Bevan Yueh

Development and validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale.

OBJECTIVE: The study goal was to validate a disease-specific health status instrument for use in patients with nasal obstruction. DESIGN, SETTINGS, AND PATIENTS: The study consisted of a prospective instrument validation conducted at 4 academic medical centers with 32 adults with nasal septal deformity. METHODS: Prospective instrument validation occurred in 2 stages. Stage 1 was the development of a preliminary (alpha-version) instrument of potential items. Stage 2 was a test of the alpha-version for item performance, internal consistency, and test-retest reliability; construct, discriminant, criterion validity, and responsiveness; and creation of the final instrument. RESULTS: Items with poor performance were eliminated from the alpha-version instrument. In testing the final instrument, test-retest reliability was adequate at 0.702; internal consistency reliability was also adequate at 0.785. Validity was confirmed using correlation and comparison analysis, and response sensitivity was excellent. CONCLUSIONS: The Nasal Obstruction Symptom Evaluation Scale is a valid, reliable, and responsive instrument that is brief and easy to complete and has potential use for outcomes studies in adults with nasal obstruction.

Incidence of Suicide in Persons With Cancer

PURPOSE The purpose of this study was to characterize suicide rates among patients with cancer in the United States and identify patient and disease characteristics associated with higher suicide rates. Prior studies, mostly in Europe, have suggested that patients with cancer may be at increased risk for suicide, but large cohort studies comparing patients with cancer with the general population have not been performed in the United States. METHODS Patients in the study were residents of geographic areas served by the Surveillance, Epidemiology, and End Results (SEER) program who were diagnosed with cancer from 1973 to 2002. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. This was a retrospective cohort study of suicide in persons with cancer. RESULTS Among 3,594,750 SEER registry patients observed for 18,604,308 person-years, 5,838 suicides were identified, for an age-, sex-, and race-adjusted rate of 31.4/100,000 person-years. In contrast, the suicide rate in the general US population was 16.7/100,000 person-years. Higher suicide rates were associated with male sex, white race, and older age at diagnosis. The highest suicide risks were observed in patients with cancers of the lung and bronchus (standardized mortality ratio [SMR] = 5.74; 95% CI, 5.30 to 6.22), stomach (SMR = 4.68; 95% CI, 3.81 to 5.70), oral cavity and pharynx (SMR = 3.66; 95% CI, 3.16 to 4.22), and larynx (SMR = 2.83; 95% CI, 2.31 to 3.44). SMRs were highest in the first 5 years after diagnosis with cancer. CONCLUSION Patients with cancer in the United States have nearly twice the incidence of suicide of the general population, and suicide rates vary among patients with cancers of different anatomic sites. Further examination of the psychological experience of patients with cancer, particularly that of patients with certain types of cancer, is warranted.

Outcomes after nasal septoplasty: Results from the Nasal Obstruction Septoplasty Effectiveness (NOSE) study ☆

OBJECTIVE: Our goal was to assess disease-specific quality of life outcomes after nasal septoplasty in adults with nasal obstruction. DESIGN, SETTINGS, AND PATIENTS: We conducted a prospective observational outcomes multicenter study with 14 sites and 16 investigators, including private practice and academic settings. Patients had had septal deviation and symptomatic nasal obstruction for at least 3 months, and medical management had failed. METHODS: Patients with septal deviation completed a validated outcomes instrument (the Nasal Obstruction Septoplasty Effectiveness (NOSE) scale) before and 3 and 6 months after septoplasty, with or without partial turbinectomy. RESULTS: Fifty-nine patients underwent surgery; there was a significant improvement in mean NOSE score at 3 months after septoplasty (67.5 versus 23.1, P < 0.0001), and this improvement was unchanged at 6 months. Patient satisfaction was very high, and patients used significantly fewer nasal medications. CONCLUSIONS: In patients with septal deformity, nasal septoplasty results in significant improvement in disease-specific quality of life, high patient satisfaction, and decreased medication use. (Otolaryngol Head Neck Surg 2004;130:283–90.)

FDG-PET/CT–guided intensity modulated head and neck radiotherapy: A pilot investigation†‡

2‐deoxy‐2[18F]fluoro‐d‐glucose–positron emission tomography (FDG‐PET) imaging can be registered with CT images and can potentially improve neck staging sensitivity and specificity in patients with head and neck squamous cell cancer. The intent of this study was to examine the use of registered FDG‐PET/CT imaging to guide head and neck intensity modulated radiotherapy (IMRT) planning.

Gene Expression Profiling Identifies Genes Predictive of Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is associated with substantial mortality and morbidity. To identify potential biomarkers for the early detection of invasive OSCC, we compared the gene expressions of incident primary OSCC, oral dysplasia, and clinically normal oral tissue from surgical patients without head and neck cancer or preneoplastic oral lesions (controls), using Affymetrix U133 2.0 Plus arrays. We identified 131 differentially expressed probe sets using a training set of 119 OSCC patients and 35 controls. Forward and stepwise logistic regression analyses identified 10 successive combinations of genes which expression differentiated OSCC from controls. The best model included LAMC2, encoding laminin-γ2 chain, and COL4A1, encoding collagen, type IV α1 chain. Subsequent modeling without these two markers showed that COL1A1, encoding collagen, type I α1 chain, and PADI1, encoding peptidyl arginine deiminase, type 1, could also distinguish OSCC from controls. We validated these two models using an internal independent testing set of 48 invasive OSCC and 10 controls and an external testing set of 42 head and neck squamous cell carcinoma cases and 14 controls (GEO GSE6791), with sensitivity and specificity above 95%. These two models were also able to distinguish dysplasia (n = 17) from control (n = 35) tissue. Differential expression of these four genes was confirmed by quantitative reverse transcription-PCR. If confirmed in larger studies, the proposed models may hold promise for monitoring local recurrence at surgical margins and the development of second primary oral cancer in patients with OSCC. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2152–62)

Predictors of wound complications after laryngectomy: A study of over 2000 patients

OBJECTIVES: To identify risk factors for and the rate of wound complications after laryngectomy in a large, prospectively collected national dataset, and to generate a predictive model. STUDY DESIGN: We used the National Surgical Quality Improvement Program (NSQIP) registry created by the Department of Veterans Affairs (VA) to identify patients undergoing total laryngectomy from 1989 to 1999 (n = 2063). We linked these data to inpatient and outpatient VA administrative records to capture data for prior radiation. Over 20 preoperative and intraoperative risk factors were analyzed using bivariate techniques. Those significant at the P < 0.01 level were analyzed with logistic regression and conjunctive consolidation to identify independent predictors of wound complications. RESULTS: The overall wound complication rate was 10.0%. In adjusted analyses, prolonged operative time (> 10 hours, odds ratio = 2.10, 95% confidence interval: 1.32-3.36), exposure to prior radiation therapy (OR =1.63, 1.07-2.46), presence of diabetes (OR = 1.78, 1.04-3.04), preoperative hypoalbumine-mia (OR =1.90, 1.32-2.74), anemia (OR =1.59, 1.07-2.36), and thrombocytosis (OR =1.48, 1.04-2.10) were independently associated with postoperative wound complications. A prognostic model using three variables—prior radiation therapy, diabetes, and hypoalbuminemia—provided excellent risk stratification into three tiers (6.3%, 13.7%, 21.7%). CONCLUSIONS: Preoperative radiation, prolonged operative time, low albumin, and diabetes were independently associated with postoperative wound infections. These results will help to identify patients at risk for wound complications, thus allowing for heightened surveillance and preventive measures where possible.

Incidence of serious complications after Uvulopalatopharyngoplasty

Objectives Uvulopalatopharyngoplasty (UPPP) is the most common surgical treatment for obstructive sleep apnea (OSA). Anatomic and physiologic abnormalities associated with OSA can make perioperative management difficult. Only single‐site case series provide current estimates of the incidence of perioperative complications, with a pooled crude serious complication rate of 3.5% and a crude mortality rate of 0.4%. The primary objective of this study was to calculate the incidence of perioperative morbidity and mortality in a large, multisite cohort of UPPP patients.

Clinical Assessment of Music Perception in Cochlear Implant Listeners

Objective: Cochlear implants (CI) have provided tremendous benefit for speech recognition in quiet for patients with severe and profound hearing impairment, but implant users still have great difficulty perceiving music. The purpose of this study was to develop a test to quantify music perception by CI listeners in a clinically practical manner that could be standardized for administration at any implant center. Study Design: Prospective convenience sample. Setting: Hearing research center at an academic hospital. Patients: Eight CI listeners, including 5 men and 3 women with implant experience ranging from 0.5 to 6 years, participated in this study. They represented a variety of implant devices and strategies. Intervention: Administration of the Clinical Assessment of Music Perception test in a standardized sound field. Main Outcome Measures: Music perception was assessed using a computerized test comprising pitch direction discrimination, melody identification, and timbre identification. The pitch subtest used a 2-alternative forced-choice adaptive procedure to determine a threshold interval for discrimination of complex pitch direction change. The melody and timbre subtests assessed recognition of 12 isochronous melodies and 8 musical instruments, respectively. Results: Testing demonstrated a broad range of perceptual accuracy on all 3 subtests. Test duration averaged less than 45 minutes. Conclusion: Clinical Assessment of Music Perception is an efficient computerized test that may be used to measure 3 different aspects of music perception in CI users in a standardized and clinically practical manner.

Genomewide Gene Expression Profiles of HPV-Positive and HPV-Negative Oropharyngeal Cancer: Potential Implications for Treatment Choices

OBJECTIVE To study the difference in gene expression between human papillomavirus (HPV)-positive and HPV-negative oral cavity and oropharyngeal squamous cell carcinoma (OSCC). DESIGN We used Affymetrix U133 plus 2.0 arrays to examine gene expression profiles of OSCC and normal oral tissue. The HPV DNA was detected using polymerase chain reaction followed by the Roche LINEAR ARRAY HPV Genotyping Test, and the differentially expressed genes were analyzed to examine their potential biological roles using the Ingenuity Pathway Analysis Software, version 5.0. SETTING Three medical centers affiliated with the University of Washington. PATIENTS A total of 119 patients with primary OSCC and 35 patients without cancer, all of whom were treated at the setting institutions, provided tissues samples for the study. RESULTS Human papillomavirus DNA was found in 41 of 119 tumors (34.5%) and 2 of 35 normal tissue samples (5.7%); 39 of the 43 HPV specimens were HPV-16. A higher prevalence of HPV DNA was found in oropharyngeal cancer (23 of 31) than in oral cavity cancer (18 of 88). We found no significant difference in gene expression between HPV-positive and HPV-negative oral cavity cancer but found 446 probe sets (347 known genes) differentially expressed in HPV-positive oropharyngeal cancer than in HPV-negative oropharyngeal cancer. The most prominent functions of these genes are DNA replication, DNA repair, and cell cycling. Some genes differentially expressed between HPV-positive and HPV-negative oropharyngeal cancer (eg, TYMS, STMN1, CCND1, and RBBP4) are involved in chemotherapy or radiation sensitivity. CONCLUSION These results suggest that differences in the biology of HPV-positive and HPV-negative oropharyngeal cancer may have implications for the management of patients with these different tumors.

Pilot Randomized Phase II Study of Celecoxib in Oral Premalignant Lesions

Purpose: Cyclooxygenase-2 (COX-2)–specific inhibition suppresses carcinogenesis in preclinical models and is a promising strategy for preventing oral cancer. In this pilot randomized phase II study, we evaluated the efficacy and safety of the COX-2 inhibitor celecoxib in patients with oral premalignant lesions (OPL). Experimental Design: Patients were randomly assigned to placebo (n = 18), celecoxib 100 mg twice daily (n = 17), or celecoxib 200 mg twice daily (n = 15) for 12 weeks. Six additional patients received celecoxib (400 mg twice daily) in an unblinded extension of the study. Biopsies were obtained at baseline and week 12. All patients entering the study were required to have at least one histologically confirmed early (atypical hyperplasia, atypical hyperkeratosis, or mild dysplasia) or advanced (moderate to severe dysplasia) OPL. Results: Forty-nine patients (46 of 50 randomized and 3 of 6 open label) were evaluable for efficacy analyses. There were no statistically significant differences between the response rates of the randomly assigned arms: placebo, 33.3% (6 of 18); celecoxib 100 mg twice daily, 41.2% (7 of 17); and celecoxib 200 mg twice daily, 20.0% (3 of 15). Two patients responded on celecoxib 400 mg twice daily. Celecoxib was generally well tolerated. Patients with higher baseline COX-2 mRNA levels had an increased risk of disease progression within 3 months. Conclusions: Celecoxib at 100 or 200 mg twice daily was ineffective in controlling OPLs in this randomized controlled trial. This result and cardiovascular toxicity results of other (large scale) randomized controlled trials of selective COX-2 inhibitors have discouraged the continued investigation of these agents in oral cancer chemoprevention. Better methods for identifying high-risk patients and more active interventions are needed for future oral cancer chemoprevention trials.