CASE REPORT |
https://doi.org/10.5005/jp-journals-10003-1386 |
Recurrent Laryngeal Papillomatosis: A Laser CO2 Surgery and Bevacizumab Intralesional Injection as Adjuvant Therapy
1–4Department of Adult and Development Age Human Pathology, University of Messina, Messina, Sicily, Italy
Corresponding Author: Cosimo Galletti, Department of Adult and Development Age Human Pathology, University of Messina, Messina, Sicily, Italy, e-mail: cosimogalletti92@gmail.com
How to cite this article: Galletti C, Bruno G, Ciodaro F, et al. Recurrent Laryngeal Papillomatosis: A Laser CO2 Surgery and Bevacizumab Intralesional Injection as Adjuvant Therapy. Int J Otorhinolaryngol Clin 2021;13(3):126–128.
Source of support: Nil
Conflict of interest: None
ABSTRACT
We present a case of recurrent respiratory papillomatosis (RRP) transformed in a lobular intraepithelial neoplasia LIN 2 vocal fold lesion treated with a microdirect laryngoscope with 10,600-nm laser CO2, in addition, adjuvant therapy is performed which consists of an intralesional bevacizumab injection on surgical site. Adjuvant therapy involves a cycle of four intralesional bevacizumab injections. The RRP is characterized as a long-life condition of the respiratory epithelium caused by the human papilloma virus (HPV), HPV 6 and 11 genotypes in most of all cases. Airway obstruction or voice correlated symptoms are the most common way of presentation, which can be variated from a low–mild form to severe which can represent, in rare cases, a situation that requires prompt treatment. This study aims to evaluate the efficacy and safety of the use of intralesional bevacizumab as adjuvant therapy in the treatment of RRP.
Keywords: Airway obstruction, Bevacizumab, HPV, Laryngology, Laser, Oncology, Surgery
BACKGROUND
Recurrent respiratory papillomatosis (RRP) has a good trophism to the respiratory ciliated mucosa of the larynx, trachea, and, in some cases, bronchi and lung parenchyma. It is a disease with a worldwide distribution and a very large spread of population, adults, and children (juvenile form). It is a rebellious and capricious disease that exposes the patient to numerous therapeutic interventions, surgical and otherwise. Associated comorbidities can pose a serious threat to the patient’s own life, the goals are focused on maintaining airway patency and voice quality.
CASE DESCRIPTION
A 47-year-old woman, a smoker of 10 cigarettes/day, came to our Otorhinolaryngology department referring hoarseness and phonasthenia for the last three years. In 2005 had surgery for a chordal polyp, in 2007, 2010, and in 2014 had surgery for RRP not well precised. The patient was in a follow-up period in another Otorhinolaryngology department of another university hospital. We performed a fiberoptic laryngoscopy examination with a flexible optic showing a mammellonate neoformation on the surface of the right true vocal cord with an invasion of the anterior commissure and the anterior third of the contralateral true vocal cord (Fig. 1).
Fig. 1: Preoperative fiberoptic laryngoscopy examination with a flexible optic showing a mamillated neoformation on the surface of the right true vocal cord with an invasion of the anterior commissure and the anterior third of the contralateral true vocal cord
Laryngoscopic examination with a 0°, 30°, and 45° rigid endoscopic detected the presence of a mammellonate neoformation in the whole of the right true vocal cord until it touches the anterior commissure and the anterior third of the left true vocal cord. Anterior subcommissural encroachment is suspected. A bicordal normomotility and a reduced respiratory glottic space are also highlighted. Derkay staging system anatomical score marks 12(3-2-2-3-2). The patient marks a voice handicap index (VHI) score of 75 on 120, a serious handicap impairment.
TREATMENT
We decided to perform a direct microlaryngoscopy CO2 laser with the exeresis of the neoformations that involves both vocal folds and the anterior commissure, at the same time a vaporization CO2 laser of the free margins of both vocal folds is done. The histopathological diagnosis was squamous papilloma with lobular intraepithelial neoplasia LIN 2, the genotype with reverse line Biot identifying were the 6 and the 66 genotypes.
After ethical committee consent and patient approval, we decided to perform a cycle of four intrachordal bevacizumab infiltrates using a laryngeal needle to inject a 7.5–12.5 mg (0.3–0.5 mL) into the areas affected (Fig. 2).
Fig. 2: Fiberoptic laryngoscopy examination with a flexible optic after the second injection of bevacizumab. The vocal fold epithelium appears intact and normotrophic with a small anterior synechia and a presence of a little chordal polyp on the right vocal fold
The patient is discharged with a precise therapeutic protocol, based on a 40-mg tablet of esomeprazole before breakfast for 30 days, and chondroitin sulfate, hyaluronic acid, and aluminum hydroxide oral stick after main meals up to the first follow-up visit, antibiotic therapy with 500-mg tablet of azithromycin for three days, and 700-mg tablet of bromelain for 30 days. The patient underwent a cycle of other four bevacizumab injections 3 weeks apart. The goal is to eradicate the RRP. After every bevacizumab injection, two control visits with fiberoptic laryngoscopy are established: the first on the day after the injection, and the other two on 14 days after the other.
OUTCOME AND FOLLOW-UP
The last follow-up visits performed showed complete eradication of papillomatosis: the vocal fold epithelium appears intact and normotrophic with a small anterior synechia (Fig. 3). To evaluate the motility, we performed a laryngeal stroboscopic examination showing a preserved vocal cords motility. Her VHI registered marks 10 on 120, low handicap impairment score.
Fig. 3: Fiberoptic laryngoscopy examination with a flexible optic on the last follow-up visit. The vocal fold epithelium seems intact and normotrophic with a small anterior synechia
Given the good outcomes of the treatment after the last injection cycle, it was decided to schedule a control visit with fiberoptic laryngoscopy at the sixth month to evaluate the outcome of the therapeutic strategy adopted.
DISCUSSION
RRP is caused by the human papillomavirus, in particular by subtypes 6 and 11, is one of the most frequent diseases of the respiratory tract in children and adults in the United States. It has been estimated that his frequency is around 4.3 for every 100 000 children and 1.8 for every 100 000 adults, and it has been evidenced how the human papilloma virus is one of the most important risk factors associated with dysphonia and dyspnea. The literature shows how RRP is a very capricious and rebellious disease due to its characteristic to reappear due to its index of cellular proliferation. The viral genome remains in the cellularity of tissues infected, this is the cause behind the recurrences of RRP. Mostly, due to an unpredictable course of the disease, RRP would need many surgeries to preserve airways permeability.1–4
Many surgical approaches are supported by the literature to restore the permeability of the upper airways. Nevertheless, there is no definitive cure. The goal of all surgical approaches must be the preservation of the anatomic structure of the larynx and at the same time maintenance of vocal function and the permeability of upper airways. The microdirect laryngoscope or endoscopic laryngoscopy with the implication of laser, microdebrider, and cold instruments are the most common surgical approaches implicated in the treatment of RRP. We can apply different types of laser, including laser CO2, KTP, and pulse dye.5–8
Due to his important tendency to recurrences, adjuvant therapy is often offered to the patient with RRP. It is estimated that 20% of patients need adjuvant therapy associated to control the advance of RRP. Actually, in the literature, we can count on many drugs implicated in the treatment of RRP such as Gardasil (Merck and Co, Inc., Whitehouse Station, NJ, USA), cidofovir (Vistide, Gilead Sciences, Inc. Foster City, CA, USA), bevacizumab (Avastin; Genentech/Roche, San Francisco, CA, USA), mumps vaccine, cimetidine, ribavirin, photodynamic therapy, aciclovir, propranolol, and indol-3-carbinol. The main goal of adjuvant therapy is to control disease course. The efficacy of the adjuvant therapy remains uncertain, due to the unpredictability of the tendency of the RRP in each patient.9–14
In the last years a great progress in the management of RRP occurred. Cidofovir is the most studied intralesional adjuvant therapy, in addition bevacizumab has recently been documented. Zeitels et al. showed how bevacizumab, an antiangiogenic agent, decrease the volume of the disease when it is used with the KTP laser, with a reduction in recurrency in 90% of treated patients.15–19
In consideration of the unpredictability of RRP, the prognosis and possible surgical interventions, the primary therapeutic objective of this study was to show us how a combined approach, laser surgery and the adjuvant therapy with intralesional bevacizumab reduces or eliminates the need for recurrent surgeries. We also consider as efficacy parameter the remission and recurrence rate, surgical interval free from disease and Derkay scores elevated before and after the therapeutic approach. The VHI is a responsible form for observe voice-related quality of life in patients with laryngeal papillomatosis and correlates with the severity of the disease in the larynx.20–21
In our case report, treatment with intralesional bevacizumab seems to be safe and that pharmacologic antiangiogenesis is successful in treating RRP and that it seems to be relatively secure locally and systemically. It is clear that a larger patient cohorts and multi-institutional studies are needed.
REFERENCES
1. Ballestas SA, Shelly S, Soriano RM, et al. Trends in recurrent Respiratory Papillomatosis Treatment. Acta Otorrinolaringol Esp (Engl Ed) 2021;72(2):109–120. English, Spanish. DOI: 10.1016/j.otorri.2019.11.001. Epub 2020.
2. Derkay CS, Bluher AE. Update on Recurrent Respiratory Papillomatosis. Otolaryngol Clin North Am 2019;52(4):669–679. DOI: 10.1016/j.otc.2019.03.011. Epub 2019.
3. Carifi M, Napolitano D, Morandi M, et al. Recurrent Respiratory Papillomatosis: Current and Future Perspectives. Ther Clin Risk Manag 2015;1:731–738. DOI: 10.2147/TCRM.S81825.
4. Sakakura A, Yamamoto Y, Takasaki T, et al. Recurrent Laryngeal Papillomatosis Developing Into Laryngeal Carcinoma with Human Papilloma Virus (HPV) Type 18: A Case Report. J Laryngol Otol 1996;110(1):75–77. DOI: 10.1017/s0022215100132773.
5. Ivancic R, Iqbal H, deSilva B, et al. Current and Future Management of Recurrent Respiratory Papillomatosis. Laryngoscope Investig Otolaryngol 2018 14;3(1):22–34. DOI: 10.1002/lio2.132.
6. Robbins KT, Woodson GE. Current Concepts in the Management of Laryngeal Papillomatosis. Head Neck Surg 1984;6(4):861–866. DOI: 10.1002/hed.2890060410.
7. Avelino MA, Zaiden TC, Gomes RO. Surgical Treatment and Adjuvant Therapies of Recurrent Respiratory Papillomatosis. Braz J Otorhinolaryngol 2013;79(5):636–642. English, Portuguese. DOI: 10.5935/1808-8694.20130114.
8. Louw L, Claassen A. HPV-Induced Recurrent Laryngeal Papillomatosis: Rationale for Adjuvant Fatty Acid Therapy. Asia Pac J Clin Nutr 2008;17(2):187–193. PMID: 18586635.
9. Fernandez-Bussy S, Labarca G, Vial MR, et al. Recurrent Respiratory Papillomatosis and Bevacizumab Treatment. Am J Respir Crit Care Med 2018;197(4):539–541. DOI: 10.1164/rccm.201702-0279LE.
10. Hermann JS, Pontes P, Weckx LL, et al. Laryngeal Sequelaeof Recurrent Respiratory Papillomatosis Surgery in Children. Rev Assoc Med Bras (1992) 2012;58(2):204–208. PMID: 22569615.
11. Gazia F, Galletti B, Freni F, et al. Use of Intralesional Cidofovir in the Recurrent Respiratory Papillomatosis: A Review of the Literature. Eur Rev Med Pharmacol Sci 2020;24(2):956–962. DOI: 10.26355/eurrev_202001_20081.
12. Wierzbicka M, Jackowska J, Bartochowska A, et al. Effectiveness of Cidofovir Intralesional Treatment in Recurrent Respiratory Papillomatosis. Eur Arch Otorhinolaryngol 2011;268(9):1305–1311. DOI: 10.1007/s00405-011-1599-6. Epub 2011.
13. Naiman AN, Ayari S, Nicollas R, et al. Intermediate-term and Long-Term Results After Treatment by Cidofovir and Excision in Juvenile Laryngeal Papillomatosis. Ann Otol Rhinol Laryngol 2006;115(9):667–672. DOI: 10.1177/000348940611500903.
14. Graupp M, Gugatschka M, Kiesler K, et al. Experience of 11 Years Use of Cidofovir in Recurrent Respiratory Papillomatosis. Eur Arch Otorhinolaryngol 2013;270(2):641–646. DOI: 10.1007/s00405-012-2221-2. Epub 2012. Erratum in: Eur Arch Otorhinolaryngol 2013;270(10)2785. PMID: 23070260.
15. Pudszuhn A, Welzel C, Bloching M, et al. Intralesional Cidofovir Application in Recurrent Laryngeal Papillomatosis. Eur Arch Otorhinolaryngol 2007;264(1):63–70. DOI: 10.1007/s00405-006-0151-6. Epub 2006.
16. Zeitels SM, Barbu AM, Landau-Zemer T, et al. Local Injection of Bevacizumab (Avastin) and Angiolytic KTP Laser Treatment of Recurrent Respiratory Papillomatosis of the Vocal Folds: A Prospective Study. Ann Otol Rhinol Laryngol 2011;120(10):627–634. DOI: 10.1177/000348941112001001.
17. Goyal A, Kapoor D, Saha R. Systemic and Intralesional Bevacizumab in Juvenile Onset Recurrent Respiratory Papillomatosis: A Report of Two Cases. Indian J Otolaryngol Head Neck Surg 2021:1–4. DOI: 10.1007/s12070-021-02814-3.
18. Rogers DJ, Ojha S, Maurer R, et al. Use of Adjuvant Intralesional Bevacizumab for Aggressive Respiratory Papillomatosis in Children. JAMA Otolaryngol Head Neck Surg 2013;139(5):496–501. DOI: 10.1001/jamaoto.2013.1810.
19. Maturo S, Hartnick CJ. Use of 532-nm Pulsed Potassium Titanyl Phosphate Laser and Adjuvant Intralesional Bevacizumab for Aggressive Respiratory Papillomatosis in Children: Initial Experience. Arch Otolaryngol Head Neck Surg 2010;136(6):561–565. DOI: 10.1001/archoto.2010.81.
20. Kupfer RA, Çadalli Tatar E, Barry JO, et al. Anatomic Derkay Score Is Associated with Voice Handicap in Laryngeal Papillomatosis in Adults. Otolaryngol Head Neck Surg 2016;154(4):689–692. DOI: 10.1177/0194599816628871. Epub 2016.
21. Loizou C, Laurell G, Lindquist D, et al. Voice and Quality of Life in Patients with Recurrent Respiratory Papillomatosis in a Northern Sweden Cohort. Acta Otolaryngol 2014;134(4):401–406. DOI: 10.3109/00016489.2013.867457. Epub 2014.
________________________
© The Author(s). 2021 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.