantly more than in normal-hearing pediatric controls. The Sylvian fissure, Virchow-Robin spaces, and lateral ventricles were most commonly affected. In the temporal bone, the percentage of subjects with concordant findings on CT and MRI was ≥92% across all anatomical structures. CONCLUSION: MRI revealed a high incidence of intracranial abnormalities, suggestive of aberrant development of auditory and nonauditory neural structures associated with SNHL. CT and MRI share a high degree of concordance in detecting temporal bone anomalies. Inclusion of MRI as part of the workup of congenital SNHL may facilitate the detection of developmental anomalies of the brain associated with SNHL.

Heterogeneity of weight loss after gastric bypass, sleeve gastrectomy, and adjustable gastric banding.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding all lead to substantial weight loss in obese patients. Long-term weight loss can be highly variable beyond 1-year postsurgery. This study examines and compares the frequency distribution of weight loss and lack of treatment effect rates after laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding. METHODS: A total of 1,331 consecutive patients at a single academic institution were reviewed from a prospectively collected database. Preoperative data collected included demographics, body mass index, and percent excess weight loss. Postoperative BMI and %EWL were collected at 12, 24, and 36 months. Percent excess weight loss was analyzed by the percentiles of excess weight lost, and the distribution of percent excess weight loss was evaluated in 10% increments. Lack of a successful treatment effect was defined as <25% excess weight loss. RESULTS: Of the 1,331 patients, 72.4% (963) underwent laparoscopic Roux-en-Y gastric bypass, 18.3% (243) laparoscopic sleeve gastrectomy, and 9.4%(125) laparoscopic adjustable gastric banding. Mean percent excess weight loss was greatest for laparoscopic Roux-en-Y gastric bypass, followed by laparoscopic sleeve gastrectomy, and then by laparoscopic adjustable gastric banding at every time point: at 2 years mean percent excess weight loss was 77.9± 24.4 for laparoscopic Roux-en-Y gastric bypass, 50.8 ± 25.8 for laparoscopic sleeve gastrectomy, and 40.8± 25.9 for laparoscopic adjustable gastric banding (P < .0001). The rates of a successful treatment effect s for laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding were 0.9%, 5.2%, and 24.3% at 1 year; 0.3%, 11.1%, and 26.0% at 2 years; and 1.0%, 25.3%, and 30.2% at 3 years. At 1 year, the odds ratio of lack of a successful treatment effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass was 6.305 (2.125-19.08; P = .0004), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass was 36.552 (15.64-95.71; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy was 5.791 (2.519-14.599; P < .0001). At 2 years, the odds ratio for laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass increased to 70.7 (9.4-531.7; P < .0001), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass increased to 128.1 (16.8-974.3; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy decreased to 1.8 (0.9-3.6; P = .09). CONCLUSION: This study emphasizes the existing variability in weight loss across bariatric procedures as well as in the lack of a treatment effect for each procedure. Although laparoscopic adjustable gastric banding has the greatest rate of a lack of a successful treatment effect, the rate remained stable over 3 years postoperatively. Laparoscopic sleeve gastrectomy showed a doubling in the rate of a lack of a successful treatment effect every year reaching 25% at year 3. The rates for lack of a successful treatment effect for laparoscopic Roux-en-Y gastric bypass remained stable at about 1% for the first 3 years postoperatively.

Mammography before and after bariatric surgery.

BACKGROUND: Morbidly obese women are at increased risk for breast cancer, and the majority of surgical weight-loss patients are older than 40 years old. OBJECTIVE: The purpose of the present study was to determine the technical and interpretive changes in mammography following bariatric surgery. SETTING: Accredited Academic Hospital. METHODS: Two breast-imaging radiologists reviewed screening mammograms performed on 10 morbidly obese women undergoing bariatric surgery both pre- and postoperatively. American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) density, imaging quality measurements, compression force, breast thickness, pectoral nipple line (PNL) length, and x-ray beam kilovoltage (kVp) and miliamperes per second (mAs) were recorded. RESULTS: The average patient age was 56 years old, with mean age at menarche of 13 years old; 70% of patients were postmenopausal (average age 49 years at menopause) and 50% had a family history of breast cancer. There was a significant reduction in both BMI (-13.2 kg/m2, P<.01) and waist circumference (-32.0 cm, P<.01) following bariatric surgery. There was a significant reduction in breast thickness (-23.8 mm), reduction in PNL length (-1.9 cm), reduction in kVp (-1.2), and reduction in mAs (-16.7) even though there was no compression force change in pre- and postoperative mammograms detected. All breast densities were fatty or scattered though there were more scattered and fewer fatty images after surgery (P = .002). CONCLUSION: Morbidly obese women can undergo quality mammograms before and after bariatric surgery; however, weight loss after bariatric surgery leads to only slightly denser mammograms. Furthermore, weight loss reduces mammographic radiation doses.

Platinum(IV)-chlorotoxin (CTX) conjugates for targeting cancer cells.

Cisplatin is one of the most widely used anticancer drugs. Its side effects, however, have motivated researchers to search for equally effective analogs that are better tolerated. Selectively targeting cancer tissue is one promising strategy. For this purpose, a platinum(IV) complex was conjugated to the cancer-targeting peptide chlorotoxin (CTX, TM601) in order to deliver cisplatin selectively to cancer cells. The 1:1 Pt-CTX conjugate was characterized by mass spectrometry and gel electrophoresis. Like most platinum(IV) derivatives, the cytotoxicity of the conjugate was lower in cell culture than that of cisplatin, but greater than those of its Pt(IV) precursor and CTX in several cancer cell lines.