Extent of maxillary sinus surgery and its effect on instrument access, irrigation penetration, and disease clearance.

BACKGROUND: Middle meatal antrostomy (MMA) provides limited access to the anteromedial and inferior aspect of the maxillary sinus (MS) often resulting in residual disease and inflammatory burden. Newer extended procedures, such as mega-antrostomy (Mega-A) and extended modified mega-antrostomy (EMMA), have been developed to address this limitation. This study assesses the effect of varying extent of MS surgery on irrigation penetration and access of instrumentation. METHODS: The MS of 5 fresh-frozen cadavers were sequentially dissected. Irrigation was evaluated with a squeeze bottle (SB) in different head positions and using different volumes of fluid. Surgical reach and visualization were examined using common sinus instruments and different angled endoscopes. A disease simulation was also performed to check for residual debris after instrumentation and irrigations. RESULTS: Irrigation penetration improved as antrostomy size increased (p < 0.0001), with a significant difference observed between the extended procedures and MMA. The effect of the volume was significant for SB (p < 0.0001) but head positions appeared irrelevant (p = 0.613). Overall visualization improved for Mega-A and EMMA. A similar trend was seen for the reach of the instruments to all sinus wall subsites. EMMA facilitated the most removal of "sinus disease" in the disease simulation model when compared with both MMA and Mega-A, due to its reach of the anteroinferior aspects of the maxillary sinus. CONCLUSIONS: High-volume irrigation using SB achieved good sinus penetration, irrespective of head position. Extended MS procedures appear to further increase irrigation penetration as well as surgical access.

Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity.

Background:Pseudomonas aeruginosa causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). P. aeruginosa exoproteins contain virulence factors and play important roles in the pathogenicity of P. aeruginosa, however their role in CRS pathophysiology remains unknown. Methods: We isolated P. aeruginosa clinical isolates (CIs) and obtained clinical information from 21 CRS patients. Elastase activity of the CIs was measured at different phases of growth. Primary human nasal epithelial cells (HNECs) were cultured at air-liquid interface (ALI) and challenged with P. aeruginosa exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence. Results: 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the in vitro elastase activity of P. aeruginosa CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans (r = 0.95, p = 0.0004) and decreased TEER (r = -0.9333, P < 0.01) after 4 h of challenge. Western blot showed a significant degradation of ZO-1, Occludin and ß-actin in relation to the elastase activity of the exoproteins. There was a highly significant correlation between the in vitro elastase activity of P. aeruginosa CIs and CRS disease severity (for log phase, r = 0.5631, p = 0.0097; for stationary phase, r = 0.66, p = 0.0013) assessed by CT imaging of the paranasal sinuses. Conclusion: Our results implicate P. aeruginosa exoproteins as playing a major role in the pathophysiology of P. aeruginosa associated CRS by severely compromising mucosal barrier structure and function.

In vitro characteristics of an airway barrier-disrupting factor secreted by Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a major contributor to the pathophysiology of chronic rhinosinusitis (CRS). Previous research has shown that S. aureus-secreted products disrupt the airway barrier. METHODS: S. aureus ATCC 13565 and 25923 strains were grown at exponential, postexponential, and stationary phases. Microbial conditioned media (CM) was collected from the cultures and ultrafiltered (UF). Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was performed on the UF-CM. UF-CM was subjected to heat and protease treatment, size fractionation, and ultracentrifugation (UC) separation. Human nasal epithelial cells grown at air-liquid interface (HNEC-ALI) cultures were exposed to purified alpha hemolysin (Hla), staphylococcal enterotoxin A (SEA), lipoteichoic acid (LTA), and UF-CM. Barrier function outcomes were measured by transepithelial electrical resistance (TEER) and apparent permeability (Papp). UC fraction exposed cultures were subjected to immunofluorescence microscopy for tight junction (TJ) protein zonula occludens-1 (ZO-1). RESULTS: LC-ESI-MS/MS identified 107 proteins, with Hla being most abundant. Hla, SEA, and LTA did not alter the HNEC-ALI barrier as measured by TEER or Papp. Barrier disruption caused by UF-CM peaked in the postexponential phase, was sensitive to heat and protease treatment, >30-kDa in size, and enriched in the UC fraction. HNEC-ALI exposed to UF-CM and UC demonstrated loss of ZO-1 localization. CONCLUSION: These results suggest that the S. aureus factor responsible for TJ disruption in HNEC-ALI cultures is either a protein-macromolecule or a combination of secreted factors. The product is enriched in the UC fraction, suggesting it is associated with large structures such as membrane components or vesicles.

Staphylococcus Aureus V8 protease disrupts the integrity of the airway epithelial barrier and impairs IL-6 production in vitro.

OBJECTIVE: Staphylococcus aureus (S. aureus) infection is known to contribute to the severity and recalcitrance of chronic rhinosinusitis (CRS), and its secreted products have been shown to alter the airway barrier. Extracellular proteases secreted by S. aureus are thought to be important in epithelial infection and immune evasion; however, their effect on airway mucosal barrier function is not known. METHODS: To investigate the impact of extracellular proteases on airway epithelial integrity, the purified S. aureus proteases V8 protease, Staphopain A, Staphopain B, Exfoliative toxin A, and serine protease-like A-F were applied to human nasal epithelial cell air-liquid interface (HNEC-ALI) cultures. Transepithelial electrical resistance (TEER), permeability (Papp) measurements, and immuno-localization of the tight junction proteins claudin-1 and ZO-1 were used to assess barrier integrity. Effects of the proteases on inflammation and cell viability were measured using interleukin-6 (IL-6) ELISA and a lactate dehydrogenase assay. RESULTS: Application of V8 protease to HNEC-ALI cultures caused a significant concentration and time-dependent decrease in TEER (22.67%, P < 0.0001), a reciprocal Papp increase (20.14-fold, P < 0.05), and a discontinuous ZO-1 immuno-localization compared to control. IL-6 production was significantly reduced in V8 protease-treated cells (153.5 pg/mL, P = 0.0069) compared to control (548.3 pg/mL), whereas no difference in cell viability was observed. CONCLUSION: S. aureus V8 protease causes dysfunction of mucosal barrier structure and function indicative of a leaky barrier. A reduction in IL-6 levels suggests that the mucosal immunity is impaired by this protease and thus has the potential to contribute to CRS recalcitrance. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E8-E15, 2018.

In vitro safety evaluation of human nasal epithelial cell monolayers exposed to carrageenan sinus wash.

BACKGROUND: Carrageenans have shown to reduce the viral load in nasal secretions and lower the incidence of secondary infections in children with common cold. Despite the widespread use of carrageenans in topical applications, the effect of carrageenans on the sinonasal epithelial barrier has not been elucidated. We investigate the effect of different carrageenans on the sinonasal epithelial barrier and inflammatory response in vitro. METHODS: Iota and Kappa carrageenan delivered in saline irrigation solutions applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells from chronic rhinosinusitis patients and controls. Epithelial barrier structure was assessed by measuring the transepithelial electrical resistance (TEER) and immunolocalization of F actin. Ciliary beat frequency (CBF), toxicity, and inflammatory response was studied. RESULTS: Kappa or Iota carrageenan in the different solutions was not toxic, did not have detrimental effects on epithelial barrier structure and CBF. Rather, application of Kappa carrageenan significantly increased TEER and suppressed interleukin 6 (IL-6) secretion in ALI cultures from CRS patients. CONCLUSION: Kappa or Iota carrageenan solution was safe and did not negatively affect epithelial barrier function. Kappa carrageenan increased TEER and decreased IL-6 production in CRS patients, indicating positive effects on epithelial barrier function in vitro.

Nano-hemostats and a Pilot Study of Their Use in a Large Animal Model of Major Vessel Hemorrhage in Endoscopic Skull Base Surgery.

Nano-hemostats are synthetic amino acid chains that self-assemble into a scaffold under certain conditions. These have been shown to be effective in stopping bleeding in small animal models of hemorrhage. Proposed mechanisms for their effect are that they form a mesh analogous to the fibrin plug in native hemostasis and that they may potentiate both platelet activation and the coagulation cascade. These may potentially become valuable adjuncts to endoscopic skull base surgery where there is the potential for both major vessel injury and smaller perforator injury to eloquent areas where bipolar cautery may not be suitable. We present a summary of the clinical studies to date and a small pilot study of nano-hemostat in an endoscopic sheep model of major vessel hemorrhage to determine its efficacy in stopping bleeding in this potentially catastrophic complication.

Stress response and communication in surgeons undergoing training in endoscopic management of major vessel hemorrhage: a mixed methods study.

BACKGROUND: Major vessel hemorrhage in endoscopic, endonasal skull-base surgery is a rare but potentially fatal event. Surgical simulation models have been developed to train surgeons in the techniques required to manage this complication. This mixed-methods study aims to quantify the stress responses the model induces, determine how realistic the experience is, and how it changes the confidence levels of surgeons in their ability to deal with major vascular injury in an endoscopic setting. METHODS: Forty consultant surgeons and surgeons in training underwent training on an endoscopic sheep model of jugular vein and carotid artery injury. Pre-course and post-course questionnaires providing demographics, experience level, confidence, and realism scores were taken, based on a 5-point Likert scale. Objective markers of stress response including blood pressure, heart rate, and salivary alpha-amylase levels were measured. RESULTS: Mean "realism" score assessed posttraining showed the model to be perceived as highly realistic by the participants (score 4.02). Difference in participant self-rated pre-course and post-course confidence levels was significant (p < 0.0001): mean pre-course confidence level 1.66 (95% confidence interval [CI], 1.43 to 1.90); mean post-course confidence level 3.42 (95% CI, 3.19 to 3.65). Differences in subjects' heart rates (HRs) and mean arterial blood pressures (MAPs) were significant between injury models (p = 0.0008, p = 0.0387, respectively). No statistically significant difference in salivary alpha-amylase levels pretraining and posttraining was observed. CONCLUSION: Results from this study indicate that this highly realistic simulation model provides surgeons with an increased level of confidence in their ability to deal with the rare but potentially catastrophic event of major vessel injury in endoscopic skull-base surgery.

Sinus Penetration of a Pulsating Device Versus the Classic Squeeze Bottle in Cadavers Undergoing Sinus Surgery.

OBJECTIVES: Nasal irrigation is standard in the management of chronic rhinosinusitis both before and after surgical intervention. Numerous irrigation devices are commercially available. The aim of this study was to compare the efficacy of a handheld pulse irrigation device against the gold standard manual squeeze bottle after endoscopic sinus surgery (ESS). METHODS: Five cadaveric specimens were prepared with video visualization ports into each sinus. Endoscopic sinus surgery was performed on each cadaver from minimal to maximal dissection. Sinuses were irrigated with fluorescein solution using both devices following each dissection. The irrigations were video recorded. A blinded independent observer scored each irrigation according to a defined scale. RESULTS: Comparison of the 2 devices using an intraclass correlation coefficient (ICC = 0.39) showed the 2 systems differed. Observation of individual sinuses showed the squeeze bottle consistently provided greater irrigation in the maxillary (P < .006), frontal (P < .0001), and sphenoid (P < .0001) sinuses. Pulse irrigation improved only in the maxillary sinus following ESS. CONCLUSION: The squeeze bottle consistently demonstrated superior irrigation in both native and operated conditions. Interestingly, saline penetration was not significantly improved after opening of the frontal and sphenoid sinuses. This is likely due to decreased backpressure in the nasal passage after opening the sinus cavities.

Staphylococcus aureus impairs the airway epithelial barrier in vitro.

BACKGROUND: Chronic rhinosinusitis (CRS) is a cluster of disorders that result in sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe and recalcitrant CRS. The purpose of our study was to investigate the effect of S. aureus on respiratory epithelial barrier structure and function. METHODS: Conditioned media from S. aureus reference strains (American Type Culture Collection [ATCC] 13565, 14458, and 25923) was applied to air-liquid interface (ALI) cultures of primary human nasal epithelial cells (HNECs) and transepithelial electrical resistance (TEER) was measured to assess cell-to-cell integrity. Electron microscopy was used to gauge the ciliated area and tight junctions (TJs). Additionally, the expression of the TJ protein zona occludens-1 (ZO-1) was examined via immunofluorescence. Statistical analysis was performed using analysis of variance (ANOVA) with pairwise Bonferroni-adjusted t tests. RESULTS: Secreted products applied to ALI cultures from S. aureus strain 13565 caused a concentration-dependent decline in electrical impedance compared to controls and reference strains 14458 and 25923 (p < 0.001). Electron microscopy showed a distinct separation between adjacent cells apically, in the region of TJs. The ciliated area was not affected; however, ZO-1 expression became discontinuous in HNECs exposed to the 13565 strain's conditioned media. CONCLUSION: Conditioned media of the S. aureus strain 13565 damages the airway epithelium by disrupting the TJs between primary HNECs grown at an ALI. These findings suggest that strain-specific S. aureus-secreted product(s) compromise epithelial barrier function, which may constitute 1 of the roles played by S. aureus in the pathophysiology of recalcitrant CRS. Further research is required to uncover the relevant molecular mechanisms.

Biofilm Quantification on Nasolacrimal Silastic Stents After Dacryocystorhinostomy.

PURPOSE: Biofilms are now recognized as potential factors in the pathogenesis of chronic inflammatory and infective diseases. The aim of this study was to examine the presence of biofilms and quantify their biomass on silastic nasolacrimal duct stents inserted after dacryocystorhinostomy (DCR). METHODS: A prospective study was performed on a series of patients undergoing DCR with O'Donoghue stent insertion. After removal, the stents were subjected to biofilm analysis using standard protocols of confocal laser scanning microscopy (CLSM) and scanning electron microscopy. These stents were compared against negative controls and positive in vitro ones established using Staphylococcus aureus strain ATCC 25923. Biofilm quantification was performed using the COMSTAT2 software and the total biofilm biomass was calculated. RESULTS: A total of nine consecutive patient samples were included in this prospective study. None of the patients had any evidence of postoperative infection. All the stents demonstrated evidence of biofilm formation using both imaging modalities. The presence of various different sized organisms within a common exopolysaccharide matrix on CLSM suggested the existence of polymicrobial communities. The mean biomass of patient samples was 0.9385 µm³/µm² (range: 0.3901-1.9511 µm³/µm²). CONCLUSIONS: This is the first study to report the quantification of biomass on lacrimal stents. The presence of biofilms on lacrimal stents after DCR is a common finding but this need not necessarily translate to postoperative clinical infection.

Powered endoscopic dacryocystorhinostomy: a decade of experience.

PURPOSE: To report a decade long experience with powered endoscopic dacryocystorhinostomy (DCR). METHODS: A retrospective review of all consecutive patients undergoing powered endoscopic DCR was performed at this institution over a period of 11 years from 2002 to 2013. All patients completed a minimum of 3 months follow up following stent removal. Patient records were reviewed for demographic data, clinical and surgical profiles, adjunctive procedures, complications, and success rates at the last follow up. Anatomical success was defined as patent ostium on irrigation and functional success as free flow of dye into ostium on functional endoscopic dye test and resolution of epiphora. RESULTS: Two hundred eighty-three powered endoscopic DCRs were performed on 214 patients. The mean age at surgery was 59.5 years (range, 3-95 years). All patients presented with epiphora. A total of 91.6% patients (196/214) had a primary DCR and 8.4% (18/214) had a revision DCR. In all, 50.4% patients (108/214) underwent adjunctive endonasal procedures. The mean follow up was 17.1 months (range, 3-103 months). At the last follow up, the final anatomical success was achieved in 96.9% cases of primary DCRs and 91.3% cases of revision DCRs. Functional success was achieved in 93% cases of primary DCRs and 86.9% cases of revision DCRs. CONCLUSIONS: Powered endoscopic DCR is a safe procedure and offers excellent results both in primary and revision DCRs. The threshold to perform adjunctive endonasal procedures should be very low when indicated.

Endoscopic direct vessel closure in carotid artery injury.

BACKGROUND: Internal carotid artery (ICA) injury represents one of the most challenging management scenarios for the endoscopic skull base surgeon. Techniques developed through use of an animal model of carotid injury have shown direct vessel closure techniques to be effective in gaining hemostasis and preventing subsequent complications. The aim of this study was to investigate the effectiveness of the novel AnastoClip vessel closure system in ICA injury. METHODS: Nine sheep underwent ICA dissection/isolation followed by the artery placement within a modified "sinus model otorhino neuro trainer" (SIMONT) model. Standardized linear injuries were made and treated endoscopically with the AnastoClip device. Specific outcome measures included attainment of primary hemostasis, procedure time, blood loss, pseudoaneurysm formation and carotid patency on follow-up magnetic resonance imaging (MRI). RESULTS: Primary hemostasis was achieved in all cases. No instances of secondary bleeding. Procedure times averaged 5 minutes and 25 seconds. Average blood loss was 146 mL. All 9 sheep reached the 3-month end point. Eight showed normal carotid flow on MRI, with 1 case of pseudoaneurysm. CONCLUSION: Direct vessel closure is an effective endoscopic technique in ICA injury. It allows for visual confirmation of hemostasis and carotid flow and permits the surgeon to continue with surgery despite the complication. The novel design of the AnastoClip can maintain normal vessel patency as well as accommodate pulsatile flow.

Endoscopic dacryocystorhinostomy and obstructive sleep apnoea: the effects and outcomes of continuous positive airway pressure therapy.

BACKGROUND: This study aims to assess the effects and outcomes of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) in patients who have undergone endoscopic dacryocystorhinostomy (DCR). DESIGN: Retrospective series in a university setting. PARTICIPANTS: A total of 205 consecutive patients were included in this study. METHODS: A 10-year retrospective review was performed of 205 consecutive patients who had undergone powered endoscopic DCR for nasolacrimal duct obstruction. Patient notes were reviewed for demographic, clinical and surgical information. In addition, all patients were contacted and asked to complete a standardized telephone survey relating to OSA, CPAP use and associated symptoms. MAIN OUTCOME MEASURE: Effects of CPAP following DCR. RESULTS: Ten of the 205 patients undergoing DCR were identified to use CPAP for obstructive sleep apnoea. Eight patients were initiated on a nasal device, while two used a full-face mask. The mean CPAP pressures were 8 cm H20 (range: 6-10 cm H20). Eighty percent (8/10) of patients complained of symptoms from the use of their CPAP following DCR. The most commonly described symptom was that of air regurgitation in 70% of patients followed by ophthalmic symptoms in 60% (6/10). 50% (5/10) of patients discontinued their CPAP as a consequence of their symptoms with 20% (2/10) discontinuing because of intolerable ophthalmic symptoms. CONCLUSION: Symptoms from CPAP use post-endoscopic DCR are a common occurrence and may contribute to poor compliance with CPAP therapy. Detailed preoperative counseling with regards to CPAP use and its effects should be mandatory in known or at risk OSA patients undergoing DCR.

Outcomes in primary powered endoscopic dacryocystorhinostomy: comparison between experienced versus less experienced surgeons.

BACKGROUND: This study compares the anatomic and functional outcomes of primary powered endoscopic dacryocystorhinostomy (DCR) in surgeons of differing levels of experience. METHODS: A retrospective interventional study was performed of all consecutive powered endoscopic DCRs performed at a tertiary institution over a period of 10 years from 2002 to 2012. All patients completed a minimum of 3 months follow-up after stent removal. Patient records were reviewed for demographic data, clinical and surgical profiles, adjunctive procedures, complications, and success rates at last follow-up. The level of surgeon's experience performing the DCR was also documented. Anatomic success was defined as patent ostium on irrigation and functional success as free flow of dye into ostium on functional endoscopic dye test and resolution of epiphora. RESULTS: Among the 160 DCRs performed by the consultant, all except four underwent intubation; 54.4% (68/125) of these patients required adjunctive procedures. There were no major complications in this group and at a long-term mean follow-up of 14.2 months, the anatomic and functional success rates were 98.1 and 95.6%, respectively. Among the 100 DCRs performed by the fellows, all underwent intubation and 40.8% (29/71) of the patients required adjunctive procedures. The complications include three cases of ostium granulomas and two patients each with postoperative bleeding, stent prolapse, and turbinoseptal synechiae. At the mean follow-up of 10.9 months, the final anatomic success was achieved in 95% of the cases and functional success in 89% of the cases. CONCLUSION: Powered endoscopic dacryocystorhinostomy is an effective procedure and offers excellent results in the hands of experienced surgeons. A good transfer of knowledge and skills along with supervision when required ensures a good surgical success rate, even when the training fellows operate.