|Year : 2012 | Volume
| Issue : 1 | Page : 30-34
Remission in juvenile-onset recurrent respiratory papillomatosis
Sachin Gandhi, Reba Jacob
Department of ENT, Deenanath Mangeshkar Hospital and Research Centre, Pune, Maharashtra, India
|Date of Web Publication||9-Apr-2012|
Department of ENT, Deenanath Mangeshkar Hospital and Research Centre, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a distressing disease due to relentless recurrence and progression. In JORRP, recurrence is a rule, but remission can be considered if the disease-free period after a particular treatment modality is more than one year. Objective : The present study was undertaken with the aim to address this dilemma of remission in JORRP. Materials and Methods: A total of 30 patients of JORRP presenting over 2 years were included. Detailed history, aggressiveness of disease, number of surgical interventions, and surgical modality used were elicited. Videolaryngostroboscopy was performed in all patients using Kays RLS 9100B stroboscope. Papilloma excision was done using CO 2 laser and all patients were followed up three monthly for 1 year, then were kept on yearly follow-up. Results: It was observed that majority of the patients (83%) underwent recurrent excision of papillomas for 1 to 5 times. Of the 30 patients, 15 (50%) showed remission. Eleven of the 30 patients (36.67%) had minimal papillomas and symptomatic recurrence of papilloma was seen in four of the 30 patients (13.33%) and required further surgeries. Nine of the 30 patients who showed remission were diagnosed and managed within 1- to 15-year age group. Six of the 30 patients who presented with recurrence and minimal papillomas were in the age group 31 to 45 years. These patients had transition of JORRP to adult papilloma. Conclusion: The present study shows that the chance of remission is higher in children who had an early onset of JORRP. Remission was more when surgical excision was done only with CO2 laser.
Keywords: CO 2 laser, juvenile, remission, respiratory papilloma
|How to cite this article:|
Gandhi S, Jacob R. Remission in juvenile-onset recurrent respiratory papillomatosis. J Laryngol Voice 2012;2:30-4
| Introduction|| |
Recurrent respiratory papillomatosis (RRP) is an enigmatic disease which can be distressing due to relentless recurrence and progression. Papilloma arises from various sites in the aerodigestive tract, with a predilection to areas at the junction of squamous and respiratory epithelium. The most commonly involved area is the larynx. The prevalence of laryngeal papillomatosis has been estimated at between four to seven cases per million person years in the Western World. ,,
Juvenile-onset RRP (JORRP) has prevalence of 1.7 to 2.6 per 100 000 children in the United States. , Although rare, JORRP is the most common neoplasm of the upper airway in children.  The age of onset is highly variable; however, the age of first presentation of juvenile form can be as early as the first year of life. In children, 25% will present by age of 1 year and 75% by age of five years. 
Repeated growth of papilloma or warts usually in larynx and upper respiratory tract in children characterizes JORRP. It is a chronic disease diagnosed between birth and adolescence and often runs a prolonged course requiring multiple surgical procedures supplemented by drug therapy.  The viral etiology of RRP has now been confirmed by in situ hybridization and polymerase chain reaction for all RRP.  The more common virus implicated as causative for RRP is Human papilloma virus types 6 and 11. 
Mainstay for treatment for JORRP is total removal of all papillomata tailored to minimize morbidity and preserve laryngeal function with relation to voice and airway. Severity and number of surgical procedures varies with patients. In most children, the disease remits, whereas in others, it persists into adulthood. , The American Society of Pediatric Otolaryngology and the American Broncho-esophageal Association showed that 33% of children needed more than 20 operations with 7% requiring more than 100 surgical procedures in their life time. 
The low prevalence of JORRP limits the number of patients at any one institution, and many questions about the disease remain unanswered. 
Remission of JORRP still remains a subject of controversy. Reports mention that JORRP continues and recurs irrespective of the modality of treatment.
Thus, in JORRP, recurrence is a rule, but remission can be considered if the disease-free period after a particular treatment modality is more than one year. The present study is undertaken with the aim to address this dilemma of remission JORRP.
| Materials and Methods|| |
The present study was a retrospective study in patients over 2-year period from February 2008 to February 2010. Study sample included 30 patients presenting to a tertiary care laryngology center with complaints of hoarseness of voice and/or breathlessness and diagnosed of juvenile recurrent laryngeal papillomatosis. Patients less than 15 years of age with histopathology report of papilloma were included. Patients with glottic web or excessive vocal cord scaring most likely due to previous interventions were excluded.
A detailed history of age at onset, aggressiveness, number of surgical interventions, surgical modality, and use of adjuvant therapy was noted. Symptoms suggestive of dysphagia, dyspnea, reflux disease, and aspiration were noted.
Videolaryngostroboscopy was performed in all patients with Kays RLS 9100B stroboscope and the clinical diagnosis was confirmed. The specific features looked for in scopy was the extent of papilloma and finding related to past surgeries.
Surgery was performed under general anesthesia with cuffed metal endotracheal tube (Laserflex) or uncuffed metal endotracheal tube (Oswal Hunton) or jet (high frequency) ventilation or an apneic ventilation as per the clinical presentation. Zeiss operating microscope with 400-mm objective lens was used coupled with the CO 2 laser. Anterior commissure laryngoscope was inserted and 4-mm laparoscope used to assess the extent of papilloma. Papilloma excision was done using CO 2 laser used at 6 W at bursts of 0.2 seconds in an interrupted or pulsed mode. All patients were followed up three monthly for 1 year, then were kept on yearly follow-up.
On each visit, Videolaryngostroboscopy was done. Patients were assessed on follow-up after one year of excision of papillomas by stroboscopy and classified as per symptoms and videostroboscopic finding into either of the following three:
All analyses were performed using statistical software Minitab 15 and P value <0.05 was considered as statistically significant.
- Remission defined as no evidence of papillomas on videolaryngostroboscopy.
- Minimal recurrence defined as evidence of few papillomas on stroboscopy, but patients were asymptomatic and required no intervention.
- Recurrence defined as evidence of papillomas on stroboscopy and patients were symptomatic with the need of surgical intervention.
| Result|| |
A total of 30 cases of JRRP were included in the study. This comprised of 20 males and 10 females.
The onset of papillomas was seen more commonly in the age group of 3 to 4 years and 7 to 8 years. [Figure 1] shows the distribution of patients with respect to age of onset of papilloma.
|Figure 1: Distribution of patients with respect to age of onset of papilloma|
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Majority of the patients (20/30, 67%) with the disease underwent excision for papillomas without the need of a tracheostomy. Of the 10/30 patients in whom tracheostomy was done, six patients could be decannulated. Of the four patients who could not be decannulated, two had tracheobronchial disease.
The patient distribution in respect to number of surgeries was observed. It was observed that majority of the patients (83%) underwent recurrent excision of papillomas 1 to 5 times [Figure 2].
Of the 30, 16 (53.3%) patients were operated by combination of cold instruments and CO 2 Laser, and 13 patients were operated by CO 2 Laser only. One patient was operated only with cold instruments.
The number of patients with respect to remission of disease is as per [Table 1]. It was observed that 15 of 30 patients (50%) showed remission. Eleven of 30 patients (36.67%) had minimal papillomas on stroboscopy but were asymptomatic and hence no surgical intervention was needed. Symptomatic recurrence of papilloma was seen in four of 30 patients (13.33%) and required further surgeries [Table 1].
Nine of 30 patients who showed remission were in the 1-15 year age group. Six of 30 patients who presented with recurrence and minimal papillomas were in the age group 31 to 45 years. These patients had transition of JORRP to adult papilloma. Chi-square test was done to analyze the significance of age and remission. A significant association was observed for the same with P value <0.05, suggesting that lower the age group, better was the remission [Table 2].
No significant co-relation was found between age of onset of papilloma and remission. P>0.05 by Chi square test.
On studying the remission pattern and type of surgery, it was observed that the remission of papilloma has occurred in maximum number of patients when surgical excision was done using CO 2 laser alone [Figure 3].
|Figure 3: Number of patients of JORRP with respect to type of surgery and remission|
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| Discussion|| |
The present study was carried out on 30 patients of Juvenile recurrent laryngeal papillomatosis.
Although RRP is a benign disease, it is frequently associated with substantial morbidity and mortality. Majority of our patients (66%) were males. This gender difference is comparable with other reported studies. A study of 110 patients by Strong et al.,  in 1976 had 59% males, and that by Diouf et al.,  in 1989 too showed a male preponderance.
The information about the age of onset was obtained from the parents, and considered accurate. In the present study, 19 of 30 (63.3%) patients had onset of disease before the age of six years, which is consistent with reports in literature. A study by Kashima et al., in 1996 reported that in children with JORRP, 25% present by the age of one year and 75% present by the age of five years. 
In the present study, it was observed that if the disease had an onset at an early age, the chance of remission was higher, compared with those cases in which the onset of disease was at a later date. However, this result was not statistically significant when analyzed using chi square test, (P>0.05). Study by Ruparelia et al., in 2003 stated that patients whose conditions were diagnosed at an older age were 1.13 times more likely than younger patients to experience disease remission.  There are many previous studies which have conflicting results concerning the age that best discriminates between aggressive and non-aggressive disease. Armstrong et al., in 1999, in one of the largest study, found that children with an age of onset younger than 3 years were 3.6 times more likely than children diagnosed at an older age to have more than four surgical procedures per year.  This aberration in the present series may be due to the fact of early intervention of mode of surgery for the excision of papilloma in majority of cases. However, this is one of the essential result recorded in this study and may reflect that if early intervention is done in excision of papillomata, which have an onset at an early age, it can lead to remission of disease.
RRP is marked by frequent recurrences and disease exacerbations; the capricious nature of RRP makes counselling patients and their families a difficult task. Although spontaneous remission has been reported, its occurrence is highly variable and unpredictable. One of the aims of this study was to find out the remission rates after surgical excision of RRP. The present study has also come out with the similar fact that there is association between the remission following treatment and the age of patient. The remission rates were higher if the age of patient at the time of treatment was less. Among 14 children of RRP who were operated in the age group 1 to 15 years, 64% (9/14) showed disease remission.
In contrast to this, those who were operated in the age group of 31 to 60 years, only 20% (2/10) showed disease remission. When comparing this issue to those of in literature, there are some supporting and some contrasting reports. Silverberg et al.,  noted that younger children required more frequent surgeries and that two-third of children underwent less frequent surgeries over time. The present study has come out with the similar fact that there is association between the outcome of patient clinical condition and remission following treatment at a younger age, which corresponds to a higher remission rate and hence a very important result of the present study, given the fact that the disease is very aggressive at younger age. 
This study also had another important result in terms of remission. It was found that 15 of 30 patients had a remission of disease. Thus, 50% of children showed disease remission. Definition of disease remission used was no papillomas on follow-up with stroboscopy 1 year after surgery. There is no standard and validated instrument to measure remission based on clinical examination, so we used this measure and the same has been used by earlier similar studies.  It is interesting to note that remission was more in patients in whom CO 2 laser was used for excision of papillomata.
One of the important observations of the study was that majority of patients were not on tracheostomy (86%). In 66% of patients, tracheostomy was not needed. In 20% of patients, tracheostomy was done but later on, successful decannulation was achieved. In four (13%) patients, tracheostomy was done and patients could not be decannulated. The possible reason for failure of decannulation in two of these patients was due to tracheal involvement of RRP and the other two due to extensive subglottic lesions, which in effect, relates to aggressive disease. The propensity of tracheal involvement in RRP in patients with tracheostomy has been described in many studies. In 1964, Majoros et al.,  reported subglottic extension of disease in 56% of patient with tracheostomy, compared with 8% who were not tracheostomized. Cole et al., in his study and review of literature documented incidences of tracheal spread ranging between 7-76%.
It was observed that remission occurred in 69.3% (9/13) of patients, when only CO2 laser was used in scanner mode for excision of papilloma. The possible explanation of efficacy of CO2 laser is that it ablates all visible papilloma on a bloodless field and reduces the tumor burden to invisible proportions; the best that can be hoped for is that immune response of the host will be sufficient to contend with the invisible residue and promote a remission. Various other studies also suggest CO2 laser to be the mainstay of treatment.  Cold instruments were method of choice in past and are still used in certain centers. Recently, some studies also suggest use of microdebrider and report them to be superior to laser surgery. However, the reported superiority of microdebrider is based on safety and cost and not on the basis of remission factor. 
Thus, many interesting findings from this study have been discussed which are of importance and increase our knowledge about the behavior of JORRP.
| Conclusions|| |
The present study shows that the chance of remission is higher in children who had an early onset of JORRP. Those children who transited from JORRP to adult papilloma had less chance of remission. Remission was more when surgical excision was done only with CO 2 laser. The limitation to the present study is the limited number of patients and short follow-up. However, considering the important and promising results drawn from the study, this subject does call for a multi-centric study with a longer follow-up.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]