Otolaryngologists, Surgical Specialist
22 years of experience

Accepting new patients
19900 Haggerty Rd
Ste 103
Livonia, MI 48152
734-432-7666
Locations and availability (4)

Education ?

Medical School Score Rankings
University of Michigan Medical School (1988)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Awards  
Castle Connolly America's Top Doctors® (2010 - 2014)
Associations
American Academy of Otolaryngology: Head and Neck Surgery
Member
National Spasmodic Dysphonia Association
Member

Affiliations ?

Dr. Hogikyan is affiliated with 3 hospitals.

Hospital Affilations

Score

Rankings

  • University of Michigan Hospitals & Health Centers *
    Otolaryngology
    1500 E Medical Center Dr, Ann Arbor, MI 48109
    • Currently 4 of 4 crosses
    Top 25%
  • University of Michigan Health System
  • Ann Arbor Veterans Affairs Medical Center
    2215 Fuller Rd, Ann Arbor, MI 48105
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Hogikyan has contributed to 45 publications.
    Title Chemotherapy Alone for Organ Preservation in Advanced Laryngeal Cancer.
    Date December 2010
    Journal Head & Neck
    Excerpt

    For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy.

    Title Demographics and Efficacy of Head and Neck Cancer Screening.
    Date September 2010
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    This study was designed to 1) describe the demographics and 2) determine the efficacy of a head and neck cancer screening program to optimize future programs.

    Title Awake Extracorporeal Membrane Oxygenation for Management of Critical Distal Tracheal Obstruction.
    Date April 2010
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Disorders of Cranial Nerves Ix and X.
    Date April 2009
    Journal Seminars in Neurology
    Excerpt

    The glossopharyngeal and vagus nerves mediate the complex interplay between the many functions of the upper aerodigestive tract. Defects may occur anywhere from the brainstem to the peripheral nerve and can result in significant impairment in speech, swallowing, and breathing. Multiple etiologies can produce symptoms. In this review, the authors broadly examine the normal functions, clinical examination, and various pathologies of cranial nerves IX and X.

    Title Development and Characterisation of an Experimental Recurrent Laryngeal Nerve Injury Model for the Study of Viral Gene Therapy.
    Date August 2008
    Journal The Journal of Laryngology and Otology
    Excerpt

    OBJECTIVES: To develop and characterise an experimental model of recurrent laryngeal nerve injury for the study of viral gene therapy. METHODS: Twenty rats underwent unilateral recurrent laryngeal nerve injury. After vocal fold mobility was observed, larynges were serially sectioned, and immunohistochemical techniques were employed to stain for neurofilament and motor endplates in order for a blinded investigator to determine the percentage of nerve-endplate contact, as a histological indicator of an intact neuromuscular connection. RESULTS: All animal procedures resulted in complete, ipsilateral vocal fold paralysis that recovered by three weeks. The mean nerve-endplate contact percentage was 11.6 per cent at one week, 53.9 per cent at two weeks, 88.6 per cent at three weeks, 81.7 per cent at four weeks and 86.6 per cent at five weeks. The differences between results at week one and week three were statistically significant (p < 0.01). The mean nerve-endplate contact percentage on the control side was 86.8 per cent. CONCLUSIONS: There was a dramatic, measurable decrease in nerve-endplate contact percentage following crush injury to the recurrent laryngeal nerve. Spontaneous recovery was observed by three weeks post-injury. This model will be used to investigate the potential therapeutic role of viral gene therapy for the treatment of recurrent laryngeal nerve injury.

    Title Quality of Life and Voice: Study of a Brazilian Population Using the Voice-related Quality of Life Measure.
    Date December 2007
    Journal Folia Phoniatrica Et Logopaedica : Official Organ of the International Association of Logopedics and Phoniatrics (ialp)
    Excerpt

    OBJECTIVE: The goal of the present study was to characterize a large population of Brazilian individuals using the Brazilian Portuguese version of the Voice-Related Quality of Life (V-RQOL) Measure. PATIENTS AND METHODS: We studied a population of 2,214 Brazilian subjects who completed the V-RQOL questionnaire consisting of 10 questions from two domains: physical functioning and social-emotional functioning. The subjects were divided into two groups according to the presence of vocal complaints: group 1, with vocal complaints (1,304 individuals); group 2, without vocal complaints (910 individuals). Subject age ranged from 14 to 90 years in both groups. All subjects self-rated their voice quality upon a five-point categorical scale ranging from poor to excellent. Moreover, the respondents' professions were classified into four categories according to their level of voice usage. RESULTS: Results indicate that the worse the self-assessment of the voice, the lower the V-RQOL scores, with higher significance in the group with vocal complaints. The total V-RQOL score was 97 for excellent voices, 92 for very good, 84 for good, 65 for fair, and 45 for poor voices. Main correlations for both groups were: total and physical scores (0.96), total and social-emotional scores (0.82); physical and social-emotional scores (0.69); self-assessment of the voice and total score (0.61); self-assessment of the voice and physical score (0.58), and self-assessment of the voice and social-emotional score (0.52). Two interesting negative correlations were found between age and self-assessment of the voice (-0.271), and age and social-emotional score (-0.184). Group 1, with vocal complaints, presented lower scores than group 2. CONCLUSIONS: The relationship between self-assessment of voice quality and V-RQOL scores was very clear and statistically significant, especially when considering the group with a known voice disorder.

    Title Dysfunction of the Recurrent Laryngeal Nerve and the Potential of Gene Therapy.
    Date August 2007
    Journal The Annals of Otology, Rhinology, and Laryngology
    Excerpt

    Injury to the recurrent laryngeal nerve causes vocal fold paresis or paralysis resulting in poor voice quality, and possibly swallowing dysfunction and/or airway compromise. Injury can occur as part of a neurodegenerative disease process or can be due to direct nerve trauma or tumor invasion. Management depends upon symptoms, the cause and severity of injury, and the prognosis for recovery of nerve function. Surgical treatment techniques can improve symptoms, but do not restore physiologic motion. Gene therapy may be a useful adjunct to enhance nerve regeneration in the setting of neurodegenerative disease or trauma. Remote injection of viral vectors into the recurrent laryngeal nerve is the least invasive way to deliver neurotrophic factors to the nerve's cell bodies within the nucleus ambiguus, and in turn to promote nerve regeneration and enhance both nuclear and nerve survival. The purpose of this review is to discuss the potential role for gene therapy in treatment of the unsolved problem of vocal fold paralysis.

    Title Prevention of Wound Complications Following Salvage Laryngectomy Using Free Vascularized Tissue.
    Date June 2007
    Journal Head & Neck
    Excerpt

    BACKGROUND: Total laryngectomy following radiation therapy or concurrent chemoradiation therapy is associated with unacceptably high complication rates because of wound healing difficulties. With an ever increasing reliance on organ preservation protocols as primary treatment for advanced laryngeal cancer, the surgeon must develop techniques to minimize postoperative complications in salvage laryngectomy surgery. We have developed an approach using free tissue transfer in an effort to improve tissue vascularity, reinforce the pharyngeal suture line, and minimize complications in this difficult patient population. The purpose of this study was to outline our technique and determine the effectiveness of this new approach. METHODS: We conducted a retrospective review of a prospective cohort and compared it with a historical group (surgical patients of Radiation Therapy Oncology Group (RTOG)-91-11 trial). Eligibility criteria for this study included patients undergoing salvage total laryngectomy following failed attempts at organ preservation with either high-dose radiotherapy or concurrent chemo/radiation therapy regimen. Patients were excluded if the surgical defect required a skin paddle for pharyngeal closure. The prospective cohort consisted of 14 consecutive patients (10 males, 4 females; mean age, 58 years) who underwent free tissue reinforcement of the pharyngeal suture line following total laryngectomy. The historical comparison group consisted of 27 patients in the concomitant chemoradiotherapy arm of the RTOG-91-11 trial who met the same eligibility criteria (26 males, 1 female; mean age, 57 years) but did not undergo free tissue transfer or other form of suture line reinforcement. Minimum follow-up in both groups was 12 months. RESULTS: The overall pharyngocutaneous fistula rate was similar between groups-4/14 (29%) in the flap group, compared with 8/27 (30%) in the RTOG-91-11 group. There were no major wound complications in the flap group, compared with 4 (4/27, 14.8%) in the RTOG-91-11 group. There were no major fistulas in the flap group, compared with 3/27 (11.1%) in the RTOG-91-11 group. The rate of pharyngeal stricture requiring dilation was 6/14 (42%) in the flap group, compared with 7/27 (25.9%) in the RTOG-91-11 group. In our patients, the rate of tracheoesophageal speech was 14/14 (100%), and complete oral intake was achieved in 13/14 (93%) patients. Voice-Related Quality of Life Measure (V-RQOL) and Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) scores suggest that speech and swallowing functions are reasonable following free flap reinforcement. CONCLUSIONS: Free vascularized tissue reinforcement of primary pharyngeal closure in salvage laryngectomy following failed organ preservation is effective in preventing major wound complications but did not reduce the overall fistula rate. Fistulas that developed following this technique were relatively small, did not result in exposed major vessels, and were effectively treated with outpatient wound care rather than readmission to the hospital or return to operating room. Speech and swallowing results following this technique were comparable to those following total laryngectomy alone.

    Title Voice and Swallowing Outcomes of an Organ-preservation Trial for Advanced Laryngeal Cancer.
    Date January 2006
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    INTRODUCTION: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. SUBJECTS: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU 1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease. METHODS: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months. RESULTS: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09). CONCLUSIONS: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.

    Title Cidofovir for the Treatment of Recurrent Respiratory Papillomatosis: a Review of the Literature.
    Date October 2005
    Journal Pharmacotherapy
    Excerpt

    Recurrent respiratory papillomatosis (RRP) is a rare but potentially severe disease caused by papillomavirus, most often types 6 and 11. The disease, which occurs in both juvenile and adult forms, is characterized by benign epithelial tumors of the airway that most frequently affect the larynx but can also spread along the entire aerodigestive tract. Recurrent respiratory papillomatosis is the most common benign neoplasm of the larynx in children and the second most frequent cause of childhood hoarseness. Standard treatment, which is palliative only, consists of surgical excision of papillomata to maintain airway patency and improve voice quality. Recurrence despite repeated surgical procedures is the rule. To date, incorporation of adjuvant treatments has not been reliably beneficial in altering the disease course. Several case series have described promising results with cidofovir, a cytosine nucleoside analog with antiviral activity. To evaluate the data available on the safety and efficacy of cidofovir for the treatment of RRP, we conducted a MEDLINE search for all case reports or series from January 1966-August 2004 describing cidofovir therapy in either adults or children with RRP. The bibliographies of qualifying articles were also searched for relevant references. In both adults and children with mild-to-severe RRP, intralesional administration of cidofovir directly into the site of papillomata was associated with partial-to-complete regression of papillomata, improvement in voice quality and airway status, and decreased need for surgery. Wide variation in intralesional cidofovir dose (2-57 mg), frequency (every 2-8 wks), and duration (4 mo-4 yrs) was found. Successful outcomes have also been reported with intravenous cidofovir, but data are limited to three case reports. Rash, headache, and precordialgia were the only adverse effects reported with intralesional cidofovir. Nephrotoxicity and neutropenia secondary to either intralesional or intravenous cidofovir were not observed. Long-term risks associated with intralesional administration remain to be seen. Further studies are necessary to determine the most appropriate dose, frequency, and duration of therapy, and to fully characterize the safety profile profile of cidofovir when given intralesionally.

    Title Length-tension Relationship of the Feline Thyroarytenoid Muscle.
    Date May 2005
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    Vocal fold tension during phonation is generated by coordinated contraction of the intrinsic laryngeal muscles. The thyroarytenoid muscle has been found to have increased stiffness at various levels of strain when compared with other intrinsic laryngeal muscles. The objective here is to test the hypothesis that the thyroarytenoid muscle exhibits high passive tension during maximal isometric tetanic force generation, and to test the hypothesis that the thyroarytenoid maintains the ability to generate contractile force at high levels of strain more effectively than other skeletal muscle. The thyroarytenoid muscles (n=9) and digastric muscle strips (n=7) were removed from adult random-bred cats. Maximal isometric tension and passive tension at optimum length were measured from each muscle in vitro. Active and passive length-tension curves were constructed for each muscle. The contractile properties of the thyroarytenoid group were compared with those of the digastric muscle group. The thyroarytenoid muscle group required on average 140 mN of passive tension to generate maximal isometric tetanic tension. This represented 39% of the average maximal isometric tetanic tension generated by the muscles. These results were significantly higher than the digastric muscle group, which required on average 28 mN of passive tension (9% of maximal isometric tetanic tension, p<0.05). At 110% of optimum length, the thyroarytenoid muscle maintained 89.8% of maximal isometric tetanic force, whereas the digastric muscle group maintained 67.7% of maximal isometric tetanic force (p<0.05). The thyroarytenoid muscle exhibits higher passive tension when generating maximal isometric tension than the digastric muscle control group. The thyroarytenoid muscle maintains higher levels of active tension at high strain than the digastric muscle control group. We conclude that these findings are related to the ability of the thyroarytenoid muscle to function as a fine tensor of the vocal fold in a high strain environment.

    Title The Relationship Between Ratings of Voice Quality and Quality of Life Measures.
    Date February 2005
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    In the past several years, a number of scales have been developed that elicit a patient's self-assessment of the severity of his or her voice problem. The Voice Related Quality of Life Measure (V-RQOL) assesses a patient's perception of the impact of the voice problem on quality of life. Although this tool assesses the patient's perception of the voice disorder, it may not reflect the severity of dysphonia as perceived by a clinician. The GRBAS is an auditory-perceptual scale developed in Japan and used by clinicians to categorize the voice using five descriptive perceptual parameters: overall grade or severity (G), roughness of the voice (R), breathiness (B), asthenia (A), and strain (S). The purpose of this research is to determine the relationship between the patient's perception of voice related quality of life using the V-RQOL and the clinician's perception of voice severity using the GRBAS scale. Fifty patients with a complaint of a voice disorder completed the V-RQOL prior to their examination. In addition, 45 patients without voice complaints (controls) also completed the V-RQOL. All patients and control subjects were assessed by one of the voice clinicians using the GRBAS. For 25 of the subjects, both clinicians provided GRBAS perceptual ratings. Each of the two groups, were subsequently divided into subgroups consisting of those age 66 years and under and those over 66 years of age. The results indicate that the two clinicians were highly reliable in rating severity in the normal and voice disordered groups using the GRBAS scale. The results also indicate that perceived voice severity and voice-related quality of life are related; however, the relationship is a moderate one, which suggests that factors other than those directly related to voice quality may contribute to responses on voice assessment scales completed by patients. The relationship was stronger for the subgroup under 66 years old compared with the subgroup 66 years and older.

    Title Disability in Patients with Head and Neck Cancer.
    Date July 2004
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    BACKGROUND: Patients with head and neck cancer often experience debilitating speech, eating, and respiratory problems as well as the psychological effects of loss of function and change in body image. These patients often become unemployed as a result of their disease process, which adds financial burden to their already stressful lives. Yet the specific factors associated with unemployment have not been systematically studied. METHODS: This multisite study used survey and chart data to determine the predictors of work-related disability. RESULTS: Of the 384 patients who were working prior to their diagnosis of head and neck cancer, 52% (n = 201) were disabled by their cancer treatment. Multivariate analysis demonstrated significant links between disability and chemotherapy (odds ratio [OR], 3.4; P <.001), neck dissection status (OR, 2.3; P =.01), pain scores (OR, 1.2; P =.01), and time since diagnosis (OR, 0.9; P =.04). CONCLUSIONS: More than half of the patients in this study were disabled by their head and neck cancer or treatment. Patients with head and neck cancer who have undergone chemotherapy or neck dissection or have high pain scores are at increased risk for disability from their cancer or their treatment. Efforts to prevent (if possible), better assess, and treat pain and other adverse effects of head and neck cancer treatments may also have the potential to reduce patient disability.

    Title Longitudinal Effects of Botox Injections on Voice-related Quality of Life (v-rqol) for Patients with Adductory Spasmodic Dysphonia: Part Ii.
    Date May 2004
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To investigate the longitudinal effects of botulinum toxin type A (Botox) injections on voice-related quality of life (V-RQOL) for patients with adductory spasmodic dysphonia. DESIGN: Prospective study. SETTING: Academic tertiary care referral center. PARTICIPANTS: Forty-two patients who presented to our institution with dysphonia and were diagnosed as having adductory spasmodic dysphonia during a 38-month period. INTERVENTION: Patients received Botox injections into both thyroarytenoid muscles via the cricothyroid membrane. The typical starting dose was 1.0 U per vocal fold. If necessary, the dosage was adjusted in subsequent injections to reduce adverse effects or to enhance duration of benefit. MAIN OUTCOME MEASURES: Patients filled out questionnaires, including the V-RQOL Measure and a self-assessed overall voice rating, before each injection. Postinjection questionnaires were completed 6 to 8 weeks after each treatment. Mean pretreatment and posttreatment scores were calculated for each treatment. RESULTS: The number of treatments per patient ranged from 1 to 7. Statistically significant improvements in mean total and domain V-RQOL scores were calculated for every injection (P<.01) (no postinjection questionnaires were available for the seventh injections). The magnitude of the effect remained constant for later injections. Eighty-two percent of the population recorded at least 1 category of improvement in overall self-assessed voice rating with each injection. CONCLUSIONS: Botox has a significant beneficial effect on V-RQOL for at least 6 injection cycles. This study demonstrates the efficacy of Botox for treating patients with adductory spasmodic dysphonia and further illustrates the usefulness and validity of the V-RQOL Measure in evaluating patients with dysphonia.

    Title Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer.
    Date October 2003
    Journal World Journal of Surgery
    Excerpt

    The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

    Title Immune Reactivity Does Not Predict Chemotherapy Response, Organ Preservation, or Survival in Advanced Laryngeal Cancer.
    Date September 2002
    Journal The Laryngoscope
    Excerpt

    OBJECTIVE: To determine whether pretreatment lymphocyte subpopulations correlate with tumor response to induction chemotherapy as part of an organ preservation treatment approach in patients with advanced laryngeal cancer. STUDY DESIGN: A prospective clinical trial in patients with advanced laryngeal cancer was undertaken to determine whether the frequency of late salvage laryngectomy and overall survival could be improved using one cycle of neoadjuvant chemotherapy to select patients for organ preservation. Pretreatment peripheral blood lymphocyte subpopulations for CD3, CD4, CD8, NK, and B cells were correlated with tumor response to induction chemotherapy, larynx preservation, and survival, to determine whether immune parameters could be useful in patient selection. METHODS: The study setting was a tertiary referral academic health center. Studied were 53 patients with stage III (42%) or IV (57%) larynx cancer. Most patients had supraglottic cancers (73%) and positive clinical nodes (51%). Sixty-eight percent had greater than 50% tumor response after one cycle of induction chemotherapy and then received concurrent chemoradiation and two cycles of adjuvant chemotherapy. Lymphocyte subpopulations were measured in 39 patients. Mean follow-up was 23.3 months (range, 5-61 mo). RESULTS: A total of 18 (34%) patients underwent laryngectomy. Only 4 cases were late salvage resections (13-35 mo after treatment). Fourteen cases were planned surgery after initial chemotherapy. Of the lymphocyte subpopulations measured, CD8 levels were significantly lower in stage IV patients and tended to be lower in patients with successful organ preservation. However, no significant differences in lymphocyte subpopulations were found among responders and nonresponders to chemotherapy. Overall survival was 88%. CONCLUSIONS: One cycle of neoadjuvant chemotherapy was effective in selecting patients for organ preservation. The regimen of definitive concurrent and adjuvant chemotherapy was associated with an unexpectedly high 2-year survival rate. Lymphocyte subsets were not significant predictors of responding patients or survival. Further study of other biological markers useful in selecting patients for organ preservation are needed.

    Title A Review of Outcome Measurements for Voice Disorders.
    Date July 2002
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    There has been great interest in the medical and associated communities in the development and use of patient-based outcome measures such as quality-of-life and handicap indexes. This area of assessment of initial disability and response to subsequent treatment is especially applicable to the field of laryngology and voice disorders given the limitations of perceptual analysis and objective vocal function studies. In this review, we outline the development and importance of patient-based outcome measures in general, and their application for voice disorders specifically. In addition, several voice-specific instruments are discussed in detail and provided. One of the primary goals of this review is to educate and facilitate the future use of these simple but important patient-based outcome instruments for otolaryngologists who care for patients with voice disorders.

    Title Longitudinal Effects of Botulinum Toxin Injections on Voice-related Quality of Life (v-rqol) for Patients with Adductory Spasmodic Dysphonia.
    Date June 2002
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    Adductory spasmodic dysphonia is a focal dystonia of laryngeal muscles. Patients with this disorder typically have severe vocal difficulties, with significant functional, social, and emotional consequences. There is no widely accepted cure for this condition, however, botulinum toxin injections of the thyroarytenoid muscles are considered by most voice clinicians to be the state of the art treatment. Based on extensive experience treating patients for adductory spasmodic dysphonia, we feel that traditional means of voice assessment do not adequately measure either the disease severity or the treatment outcomes. That is, listening to or acoustically analyzing limited phonatory samples does not capture the functional, social, and emotional consequences of this disorder. These consequences will be reflected in a patient's voice-related quality of life (V-RQOL). Using a validated voice outcomes instrument, the V-RQOL Measure, the purpose of this study was to quantify longitudinal changes in the V-RQOL of patients with adductory spasmodic dysphonia who are undergoing botulinum toxin injections. Twenty-seven consecutive new patients presenting with dysphonia to our institution during an 18-month period were diagnosed with adductory spasmodic dysphonia, and treated patients were evaluated prospectively using the V-RQOL Measure. Results indicated that (1) V-RQOL was initially very low for these patients, (2) botulinum toxin injections improved it significantly for each injection cycle studied, and (3) the magnitude of the treatment effect appears to change across injections.

    Title Management of Common Voice Problems: Committee Report.
    Date June 2002
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    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 aforementioned disorders.

    Title Objective Assessment of Swallowing Dysfunction and Aspiration After Radiation Concurrent with Chemotherapy for Head-and-neck Cancer.
    Date May 2002
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To objectively assess swallowing function after an intensive chemoradiation regimen for locally advanced head-and-neck cancer and to assess the clinical implications of swallowing dysfunction. PATIENTS AND METHODS: Twenty-nine patients with nonresectable Stage IV head-and-neck cancer participated in a Phase I study of radiation, 70 Gy/7 weeks, concurrent with weekly gemcitabine. Because of a high rate of mucosal toxicity, reduced drug doses were delivered to subsequent patient groups: 300, 150, 50, and 10 mg/m(2)/week. Twenty-six of these patients underwent prospective evaluation of swallowing function with videofluoroscopy and esophagogram. Studies were performed pretherapy, early post-therapy (1-3 months), and late post-therapy (6-12 months). RESULTS: Complete tests were performed pretherapy in 22 patients, early post-therapy in 20, and late post-therapy in 13. Twenty-five patients had at least one post-therapy study. Post-therapy dysfunction was characterized by reduced inversion of the epiglottis, delayed swallow initiation and uncoordinated timing of the propulsion of the bolus, opening of the cricopharyngeal muscle, and closure of the larynx, all of which promoted aspiration during and after the swallow. In addition, reduced base-of-tongue retraction with reduced contact to the posterior pharyngeal wall and incomplete cricopharyngeal relaxation resulted in pooling in the pyriform sinuses and vallecula of residue, which was frequently aspirated after the swallow. Post-therapy aspirations were typically "silent," eliciting no cough reflex, or the cough was delayed and noneffective in expelling the residue. Aspiration was observed in 3 patients (14%) in the pretherapy studies, in 13 (65%) in the early post-therapy studies, and in 8 (62%) in the late post-therapy studies (aspiration rates post-therapy vs. pretherapy: p = 0.0002). Six patients had pneumonia requiring hospitalization 1-14 months after therapy (median: 2.5 months), being the likely cause of death in 2 patients. Five cases of pneumonia occurred among 17 patients who had demonstrated aspiration in the post-therapy studies, compared with no cases of pneumonia among 8 patients who had not demonstrated aspiration (p = 0.1). Of the 4 patients who had not undergone any post-therapy study, 1 developed pneumonia. Mucositis scores, prolonged tube feeding, presence of tracheostomy tube, and gemcitabine doses were not found to be related to aspiration or pneumonia risk. CONCLUSIONS: After intensive chemoradiotherapy, significant objective swallowing dysfunction is prevalent. It promotes aspiration, which may not elicit a cough reflex and may be associated with pneumonia. Aspiration pneumonia may be an underdocumented complication of chemoradiotherapy for head-and-neck cancer. Future studies should examine whether routine post-therapy videofluoroscopy and training aspirating patients in safe swallowing strategies can reduce this risk.

    Title Remote Delivery of Raav-gfp to the Rat Brainstem Through the Recurrent Laryngeal Nerve.
    Date February 2002
    Journal The Laryngoscope
    Excerpt

    OBJECTIVE: To demonstrate that a recombinant adeno-associated viral vector (rAAV) carrying the gene for green fluorescent protein (GFP) could be delivered to the rat brainstem by remote injection into the recurrent laryngeal nerve. STUDY DESIGN/METHODS: rAAV-GFP is a serotype 2 adeno-associated vector containing the cDNA of GFP and woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) under the control of the CAG promoter (obtained from Matthew During, PhD, Thomas Jefferson Medical College). Five microliters or 10 microL of 1.4 x 109 particles/microL of rAAV-GFP were injected into the right recurrent laryngeal nerve of adult Sprague-Dawley rats. Rats were killed and perfused at 3 (n = 3) and 11 weeks (n = 3). Brainstems were removed and cryosectioned. Fluorescent in-situ hybridization (FISH) was performed on cryosections from animals killed at 3 weeks using a cDNA probe for woodchuck polyribosomal enzyme within the rAAV vector. In a third group (n = 2), Fluoro-Gold (Fluorochrome, Inc., Denver, CO) was injected into the right thyroarytenoid muscle for comparison of neuronal uptake distribution. These rats were killed and perfused at 3 weeks. RESULTS: The presence of GFP was noted in neurons throughout the medulla of all rat brainstems after unilateral rAAV-GFP injection at both 3 and 11 weeks. In contrast to the Fluoro-Gold, GFP was noted bilaterally and outside of the nucleus ambiguus. FISH confirmed the presence of virus within neurons expressing GFP at 3 weeks. CONCLUSIONS: Remote delivery of rAAV-GFP to the rat brainstem is possible through injection into the recurrent laryngeal nerve. This has important therapeutic implications for the future treatment of recurrent laryngeal nerve injury and neurodegenerative diseases.

    Title Thyroarytenoid Muscle Maintains Normal Contractile Force in Chronic Vocal Fold Immobility.
    Date February 2002
    Journal The Laryngoscope
    Excerpt

    BACKGROUND: Denervation of skeletal muscle typically results in irreversible denervation atrophy over time. This finding has generated controversy as to the efficacy of reinnervation procedures for chronic vocal fold immobility related to recurrent laryngeal nerve injury. OBJECTIVE: To test the hypothesis that chronic vocal fold immobility after recurrent laryngeal nerve injury does not result in diminished maximal isometric force generation in the thyroarytenoid muscle. STUDY DESIGN: Adult random-bred cats underwent either unilateral laryngeal denervation (n = 6) or sham surgery (n = 6). After 6 months, videolaryngoscopy was performed followed by in vitro measurement of maximal isometric tetanic force produced by the thyroarytenoid muscle. RESULTS: All animals in the denervation group showed right vocal fold paralysis after the initial denervation operation; none of these animals had return of appropriately phased movement with respiration. Four had intermittent disorganized twitching movements. One had these movements plus an occasional weak adduction, and one had no movement. Normal vocal fold mobility was observed in 6 of 6 animals undergoing sham surgery. The maximal isometric tetanic force measured from the thyroarytenoid muscle in the sham group was 438 mN (+/-92 mN standard deviation [SD]). The maximal isometric tetanic force measured from the thyroarytenoid muscle in the chronically immobile group was 405 mN (+/-107 mN SD). Differences were not statistically significant. CONCLUSION: Maximal isometric force in the thyroarytenoid muscle is not diminished in chronic vocal fold immobility after recurrent laryngeal nerve injury. We conclude that the possibility for restoration of contractile force to the chronically immobile thyroarytenoid muscle exists. This finding supports the pursuit of reinnervation procedures in the treatment of chronic vocal fold immobility.

    Title Development and Validation of the Neck Dissection Impairment Index: a Quality of Life Measure.
    Date January 2002
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVES: To validate a health-related quality-of-life (QOL) instrument for patients following neck dissection and to identify the factors that affect QOL following neck dissection. DESIGN: Cross-sectional validation study. SETTING: The outpatient clinic of a tertiary care cancer center. PATIENTS: Convenience sample of 54 patients previously treated for head and neck cancer who underwent a selective neck dissection or modified radical neck dissection (64 total neck dissections). Patients had a minimum postoperative convalescence of 11 months. Thirty-two underwent accessory nerve-sparing modified radical neck dissection, and 32 underwent selective neck dissection. MAIN OUTCOME MEASURE: A 10-item, self-report instrument, the Neck Dissection Impairment Index (NDII), was developed and validated. Reliability was evaluated with test-retest correlation and internal consistency using the Cronbach alpha coefficient. Convergent validity was assessed using the 36-Item Short-Form Health Survey (SF-36) and the Constant Shoulder Scale, a shoulder function test. Multiple variable regression was used to determine variables that most affected QOL following neck dissection RESULTS: The 10-item NDII test-retest correlation was 0.91 (P<.001) with an internal consistency Cronbach alpha coefficient of.95. The NDII correlated with the Constant Shoulder Scale (r = 0.85, P<.001) and with the SF-36 physical functioning (r = 0.50, P<.001) and role-physical functioning (r = 0.60, P<.001) domains. Using multiple variable regression, the variables that contributed most to QOL score were patient's age and weight, radiation treatment, and neck dissection type. CONCLUSIONS: The NDII is a valid, reliable instrument for assessing neck dissection impairment. Patient's age, weight, radiation treatment, and neck dissection type were important factors that affect QOL following neck dissection.

    Title Use of Speech Recognition Software: a Vocal Endurance Test for the New Millennium?
    Date December 2001
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    Speech recognition software for the personal or office computer is a relatively new area of technology. As the number of these products has increased so has use of this software. Some individuals will employ speech recognition systems due to difficulty with the conventional keyboard and mouse interface: others will use it for perceived efficiency or simply novelty. Regardless of the reason for use of this technology, the voice demands associated with extended or frequent use can be high, placing the user at risk for vocal difficulties. This paper reviews the case of an individual referred to our multidisciplinary voice care program for evaluation and treatment of vocal difficulties that began secondary to utilization of speech recognition software. We discuss medical and vocal histories, examination findings, treatment, and treatment outcomes.

    Title Conservation Laryngeal Surgery for Malignant Tumors of the Larynx and Pyriform Sinus.
    Date December 2001
    Journal Hematology/oncology Clinics of North America
    Excerpt

    Conservation surgery for cancers of the larynx and pyriform sinus is an expansive and complicated subject. A great deal of technical expertise and clinical judgement are required for appropriate surgical and oncologic outcomes. In the appropriate setting, surgery continues to play an important role in voice preservation for patients with laryngeal and hypopharyngeal carcinoma. Perhaps most importantly, options for organ preservation surgery have expanded, and the number of patients requiring total laryngectomy as primary surgical management has decreased. The medical surgical decision making is complex and requires precise delineation of tumor extent, careful patient evaluation, and thorough interdisciplinary discussion to select an optimal course of treatment for the individual patient.

    Title Selective Cricothyroid Muscle Reinnervation by Muscle-nerve-muscle Neurotization.
    Date October 2001
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: To determine if selective reinnervation of the cricothyroid muscle could be achieved with muscle-nerve-muscle neurotization. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Three consecutive patients with high vagal lesions that resulted in unilateral laryngeal paralysis. INTERVENTIONS: Patients underwent laryngeal reinnervation with ansa hypoglossi to recurrent laryngeal nerve anastomosis. In addition, patients underwent selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization technique. MAIN OUTCOME MEASURES: Objective and subjective improvement in voice quality and electromyographic evidence of selective reinnervation of the cricothyroid muscle. RESULTS: All patients recovered normal or near-normal speaking voice and had normal objective measures of voice quality. They also showed electromyographic evidence of cricothyroid muscle reinnervation. CONCLUSION: The muscle-nerve-muscle neurotization technique was successful in providing selective reinnervation of the cricothyroid muscle in our 3 patients.

    Title Motion-specific Laryngeal Reinnervation Using Muscle-nerve-muscle Neurotization.
    Date September 2001
    Journal The Annals of Otology, Rhinology, and Laryngology
    Excerpt

    There is no current treatment method that can reliably restore physiologic movement to a paralyzed vocal fold. The purposes of this study were to test the hypotheses that 1) muscle-nerve-muscle (M-N-M) neurotization can be induced in feline laryngeal muscles and 2) M-N-M neurotization can restore movement to a paralyzed vocal fold. Muscle-nerve-muscle neurotization can be defined as the reinnervation of a denervated muscle via axons that are induced to sprout from nerves within an innervated muscle and that then traverse a nerve graft interposed between it and the target denervated muscle. A paralyzed laryngeal muscle could be reinnervated by axons from its contralateral paired muscle, thus achieving motion-specific reinnervation. Eighteen adult cats were divided into sham, hemilaryngeal-denervated, and M-N-M-reinnervated thyroarytenoid muscle groups. Five of the 6 reinnervated animals had histologic evidence of axons in the nerve graft, 4 of the 6 had evoked electromyographic evidence of crossed reinnervation, and 1 of the 6 had a return of appropriately phased adduction. This technique has great potential and should be further investigated.

    Title Conformal Re-irradiation of Recurrent and New Primary Head-and-neck Cancer.
    Date June 2001
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To review the outcome of head-and-neck cancer patients re-irradiated using conformal radiation. PATIENTS AND METHODS: From 1983 to 1999, 60 patients with recurrent or new primary head-and-neck cancer received re-irradiation at the University of Michigan. Twenty patients were excluded due to the planned cumulative radiation dose being less than 100 Gy (18) and absence of prior radiation details (2), leaving 40 patients. Thirty-five patients were re-irradiated for unresectable disease, while 4 patients received adjuvant re-irradiation for high-risk disease. Thirty-eight patients had recurrences from previously treated cancer (19 regional, 14 local, 5 regional and local), and 2 patients had new primary tumors. The median time from the first course of radiation to re-irradiation was 21 months. Thirty-one patients (78%) were re-irradiated with curative intent, whereas 9 were treated with palliative intent. Re-irradiation was delivered using conformal techniques in the majority of patients and with concurrent chemotherapy in 14 patients. The median re-irradiation dose was 60 Gy. The median cumulative dose received was 121 Gy. Five patients (13%) did not complete their prescribed course of re-irradiation. RESULTS: The median survival following completion of re-irradiation was 12.5 months. The 1- and 2-year actuarial survival rates were 51.1% and 32.6%, respectively. On multivariate analysis, palliative intent of treatment, tumor bulk, and tumor site other than nasopharynx or larynx were associated with worse survival. The patients treated for unresectable disease did no worse than those treated adjuvantly. The median times to relapse-free survival, local-regional recurrence (LRR)-free survival, and ultimate LRR-free survival (allowing for surgical salvage) were 3.9 months, 7.8 months, and 8.7 months, respectively. Seven patients (18%) are presently alive with no evidence of disease, with a median follow-up of 49.9 months (range 3.3-78.9). Severe radiation-induced complications were seen in 7 patients (18%). Two other patients developed orocutaneous fistulas in the presence of tumor recurrence. Moderate fibrosis and trismus were common. CONCLUSION: Despite the use of conformal techniques, the prognosis of patients treated with re-irradiation is poor, and complications are not infrequent. A subset of patients is salvageable, and high-dose re-irradiation should be considered in selected patients.

    Title Radiation Concurrent with Gemcitabine for Locally Advanced Head and Neck Cancer: a Phase I Trial and Intracellular Drug Incorporation Study.
    Date March 2001
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Excerpt

    PURPOSE: To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. PATIENTS AND METHODS: Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. RESULTS: Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). CONCLUSION: A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

    Title Voice-related Quality of Life (v-rqol) Following Type I Thyroplasty for Unilateral Vocal Fold Paralysis.
    Date February 2001
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    Unilateral vocal fold paralysis is a common clinical problem which frequently causes severe dysphonia. Various treatment options exist for this condition, with the type I thyroplasty being one of the more commonly performed surgical procedures for vocal rehabilitation. The Voice-Related Quality of Life (V-RQOL) Measure is a validated outcomes instrument for voice disorders. This study measured the V-RQOL of patients with unilateral vocal fold paralysis who had undergone a type I thyroplasty and compared these scores to those of patients with untreated and uncompensated unilateral vocal fold paralysis and to normals. Treated patients had significantly higher domain and overall V-RQOL scores than untreated patients, but also scored lower than normals. These differences were true across gender and age. Patients who were more distant from surgery had lower V-RQOL scores than those who had more recently been treated. It is concluded that type I thyroplasty leads to a significantly higher V-RQOL for patients with unilateral vocal fold paralysis. This study also demonstrates further the utility of patient-oriented measures of treatment outcome.

    Title Simultaneous Vocal Fold and Tongue Paresis Secondary to Epstein-barr Virus Infection.
    Date January 2001
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    Dysphonia is a common presenting symptom in cases referred for otolaryngologic evaluation. Similarly, primary care physicians frequently see adolescents or young adults with symptomatic Epstein-Barr virus infection. Some of the patients with active Epstein-Barr virus infection who have severe clinical manifestations of infectious mononucleosis will be referred for otolaryngologic evaluation. Voice abnormalities in these patients, though, are usually limited to altered resonance due to pharyngeal crowding by hyperplastic lymphoid tissue. We describe a patient with infectious mononucleosis who was referred for evaluation of dysphonia and was diagnosed with unilateral tongue and vocal fold paresis. We also discuss the patient's clinical course and review the related literature. Although uncommon, cranial nerve palsies must be considered in the patient with Epstein-Barr virus infection who presents with voice or speech disturbance. Arch Otolaryngol Head Neck Surg. 2000;126:1491-1494

    Title Indirect Laryngeal Surgery in the Clinical Voice Laboratory: the Renewal of a Lost Art.
    Date July 2000
    Journal Ear, Nose, & Throat Journal
    Excerpt

    Since the advent of precision instruments and safe techniques for direct laryngoscopic surgery under general anesthesia, indirect laryngeal surgery has become very uncommon. A review of the recent literature finds that few authors advocate indirect surgery under topical anesthesia, and many otolaryngologists dismiss this technique as being either of only historical interest or an idiosyncratic method practiced only by a handful of clinicians. The societal mandate for cost-effective healthcare and the availability of relatively low-cost, high-quality endoscopes and video equipment warrant a renewed and broader interest in this type of surgery. In this article, we review a series of 27 indirect surgical procedures performed under topical anesthesia in the clinical voice laboratory. We discuss the indications, outcomes, advantages, and disadvantages of this surgery, and we present a brief analysis of its cost-effectiveness. We conclude that indirect laryngeal surgery in the clinical voice laboratory is an effective, safe, efficient, and less costly alternative to some procedures routinely performed under general anesthesia.

    Title Pain, Quality of Life, and Spinal Accessory Nerve Status After Neck Dissection.
    Date April 2000
    Journal The Laryngoscope
    Excerpt

    OBJECTIVE: To assess quality of life (QOL) in patients with head and neck cancer who underwent neck dissection and to compare QOL scores for patients in whom the spinal accessory nerve (CN XI) was resected or preserved. SETTING AND DESIGN AND OUTCOMES MEASURES: Three hundred ninety-seven patients who had undergone treatment for head and neck cancer completed the University of Michigan Head and Neck Quality of Life (HNQOL) instrument, the Medical Outcomes Study SF-12 General Health Survey, and questions on "pain despite pain medications" and headaches. RESULTS: Of the 397 patients, 222 had no neck dissection, 46 had neck dissections resecting CN XI, and 129 had dissection sparing CN XI. Of the latter group, 68 patients had dissections sparing level V and 61 dissections included level V. Age, sex, primary site distribution, and T stage were not different between the groups. Patients who had neck dissections sparing CN XI had better scores on the HNQOL pain domain (P = .002), had less shoulder or neck pain (P = .003), and took pain medications less frequently (P = .0004) compared with patients who had neck dissections sacrificing CN XI. When CN XI was preserved, patients who had no level V dissection had better pain domain scores (P = .03) and eating domain scores (P = .007) on the HNQOL, had less shoulder or neck pain (P = .006), and had less physical problems (P = .03) than patients who had level V dissected. On multivariate analysis, pain-related QOL scores after neck dissection were significantly better (P < .01) if patients had dissections with preservation of CN XI and if level V was not dissected. CONCLUSION: Neck dissections sparing CN XI are associated with better pain scores on the HNQOL, less shoulder and neck pain, and less need for medications. When CN XI is spared, not dissecting level V of the neck is associated with better HNQOL pain scores, less shoulder or neck pain, and fewer physical problems.

    Title Validation of an Instrument to Measure Voice-related Quality of Life (v-rqol).
    Date February 2000
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    When a patient presents for care of a voice disorder, the clinician attempts to diagnose the problem, quantify the degree of dysphonia, and prescribe appropriate treatment. Quantification of the degree of dysphonia is often difficult, as no universal index of vocal function exists. Decisions about the nature and intensity of treatment are often based on the magnitude of the voice-related problems experienced by the patient and the importance that the patient places on those problems, that is, the impact that the voice disorder is having on the patient's voice-related quality of life (V-RQOL). Measurement of post-treatment outcome is also not standardized. Regardless of how the clinician measures response to treatment, it will typically be measured by the patient in terms of how his or her voice-related problems are affected by the treatment. Measurement of quality of life has not been a traditional part of the evaluation of the dysphonic patient. This study was undertaken to develop and validate an instrument for measuring V-RQOL using a population of 109 voice and 22 non-voice patients. The 10-item V-RQOL measure performs well in tests of reliability, validity, and responsiveness, and it carries a low burden. Measurement of V-RQOL is a valuable addition to the evaluation of dysphonic patients and their treatment outcomes.

    Title Subglottic Carcinoma: Review of a Series and Characterization of Its Patterns of Spread.
    Date October 1999
    Journal Ear, Nose, & Throat Journal
    Excerpt

    The rarity of primary subglottic malignancies, along with the varied definitions of the anatomic confines of this region, have limited our understanding of the patterns of tumor spread within the subglottis. We conducted a retrospective chart review to analyze clinical and pathologic data in patients with subglottic carcinoma. A pattern of disease progression was identified, which is defined by the cartilaginous laryngeal framework, with the fibroelastic barriers susceptible to tumor invasion. We conclude that although cartilaginous laryngeal structures are preserved until late in the disease course, the ability of tumors to invade the fibroelastic membranes provides them with an insidious means of escape. Specifically, tumor progression occurs primarily within the paraglottic space and extralaryngeal compartments; the potential for mucosal spread is limited. The lack of mucosal disease in patients whose cartilaginous laryngeal structures are intact may present a facade of normality in patients with advanced disease, and perhaps delay the early diagnosis of subglottic malignancies by physical and radiologic examination.

    Title Transnasal Endoscopic Examination of the Subglottis and Trachea Using Topical Anesthesia in the Otolaryngology Clinic.
    Date July 1999
    Journal The Laryngoscope
    Title Vocal Fold Nodules in Adult Singers: Regional Opinions About Etiologic Factors, Career Impact, and Treatment. A Survey of Otolaryngologists, Speech Pathologists, and Teachers of Singing.
    Date June 1999
    Journal Journal of Voice : Official Journal of the Voice Foundation
    Excerpt

    This study was undertaken to better understand current regional opinions regarding vocal fold nodules in adult singers. A questionnaire was sent to 298 persons representing the 3 professional groups most involved with the care of singers with vocal nodules: otolaryngologists, speech pathologists, and teachers of singing. The questionnaire queried respondents about their level of experience with this problem, and their beliefs about causative factors, career impact, and optimum treatment. Responses within and between groups were similar, with differences between groups primarily in the magnitude of positive or negative responses, rather than in the polarity of the responses. Prevailing opinions included: recognition of causative factors in both singing and speaking voice practices, optimism about responsiveness to appropriate treatment, enthusiasm for coordinated voice therapy and voice training as first-line treatment, and acceptance of microsurgical management as appropriate treatment if behavioral management fails.

    Title A Comparison of Methods of Botulinum Toxin Injection for Abductory Spasmodic Dysphonia.
    Date December 1997
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    Treatment of abductory spasmodic dysphonia with botulinum toxin injection into the posterior cricoarytenoid muscles often results in only partial symptom relief. In contrast, excellent results can be achieved after thyroarytenoid injection for the adductory type of spasmodic dysphonia. One reason for disappointing results may be inaccurate placement of the botulinum toxin into the posterior cricoarytenoid muscles. We describe a new approach to posterior cricoarytenoid injection used in 18 patients for treatment of abductory spasmodic dysphonia. Of the 30 patients treated for abductory spasmodic dysphonia at Loyola University-Chicago, 6 underwent both a retrocricoid approach and the newer transcricoid method, thus allowing patient and clinician comparison of techniques. We and all six of our patients preferred the transcricoid approach because of less discomfort, equivalent or better voice results, and fewer side effects.

    Title Endoscopic Co2 Laser Excision of Large or Recurrent Laryngeal Saccular Cysts in Adults.
    Date March 1997
    Journal The Laryngoscope
    Excerpt

    Saccular cysts are uncommon disorders that represent cystic dilatation of the laryngeal saccule. They are distinguished from laryngoceles by their lack of lumenal continuity with the endolarynx, and the fact that they are not air filled. Voice change is the most common clinical presentation in adults, whereas airway compromise is more common in infants. Management recommendations range from observation of asymptomatic lesions, to endoscopic marsupialization or excision, to excision through a laryngotomy or the thyrohyoid membrane. The literature states that large or recurrent saccular cysts require the exposure afforded by a transcervical approach. This report describes complete endoscopic laser excision of large, symptomatic saccular cysts in seven adults. Four of the seven patients were referred with recurrent cysts after the failure of endoscopic marsupialization procedures. None required tracheotomy, and only three of seven were observed overnight in the hospital. Surgical technique with emphasis on complete excision, pre- and postoperative radiographic and surgical anatomy, and treatment outcome are discussed.

    Title Development of Thrombosis Models in the Rabbit.
    Date October 1994
    Journal Archives of Otolaryngology--head & Neck Surgery
    Excerpt

    OBJECTIVE: In an effort to decrease the probability of thrombosis at microvascular anastomotic sites, researchers have examined techniques for decreasing the probability of thrombus formation at these sites. Identification of an appropriate animal model that is relatively easy to perform, reliable, and reproducible was attempted in this study. The goal of this study is to provide other investigators with a comparison and critical appraisal of various thrombosis models allowing a more directed selection of models for their own research. DESIGN: A prospective, nonblinded animal study was designed that compared features of thrombosis models previously described in the literature with each other and with a new model (the "tuck" model), herein described. MAIN OUTCOME MEASURES: Ease of dissection, time to thrombosis, and other technical details were recorded. Additionally, validation of clot histologic features in the tuck model was performed. RESULTS: The inversion graft models were found to be the most highly predictable and reliably thrombogenic, although technically quite difficult. The tuck model produces clot analogous to that produced clinically and is easy to perform, although a predictable number of vessels will not thrombose. CONCLUSIONS: The results of this study comparing various animal models of anastomotic thrombosis suggests that the tuck model is the model of choice for most thrombus prevention studies. When predictability of thrombosis is a critical factor, the inversion graft model should be chosen.

    Title Effect of Blood Transfusion on Recurrence of Head and Neck Carcinoma. Retrospective Review and Meta-analysis.
    Date September 1992
    Journal The Annals of Otology, Rhinology, and Laryngology
    Excerpt

    To study the effect of transfusion on recurrence of squamous cell carcinoma of the head and neck, we analyzed the records of 143 patients with stage II through IV squamous cell carcinoma of the supraglottic larynx or hypopharynx for whom follow-up to recurrence or 5 years after surgical therapy was available. Variables studied were age, gender, TNM staging, duration of operation, estimated blood loss, units of blood products transfused, surgical margins, number of pathologic nodes, radiotherapy, chemotherapy, hematocrit, and serum albumin. Multivariate logistic regression demonstrated that transfusion, number of pathologic nodes, and preoperative hematocrit were significantly related to recurrence. The univariate odds ratio for tumor recurrence in patients receiving any blood products was 3.2 (95% confidence interval 1.5 to 6.9; p = .004). Based on a meta-analysis of the data from this study and the five published studies, the combined odds ratio for recurrence after transfusion was 2.6 (95% confidence interval 1.9 to 3.7; p less than .0001). These data identify a clinically important adverse effect of transfusion of blood products on tumor recurrence in patients with advanced head and neck cancer. We recommend a policy of blood conservation surgery to enhance cancer control, and we encourage further research to clarify the mechanism(s) of this effect.

    Title Cutaneous Photoprotection Using a Hydroxyl Radical Scavenger in Photodynamic Therapy.
    Date June 1991
    Journal American Journal of Otolaryngology
    Excerpt

    Photodynamic therapy (PDT) is emerging as an effective therapy for a variety of malignant diseases, including head and neck cancer. Prolonged cutaneous photosensitivity following therapy, however, remains the most significant side effect. The biochemical mechanism of this sensitivity, and indeed of the tumoricidal effect of PDT, is uncertain, but is believed to involve formation of singlet oxygen and possibly other oxygen-derived free radicals. This laboratory recently reported that a singlet oxygen scavenger, diphenylisobenzofuran (DPIBF), afforded cutaneous photoprotection to 67% of animals treated with PDT. Those results, the first from an in vivo study, supported the idea that singlet oxygen plays a significant role in PDT and its associated toxicity. They also, however, suggested that it is not the sole intermediate. The current study looks at the photoprotective effects of the hydroxyl radical scavenger dimethyl thiourea, alone and in conjunction with DPIBF. Our results strongly support a role for the hydroxyl radical in producing the cutaneous phototoxicity associated with PDT.

    Title A Deletion Involving Alu Sequences in the Beta-hexosaminidase Alpha-chain Gene of French Canadians with Tay-sachs Disease.
    Date December 1987
    Journal The Journal of Biological Chemistry
    Excerpt

    French Canadians living in eastern Quebec are carriers of a severe type of Tay-Sachs disease, known as the classic form, 10 times more often than the general population. The alpha-chain of beta-hexosaminidase A, a lysosomal enzyme composed of two chains (alpha, beta), bears the mutation in this inherited disorder. We previously reported that the 5' end of the alpha-chain gene was deleted in two such patients (Myerowitz, R., and Hogikyan, N.D. (1986) Science, 232, 1646-1648). The present study reports the size, precise location, and environment of the deletion. A clone encompassing the deletion was isolated from a genomic library constructed in lambda EMBL3 with DNA from a patient's fibroblasts. Comparison of the restriction maps of the clone with that of the normal gene (Proia, R.L., and Soravia, E. (1987) J. Biol. Chem. 262, 5677-5681) showed that the deletion was 7.6 kilobases long and included part of intron 1, all of exon 1 and extended 2000 base pairs upstream past the putative promotor region of the alpha-chain gene. These data are consistent with the inability to detect mRNA and immunoprecipitable alpha-chain protein in this mutant. Sequence analysis of the deletion junction in the mutant and corresponding regions of the normal gene demonstrated the presence of similarly oriented Alu sequences at the 5' and 3' deletion boundaries. The data are in accord with the possibility that the deletion may have arisen during homologous recombination from unequal crossing over between Alu sequences.

    Title Different Mutations in Ashkenazi Jewish and Non-jewish French Canadians with Tay-sachs Disease.
    Date July 1986
    Journal Science (new York, N.y.)
    Excerpt

    Tay-Sachs disease patients of Ashkenazi Jewish and non-Jewish French Canadian origin are affected with a clinically identical form of this inherited disease. Both have a similar gene frequency for the disorder, which is tenfold higher than that found in the general population. Unlike other patients with the disease, who often display variation at the clinical or biochemical level, the absence of such differences between these two groups has prompted the idea that they may harbor the same mutation. In this report, a complementary DNA clone coding for the alpha chain of human beta-hexosaminidase has been used to analyze the genetic lesions in the alpha-chain locus of two patients with Tay-Sachs disease from each of these groups. On the basis of DNA hybridization analyses, the alpha-chain gene of the Ashkenazi patients appears intact while the alpha-chain gene of French Canadian patients has a 5' deletion of approximately 5 to 8 kilobases.

    Title The Effect of Depot Parenteral Zinc on Copper Metabolism in the Rat.
    Date January 1985
    Journal The Journal of Nutrition
    Excerpt

    The effect of depot parenteral injections of zinc (110 mg Zn/kg body weight) on copper metabolism in young, male rats was investigated. Individually caged rats, fed known amounts of stock diet and deionized-distilled water, were injected s.c. weekly for the first 4 weeks and biweekly for the next 17 weeks with zinc in sesame oil or the oil vehicle only. No significant differences in body weight, hemoglobin, hematocrit and fecal copper excretions were observed between treatments. However, 2 weeks after the initial injections, urinary copper excretion was elevated in the zinc-injected animals and remained elevated throughout the rest of the study. Plasma copper concentrations were significantly higher in the zinc-injected animals from week 2 to 8 of the study, and plasma zinc concentrations of these injected animals were elevated (P less than 0.05) from week 2 and throughout the remainder of the study. Zinc concentrations were significantly higher in the liver, heart, kidney and spleen (P less than 0.05) and copper concentrations were lower in the liver (P less than 0.07), kidney and spleen (P less than 0.05) of zinc-injected animals compared to the vehicle-treated control animals. The data indicate that when zinc is administered by a non-gastrointestinal route, the fecal excretion of copper, the major route of copper excretion, is not altered. Thus, a negative copper balance is not initiated by high levels of zinc administered by the depot technique, in contrast to the negative copper balance stimulated by the gastrointestinal administration of zinc.

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