Long-term results of surgical treatment for recurrent respiratory papillomatosis

CONCLUSIONS: The presented results add further support to the observation that laser microsurgery is the preferential surgical treatment for recurrent respiratory papillomatosis (RRP). A meticulous follow-up for early recognition of local recurrence and malignant transformation is recommended. OBJECTIVES: Endoscopic microsurgery continues to be the treatment of choice for RRP. The aim of this study was to evaluate the outcome of patients treated surgically. We focused on demographic data, recurrence rates, and treatment-related complications. PATIENTS AND METHODS: The charts of 194 patients treated at our institution between 1963 and 1993 were analyzed retrospectively. RESULTS: In all, 64 patients (33%) underwent a total of 137 operations using the CO2 laser; 130 patients (67%) underwent a total of 565 microlaryngeal operations by surgery with cold instruments. Five percent of the patients treated with conventional microlaryngeal surgery and none of the patients treated with laser surgery required tracheostomy (p<0.05). Postoperative glottic webs and scar formations were found in 6% of all patients after laser surgery and 20% after conventional surgery (p<0.05). The different methods of treatment did not affect the rate of recurrence (p=0.61) Malignant transformation or secondary airway carcinoma were observed in 4% of all patients.     

Long-term results of surgical treatment for recurrent respiratory papillomatosis

Conclusions. The presented results add further support to the observation that laser microsurgery is the preferential surgical treatment for recurrent respiratory papillomatosis (RRP). A meticulous follow-up for early recognition of local recurrence and malignant transformation is recommended. Objectives. Endoscopic microsurgery continues to be the treatment of choice for RRP. The aim of this study was to evaluate the outcome of patients treated surgically. We focused on demographic data, recurrence rates, and treatment-related complications. Patients and methods. The charts of 194 patients treated at our institution between 1963 and 1993 were analyzed retrospectively. Results. In all, 64 patients (33%) underwent a total of 137 operations using the CO₂ laser; 130 patients (67%) underwent a total of 565 microlaryngeal operations by surgery with cold instruments. Five percent of the patients treated with conventional microlaryngeal surgery and none of the patients treated with laser surgery required tracheostomy (p<0.05). Postoperative glottic webs and scar formations were found in 6% of all patients after laser surgery and 20% after conventional surgery (p<0.05). The different methods of treatment did not affect the rate of recurrence (p=0.61) Malignant transformation or secondary airway carcinoma were observed in 4% of all patients.     

Intralesional cidofovir for pediatric recurrent respiratory papillomatosis

OBJECTIVE: To compare disease response among children with recurrent respiratory papillomatosis (RRP) who underwent combined surgical debulking and intralesional cidofovir injections vs repeated surgical debulking only. DESIGN: Retrospective medical record review; follow-up range: 16 to 56 months. SETTING: Tertiary care children's hospital. PATIENTS: Seven children with RRP, including 4 subjects treated with cidofovir and 3 controls matched for age and initial papilloma staging score. INTERVENTIONS: Subjects treated with cidofovir underwent combined surgical debulking and intralesional cidofovir injection every 2 months until disease remission. Control subjects underwent repeated surgical debulking at individually determined intervals. MAIN OUTCOME MEASURES: Intraoperative endoscopic photographs were retrospectively assigned papilloma staging scores. Cidofovir and control group comparisons were made using nonparametric 2-sample Wilcoxon rank-sum (Mann-Whitney) testing, and comparisons of initial and final papilloma staging scores were made using nonparametric matched-pair Wilcoxon signed-rank testing. RESULTS: The final cidofovir group scores were significantly lower than the control group scores (P < .05). Within-group differences between initial and final scores were not significant (cidofovir group, P = .07; control group, P = .29). CONCLUSIONS: Four children with RRP were safely and successfully treated with intralesional cidofovir injection. Consideration should be given to using cidofovir more widely for treatment of pediatric RRP. Larger numbers in the cidofovir and control groups are needed in future studies to determine the true impact of cidofovir on management of this disease.     

Cimetidine treatment for recurrent respiratory papillomatosis

Effective adjuvant treatment for recurrent respiratory papillomatosis (RRP) is at present limited to alpha-interferon, which may have significant side effects including rebound growth of papillomata following its withdrawal, is given by injection and is expensive. High dose cimetidine is known to have immunomodulatory side effects and has been reported as a useful treatment for cutaneous warts. We report a case of very advanced RRP with tracheo-bronchial-pulmonary involvement treated with adjuvant cimetidine at a dose of 40 mg/kg for 4 months. The patient enjoyed a remarkable improvement in her clinical condition following treatment. The literature regarding cimetidine treatment for cutaneous warts is reviewed.     

复发性呼吸道乳头状瘤治疗新进展

复发性呼吸道乳头状瘤（recurrent respiratory papillomatosis，RRP）是由人乳头状瘤病毒（human papillomavirus，HPV）引起的气道结节性良性上皮肿瘤，病毒传播及发病机制仍不清楚。临床症状及体征存在个体差异。当病变波及下呼吸道时，患者的死亡率明显上升，故此病具有潜在的致命性。目前尚无理想的治愈方法，现有的治疗方案均以减轻症状为主，手术仍是目前最为主要的治疗方式。近年来尝试的联合治疗方法包括干扰素、维甲酸、吲哚三甲醇、光动力学疗法等，但没有一种治疗方法被证明是完全可靠的。目前认为较为有效和有前景的治疗呼吸道复发性喉乳头状瘤的方法是手术联合局部注射抗病毒新药西多福韦。     

Topical measles-mumps-rubella vaccine in the treatment of recurrent respiratory papillomatosis: results of a preliminary randomized, controlled trial

We conducted a study to test the hypothesis that the measles-mumps-rubella (MMR) vaccine can either prevent further recurrences of recurrent respiratory papillomatosis (RRP) or prolong its remission. Our study population was made up of 26 children with RRP. All patients underwent surgical excision of their lesions. After the lesions were removed, half of these patients were prospectively randomized to receive a topical coating of the MMR vaccine on the site of their excised lesion (intervention group); the other half were treated with excision alone (control group). The patients in the intervention group experienced a longer period of recurrence-free remission than did those in the control group (median: 160 and 133 days, respectively), but the difference was not statistically significant. Therefore, it appears that topical MMR vaccine as an adjunct to routine surgical management may not be beneficial in preventing or slowing the return of RRP. However, we believe that further studies with larger patient populations are warranted.     

儿童复发性呼吸道乳头状瘤的外科治疗

目的探讨儿童复发性呼吸道乳头状瘤病的外科治疗方法及手术并发症的预防对策。方法回顾性分析1993年5月到2006年3月56例儿童复发性呼吸道乳头状瘤病的临床资料，采用支撑喉镜喉显微外科手术，手术方式包括喉钳直接切除、喉钳咬除配合激光手术、电动吸割配合激光手术，其中8例行气管切开术。结果平均手术间歇期6．5月，4岁前平均手术间期3．2月，4岁后平均手术间期7．8月；随访3年以上未复发23例，失随访9例，22例仍在继续治疗中，死亡2例，包括术中窒息死亡1例，心肺功能衰竭死亡1例，短暂窒息8例，远期喉狭窄6例，喉气管狭窄3例。结论外科干预是目前治疗儿童复发性呼吸道乳头状瘤病最有效的方法，应用喉显微外科手术，配合电动吸割系统及激光手术，能有效减少手术创伤，延长手术间期，降低近、远期并发症。     

Long-term follow-up of pediatric recurrent respiratory papillomatosis managed with intralesional cidofovir

OBJECTIVE: Cidofovir is an acyclic nucleotide phosphonate antiviral medication that has been used intralesionally for the treatment of severe respiratory papillomatosis (RRP) in pediatric patients. The long-term efficacy of this medication was assessed in 11 children with severe RRP who previously required operative debulking every 2 to 6 weeks to maintain airway patency. STUDY DESIGN: Clinical case series. RESULTS: Ten of these children have completed therapy. Five are disease free over a mean follow-up period of 51.6 months. Five other patients with active RRP decreased their mean severity scores from 17.8 (range 11-26) to 4.0 (range 2-6) and no longer require cidofovir. One patient continues to receive cidofovir for recurrent disease after an initial favorable response. Throughout the 6-year observational period, no patients demonstrated any adverse effects, laboratory abnormalities, or evidence of carcinogenesis. CONCLUSION: Intralesional cidofovir is a useful adjunct for managing children with tenuous airways caused by previously uncontrolled papilloma.     

Surgical treatment and adjuvant therapies of recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis or recurrent laryngeal papillomatosis is a disease of the larynx caused by human papilloma virus, characterized by verrucous epithelial lesions and usually recurring. In the literature there are several types of treatment, such as surgery to cold, laser and/or use of microdebrider, as of adjuvant therapies; all possible to decrease the permanent sequelae of the disease.ObjectiveTo review the literature regarding this disease with emphasis on surgical techniques and adjuvant therapies used today.MethodWe used the literature review, through surveys based electronic data in the public domain, to search for articles between 1992-2012, using keywords: papilloma, human pappiloma virus infection, larynx, therapeutic, papilloma virus vaccine.ResultsWe surveyed 357 articles, of which 49 were used as the basis for this review. Scientific studies indicate a reduction of relapse in most adjuvant therapeutic presented. However, the survey showed different methodologies and samples, which did not allow to compare the types of treatment and adjuvant therapies.ConclusionThe choice of surgical technique varies among studies, but there is a trend to use the microdebrider. The newer adjuvant therapies, such as cidofovir, quadrivalent vaccine against human papilloma virus and bevacizumab, require further studies.     

Pathogenesis and treatment of juvenile onset recurrent respiratory papillomatosis

Juvenile onset recurrent respiratory papillomatosis is the most common cause of laryngeal tumors in children. This disease is caused by infection of the human papillomavirus, a virus whose complete genetic structure is now known. New, more directed agents show promise for improved control of papillomatosis in preliminary studies. Concurrently, there is an increasing awareness of methods to reduce surgical morbidity. At present, the role of preventive efforts including elective caesarian section remains uncertain.     

Effectiveness of cidofovir intralesional treatment in recurrent respiratory papillomatosis

To present the results of recurrent respiratory papillomatosis (RRP) treatment with surgical excision and adjuvant anti-viral cidofovir intralesional use and to examine the correlation between the cidofovir effectiveness and the patient previous history of multiple larynx procedures, age, extension of lesion and dose. 32 patients with laryngeal papillomas were treated with cidofovir in our Department between I.2009 and I.2011. The number of previous RRP debulking procedures ranged from 1 to 100. The intensity of papillomatosis differed from one anatomic site and moderate growth to four or five localizations with heavy extension. The number of injections per patient varied from 1 to 7, and the total volume of 5 mg/ml solution varied from 2 to 33 ml. The injections were combined with laser debulking of the lesions. In disperse papillomata, the injections were administered in particular anatomical sites in 4–6 weeks intervals, in massive lesions injections were repeated in the same anatomical site in 2–4 weeks. Complete remission was observed in 18 out of 32 patients. 13 patients showed remission in a place of cidofovir injection. One patient did not react to the drug. In four patients, new changes in injection places appeared. In two patients, hepatic toxic side effects were observed. Intralesional cidofovir injection has been shown to be an effective and safe therapy for laryngeal papillomatosis and should be considered in those patients who experienced disease relapse.     

儿童复发性呼吸道乳头状瘤病的联合治疗

目的：探讨儿童复发性呼吸道乳头状瘤病（JO-RRP）的治疗方法。方法：回顾性分析36例JO-RRP患儿的临床资料，针对病情分别采用支撑喉镜下激光切除术（27例）和喉裂开造口激光切除术（9例），对复发≥2次／年或（和）病变范围累及≥2个解剖亚区的28例患儿术后1周给予干扰素治疗。结果：全部患儿术后均无明显误咽，28例（77．8％）已拔除气管套管。并发症包括：声音嘶哑8例，喉狭窄6例，肺部感染3例。结论：支撑喉镜下激光切除术和喉裂开造口激光切除术是治疗JO-RRP的有效术式，术后联合干扰素治疗可抑制复发。     

3.5-Year follow-up of intralesional cidofovir protocol for pediatric recurrent respiratory papillomatosis

OBJECTIVES: Intralesional injection of cidofovir has been described as an adjunctive treatment for pediatric recurrent respiratory papillomatosis (RRP). However, questions remain regarding the optimal dosing schedule and side-effect profile. The objective of this study was to describe patient outcomes following a standardized cidofovir protocol. METHODS: Eleven pediatric patients originally treated with a standardized stepped-dose protocol of intralesional cidofovir for RRP were followed for an extended observational period. Additional interventions, disease severity, and adverse outcomes were recorded. RESULTS: Five of 11 patients have required no further treatments following the original cidofovir protocol. Two patients initially achieved remission but have subsequently required additional treatment for recurrent disease. Four patients never achieved remission and have undergone multiple additional interventions. Mean follow-up time for all patients from the conclusion of the original study was 30.2 months (10-45). No adverse outcomes were noted. CONCLUSIONS: Intralesional injection of cidofovir may have some potential as an adjunct in the treatment of RRP. Response to cidofovir is unpredictable. Further study of cidofovir is necessary to more clearly define whether the favorable responses observed represent a true treatment effect or simply reflect the natural history of the disease. Perhaps as important is to refine treatment protocols and informed consents that reflect the concern about the carcinogenic potential of cidofovir and to better characterize the drug's side-effect profile.     

Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis

Recurrent respiratory papillomatosis (RRP) is a chronic and difficult to treat disease of the larynx. In 1998, the first article was published that described the use of the antiviral substance cidofovir to treat this disease. Although the results are promising, there remains some concern about the potential carcinogenicity of cidofovir. There is a demand for a qualitative review of the side-effects of this medicine. In this review, the side-effects of cidofovir are investigated. Special attention was given to the potential carcinogenicity of cidofovir. For this review a search is performed in PubMed and EMBASE for relevant articles in which the use of intralesional cidofovir for patients with RRP is described. Eventually, 31 articles could be included for this review. In these articles a total of 188 patients with RRP were described who underwent therapy with intralesional cidofovir. Five of these patients have developed dysplasia of the larynx during the treatment with cidofovir. This is a percentage of 2.7. This percentage is concurrent with the incidence of spontaneous malignant degeneration of RRP (2-3%). Based on this review, it can be concluded that the use of intralesional cidofovir does not increase the risk of laryngeal dysplasia. Apart from the articles that describe the intralesional administration of cidofovir, some articles have been published in which the use of intravenous cidofovir is described as a therapy for RRP. Therefore, a summary is given on the side-effects of intralesional cidofovir as well as a summary on the reported side-effects of the intravenous administration of cidofovir. Based on the outcomes of this review, recommendations are given for a safe use of cidofovir for treatment of recurrent respiratory papillomatosis in the future.