Early Infancy Ureteral Reimplantation for Distal Ureteral Obstruction

Initial evaluation and determining if surgery is indicated:

Prenatal diagnosis: patient will get renal ultrasound at 2-7 days of birth and will be
started on prophylaxis with amoxicillin or Keflex. At 6 weeks a VCUG, renal ultrasound and
mag 3 will be done per local protocols.

Patients considered for reimplant will have:

1. SFU grade 3 and 4 hydroureteronephrosis

2. Normal contralateral kidney (VUR grade 1-3 ok) as defined above plus

3. Obstruction As defined by the BAPU (British Association of Paediatric Urologists
consensus statement on the management of the primary obstructive megaureter)

If the patient meets criteria they will be consented for this observational study (before the
surgery) and will have an extravesical ureteral reimplant in the next 0-2 months.

After the patient has been consented to participate in the study and before surgery, the
investigators need to notify the main study site (Omaha) about the new patient and
information will be recorded at the main site about the patient without patient identifiers.
This is done so that they study can be analyze as an intention to treat.

Please note that this is an observational study: patients will have the same interventions
and diagnostic tests regardless whether they chose or not to participate in the study. The
investigator does not assign specific interventions to the subjects of the study. The
protocol is only a suggested guideline to standardize details of the surgery and follow up of
the patients among the different centers.

Postnatal diagnosis: patients with no history of prenatal hydronephrosis presenting with
febrile UTI. If under 6 weeks of age they will be placed on prophylaxis with amoxicillin or
Keflex. At 6 weeks a VCUG, renal ULTRASOUND and mag 3 will be done per local protocols. If
presenting in between 6 weeks and 6 months of life they will undergo VCUG and Mag 3 after
completing antibiotics course (7-10 days). Patients with febrile UTI not responding to
antibiotics can be diverted with a percutaneous nephrostomy and once stable undergo testing.

Patients considered for reimplant will have:

1. SFU grade 3 and 4 hydroureteronephrosis

2. Normal contralateral kidney as defined above plus

3. Obstruction As defined by the BAPU If the patient fulfills criteria and the reimplant
can be scheduled before age 7 months, they will be consented for the study.

After the patient has been consented to participate in the study and before surgery, the
investigators need to notify the main study site (Omaha) about the new patient and
information will be recorded at the main site about the patient without patient identifiers.
This is done so that they study can be analyze as an intention to treat.

Patients initially not meeting criteria for surgery who had breakthrough UTI's Patients with
unilateral megaureter but either no obstruction as defined above or no differential function
loss can be considered for the study if they have Breakthrough UTI's while on prophylaxis and
the surgery will be done at less than 7 months of age.

Follow up If patient does not meet criteria for surgery, follow up will be done as per local
protocols with renal US +/- Mag 3 renal scans.

Follow up US can be done every 6-12 weeks. If US shows worsening patient can proceed with
surgery or a Mag 3 can be done alternatively and any worsening >5% DFx on the mag 3 can could
indicate surgery.

Below is a summary of patients eligible for surgery (all surgeries will have to be done under
7 months of age to enter into the study as well as inclusion and exclusion criteria must be
followed):

1. Prenatally diagnosed unilateral distal obstruction that at 6 weeks have less than 40%
DFx and SFU 3 or 4 hydronephrosis.

2. Patients who present postnatally with a febrile UTI and unilateral distal ureteral
obstruction and on evaluation are found to have less than 40% DFx, and SFU 3 or 4
hydronephrosis.

3. Prenatally or postnatally diagnosed patients with distal obstruction who on initial
evaluation did not meet criteria, but then subsequently had a Breakthrough febrile UTI's
while on abx prophylaxis.

4. Prenatally or postnatally diagnosed patients with distal obstruction who on initial
evaluation did not meet criteria, but on follow up US showed worsening hydronephrosis.
Alternatively for these patients a Mag 3 can be repeated with surgery done for worsening
parameters on the mag 3 (loss of more than 5% of function) .

Operative considerations Pfannenstiel incision. Fascial incision can be vertical or
horizontal. Ureter dissected and divided at the bladder with 4-0 polydioxanone (suture
ligation) if megaureter or as distal as possible/safe for ectopic ureter. Distal narrow or
diseased looking segment excised.

Using 4 4-0 silk stay sutures, the borders or the detrusorrhaphy will be marked posterior
laterally. A 3 cm detrusorrhaphy (minimum) down to mucosa will be done next.

Tapering (optional). Ureters more than 8-10 mm in diameter could be tapered. Based on some
computer models research done by us, would recommend tapering just the distal ureter down to
4-5 mm in diameter over a stent left for 6 weeks. Ureter should not be tapered for more than
a few centimeters in length to avoid devascularization. Alternatively, tapering can be left
to the discretion of the surgeon.

The ureter will be anastomosed with running 5-0 or 6-0 polyglactin to the distal
detrusorrhaphy making only a small mucosal opening.

A distal advancement suture will be placed to secure the UO distally in the bladder.

The detrusor will be then closed with interrupted 3-0 polyglactin stitches making sure no to
obstruct the ureter proximal at the hiatus.

For non tapered reimplants, a stent will be sutured to the foley and removed in 5-7 days.

Drain at the discretion of the surgeon (preferably no drain) Foley will be left for 5-7 days
in everyone. Overnight observation for all patients with extended hospital stay as needed for
complications.

Follow up Antibiotic prophylaxis until first VCUG. (sulfamethoxazole/trimethoprim 3-4
mg/kg/day) 3 months: renal US, and VCUG. Mag 3 only for cases where the renal US showed no
improvement (renal US stable or worse). Mag 3 can be done per the discretion of the surgeon
too.

Continue antibiotic prophylaxis for girls and uncircumcised boys with VUR. May stop
antibiotic prophylaxis for circumcised boy with VUR.

1 year: renal US, and VCUG (if previous VCUG showed VUR). Mag 3 only for cases where the
renal US showed no improvement (renal US stable or worse). Mag 3 can be done per the
discretion of the surgeon too.

Recurrent Febrile UTI's: will document any febrile UTI's defined at temp more than 38.5 with
urine analysis with >10 white blood cells per high power field on microscopic exam and a
positive urine culture more than 1 months after removal of foley or stent. Febrile UTI's
within a month of the removal of foley or stent will be considered operative complications.

Inclusion criteria:

- Children younger 6 months of age who have been recommended by their urologist to have
a unilateral ureteral reimplant.

- Unilateral obstructive disease (as defined by the BAPU)

- Ipsilateral Single system

- Ipsilateral VUR is ok

- Contralateral reflux grades 1-3 ok as long as the reflux will be observed

Exclusion criteria

- Duplicated systems

- First Febrile UTI's and megaureter or ectopic ureter but no evidence of obstruction or
loss of function

- Neurogenic bladder, valves

- Contralateral reflux grade 4-5