A comparison of radiation-induced and presbylaryngeal dysphonia.

OBJECTIVE: The goal of this study was to assess voice after radiotherapy compared with patients with presbylaryngeal dysphonia. STUDY DESIGN AND SETTING: Prospective assessment of 20 patients aged 60+ years who remained free of disease longer than 1 year after radiotherapy for T1 squamous cell carcinoma and retrospective review of 46 patients aged 60+ with presbylaryngeal dysphonia, conducted at a tertiary care, academic hospital. Assessment data included videostroboscopy, spectrography, voice range profile, and Voice Handicap Index. RESULTS: Eighty percent of the radiotherapy patients reported a voice disorder. Acoustic data and functional measures reflected similar limitations and abnormalities for both groups. A high incidence of glottal gap in all patients may have been associated with increased mucosal stiffness in the radiotherapy group and vocal fold atrophy in the presbylaryngeal group. CONCLUSION: Patient perception and functional outcome of voice were similar for both groups, despite differences in etiology of abnormal vocal fold vibratory behavior. SIGNIFICANCE: Radiotherapy in older individuals may yield dysphonia that is no greater than that caused by normal aging.

Ondansetron with propofol reduces the incidence of emesis in children following tonsillectomy.

PURPOSE: This study tested the hypothesis that the antiemetic effects of a combination of ondansetron and propofol were superior to propofol alone in children undergoing tonsillectomy surgery. METHODS: A prospective, randomized, double-blind, placebo-controlled study design was employed. Young children underwent mask induction with halothane, nitrous oxide and oxygen and then had i.v. access established: older children had i.v. induction with propofol. All patients received 0.3 mg x kg(-1) mivacurium and 2-4 microg x kg(-1) fentanyl i.v. and 30 mg x kg(-1) acetaminophen pr to a maximum dose of 650 mg. Following induction, patients received either 100 microg x kg(-1) ondansetron or placebo. Anaesthesia was maintained with 120-140 microg x kg(-1) x min(-1) propofol, nitrous oxide and oxygen to maintain vital signs within 20% of baseline. After surgery, in all patients the tracheas were extubated in the operating room without use of neuromuscular reversing agents. Episodes of emesis were recorded by PACU nurses for four to six hours. A telephone interview on the following day was also used for data recovery. Groups were compared in relation to age using the Mann-Whitney test, and with respect to sex and number of episodes of vomiting using the Fisher Exact Test. RESULTS: Three of the 45 patients who received ondansetron vomited (6.7%), whereas 10 of the 45 patients who received placebo vomited (22.2%). (P = 0.035) CONCLUSION: Ondansetron in a dose of 100 microg x kg(-1), when combined with propofol for children undergoing tonsillectomy reduced the incidence of postoperative vomiting to very low levels.

Efficacy of DHE photodynamic therapy for respiratory papillomatosis: immediate and long-term results.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis is a potentially life-threatening disease that affects both children and adults and can result in complete respiratory obstruction. Conventional therapies cannot prevent multiple recurrences. The authors have been evaluating photodynamic therapy (PDT) to treat this disease since 1988. This study compared the efficacy of PDT with dihematoporphyrinether (DHE) with traditional therapy. STUDY DESIGN: This was a randomized prospective trial of DHE-PDT. Patients were randomly assigned to receive one of two doses of DHE--3.25 mg/kg or 4.25 mg/kg body weight. They were compared with a concurrent control group. Disease extent was evaluated by direct laryngoscopy before treatment and over a 1-year period following treatment. Results were also compared with two historical cohorts of patients treated with lower doses of DHE. METHODS: Eighty-one patients, ages 4 to 74 years, with moderate to severe recurrent disease were enrolled. Forty-eight received PDT and 33 in the control group were treated with conventional therapy. Both PDT groups received 50 J laser light to activate the drug. Patients received an intravenous infusion of DHE as outpatients 48 to 72 hours before treatment. During direct laryngoscopy, light (630 nm) was delivered by an argon-pumped dye laser. Tissue biopsies were analyzed for presence of human papillomavirus (HPV). RESULTS: There was notable improvement with either drug dose over the first year. Those receiving 4.25 mg/kg DHE experienced a significantly larger decrease in papilloma growth rate. Three-year follow-up of a subset of patients confirmed that improvement was maintained. There was no impact of DHE-PDT on persistence of HPV DNA. CONCLUSION: This therapy holds promise for the treatment of laryngeal papillomas.

Clear plastic cups: a childhood choking hazard.

The disposable plastic beverage cup is not usually regarded as hazardous to young children. Certain varieties of these products however, are manufactured from a brittle, clear plastic that easily cracks and fragments. While most conscientious parents keep their children safe from peanuts, balloons, and other known choking hazards, a child can surreptitiously bite a cup edge and aspirate the fragment. We report two cases of foreign body aspiration involving clear plastic cups that went undetected one of which remained 21 months following a negative rigid bronchoscopy. Diagnostic difficulties are related to the transparency and radiolucency of these objects. When suspicious of foreign body aspiration in children, otolaryngologists should inquire about the availability of clear plastic cups in the household and be mindful of the diagnostic pitfalls. Further investigations including CT scanning and repeat bronchoscopy may be helpful in cases of suspected missed foreign bodies. An educational campaign aimed at prevention and placement of product package warning labels should be established.

Globe ptosis secondary to maxillary sinus mucocele.

Six patients were treated for gradual onset of enophthalmos, a deep superior sulcus and globe ptosis. There was no history of orbital trauma or sinusitis. CT scan showed an opacified shrunken maxillary sinus with dehiscence and depression of the orbital floor and downward displacement of the orbital contents. Pathological review of the surgical specimens showed a respiratory mucosal lining with thick mucoid secretions, new bone formation, but no purulence. The etiology is thought to be maxillary sinus mucocele. Surgical treatment with an otolaryngologist consisted of a Caldwell-Luc procedure to evacuate the maxillary sinus with nasal antrostomy and an orbital floor exploration with insertion of a methylmethacrylate implant molded at the time of surgery to reform the orbital floor and reposition the globe. Follow-up of 2 1/2-4 years shows excellent functional and cosmetic results.

Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model.

OBJECTIVE: To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems. DESIGN: Nonrandomized control trial. SETTING: Division of ear, nose, and throat research at a tertiary care teaching hospital. MATERIALS: Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines. INTERVENTION: Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light. OUTCOME MEASURES: Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response. RESULTS: The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2. CONCLUSIONS: m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.

Variable light-dose effect on photodynamic therapy for laryngeal papillomas.

OBJECTIVE: We investigated photodynamic therapy (PDT) as an alternative treatment modality for recurrent respiratory papillomatosis. To optimize the effect of PDT, the light dose in this study was increased from 50 to 80 J/cm2. The clinical effect of these two light doses will be discussed and compared. DESIGN: Each patient's response was based on the growth rate of their papilloma before and after PDT. Disease response following 50 J/cm2 was compared with that after 80 J/cm2. The two study groups were also compared with a control group. SETTING: Each patient received the dihematoporphyrin ether as an outpatient and underwent direct laryngoscopy and PDT at our institution. PATIENTS: Twenty-eight patients (16 male and 12 female) with moderate to severe laryngeal disease and an age range of 18 months to 80 years were treated with a light dose of 80 J/cm2, 11 of those had been previously treated with 50 J/cm2. Seven patients had undergone photoactivation to the trachea. INTERVENTION: Twenty-four hours prior to photoactivation, patients received 2.5 mg/kg of dihematoporphyrin ether intravenously. Photodynamic therapy was given using an argon pump dye laser system. MAIN OUTCOME MEASURE: Reduction in disease severity greater than that achieved with 50 J/cm2. RESULTS: For patients treated initially with 80 J/cm2, the mean rate of papilloma growth decreased by approximately 50%, the same response seen with 50 J/cm2 of treatment. No additional benefit was found for those patients initially activated at 50 J/cm2 and then re-treated at 80 J/cm2. CONCLUSION: Although PDT has a beneficial effect on laryngeal papilloma growth rate, no significant change in response was obtained by increasing the light dose from 50 to 80 J/cm2.

Enriched HLA-DQ3 phenotype and decreased class I major histocompatibility complex antigen expression in recurrent respiratory papillomatosis.

Respiratory papillomas, caused by human papillomaviruses, are benign tumors that recur following removal. We evaluated immune function and major histocompatibility complex (MHC) phenotype and expression in these patients. MHC-independent immune function appeared normal. The frequency of peripheral blood MHC class II phenotypes was highly enriched for DQ3 and DR11, one split of DR5. Class I MHC antigen expression on papilloma tissue was markedly reduced. Together, these phenomena may facilitate papillomavirus evasion of the cellular immune response.

Carcinoma in situ of the glottic larynx.

Carcinoma in situ (CIS) is part of the histopathologic spectrum of laryngeal disorders where invasive squamous cell carcinoma is the endpoint of cellular disarray. Few reports consider prognostic indicators that predict which lesions become invasive. Forty-one patients with CIS of the glottic larynx were analyzed for risk factors that would predict invasive cancer. Anterior commissure involvement by CIS resulted in 92% conversion to invasive squamous cell cancer compared to 17% of lesions limited to the mobile fold. Epidermal growth factor receptors were also analyzed and were found not to be helpful in predicting invasion. Lesions of the mobile fold should be removed endoscopically and the patient should be observed closely for recurrence. Anterior commissure involvement that is inaccessible to complete laser ablation should be radiated, and the patient should be observed carefully.

Microbial adherence to and disinfection of laryngoscopes used in office practice.

This study reports the appropriate disinfection methods for flexible and rigid laryngoscopes when used in an outpatient setting. This investigation presents evidence that an appreciable number of laryngoscopes are contaminated during use. A brief tap water rinse serves to eliminate gross soil of host origin known to interfere with disinfectant efficacy. Disinfection with 3.2% glutaraldehyde (Cidexplus) for 10 minutes effectively eliminated microbial contaminants. Since potentially harmful microorganisms were included among the more than 100 isolates during our baseline experiments, the need to eliminate bacteria, viruses, fungi, and protozoa from laryngoscopes is obvious and can be attained readily.

Clinical exacerbation of systemic lupus erythematosus after photodynamic therapy of laryngotracheal papillomatosis.

Photodynamic therapy was used to treat a patient with recurrent laryngotracheal papillomatosis who had a history of systemic lupus erythematosus (SLE). At the time of photoactivation, the patient's SLE was in remission for 2 years. Postoperatively, the patient was not compliant in avoiding sunlight exposure and developed photosensitive skin reactions of his face and hands. In addition, he had clinical activation of his SLE following that exposure.

Human papillomavirus type 6a DNA in the lung carcinoma of a patient with recurrent laryngeal papillomatosis is characterized by a partial duplication.

Transcriptionally active human papillomavirus type 6a (HPV-6a) DNA was detected in a lung carcinoma of a patient with recurrent laryngeal papillomatosis. The carcinoma contained episomal HPV-6a genomes that had a duplication of the upstream regulatory region, the late region and a portion of the early region. HPV-6a genomes found in benign laryngeal papillomas from the same patient did not contain this duplication. A role for the mutant molecules in the pathogenesis of the malignancy is suggested.

Clinical effects of photodynamic therapy on recurrent laryngeal papillomas.

Thirty-three patients with moderate to severe recurrent laryngeal papillomatosis underwent photodynamic therapy at our institution. All received 2.5 mg/kg of dihematoporphyrin ether intravenously either 48 or 72 hours prior to photoactivation with an argon pump dye laser system. Photosensitivity was the only side effect seen. Statistical analysis showed a significant decrease, by approximately 50%, in the average rate of laryngeal papilloma growth following treatment. The response was especially pronounced in patients with the worst disease. In addition, three patients have now remained free of disease for extended periods following photodynamic therapy. Latent infection with human papillomavirus continues to persist in clinically normal tissue following photodynamic therapy. The results and potential of this exciting new therapy for laryngeal papillomatosis are described.

In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid.

We have defined conditions permitting the in vitro growth of human laryngeal papilloma cells at the air-liquid interface. Using this model system, retinoic acid has been found to modulate the differentiation of human laryngeal papilloma cells along two different pathways. At low concentrations of retinoic acid [10(-9) mol/L and 10(-8) mol/L], the cells formed a stratified squamous epithelium with a differentiation-specific protein staining pattern identical to that found in vivo. At higher concentrations of retinoic acid [10(-7) mol/L and 10(-6) mol/L], the cells differentiated into a columnar epithelium with occasional ciliated cells, lacking the markers of squamous differentiation. Analysis of the human papillomavirus DNA content revealed that as the concentration of retinoic acid increased, the viral DNA content decreased. This system is proposed as a model to further investigate the differentiation defects of human laryngeal papilloma cells and the regulatory role of retinoic acid in the clinical expression of human laryngeal papillomatosis.

Endolaryngeal jet ventilation: a 10-year review.

Jet ventilation for microsurgery of the larynx has been in common use at our institution since 1978. There were 942 cases performed, with ages ranging from 7 days to 90 years. A specially modified laryngoscope with multiple ports into which a 14- or 16-gauge ventilation needle can be advanced just distal to the vocal cords simplifies this form of anesthesia and ventilation. Jet ventilation has been advocated in place of conventional ventilation methods during carbon dioxide laser surgery because it eliminates the potential fire hazard of the endotracheal tube and allows superior visibility of the vocal cords. Despite these advantages, it is still not in common use. We will review the airway mechanics and special anesthesia considerations that make jet ventilation a safe and time-proven technique.

Retinoic acid regulates, in vitro, the two normal pathways of differentiation of human laryngeal keratinocytes.

We have investigated the regulation of the two normal differentiation pathways followed by laryngeal epithelium. Using a tissue culture system that permits growth of cells at the air-liquid interface in serum-free medium, we found that modulating the concentration of retinoic acid is sufficient to determine which pathway is used. At 10(-8) M retinoic acid, the cells form a stratified squamous epithelium which expresses the differentiation-specific keratin K13. At 10(-7) M retinoic acid, the cells form a ciliated pseudostratified epithelium, with no expression of K13. These results are distinct from those seen with foreskin keratinocytes, which have only a single pathway of normal differentiation.

Abnormal differentiation of human papillomavirus-induced laryngeal papillomas.

We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.

The pathologic and thermal effects of gold vapor laser photodynamic therapy on the larynx. Experimental study.

A gold vapor laser, which emits short pulses of light at a wavelength of 628 nm, was used to deliver varying amounts of energy (30 to 120 J/cm2) to the presensitized (dihematoporphyrin ether) canine larynx. Between 30 and 60 J/cm2, the larynx appeared normal, and when 70 to 100 J/cm2 was applied, only mild edema and erythema were seen. Simultaneously, a thermocouple probe was used and a 0.4 degrees C to 1.5 degrees C temperature rise found. Thus, the gold vapor laser seems capable of achieving the therapeutic photosensitizing effect without causing significant laryngeal edema or thermal activity.

Is papillomavirus detectable in the plume of laser-treated laryngeal papilloma?

The carbon dioxide laser is widely used for the vaporization of lesions in patients with laryngeal papillomatosis. In this study, the smoke plume resulting from the laser treatment of laryngeal papillomas was analyzed for the presence of human papillomavirus DNA. Plumes were collected with a suction tip and trapped in phosphate-buffered saline. The aspirates were then analyzed for the presence of human papillomavirus DNA by Southern blot hybridization. Human papillomavirus DNA cannot be detected in the smoke plume from vaporization of laryngeal papillomas unless direct suction contact is made with the papilloma tissue during surgery. The implications of these findings are discussed.