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.