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1/14. An aggressive and invasive growth of juvenile papillomas involving the total respiratory tract.

    A malignant course of juvenile laryngeal papillomatosis has rarely been reported. In the present case the patient had had laryngeal papillomas since the age of three years. The papillomas gradually spread to the entire respiratory system, and during 30 years the patient was operated on more than 80 times. At present an invasive tumour spreading from the tongue into the parapharyngeal space, extending to the cranial base, has been demonstrated by magnetic resonance imaging (MRI). Intralesional therapy with Cidofovir, a promising antiviral drug against human papillomavirus (HPV) infection, was started with some clinical effect, although only on the superficial tumour growth. histology of removed tumour tissue has demonstrated a mixture of exophytic and inverted growth pattern, and has mainly been interpreted as benign, in spite of a focally high mitotic index and an intermittent lack of maturation in the epithelium. In the most recent biopsies a verrucous carcinoma has been diagnosed. Expression of p53 was noted to increase in papillomas with time. All samples have been shown to harbour HPV 11, but no other HPV types.
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2/14. Systemic cidofovir in papillomatosis.

    An 8-year-old patient with severe recurrent respiratory papillomatosis and pulmonary spread was treated by systemic administration of cidofovir in association with laser treatment for tracheal lesions. Complete disappearance of the lesions in the pharynx and larynx and a significant yet incomplete regression in the bronchi and lung parenchyma were observed without deleterious side effects. This is the first case report of systemic use of cidofovir to treat recurrent respiratory papillomatosis.
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3/14. Topoisomerase alpha II, retinoblastoma gene product, and p53: potential relationships with aggressive behavior and malignant transformation in recurrent respiratory papillomatosis.

    Recurrent respiratory papillomatosis (RRP) has a juvenile aggressive form and an adult more indolent form. Most cases of RRP are cytologically benign; however, some undergo malignant transformation. At present, there are no known markers that help identify patients at risk for aggressive disease. We investigated by immunohistochemistry expressions of topoisomerase alpha II, MIB-1, p53, p21, E-cadherin, retinoblastoma (RB) gene protein product, HER-2/neu, and steroid hormone receptors in a case of juvenile respiratory papillomatosis with malignant transformation to determine whether these markers are associated with malignant transformation. Histologic examination of the pulmonary lobectomy specimen revealed well-differentiated squamous carcinoma and invasive papillomatosis. Increased staining was found in areas of invasive papillomatosis for topoisomerase alpha II, p53, and MIB-1, with highest labeling indices in areas of squamous carcinoma. Staining intensity for RB gene protein product showed gradual decline from benign papilloma (3 ) and invasive papillomatosis (2 ) to squamous carcinoma (0-1 ). Expression of p21 was similar in benign papilloma and invasive papillomatosis but showed reduction in squamous carcinoma. Expressions of E-cadherin, HER-2/neu, and steroid hormone receptors did not appear to correlate with biologic behavior. Increased topoisomerase alpha II and p53 expression along with reduced RB gene protein product and p21 expression may serve as markers of transformation to invasive papillomatosis and squamous carcinoma.
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4/14. latex allergy: an update for the otolaryngologist.

    OBJECTIVE: To describe the clinical manifestations of latex allergy in otolaryngology patients. DESIGN: Descriptive case series. SETTING: Tertiary academic otolaryngology practice. patients: otolaryngology patients with documented allergic reactions to latex during surgery and confirmatory laboratory test results for latex allergy. MAIN OUTCOME MEASURES: Clinical description of latex reactions; identification of risk factors for latex allergy. RESULTS: We describe 3 patients, 2 children and 1 young adult, with severe latex allergy manifested by intraoperative cardiorespiratory changes and confirmed by positive latex-specific IgE test results. A 9-year-old boy with a tracheotomy and a history of multiple procedures for laryngeal stenosis developed a rash and unexplained bronchospasm during an open laryngeal procedure. Surgery was aborted, and subsequent surgery was performed uneventfully 4 weeks later using a latex-safe environment. A 13-year-old boy with recurrent respiratory papillomatosis and a ventriculoperitoneal shunt had sudden unexplained arterial oxygen desaturation and a rash during laser endoscopy. He was then treated successfully using latex-safe protocols. A 23-year-old man with a parotid malignancy developed unexplained hypotension and ventilatory difficulties in the operating room during preparation for surgery. He responded to medical treatment for anaphylaxis. CONCLUSION: The otolaryngologist should share in the increased awareness of latex allergy. Our patients who have had multiple surgical procedures or who are exposed to latex on a long-term basis may be at increased risk. latex allergy should be considered when unexplained cardiorespiratory compromise occurs during surgery.
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5/14. Lower airway papillomatosis in children.

    Laryngeal papilloma in children is a frequent disease caused by human papilloma virus (HPV) type 6 or type 11. This disease has a tendency to recur and the changes are histologically benign. In some cases papilloma may affect the lower levels of the respiratory tract. In this study, among 90 patients treated for laryngeal papillomatosis, in four children papilloma of trachea, bronchi and lung tissue were detected in endoscopic and radiological examination. This constitutes 4.4% of all patients. Compact nodules and acquired cysts between 5 and 50 mm long were found in chest x-rays and in computerised tomography. These cysts appeared from 4 to 8 years after establishing a diagnosis of laryngeal papilloma, and 1 year after recognising papilloma in the trachea. In all four children the presence of nodules and cysts in the lungs was preceded by recurrent pneumonia, emphysema or atelectasis of the lungs. All children with laryngeal papillomatosis should have a chest X-ray. Detection of acquired cyst-like changes in lung tissue in children with laryngeal papillomatosis is a warning of future papilloma in the trachea and bronchi, with involvement of lung tissue. In differential diagnosis of these changes in the lungs we should take into consideration the presence of papilloma in the bronchi. A prognosis of papillomatosis in the lower airways in children is always serious.
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keywords = papilloma
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6/14. diagnosis and management of pulmonary metastasis from recurrent respiratory papillomatosis.

    OBJECTIVE: We sought to review the current and proposed management, as well as bring about discussion, of managing the patient with distal tracheal and pulmonary parenchymal involvement by recurrent respiratory papillomatosis (RRP). DESIGN, SETTING, AND patients: We conducted a review of 6 patients with pulmonary metastasis from RRP at 3 academic tertiary care hospitals. Interventions included surgical and medical management with antiviral, chemotherapeutic, and/or immune-modulating agents. RESULTS: Although treatment with alpha-2-beta interferon, isotretinoin, and methotrexate have not proved to eradicate pulmonary involvement by RRP, possible epithelial stabilization and slowing of disease progression are noted. CONCLUSIONS: The rates of distal tracheal and pulmonary metastasis as seen in our cohort were higher than previously reported. Approximately 12% of our patients with RRP have distal tracheal spread and as many as 7% of all patients with RRP at our institutions have pulmonary dissemination. Also, high suspicion for malignant conversion to squamous carcinoma in the patient with pulmonary spread should be maintained. In addition, aggressive treatment, although not proved to eradicate the pulmonary disease, should be undertaken due to the high morbidity and mortality associated with pulmonary dissemination of RRP in our cohort.
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7/14. Recurrent respiratory papillomatosis in a survivor of extreme prematurity.

    Recurrent respiratory papillomatosis (RRP) is a rare disease in children. Previous reports suggested that prematurity and early age of presentation were poor prognostic factors. We report on a 24-week premature infant who presented with stridor, weak cry, and hoarseness of voice at age 9 months (corrected age), in whom the diagnosis of RRP was not made until age 21 months (corrected age). Laser excision of RRP was subsequently performed, and the child is still surviving at age 2.5 years. RRP should be considered in the differential diagnosis of airway problems in survivors of extreme prematurity; the prognosis is not uniformly poor in premature infants.
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keywords = papilloma
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8/14. Recurrent respiratory papillomatosis: cytopathological findings in an unusual case.

    Recurrent respiratory papillomatosis (RRP) primarily is a disease of children and adolescents. Most patients experience spontaneous regression at a later age, while others continue to be affected throughout their lives. Here, we present the case of a 26-yr-old man who presented with persistent cough, worsening dyspnea, and development of pneumothorax. Eight years prior, he had presented with similar complaints and an evaluation at that time had showed RRP. Follow-up since that time showed recurrent disease managed by multiple surgical procedures. At the most current admission, an ultrasound-guided fine-needle aspiration (FNA) of the lung showed numerous papillary tissue fragments and single atypical squamous cells consistent with recurrent RPR. To our knowledge, morphological findings of RRP have been reported rarely.
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9/14. Malignant transformation in non-irradiated recurrent respiratory papillomatosis.

    The clinical, radiographic and post mortem findings occurring in a 6-year-old female with a four-year history of recurrent respiratory papillomatosis (RRP) are described. At autopsy, there were two separate foci of malignant transformation (malignant degeneration) in the bronchioloalveolar papillomata. This patient is the youngest in whom such changes have been described. Malignant transformation is a rare occurrence and is usually seen in older patients with longstanding papillomatosis, therapeutic irradiation, or a history of smoking. Pulmonary spread represents the majority of cases with "spontaneous" malignant transformation.
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keywords = papilloma
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10/14. isotretinoin therapy for recurrent respiratory papillomatosis.

    Retinoic acid has been advocated for use in several premalignant and malignant epithelial lesions of the head and neck, including benign recurrent respiratory papillomatosis, with varying results. We describe a 24-year-old man with extensive tracheoesophageal and bronchoalveolar papillomatosis that degenerated into squamous cell carcinoma. Multiple endoscopic carbon dioxide laser excisions, at one point performed on a weekly basis, as well as a prolonged trial of interferon, failed to control the progression of his disease. isotretinoin (13-cis-retinoic acid) therapy (1 mg/kg per day) was instituted, with dramatic clinical, radiographic, and functional improvement. The patient experienced no significant toxic effects and required no endoscopic procedures over a 6-month period. We propose that isotretinoin may be an effective adjuvant therapy for aggressive respiratory papillomatosis.
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