Discussion
Despite the optimal management of reflux has been discussed over more than thirty years several times in the literature, it is still contradictory which type of treatment, medical or surgical is superior [1]. The main two aims of treating reflux is to avoid the development of new renal scars and to avoid the urinary tract infections in attempt to preserve kidney function [3]. From past to present treatment management has been based on age, sex, presence of renal scar, grade of reflux, laterality of reflux, presence of bladder dysfunction and toilet training. Starting from this contradiction about treatment of reflux, EAU published guidelines on VUR in second half of 2012 [6]. In the guidelines patients are grouped into three groups, according to being symptomatic/asymptomatic, gender, before or after toilet training (age), grade of reflux, presence of LUTD and kidney status. As well, initial and follow up treatment methods are suggested for each group.
According to EAU guidelines the hallmarks of low risk disease are normal kidneys, low grade reflux (grade 1-3) and absence of LUTD. In the low risk group, there are two options of initial treatment: either no treatment or CAP, similar to the AUA guidelines [6, 7]. In the classical and new guidelines, surgery is not offered to patients with grades 1-2 reflux, in the absence of breakthrough infections or new renal scars. With a minor difference in classical view, grade 3 reflux was not accepted as low grade and surgery was an option if persistent after 5 years of age [8]. Although it is not recommended to do surgery initially in low risk group, use of CAP in every reflux patient or observational management in primary reflux is still controversial. There are several studies declaring the efficacy of CAP, such as the well- known randomized studies; the PRIVENT study, the RIVUR study and Swedish Reflux Trial [9-14]. Nevertheless, a large number of studies supporting the insignificant difference between CAP and observational management in VUR were also carried out [15-18]. In our study, CAP was preferred in the initially conservatively treated group rather than no treatment. However, despite the guidelines there might be increased tendency to surgical interventions in the low risk group after 2013 but not significant.
In the moderate risk group, CAP is the offered initial treatment method and intervention may be considered in case of breakthrough infections and persistent reflux. Also LUTD treatment should be given if needed. In all groups treatment for LUTD was given initially and it was seen to be effective on clinical success of reflux treatment. In our study, performing surgery as initial treatment approach increased significantly in the moderate group after 2013 that might be partially related to the parental incompliance.
Increased surgical preference (UNC/endoscopic) as an initial treatment method in low (it was not significant though) and moderate risk groups might seem controversial but considered to reflect our cultural attitude towards definitive treatment. Initial preference of surgical treatments in these low grade refluxes (72 patients) representing incompatibility with the EAU guidelines, could be attributed to parental preference and patients coming from rural areas because of difficult follow up. The centers included in the study are referral centers and the patients usually come from distant regions. Thus the follow up could be problematic. The increase could also be attributed to increased surgical expertise and confidence in pediatric urology practice over the years in our country. In addition, our study has a retrospective design and nine clinics were included from different parts of the country. Due to the fact that pediatric urologists from different centers might have different treatment tendencies for the patient with similar clinical variables, this could be another reasonable explanation for the increased preference for surgical treatment modalities. In the study by Prisca et al. parental incompliance was a negative predictive factor in VUR resolution and these patients had a worsening tendency because of being un-followed. The authors proposed that parental compliance should be considered in EAU guidelines application[19].
The high risk disease is defined as high grade reflux (grade 4-5) and abnormal kidneys and the initial treatment is mostly suggested surgical in the EAU guidelines (greater possibility or may be considered) and definitely surgical in classical management strategies. In the high risk groups, the priority of open surgery, after the treatment of LUTD if needed (in symptomatic cases after toilet training with high grade reflux and abnormal kidney) [6]. In our study we determined increased preference of surgical treatments as initial method in the high risk group after 2013. This is usual and in concordance with the guidelines. The result was in compliance with the recommendations of the guidelines. Consequently, there was preference of surgical methods in all groups after 2013. Before 2013 we were classically treating patients surgically according to age (being <1, 1-5 or >5), gender (female), grade of reflux, presence of additional ureteral anomaly and renal functions-renal scar on DMSA scan [8]. In the meantime, we accepted persistent reflux-hydronephrosis and new renal scar formation or breakthrough infections while the patient is under antibiotic prophylaxis as surgical indications in low-moderate risk groups.
Success rates of treatment in high risk group were not different after 2013, because of the same attitude towards the more successful UNC before and after 2013. In low and moderate risk groups guidelines prefer conservative methods first and if necessary surgery as the next step. However, performing surgery as the initial treatment approach increased in all groups after 2013 as patients were increasingly referred from rural areas (risk of lost to follow up and parental preference). The decreased success rate after 2013 in initially surgically treated group could be attributed to multiple factors. Pediatric urology is still evolving in our country within time and all the institutions included in this study are training centers. Thus there is increasing variability and divergence in treatment attitudes among regions effecting success rates throughout the country. There is surely increasing population and immigration in our country and easy transportation facilities have been causing increased referral. This decrease in success rate should alert us about more serious consideration and concordance with the new EAU guidelines on VUR. These factors might be also related to our overall surgical success rate for reflux surgery (both endoscopic and UNC) that was 72.6%. Success rates of endoscopic and UNC operations were 65% and 92.9% before 2013, 60% and 78.5% after 2013, respectively. Thus the overall success rate for surgery was 72.6%. There was significant difference between success rates of UNC operations before and after 2013(p=0.000), while the difference was not significant in the STING group (p=0.076).This could be partly due to increased preference of surgical treatments as initial method in the high risk group after 2013. The high risk disease is high grade reflux (grade 4-5) that is usually treated with UNC and more technically demanding compared to UNC’s done for lower grades of reflux. Also the centers included in the study were referral (complicated cases) and teaching institutions.
The main limitations of the study are being retrospective and multi-central. Thus, institutional preferences and success achievements could be variable. However, the study represents large number of patients and a wide and scattered spectrum of treatment attitude towards reflux treatment in our country. All the centers included known to be experienced in pediatric urology in our country and patients were accepted from pediatric nephrologists when the medical treatment fails thus the study reflects a selection bias for surgery. Pediatric nephrologists follow-up successful patients with medical therapy and refers urologists unsuccessful patients for the surgical option so this results in uneven distribution of the sample.