•In children with dysfunctional voiding due to Hinman syndrome, it is important to ensure:

–Timed voiding with or without biofeedback

–A regular bowel regimen

–Intermittent catheterization

8.7.4Surveillance

•In general, low-grade reflux (grades I–II) have high rates of spontaneous resolution, usually more than 80 %.

•High-grade reflux, especially grade V, is much less likely to resolve.

•Surveillance is infrequently used among those with high-grade VUR.

•Surveillance is still frequently used among older children with VUR, especially boys who have never had a UTI.

•Children with low-grade VUR, especially those who have never had UTI, are sometimes followed on surveillance without antibiotic prophylaxis.

8.8Surgical Therapy of VUR

8.8.1Indications for Surgical Interventions

•Absolute indications for surgical interventions include:

–Breakthrough pyelonephritis

–Progressive renal scarring in patients receiving antibiotic prophylaxis

–An associated ureterovesical junction abnormality

•Relative indications for surgical interventions of VUR include:

–Grades IV and V VUR

–Persistent VUR despite medical prophylaxis (beyond 3 years)

–Breakthrough UTIs in patient who are receiving antibiotic prophylaxis

–Lack of renal growth

–Multiple drug allergies that preclude the use of prophylaxis

–A desire to terminate antibiotic prophylaxis (either by the physician or the patient/ parents)

–Medical noncompliance

8.8.2Indications for Surgical Interventions Based on Age at Diagnosis and the Presence or Absence of Renal Lesions

Children without renal lesions at diagnosis:

•In patients diagnosed with VUR in infancy (<1 year):

–Surgical repair may be recommended in patients with persistent unilateral grades IV–V reflux or bilateral grades III–V reflux after a period of antibiotic therapy should the parents prefer definitive therapy over watchful management plus antibiotic prophylaxis.

•In children diagnosed at age 1–5 years:

–Continuous antibiotic prophylaxis is the preferred option as an initial therapy for those with unilateral grade IV reflux; however, surgical repair is a reasonable alternative for grades IV and V reflux.

–In patients with bilateral grade IV and V reflux, surgical repair is recommended.

–Surgery is recommended for children with persistent grades III–V reflux who have not remained infection-free with antibiotic therapy.

–Endoscopic treatment may be recommended in children with grade III–IV who have not shown any improvement in the reflux grade, who do not wish to receive further antibiotics, or who have had UTI.

•In children diagnosed at age 6–10 years:

–In patients with bilateral grades III–IV reflux, surgical repair is the preferred option, although continuous antibiotic therapy is a reasonable alternative.

–Patients with grade V reflux should undergo surgical repair.

–In patients with persistent grades I–II reflux after a period of antibiotic prophylaxis,

consensus is lacking regarding the role of continued antibiotics versus surgery.

–Surgery is an option for persistent reflux in children with grades III–IV reflux in whom initial antibiotic therapy has failed; either an open surgical or an endoscopic approach may be used.

Children with renal lesions at diagnosis:

•In patients diagnosed with VUR in infancy (<1 year):

–In children with grade V reflux and scarring, continuous antibiotic prophylaxis is the preferred option as an initial treatment; primary surgical repair is a reasonable alternative.

–If the kidney is noted to have poor function (<15 % on DMSA scan) consider removing the kidney and the ureter down to the bladder.

–Consensus is lacking regarding the role of continued antibiotics versus surgery in patients with persistent grades I–II reflux after a period of antibiotic prophylaxis. These patients may be candidates for endoscopic treatment.

–In boys with persistent unilateral grades III–IV reflux, surgical repair is the preferred option.

–Boys with persistent bilateral grades III–IV reflux, girls with persistent unilateral and/ or bilateral grades III–IV reflux, and any children with persistent grade V reflux should undergo surgical repair, with an option for endoscopic treatment in grades II–IV.

•In children diagnosed at age 1–5 years:

–In children with bilateral grades III–IV reflux and renal lesions, antibiotic therapy is the preferred option; however, surgical repair is a reasonable alternative.

–Patients with unilateral and/or bilateral grade V disease and scarring should undergo surgical repair as initial treatment or nephroureterectomy if the kidney has been shown to have little or no function on DMSA scan.

–Consensus is lacking regarding the role of continued antibiotics versus surgery for patients with persistent grades I–II reflux after a period of antibiotic prophylaxis.

–Girls with persistent unilateral and/or bilateral grades III–IV reflux and boys with persistent bilateral grades III–IV reflux should undergo surgical repair, either open or endoscopic.

–Surgery is also an option for boys with persistent unilateral grades III–IV reflux.

–For patients with persistent grade V reflux who have not undergone surgery as initial treatment, surgical repair is recommended.

•In children diagnosed at age 6–10 years:

–Patients diagnosed with bilateral grades III–IV reflux or grade V reflux can undergo surgical repair as initial treatment.

–Consensus is lacking regarding the role of continued antibiotics versus surgery for patients with persistent grades I–II reflux after a period of prophylaxis.

–Patients with persistent unilateral grades III–IV reflux who have not undergone surgery as initial treatment should be offered either open surgical repair or endoscopic treatment.

•Surgical therapy options for VUR include:

–Open surgical procedures

•Leadbetter-Politano procedure

•Cohen procedure

–Endoscopic injection (STING/HIT procedures)

–Laparoscopic repair

–Robotic assisted repair

8.8.3Endoscopic Injection

•The most dramatic change in the treatment of vesicoureteral reflux over the past decade has been the rapid growth in the use of endoscopic treatment.

•Endoscopic treatment of VUR was popularized by Puri and O’Donnell in 1980s.

•Currently, it is the surgical treatment of choice for children with VUR.

•The principle of the procedure is to inject, under cystoscopic guidance, a biocompatible bulking agent underneath the intravesical portion of the ureter in a submucosal location.

Indications for Surgical Treatment of VUR

•Breakthrough febrile UTIs despite adequate antibiotic prophylaxis

•Severe reflux (grade V or bilateral grade IV) that is unlikely to spontaneously resolve, especially if renal scarring is present

•Mild or moderate reflux in females that persists as the patient approaches puberty, despite several years of observation

•Poor compliance with medications or surveillance programs

•Poor renal growth or function or appearance of new scars

•The bulking agent elevates the ureteral orifice and distal ureter in such a way that the lumen is narrowed, preventing regurgitation of urine up the ureter but still allowing its antegrade flow.

•The procedure became popular and has several advantages:

–It is performed with general anesthesia on an outpatient basis

–A short surgical time

–Low surgical morbidity

–Comparable success rates

–Preservation of the option for subsequent open surgical repair

–It can be repeated

–It can be used to treat different grades of VUR and some authors are using this technique to treat even grade IV and V VUR.

•Some clinicians and because of these advantages are now advocating endoscopic treatment as initial management for newly diagnosed vesicoureteral reflux.

•They argue that immediate antireflux surgery obviates the need for long-term antibiotics and repeated imaging studies.

•This however, inevitably results in the overtreatment of a large number of children

because VUR is known to spontaneously resolve in most children, and even those with persistent VUR may not have a clinical indication for antireflux surgery.

•Add to this, the fact that the true long-term success rates for endoscopic treatment are still to be determined.

•Endoscopic injection involves applying a gel around the ureteral opening to create a valve like function which stop urine from flowing back up the ureter.

•Some authors emphasize the importance of creating a large mound or “volcanic” appearance of the bulking agent under the orifice, compressing the orifice into a slit.

Advantages of Endoscopic Treatment of VUR

•It is performed on an outpatient basis

•A short surgical time

•Low surgical morbidity

•Comparable success rates

•Preservation of the option for subsequent open surgical repair

•It can be repeated

•Other authors have described an intramural injection, in which the distal ureter is distended with a jet of saline from the cystoscope, allowing the injection needle to be advanced into the submucosa of the intramural ureter at 6 o’clock.

•The gel consists of two types of sugar-based molecules called dextranomer and hyaluronic acid.

•Trade names for this combination include Deflux and Zuidex.

•Both are biocompatible, which means that they do not cause significant reactions within the body.

•The procedure of endoscopic treatment of VUR:

–The procedure is performed under general anesthesia and complete aseptic technique.

–The patient is placed in the lithotomy position.

–Cystourethroscopy is performed and the bladder and ureteral orifices are inspected.

–An injection needle is then introduced advanced, bevel up to the ureteral orifice.

–The orifice is kept open by hydrodistending it with irrigation fluid.

–The needle is then advanced into the ureter.

–A submucosal puncture is made and the bulking material is slowly injected.

–As it spreads in the submucosal space, the material elevates the intravesical ureter, and the orifice acquires an inverted smile appearance.

–The needle is slowly withdrawn after between 0.5 and 2 mL of material has been injected.

–A second injection may be carried out at the base of the newly created mound to further elevate the ureteral orifice.

–The bladder is emptied and reinspected.

–Any bleeding vessels may be cauterized with a Bugbee electrode.

–Some authors have described an intramural injection, in which the distal ureter is distended with a jet of saline from the cystoscope, allowing the injection needle to be advanced into the submucosa of the intramural ureter at 6 o’clock.

•In general, the success rates with endoscopic treatment are significantly lower than those reported for open antireflux surgery.

•Most studies of endoscopic treatment have found that success rates are lower for higher grades of vesicoureteral reflux.

•The reported success rate of grade IV VUR was 63 % after one injection.

•Polytetrafluoroethylene (Teflon) was used but concerns over its safety have limited its use.

•Other bulking agents that have been reported include:

–Autologous fat

–Blood

–Chondrocytes

–Bovine collagen

–Polydimethylsiloxane

•Concerns over particle migration, carcinogenesis, and technical handling problems have limited their use.

•Children who undergo endoscopic antireflux surgery need continued follow-up.

–They require post procedure imaging, including voiding cystourethrography (VCUG) at 3–4 months postsurgery.

–Patients should be maintained on antibiotic prophylaxis until resolution of vesicoureteral reflux is confirmed.

•It is important to note that as many as 25 % of children whose VUR was cured on the initial post endoscopic injection VCUG (3–4 months) subsequently had recurrence of VUR on delayed VCUG (12 months).

•This is attributed to several factors including:

–Reabsorption of the injected material

–Migration of the injected material

–Associated dysfunctional voiding

•It was shown that on long term, DHA implants can strongly resemble a stone in the distal ureter on CT scanning, apparently due to calcification of the DHA implant.

•Persistent vesicoureteral reflux after open antireflux surgery:

–The initial management is a repeat injection.

–Many investigators routinely use up to three separate injections.

–Patients who fail multiple injections should be reevaluated and treated for causes of secondary VUR.

–Patients with persistent VUR and in the presence of a surgical indications for correction of VUR should have open surgery.

Bulking Agents Used Endoscopically to Treat VUR

•Dextranomer and hyaluronic acid (DHA) (Deflux and Zuidex)

•Polytetrafluoroethylene (Teflon)

•Autologous fat

•Blood

•Chondrocytes

•Bovine collagen

•Polydimethylsiloxane