INDEX
Reflux in Contralateral Ureter after Successful Correction of Unilateral Vesicouretaral Reflux

Authors: Yutaro Hayashi, Nobuaki Asai, Takahiro Yasui, Kentaro Mizuno, Akihiro Nakane, Akiko Uda, Yoshiyuki Kojima, Tetsuji Maruyama, Mihoko Mogami, Kenjiro Kohri
Affiliation: Department of Nephro-urology, Nagoya City University, Graduate School of Medical Science
Address: 1-Kawasumi, Mizuho-cho, Muzuho-ku, Nagoya, Japan, 467-8601
Key Words: vesico-ureteral reflux, ureter, bladder, reimplantation
Runnning title: Contralateral reflux after ureteroneocystostomy
Address of correspondence: 1-Kawasumi, Mizuho-cho, Muzuho-ku, Nagoya, Japan, 467-8601

ABSTRACT
Contralateral vesicoureteral reflux is one of the most detestable complications after successful unilateral ureteral reimplantation of unilateral reflux. We searched for the risk factors for the new onset of contralateral reflux postoperatively. We reviewed 18 cases of unilateral reflux we had treated with unilateral ureteroneocystostomy. To determine the predictive factors of contralateral reflux, we investigated several factors including sex, age, laterality, reflux grade and surgical procedure.
Contralateral reflux occurred in 4 patients after unilateral ureteroneocystostomy. No statistically significant prognostic factor was proved with a new onset of contralateral reflux. However, female patients(50%), those patients 5 years old or younger(36.5 %), and those who underwent the Cohen procedure(30%) had a greater tendency of developing contralateral reflux compared to male patients(14%), patients more than 5 years old(10%), and those who underwent the Politano-Leadbetter procedure(14%). Although we could not statistically identify any risk factor for a new onset of contralateral reflux from the preoperative evaluation, we realized that those who underwent ipsilateral reimplantation should be carefully followed if they are female or less than 5 years old.

INTRODUCTION
Contralateral reflux after unilateral anti-reflux surgery is a very troublesome situation. However, bilateral anti-reflux surgery may not be acceptable as a maneuver to avoid the presentation of contralateral reflux in those who have a unilateral vesicoureteral reflux. We tried to pinpoint the preoperative findings that may help to predict those patients in whom contralateral reflux after unilateral reimplantation is most likely to develop, by reviewing 18 cases of unilateral reflux we treated with unilateral ureteroneocystostomy. We compared our findings with those reported in the literature.

PATIENTS AND METHODS
This is a retrospective study where the patients' medical charts have been reviewed. While total number of patients who repaired vesicoureteral reflux surgically was 47, eighteen of them underwent unilateral ureteroneocystostomy.
The initial surgery for vesicoureteral reflux was performed by the Politano-Leadbetter procedure in 23 cases. Bilateral ureteroneocystostomy was performed on 15 patients and unilateral ureteroneocystostomy for unilateral reflux in 8 patients.
The initial repair of vesicoureteral reflux was performed by the Cohen procedure in 24 cases. Bilateral ureteroneocystostomy was performed on 14 patients and unilateral ureteroneocystostomy for ipsilateral reflux in 10 patients.
In total, 18 patients underwent ipsilateral anti-reflux surgery for unilateral vesicoureteral reflux. We made it a rule to perform voiding cystourethrography (VCUG) 6 months after the surgery in order to identify the contralateral reflux as well as to confirm the disappearance of the ipsilateral reflux. To determine the predictive factors of contralateral reflux after unilateral reimplantation, we investigated several factors including sex, age, laterality, reflux grade and surgical procedure. Stastistical studies were conducted with the chi-square test.

RESULTS
Contralateral reflux occurred in 4 of the 18 patients after unilateral ureteroneocystostomy for unilateral vesicoureteral reflux (Table 1).
Case 1: A 3-year-old female with right side, grade 3 reflux underwent unilateral ureteroneocystostomy by the Cohen procedure. VCUG performed 6 months after the surgery demonstrated contralateral grade 2 reflux. Since VCUG was not done, the presence or absence of contralateral reflux is unknown, but no episodes of urinary infection have occurred to date without any medication of antibiotics.
Case 2: A 7-year-old male with left side, grade 4 reflux underwent unilateral ureteroneocystostomy by the Cohen procedure. VCUG performed 6 months later showed contralateral grade 1 reflux. VCUG conducted 1 year later revealed that the contralateral reflux spontaneouly disappeared without any additional surgical procedures.
Case 3: A 1-year-old male with grade 4 reflux on his right duplex system underwent unilateral ureteroneocystostomy by the Cohen procedure. VCUG showed contralateral grade 2 reflux. Since contralateral reflux persisted for 3 years and the grade advanced to grade 3, endoscopic injection therapy was performed and the reflux was resolved.
Case 4: A 5-year-old female with grade 5 reflux on her left duplex system underwent unilateral ureteroneocystostomy with the Politano-Leadbetter procedure. VCUG demonstrated contralateral grade 1 reflux. Since VCUG has not been done since then, the presence or absence of contralateral reflux is unknown, but no episodes of urinary tract infection have occurred for 9 years with no medication of antibiotics.

Contralateral reflux occurred in only 2 of 14 male patients(14%), but in 2 of the 4 female patients(50%). No significant sexual difference was detected (Table 2).
Contralateral reflux occurred in 3 of the 8 patients (36.5 %) from 1 to 5 years old and only 1 of the 10 patients (10%) older than 5 years old. However, there was no significant difference between these two age groups (Table 3).
Laterality of initial unilateral vesicoureteral reflux did not have any influence on the appearance of contralateral reflux after unilateral anti-reflux surgery (Table 4).
Although the patients with high grade reflux had a tendency of contralateral reflux(33.3%) compared to those with low grade reflux(20%), a statistical study did not reveal any significant difference (Table 5).
The incidence of contralateral reflux was higher with the Cohen procedure (30%) than with the Pollitano-Leadbetter procedure (14.3%), although the difference was not significant (Table 6).

DISCUSSION
The 3 widely held hypotheses for the development of contralateral reflux are 1) surgical distortion of the contralateral trigone during ureteral reimplantation, 2) elimination of a low pressure bladder pop-off mechanism and 3) intermittent contralateral reflux that was missed on initial voiding cystography.
The first hypothesis, surgical distortion of the contralateral trigone during ureteral reimplantation, indicates that cross-trigonal reimplants may be more likely to disturb the tenuous valve of the contralateral ureter, unmasking the tendency for reflux on that side. Ross mentioned that postoperative contralateral reflux was more common in those who underwent cross-trigonal repair although the numbers of cases analyzed was so small that no statistical differences could be demonstrated1). Kumar and Puri advocated this hypothesis because of the low incidence (7%) of contralateral reflux after endoscopic correction of unilateral vesicoureteral reflux, which appeared most likely to be due to the absence of contralateral trigone distortion with the endoscopic technique2). Those who conducted unilateral extravesical detrusorrhaphy which also avoids contralateral trigone distortion experienced a low incidence of contralateral reflux, for instance, 2.5% by Zaontz3), 2% by Wacksman4) and 5.6% by Minevich5). On the other hand Diamond et al. identified no difference in the incidence of contralateral reflux between the Cohen procedure (19%), Glenn-Anderson procedure(17%) and extravesical detrusorrhaphy(22%)6). Moreover, Quinlan and O'Donnel reported a higher incidence of contralateral reflux in patients undergoing reimplantation by the Politano-Leadbetter procedure than in those undergoing the Cohen procedure7). They insisted that surgical distortion of the contralateral trigone during ureteral reimplantation is not the main cause of new onset contralateral reflux after unilateral reflux repair. However, nephrectomy was eventualy undertaken because of the dysplastic kidney in those who underwent the unilateral reflux repair with the Politano-Leadbetter procedure and encountered the contralateral reflux postoperatively. We presume that Quinlan and O'Donnel might have tended to elect the Politano-Leadbetter procedure for patients who were supposed to undergo the second surgery. Since contralateral reflux after unilateral ureteroneocystostomy occurred in those repaired by the Cohen procedure more often than those repaired by the Politano-Leadbetter procedure in our series, we decided to avoid performing the Cohen procedure.
The pop-off mechanism was supported by Diamond et al. who stated that as the grade of corrected reflux increased, a significant trend toward development of contralateral reflux was noted6). In contrast, Kumar and Puri reported a low incidence of contralateral reflux after endoscopic correction of even high grade reflux2). Although our statistical study showed no significant difference to support the pop-off mechanism for the contralateral, we believe we should take it into consideration.
The theory of intermittent contralateral reflux was first described by Ross et al1). They speculated that contralateral reflux may be intermittent and might have recurred without ipsilateral reimplantation. Sparr et al. observed that new onset contralateral reflux developed in a third of the patients initially diagnosed with unilateral disease while they were followed nonoperatively8). They suggested that the incidence of intermittent reflux may be higher than before because the majority of naturally developing new onset contralateral reflux was low grade after unilateral surgery as it was in the nonoperated patient. Koyanagi et al. applied betanechol chloride-aided voiding cystourethrography to the detection of missing vesicoureteral reflux9). They proposed that betanechol chloride affected the neuromuscular integrity of the borderline ureterovesical junction in some unknown way to allow reflux. Hoenig et al. performed intraoperative cystography after unilateral reimplantation to discover contralatreal reflux10). Liu et al. implied that the contralateral reflux preexisted because renal scars had been detected in 5 of the 6 patients in whose contralateral kidney postoperative vesicoureteral reflux developed and that scars in the contralateral kidney seen on DMSA scan predict contralateral reflux after unilateral antireflux surgery11).
Definitively established prognostic factors enable us to determine preoperatively the patients who are at risk for contralateral reflux and, thus, those who are better candidates for bilateral reimplantation. Several factors have been mentioned as a risk factor for contralateral reflux.
Ross et al. found that patients 3 years old or younger seemed to be at higher risk for contralateral reflux1). On the other hand, Kumar and Puri mentioned that the mean age of the contralateral reflux group was 5 years old while that of the group as a whole was 3 years old2). Moreover Diamond et al. described that the mean age of their contralateral reflux group(7 years old) was identical to that of the group as a whole6). In our series those patients 5 years old or younger had a greater tendency of developing contralateral reflux compared to older patients.
Ross et al. subdivided their patients into those with and without previous contralateral reflux1). Postoperatively contralateral reflux developed in 5 out of 11 children(45%) with a history of bilateral reflux compared to 4 out of 42(10%) without previous contralateral reflux. In addition, Warren et al. reported the incidence of contralateral reflux to be 55% for the patients who had had bilateral reflux at some time preoperatively12). The incidence reported by Hirsch and Fitzgerald was also similar (57%) 13).
Gibbons and Gonzales insisted that the low rate of contralateral reflux in recent reviews was attributable largely to the philosophy of performing bilateral reimplantation in the child with unilateral reflux when the contralateral orifice endoscopically showed abnormal morphology14). Warren et al. recommended bilateral ureteral reimplantation when the orifice of the contralateral nonrefluxing ureter appeared abnormal12). On the other hand, several investigators have found that cystoscopy does not offer sufficiently accurate information on which to base this decision10, 13,15,16,17).
Although we could not determine the exact prognostic factors of contralateral onset after unilateral ureteroneocystostomy, we realized that those who underwent ipsilateral reimplantation should be carefully followed if they are female or less than 5 years old. In addition the Politano-Leadbetter procedure would be a recommendable choice compared to the Cohen procedure in order to avoid the postoperative onset of contralateral reflux.

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Nagoya City University
Medical School