Evaluation and management of bilateral vocal cord immobility.

Bilateral vocal cord immobility can be life threatening for some patients. Others, who have an open glottic chink, may have a breathy dysphonia, intermittent dyspnea, and stridor. These signs and symptoms may also be found in a number of other conditions that cause weakness or paradoxical motion of the vocal cords that mimics paralysis. These other conditions include central nervous system diseases, neuromuscular disorders, laryngospasm, and psychogenic disorders. In addition, patients with cricoarytenoid joint immobility or interarytenoid scar can also have similar symptoms at presentation. It is critical to consider the differential diagnosis of an assumed bilateral vocal cord paralysis and understand the management of paradoxical movement, weakness, joint fixation, interarytenoid scar, laryngospasm, and psychogenic disorders. The treatment for bilateral immobility should proceed only after a thorough evaluation, which might include electromyography and/or examination during general anesthesia under dense anesthetic paralysis. Reconstructive procedures are the treatments of choice, and destructive procedures should be chosen only as a last resort.

Risk factors for juvenile onset recurrent respiratory papillomatosis.

BACKGROUND: Children born to condylomatous mothers are at risk for developing juvenile onset recurrent respiratory papillomatosis (JORRP). We inquired whether the triad of vaginal delivery, being firstborn and maternal age of <20 years are also risk factors for JORRP. METHODS: Data for JORRP and adult onset recurrent respiratory papillomatosis cases were obtained from questionnaires answered by patients or their parents for the Recurrent Respiratory Papillomatosis Foundation. The observed numbers of cesarean births, first order births and births to mothers <20 years old were compared with expected numbers for the same variables, which were computed by distributing the cases by year of birth and then applying to them national annual statistics for the year of birth. In addition observed and expected numbers of first order births to mothers <20 years old were compared with corresponding numbers in mothers 20 years old or older. RESULTS: In JORRP cases the relationships be tween observed and expected numbers of cases were as follows: cesarean births, 4.6-fold less; first order births, 1.6-fold greater; maternal age <20 years old, 2.6-fold greater. All these differences were statistically highly significant. The observed parity effect was mediated to a large extent by maternal age. In contrast there were no significant differences between observed and expected numbers of adult onset recurrent respiratory papillomatosis cases with respect to any of the above variables. CONCLUSIONS: Young primiparous mothers with condylomas are at a high risk for transmission of JORRP to their infants. The option of cesarean delivery should be discussed with a mother who has condyloma at the time of delivery.

Endoscopic management of a combined laryngocele.

A 70-year-old women presented with hoarseness, foul sputum, and a softneck mass. Clinical and radiographic examination disclosed findings consistent with a combined internal and external laryngopyocele. Antibiotics, throat irrigations, and warm packs applied to the neck resulted in full resolution of the neck mass and subtotal regression of the supraglottic swelling. Endoscopic vestibulectomy was performed with a carbon dioxide laser; neither residual neck mass nor a tract leading to the extralaryngeal neck swelling was detected. The immediate and long-term clinical course has been uneventful. This report is the first description of the definitive endoscopic management of a combined laryngocele. The pathogenesis of the laryngocele and the rationale and technique for endoscopic management are discussed.

Coinfection of HPV-11 and HPV-16 in a case of laryngeal squamous papillomas with severe dysplasia.

Human papillomavirus (HPV) types 6 and 11 have been associated with benign laryngeal papilloma, while HPV-16 is occasionally associated with laryngeal carcinoma. In this study, a case of laryngeal squamous papillomas with severe dysplasia was evaluated for the presence of HPV infection. The biopsy specimens were taken from a 58-year-old female patient at two different time points 3 months apart. Architecturally, the tumor showed papillary configuration reminiscent of squamous papilloma. Cytologically, the lesion showed morphologic features characteristic of severe squamous epithelial dysplasia. HPV infection was determined by DNA in situ hybridization using type-specific HPV-DNA probes. HPV-11 probes demonstrated homogeneous nuclear staining, suggesting productive viral replication. In contrast, HPV-16 probe produced a speckled pattern, suggesting HPV-16 DNA integration. Normal laryngeal epithelium did not yield specific hybridization. The presence of HPV-11 and HPV-16 was confirmed by PCR using HPV type-specific primers. Immunocytochemical staining was performed to detect Ki-67, a proliferation marker, and p53. Ki-67 expression was demonstrated throughout the whole thickness of epithelium. Staining for p53 was negative. This study suggests that multiple HPV infections can occur in the same lesion and that HPV-16 infection and its DNA integration may contribute to the occurrence of severe dysplasia in the lesion described.

Recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is an uncommon clinical disorder of the respiratory epithelium caused by HPV. It shares an identical viral etiology with genital condyloma and, in all likelihood, is transmitted at the time of birth (juvenile onset RRP) or through intimate sexual contact (adult onset RRP). Despite the precision of the surgical laser under magnification of the operating microscope, a substantial proportion of patients with RRP, adults as well as pediatric, require repeated operations at frequent intervals because of severe hoarseness and upper airway obstruction. For the management of at least a subset of patients, the efficacy of adjuvant agents (interferon is a leading choice) should be investigated in a multi-institutional clinical trial. For the potential prophylactic benefit, cesarean sections in selected high-risk expectant mothers should be considered.

Association of human papillomavirus with nasal neoplasia.

Since HPV-57b has been identified by two different techniques in benign, premalignant, and malignant lesions of the nasal cavity, but not in cases of chronic sinusitis, HPV-57 should be recognised as at least a co-factor in the aetiology of nasal neoplasia. Paraffin sections of 22 histologically confirmed nasal tumours were screened by in-situ hybridisation with riboprobes specific for HPV-57b. Virus was demonstrated in 6 of 7 fungiform papillomas, 6 of 8 inverted papillomas, 1 of 3 inverted papillomas with dysplasia, and 2 of 4 inverted papillomas with carcinoma. The presence of HPV-57b was confirmed with the polymerase chain reaction, which identified an additional 4 positive samples, bringing the total to 86% positive specimens. The results underscore the importance of HPVs in the aetiology of cancers at extragenital sites.

Human papillomavirus in sinonasal papillomas and squamous cell carcinoma.

The diagnostic and prognostic relevance of human papillomavirus (HPV) types 6, 11, 16, and 18 in squamous papilloma, inverted papilloma, and squamous carcinoma of the sinonasal epithelium was examined using the polymerase chain reaction (PCR) technique. Four (15%) of 26 squamous papillomas, 7 (24%) of 29 inverted papillomas, and 1 (4%) of 24 squamous carcinomas were positive for HPV when examined using the PCR amplification technique. Human papillomavirus 6 was present in 5 specimens (3 squamous and 2 inverted papillomas); HPV-11 was present in 6 specimens (1 squamous and 5 inverted papillomas); and HPV-18 was present in 1 of 24 squamous carcinomas. HPV-16 was not identified in any specimen. The proportion of tissue samples showing HPV presence, and the association of HPV types 6 and 11 with benign lesions and HPV-18 with malignant lesions, are both in accord with findings from prior investigations. Two major questions regarding nasal papilloma are the probability for lesion recurrence after surgical excision and the risk for malignant transformation. There is no unanimity of opinion regarding the prognostic value of histopathologic dysplasia to forecast these outcomes. HPV is etiologically related to a subset of sinonasal papillomas and squamous carcinoma, and those with benign and malignant clinical course are separable on basis of HPV type. Because of the paucity of these nasal lesions, a multi-institutional prospective collaborative study is the ideal way to address these questions.

Antibody response to human papillomavirus (HPV) type 11 in children with juvenile-onset recurrent respiratory papillomatosis (RRP).

We previously established, using an ELISA, the presence of specific antibodies directed at human papillomavirus (HPV) type 11 virions in the sera of patients with condylomata acuminata, mostly a disease of young adults that, like recurrent respiratory papillomatosis (RRP), is caused by two closely related HPVs, types 6 and 11. The present study was done to investigate if children with RRP can make viral-specific antibodies to an infection that is acquired at birth. Using the same ELISA, we studied the sera of 32 children with biopsy-documented juvenile-onset RRP and compared them to the sera of 31 control children. The median (and interquartile range) of the OD values in the controls and the cases was 0.078 (0.003, 0.101) and 0.230 (0.063, 0.725), respectively, a statistically significant difference (P = 0.001). Among the cases, there was no difference in seroreactivity between children with HPV-11-induced RRP and those with HPV-6-induced RRP (P = 0.31). Since HPV-11 viral particles do bind to the ELISA plate and remain intact and accessible to antibodies, we conclude that children with RRP, like adults with condylomata acuminata, develop antibodies directed at HPV-11 virions.

A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis.

The clinical triad of a firstborn delivered vaginally to a young (teenage) mother has been previously noted among juvenile onset recurrent respiratory papillomatosis (JO-RRP) patients. This study was based on a questionnaire survey of JO-RRP patients, adult onset recurrent respiratory papillomatosis (AO-RRP) patients, and juvenile and adult controls. The survey results revealed that the complete or partial triad was observed in 72% of JO-RRP patients, 36% of AO-RRP patients, 29% of juvenile controls, and 38% of adult controls. As compared with juvenile controls, JO-RRP patients were more often firstborn (P less than .05), delivered vaginally (P less than .05), and born to a teenage mother (P less than .01). Among adult participants, AO-RRP patients reported more lifetime sex partners (P less than .01) and a higher frequency of oral sex (P less than .05) than reported by adult controls. AO-RRP and JO-RRP appear to have distinguishable epidemiologic features indicating that the mode of human papillomavirus (HPV) transmission is different in these two disorders.

Bilateral vocal fold motion impairment: pathophysiology and management by transverse cordotomy.

Although bilateral vocal fold paralysis (BVFP) is an uncommon disorder, bilateral vocal fold motion impairment (BVFMI) resulting from a variety of laryngeal derangements is encountered with increasing frequency. Moreover, pure BVFP accounts for only a small proportion of BVFMI. When antecedent factors associated with BVFP are absent, recognition of BVFMI is often delayed and frequently overlooked. The requirements for assessment and successful management of BVFMI are 1) recognition of its presence, 2) identification of the constituent factors restricting vocal fold motion, 3) objective assessment of airway patency, and 4) selection of a reliable management plan. More often than not, two or more BVFMI-causing factors are present; only rarely is BVFMI attributable to a single vocal fold motion-limiting cause. The clinical and endoscopic examinations should evaluate the relative contributions of vocal fold paralysis, cricoarytenoid joint fixation, infiltrative disorders, and webs and synechiae that cause restricted vocal fold motion. The flow-volume loop examination documents airflow rate and volume and the site, nature, and severity of the obstructing lesion(s). This presentation describes the evaluation and rationale for management in BVFMI. The surgical techniques currently used to address BVFMI are compared to determine their respective merits and drawbacks, depending upon the constituent factors causing vocal fold motion limitation.

Long-term response of recurrent respiratory papillomatosis to treatment with lymphoblastoid interferon alfa-N1. Papilloma Study Group.

BACKGROUND: We earlier reported that patients with recurrent respiratory papillomatosis responded to six months of treatment with lymphoblastoid interferon alfa-n1. Because another study of patients treated for one year with leukocyte interferon alfa-n3 found that the growth rate of papillomas was slowed in the first six months but returned to base line during months 7 through 12 despite persistent interferon treatment, we now report the long-term results in our original study patients who were followed for a median of four years after the original one-year crossover study. METHODS: After the patients in our study had completed the first study year, their physicians could continue or recommence treatment with lymphoblastoid interferon alfa-n1 in a dose of either 2 MU per square meter of body-surface area per day or 4 MU per square meter every other day. The extent of disease was measured by endoscopy when clinically indicated. RESULTS: Data on late-follow-up were obtained for 60 of the 66 patients. There were 22 complete remissions and 25 partial remissions; 13 patients had no response. The median duration of the complete remissions was 550 days, and 15 patients continued to be in complete remission. The median duration of partial remissions was 400 days and seven patients were still in partial remission. Thirteen of 28 patients responded to a second course of interferon after an interruption in treatment of at least one month. The rate of response in the 11 of 53 patients who had neutralizing antibody to interferon was the same as in the patients without the antibody. CONCLUSIONS: Patients with severe recurrent respiratory papillomatosis may have a sustained or repeated response to treatment with lymphoblastoid interferon alfa-n1. We recommend that patients with recurrent respiratory papillomatosis who require surgery every two to three months be given a six-month trial of interferon alfa-n1.

Polymerase chain reaction identification of human papillomavirus DNA in CO2 laser plume from recurrent respiratory papillomatosis.

Human papillomavirus (HPV) DNA was identified in the plume produced during CO2 laser vaporization of respiratory tract papillomata. The plume produced from CO2 vaporization was collected on Gelfoam pledgets that were affixed to suction tips evacuating the vapor plume from the operative field. The Gelfoam pledgets were snap frozen in liquid nitrogen, processed, and examined for HPV-6 and HPV-11 DNA by a polymerase chain reaction technique. Tissue and vapor-plume specimens were collected from 22 patients undergoing CO2 laser excision of laryngeal lesions. Seven patients had adult-onset recurrent respiratory laryngeal papillomatosis (RRP), 12 had juvenile-onset RRP, two had laryngeal carcinoma, and one had nonspecific laryngitis. HPV-6 or HPV-11 was identified in 17 of 27 vapor-plume specimens from RRP and in none of three from non-RRP lesions. All but one RRP tissue specimen contained HPV-DNA, and none of the non-RRP tissues contained HPV-DNA. When HPV was present in vapor, the same HPV type was found in the corresponding tissue specimen. Identification of HPV-DNA in the laser plume raises concern regarding potential risks from exposure to the plume--particularly to the endoscopic surgeon and the operating team. The practical concerns and effectiveness of the plume scavenging systems are discussed.

Human papillomavirus in squamous cell carcinoma, leukoplakia, lichen planus, and clinically normal epithelium of the oral cavity.

Tissue specimens of carcinoma, leukoplakia, and clinically normal epithelium obtained at sites separate from the lesions were examined for the presence of human papillomavirus (HPV). Twenty-two paraffinized specimens of previously diagnosed oral lichen planus were also studied. The carcinoma and leukoplakia specimens were examined by Southern transfer hybridization and reverse blot hybridization; specimens HPV-positive by Southern hybridization were additionally examined by in situ hybridization and an immunoperoxidase technique. The lichen planus specimens were examined by in situ hybridization and immunoperoxidase techniques only. The HPV identification rates were in the range reported in previous studies, and the detection rates were similar for carcinoma, leukoplakia, histologically normal epithelium, and lichen planus. The clinical significance of HPV presence in carcinoma, leukoplakia, and lichen planus was not evaluable because of the short duration of follow-up.

3-D CT for cranial facial and laryngeal surgery.

Three-dimensional imaging is a new digital technology which interpolates two-dimensional computer tomography information to render a "life-like" anatomic display of the diagnostic information. We have found that this new methodology significantly improves the assessment and therapy of patients undergoing surgical procedures of the head and neck. The technique has been used in cranial-facial and laryngeal pathology, and in preoperative planning of tumor resection, particularly skull-base neoplasms. The use of three-dimensional computer tomography improves the display of the location and volume of pathology and affords accurate therapeutic and surgical planning. The choice and extent of surgery is better defined, and precise bone removal can be performed. In reconstructive surgery, an accurate prefabricated model of the bony defect can be made to aid reconstruction. Representative cases demonstrating the use of three-dimensional computer tomography in head and neck surgery, and its benefits in saving operative time and improving the postoperative result, will be discussed.

Randomized surgical adjuvant trial of interferon alfa-n1 in recurrent papillomatosis.

Sixty-six patients with recurrent respiratory papillomatosis of juvenile onset were treated for six months with interferon alfa-n1 (Wellferon) in a randomized crossover trial. Half received interferon alfa-n1 intramuscularly at a dosage of 5 megaunits per square meter daily for 28 days and then thrice weekly for five months, followed by six months of observation. The other half were observed for six months and then treated. Operations were performed every two months to assess disease extent by a scale developed for this purpose. The score for the patients during the first observation period was stable. There was a statistically significant lowering of score in patients receiving interferon alfa-n1 during both periods of drug administration. Eight of 57 patients with assessable airway disease achieved complete remission, as did one additional patient with disease limited to the nasopharynx. No patients achieved complete remission during six months of observation alone. This difference was statistically significant. Patients without tracheostomy were significantly more likely to achieve remission than those with a tracheostomy. The patients who were observed after discontinuation of the drug therapy showed a significant rise in score within four months. Symptoms of toxicity included transient fever, fatigue, nausea, and headache. Elevations in serum aspartate aminotransferase levels occurred in 64% of the patients. There was an inverse correlation between age and the ability to tolerate the medication. The dose studied may be close to the maximum tolerated dose. It appears that interferon alfa-n1 as an adjuvant to routine surgical management is effective in slowing the growth of respiratory papillomas.

Fine-needle aspiration cytology of monomorphic adenomas.

The diagnostic accuracy of fine-needle aspiration of salivary gland lesions is now widely accepted. The cytologic appearance of two rare monomorphic variants of pleomorphic adenomas is described. The trabecular-tubular adenoma consisted of a trabecular arrangement of uniform small cells with scant basophilic cytoplasm and round nuclei. No mucoid spheres were present. The canalicular adenoma also had a distinctive cytologic appearance consisting of papillae and interconnected canaliculi lined by a layer of columnar epithelium. Monomorphic adenomas have unique morphologic appearances that can be recognized in fine-needle aspiration cytology. Preoperative diagnosis can greatly aid the surgeon in the planning of definitive surgical excision of salivary gland neoplasms.

Recurrent respiratory papillomatosis. Clinical overview and management principles.

Recurrent respiratory papillomatosis is an uncommon clinical disorder of respiratory epithelium caused by HPV. It shares the identical viral etiology with genital condyloma and in all likelihood is transmitted at the time of birth (juvenile-onset disease) and through intimate sexual contact (adult-onset disease). The recent establishment of viral etiology modifies our concepts regarding the nature of the disease, its epidemiology, and its treatment.