Clinical trial of photodynamic therapy with meso-tetra (hydroxyphenyl) chlorin for respiratory papillomatosis.
ABSTRACT To determine the efficacy of photodynamic therapy (PDT) with meso-tetra (hydroxyphenyl) chlorin (m-THPC) photosensitizer for recurrent respiratory papillomatosis.
Parallel-arm, randomized trial of patients requiring surgery at least 3 times yearly with single PDT 6 or 18 months after enrollment and 12-month follow-up. Disease extent was scored and papillomas were removed during direct endoscopy every 3 months after enrollment.
Tertiary medical centers.
Of 23 patients aged 4 to 60 years enrolled in the study, 15 patients, plus 2 in the late group without PDT owing to airway risk, completed the study. Six patients withdrew voluntarily after PDT.
Intravenous administration of m-THPC 6 days before direct endoscopic PDT with 80 to 100 J of light for adults and 60 to 80 J for children.
Difference in severity scores between the early and late groups and between pre- and post-PDT scores for all patients. Secondary measures were the associations between baseline characteristics and response and changes in immune response and the prevalence of latent viral DNA.
There were significant differences between groups, with marked improvement in laryngeal disease across time after PDT (P = .006). Five of 15 patients were in remission 12 to 15 months after treatment, but there was recurrence of disease after 3 to 5 years. Tracheal disease was not responsive to PDT. No change occurred in the prevalence of latent human papillomavirus DNA. The immune response to virus improved with clinical response.
Use of m-THPC PDT reduces the severity of laryngeal papillomas, possibly through an improved immune response. Failure to maintain remission with time suggests that this is not an optimal treatment.
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ABSTRACT: Recurrent respiratory papillomatosis (RRP), characterized by the recurrent growth of benign tumors of the respiratory tract, is caused by infection with human papillomavirus (HPV), predominantly types 6 and 11. Surgical removal of these lesions can be required as frequently as every 3-4 weeks to maintain a patent airway. There is no approved medical treatment for this disease. In this study we have characterized the T(H)2-like chemokine profile (CCL17, CCL18, CCL20, CCL22) in patients with RRP and asked whether it was modulated in patients who had achieved significant clinical improvement. CCL17, CCL18 and CCL22 mRNAs were increased in papillomas compared to clinically normal laryngeal epithelium of the RRP patients. Overall, CCL20 mRNA expression was not increased, but there was intense, selective CCL20 protein expression in the basal layer of the papillomas. Patients with RRP expressed more CCL17 (p=0.003), CCL18 (p= 0.0003), and CCL22 (p= 0.007) in their plasma than controls. Plasma CCL18 decreased over time in three patients enrolled in a pilot clinical trial of celecoxib and the decrease occurred in conjunction with clinical improvement. There was a significant correlation between sustained clinical remission in additional patients with RRP and reduced levels of CCL17 (p=0.013), CCL22 (p=0.0019) and CCL18 ( p=0.048). Thus, the change in expression of these three plasma T(H)2-like chemokines may, with future studies, prove to serve as a useful biomarker for predicting disease prognosis.Molecular Medicine 09/2012; · 4.47 Impact Factor
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ABSTRACT: To demonstrate the role of oral acyclovir in monthly regimes after microdebrider assisted excision in 3 patients with adult recurrent respiratory papillomatosis (ARRP). Three patients with ARRP who presented to a tertiary referral hospital in stridor were initially treated with a tracheostomy in order to secure airway. On further evaluation by videolaryngoscopy extensive bilateral laryngeal papillomatosis was noted with history of similar conditions in the past for which they were repeatedly operated. They were admitted and underwent Microlaryngeal surgery and laryngeal microdebrider assisted surgery under general anesthesia. Post operatively a course of oral acyclovir at 800 mg/5 times/day for 5 days was administered. On repeat assessment with videolaryngoscopy at monthly intervals a complete remission of the disease was noted with no residual disease at the end of 1 year in 2 cases. One case had a recurrence. Renal parameters were monitored periodically. It may be concluded that the action of anti viral drugs at regular intervals in addition to a short course of oral steroids lead to rapid recovery and prevented latent virus activation within the laryngo tracheal system hence maintaining long term improvement. This can avoid multiple laryngeal surgeries, repeated respiratory emergencies and risk for malignant transformation in the future thereby reducing morbidity and effect on quality of life.Indian Journal of Otolaryngology and Head & Neck Surgery 01/2014; · 0.05 Impact Factor