Comparison of Yang-Monti ileal ureter-bladder anastomosis versus Yang-Monti ileal ureter-ureteral anastomosis for the treatment of ureteral stenosis: a randomized controlled trial in a miniature pig model

With the widespread development of urological endoscopic surgery, iatrogenic injury has become one of the most common causes of ureteral injury [1], and the incidence of long-term ureteral injury is increasing. The most serious complication of ureteroscopy is ureteral avulsion, with an incidence of 0.06–0.45% [2‐5]. Most cases of lower ureteral avulsion are treated with ureteral bladder replantation. However, multiple operations cause adhesions and stenosis in the lower ureter, poor blood supply to the ureter, difficulty in healing postoperatively, scarring, and result in a ureter with a small diameter and thin wall, which is not conducive to anastomosis.

The Yang-Monti technique for ileal ureteral reconstruction is used in clinical practice and has good curative effects [6‐8]. The characteristics of this method are that the alternative ureteral tube diameter is the same as that of the original ureter, the intestinal tube is short, the diameter of the replacement tube is small, and the intestinal tube is saved. In addition, the absorptive and secretive functions of the intestinal segment used in ureteral reconstruction are decreased because the absorbent surface area is limited and the mucous production is decreased, preventing occlusion of the lumen and postoperative metabolic abnormalities.

It remains controversial whether there is a need for an anti-reflux procedure in ureteral reconstruction. Some studies report that there is no need to establish an anti-reflux anastomosis, while others advocate the establishment of anti-reflux procedures [9‐11]; furthermore, there is reportedly no difference in efficacy in accordance with the performance of an anti-reflux procedure [12]. In the non-anti-reflux procedure, the ileal ureter was implanted into the bladder directly. The operation is relatively simple and convenient, the operation time is short, and the incision is small. However, there may be a backflow of urine from the bladder to the replacement ureter or ipsilateral kidney, resulting in postoperative intestinal dilatation, ascending infection, pyelonephritis, hydronephrosis, and impaired renal function [13]. To reduce the incidence of such complications, anti-reflux anastomosis involves the insertion of a nipple structure at the ileal bladder junction [14], a proximal ileal wall tunnel anti-reflux procedure [15, 16], and an extra-urinary ureter tunnel extension (Lich-Gregoir method) [7, 12].

When the lower ureter is well preserved, the ileal ureter can be anastomosed to the lower ureter, but this may cause postoperative complications such as mucus obstruction and anastomotic stenosis. If the lower ureter cannot be anastomosed, the intestinal ureter needs to be re-implanted in the bladder to prevent reflux. This is achieved via Yang-Monti ileal ureter and bladder anastomosis or Yang-Monti ileal ureter and lower ureteral anastomosis [7]. We established animal models of the Yang-Monti ileal ureter and bladder anastomosis and the Yang-Monti ileal ureter and lower ureteral anastomosis to evaluate which method is more convenient to perform, and to compare the advantages and disadvantages of both methods.

The operation was successfully completed in all 14 miniature pigs. In group A, one pig died from an anesthetic accident, and another died from a lung infection on postoperative day 4. In group B, one pig died from adhesive intestinal obstruction on postoperative day 7. The overall survival rate was 78.6%, and the 11 surviving pigs had no urinary or intestinal fistulae. Compared with group B, group A had a significantly longer operation time (p = 0.01) and skin incision length (p = 0.02) (Table 1). The serum creatinine and urea nitrogen concentrations did not significantly differ between groups at any timepoint (p > 0.05). All pigs had normal renal function pre- and postoperatively (Table 2). Intravenous pyelography showed no stenosis or obstruction (Fig. 3a, b). The narrowest diameter of the ureter in group A was significantly larger than that in group B (p = 0.01) (Table 3). No contrast agent returned to the upper urinary tract in either group (Fig. 3c, d). Escherichia coli was detected in postoperative urine cultures from four pigs in group A and four pigs from group B.

Gross examination of the collected specimens revealed complete obstruction of the distal ends of the inferior and lower ureters and narrowing of the other ends of the inferior and lower ureters in two pigs from group A. There was marked adhesion around the two anastomoses and obstructive stenosis distal to the intestinal ureter. The kidneys were atrophic with marked hydronephrosis and thin and transparent renal parenchyma (Fig. 4a).

In group B, one pig had moderate hydronephrosis and mild dilation of the intestinal ureter at 12 months postoperatively; however, the ileal ureter and anastomoses were patent (Fig. 4b). The rest of the pigs in group B had patent intestinal ureters and smooth anastomoses. The intestinal ureters were a reddish color, with a shape that was similar to that of the normal ureter. The intestinal ureters were slightly thicker than the normal ureters, and were surrounded by fibrous tissue and adipose tissue. There was continuous, intestinal mucosal atrophy on the surface of the intestinal ureters, with no signs of hydronephrosis.

The ileal ureteral diameter was significantly larger in group A than group B (p = 0.02) (Table 3).

Histological examination showed that two pigs in group A had separation between the transitional epithelium of the upper and lower ends of the ureters and the columnar epithelium, with granulation tissue hyperplasia. Two pigs in group A with ureteral obstruction had fibrous tissue and smooth muscle tissue hyperplasia and support stenosis at the anastomosis site (Fig. 5a, b). In the six surviving pigs in group B, the two types of epithelial tissue were close together in the ureteral ureters at both ends of the anastomosis (Fig. 5c, d). In both groups, the replacement intestinal segments had shortened and atrophied villi compared with normal intestinal villi (Fig. 5e, f).

In the present study, we successfully established an animal model of ileal ureter-bladder anastomosis and ileal ureter-ureteral anastomosis using the Yang-Monti technique. The serum creatinine and urea nitrogen concentrations did not significantly differ between the two groups at 2, 6, and 12 weeks postoperatively. The renal function was stable, with no postoperative renal dysfunction or failure.

The average operation time and length of the surgical incision in group A were significantly longer than in group B. This may be because the operational procedures in group B were relatively easier to perform than those in group A. In group A, the anastomosis between the intestinal ureter and the native ureter required the lower ureter to be fully freed. As the lower ureter is deeply located, the operational space available for the anastomosis was relatively small. In contrast, the intestinal ureter in group B was directly anastomosed to the bladder, and the lower segment of the ureter was not required. The bladder of the miniature pig is more easily recognized when it is full, and the apex wall, the two lateral walls, and the anterior and posterior walls of the bladder are not connected to the surrounding pelvic wall. As the position of the bladder in the pelvic cavity is not fixed, the bladder is movable and easier to find than the lower part of the ureter. Furthermore, it is easy to re-integrate the ureter and the left side of the bladder, and the operational space is large.

The most common complication of ileal ureteral surgery is urinary tract infection, which is related to bladder ileal reflux and intestinal mucus secretion; this complication is difficult to control and is often recurrent, eventually leading to hydronephrosis or multiple renal cortex abscesses and pyelonephritis [7, 18, 19]. Urine culture results show that the most frequently cultured organism is E. coli, followed by Klebsiella pneumoniae [12]. Yao et al. [20] performed short- and long-term observations of 60 patients with ileal ureters, and found abnormal changes in the urine (including a small amount of protein, white blood cells, pus balls, and intestinal mucus); however, only four patients had clinical symptoms of urinary tract infection, and the symptoms disappeared after treatment with antibiotics. Therefore, urinary changes do not necessarily indicate the presence of urinary tract infection, and antibiotic treatment is needed only when symptoms of acute infection occur [20]. The E. coli colonization seen in urine cultures in the present study is consistent with the literature. E. coli is a pathogenic pathogen of the intestine, and may move from the intestine to the urinary tract during surgery; no antibiotic treatment is required for such asymptomatic bacterial urinary infection.

The two methods used in ileal ureteral surgery and bladder anastomosis are non-anti-reflux and anti-reflux. In the non-anti-reflux procedure, the ileal ureter replaces the ureter directly after the bladder. The operation is relatively simple, the operation time is short, and the incision is small. However, there may be postoperative intravesical urine reflux to the replacement ureter or ipsilateral kidney, resulting in postoperative intestinal dilatation, ascending infection, pyelonephritis, hydronephrosis, and impaired renal function [13]. The incidences of such complications are reduced by the performance of anti-reflux anastomosis. In the present study, there was no stenosis obstruction observed in either group. However, the narrowest diameter of the intestinal ureter was significantly larger in group A than in group B.

On intraoperative measurement, the reconstructed intestinal ureteral diameter was still larger than the normal ureteral tube diameter. In group A, the ureter was cut longitudinally before the intestinal ureter and the lower ureter were anastomosed. Thus, the anastomosis is relatively small, the ileum is more stretched than the ureter, and the urine flows through the relatively narrow lower ureter after passing through the wide intestinal ureter. The urine flow rate is slowed, the stagnation time is long, and urine is retained in the intestinal ureter, which causes the intestinal ureter to expand; the indwelling endoscopic tube also causes postoperative expansion. In contrast, the intestinal ureter in group B was directly matched with the bladder, and the anastomosis was wider than that in group A. Venous pyelography showed that the contrast agent quickly entered the bladder through the intestinal ureter without being retained. This may be why the intestinal ureteral diameter in group B was smaller than that in group A.

As the Yang-Monti ileal ureter is directly matched with the bladder, the anastomosis is large, which may increase the likelihood of reflux. In the present study, no contrast agent returned to the upper urinary tract in either group. In group A, there was no reflux because the intestinal ureter and the lower ureter were anastomosed and the anti-reflux mechanism between the ureter and the bladder was retained. There was also no reflux in group B, even though the anastomosis of the intestinal ureter was large and directly opened to the bladder. The absence of reflux in group B may be because the intestinal ureteral diameter was close to that of the normal ureter, and the intestinal ureter had good elasticity and a long length. The ileum retains its peristaltic function after replacing the ureter, which is beneficial in preventing intravesical pressure [7, 12]. However, confirmation of this requires measurement of the intestinal ureter, renal pelvis, and intravesical pressure. Other possible reasons for the absence of reflux in group B are that the miniature pig has a short urethra, good bladder elasticity, and rapid urine emptying. Therefore, there is little need to establish an anti-reflux mechanism in the Yang-Monti ileal ureter in miniature pigs.

The intestinal epithelium is a single-layer columnar epithelium, while the urinary tract is a transitional epithelium. The examination of the intestinal tract after ileal ureter replacement showed that all of the anastomotic regions had unobstructed lumens, no epithelial proliferative changes in the junctional zone, and were located less than 1 cm from the adjacent junctional zone; this very short distance is covered by migration epithelial metaplasia [21]. In a previous study of ileal ureter reconstruction via the Yang-Monti method in rabbits, histological sections obtained 12 weeks postoperatively showed that stratified transitional epithelial cells had spread toward and covered part of the intestinal mucosa at the site of the anastomosis, and the intestinal mucosa on the inner surface of the ureter was obviously atrophied [22]. In another study in which ileal ureteral surgery was performed on miniature pigs, the columnar epithelium was still visible in the middle ileum at 3 years postoperatively; however, the villi were atrophied and some of the villi had become shorter and wider than normal [23]. In the present study, histological examination of the intestine and ureter was consistent with the findings of these previous studies. After the ileum was used to replace the ureter, its histological characteristics changed to adapt to the urinary environment. The transitional epithelium and the columnar epithelium were continuous and replaced the segmental columnar epithelium, indicating that the ileum that replaced the ureter maintained the shape and integrity of the epithelium, which may still have a mucosal barrier. Further experimental studies are needed to confirm whether the intestinal mucosal barrier changes in the urinary environment. In addition, after the ileum was used to replace the ureter, the intestinal mucosa shrank, the villi became shorter, and the absorption and secretion functions of the intestinal mucosa were correspondingly weakened. This may be related to the absence of obvious metabolic abnormalities and mucus secretion after Yang-Monti ileal ureteral reconstruction in the clinical setting, but requires confirmation in further studies of the absorption and secretion functions of intestinal mucosal epithelial cells.

In group A, the distal end of the inferior ureter and the lower end of the ureter were completely obstructed and stenotic, and there was marked hydronephrosis. In group B, one pig had hydronephrosis and mild dilation of the intestinal ureter, although the anastomosis was smooth. Histological examination showed that group A had hyperplasia of fibrous tissue and smooth muscle at the anastomosis site, suggesting the presence of stenosis or obstruction. In group A, the intestinal ureter was anastomosed with the lower ureter, which means that the lower ureter needed to be separated from the surrounding tissue. The thin ureteral wall may lead to poor blood supply in the lower ureter; thus, although there is good blood supply to the ileal ureter, there may be poor blood supply between the intestinal ureter and the lower ureter after anastomosis, resulting in fibrosis or scarring postoperatively. This may be why the incidence of stenosis or obstruction and hydronephrosis was higher in group A than in group B. In group B, the intestinal ureter was directly matched with the rich blood supply of the bladder, which limited the occurrence of postoperative stenosis or obstruction. Although there was no evidence of hydronephrosis and regurgitation on intravenous pyelography and cystography in group B, visual observation suggested the presence of hydronephrosis and mild dilation of the intestinal ureter. Furthermore, although the short-term imaging examination revealed no abnormal changes, the inguinal ureter may undergo compensatory changes over time after countering the persistent intravesical pressure.

We successfully established an animal model of Yang-Monti ileal ureteral reconstruction. Compared with the Yang-Monti ileal ureter-ureteral anastomosis, the Yang-Monti ileal ureter-bladder anastomosis is simpler, more reliable, and results in fewer complications.