Ureteroscopy for Stone Disease in Paediatric Population is Safe and Effective in Medium-Volume and High-Volume Centres: Evidence from a Systematic Review

Purpose of Review The incidence of urinary stone disease among the paediatric population is increasing. Whilst there has been a rise in the number of original studies published on ureteroscopy (URS) in children, critical review still remains under-reported. Recent Findings A Cochrane style systematic review was performed to identify all original articles on URS (minimum of 25 cases) for stone disease in paediatric patients between Jan. 1996 and Dec. 2016. Based on the number of reported cases, centres were divided into medium (25–49 cases) and high (≥ 50 cases) volume studies. Thirty-four studies (2758 children) satisfied our search criteria and were included in this review. The mean stone size was 8.6 mm with an overall stone-free rate (SFR) of 90.4% (range 58–100). Medium-volume centres reported a mean SFR of 94.1% (range 87.5–100), whilst high-volume centres reported a mean SFR of 88.1% (range 58–98.5). Mean number of sessions to achieve stone-free status in medium-volume and high-volume groups was 1.1 and 1.2 procedures/patient respectively. The overall complication rate was 11.1% (327/2994). Breakdown by Clavien grade was as follows: Clavien I 69% and Clavien II/III 31%. There were no Clavien IV/V complications, and no mortality was recorded across any of the studies. The overall failure to access rate was 2.5% (76/2944). Medium-volume and high-volume studies had overall complication rates of 6.9% (37/530) and 12.1% (287/2222) respectively, but there was no significant difference in major or minor complications between these two groups. Summary Ureteroscopy is a safe and effective treatment for paediatric stone disease. Medium-volume centres can achieve equally high SFRs and safety profiles as high-volume centres. Despite the rarity of paediatric stone disease, our findings might increase the uptake of paediatric URS procedures.


Introduction
The incidence of urinary stone disease among the paediatric population is rising [1]. This has led to the development of minimally invasive and effective endourological interventions that can yield a high stone clearance whilst preserving renal function with low morbidity in these children. In the adult population, application of ureteroscopy (URS) globally has expanded over 200% in the past decade [2•]. This shift owes largely to major advances in surgical technique, laser technology and equipment minimisation. Similar changes have been mirrored in the management of paediatric stone disease, although Ritchey et al. first described URS in a young child in 1988 [3]. Whilst there has been a rise in the number of original studies published on this topic, critical evaluation of the safety and efficacy of URS for paediatric cases remains under-reported. The objective of this study was to therefore formally appraise the existing evidence. Furthermore, given the dissemination of URS and that its uptake is no longer limited to specialist centres, we sought to determine if there were any differences in clinical outcomes among these high-volume centres compared to those reporting medium volumes. All study types were considered for potential inclusion. A time restriction was applied to include relevant studies published between January 1990 and December 2016. Paediatric age was defined as 18 years or less. Studies combining adult and paediatric populations with no breakdown of results were excluded.

Secondary Outcomes
& Comparison of outcomes for ureteroscopy performed in medium-volume centres (reporting 25-49 procedures) and high-volume centres (reporting ≥ 50 procedures).

Data Extraction and Analysis
Both the search process and data extraction were performed by two authors (SR, PJ) independently and overseen by the senior author (BKS). Information was also collected on patient characteristics, total number of procedures performed and stone location. For the purposes of this review, centres reporting on 25-49 procedures were termed 'medium-volume' and ≥ 50 procedures as 'high-volume' centres. We did not include studies from centres that reported on < 25 procedures, which were deemed to be low-volume centres.
Complications recorded intra-operatively or within the study follow period were included for analysis. Chi-squared test and independent t test were used for dichotomous and continuous data respectively (SPSS version 21).

Outcome Measures
All studies reported SFR, with an overall SFR of 90.4% (range 58-100). Medium-volume centres reported a mean SFR of 94.1% (range 87.5-100). High-volume centres reported a mean SFR of 88.1% (range 58-98.5). Mean number of sessions to achieve stone-free status in medium-volume and high-volume groups was 1.1 and 1.2 procedures/patient respectively ( Table 2).
Across all the included studies, the overall complication rate was 11.1% (327/2994). Breakdown by Clavien grade was as follows: Clavien I 69% and Clavien II/III 31% (Table 3). There were no Clavien IV/V complications, and no mortality was recorded across any of the studies.
Medium-volume and high-volume studies had overall complication rates of 6.9% (37/530) and 12.1% (287/2222) respectively. There was no significant difference in major or minor complications between these two groups. The overall failure rate was 2.5% (76/2944). Most of them were due to failure to access the paediatric ureter.

Findings and Implications of Our Review
This is the largest review on paediatric URS to date and reveals an overall SFR of 90.4% and an overall complication rate of 11.1%. Over two thirds of these complications were Clavien I. Importantly, there was no significant difference in SFR or complication rates between medium-volume and high-volume centres.

PCNL in Paediatric Population
Percutaneous nephrolithomy (PCNL) and shockwave lithotripsy (SWL) represent the key alternative interventions to URS. Whilst the former can achieve high stone-free rates in a single procedure and is not limited by failure to access the ureter such as can occur in URS, it carries a worse morbidity profile, notably in the form of haemorrhagic complications. Bhageria et al. reported transfusion rate of 9% in their retrospective cohort of 95 children undergoing PCNL [38]. Miniaturisation of standard equipment (< 24Fr) has delivered a key strategy for improving its safety status both in adult and paediatric populations. Multiple studies have confirmed higher incidence of haematuria and renal extravasation associated with the use of larger tract sizes [39]. PCNL can now even be delivered in the 'micro' format using a 4.5Fr tract with final SFRs reported between 80 and 100% [39]. Its use for treatment of ureteric stones however remains less valuable [40].

SWL in Paediatric Population
Shockwave wave lithotripsy is a minimally invasive option, with a relatively short learning curve and generally minor complications [40]. It has traditionally been the first-line intervention for paediatric stone disease. However, it can necessitate multiple sittings and in children generally requires administration of general anaesthetic. Additionally, SFRs are less predictable with stone recurrences commonly due to incomplete stone clearances [41].

Future Trends in Ureteroscopy
With increased uptake of URS, it looks set to reach an increasing number of endourological milestones. URS has also undergone the miniaturisation process. Utangac et al. recently reported using a micro-ureteroscope (4.5Fr along entire length) in 11 children with a median stone size of 10.5 mm [41]. Stone-free status was achieved in all cases. There were no intra-operative complications and only one case of transient haematuria post-operatively. This novel modification may prove extremely valuable and allow better ureteric cannulation/navigation with fewer cases of access failure. However, further studies are needed comparing it with standard URS.

Limitations of Our Study
Whilst this study represents the largest review to date on paediatric URS, there are certain limitations, which the authors acknowledge. Results have been included from predominantly retrospective studies with age ranges spanning development of the urinary tract from infancy to adult state. The heterogeneity of available evidence did not allow for formal metaanalysis to be performed. In comparison, we did find a relatively higher stone-free rate with lower complications in medium-volume centres. However, we feel that this might reflect higher complexity of cases in established endourology high-volume centres. Similarly, training and guidance on 'tips and tricks' of ureteroscopy might help improve outcomes in less well-established paediatric stone centres [42,43].

Conclusion
URS is a safe and effective treatment for the treatment of stone disease among the paediatric population. Medium-volume centres can achieve equally high SFRs and safety profiles as high-volume centres. The findings of this review may therefore support increased uptake of URS in centres performing fewer procedures each year.

Compliance with Ethical Standards
Conflict of Interest Shazna Rob, Patrick Jones, Amelia Pietropaulo, Stephen Griffin and Bhaskar K. Somani each declare no potential conflicts of interest.
Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
Open Access This article is distributed under the terms of the Creative Comm ons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.