The ultimate outcomes of ureteral strictures are functional obstruction or renal failure in short period if untreated. To preserve renal function and eliminate ureteric obstruction, a multitude of surgical procedures have been described (4–6). For short ureteral strictures, primary ureteroureterostomy is advisable. Distal ureteral strictures can be resolved by direct ureteral reimplantation. Mid-ureteral strictures or long strictures near the pelvic brim can be managed by ureteroneocystostomy using a bladder elongation procedure with a psoas hitch or Boari flap.
Long stricture or defect of the upper ureter present a challenging problem for urologists and require ileal replacement or renal autotransplantation. Both procedures are of considerable magnitude and are associated with complications such as mucous plugging, stone formation, pyelonephritis, metabolic acidosis and vascular complications (7, 8). These issues have prompted urologists to search for a less invasive treatment for upper ureteral strictures. Tissue engineering offers a promising option for urethral reconstruction (23), but tissue-engineered ureters have been confined to pre-clinical investigations. Published research in this area is controversial and scarce (24).
The successful use of buccal mucosal grafts in urethral replacement has led to interest in the use of a similar approach in ureteric reconstruction. Naude first reported the use of buccal mucosa in ureteroplasty in 1999 (12). Recently, several studies have shown its clinical application, with promising results (10, 11, 13–15). However, the harvest of buccal mucosal graft leads to donor site morbidity, such as salivatory duct damage, facial hematoma, neural damage causing paraesthesia, and limited mouth opening (16–18). More importantly, for long ureteral strictures, which require a larger supply of graft tissue, buccal mucosa alone may be insufficient.
LMGs have the same features of buccal mucosal grafts, including resistance to infection, rapid revascularization and compatibility with wet environments (19, 20). The ventral and lateral surfaces of the tongue have no particular functions and can be used for a mucosa graft up to 14–16 cm long. In addition, compared to buccal mucosa, the LMG harvesting procedure is easier and associated with less donor site morbidity (20–22). Therefore, LMGs can be another reliable substituted material, used alone or combined with buccal mucosal grafts for long ureteral reconstruction (25).
In our animal study, macroscopic examination and IVU results demonstrated that the LMGs were well incorporated into the ureteral wall, maintained a wide caliber and had excellent drainage. The ureteral diameter of the proximal ureter did not significantly differ from that of the distal ureter, which verifies the absence of proximal ureteral obstruction. Only one dog in group C developed a mild ureteral stricture near the proximal anastomosis. Macroscopic examination showed a lack of omentum around the proximal anastomosis. We ascribed the formation of stricture to insufficient omental wrapping. The omentum has an excellent vascular bed, which can offer additional blood supply for the graft (26). After we gained experience and optimized techniques, the other animals in the three groups had excellent outcomes. We concluded that leakage-free anastomosis and proper omental wrapping around the graft are key points for success. In our study, LMGs were found to repair ureteral defects with a length of 10 cm. We believe that if more omentum can be mobilized downward to the pelvis brim in the dog, longer ureteral defects can be repaired.
It is well known that neovascularization is a reliable indicator for the viability of an engrafted tissue. CD31 antibody was used to identify capillaries (neovascularization) because of its specificity as an endothelial marker (27). In this experiment, IHC staining with CD31 showed the formation of new capillaries under the epithelium, confirming that the LMG can survive in situ. We conserved half of the ureteral wall as a ureteral plate, and the ureteral defect was repaired by a graft patch in an onlay fashion. This technique is similar to nontransecting urethral reconstruction (28), with the advantage that the residual ureteral plate preserves blood supply to the graft.
Collagen proliferation or fibrosis in connective tissue under urothelium is a major cause leading to stricture recurrence. Leakage-free anastomosis is essential. In our study, well-formed collagen and smooth muscle fibers around the LMG were observed with Masson’s trichrome staining in postoperative 12 months.
To observe changes in the engrafted lingual mucosa, we performed histological analysis. Fairbanks et al. described the process in their experimental study with bladder mucosal grafts in rabbits. Their hypothesis was that the bladder mucosa underwent partial degeneration, followed by regeneration of the urethral epithelium from the graft margins (29). In the study of colonic mucosal grafts for urethral reconstruction performed by Yuemin Xu, they found that the colonic mucosa underwent metaplasia from unilaminar cylindrical epithelium to urethral epithelium (30). In our study, histological examination showed that the LMG survived inside the ureteral lumen and maintained its typical squamous epithelium at 6 months postoperation. At the same time, the expression of uroplakin on the surface of the LMG, as identified by IHC staining with UP-II, was intermittent, which may exclude the possibility of urothelium crawling from the graft margins. At 12 months after surgery, only a fraction of typical squamous epithelium remained. Most importantly, it appeared that this fraction of squamous epithelium was not completely exposed to urine. The epithelium of the LMG resembled urothelium, with intermittent expression of uroplakin. Based on these findings, we are more inclined to accept the hypothesis of metaplasia. However, further study is needed to investigate the mechanism of histological changes after the LMG is exposed to urine.
One limitation of this experimental study is that it is based on a very small series, with only 4 subjects in each group and a follow-up of only 1 year. Perhaps a larger group of subjects and a longer follow-up period would further demonstrate the viability of this surgical technique.