RRP Medical Reference Service



An RRP Foundation Publication

edited by

Dave Wunrow and Bill Stern





















Winter 1998
___________________

Volume 5 Number 1












Preface

The RRP Medical Reference Service is intended to be of potential interest to RRP patients/families seeking treatment, practitioners providing care, micro biological researchers as well as others interested in developing a comprehensive understanding of recurrent respiratory papillomatosis.
This issue focuses on a selection of references with abstracts from recent (1996 and later) RRP related publications.These listings are sorted in approximate reverse chronological order as indicated by the "Unique Identifier" numbers. Each listing is formatted as follows:
Journal or reference
Title
Language (if it is not specified assume article is in English)
Author(s)
Primary affiliation (when specified)
Abstract
Unique identifier

If copies of complete articles are desired, we suggest that you request a reprint from one of the authors. If you need assistance in this regard or if you have any other questions or comments please feel free to contact:
Bill Stern
RRP Foundation
P.O. Box 6643
Lawrenceville NJ 08648-0643
(609) 530-1443 or (609)452-6545
E-mail: rrpf@aol.com or wfs@gfdl.gov
Dave Wunrow
210 Columbus Drive
Marshfield WI 54449
(715) 387-8824
E-mail: wunrowd@tznet.com


RRPF Selected Articles and Abstracts



Pediatr Infect Dis J 1998 (In Press)

Risk factors for juvenile-onset recurrent respiratory papillomatosis.

Shah KV, Stern WF, Shah FK, Bishai D, Kashima HK

Department of Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD 21205, USA

BACKGROUND: Children born to condylomatous mothers are at risk for developing juvenile-onset recurrent respiratory papillomatosis (JORRP). We inquired if the triad of vaginal delivery, being first-born, and maternal age of less than 20 years are also risk factors for JORRP. METHODS: Data for JORRP and adult-onset (AO) RRP 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 less than 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 less than 20 years old were compared with corresponding numbers in mothers 20 years old or older. RESULTS: In JORRP cases, the relationships between observed and expected numbers of cases were as follows: cesarean births, 4.6 fold less; first order births, 1.6 fold greater; maternal age less than 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 AORRP cases with respect to any of the above variables. CONCLUSIONS: Young, primiparous mothers with condylomas are at 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.

Unique Identifier: [Not yet assigned]
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Clin Otolaryngol 1997 Aug;22(4):382-386

Laryngeal dysplasia and the human papillomavirus.

Lindeberg H, Krogdahl A

Department of Maxillo-Facial Surgery and Oral Pathology, Royal Dental College,Aarhus, Denmark.

The relationship between the human papillomavirus (HPV) and cancer of the upper aerodigestive trace is controversial. There is no doubt that at least some nasal, oral, pharyngeal and laryngeal carcinomas contain HPV DNA. However, the diversity in the reported incidence of HPV in these tumours represents a major problem. In the present study we have examined 30 laryngeal dysplastic lesions for HPV by the polymerase chain reaction, using three different pairs of consensus primers (GP5+/GP6+, MY09/MY11 and CPI/CPII). The single HPV-positive specimen was from a recurrent laryngeal papilloma. The HPV type present could not be determined, but it was not type 6, 11, 16, 18, 30, 31, 33 or 45. Restriction fragment length polymorphy analysis suggested a yet unknown HPV-type in this lesion. This investigation does not support the idea of HPV as an oncogenic cofactor in most laryngeal carcinomas as HPV was present in only 1/30 precancerous laryngeal lesions.

Unique Identifier: 97443947
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Dtsch Med Wochenschr 1997 Aug 22;122(34-35):1033-1036

[The treatment of juvenile laryngeal papillomatosis with argon plasmacoagulation]. [Article in German]

Bergler W, Riedel F, Gotte K, Hormann K

Hals-Nasen-Ohren-Klinik, Fakultat fur Klinische Medizin Mannheim, UniversitatHeidelberg.

HISTORY AND CLINICAL FINDINGS: At 3 years of age a girl known for one year to have progressive juvenile laryngeal papillomatosis with involvement of the lower respiratory tract was seen by her general practitioner because of increasing hoarseness. As about 20 sessions of CO2-laser treatment and adjuvant administration of interferon-alpha had failed to prevent increasing glottal stenosis and spread of the tracheal involvement, a tracheostomy had to be performed. Removal of the papilloma became progressively more difficult and at the age of 6 years she was admitted for further treatment. INVESTIGATIONS: She had marked inspiratory and expiratory stridor. Results of laboratory tests were unremarkable. Examination of the respiratory tract with a flexible endoscope revealed obstruction of the tracheal lumen by the papilloma. TREATMENT AND COURSE: The papilloma was removed by argon plasma coagulation (APC) under general anaesthesia during intermittent apnoeic phases. After four treatment sessions no papilloma could be seen endoscopically. There were no side effects or complications. The interval between treatments has become progressively longer. Further removal of papilloma is only rarely necessary nowadays. CONCLUSION: APC via a flexible endoscope is a promising method in the treatment of juvenile laryngeal papillomatosis involving the lower respiratory tract. It achieves precise, circumscribed tissue penetration without carbonisation or steaming-up, while bleeding can be controlled.

Unique Identifier: 97441612
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Int J Pediatr Otorhinolaryngol 1997 Jul 18;41(1):37-46

Observer agreement about laryngoscopic assessment of papilloma.

Todd NW

Department of Otolaryngology, Emory University School of Medicine, Atlanta,Georgia 30322, USA. ntodd@emory.edu

BACKGROUND: Observer bias may confound the assessment of therapies utilized for recurrent respiratory papilloma, a recidivistic fluctuating disease. Any convincing change in a patient's disease must exceed the imprecision of the measuring system. MATERIALS AND METHODS: Videotapes of ten children, who had airway endoscopy for care of laryngeal papilloma, were edited. The videotapes were independently reviewed by six otolaryngologists, of whom five repeated their assessments 5 to 20 weeks later. The 'reference standard' was the operating surgeon's categorization of his patient's videotape. Agreement was calculated by the kappa statistic, the observed proportions of positive and negative agreement, and the proportion categorized as exact opposites, for each of twelve anatomic sites. RESULTS: Moderate agreement was found for both (a) the operative findings versus the later-determined 'reference standard', and (b) the 'reference standard' versus categorizations by other otolaryngologists. Intra-observer agreements were better than inter-observer agreements. Agreement as to whether or not papilloma involved each of twelve sites was within about 20% for the five pediatric otolaryngologists vs the 'reference standard', and within about 10% for the same reviewer. CONCLUSION: Videotapes may add objectivity to the assessment of laryngeal papilloma. For changes to be considered significant, an observer should identify a 10% change in the number of sites involved, or a 30% change in the extent of overall airway obstruction. For different observers, changes would have to be even greater to be meaningful.

Unique Identifier: 97425584
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Vestn Otorinolaringol 1997;4:13-15

[Antibodies against alpha-2 and gamma-interferons affect the course of juvenile respiratory papillomatosis in children treated with alpha-2 interferon preparations]. [Article in Russian]

Kol'tsov VD, Onufrieva EK, Nurmukhamedov RKh, Malinovskaya VV, Yershov FI

Laboratoriya vosstanovitel'noy khirurgii gortani i trakhei dlya detey MMA im. I.M. Sechenova na baze MGDB Sv. Vladimira i NIIEM im. N.F. Gamalei RAMN.

1-year or longer treatment of juvenile respiratory papillomatosis (JRP) with alpha-2 interferons (A21) leads to emergence of antibodies to A21 in 54.3% of the patients. The greatest percentage of the antibody positives (94.4%) was found among JRP patients treated with intramuscular recombinant human A21 (reaferon). The proportion of the antibodies carriers fell to 15.4% if reaferon was used as a component of the new preparation viferon. JRP patients have also autoantibodies to A21 and gamma-interferon (8.74 and 33.3%, respectively). Patients with autoantibodies to gamma-interferon responded well to treatment with A21. Antibodies to A21 seem to have no negative effect on interferon therapy of JRP. Reaferon and viferon can be effectively used in JRP treatment.

Unique Identifier: 97417863
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Orv Hetil 1997 Jul 27;138(30):1891-1895

[Detection of human papillomavirus gene sequences in laryngeal tumors and premalignant changes by polymerase chain reaction]. [Article in Hungarian]

Czegledy J, Major T, Juhasz A, Repassy G, Gergely L

Debreceni Orvostudomanyi Egyetem, Debrecen Mikrobiologiai Intezet.

Human papillomavirus gene sequences have been detected in a number of malignant and benign tumours. Non-oncogenic types 6 and 11 are etiological factors of benign mucosal tumours. Types 16 and 18 can be detected in malignancies most often but their role in the etiopathogenesis of cancers is still unclear. In our study we examined formalin-fixed and paraffin-embedded archive laryngeal tissues containing squamous cell carcinoma, papilloma and precancerous lesions for the presence of human papillomavirus genes. As a control we also examined tissues harbouring laryngeal nodules which represented the normal larynx in our study. After DNA preparation from the paraffin blocks we performed polymerase chain reaction to detect the DNA of human papillomavirus types 6, 11, 16 and 18. In the squamous cell carcinomas, papillomas and precancerous lesions the presence of human papillomavirus gene sequences was significantly higher than in the control group. To verify the integrity of DNA we also amplified a sequence deriving from the cellular beta-globin gene. Based on the 100% positivity for this gene we declare that the combination of our DNA preparation and polymerase chain reaction is a reliable method for detecting DNA sequences from formalin-fixed and paraffin-embedded tissues.

Unique Identifier: 97410605
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Clin Dermatol 1997 May;15(3):399-413

HPV-associated diseases of oral mucosa.

Praetorius F

Department of Oral Pathology, School of Dentistry, University of Copenhagen, Denmark.

[No abstract available]

Unique Identifier: 97399319
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Med Lett Drugs Ther 1997 Aug 1;39(1006):69-76

Drugs for non-HIV viral infections.

[No abstract available]

Unique Identifier: 97399109
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An Otorrinolaringol Ibero Am 1997;24(3):269-280

[The detection of human papillomavirus in papillomas of the larynx and tonsils through immunohistochemistry and DNA in situ hybridization].
[Article in Spanish]

Lopez Amado M, Garcia Caballero T, Lozano Ramirez A, Labella Caballero T

Universidad de Santiago de Compostela, Compleio Hospitalario Universitario de Santiago, Santiago de Compostela, Catedra de Otorrinolaringologia.

Presenting a study about Human Papillomavirus (HPV) determination by immunohistochemistry and "in situ" hybridization, in 25 samples of squamous cell papillomata (15 tonsilar and 10 laryngeal lesions). Five cases resulted positive for HPV: 2 of them for immunohistochemical probes, other 2 for "in situ" hybridization and only 1 cas showed its positivity for both techniques. All these samples belonging to laryngeal cases. No significant differences were found in antecedents, clinical and histological features related with results obtained. Two patients developed a laryngeal carcinoma after papilloma and they had positive "in situ" hybridization. Literature about diagnosis of HPV-infection was revised.

Unique Identifier: 97398732
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Hepatology 1997 Aug;26(2):473-477

Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial.

Bodenheimer HC Jr, Lindsay KL, Davis GL, Lewis JH, Thung SN, Seeff LB

Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029-6504, USA.

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.

Unique Identifier: 97394443
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Laryngoscope 1997 Jul;107(7):942-947

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

Lin KY, Westra WH, Kashima HK, Mounts P, Wu TC

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.

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.

Unique Identifier: 97360108
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Laryngoscope 1997 Jul;107(7):915-918

Pediatric respiratory papillomatosis: prognostic role of viral typing and cofactors.

Rimell FL, Shoemaker DL, Pou AM, Jordan JA, Post JC, Ehrlich GD

Division of Pediatric Otolaryngology, University of Minnesota, Minneapolis 55455, USA.

Children with recurrent respiratory papillomatosis vary greatly in their clinical disease course. Many have mild disease with eventual remission while others present with an early aggressive airway obstructive course. This study consisted of 24 pediatric patients whose specimens underwent polymerase chain reaction analysis for cytomegalovirus (CMV), herpes simplex virus (HSV), and human papillomavirus (HPV) type. Nineteen of 24 specimens contained enough DNA for this study. None of the specimens were found to contain DNA from HPV-16, -18, -31, -33; CMV; or HSV, which contrasts with our previous findings in adults. Ten patients were infected by HPV-11 and seven of these underwent tracheotomy because of an aggressive tumorigenic clinical course. Nine patients were infected by HPV-6 alone of whom only two required a tracheotomy (P = 0.05, Fisher's Exact Test). The early airway obstructive course associated with HPV-11, however, had no bearing on achieving eventual disease remission, with decannulation achieved in eight of nine children.

Unique Identifier: 97360102
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J Environ Pathol Toxicol Oncol 1996;15(2-4):195-199

Some etio-pathogenetic factors in laryngeal carcinogenesis.

Sugar J, Vereczkey I, Toth J

National Institute of Oncology, Budapest, Hungary.

Chemical influences, mainly heavy tobacco smoking, chewing snuff, excessive alcohol consumption, and some occupational hazards, are known to be important etiologic factors in laryngeal carcinogenesis. The synergistic or cooperative interaction of human papilloma virus (HPV) infection with these chemical factors are serious considerations in the development of laryngeal carcinoma. With the development during the last decade of Southern blot hybridization and polymerase chain reaction (PCR), extensive and comprehensive studies have been conducted to determine the presence and biological (etiologic) significance of HPV. Developed cancer, as well as juvenile and adult multiple and single papilloma of the larynx, have been the subject of clinical and molecular-pathological investigation. Our previous study showed that cancer may develop on the basis of leukoplakia and adult-onset papilloma. Extensive kilocytes, an indication of HPV infection, can be seen by histological examination in papillomas and carcinoma. Literary data suggest that in laryngeal squamous cell carcinoma, including varicoses carcinoma, HPV 16, HPV 18, and HPV 33 DNA have been detected. Both in juvenile and adult-onset respiratory papillomatosis, patients could have either HPV type 6 or 11 DNA sequences. Molecular biological and PCR studies indicate that HPV may play an etiologic role in the development of human malignancies of the upper aerodigestive tract and uterine (cervical) origin. However, evidence that unequivocally links HPV infection with laryngeal squamous cell carcinoma is still lacking. In laryngeal cancer, p53 abnormalities are related to smoking-induced mutagenesis rather than HPV. Studies have postulated an interaction between HPV infection and chemical carcinogens and have concluded that HPV possibly are co-adjuvants during the multistage process of neoplastic transformation.

Unique Identifier: 97359890
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Acta Otolaryngol Suppl (Stockh) 1997;527:128-130

Adjuvant therapy with hydrolytic enzymes in recurrent laryngeal papillomatosis.

Mudrak J, Bobak L, Sebova I

Department of Otorhinolaryngology, P.J. Safarik University Hospital, Kosice, Slovak Republic.

The subject of this study is systemic enzymotherapy as adjuvant treatment in recurrent laryngeal papillomatosis. The authors analyze their observations of 5 adult patients with recurrent laryngeal papillomatosis when after surgical extirpation and subsequent application of peroral proteases there was a significant improvement of their clinical state and laboratory results. The patients have been disease-free from 10 to 18 months. In the authors' experience, the adjuvant enzymotherapy seems to be a suitable replacement of the supplementary treatment in larynx papillomatosis, and it promises to decrease the recurrence rate as well.

Unique Identifier: 97341027
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Acta Otolaryngol Suppl (Stockh) 1997;527:120-124

Human papillomavirus infection and expression of p53 and c-erbB-2 protein in laryngeal papillomas.

Luzar B, Gale N, Kambic V, Poljak M, Zidar N, Vodovnik A
Institute of Pathology, Medical Faculty, University of Ljubljana, Slovenia. luzar@ibmi.mf.uni-lj.si
Laryngeal papilloma (LP) is the most frequent benign laryngeal epithelial tumor caused by human papillomaviruses (HPV) types 6 and 11. In the present study, we were interested in whether we can find any prognostic markers which might reflect the biological behavior of the covering epithelium in LP. We focused our attention on the determination of HPV infection, the detection of p53 protein, and c-erbB-2 protein in 24 biopsy specimens of LP. We confirmed the HPV 6 and 11 etiology in 23 of 24 LP. In these lesions the overexpression of p53 protein increased with the grade of epithelial abnormalities. The distribution of positive cells changed from scattered and focal, in simple and abnormal hyperplasia, to diffuse in atypical hyperplasia. It has been shown that in the presence of HPV types 6 and 11 found in LP, p53 can still preserve its tumor suppressor activity. Infection with HPV types 6 and 11 might therefore account for the significantly lower rate of malignant transformation in LP. Two staining patterns for c-erbB-2 protein were observed in the hyperplastic epithelium covering LP: membranous and cytoplasmic. With the increasing grade of epithelial abnormalities, cytoplasmic staining became predominant, and c-erbB-2 positivity sometimes occupied the whole epithelial thickness. This may represent either an alteration in the processing stability of the c-erbB-2 mRNA, gene amplification, or even an artefact.

Unique Identifier: 97341025
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Acta Otolaryngol Suppl (Stockh) 1997;527:111-113

Sudden death caused by laryngeal papillomatosis.

Balazic J, Masera A, Poljak M
Institute of Forensic Medicine, Medical Faculty, University of Ljubljana, Slovenia.

Laryngeal papillomatosis (LP) is the most frequent benign neoplasm of the larynx. Clinically it causes hoarseness and upper airway obstruction. Though the LP has the potential to endanger life by asphyxiation, this unfortunate outcome is extremely rare. We report the case of a 19-year-old female who suddenly died of asphyxiation caused by massive LP.

Unique Identifier: 97341022
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Acta Otolaryngol Suppl (Stockh) 1997;527:100-102

Laryngeal papilloma--precancerous condition?

Klozar J, Taudy M, Betka J, Kana R

Department of Otorhinolaryngology, Head and Neck Surgery General Faculty Hospital, The First Medical Faculty, Charles University in Prague, Czech Republic.

In a group of 179 patients treated for recurrent laryngeal papillomatosis 668 surgeries were performed in the years 1982-1995 in the Department of Otorhinolaryngology, Head and Neck Surgery in Prague. The group was divided into 77 patients with a juvenile form of papillomatosis and 102 patients with an adult form. The adult form was then divided into a multiple (65 patients) and solitary form (37 patients). Three patients with a juvenile form of papillomatosis were irradiated in advance. None of these patients developed a carcinoma. There were 3 cases (1.7%) of carcinoma in the whole group of patients with histologically verified papillomas during repeated previous surgeries. All 3 patients with malignancy had an adult form of papillomatosis, two with a multiple form and one with a solitary form. The intervals between the first treatment for papilloma and the diagnosis of carcinoma was 8, 3 and 2 years.The rates of malignant transformation of papillomas vary in the literature. We suppose, that because of the generally long interval between the diagnosis of papilloma and that of carcinoma, to make a final conclusion of a certain ratio is very difficult. We envisage that in our group of patients with papillomatosis new cases of carcinoma will occur in the future.

Unique Identifier: 97341019
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Eur Arch Otorhinolaryngol 1997;254(5):219-222

Prognostic value of clinical findings in histologically verified adult-onset laryngeal papillomas.

Aaltonen LM, Peltomaa J, Rihkanen H

Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland.

A retrospective study of adult-onset laryngeal papilloma was performed to clarify whether any clinical features at the time of diagnosis could predict its course. All patients had a histologically confirmed diagnosis of laryngeal papillomas and were treated at Helsinki University Hospital between 1975 and 1994. Those with adult-onset disease and follow-up exceeding 1 year (n = 74) entered the study. Based on the case records surveyed, results suggested two risk factors for frequent laryngeal procedures: young age at onset of papilloma and a lesion extending to the anterior third to the vocal folds. It was not possible to predict the course of the disease by such clinical findings as symptoms or size or number of primary papilloma lesions. As regards the recurrence of disease, the classic division of adult-onset laryngeal papilloma into solitary and multiple type was not found to be clinically relevant.

Unique Identifier: 97338585
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Rev Prat 1997 Mar 15;47(6):646-651

[Drugs active against respiratory viruses].
[Article in French]

Freymuth F, Vabret A

Laboratoire de virologie humaine et moleculaire CHU, Caen.
Few molecules are active against respiratory viruses. In upper respiratory tract infections, which are frequent and fortunately not severe, their deficiency is not a problem. However some molecules are able to block in vitro the interaction between a rhinovirus and its receptor: anti-receptor antibodies, soluble ICAM-1, capsid-binding agents. The lower respiratory tract infections (bronchiolitis, pneumonia...), mainly due to respiratory syncytial virus and influenza viruses are potentially more severe, and 2 groups of compounds are or have been used in these infections: amantadine and ribavirin. Ribavirin is effective in respiratory infections due to respiratory syncytial, influenza and parainfluenza viruses, and on many other viruses. Its toxicity needs to administrate it as an aerosol, and in France, ribavirin is used as compassional treatment in severe forms of bronchiolitis or pneumonia due to respiratory syncytial virus, and in high-risk children. Anti-parkinsonian drugs, related to amantadine (Mantadix, Roflual) are no longer on sale. Therefore there is no active molecule yet available against these viruses.

Unique Identifier: 97327152
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J Laryngol Otol 1997 Apr;111(4):381-384

Treatment of recurrent respiratory papillomatosis with argon plasma coagulation.

Bergler W, Honig M, Gotte K, Petroianu G, Hormann K

Department of Otorhinolaryngology, University Clinic Mannheim, Germany.

Extension of recurrent respiratory papillomatosis (RRP) to the lower airway in children is life-threatening and an extremely difficult condition to treat. We present the case of a seven-year-old girl with progressive RRP since the age of two. Repeated CO2 laser treatment and interferon-alpha treatment could not prevent tracheotomy and spread to the trachea. We used argon plasma coagulation (APC) with flexible endoscopy for the first time for the treatment of RRP. APC gives a controlled limited penetration into the tissue and good control of bleeding. There is no carbonization or vaporization which makes it a suitable method for the treatment of lower airway RRP. After a few treatments with APC, we gained very good control of the disease with no side-effects or complications. The described application of APC seems to be a promising way to treat lower airway RRP.

Unique Identifier: 97319734
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Anesth Analg 1997 Jun;84(6):1395-1396

Juvenile papillomatosis and airway obstruction.

Berry FA

Comment on: Anesth Analg 1996 Dec;83(6):1332-4 [No abstract available]

Unique Identifier: 97317065
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J Natl Cancer Inst 1997 May 21;89(10):718-723

Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans.

Michnovicz JJ, Adlercreutz H, Bradlow HL

Rockefeller University Hospital and The Institute for Hormone Research, New York, NY 10016, USA.

BACKGROUND: The oxidative metabolism of estrogens in humans is mediated primarily by cytochrome P450, many isoenzymes of which are inducible by dietary and pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g., cabbage and broccoli). PURPOSE: Because the pool of available estrogen substrates for all pathways is limited, we hypothesized that increased 2-hydroxylation of estrogens would lead to decreased activity in competing metabolic pathways. METHODS: Urine samples were collected from subjects before and after oral ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C for 1 week; in the second study, 10 women received I3C for 2 months. A profile of 13 estrogens was measured in each sample by gas chromatography-mass spectrometry. RESULTS: In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16alpha-hydroxyestrone, were lower after I3C treatment. CONCLUSIONS: These findings support the hypothesis that I3C-induced estrogen 2-hydroxylation results in decreased concentrations of several metabolites known to activate the estrogen receptor. This effect may lower estrogenic stimulation in women. IMPLICATIONS: I3C may have chemopreventive activity against breast cancer in humans, although the long-term effects of higher catechol estrogen levels in women require further investigation.

Unique Identifier: 97311470
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Proc Natl Acad Sci U S A 1997 May 27;94(11):5826-5830

Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid.

Huang C, Ma WY, Dawson MI, Rincon M, Flavell RA, Dong Z
The Hormel Institute, University of Minnesota, 801 16th Avenue, N.E., Austin, MN 55912, USA.

Retinoic acid is one of the most promising drugs for chemotherapy and chemoprevention of cancer. Either blocking activator protein-1 (AP-1) activity or activating retinoic acid response element (RARE) have been proposed to be responsible for its antitumor activity. However, evidence for this hypothesis is lacking in vivo studies. To address this issue, we used an AP-1-luciferase transgenic mouse as a carcinogenesis model and new synthetic retinoids that are either selective inhibitors of AP-1 activation or selective activators of the RARE. The results showed that the SR11302, an AP-1 inhibition-specific retinoid, and other AP-1 inhibitors such as trans-retinoic acid and fluocinolone acetonide, markedly inhibit both 12-O-tetradecanoylphorbol-13-acetate-induced papilloma formation and AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse skin (P < 0.05). In contrast, repeated applications of SR11235, a retinoid with RARE transactivating activity, but devoid of AP-1 inhibiting effect, did not cause significant inhibition of papilloma formation and AP-1 activation (P > 0.05). These results provide the first in vivo evidence that the antitumor effect of retinoids is mediated by blocking AP-1 activity, but not by activation of RARE.

Unique Identifier: 97303216
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Laryngoscope 1997 May;107(5):675-679

Posterior glottic stenosis mechanism and surgical management.

Hoasjoe DK, Franklin SW, Aarstad RF, Day TA, Stucker FJ

Department of Otolaryngology/Head & Neck Surgery, Louisiana State University School of Medicine, Shreveport 71130, U.S.A.

Posterior glottic stenosis with arytenoid fixation is an uncommon complication of laryngeal injury. Though etiologies vary; the most common is prolonged intubation. Patients with this problem are tracheotomy dependent and have compromised voice production. There has been no acceptable approach to reconstruction of the larynx, the majority of patients being treated with some type of vocal fold lateralization. The success rate with this approach varies, and this procedure does not take advantage of the intact neuromuscular status of the larynx. Over the past 3 years we have utilized an alternative approach, to repair the stenosis and mobilize the arytenoids in 10 patients. Our surgical technique involves laryngeal exposure via a laryngofissure, the removal of posterior glottic cicatricial tissues, and the application of an autologous graft. Subsequently, all but one of the patients were able to be decannulated. Subjective postoperative voice analysis showed improved voice production. The pathophysiology for this disorder and a review of different treatment modalities are discussed.

Unique Identifier: 97293120
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Laryngorhinootologie 1997 Mar;76(3):150-154

[Malignant degeneration of juvenile laryngeal papillomatosis]? [Article in German]

Schick B, Kronsbein H, Heil M, Draf W
Klinik fur HNO-Krankheiten, Kopf-, Hals- und Plastische Gesichtschirurgie, Kommunikationsstorungen.

BACKGROUND: Spontaneous malignant transformation of laryngeal papillomatosis was in the past mostly negated, or the discussion in literature was rather toned down and reserved. Therefore, from a biological and prognostic point of view, HPV infection of the larynx seems to carry a different weight than a viral infection in genital region. According to general consensus, secondary, malignant transformation in juvenile papillomatosis occurs in irradiated patients and leads to the conclusion that radiation therapy of this disease is presently contraindicated. Because there is as yet no causal and curative treatment, repeated and frequent removal of papillomatous tissue by microlaryngoscopy may often be necessary to keep the airway patent. PATIENT, METHOD AND RESULTS: We diagnosed and treated an advanced laryngeal squamous cell carcinoma with lymphatic metastasis in a 50-year old male. Juvenile papillomatosis had been diagnosed already at the age of five, and at the patient's last presentation 5 years ago (age 45), typical clinical and histological features of laryngeal papillomatosis had been observed. Furthermore, virus infection of the papillomatous tissue (HPV-6/11) was proved by using the technique of in-situ hybridisation. Risk factors for malignant transformation, such as smoking, alcohol or radiation, were denied by the patient. CONCLUSIONS: From these aspects, a spontaneous, malignant transformation of laryngeal papillomatosis must be considered with regard to six similar observations in the German and English literature. In the reported case, a tumoural origin in the flat laryngeal mucosa in close neighbourhood to the former site of papillomas, is less probable, albeit not ruled out completely, since continuous changes from benign squamous papilloma to atypical, invasive tumour and a HPV-infection in the carcinomatous tissue could not be proved by in-situ hybridisation.

Unique Identifier: 97280159
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Laryngorhinootologie 1997 Mar;76(3):142-149

[High-risk HPV types in oral and laryngeal papilloma and leukoplakia].
[Article in German]

Arndt O, Johannes A, Zeise K, Brock J

HNO-Abteilung des Marienkrankenhauses Hamburg.

BACKGROUND: Juvenile and adult laryngeal papillomas (JLP and ALP) and oral papillomas (OP) are important benign tumors of the head and neck. Laryngeal leukoplakia (LL) may be a precancerous lesion. The etiology of the papillomas is associated with human papillomavirus infection (HPV). The important noxes for the development of laryngeal leukoplakias are nicotine, alcohol, and HPV. Adult laryngeal papillomas and OP can also undergo malignant conversion. Today, there is no marker known to distinguish in progressive lesions and in those which show a regression. Different types of HPV were detected in head and neck cancer too. There is a important similarity to the genesis of cervical cancer. The 77 known HPV types were divided into benign types, e.g., 6 and 11, and those with oncogene potential, e.g., 16, 18, 31, 33, and 35. The detection of oncogene HPV may be a sensitive marker for prognosis of primary benign lesions. PATIENTS AND METHODS: In this study, the presence of HPV genomes 6, 11, 16, 18, 31, 33, and 35 in 17 JLP, 27 ALP, 15 OP, and 11 LL was examined. DNA extracted from archived samples embedded in paraffin was amplified using the E6 specific polymerase chain reaction (PCR). The products were visualized by electrophoresis, and positive identification was achieved by Southern blot analysis and hybridization to specific biotinylated oligonucleotide. RESULTS: Our data show the presence of HPV 6/11 in all JLP (17 of 17), in all ALP (27 of 27), in 13 of 15 (87%) OP, and in seven of 11 (63%) LL. The "malignant" types HPV 16, 18, and 33 were found in six of 27 (22%) of the ALP, in three of 15 (20%) of the OP, and in four of 11 (36%) of the LL. the dominant type was HPV 16, HPV 31 and 35 were not detectable. Three ALP, one OP, and the four LL of the cases with oncogene HPV showed histologic features of moderate dysplasia. CONCLUSIONS: The role of HPV in malignant transformation of infected cells remains unclear. It is well known that the carcinogenesis must depend on promoters such as alcohol, tobacco, and metabolites of chronic inflammations. All patients with positive biopsies confirming HPV 16, 18, or 33 must receive special care to prevent the development of a carcinoma.

Unique Identifier: 97280158
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Otolaryngol Pol 1996;50(6):567-578

Recurrent laryngeal papillomatosis. Retrospective analysis of 95 patients and review of the literature.

Mahnke CG, Frohlich O, Lippert BM, Werner JA

BACKGROUND: Laryngeal papillomatosis is a benign neoplastic disease which is associated with and probably by the Human Papilloma Virus. It can be of significant importance for affected patients because of its recurrent clinical course. A great variety of therapeutic measures have been described including surgical removal either with conventional instruments or by using the laser. The aim of this study was to compare these two methods. PATIENTS: The clinical courses of all patients (53 male, 42 female) treated at the Dept. of Otolaryngology, Head and Neck Surgery, University of Kiel since 1960 were analysed retrospectively. The two most common forms of treatment, surgical removal either conventionally or with the use of the laser, were compared. RESULTS: Laryngeal papillomatosis is a disease of all ages, but often initially diagnosed in the first and fourth decade. In 25 cases the onset was before the age of 16. Puberty had no effect on the clinical course. A malignant degeneration was observed in four cases. Although the different forms of treatment did not affect the rate of recurrence, the rate of complications such as tracheostomy and glottic webs was significantly reduced after laser surgery. Since the introduction of this new form of therapy no further tracheostomies had to be performed on these patients. CONCLUSION: The term juvenile laryngeal papillomatosis should be replaced by recurrent respiratory papillomatosis. One could then make a distinction according to the age of onset, i.e. in children below the age of 16 years and in adolescents and adults older than 15 years. The occurrence of squamous cell carcinomas in patients previously treated for papillomas underlines the need for repeated histological studies. Our studies have shown that surgical treatment remains the mainstay in the management of laryngeal papillomatosis, with laser surgical technique being superior to conventional removal.

Unique Identifier: 97267183
Am J Ophthalmol 1997 Apr;123(4):551-552

Female genital tract papillomavirus in conjunctival papillomas of infancy.

Egbert JE, Kersten RC

Department of Ophthalmology, University of Cincinnati, College of Medicine, OH, USA.

PURPOSE: To show the association between conjunctival papillomas present during infancy and maternal infection with human papillomavirus. METHOD: Case report of conjunctival papillomas occurring in an infant born to a mother with a human papillomavirus infection of the vulva during pregnancy. RESULT: The infant developed conjunctival papillomas caused by human papillomavirus of the female genital tract. CONCLUSIONS: Conjunctival papillomas present during infancy may be caused by vertical transmission of the human papillomavirus from mother to infant during delivery. Mothers of infants with conjunctival papillomas should be examined for diseases associated with human papillomavirus.

Unique Identifier: 97255158
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Dermatol Clin 1997 Apr;15(2):331-340

Therapeutic approaches to papillomavirus infections.

Baker GE, Tyring SK

Department of Dermatology, Microbiology/Immunology, University of Texas Medical Branch, Galveston, USA.

Human papillomaviruses (HPVs) cause benign tumors (i.e., warts) and are occasionally responsible for malignant tumors such as squamous-cell carcinomas. Therapy for most warts is commonly via surgical or cytodestructive methods. Presently, only one antiviral/immunomodulatory drug is available for wart therapy; this agent, interferon alpha (IFN alpha), is approved only for genital warts (condylomata acuminata) and is expensive, relatively difficult to use, associated with systemic side effects, and somewhat slow acting. Two new antiviral/immunomodulatory drugs, imiquimod and cidofovir, have been proved to be effective and able to overcome many of the shortcomings of IFN alpha. While these two agents are pending approval, other treatments are being evaluated, such as antisense oligonucleotides and therapeutic HPV vaccines. In contrast to surgical and cytodestructive therapies, the goal of these new antiviral/immunomodulatory agents is not just to remove the tumor but also to reduce sufficiently the amount of latent and subclinical HPV so as to reduce the rate of recurrence.

Unique Identifier: 97253199
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Ann Otolaryngol Chir Cervicofac 1996;113(5):243-249

[CO2 laser in pediatric laryngology]. [Article in French]

Nicollas R, Triglia JM, Belus JF, Bonneru JJ, Marty JY

Unite d'ORL Pediatrique, Federation ORL, Hopital de la Timone, Marseille.

Carbon dioxide Laser is a recently developed instrument which has became essential in laryngology, especially in its pediatric applications. Authors report 86 cases of children with a laryngeal pathology treated by CO2 Laser at the Childrens Hospital of La Timone in Marseille. Four groups emerge from this study. They are composed of laryngomalacia (n = 34), subglottic angiomas (n = 12), laryngeal papillomatosis (n = 12) and laryngeal stenosis (n = 14). Other patients (n = 14) made up a miscellaneous population (granulomas, laryngeal paralysis, benign tumors). Post-operative data are analyzed and compared with those of literature. The result is that this therapeutic method, used within the limits of precise indications and, if necessary, with divided sequences, can offer rapid curative care with few complications.

Unique Identifier: 97252271
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AANA J 1996 Aug;64(4):362-368

Anesthetic management of children with recurrent, viral laryngeal papillomatosis: a case report.

Rietz CS, Tobias JD

Division of Pediatric Anesthesia, Vanderbilt University, USA.
The authors report the case of a 4-year-old boy who required anesthetic care during laser excision of respiratory papillomatosis. The perioperative issues surrounding this disease process are discussed including anesthetic induction in the patient with a compromised airway, maintenance anesthetic techniques, methods used for ventilation during laser surgery of the upper airway, and infectious disease risks to the operating room personnel. In addition, the psychological and emotional impacts of recurrent surgical procedures during childhood are addressed.

Unique Identifier: 97249884
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Pediatr Pulmonol 1997 Feb;23(2):117-119

A pedunculated papilloma causing ball valve obstruction of the larynx in a two-year-old child.

Massie RJ, Mellis CM, van Asperen PP

Department of Respiratory Medicine, Royal Alexandra Hospital for Children, Camperdown, New South Wales, Australia.

[No abstract available]

Unique Identifier: 97218513
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Pediatr Pathol Lab Med 1997 Jan;17(1):53-64

Juvenile laryngeal papillomatosis in a pediatric population: a clinicopathologic study.

Somers GR, Tabrizi SN, Borg AJ, Garland SM, Chow CW

Department of Anatomical Pathology, Royal Children's Hospital, Parkville, Victoria, Australia.

A series of 22 children with juvenile laryngeal papillomatosis treated over a 31-year period is presented. The majority of patients were diagnosed when less than 5 years of age. Two patients died from the disease and four patients still had active disease at the completion of the study period. The duration of disease and number of recurrences were extremely variable. The number of recurrences was inversely related to the age of onset. The histologic findings were very similar in all patients, and no particular histologic feature had prognostic significance. In 20 patients, laryngeal biopsies were positive for human papillomavirus (HPV) 6/11 by either in situ hybridization (17) or polymerase chain reaction (19) or both (16). The number of patients who were HPV negative was small (two); interestingly, neither case had aggressive disease. Our findings suggest that age of onset and HPV status may be of prognostic value in determining the clinical course of the disease.

Unique Identifier: 97202541
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Int J Pediatr Otorhinolaryngol 1996 Mar;35(1):31-38

Role of cesarean section in prevention of recurrent respiratory papillomatosis--is there one?

Kosko JR, Derkay CS

Department of Otolaryngology--Head and Neck Surgery, Eastern Virginia Medical School, Norfolk 23507, USA.

Recurrent respiratory papillomatosis (RRP) is a benign yet aggressive neoplasm that produces considerable morbidity in children. Previous studies have linked RRP in children to mothers with genital tract human papillomavirus infections (HPV). Risk factors for vertical transmission have not been well identified. Controversy exists among obstetricians and otolaryngologists regarding the role of cesarean section in preventing the transmission of HPV disease from mother to child. We address this issue by presenting the results of a national survey of otolaryngologists, the American College of Obstetrics and Gynecology position statement, the relevant literature regarding the association between RRP and maternal HPV, and the proposed mechanisms for HPV transmission at birth. We postulate a very limited role for cesarean section in preventing transmission of RRP, given our present knowledge of this disease.

Unique Identifier: 97036459


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