Emergency department visits following endoscopic skull base surgery: An opportunity for improvement.

BACKGROUND: Readmissions are major healthcare expenditures, key hospital metrics, and are often preceded by an evaluation in the emergency department (ED). The purpose of this study was to analyze ED visits within 30 days of endoscopic skull base surgery (ESBS), risk factors for readmission once in the ED, and ED-related evaluation and outcomes. METHODS: Retrospective review from January 2017 to December 2022 at a high-volume center of all ESBS patients who presented to the ED within 30 days of surgery. RESULTS: Of 593 ESBS cases, 104 patients (17.5%) presented to the ED following surgery within 30 days, with a median presentation of 6 days post-discharge (IQR 5-14); 54 (51.9%) patients were discharged while 50 (48.1%) were readmitted. Readmitted patients were significantly older than discharged patients (median 60 years, IQR 50-68 vs. 48 years, 33-56; p < 0.01). Extent of ESBS was not associated with readmission or discharge from the ED. The most common discharge diagnoses were headache (n = 13, 24.1%) and epistaxis (n = 10, 18.5%); the most common readmitting diagnoses were serum abnormality (n = 15, 30.0%) and altered mental status (n = 5, 10.0%). Readmitted patients underwent significantly more laboratory testing than discharged patients (median 6, IQR 3-9 vs. 4, 1-6; p < 0.01). CONCLUSIONS: Approximately half of patients who presented to the ED following ESBS were discharged home but underwent significant workup. Follow-up within 7 days of discharge, risk-stratified endocrine care pathways, and efforts to address the social determinants of health may be considered to optimize postoperative ESBS care.

Changes in otolaryngology application requirements and match outcomes: Are we doing any better?

Objectives: Otolaryngology-specific requirements were piloted to minimize applicant and program burdens. We investigated the impact of introducing and then removing these requirements on Match outcomes. Methods: 2014-2021 National Resident Matching Program® data were examined. The primary outcome was the impact of Otolaryngology Resident Talent Assessment (ORTA; prematch 2017, postmatch 2019) and Program-Specific Paragraph (PSP; implemented 2016, optional 2018) on applicant numbers and match rates. Secondary survey analysis assessed candidate perceptions of PSP/ORTA. Results: Applicant numbers declined significantly during PSP/ORTA (18.9%; p = 0.001). With the optional PSP and postmatch ORTA, applicant numbers increased significantly (39.0%; p = 0.002). Examined individually, mandatory PSP was associated with a significant decline in applicants (p = 0.007), whereas postmatch ORTA was associated with significant increases in applicants (p = 0.010). ORTA and PSP negatively impacted the decision to apply to otolaryngology in 59.8% and 51.3% of applicants, respectively. Conversely, match rate success improved significantly from 74.8% to 91.2% during PSP/ORTA (p = 0.014), followed by a significant decline to 73.1% after PSP was made optional and ORTA moved to postmatch (p = 0.002). Conclusions: ORTA and PSP correlated with decreased applicant numbers and increased match rate success. As programs seek ways to remove barriers to applying to otolaryngology, the potential consequences of an increasing pool of unmatched candidates must also be considered.

Endoscopic multiport resection of a transspatial, retromaxillary tumor.

Tumors of the retromaxillary tissues can grow to involve multiple deep, skull base spaces, including the pterygopalatine fossa, infratemporal fossa, and the parapharyngeal space. Management of these tumors must account for heterogeneous pathology as well as the critical neurovasculature in and surrounding these spaces. Traditionally, these tumors have been approached the open skull base or anterior craniofacial approaches. Modern endoscopic endonasal and multiport approaches have increasingly become favored for certain tumors in the retromaxillary skull base region. In this report, we present the case of a 42-year-old male presented with refractory headache and was found to have a left-sided 5.0 cm tumor of the retromaxillary spaces with widening of foramen ovale. Differential diagnosis included schwannoma of the mandibular nerve, paraganglioma, salivary gland tumor, or soft tissue tumor. The tumor was approached via an expanded endoscopic approach to the pterygopalatine fossa and augmented with a Caldwell-Luc maxillotomy, to access the posterolateral extent of the tumor. A 2-surgeon team utilized visualization and instrumentation through both the transnasal and transmaxillotomy corridors to completely mobilize and remove the tumor. Post-resection imaging demonstrated complete removal of the tumor and pathology confirmed the diagnosis of schwannoma. Custom, multiport surgery can be a safe, less invasive approach for successful management of well selected retromaxillary skull base tumors.

Fascia Lata: Another Workhorse for Complex Skull Base Reconstruction.

BACKGROUND: Multiple methods exist for skull base reconstruction of defects created by expanded endonasal approaches. While the nasoseptal flap (NSF) has been well established as the workhorse of mucosal reconstruction in complex skull base defects in multi-layered closures, a variety of options exist for the inner layer of multilayer reconstruction, including fascia lata (FL). OBJECTIVE: To present our experience and outcomes in utilizing FL in multiple ways to reconstruct a wide variety of complex skull base defects. METHODS: Retrospective review was performed from May 2017 to February 2022 to identify 50 consecutive patients who underwent endoscopic skull base reconstruction using FL. RESULTS: FL was employed for reconstruction in 50 patients included in the study: 37 undergoing primary expanded endonasal skull base surgery and 13 revision cases. A wide range of complex pathology was treated, with meningioma and craniopharyngioma being the two most common. FL was utilized as a "button" graft (34/50, 68.0%), free graft inlay/onlay (13/50, 26.0%), and as a button graft combined with onlay (3/50, 6.0%). Expanded surgery defects addressed included tuberculum sella/sphenoid planum (36/50, 72.0%), clivus (6/50, 12.0%), and cribriform/planum (8/50, 16.0%). Successful reconstruction with fascia lata was accomplished in 46/50 cases (92%), with only 4 cases (8%) requiring revision for post-op CSF leak. Donor-site complications were rare with only 1 case (2.0%) of post-op seroma. CONCLUSION: FL, usually with NSF, offers a versatile option for the reconstruction of challenging defects with excellent outcomes and minimal morbidity. FL is emerging as a workhorse for reconstruction of the inner layer of complex skull base defects.

Biologics for Nasal Polyps: Synthesizing Current Recommendations into a Practical Clinical Algorithm.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) has been traditionally managed with a combination of topical and systemic medical therapy as well as endoscopic sinus surgery. The emergence of biologic therapies that target specific aspects of the inflammatory cascade has ushered in a potentially new paradigm in the management options available for CRSwNP. PURPOSE: To summarize the current literature and recommendations supporting the use of available biologic therapies for CRSwNP and to develop an algorithm to aid clinical decision-making regarding treatment selection. METHODS: A review of available literature and studies that demonstrated the clinical efficacy of biologic agents for the treatment of CRSwNP informing current CRSwNP consensus algorithms. RESULTS: Current biologic medications target immunoglobulin E, interleukins, or interleukin receptors implicated in the Th2 inflammatory cascade. Institution of biologic therapy is now an option for patients who have disease refractory to topical medical therapy and endoscopic sinus surgery, those who cannot tolerate surgery, or patients with other comorbid Th2 diseases. Response to treatment should be monitored at 4-6 months and 1 year after initiating therapy. Across multiple indirect comparisons, dupilumab appears to have the largest therapeutic benefit across multiple subjective and objective outcomes. The choice of therapeutic agent also depends on drug availability, patient tolerance, presence of comorbid illnesses, and cost. CONCLUSIONS: Biologics are emerging as an important option in the management of patients with CRSwNP. While more data is required to fully inform indications, treatment selection, and health economics related to their use, biologics may offer robust symptom relief to patients who have failed other interventions.

Analysis of Otolaryngologic Readmissions at a High-Volume Quaternary Referral Center.

OBJECTIVES: To identify common reasons for readmission following otolaryngologic surgery at a high-volume center and identify possible risk factors for readmission. METHODS: Retrospective chart review of readmissions identified by hospital-based electronic medical record reporting mechanism. RESULTS: From January 2019 to September 2020, there were 87 readmissions following 808 index surgeries. The most common reason for readmission was for planned surgery (23%), followed by post-operative neck infection, bleeding, or pneumonia. Patients with unplanned readmissions had significantly longer index admission duration than patients who were not readmitted (median 7 days vs. median 5 days, resp.; p = 0.0056). Analysis of cases of unplanned readmission for neck infection and bleeding identified the oral cavity/pharynx as the most common site of initial surgery and that a majority of patients had a history of radiation therapy. CONCLUSION: Neck infection, bleeding, and pneumonia were the most common reasons for unplanned readmission following otolaryngologic surgery, and a large portion of patients required additional procedures during readmission. Unplanned readmissions for bleeding were significantly more costly than readmissions for neck infections. Long-index hospitalizations, index surgery involving the oral cavity and pharynx, and a history of radiation therapy may be useful clinical features that could stratify the risk of readmission. LEVEL OF EVIDENCE: 4, retrospective chart review Laryngoscope, 133:2546-2552, 2023.

Anatomic Considerations of Microvascular Free Tissue Transfer in Endoscopic Endonasal Skull Base Surgery.

Objective Though microvascular free tissue transfer is well established for open skull base reconstruction, normative data regarding flap design and inset after endoscopic endonasal skull base surgery (ESBS) is lacking. We aim to describe anatomical considerations of endoscopic endonasal inset of free tissue transfer of transclival (TC) and anterior cranial base resection (ACBR) defects. Design and Setting Radial forearm free tissue transfer (RFFTT) model. Participants Six cadaveric specimens. Main Outcome Measures Pedicle orientation, pedicle length, and recipient vessel intraluminal diameter. Results TC and ACBR defects averaged 17.2 and 11.7 cm 2 , respectively. Anterior and lateral maxillotomies and endoscopic medial maxillectomies were prepared as corridors for flap and pedicle passage. Premasseteric space tunnels were created for pedicle tunneling to recipient facial vessels. For TC defects, the RFFTT pedicle was oriented cranially with the flap placed against the clival defect (mean pedicle length 13.1 ± 0.6 cm). For ACBR defects, the RFFTT pedicle was examined in three orientations with respect to anterior-posterior axis of the RFFTT: anteriorly, posteriorly, and laterally. Lateral orientation offered the shortest average pedicle length required for anastomosis in the neck (11.6 ± 1.29 cm), followed by posterior (13.4 ± 0.7cm) and anterior orientations (14.4 ± 1.1cm) ( p < 0.00001, analysis of variance). Conclusions In ACBR reconstruction using RFFTT, our data suggests lateral pedicle orientation shortens the length required to safely anastomose facial vessels and protects the frontal sinus outflow anteriorly while limiting pedicle exposure through a maxillary corridor within the nasal cavity. With greater understanding of anatomical factors related to successful preoperative flap planning, free tissue transfer may be added to the ESBS reconstruction ladder.

Long Term Incidence and Outcomes of Sinonasal and Otologic Disease in Patients With Pyriform Aperture Stenosis and Choanal Atresia.

ABSTRACT: Pyriform aperture stenosis (PAS) and choanal atresia (CA) are 2 anatomic causes of newborn nasal obstruction. The goal of management of PAS and CA is to establish a patent nasal airway, often requiring surgery. No previous study has sought to assess the long term sinonasal and otologic disease incidence and outcomes in the PAS and CA population after surgical intervention. The goal of this study was to investigate whether surgical intervention in PAS and CA is correlated with the long-term development of sinonasal disease or otologic disease (either recurrent acute otitis media or chronic otitis media with effusion). Patients with a diagnosis of PAS or CA who underwent surgical intervention were retrospectively identified. Pertinent demographic risk factors, medical and syndromic diagnoses, number of surgical interventions, types of surgical interventions, and presence of sinonasal and otologic diseases were assessed. Fifty-three patients were included in the study: 8 patients with PAS and 45 with CA. The average follow-up time was 2.9 years. No PAS patients developed otologic or sino-nasal disease. Four of 45 patients with CA developed recurrent acute sinusitis (3 non-syndromic and 1 syndromic) and 19 of 45 patients developed otologic disease (9 non-syndromic and 10 syndromic). Coloboma, Heart, Choanal Atresia, Growth Retardation, Genitourinary, Ear Syndrome and unilateral CA correlated significantly with the subsequent development of otologic disease; however, the number of surgeries did not. This study suggests that surgery for PAS and CA do not increase the risk of long-term development of sinonasal or otologic disease.

Pain and Pain Control With Opioid and Nonopioid Medications After Otologic Surgery.

OBJECTIVE: To prospectively analyze pain and pain medication use following otologic surgery. STUDY DESIGN: Prospective cohort study with patient reported pain logs and medication use logs. SETTING: Tertiary academic hospital.Patients: Sixty adults who underwent outpatient otologic surgeries. INTERVENTIONS: Surveys detailing postoperative pain levels, nonopioid analgesic (NOA) use, and opioid analgesic use. MAIN OUTCOME MEASURES: Self-reported pain scores, use of NOA, and use of opioid medications normalized as milligrams morphine equivalents (MME). RESULTS: Thirty-two patients had surgery via a transcanal (TC) approach, and 28 patients had surgery via a postauricular (PA) approach. TC surgery had significantly lower reported pain scores than PA surgery on both postoperative day (POD) 1 (median pain score 2.2, IQR 0-5 vs. median pain score 4.8, IQR 3.4-6.3, respectively; p = 0.0013) and at POD5 (median pain score 0, IQR 0-0 vs. median pain score 2.0, IQR 0-3, respectively; p = 0.0002). Patients also used significantly fewer opioid medications with TC approach than patients who underwent PA approach at POD1 (median total MME 0, IQR 0-5 vs. median total MME 5.0, IQR 0-15, respectively; p = 0.03) and at POD5 (median total MME 0, IQR 0-0 vs. median total MME 0, IQR 0-5, respectively; p = 0.0012). CONCLUSIONS: Surgery with a postauricular approach is associated with higher pain and opioid use following otologic surgery. Patient- and approach-specific opioid prescribing is feasible following otologic surgery.

HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma.

BYL719 is a PI3K inhibitor that has demonstrated efficacy in the treatment of head and neck squamous cell carcinoma. BYL719 exerts its therapeutic effect by suppressing AKT and other proliferative signaling mechanisms. Despite PI3K inhibition and AKT suppression, residual activity of protein S6, a core marker of proliferative activation, has been observed. HER3, either via dimerization or activation by its ligand neurgeulin (NRG), is known to activate PI3K. Thus, we hypothesized that co-targeting HER3 and PI3K would lead to greater suppression of the PI3K-AKT signaling pathway and greater tumor suppression than with BYL719 alone. We investigated biochemical expression and activation of the HER3-PI3K-AKT-S6 pathway in HNSCC cell lines and patient-derived xenografts (PDXs). Antitumor effects of HER3 and PI3K inhibitors alone and in combination were evaluated in cell culture and murine models. Treatment of HNSCC cell lines with BYL719 significantly reduced AKT activation and suppressed tumor growth. However, S6 was persistently activated despite suppression of AKT. Combination treatment with KTN3379, a monoclonal antibody targeted against HER3, and BYL719 led to enhanced suppression of in vitro and in vivo cancer growth and durable suppression of AKT and S6. Therefore, inhibition of HER3 with KTN3379 enhanced the effects of PI3K inhibition in pre-clinical HNSCC models. These data support co-targeting HER3 and PI3K for the treatment of HSNCC.

TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression.

Purpose: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCCs), raising the possibility of an anti-apoptotic role in malignant cells. This study investigated this using a multimodal, translational investigation.Experimental Design: Combination of (i) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression (ii) in vivo studies assessing similar outcomes, and (iii) molecular and staining analysis of human HNSCC samples.Results: TMEM16A expression was found to correlate with greater tumor size, increased Erk 1/2 activity, less Bim expression, and less apoptotic activity overall in human HNSCC. These findings were corroborated in subsequent in vitro and in vivo studies and expanded to include a cisplatin-resistant phenotype with TMEM16A overexpression. A cohort of 41 patients with laryngeal cancer demonstrated that cases that recurred after chemoradiation failure were associated with a greater TMEM16A overexpression rate than HNSCC that did not recur.Conclusions: Ultimately, this study implicates TMEM16A as a contributor to tumor progression by limiting apoptosis and as a potential biomarker of more aggressive disease. Clin Cancer Res; 23(23); 7324-32. ©2017 AACR.

TMEM16A/ANO1 suppression improves response to antibody-mediated targeted therapy of EGFR and HER2/ERBB2.

TMEM16A, a Ca2+ -activated Cl- channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl- channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl- channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride-deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A cotargeting, tumor cells may acquire resistance to EGFR/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR/HER family members.