Creation of effective antireflux mechanism without creation of submucosal tunnel in surgical correction of vesicoureteric reflux: Myth or reality?-An experimental study.

OBJECTIVE: To evaluate the possibility of creating an effective antireflux mechanism without the need to create submucosal tunnel in surgical correction of vesicoureteric reflux.
MATERIALS AND METHODS: Ethical clearance was obtained from the institute ethical committee. The prospective experimental study was conducted on fresh postmortem specimens comprising of intact ureter-bladder-urethra of slaughtered lamb. Through perurethral tube, bladder distension revealed intact antireflux mechanism which disappeared following a cephalad slit of ureteric orifice. After intravesical advancement, mobilized ureters were anchored to the hiatus and the exposed detrusor along the proposed submucosal tunnel after stripping the bladder mucosa. Limited nonobstructed narrowing of the advanced ureteric ends was fashioned. After closure, bladder was distended and reflux was observed through proximal transected ureteric orifices with check cystogram. In second part of experiment, in a rectal reservoir, two intestinal segments as dilated ureters were implanted without creating submucosal tunnel, but anchoring the intrarectal segment to exposed submucosa. Intraluminal end of one segment was narrowed, while other left as such. Reservoir distension test was done to notice the status of reflux. In 24 months, 12 experiments were conducted.
RESULTS: In first part of experiment, successful antireflux mechanism was created in 11 ureters. In second part of experiment, reflux persisted in the ureteral segment implanted with obliquity but without distal nonobstructed narrowing, while there was no reflux in the ureteral segment with both obliquity and narrowing.
CONCLUSION: Advancement and anchoring of the ureteral segment to the exposed detrusor with creation of nonobstructive and limited narrowing can create effective antireflux mechanism without the need to create submucosal tunnel.

INTRODUCTION

Whenever the surgical correction of vesicoureteric reflux is indicated, all described surgical procedures follow certain basic principles of antireflux surgery.[12345678] These principles include adequate mobilization of distal ureter without tension or damage to its delicate blood supply, creation of submucosal tunnel, that is generous in caliber and satisfies the 5:1 ratio of length to width recommended by Paquin,[3] placement of ureter in the submucosal tunnel with muscular backing of detrusor without angulation or twist and, ureteromucosal anastomosis.[9] In certain clinical settings like exstrophy bladder with an abnormal mucosa, neurogenic bladder with detrusor hypertrophy and, in bladders with chronic inflammatory cystitis, creation of submucosal tunnel is almost impossible, while ureters can still be mobilized in correct plane. Endoscopic injection treatment of vesicoureteric reflux relies on enhancing the obliquity of intramural course of ureter and creation of some narrowing at intravesical ureteric orifice.[10] In situations of abnormal vesicoureteric junction, bladder diverticulum and exstrophy bladder, and endoscopic injection may not work. Therefore, there is a need to search for an alternative provision in antireflux surgery that could obviate the need to create submucosal tunnel.

This experimental study was undertaken to answer the following research question; “can effective antireflux mechanism be created in surgical correction of vesicoureteric reflux offsetting the need to develop the submucosal tunnel?”

MATERIALS AND METHODS

Study design

This prospective experimental study was conducted in a lab on fresh postmortem organ specimens of the lamb retrieved from the nearby approved slaughterhouse as a routine byproduct. Ethical clearance for this experimental study was obtained from the institute ethical committee. For the first part of experiment, the fresh organ specimens retrieved from the lamb consisted of intact bladder continued with the urethra distally and the ureters transected at renal pelvis but maintained distal continuity up to the ureterovesical junction. The first part of experiment was conducted in six specimens over a period of 12 months. For the second part of experiment, fresh organ specimens retrieved from the lamb consisted of an 8” segment of rectum to function as reservoir and two segments of small intestine each 10” long, cleared of its mesentery to function as dilated ureteral conduits. Second part of experiment was conducted in six specimens over a period of 12 months. Before the experiment, the specimens were mounted and stabilized on a working platform [Figure 1a].

Figure 1

(a) Fresh postmortem specimen of intact ureter-bladder-urethra of slaughtered lamb, mounted on working platform, (b) Distension of bladder with saline via perurethral catheter to confirm intact antireflux mechanism in this experimental specimen, (c) Entering the bladder through anterior wall and creation of iatrogenic reflux on both sides by slitting open the ureteric orifices superiorly up to 3-4 mm cephalad, (d) Closure of bladder and its redistension with saline via perurethral catheter demonstrating leakage of saline through proximal transected ends of ureters

Experimental techniques

Experiment I: A feeding tube was passed per urethra into the bladder and anchored. The bladder was distended by filling it with urografin diluted with saline via perurethral feeding tube that demonstrated intact antireflux mechanism on both sides as diluted urografin was not leaking via open ends of ureters [Figure 1b]. A check cystogram also confirmed the same.

The bladder was then entered through vertical midline incision of anterior bladder wall. Fine feeding tube was passed from each proximal transected ureteric end into the bladder and bilateral ureteric orifices at bladder trigone were identified. These orifices were slit open superiorly up to 3-4 mm cephalad to widen the ureteric orifices and shorten the obliquity of the transvesical course of the ureter [Figure 1c]. The bladder was closed with watertight running suture. Feeding tubes from the ureters were withdrawn. The bladder was redistended via per urethral feeding tube with urografin contrast diluted with saline. Leaking of diluted contrast from the proximal transacted ends of both ureters was noted [Figure 1d]. The reflux was also confirmed with check cystogram.

The bladder was reopened by removing the continuous suture. From combined extravesical and intravesical dissection, the ureters were mobilized to gain sufficient intravesical length to satisfy the length to width ratio of at least 5:1. The ureteral wall was anchored to the detrusor at the bladder hiatus. Remaining bladder hiatus was closed with interrupted sutures. Widened end of distal ureter was beveled and narrowed with two interrupted stitches to permit the passage of same size of feeding tube as passed before mobilizing the ureters. Along the proposed course of submucosal tunnel, the bladder mucosa was simply stripped off to expose the detrusor and the ureters were anchored to the detrusor with single row of three or four interrupted sutures. Tip of the ureter was anastomosed to the bladder mucosa [Figure 2a]. A feeding tube was put through the proximal transected end of the ureter, connected to a manometer and saline reservoir. Free flow of saline from distal ureteric orifice at low pressure was checked to rule out ureteral obstruction at neoureteric orifices that might have occurred in course of surgical maneuver. Bladder was again closed with running prolene suture. Reservoir, manometeric attachment, and feeding tubes were removed. Bladder was redistended via perurethral catheter with urograffin contrast diluted with saline. Leakage or no leakage of diluted contrast through the proximal transected end of ureter was checked [Figure 2b]. At this stage, cystogram was obtained to rule out/establish the occurrence of reflux after the procedure.

Figure 2

(a) Reopening of bladder and mobilization of ureters to gain sufficient intravesical length and anchoring to denuded detrusor after stripping of mucosa along proposed course of submucosal tunnel. Terminal distal end of ureter is bevelled and narrowed to allow free flow of saline into bladder and, anastomosed with bladder mucosa. (b) Reclosure and redistension of bladder with saline via perurethral catheter to check for reflux of saline showing no leakage of saline through proximal transected ends of ureters. (c) Shows specimen of 8” long segment of rectum clamped on both end to simulate as rectal reservoir in which two 10” long segments of small intestine simulating as dilated ureters have been reimplanted by anchoring them to the submucosa after stripping the mucosa without creating submucosal tunnel. Distension of reservoir with saline shows no reflux of saline.

Experiment II: A 8” long segment of rectum, washed, and cleaned with saline, was taken to simulate the bladder reservoir and two about 10” long segments of small intestine, cleared off its mesentery and lumen washed with saline, were taken to simulate the dilated ureters and were termed as ureteric substitutes. These two small intestinal segments were implanted in the already prepared and cleaned segment of the rectum [Figure 2c]. In first, after passing the dilated ureteric substitute through the hiatus, obliquity was created by anchoring the ureteric substitute to the submucosa after stripping the mucosa without creating submucosal tunnel, but orifice of dilated ureteric substitute was not narrowed. While in the second, after passing through a different hiatus in the same reservoir, narrowing of the orifice of ureteric substitute to admit 6fr feeding tube similar to natural ureteric orifices was also done in addition to maintain the obliquity of the dilated ureteric substitute. The manometeric flow studies through both ureteral substitutes demonstrated free flow of saline without obstruction. Rectal reservoir was closed. Through a small opening in the rectal reservoir, a 6fr feeding tube was inserted and secured with purse-string suture to prevent leakage. Through the feeding tube, saline distension test was done and the status of reflux was noted.

The findings of both experiments were recorded and analyzed.

RESULTS

Experiment I: In all six specimens of ureter-bladder-urethra, on bladder distension with urograffin diluted with saline, intact antireflux mechanism was found as there was no leakage through the proximal transected ends of ureters Figure 1 b. Cystogram substantiated the same findings. Bladder capacity on full distension ranged from 50 to 70 cc (mean: 61 cc).

After slitting open the intravesical ureteric orifices for 3-4 mm cephalad [Figure 1c], the reflux was demonstrated in all six specimens (12 ureteral units) [Figure 1d].

After reimplantation of ureters in six specimens with the described techniques, no reflux was noted in four specimens (eight ureteral units); while in one specimen, reflux occurred initially that disappeared with further bladder distension. In remaining one specimen, though no reflux occurred through the proximal transected ends of ureters, but leakage through one bladder hiatus was seen requiring placement of revision sutures at the bladder hiatus. Placement of revision sutures at the bladder hiatus resulted in obstruction at revision suture site, as demonstrated on manometeric study, so outcome regarding reflux could not be assessed.

Experiment II: Study of occurrence of reflux in six specimens after distending the rectum with 70-100 cc saline demonstrated leakage of saline through ureteral substitute units where though obliquity was maintained, but distal ends were left wide and patulous. However, in those units where in addition to creation of obliquity, the nonobstructed narrowing of distal end of ureteric substitute was performed, no reflux was demonstrated.

DISCUSSION

Vesicoureteric reflux is prevented in normal circumstances by the combination of several factors related to ureter, anatomic design of ureterovesical junction, and the functional dynamics of the bladder.[9] There are active as well as passive mechanisms leading to the unidirectional flow of urine from the ureters to the bladder without functional obstruction. Active mechanisms include active neuromuscular propagation of the urine bolus through the ureter facilitating the antegrade flow of urine.[11] Active contraction of ureteral smooth muscle also leads to the shortening of the distance between extravesical and intravesical ureteral hiatus with resultant widening of the ureter and reduction of obliquity for antegrade urinary passage. Lengthening of submucosal tunnel during relaxation provide a compression valve on the ureter; where in long oblique submucosal tunnel, the pressure is transmitted through the bladder mucosa to the ureteral wall anteriorly with stabilization of the posterior wall of ureter against detrusor backing.[9]

Since the time of first successful surgical treatment of vesicoureteric reflux by Hutch,[1] various techniques have been described for correction of vesicoureteric reflux.[2345678] Basic goal of all these techniques involves restoration of flap valve mechanism by creating a submucosal tunnel of adequate length according to Paquin's rule,[3] with adequate bladder muscle backing.

In the described experimental setup, a fixed extravesical hiatus was created. In place of creating a long submucosal tunnel, stripping of the bladder mucosa was done along the proposed course of submucosal tunnel and sufficient length of intravesical ureter, maintaining at least 5:1 length to width ratio, was anchored with interrupted sutures to the detrusor or submucosa in rectal reservoir, exposed by incising the mucosa. Thus, detrusor in bladder and smooth muscle in rectal reservoir provided a backwall for stabilization of posterior wall of ureter. Anterior compression valve was provided by the anterior wall of the intravesical segment of ureter itself or ureteral substitute in rectal reservoir without the cover of submucosal tunnel. However, this maneuver alone was insufficient to prevent reflux as fluid can easily move in retrograde fashion into proximal ureter or ureteral substitute. Therefore, creation of high-pressure zone at distal most ureteric segment is also needed in addition to creation of obliquity.

To create a high-pressure zone near the intravesical hiatus and low-pressure zone near the extravesical hiatus, terminal ureter was tapered with 2-3 stitches giving a pencil tip appearance. According to Hagen–Poiseuille law [Figure 3], with reduction in radius of terminal ureter, the intraluminal pressure increases by fourth power. Thus, intraluminal pressure is high at narrowed intravesical ureteric orifice as compared with the intravesical segment of ureter towards the bladder hiatus, where intraluminal pressure remains low. This high pressure at intravesical ureteric orifice is sufficient to prevent retrograde flow of urine at low intravesical pressure. With rising intravesical pressure, the intravesical segment of ureter toward the bladder hiatus starts acing as flap valve, thus preventing the reflux. In the current experimental setup, these maneuvers without creating submucosal tunnel provided a reliable antireflux mechanism without causing impediment to flow of urine from the ureter to the bladder as revealed by low-pressure free passage of saline from the ureter into the bladder.

Figure 3

Shows the pressure difference in the mercury column while water flows from a tube of wide diameter to tube of narrow diameter

It is assumed that in live creature after performing this procedure, the bladder mucosa will grow across the intravesical-anchored segment of ureter in several days forming the automatic submucosal tunnel. Further study is needed to confirm this assumption. Another question remains to be answered is whether during the course of healing, stenosis of the terminal end of the ureter may not occur. It can be addressed in live animal studies after necessary ethical clearance. The preliminary findings of this experimental study are encouraging and form the basis for future studies to develop antireflux procedure without the need to create submucosal tunnel.

CONCLUSION

Finding of this experimental in vitro study indicate toward the following facts:

In fresh postmortem specimen of ureter-bladder-urethra in lamb, intact antireflux mechanism is present.

In addition to the oblique course of the intramural ureter, nonobstructing narrowing at distal most ureter creating high-pressure zone is also important part of antireflux mechanism.

Antireflux mechanism can be created even without creating submucosal tunnel by simply anchoring the intravesical ureter to the denuded detrusor maintaining the ratio of 5:1 length to width of the ureter.