MRI Safety of Stapes Prostheses: A Systematic Review.

OBJECTIVE: To assess magnetic resonance imaging (MRI) safety of stapes prostheses. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched from inception to November 2021 following PRISMA guidelines. REVIEW METHODS: Studies reporting evidence of stapes prosthesis displacement or interaction in adult or pediatric implant recipients undergoing MRI. Cadaveric, animal, and basic studies with nonhuman data were also included. RESULTS: From an initial search of 123 articles, 42 full-text studies were evaluated for eligibility and 19 studies that met the inclusion criteria were included. Motion artifact was reported in a few stainless steel prosthesis types in vitro; however, such displacement was not observed in human cadaver temporal bone studies and had no adverse reported outcomes. A small subgroup of patients in the 1980s received a ferromagnetic stainless steel stapes implant that was recalled and has not been used since 1987. Patients with implants performed in the 1980s should be directed to 1.5T scanners from an abundance of caution. CONCLUSION: Modern (post-1987) stapes prostheses do not pose a risk in vivo when exposed to the magnetic fields of MRI scanners.

Combining Intraoperative Electrocochleography with Robotics-Assisted Electrode Array Insertion.

OBJECTIVE: To describe the use of robotics-assisted electrode array (EA) insertion combined with intraoperative electrocochleography (ECochG) in hearing preservation cochlear implant surgery. STUDY DESIGN: Prospective, single-arm, open-label study. SETTING: All procedures and data collection were performed at a single tertiary referral center. PATIENTS: Twenty-one postlingually deaf adult subjects meeting Food and Drug Administration indication criteria for cochlear implantation with residual acoustic hearing defined as thresholds no worse than 65 dB at 125, 250, and 500 Hz. INTERVENTION: All patients underwent standard-of-care unilateral cochlear implant surgery using a single-use robotics-assisted EA insertion device and concurrent intraoperative ECochG. MAIN OUTCOME MEASURES: Postoperative pure-tone average over 125, 250, and 500 Hz measured at initial activation and subsequent intervals up to 1 year afterward. RESULTS: Twenty-two EAs were implanted with a single-use robotics-assisted insertion device and simultaneous intraoperative ECochG. Fine control over robotic insertion kinetics could be applied in response to changes in ECochG signal. Patients had stable pure-tone averages after activation with normal impedance and neural telemetry responses. CONCLUSIONS: Combining robotics-assisted EA insertion with intraoperative ECochG is a feasible technique when performing hearing preservation implant surgery. This combined approach may provide the surgeon a means to overcome the limitations of manual insertion and respond to cochlear feedback in real-time.

Natural History of Serviceable Hearing During Active Surveillance of Nongrowing Sporadic Vestibular Schwannoma Supports Consideration of Initial Wait-and-Scan Management.

OBJECTIVE: The treatment paradigm of vestibular schwannoma (VS) focuses on preservation of neurologic function, with small tumors increasingly managed with active surveillance. Often, tumor size and hearing outcomes are poorly correlated. The aim of the current work was to describe the natural history of hearing among patients with nongrowing VS during observational management. STUDY DESIGN: Historical cohort study. PATIENTS: Adults with sporadic VS. INTERVENTION: Wait-and-scan management. MAIN OUTCOME MEASURE: Maintenance of serviceable hearing (SH) after diagnosis. RESULTS: Among 228 patients with nongrowing VS, 157 patients had SH at diagnosis. Rates of maintaining SH (95% CI; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (89-98; 118), 81% (74-89; 65), and 78% (71-87; 42), respectively. Poorer hearing at diagnosis (hazard ratio [HR] per 10 dB hearing level increase in pure-tone average of 2.51, p < 0.001; HR per 10% decrease in word recognition score of 1.70, p = 0.001) was associated with increased likelihood of developing non-SH during observation. When controlling for baseline hearing status, tumors measuring 5 mm or greater in the internal auditory canal or with cerebellopontine angle extension were associated with significantly increased risk of developing non-SH (HR, 4.87; p = 0.03). At 5 years after diagnosis, 95% of patients with nongrowing intracanalicular VS measuring less than 5 mm maintained SH. CONCLUSIONS: Hearing worsens during periods of nongrowth in sporadic VS. Patients with small (<5 mm) intracanalicular tumors demonstrate robust maintenance of SH over time, reinforcing the consideration of initial observation in this patient subset.

Multi-Disciplinary Approach to Skull Base Paragangliomas.

The treatment of skull base paragangliomas has moved towards the use of cranial nerve preservation strategies, using radiation therapy and subtotal resection in instances when aiming for gross total resection would be expected to cause increased morbidity compared to the natural history of the tumor itself. The goal of this study was to analyze the role of surgery in patients with skull base paragangliomas treated with CyberKnife stereotactic radiosurgery (SRS) for definitive tumor control. A retrospective review identified 22 patients (median age 65.5 years, 50% female) treated with SRS from 2010-2022. Fourteen patients (63.6%) underwent microsurgical resection. Gross total resection was performed in four patients for tympanic paraganglioma (n = 2), contralateral paraganglioma (n = 1), and intracranial tumor with multiple cranial neuropathies (n = 1). Partial/subtotal resection was performed for the treatment of pulsatile tinnitus and conductive hearing loss (n = 6), chronic otitis and otorrhea (n = 2), intracranial extension (n = 1), or episodic vertigo due to perilymphatic fistula (n = 1). Eighteen patients had clinical and imaging follow-up for a mean (SD) of 4.5 (3.4) years after SRS, with all patients having clinical and radiological tumor control and no mortalities. Surgery remains an important component in the multidisciplinary treatment of skull base paraganglioma when considering other outcomes besides local tumor control.

Middle Cranial Fossa Approach for Sporadic Vestibular Schwannoma: Patient Selection, Technical Pearls, and Hearing Results.

The middle fossa approach is an excellent technique for removing appropriate vestibular schwannomas in patients with serviceable hearing. Knowledge of the intricate middle fossa anatomy is essential for optimal outcomes. Gross total removal can be achieved with preservation of hearing and facial nerve function, both in the immediate and long-term periods. This article provides an overview of the background and indications for the procedure, a description of the operative protocol, and a summary of the literature on postoperative hearing outcomes.

Approach to Cochlear Implantation in Patients With Ventriculoperitoneal Shunts.

OBJECTIVE: To evaluate the safety and outcomes of cochlear implantation (CI) in patients with ventriculoperitoneal (VP) shunts to inform clinical practice. STUDY DESIGN: Historical cohort study. SETTING: Tertiary referral centers. METHODS: A multi-institutional historical cohort of patients with VP shunts and CI was identified and analyzed. RESULTS: A total of 46 patients (median age 8 years [interquratile range, IQR: 2-46]) with VP shunts and CI were identified. Of these, 41 (89%) patients had a VP shunt prior to CI. Based on institutional preference and individual patient factors, CI was performed contralateral to a pre-existing VP shunt in 24 of these 41 cases (59%) and ipsilateral in 17 (41%). Furthermore, pre-CI relocation of the VP shunt was performed in 3 cases (7%), and 2 patients (5%) underwent planned revision of their VP shunt concurrent with CI. In total, 2 of 27 pediatric patients (7%) required unanticipated revision shunt surgery, both contralateral to CI device placement, given VP shunt malfunction. One of 19 adult patients (5%) required shunt revision during CI due to shunt damage noted intraoperatively. Among 43 patients with available follow-up, 38 (88%) are regular CI users, with a median consonant-nucleus vowel-consonant word: score of 58% (IQR: 28-72). CONCLUSION: CI can be performed at low risk, either contralateral or ipsilateral, to a VP shunt, and does not mandate shunt revision in most cases. Additional considerations regarding CI receiver-stimulator placement are necessary with programmable shunts to mitigate device interaction. Preoperative planning, including coordination of care with neurosurgery, is important to achieving optimal outcomes.

Anterior and Lateral Skull Base Spontaneous CSF Leaks: Evaluation of Comorbidities and Treatment Outcomes.

OBJECTIVES: To evaluate clinical characteristics and outcomes of patients diagnosed with anterior (ASB) or lateral skull base (LSB) spontaneous cerebrospinal fluid (sCSF) leak. METHODS: Single center retrospective review of patients diagnosed with sCSF leaks of ASB or LSB between 1/1/2009 and 11/1/2019 (n = 69). Body mass index (BMI), gender, age at diagnosis, origin of CSF leak (ASB vs LSB), surgical approach, lumbar drain use, recurrence, pre-operative diagnosis of diabetes mellitus (DM), and obstructive sleep apnea (OSA) were collected. RESULTS: 69 patients included in this study met criteria for sCSF leak without a traumatic or iatrogenic cause (Female: 51 (74%); average BMI: 37.0 ± 7.9). Forty-eight (70.0%) presented with sCSF leaks of the lateral skull base. All ASB leaks were treated with an endoscopic transnasal approach. Eleven (22.9%) LSB leak patients were treated using transmastoid approaches and 35 (72.9%) patients with a middle cranial fossa approach. Eleven patients (15.9%) reported sCSF leak recurrence. Two patients (9.5%) with anterior skull base and 9 patients (18.8%) with lateral skull base leaks had recurrence. LSB sCSF leaks had a relative risk of 2.192 of recurrence compared to ASB leaks (95% CI: 0.431-11.157, P = .483). A 5.017 times increased risk (95% CI: 1.285-19.583, P = .020) was reported for patients with OSA, while the risks for DM and BMI were 1.351 (95% CI: 0.67-9.105, P = .177) and 1.026 (95% CI: 0.963-1.094, P = .426) respectively. Patients with sCSF leak recurrence had significantly lower lumbar drain use (33.3%) than those without recurrence (72.7%) (P = .049). CONCLUSION: Spontaneous CSF leak recurrence is complex and multifactorial, and while patients with both DM and OSA had the higher risk of recurrence, OSA is likely an independent clinical risk factor for sCSF leak recurrence in this patient population.

Chronic Invasive Fungal Sinusitis With Negative Histopathology: A Diagnostic Challenge.

Although the diagnosis of chronic invasive fungal sinusitis relies chiefly on identification of invasive fungi on histology, the insidious nature of the disease can preclude detection of fungal organisms. Here, we present a case of chronic invasive fungal sinusitis with negative histopathologic findings and a definitive diagnosis made through fungal DNA detection. Clinicians should consider polymerase chain reaction an important complement to histology and culture in the diagnosis of chronic invasive fungal sinusitis.

The Use of 0° and 70° Endoscopes in Maxillary Antrostomy.

BACKGROUND AND OBJECTIVES: Performing an effective maxillary antrostomy is critical to improving chronic maxillary sinusitis symptomatology. Incomplete dissection of the uncinate process and failure to incorporate the natural drainage pathway may lead to recirculation and need for revision surgery. The purpose of this study is to determine if 70° endoscopes provide added value in determining incomplete dissection or residual disease. METHODS: Prospective study of 35 sinuses from 18 patients undergoing FESS for Chronic Rhinosinusitis (CRS) between 11/1/2020 and 4/30/2021. Two fellowship trained Rhinologists initially performed maxillary antrostomies exclusively using a 0° endoscope, then transitioned to a 70° endoscope. Surgeons completed a survey to assess completion of the antrostomy prior to use of 70° endoscope, sino-nasal anatomy, and difficulty of the operation. Intraoperative photographs before and after using a 70° endoscope were evaluated by a third party. Pre-operative CT scans were used to evaluate the sphenoid keel-caudal septum-nasolacrimal duct (SK-CS-NL) angle. RESULTS: Of 35 sinuses from 18 patients all 35 sinuses had CRS with 48.5% having nasal polyposis and 42.9% having active infection. There was residual inflammatory tissue in the anterior maxillary sinus, including polypoid tissue and uncinate process prior to using the 70° endoscope in 82.9% of sinuses. The natural drainage pathway was not incorporated into the dissection in 28.6% of sinuses before converting to 70° endoscope. Incomplete dissection with 0° endoscope was not associated with nasal polyposis (P = .086) or uncinate position (0.741). Narrow SK-CS-NL angles were associated with incomplete dissection of the anterior maxillary sinus with 0° endoscope (16.0° ± 3.0° vs 20.6° ± 3.2°; P = .013). CONCLUSION: Use of 70° endoscope in maxillary antrostomy may be beneficial in identifying and resecting disease within the anterior maxillary sinus that may otherwise be difficult to find using a 0° endoscope. This is especially true in patients with narrow nasolacrimal duct positioning.

Hearing Preservation in Observed Sporadic Vestibular Schwannoma: A Systematic Review.

OBJECTIVE: To characterize the natural history of hearing loss for patients presenting with serviceable hearing (SH) who undergo a wait-and-scan approach for sporadic vestibular schwannoma (VS) using aggregate time-to-event survival analysis. STUDY DESIGN: Systematic review. SETTING: Published international English literature, January 1, 2000 to May 31, 2020. PATIENTS: Patients with sporadic VS entering a wait-and-scan approach with SH at diagnosis. INTERVENTIONS: Observation with serial MRI and audiometry. RESULTS: In total, 3,652 patients from 26 studies were included for analysis. Mean age at diagnosis was 58.8 years (SD, 4.1). Mean follow-up was 49.2 months (SD, 26.5). In total, 755 patients (21%) failed conservative treatment and underwent radiosurgery or microsurgery at the time of last follow-up. The average loss to follow-up was 6.9% (SD, 11.1). A total of 1,674 patients had SH at the time of diagnosis. Survival rates for maintaining SH were 96% at 1 year, 77% at 3 years, 62% at 5 years, and 42% at 10 years following diagnosis. CONCLUSION: In this systematic review, aggregate data from 3,652 patients across 26 studies show consistent patterns in progression of hearing loss during observation for patients with sporadic VS as a function of time. As an easy-toremember conservative benchmark for those presenting with SH at diagnosis: approximately 75% retain SH at 3 years, 60% at 5 years, and 40% at 10 years.

Intraoperative Use of Electrical Stapedius Reflex Testing for Cochlear Nerve Monitoring During Simultaneous Translabyrinthine Resection of Vestibular Schwannoma and Cochlear Implantation.

OBJECTIVE: To report the novel use of intraoperative electrically evoked stapedial reflex (eSR) for cochlear nerve monitoring during simultaneous translabyrinthine resection of vestibular schwannoma (VS) and cochlear implantation. STUDY DESIGN: Clinical capsule report with video demonstration. SETTING: Tertiary academic referral center. PATIENT: A 58-year-old female presented with a small right intracanalicular VS with associated asymmetrical right moderate to severe sensorineural hearing loss, poor word recognition, tinnitus, and disequilibrium. Based on patient symptomatology and goals, simultaneous CI with translabyrinthine resection of the VS was performed. INTERVENTION: Cochlear implantation before the tumor was resected facilitated intraoperative eSRs by delivering repeated single-electrode stimulations through the cochlear implant (CI) electrode during tumor resection. A pulse duration of 50-us and a current amplitude of 200-CL or 648-us was used to elicit eSRs visible through the facial recess. Intraoperative eSR was monitored in conjunction with electrically evoked compound action potentials via neural response telemetry and electrical auditory brainstem response. RESULTS: Despite the transient evoked compound action potentials amplitude and electrical auditory brainstem response latency changes, the visually observed eSR was preserved and remained robust throughout tumor dissection, indicating an intact cochlear nerve. Four weeks postoperatively, the patient exhibited open-set speech capacity (14% CNC and 36% AzBio in quiet). CONCLUSION: The current study demonstrates the feasibility of using intraoperative eSR via a CI electrode to monitor cochlear nerve integrity during VS resection, which may indicate successful CI outcomes. These preliminary findings require further substantiation in a larger study.

Jugular foramen capillary hemangioma masquerading as a paraganglioma.

Capillary hemangiomas are benign vascular lesions that are common in head and neck, but hemangiomas of jugular foramen and temporal bone are rare with only a few cases reported in the literature. We present a case report of this rare disease entity highlighting the subtle radiographic nuances that can benefit clinicians when encountered with similar unusual clinical scenario. Although radiographic features of capillary hemangioma can be distinctive, they are not specific. In this case, the lack of significant involvement of the jugular bulb and the absence of the typical pattern of osseous erosion of the jugular carotid spine led to the alternative diagnosis of a rare capillary hemangioma of the jugular foramen.

Comparison of Materials Used for 3D-Printing Temporal Bone Models to Simulate Surgical Dissection.

OBJECTIVE: To identify 3D-printed temporal bone (TB) models that most accurately recreate cortical mastoidectomy for use as a training tool by comparison of different materials and fabrication methods. BACKGROUND: There are several different printers and materials available to create 3D-printed TB models for surgical planning and trainee education. Current reports using Acrylonitrile Butadiene Styrene (ABS) plastic generated via fused deposition modeling (FDM) have validated the capacity for 3D-printed models to serve as accurate surgical simulators. Here, a head-to-head comparison of models produced using different materials and fabrication processes was performed to identify superior models for application in skull base surgical training. METHODS: High-resolution CT scans of normal TBs were used to create stereolithography files with image conversion for application in 3D-printing. The 3D-printed models were constructed using five different materials and four printers, including ABS printed on a MakerBot 2x printer, photopolymerizable polymer (Photo) using the Objet 350 Connex3 Printer, polycarbonate (PC) using the FDM-Fortus 400 mc printer, and two types of photocrosslinkable acrylic resin, white and blue (FLW and FLB, respectively), using the Formlabs Form 2 stereolithography printer. Printed TBs were drilled to assess the haptic experience and recreation of TB anatomy with comparison to the current paradigm of ABS. RESULTS: Surgical drilling demonstrated that FLW models created by FDM as well as PC and Photo models generated using photopolymerization more closely recreated cortical mastoidectomy compared to ABS models. ABS generated odor and did not represent the anatomy accurately. Blue resin performed poorly in simulation, likely due to its dark color and translucent appearance. CONCLUSIONS: PC, Photo, and FLW models best replicated surgical drilling and anatomy as compared to ABS and FLB models. These prototypes are reliable simulators for surgical training.

Atypical Schwannoma: A 10-year experience.

OBJECTIVE: The goal of this study was to describe the clinical presentation associated with atypical schwannoma of the cerebellopontine angle, characterize the pathologic findings and describe the long-term outcome. MATERIALS AND METHODS: The study design was retrospective case review of patients with the histopathologic diagnosis of atypical and benign schwannoma of the cerebellopontine angle diagnosed at the study institution over a 10-year period. SETTING: Tertiary referral center. MAIN OUTCOMES MEASURE: Demographic data of the cohort were recorded. Findings on pathology were evaluated. Initial treatment and post-operative course was recorded. Main outcome measures were clinical presentation, including cranial nerve deficits at the time of presentation, complication and recurrence rates. RESULTS: At presentation, a somewhat accelerated course of cranial nerve deficit was noted among patients with atypical schwannoma as compared to benign schwannoma. In the immediate post-operative period, there were no differences noted in the complication rate. Atypical schwannomas appear to have higher recurrence rate compared to benign schwannomas. CONCLUSIONS: Atypical schwannoma is an intermediate disease process with an accelerated clinical course and higher recurrence rate as compared to vestibular schwannoma. Traditional operative approaches may be employed without increased concern for post-operative complications. Thorough counseling and close follow-up should be offered to these patients given the higher recurrence rate. Larger studies are required to determine if these patients need more frequent MRIs for long-term surveillance.

Poorly differentiated plasmacytoid squamous cell carcinoma: Case report of a rare malignancy.

Plasmacytoid squamous cell carcinoma is an especially aggressive variant of squamous cell carcinoma that has previously been described in the literature as a variant of oral cancers and most extensively, in vulvular [3], transitional cell, and urothelial carcinomas [2,13,15-20]. In this case report, we present a 36-year-old man with 6 to 8 weeks of a progressively enlarging mass over the lateral third of his clavicle, acromion process, and deltoid. The mass was resected, and the supraclavicular defect was reconstructed using an anterolateral thigh free flap. Final pathology determined the specimen was an invasive poorly differentiated squamous cell carcinoma with spindle cell and plasmacytoid features of cutaneous origin. Plasmacytoid squamous cell carcinomas have previously been described in the oral cavity, but in no other subsite of the head and neck. This article describes the patient's case and provides a literature review of the available reports related to plasmacytoid variant of squamous cell carcinoma.

Comparative techniques of medial rectus muscle retraction for endoscopic exposure of the medial intraconal space.

OBJECTIVE: The medial rectus muscle (MRM) is the medial boundary to the intraconal space of the orbit, and retraction of the MRM is oftentimes necessary for endoscopic removal of intraconal tumors, e.g., orbital hemangioma. We evaluated each of the reported methods of MRM retraction for endoscopic orbital surgery and quantified the degree of intraconal exposure conferred by each method. METHODS: Eight orbits from four cadaver heads were dissected. In each orbit, medial orbital decompression was performed and the MRM was retracted by using four previously described techniques: (1) external MRM retraction at the globe insertion point by using vessel loop (external group), (2) transseptal MRM retraction by using vessel loop (transseptal group), (3) transchoanal retraction of the MRM by using vessel loop (choanal group), and (4) transseptal four-handed technique by using double ball retraction by a second surgeon (transseptal double ball group). The length, height, and area of exposure of the medial intraconal space were quantified and compared. RESULTS: The average ± standard deviation (SD) anterior-posterior exposures for the external group, transseptal group, and transseptal double ball group were 17.51 ± 3.39 mm, 16.59 ± 4.16 mm, and 18.0 ± 15.25 mm, respectively. The choanal group provided significantly less exposure (12.39 ± 3.44 mm, p = 0.049) than the other groups. The average ± SD vertical exposures for the transseptal group, choanal group, and transseptal double ball group were 12.53 ± 4.38 mm, 13.05 ± 5.86 mm, and 13.57 ± 3.74 mm, respectively. The external group provided significantly less exposure (4.51 ± 1.56 mm, p = 0.0072) than the other groups. The transseptal and transseptal double ball groups provided the greatest total access by surface area (58.88 ± 26.96 mm(2) and 62.94 ± 34.74 mm(2), respectively) compared with the external and choanal groups (34.82 ± 23.37 mm(2) and 43.10 ± 23.68 mm(2), respectively). Although the transseptal trajectory of MRM retraction was optimal, the difference in total area of exposure between the static vessel loop retraction and the dynamic, four-handed technique with double ball instrument retraction was not significant. Of note, the exposure provided by the choanal technique required the surgeon to work both above and below the muscle. CONCLUSION: Retraction of the MRM toward the choanae provided the least length of exposure, and external retraction exposed the least height and total area. Transseptal MRM retraction was most favorable and provided the largest endoscopic corridor to the medial intraconal space. A four-handed approach for endoscopic intraconal surgery of the orbit may offer advantages in dynamic adjustments in retraction.

P-glycoprotein regulates Staphylococcus aureus enterotoxin B-stimulated interleukin-5 and thymic stromal lymphopoietin secretion in organotypic mucosal explants.

BACKGROUND: T-helper 2 (Th2) inflammation is a hallmark of chronic rhinosinusitis with nasal polyps (CRSwNP) although the pathogenesis is poorly understood. P-glycoprotein (permeability glycoprotein, P-gp) is an efflux pump that is capable of regulating cytokine transport and is expressed within sinonasal mucosa. The purpose of this study was to examine if the oversecretion of interleukin 5 (IL-5) and thymic stromal lymphopoietin (TSLP) in CRSwNP could be explained through P-gp-mediated secretory pathways. METHODS: Fifteen ethmoid mucosal explants were harvested from patients with CRS (n = 10) and CRSwNP (n = 10) and stimulated with Staphylococcus aureus enterotoxin B (SEB). P-gp was inhibited using zosuquidar trihydrochloride (herein Zosuquidar). P-gp expression was measured using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-5, IL-8, and TSLP secretion were quantified using ELISA. RESULTS: P-gp protein was overexpressed in CRSwNP (28.32 ± 25.94 ng/mL per mg explant) as compared to CRS (10.74 ± 8.61; p = 0.01, 2-tailed Mann-Whitney U test). There was no difference in messenger RNA (mRNA) expression. SEB induced a significant increase in IL-5 and TSLP but not IL-8 secretion relative to control in the CRSwNP explants only. Subsequent P-gp inhibition significantly reduced IL-5 and TSLP secretion (p = 0.04 for both, 2-tailed Student t test) to control levels. The concentration of IL-5 and TSLP secretion were strongly and significantly correlated to the concentration of P-gp within the same explant (IL-5: r = 0.791, p = 0.001; TSLP: r = 0.687, p = 0.003; 2-tailed Spearman's rank-order correlation). CONCLUSION: P-gp protein is expressed at higher concentrations in CRSwNP as compared to CRS. This overexpression directly contributes to the relative hypersecretion of IL-5 and TSLP. These findings suggest a novel mechanism for Th2 skewing in CRSwNP.

Verapamil modulates interleukin-5 and interleukin-6 secretion in organotypic human sinonasal polyp explants.

BACKGROUND: Verapamil is an L-type calcium channel blocker (CCB) that has been shown to have immunomodulatory properties in a variety of tissues. The goal of this study was determine whether verapamil is capable of regulating cytokine secretion in sinonasal polyps and to compare this effect to dexamethasone, an established immunosuppressive corticosteroid. METHODS: This was an institutional review board (IRB)-approved study in sinonasal polyp explants derived from 8 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyps were incubated with dexamethasone or verapamil for 24 hours followed by an additional 24 hours with Staphylococcal enterotoxin B (SEB). Concentrations of secreted cytokines over each exposure period were determined by enzyme-linked immunosorbent assay (ELISA) and are expressed as a percent. Results were compared using a 2-tailed Student t test. RESULTS: The percent of SEB-stimulated interleukin-5 (IL-5) secretion (mean ± standard deviation [SD], 339.94% ± 315.48%) between the second and first treatment periods was significantly reduced following exposure to dexamethasone (74.08% ± 26.77%, p < 0.05) and verapamil (119.99% ± 69.32%, p < 0.05). The percent of SEB-stimulated IL-6 secretion (217.53% ± 89.51%) was also significantly reduced following exposure to verapamil (148.82% ± 79.15%, p < 0.05) but not dexamethasone (148.86% ± 145.24%). Finally, the percent of SEB-stimulated thymic stromal lymphopoietin (TSLP) secretion (37.86% ± 18.88%) demonstrated a nonsignificant trend toward reduction with both dexamethasone (31.15% ± 35.28%) and verapamil (20.14% ± 12.10%). CONCLUSION: Although the mechanism has yet to be fully understood, L-type CCBs are capable of reducing inflammation in multiple tissues. Verapamil was specifically found to reduce airway goblet cell hyperplasia and eosinophilic infiltration in a murine asthma model. Our data support these findings suggesting that verapamil can modulate T-helper cell type 2 (Th2)-associated cytokine secretion in sinonasal polyp explants. This data points to a possible therapeutic role for CCBs in the management of CRSwNP.