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recurrent respiratory papillomatosis
- 3. OBJECTIVES • Introduction • Epidemiology • Etiology • Histology • Transmission • Clinical assessment • Management
- 5. EPIDEMIOLOGY • estimated that between 80 and 1500 new cases of childhood-onset RRP occur in the United States each year. • incidence among children in the United States is estimated at 4.3 per 100,000 children, the incidence among adults is 1.8 per 100,000 • more than 10,000 surgical procedures annually for children with RRP in the United States. • In 75% of children with RRP, diagnosis was made before the fth birthday
- 6. Adult Juvenile – Often dx 2-4 yrs old – boys = girls – No gender/ethnic difference regarding surgical frequency – More aggressive _ 4.4 per year for <3yr - More anatomic site affected – Peaks btwn 20-40 yrs – Slight male predominance – Less aggressive – 50% pts need < 5 procedures over their lifetime
- 7. ETIOLOGY • HPV • DNA virus • epitheliotropic and infects epithelial cells • most common types identified in the airway are HPV 6 and HPV 11—the same types responsible for more than 90% of genital condylomas. • – Other types identified • Type 16 and 18 (most malignant potential) • Type31and33 (intermediate malignant potential) • HPV – DNA virus • 7,900 bp long dsDNA – Nonenveloped, icosahedral – HPV type 6 and 11 • Also cause genital warts • Type 11= more severe – Other types identified • Type 16 and 18 (most malignant potential) • Type 31 and 33 (intermediate malignant potential)
- 8. Children infected with HPV 11 appear to have more • aggressive papilloma growth • more obstructive airway course early in the disease • greater likelihood of undergoing tracheotomy to maintain a safe airway ETIOLOGY HPV 11
- 9. HISTOLOGICALLY Microscopicaly • multiple finger like projections with a central hyper vascular core covered by stratied squamous epithelium Macroscopicaly • exophytic growth pattern, they appear grossly as “cauliflower” or “grapelike” projections • papilloma lesions may be sessile or pedunculated and often occur in irregular exophytic clusters. • Typically, the lesions are pinkish to white in color. • predominant sites are where there is a change of epithelium (e.g. from squamous to ciliated) and especially the tonsillar pillars, uvula, vocal folds and laryngeal commissure.
- 10. TRANSMISSION • Vertical transmission that occurs during delivery through an infected birth canal is presumed to be the major mode of transmitting • in utero and transplacental, sexual abuse, and direct contact play a minor role. • cesarean delivery of children seems to be preventive to some extent. • Patients with childhood-onset RRP are more likely to be first born and vaginally delivered
- 11. CESAREAN SECTION? Seems to be an obvious risk reducer for RRP transmission, but... – Higher morbidity and mortality for the mother – Higher cost compared to vaginal delivery – Approx. 1 in 400 children delivered vaginally to mothers with active condylomatous lesions will contract RRP. – Presently, not enough evidence to warrant C- section in all pregnant mothers with condylomata.
- 12. CLINICAL FEATURE • hoarseness is the principal presenting symptom in RRP • Stridor is often the second clinical symptom to develop, beginning as an inspiratory noise and becoming biphasic with progression of the disease. • Less commonly, chronic cough, recurrent pneumonia, failure to thrive, dyspnea, dysphagia, or acute life-threatening events may be the presenting symptoms. • Because of the rarity of RRP and the slowly progressive nature of the disease, some cases may go unrecognized until respiratory distress results from papillomas that obstruct the airway
- 14. the onset of stridor and dysphonia is gradual and progressive through weeks or months, neoplastic growth that compromises the airway must be considered and investigated. HISTORY • time of onset of symptoms • airway trauma, ,previous intubation • characteristics of the cry • perinatal period may reveal a history of maternal or paternal condylomas. • Associated symptoms such as • feeding difculties, allergic symptoms • vocal abuse • the presence of hereditary congenital anomalies
- 15. PHYSICAL EXAMINATION • respiratory rate and degree of distress must be assessed. • If a child is gravely ill, additional examination should done where resuscitation equipment for intubation of the airway, endoscopic evaluation, and possible tracheotomy is readily available. • Using bell off the stethoscope and listen over these areas with the open tube. The respiratory cycle, which is normally composed of a shorter inspiratory phase and a longer expiratory phase • Pulse oximetry can add objective information on the child’s respiratory status. • In the stable patient in whom asthma is a likely diagnosis, pulmonary function testing may also be helpful.
- 16. AIRWAY ENDOSCOPY • It allows estimation of lumen size and vocal cord mobility and determines the urgency of operative intervention. • Small scoped 1.8 mm in diameter, combined with the newest low- light, distal-chip endoscopic cameras allow passage in even the smallest newborns. • endoscopy in the OR under anesthesia is warranted in any child suspected to have RRP who cannot be fully examined in the outpatient setting.
- 17. Limen vestibuli Nasopharyngea l surface of soft palate Laryngeal surfaceof epiglottis Upper/lower margins of ventricle Undersurface of vocal folds Carina & Bronchial spurs MOST COMMON RRP SITES Pruess et al. Acta Oto-Laryngologica, 2007; 127: 11961201
- 18. TRACHEOSTOMY • tracheotomy may activate or contribute to the spread of disease lower in the respiratory tract. • Cole and colleagues59 reported that tracheal papillomas developed in half of their tracheotomy patients and that despite attempts to avoid this procedure, 21% of their patients still required a long-term tracheotomy. • Most authors agree that tracheotomy is a procedure to be avoided unless absolutely necessary. • When a tracheotomy is not avoidable, decannulation should be considered as soon as the disease is managed effectively with endoscopic techniques.
- 19. MALIGNANT TRANSFORMATION • It has been documented in several case reports of RRP transfer into squamous cell carcinoma A total of 26 patients were identified as having progressed to squamous cell carcinoma in the task force survey. • Dedo reported malignant transformation in 4 of 244 RRP patients (1.6%) treated over two decades.
- 20. CAUSE OF DEATH • When death occurs in a patient with RRP, it is usually as • a complication of frequent surgical procedures • respiratory failure because of distal disease progression.
- 22. Staging assessment sheet for recurrent respiratory papillomatosis. (From Derkay CS, Malis DJ, Zalzal G, et al. A staging system for assessing severity of disease and response to therapy in recurrent respiratory papillomatosis. Laryngoscope 1998
- 23. TREATMENT • At present, there is no “cure” for RRP, and no single modality has consistently been shown to be effective in its eradication.
- 24. TREATMENT – Microlaryngoscopy with cups forceps removal – Microdebrider – CO2 laser – Phono-Microsurgical – KTP/Nd:YAG laser – α-Interferon – Indole-3 – Photodynamic therapy – Acyclovir – Ribavirin – Retinoic acid – Mumps vaccine – Methotrexate – Hsp E7 – Cidofovir -carbinol Surgical Adjuvant The aim of surgical treatment is the removal of papil- lomas and restoration of a safe and patent airway while minimizing trauma to the mucosa and vocal cords.
- 25. CO2 LASER Debrider • voice quality deteriorated with increased usage of the CO2 laser
- 26. CO2 LASER • Most commonly used • It convert light to thermal energy which vaporize water inside the cell for its destruction , and it cauterizes tissue surfaces. • Advantages : precision ,minimal bleeding, no-touch technique, it minimizes damage to the vocal cords and limits scarring • Disadvantage : • safety of the OR personnel, Surgeon , Patient , • hit areas on the patient that are not protected by a wet towel , heating of the endotracheal tube • smoke contain active viral DNA • unacceptable scarring • aggressive use of the laser may also cause injury to tissues that are not affected and can create an environment suitable for implantation of viral particles • delayed local tissue damage
- 27. KTP LASER Can be used through the working channel of a flexible bronchoscope. This laser has also been used to manage vascular ectasia of the glottis 1 2 3 Proponents of the KTP laser favor its use because of its lower cost and the ability to use narrow gauge fibers, which limits some of the mechanical problems present with use of other lasers The KTP laser delivers light absorbed by oxyhemoglobin
- 29. MICRODEBRIDER • have good disease clearance, require a shorter procedure and experience less post- operative pain • In a small, randomized study, Pasquale and colleagues79 observed improved voice quality, less OR time, less mucosal injury, and a cost benefit in direct comparison of the microdebrider and the CO2 laser. • El-Bitar and Zalzal80 and Patel and others81 have observed similar improved outcomes with the use of the endoscopic microdebrider. • A web-based survey of members of the American Society of Pediatric Otolaryngology found the majority of respondents now favoring the use of “shaver” technology.
- 30. COBLATION® • Coblation® is a minimally invasive low-heat technology that delivers a plasma layer to dissolute target tissue while maintaining the integrity of surrounding tissues. The wands (Figure 32.4) are designed to function at tempera- tures as low as 40–70 degrees Celsius (°C), thus minimiz- ing rapid heating, charring or burning. In comparison, commonly used bipolar devices function at temperatures of approximately 400°C. There are very limited data on the use of Coblation® for JORRP, with most of the litera- ture being case reports or retrospective results on small number of patients.30, 31 A recent cross- sectional study in the United Kingdom showed that Coblation® procedures accounted for 3% of interventional treatment conducted in the UK RRP population.32
- 31. INTERFERON • Interferon is one of the initial and formerly the most common adjuvant therapy for treatment of RRP. • enzymes that are produced block the viral replication of RNA and DNA and alter cell membranes to make them less susceptible to viral penetration. • A more recent survey of pediatric otolaryngologists documented its current use to be less than 4%. This decrease is due to high side-effects & emergence of cidofovir. • recently been taken off the market and replaced by peginterferon alfa-2a (Pegasys, Roche), which has a better safety product less side effects simpler dosing regimen
- 32. CIDOFOVIR • intralesional injection of cidofovir, • Based on animal studies that demonstrated a high level of carcinogenicity, and based on case reports of progressive dysplasia in patients with RRP, • cidofovir is recommended in • patients who require more than six surgeries per year or have extrala- ryngeal spread.
- 33. • Indole-3-carbinol (I-3-C) • Mumps vaccine • Retinoids • Photodynamic therapy • Celecoxib • Antire ux Therapy • Bevacizumab • Human Papillomavirus Therapeutic Vaccines
- 34. VACCINES • Cervarix® is bivalent vaccine against HPV 16 and 18. • Gardasil® is a quadrivalent vaccine against HPV 6, 11, 16 and 18 • three intra- muscular injections: the initial dose, 2 months later, and nally 6 months after the initial injection • 9 years old, prior to them becoming sexually active • Universal vaccination with the quadrivalent vaccine also holds promise to eliminate the maternal and paternal reservoir of HPV and to lead to a near eradication of RRP caused by HPVs 6 and 11.