Faculty Bibliography

Introduction: Thyroidectomy is commonly performed in otolaryngology. Complications such as recurrent laryngeal nerve (RLN) injury and severe hypocalcemia have reported incidences in national studies as high as 3% and 8%, respectively. Narcotic pain medications are commonly used for postoperative pain management. Here, we present the long-term results of a thyroidectomy quality and safety improvement program, with an emphasis on reducing narcotic use.
Method(s): All surgeons who perform thyroidectomy established standards for antibiotic administration, postoperative calcium management, and narcotics use. The program was established in 2018 and data on adverse events, length of stay, antibiotic and narcotic use were recorded prospectively from June 2018 to January 2021. Data trends were analyzed throughout the course of the study.
Result(s): During the study period, 542 thyroidectomies were performed by 14 surgeons. The average length of stay was less than 24 hours. Five (0.9%) adverse events were recorded: 1 (0.2%) temporary RLN dysfunction, 3 (0.6%) hematomas, 1 (0.2%) surgical site infection, and 1 (0.2%) temporary hypocalcemia. The average number of narcotics prescribed declined from 18 doses (95%CI: 16.8-18.5) in 2019 to 9 in 2020 (95%CI: 8.5-9.6) (p<0.0001), without an increase in need for refills. No instances of permanent hypocalcemia or permanent RLN injury were identified.
Conclusion(s): By implementing a thyroidectomy quality improvement program, we achieved extremely low rates of adverse events and significantly reduced the use of narcotics without adverse effects. These data can inform practitioners and the public about expected outcomes of thyroid surgery, and establish benchmarks for quality and safety.
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INTRODUCTION/BACKGROUND:There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs. METHODS:) was calculated to assess inter-rater reliability. RESULTS:= 0.79 (95% CI: 0.61-0.98). CONCLUSION/CONCLUSIONS:p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.

In contrast to adults, meningiomas are uncommon tumors in childhood and adolescence. Whether adult and pediatric meningiomas differ on a molecular level is unclear. Here we report detailed genomic analyses of 37 pediatric meningiomas by sequencing and DNA methylation profiling. Histologically, the series was dominated by meningioma subtypes with aggressive behavior, with 70% of patients suffering from WHO grade II or III meningiomas. The most frequent cytogenetic aberrations were loss of chromosomes 22 (23/37 [62%]), 1 (9/37 [24%]), 18 (7/37 [19%]), and 14 (5/37 [14%]). Tumors with NF2 alterations exhibited overall increased chromosomal instability. Unsupervised clustering of DNA methylation profiles revealed separation into three groups: designated group 1 composed of clear cell and papillary meningiomas, whereas group 2A comprised predominantly atypical meningiomas and group 2B enriched for rare high-grade subtypes (rhabdoid, chordoid). Meningiomas from NF2 patients clustered exclusively within groups 1 and 2A. When compared with a dataset of 105 adult meningiomas, the pediatric meningiomas largely grouped separately. Targeted panel DNA sequencing of 34 tumors revealed frequent NF2 alterations, while other typical alterations found in adult non-NF2 tumors were absent. These data demonstrate that pediatric meningiomas are characterized by molecular features distinct from adult tumors.

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.

OBJECTIVES:Sinonasal mucosal melanoma (SNMM) is an aggressive cancer usually managed with surgical resection. This study evaluates the impact of treatment modality and positive surgical margin (PSM) on survival following resection of SNMM. STUDY DESIGN:Retrospective study of a national cancer registry. METHODS:The National Cancer Database was queried for cases of SNMM from 2010 to 2015. Data regarding patient demographics, tumor staging, and treatment modality were obtained. Survival rates were compared by margin status: PSM, negative (NSM), and no operation (0SM) using Kaplan-Meier analysis and log rank test. RESULTS:A total of 446 patients met inclusion criteria. Most cases were elderly (>66 years-old) (67.3%), female (54.3%), and white (89.5%). Cases of SNMM most commonly involved the nasal cavity (81.6%), were Stage 3 (60.0%), and underwent surgical resection at an academic center (65.0%). NSM and PSM were present in 59.0% and 26.9% of cases, respectively, while 14.1% of cases did not undergo surgical resection (0SM). Factors predictive of PSM included resection at a community hospital (OR 2.47) and Stage 4 disease (OR 2.07). The 2-year survival rates were 72.1% (95% CI 69.4-75.4%), 36.3% (95% CI 22.0-48.9), and 16.0% (95% CI 8.2-25.4%) for NSM, PSM and 0SM, respectively. Survival was statistically significant between NSM and PSM (Log rank <0.001) but not between 0SM and PSM (Log rank = 0.062). CONCLUSION:Our study emphasizes the need for NSM for SNMM as PSM did not demonstrate any significant improvement in survival when compared to 0SM. Our findings suggest that cases of SNMM are best managed at academic centers. LEVEL OF EVIDENCE:4 Laryngoscope, 131:2429-2435, 2021.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

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.

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.