Endoscopic treatment of Vesico-ureteric reflux in Children Paediatric Surgical Centre Kowloon Central & East Cluster Hospital Authority, Hong Kong SAR Dr. Beatrice Wong

Vesico-ureteric reflux (VUR) Flap-valve mechanism at UVJ Retrograde flow of urine from the bladder back up the ureters Primary Vs Secondary

Primary VUR 1% of children in normal population M: F= 1: % of children with UTI Major cause of end stage renal failure in children and young adults Siblings of children with VUR have a much higher incidence of VUR

The International Reflux Classification A: Grade I reflux B: Grade II reflux C: Grade III reflux D: Grade IV reflux E: Grade V reflux. A BC DE

Complications of VUR Recurrent UTI with pyelonephritis  Renal scars  Atrophic kidneys  Hypertension  Renal insufficiency  Renal failure

Acute Renal Damage after First UTI 57 neonates (  8 weeks) (114 kidneys) Cascio S, Puri P, Kelleher J. et al, Pediatr Nephrol 17: , 2002 VCUG findingsNormal DMSAFocal scars VUR2019 No VUR5025 Total70 (61%)44 (39%)

Acute renal damage in male infants with high grade VUR after First UTI Cascio S, Puri P, J Urol 168: , male infants (3 w – 1 yr) ( ) 236 refluxing ureters Renal parenchymal damage in 44% 204 male infants ( ) 343 refluxing ureters Renal parenchymal damage in 39% Italkid Project Marra et al, J Pediatr 144:677-81, May 2004

Management Two principles: –Determine primary Vs secondary VUR –Prevent UTIs Treat the underlying causes Medical/ Surgical + Surveillance

Treatment of Primary VUR General measures –Perineal hygiene –Adequate hydration/ Treat constipation –Bladder training Drug therapy –Continuous antibiotic prophylaxis –Intermittent antibiotic therapy for breakthrough UTI –Anticholinergics ( oxybutynin) Open ureteric reimplantation ENDOSCOPIC TREATMENT

Analysis of Observation therapy in high grade VUR Birmingham Reflux study 51% 5% Toronto Sick Children 60% 8% International Reflux Study (IRSC) 91% (bilateral) 12% 61% (unilateral) 7% Persistence of VUR at 5 years Development of new renal scars

Reflux resolution (AUA, 1997) OBSERVATION THERAPY (at 5 years) –90% Grade I –80% Grade II –60% Grade III –45% Grade IV unilateral –9.9% Grade IV bilateral SURGICAL THERAPY (n=8061 ureters) –99% Grade I –99.1% Grade II –98.3% Grade III –98.5% Grade IV –80.7% Grade V

Obstruction rate after ureteric reimplantation requiring reoperation AUA, 1997 (33 studies) 0.3 to 9.1%

Endoscopic treatment of Vesico-ureteric reflux STING March 1984 P. Puri, B. O’ Donnell

Endoscopic treatment of Vesico-ureteric reflux

Technique of STING

Endoscopic treatment of VUR using PTFE: multicenter survey paediatric urologist & paediatric surgeons at 41 centres worldwide 8332 patients (1921 boys, 6411 girls) Mean age 4.5 years (ranging 3m-14 years) Follow-up 1-13 years refluxing ureters Claudio and Puri, J Urol 1998; 160:

Grade I 407 (3.3%) Grade II 3832 (31.2%) Grade III 5213 (42.5%) Grade IV 2218 (18.1%) Grade V 581 (4.7%) USG & VCUG at 3 m, 1, 3 years Endoscopic treatment of VUR using PTFE: Multicenter survey

Endoscopic treatment of VUR INITIAL RESULTS IN URETERS

Endoscopic treatment of VUR LONG-TERM RESULTS IN ureters >90% ureters followed up for > 2 years 182 (1.7%) endoscopically corrected refluxing ureters lost FU or refused VCUG Resolution of VUR (95.6%) Recurrence of VUR 326 (2.8%) Ureteric obstruction requiring reop 41 (0.33%) No clinically untoward effects in all patients

Tissue-augmenting substances Teflon (Polytetrafluroethylene,PTFE) –Migration to CNS, lungs  VUR recurrence –Potential granuloma formation Bovine cross-linked collagen Polydimethysiloxane Deflux (Dextranomer in sodium hylauronan) Introduced in 1995 Approved by FDA Introduced into HK in 2003

DEFLUX® Dextranomer microspheres 80 to 250 µm in 1% sodium hyaluronic acid solution Biodegradable, non- immunogenic properties, no potential for malignant transformation

Endoscopic Treatment of VUR using Deflux® ( ) (n=396) 273 girls & 123 boys Median age 2.1 yrs (Ranged 3 m to 13.6 yrs) Bilateral (n=228); Unilateral (n=168) 41 (6.6 %) duplex systems 624 refluxing ureters (Grade II-IV) P Puri et al, J Urol. Oct 2003; 170:

Follow Up Outpatient procedure Voiding cystourethrography at 3 months Renal and bladder ultrasound at 3 months and annually Median follow-up: 24 months ( range 6 months – 42 months)

Endoscopic treatment of Grade II-V VUR using Deflux 624 URETERS

3.5 YEAR FOLLOW UP n= patients presented with UTI No evidence of VUR on VCUG USG: no evidence of delayed VUJ obstruction or any change in the sonographic appearance of Deflux® implant

Deflux implantation for VUR: randomized comparison with antibiotic prophylaxis Grade II-IV Deflux group (n=40) Vs Observation therapy (n=21) VUR resolution at 1 year –Deflux® group 69% –Observation therapy 38% No adverse events in either group Parenchymal damage – Deflux group 1 patient Vs observation group 3 patients Capozza and Caione. J Pediatrics 140:230;2002

Treatment of VUR: a new algorithm based on Parental preference Parents questioned (n=100) –80 % preferred endoscopic treatment –5 % antibiotic prophylaxis –2 % open surgery –13 % undecided Capozza et al BJU Inter 92(3): 285-8, 2003

Our early experience ® employed in 7 patients with Grade III-IV VURDeflux® employed in 7 patients with Grade III-IV VUR ( ) 5 unilateral; 2 bilateral5 unilateral; 2 bilateral Mean follow-up: 8 monthsMean follow-up: 8 months Complete resolution after single injection in allComplete resolution after single injection in all Prospective randomised control study on Deflux® injection Vs antibiotic prophylaxisProspective randomised control study on Deflux® injection Vs antibiotic prophylaxis

Conclusion Endoscopic subureteric injection of tissue- augmenting substances has become an established alternative to long-term antibiotic prophylaxis and open surgery in the management of VUR in children ®Deflux® seems to be a promising agent but long- term results are awaited

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