Kristin A. Seiberling

Superantigens and chronic rhinosinusitis: detection of staphylococcal exotoxins in nasal polyps.

Objective/Hypothesis: The role of infectious agents in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unclear. Recent studies have provided indirect evidence of exposure to staphylococcal exotoxins in the blood and polyp tissue of patients with CRSwNP. These exotoxins have the capacity to act as superantigens, bypassing normal antigen processing and directly stimulating a massive inflammatory response. The objective of the study was to analyze mucus and polyp tissue samples from patients with CRSwNP for the presence of staphylococcal exotoxins.

Role of Intrathyroidal Calcifications Detected on Ultrasound as a Marker of Malignancy

Objectives: Clinically palpable thyroid nodules are present in between 4% and 7% of the population, with only a small percentage of those harboring malignancy. Thus, it is important to find a cost‐effective way to determine which nodules are more likely to be malignant. The purpose of this study was to evaluate the use of intrathyroidal calcifications detected on ultrasound as a risk factor for malignancy.

Staphylococcal exotoxins and nasal polyposis: Analysis of systemic and local responses

Background Staphylococcal exotoxins have been implicated in the pathogenesis of several chronic inflammatory diseases including atopic dermatitis (AD), asthma, and, most recently, chronic rhinosinusitis with nasal polyposis (CRS/NP). In severe AD, these toxins act both as superantigens (SAg), triggering massive T-cell activation, and as conventional allergens, triggering toxin-specific immunoglobulin E (IgE) in the serum. In CRS/NP, evidence for both processes has been reported but it is unclear whether these processes are linked. The aim of this study was to correlate SAg activity as inferred by staphylococcal-specific T-cell receptor (TCR) V-β expansion in the polyp and blood of CRS/NP patients with staphylococcal-specific anti-IgE antibodies in the serum. Methods IgE antibodies to staphylococcal exotoxin A (SEA), staphylococcal exotoxin B (SEB), and toxic shock syndrome toxin (TSST) 1 were measured in the serum of 12 individuals with CRS/NP before functional endoscopic sinus surgery. Flow cytometry was used to analyze the SEA, SEB, and TSST-1–specific TCR V-β domains on the T cells from the polyp and blood of these patients. Results Serum SEA-, SEB-, and TSST-1-specific IgE antibodies were detected in 0/12 (0%), 6/12 (50.0%), and 9/12 (75%) of CRS/NP patients, respectively. Evidence of SAg effect in the polyp lymphocytes (TCR V-β expansion in both CD4+ and CD8+ subsets) was noted in 7/12 (58.3%) patients. Five of 6 CRS/NP patients had overlapping evidence of a systemic IgE response and TCR V-β expansion, suggestive of exposure to the same exotoxin. No patients had evidence a SAg effect in blood lymphocytes. Nine of 12 subjects also had coexistent asthma. Conclusion These results provide evidence for a local SAg effect in 7/12 (58.3%) polyp patients and establish a positive correlation of V-β expansion with the presence of corresponding toxin-specific IgE in the serum.

Superantigens and chronic rhinosinusitis: Skewing of T-cell receptor Vβ-distributions in polyp-derived CD4+ and CD8+ T cells

Background Recent studies have suggested that Staphylococcus aureus secrete superantigenic toxins that play a role in the etiology of chronic rhinosinusitis with nasal polyposis (CRSwNP). Twenty S. aureus superantigens (SAgs) have been identified, each of which bind the Vβ-region of the T-cell receptor (TCR) outside the peptide-binding site. Approximately 50 distinct Vβ-domains exist in the human repertoire, and distinct SAgs will bind only particular domains generating a pattern of Vβ-enrichment in lymphocytes dependent on the binding characteristics of a given toxin. The aim of this study was to analyze the pattern of Vβ-expression in polyp-derived lymphocytes from CRSwNP patients. Methods Polyps were harvested from 20 patients with CRSwNP and 3 patients with antrochoanal polyps. Flow cytometry was used to analyze the Vβ-repertoire of polyp-derived CD4+ and CD8+ lymphocytes. Data were analyzed in light of the known skewing associated with SAg exposure in vivo and in vitro. Skewing was defined as a percentage of Vβ-expression >2 SD of that seen in normal blood. Results Seven of 20 subjects exhibited skewing in Vβ-domains with strong associations with S. aureus SAgs. The three antrochoanal polyps failed to show any significant Vβ-skewing. Conclusion This study establishes evidence of S. aureus SAg–T-cell interactions in polyp lymphocytes of 35% of CRSwNP patients. Although these results are consistent with intranasal exposure of polyp lymphocytes to SAgs, additional study is necessary to establish the role of these toxins in disease pathogenesis.

Endoscopic management of frontal sinus osteomas revisited

Background Recent articles have published guidelines regarding the role of endoscopic surgery in the removal of frontal sinus osteomas. These guidelines recommend the endoscopic approach for small osteomas but recommend an osteoplastic flap for larger tumors. This study presents a series of endoscopically resected tumors both large and small. Methods Retrospective chart reviews were performed. Charts were reviewed of all patients who underwent surgical resection of a frontal sinus osteoma from 1998 to 2008. Sinus CT scans were reviewed and each tumor was staged according to Kennedys grading system proposed in 2005. Results Twenty-three patients, 8 with a grade IV tumor, 6 with a grade III tumor, and the remaining with a grade I or II tumor, underwent endoscopic resection of a frontal sinus osteoma. In 15 patients a modified Lothrop procedure was performed for tumor removal. In addition, a blepharoplasty incision was used in one patient for removal of a large orbital extension of the tumor and another underwent an enlarged frontal sinus trephine performed via a browline incision. In the remaining patients a frontal sinusotomy with minitrephination provided enough access for tumor removal. Over an average follow-up of 36 months no recurrences were noted. Symptoms improved in all but one patient. There were no postoperative complications. Conclusion Endoscopic resection of both large and small frontal sinus osteomas is feasible. In this article we have shown successful removal of large osteomas that fill the entire frontal sinus with the modified Lothrop procedure.

The role of itraconazole in recalcitrant fungal sinusitis

Background Oral itraconazole is an antifungal that has been shown to be of benefit to patients with allergic bronchopulmonary aspergillus (ABPA). It is hypothesized that itraconazole may similarly benefit patients with allergic fungal sinusitis (AFS), a disease similar to ABPA. This study was designed to evaluate the therapeutic response of itraconazole in patients with refractory chronic fungal sinusitis who have failed maximal medical and surgical therapy. Methods A retrospective chart review was performed of 23 patients with AFS and nonallergic eosinophilic fungal sinusitis treated with oral itraconazole. Charts were reviewed for patient demographics, comorbidities, allergies, fungal cultures, type of surgery performed, and amount of oral steroids used before and after itraconazole. All patients were given a 6-month dose of itraconazole (100 mg b.i.d.) when recurrence developed after surgery. Time to next recurrence, change in oral steroid use, and outcomes were noted. Liver function tests were taken at monthly intervals while on itraconazole. Results Twenty-three patients, 13 men and 10 women, were started on oral itraconazole for recurrent fungal sinusitis. Nineteen patients responded to the medication with a decrease in symptoms and fungal mucin/polyps on endoscopy. Three patients had to stop because of elevated liver enzymes. In the remaining 16 patients a decrease in oral steroid use was noted. In addition, 11 of the 16 patients are disease free to date at a mean follow-up of 15.7 months. No permanent complications occurred from the use of the medication. Conclusion Oral itraconazole may be of benefit to those patients with recalcitrant fungal sinusitis who have failed maximal medical and surgical therapy. Itraconazole may prolong the time to next recurrence and may enable the patient to significantly decrease or stop oral steroids.

Superantigens and chronic rhinosinusitis II: Analysis of T-cell receptor Vβ domains in nasal polyps

Background The superantigen (SAg) hypothesis of chronic rhinosinusitis (CRS) suggests that toxins within the nose stimulate massive oligoclonal expansion of T-cell populations with subsequent eosinophil recruitment and tissue inflammation. SAgs are capable of activating 1 × 104 more lymphocytes than conventional antigens by binding specific Vβ-domains of the T-cell receptor (TCR). The net effect is skewing from the normal Vβ-profile by oligoclonal expansion of specific domains. This study will assess polyp tissue for evidence of an SAg response in CRS with nasal polyps (CRSwNP). Methods This study consists of a prospective analysis of 18 CRSwNP subjects undergoing sinus surgery. Flow cytometry was used to analyze the distribution of 24 specific TCR Vβ-domains in lymphocytes from polyp tissue and blood. Evidence of oligoclonal expansion was tabulated for each specimen and defined as mean normative percentage + 2 SD. Results Eighteen of 18 CRSwNP subjects showed expansion of polyp lymphocytes expressing TCRs with specific Vβ-domains. The average number of Vβ-clones per CRSwNP subject was seven in polyp lymphocytes but only two in blood lymphocytes. Conclusion The current results indicate that polyp lymphocytes exhibit significant oligoclonal expansion of specific Vβ-domains. These data are considered diagnostic of a SAg effect. The corresponding blood profile is much less, suggesting that the nose is the primary source of stimulus. Although the trigger(s) for this expansion are unknown, these data are consistent with the hypothesis that staphylococcal toxins are central to the development of CRSwNP.

Ultrasound-guided fine needle aspiration biopsy of thyroid nodules performed in the office.

Introduction: The majority of thyroid fine needle aspiration biopsies (FNAB) today are performed in the office freehand by palpation. Not infrequently, patients are sent to radiology for an ultrasound‐guided FNAB (USG‐FNB). Real‐time ultrasound (US) allows for continuous visualization of the needle during insertion and sampling. Historically, USG‐FNAB has been a procedure performed by a radiologist in a designated radiology suite. In more recent years, with the development of smaller more portable US machines, there has been a push for clinicians other than radiologists to perform the procedure.

Surgical outcomes of endoscopic management of adenocarcinoma of the sinonasal cavity

OBJECTIVE To report the surgical outcomes of endoscopic resection of adenocarcinomas of the Sinonasal cavity. METHODS Retrospective chart review of patients presenting with adenocarcinoma of the anterior skull base between 1998-2008. All patients who underwent wholly endoscopic resection were included in the study. RESULTS Twelve patients presented with adenocarcinoma involving the sino-nasal cavity. At diagnosis 6 patients were staged as a T2, 5 as a T3 and one as a T4. All of the patients had successful removal of the tumour entirely endoscopically. Three patients recurred: 2 locally and 1 with distant metastases. Overall, 11 patients are alive and free of disease and 1 patient dead of disease. We found an overall disease free survival rate and overall survival rate of 91.6%. The follow-up period ranged from 10 to 96 months with a median of 30 months. CONCLUSION Endoscopic management of adenocarcinoma of the sino-nasal cavity can be a viable treatment option to craniofacial resection. With the advancement in endoscopic equipment and surgeon skill, larger tumours may be managed wholly endoscopically.

Canine fossa trephine for the severely diseased maxillary sinus

Background The appropriate surgical approach to the severely diseased maxillary sinus is still debatable. Some advocate creating a wide maxillary antrostomy to allow for increased ventilation and improved delivery of postoperative medication. Others, however, recommend more aggressive surgery with complete clearance of all diseased tissue. The aim of this study was to evaluate the outcome of canine fossa puncture and canine fossa trephine (CFT) for the severely diseased maxillary sinus. Methods A retrospective chart review was performed on 97 patients who underwent a CFT as a part of endoscopic sinus surgery or modified Lothrop procedure. Outcomes were measured in terms of the maxillary sinus endoscopy grade at last follow-up and need for revision surgery. Two groups were formed: those who experienced recurrence of disease and those who were disease free at last follow-up. A comparison was made between the two groups and differences were noted. Results A CFT was performed in 97 patients with nasal polyposis (NP) who had an average number of 2.38 previous sinus surgeries. At an average follow-up of 27.8 months, 80 of the patients were disease free. In 17 patients disease recurred, and 11 of those required revision surgery with a CFT. Those patients who had recurrence of disease tended to be more allergic, have higher Lund-Mackay score, and had an increased number of prior sinus surgeries. In addition, allergic fungal sinusitis was associated with a poorer prognosis after CFT. Conclusion CFT allows for complete clearance of all gross disease in the maxillary sinus. CFT decreases the chance of disease recurrence in patients with severe NP.