Ureteral replacement using small-intestinal submucosa and a collagen inhibitor in a porcine model

Purpose: Small-intestinal submucosa (SIS) has been successful as an onlay graft in ureteral repair, but tubularized segment interposition of SIS has been unsuccessful. Our objective was to evaluate whether a type I collagen inhibitor, halofuginone, would prevent stricture formation in tubularized SIS interposition. Materials and Methods: We performed either laparoscopic partial ureteral excision followed by an SIS on-lay graft (N = 5) or complete laparoscopic ureteral excision followed by an SIS interposition graft (N = 7) in domestic pigs. Animals received either no (N = 3), low-dose (N = 5), or high-dose (N = 4) halofuginone. Animals had ureteral stenting for 2 weeks after surgery and were permitted to survive for 6 or 9 weeks. An intravenous urogram (IVU) was performed prior to sacrifice. Kidneys were examined grossly and histologically. Results: One animal that received an onlay graft died of an unrelated illness. The remaining four ureteral onlay animals, including one control and two low-dose and one high-dose pig, had grossly normal kidneys at harvest. The IVU was normal in the control and high-dose animal but showed delayed excretion with mild hydroureteronephrosis in the low-dose animals. Pathologic examination of the SIS site revealed circumferential reepithelialization with inflammation and mild fibrosis. All seven tubularized interposition graft kidneys demonstrated either severe hydroureteronephrosis (N = 5) or renal atrophy (N = 2), and all had complete obstruction on IVU. Pathologic examination revealed a stenotic ureteral lumen with extensive surrounding inflammation and fibrosis. Conclusions: An SIS onlay graft was successful in the porcine model of ureteral injury. Halofuginone, a type I collagen inhibitor, did not demonstrate a significant beneficial effect in this technique. Ureteral tubularized interpositions with SIS are unsuccessful and not improved by halofuginone.