Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population-based sample.

BACKGROUND: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings. OBJECTIVE: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample. METHODS: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS ) was based on guideline criteria, and objective radiologic inflammation (CRSO ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRSS+O . Using weighted analysis, we calculated estimates for the source population. RESULTS: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRSO ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses. CONCLUSION: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O .

Longitudinal Evaluation of Chronic Rhinosinusitis Symptoms in a Population-Based Sample.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent and disabling condition of the nose and sinuses. The natural history of CRS symptoms in a general population sample has not been previously studied. OBJECTIVE: In a general population-based sample from Pennsylvania, we used 2 questionnaires mailed 6 months apart to estimate the prevalence of, and identify predictors for, stability or change in symptoms over time. METHODS: We mailed the baseline and 6-month follow-up questionnaires to 23,700 primary care patients and 7,801 baseline responders, respectively. We categorized nasal and sinus symptoms using European Position Paper on Rhinosinusitis (EPOS) epidemiologic criteria. We defined 6 symptom groups over time on the basis of the presence of CRS symptoms at baseline and follow-up. We performed multivariable survey logistic regression controlling for confounding variables comparing persistent versus nonpersistent, recurrent versus stable past, and incident versus never. RESULTS: There were 4,966 responders at follow-up: 558 had persistent symptoms, 190 recurrent symptoms, and 83 new symptoms meeting EPOS criteria for CRS. The prevalence of persistent symptoms was 4.8% (95% CI, 3.8-5.8), whereas the annual cumulative incidence of new symptoms was 1.9% and of recurrent symptoms was 3.2%. More severe symptoms at baseline were associated with persistence, whereas minor symptoms, allergies, and multiple treatments were associated with the development of new symptoms. CONCLUSIONS: Less than half with nasal and sinus symptoms meeting CRS EPOS criteria in our general, regional population had symptom persistence over time, with symptom profiles at baseline and age of onset being strongly associated with stability of symptoms.

Lingual thyroid carcinoma with nodal metastasis.

OBJECTIVES: To discuss treatment options and surgical management of lingual thyroid carcinoma with cervical metastasis. STUDY DESIGN: Lingual thyroid is relatively uncommon, and carcinoma of the lingual thyroid is extremely rare, with only 40 cases reported. We report a new case of a young female who presented with a cervical neck mass found to represent metastatic papillary thyroid carcinoma. Further workup revealed the patient's only thyroid tissue was located at the tongue base and was the site of the primary tumor. Management of lingual thyroid carcinoma and review of the literature is discussed. METHODS: A case report and review of the literature of lingual thyroid carcinoma. RESULTS: A young female presented with a left neck mass diagnosed as metastatic papillary thyroid carcinoma. Review of the computed tomography scan of the neck revealed a tongue base mass, absence of an othotopic thyroid gland and bilateral cervical lymphandenopathy. Bilateral selective neck dissections with removal of the tongue base lesion confirmed the diagnosis of lingual thyroid carcinoma with multiple left cervical nodal metastases. CONCLUSIONS: A case of lingual papillary thyroid carcinoma with cervical metastasis is reported. Treatment is best managed with surgical excision of all thyroid tissue followed by radioactive iodine ablation. Surgical approaches to the tongue base need to be considered based on the size of the lingual primary tumor and the need to address lymph node metastases gland. This is the first reported case in the literature of lingual papillary thyroid carcinoma presenting with cervical nodal metastasis in a female with absence of an orthotopic thyroid gland. This is also the first report to show that papillary and not follicular cell carcinoma is the predominating histopathology in lingual thyroid carcinoma.

Morphoproteomic and pharmacoproteomic rationale for mTOR effectors as therapeutic targets in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has a relatively high mortality rate and poor prognosis. Recently, we showed that overexpression of phosphorylated (p) nuclear factor-kappaB (NF-kappaB) in squamous cell carcinoma of the tonsil (SCCT) and high grade dysplasia is associated with a poor prognosis. Because the mammalian target of the rapamycin (mTOR) pathway contributes to the activation of NF-kappaB through immunophilin/mTOR signaling, we investigated: (a) the immunohistochemical expression and state of activation and potential clinical significance of components of the mTOR signal transduction pathway in SCCT patients (morphoproteomics); and (b) the inhibitory effects of rapamycin on the growth and state of activation of mTOR in 2 HNSCC cell lines (pharmacoproteomics). Archival biopsy materials from 39 patients with SCCT were studied by immunohistochemistry for the expression of p-mTOR (Ser 2448), and p-p70S6K (Thr 389), and/or cyclin D1. Results for SCCT were compared with adjacent non-neoplastic epithelium, when present, and with normal tonsillar epithelium from approximately age-matched controls; clinical outcomes were also assessed. SCCT showed mTOR (Ser 2448) expression in 93% (30/32 cases) with 2+ or 3+ plasmalemmal and/or cytoplasmic intensity in 84% vs 42% in surface epithelium from normal tonsils (p <0.001). The mean combined expression score (signal intensity x percentage of positive cells) for p-p70S6K was significantly greater in the SCCT group vs adjacent non-neoplastic squamous epithelium and normal tonsillar epithelium of the control group (p <0.05). A relationship existed between higher p-p70S6K expression levels in the non-neoplastic squamous epithelium adjacent to the SCCT and increased risk of death from disease (hazard ratio = 7.9; 95% confidence interval (CI) = 2.1 to 29.9; p = 0.002). There was also a relationship between nuclear expression of cyclin D1 in SCCT and shortened recurrence-free survival (p = 0.015). Two human HNSCC cell lines, SCC-15 and FaDu, were incubated with and without rapamycin to assess its impact on growth and on the expression of p-mTOR. Rapamycin in a dose-dependent fashion inhibited growth more in SCC-15, which correlated with a greater reduction in constitutively activated p-mTOR (Ser 2448) as shown by Western blotting. In conclusion, these morphoproteomic and pharmacoproteomic data collectively provide a rationale for selecting mTOR effectors as therapeutic targets in HNSCC.

Nuclear factor-kappaB pathway as a therapeutic target in head and neck squamous cell carcinoma: pharmaceutical and molecular validation in human cell lines using Velcade and siRNA/NF-kappaB.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is synthesized in the cytoplasm, complexed with its inhibitor, I-kappaB, and NF-kappaB is released in an activated (phosphorylated) form following phosphorylation of I-kappaB and proteasomal degradation of the NF-kappaB.p-kappaB complex. The free p-NF-kappaB can then be translocated to the nucleus where it effects transcriptional activation of genes leading to the synthesis of proteins that are generally pro-growth and anti-apoptosis. OBJECTIVE: To gain insight into the role of the NF-kappaB pathway in head and neck squamous cell carcinoma (HNSCC), we selected two HNSCC cell lines, SCC-15 of lingual origin and FaDu of pharyngeal origin, with constitutively activated (phosphorylated) NF-kappaB. We assessed the impact of interrupting the NF-kappaB pathway at the level of proteasomal degradation using Velcade (bortezomib), a proteasome inhibitor, and at the pretranslational level in the synthesis of NF-kappaB using a small interfering RNA (siRNA). RESULTS: Velcade produced a dose-dependent inhibition of cell growth in both cell lines. At 30 nM, Velcade inhibited cell growth in the SCC-15 cell line by 40%. In both cell lines, Velcade induced nuclear overexpression of p21(WAF1), an inhibitor of G1 cell cycle progression, which appeared to be independent of p53 expression. Addition of siRNA augmented the inhibitory effects of Velcade in FaDu cells; siRNA/NF-kappaB alone led to a 48% decline in basal expression of NF-kappaB protein levels and effected a 25% inhibition of cell growth. In the presence of Velcade (30 nM), siRNA/NF-kappaB increased growth inhibition from 43 to 65%. CONCLUSIONS: The mechanisms involved in growth inhibitory effects of Velcade on HNSCC cell lines include the NF-kappaB pathway, suggesting the possible therapeutic use of Velcade or other NF-kappaB pathway inhibitors (eg, curcumin). The data also suggest that combining siRNA/NF-kappaB with Velcade might achieve greater reduction in the growth of HNSCC in patients with constitutively activated NF-kappaB.

Occupational and environmental risk factors for chronic rhinosinusitis: a systematic review.

BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent and disabling paranasal sinus disease, with a likely multifactorial etiology potentially including hazardous occupational and environmental exposures. We completed a systematic review of the occupational and environmental literature to evaluate the quality of evidence of the role that hazardous exposures might play in CRS. METHODS: We searched PubMed for studies of CRS and following exposure categories: occupation, employment, work, industry, air pollution, agriculture, farming, environment, chemicals, roadways, disaster, and traffic. We abstracted information from the final set of articles across 6 primary domains: study design; population; exposures evaluated; exposure assessment; CRS definition; and results. RESULTS: We identified 41 articles from 1080 manuscripts: 37 occupational risk papers, 1 environmental risk paper, and 3 papers studying both categories of exposures. None of the 41 studies used a CRS definition consistent with current diagnostic guidelines. Exposure assessment was generally dependent on self-report or binary measurements of exposure based on industry of employment. Only grain, dairy, and swine operations among farmers were evaluated by more than 1 study using a common approach to defining CRS, but employment in these settings was not consistently associated with CRS. The multiple other exposures did not meet quality standards for reporting associations or were not evaluated by more than 1 study. CONCLUSION: The current state of the literature allows us to make very few conclusions about the role of hazardous occupational or environmental exposures in CRS, leaving a critical knowledge gap regarding potentially modifiable risk factors for disease onset and progression.

Strobovideolaryngoscopy in the management of acute laryngeal trauma.

Surgical intervention in the management of acute laryngeal trauma can sometimes pose a difficult decision. The objective of this study is to evaluate the effectiveness of strobovideolaryngoscopy (SVL) in determining the course of management for patients sustaining acute laryngeal trauma. A 20-year retrospective study of patients presenting with acute laryngeal trauma was performed in order to determine if the addition of SVL during the study period changed the management of certain acute laryngeal injuries. Patients sustaining blunt laryngeal trauma evaluated at our institution from 1981 to the present were reviewed. There were 40 patients identified that were grouped by severity according to the Schaefer classification. Analysis included mechanism of injury, clinical presentation, assessment, treatment, and outcome. Group 1 injuries were the most common, with motor vehicle accident (MVA) the most frequent mechanism of injury. Initial assessment included fiberoptic laryngoscopy and computed tomography (CT) imaging in all patients not requiring immediate exploration. SVL was used in 20 patients, with 7 undergoing stroboscopy within 24 hours of presentation. All 7 patients were managed conservatively without surgical intervention or the need to establish an alternative airway. SVL improves the clinical assessment of patients with acute laryngeal injury. This study supports its use and found it to be an important factor in determining the need for surgical intervention. SVL may also shorten the hospital stay in these patients.

Outdoor grilling hazard: wire bristle esophageal foreign body--a report of six cases.

Esophageal foreign bodies are frequently encountered, with coin ingestion the most common in the pediatric population and fish bone ingestion the most common in the adult population worldwide. Many people cook with outdoor grills and use wire brushes to clean them. We present the largest case series with six adult cases involving ingestion of wire brush bristles from food prepared on outdoor grilling surfaces. The occurrence of six cases within a small geographic area over a relatively brief time span raises important safety concerns and warrants attention to prevent serious complications.

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis.

Intracellular signals along the epidermal growth factor receptor (EGFR)-Akt-nuclear factor-kappa B (NF-kappaB) pathway have been associated with carcinogenesis in various malignant neoplasms. This investigation was to evaluate the expression of EGFR, phosphorylated(p)-Akt and p-NF-kappaB and correlate them with clinical outcomes in patients with squamous cell carcinoma of the tonsil. A total of 45 patients with squamous cell carcinoma of the tonsil were studied by immunohistochemistry to evaluate the expression levels of EGFR, p-Akt and p-NF-kappaB. Results for squamous cell carcinoma of the tonsil were compared with those for associated high-grade dysplasia and adjacent normal appearing epithelium, when present. In addition, tonsillar epithelium from non-neoplastic specimens of age-matched patients also was stained for the same markers. High-grade dysplasia and squamous cell carcinoma of the tonsil demonstrated a similar pattern of expression, which differed from the pattern seen in the adjacent normal epithelium and tonsillar epithelium from normal controls (an overexpression for each of these three protein analytes in high-grade dysplasia and squamous cell carcinoma of the tonsil as demonstrated by immunohistochemistry). When markers from squamous cell carcinoma of the tonsil were correlated with survival status, only increasing levels of p-NF-kappaB immunoreactivity (a relative overexpression) were statistically significant predictors of poor survival. No markers in squamous cell carcinoma of the tonsil were significantly related to rate of recurrence. When analyzing marker scores from tissue with high-grade dysplasia, relative overexpressions of both p-Akt and p-NF-kappaB were significantly related to poor survival. Additionally, increasing levels of p-NF-kappaB immunopositivity from tissue with high-grade dysplasia were also significantly related to rate of recurrence. In summary, p-NF-kappaB, overexpressed in high-grade dysplasia and squamous cell carcinoma of the tonsil, is associated with worse prognosis in terms of high recurrence and poor survival, respectively. This significant finding in patients with squamous cell carcinoma of the tonsil, in combination with previous animal and in vitro studies, suggests that p-NF-kappaB represents a potential therapeutic target in head and neck squamous cell carcinoma.