Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS:We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS:The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status ( P = .041) and treatment with TT ( P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS ( P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS ( P = .017), triple-negative breast cancer ( P = .002), a Karnofsky Performance Status of <80 at first SRS ( P = .002), and active systemic disease at last follow-up ( P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION/CONCLUSIONS:Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.

OBJECTIVES/OBJECTIVE:For transwomen undergoing voice feminization interventions, fundamental frequency (F 0 ; vocal pitch) is a commonly reported functional outcome measure in the literature. However, F 0 may not correlate well with improvement in quality of life (QoL). Several validated voice-related QoL instruments have been used to assess QoL improvement in these patients, yet there is no consensus on the most appropriate instrument. This systematic review and meta-analysis aimed to assess the relationship between change in F 0 and QoL improvement following voice feminization, and to compare validated QoL instruments commonly used in this population. DATA SOURCES/METHODS:PubMed, Cochrane, and Embase. REVIEW METHODS/METHODS:A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Primary studies of transwomen undergoing voice feminization, reporting validated QoL outcomes were included. Meta-analyses for associations between mean change in QoL score and mean change in F 0 , as well as variations in mean change in QoL score by QoL instrument, were performed using a multilevel mixed effects model. RESULTS:No statistically significant correlation was found between change in F 0 and QoL score improvement post-intervention. Different validated instruments showed statistically significant variation in QoL score change, with the Trans Women Voice Questionnaire (TWVQ) capturing a greater improvement in QoL score relative to other instruments. CONCLUSIONS:Lack of correlation between changes in F 0 and QoL improvement further supports that F 0 alone is insufficient to assess the efficacy of voice feminizing interventions. Validated QoL measures are useful adjuncts. Of these, the TWVQ appears to be the most sensitive for measurement of QoL improvement following voice feminization.

UNLABELLED:Management of Enlarging tracheoesophageal fistula (TEF) with Voice Prosthesis in Laryngectomized Head and Neck Cancer Patients. OBJECTIVES/OBJECTIVE:An enlarging TEF following voice prosthesis placement impacts patient quality of life, risks airway compromise, and can lead to aspiration pneumonia. Pharyngoesophageal strictures have previously been reported to be associated with TEF enlargement and leakage. We describe a series of patients with enlarging TEFs after Tracheoesophageal puncture (TEP) for voice prosthesis who required pharyngoesophageal reconstruction. METHODS:Retrospective case series of laryngectomized H&N cancer patients with primary or secondary TEP who underwent surgical management for enlarging TEF site between 6/2016-11/2022. RESULTS:Eight patients were included. The mean age was 62.8 years old. Seven patients had a history of hypothyroidism. Of seven with prior H&N radiation history, two had both historical and adjuvant radiation. Two of the eight TEPs were placed secondarily. Mean time from TEP to enlarging TEF diagnosis was 891.3 days. Radial forearm-free flaps were used in five patients. Six had stenosis proximal to the TEF whereas one had distal stenosis and one had no evidence of stenosis. Mean length of stay was 12.3 days. Mean follow-up was 400.4 days. Two required a second free flap for persistent fistula. CONCLUSION/CONCLUSIONS:Surgical reconstruction of enlarging TEFs due to TEP/VP placement is effective in combination with addressing underlying pharyngeal/esophageal stenosis contributing to TEF enlargement and leakage. Radial forearm-free flaps have the additional benefit of a long vascular pedicle to access more distant and less-irradiated recipient vessels. Many fistulae are resolved after the first flap reconstruction, but some may require subsequent reconstruction in case of failure. LEVEL OF EVIDENCE/METHODS:Level IV Laryngoscope, 2023.

OBJECTIVE:Simulation may be a valuable tool in training laryngology office procedures on unsedated patients. However, no studies have examined whether existing awake procedure simulators improve trainee performance in laryngology. Our objective was to evaluate the transfer validity of a previously published 3D-printed laryngeal simulator in improving percutaneous injection laryngoplasty (PIL) competency compared with conventional educational materials with a single-blinded randomized controlled trial. METHODS:Otolaryngology residents with fewer than 10 PIL procedures in their case logs were recruited. A pretraining survey was administered to participants to evaluate baseline procedure-specific knowledge and confidence. The participants underwent block randomization by postgraduate year to receive conventional educational materials either with or without additional training with a 3D-printed laryngeal simulator. Participants performed PIL on an anatomically distinct laryngeal model via trans-thyrohyoid and trans-cricothyroid approaches. Endoscopic and external performance recordings were de-identified and evaluated by two blinded laryngologists using an objective structured assessment of technical skill scale and PIL-specific checklist. RESULTS:Twenty residents completed testing. Baseline characteristics demonstrate no significant differences in confidence level or PIL experience between groups. Senior residents receiving simulator training had significantly better respect for tissue during the trans-thyrohyoid approach compared with control (p < 0.0005). There were no significant differences in performance for junior residents. CONCLUSIONS:In this first transfer validity study of a simulator for office awake procedure in laryngology, we found that a previously described low-cost, high-fidelity 3D-printed PIL simulator improved performance of PIL amongst senior otolaryngology residents, suggesting this accessible model may be a valuable educational adjunct for advanced trainees to practice PIL. LEVEL OF EVIDENCE/METHODS:N/A Laryngoscope, 2023.

OBJECTIVE:To compare improvement in patient-reported outcomes (PROM) in persons undergoing endoscopic and open surgical management of Zenker diverticula (ZD). METHODOLOGY/METHODS:Prospective, multicenter cohort study of all individuals enrolled in the Prospective OUtcomes of Cricopharyngeus Hypertonicity (POUCH) Collaborative who underwent surgery for ZD. Patient survey, radiography reports, and the 10-item Eating Assessment Tool (EAT-10) pre- and post-procedure were abstracted from a REDCap database, which summarized means, medians, percentages, and frequencies of. Outcome based on operative intervention (endoscopic vs. open) was compared using t-test, Wilcoxon rank sum test or chi-square test, as appropriate. RESULTS:One hundred and forty-seven persons were prospectively followed. The mean age (SD) of the cohort was 68.7 (11.0). Overall, 66% of patients reported 100% improvement in EAT-10; 81% of patients had greater than 75% improvement; and 88% had greater than 50% improvement. Endoscopic was used for n = 109 patients, and open surgical intervention was used for n = 38. The median [interquartile range, IQR] EAT-10 percent improvement for endoscopic treatment was 93.3% [72, 100], and open was 100% [92.3, 100] (p = 0.05). The incidence of intraoperative complications was 3.7% for endoscopic and 7.9% for open surgical management. The median [IQR] in follow-up was 86 and 97.5 days, respectively. CONCLUSION/CONCLUSIONS:Both endoscopic and open surgical management of ZD provide significant improvement in patient-reported outcomes. The data suggest that open diverticulectomy may provide a modest advantage in symptomatic improvement compared to endoscopic management. The data suggest that the postoperative complication rate is higher in the open surgical group. LEVEL OF EVIDENCE/METHODS:Level 3 Laryngoscope, 2023.

Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. However, timely molecular diagnostic testing for patients with brain tumors is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. In this study, we developed DeepGlioma, a rapid (<90 seconds), artificial-intelligence-based diagnostic screening system to streamline the molecular diagnosis of diffuse gliomas. DeepGlioma is trained using a multimodal dataset that includes stimulated Raman histology (SRH); a rapid, label-free, non-consumptive, optical imaging method; and large-scale, public genomic data. In a prospective, multicenter, international testing cohort of patients with diffuse glioma (n = 153) who underwent real-time SRH imaging, we demonstrate that DeepGlioma can predict the molecular alterations used by the World Health Organization to define the adult-type diffuse glioma taxonomy (IDH mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular classification accuracy of 93.3 ± 1.6%. Our results represent how artificial intelligence and optical histology can be used to provide a rapid and scalable adjunct to wet lab methods for the molecular screening of patients with diffuse glioma.

INTRODUCTION:Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. Access to timely molecular diagnostic testing for brain tumor patients is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment. METHODS:By combining stimulated Raman histology (SRH), a rapid, label-free, non-consumptive, optical imaging method, and deep learning-based image classification, we are able to predict the molecular genetic features used by the World Health Organization (WHO) to define the adult-type diffuse glioma taxonomy, including IDH-1/2, 1p19q-codeletion, and ATRX loss. We developed a multimodal deep neural network training strategy that uses both SRH images and large-scale, public diffuse glioma genomic data (i.e. TCGA, CGGA, etc.) in order to achieve optimal molecular classification performance. RESULTS:One institution was used for model training (University of Michigan) and four institutions (NYU, UCSF, Medical University of Vienna, and University Hospital Cologne) were included for patient enrollment in the prospective testing cohort. Using our system, called DeepGlioma, we achieved an average molecular genetic classification accuracy of 93.2% and identified the correct diffuse glioma molecular subgroup with 91.5% accuracy within 2 minutes in the operating room. DeepGlioma outperformed conventional IDH1-R132H immunohistochemistry (94.2% versus 91.4% accuracy) as a first-line molecular diagnostic screening method for diffuse gliomas and can detect canonical and non-canonical IDH mutations. CONCLUSIONS:Our results demonstrate how artificial intelligence and optical histology can be used to provide a rapid and scalable alternative to wet lab methods for the molecular diagnosis of brain tumor patients during surgery.

In situ simulation has frequently been used to improve team performance and provide an opportunity for the practice of critical skills and identify latent safety threats, which are undetected risks that may lead to adverse outcomes. However, the use of known quality improvement tools to prioritize and mitigate these safety threats is an area requiring further study. Over the course of 9 in situ simulations of a pediatric shock case, postcase debriefs were held to identify latent safety threats in an emergency department and a mixed pediatric and adult inpatient unit. Latent safety threats identified included structure-related threats such as inability to locate critical equipment, knowledge-based threats relating to rapid intravenous fluid administration, and communication-based threats such as lack of role designation. Identification of latent safety threats in the health care environment may assist clinician leaders in mitigating risk of patient harm. The protocol described may be adopted and applied to other critical event simulations, with structured debriefing used as a tool to identify and mitigate threats before they affect the patient.

OBJECTIVE:To characterize the efficacy of human papillomavirus (HPV) vaccination as an adjuvant therapy in recurrent respiratory papillomatosis (RRP). DATA SOURCES:PubMed, Embase, Cochrane, Google Scholar, ClinicalTrials.gov, and Web of Science databases were queried for articles published before April 2021. REVIEW METHODS:All retrieved studies (n = 870) were independently analyzed by two reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement using predefined inclusion and exclusion criteria. 13 studies met inclusion criteria. A random-effects meta-analysis was performed to study intersurgical interval (ISI) and number of surgical procedures per year before and after vaccination. RESULTS:The systematic review included 13 studies, comprising 243 patients. All studies utilized the Gardasil® quadrivalent vaccine, and one study (Yiu et al. 2019) utilized both the quadrivalent and Gardasil® 9-valent vaccines. Our meta-analysis included 62 patients with ISI data across 4 studies, and 111 patients with data on the number of surgical procedures per month across 7 studies. The mean number of surgical procedures decreased by 4.43 per year after vaccination (95% CI, -7.48 to -1.37). Mean ISI increased after vaccination, with a mean difference of 15.73 months (95% CI, 1.46-29.99). Two studies reported on HPV sero-conversion, with HPV seropositivity of 100% prior to vaccination and 25.93% after vaccination. CONCLUSION:The addition of HPV vaccination was associated with an increase in time between surgeries and reduction in the number of surgical procedures required. HPV vaccination may be a beneficial adjuvant treatment for RRP. LEVEL OF EVIDENCE:NA Laryngoscope, 133:2046-2054, 2023.