32nd ESPU Congress in Ghent, Belgium

S04: VESICOURETERAL REFLUX

Moderators: Anju Goyal (UK), Yazan Rawashdeh (Denmark)

ESPU Meeting on Thursday 9, June 2022, 08:20 - 09:15


08:20 - 08:23
S04-1 (OP)

★ LONG-TERM RESULTS OF RANDOMIZED CLINICAL TRIAL BETWEEN POLYACRYLATE-POLYALCOHOL COPOLYMER (PPC) AND DEXTRANOMER-HYALURONIC ACID COPOLYMER (DX/HA) AS BULKING AGENTS FOR ENDOSCOPIC TREATMENT OF PRIMARY VESICOURETERAL REFLUX (VUR)

Luis GARCIA-APARICIO 1, Oriol MARTIN-SOLE 2, Isabel CASAL-BELOY 2, Clara MASSEGUER 2, Mario CUESTA 2 and Sonia PEREZ-BERTOLEZ 2
1) Sant Joan de Deu-Barcelona Children's Hospital. University of Barcelona, Pediatric Urology Div. Pediatric Surgery Dept., Barcelona, SPAIN - 2) Sant Joan de Deu, Barcelona Children's Hospital. University of Barcelona, Pediatric Urology Div. Pediatric Surgery Dept., Barcelona, SPAIN

PURPOSE

To compare long-term outcome of endoscopic treatment of VUR using PPC or Dx/HA 

MATERIAL AND METHODS

From October 2014 to April 2017 patients with VUR >= 3 that needed endoscopic treatment (ET) were eligible for this randomized clinical trial. Patients were randomized in two groups: PPC group and Dx/HA group.  After endoscopic treatment a voiding cystourethrography (VCUG) was performed at 6 months; if VUR was still present a second and last ET was performed.  

A VCUG was performed 36 months postoperatively in successful patients in order to compare long-term outcome. 

RESULTS

Short-term results. Forty six patients were eligible but 2 did not accept the trial, then 44 patients with 63 refluxing ureters (RU)>=3 were included. PPC group: 21 patients (29 RU); and Dx/HA group: 23 patients (34 RU). Short-term radiological success rate was 82.75% of RU in PPC group and 79.4% in Dx/HA group (p=0.496).  

Long-term results. Thirty six patients (51 RU) were successfully treated.  Three patients were lost in long-term follow-up, and then 33 patients (48RU) were included. PPC group: 18 patients (23 RU); and DX/HA group 15 patients (25 RU). VCUG at 36 months showed a success rate of 91.3% (21/23) of RU in PPC group and 92% (23/25)of DX/HA group (p>0.05). 

Overall radiologicaL successful rate was during this period was 21/28 RU (75%) in PPC group and 23/32 (71.8%) with no statisticall diferences.

Mean follow-up was 38.7 (36.9-40.1) months in PPC group and 39.36 (35.1-46.3) months in PPC group with no statistical differences.

Two patients with 2RU in PPC group had late ureteral obstruction that needed ureteral reimplantation, 41 and 62 months after successful injection, but there were no statistical diferences with Dx/HA group.

CONCLUSIONS

PPC and Dx/HA has similar short and long-term outcome. We must warn that ureteral obstruction could be present at long-term follow-up in those patients treated with PPC.


08:23 - 08:26
S04-2 (OP)

IS ENDOSCOPIC INJECTION BETTER THAN ANTIBIOPROPHYLAXIS FOR THE MANAGEMENT OF OCCULT VESICOURETERAL REFLUX DETECTED BY PIC CYSTOGRAPHY IN CHILDREN ? A PROSPECTIVE STUDY FROM TWO CENTERS.

Anthony KALLAS CHEMALY 1, Chebl MOURANI 2, Paul-Henri TORBEY 2, Carla HABER 2, Fouad AOUN 3, Darwich SERHAL 4, Jean BOULOS 5, Marie-Thérèse MERHEJ 5, Ghazi SAKR 6 and Maroun MOUKARZEL 3
1) Hôtel-Dieu de France University Hospital, Paediatric Urology, Beirut, LEBANON - 2) Hôtel-Dieu de France University Hospital, Paediatrics, Beirut, LEBANON - 3) Hôtel-Dieu de France University Hospital, Urology, Beirut, LEBANON - 4) Mount Lebanon Hospital, Gharios Medical Center, Pediatrics, Beirut, LEBANON - 5) Mount Lebanon Hospital, Gharios Medical Center, Paediatrics, Beirut, LEBANON - 6) Mount Lebanon Hospital, Gharios Medical Center, Urology, Beirut, LEBANON

PURPOSE

When standard VCUG doesn't show VUR in children with recurrent febrile UTIs, clinical management is controversial. PIC cystography may reveal occult VUR. The objective of our study is to compare the efficacy of endoscopic injection to continuous antibiotic prophylaxis (CAP) for the treatment of occult VUR in children.

MATERIAL AND METHODS

Between 2015 and 2018, we prospectively enrolled 47 patients with recurrent febrile UTIs, normal standard VCUG and occult VUR on PIC cystography. Patients with associated uropathy, LUTD and severe constipation were excluded. Patients were divided into two groups. Group A had STING injection with dextranomer/hyaluronic acid copolymer. Group B received trimethoprim/sulfametoxazole at a dose of 2mg/kg daily for 3 years. DMSA renal isotope was performed on initial evaluation. Recurrent febrile UTIs were reported. Redo-PIC cystography was performed in breakthrough febrile UTI cases and at 3 years from treatment.

RESULTS

During this 3-year period, 39 patients were included (21 patients in group A and 18 patients in group B) with a follow-up of 3 years. The two groups were homogeneous according to age, sex, renal function on initial evaluation, grade and laterality of VUR. All cases were grade I to III VUR. Recurrent febrile UTIs on follow-up were similar between the two groups, reported in 4.8% of group A and 11% of group B , p=0.58. Redo-PIC cystography in these cases showed persistent VUR treated by ureteral reimplantation. Redo-PIC cystography at 3 years of follow-up in each group revealed persistent VUR in 5% of group A versus 25% of group B , p=0.03. These cases were managed by ureteral reimplantation.

CONCLUSIONS

Endoscopic injection shows similar efficacy as CAP for the prevention of recurrent febrile UTIs in occult VUR in children. Resolution rate of occult VUR at 3 years of follow-up is higher with endoscopic injection treatment. However, this conclusion needs to be confirmed by randomized studies with large groups.


08:26 - 08:29
S04-3 (OP)

IS "ROUTINE" VOIDING CYSTOURETHROGRAM (VCUG) NECESSARY AFTER ROBOTIC URETERAL REIMPLANTATION FOR PRIMARY VESICOURETERAL REFLUX IN PEDIATRIC AGE GROUP?

Amr A. ELBAKRY 1, Khaled ALDABEK 2, Tyler TRUMP 1 and Osama AL-OMAR 1
1) West Virginia University Hospital, Urology, Morgantown, USA - 2) West Virginia University School of Medicine, Urology, Morgantown, USA

PURPOSE

American Urological Association guidelines recommend follow-up VCUG after endoscopic management, however it is listed as an “Option” after open reimplantation giving high resolution rate after open surgery 98.1% (95% CI: 95.1-99.1). There was no recommendation regarding robotic reimplantation. We are aiming to shed the light on this topic in our study.  

MATERIAL AND METHODS

We retrospectively reviewed all pediatric patients who underwent robotic reimplantation. We identified 29 patients between July 2018 and December 2021. We excluded 5 patients who did not have follow-up VCUG. The remaining 24 patients were included in this study. Patients’ demographics, perioperative data, and outcomes were collected and reviewed.

RESULTS

24 patient (25 ureters) had postoperative VCUG (83%). Patients’ mean age is 6 (SD 2.1) years. Most patients (52%) had grade 3 reflux. One patient underwent bilateral reimplantation. Mean operative time was 157 min (SD 29.3). The tunnel length was 3.4 (SD 0.5) cm. No reported intraoperative complications. Hospital stay was less than 24 hours in 23 (95.8%) patients. Urinary extravasation that required stent placement was reported in a bilateral reimplantation.  Subsequent evaluation showed complete healing with no long-term consequences.  Postoperative VCUG showed complete resolution of reflux in all ureters except one patient (96%), who showed improvement from grade 4 down to 1. Also, 4 patients (16.6%) developed de novo contralateral grade 1 reflux.

CONCLUSIONS

Giving similar success rate of robotic ureteral reimplantation to those in open approach, we suggest that VCUG should not be “routinely” done after robotic ureteral reimplantation once the surgeon complete the learning curve. 


08:29 - 08:32
S04-4 (OP)

IN THE DIAGNOSIS OF VESICOURETERAL REFLUX, IS CYSTOGRAPHY UNDER GENERAL ANESTHESIA AS ACCURATE AS CYSTOGRAPHY UNDER LIGHT SEDATION?

Michael FRUMER, Bezalel SIVAN, Tal MAY, Roy MORAG, Dmitry KHUNOVICH and David BEN MEIR
Schneider Children's Medical Center of Israel, Urology, Petah Tikva, ISRAEL

PURPOSE

To alleviate children's anxiety, there are institutes where catheter insertion and cystography are performed under general anesthesia. This study compares cystography under light sedation to cystography under general anesthesia, in the same subjects.

MATERIAL AND METHODS

Data were collected on children who were diagnosed with vesicoureteral reflux (VUR) by cystography performed under light sedation and underwent endoscopic injection to correct the VUR. Children who also underwent cystography under general anesthesia, on the operating table prior to injection, were included. This cystography was compared to the cystography performed without general anesthesia. Chi-square and Mann–Whitney U tests were used.

RESULTS

Between 10/2017 and 8/2021, 56 children were operated on and performed both cystographies. Median age was 3 years (IQR 1.5-5). Median time from cystography without to cystography with general anesthesia was 3.8 months (IQR 2.7- 5.9). Among 56 children, 88 cases of VUR were found in the cystography without general anesthesia, considered as gold standard.

Cystography under general anesthesia was found to have sensitivity, specificity, negative and positive predictive value of 0.44, 0.83, 0.29 and 0.91 (Table). Cohen’s Kappa coefficient 0.16.

Renal units with VUR Renal units without VUR Total
Cystography under general anesthesia VUR was detected 39 4 43
VUR was not demonstrated 49 20 69
Total 88 24 112

No significant difference was found in sensitivity or negative predictive value of cystography under general anesthesia between groups divided by: the presence of hydronephrosis or the presence of a hydroureter, VUR grades 1-2 versus grades 3-5 or a ureteral diameter ratio below versus above 0.25. 

CONCLUSIONS

The sensitivity and negative predictive value of cystography under general anesthesia are very low. Clinical decision relying on this cystography is questionable.


08:32 - 08:46
Discussion
 

08:46 - 08:49
S04-5 (OP)

★ THE ROLE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO AS A PREDICTOR OF SPONTANEOUS RESOLUTION OF PRIMARY VESICO-URETERAL REFLUX IN PATIENTS WITH ASSOCIATED ACUTE PYELONEPHRITIS

Carlos DELGADO-MIGUEL 1, Antonio MUÑOZ-SERRANO 1, Lucas MORATILLA 1, Virginia AMESTY 2, Susana RIVAS 2, Roberto LOBATO 2, Pedro LÓPEZ-PEREIRA 2 and María José MARTINEZ-URRUTIA 2
1) La Paz Children's Hospital, Pediatric Surgery, Madrid, SPAIN - 2) La Paz Children's Hospital, Pediatric Urology, Madrid, SPAIN

PURPOSE

Neutrophil-to-Lymphocyte ratio (NLR) has been recently postulated as an inflammatory biomarker for the diagnosis of vesico-ureteral reflux (VUR). The aim of this study is to determine the role of NLR as a predictor of spontaneous resolution of primary VUR in patients with associated acute pyelonephritis (APN).

MATERIAL AND METHODS

A retrospective single-center case-control study was performed in patients with APN episodes with associated primary VUR diagnosed between 2012-2018. Patients were divided into two groups according to the evolution of primary VUR after APN: group A (spontaneous resolution before 3 years of age) and group B (no spontaneous resolution after 3 years of age). Demographic, prenatal, laboratory, microbiological and radiological variables were analysed. Sensitivity and specificity for spontaneous resolution of VUR was determined by ROC curves.

RESULTS

A total of 1,146 episodes of APN were analysed of which 294 patients with APN and associated primary VUR were finally included in the study, with a median age at APN diagnosis of 11 months. No differences in demographic, prenatal, microbiological and radiological characteristics were observed between the two groups. Patients in group B had significantly higher levels of leukocytes, neutrophils, INL, C-reactive protein and creatinine. NLR was the parameter with the highest area under the curve (AUC=0.966) for predicting the absence of spontaneous resolution of VUR (cut-off point=3.41) with a sensitivity of 92.7% and specificity of 91.1%.

CONCLUSIONS

NLR is postulated as a simple and cost-effective predictor of clinical outcome of VUR, which correlates negatively with spontaneous resolution of primary VUR after an episode of APN.


08:49 - 08:52
S04-6 (OP)

VESICOURETERAL REFLUX INDEX; FROM MEDICAL PUBLICATION TO CLINICAL APPLICATION

Ahmed ELHELALY 1, Abdulhakim ALOTAY 1, Abdullah ALROMAIH 2, Abdullah ALHUSSAIN 1 and Osama SARHAN 3
1) Prince Sultan Military Medical City, Urology, Riyadh, SAUDI ARABIA - 2) King Faisal Specialist Hospital and RC, Dept. of Urology,, Riyadh, SAUDI ARABIA - 3) King Fahad Specialist Hospital,, Dept. of Urology, Dammam, SAUDI ARABIA

PURPOSE

Vesicoureteral reflux (VUR) is the commonest urological pathology found in children with febrile urinary tract infections. The aim of management is to save the kidneys. VUR index (VURx) is a 6-point scale that predicts VUR resolution in children. Two publications validate the index in children, the first for children below 2 years and the other revalidated in children above 2 years age. We aimed to revalidate VURx, irrespective of the patient age, to predict spontaneous VUR resolution/improvement.

MATERIAL AND METHODS

Ninety three patients were identified in the period between (2010-2017) with VUR. Medical records were reviewed for patients' sex, age at diagnosis, antenatal history, clinical presentation, timing and grade of VUR on voiding cystourethrogram (VCUG), ureteral anomalies, indications for surgical intervention, and surgical approaches. We assigned a 1-6 point scale as follows: early to mid-filling reflux (3 points), late filling (2 points), voiding-only (1 point), female gender (1 point), VUR grades IV-V (1 point), complete duplicate ureter and/or paraureteral diverticulum (1 point). Grades of VUR were recorded based on the initial and by end-of-follow-up VCUG. Improvement is defined as ≥2 grades downgrading of VUR. Clinical and radiological outcomes were assessed.

RESULTS

Ninety two patients were included. Numbers of patients with VURx (1-5) were 11 (11.9%), 32 (34%), 28 (30.4%), 13 (14.1%), 8 (8.6%) respectively and patients with VURx 6 were 2, so grouped with VURx 5. After median follow up period of 8 years, patients with VURx 1,2,3,4,5 have had spontaneous resolution/improvement rates of 90%, 89% 84, 30 and 15%(p-value is < 0.00001) . Surgical intervention rates were 2%, 5%, 8%, 16% and 60% in patients with VURx of 1-5 respectively.

CONCLUSIONS

VURx is an effective clinical tool for physicians who are managing children with congenital primary VUR in providing a care-plan for them together with counseling of their families. It provides a reproducible indicator regarding chance of resolution/improvement and possibility of surgical intervention.


08:52 - 08:55
S04-7 (OP)

DOES THE SONIC HEDGEHOG SIGNALLING PATHWAY PLAY ROLE IN ANTI-REFLUX MECHANISM OF BLADDER IN CHILDREN?

Eda TOKAT 1, Mustafa Ozgur TAN 2 and Serhat GUROCAK 2
1) Ankara Research and Training Hospital, Urology, Ankara, TURKEY - 2) Gazi University School of Medicine, Paediatric Urology, Ankara, TURKEY

PURPOSE

A hedgehog family ligand namely Sonic Hedgehog (SHH) was reported to be important in development of bladder and ureter smooth muscle. In this study we aimed to determine protein expression of SHH in resected ureterovesical junction segments of children with vesicoureteral reflux (VUR).

MATERIAL AND METHODS

The study group included 19 children; 12 (63%) girls, 7 (37%) boys, who had ureteroneocystostomy (UNC) operation; 3(15.7%) right sided, 7(36.8%) left sided, 9(47.3%) bilateral, due to primary VUR between years 2015-2018. Totally 28 ureterovesical junction segments were examined for Western Blot analysis to determine related protein expression levels of SHH genes signalling pathway in the ureterovesical junction specimens.

RESULTS

The mean Western blot band area of SHH gene pathway related protein was 3880.69 (2059.55-13941.61) while the mean area of β-Actin, the house-keeping gene, was 20180.25 (9530.39-26709.75) (p=0.001). Correlation analyses between grade of reflux and protein expression of SHH gene pathways revealed no significant relation (p=0.300). When the UV samples were grouped as low and high grade reflux and compared in terms of SHH protein expression levels, no statistically significant difference was found between reflux groups (p= 0.818). Analysis comparing the specimens according to presence of scar formation revealed no statistically significant difference in terms of SHH protein expression (p=0.915). Additionally, there was no statistically significant difference between ≥40% and <40% differential function groups regarding SHH band area (p=1).

CONCLUSIONS

We concluded SHH signalling molecule which is effective in development of bladder and ureter smooth musculature, might also be effective in etiopathology of vesicoureteral reflux.


08:55 - 08:58
S04-8 (OP)

MATHEMATICAL ANALYSIS OF INDIVIDUAL BIOMARKER PROFILES OF KIDNEY DAMAGE IN CHILDREN WITH VESICOURETERAL REFLUX

Karmina DEMIDOVA, Vera ROSTOVSKAYA, Galina KUZOVLEVA and Eduard AYRYAN
I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Москва, RUSSIAN FEDERATION

PURPOSE

To determine the degree of damage of the renal parenchyma in children with grade II-IV VUR by hierarchical clustering based on the analysis of individual profiles of urinary biomarkers.

MATERIAL AND METHODS

The study compared the levels of urinary biomarkers IL-8, IL-18, MCP-1, VEGF, TGF-β1 excretion with clinical and anamnestic data of 101 patients with grade II-IV VUR aged 1 to 17 years (mean age 4.9±3.1 years) with a normal level of glomerular filtration rate. The control group consisted of healthy children (n=25) without kidney diseases.

RESULTS

he pathological excretion profile of urinary biomarkers with different composition and ratio of increase in their levels was noted in all patients, regardless of the degree and severity of reflux, age and gender (p>0.05). Using cluster analysis, patients were divided into three clusters depending on the similarity of individual biomarker profiles. Three main patterns of the spectrum of biomarkers determining the degree of tubulointerstitial kidney injury (TIKI) are identified. The first (I) pattern with low levels of excretion of all the studied markers (p<0.001) characterized a mild degree of TIKI and was noted in 61.5% of children. The second (II) pattern with average excretion rates of IL-8, IL-18, MCP-1, TGF-β1 (p<0.01) and high VEGF values (p<0.001) was regarded as a moderate degree of TIKI, observed in 32.2% of patients. The third (III) pattern with an excess of IL-8, IL-18, MCP-1 and VEGF levels by 2.5-17 times compared to the I and II patterns (p<0.01) determined the pronounced degree of TIKI and occurred in 6.1% of patients. With the same degree of VUR, there are different types of biomarker patterns.

CONCLUSIONS

The clustering method allows us to correlate individual profiles of urinary biomarkers of each patient with the selected patterns and stratify them into groups according to the severity of tubulointerstitial kidney damage, which is often not diagnosed according to imaging diagnostic methods.


08:58 - 09:15
Discussion