Endoscopic management of acquired paediatric cholesteatoma: a retrospective cohort study

Introduction

Acquired cholesteatoma is considered a more aggressive condition in the paediatric population compared to the adult. A 2–3 fold increased rate of recidivism has been reported in the literature (1-4), as well as higher rates of ossicular erosion and higher stage on the proposed joint European Academy of Otology & Neurotology (EAONO) and Japanese Otological Society (JOS) classification (5). It has been suggested that the higher rates of otitis media and therefore proinflammatory mediators, or higher levels of circulating growth factors in children may lead to more proliferative and locally aggressive phenotypes (6).

Molecular and histopathological studies are now giving insight into potential reasons for this difference. One study has shown increased expression of MIB-1, a nuclear antigen upregulated in cells progressing through the cell cycle, in paediatric acquired cholesteatomas (7). Paediatric acquired cholesteatomas have also been shown to have thicker epithelial matrices with more pro-inflammatory profiles and higher expression of matrix metalloproteinases, enzymes involved in extracellular matrix degradation (8).

A recent systematic review examining operative approach in paediatric cholesteatoma surgery demonstrated lower rates of residual disease with endoscopic than with microscopic methods (9). Piras et al. reported on 105 Canal Wall Up Mastoidectomy (CWUM) operations in paediatric cholesteatoma patients with a residual disease rate of 21%, with the majority being in the retrotympanum and protympanum (10). Glikson et al. reported a residual rate of 10% in 30 paediatric patients undergoing endoscopic ear surgery (EES) with residual disease occurring in the epitympanum/attic (11). Multiple studies have also looked at endoscopic examination for residual cholesteatoma after microscopic clearance of disease and have reported residual cholesteatoma rates between 16% and 38% (12-16). Common areas of residual cholesteatoma after microscopic surgery, identified on endoscopic examination, included the sinus tympani, attic, retrotympanum and epitympanum (9,12).

The aim of this paper is to determine the recidivism rate in paediatric patients undergoing EES for acquired cholesteatoma and identify risk factors for recidivism, to help inform future surgical decisions and reduce the rates of treatment failure. We present this article in accordance with the STROBE reporting checklist (available at https://www.theajo.com/article/view/10.21037/ajo-23-53/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Ethical approval for this research was granted by North Sydney Local Health District Research Committee under existing approvals for outcomes in EES (HREC reference: LNR/18/HAWKE/38). Because of the retrospective nature of the research, the requirement for informed consent was waived.

A retrospective chart review of paediatric patients treated for primary or secondary acquired cholesteatoma by four specialist, tertiary referral otologists between 2014 and 2021 was undertaken. A paediatric patient was defined as any patient 18 years or younger at the time of surgery. Only patients who were treated with EES techniques (i.e., Massachusetts Class 2A/B or 3) (17) were included. Exclusion criteria included previous cholesteatoma surgery from a different surgeon (i.e., revision surgery) and follow-up of less than 12 months from primary surgery.

Patients underwent pre- and post-op audiology and imaging as per surgeon preference. Surveillance was either by second-look surgery, clinical examination, imaging [computed tomography (CT) or non-echo planar imaging diffusion weighted imaging magnetic resonance imaging (non-EPI DWI MRI) or both], or a combination as per surgeon preference. Surgical exposure techniques such as canaloplasty, atticotomy or mastoidectomy were recorded for each patient. The extent of surgery completed via EES was graded by the surgeon at time of surgery using the Massachusetts grading system (Table 1) (17). Myringoplasty, attic reconstruction and ossicular chain reconstruction (OCR) were recorded including timing of OCR (primary or secondary). Post-operative audiology was undertaken after planned OCR if staged at the time of primary surgery.

Patients’ follow-up data were recorded including duration, method of surveillance, presence of complications, residual, or recurrent disease. Residual disease was defined as disease present after previous surgery thought to be from incomplete removal of cholesteatoma matrix and recurrence as cholesteatoma formation associated with new retraction or perforation after previous complete surgical cholesteatoma removal (18). Recidivism was used to describe combined recurrent and residual disease.

Data was collated and descriptive statistics were performed in Microsoft Excel and further statistical analysis was performed in SPSS 28 (IBM). Fisher’s exact or Chi square test, univariate and multivariate regression analysis were performed to explore the relationship between recidivism, audiometric results, and type/extent of surgery with demographic and pathological characteristics.

Results

Demographics

A total of 49 paediatric ears were operated upon for cholesteatoma between 2014 and 2020. A majority of the patients were male (28 vs. 17) with 30 male and 19 female ears. Distribution of side was essentially equal, with one more right ear than left (25 vs. 24). The average age at time of surgery was 11.2 years (range, 4–18 years).

Pathological features

The epitympanum was the most affected site (n=27) followed by the retrotympanum and mesotympanum (24 and 23 respectively) (Table 2). It was most common for 2 subsites to be involved (40.8%) followed by 1 subsite (26.5%). To delineate whether the extent and type of surgery was affected by number of subsites affected by cholesteatoma, the number of subsites (1, 2, 3, 4 or more) was explored using Fisher’s exact test against EES grade, need for OCR and need for access procedure. Increasing number of subsites affected by cholesteatoma accurately predicted decreasing use of the endoscope (P>0.0005), increased need for OCR (P>0.012) and access procedures (mastoidectomy, P>0.0005; canaloplasty, P>0.021). The Fisher’s exact test was used due to small numbers in each group and therefore no effect size metric calculated.

Operative details

Most ears, 32 overall, underwent total EES (65.3%) (EES Grade 3) and a further 12 (24.5%) had the majority of the operation performed endoscopically (EES Grade 2b). A total of 33 ears required at least 1 access procedure, including 31 atticotomies, 13 CWUM and 4 canaloplasties. A total of 10 ears required atticotomy and mastoidectomy and 2 ears required canaloplasty, mastoidectomy and atticotomy. The atticotomy was reconstructed with cartilage in 29 of 31 cases and myringoplasty was performed in all 49 ears, with 47 using cartilage. A total of 31 ossicular chains reconstructions (OCRs) were performed of which 11 were primary and 20 were secondary. One patient was pending an OCR at time of data collection and 1 patient had a dehiscent facial nerve prolapsing over the oval window and therefore no OCR was performed. Operative details are summarised in Table 3.

Follow-up and residual/recurrent disease

Average follow-up time was 30.6 months with a range of 12.2 to 74.6 months. A total of 32 patients underwent planned second-stage surgery, either for confirmation of disease clearance or OCR with a mean time to second-stage surgery of 12 months (range, 2–31 months). Two patients had surgery for recurrence, bringing the total number of patients who had further surgery to 34. Overall, 35 ears had at least one surveillance scan with the most recent scan being CT in 16 ears, MRI in 8 and CT/MRI in 11.

There was a total of 16 residual cholesteatomas (32.7%) and 1 recurrent cholesteatoma. There were an additional 5 patients who developed recurrent retractions (1 grade I, 2 grade II, 1 grade III, 1 grade IV); 25% (4/16) of disease recidivism occurred more than 2 years after primary surgery. Due to the low numbers of recurrent disease, analysis of risk factors was restricted to residual disease. Univariate logistic regression was used to determine predictors of residual disease (Table 4). The need for atticotomy and disease within the epitympanum were significant predictors of residual disease. A multivariate analysis was performed but only epitympanic disease was significant, yielding the same results as the univariate model for residual disease.

To determine the effect of mastoidectomy on residual disease in patients with epitympanic disease, patients with epitympanic disease with and without recurrence were compared with respect to whether mastoidectomy was performed. In patients who had mastoidectomy, 4 had recurrence (4/11=36%) compared to those who 9 did not have mastoidectomy (9/16=56%) although this difference was not significant (P=0.4401).

One patient developed an external canal pearl that was exteriorised in clinic. Three patients underwent revision OCR—two for primary OCR failure and one due to residual disease. One patient had a residual tympanic membrane perforation that was monitored.

Audiological outcomes

Audiological outcomes were analysed for 47 of the 49 ears. Improvement of hearing occurred in 37 out of 47 (78.7%) (range, 1.25–45 dB). Seven patients had a mild reduction in hearing post-treatment (range, 1.25–15 dB) and 3 had no change in their pure tone average (PTA). A summary of audiometric results is found in Table 5. The PTA change was statistically significant with a mean difference of 16.0 decibels (95% CI: 11.5–20.6, P<0.001). Comparison of pre and post-operative PTA is displayed in Figure 1. Change in PTA was compared between timing of OCR (primary vs. secondary) and type of OCR (total vs. partial) with no statistically significant difference found (P=0.069, P=0.4735). PTA of patients with residual cholesteatoma was compared to those without residual cholesteatoma, with no statistically significant difference in post-treatment PTA (P=0.442).

Figure 1 Pre- and post-operative PTA. PTA, pure tone average.

Discussion

Paediatric cholesteatoma has been reported to have higher rates of recidivism than adult populations (19). Inconsistent periods of follow-up across the literature make comparisons of recidivism rates difficult. Different methods of estimating recurrence rates can produce markedly different results, with one study showing a range of 30–67% from the same data (20).

Reported recidivism rates in paediatric acquired cholesteatoma vary widely across the literature, with large differences reported depending on surgical approach, length of follow-up, type of cholesteatoma (i.e., congenital and/or acquired) and cohort size. Pareschi et al. reported a paediatric recidivism rate of 10.1% (residual 8.6%, recurrence 1.5%) in 895 patients with 10 or more years of follow-up after Canal Wall Down Mastoidectomy (CWDM) as primary surgery for cholesteatoma (21). Darrouzet et al. reported a residual rate of 21.5% and recurrence rate of 9.8% in 215 paediatric ears treated with a variety of microscopic techniques with minimum follow-up of 25 months (22). Another large study of 236 paediatric ears with a minimum of 4 years follow-up demonstrated an overall recurrence rate of 13.6% with a significant difference between patients undergoing CWUM c.f CWDM (21% vs. 7.6% respectively) (10). Smaller studies of less than 50 patients have reported recurrence rates as high as 46% (23,24).

A randomized control trial comparing residual cholesteatoma after endoscopic CWUM and traditional CWUM showed a statistically significant reduction in recurrence for pars tensa cholesteatoma with endoscope use (13.3% vs. 47.1%) (25). Sarcu et al. reported on residual cholesteatoma rates after endoscopically assisted cholesteatoma removal with and without planned second-look surgery (13). Overall recurrence rate was 16.7% (7/42) but was higher in the group undergoing planned second-look surgery 42% (5/12) compared to those without 7% (2/30). Another small study of 30 paediatric patients demonstrated a recidivism rate of 20% (relapse 10%, recurrence 10%) with a minimum follow-up of 12 months (11).

The recidivism rates in this study sit at the higher end of the rates reported in the literature, which may reflect the higher rates of re-look surgery, paediatric cohort and longer periods of follow-up reported than other studies. The low rate of true recurrent cholesteatoma in this cohort may reflect the almost universal use of cartilage to reconstruct atticotomy defects and for tympanic membrane reconstruction.

Multiple risk factors for cholesteatoma recidivism have been reported in the literature. Decreasing age has been associated with increased risk of recidivism (26,27) with multiple recidivism more common in younger cohorts than single (28). Size of cholesteatoma has also been associated with increasing rates of recidivism including, increasing size (26), multiple sites (28) and certain subsites such as sinus tympani and facial nerve recess (29). Ossicular chain involvement and inability to Valsalva have also been associated with higher rates of recidivism (26).

The findings of this study demonstrate a significant increase in the risk of residual disease with epitympanic disease, as demonstrated by higher rates of residual in patients undergoing atticotomy and those with epitympanic cholesteatoma. Similarly, Hermann et al. reported on patients requiring at least 3 surgeries for cholesteatoma eradication and demonstrated increasing rates of combined mesotympanic and epitympanic disease with increasing number of residual disease (28). The cause for the higher rates of residual disease in patients with epitympanic disease may be due to poor superior and lateral access with endoscopes, particularly in patients with large pneumatized attics. The high residual rate in a relatively small number of cases in this cohort spread across 4 surgeons, may also reflect the learning curve in managing attic cholesteatoma endoscopically.

Kwinter et al. reported no difference in audiological outcomes in ossicular chain reconstruction between endoscopic and microscopic approaches after previous cholesteatoma surgery in a paediatric population (30). They also reported a serviceable hearing rate (defined as PTA of less than 30 dB) of only 50%, significantly less than the 79.6% achieved in this cohort. The rates of post-operative normal hearing in this cohort of 57% (PTA of 20 dB or less) is also significantly higher than the 34–48% rate reported in the literature (30,31). Although there are only small numbers in this study cohort, no significant difference in audiological outcome was seen between patients with and without recidivism. This finding was also demonstrated in cohorts requiring multiple re-operations for recurrence, with no statistically significant reduction in hearing outcomes with increasing number of surgeries (28).

Based on the findings above, totally endoscopic approaches for cholesteatoma appear particularly useful in patients with mesotympanic, protympanic and isolated retrotympanic disease with low rates of recidivism and good audiometric outcomes. In contrast, disease involving the epitympanum and antrum may be considered for more posterior approaches including EES assisted CWUM and posterior atticotomy to reduce rates of recidivism.

Ultimately, deciding on a surgical approach in paediatric cholesteatoma should not only consider recidivism rates and the need for multiple operations/general anaesthetics, but also the hearing and long-term quality of life impact of surgery with respect to external scars and the need for mastoidectomy cavity maintenance. CWDM is likely to have the lowest rates of disease recidivism at a cost increased morbidity, particularly in paediatric patients that may require lifelong follow-up.

Avoiding mastoidectomy and minimising recurrence requires careful consideration of the pathological characteristics of the individual patient. As previously discussed, traditional CWUM recurrences are generally found within the retrotympanum and protympanum, areas that are particularly amenable to endoscopic examination and therefore may be best approached via ESS. In contrast, as demonstrated by the findings of this study, EES is more likely to fail in the attic and therefore disease present there should prompt consideration of more invasive techniques to avoid high rates of recurrence.

This study is limited by its retrospective nature and lack of a comparative cohort to compare the differing surgical techniques. Follow-up periods, although longer than other studies reported in the literature, was inconsistent across the cohort and not all patients reached the three-to-five years follow-up period that had a high number of recurrences. The patients were also managed by 4 different surgeons with widely varying surgical numbers (range, 3–24) and individualised treatment plans without protocolised management. Follow-up of patients was not standardised, and in particular surveillance method was variable which may lead to under reporting of residual disease in those patients not undergoing repeat imaging or planned second-look surgery.

Conclusions

EES has very low rates of recidivism for mesotympanic and retrotympanic disease in paediatric acquired cholesteatoma. In patients with epitympanic disease, endoscopically assisted CWUM to reduce the rates of recidivism, may be warranted.

Acknowledgments

This work was supported by remunerated statistical analysis from R. Maldonado. Data in this study was presented at EES 2022 4^th World Congress on Endoscopic Ear Surgery at Kyoto, Japan Dec 5^th-8^th 2022 as “Predictive factors of Recidivism in Paediatric Acquired Cholesteatoma treated with Endoscopic Ear Surgery”.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://www.theajo.com/article/view/10.21037/10.21037/ajo-23-53/rc

Data Sharing Statement: Available at https://www.theajo.com/article/view/10.21037/ajo-23-53/dss

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-23-53/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-23-53/coif). A.S. serves as an unpaid editorial board member of Australian Journal of Otolaryngology from January 2019 to December 2024. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Ethical approval for this research was granted by North Sydney Local Health District Research Committee under existing approvals for outcomes in endoscopic ear surgery (HREC reference: LNR/18/HAWKE/38). Because of the retrospective nature of the research, the requirement for informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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