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We conducted a study to analyze hospital and patient costs, outcomes, and patient satisfaction among adults undergoing in-office and operating room procedures for the treatment of recurrent respiratory papillomatosis. Our final study population was made up of 17 patients—1 man and 16 women, aged 30 to 86 years (mean: 62). The mean number of in-office laser procedures per patient was 4.2, and the mean interval between procedures was 5.4 months (although 10 patients underwent only 1 office procedure); the mean number of operating room procedures was 13.5, and the mean interval between procedures was 14.3 months. An equal number of patients reported complications or adverse events with the two types of procedures—5 each. The difference in cost between the office procedure (mean: $3,413.00) and the operating room procedure (mean: $12,382.59) was almost $9,000, but these savings were offset by the fact that the office procedures needed to be performed three times as often. Patients reported slightly more anxiety and discomfort during the office procedures and, overall, they appeared to prefer the operating room procedure. We conclude that office procedures are significantly more cost-effective than operating room procedures, but their use may be limited by patient tolerance and the increased frequency of the procedure.

Objectives/Hypothesis To see if there has been a decrease in patient delay, professional delay, diagnostic delay, and treatment delay in laryngeal cancer. Study Design Institutional review board–approved retrospective chart review of patients diagnosed with laryngeal cancer. Methods Nine hundred sixty-six patients with International Classification of Diseases, Ninth Revision code for laryngeal cancer were identified from 1993 to 2013. Two hundred fifty patients met inclusion criteria. Patients were placed into two groups based on time at presentation to primary care physician, 1993 to 2004 and 2005 to 2013. Patient delay, professional delay, diagnostic delay, and treatment delay were calculated. Statistical analysis was applied using the Student t test and generalized linear model. Results From 1993 to 2004, patient delay was 88.7 days, professional delay was 40.9 days, diagnosis delay was 33.1 days, and treatment delay was 24.7 days. From 2005 to 2013, patient delay was 119.2 days, professional delay was 37.9 days, diagnosis delay was 23.8 days, and treatment delay was 23.2 days. Comparison using the Student t test demonstrated the difference in patient delay (shorter before 2005) was statistically significant (P = .045), whereas professional delay (P = .269), diagnosis delay (P = .289), and treatment delay (P = .328) did not reveal any significant differences. There was no association between stage at initial diagnosis and days prior to ear, nose, and throat visit (P = .402). Conclusions Delays in the presentation of patients to primary care physicians and otolaryngologists have significantly increased in the past 9 years. Earlier referral to otolaryngologists from primary care physicians in high-risk patients with voice changes will lead to more prompt diagnosis and treatment of laryngeal cancer. Level of Evidence 4. Laryngoscope, 2015

Background Characteristic features of hypokinetic dysarthria develop in Parkinson disease (PD). We hypothesized that quantified acoustic changes of voice might provide a correlate of disease severity. Objective To determine if there are significant differences in acoustic measures of voice between mild and moderate PD; 2) To evaluate correlations between acoustic parameters of voice and subtests of the UPDRS in mild and moderate PD. Methods Twenty six participants with PD underwent vocal acoustic testing while off PD medication, for comparison to 22 healthy controls. Participants with PD were divided into two groups based upon UPDRS activities of daily living (ADL) ratings: summed scores were used to define mild and moderate PD. Participants voiced /i/ ("ee") at comfort, high, and low pitch (3 trials/pitch). The CSpeech Waveform Analysis Program was used to analyze cycle-to-cycle frequency ("jitter") and amplitude ("shimmer") irregularities of the vocal signal, signal-to-noise ratio, and maximum phonation frequency range converted to semitones. Sections of UPDRS scores were correlated to acoustic variables of voice. Results Key findings included a significant difference between the semitone range of the control subjects and the moderate PD group (p = 0.036). Further analyses revealed significant differences in semitone range for males between the controls vs. mild PD (p = 0.014), and controls vs. moderate PD (p = 0.005). Significant correlations were also found between acoustic findings and both the ADL and motor portions of the UPDRS. Conclusions Acoustic analysis of voice, particularly frequency range, may provide a quantifiable correlate of disease progression in PD.

A tissue field of somatic genetic alterations precedes the histopathological phenotypic changes of carcinoma. Genomic changes could be of potential use in the diagnosis and prognosis of pre-invasive squamous head and neck carcinoma (HNSCC) lesions and as markers for cancer risk assessment. Studies of sequential molecular alterations and genetic progression of pre-invasive HNSCC have not been clearly defined. Studies have shown recurring alterations at chromosome 9p21 (location of the CDKN2A) and TP53 mutations in the early stages of HNSCC. However, gene silencing via hypermethylation is still a relatively new idea in the development of HNSCC and little is known about the contribution of epigenetics to the development of neoplasia, its transformation, progression, and recurrence in HNSCC. This review examines the role of promoter hypermethylation of tumor suppressor genes in the progression continuum from benign papillomas to malignancy in HNSCC.

Objectives/Hypothesis To determine the added cost of care and analyze risk factors in patients who suffered vocal fold paralysis (VFP) after thyroid surgery. Study design Retrospective cohort study. Methods Seventy-six patients who developed unilateral or bilateral VFP after thyroidectomy from 2005 through 2009, and a control group of 238 patients who underwent the same surgery without developing VFP, were compared on hospital charges, hospital and intensive care unit (ICU) length of stay (LOS), unplanned intubation, tracheotomies, respiratory failure, readmission, death, pathology, body mass index (BMI), gland weight, swallowing studies, and need for indwelling feeding tube. Differences between outcomes for unilateral VFP patients versus bilateral VFP patients were analyzed. Rate of recovery of VFP and need for further surgery after thyroidectomy were described. Results Patients who developed VFP after thyroidectomy had significantly greater rates of all the parameters listed above. BMI, gland weight, and pathology (malignant vs. benign) were not significantly different between the two groups. VFP group underwent additional surgeries after thyroidectomy related to the VFP. Thirty-three% of unilateral VFP patients with long-term follow-up recovered fully. Patients with bilateral VFP with long-term follow-up, had recovery of one vocal fold in 50% and both in 23% of cases. Conclusions Patients with unilateral or bilateral VFP after thyroidectomy experience significantly more morbidity and incurred significantly more health care charges after surgery than similar patients who do not have VFP after thyroidectomy. The likelihood of VFP was not related to malignancy, BMI, or thyroid gland weight in this series.

ObjectiveThe goal was to determine the prevalence of high-risk HPV16 using saliva in a screening population in Detroit, Michigan.Materials and MethodsReal-time quantitative polymerase chain reactio...

The larynx can be viewed in several different ways. Indirect laryngoscopy with a mirror is the simplest method and is successful in approximately 2/3 of patients. This is often adequate to rule out many pathologies. The mirror exam also provides a better appreciation of color of the larynx, since no video or lens is involved, which could distort color. For those patients in whom indirect laryngoscopy is not possible, due to an overly sensitive gag reflex, difficult anatomy, the patient’s inability to do the task, or certain anatomy cannot be adequately seen (anterior commissure), flexible fiber-optic laryngoscopes are used. This allows a clear view of all regions of the larynx, with the possible exception of the subglottis. Also, motion of the vocal folds can be best assessed with the flexible scope, since it allows the patient to sniff to maximally stimulate the posterior cricoarytenoid muscles, something not possible, or at least very difficult, with transoral examination with a mirror or rigid scope. The transoral route, which involves grasping the extended tongue, can cause the appearance of excessive tension, which may be induced by the exam and not how the person typically phonates, leading to a misdiagnosis of muscle tension dysphonia.

IntroductionMicroRNAs (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 identify laryngeal squamous cell cancer (LSCC)-specific miRNAs.Materials and methodsA retrospective cohort of 10 LSCC and five normal laryngeal squamous epithelium samples were examined using a global miRNA profiling approach (HTG, Tucson, AZ, USA, 800 human miRNAs plus 10 endogenous control miRNAs). The expression status of selected dysregulated miRNAs that were significantly different from normal were verified by real-time quantitative PCR (qPCR).ResultsTwenty-three of the 800 human miRNAs had significantly different expression levels (p < 0.05) between LSCC and normal tissues. Fifteen of the 23 have not been previously reported in HNSCC and include: miR-663b, miR-663, miR-193b, miR-1291, miR-720, miR-191, miR-1224-3p, miR-214, miR- 1285, miR-1207-5p, miR-483-5p, miR-1225-3p, miR-1228, miR-1280 and miR-638. Consistently upregulated miR-31 and miR- 193b and differentially expressed miR-663b in LSCC were verified by qPCR.ConclusionThe 15 novel miRNAs identified in this exploratory study, pending further confirmation and validation, may have clinical utility as LSCC-specific markers.How to cite this articleChen KM, Stephen JK, Havard S Shah V, Gardner G, Schweitzer VG, Worsham MJ. Novel Dysregulated MicroRNAs in Primary Laryngeal Squamous Cell Cancer. Int J Head Neck Surg 2012;3(2):76-81.

Benign inverted papillomas have been reported as monoclonal but lacking common genetic alterations identified in squamous cell carcinoma of the head and neck. Epigenetic changes alter the heritable state of gene expression and chromatin organization without change in DNA sequence. We investigated whether epigenetic events of aberrant promoter hypermethylation in genes known to be involved in squamous head and neck cancer underlie the pathogenesis of sinonasal papillomas. Ten formalin-fixed paraffin DNA samples from three inverted papilloma cases, two exophytic (everted) papilloma cases, and two cases with inverted and exophytic components were studied. DNA was obtained from microdissected areas of normal and papilloma areas and examined using a panel of 41 gene probes, designed to interrogate 35 unique genes for aberrant methylation status (22 genes) using the methylation-specific multiplex-ligation-specific polymerase assay. Methylation-specific PCR was employed to confirm aberrant methylation detected by the methylation-specific multiplex-ligation-specific polymerase assay. All seven cases indicated at least one epigenetic event of aberrant promoter hypermethylation. The CDKN2B gene was a consistent target of aberrant methylation in six of seven cases. Methylation-specific PCR confirmed hypermethylation of CDKN2B. Recurrent biopsies from two inverted papilloma cases had common epigenetic events. Promoter hypermethylation of CDKN2B was a consistent epigenetic event. Common epigenetic alterations in recurrent biopsies underscore a monoclonal origin for these lesions. Epigenetic events contribute to the underlying pathogenesis of benign inverted and exophytic papillomas. As a consistent target of aberrant promoter hypermethylation, CDKN2B may serve as an important epigenetic biomarker for gene reactivation studies.

To see if there has been a decrease in patient delay, professional delay, diagnostic delay, and treatment delay in laryngeal cancer.Institutional review board-approved retrospective chart review of patients diagnosed with laryngeal cancer.Nine hundred sixty-six patients with International Classification of Diseases, Ninth Revision code for laryngeal cancer were identified from 1993 to 2013. Two hundred fifty patients met inclusion criteria. Patients were placed into two groups based on time at presentation to primary care physician, 1993 to 2004 and 2005 to 2013. Patient delay, professional delay, diagnostic delay, and treatment delay were calculated. Statistical analysis was applied using the Student t test and generalized linear model.From 1993 to 2004, patient delay was 88.7 days, professional delay was 40.9 days, diagnosis delay was 33.1 days, and treatment delay was 24.7 days. From 2005 to 2013, patient delay was 119.2 days, professional delay was 37.9 days, diagnosis delay was 23.8 days, and treatment delay was 23.2 days. Comparison using the Student t test demonstrated the difference in patient delay (shorter before 2005) was statistically significant (P = .045), whereas professional delay (P = .269), diagnosis delay (P = .289), and treatment delay (P = .328) did not reveal any significant differences. There was no association between stage at initial diagnosis and days prior to ear, nose, and throat visit (P = .402).Delays in the presentation of patients to primary care physicians and otolaryngologists have significantly increased in the past 9 years. Earlier referral to otolaryngologists from primary care physicians in high-risk patients with voice changes will lead to more prompt diagnosis and treatment of laryngeal cancer.4. Laryngoscope, 126:1612-1615, 2016.

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.

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.

Objectives:Examine the efficacy of three separate pain regimen groups for patients who have undergone tonsillectomies by multiple otolaryngologic surgeons at one institution.Methods:This study was an institutional review board (IRB) approved prospective randomized cohort study comparing the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen/hydrocodone, and acetaminophen/codeine for post-operative tonsillectomy pain control. Setting: A tertiary referral hospital. Patients of any age undergoing tonsillectomy from June 2011 until the present were randomized into one of three post-op pain regimen groups. All tonsillectomy procedures were performed using the same technique, no preoperative local anesthetic injections were given, and no post-operative antibiotics were provided. Patients/families were given a packet of information to complete that included pain control, time to return to diet, school/work, and baseline activity. Pain control was measured using a validated faces pain scale ...

Summary Objective/Hypothesis To analyze vocal fold vibration after photofrin-mediated photodynamic therapy (PDT) for the treatment of Tis and T1N0M0 squamous cell carcinoma (SqCCa) tumors of the larynx. It was hypothesized that key attributes of vocal fold vibration would return to baseline within 1–6 months of treatment. Study Design Retrospective. Methods Laryngovideostroboscopic data were retrospectively analyzed for eight patients with Tis-T1N0M0 SqCCa tumors of the larynx treated with photofrin-mediated PDT. Baseline and posttreatment videostroboscopy images of select vibratory characteristics of the vocal folds were randomized and analyzed by a speech-language pathologist and fellowship-trained laryngologist specializing in voice disorders. Results Significant improvement in mucosal wave ( P =0.003) and amplitude of vibration ( P =0.004) occurred at greater than or equal to 20 weeks post-PDT compared with baseline. Comparing results within 5 weeks postprocedure to 10–19-weeks postprocedure revealed significant improvement in amplitude of vibration ( P =0.013) and nonvibrating portion of the vocal fold ( P =0.020). Comparing results within 5-weeks postprocedure to 20 or more weeks postprocedure revealed significant improvement in amplitude of vibration ( P =0.001), mucosal wave ( P =0.001), and nonvibrating portion of the effected fold ( P =0.001). Conclusion Photofrin-mediated PDT allows for preservation of function and structure of the larynx without systemic toxicity; however, it may take 4–5 months or more for key vibratory characteristics of the vocal folds to recover posttreatment.

Present measurement techniques for middle ear function have inherent limitations because they are either spatially insensitive (acoustic immittance) or descriptive and qualitative in nature (otoscopy). By integrating advances in electrooptic technology (fiber optics, miniature diode lasers, solid-state detector arrays) and digital processing, further advances are possible. On the basis of measurements taken with electronic speckle-pattern interferometry on human temporal bones and models, we demonstrate quantitative static and dynamic vibration/displacement characteristics of the tympanic membrane with high spatial resolution. Our presentation emphasizes advantages of optically based methods and demonstrates computerized signal processing capable of fringe localization, enhancement, and counting. Miniaturization and real-time digital image processing in the clinical setting is the goal of this research.

Endoscopic evaluation is a crucial component in the assessment of chronic airway obstruction. Acute airway obstruction is a potentially devastating complication of this invasive procedure. This article discusses a systematic approach to endoscopically assessing the airway safely and obtaining the information necessary for longterm management of the chonically obstructed airway.

Surgical techniques for the removal of vocal fold (VF) disorders that arise within the lamina propria must permit the preservation and/or restoration of VF vibratory characteristics. The endoscopic VF microflap is designed to do such. A retrospective study was undertaken to evaluate the efficacy of this procedure. Forty microflaps (7 bilateral, 1 revision) were performed on 32 patients. Charts and surgical pathology findings were reviewed. Preoperative and 3-month postoperative video recorded voice samples and stroboscopic examination results were compared. Findings on perceptual voice analysis did not significantly change. Stroboscopic examinations revealed improved postoperative VF closure in 27 of 29 patients with impaired preoperative closure and return of mucosal wave in 18 of 24 VFs operated on for the excision of cysts or polyps. When present preoperatively (6 patients), the mucosal wave was preserved. Most patients (28 of 30) rated themselves as clinically improved. The endoscopic VF microflap is efficacious in the treatment of selected VF disorders. The surgical technique is discussed.

Laser holography is a technique that creates a three-dimensional image of a static object. This technique can be applied to the analysis of vibrating structures. Electronic speckle pattern interferometry uses a laser for illumination of the vibrating object and solid state detectors and digital hardware technology for capturing and processing the image in real time. This was performed on a human cadaver larynx and is the first time an interferogram of vibrating vocal cords has ever been obtained. Dark and bright interference fringes are seen that represent the vibratory motion of the vocal folds. These are presented in still photos as well as real-time on videotape. This method can provide advantages over current techniques of laryngeal study: it is sensitive to motion in the vertical dimension, and the digital data can be quantitatively analyzed. Application of this technique to study the larynx should eventually be a valuable clinical tool and provide quantitative research data.

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 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...

Human papillomavirus (HPV), particularly HPV16, is a causative agent for 25% of head and neck squamous cell cancer, including laryngeal squamous cell cancer (LSCC). HPV-positive (HPV+ve) patients, particularly those with oropharyngeal SCC, have improved prognosis. For LSCC patients, this remains to be established. The goal was to determine stage and survival outcomes in LSCC in the context of HPV infection.Historical cohort study.Primary care academic health system.In 79 patients with primary LSCC, HPV was determined using real-time quantitative polymerase chain reaction. χ(2) or Fisher exact test was used to test the association of HPV+ve with 21 risk factors including race, stage, gender, age, smoking, alcohol, treatment, and health insurance. Kaplan-Meier and log-rank tests were used to study the association of HPV and LSCC survival outcome.HPV16 was detected in 27% of LSCC patients. Caucasian American (CA) patients had higher HPV prevalence (33%) than did African American (AA) LSCC patients (16%; P = .058). HPV was significantly associated with gender (P = .016) and insurance type (P = .001). There were no differences in survival between HPV+ve and HPV-negative (HPV-ve) patients. There was no association with HPV and other risk factors including stage (early vs late).We found a high prevalence of HPV in men and a lower prevalence of HPV infection in AA compared with CA. Despite the strikingly better survival of patients with HPV+ve oropharyngeal tumors, even when adjusted for smoking, this correlation does not seem to hold true in the larynx. Larger multiethnic LSCC cohorts are needed to more clearly delineate HPV-related survival across ethnicities.

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 ...

Objective: Oncogenic human papillomavirus (HPV) has been established as a causative agent for 25% of head and neck squamous cell cancer (HNSCC), including laryngeal squamous cell cancer (LSCC). HPV-positive oropharyngeal patients have improved prognosis. We determined outcomes in LSCC in the context of HPV infection.Method: Seventy-nine primary LSCC were examined for 21 risk factors. HPV status was determined using real-time quantitative PCR. Chi-square/Fisher exact test were used to test association of HPV-positive with the other risk factors. Kaplan-Meier and log rank test were used to study the risk of HPV-positive status for overall survival.Results: HPV-16 was detected in 21 out of 77 (27%) primary LSCC, 16% (5/32) African American (AA) and 33% (15/45) Caucasian American (CA). Significance between race and HPV status was marginal (P = .058). HPV-positive status was significantly associated with male gender (P = .017) and insurance type (P = .001). HPV-positive LSCC had longer median survival (6.64 ye...

IntroductionThis study examined the contribution of promoter hypermethylation to the pathogenesis of respiratory papillomatosis (RP), including recurrences (RRP) and progression to squamous cell carcinoma (SSC).Materials and methodsA retrospective cohort of 25 laryngeal papilloma cases included 21 RRP, two of which progressed to SCC. Aberrant methylation status was determined using the multigene (22 tumor suppressor genes) methylation-specific multiplex ligationdependent probe amplification assay and confirmed using methylation specific PCR.ResultsTwenty genes had altered DNA methylation in 22 of 25 cases. Aberrant methylation ofCDKN2BandTIMP3was most frequent. Promoter hypermethylation ofBRCA2, APC, CDKN2AandCDKN2Bwas detected in 2 RRP cases with subsequent progression to SCC. Of the 25 cases, 22 were positive for HPV-6, 2 for HPV-11 and 1 for HPV-16 and 33.ConclusionConsistent aberrant methylation of multiple tumor suppressor genes contributes to the pathogenesis of laryngeal papillomas. Persistent aberrant DNA methylation events in 2 RRP cases that progressed to cancer indicate an epigenetic monoclonal progression continuum to SCC.

Summary Vocal cord injection and thyroplasty are two techniques available for the treatment of unilateral vocal cord paralysis. The goal of surgery is to restore the voice to as near-normal quality as possible and to prevent aspiration. The status of the mucosal wave of the vocal folds has a significant relationship to the quality of the voice. It has been noted by several authors that injection of Teflon often results in a stiff vocal cord with poor voice quality. It has also been observed that thyroplasty may preserve the mucosal wave. We used video stroboscopy to assess the status of vocal fold vibration and the mucosal wave in a series of patients who had undergone vocal cord injection or thyroplasty. A total of 21 patients were studied, and the results were analyzed with regard to status of the mucosal wave and presence of nonvibrating segments of the vocal folds. The results suggest that Teflon injection is more likely to decrease the mucosal wave and to stiffen the vocal fold.

OBJECTIVE:This report provides the reader with a state-of-the-art update on a number of common voice problems that require phonosurgical intervention.STUDY DESIGN AND SETTING:This multiauthor review is not a position statement of the American Academy of Otolaryngology–Head and Neck Surgery (AAOHNS) and may reflect institutional preference and/or bias. It arose from a panel discussion at the AAOHNS meeting in 2000.RESULTS:We provide a review of the genesis and management of papillomatosis, dysplastic glottal epithelium, arytenoid granulomas, Reinke's edema, and vocal-fold paralysis.CONCLUSIONS AND SIGNIFICANCE:In the past decade, there has been a dramatic expansion of knowledge regarding a variety of voice disorders and associated treatment. There has been a convergence of basic science investigations in anatomy, physiology, and pathology with clinical trials of treatment, both surgical and nonsurgical. This information should provide the reader with current insight into critical management issues of the a...

Background: Spasmodic dysphonia (SD) is a focal dystonia of the larynx. Although individuals with SD have variable degrees of difficulty in everyday communication and speaking, many report significant impairments. The impact of SD on the quality of life of people with the disorder has not been well measured. Objectives: To assess the impact of SD using a voicespecific, validated outcomes instrument, the Voice Handicap Index (VHI), and to evaluate the effect of botulinum toxin treatment on quality of life. Methods: The VHI measures 3 subscales (physical, functional, and emotional) of impact of a voice disorder as well as a total impact score. The VHI was completed by 30 consecutive patients with SD before receiving botulinum toxin injection and 2 to 4 weeks after injection. Pretreatment scores on the VHI were compared with posttreatment scores. Results: Pretreatment scores on the VHI showed significant impairment in all 3 subscales (physical, 25.5; functional, 21.4; and emotional, 20.4) and the total score (67.6). Statistically significant improvements occurred in all 3 subscale scores and the total score (P=.001) for the 22 patients who completed the posttreatment survey. Conclusions: Spasmodic dysphonia has a significant impact on patients’ perception of quality of life as measured by the VHI. Significant improvements in all 3 subscale scores and the total score on the VHI occur after treatment with botulinum toxin. Arch Otolaryngol Head Neck Surg. 2001;127:1083-1085

A case of bilateral vocal cord hematomas caused by a shoulder harness injury is presented. The patient was restrained by a three-point belt system and was involved in a front-end collision. She presented with mild facial and chest injuries and a contusion of the neck. One hour after injury she began to complain of hoarseness without airway compromise. Fiberoptic laryngoscopy showed bilateral true vocal cord hematomas. The patient had an uneventiul hospital course and a full recovery. The importance of the mechanism of injury and associated injuries is discussed.

Many surgeons find that patients have increased morbidity after supraglottic laryngectomy if postoperative irradiation is given, but this remains poorly documented. Twenty-nine patients undergoing supraglottic laryngectomy were retrospectively reviewed. Seventeen received postoperative radiotherapy, and 12 did not. The mean follow-up was 64 months. When compared to patients treated with supraglottic laryngectomy alone, irradiated patients had a significantly higher incidence of lifelong gastrostomy dependency (35% versus 0%; p = .03) and acute upper airway obstruction (29% versus 0%; p = .05). There was a trend toward greater tracheotomy dependency (24% versus 0%), aspiration pneumonia (35% versus 9%), and delayed independent swallowing (34.8 weeks versus 7.8 weeks) in the patients treated with combined therapy, but this difference was not significant. A morbidity index score was developed to evaluate the overall lifelong morbidity of these patients, and this was found to be significantly higher in patients treated with surgery and radiotherapy (2.29 versus 0.83; p = .04). Overall survival was equal in both groups. We have shown that radiotherapy increases the morbidity of supraglottic laryngectomy. This should be considered when planning treatment for patients with supraglottic carcinoma.

Human papilloma virus (HPV) is a known causative agent for oropharyngeal squamous cell cancer (OPSCC). The goal of our study was to determine the relationship of HPV type 16 (HPV16) infection and methylation status in an OPSCC cohort. HPV16 was detected using real-time quantitative PCR (qPCR) in a retrospective cohort of 111 primary OPSCC. A 24 tumor suppressor gene candidate panel was assessed for methylation using the methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) assay. Univariate associations with HPV and gene methylation, age, gender, race and smoking were analyzed using Fisher's exact tests and logistic regression. A final multiple logistic regression model, to include patient characteristics and genes significant on univariate analysis, was built using backwards selection of genes. Statistical significance was set at p Citation Format: Kang Mei Chen, Josena K. Stephen, Meredith Mahan, Shaleta Havard, George Divine, Glendon Gardner, Vanessa P. Schweitzer, Maria J. Worsham. IGSF4 methylation is an independent marker of HPV positive OPSCC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 650. doi:10.1158/1538-7445.AM2013-650

Electronic Speckle Pattern Interferometry (ESPI) is a nondestructive optical evaluation technique that is capable of determining surface and subsurface integrity through the quantitative evaluation of static or vibratory motion. By utilizing state of the art developments in the areas of lasers, fiber optics and solid state detector technology, this technique has become applicable in medical research and diagnostics. Based on initial support from NIDCD and continued support from InterScience, Inc., we have been developing a range of instruments for improved diagnostic evaluation in otolaryngological applications based on the technique of ESPI. These compact fiber optic instruments are capable of making real time interferometric measurements of the target tissue. Ongoing development of image post- processing software is currently capable of extracting the desired quantitative results from the acquired interferometric images. The goal of the research is to develop a fully automated system in which the image processing and quantification will be performed in hardware in near real-time. Subsurface details of both the tympanic membrane and vocal cord dynamics could speed the diagnosis of otosclerosis, laryngeal tumors, and aid in the evaluation of surgical procedures.

Optical fibers have long been used for visual inspection inside the human body for medical diagnoses and treatment. By making use of sophisticated optical interferometric and ultra- small imaging techniques, combined with automated image processing, it is possible to extract significantly increased information for more accurate medical diagnoses. With support from NIH under the SBIR program, we have been developing a range of such instruments. One of these supported by the NIDCD is capable of providing detailed spatial information on the vibratory response of the tympanic membrane (TM). This instrument involves the examination of the TM by means of high speed electronic speckle pattern interferometry (ESPI). This provides a real time view of the vibration patterns of the TM for clinical diagnosis. This Interferometric Otoscope consists of mode conserving fiber optics, miniature diode lasers and high speed solid state detector arrays. We present the current status of the research including holography and ESPI of TM models and excised temporal bone preparations. A second instrument, also developed with support from NIDCD, is for application to the larynx. This system is also ESPI based but will incorporate features for direct vocal cord (VC) examination. By careful examination of the vibratory response of the VC during phonation, the characteristics of the mucosal wave may be examined. Adynamic regions of the cords can signal the start of lesions or cysts. Results of surgery can be evaluated in a quantitative manner. The design of a clinical prototype and preliminary electro-optic experiments on excised larynges and VC models will be presented.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Fifty-six patients who had undergone surgery for unilateral vocal cord paralysis (UVCP) were reviewed retrospectively. The etiologies; indications for surgery; timing of onset, diagnosis and surgery; complications; and survival rates are presented. Forty patients had neoplasms of which 32 were malignant and 8 were benign. UVCP was due to direct tumor involvement in 16 cases and surgical trauma in 21 cases. Mean survival for patients who presented with UVCP which was due directly to a malignancy was 5 months versus 22 months for those patients with UVCP due to surgical trauma during resection of malignancies. Mean survival for lung cancer patients was 5 months versus 24 months for patients with other malignancies. The etiology and manner of presentation of UVCP are important prognostic indicators which should be considered when planning surgical intervention for UVCP.

Objective To investigate the contribution of promoter methylation-mediated epigenetic events in recurrent respiratory papillomatosis tumorigenesis. Design Archival tissue DNA, extracted from microdissected papilloma lesions, was interrogated for methylation status by means of the novel, multigene methylation-specific multiplex ligation-dependent probe amplification assay. Subjects Fifteen subjects with recurrent respiratory papillomatosis, 3 females and 12 males, all with adult onset of illness (age range, 23-73 years) except for 1 female patient with juvenile onset (1 year old). Results Promoter hypermethylation was recorded in 14 of 15 cases, and 19 of 22 unique methylation-prone cancer genes in the multigene panel had altered DNA methylation in at least 1 laryngeal papilloma biopsy specimen. Identical abnormally methylated genes were found in 5 of 15 recurrent cases, of which the CDKN2B gene was hypermethylated in all 5 cases. Dissimilar epigenetic events were noted in the remaining cases. Conclusions A clonal origin was derived for 5 of 15 recurrent respiratory papillomatosis biopsy specimens based on identical epigenetic events. The high frequency of epigenetic events, characterized by consistent promoter hypermethylation of multiple tumor suppressor genes, points to the use of gene silencing mechanisms in the pathogenesis of recurrent respiratory papillomatosis.

Several familial cancer syndromes have been identified. The syndrome of sarcomas, breast cancer and other neoplasms, known as Li-Fraumeni syndrome, is characterized by several different neoplasms presenting at young ages with autosomal dominant transmission and a high incidence of second primaries. In this paper, we studied six generations (51 people) of the family of a 24-year-old man with osteogenic sarcoma of the mandible. Twelve malignancies in 11 people, including several rare tumors, were revealed. Mean age of presentation was 24 years old. Nine of the 11 patients died of disease. One developed a second primary. Two tumors presented in the head and neck. Transmission was autosomal dominant. The karyotypes of two family members were normal. Identification of Li-Fraumeni syndrome in a family is important in determining appropriate follow-up for the patient and family. Such families are models for studying carcinogenesis.