Onset Recurrent Respiratory Papillomatosis Research Articles

Gardasil® as adjunctive therapy for respiratory papillomatosis at Red Cross Children’s Hospital, Cape Town

Background: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is an incurable condition caused by human papilloma virus (HPV) types 6 and 11, often requiring repeated surgeries and in severe cases, tracheostomy. This imposes a significant socioeconomic burden on patients and families. Gardasil®, a proven prophylactic HPV vaccine, is emerging as a potential adjuvant therapy. We studied its response on JoRRP patients at our center.Methods: We conducted a retrospective review at Red Cross War Memorial Children’s Hospital from January 2015 to June 2022 on histologically confirmed JoRRP cases. Age at diagnosis, baseline and post-dosing Derkay-Coltrera (DC) scores (disease severity measure), inter-surgical intervals and tracheostomy, were collected.Results: Twenty-five of 30 confirmed cases were included. Average age at diagnosis was 60 months (about 5 years old), with HPV Type 6 in 40% and Type 11 in 48% of patients. All patients received at least one Gardasil® dose, 84% received a second dose and 64% a third dose. Total population DC score decreased from an average of 17 (range: 4-34) pre-first dose to 8 (range: 0-16) after three doses, indicating a 50% reduction. Surgical intervals modestly increased. More significant improvements were seen in patients with aggressive forms of the disease.Conclusion: This is the first study in Southern Africa highlighting Gardasil® as adjuvant therapy. Despite our limited sample size, new cases observed a linear reduction in DC scores and tracheostomy rates.Contribution: This suggests that Gardasil® as adjuvant therapy has the potential to reduce disease severity and extend surgical intervals.

Management Challenges And Outcome Of Juvenile Onset Respiratory Papillomatosis In A Tertiary Hospital In North Central Nigeria: A Preliminary Study

Background/Aim: Juvenile Onset Recurrent Respiratory Papillomatosis (JoRRP) is a benign tumour attributed to human papillomavirus infection with a high propensity to recur despite appropriate treatment. It is relatively rare but the commonest benign tumour of the larynx in children. This study is aimed at evaluating its management challenges.
 Materials and methods: This was a retrospective review of patients with JoRRP at Ear, Nose and Throat (ENT) Department, University of Ilorin Teaching Hospital over a 7-year period. The patients' biodata, mode of presentations, surgical care, histopathological findings and management outcome were reviewed.
 Results: A total number of ten patients were diagnosed with JoRRP during the study period. Male to female ratio was 1:1. All the children were delivered per vaginal and sixty percent were first children of their mothers. Hoarseness, breathy voice and worsening difficulty in breathing were the presentation in 7 (70%) of cases, while 3 (30%) presented with only hoarseness and breathy voice. They all presented first to General Practitioners and Paediatricians before ENT Specialist assessment and six (60%) patients presented to ENT department 6 months or more after the onset of symptoms. They all had direct laryngoscopy and excisional biopsy of laryngeal papillomatous lesions. Thirty percent had tracheostomy done. There is a statistical significant relationship between tracheostomy rate and recurrence rate of JoRRP.
 Conclusion: JoRRP is a rare but potentially life-threatening benign tumor of the respiratory tract. Most of our patients presented late and were misdiagnosed at presentation. The key to good management outcome remains early diagnosis, adequate management and regular follow-up.

A user-centered smart inhaler algorithm for targeted drug delivery in juvenile onset recurrent respiratory papillomatosis treatment integrating computational fluid particle dynamics and machine learning

Recurrent respiratory papillomatosis (RRP) is a chronic condition primarily affecting children, known as juvenile onset RRP (JORRP), caused by a viral infection. Antiviral medications have been used to reduce the need for frequent surgeries, slow the growth of papillomata, and prevent disease spread. Effective treatment of JORRP necessitates targeted drug delivery (TDD) to ensure that inhaled aerosolized drugs reach specific sites, such as the larynx and glottis, without harming healthy tissues. Using computational fluid particle dynamics (CFPD) and machine learning (ML), this study (1) investigated how drug properties and individual factors influence TDD efficiency for JORRP treatment and (2) developed personalized inhalation therapy using an ML-empowered smart inhaler control algorithm for precise medication release. This algorithm optimizes the inhaler nozzle position and diameter based on drug and patient-specific data, enhancing drug delivery to the larynx and glottis. CFPD simulations show that particle size significantly affects deposition fractions in the upper airway, emphasizing the importance of particle size selection. Additionally, optimal nozzle diameter and delivery efficiency depend on particle size, inhalation flow rate, and release time. The ML-based TDD strategy, employing a classification and regression tree model, outperforms conventional inhalation therapy by achieving a higher delivery efficiency to the larynx and glottis. This innovative concept of an ML-empowered smart inhaler represents a promising step toward personalized and precise pulmonary healthcare through inhalation therapy. It demonstrates the potential of AI-driven smart inhalers for improving the treatment outcomes of lung diseases that require TDD at designated lung sites.

Use of adjuvant intravenous bevacizumab for aggressive recurrent respiratory papillomatosis- A case report

Recurrent Respiratory Papillomatosis (RRP) is a benign condition which needs frequent surgical interventions for debulking of papillomatosis lesions for securing the airway. There is no definitive treatment for the management of RRP so far. Bevacizumab either intralesional or systemic has emerged as a promising solution for RRP patients undergoing repeated surgeries. We are reporting a case of a 6-year-old child with juvenile onset RRP who was treated by surgical excision of lesion with adjuvant systemic bevacizumab therapy.

Role Of CO2 Laser & Microdebrider In The Treatment Of Juvenile Onset Recurrent Respiratory Papillomatosi.

To compare the efficacy of two main treatment modalities of microdebrider and carbon dioxide laser excision for juvenile onset recurrent respiratory papillomatosis. The retrospective study was conducted in May 2021 at the Combined Military Hospital, Kharian, Pakistan, and comprised data from July 1, 2007, to January 31, 2020, of patients of either gender aged 2-12 years who were treated for juvenile onset recurrent respiratory papillomatosis either with microdebrider excision in group A or carbon dioxide laser excision in group B. Extent and severity of disease was documented as per the Derkay-Coltrera grading system. Data was analysed using SPSS 20. Of the 39 patients, 23(59%) were girls and 16(41%) were boys. The overall mean age at the time of procedure was 6.62±2.06 years. Group A had 22(56.4%) subjects; 15(68.2%) girls and 7(31.8%) boys, while group B had 17(43.6%) cases; 8(47%) girls and 9(53%) boys. The mean operative time for group A was 40.91±11.50 minutes and for group B it was 60.59±19.51 minutes. Postoperative breathing and oedema status was better for group A (p<0.05), while there was no significant difference regarding postoperative pain, residual disease and repeat surgeries (p>0.05). Microdebrider was found to be superior to carbon dioxide laser excision in the treatment of juvenile onset recurrent respiratory papillomatosis.

The incidence of juvenile onset recurrent respiratory papillomatosis at Starship Children's Hospital before and after a national HPV vaccination programme: a retrospective review.

To review and compare the incidence of juvenile onset recurrent respiratory papillomatosis (JRRP) at Starship Children's Hospital (SSH) before and after the introduction of a national HPV vaccination programme. Patients treated for JRRP at SSH were identified retrospectively using ICD-10 code D14.1 over a 14-year period. The incidence of JRRP in the 10-year period prior to the introduction of HPV vaccination (1 September 1998 to 31 August 2008) was compared with the incidence after its introduction. A second comparison was made between the pre-vaccination incidence with the incidence over the most recent 6 years when the vaccination became more widely available. All New Zealand hospital ORL departments that referred children with JRRP to SSH exclusively were included. SSH manages about half of the New Zealand paediatric population with JRRP. The incidence of JRRP before the introduction of the HPV vaccination programme was 0.21 per 100,000 per year in children 14 years of age and younger. This remained stable between 2008 and 2022 (0.23 vs 0.21 per 100,000 per year). The mean incidence in the later post-vaccination period was 0.15 per 100,000 per year based on small numbers. The mean incidence of JRRP before and after the introduction of HPV has remained unchanged in children treated at SSH. More recently, a reduction in incidence has been noted, although this is based on small numbers. The low HPV vaccination rate (≤70%) may explain why a significant reduction in the incidence of JRRP seen overseas has not been observed in New Zealand. Ongoing surveillance and a national study would provide more insight into the true incidence and evolving trends.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange Augments Oxygenation in Children With Juvenile Onset Recurrent Respiratory Papillomatosis During Surgery: A Prospective Randomized Crossover Controlled Trial.

Evidence is lacking regarding the efficacy of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in tubeless anesthesia, especially in pediatric patients. This study aimed to evaluate the use of THRIVE for juvenile onset recurrent respiratory papillomatosis (JORRP) patients. Twenty-eight children aged 2 to 12 years with JORRP, abnormal airways, and ASA physical status II-III that presented for surgical treatment under general anesthesia were included in this study. Each patient received 2 interventions in random order, with a 5-minute washout period between treatments: apnea without oxygen supplementation and apnea with THRIVE intervention. The primary outcome apnea time was defined as the duration from withdrawal of intubation to reintubation and resumption of controlled ventilation. The secondary outcomes were the mean transcutaneous carbon dioxide (tcco2) increase rate, the minimum pulse oxygen saturation (Spo2) during apnea, and the occurrence of unexpected adverse effects. The median apnea time in the THRIVE period was significantly longer than that in the control period (8.9 [8.6-9.4] vs 3.8 [3.4-4.3] minutes; mean difference [95% confidence interval (CI)], 5.0 [4.4-5.6]; P < .001) for all patients. The rate of CO2 change in the control period was higher than that in the THRIVE period both for patients aged 2 to 5 years old (6.29 [5.19-7.4] vs 3.22 [2.92-3.76] mm Hg min-1; mean difference [95% CI], 3.09 [2.27-3.67]; P < .001) and for patients aged 6 to 12 years old (4.76 [3.7-6.2] vs 3.38 [2.64-4.0] mm Hg min-1; mean difference [95% CI], 1.63 [0.75-2.56]; P < .001). The minimum Spo2 was significantly higher in the THRIVE period than in the control period (mean difference [95% CI], 19.7 [14.8-22.6]; P < .001). Our findings demonstrate that THRIVE safely increased the apnea time among children with JORRP undergoing surgery and decreased the rate of carbon dioxide increase. THRIVE is clinically recommended as an airway management technique for tubeless anesthesia in apneic children.

Recurrent laryngeal papillomatosis: multimodal therapeutic strategies. Literature review and multicentre retrospective study.

Recurrent respiratory papillomatosis (RRP) is a benign, rare disease caused by Human Papilloma Virus (HPV) that can be divided into juvenile and adult forms. The course of the disease is variable, but is usually more aggressive in the juvenile form. The standard surgical treatment is represented by CO2 laser resection, although photoangiolytic lasers represent a valid alternative. Adjuvant therapies have been proposed for disease control in case of frequent surgical resections or spreading into the lower airways. In recent years, the development of immunotherapy led to the use of bevacizumab either intratumorally or intravenously, but the most promising therapeutic development is represented by HPV vaccination. This paper aims to present a narrative review of the literature and the experience of three different University Centres in the treatment of RRP. A retrospective analysis of the clinical charts of all patients affected by laryngeal papillomatosis and treated in three different University Centres between 2002 and 2022 was performed. The following parameters were collected: sex, age at first evaluation, sites of larynx involved, HPV type, type of first surgical treatment, presence and number of recurrences, surgical treatment of recurrences, adjuvant therapies, side effects and status at last follow-up. Seventy-eight patients were available for evaluation. Of these, 88% had adult onset RRP (Ao-RRP) and 12% juvenile onset RRP (Jo-RRP). The glottis was the most frequently involved subsite; all patients were submitted to surgical resection with CO2 laser under general anaesthesia. Recurrences appeared in 79% of the patients, the patients who did not recur were all adults. The mean number of recurrences was 9 (range 1-110). Recurrences were more frequent in children (M = 20; range 2-110) than adults (M = 5; range 1-21). Thirty-two (52%) of the 62 patients who recurred were re-treated with CO2 laser under general anaesthesia, while office-based treatment with a photoangiolytic laser was preferred in the remaining 30 (48%) patients. Adjuvant treatments were applied in 26 patients. The analysis of the course of the disease showed that in the 9 patients with Jo-RRP, 6 (67%) were free of lesions at the last follow-up, while the other 3 (33%) had papillomas. Of the 69 patients with Ao-RRP, 53 (77%) were alive and free of disease at the last visit, 14 (21%) were alive with disease, 1 (1%) was lost at follow-up and 1 (1%) died for other disease. Severe side effects were not observed except for 2 patients, who developed posterior glottic stenosis. Our results confirmed the literature review. RRP is a potentially aggressive disease, especially in juvenile onset. Surgical resection is still first-line treatment, but in case of multiple recurrences the use of adjuvant therapies must be taken into consideration.

Intralesional Bevacizumab as Adjuvant Therapy for Juvenile Onset Recurrent Respiratory Papillomatosis: A Systematic Review.

Background: Respiratory papillomatosis is one of the common benign lesions of the airway that is often difficult to treat and carries significant morbidity. Bevacizumab is a monoclonal antibody that acts upon vascular endothelial growth factor receptor and is known to have an effect in respiratory papillomatosis. This study aims to systematically review the literature on efficacy of intralesional Bevacizumab in juvenile onset respiratory papillomatosis. Materials and methods. A systematic search of literature in various databases was conducted. The search was restricted to the English language, however, no restrictions were made regarding the date of publication keeping December 31st, 2020 as the last date of publication. We strictly complied with the PRISMA guidelines. Results. Of 145 articles analyzed, only 3 were selected as eligible and a total of twenty-one cases were evaluated. There was improvement in anatomic Derkay score after initiating intralesional Bevacizumb with reduction in the number of surgeries. Where reported, voice related functional outcomes also were also improved. No adverse effect related to the drug was reported. Conclusion: Intralesional Bevacizumab can be a promising efficacious, and safe adjuvant in the management of JORRP. Well-designed studies are further required in the future to prove its efficacy and safety over other adjuvants available.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2020.

For 27 years, national prospective data on selected rare childhood diseases have been collected monthly by the Australian Paediatric Surveillance Unit (APSU) from paediatricians and other clinical specialists who report cases in children aged up to 16 years. We report here the annual results of APSU surveillance in 2020 for ten rare communicable diseases and complications of communicable diseases, namely: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV) infection; neonatal herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV); paediatric HIV infection; severe complications of seasonal influenza; juvenile onset recurrent respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. We describe the results for each disease in the context of the total period of study, including demographics, clinical characteristics, treatment and short-term outcomes. Despite challenges presented by the coronavirus disease 2019 (COVID-19) pandemic in 2020, more than 1,400 paediatricians reported regularly to the APSU and an overall monthly reporting rate of > 90% was achieved. The minimum AFP target of 1 case per 100,000 children aged less than 15 years was achieved and there were few cases of vaccine-preventable diseases (JoRRP, rubella, varicella). However, high cases of congenital CMV, neonatal HSV and perinatal exposure to HIV persist. There were no severe complications of seasonal influenza reported for the first time in 13 years. This is consistent with other surveillance data reporting a decline of influenza and other communicable diseases in 2020, and likely reflects the wider effects of public health measures to reduce transmission of SARS-CoV-2 in the Australian community.

Experience with Systemic Bevacizumab in Advanced Juvenile Recurrent Respiratory Papillomatosis.

Vascular Endothelial Growth Factor has been demonstrated in squamous papillomas of Recurrent Respiratory Papillomatosis patients. This case series aimed at studying the feasibility and efficacy of systemic use of VEGF inhibitor Bevacizumab in advanced Juvenile Onset Recurrent Respiratory Papillomatosis (JORRP) patients. Three pediatric patients with advanced RRP were included in this study. A detailed bronchoscopic and radiological follow-up is presented. All patients responded well to the treatment. We conclude that systemic Bevacizumab can be tried as a feasible and rational adjuvant treatment in advanced JORRP patients.

A RARE CASE OF PROGRESSIVE PULMONARY CAVITARY LESIONS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Recurrent respiratory papillomatosis (RRP) is a rare and often benign condition caused by a human papilloma virus (HPV) infection that results in papilloma growth throughout the respiratory tract. It is placed into 2 categories: juvenile (<18 years) and adult (>18 years) onset. The incidence of juvenile onset RRP (JORRP) is estimated to be 2 cases per 100,000 children. Here, we discuss a case of JORRP in a middle-aged male presenting with recurrent dyspnea and cough. CASE PRESENTATION: A 37-year-old male with a history of JORRP, diagnosed at age 2 with over 50 debulking procedures by the age of 28, presented to the pulmonary clinic with progressive dyspnea and cough. He was noted to be tachycardic with bilateral rales, room air oxygen saturation of 90% and other vital signs stable. Chest radiography revealed patchy ground-glass nodules, cavities and a mass-like opacification in the right lower lobe with air fluid levels. Flexible bronchoscopy revealed diffuse papillomas involving the laryngeal vestibule, glottis, subglottis and trachea down to carina as well as evidence of pus in his left mainstem bronchus. Treatment with antibiotics for post obstructive pneumonia resulted in symptomatic improvement. Weeks later, he represented with similar symptoms and was retreated for post obstructive pneumonia. Computed tomography (CT) chest revealed multiple bilateral peribronchovascular cavitary lesions, scattered solid nodules, dense airspace consolidation in the bilateral lower lobes and bulky bilateral subcarinal lymphadenopathy. Imaging was consistent with RRP but also concerning for infection or malignant transformation to squamous cell carcinoma (SCC). CT-guided lung biopsy showed squamous papilloma with areas of necrosis and rare foci suspicious for invasion. Given concern for malignant transformation, repeat biopsy revealed mild to moderate dysplasia but no evidence of invasion. PET-CT to evaluate for malignancy was recommended following completion of antibiotics. DISCUSSION: JORRP is an acquired infection that occurs during vaginal delivery with symptoms of respiratory obstruction starting in childhood. Dysphonia is commonly noted due to papilloma growth on the vocal cords disrupting normal vibration. It is primarily managed by surgical resection including micro-debridement and laser resection. Adjuvant therapies include interferon alpha, antivirals and bevacizumab. Malignant transformation of RRP into invasive SCC is reported to be 3-7% in adults and thought to be from a mutation in the HPV viral genome. CONCLUSIONS: JORRP is the most aggressive form of RRP with no curative therapy. Diagnosis is established by laryngoscopy and first seen in the vocal folds. Post-obstructive pneumonia and malignant transformation to SCC should always be considered given the nature of RRP. REFERENCE #1: Fortes, H. R et al.(2017).Recurrent respiratory papillomatosis:A state-of-the-art review. Resp. Medicine,126,116-121. REFERENCE #2: Ivancic, R. et al. (2018). Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investigative Otolaryngology, 3(1), 22-34. REFERENCE #3: Karatayli-Ozgursoy, S. et al. (2015). Risk factors for dysplasia in recurrent respiratory papillomatosis in an adult and pediatric population. Annals of Otology, Rhinology & Laryngology, 125(3), 235-241. DISCLOSURES: No relevant relationships by Kathy Chan, source=Web Response No relevant relationships by George Moran, source=Web Response No relevant relationships by Sudhir Rajan, source=Web Response No relevant relationships by Eduardo Solbes, source=Web Response

Clinical implications of alpha, beta, and gamma HPV infection in juvenile onset recurrent respiratory papillomatosis

PurposeThe aim of our study was to evaluate the prevalence of different HPV genera—alpha, beta and gamma—in Juvenile onset Recurrent Respiratory Papillomatosis (JoRRP) and examine the association of type and genus-specific viral features with the clinical outcome of disease.MethodsThis retrospective observational study included consecutive patients with JoRRP who were treated in a referral centre between October 2000 and October 2020. All patients underwent cold excision and laser vaporisation of papillomatous lesions. Samples were analysed for the presence of 120 viral genotypes (22 alpha-HPV, 46 beta-HPV, 52 gamma-HPV) using a highly sensitive multiplex genotyping assay.ResultsTwenty patients with JoRRP, aged 0.3–11 years, were included, with a median follow-up of 13.5 years. All samples were HPV DNA positive: 20 (100%) for alpha-HPV DNA; 7 (35%) for beta—HPV DNA; 0 for gamma-HPV DNA. Three groups were defined according to the number of infections: seven cases (35%) with HPV mono-infection; ten cases (50%) with HPV double-infection; three cases (15%) with ≥ 3 HPV infections. At diagnosis, patients with ≥ 3 HPV infections reported higher median Derkay’s score than those with mono-infection (21 vs 14, P = 0.018). Number of HPV infections was also associated with clinical outcomes, with an average of 0.5 surgical procedures/year in patients with mono-infection, 1.2 for double-infection, 2.6 for ≥ 3 infections (P = 0.006).ConclusionDespite the small sample size, these preliminary data support an association between the number of different alpha and beta HPV co-infections and the clinical severity of the disease.

Systemic and Intralesional Bevacizumab in Juvenile Onset Recurrent Respiratory Papillomatosis: A Report of Two Cases.

Recurrent respiratory papillomatosis (RRP) is a stubborn disease. Despite volumes of researches done for a definite cause and management, the scientific community offers only theories for causation and options for treatments. Bevacizumab has emerged as a promising solution to the fear of sufferers of RRP of undergoing repeated surgeries. The patients who received bevacizumab, either systemically or intralesionally, show decreased need for surgeries mostly and even remission in a few. Till date there are limited studies of use of bevacizumab, in adults, but only reports of its use in pediatric population. This is a report of two cases of juvenile onset RRP with use of systemic bevacizumab infusion in a child and intralesional injection in an adult.

Long-term Outcomes of Juvenile Onset Recurrent Respiratory Papillomatosis with Pulmonary Involvement.

To investigate the clinical characteristics and long-term outcomes of juvenile onset recurrent respiratory papillomatosis (JORRP) with or without pulmonary involvement. A group of patients with JORRP who had clinical course over an extended period of time (at least 5 years) in the Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital were included in this retrospective study. Lung/bronchus involvement was revealed by lung imaging. Data on mortality rate, frequency of surgical interventions, and age of disease onset were collected and analyzed. The 192 patients (107 male and 85 female) included had a median [quartiles] age of JORRP onset of 2 [1, 4] years, and median follow-up duration of 10 [7, 13] years; 17 patients (8.9%) had papilloma with bronchial and pulmonary involvement 7.0 [4.0, 12.5] years after the onset of the disease. Compared to patients without lung involvement, patients with lung involvement had a younger age of disease onset (P= .001), higher frequency of surgical interventions (P< .001), higher mortality rate (OR=94.909), and an increased risk of tracheotomy that could not be decannulated (P< .001). They also had a younger age of disease onset, and a higher frequency of surgical interventions and mortality compared to patients with tracheotomy but free from lung involvement (P< .001). Children with JORRP and with pulmonary involvement have a higher average number of operations per year than those without pulmonary involvement, and pulmonary involvement indicates a higher incidence of tracheotomy that cannot be decannulated. 4 Laryngoscope, 131:E2277-E2283, 2021.

Challenges in Managing Sars-Cov-2 Positive Child with Juvenile Onset Recurrent Respiratory Papillomatosis: A Case Report with Review of Literature

Juvenile-Onset Recurrent Respiratory Papillomatosis (JORRP) is a viral infection caused by Human papilloma virus 6, 11 which presents as hoarseness, shortness of breath and in severe form may present with acute airway obstruction because of papillomatous growth obstructing the larynx. Urgent surgical intervention may be needed to secure the airway. In the present situation of Coronavirus disease-2019 (COVID-19) pandemic, the case of JORRP with COVID-19 positive state is a challenging situation because any laryngeal or airway surgery is associated with high amount of aerosol generation. Air borne transmission is one of the major routes of transmission for SARS-Cov-2 virus which may result in spread of COVID-19 among to the health care provider.&#x0D; In this situation, it is better to avoid delay laryngeal surgery if the patient is not in acute airway obstruction requiring urgent surgical intervention. Otherwise, if the urgent surgery has to be done, then it should be done properly by following institutional guidelines to avoid the spread of the disease and to be done with all precautionary biosafety measures like use of personal protective equipment (PPE), N95 mask and proper donning and doffing.

Systemic Bevacizumab (Avastin) for Juvenile-Onset Recurrent Respiratory Papillomatosis: A Systematic Review.

Juvenile onset recurrent respiratory papillomatosis (JORRP) can cause severe or disseminated disease. Surgical treatment may be inadequate. Systemic bevacizumab has shown initial success for severe JORRP. The objective of this systematic review was to assess usage, effectiveness, and safety of this treatment. We searched PubMed, Embase, and Web of Science for studies of humans with JORRP treated with systemic bevacizumab. Two researchers independently reviewed the studies to determine inclusion and aggregate data on patient characteristics, dosing protocols, treatment response, adverse events, and level of evidence. Of 80 identified articles, 12 studies were included detailing 20 distinct cases. At a mean age of 12.8 years (range = 1-43 years) patients received initial dosing of 5 to 10 mg/kg of bevacizumab followed by ongoing doses at a mean 3-week intervals (range = 2-5 weeks). All patients had clinically significant disease reduction with reduced need for surgery. Six patients (30%) had complete response in at least one involved anatomic site. Eleven (55%) required no surgery after initiating treatment. There was recurrence in all four patients whose treatment was stopped, but had rapid improvement with treatment resumption. Six (30%) experienced mild or moderate adverse events. Marked improvement in severe JORRP has been reported from systemic bevacizumab. Treatment protocols vary, and treatment discontinuation was not feasible in any reported patient. Based on currently available data, systemic bevacizumab can be considered for severe JORRP as it appears to be well tolerated and effective. A clinical trial could enhance the understanding of its safety and efficacy for this indication. Laryngoscope, 131:1138-1146, 2021.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2019.

The Australian Paediatric Surveillance Unit (APSU) has been prospectively collecting national data on rare childhood conditions since 1993, with monthly reporting of cases by paediatricians. In this report we describe annual results from studies for ten communicable diseases and complications of communicable diseases that were conducted using APSU surveillance in 2019 and place these in an historic context. Results are reported on acute flaccid paralysis, congenital cytomegalovirus infection, neonatal herpes simplex virus infection, perinatal exposure to HIV, paediatric HIV infection, severe complications of seasonal influenza, juvenile onset recurrent respiratory papillomatosis (JoRRP), congenital rubella syndrome, congenital varicella syndrome and neonatal varicella infection. APSU provides rich clinical data to complement data collected from other surveillance systems and to improve understanding and response to rare childhood infections.

Long Term Outcome Of Juvenile Onset Recurrent Respiratory Papillomatosis In Universiti Kebangsaan Malaysia Medical Centre

Objective: To review the long term outcome of juvenile onset recurrent respiratory papillomatosis (JORRP) in University Kebangsaan Medical Centre (UKMMC). Methods: A sixteen-year retrospective study – from January 2002 to June 2019 – of patients who presented with JORRP at our hospital was carried out. Results: Nineteen cases were identified with the youngest age of presentation being eight months old. The mean follow-up time was 4.8 years. All patients had glottic papilloma, ten had multi-site involvement, namely at the subglottic, trachea, oropharynx and one case of distal spread to the lungs. The majority (71.4%) of patients with tracheostomy had extralaryngeal spread and shorter surgical intervals (a mean of 3.2 procedures per year). All our patients were treated surgically. Two patients with aggressive disease received a trial of the adjuvant therapies Gardasil and Cidofovir. However, no improvement was observed. Conclusion: The worst prognosis is seen in younger-onset JORRP. Surgery is the mainstay of treatment and patients with aggressive disease may need adjuvant therapy. Unfortunately, there is a lack of a standard protocol for adjuvant therapies. Tracheostomy increases the risk of extralaryngeal spread and aggressive disease, and thus should be reserved for patients with severe airway compromise.

Use of intralesional cidofovir in the recurrent respiratory papillomatosis: a review of the literature.

Recurrent respiratory papillomatosis (RRP) is characterized by exophytic, benign, and papillary lesions infected by the virus in the epithelium of the upper aerodigestive tract. RRP is caused by persistent infection of the respiratory epithelium by human papillomavirus (HPV) HPV6 and-11. The clinical course of RRP is unpredictable, frequently relapsing, and may be lifelong. The aim of this study is to evaluate the efficacy and safety of the use of intralesional Cidofovir in the treatment of RRP. We have selected articles on the use of cidofovir as adjuvant therapy in laryngeal papillomatosis. We reviewed 20 reports that enrolled 185 patients with "adult onset recurrent respiratory papillomatosis" (AORRP) and 85 patients with "juvenile onset recurrent respiratory papillomatosis" (JORRP). We evaluated concentration of cidofovir, number of injections, injection interval, therapeutic response, side effects, and progression to dysplasia. The mean concentration of cidofovir was 7.5 mg/ml at injection. The mean number of injections per patient is 6 with 26 days between injections. The percentage of patients with dysplasia after use of cidofovir is 1.48%. The AORRP response to cidofovir is better with a 74% complete response rate, compared to 56.5% of the JORRP. Intralesion use of cidofovir has a good adjuvant action in RRP increasing the complete remission of the disease. The treatment does not increase the risk of laryngeal dysplasia.