Uterus transplantation model in sheep with heterotopic whole graft and aorta and cava anastomoses.

Uterine transplantation in the sheep model has been described as a partial or whole orthotopic graft from a living donor with vascular anastomoses. As an alternative to surrogate pregnancy or adoption uterus transplantation might be indicated for cases of infertility of uterine origin. The main complications might be rejection and thrombosis. The objective of this work was to develop a model of whole uterus transplantation that was applicable to the human setting, using grafts obtained from brain-dead donors, and suitable for immunologic and viability follow-up with a reduced risk of thrombosis. Two donors and 1 recipient were operated. The first graft was used for an anatomic study; the second was used for transplantation. The donor operation consisted of an en bloc harvest of the uterus, adnexa, and proximal vagina with the distal aorta and cava. After harvest the donor sheep was humanely killed. In the recipient ewe, heterotopic implantation was performed in the lower abdomen. An End-to-side anastomoses of aorta and cava were performed below the recipient's renal vessels. A cutaneous vaginal stoma was performed in the right lower quadrant. The recipient ewe was humanely killed for an autopsy study. The anatomy of uterine veins of the ewe differs from the human. The uterine and ovarian veins join, forming the utero-ovarian vein, which drains at the confluence of the common iliac to the cava. En bloc harvesting allows for rapid graft preparation, with vascular cuffs easily anastomosed with a low risk of thrombosis. The vaginal stoma seems appropriate to facilitate follow-up and graft biopsy. This approach can be a suitable experimental model applicable to humans using grafts from brain-dead donors.

Association between panel reactive antibodies and acute small bowel rejection: analysis of a series of 324 intestinal transplants.

INTRODUCTION: Panel reactive antibodies (PRA) to class I and II HLA molecules have been associated with acute kidney graft rejection, but their role in small bowel transplantation has not been characterized. METHODS: Since 1994, 324 SBT, alone or as multivisceral transplantation (MVT), have been performed in 286 patients. Routine and surveillance biopsies were performed to rule out or confirm acute rejection (AR), and PRA quantification was performed at varying intervals. We obtained data from 110 patients and 651 PRA measurements. While AR grade (mild to severe, grades 1-3) was determined by histopathological analysis, the status of no AR was determined also by clinical data. When biopsy samples or PRA measurements were frequent around an AR episode within periods of 7 days, the highest value was used. RESULTS: A comparison could be made between 259 instances in which there was a PRA measurement and simultaneous rejection evaluation. Positive PRA showed association with AR (P < 0.001). The positive and negative predictive values were 44% and 79%, respectively. No correlation was found in the severity of rejection. CONCLUSION: The presence of increased levels of PRA is a risk factor of rejection in small bowel transplantation. Alloantibody-mediated injury to the graft contributes frequently to acute rejection of small bowel, and it is associated with cell-mediated immunity in variable proportion.

Exclusions and deaths on the liver transplant waiting list.

OBJECTIVE: To analyze the characteristiscs, evolution and survival of patients included on the waiting list (WL) for liver transplantation (OLT). PATIENTS AND METHODS: Between February 2002 and April 2009, 254 patients were included on WL to receive a first graft. Two hundred twenty-two patients (87.4%) were transplanted (group T); 7 (2.8%) died on the WL and 25 (9.8%) were excluded, namely, 13 (52%) due to improvement (group IE) and 12, for other reasons (group OE). Data collected prospectively were analyzed retrospectively. RESULTS: Indications for transplant were cirrhosis (58%), hepatocellular carcinoma (HCC; 29%) and other etiologies (13%.) Average time on the WL was 60.3 +/- 62.9 days. Significant differences were not observed among the groups with respect to age, gender, or indication for OLT. The probability for exclusion due to progression and/or death was not significantly greater among patients included for HCC than for other reasons (P = .6). Survivals at 1, 3, and 5 years after WL inclusion were 81.2%, 73.3%, and 68.6%, respectively, in the whole series; and 85,4%, 76,9%, and 71.7% in group T. All group OE patients died before the first year, while group IE showed a survival of 100%, 91.7% and 91.7% at 1, 3, and 5 years, respectively. Survival was not different between groups T and IE (P = .03), but was lower in group OE than in groups T or IE (P < .001). CONCLUSION: The list mortality rate in our series was low, probably in relation to the short waiting time. The rate of exclusion from WL was 10%. Patient with hepatocellular carcinoma were not at an increased risk of WL exclusion. Patients excluded due to improvement displayed excellent survivals during the 5 years following exclusion.

Portoumbilical anastomosis as a simple method of transient portosystemic shunt during liver transplantation.

BACKGROUND: This article describes a new method of transient intraoperative portosystemic shunting, Splachnic edema after portal cross-clamping can be a dangerous complication during the anhepatic phase of the liver transplant operation. The current method seeks to avoid this problem, without the use of external venovenous bypass pump, by a temporary portocaval shunt, with retrohepatic cava preservation as first described experimentally in dogs by Fonkalsrud et al in 1966. METHODS AND RESULTS: Among 227 liver transplant operations, we utilized a transient portosystemic shunt in 29 cases. The indication to perform a temporary shunt in all cases was the development of splachnic edema. In 3 instances, we performed a portoumbilical anastomosis using a prominent umbilical vein. The other 26 procedures employed the usual portocaval shunts. In these cases, splachnic congestion and onset of edema developed after cross-clamping of the round ligament and the portal vein, which resolved after the portoumbilical anastomosis. DISCUSSION: The flow in the shunt was in all cases greater than 1 L/min. The most important risk factor for the development of splachnic edema was the presence of a patent umbilical vein, which occurred in 34.5% of shunted patients. CONCLUSION: The use of a patent umbilical vein to perform a portoumbilical shunt was an effective, easy method to decompress the splachnic area, avoiding dangerous congestion and edema.

Renoportal anastomosis as a rescue technique in postoperative portal thrombosis in liver transplantation.

Renoportal anastomosis has been used as the primary portal revascularization technique in grade 4 portal thrombosis, but never after posttransplant portal thrombosis. A cirrhotic patient with hepatocellular carcinoma and partial portal thrombosis of two-thirds of the lumen was transplanted. The thrombus was removed and good portal flow obtained upon reperfusion (2.8 L/min). On the ninth postoperative day Doppler ultrasound revealed complete portal thrombosis extending from the splenomesenteric confluence. At emergency reoperation, we removed the newly formed thrombus. Portal vein branches were flushed with heparin and urokinase. After reconstruction of the anastomosis, we achieved a flow of 1.1 L/min. Rethrombosis occurred again on day 13. At reoperation, thrombus was removed again. However, this time portal flow was not recovered, due to hepatofugal flow associated with both the presence of collaterals and pancreatic edema. A left renoportal anastomosis was performed using an interposed iliac vein graft. A catheter was placed into the portal vein through a recanalization of the umbilical vein of the graft. After urokinase perfusion, portal inflow was 1.7 L/min. The postoperative course was satisfactory, with progressive normalization of liver tests and no further thrombosis. Persistent ascites improved with treatment. Angiography on day 41 showed good portal flow from the renal vein, with uniform distribution within the liver. A renoportal anastomosis can be useful for recovery of liver failure after posttransplant portal thrombosis, in the absence of portal flow.

Five-year follow-up of a trial comparing Tacrolimus and cyclosporine microemulsion in liver transplantation.

We evaluate 5-year results of a prospective randomized trial that compared cyclosporine microemulsion (CsA-me) and Tacrolimus (Tac) for primary immunosuppression. One hundred one adult patients undergoing liver transplantation were randomized to receive Tac (n = 50) or CsA-me (n = 51). The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism. Survival rates at 1, 3, and 5 years were 86%, 75%, and 72%, respectively; there was no significant difference between CsA-me versus Tac arms. Acute rejection occurred in 30 cases (30%), independent of the type of primary immunosuppression. Serious adverse events were reported significantly more among patients under CsA-me (48 episodes) than under Tac (32 episodes). Nineteen patients were switched to the other calcineurin inhibitor. The switch was much more frequent from CsA-me to Tac (n = 15; 29.4%), mainly because of lack of efficacy (n = 10; 19.6%). There were no cases of chronic rejections in the Tac arm. Four patients were switched from Tac to CsA-me for side effects; only 1 remains alive, after treatment was changed from CsA-me to an antimetabolite. There were no statistical differences in renal dysfunction, diabetes, hypertension, neurologic disorders, new-onset malignancies, or infections. There were no differences in survival or rejection among the intention-to-treat groups. Serious adverse events, total patients with switch of calcineurin inhibitor, as well as switches due to lack of efficacy, were statistically more frequent under CsA-me. Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation.