Glendon M. Gardner

Assessing outcomes for dysphonic patients

This study was designed to evaluate a disease-specific outcome measure for patients with selected voice disorders and to relate this instrument to a standardized quality of life measurement. In addition, the study attempts to document the degree of handicap for dysphonia patients globally, between different vocal pathologies, and in comparison to other chronic diseases. In this prospective, observational study, 260 adult patients evaluated for alterations of voice completed a general quality of life measure (the Medical Outcomes Trust Short Form 36-Item[SF-36]) and a voice-specific instrument (Voice Handicap Index [VHI]) pretreatment. The highest correlation was between the social functioning score of the SF-36 and the total score of the VHI and the physical, emotional, and functional subscales (p < 0.001) of the VHI. Significant correlation was also obtained for the SF-36 domains mental health (p < 0.01), general health (p < 0.01), and role functioning emotional (p < 0.017) with the three VHI domains and the total VHI score. Patients had significantly lower scores than the general U.S. population in five of the eight domains of SF-36. Patients with vocal fold paralysis had the highest level of pretreatment disability as measured on both the VHI and SF-36 among voice patients. The patients with dysphonia had a lower level of physical functioning than the patients with chronic sinusitis (p < 0.01), reflecting a greater handicap. In addition, the dysphonia group had lower levels of social functioning than the angina (p < 0.01) and sciatica (p < 0.01) groups and a lower score for mental health than the angina group (p < 0.01). The SF-36 correlates with the VHI in the domains of social functioning, mental health, and role functioning emotional. The baseline handicap for voice disorders represents a significant disability even in comparison to conditions such as angina pectoris, sciatica, and chronic sinusitis.

Pediatric vocal fold medialization with silastic implant: intraoperative airway management

Vocal fold immobility accounts for 10% of all congenital laryngeal abnormalities, second only to laryngomalacia. Acquired unilateral vocal fold immobility (UVFI) is generally due to surgical trauma. The problems associated with this condition include a breathy dysphonia, weak cough, and aspiration. Treatment involves observation, voice and swallowing therapy, and various surgical options. Medialization laryngoplasty with silastic implant (ML-s) is a very successful procedure with consistent results in the adult population. It is usually done under local anesthesia with sedation to allow the voice to be monitored during the procedure. The surgeon can then fashion a custom implant or use a specific prefabricated implant. Additionally, use of the flexible fiberoptic nasopharyngolaryngoscope (FFNPL) allows the surgeon to see the endolarynx during the procedure, thus avoiding overmedialization and airway obstruction. Children, however, do not tolerate such invasive procedures under local anesthesia and sedation, have much smaller airways and, therefore, present several problems when addressing this problem surgically. Management of the pediatric airway during ML-s can be achieved using a laryngeal mask airway (LMA) and the FFNPL. While this does not allow the voice to be assessed intraoperatively, appropriate medialization of the vocal fold can be judged via the FFNPL, and airway obstruction avoided. ML-s using the LMA and FFNPL was performed in two children aged 8 and 4 years old. Both had excellent voice results and no complications. The details of these cases are reported. The literature on treatment of UVFI in children is reviewed, and practical and theoretical issues discussed.

Human papilloma virus prevalence in a multiethnic screening population.

Objective The goal was to determine the prevalence of high-risk HPV16 using saliva in a screening population in Detroit, Michigan. Materials and Methods Real-time quantitative polymerase chain reaction was applied to detect HPV16 in saliva DNA from 349 screening subjects without head and neck cancer (HNC), 156 with HNC, and 19 controls. Cut points for human papilloma virus (HPV) positivity were >0 and >0.001 copy/cell. Proportions were compared between groups using exact χ2 or Fisher exact tests (P < .05). Results At a cut point >0, each group had an overall HPV prevalence of more than 5%, with a higher prevalence of 30.8% in the HNC patient group. At a cut point >0.001, the prevalence was lower: 0% in the control, 1.2% in the screening, and 16.7% in the HNC group. In the latter, for both cut points, HPV prevalence was different across sites (<0.001) and significantly higher in the oropharynx than larynx or site as other after Hochberg’s adjustment. At >0, women in the screening group had a higher prevalence of HPV than did men (P = .010), and at >0.001, the prevalence was higher for men in the HNC group than for women (P = .035). In the screening group, at >0, only African Americans had a higher prevalence than Caucasian Americans (P = .025). Conclusions In the screening group, a 6.9% and 1.2% screening rate was noted at cut points >0 and >0.001, respectively. The results provide data to inform public health considerations of the feasibility of saliva as a screening tool in at-risk populations with the long-term goal of prophylactic vaccination against oral HPV.

Assessing delays in laryngeal cancer treatment

To see if there has been a decrease in patient delay, professional delay, diagnostic delay, and treatment delay in laryngeal cancer.

Delayed Failure after Endoscopic Staple Repair of an Anterior Spine Surgery Related Pharyngeal Diverticulum

We present a rare complication of endoscopic staple repair of a pharyngeal diverticulum related to prior anterior cervical spine surgery. A 70-year-old male developed a symptomatic pharyngeal diverticulum 2 years after an anterior cervical fusion that was repaired via endoscopic stapler-assisted diverticulectomy. He initially had improvement of his symptoms after the stapler-assisted approach. Three years later, the patient presented with dysphagia and was found to have erosion of the cervical hardware into the pharyngeal lumen at the site of the prior repair. We present the first reported case of late hardware erosion into a pharyngeal diverticulum after endoscopic stapler repair.

HPV prevalence in a multi-ethnic screening population

Objective: For optimal feasibility using saliva rinse screening of HPV for head and neck cancer (HNC), the prevalence should be 5% or higher in the population screened. The aim of our study was to determine the prevalence of HPV16 infection in a screening population in Detroit, MI. Method: Real time quantitative PCR was applied to detect HPV16 in saliva DNA from 349 screening subjects without HNC, 157 HNC, and 19 controls. Cut points for HPV positivity were: >0 and >0.001 copy/cell. Proportions were compared between groups using exact chi-square or Fisher’s exact tests as appropriate (set at P < .05). Results: At cut point >0, each group had an overall HPV prevalence of over 5%, with a much higher prevalence of 31.2% in the HNC patient group. At cut point >0.001, the prevalence was lower in each group, 0% in the control, 1.2% in the screening, and 17.2% in the HNC group. At >0, females in the screening group had a higher prevalence of HPV than males (P = .010), and at >0.001, prevalence was higher for males in the HNC group than females (P = .043). In the screening group, at >0, only AA had higher prevalence than CA (P = .025). Conclusion: In the screening group, a 5% and 1.2% screening rate was noted at cut-points >0 and >0.001, respectively. The results provide data to inform public health considerations of the feasibility of saliva as a screening tool in at-risk populations with the long term goal of prophylactic vaccination against oral HPV.

Novel MicroRNA miR-923 Is Dysregulated in Primary LSCC

Objective: MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs of 17 to 25 nucleotides that regulate approximately 30% of human genes. They are differentially expressed in various types of cancers compared with noncancerous tissues, suggesting that they may have crucial roles in tumorigenesis. The objective of this study was to discover LSCC-specific miRNAs. Method: Global miRNA profiling (800 human miRNAs plus 10 endogenous control miRNAs) was performed on 8 formalin-fixed archival LSCC samples and 5 normal laryngeal squamous epithelium (HTG, Tucson, AZ, USA). Quantitative real-time PCR (qRT-PCR) approach was employed to verify expression status of selected miRNAs that were significantly different from normal controls. Results: Thirty-one of the 800 human miRNAs were significantly differentially expressed (P < .05) between LSCC vs normal tissues. Selected miRNAs (miR-31, miR-193b, miR-663b, miR-923, and miR-1826), by qRT-PCR, verified expression of consistently upregulated miR-31 and miR-193b as well as differentially expressed miR-663b, miR-923, and miR-1826. Dysregulation of miR-923 was newly observed and showed upregulation in 3 out of 8 and downregulation in 5 out of 8 LSCC. Conclusion: We have identified a group of 31 aberrantly expressed miRNAs in LSCC. miR-923 has not been previously reported in HNSCC, including LSCC. Further detailed examinations of this miRNA will provide opportunities to dissect the complex molecular abnormalities driving LSCC.

Miniseminar: Benign Lesions of the Vocal Folds: If and When to Operate

The general otolaryngologist will see many patients who present with dysphonia and have benign-appearing lesions of the vocal folds. The tendency is to operate on these patients immediately. However, not all patients in this situation will require surgery. Some will benefit greatly from nonsurgical interventions and some will be scarred by surgery, creating a problem more difficult to repair than most. This symposium will cover the evaluation of patients (adult and pediatric) with benign vocal fold lesions and nonsurgical therapies including medicine and voice therapy. The factors that influence the decision whether to operate are reviewed and the timing of surgery and postoperative care are presented. Didactic presentations and case reports with video will be used to illustrate these points. (If this is an 80-minute seminar, this will be an audience-interactive presentation to help determine what the current prevailing attitudes among general otolaryngologists are and whether they differ from the state-of-the-art significantly and whether they are altered by this symposium.)

10:20 AM: Consistent Epigenetic Events in Laryngeal Papillomas

PROBLEM: The researchers investigated alterations in DNA methylation to assess the contribution of epigenetic events to the process of tumorigenesis of laryngeal papillomas. Studies strongly suggest that the spontaneous transformation of recurrent papillomas to squamous cell carcinoma is not characterized by a histologic progression through dysplasia over time. Thus, these lesions may be very difficult to diagnose histologically and clinically early in the course of the transformation of the disease. METHODS: The laryngeal papilloma cohort comprised 27 subjects, 4 females and 23 males, all adult onset, ranging in age from 23 to 73 years except for 1 female juvenile onset (1-yearold). Archival tissue DNA, extracted from microdissected laryngeal papilloma lesions, was interrogated for aberrant methylation status using the novel, multi-gene methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. RESULTS: Promoter hypermethylation was recorded in 25 of 27 cases. All 22 methylation-prone cancer genes in the multigene panel had altered DNA methylation in at least one or more laryngeal papilloma tissues. Aberrant methylation of TIMP3 and APC genes was most frequent, occurring in 11 of 27 cases (41%), followed by CDKN2A and CDKN2B genes in 10 of 27 cases, the VHL gene in 7, DAPK1, TP73, and GSTP1 in 6, and ESR1 and KLK10 in 5 of 27 cases. CONCLUSION: The high frequency of epigenetic events, characterized by consistent aberrant methylation of multiple tumor suppressor genes points to the utilization of gene silencing mechanisms as one of the driving forces behind the growth of laryngeal papillomas. SIGNIFICANCE: Because promoter hypermethylation is potentially reversible, the molecules that regulate methylation status of DNA are considered promising targets for new cancer therapies. Identifying epigenetic alterations in a precancerous lesion may lead to the discovery of biomarkers that add to the knowledge of risk assessment and early detection, and may provide molecular targets for chemopreventive interventions. SUPPORT: R01 NIH DE 15990.