Integrated Molecular and Histological Insights for Targeted Therapies in Mesenchymal Sinonasal Tract Tumors.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of mesenchymal sinonasal tract tumors (STTs), a distinct subset of STTs. Despite their rarity, mesenchymal STTs represent a unique clinical challenge, characterized by their rarity, often slow progression, and frequently subtle or overlooked symptoms. The complex anatomy of the sinonasal area, which includes critical structures such as the orbit, brain, and cranial nerves, further complicates surgical treatment options. This underscores an urgent need for more advanced and specialized therapeutic approaches. RECENT FINDINGS: Advancements in molecular diagnostics, particularly in next-generation sequencing, have significantly enhanced our understanding of STTs. Consequently, the World Health Organization has updated its tumor classification to better reflect the distinct histological and molecular profiles of these tumors, as well as to categorize mesenchymal STTs with greater accuracy. The growing understanding of the molecular characteristics of mesenchymal STTs opens new possibilities for targeted therapeutic interventions, marking a significant shift in treatment paradigms. This review article concentrates on mesenchymal STTs, specifically addressing sinonasal tract angiofibroma, sinonasal glomangiopericytoma, biphenotypic sinonasal sarcoma, and skull base chordoma. These entities are marked by unique histopathological and molecular features, which challenge conventional treatment approaches and simultaneously open avenues for novel targeted therapies. Our discussion is geared towards delineating the molecular underpinnings of mesenchymal STTs, with the objective of enhancing therapeutic strategies and addressing the existing shortcomings in the management of these intricate tumors.

Management of Chronic Sialadenitis due to Sjogren's Syndrome and Radioactive Iodine Therapy Using Sialendoscopy.

INTRODUCTION: Sialendoscopy is a minimally invasive technique for the management of salivary gland disease. This work characterizes its utility for treating chronic sialadenitis due to Sjogren's syndrome and radioactive iodine (RAI) therapy. METHODS: A single-center, retrospective review of patients undergoing sialendoscopy between March 2013 and May 2019 for the treatment of chronic sialadenitis due to Sjogren's or prior RAI therapy was performed. RESULTS: Thirty-four patients with Sjogren's and 25 patients who received RAI were identified, undergoing a total of 86 procedures. Median age at presentation was 53 years with mean follow-up time of 14.3 months. Seventy-two procedures were performed on the parotid gland, four on the submandibular gland, and ten on both glands. Corticosteroid injection and duct dilation were performed most commonly. Sixteen patients required repeat procedure. All patients were symptomatically improved at follow-up visit. DISCUSSION/CONCLUSION: These results support the idea that sialendoscopy offers symptomatic benefit for patients with chronic sialadenitis due to Sjogren's or RAI.

Optimizing Perioperative Care in Transsphenoidal Pituitary Surgery: Considerations for Enhanced Recovery After Surgery.

OBJECTIVE: To identify key recommendations for maximizing the efficiency and efficacy of perioperative care in transsphenoidal pituitary surgery. METHODS: The authors performed a comprehensive literature search of Enhanced Recovery After Surgery protocols implemented for patients undergoing transsphenoidal adenomectomy (TSA); individual recommendations were abstracted, and the evidence base thoroughly reviewed. RESULTS: The authors identified 19 individual recommendations pertinent to the care of patients undergoing TSA, which were subdivided into preoperative (n=6), intraoperative (n=6), and postoperative (n=7) interventions. Key factors recommended for minimizing length of stay, preventing readmission, and improving patient outcomes included comprehensive patient education, multidisciplinary evaluation, avoidance of routine lumbar drain placement and nasal packing, and rigorous postoperative monitoring of pituitary function and salt-water imbalances. The overall level of evidence for 7/19 (37%) implemented recommendations was found to be low, suggesting a need for continued research in this patient population. CONCLUSION: Several key interventions should be considered in the development of Enhanced Recovery After Surgery protocols for TSA, which may aid in further decreasing length of stay and promoting positive patient outcomes.

Effectiveness of endoscopic sinus surgery and aspirin therapy in the management of aspirin-exacerbated respiratory disease.

Background: Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). Objective: To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. Methods: A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. Results: A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). Conclusion: ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.

Management of a Unique Sinonasal Undifferentiated Carcinoma Subtype in the Era of SARS-CoV-2.

The novel coronavirus (SARS-CoV-2) pandemic has influenced the timeliness of care for patients with both common and rare conditions, particularly those affecting high-risk operative sites such as the upper aerodigestive tract. Sinonasal undifferentiated carcinoma (SNUC) represents a rare malignancy of the sinonasal tract, a unique subset of which has never been previously reported in the otolaryngology literature and is characterized by inactivation of the SMARCB (INI-1) tumor suppressor gene. This subtype exhibits a particularly poor prognosis and is characterized pathologically by its rhabdoid appearance. Here we present the case of an individual who was diagnosed with a sinonasal mass during the SARS-CoV-2 pandemic, which was ultimately found to be SMARCB (INI-1)-deficient sinonasal carcinoma. Advanced imaging was deferred in the interest of limiting the patient's exposure to the virus, and expedited operative management was performed which facilitated prompt referral for adjuvant chemoradiation. The SARS-CoV-2 pandemic presents unique challenges, but the work-up of high-risk lesions must be prioritized; this continues to be paramount as SARS-CoV-2 resurges in many cities across the USA.

Tissue-Dependent Expression of Bitter Receptor TAS2R38 mRNA.

TAS2R38 is a human bitter receptor gene with a common but inactive allele; people homozygous for the inactive form cannot perceive low concentrations of certain bitter compounds. The frequency of the inactive and active forms of this receptor is nearly equal in many human populations, and heterozygotes with 1 copy of the active form and 1 copy of the inactive form have the most common diplotype. However, even though they have the same genotype, heterozygotes differ markedly in their perception of bitterness, perhaps in part because of differences in TAS2R38 mRNA expression. Other tissues express this receptor too, including the nasal sinuses, where it contributes to pathogen defense. We, therefore, wondered whether heterozygous people had a similar wide range of TAS2R38 mRNA in sinonasal tissue and whether those with higher TAS2R38 mRNA expression in taste tissue were similarly high expressers in nasal tissue. To that end, we measured gene expression by quantitative PCR in taste and sinonasal tissue and found that expression abundance in one tissue was not related to the other. We confirmed the independence of expression in other tissue pairs expressing TAS2R38 mRNA, such as pancreas and small intestine, using autopsy data from the Genotype-Tissue Expression project (although people with high expression of TAS2R38 mRNA in colon also tended to have higher expression in the small intestine). Thus, taste tissue TAS2R38 mRNA expression among heterozygotes is unlikely to predict expression in other tissues, perhaps reflecting tissue-dependent function, and hence regulation, of this protein.

Monitoring Viral Genetic Variation as a Tool To Improve Molecular Diagnostics for Mumps Virus.

Here, we report how the analysis of viral genetic variation using next-generation sequencing (NGS) can be used as a tool to improve mumps virus diagnostics. Analysis of NGS data from recently circulating mumps virus isolates allowed optimization of the current mumps virus real-time reverse transcription-PCR (RT-PCR) by primer and probe modifications due to nucleotide variations. The modified assay showed a higher efficiency and sensitivity than the previously used CDC protocol for the detection of currently circulating mumps virus strains and could therefore offer better support for outbreak control. The NGS sequence data were also used to make predictions of changes in the hemagglutinin-neuraminidase protein structure that could explain possible immune escape mechanisms.

Sialendoscopy for Definitive Management of a Submandibular Abscess following Radiotherapy for Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Sialendoscopy has as yet been shown to be ideal for the management of sialolithiasis and chronic inflammatory diseases of the salivary gland. However, its applicability to the management of a broad range of salivary gland disease is continually growing. METHODS: Here we present a case report where sialendoscopy was used to successfully manage an intraparenchymal submandibular gland abscess in a patient with oropharyngeal squamous cell carcinoma managed with primary chemoradiation. RESULTS: The use of sialendoscopy enabled visualization of the patency of salivary ducts, drainage of abscess, and irrigation of antibiotic-impregnated fluid. In this particular patient, we were able to avoid a transcervical approach through a previously irradiated field, which would have necessitated concurrent tracheostomy and placed undue risk to surrounding neurovascular structures. CONCLUSION: Sialendoscopy should thus, in select patients, be considered as an initial intervention for patients with intraparenchymal salivary gland abscesses in which prior therapy creates an increased risk of complication from an open transcervical approach.

Caffeine Bitterness is Related to Daily Caffeine Intake and Bitter Receptor mRNA Abundance in Human Taste Tissue.

We investigated whether the abundance of bitter receptor mRNA expression from human taste papillae is related to an individual's perceptual ratings of bitter intensity and habitual intake of bitter drinks. Ratings of the bitterness of caffeine and quinine and three other bitter stimuli (urea, propylthiouracil, and denatonium benzoate) were compared with relative taste papilla mRNA abundance of bitter receptors that respond to the corresponding bitter stimuli in cell-based assays ( TAS2R4, TAS2R10, TAS2R38, TAS2R43, and TAS2R46). We calculated caffeine and quinine intake from a food frequency questionnaire. The bitterness of caffeine was related to the abundance of the combined mRNA expression of these known receptors, r = 0.47, p = .05, and self-reported daily caffeine intake, t(18) = 2.78, p = .012. The results of linear modeling indicated that 47% of the variance among subjects in the rating of caffeine bitterness was accounted for by these two factors (habitual caffeine intake and taste receptor mRNA abundance). We observed no such relationships for quinine but consumption of its primary dietary form (tonic water) was uncommon. Overall, diet and TAS2R gene expression in taste papillae are related to individual differences in caffeine perception.

Taste Receptors Mediate Sinonasal Immunity and Respiratory Disease.

The bitter taste receptor T2R38 has been shown to play a role in the pathogenesis of chronic rhinosinusitis (CRS), where the receptor functions to enhance upper respiratory innate immunity through a triad of beneficial immune responses. Individuals with a functional version of T2R38 are tasters for the bitter compound phenylthiocarbamide (PTC) and exhibit an anti-microbial response in the upper airway to certain invading pathogens, while those individuals with a non-functional version of the receptor are PTC non-tasters and lack this beneficial response. The clinical ramifications are significant, with the non-taster genotype being an independent risk factor for CRS requiring surgery, poor quality-of-life (QOL) improvements post-operatively, and decreased rhinologic QOL in patients with cystic fibrosis. Furthermore, indirect evidence suggests that non-tasters also have a larger burden of biofilm formation. This new data may influence the clinical management of patients with infectious conditions affecting the upper respiratory tract and possibly at other mucosal sites throughout the body.

Complicated Odontogenic Sinusitis: Extrasinus Infectious Spread.

Odontogenic sinusitis (ODS) is a common cause of orbital, intracranial, and osseous infectious extrasinus complications. Dental infections can spread to the orbital or intracranial spaces though the sinuses via thrombophlebitis or direct extension, or from the dentition or oral cavity via vascular channels in the maxillary alveolar bone. ODS typically presents with unilateral involvement both clinically and radiographically. Any suspicion for extrasinus spread based on history and physical examination should be followed by appropriate imaging, formal dental evaluation, and, when appropriate, ophthalmology and neurosurgery consultations. This multidisciplinary approach ensures appropriate management of both the acute orbital and intracranial complications.

Assessing adequacy of surgical extent in CRSwNP: The Completion of Surgery Index.

BACKGROUND: Endoscopic sinus surgery (ESS) maximized for topical steroid irrigations is highly effective for polyp disease. As extent and completeness of ESS varies widely by situation and practitioner, it is important to understand when revision surgery is appropriate, particularly in the era of biologic treatments. METHODS: A Completion of Surgery Index (CoSI) was developed to assess operative changes in polyp patients using pre- and postoperative computed tomography scans. The CoSI was then applied and tested in a cohort of consecutive chronic rhinosinusitis with nasal polyps (CRSwNP) patients, and examined within the context of quality-of-life improvements. RESULTS: The CoSI assesses surgical extent on a scale of 0-100, with 100 representing the highest possible degree of surgical completeness. Among 100 consecutive CRSwNP patients undergoing ESS in 2021 with postoperative topical steroid irrigations, including 75 revision surgeries, SNOT-22 scores improved at 6 months postoperatively, with durable and consistent improvement at 24 months (p < 0.001). Preoperative CoSI scores in revision surgery patients were 49.4 ± 26.0, improving to 91.0 ± 8.1 postoperatively. SNOT-22 scores for primary ESS patients and patients with a preoperative CoSI score of less than 70 improved by 26.4 and 28.1 points, respectively, in contrast to patients with a preoperative CoSI of 70 or greater (14.1 points, p = 0.029). CONCLUSIONS: It is important to define extent of surgery in CRSwNP to stratify postsurgical patients based on likelihood to benefit from revision surgery or alternative medications. The CoSI can be utilized to identify patients who are likely to improve significantly with revision surgical intervention.

American Rhinologic Society expert practice statement part 2: Postoperative precautions and management principles following endoscopic skull base surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence regarding postoperative precautions for patients following endoscopic skull base surgery for intradural pathology. These topics include the administration of postoperative nasal hygiene; patient mobilization and activity level; the resumption of continuous positive airway pressure in patients with obstructive sleep apnea; and the timing and capacity with which a patient may be subjected to barotrauma, such as air travel postoperatively. This EPS was developed following the recommended methodology and approval process as previously outlined. Given the diverse practices and limited agreement on the accepted principles regarding postoperative precautions for patients following skull base surgery, this EPS seeks to summarize the existing literature and provide clinically relevant guidance to bring clarity to these differing practice patterns. Following a modified Delphi approach, four statements were developed, all of which reached consensus. Because of the paucity of literature on these topics, these statements represent a summation of the limited literature and the experts' opinions. These statements and the accompanying evidence are summarized below, along with an assessment of future needs.

American Rhinologic Society expert practice statement part 1: Skull base reconstruction following endoscopic skull base surgery.

The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs.

Combined Transnasal, Transoral Excision of Odontogenic Cysts Offers Reduced Recurrence Rates and Favorable Sinonasal Outcomes.

Odontogenic cysts impact the adjacent dentition and maxillary sinus. A combined transnasal, transoral approach for removal offers reduced recurrence rates and favorable sinonasal outcomes compared with historic transoral-only approaches.

Choice of Adjuvant Radiotherapy Facility in Sinonasal Squamous Cell Carcinoma.

OBJECTIVE: Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS compared with separate facilities in sinonasal squamous cell carcinoma (SNSCC). METHODS: The 2006 to 2017 National Cancer Database was queried for patients with SNSCC undergoing surgery at an academic facility followed by aRT with or without adjuvant chemotherapy. Multivariable binary logistic and Cox proportional hazards regression models were implemented. RESULTS: Of 419 patients satisfying inclusion criteria, 299 (71.4%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.75, 95% confidence interval [CI] 1.02-2.99, p = 0.042) and surgical facility case volume (aOR 2.51, 95% CI 1.21-5.21, p = 0.014) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.05). Five-year OS was higher among patients undergoing surgery and aRT at the same academic facility (64% vs. 55%, p = 0.039). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.90, 95% CI 1.09-3.32, p = 0.023). CONCLUSION: Undergoing surgery and aRT at the same academic facility is associated with higher OS in SNSCC. Academic physicians should carefully consider the recommendation of aRT treatment facility based on the level of benefit that the patient may derive from coordinated multidisciplinary care. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Time is money: An analysis of cost drivers in ambulatory sinus surgery.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is one of the most commonly performed otolaryngologic procedures and is associated with significant cost variability. METHODS: We performed a retrospective analysis of all inflammatory sinus surgeries at a single tertiary care medical center from July 2021 to July 2023. The electronic medical record was reviewed for patient factors and cost variables for each procedure, and multivariable analysis was performed. RESULTS: A total of 221 patients were included in analysis with a mean age of 48.2 years. There was a 44.8% incidence (n = 99) of nasal polyps and 31.2% (n = 69) of cases were revision surgeries. The average total cost for the surgical encounter was $8960.31 (standard deviation $1967.97). Operating room time represented $4912.46 (54.8% of all costs), while average operating room supply costs were $1296.06 (14.5%) and recovery room costs were $919.48 (10.3%). Total costs were significantly associated with length of surgery ($7.83/min, p = 0.04), in addition to presence of nasal polyps ($531.96, p = 0.04). There was no significant association between total costs and the remaining clinical and demographic factors. CONCLUSIONS: Costs associated with ambulatory FESS for inflammatory sinus disease vary across patients and this cost variability is predominantly driven by time efficiency within the operating room, as well as supply utilization and nasal polyposis to a lesser degree. As a result, operating room efficiency represents a primary target for cost-related interventions. Additionally, our data provide a framework for surgeons and hospitals to make evidence-based decisions on intraoperative equipment in a tradeoff between efficiency and supply costs. Our findings indicate that an approach focused on streamlining efficiency across the entire ambulatory surgery encounter will have the greatest impact on reducing healthcare expenses for both the patient and the health system.

Longer-term surveillance imaging and endoscopy critical for majority of patients in detection of sinonasal malignancy recurrence.

BACKGROUND: Sinonasal malignancy surveillance paradigms are often based on Head and Neck National Comprehensive Cancer Network guidelines, which do not recommend standard surveillance imaging beyond 6 months without concerning symptomatology or physical examination findings. METHODS: This was a retrospective analysis of all patients who underwent resection of sinonasal malignancy at a tertiary care center over a 20-year period from 2000 to 2020, with an ensuing surveillance period demonstrating recurrence. RESULTS: Fifty-two patients with sinonasal malignancy recurrence were included, with an average time to recurrence of 30.9 months and a follow-up period of over 60 months. Recurrence was diagnosed by routine imaging or endoscopy in asymptomatic patients in a majority (60%) of cases, while the remaining minority of diagnoses followed new symptomatology. Asymptomatic recurrence was associated with perineural spread of tumor at initial resection (p = 0.025), but not with age (p = 0.85) or stage at diagnosis (p = 0.68). Expectedly, positron emission tomography/computed tomography (CT) more often detected regional or distant recurrence, while structural imaging (CT/magnetic resonance imaging) demonstrated more frequent detection of recurrence in those with perineural spread of tumor (p = 0.01). CONCLUSIONS: Our findings support high rates of asymptomatic recurrence in sinonasal malignancy, with the majority of recurrences diagnosed by routine endoscopy or imaging. Tailored and extended surveillance guidelines are necessary relative to those utilized for other head and neck mucosal cancers, and are especially appropriate when features such as perineural spread are present.

Matrix metalloproteinase-11 regulates inverted papilloma epithelial cell migration and invasion.

BACKGROUND: Inverted papilloma (IP) is a benign tumor characterized by epithelial proliferation, which has the potential for malignant transformation. However, the mechanisms driving this transformation are poorly defined. Matrix metalloproteinase-11 (MMP-11), a regulator of the tumor microenvironment that degrades extracellular matrix, is upregulated in IP with dysplasia. Here, we aim to investigate the role of MMP-11 in IP epithelial migration and invasion. METHODS: Human IP and contralateral normal sinus mucosa (control) samples were obtained. IP-derived epithelial cultures and normal mucosa-derived epithelial cultures were grown in air‒liquid interface, followed by immunostaining to assess MMP-11 expression in IP. Migration and invasion assays were used to evaluate the role of an anti-MMP-11 antibody on IP and control epithelial cultures. RESULTS: IP-derived cultures demonstrated strong MMP-11 expression compared to controls. Treatment with anti-MMP-11 blocking antibody significantly reduced epithelial migration only in IP-derived cells compared to non-treated IP cells, as seen by incomplete wound closure and reduced transepithelial resistance. In addition, inhibition of MMP-11 reduced IP epithelia's ability to invade through collagen-coated transwells, suggesting that MMP-11 plays a role in invasion. CONCLUSION: We established an in vitro model to study IP-derived epithelial cells. MMP-11 is uniquely expressed in IP epithelial cultures compared to control epithelial cultures. Inhibition of MMP-11 limits IP epithelial migration and invasion to levels similar to that of normal sinus mucosa. MMP-11 does not appear to have a functional role in normal sinus epithelium, suggesting that MMP-11 has a role in malignant transformation of IP.

Endoscopic Repair of Anterior Skull Base Cerebrospinal Fluid Leaks is Successful in Frail Patients.

OBJECTIVE: Surgical frailty estimates a patient's ability to withstand the physiologic stress of an intervention. There is limited data regarding the impact of frailty on endoscopic cerebrospinal fluid (CSF) leak repair. METHODS: Patients undergoing CSF leak repair at two tertiary academic skull base programs were retrospectively reviewed. Demographic, treatment, and postoperative outcomes data were recorded. Frailty was calculated using validated indices, including the American Society of Anesthesiologists (ASA) classification, Charlson Comorbidity Index (CCI), and the Modified 5-Item Frailty Index (mFI-5). Outcomes included 30-day medical and surgical complications and readmission. RESULTS: A total of 185 patients were included with 128 (69.2%) female patients and average age of 54 ± 14 years. The average body mass index was 34.6 ± 8.5. The most common identified etiology was idiopathic intracranial hypertension (IIH) in 64 patients (34.6%). A total of 125 patients (68%) underwent perioperative lumbar drain placement (primarily to measure intracranial pressures and diagnose IIH). Most patients were ASA class 3 (48.6%) with mean CCI 2.14 ± 2.23 and mFI-5 0.97 ± 0.90. Three patients had postoperative CSF leaks, with an overall repair success rate of 98.4%. There was no association between increased frailty and 30-day medical outcomes, surgical outcomes, or readmission (all p > 0.05). CONCLUSIONS: Endoscopic CSF leak repair in a frail population, including lumbar drain placement and bed rest, was not associated with an increased rate of complications. Previous data suggests increased complications in open craniotomy procedures in patients with significant comorbidities. This study suggests that the endoscopic approach to CSF leak repair is well tolerated in the frail population. LEVEL OF EVIDENCE: IV Laryngoscope, 134:2713-2717, 2024.