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    Research Articles (2007-6)

    Severity of juvenile onset recurrent respiratory papillomatosis is not associated with socioeconomic status in a setting of universal health care.

    Int J Pediatr Otorhinolaryngol. 2007; 71(6):965-72 (ISSN: 0165-5876)
    Leung R; Hawkes M; Campisi P
    Hospital for Sick Children and the Department of Otolaryngology-Head and Neck Surgery (Leung, Campisi), 555 University Ave., 6th floor Elm, Toronto, Ontario M5G 1X8, Canada.

    BACKGROUND: Juvenile onset recurrent respiratory papillomatosis (JORRP) results from HPV transmission. Cervical cancer, also transmitted via HPV, is known to be correlated with socioeconomic status (SES). This study aims to determine if an association exists between SES and severity of JORRP. METHODS: Cross-sectional study of all active JORRP patients at the Hospital for Sick Children in Toronto in 2005. SES information from Hollingshead surveys, Postal walk Census data, and Low Income Cutoff Data were compared with Derkay-Wiatrak disease severity scores, peak annual surgical frequency, and age of diagnosis. Statistical analysis was performed using Spearman, Mann-Whitney, and linear regression analyses. RESULTS: Twenty-one patients were surveyed. Hollingshead results were as follows: two patients (10%) were class I (major business and professional); 11 patients (52%) were class II (medium business, minor professional, technical); 4 patients (19%) were class III (skilled craftsmen, clerical, sales workers); 4 patients (19%) were class IV (machine operators, semiskilled workers); 0% were from class V (unskilled laborers, menial service workers). Interestingly, based on postal code data nine patients (45%) were below the low income cutoff as compared to the Toronto (metropolitan) and Ontario (provincial) rates of low income (17% and 14%, respectively). There was significant correlation between each of the SES measures and between disease severity measures. However, analysis of the SES measures versus disease severity measures did not demonstrate any significant relationship. CONCLUSIONS: Though almost half the patients lived below the low income cutoff, this study did not demonstrate a significant correlation between socioeconomic status and severity of disease in JORRP. One possible explanation is that universal access to the Canadian health care system is able to provide support despite a large proportion of patients being socioeconomically vulnerable. A national level study is underway to further detect any relationship between SES and JORRP severity in the general population. ]

    Antiviral agents for the treatment of recurrent respiratory papillomatosis: a systematic review of the English-language literature.
    Otolaryngol Head Neck Surg. 2007; 136(6):863-9 (ISSN: 0194-5998)
    Chadha NK; James AL
    Department of ENT Otolaryngology-Head and Neck Surgery, Torbay Hospital, Torquay, Devon, United Kingdom. neil@chadhanet.com

    OBJECTIVE: To determine the efficacy of antiviral agents for recurrent respiratory papillomatosis (RRP) in children and adults. STUDY DESIGN: Systematic review to include randomized controlled trials (RCTs), comparative studies (historical and/or nonrandomized), case series, and case reports. RESULTS: Twenty-six original studies were included (one case-control series, 21 noncomparative trials, four case reports, and no RCTs). Meta-analysis was not possible. The antiviral modalities included acyclovir, ribavirin, intravenous cidofovir, and intralesional cidofovir injections. The strongest evidence was for intralesional cidofovir, with 17 studies including 158 patients. Of these, 90 patients (57%) demonstrated complete resolution, 55 patients (35%) a partial response, and 13 patients (8%) showed no improvement. CONCLUSIONS: Insufficient evidence from controlled trials exists for reliable conclusions, but several series indicate intralesional cidofovir may have some efficacy. A well-designed placebo-controlled, double-blinded, randomized controlled trial is needed. SIGNIFICANCE: This study provides the background for future study design and a comprehensive review of the available evidence.

    Immunocompetency in children with recurrent respiratory papillomatosis: prospective study.
    Ann Otol Rhinol Laryngol. 2007; 116(3):169-71 (ISSN: 0003-4894)
    Stern Y; Felipovich A; Cotton RT; Segal K
    Dept of Pediatric Otolaryngology, Schneider Children's Medical Center of Israel, Petah Tiqwa 49202, Israel.

    OBJECTIVES: We sought to investigate the immunologic status of children with recurrent respiratory papillomatosis and to evaluate possible correlations between the patients' immunocompetency and the clinical course of the disease. METHODS: Twenty children with recurrent respiratory papillomatosis underwent immunologic evaluation every 6 months for determination of complete blood count, serum immunoglobulin levels, lymphocyte subpopulations, lymphocyte response to mitogen stimulation, and natural killer cell function. The patients were observed prospectively (42 to 56 months), and their clinical course was recorded. The findings were compared with those in healthy age-matched controls. RESULTS: The CD4/CD8 ratio and the lymphocyte response to mitogen stimulation were significantly reduced in the study children compared to normal controls. A reduction in lymphocyte response to mitogen stimulation was significantly correlated to a high number of papilloma sites and more frequent recurrences. Abnormal natural killer cell function was significantly correlated to more frequent recurrences. CONCLUSIONS: A compromised cell-mediated immune response may be associated with repeated or persistent human papillomavirus infections, leading to the development of recurrent respiratory papillomatosis. Patients with an aggressive clinical course may have underlying cell-mediated immunodeficiency. Long-term prospective investigations are needed to establish the role of the host immune system in the pathogenesis of recurrent respiratory papillomatosis in children.

    Juvenile recurrent respiratory papillomatosis: still a mystery disease with difficult management.
    Head Neck. 2007; 29(2):155-62 (ISSN: 1043-3074)
    Stamataki S; Nikolopoulos TP; Korres S; Felekis D; Tzangaroulakis A; Ferekidis E
    ENT Department, Johns Hopkins Hospital, Baltimore, Maryland, USA.

    Juvenile recurrent respiratory papillomatosis (RRP) is the most common benign neoplastic disease of the larynx in children and adolescents and has a significant impact on patients and the health care system with a cost ranging from $60,000 to $470,000 per patient. The aim of this paper is to review the current literature on RRP and summarize the recent advances. RRP is caused by human papillomavirus (HPV; mainly by types 6 and 11). Patients suffer from wart-like growths in the aerodigestive tract. The course of the disease is unpredictable. Although spontaneous remission is possible, pulmonary spread and malignant transformation have been reported. Surgical excision, including new methods like the microdebrider, aims to secure an adequate airway and improve and maintain an acceptable voice. Repeated recurrences are common and thus overenthusiastic attempts to eradicate the disease may cause serious complications. When papillomas recur, old and new adjuvant methods may be tried. In addition, recent advances in immune system research may allow us to improve our treatment modalities and prevention strategies. A new vaccine is under trial to prevent HPV infection in women; the strongest risk factor for juvenile RRP is a maternal history of genital warts (transmitted from mother to child during delivery). Better understanding of the etiology of the disease and the knowledge of all available therapies is crucial for the best management of the affected patients.

    Surgical therapy for recurrent respiratory papillomatosis.
    Ear Nose Throat J. 2007; 86(2):68, 71 (ISSN: 0145-5613)
    Alexander RE; Fried MP

    Unusual malignant transformation of juvenile recurrent respiratory papillomatosis.
    Otolaryngol Head Neck Surg. 2007; 136(2):321-3 (ISSN: 0194-5998)
    Sidhu TS; Sharma AK; Sharma N; Sen AK; Das BC
    Department of Otolaryngology, Dr. RML Hospital, New Delhi, India.

    Protein expression of the tumor suppressors p16INK4A and p53 and disease progression in recurrent respiratory papillomatosis.
    Laryngoscope. 2007; 117(2):253-7 (ISSN: 0023-852X)
    Pham TT; Ongkeko WM; An Y; Yi ES
    Department of Pathology, University of California - San Diego, San Diego, California, USA.

    BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a benign condition that rarely metastasizes as invasive squamous cell carcinoma. Although this disease is associated with human papillomavirus, the role of this virus in tumorigenesis is unclear. OBJECTIVES: The aim of this study is to assess the involvement of the tumor suppressors P16INK4A and p53 in RRP tumor progression. DESIGN: Immunohistochemistry of p16INK4A and p53 was performed on biopsies of recurrent squamous papillomas and invasive lesions in nine patients. RESULTS: Twenty biopsies were graded as papillomas (RP), three as papillomas with high-grade dysplasia/carcinoma in situ (HGD/CIS), and two as invasive squamous cell carcinoma (SCCA). Forty-five percent of RP and 60% of HGD/CIS/SCCA expressed p16INK4A. Fifty percent of RP and 100% of HGD/CIS/SCCA expressed p53. The difference in the frequency of p53-positive staining between HGD/CIS and SCCA (100% of tissues examined) and RP (50% of tissues examined) approached statistical significance. Neither p16INK4A nor p53 was predictive of invasive transformation. CONCLUSIONS: Expression of p16INK4A, which is a surrogate for the tumor suppressor retinoblastoma (Rb), did not immediately lead to invasive disease. There is no correlation between disease severity of RRP and level of p16INK4A.

    Efficacy of treating children with anterior commissure and true vocal fold respiratory papilloma with the 585-nm pulsed-dye laser.
    Arch Otolaryngol Head Neck Surg. 2007; 133(2):127-30 (ISSN: 0886-4470)
    Hartnick CJ; Boseley ME; Franco RA; Cunningham MJ; Pransky S
    Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston 02114, USA. Christopher_Hartnick@meei.harvard.edu

    OBJECTIVE: To report preliminary results regarding the safety and efficacy of the 585-nm pulsed-dye laser (PDL) for the treatment of juvenile-onset recurrent respiratory papillomatosis (JORRP) in the pediatric population. DESIGN: Prospective longitudinal cohort study. SETTING: Two pediatric otolaryngology referral centers. PATIENTS: Twenty-three pediatric patients ranging in age from 6 months to 17 years. INTERVENTIONS: The 585-nm PDL was used for at least 1 treatment on each of these patients to treat JORRP of the true vocal folds or anterior commissure. MAIN OUTCOME MEASURES: Complications from the use of the 585-nm PDL in the treatment of JORRP. RESULTS: There was no evidence of anterior commissure webbing or true vocal fold scarring in this group of 23 patients followed up for 3 months to 1 year. CONCLUSIONS: The 585-nm PDL seems to be a safe instrument for treatment of JORRP. There is the potential that improved voice outcomes may be apparent when compared with traditional therapies because the vocal fold epithelium seems to be unharmed when treated with this method. Furthermore, the lack of epithelial damage incurred by the 585-nm PDL should enable more aggressive surgical excision of anterior commissure disease. Further prospective longitudinal studies examining voice outcomes are needed.

    Cost savings of unsedated office-based laser surgery for laryngeal papillomas.
    Ann Otol Rhinol Laryngol. 2007; 116(1):45-8 (ISSN: 0003-4894)
    Rees CJ; Postma GN; Koufman JA
    Department of Otolaryngology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

    OBJECTIVES: Unsedated office-based laryngeal laser surgery (UOLS) is now an effective alternative to traditional operating room-based suspension microdirect laryngoscopy under general anesthesia. This procedure includes pulsed dye laser (PDL) treatment of recurrent respiratory papillomas, granulomas, leukoplakia, and polypoid degeneration. The objective of this study was to determine the magnitude of the cost savings derived by moving these types of procedures from the operating room to the office setting. METHODS: Retrospective cost-identification analysis was performed by comparing the billing records of patients who underwent surgical laser treatment for recurrent respiratory papillomatosis in the operating room to the costs and charges for patients who underwent similar procedures with the in-office PDL. RESULTS: In performing surgery with the PDL in the office, the average cost savings was more than $5,000 per case. Current reimbursement rates do not cover the cost of performing UOLS. CONCLUSIONS: The potential cost savings of UOLS are tremendous; however, at present significant financial disincentives prevent proliferation of this technology.

     

    Human papilloma virus in hyperplastic tonsillar and adenoid tissues in children.
    Pediatr Infect Dis J. 2006; 25(12):1158-62 (ISSN: 0891-3668)
    Mammas IN; Sourvinos G; Michael C; Spandidos DA
    Laboratory of Virology, School of Medicine, University of Crete, Heraklion, Greece.

    BACKGROUND: Human papillomavirus (HPV) in childhood causes skin and anogenital warts as well as the recurrent respiratory papillomatosis, a life-threatening cause of upper airway obstruction in children. To date, the information on HPV infection in tonsillar and adenoid hyperplasia in children is limited. PURPOSE: The purpose of this study was to investigate the presence of HPV DNA in children with benign tonsillar and/or adenoid hyperplasia. METHODS: One hundred six samples of paraffin-embedded adenoid and/or tonsillar tissues from 102 children, 57 girls and 45 boys (age range, 2-14 years), were tested for the presence of HPV DNA using polymerase chain reaction (PCR) with general primers GP5+/GP6+. HPV typing was performed by PCR with specific primers for HPV-16, -18, -33 and -11. RESULTS: HPV DNA was detected in 9 (8.5%) of the 106 collected specimens. The frequencies of HPV typing were 6 of 9 (66.7%) for HPV-16, 2 of 9 (22.2%) for HPV-11, zero of 9 (0%) for HPV-33 and HPV-18, whereas one HPV-positive sample remained untyped. No multiple HPV infection was detected. HPV was detected in 6 (9.4%) children with tonsillar hyperplasia and in 3 (7.1%) with adenoid hyperplasia. The mean age of children with HPV-positive specimens was lower than that of HPV-negative children (P = 0.006). No statistical correlation in the prevalence of HPV infection was observed according to children's sex, origin or residence (urban or rural). CONCLUSION: Although the significance of the presence of HPV DNA in tonsillar and adenoid hyperplasias remains obscure, the PCR detection of high-risk HPV DNA should be evaluated cautiously.

    Children and partners of patients with recurrent respiratory papillomatosis have no evidence of the disease during long-term observation.
    Int J Pediatr Otorhinolaryngol. 2006; 70(12):2061-6 (ISSN: 0165-5876)
    Gerein V; Soldatski IL; Babkina N; Onufrieva EK; Barysik N; Pfister H
    Department of Pediatric Pathology, Institute of Pathology, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. v.gerein@web.de

    OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm affecting the larynx and upper respiratory tract. The aim of our study was to investigate whether children and partners of patients with RRP develop the same disease and to determine whether there is an impact of pregnancy on the course of RRP. PATIENTS AND METHODS: Thirty-eight of 42 patients with RRP were accepted for a multicenter prospective study in Germany in 21.06.83-12.03.90. Mean follow-up duration was 15.3+/-1.8 years. The data of partners of patients with RRP was collected during the period of observation and then updated via interviews in January 2006. Twenty-nine children and four grandchildren were born to 14 patients with RRP. Fifteen of 448 cases of patients with RRP were treated in Saint Vladimir Moscow Children's Hospital in Russia in 1988-2003 and analyzed retrospectively. Sixteen children and one grandchild were born to 15 patients with RRP from Russia. In both studies, the virus type of patients with RRP was identified by nested PCR or Southern blot hybridization. Statistical analysis was performed using Fisher's exact test (probability value set at p<0.05). RESULTS: All children born to patients with RRP were healthy. RRP was not diagnosed in any of them on the basis of clinical or histological examination. Four of 45 children developed dysphonia, two of them had vocal cord nodules. None of the sexual partners of patients has developed RRP during the follow-up period. Pregnancy was accompanied by excessive growth of papillomas in all women (100%) with RRP associated with HPV type 11, and only in 16.7% of women with RRP associated with HPV type 6 (p=0.001). CONCLUSIONS: Patients with RRP are able to have healthy children regardless of the stage of the disease. Partners of RRP patients do not develop RRP during an observation period of 15 years. Pregnancy has a negative impact on the course of RRP and local laryngeal status in patients; it is more significant in HPV type 11 associated cases as it is manifested by more rapid papillomas growth and more frequent recurrence.

    [Quantitative evaluation of the focus range of juvenile onset recurrent respiratory papillomatosis]
    Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006; 20(21):970-2 (ISSN: 1001-1781)
    Lei W; Su Z; Wen W; Chai L; Jiang A; Luo G; Li J
    Otorhinolaryngology Hospital, Otorhinolaryngology Institute, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

    OBJECTIVE: To investigate the clinical application of quantitative evaluation of the focus range of juvenile onset recurrent respiratory papillomatosis (JO-RRP). METHOD: Disease severity was scored as the sum of ratings of 1 (minimal), 2 (moderate), or 3 (severe) for involvement of 22 areas of the respiratory tract and digestive tract. Sixty-eight cases with JO-RRP patients underwent 238 procedures were removed papillomas. A Storz laryngoscope was used to exposed and suspend the larynx, and an endoscope video system was used to display the pathological changes. RESULT: The score of these cases range from 2 to 20, most of them range from 7 to 14. Papillomas were found in the larynx in each case, vocal cords and false vocal cords were the most common places involved. Nose, pharynx, hard palate, lung or esophagus involved was seldom found. The score declined as the patients underwent more procedures. It is in accord with the clinical characteristic of JO-RRP. CONCLUSION: We concluded that our means of JO-RRP focus range quantitative evaluation could evaluate the severity and clinical curative effect objectively. It was a scientific and convenient way, and worth to be generalized.

    Recurrent respiratory papillomatosis in children: masquerader of common respiratory diseases.
    Pediatrics. 2006; 118(5):1925-31 (ISSN: 1098-4275)
    Zacharisen MC; Conley SF
    Department of Pediatrics, Section of Allergy and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. mzach@mcw.edu

    BACKGROUND: Recurrent respiratory papillomatosis in children is an uncommon but potentially life-threatening benign tumor of the respiratory tract with laryngeal predilection. The diagnosis of recurrent respiratory papillomatosis may be challenging unless there is a high index of suspicion and awareness of the variable presentations. METHODS: We reviewed the medical charts of children with recurrent respiratory papillomatosis treated at a tertiary children's hospital. The presentation of recurrent respiratory papillomatosis is illustrated by a series of case reports. We provide a paradigm to assist in the early diagnosis of children with recurrent respiratory papillomatosis. RESULTS: Five patients, aged 2 to 6 years, were erroneously diagnosed with recurrent croup, asthma, laryngeal hemangioma, and tracheomalacia after presenting with variable degrees of chronic dyspnea, cough, stridor, dysphonia, weak cry, and syncope. Once the diagnosis of recurrent respiratory papillomatosis was made, recurring surgical ablation of papillomata was initiated. CONCLUSIONS: Any child presenting with a voice disturbance with or without stridor is recommended to have diagnostic flexible fiber-optic laryngoscopy. Recurrent respiratory papillomatosis should be considered in children when other common pediatric airway diseases either do not follow the natural history or do not respond to treatment of the common disorder

    [The combined treatment of juvenile outset recurrent respiratory papillomatosis]
    Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006; 20(21):975-7 (ISSN: 1001-1781)
    Xie J; Dong P; Li K; Wang J; Jin B; Zhang J
    Department of Otolaryngology-Head and Neck Surgery, Shanghai First People's Hospital, Shanghai 200080, China. lancet11@yahoo.com.cn

    OBJECTIVE: To explore the effective treatment of juvenile outset recurrent respiratory papillomatosis (JO-RRP). METHOD: Thirty six patients of JO-RRP from 1993 to 2004 were analyzed retrospectively. Twenty seven patients were underwent laser excision by laryngoscope and nine patients were underwent laser excision through laryngostomy. Twenty eight patients who recurrenced more than two times in one year or involved extent of disease more than two anatomical subregion were give interferon after operation one week in addition. RESULT: All patients had normal deglutia, 28 cases (77.8%) had been succeed in decannulation. The complications included hoarseness in 8 cases, laryngeal stenosis in 6 cases and pulmonary infection in 3 cases. CONCLUSION: The laser surgery by lary noscope and laryngostomy are two kinds of effective treatments for JO-RRP. The interferon therapy after the operation can restrain the recrudescence effectively.


    3.5-Year follow-up of intralesional cidofovir protocol for pediatric recurrent respiratory papillomatosis.
    Int J Pediatr Otorhinolaryngol. 2006; 70(11):1911-7 (ISSN: 0165-5876)
    Chung BJ; Akst LM; Koltai PJ
    Head & Neck Institute, Cleveland Clinic Foundation, Desk A71, 9500 Euclid Avenue, Cleveland, OH 44195, United States. chungb@ccf.org

    OBJECTIVES: Intralesional injection of cidofovir has been described as an adjunctive treatment for pediatric recurrent respiratory papillomatosis (RRP). However, questions remain regarding the optimal dosing schedule and side-effect profile. The objective of this study was to describe patient outcomes following a standardized cidofovir protocol. METHODS: Eleven pediatric patients originally treated with a standardized stepped-dose protocol of intralesional cidofovir for RRP were followed for an extended observational period. Additional interventions, disease severity, and adverse outcomes were recorded. RESULTS: Five of 11 patients have required no further treatments following the original cidofovir protocol. Two patients initially achieved remission but have subsequently required additional treatment for recurrent disease. Four patients never achieved remission and have undergone multiple additional interventions. Mean follow-up time for all patients from the conclusion of the original study was 30.2 months (10-45). No adverse outcomes were noted. CONCLUSIONS: Intralesional injection of cidofovir may have some potential as an adjunct in the treatment of RRP. Response to cidofovir is unpredictable. Further study of cidofovir is necessary to more clearly define whether the favorable responses observed represent a true treatment effect or simply reflect the natural history of the disease. Perhaps as important is to refine treatment protocols and informed consents that reflect the concern about the carcinogenic potential of cidofovir and to better characterize the drug's side-effect profile.

    Prevention of recurrent respiratory papillomatosis: role of HPV vaccination.
    Int J Pediatr Otorhinolaryngol. 2006; 70(10):1799-803 (ISSN: 0165-5876)
    Freed GL; Derkay CS
    Department of Otolaryngology, Eastern Virginia Medical School, 825 Fairfax Avenue, Suite 510, Norfolk, VA 23507, United States.

    Recurrent respiratory papillomatosis is a rare, but devastating, cause of airway lesions in children and adults. This disease is caused by human papilloma virus subtypes 6 and 11. At this time there are two vaccines in late stages of development seeking Food and Drug Administration (FDA) approval to prevent cervical cancer, which is also caused by human papilloma virus. One of these vaccines has been developed to stimulate immunity to the most common subtypes that cause cervical cancer but also includes those responsible for recurrent respiratory papillomatosis. With the possibility this could drastically reduce the incidence of RRP, the otolaryngology community should advocate for implementation of a vaccine program that provides effective prevention of HPV infection with subtypes 6 and 11.

    Recurrent respiratory papillomatosis causing chronic stridor and delayed speech in an 18-month-old boy.
    Can Respir J. 2006; 13(7):381-3 (ISSN: 1198-2241)
    Alharbi A; Drummond D; Pinto A; Kirk V
    Department of Pediatrics, Division of Respiratory Medicine, University of Calgary, Calgary, Alberta.

    Recurrent respiratory papillomatosis is a relatively uncommon disease that presents clinically with symptoms ranging from hoarseness to severe dyspnea. Human papilloma virus types 6 and 11 are important in the etiology of papillomas and are most probably transmitted from mother to child during birth. Although spontaneous remission is frequent, pulmonary spread and/or malignant transformation resulting in death has been reported. CO2 laser evaporation of papillomas and adjuvant drug therapy using lymphoblastoid interferon-alpha are the most common treatments. However, several other treatments have been tried, with varying success. In the present report, a case of laryngeal papillomatosis presenting with chronic stridor and delayed speech is described

    Organotypic (raft) culture of biopsy-derived upper respiratory epithelium.
    Laryngoscope. 2006; 116(9):1600-2 (ISSN: 0023-852X)
    Schweinfurth JM; Meyers C
    Department of Otolaryngology, University of Mississippi Medical Center, Jackson, Mississippi, USA. JSchweinfurth@ent.unsmed.edu

    OBJECTIVE: The objective of this study was to derive a reliable technique for culturing biopsy-derived upper respiratory epithelium in a system that supports epithelial differentiation and simulates the normal epithelial life cycle. STUDY DESIGN: The authors conducted a prospective study of modification and development of an in vitro tissue culture method. METHODS: Thirty biopsy specimens from 16 individuals with recurrent respiratory papillomatosis and chronic tonsillitis, pretreated to prevent bacterial and fungal overgrowth, were digested with trypsin to create a supernatant of individual cells. The cells were plated and incubated. At 14 to 16 days, the resulting colonies were placed on a wire cloth raft and fed through diffusion from the underlying culture medium in an air-liquid interface. RESULTS: Eight specimens were successfully cultured for an average of over 32 days. The longest duration of sustained growth was 60 days. Low-risk human papillomavirus specimen-based cultures reproduced infection in cultured squamous epithelium with corresponding histopathologic features indicating a high level of stratification and differentiation. CONCLUSIONS: Unlike commercially available cell lines, biopsy-derived material is predisposed to contamination, and successful in vitro culture and experimentation creates many unique challenges. An organotypic culture system, capable of reproducing the differentiation-dependent replication cycle of human papillomavirus, may be used for culturing biopsy-derived specimens for a variety of studies.

    Intermediate-term and long-term results after treatment by cidofovir and excision in juvenile laryngeal papillomatosis.
    Ann Otol Rhinol Laryngol. 2006; 115(9):667-72 (ISSN: 0003-4894)
    Naiman AN; Ayari S; Nicollas R; Landry G; Colombeau B; Froehlich P
    Department of Otolaryngology, Edouard Herriot Hospital, Lyon, France.

    OBJECTIVES: We assessed the intermediate-term and long-term efficacy of intralesional injection of cidofovir used with surgical excision in juvenile-onset recurrent respiratory papillomatosis. METHODS: The protocol was revised during the study, from endoscopy at 4-week intervals with intralesional injection of cidofovir at 5 mg/mL, to a 2-week interval and a 7.5-mg/mL dosage. Partial surgical excision of hypertrophic papillomas was performed before the initiation of injection. Further injections at 4-week (or 2-week) intervals were performed until complete remission. RESULTS: Sixteen patients received a mean 8.9 injections. Complete remission was obtained in 12 patients (75%) after a mean 7.2 endoscopic treatments. Remission was stable at a mean 33.6 months' follow-up. Five of these 12 patients received 5.2 injections and remained disease-free at a mean 39.3 months' follow-up. Seven of the 12 had 1 relapse; they needed complementary treatment to become disease-free, and remained so thereafter over a mean 27.3 months' follow-up. The other 4 of the 16 patients (25%) continued to present active disease. CONCLUSIONS: Active endoscopic treatment until complete remission led to a higher-than-expected complete remission rate on intermediate-term to long-term follow-up, with or without relapse. Transient relapse was associated with a long delay in initiating cidofovir treatment.

    Recurrent respiratory papillomatosis.
    Arch Dis Child. 2006; 91(8):689-91 (ISSN: 1468-2044)
    Tasca RA; Clarke RW
    Leighton Hospital, Crewe, UK. r.tasca@btinternet.com

    Recurrent respiratory papillomatosis (RRP) is a benign, often multi-focal neoplasm. A potentially fatal manifestation of human papilloma virus infection, the condition is characterised by multiple warty excrescences on the mucosal surface of the respiratory tract. RRP is rare--incidence is estimated at 3.5 per million person-years, with a prevalence of 4 in 100,000 children. Affected children usually require multiple interventions; the impact on patients, their families, and the healthcare system is considerable. Treatment of RRP accounts for an estimated dollar 109 million annual expenditure in the USA.

    [Clinical study of tracheotomied children with juvenile onset recurrent respiratory papillomatosis]
    Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2006; 20(15):704-6 (ISSN: 1001-1781)
    Ma L; Wang J; Han D; Ye J; Xu W
    Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing, 100730, China.

    OBJECTIVE: To analysis the clinical characteristics of tracheotomied children with Juvenile-onset recurrent respiratory papillomatosis (JORRP) and to discuss the time of decannulation. METHOD: Thirty-one children with JORRP, who underwent tracheotomy and treated with CO2 laser in Otorhinolaryngololgy department of Tongren Hospital between 1993 and 2005, were reviewed in this essay. We analysis the age, the site of intratracheal papilloma, invasion fashion of lesion, et al. RESULT: Thirty-one tracheotomied children underwent 32 tracheotomy, 20 cases was decannulated. Among the 32 tracheotomied cases, three cases were decannulated in 1 month post operation and the intratracheal lesions were not found. There were presented intratracheal lesions in 29 cases. Intratracheal lesions were not presented in 20 cases after three months of decannulation. CONCLUSION: The tracheotomy should strive to be avoided to JORRP patients. If a JORRP patient was underwent tracheotomy, he should be decannulated as early as possible. The time of decannulation was performed in the operation or post operation when the intratracheal lesions was less.

    Unique challenges of obtaining regulatory approval for a multicenter protocol to study the genetics of RRP and suggested remedies.
    Otolaryngol Head Neck Surg. 2006; 135(2):189-96 (ISSN: 0194-5998)
    Sherwood ML; Buchinsky FJ; Quigley MR; Donfack J; Choi SS; Conley SF; Derkay CS; Myer CM; Ehrlich GD; Post JC
    Center for Genomic Sciences at Allegheny Singer Research Institute, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212-4772, USA.

    OBJECTIVE: Investigations that seek to generalize findings or to understand uncommon diseases must be conducted at multiple centers. This study describes the process of obtaining regulatory approval for a minimal risk genetic study in a multi-center setting as undertaken by the Recurrent Respiratory Papillomatosis (RRP) Task Force. STUDY DESIGN AND SETTING: Sequential cohort of American children's hospitals. A single protocol was submitted to each Institutional Review Board (IRB). RESULTS: Documentation was prepared for 14 IRBs over 2.5 years. The median time between enlistment and approval at the first 8 sites was 15 months. Institutions varied considerably in their requirements and in the issues that were raised. Protocols were submitted sequentially and accumulated experience was used in the preparation of applications to subsequent IRBs. Nevertheless, there was no correlation between the accumulated experience and the number of issues that were raised. CONCLUSION: Despite uniform federal standards, all local IRBs required unique and individualized submissions. For multicenter studies, investigators should seriously consider the establishment of cooperative authorization agreements. On a simpler level, a standardized format for applications needs to be adopted nationwide.

    British Association of Paediatric Otorhinolaryngology members experience with recurrent respiratory papillomatosis.
    Int J Pediatr Otorhinolaryngol. 2006; 70(7):1183-7 (ISSN: 0165-5876)
    Tasca RA; McCormick M; Clarke RW
    Department of ENT, Royal Liverpool Children's Hospital Alder Hey, Eaton Road, Liverpool L12 2AP, United Kingdom. r.tasca@btinternet.com

    OBJECTIVES: To establish current practice in the treatment of recurrent respiratory papillomatosis (RRP) in the UK. METHODS: Consultant members of the British Association of Paediatric Otorhinolaryngology (BAPO) were sent a questionnaire on current practice concerning the management of recurrent respiratory papillomatosis in the paediatric population. RESULTS: The response rate was 39.4% perhaps reflecting the relatively small number of otolaryngologists who treat this condition. Data were analysed from 41 respondents representing 27 departments for a total of 103 patients. A total of 13 patients (12.6%) received adjuvant medical therapies with the antiviral agent cidofovir accounting for 10 patients. Distal spread of RRP has occurred in 27 (26.2%) patients. There were six reported deaths due to progressive RRP. Various lasers (CO(2), KTP, and pulsed dye) are the preferred method of surgical removal of RRP in children. Spontaneous ventilation (65.3%) is the preferred method of anaesthesia. Half of the consultants do not routinely send for HPV subtyping and 75% send lesions for histological examination if there is a change in growth pattern. Two thirds of respondents do not routinely treat their patients with antireflux medication. CONCLUSION: There is a need for the establishment of a centralized national base to which all treating consultants can report their cases. The time has come for national multicenter controlled trials on the use of adjuvant interventions for the treatment of both severe and less severe RRP disease. Both of the above can be organized under the umbrella of BAPO.

    Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis.
    Arch Otolaryngol Head Neck Surg. 2006; 132(7):711-5 (ISSN: 0886-4470)
    Maloney EM; Unger ER; Tucker RA; Swan D; Karem K; Todd NW; Reeves WC
    Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. evm3@cdc.gov

    OBJECTIVES: To measure human papillomavirus (HPV) 6 and 11 viral load and antibody response in longitudinal specimens obtained from children with recurrent respiratory papillomatosis and to examine the association of type-specific viral load with clinical severity of disease. DESIGN: Longitudinal pilot study with a median follow-up of 5.4 months. SUBJECTS: The study included 15 children undergoing therapy for recurrent respiratory papillomatosis at the Egleston Children's Hospital, Atlanta, GA, between January 22, 1999, and June 13, 2000. MAIN OUTCOME MEASURES: The kinetics of HPV-6 and HPV-11 viral load and antibody level were examined over time. Longitudinal HPV-6 and HPV-11 viral loads were analyzed for associations with clinical indicators of disease severity. RESULTS: Four children were infected with HPV-11, 4 were infected with HPV-6, and 7 had mixed infections. The HPV-6 and HPV-11 viral loads were stable over time in most of the children. Among children with mixed infections, HPV-6 viral loads were inversely correlated with those of HPV-11 (r = -0.80, P<.001). The HPV-11 infection was significantly associated with more annual surgical procedures (P=.02). Neither HPV-6 nor HPV-11 viral loads were associated with demographic factors or markers of clinical severity. None of the children had detectable antibodies against HPV-6, and only 3 had detectable antibodies against HPV-11 virallike particles. CONCLUSIONS: Our data support the association of HPV-11 infection with clinical severity. Measures of HPV-6 and HPV-11 viral loads are relatively stable over time in most children with recurrent respiratory papillomatosis, suggesting that multiple samples may not be necessary. Cytobrush samples may substitute for tissue biopsy specimens in HPV detection and typing, but not for absolute viral load determination.

    Is intralesional cidofovir worthwhile in juvenile recurrent respiratory papillomatosis?
    J Laryngol Otol. 2006; 120(7):561-5 (ISSN: 1748-5460)
    Sheahan P; Sexton S; Russell JD
    Department of Otorhinolaryngology-Head and Neck Surgery, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland. sheahanp@eircom.net

    OBJECTIVE: To investigate the efficacy of intralesional cidofovir in the treatment of recurrent respiratory papillomatosis (RRP) in children. METHODS: Prospective observational study of four consecutive children with RRP treated at an academic tertiary children's hospital. Laryngo-bronchoscopy was performed at three- to five-weekly intervals. Photodocumentation was obtained and disease severity assessed using an anatomical RRP severity score. Surgical debulking of large papillomas was then performed, and cidofovir (5 mg/ml) injected into any remaining papillomas as well as submucosally at the sites of resected papillomas. The efficacy of cidofovir was assessed by the change in papilloma severity score over the course of the treatment. RESULTS: Complete disease remission was obtained in one patient, with a partial response seen in two others. One patient showed no significant response. The greatest beneficial effect was seen after the fourth cidofovir injection; however, two patients demonstrated a deterioration in severity scores after treatment was withheld at this point. Both responded well to further cidofovir injections. However, a clear plateau in the response to cidofovir was seen in all patients by the eighth injection. CONCLUSION: Intralesional cidofovir may help control papilloma regrowth and reduce disease severity in many children with RRP. In most cases, cidofovir would appear to be less efficacious in causing disease eradication. There appears to be little evidence to support prolonged treatment regimes (i.e. more than eight treatments.

    Four mutations in Epidermodysplasia verruciformis 1 (EVER1) gene are not contributors to susceptibility in RRP.
    Int J Pediatr Otorhinolaryngol. 2006; 70(7):1235-40 (ISSN: 0165-5876)
    Donfack J; Buchinsky FJ; Derkay CS; Steinberg BM; Choi SS; Conley SF; Meyer CM; McClay JE; Campisi P; Hu FZ; Preston RA; Abramson AL; Ehrlich GD; Post JC
    Allegheny General Hospital, Allegheny-Singer Research Institute, 320 East North Avenue, 11th Floor, South Tower, Room 1171, Pittsburgh, PA 15212-4772, USA.

    OBJECTIVE: Epidermodysplasia verruciformis is a skin disease characterized by abnormal susceptibility to human papilloma viruses. Recently four mutations in the Epidermodysplasia verruciformis 1 gene (EVER1, also known as TMC6) have been associated with the disease. Because of the phenotypic similarity between Epidermodysplasia verruciformis and recurrent respiratory papillomatosis, we decided to investigate whether any of these mutations accounts for the susceptibility to human papilloma viruses in subjects with recurrent respiratory papillomatosis (RRP). METHODS: Allele-specific PCR and restriction fragment length polymorphisms (RFLPs) were employed for genotyping a cohort of 101 patients with recurrent respiratory papillomatosis. RESULTS: None of these four mutations were found in the studied subjects. CONCLUSION: The absence of these mutations in RRP patients might indicate that EVER 1 alleles are not associated with susceptibility to RRP, or that other, as yet unidentified, mutations in the Epidermodysplasia verruciformis 1 gene, might account for the susceptibility to RRP.

    Pediatric laryngotracheal obstruction: current perspectives on stridor.
    Laryngoscope. 2006; 116(7):1059-70 (ISSN: 0023-852X)
    Bent J
    Department of Otolaryngology, Albert Einstein School of Medicine, New York, NY, USA. j.bent3@verizon.net

    OBJECTIVES/HYPOTHESIS: To assess how medical advances have impacted the diagnosis, management, and outcomes of pediatric laryngotracheal obstruction, and to describe the advantages of audio-video documentation of stridorous children. STUDY DESIGN AND METHODS: Retrospective. METHODS AND MATERIALS: 268 patients were referred for suspected laryngotracheal obstruction during the 30 months between September 1, 1995 and March 1, 1998: 173 had 206 flexible fiberoptic laryngoscopies, and 160 had 273 direct laryngoscopies. One hundred and forty-one children were identified with laryngotracheal obstruction, yielding 40 different diagnoses that could be classified into 9 major categories. Thirty-six children (25.5%) had multiple sites of upper airway obstruction. RESULTS: 138 children had follow-up >1 month. Twelve children died (8.7%), leaving 126 survivors (mean follow-up=21.1 months). Outcomes were classified as resolved (44.2%), improved (37.0%), stable (9.4%), failed (0.7%), or death (8.7%). Better outcomes were seen in more readily treated diagnostic categories, such as tracheobronchial foreign body, chronic laryngitis, and suprastomal granulation tissue; laryngeal stenosis, tracheomalacia, and recurrent respiratory papillomatosis, had less favorable outcomes (P<.001). The former group also showed superior outcome compared to laryngomalacia (P<.001) and vocal cord mobility disorders (P=.004). Ninety-four patients (68.1%) had comorbidities complicating their management. Comorbid conditions were universal among deceased patients and least common in the resolved outcomes category (56.7%), supporting the premise that patients with poor outcomes are more likely to have comorbidities than patients with resolution of laryngotracheal symptoms (P=.034). CONCLUSIONS: Audio-video recording of pediatric laryngotracheal obstruction offers numerous advantages. Children classified into an array of diagnostic categories usually have favorable outcomes, but opportunities for continued advances exist, particularly regarding management of comorbidity and chronic obstruction.

    Patient tolerance of in-office pulsed dye laser treatments to the upper aerodigestive tract.
    Otolaryngol Head Neck Surg. 2006; 134(6):1023-7 (ISSN: 0194-5998)
    Rees CJ; Halum SL; Wijewickrama RC; Koufman JA; Postma GN
    Center for Voice and Swallowing Disorders, Department of Otolaryngology, Medical College of Georgia, Augusta, GA 30912-4060, USA.

    INTRODUCTION: Recent advances in technology have facilitated a movement toward unsedated in-office treatment of laryngeal, tracheal, and esophageal lesions. The objective of this study was to determine patient tolerance of in-office pulsed-dye laser (PDL) treatment of upper aerodigestive tract pathoses via the transnasal esophagoscope. METHODS: Three hundred twenty-eight unsedated in-office PDL cases were performed at a university-based tertiary referral center in 131 patients. These procedures were performed for various upper aerodigestive pathoses, including recurrent respiratory papillomatosis, chronic granulomas, and recurrent leukoplakia. Eighty-nine subjects completed a phone survey concerning their discomfort level after the PDL procedure. They were also asked specific questions about recovery time, pain medication, and preference of operating room versus in-office procedures. RESULTS: The average comfort score was 7.4 (10 being minimal discomfort). Eighty-four percent did not use any pain medication; 87% stated that, if possible, they would prefer to undergo unsedated in-office procedures rather than surgeries under general anesthesia for further treatment of their upper aerodigestive tract pathosis. CONCLUSIONS: Unsedated transnasal treatment of upper aerodigestive tract pathoses is readily accepted and well-tolerated by otolaryngology patients. Patients overwhelmingly prefer the in-office PDL over surgeries under general anesthesia. EBM RATING: C-4.

    Virtual bronchoscopy for diagnosis of recurrent respiratory papillomatosis.
    J Formos Med Assoc. 2006; 105(6):508-11 (ISSN: 0929-6646)
    Chang CH; Wang HC; Wu MT; Lu JY
    Section of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

    Virtual bronchoscopy is a new method for viewing helical/spiral computed tomography (CT) images of the tracheobronchial trees. Using commercially available software to process the CT data, the tracheobronchial trees can be inspected through a series of three-dimensional images. Recently, this technique has been increasingly used to detect benign and malignant airway stenosis. We report the findings of virtual bronchoscopy in a 41-year-old man with recurrent respiratory papillomatosis (RRP). Several tiny nodules were evident in the lower trachea. Fiberoptic bronchoscopy was performed 1 month later during a planned surgery for laryngeal papillomas, and the findings were in agreement with virtual bronchoscopy. Detection of intrabronchial spreading in RRP is important since peripheral seeding of RRP can cause complications, including recurrent pneumonia, obstructive atelectasis, hemoptysis, and, rarely, may degenerate to squamous cell carcinoma. Virtual bronchoscopy is an alternative method for inspecting the tracheobronchial trees in patients with RRP when laryngeal papillomas impede fiberoptic bronchoscopy.

    Airway reconstruction in children with recurrent respiratory papillomatosis.
    Int J Pediatr Otorhinolaryngol. 2006; 70(6):1097-101 (ISSN: 0165-5876)
    Boston M; Rutter M; Myer CM; Cotton RT
    The Division of Pediatric Otolaryngology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.

    OBJECTIVE: To determine if children with recurrent respiratory papillomatosis were at increased risk of complications due to their disease following major airway reconstruction. METHODS: We retrospectively reviewed our airway surgery database and the medical records of all children diagnosed with recurrent respiratory papillomatosis who were evaluated at Cincinnati Children's Hospital Medical Center between January 1998 and August 2003. All patients with active airway papillomas or a history of recurrent respiratory papillomatosis who underwent open airway reconstruction at our institution were included in the study. RESULTS: Seven children with recurrent respiratory papillomatosis underwent major airway reconstruction. Six children had tracheotomies and five are now decannulated following their airway reconstruction. Five children had active papillomas at the time of surgery and none had significant worsening of their papillomas following their procedures. Two patients in remission underwent airway reconstruction without recurrence of their papillomas. CONCLUSIONS: Major airway reconstruction can be safely performed in children with recurrent respiratory papillomatosis.

    Treatment of recurrent respiratory papillomatosis with microsurgery in combination with intralesional cidofovir--a prospective study.
    Eur Arch Otorhinolaryngol. 2006; 263(5):440-3 (ISSN: 0937-4477)
    Dikkers FG
    Department of Otorhinolaryngology, University Medical Center Groningen, The Netherlands. f.g.dikkers@kno.umcg.nl

    Recurrent respiratory papillomatosis (RRP) is an uncommon disease that may cause symptoms ranging from hoarseness to severe obstruction of the airway. Several treatment modalities have been tried, all with varying success. The goal of this study is to assess the benefit of the intralesional injection of cidofovir as an adjunct to microsurgical excision in treatment of laryngeal papillomatosis. All patients with RRP who presented between 1999 and 2004 at the University Medical Center Groningen were prospectively analyzed, regardless of the patients' age at presentation or duration of the disease. Not all patients were treated with cidofovir. To be included, all patients required a history of repeated microsurgery because of severe recurrence of RRP or because of severe technical difficulties in excising or vaporizing the lesion. Local microsurgery was performed, and then cidofovir, 2.5 mg/ml, was injected intralesionally. Treatment was repeated after 6, 12, 18, 24 and 30 weeks. Six male and three female patients were treated with cidofovir. Localization was the glottis in seven and the technically inaccessible dorsum epiglottidis and subglottis in one case each. The seven patients with glottic localization were cured. The two other patients showed recurrences, but at a lower rate than previously. Several times, however, more than six procedures were necessary. Cumulative doses of cidofovir ranged from 10.5 to 128 mg per patient. Cidofovir is a promising and powerful therapeutic approach for the treatment of RRP. Currently, the combination of microsurgery with intralesional cidofovir seems to be the treatment of choice for RRP.

    The natural chemopreventive compound indole-3-carbinol: state of the science.
    In Vivo. 2006; 20(2):221-8 (ISSN: 0258-851X)
    Rogan EG
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA. egrogan@unmc.edu

    The hydrolysis product of glucobrassicin, indole-3-carbinol (I3C), is metabolized to a variety of products, including the dimeric 3,3'-diindolylmethane (DIM). Both I3C and DIM exert a variety of biological and biochemical effects. Most of these effects appear to occur because I3C modulates several nuclear transcription factors. I3C induces phase I and phase II enzymes that metabolize carcinogens, including estrogens. Administration of either I3C or DIM results in increased 2-hydroxylation of estrogens. I3C also enhances DNA repair by affecting several of the proteins involved in this process. I3C induces both G1 cell cycle arrest and apoptosis. All of these activities lead to anticancer effects. Although I3C has been shown to protect against tumor induction by some carcinogens, it has also been observed to promote tumor development in animal models. In humans, I3C and DIM affect the metabolism of estrogens. Concerns have been raised that I3C might increase the formation of estrogen metabolites that induce or promote cancer, but this has not been demonstrated. I3C has been found to be effective in treating some cases of recurrent respiratory papillomatosis, and it may have other clinical uses.

    Identification of HPV DNA in patients with juvenile-onset recurrent respiratory papillomatosis using SYBR Green real-time PCR.
    Int J Pediatr Otorhinolaryngol. 2006; 70(3):469-73 (ISSN: 0165-5876)
    Draganov P; Todorov S; Todorov I; Karchev T; Kalvatchev Z
    Laboratory of Molecular Virology, Department of Virology, National Center of Infectious and Parasitic Diseases, 44-A Stoletov Blvd., 1233 Sofia, Bulgaria.

    OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is the most common benign neoplasm affecting the larynx and upper respiratory tract in children. Human papillomavirus (HPV) has been implicated as the cause of RRP, most commonly types 6 and 11. The present study was undertaken to evaluate the occurrence of HPV types in a group of patients with juvenile-onset RRP (JORRP). METHODS: The study group consists of 23 patients with JORRP. The clinical records of the patients were reviewed, and JORRP was classified as non-aggressive or aggressive. The laryngeal biopsies were taken and investigated for HPV DNA presence using real-time polymerase chain reaction (PCR) with a set of consensus primers (MY09/11). Viral typing was subsequently performed by real-time PCR with type-specific primers for HPV types 6, 11, 16, 18, 31, and 33. RESULTS: HPV presence was detected in all samples with amplifiable DNA. HPV-11 was revealed in 61.9% of the patients and HPV-6 in 23.8%. Double positivity for HPV types 6 and 11 was identified in 14.3%. Our findings suggest that RRP runs a more aggressive clinical course when HPV-11 infection is present (p=0.0265). CONCLUSIONS: Our results suggest a high frequency of HPV infection in the upper respiratory tract of the studied patients. We believe that the routine application of molecular techniques such as PCR for detection and analysis of HPVs in patients with RRP has diagnostic and prognostic significance.

    Natural history of adult-onset laryngeal papillomatosis following multiple cidofovir injections.
    Ann Otol Rhinol Laryngol. 2006; 115(3):175-81 (ISSN: 0003-4894)
    Naiman AN; Abedipour D; Ayari S; Fresnel E; Coulombeau B; Bour JB; Froehlich P
    Department of Otolaryngology, Edouard Herriot University Hospital, Lyon, France.

    OBJECTIVES: A prospective study was performed to assess the intermediate and long-term efficacy of intralesional cidofovir therapy associated with surgical excision in laryngeal papillomatosis in adults. METHODS: Endoscopy with intralesional injection of cidofovir 5 mg/mL was performed 3 times at 4-week intervals. The concentration was later increased to 7.5 mg/mL and the interval between injections shortened to 2 weeks. Further treatment was performed at 3 or 6 months, depending on the evolution of the papillomas. After complete remission, the treatment was stopped and the patients were reviewed every 6 months. RESULTS: Nineteen patients completed the protocol, with a mean of 4.5 injections each. Complete remission was obtained in 17 cases (89%) after a mean of 3.8 procedures. Remission was stable after a mean follow-up of 24 months (range, 8 to 57 months). With higher cidofovir concentrations at shorter intervals, patients needed fewer injections to achieve remission (mean, 2.1 versus 4.7 injections). CONCLUSIONS: The effectiveness of intralesional cidofovir therapy in adult-onset recurrent respiratory papillomatosis was impressive. Once obtained, complete remission was stable on intermediate or long-term follow-up. The concentration and the interval between injections seemed to influence the number of injections necessary to achieve remission.

    High level expression of human epithelial beta-defensins (hBD-1, 2 and 3) in papillomavirus induced lesions.
    Virol J. 2006; 3:75 (ISSN: 1743-422X)
    Chong KT; Xiang L; Wang X; Jun EL; Xi LF; Schweinfurth JM
    Department of Otolaryngology & Communicative Sciences, University of Mississippi Medical Center, Mississippi, USA. kchong@ent.umsmed.edu

    BACKGROUND: Epithelial defensins including human beta-defensins (hBDs) and alpha-defensins (HDs) are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. RESULTS: Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP) and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p < 0.01) suggesting that they were co-inducible in papillomavirus induced lesions. Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in oral mucosa. CONCLUSION: Human beta-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

    Recurrent respiratory papillomatosis.
    Ann Otol Rhinol Laryngol. 2006; 115(1):1-11 (ISSN: 0003-4894)
    Derkay CS; Darrow DH
    Department of Otolaryngology, Eastern Virginia Medical School, 825 Fairfax Ave, Suite 510, Norfolk, VA 23507, USA.

    Recurrent respiratory papillomatosis is a frustrating and challenging disease for surgeons, patients, and patients' families. Although the voice and airway manifestations are managed surgically, a "cure" for this disease remains elusive. In this edition of the "Seminar Series," we endeavor to review the current literature regarding the epidemiology, etiology, clinical manifestations, and surgical and medical treatments of this disorder. The key to future management of recurrent respiratory papillomatosis may lie in its prevention, if current efforts to develop an effective vaccine come to fruition.