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Laryngeal papillomatosis

Laryngeal papillomatosis is a rare medical condition, caused by an HPV infection of the throat. It causes assorted tumors, papillomas, to develop over a period of time. This condition obstructs the airway, and without treatment, it is potentially fatal.

Treatment

  • Traditional surgery to remove affected tissue.
  • Carbon dioxide laser surgery: "no touch" removal of affected tissue.
  • Tracheotomy: rereouting of air around the affected area.
  • Photodynamic therapy: controls tumors by using targeted dyes to irradiate any cancerous tissue.
  • Chemotherapy
  • Antibiotics
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POWERED MICRODEBRIDEMENT TREATMENT FOR RECURRENT RESPIRATORY PAPILLOMATOSIS
From Australian Journal of Oto-Laryngology, 12/1/03 by O'Neill, John

Laryngeal papillomatosis is a benign disease of the larynx caused by human papilloma virus. The disease has a variable clinical course and treatment focuses on debridement until clinical remission. The most common technique for removing the papilloma is by carbon dioxide laser ablation. Powered microdebridement, which is more familiar to endoscopic sinus surgeons, has been adapted for use in the larynx. We would like to report on this technique for removal of respiratory papillomas that we believe to be safer for both patients and staff. The cases of seven paediatric patients with recurrent respiratory papillomatosis treated with microdebridement of their papillomas have been retrospectively reviewed.

Key words: Laryngeal papillomatosis, Papilloma, Human papilloma virus, laryngeal shaver.

Introduction

Laryngeal papillomas are the most common benign laryngeal growths in children. The condition is due to human papilloma virus (HPV) infection of the laryngeal mucosa. There are many subtypes of HPV with the most common in recurrent respiratory papillomatosis being 6 and 11. The most common presentation is altered voice quality in a three to seven year old. Patients however may present earlier or later with airway compromise1. (Figure 1)

Current treatment is removal the lesions to maintain an adequate safe airway. This involves repeated examinations over varying time periods depending on the severity of the papillomas. Carbon dioxide vaporization is the current standard technique used in most paediatric centres. This has been shown in many articles to be an excellent means of removing papillomatous lesions2. There is the require-ment for specialised theatres and anaesthetic equipment to perform these operations and sometimes, anatomical limitations may restrict removal of some papillomas2,3. Laryngeal complications are not uncommon with treatment and can in themselves compromise the airway.4

We would like to report on our experience in removing papillomas with the Xomed Laryngeal shaver. We feel it leads to less scar tissue formation and is simpler and safer for both patient and staff.

Method

This is a retrospective case note review of a cohort of seven patients treated at our department between January 2000 and December 2002. The Mater Childrens Hospital is a tertiary paediatric hospital that services Southern Queensland and Northern NSW.

From the case notes, we obtained demographic data of the patients in the study group. We recorded treatment prior to attendance at our institute. The anatomic extent of papillomatosis prior to each treatment was ascertained, together with the number of treatments and the duration between each treatment. Adverse outcomes were assessed and recorded.

Operative technique

The patient is intubated and anaesthetized using spontaneous respiration. An endotracheal tube appropriate for the patient is inserted. The patient is positioned with shoulder elevation and small head ring to place the neck in extension and head slightly flexed. The patient is draped and suspension laryngoscopy is performed using a paediatric Lindholm laryngoscope. A zero degree telescope is then attached to a camera system to evaluate the larynx. Neurosurgical patties soaked in 1:10000 adrenalin solution are then applied to the surfaces of papilloma to undergo removal for approximately 2 mins.

The Xomed Straightshot laryngeal skimming blade is used to remove papillomas using gentle suction. (Figures 2, 3) This suction is attached to a high flow/ low-pressure unit and adjusted so when applied to normal laryngeal mucosa there is limited tissue removal. The suction is probably one of the most critical steps to avoid tissue injury. Following laryngeal papilloma debridement, the endotracheal tube is replaced by a nasopharyngeal airway, with the patient spontaneously breathing volatile agents. Improved access to the subglottis and posterior larynx allows papillomata debridement from these areas. Aspiration of blood is extremely uncommon as the suction device causes minimal bleeding. If there is any concern over maintenance of ventilation, an endotracheal tube is place by the surgeon via the laryngoscope. Intermittent removal of the endotrachea) tube is performed to allow clearance of papillomata.

At the end of the procedure the patient is woken, observed for 2 hours in recovery and then discharged. If there are complicating medical problems or this is the first time the patient has undergone the procedure they are admitted overnight usually to the paediatric ENT ward.

Results (table1)

Seven patients (five male, two female) have been treated for laryngeal papillomatosis using a microbrider technique. The age of diagnosis ranged from one to ten years.

All but one patient had undergone prior treatment before we commenced debridement for papillomas. Three patients had undergone greater than 20 procedures. Most prior treatments consisted of laser debridement. Two patients are currently undergoing adjuvant treatment with cidofovir.

The average time of each procedure was similar despite the condition of their larynx, ranging from 12 to 28 minutes. The number of treatments for each individual in our series ranges from 4 to 10.

The severity of the condition was determined by the timing of repeat intervention. Most patients have improved. Three are currently free of disease.

Other laryngeal lesions evident in this cohort of patients include two patients with small anterior webs with one of these patients also having some early posterior glottic webbing. Both these patients were noted to have these lesions at the first endoscopy at our institution.

Discussion

Laryngeal papillomatosis is the most common benign neoplastic condition affecting the paediatric larynx. It is due to infection of the laryngeal mucosa by human papilloma virus subtypes 6 and 11. Presentation is usually with hoarse voice or rarely airway compromise. There are two peaks in presentation, one in the 3-7 year old age and one in the 20's. The transmission of both is thought to be from the female genital tract although the exact process is only theoretical1,2,5. The risk of transmission via vaginal delivery of mothers with known genital warts is around 1:400(6,5).

The human papilloma virus is a DNA virus, which on infecting the cell incorporates its DNA into the host's nuclear material and allows production of viral DNA. Pathology of these lesions is typically that of other papillomatous lesions throughout the body. They are composed of benign proliferative squamous cells with fibrovascular cores. If these lesions are subtyped they commonly contain HPV 6 and 11 DNA. Other HPV subtypes can affect the larynx and are thought to be involved in the formation of some malignant laryngeal lesions1,2.

The natural history of recurrent respiratory papillomatosis is variable1,2. Most patients require treatment for some time then the condition tends to settle. Other patients may require tracheostomy to maintain an airway. The condition can disseminate throughout the respiratory tract and lead to pulmonary papillomatosis. Human papilloma virus infection of the larynx may predispose epithelium to malignant transformation, as seen in cases of cervical papillomatosis7. Viral proteins have been shown to bind and then alter the function of tumour suppressor genes p53 and Rb gene.8 The more aggressive papilloma subtypes have demonstrated higher binding affinity to these proteins than other subtypes7. Although an individual's prognosis cannot be predicted, it has been shown that diagnosis before 3 years has a more aggressive course2,9. In our small series the most aggressive diseases tended to be those who were diagnosed before 3 years.

There is no uniform staging system for recurrent respiratory papillomatosis at present. Derkay et al (1998) has developed a staging system which is being used in North America that incorporates anatomical information as well as clinical information with regards to laryngeal function9. This staging has not formally been introduced into our series as information on laryngeal function has not been reliably recorded. We feel the frequency of treatments corresponds to the disease state. The less time between treatments means the disease is more active and consideration towards adjuvant or more aggressive airway management needs to be considered. Our most severe cases were requiring fortnightly to monthly treatments until we began adjuvant treatment. Knowing when to time the treatments comes with experience and common sense. The more uncomfortable you are with the airway means you will repeat the examination sooner.

Current treatment strategies involve removing the papillomatous lesions from the airway on a regular basis until the condition goes into clinical remission. The most popular method for this has been CO2 laser resection3,4. This technique has been demonstrated to be effective in controlling papillomas and limiting damage to normal mucosa4. We have presented another technique for removal of papillomas. This is becoming popular due to ease and effectiveness of removal. It is not a new technique with it being described previously in several papers11,12,13. We agree with these papers that it is safer for patient and staff. Contamination of staff and patient with virus-laden particles that have been identified in laser plume is thought to be extremely unlikely given that the tissue is cut inside the suction tube14,15. Also laser complications can be avoided16.

Operating time for shaver removal is minimal with the average time in our small series being 20 minutes. Most ENT theatres use shavers for endoscopic sinus surgery and besides the blade attachment the rest of the set up is the same. No specialized theatre precautions are required and no compulsory laser safety officers are required. All this adds up to more efficient use of operating theatre time17.

Damage to the voice and scarring in the larynx may be avoided with microdebridement. Fibrosis has been demonstrated in animal vocal cords when treated with laser compared with stripping.18 In our series there are two patients with laryngeal web formation. Both occurred prior to our involvement with them and were due to previous treatments. One patient with a laryngeal web had previously been treated by laryngeal microdebridement. The web is likely a result of excessive removal of the papilloma in the glottic region. Control of the suction is as important as positioning the patient to limit damage and we routinely adjust the level of suction in each case prior to removing papilloma. Staged removal would be best in the severe cases, as they always require repeated treatment.

The use of adjuvant treatments have been tried in an effort to eradicate the disease and need for repeated treatments. These include the use of Indole 3-carbinol, alpha Interferon, acyclovir and more recently cidofovir. These medical therapies are aimed at reducing the viral load and hence induce early remission.

Alpha interferon is historically the most common medical treatment of respiratory papillomatosis. Interferon is naturally produced by lymphocytes in response to viral infection. The therapy aims to use this natural response to the interferon, to activate cellular endonuclease, which degrades viral mRNA. In addition, there is heightened expression of surface antigens and activity of natural killer cells. The interferon is given via subcutaneous, intramuscular or intravenous route. Side effects are common and range from flu like symptoms to liver dysfunction and marrow suppression. Due to these side effects the use of interferon has been reserved for the more severe cases.19 Interferon is effective in a proportion of patients.

Indole 3-carbinol is found in cruceriform vegetables (broccoli, cabbage and Brussels sprouts) and is thought to alter oestrogen balance in tissues, thus increasing viral resistance. Another indole is being made at present to trial but no long-term data for either medication currently exists.20

Specific antiviral therapies have been used in the past. Acyclovir was reported to have worked in some patients but the human papilloma virus lacks thiamine kinase to activate acyclovir. It may have worked because of coinfection with another virus such as herpes.21 Cidofovir is another nucleoside analogue currently approved for systemic use in HIV patients with CMV retinitis. Studies have shown reduction in the number of treatments with this technique.22 It is believed to cause destruction of viral infected cells that do not show papillomatous change and are therefore not usually removed. Nephritis and iritis are rare side effects of systemic use that have not as yet been demonstrated in the limited studies with intralesional use.23

Two patients in our series have undergone treatments with intralesional cidofovir. They were started on treatment because the severity of their disease required almost fortnightly debridement. We can report a marked response to only a few treatments. It would be too early to make further comment on this. (Figure 4)

In summary we have presented a review of our experience with laryngeal shavers in the resection of laryngeal papillomas. It is cost effective, as most units have the equipment for powered sinus surgery and this only requires the addition of a blade. The risk of transmission to staff and seeding the respiratory tract is low due to the suction cutting. The technique allows access to difficult to reach areas that can be a cause of more frequent laser procedures. The technique is safe to the patient. Side effects such as web formation still occur if overzealous removal of papilloma occurs. Several papers support this approach, also emphasizing both the safety and cost effectiveness of this technique" 11,12,13,15, 17.

Further adjuvant treatments should be investigated to minimize airway manipulation.

References

1. Aaltonen LM, Rihkanen H, Vaheri A. Human Papillomaviriis in larynx. Laryngoscope 2002; 112:700-707

2. Derkay C. Recurrent Respiratory Papillomatosis. Laryngoscope 2001; 111:57-69

3. Derkay C. Taskforce on recurrent respiratory papillomalosis. Arch Otolaryngol Head and Neck Surg 1995; 121:1386-1391

4. Ford CN. Advances and refinements in phonosurgery. Laryngoscope 1999; 109: 1891-1900

5. Kashima HK, Shah F Lyles A, et al. A comparison of risk factors in juvenile onset and adult onset respiratory papillomas. Laryngoscope 1992; 102:9

6. Kashima HK, Mounts P, Shah K. Recurrent respiratory papillomatosis. Obstet Gynecol Cin North Am 1996; 23: 699-706

7. Dalstein V. Riethmuller D. Pratet JL. et al. Persistence and load of high-risk HPV are predictors for development of high-grade cervical lesions: A longitudinal French cohort study. International Journal of Cancer. 2003; 106(3):396-403

8. Sclebos RJ, Kessis T.D, Chen A, et al. Functional consequences of directed mutations in human papilloma virus E6 protein: Abrogation of p53 cell cycle arrest correlates with p53 binding and degradation in vitro. Virology 1995; 208:111-120

9. Armstrong LR, Derkay CS, Reeves WC. Initial results from the National Registry for juvenile onset recurrent respiratory papillomalosis. Arch Otolaiyiigol Head Neck Surg, 1999;125:743-748

10. Derkay CS, Malis D, Zalzal G, Wiatrak B, et al. A Staging System for Assessing Severity of Disease and Response to Therapy in Recurrent Respiratory Papillomatosis. Laryngoscope 1998; 108(6):935-937

11. Myer C, Willging J, McMurry S, Cotton R. Use of laryngeal microresector system. Laryngoscope 1999; 109: 1165-1166

12. Patel N, Rowe M and Trunkel D. Powered laryngeal shavers and laryngeal papillomatosis: a preliminary report. Ann Otol Rhinol anil Laryngol. 2003; 112: 7-10

13. Patel R and Mackenzie K. Treatment of recurrent respiratory papillomalosis in children with microdebrider. Clin Otol. 2000; 25: 358-360

14. Kashiina HK, Kcssis T, Mounts P, Shah K. Polymerase chain reaction identification of human papillomavirus DNA in CO2 laser plume from recurrent respiratory papillomatosis. Otolaryngol Head Neck surg. 1991;104:191-195

15. El-Bitar MA, Zalzal G. Powered instrumentation in the treatment of Recurrent Respiratory Papillomatosis: an alternative to carbon dioxide laser. Arch Otolaryngol Head Neck Surg. 2002;128:425-428

16. Salaloff R, Spegiel J, Hawkshaw M and Jones A. Laser surgery of the larynx: The case for caution. Ear Nose Throat J. 1992; 71: 593-5

17. Pasquale K, Wistrunk B, Woolley A. Microdebrider Vs CO2 laser removal of recurrent respiratory papillomas. A prospective analysis. Laryngoscope. 2003; 113(1) 139-143

18. Durkin GE, Duncavage JA, Toohill RJ, et al. Wound healing of true vocal cord squamous epithelium after CO2 laser ablation and cups forceps stripping. Otolaryngol Head Neck Surg. 1986; 95:273-277

19. Leventhal BG, Kashima HK, Mounts P, et al. Long term response of recurrent respiratory papillomatosis to treatment with lymphoblastoid Interferon alfa-N1. N Engl J Med. 1991; 325:613-617

20. Rosen CA, Woodson GE, Thompson JW, et al. Preliminary results of the use of indole 3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998; 118:810-815

21. Pou AM, Rimell FL, Jordan JA, et al. Adult respiratory papillomatosis: Human papillomavirus and viral coinfections as predictors of prognosis. Ann Otol Rhinol Laryngol. 1995; 104:758-762

22. Bielamowicz S, Villagomez, V, Stager S, Wilson W. Intralesional Cidofovir therapy for laryngeal papilloma in an adult cohort. Laryngoscope 2002; 112:696-699

23. Pransky S, Brewster D, Magit A, Kearns D. Clinical update on 10 children treated with intralesional Cidofovir injections for severe recurrent respiratory papillomatosis. Arch Otolaryngol head Neck Surg. 2000; 126:1239-1246

JOHN O'NEILL and ROBERT BLACK

Mater Children's Hospital,

South Brisbane,

Queensland, Australia

Dr John O'Neill MBBS (Qld)

Dr Robert Black MBBS, FRACS, FRCS(Ed), FACS

Associate Professor, University of Queensland

Mater Children's Hospital

South Brisbane

Queensland, Australia

Correspondence to:

Dr John O'Neill

ENT Department

Princess Alexandra Hospital

Ipswich Road, Woolloongabba 4102

Queensland, Australia

Phone: 07 3240 2111

Fax: 07 3240 2502

Email: johnwyn@ozemail.com.au

Copyright Australian Society of Otolaryngology Head & Neck Surgery Ltd. Dec 2003
Provided by ProQuest Information and Learning Company. All rights Reserved

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