Serial full-thickness excision of dysplastic vocal fold leukoplakia: Diagnostic or therapeutic?

OBJECTIVES/HYPOTHESIS: A previous study proposed that serial full-thickness excisional biopsies of vocal fold leukoplakia therapeutically decreased dysplasia grade. The current investigation aimed to 1) analyze the pathological evolution and natural history of these lesions and 2) re-examine the role of serial excisions in dysplasia grade regression in long-term follow-up. STUDY DESIGN: Retrospective case series. METHODS: Patients treated for vocal fold dysplasia (1994-2013) with serial full-thickness microflap-type excisions were identified and followed longitudinally. Excluded were those with one excision, invasive cancer at initial excision, or history of laryngeal cancer or radiation. Data from surgical procedures, associated pathology, and patient characteristics were recorded. Weighted repeated measures ordinal logistic regression measured associations with pathology findings. RESULTS: Of 55 patients (median age = 65 years, interquartile range = 54-73 years, 89% male, 63% ever smokers, 27% alcohol users), 31 met inclusion criteria. During the study period, patients had two to 44 excisions, with a median time between excisions of 4.0 months. Each additional excision increased odds of higher-grade pathology by 4% (odds ratio = 1.04, 95% confidence interval = 1.01-1.06; P = .007). A transition model demonstrated that patients with moderate dysplasia, severe dysplasia, or carcinoma in situ on a prior biopsy had 2.64-, 5.64-, and 8.73-times increased odds of the same or higher pathology grade at the next excision, respectively. CONCLUSIONS: Data do not support the hypothesis that serial full-thickness excisions decrease dysplasia grade. Progression of dysplasia appears to be nonlinear, but higher-grade dysplasia is more likely to progress to malignancy. LEVEL OF EVIDENCE: 4.

Natural progression of dysplasia in adult recurrent respiratory papillomatosis.

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is often described as a benign disease. However, the natural progression of dysplasia and transformation to squamous cell carcinoma has not been elucidated for RRP. This study delineates our extensive experience with dysplasia in RRP. STUDY DESIGN/SETTING: Case series with chart review. SUBJECTS AND METHODS: Demographic data and surgical pathology were analyzed for patients diagnosed with RRP at greater than 18 years of age who underwent operative intervention without cidofovir treatment for RRP between 2004 and 2009. RESULTS: Fifty-four patients were identified. Dysplasia was identified in 27 of 54 patients (50%). Of the 54 patients, 50% had no dysplasia, 26% had mild dysplasia (grade 1), 11% had moderate dysplasia (grade 2), 4% had severe dysplasia (grade 3), 7% had carcinoma in situ, and 2% had squamous cell carcinoma as the highest documented degree of dysplasia. Thirty of 54 patients (55.6%) had 2 or more operative interventions. Nine of the 30 patients (30%) developed a higher dysplastic grade during the course of treatment. Time to progression averaged 16.2 ± 8.7 months for patients with initially benign disease. Of those patients with dysplasia progression, only 1 of 9 (11.1%) developed squamous cell carcinoma. Patients presenting with benign or mild dysplasia typically did not progress beyond mild dysplasia (22 of 24, 91.7%). CONCLUSIONS: Dysplasia is common in RRP. Progression of dysplasia, especially with an initial dysplastic grading of benign or mild disease, is rare.

Fellowship and career path preferences in residents of otolaryngology-head and neck surgery.

OBJECTIVES/HYPOTHESIS: Assess fellowship and academic/private practice career track preferences in residents of otolaryngology-head and neck surgery. STUDY DESIGN: Cross-sectional survey. METHODS: A total of 1,364 U.S. otolaryngology residents were surveyed. Questions addressed demographics, work hours and sleep, fellowship preference, and career track preference (academic/private practice). Trends in fellowship and career track preference were analyzed by year of clinical otolaryngology training. Data were additionally analyzed after stratification by sex. RESULTS: The response rate was 50%. The desire to complete a fellowship declined from 62% (year 2) to 58% (year 5), whereas the desire to not complete a fellowship increased from 31% (year 2) to 41% (year 5). Fellowship interest increased for rhinology and head and neck surgery by training year, whereas interest declined for neurotology and facial plastics. Expectation of an academic path increased from 29% (year 2) to 38% (year 5), whereas expectation of private practice declined slightly from 59% (year 2) to 57% (year 5). Women were initially more interested in both completing a fellowship (69% women, 60% men) and academics (40% women, 27% men). At the end of training, these sex differences were eliminated or reversed (59% men, 54% women for fellowship; 39% men, 35% women for academics). Residents interested in pursuing fellowship or academics reported working 2 hr/week more than those interested in no fellowship or private practice, respectively (P < 0.01). CONCLUSIONS: Fellowship and career track preferences suggest trends that may be useful to residency/fellowship program directors and residents making career choices. Inequalities producing differences according to sex should be addressed.

Acute dysphonia secondary to vocal fold hemorrhage after vardenafil use.

Owing to their vasodilatory effects, the phosphodiesterase-5 inhibitors have become widely used for the treatment of erectile dysfunction. Among the reported adverse events of these agents are epistaxis, variceal bleeding, intracranial hemorrhage, and hemorrhoidal bleeding. We report a case of vocal fold hemorrhage that occurred after vardenafil use in a 31-year-old man who was a professional singer.

Regenerative effects of basic fibroblast growth factor on extracellular matrix production in aged rat vocal folds.

OBJECTIVES: We investigated acute changes in extracellular matrix (ECM) gene expression and histologic changes in the deposition of collagen and hyaluronan (hyaluronic acid; HA) after basic fibroblast growth factor (bFGF) treatment of the aged rat vocal fold. METHODS: For the polymerase chain reaction (PCR) experiments, we divided ten 18-month-old Sprague-Dawley rats into two groups that received serial injections of sham (saline solution) or bFGF (2 ng/microL) and euthanized them 2 weeks after the initial injection to investigate acute changes in ECM gene expression. We treated a separate group of 5 animals unilaterally and sacrificed them 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA. RESULTS: Real-time PCR revealed significantly up-regulated HA synthase (HAS)-2, HAS-3, matrix metalloproteinase (MMP)-2, and procollagen type I gene expression in the bFGF treatment group as compared to the sham treatment group. Histologic staining revealed significantly increased deposition of HA in the bFGF-treated vocal fold as compared to the sham-treated vocal fold. No differences in ECM collagen levels were observed between treatment sides. CONCLUSIONS: Basic fibroblast growth factor induced the up-regulation of HAS-2, HAS-3, MMP-2, and procollagen type I. Histologically, aged vocal folds treated with bFGF revealed increased deposition of HA as compared to sham-treated vocal folds.

Regeneration of aged rat vocal folds using hepatocyte growth factor therapy.

OBJECTIVES/HYPOTHESIS: We investigated acute changes in extracellular matrix gene expression and histologic changes in the deposition of collagen and hyaluronan (HA) from hepatocyte growth factor (HGF) treatment of the aged rat vocal fold. We hypothesized that: 1) HGF induces matrix metalloproteinase gene expression, which might contribute to the downregulation of collagen; and 2) HGF induces hyaluronan synthase (HAS) gene expression, which might play a role in the upregulation of extracellular matrix HA. STUDY DESIGN: Prospective animal study. METHODS: Fifteen, 18-month-old, Sprague-Dawley rats were involved in this study. For gene expression analyses, 10 rats were divided into two groups and received serial injections of sham (saline) or HGF (2 ng/microL) and sacrificed 2 weeks after the initial injection to investigate acute changes in extracellular matrix gene expression. A separate group of five animals received the above treatment and were sacrificed 4 weeks after the initial injection to investigate histologic changes in the deposition of collagen and HA. RESULTS: Real-time polymerase chain reaction revealed significantly upregulated matrix metalloproteinase(MMP)-2, -9, and HAS-3 messenger RNA (mRNA) expression and significantly downregulated procollagen type I mRNA expression in the HGF-treatment group, compared to the sham-treatment group. Histologic staining revealed significantly reduced collagen deposition and increased deposition of HA in the HGF-treated vocal fold, compared to the sham-treated vocal fold. CONCLUSIONS: HGF induced the upregulation of MMP-2, -9, and HAS-3, and downregulated the expression of procollagen type I. Histologically, aged vocal folds treated with HGF revealed decreased collagen deposition, and increased deposition of HA, compared to sham-treated vocal folds.

Effect of hepatocyte growth factor on gene expression of extracellular matrix during wound healing of the injured rat vocal fold.

OBJECTIVES: We performed a prospective, sham-controlled animal study to investigate the effects of hepatocyte growth factor (HGF) manipulation of the extracellular matrix on vocal fold gene expression during acute injury. METHODS: Bilateral vocal fold wounds were created in 40 rats. The rats were randomly assigned to 1 of 2 groups (sham treatment or HGF treatment) and received treatment of the injured area at the time of wounding and on alternate posttreatment days. The injured vocal fold specimens were harvested on post-treatment days 1, 3, 7, and 14. We used real-time reverse transcription polymerase chain reaction to quantify messenger RNA expression of transforming growth factor (TGF)-beta1, procollagen types I and III, hyaluronan synthase (HAS)-1, HAS-2, and HAS-3. RESULTS: A multivariate analysis of variance revealed a significant interaction between treatment group and post-treatment day for TGF-beta1, procollagen type I, procollagen type III, and HAS-2. Post hoc testing revealed significantly lower expression of procollagen type III and significantly higher expression of HAS-2 on post-treatment day 14 in the HGF treatment group than in the sham treatment group. CONCLUSIONS: Results provide evidence of HGF treatment effects on procollagen type III and HAS-2 gene expression pathways.

Burnout in academic faculty of otolaryngology-head and neck surgery.

OBJECTIVE/HYPOTHESIS: To characterize burnout in academic faculty of otolaryngology-head and neck surgery. To identify associated modifiable factors to reduce burnout and improve the health of the field. STUDY DESIGN: Mailed survey. METHODS: A cross section of US academic otolaryngologists was sampled through a mailed survey. Content included the Maslach Burnout Inventory-Human Services Study (MBI-HSS) and questions assessing potential burnout predictors such as demographic information, professional stressors, satisfaction, self-efficacy, and support systems. RESULTS: Burnout was common among academic otolaryngologists. High burnout was observed in 4% of faculty, moderate burnout in 66%, and low burnout in 30%. Women experienced a statistically higher level of emotional exhaustion than men. In addition, associate professors were significantly more burned out than full professors and microvascular surgeons were notably more burned out than all other subspecialists. The strongest predictors of burnout were dissatisfaction with the balance between personal and professional life, low self-efficacy, inadequate research time, and inadequate administration time. A significant association was seen between high burnout and likelihood to leave academic medicine within the next 1 to 2 years. CONCLUSIONS: Burnout was prevalent among US academic otolaryngologists, although levels were lower than those of otolaryngology chairs and residents. Modification of risk factors, such as allowing sufficient faculty time for research and administrative activities, should be undertaken to curb the development of burnout and its deleterious sequelae.

Factors associated with perception of singing voice handicap.

OBJECTIVE: This study will determine factors that influence the self-perceived handicap associated with singing voice problems. STUDY DESIGN: A prospective cohort. SUBJECT AND METHODS: Singers presenting to a voice clinic prospectively completed the Singing Voice Handicap Index (SVHI) before evaluation and treatment. Demographic data, singing style, professional status, duration of symptoms, medical problems, and diagnosis were collected. Univariate and multivariate analysis was performed. RESULTS: One hundred seventy-one singers completed the SVHI. The duration of symptoms, being an amateur singer or singing teacher, benign vocal fold lesions, and neurologic voice disorders were associated with increased SVHI scores (P < 0.05, multiple linear regression). Age greater than 50 years and gospel singing were predictive of increased SVHI scores only on univariate analysis (P < 0.05, t test). CONCLUSION: Singers experience significant handicap as a result of their singing problems with certain factors associated with greater impairment. Targeting interventions at patients more severely affected may improve outcomes.

Experimentally induced phonation increases matrix metalloproteinase-1 gene expression in normal rabbit vocal fold.

OBJECTIVES: An in vivo rabbit model was used to study the effect of 3 hours of experimentally induced phonation on messenger RNA expression of the normal vocal fold. STUDY DESIGN: Prospective; animal model. SUBJECTS AND METHODS: Ten rabbits received experimental phonation for 3 hours, followed by 1 hour of recovery. A separate group of 5 rabbits served as no-phonation controls. We measured messenger RNA expression of matrix metalloproteinase-1, MMP-9, and interleukin-1beta using real-time reverse-transcribed polymerase chain reaction. Gene expression ratios from phonation and control animals were assessed with the Mann-Whitney U test. RESULTS: Phonation (77 +/- 3 dB; 429 +/- 141 Hz) resulted in increased matrix metalloproteinase-1 gene expression from rabbits receiving experimental phonation compared with controls, and a nonsignificant increase in matrix metalloproteinase-9 and interleukin-1beta gene expression. CONCLUSION: Matrix metalloproteinases play a role in maintaining tissue homeostasis. Investigation of cellular responses to experimental phonation may provide insight into how matrix metalloproteinases and other extracellular matrices contribute to maintenance of the vocal fold and development of pathology.

Preparation techniques for the injection of human autologous cartilage: an ex vivo feasibility study.

OBJECTIVES: To determine the optimum donor site and preparation technique for injecting human autologous cartilage as a potentially permanent implant material for vocal fold medialization. STUDY DESIGN: Prospective ex vivo experimental model. METHODS: Human nasal septal and auricular cartilage was obtained from eight surgical cases after institutional review board approval. The auricle and nasal septum were chosen as potential donor sites because of ease of accessibility, volume of cartilage potentially available, and minimal subsequent cosmetic deformity after the tissue harvesting procedure. Various preparation techniques readily available in most operating rooms were tested for their efficacy in generating an injectable cartilage slurry. The various cartilage slurries were injected through sequentially smaller needles and examined cytologically. RESULTS: The best injection properties for both nasal septal and auricular cartilage were obtained by drilling the cartilage down with a 5 mm otologic cutting bur, which allowed free passage through an 18 gauge needle. Cytologic examination of drilled septal cartilage showed good uniformity of cartilage pieces with a mean largest dimension of 0.44 +/- 0.33 mm, and 33% of lacunae contained viable-appearing chondrocytes. Cytologic examination of drilled auricular cartilage was similar, except only 10% of lacunae were occupied by chondrocytes. Other techniques tested (knife, morselizer, and cartilage crusher) did not yield injectable cartilage slurries. CONCLUSIONS: Both nasal septal and auricular cartilage can be prepared for injection via an 18 gauge needle using a cutting otologic bur. Further testing of in vivo viability and long-term volume retention is needed.

Creation and validation of the Singing Voice Handicap Index.

OBJECTIVES: We developed and validated a disorder-specific health status instrument (Singing Voice Handicap Index; SVHI) for use in patients with singing problems. METHODS: Prospective instrument validation was performed. Of 81 original items, those with poor statistical validity were eliminated, resulting in 36 items. The ability to discriminate dysphonic from normal singers, test-retest reliability, internal consistency, and construct validity were assessed. RESULTS: We included 112 dysphonic and 129 normal singers, professional and nonprofessional, of classical, country, rock, choral, and gospel repertoire. Dysphonic singers had worse SVHI scores than normal singers (p < or = .001, rank sum test). Test-retest reliability was high (Spearman correlation, 0.92; p < or = .001). Internal consistency demonstrated a Cronbach's alpha of .97, and the correlation between the SVHI and self-rated singing voice impairment was .63 (p < or = .001, Spearman correlation). CONCLUSIONS: The SVHI is a reliable and valid tool for assessing self-perceived handicap associated with singing problems.

Burnout in residents of otolaryngology-head and neck surgery: a national inquiry into the health of residency training.

PURPOSE: To characterize resident burnout on a national scale with a large sample size and to identify associated modifiable factors to minimize burnout and improve the quality of residency education. METHOD: A survey was mailed to all 1,364 U.S. residents of otolaryngology-head and neck surgery in September 2005. The main outcome measures were the Maslach Burnout Inventory-Human Services Study, demographic information, and potential burnout predictors, including stressors, satisfaction, self-efficacy, and support systems. RESULTS: The response rate was 50% (684/1,364). Current second-year through fifth-year residents were included for further analysis (514). Burnout was extremely common among otolaryngology residents. High burnout was seen in 10% of residents (51), moderate burnout in 76% (391), and low burnout in 14% (72). The strongest associated demographic factor was work hours (P < .001). Hours worked was predictive of emotional exhaustion, with exhaustion scores rising by 0.19 for each hour worked (P < .001). Furthermore, there was an 8% (41 resident) reported violation rate of the Accreditation Council for Graduate Medical Education (ACGME) 80-hour-workweek limitation. Satisfaction with the balance between personal and professional life, relationship stability, and satisfaction with career choice were negatively associated with burnout (all P < .001). CONCLUSIONS: Burnout is widely prevalent among U.S. otolaryngology residents and is present at greater levels than those seen in chairs or faculty of the same specialty. Work hours predict emotional exhaustion, and adherence to the ACGME 80-hour workweek may help protect against burnout and its deleterious consequences in residents of all specialties.

Voice-related quality of life in T1 glottic cancer: irradiation versus endoscopic excision.

OBJECTIVES: Several studies have explored posttreatment voice outcomes for early glottic cancer with varying results. To further clarify the voice-related quality of life (QOL) of T1 glottic cancer patients treated by external beam radiotherapy (EBRT) compared to endoscopic carbon dioxide laser excision (CLE), we performed a meta-analysis. METHODS: We performed a meta-analysis review for the years 1966 to 2005 for the Voice Handicap Index (VHI), laryngeal cancer, voice outcome, voice quality, and quality of life. Studies in which the VHI was assessed at least 3 months after treatment for T1 glottic cancer were identified and analyzed by meta-analysis techniques. RESULTS: Six studies with 208 patients (6 T1b and 202 T1a) treated with CLE and 91 patients (6 T1b and 85 T1a) treated with EBRT were identified. The posttreatment VHI scores were similar for the EBRT- and CLE-treated patients (p = .1, Wilcoxon rank sum test). CONCLUSIONS: We conclude that CLE and EBRT provide comparable levels of voice handicap for patients with T1 glottic cancer.

Burnout in academic chairs of otolaryngology: head and neck surgery.

BACKGROUND: Burnout can be characterized by a low degree of personal accomplishment and a high degree of emotional exhaustion and depersonalization using the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). With increasing demands and constraints placed on academic department chairs, the risk of developing burnout may be increasing. The prevalence of burnout in chairs of academic departments of otolaryngology and the factors associated with it have not been previously described. OBJECTIVES/HYPOTHESIS: The purpose of this study was to determine the prevalence of burnout in otolaryngology chairs and to identify the factors that are associated with burnout development. Understanding these elements can lead to improved prevention, recognition, and treatment of professional burnout. STUDY DESIGN: A cross-sectional questionnaire-based study of 120 academic chairs of otolaryngology in the United States was performed. METHODS: A confidential questionnaire was mailed to U.S. otolaryngology chairs. The questionnaire consisted of six parts assessing the following elements: 1) demographic information, 2) professional stressors, 3) personal and professional life satisfaction, 4) a self efficacy survey, 5) a spousal support survey, and 6) the MBI-HSS. Statistical analyses were performed using Pearson correlation and analysis of variance, and burnout data were compared with previously reported data from other department chairs and physicians. RESULTS: Questionnaires were returned from 107 department chairs for a response rate of 89%. Chairs were on average 56 years of age, serving as chair for a mean of 11 years. Average work week was 68 hours and did not vary significantly with increasing duration as chair. Sixty-six percent of time was spent delivering patient care, 8% in research, and 26% performing administrative duties. MBI-HSS scores demonstrate 3% of chairs experiencing high burnout, 81% of chairs with moderate burnout, and 16% of chairs with low burnout. On average, chairs have low depersonalization scores, low-moderate emotional exhaustion scores, and low-moderate personal accomplishment scores. High emotional exhaustion or depersonalization was correlated with low self-efficacy, low spousal support, disputes with the dean, department budget deficits, working nights and weekends, Medicare audits, loss of key faculty, and being a malpractice defendant. High personal accomplishment was correlated with increased time spent performing administrative duties. When compared with other physician specialties, otolaryngology chairs demonstrate less sense of emotional exhaustion and depersonalization but also slightly less sense of personal accomplishment. Duration as chair, age, and hours worked per week were not associated with increased burnout. CONCLUSIONS: Most otolaryngology chairs experience moderate levels of burnout. The biggest risk factors for burnout include low self-efficacy, low spousal support, disputes with the medical school dean, department budget deficits, and nights/weekends worked. These findings may help department chairs identify and prevent burnout and may help in developing programs to minimize burnout in our field's academic leaders.

Otolaryngology-head and neck surgery residency match: applicant survey.

OBJECTIVE: To examine satisfaction with the match process and reported failures to comply with the match rules among applicants of the January 2002 Otolaryngology-Head and Neck Surgery match. DESIGN: A survey was mailed to all applicants completing the 2002 San Francisco Matching Program match. PARTICIPANTS: Surveys were mailed to 312 applicants, and the 151 returned surveys were entered into a database, which was then subjected to statistical analysis. MAIN OUTCOME MEASURES: Survey questions asked whether the applicant matched and how highly, how well the applicant considers the match to fulfill its goals, how many interviews the applicant attended, and how many of these included perceived noncompliance with San Francisco Matching Program rules by region of the country. RESULTS: Satisfaction with the match correlated significantly (P<.001) to how highly the applicant matched among those successfully matching. The satisfaction among matching applicants was significantly better (P<.001) than those not matching. The 151 respondents had a total of 970 interviews. The respondents reported that they identified noncompliance with the match rules in 42 (4.3%) of these encounters. Most (87%) respondents reported full adherence to the match rules, and the degree of adherence did not correlate significantly to applicants' satisfaction (P =.71). CONCLUSIONS: Applicants' satisfaction with the match process depended significantly on their match outcome. Rule noncompliance was rare and not significantly related to applicant satisfaction. This study suggests that otolaryngology applicants perceive high levels of satisfaction with the match and infrequent breaches of stated match rules.

Quality-of-life outcomes following laryngeal endoscopic surgery for non-neoplastic vocal fold lesions.

Preservation of the vocal fold cover during laryngeal surgery should optimize vocal outcomes for patients with benign glottal lesions. The aim of this study was to evaluate changes in the quality of life, perceptual voice evaluation, and acoustic and aerodynamic measures of patients before and after endoscopic laryngeal microsurgery for true vocal fold cysts, polyps, and scarring. Preoperative and postoperative Voice Handicap Index (VHI) scores, Short Form 36 scores, and perceptual, acoustic, and aerodynamic voice measures were obtained prospectively from 42 patients who underwent phonomicrosurgery from February 2000 through May 2003. The mean (+/-SD) preoperative VHI was 49.6 +/- 21. The mean postoperative VHI score at a minimum of 3 months after surgery decreased to 26.8 +/- 21 (p < .001). When divided by lesion type, VHI scores improved significantly after surgery for vocal fold polyps and cysts. Although patients with vocal fold scarring demonstrated improvement in VHI scores after surgery, statistical significance was not achieved. For the entire group, the Short Form 36 scores were not significantly different from US norms either before or after operation. The acoustic data showed statistically significant decreases in jitter (2.05% to 1.26%), shimmer (7.06% to 4.03%), and noise-to-harmonics ratio (0.18 to 0.13) after surgery (p < .05) in female patients. The upper pitch limit increased after surgery in women (495.3 Hz to 654.9 Hz, p < .001). These results indicate that the voice-related quality of life and some acoustic parameters improve significantly for patients who have undergone laryngeal microsurgery for vocal fold cysts and polyps. Vocal fold scarring remains a difficult clinical problem with less favorable outcomes following surgical treatment in this patient set.