Ergonomic analysis of microlaryngoscopy.

OBJECTIVES/HYPOTHESIS: To apply ergonomic principles in analysis of three different operative positions used in laryngeal microsurgery. STUDY DESIGN: Prospective case-control study. METHODS: Laryngologists were studied in three different microlaryngeal operative positions: a supported position in a chair with articulated arm supports, a supported position with arms resting on a Mayo stand, and a position with arms unsupported. Operative positions were uniformly photographed in three dimensions. Full body postural data was collected and analyzed using the validated Rapid Upper Limb Assessment (RULA) tool to calculate a risk score indicative of potential musculoskeletal misuse in each position. Joint forces were calculated for the neck and shoulder, and compression forces were calculated for the L5/S1 disc space. RESULTS: Higher-risk postures were obtained with unfavorably adjusted eyepieces and lack of any arm support during microlaryngeal surgery. Support with a Mayo stand led to more neck flexion and strain. Using a chair with articulated arm supports leads to decreased neck strain, less shoulder torque, and decreased compressive forces on the L5/S1 disc space. Ideal postures during microlaryngoscopy place the surgeon with arms and feet supported, with shoulders in an unraised, neutral anatomic position, upper arms neutrally positioned 20 degrees to 45 degrees from torso, lower arms neutrally positioned 60 degrees to 100 degrees from torso, and wrists extended or flexed <15 degrees. CONCLUSIONS: RULA and biomechanical analyses have identified lower-risk surgeon positioning to be utilized during microlaryngeal surgery. Avoiding the identified high-risk operative postures and repetitive stress injury may lead to reduced occupationally related musculoskeletal pain and may improve microsurgical motor control.

Genetic screening for oral human papillomavirus infections and cancers of the head and neck.

Detection and type-specific identification of human papillomavirus infection obtained from oral rinse sampling may have future clinical utility for identifying individuals at higher risk for a subset of oropharyngeal cancers.

Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in head and neck squamous cell carcinoma (HNSCC) where expression levels correlate with decreased survival. Therapies that block EGFR have shown limited efficacy in clinical trials and primarily when combined with standard therapy. The most common form of mutant EGFR (EGFRvIII) has been described in several cancers, chiefly glioblastoma. The present study was undertaken to determine the incidence of EGFRvIII expression in HNSCC and the biological consequences of EGFRvIII on tumor growth in response to EGFR targeting. EXPERIMENTAL DESIGN: Thirty-three HNSCC tumors were evaluated by immunostaining and reverse transcription-PCR for EGFRvIII expression. A representative HNSCC cell line was stably transfected with an EGFRvIII expression construct. EGFRvIII-expressing cells and vector-transfected controls were compared for growth rates in vitro and in vivo as well as chemotherapy-induced apoptosis and the consequences of EGFR inhibition using the chimeric monoclonal antibody C225/cetuximab/Erbitux. RESULTS: EGFRvIII expression was detected in 42% of HNSCC tumors where EGFRvIII was always found in conjunction with wild-type EGFR. HNSCC cells expressing EGFRvIII showed increased proliferation in vitro and increased tumor volumes in vivo compared with vector-transfected controls. Furthermore, EGFRvIII-transfected HNSCC cells showed decreased apoptosis in response to cisplatin and decreased growth inhibition following treatment with C225 compared with vector-transfected control cells. CONCLUSIONS: EGFRvIII is expressed in HNSCC where it contributes to enhanced growth and resistance to targeting wild-type EGFR. The antitumor efficacy of EGFR targeting strategies may be enhanced by the addition of EGFRvIII-specific blockade.

Differential diagnosis of eosinophilic chronic rhinosinusitis.

Eosinophilic chronic rhinosinusitis (ECRS) encompasses a wide variety of etiologies. To date, a unifying pathophysiologic mechanism remains elusive. Eosinophilia is frequently, but not exclusively, caused by immunoglobulin (Ig)E-mediated hypersensitivity and is dominated by the associated cytokine milieu of Th2 inflammation. The provisional subcategories of ECRS include superantigen-induced eosinophilic chronic rhinosinusitis, allergic fungal sinusitis, nonallergic fungal eosinophilic chronic rhinosinusitis, and aspirin-exacerbated eosinophilic chronic rhinosinusitis. Within each subcategory, recent findings supporting distinct mechanisms that promote eosinophilic infiltration are presented, and, therefore, targeted therapeutic interventions with specific antibacterial, antifungal, or immune modulation may be indicated.

Signaling through the epidermal growth factor receptor during the development of malignancy.

The epidermal growth factor receptor (EGFR) is overexpressed and/or constitutively activated in a variety of human malignancies. Detection of increased expression levels of EGFR in cancer and the association between overexpression and decreased patient survival has led to the development of several therapeutic strategies to target this receptor. The results of early-phase clinical trials to date suggest that targeting EGFR alone may not be sufficient to eradicate established tumors. This limited antitumor efficacy as monotherapy has led to combining EGFR inhibitors with chemotherapy or radiation therapy for advanced disease, or incorporating EGFR inhibition to cancer prevention approaches. This review will discuss the role of EGFR signaling in carcinogenesis and the rationale for EGFR inhibition as a clinical prevention and treatment strategy.

Tissue-specific gene expression of head and neck squamous cell carcinoma in vivo by complementary DNA microarray analysis.

OBJECTIVES: To identify distinct gene expression profiles of human head and neck squamous cell carcinomas (HNSCCAs) using complementary DNA (cDNA) microarray analysis and to create a preliminary, comprehensive database of HNSCCA gene expression. PATIENTS AND METHODS: Nine patients with histologically confirmed HNSCCAs, staged according to the American Joint Committee on Cancer, were enrolled. The HNSCCA tumor tissue and normal mucosal tissue were harvested at the time of surgery. A cDNA library was constructed from the paired fresh-frozen human surgical specimens of HNSCCAs and nonmalignant epithelial tissues. Biotinylated RNA was transcribed from the cDNA library and hybridized to high-density microarrays containing approximately 12 000 human genes. Altered gene expression of HNSCCAs was identified by comparison to corresponding normal mucosal tissues after a bayesian statistical analysis of variance. Results were analyzed using the gene database of the National Institutes of Health. Hierarchical clustering of the genomic data sets was determined by similarity metrics based on Pearson correlation. RESULTS: Hierarchical clustering analysis revealed that the gene expression profiles obtained from the nonselected panel of 12 000 genes could distinguish the tumors from nonmalignant tissues. Gene expression changes were reproducibly observed in 227 genes representing previously identified chemokines, tumor suppressors, differentiation markers, matrix molecules, membrane receptors, and transcription factors that correlated with neoplasia, including 46 previously uncharacterized genes. Moreover, significant expression of the collagen type XI alpha1 gene and a novel gene was reproducibly observed in all 9 tumors, whereas these genes were virtually undetectable in their corresponding, adjacent nonmalignant tissues. CONCLUSIONS: Complementary DNA microarray analysis of human HNSCCAs has produced a preliminary, comprehensive database of tumor-specific gene expression profiles and provided important insights into modeling gene expression changes implicated in carcinogenesis. A large-scale analysis of gene expression carries the future potential of identifying sensitive molecular markers for early tumor detection, prognosis, and novel targets for interceptive therapeutics.