Background. The aim of our study was to examine the feasibility of allogeneic uterine transplantation in a large animal model.Methods. We performed heterotopic uterine transplants in genetically defined mini-pigs. Immunosuppression was tacrolimus administered intravenously for the first 12 days posttransplantation followed by oral cyclosporine maintenance immunosuppression. The graft was transplanted heterotopically in the lower abdominal cavity of the recipient. The vaginal vault was exteriorized as a stoma in the lower right abdominal wall. The uterine grafts were followed with endoscopies and biopsies.Results. Ten transplants were performed. Follow-up was until July 2008. At the end of the follow-up period, 5 animals were alive and healthy, 0.5 to 12 months posttransplantation. There were 5 deaths due to pneumonia (n=1), intussusception of the graft (n=1), cardiorespiratory arrest during anesthesia (n=1), and complications of the stoma (n=2). Acute rejections of the graft presented during the 2nd and 3rd month posttransplantation were treated successfully with increase of the maintenance immunosuppression and steroids. Other complications included prolapse and infections of the graft stoma. Pathological changes seen in the endometrial biopsies included acute rejection and acute endometritis.Conclusion. These findings demonstrate that successful uterus transplantation in a large animal model (miniature swine) is feasible using this heterotopic model, and it can be useful for the study of these transplants.
A technical innovation of a novel ureter implantation technique on rat kidney allograft transplantation is described. The left kidney graft is transplanted heterotopically into the left infrarenal position, using vascular conduits from donor abdominal aorta and inferior vena cava in continuity to renal vessels, to perform arterial and venous end‐to‐side anastomoses to the recipient vessels. A new ureter implantation technique was employed by placing a purse‐string suture around the uretero‐vesical anastomosis and ligated at the end of the anastomosis to invaginate the ureter and relieve tension at its junction to the bladder. This functions as an anti‐reflux procedure, also preventing urine leakage. Bilateral native kidneys nephrectomy of the recipient was performed a week post‐transplant. This model of rat kidney transplantation was associated with high survival rate (87%) 2 weeks post‐transplant with no evidence of vascular anastomoses complications or other technical failures. The technique is easy, reliable, and can be routinely applied to other microvascular transplantation procedures. © 2007 Wiley‐Liss, Inc. Microsurgery, 2007.
Intrahepatic cholangiocarcinoma (ICC) is well known to have a very poor prognosis. Aggressive surgical strategies in the treatment of ICC, including major hepatectomy, have been reported to afford patients the best chance for significant survival. Recent advancements in surgical techniques concerning live donor liver transplantation have dramatically improved the results of major hepatectomy. However, surgical treatment of biliary malignancy is complex and is known to increase the likelihood of blood transfusion. We describe a Jehovah's Witness patient with ICC and concomitant bile duct invasion who had a successful right trisectionectomy with bile duct resection, lymph node dissection, and Rouxen-Y hepatico-jejunostomy without blood transfusion. A multidisciplinary preparation was crucial in obtaining this positive outcome. Importantly, bloodless liver transection techniques with inflow clamping, meticulous dissection, and hemostasis should be utilized for major hepatectomy in a Jehovah's Witness. The success of this case may alert clinicians to consider a hepatectomy as a possible option in the treatment of ICC in a Jehovah's Witness.
Introdução: O objetivo deste estudo foi relacionar os níveis de citrulina sérica à rejeição celular aguda após transplante intestinal, avaliando a citrulina como método laboratorial menos invasivo e de menor custo que a biópsia endoscópica para diagnosticar a mais importante complicação após transplante intestinal. Métodos: Estudo aprovado pelo Comitê de Ética em Pesquisa com Animais e realizado em caráter experimental no Batchelor Research Institute da Universidade de Miami, no período de agosto a dezembro de 2004. Foram realizados cinco transplantes heterotópicos de intestino, com duas estomias e vascularização da artéria mesentérica superior na aorta e drenagem venosa do mesentério na veia cava. Amostras de sangue foram colhidas no 3º, 5º e 7º dias pré- e pós-operatórios. Resultados: Os níveis de citrulina sérica variaram de 78 a 99 µmol/L no pré-transplante, de 44 a 54 µmol/L no pós-transplante 3, de 62 a 73 µmol/L no pós-transplante 5 e de 36 a 60 µmol/L no pós-transplante 7. Os níveis médios de citrulina sérica nos pós-transplante 3,5 e 7 foram significativamente menores comparados ao correspondente no pré-transplante. Conclusão: Os níveis séricos diminuíram durante a rejeição celular aguda, o que pode indicar a citrulina como marcadora precoce de episódios de rejeição celular aguda no transplante intestinal.
Anastomotic healing is impaired after intestinal surgery because of ischemia and reperfusion injury (IRI), which can result in intestinal leaks leading to increased mortality. The objective of this study was to determine the effects of transplant IRI and immune mechanisms on intestinal graft anastomotic healing. Orthotopic intestinal transplantations (OIT) were performed in rats. The experimental design consisted of six groups A–F ( n = 5/group): A, allogeneic OIT treated with tacrolimus (1mg/kg/day); B, syngeneic OIT treated with tacrolimus; C, syngeneic OIT; D, allogeneic OIT; E, proximal and distal anastomoses performed in nontransplanted animals; F, same as in group E but treated with tacrolimus. Anastomotic bursting pressure (ABP), hydroxyproline content (HPC), and mucosal inflammatory infiltrate (MII) were determined at the anastomotic sites (proximal and distal) and compared between groups. ABP was significantly ( p < 0.001) reduced in OIT groups A, B, C, and D compared to control groups E and F at both the proximal and distal anastomotic sites. HPC was ∼1 μg/mg of tissue in groups A, B, C, and D, and ∼5μg/mg of tissue in groups E and F. This demonstrates a significant ( p < 0.001) reduction in HPC after OIT. MII was significantly ( p < 0.001) increased in OIT groups when compared to nontransplanted control groups. MII was also significantly ( p < 0.05) increased in allogeneic OIT groups A and D compared to syngeneic OIT groups B and C. Generally, ABP and HPC were inversely proportional to MII in both nontransplanted control and OIT groups. Reduced anastomotic strength was demonstrated in both syngeneic and allogeneic OIT anastomotic sites irrespective of immunosuppressive therapy, and is probably related to IRI.
Pre-transplant blood transfusions are given as a means of desensitization to reduce the required dose of cyclosporin A (CsA). In this study, the effect of pretransplant blood transfusion on host survival and T-cell function against alloantigen were investigated. Male Lewis rats (RT11) were used as the recipients in all experiments, and male DA rats (RT1a) were used as the blood and small bowel donors, and as a source of allogeneic stimulator cells. Male BUF rats (RT1b) were used as donors of third party blood, and of allo-stimulator cells in a delayed-type hypersensitivity (DTH) response. In our experimental design, Lewis rats were divided into the following groups according to the type of administration: (1) a donor-specific blood transfusion (DST) 8 days preoperatively and a concurrent 5-day course of CsA at 10 mg/kg per day; (2) a nonspecific third party blood transfusion (NST) and CsA at 10 mg/kg per day from day 8 to day 4 preoperatively; (3) CsA alone from day 8 to day 4 preoperatively; (4) DST alone 8 days preoperatively; or (5) no treatment, being the control group. Postoperative treatment consisted of CsA at 2.5 mg/kg per day for 30 days. Rats conditioned with NST plus CsA, CsA alone, DST alone, and the untreated control rats survived for 7.2 ±1.2, 9.0 ± 2.2, 6.8 ± 0.4, and 7.4 ± 1.6 days, respectively. In contrast, the five rats conditioned with DST plus CsA survived for 100 days or more. This study demonstrates that long-term survival of a small bowel allograft can be achieved by host-conditioning with a combined treatment of DST and low-dose CsA.