The use of different intranasal splints Doyle splints versus Reuter bivalve splints versus no splints in primary septal surgeries: A randomised clinical trial looking at morbidity.

OBJECTIVE: The objective of this study is to compare the morbidity of different types of intranasal splints (Doyle splints and Reuter bivalve splints) with no intranasal splints in primary septal surgeries and concomitant submucosal reduction of the inferior turbinate. DESIGN: Randomised clinical trial SETTING: Single-Center trial at a tertiary care facility PARTICIPANTS: In this randomised clinical trial, 123 consecutive patients underwent primary septoplasty with bilateral submucosal reduction of the inferior turbinate, with no other concurrent procedure. Patients were randomised into three groups: Doyle splints, Reuter bivalve splints and patients with no splints placed. MAIN OUTCOME MEASURES: Following surgery, the patients were seen at three consecutive visits. During each visit, the Visual Analogue Scale score for headache, nasal obstruction, overall pain and bleeding and an endoscopic score for secretions, oedema and synechiae was filled. RESULTS: Patients were randomised into three groups, 42 received Doyle splints, 41 Reuter bivalve splints and 40 had no splints inserted. When comparing the three groups, the first two post-op visits were scheduled significantly earlier in patients with splints (p < .05). The scores from both groups with splints were statistically higher for headache, nasal obstruction and pain, for the first visit only (p < .05). There was no statistical difference between groups when looking at each subset of the endoscopic score, at each visit (p > .05). CONCLUSION: Increased post-operative pain, headaches and nasal obstruction scores were encountered in patients who had splints after surgery. However, endoscopic scores were statistically similar across the three groups with no difference in post-operative endoscopic scores at each visit. and no difference was seen in symptom scores and endoscopic scores between patients with different splints.

Airway surface mycosis in chronic TH2-associated airway disease.

BACKGROUND: Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. OBJECTIVE: To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. METHODS: Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. RESULTS: Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). CONCLUSIONS: The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.

IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

RATIONALE: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. OBJECTIVES: The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. METHODS: Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. CONCLUSIONS: These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

Pilot study comparing total intravenous anesthesia to inhalational anesthesia in endoscopic sinus surgery: novel approach of blood flow quantification.

OBJECTIVES: We compared anesthesia with sevoflurane-remifentanil hydrochloride (SR) to total intravenous anesthesia with propofol-remifentanil hydrochloride (PR) in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis in terms of sinonasal mucosal blood flow, the surgical field visualization score, and blood loss. METHODS: We performed a double-blinded prospective study at a tertiary care center in 23 adults scheduled to undergo endoscopic sinus surgery for chronic rhinosinusitis. The patients were randomized to receive SR or PR. The sinonasal mucosal blood flow was measured by optical rhinometry. The surgical field visualization score was based on the Boezaart scale. RESULTS: The groups had similar clinical characteristics. During the 60- to 90-minute and 90- to 120-minute operative time windows, the blood flow was significantly greater in the PR group than in the SR group (p = 0.04 and p = 0.03, respectively). The amounts of blood loss in the PR and SR groups were 152.9 +/- 161.3 mL and 355.9 +/- 393.4 mL, respectively (p = 0.12). The median ratios of the surgical field visualization score to the number of sinuses operated on in the PR and SR groups were 2.1 and 1.8, respectively (p = 0.52). CONCLUSIONS: The intraoperative blood flow, as determined by optical rhinometry, was significantly greater with anesthesia with PR than with anesthesia with SR, 1 hour into the procedure; however, this difference did not translate into differences in the amounts of operative blood loss or in the surgical field visualization scores.

Esthesioneuroblastoma: 25-year experience at a single institution.

OBJECTIVES: To evaluate outcomes for patients with esthesioneuroblastoma treated at a single institution during a 25-year period. DESIGN: Eighteen patients with pathologic diagnosis of esthesioneuroblastoma between 1980 and 2004 were retrospectively identified. RESULTS: Two patients had Kadish A, seven had Kadish B, and nine had Kadish C disease. The mean follow-up was 71 months. Treatment regimens consisted of surgery alone (four patients), surgery followed by postoperative radiation (six patients), surgery followed by postoperative chemoradiotherapy (three patients), preoperative radiotherapy (two patients), preoperative chemoradiotherapy (one patient), chemoradiotherapy (one patient), and surgery plus chemotherapy (one patient). Surgical approaches (n = 17) consisted of 13 traditional craniofacial resections, one endoscopic-assisted cranionasal resection, and three minimally invasive endoscopic resections. The 10-year disease-specific survival was 80%. The overall recurrence-free survival at five and 10 years was 62% and 46%, respectively. Positive surgical margins and TNM staging predicted survival. CONCLUSION: Both endoscopic and open surgical approaches have been successful in treating a small number of esthesioneuroblastoma patients with high survival and low rate of surgical complications.

Analgesic Effects of Intravenous Acetaminophen vs Placebo for Endoscopic Sinus Surgery and Postoperative Pain: A Randomized Clinical Trial.

Importance: Intravenous acetaminophen is a commonly prescribed analgesic for the prevention and treatment of postsurgical pain. Its efficacy in the context of endoscopic sinus surgery (ESS) has yielded mixed results. Objective: To compare the efficacy of perioperative intravenous acetaminophen (IVAPAP) with that of placebo in improving early postoperative pain after endoscopic sinus surgery (ESS). Design, Setting, and Participants: A prospective, randomized clinical trial including 62 patients undergoing ESS for chronic rhinosinusitis in a single tertiary referral hospital. Interventions: Participants were randomized to receive 1 g of IVAPAP or 100 mL of placebo consisting of saline infusions immediately before the start of surgery and 4 hours after the initial dose. Main Outcomes and Measures: The primary outcome was postoperative pain measured by visual analog scale (VAS) scores up to 24 hours after surgery by blinded observers. Secondary endpoints included postoperative opioid (intravenous and oral) use and adverse events in the 24-hour postoperative period. Results: Of the 62 enrolled adult participants, 60 were randomized (31 to IVAPAP intervention and 29 to placebo). The mean (SD) age of participants was 53.7 (14.7) years and 35 (58%) of the participants were men and 25 (42%) were women. Within the first hour, mean pain scores were reduced in the IVAPAP group compared with the control group, reaching a maximum difference of 7.7 mm on a VAS scale favoring the treatment group with a true difference possibly as high as 22 mm, and the data are compatible with a clinically meaningful difference. At 12- and 24-hours, average pain scores were less in the placebo group and the data are compatible with a clinically meaningful difference of 5.8 (-5.2 to 16.8) and 8.2 (-1.9 to 18.4), respectively, favoring the placebo group. However, at all time points the CIs included the null value and were wide, thus preventing definitive conclusions. Inspection of the secondary outcomes favored IVAPAP, but the wide range of the CIs and inclusion of the null value prevent definitive conclusions. Conclusions and Relevance: The results of this study are inconclusive. The data suggest that perioperative intravenous acetaminophen may reduce immediate postoperative pain and opioid requirements compared with placebo and these differences could be clinically meaningful. Unfortunately, the imprecision of the estimates prevents definitive conclusion. Use of IVAPAP does not seem to increase adverse events. Trial Registration: clinicaltrials.gov Identifier: NCT01608308.

Endoscopic management of orbital abscesses.

Orbital complications of sinusitis have declined in the postantibiotic era. Nonetheless, the development of a subperiosteal or intraorbital abscess remains a serious condition that is best managed through a multidisciplinary approach. Surgical management is almost always indicated when orbital collections are present, and medical therapy plays a complimentary role. The endoscopic approach of draining a medial orbital collection offers significant advantages over the traditional external approach. The preoperative and intraoperative use of computer-aided technology may be a useful adjunct in the endoscopic management of orbital abscesses.

Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma describe inflammation of the upper and lower airway, respectively. Not surprisingly, the prevalence of CRS and asthma has been linked, with up to 50% asthma prevalence in CRS with nasal polyposis (CRSwNP) patients. However, these prevalence rates do not address subtypes of CRSwNP including allergic fungal rhinosinusitis (AFRS). This study sets out to objectively determine asthma prevalence in CRS subtypes prospectively. METHODS: A prospective prevalence study of adult CRS patients was conducted over a 1-year period at a tertiary care center. Patients were grouped into CRSwNP, CRS without nasal polyposis (CRSsNP), or AFRS. Patients were administered the Asthma Screening Questionnaire (ASQ) and asthma was confirmed by pulmonary function testing (PFT) if positive on the ASQ. Chi square analysis was performed to compare the asthma prevalence among the CRS subtypes. RESULTS: A total of 410 patients (age 48.1 ± 16.4; 53.5% male) were included. Of these, 178 (43.4%) had CRSwNP, 166 (40.5%) had CRSsNP, and 66 (16.1%) met criteria for AFRS. Analysis revealed that 48.3% of CRSwNP patients, 16.5% of CRSsNP patients, and 23.6% of AFRS patients had asthma confirmed by PFTs. Chi square analysis showed a significant difference in asthma prevalence between CRSwNP and AFRS (p = 0.0016) and CRSwNP and CRSsNP (p = 0.0000), but no significant difference between CRSsNP and AFRS (p = 0.2380). CONCLUSION: There is a significant difference in the prevalence of asthma between CRSwNP and AFRS, suggesting a fundamental distinction in their etiologies despite similar immunologic profiles. Further efforts to delineate these biological disparities are underway.

Transnasal endoscopic resection of lesions of the clivus: a preliminary report.

OBJECTIVE: To review our experience with transnasal endoscopic resection of clival lesions. BACKGROUND: Because of the surrounding vital structures and the difficulties in achieving wide surgical exposure, the treatment of clival lesions is challenging. In an effort to overcome these obstacles, many centers use facial incisions and osteotomies to approach clival lesions. Minimally invasive endoscopic techniques have the potential to minimize morbidity while yielding similar surgical results. STUDY DESIGN: Retrospective chart analysis. MATERIALS AND METHODS: Patients with tumors involving the clivus that underwent endoscopic resection between 2000 and 2004 were identified. Charts were reviewed for clinical characteristics, previous therapies, diagnosis, tumor extent, management modalities, length of hospital stay, complications, and outcome. RESULTS: A total of six patients were identified. There were four males and two females with a mean age of 50 years, ranging from 29 to 66 years. The most common presenting symptoms were visual disturbances. Three patients had prior craniotomy with subtotal tumor resection. The pathology included three clival chordomas, and one each of meningioma, adenoid cystic carcinoma, and sinonasal undifferentiated carcinoma. All patients were managed with computer-aided transnasal endoscopic tumor resection with neurosurgical standby or involvement. None of the patients required additional craniotomies. The mean follow-up was 13 (range, 8-24) months. Intensity-modulated radiation therapy was used in three patients, and two patients are currently undergoing proton beam radiation therapy (PBRT). The average length of hospital stay was 2 (range, 2-3) days. There were no major postoperative complications. At the last follow-up, five patients were alive with two patients being free of disease. Two patients with residual disease are currently undergoing PBRT, and one patient developed distant metastasis. One patient died of unrelated causes. CONCLUSIONS: This preliminary report suggests that transnasal endoscopic management of clival lesions is a viable option to traditional open approaches with acceptable morbidity and mortality. The use of computer-aided surgery further minimizes surgical risks while maximizing tumor resection.

Isolated sphenoid sinus disease: etiology and management.

OBJECTIVE: To evaluate the diagnosis and management of isolated sphenoid sinus disease by using the current rhinologic standard of care. STUDY DESIGN: Retrospective chart review. RESULTS: Fifty sequential, symptomatic patients were studied. Presenting symptoms included headache or facial pain (88%), rhinorrhea (46%), and nasal congestion (26%). All patients underwent CT imaging, demonstrating bony changes or dehiscences (42%), a mass (24%), or complete opacification of the sphenoid sinus (22%). Eighty percent required surgical intervention. The most frequent diagnoses were as follows: sinusitis (38%), fungal ball (20%), neoplasm (16%), and mucocele (12%). Treatment resulted in clinical or endoscopic improvement or resolution in 87% of the patients. CONCLUSION: The presenting symptoms of isolated sphenoid sinus disease can be nonspecific and may result in an inordinate delay in diagnosis. Nasal endoscopy and radiologic imaging are central to making an accurate and timely diagnosis. Medical treatment or minimally invasive surgical techniques can successfully manage the majority of patients with persistent or refractory symptoms.

Microbial superantigens induce glucocorticoid receptor beta and steroid resistance in a nasal explant model.

OBJECTIVE: To study the role of superantigen (SAg) in inducing glucocorticoid (GC) receptor beta and steroid resistance in an explant model of nasal tissue. METHODS: Nasal tissue was obtained from inferior turbinates of controls and ragweed (RW)-sensitive patients. Tissue samples were incubated with SAg of staphylococcal enterotoxin B. In addition, tissue samples from RW-sensitive patients were incubated with RW allergen in the presence and absence of both SAg and dexamethasone (DEX). The expression of GC receptor beta was assessed by immunocytochemistry. The expression of interleukin (IL)-2 and IL-4 mRNA was assessed by in situ hybridization. RESULTS: SAg induced an increase in the expression of GC receptor beta in atopic tissue and to a lesser extent in nonatopic tissue. The most significant induction of GC receptor beta was observed in response to SAg and RW in atopic tissue. Stimulation of atopic tissue with RW alone and SAg alone induced IL-4 and IL-2 mRNA, respectively. Incubation of atopic tissue with both SAg and RW induced both IL-2 and IL-4 mRNA. The increase in IL-4 mRNA expression was blunted by the addition of DEX to atopic tissue stimulated with RW alone but not to tissue stimulated by both RW and SAg. CONCLUSION: Our results demonstrate that SAgs induce steroid resistance in atopic nasal explant tissue by up-regulating the expression of GC receptor beta. Furthermore, we have shown that the up-regulation of GC receptor beta is a local event that is associated with the coexpression of IL-2 and IL-4 mRNA.

Considerations against concurrent functional endoscopic sinus surgery and rhinoplasty.

Over the last decade, functional endoscopic sinus surgery (FESS) has become the surgical modality of choice in the treatment of inflammatory sinus disease refractory to medical therapy. During the same interval, interest in cosmetic surgery procedures, including rhinoplasty, has exploded. Some of the published literature endorses the performance of concurrent FESS and rhinoplasty. This article addresses some of the concerns regarding the combined approach and its limitations. It offers the reader a framework for surgical risk assessment when concurrent procedures are considered.

Staphylococcus aureus prevalence in allergic fungal rhinosinusitis vs other subsets of chronic rhinosinusitis with nasal polyps.

BACKGROUND: The pathogenesis of allergic fungal rhinosinusitis (AFRS) is thought to represent an immunological reaction to fungal antigens. Recent studies have implicated superantigens and non-immunoglobulin E (IgE)-mediated mechanisms in the development of AFRS. The objective of this study is to assess the prevalence of Staphylococcus aureus in AFRS vs other subsets of chronic rhinosinusitis with polyps (CRSwNP, also termed non-AFRS). METHODS: A case series with retrospective review of 19 patients with AFRS and 21 patients with CRSwNP was performed at a tertiary referral center. The diagnosis of AFRS required the presence of defined criteria described by Bent and Kuhn. Bacterial cultures and fungal cultures were analyzed for each group. RESULTS: S. aureus was significantly more prevalent in the AFRS group compared with the non-AFRS group (63.2% vs 24.1%, p = 0.005). CONCLUSION: S. aureus has been implicated as a disease modifier in CRSwNP through superantigen-mediated mechanisms. This study demonstrates a higher prevalence of S. aureus in patients with AFRS vs patients with other subsets of CRSwNP (non-AFRS). These results support a potential role for S. aureus in the pathogenesis of AFRS.

Endoscopic trans(naso)orbital management of supraorbital mucoceles with biliary T-tube stenting.

The objective of this article is to describe our surgical technique for accessing orbital and supraorbital ethmoid sinus mucoceles and the novel application of a biliary T-tube to stent and redirect mucociliary flow into the frontal recess. We describe in technical terms our surgical approach and the use of an 8-Fr pediatric biliary T-tube as a paranasal sinus stent with demonstrative case reports. Four patients have been successfully managed employing the endoscopic trans(naso)orbital approach to access and marsupialize supraorbital and superiorly located orbital mucoceles without egress to the frontal recess. Patency of drainage was maintained by utilizing a flexible, pediatric, biliary T-tube that is inserted via an above (trephination) and below (endoscopic) approach in three patients, and without the need for stenting in one patient (median follow-up, 14.5 months). The presented surgical strategy is safe and effective in accessing and maintaining long-term patency of problematic supraorbital and superiorly located intraorbital mucoceles without communication to the frontal recess.

End-organ testing for allergic rhinitis with fungi is poorly correlated with fungal sensitivity.

OBJECTIVE: To evaluate optical rhinometry (ORM) using nasal provocation testing (NPT) as an objective tool to diagnose fungal allergic rhinitis (AR). STUDY DESIGN: Prospective. SETTING: Tertiary academic center. METHODS: We prospectively enrolled healthy controls (HCs) and subjects with a clinical history of AR and positive skin prick test to Alternaria or Aspergillus antigens. Baseline measurements with an optical and acoustic rhinometer (AcR) were taken, and all subjects underwent NPT with increasing concentrations of Alternaria and then Aspergillus in each nasal cavity. Optical density (OD), nasal mean cross-sectional area (MCA), visual analog scale (VAS), and nasal allergen provocation scale (NAP) were measured after each provocation. A NAP score ≥ 3 was considered positive. Receiver operating characteristic (ROC) curve analysis was performed on measured parameters. RESULTS: Eleven HCs and 11 AR subjects were enrolled. Of the 8 AR patients with an Alternaria-positive skin test, 50% had a positive NAP score (4/8) vs 0% in HCs (0/11, P = .01). Although VAS could differentiate Alternaria-sensitive patients from controls, change in OD and MCA could not. Of the 7 skin test-positive Aspergillus patients, 43% had a positive NAP score (3/7) vs 0% in HCs (0/11, P = .02). The VAS and change in OD and MCA did not differentiate Aspergillus-sensitive patients from controls. CONCLUSION: In this study, fungal antigens caused irritation but did not elicit early phase changes in nasal patency or blood flow in fungal-sensitive AR patients. The poor correlation of skin testing and objective nasal response to fungi argues against a pure IgE-mediated immune response in the nasal cavity.

Optical rhinometry in nonallergic irritant rhinitis: a capsaicin challenge study.

BACKGROUND: Patients with nonallergic irritant rhinitis (NAIR) have symptoms of nasal congestion, nasal irritation, rhinorrhea, and sneezing in response to nasal irritants. We currently have no reliable objective means to quantify these patients' subjective symptoms. In this study, we used the transient receptor potential vanilloid receptor (TRPV1) receptor agonist, capsaicin, as an intranasal challenge while comparing the changes in blood flow with optical rhinometry between subjects with NAIR and healthy controls (HCs). METHODS: Six HCs and 6 NAIR subjects were challenged intranasally with saline solution followed by increasing concentrations of capsaicin (0.005 mM, 0.05 mM, and 0.5 mM) at 15-minute intervals. We recorded maximum optical density (OD) and numeric analog scores (NAS) for nasal congestion, nasal irritation, rhinorrhea, and sneezing for each subject after each challenge. Correlations between NAS and maximum OD were calculated. RESULTS: Maximum OD increased with increasing concentrations of intranasal capsaicin in NAIR subjects. There were significant differences in maximum OD obtained for 0.05 mM and 0.5 mM capsaicin between NAIR subjects and HCs. Significant differences were found in the NAS for nasal irritation at 0.005 mM, 0.05 mM, and 0.5 mM, and nasal congestion at 0.5 mM. Correlation between maximum OD and mean NAS was most significant for 0.05 mM capsaicin. CONCLUSION: Optical rhinometry with intranasal capsaicin challenge could prove a viable option in the diagnosis of NAIR. Further studies will investigate its use to monitor a patient's response to pharmacologic therapy and provide further information about the underlying mechanisms of NAIR.

Sinonasal undifferentiated carcinoma (SNUC): morphoproteomic-guided treatment paradigm with clinical efficacy.

Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly malignant tumor that occurs in the nasal cavity and/or paranasal sinuses. Prognosis is poor despite multimodality treatment. Currently, there is no optimal standard of treatment, partially due to a lack of research defining the biology of such tumors. This report discusses two SNUC cases where patients received a novel chemotherapeutic approach using cisplatin, etoposide, Adriamycin (doxorubicin), metformin, and adjuvant melatonin therapies based on morphoproteomic-guidance, followed by consolidation with chemoradiation therapy. This resulted in excellent and objective tomographic and magnetic resonance imaging and clinical responses including complete responses in the induction phase utilizing morphoproteomic-guided therapies. Later, endoscopic excision of the tumor bed failed to reveal any residual tumor. Morphoproteomics helped to define the biology of these SNUC tumors and provided targets for the agents employed, creating a new treatment paradigm for such tumors. This treatment regimen poses a new effective regimen to treat SNUC.