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.

A prospective, multicenter study of once-daily extended-release tacrolimus in de novo liver transplant recipients.

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.

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.

Liver transplantation complications in the intensive care unit and at 6 months.

OBJECTIVE: This study sought to determine the factors that influence the 6-month outcomes of liver transplants. PATIENTS AND METHODS: One hundred ninety-six variables (donor, recipient, operation, intensive care unit [ICU], evolution at 3 and 6 months) were collected from the first 74 consecutive liver transplantation performed from 2002 to 2004. The primary endpoint was patient survival at 6 months. The statistical analysis included a screening univariate analysis followed by a stepwise logistic regression with forward inclusion to test independent associations and finally generation of receiver-operator characteristic (ROC) curves to evaluate predictive factors. RESULTS: Patient survival at 6 months was 86%, namely 10 deaths, including 4 intraoperatively and 6 postoperatively due to sepsis. Complications in the ICU were classified as reoperations due to biliary problems, vascular complications, and peritonitis. Late complications included 51% rejection episodes, 24% infections, 11% pleural effusions, and 16% diabetes mellitus. Logistic regression analysis showed independent negative predictors of survival were the number of packed red cells during transplantation, the number of fresh frozen plasma units administered in the ICU, blood urea nitrogen (BUN) concentration in the ICU, and graft complications. The odds ratios of these variables were 10.2, 5.2, 42.1, and 36.9, respectively. The area under the curve (AUC) of the ROC was 0.99; the sensitivity was 94%; and the specificity was 100%. The independent predictors of surgical complications were the length of the operation, the need for pressor support, and the number of fresh frozen plasma units administered in the operating room, with odds ratios of 1.0, 7.7, and 1.1, respectively. CONCLUSION: This study revealed specific operative and ICU variables that correlated with the evolution of our patients.

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.

Primitive neuroectodermal peripheral tumour of the retroperitoneum.

Retroperitoneal primitive neuroectodermal tumour is an uncommon disease. The main treatment consists of surgical resection, which can require resection of great vessels, depending on the location. We present a single case of a 19-year-old male with a large tumour. To achieve R0 resection we needed to remove the vena cava. Venous flow reconstruction was performed with a cava prosthesis.

Primitive neuroectodermal peripheral tumour of the retroperitoneum

Retroperitoneal primitive neuroectodermal tumour is an uncommon disease. The main treatment consists of surgical resection, which can require resection of great vessels, depending on the location. We present a single case of a 19-year-old male with a large tumour. To achieve R0 resection we needed to remove the vena cava. Venous flow reconstruction was performed with a cava prosthesis (AU)

No disponible

Colangitis esclerosante primaria como causa de un pseudotumor de la confluencia de la vía biliar / Primary sclerosing cholangitis as a cause of bile duct confluence pseudotumor

No disponible

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.

Long-term biliary complications after liver surgery leading to liver transplantation.

Chronic biliary obstruction with repeated bouts of cholangitis adversely affects quality of life and may lead to secondary biliary cirrhosis with liver failure. We reviewed our experience with chronic biliary complications after surgical treatment of various diseases that at the end needed a liver transplantation. Twelve patients with previous biliary surgery developed secondary biliary cholangitis, secondary biliary cirrhosis, or both. Seven had surgery for liver hydatid disease by Echinococcus granulosus, another four had complicated biliary surgery unrelated to hydatid disease, and one had a history of a traffic accident with liver trauma and hepatectomy with chronic biliary fistula. The repeated cholangitis attacks and in two cases of hydatid disease the development of biliary-bronchial fistulas made these patients' lives miserable. All had had previous surgical procedures that made the transplantation procedure more difficult. Nevertheless, patient survival and graft actuarial survival after liver replacement were 75.0% and 69.2%, respectively, at 5 years.

Choledochocholedochostomy conversion to hepaticojejunostomy due to biliary obstruction in liver transplantation.

Choledochocholedochostomy with tutor (CC-T) or without (CC) is the technique of choice for biliary reconstruction in orthotopic liver transplantation (OLT), however, its rate of complications is high and does not decrease significantly over the years. Biliary obstruction is the most frequent complication and surgical treatment frequently involves conversion to hepaticojejunostomy (H-J). Out of 412 patients (448 OLTs) analyzed retrospectively, 74 (18%) presented biliary complications and 25 (6%) required conversion to H-J because of biliary obstruction, generally due to anastomotic stenosis (17 patients, 68%). Sixteen out of the 25 presented after the first 3 months, and in two patients, stenosis was secondary to arterial thrombosis. Anastomotic stenosis was more frequent in the CC group than in the CC-T group (9.9% versus 2.6%, p < 0.05). Sixteen patients (64%) underwent percutaneous dilatations, but the response was only transitory. There were no postoperative deaths. At the follow-up, three (12%) of the 17 surviving patients presented episodes of cholangitis which required percutaneous dilatations (1), revision of the H-J (1), or conversion to hepaticojejunoduodenostomy (1). Mean survival of patients with H-J was 70.9%, and the actuarial survival rate was 68% at 5 years. This does not differ from the actuarial survival in our series of transplanted patients (65%). CC or CC-T (in selected cases) is an adequate biliary reconstruction for OLT, in spite of the fact that a small number of patients will require conversion to H-J. H-J is an excellent technique of rescue in cases of biliary obstruction that are not possible to resolve by percutaneous dilatations.

Liver transplantation and hepatitis C virus. Results in a Spanish center since 1989.

BACKGROUND/AIMS: Hepatitis C-related liver disease is the main indication for liver transplantation in many centers. Viral RNA remains after transplantation in almost 100% of the patients, and more recent reports show a graft hepatitis rate of about 90%. The progression of this hepatitis seems to be quicker than in the nontransplant setting. METHODOLOGY: From June 1989 to October 2000, 197 adult patients had 213 for HCV-related liver disease at our institution. Basal immunosuppression consisted of a triple therapy with cyclosporine, azathioprine and steroids, or dual therapy with tacrolimus and steroids. None of the patients was treated with antivirals after liver transplantation. RESULTS: Pure HCV-related cirrhosis was the indication for liver transplantation in 114 patients, another 14 with hepatocellular carcinoma, 8 associated metabolic diseases, 43 high alcohol intake, 4 hepatitis B, 5 cholestatic diseases, and 3 other diseases. Six patients out of the 197 transplanted in this period were already grafted before this time, and had their first retransplantation of the liver after 1989 (their first liver transplantation was done when HCV was not known). Sixteen additional retransplantation procedures were done in the period considered. Hepatitis was diagnosed in 84.3% of the grafts biopsied later than 90 days after liver transplantation (118/140), and in 92.9% if it was done after one year (92/99). Cirrhosis was diagnosed in 21 grafts at a mean time of 1004.7 days, 21.2% of the grafts biopsied after 1 year and 28.6% after 2 years. Nine grafts in 8 patients were diagnosed as fibrosing cholestatic hepatitis. Patient actuarial survival was 80.9%, 69.7%, 67.5% and 50.6% at 1, 3, 5 and 10 years. Liver failure and hepatoma recurrence were the cause of death in 42.4% of the patients. Actuarial graft survival was 75.2%, 64.9%, 63.5% and 48.6% at 1, 3, 5 and 10 years, and was significantly affected by Child stage (B vs. C, P = 0.004). When compared to 228 non-HCV- infected patients with chronic parenchymatous disease, these had an almost significantly better patient survival (P = 0.0577), but a nonsignificant difference in graft survival. Graft loss related to liver causes was 17.6% in HCV+ patients 14.6% in HCV- patients. Liver causes of death were 14.0% in HCV+ patients and 4.8% in HCV-patients (P = 0.002). CONCLUSIONS: HCV infected liver transplantation recipients present very often graft hepatitis, which may progress to advanced stages in a quite short interval. Mid-term patient and graft survival is comparable to those of non-HCV recipients, but causes of death related directly to liver disease are more common in HCV+. This makes one think that long-term prognosis (more than 10 or 15 years) will be worse in HCV patients.