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.