Effects of a transsphenoidal surgery quality improvement program on patient outcomes and hospital financial performance.

OBJECTIVE: A comprehensive quality improvement (QI) program aimed at all aspects of patient care after pituitary surgery was initiated at a single center. This initiative was guided by standard quality principles to improve patient outcomes and optimize healthcare value. The programmatic goal was to discharge most elective patients within 1 day after surgery, improve patient safety, and limit unplanned readmissions. The program is described, and its effect on patient outcomes and hospital financial performance over a 5-year period are investigated. METHODS: Details of the patient care pathway are presented. Foundational elements of the QI program include evidence-based care pathways (e.g., for hyponatremia and pain), an in-house research program designed to fortify care pathways, patient education, expectation setting, multidisciplinary team care, standard order sets, high-touch postdischarge care, outcomes auditing, and a patient navigator, among other elements. Length of stay (LOS), outcome variability, 30-day unplanned readmissions, and hospital financial performance were identified as surrogate endpoints for healthcare value for the surgical epoch. To assess the effect of these protocols, all patients undergoing elective transsphenoidal surgery for pituitary tumors and Rathke's cleft cysts between January 2015 and December 2019 were reviewed. RESULTS: A total of 609 adult patients who underwent elective surgery by experienced pituitary surgeons were identified. Patient demographics, comorbidities, and payer mix did not change significantly over the study period (p ≥ 0.10). The mean LOS was significantly shorter in 2019 versus 2015 (1.6 ± 1.0 vs 2.9 ± 2.2 midnights, p < 0.001). The percentage of patients discharged after 1 midnight was significantly higher in 2019 versus 2015 (75.4% vs 15.6%, p < 0.001). The 30-day unplanned hospital readmission rate decreased to 2.8% in 2019 from 8.3% in 2015. Per-patient hospital profit increased 71.3% ($10,613 ± $19,321 in 2015; $18,180 ± $21,930 in 2019), and the contribution margin increased 42.3% ($18,925 ± $19,236 in 2015; $26,939 ± $22,057 in 2019), while costs increased by only 3.4% ($18,829 ± $6611 in 2015; $19,469 ± $4291 in 2019). CONCLUSIONS: After implementation of a comprehensive pituitary surgery QI program, patient outcomes significantly improved, outcome variability decreased, and hospital financial performance was enhanced. Future studies designed to evaluate disease remission, patient satisfaction, and how the surgeon learning curve may synergize with other quality efforts may provide additional context.

Heterogeneity in Outcome Reporting in Endoscopic Endonasal Skull Base Reconstruction: A Systematic Review.

Objective Presently, there are no standards for reporting outcomes of endoscopic endonasal skull base reconstruction (ESBR). This is problematic as a lack of consistent reporting makes synthesizing findings in systematic reviews and meta-analysis challenging. Thus, the aim of this study was to systematically review and describe the patterns of reporting outcomes in ESBR as a foundation for developing reporting guidelines. Study Design Present study is a systematic review. Methods Embase, PubMed, CINAHL, Cochrane Library, and Web of Science were searched for all publications with ≥25 patients and a focus on ESBR. The reporting patterns of each study's variables and outcomes were assessed. Results A total of 112 studies were included in the review. The most commonly reported demographic variables were the number of included patients ( n = 112, 100%) and types of pathologies treated ( n = 104, 92.9%). Meanwhile, the most routinely described preoperative variable was history of prior treatment ( n = 48, 42.9%). Type of reconstruction was a commonly reported intraoperative variable ( n = 110, 98.2%), though the rate of intraoperative cerebrospinal fluid (CSF) leak was noted in only 76 studies (67.9%). With regard to postoperative outcomes, postoperative CSF leak rate was routinely provided ( n = 101, 90.2%), but reporting of other surgical complications was more inconsistent. Ultimately, of the 43 variables and outcomes reviewed, a median of 12 (range: 4-22) was reported in each study. Conclusion There is significant heterogeneity in the outcomes reported in studies relating to ESBR. This highlights the need for the development of standard reporting guidelines to minimize bias and improve interstudy comparability.

Postoperative Oral Antibiotics and Sinonasal Outcomes Following Endoscopic Transsphenoidal Surgery for Pituitary Tumors Study: A Multicenter, Prospective, Randomized, Double-Blinded, Placebo-Controlled Study.

BACKGROUND: Postoperative prophylactic antibiotics are commonly used in pituitary surgery, but evidence supporting their use is lacking, which has implications for antibiotic stewardship. OBJECTIVE: To evaluate whether receipt of postoperative oral antibiotics results in superior sinonasal quality of life (QOL) compared with placebo among patients who undergo endoscopic endonasal transsphenoidal pituitary surgery. METHODS: Patients were randomized to receive either oral placebo or cefdinir (trimethoprim-sulfamethoxazole in patients intolerant to cefdinir) for 7 d after surgery. They were monitored for 12 wk. The primary outcome measure was sinonasal QOL at 2 wk on the Anterior Skull Base Nasal Inventory-12. Supplementary end points included sinonasal QOL reported on the Sinonasal Outcome Test-22 and objective endoscopy scores to assess nasal healing according to the Lund-Kennedy method. RESULTS: A total of 461 patients were screened, 131 were randomized, and 113 (placebo arm: 55; antibiotic arm: 58) were analyzed. There was no clinically meaningful or statistically significant difference in sinonasal QOL at any measured time point (P ≥ .24) using either instrument. Nasal cavity endoscopy scores were not significantly different at 1 to 2 wk after surgery (P = .25) or at 3 to 4 wk after surgery (P = .08). CONCLUSION: Postoperative prophylactic oral antibiotics did not result in superior sinonasal QOL compared with placebo among patients who underwent standard endoscopic transsphenoidal surgery.

Assessment of the Validity of the Sinonasal Outcomes Test-22 in Pituitary Surgery: A Multicenter Prospective Trial.

OBJECTIVES/HYPOTHESIS: Sinonasal Outcomes Test-22 (SNOT-22) is used widely as a patient-reported sinonasal quality-of-life (QOL) instrument for endoscopic endonasal pituitary surgery. However, it has never been validated in this population. This study explores the psychometric validity of SNOT-22 to determine if it is a valid scale in patients undergoing endoscopic pituitary surgery. STUDY DESIGN: Multicenter prospective trial. METHODS: Adult patients (n = 113) with pituitary tumors undergoing endoscopic surgery were enrolled in a multicenter study. Patient-reported QOL was assessed using SNOT-22 and the Anterior Skull Base Nasal Inventory-12. Face validity, internal consistency, responsiveness to clinical change, test-retest reliability, and concurrent validity were determined using standard statistical methods. RESULTS: Internal consistency using Cronbach's alpha at baseline and 2 weeks postoperatively were 0.911 and 0.922, indicating SNOT-22 performed well as a single construct. Mean QOL scores were significantly worse at 2 weeks than baseline (16.4 ± 15.1 vs. 23.1 ± 16.4, P < .001), indicating the scale is responsive to clinical change. However, only 11/22 items demonstrated significant changes in mean scores at 2 weeks. Correlation between scores at 2 and 3 weeks was high, suggesting good test-retest reliability, r(107) = 0.75, P < .001. Factor analysis suggests the five-factor solution proposed for the SNOT-22 in rhinosinusitis patients is not valid in pituitary surgery patients. CONCLUSIONS: The SNOT-22 is a valid QOL instrument in patients undergoing endoscopic pituitary surgery. However, because it includes 22 items, can be applied only as a single construct, 50% of the items do not demonstrate changes after surgery, and is not as sensitive to change as other scales, shorter instruments developed specifically for this patient population may be preferable. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E2757-E2763, 2021.

Radiologic Analysis of Balloon Sinuplasty in a Human Cadaver Model: Observed Effects on Sinonasal Anatomy.

BACKGROUND: Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature. OBJECTIVE: The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model. METHODS: Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically. RESULTS: Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time. CONCLUSIONS: While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.

A Comparison of Sphenoid Sinus Osteoneogenesis in Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by excessive leukotriene production, diffuse polyp burden and osteitic bone changes. These bony changes have not been previously characterized. OBJECTIVE: The aim of this radiographic study is to characterize the bony changes noted on computed tomography (CT) scans of the sphenoid sinus in patients with AERD compared to other diseased sinonasal inflammatory states and non-diseased controls. METHODS: A retrospective review of 43 patients with clinically confirmed AERD were included and compared to 22 non-diseased, 9 allergic fungal sinusitis, and 43 chronic rhinosinusitis controls (23 without polyps and 18 with polyps). Comparative measurements were performed using fine-cut CT scans. Sites of comparison were the intersinus septum, the left and right lateral sphenoid wall, the roof, and left and right floor of the sphenoid sinus. Standardized measurements were averaged by two separate rhinologists. RESULTS: Patients with AERD had an average statistically significant increase in bone thickness compared to healthy and diseased controls in nearly every site with the most pronounced changes in the intersinus septum (p < 0.05). CONCLUSION: Patients with AERD have significantly increased thickness of the sphenoid bone compared to control groups with the most pronounced difference in the intersinus septum. These findings may help clinicians increase suspicion for a diagnosis of AERD who clinically have diffuse nasal polyposis.

Transorbital approach for endoscopic repair of encephalocele.

This video demonstrates the transorbital approach for endoscopic repair of an anterior skull base encephalocele. The patient is a 77-year-old man with morbid obesity and a 2-year history of left-sided cerebrospinal fluid (CSF) rhinorrhea and radiographic evidence of an anterior skull base defect with an encephalocele. An endoscopic transorbital approach was chosen for repair because of its minimally invasive access to the anterolateral skull base. The patient had an excellent clinical outcome with resolution of the CSF rhinorrhea and preservation of full vision and extraocular muscle function. The video can be found here: https://youtu.be/oDhZgnaiZ00.

Nasopharyngeal Hyalinizing Clear Cell Carcinoma: A Case Report and Review of the Literature.

BACKGROUND: Hyalinizing clear cell carcinomas (HCCCs) are rare, low-grade, malignant tumors which most often arise from the minor salivary glands primarily in palate and tongue but can arise in any location with minor salivary glands including the nasopharynx. METHODS: A case report of primary nasopharyngeal HCCC is presented. Because of the rarity of this tumor and location, a literature search was conducted to determine the most common presenting symptoms, treatment strategies, and outcomes. RESULTS: A 48-year-old man underwent biopsy of a 4.5 cm mass of the right nasopharynx with pathology suggesting an intermediate grade mucoepidermoid carcinoma. After discussing management with the patient, an endoscopic resection was performed. Final pathology revealed an HCCC which was confirmed after negative Mastermind-like 2 (MAML2) and positive Ewing sarcoma breakpoint region 1 (ESWR1) gene rearrangements on fluorescence in situ hybridization (FISH) studies. Literature review of other nasopharyngeal HCCC cases shows diverse presentation and overall excellent prognosis through surgical and radiation therapy. CONCLUSION: HCCCs are rare, low-grade malignant tumors of the minor salivary glands and can present as a nasopharyngeal mass. Presenting symptoms are diverse but frequently involve otologic and sinonasal disturbances. HCCC is an indolent tumor with an excellent prognostic outcome when treated appropriately with surgical resection and adjuvant radiotherapy.

Establishing Urinary Leukotriene E4 as a Diagnostic Biomarker for Chronic Rhinosinusitis with Comorbid Asthma and Atopy.

OBJECTIVE: While urinary leukotriene E4 (uLTE4) is a validated biomarker for the cysteinyl leukotriene pathway, which is central to the pathophysiology of asthma, atopy, and chronic rhinosinusitis (CRS), the contributions of comorbid asthma and atopy to uLTE4 levels in various CRS subtypes have not been previously characterized. We sought to (1) identify reference values for uLTE4 in subjects with and without CRS and (2) determine how the presence of comorbid atopy and asthma affects uLTE4 levels in CRS. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: A prospective case-control study was conducted to compare uLTE4 levels between patients with CRS and healthy controls. Urinary LTE4 levels were measured by enzyme immunoassay and were adjusted for urinary creatinine concentrations (pg/mg Cr). Patients with CRS were stratified by the clinical comorbidities to determine normative uLTE4 values for patients with CRS with and without comorbid asthma or atopy. RESULTS: A total of 153 patients (mean age, 47.3; 47.1% female) were included in the study. Patients with CRS demonstrated significantly higher concentrations of uLTE4 than healthy controls (1652 vs 1065 pg/mg Cr, P = .032). Within the group of patients with CRS, comorbid asthma also individually correlated with elevated uLTE4 levels (1597 pg/mg Cr, P = .0098). Patients with CRS who did not have comorbid allergy and asthma, in contrast, did not have statistically higher uLTE4 levels than healthy controls (1142 pg/mg Cr, P = .61). CONCLUSION: Urinary LTE4 serves as a noninvasive measure of the inflammatory state in CRS. Comorbid asthma and atopy contribute to elevated uLTE4 levels in CRS.

Clinical and functional outcomes after total laryngectomy and laryngopharyngectomy: Analysis by tumor subsite, salvage status, and extent of resection.

BACKGROUND: Outcomes following surgical intervention for laryngeal and hypopharyngeal tumors are dependent on several factors. In the present study, we sought to determine whether tumor subsite, salvage status, and extent of resection influenced postoperative outcomes. METHODS: Retrospective review of 107 patients at a single institution who underwent total laryngectomy or partial/total laryngopharyngectomy. RESULTS: Hypopharyngeal subsite and total laryngopharyngectomy subgroups had inferior speech and swallow outcomes compared to their respective cohorts (P < .05). Salvage patients had inferior 3-year overall survival (P < .05) and swallow outcomes (P < .001). Previously radiated patients had increased fistula rates (29.9% vs 10%, P = .02), and the use of tissue coverage in salvage total laryngectomy had a protective effect on fistula formation (10% vs 37%, P = .04). CONCLUSIONS: By stratifying patients across multiple subgroups, we provide a detailed narrative in surgical outcomes that can be incorporated into treatment planning. Further prospective studies are needed to compare surgical outcomes to those of organ preservation therapy.

Changes in Transcranial Ultrasound Velocities in Children with Sickle Cell Disease Undergoing Adenotonsillectomy.

Objectives (1) To assess for changes in cerebral blood flow velocity in children with sickle cell disease and obstructive sleep apnea (OSA) following adenotonsillectomy. (2) To determine if clinical factors such as OSA severity affect cerebral blood flow velocity values. Study Design Case series with chart review over 10 years. Settings Two tertiary children's hospitals. Subjects and Methods Children aged 2 to 18 years with a history of sickle cell disease and OSA, as defined by an apnea hypopnea index (AHI) >1 on polysomnography, were eligible for inclusion. Transcranial Doppler ultrasonography was used to assess cerebral blood flow velocity before and after adenotonsillectomy. Results Fifteen patients met inclusion criteria; 73% (n = 11) were female. The mean preoperative AHI was 8.9 (range, 1.2-22.2). Six (40%) patients had severe OSA (AHI >10). Following adenotonsillectomy, there was a significant reduction in mean (95% CI) cerebral blood flow velocities of the left terminal internal cerebral artery, 91.2 (79.4-103.1) to 75.7 (61.7-89.8; P = .018), and the right middle cerebral artery, 134.3 (119.2-149.3) to 116.5 (106.5-126.5; P = .003). There was not a significant correlation between baseline AHI and change in cerebral blood flow velocities. Conclusion Adenotonsillectomy may result in a reduction in some cerebral blood flow velocities. Further research is needed to determine if changes in cerebral velocities as assessed by transcranial Doppler ultrasonography translate into a reduced risk of stroke for children with sickle cell disease and OSA.

Evaluation of the PROPEL® mini sinus implant for the treatment of frontal sinus disease.

INTRODUCTION: Propel and Propel Mini sinus implants are mometasone furoate-coated bioabsorbable stents used as an adjunct in the management of chronic rhinosinusitis after endoscopic sinus surgery. The original sinus implant was deployed in the ethmoid sinuses to provide medialization of the middle turbinate, decrease scarring and mucosal adhesions, limit polyp regrowth, and reduce mucosal inflammation. A structurally smaller version of the Propel, the Propel Mini, was developed and now has been approved for endoscopic placement in the frontal sinuses. Areas covered: This evaluation will focus on the technical details of the Propel mini, previous studies documenting Propel's success in the ethmoid sinuses, and the safety and efficacy of the Propel mini implants in frontal sinus surgery. Expert opinion: Devices such as the Propel and Propel Mini stents are the beginning of a trend towards medication-coated bioabsorbable implants that can be used for sinonasal disease to minimize complications or possible side effects of surgical treatment by an increase of topical drug delivery locally.

Implantable Devices/Drugs in the Management of Nasal Polyps.

The use of biomaterials, which include nasal packing and sinus stents, has an evolving role in the postoperative management of patients with chronic rhinosinusitis with polyps. Some of these biomaterials include drug-eluting properties. The usage of biomaterials postoperatively is both surgeon and patient specific. The published literature supports the use of these products and demonstrates the ability to limit swelling, lateralization and reduce polyp regrowth postoperatively. However, there are heterogeneity in both available materials and results that the otolaryngologist must factor in to the decision-making algorithm.

Bone-anchored hearing aid implantation in a patient with Goldenhar syndrome.

Patients with Goldenhar syndrome exhibit a number of characteristic symptoms, including middle and internal ear malformations that may cause profound hearing loss. Bone-anchored hearing aids have been used to treat these patients in the past, although complications may arise due to the nature of the disease. Herein we present the case of a pediatric patient with Goldenhar syndrome whose hearing aid abutment extruded spontaneously because of poor bone quality, despite adequate thickness. We provide a brief review of the literature and suggest a flexible surgical plan for any syndromic pediatric patient.

Preclinical validation of AR42, a novel histone deacetylase inhibitor, as treatment for vestibular schwannomas.

OBJECTIVES/HYPOTHESIS: Recent studies indicate that vestibular schwannomas (VSs) rely on phosphatidylinositol 3-kinase/AKT activation to promote cell proliferation and survival; therefore, targeting AKT may provide new therapeutic options. We have previously shown that AR42, a novel histone deacetylase inhibitor, potently suppresses VS growth in vitro at doses correlating with AKT inactivation. The objectives of the current study were translational: 1) to examine the end biologic effects of AR42 on tumor growth in vivo, 2) to validate AKT as its in vivo molecular target, 3) to determine whether AR42 penetrates the blood-brain barrier (BBB), and 4) to study the pharmacotoxicity profile of AR42. STUDY DESIGN: In vivo mouse studies. METHODS: AR42 was dosed orally in murine schwannoma allografts and human VS xenografts. Magnetic resonance imaging was used to quantify changes in tumor volume, and intracellular molecular targets were analyzed using immunohistochemistry. BBB penetration was assayed, and both blood-chemistry measurements and histology studies were used to evaluate toxicity. RESULTS: Growth of schwannoma implants was dramatically decreased by AR42 at doses correlating with AKT dephosphorylation, cell cycle arrest, and apoptosis. AR42 penetrated the BBB, and wild-type mice fed AR42 for 6 months behaved normally and gained weight appropriately. Blood-chemistry studies and organ histology performed after 3 and 6 months of AR42 treatment demonstrated no clinically significant abnormalities. CONCLUSIONS: AR42 suppresses schwannoma growth at doses correlating with AKT pathway inhibition. This orally bioavailable drug penetrates the BBB, is well tolerated, and represents a novel candidate for translation to human VS clinical trials.

AR42, a novel histone deacetylase inhibitor, as a potential therapy for vestibular schwannomas and meningiomas.

Neurofibromatosis type 2 (NF2) is an autosomal-dominant disease that results in the formation of bilateral vestibular schwannomas (VSs) and multiple meningiomas. Treatment options for NF2-associated tumors are limited, and to date, no medical therapies are FDA approved. The ideal chemotherapeutic agent would inhibit both VS and meningiomas simultaneously. The objectives of this study are (1) to test the efficacy of AR42, a novel histone deacetylase inhibitor, to inhibit VS and meningioma growth and (2) to investigate this drug's mechanisms of action. Primary cultures of human VS and meningioma cells were established. Nf2-deficient mouse schwannoma and benign human meningioma Ben-Men-1 cells were also cultured. Cells were treated with AR42, and the drug's effects on proliferation and the cell cycle were analyzed using a methanethiosulfonate assay and flow cytometry, respectively. Human phospho-kinase arrays and Western blots were used to evaluate the effects of AR42 on intracellular signaling. The in vivo efficacy of AR42 was investigated using schwannoma xenografts. Tumor volumes were quantified using high-field, volumetric MRI, and molecular target analysis was performed using immunohistochemistry. AR42 inhibited the growth of primary human VS and Nf2-deficient mouse schwannoma cells with a half maximal inhibitory concentration (IC(50)) of 500 nM and 250-350 nM, respectively. AR42 also inhibited primary meningioma cells and the benign meningioma cell line, Ben-Men-1, with IC(50) values of 1.5 µM and 1.0 µM, respectively. AR42 treatment induced cell-cycle arrest at G(2) and apoptosis in both VS and meningioma cells. Also, AR42 exposure decreased phosphorylated Akt in schwannoma and meningioma cells. In vivo treatment with AR42 inhibited the growth of schwannoma xenografts, induced apoptosis, and decreased Akt activation. The potent growth inhibitory activity of AR42 in schwannoma and meningioma cells suggests that AR42 should be further evaluated as a potential treatment for NF2-associated tumors.