Faculty Bibliography

Patients with oral potentially malignant disorders (OPMDs), including oral leukoplakia and erythroplakia, proliferative verrucous leukoplakia, oral submucous fibrosis, and oral lichen planus/lichenoid lesions can be challenging to manage. A small proportion will undergo cancer development and determining a patient's cancer risk is key to making management decisions. Yet, our understanding of the natural history of OPMDs has not been fully elucidated, and a precision approach based on the integration of numerous predictive markers has not been validated by prospective studies. Evidence-based health promotion by clinicians and healthcare systems is not embraced universally. Medical and surgical interventions evaluated by rigorous research measuring important endpoints, such as cancer development, mortality, or survival are difficult and expensive to run. Most of these studies employ non-ideal surrogate endpoints and have deep methodologic flaws. Diagnostic criteria for enrolling research subjects are not uniform, and patients with the highest risk for cancer development comprise small proportions of those enrolled. Few studies explore quality of life and patient preferences. It is time to rethink how we approach the management of these patients, across each OPMD, and considering the healthcare infrastructure and cost effectiveness. Global networks with well-characterized patient populations with OPMDs and well-designed interventional trials using validated outcome measures are needed.

PURPOSE/OBJECTIVE:Fertility preservation (FP) services are part of comprehensive care for those newly diagnosed with cancer. The capacity to offer these services to children and adolescents with cancer is unknown. METHODS:A cross-sectional survey was sent to 220 Children's Oncology Group member institutions regarding institutional characteristics, structure and organization of FP services, and barriers to FP. Standard descriptive statistics were computed for all variables. The association between site-specific factors and selected outcomes was examined using multivariable logistic regression. RESULTS:One hundred forty-four programs (65.5%) returned surveys. Fifty-three (36.8%) reported a designated FP individual or team. Sperm banking was offered at 135 (97.8%) institutions, and testicular tissue cryopreservation at 37 (27.0%). Oocyte and embryo cryopreservation were offered at 91 (67.9%) and 62 (46.6%) institutions, respectively; ovarian tissue cryopreservation was offered at 64 (47.8%) institutions. The presence of dedicated FP personnel was independently associated with the ability to offer oocyte or embryo cryopreservation (odds ratio [OR], 4.7; 95% CI, 1.7 to 13.5), ovarian tissue cryopreservation (OR, 2.7; 95% CI, 1.2 to 6.0), and testicular tissue cryopreservation (OR, 3.3; 95% CI, 1.4 to 97.8). Only 26 (18.1%) participating institutions offered all current nonexperimental FP interventions. Barriers included cost (70.9%), inadequate knowledge or training (60.7%), difficulty characterizing fertility risk (50.4%), inadequate staffing (45.5%), and logistics with reproductive specialties (38%-39%). CONCLUSION/CONCLUSIONS:This study provides the most comprehensive view of the current landscape of FP infrastructure for children and adolescents with cancer and demonstrates that existing infrastructure is inadequate to offer comprehensive services to patients. We discuss modifiable factors to improve patient access to FP.

The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only FDA-approved oncogene-targeting therapy for head and neck squamous cell carcinoma (HNSCC). Despite variable treatment response, no biomarkers exist to stratify patients for cetuximab therapy in HNSCC. Here, we applied unbiased hierarchical clustering to reverse-phase protein array molecular profiles from patient-derived xenograft (PDX) tumors and revealed 2 PDX clusters defined by protein networks associated with EGFR inhibitor resistance. In vivo validation revealed unbiased clustering to classify PDX tumors according to cetuximab response with 88% accuracy. Next, a support vector machine classifier algorithm identified a minimalist biomarker signature consisting of 8 proteins - caveolin-1, Sox-2, AXL, STING, Brd4, claudin-7, connexin-43, and fibronectin - with expression that strongly predicted cetuximab response in PDXs using either protein or mRNA. A combination of caveolin-1 and Sox-2 protein levels was sufficient to maintain high predictive accuracy, which we validated in tumor samples from patients with HNSCC with known clinical response to cetuximab. These results support further investigation into the combined use of caveolin-1 and Sox-2 as predictive biomarkers for cetuximab response in the clinic.

INTRODUCTION/BACKGROUND:Neonates with severe Pierre Robin sequence (PRS) can be treated by mandibular distraction osteogenesis (MDO), tongue-lip adhesion, or tracheostomy; however, there is an active debate regarding the indications of MDO in this patient population. Published algorithms identify tracheomalacia, bronchomalacia, laryngomalacia, hypotonic syndromes, and central sleep apnea as contraindications for MDO and indications for tracheostomy, but these comorbidities may exist along a spectrum of severity. The authors propose that appropriately selected neonates with PRS who concurrently express 1 or more of these traditional contraindications may be successfully treated with MDO. METHODS:The authors performed a 5-year retrospective chart review of all neonates who underwent MDO for treatment of severe PRS. All patients expressed a comorbidity previously identified as an indication for tracheostomy. Pre- and postoperative characteristics were recorded. Apnea/hypopnea index (AHI) before and after MDO were compared using 2-tailed repeated measures t-test. RESULTS:The authors identified 12 patients with severe PRS and conditions associated with contraindications to MDO: 9 (75.0%) patients had laryngomalacia, 6 (50.0%) patients had tracheomalacia, 2 (16.6%) patients had bronchomalacia, 1 (8.3%) patient had central sleep apnea, and 3 (25.0%) patients had hypotonia. Five (41.7%) patients underwent concurrent gastrostomy tube placement due to feeding insufficiency. Average birthweight was 3.0 kg. Average pre-op AHI was 34.8. Average post-op AHI was 7.3. All patients successfully underwent MDO with avoidance of tracheostomy. CONCLUSIONS:By employing an interdisciplinary evaluation of patient candidacy, MDO can safely and effectively treat upper airway obstruction and avoid tracheostomy in higher-risk neonatal patients with traditional indications for tracheostomy.

OBJECTIVE:Concurrent bilateral congenital aural atresia (CAA) and profound sensorineural hearing loss are rare. While not a contraindication, temporal bone and cochleovestibular abnormalities are an important consideration for cochlear implantation (CI) candidacy. Intraoperative image-guided surgical navigation may play a role during CI surgery in patients with complex anatomy, such as CAA. PATIENT/METHODS:One patient with bilateral CAA, cochlear dysplasia, speech delay, and profound sensorineural hearing loss underwent candidacy evaluation for cochlear implantation. INTERVENTIONS/METHODS:Cochlear implantation using intraoperative image-guided navigation. MAIN OUTCOME MEASURES/METHODS:(1) Registration accuracy, (2) surgical outcomes, (3) audiometry. RESULTS:A four-year-old girl with complete bilateral CAA and profound sensorineural hearing loss successfully underwent a right transmastoid approach for CI using intraoperative image-guided navigation with sticker fiducials. Bony landmarks included the mastoid tip, tympanomastoid suture line, helical root, zygomatic root, and lateral brow. A registration accuracy of 0.9 mm was achieved. There were no intraoperative or immediate postoperative complications. Postoperatively, Neural Response Imaging was confirmed on 9 electrodes and behavioral testing demonstrated Ling-6 access at 30 dB. On most recent follow-up, she has demonstrated gains in language development, vocalizations, and uses total communication in a hearing-impaired educational environment. CONCLUSIONS:Children with CAA and profound sensorineural hearing loss may be candidates for cochlear implantation, with successful outcomes in the setting of complex anatomy. Surgical navigation may play a role corroborating intraoperative landmarks.

OBJECTIVE:To present a case of an iatrogenic inner ear third window after vestibular schwannoma microsurgery. PATIENTS:A 42-year-old male presented 9-months after left-sided retrosigmoid approach for an intracanalicular vestibular schwannoma with hearing-preservation attempt performed elsewhere. Immediately postoperatively, he developed the following disabling and persistent symptoms on the ipsilateral side: autophony, pulsatile tinnitus, high-pitched ringing tinnitus, and hearing his footsteps. He denied vertigo. Otoscopy was normal. Tuning fork (512-Hz) lateralized to the left and Rinne was negative on the left. Audiogram demonstrated a severe mixed hearing loss and 10% aided word-recognition score. High-resolution CT demonstrated violation of the common crus and dehiscence of bone along the medial vestibule suggestive of an iatrogenic inner ear third window. INTERVENTIONS:Labyrinthectomy and concurrent cochlear implantation. MAIN OUTCOME MEASURES:Resolution of third window symptoms, open-set speech recognition, tinnitus suppression. RESULTS:Patient reported immediate resolution of third window symptoms after labyrinthectomy and cochlear implantation. He demonstrates open-set word recognition of 64% at 1-year postoperatively and tinnitus suppression with his cochlear implant on. CONCLUSIONS:Iatrogenic third window symptoms can occur after hearing-preservation vestibular schwannoma microsurgery. Patients with sufficient hearing preservation who are disabled by third window symptoms yet lack sound clarity and useful hearing may be considered for labyrinthectomy and concurrent cochlear implantation. This intervention effectively extinguishes third window symptoms by destroying residual auditory function and simultaneously provides an opportunity to restore useful hearing and suppress tinnitus, thereby enhancing overall quality of life.

OBJECTIVE:To determine the frequency with which postoperative opioid prescriptions are required after ambulatory otologic surgery. STUDY DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Tertiary otology-neurotology practice. PATIENTS/METHODS:Patients (n = 447) given over-the-counter acetaminophen and ibuprofen following ambulatory otologic surgery between July 1, 2018 and June 30, 2020. INTERVENTION/METHODS:Opioid prescription upon request. MAIN OUTCOME MEASURES/METHODS:Patient, disease, and surgical variables such as age, sex, past medical history, chronic pain condition, surgical procedure, primary versus (vs.) revision surgery, and endoscopic vs. microscopic approach were examined for relationship to ad hoc opioid prescription rate. RESULTS:Of 370 adult patients (mean age 49.0 yrs, range 18.0-88.5 yrs), 75 (20.3%) were prescribed opioids for postoperative pain, most commonly oxycodone-acetaminophen 5/325 mg. Of 77 pediatric patients (mean age 8.8 yrs, range 0.7-17.9 yrs), 5 (6.5%) were prescribed postoperative opioid analgesia. In the adult population, chronic pain condition, pain medication use at baseline, canal wall up mastoidectomy, tympanoplasty, tympanomeatal flap, bone removal of the mastoid, postauricular incision, and intraoperative microscopy were independent predictors of opioid pain prescription. When controlling for all significant variables, only chronic pain condition remained significant (odds ratio = 3.94; p = 0.0007). In the pediatric population, atresiaplasty, meatoplasty, and conchal cartilage removal were independently associated with opioid prescription, but none remained significant when analyzed in a multivariate linear model. CONCLUSIONS:Pain following ambulatory otologic surgery may be adequately managed with over-the-counter pain medications in the majority of cases. Opioids may be necessary in adults with preexisting pain conditions.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:Vocal fold fibrosis remains a significant clinical challenge. Estrogens, steroid hormones predominantly responsible for secondary sexual characteristics in women, have been shown to alter wound healing and limit fibrosis, but the effects on vocal fold fibrosis are unknown. We sought to elucidate the expression of estrogen receptors and the effects of estrogens on TGF-β1 signaling in rat vocal fold fibroblasts (VFFs). STUDY DESIGN/METHODS:In vitro. METHODS: M) were employed as antagonists of ERα or GPR30, respectively. qPCR was employed to determine estrogen receptor-mediated effects of E2 on genes related to fibrosis. RESULTS: M) and TGF-β1 significantly increased Smad7 (P = .03) and decreased Col1a1 (P = .04) compared to TGF-β1 alone; this response was negated by the combination of ICI and G36 (P = .009). CONCLUSIONS:E2 regulated TGF-β1/Smad signaling via estrogen receptors in VFFs. These findings provide insight into potential mechanisms of estrogens on vocal fold injury with the goal of enhanced therapeutics for vocal fold fibrosis. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2020.

Initial diagnosis of peripheral vestibulopathy requires a detailed history, physical examination, and, in some cases, audiovestibular testing, radiographic imaging, or serology. Differentiation of a peripheral vestibulopathy as progressive or degenerative is often nuanced and influenced by a characterization of a patient's symptoms or natural history over time. A diverse group of vestibular pathology may fit into this category, including Ménière's disease, autoimmune conditions, congenital pathologies, ototoxic medications, radiation therapy, and perilymphatic fistula. Differentiation among these entities may be guided by initial or subsequent symptomatology, with various combinations of audiovestibular testing, serology, and imaging. Treatment options are disparate and disease-specific, ranging from observation to medical management or surgical intervention, underscoring the need for astute investigation and diagnosis.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To document the history of hearing seeing in children and adults. STUDY DESIGN/METHODS:A literature search in all languages was carried out with the terms of hearing screening from the following sources: Pub Med, Science Direct, World Catalog, Index Medicus, Google scholar, Google Books, National Library of Medicine, Welcome historical library and The Library of Congress. METHODS:The primary sources consisting of books, scientific reports, public documents, governmental reports, and other written material were analyzed to document the history of hearing screening. RESULTS:The concept of screening for medical conditions that, when found, could influence some form of the outcome of the malady came about during the end of 19th century. The first applications of screening were to circumscribe populations, schoolchildren, military personnel, and railroad employees. During the first half of the 20th century, screening programs were extended to similar populations and were able to be expanded on the basis of the improved technology of hearing testing. The concept of universal screening was first applied to the inborn errors of metabolism of newborn infants and particularly the assessment of phenylketonuria in 1963 by Guthrie and Susi. A limited use of this technique has been the detection of genes resulting in hearing loss. The use of a form of hearing testing either observational or physiological as a screen for all newborns was first articulated by Larry Fisch in 1957 and by the end of the 20th century newborn infant screening for hearing loss became the standard almost every nation worldwide. CONCLUSIONS:Hearing screening for newborn infants is utilized worldwide, schoolchildren less so and for adults many industrial workers and military service undergo hearing screening, but this is not a general practice for screening the elderly. LEVEL OF EVIDENCE/METHODS:NA Laryngoscope, 2021.