V. Seid

An innovative model of autologous anorectal transplantation with pudendal nerve reconstruction

Fecal incontinence is an important public health problem that has a significant impact on the quality of life of individual patients. The prevalence of fecal incontinence in the United States ranges from 2 to 17%, but this may be an underestimation (1). The current treatments for severe fecal incontinence are often complex and have disappointing results (1). Anorectal transplantation may be a definitive method for restoring normal sphincter function in these patients. We and others have previously investigated anorectal transplantation in rats with promising results (2-4). However, there is a lack of pre-clinical large animal models to study the potential benefits of this procedure. In this paper, we describe an innovative surgical technique of anorectal autotransplantation, which allows for physiological studies without the immunologic effects related to allotransplantation. The technique was initially performed in three swine weighing 25-35 Kg. After general anesthesia, an abdominal and perineal incision was performed in which the rectum, anal sphincter, and skin surrounding the anus were procured en bloc. The grafts vascular pedicle contained the inferior mesenteric artery (IMA) with a patch of the aorta and inferior mesenteric vein (IMV), which was divided near the splenic vein (Figure 1A). The pudendal nerve was carefully isolated and transected. The graft was removed and immediately flushed with 250 ml of cold heparinized preservation solution through a catheter inserted in the IMA. The graft was then placed in a cooler with cold solution without heparin for a total of 20 minutes. The infrarenal aorta and vena cava were isolated and cross-clamped, and the graft was implanted by arterial and venous anastomoses between the IMA and the aorta (Figure 1B) and the IMV and vena cava (Figure 1C). After reperfusion (Figure 1D), the entire graft was placed inside the abdominal cavity, and the pudendal nerve was reconstructed (Figure 1E). Finally, the anus was placed in its original position, and the perineum was closed (Figure 1F). Digestive tract continuity was reestablished by an end-to-end colorectal anastomosis. The abdominal cavity was closed, and the animals were observed for an additional two hours. At the end of the experiment, the graft was removed for histological analysis. The average times for graft recovery and implantation (including vascular, nervous and GI reconstruction) were 57 and 99 minutes, respectively. No problems regarding graft perfusion were observed at the end of the experiment. Histological graft assessment showed normal aspects in one graft and mild ischemia-reperfusion injury in two. Figure 1 (A) An anorectal graft showing the inferior mesenteric artery (IMA) and vein (IMV) and the rectum (R). (B) The infrarenal aorta (Ao) and vena cava (IVC) were cross-clamped at the site of anastomosis

Functional outcome of autologous anorectal transplantation in an experimental model

Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats.

Allogeneic anorectal transplantation in rats: technical considerations and preliminary results.

Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal distention, diarrhea, and anal mucosa inflammation) were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies.