Search

The goal of this study was to determine whether antioxidant therapy with vitamin E would alter the rate of vascular access complications or other macrovascular complications in hemodialysis (HD) patients. A secondary goal of the study was to explore the relationship between baseline pretreatment markers of oxidative stress (the advanced glycation end product pentosidine and basal levels of vitamin Ealpha and gamma) and the subsequent development of access failure. Thirty-five stable patients treated by HD were recruited for the study. Patients were provided with vitamin E (800 IU) or placebo capsules to be taken daily. Clinical variables, vascular access function (flow meter access flow measurements), and circulating blood markers were obtained initially and every 3 months throughout the study. Vitamin Ealpha levels rose in treated patients from 12.7 +/- 4.4 to 25.1 +/- 15.1 microg/mL at 3 months and 28.6 +/- 14.8 microg/mL at 6 months. Vitamin Egamma levels fell in treated patients from 3.9 +/- 1.7 to 2.3 +/- 1.5 microg/mL at 3 months and 1.7 microg/mL at 6 months. Patients who subsequently developed repeated thrombotic vascular access events were characterized by higher baseline pentosidine content of circulating proteins. Patients who developed a myocardial infarction had higher pentosidine, lower vitamin Ealpha, and much lower vitamin Egamma than patients who did not develop thrombotic events. These findings lead to the speculation that the anti-inflammatory effects of vitamin Egamma may play a more important role in thrombotic vascular events than the antioxidant effects of vitamin Ealpha. Additional studies of these interactions are in progress.

Living donor liver transplantation was developed in response to a shortage of full-size grafts for children. The progression from reduced-size cadaveric grafts to use of living donors occurred subsequent to expansion of liver anatomy knowledge and practical use of hepatic segments. A major benefit of pediatric live donor liver transplantation is the grafting of children without using livers from the cadaver donor pool. A major drawback of the procedure relates to the need to perform surgery and assign risk to an otherwise healthy individual. The ethical challenge has been discussed in detail and, although not ideal, the procedure "passes muster" on grounds of informed consent and the good of helping another human being. Formidable success appears to have been attained with the adult-to-adult procedure thus far; however, the transplant community still awaits center-specific and compiled data to determine whether the procedure truly reduces adult waiting list times for liver transplant recipients with minimal donor risk.

Despite numerous options for pediatric transplantation, closure of the abdominal wall after liver transplantation is occasionally difficult, resulting in increased abdominal pressure and possible vascular compromise. Since 1990, we have utilized a 2-mm thick sheet of polytetrafluoroethylene (PTFE) to overcome this situation in 21 transplants for 17 patients. The median age was 0.9 months. Ten of the 21 transplants utilized full-size grafts. The donor to recipient weight ratio was 1.7+/-1.2. Cadaveric left lateral segments were used in 8 of 21 transplants (weight ratio, 7.4+/-5.9), living donor left lateral segments were used in 3 of 21 transplants (weight ratio, 13.2+/-6.7). We were able to remove 14 of 21 patches with one additional operation, whereas 4/21 patches required two operations and 3/21 required three operations. Reoperations identified two cases of hepatic artery thrombosis not previously identified by duplex ultrasonography. There were no technical problems or adverse effects associated with the use of the PTFE patch. After patch removal, the fascia was closed with a nonabsorbable suture and the skin was allowed to close by secondary intention. There were no wound infections, portal vein thrombosis, or fluid and electrolyte abnormalities. PTFE is a safe, temporary alternative to primary wound closure in liver transplantation when the size of the graft or intestinal and graft edema does not allow conventional closure of the abdomen. Infectious, fluid/electrolyte, or ventilatory complications were not noted. The necessity of a second-look operation is useful in assessing the graft and vascular patency. The majority of patches can be removed within the first postoperative week.

The aim of this study was to determine the outcome of venous conduits used in living donor liver transplantation (LDLT). We analyzed the portal vein complications in 66 LDLT recipients and 48 cadaveric reduced-size liver transplant (RLT) recipients performed from November 1989 through January 1995. Three different venous conduits were utilized in the LDLT recipients: Group 1, reconstructed vein from the living donor, n=18; Group 2, cadaveric cryopreserved iliac vein, n=37; and Group 3, cadaveric cryopreserved femoral vein, n=11. Overall, 47 percent of the patients were less than one year of age; the age distribution was not significantly different among the groups. The incidence of early thrombosis was significantly greater in LDLT Group 1, (33%) than any of the other groups (LDLT Group 2, 8%; LDLT Group 3, 9%; and RLT, 4%:P<0.0005 vs. reduced graft and < 0.03 vs. other LDLT groups). The incidence of late portal vein stenosis or thrombosis was significantly higher in the LDLT Group 2, (51%) than any of the other groups (LDLT 1, 16%; LDLT Group 3, 9%; RLT 4%;P<0.005 vs. cadaveric and < 0.02 vs. LDLT Group 1 and LDLT Group 3). Five year arterial graft and patient survival for patients who have experienced portal vein thrombosis or stenosis is 61% and 67%, respectively, versus 67% and 71% for those patients who have not experienced portal vein pathology, P=ns. Based on this experience, we recommend avoiding the use of cryopreserved iliac vein for portal vein reconstruction in liver transplantation. Every effort should be taken to eliminate the need for venous conduits in liver transplantation. If venous conduits must be utilized, cryopreserved femoral veins seem to provide superior patency rates. Careful clinical and ultrasonopraphic monitoring of patients at high risk for late venous thrombosis permits therapy with excellent graft and patient survival.

To assess the long-term outcome of kidney/pancreas transplantation, patients were identified who had good graft function at one year posttransplant and a minimum of 3 years' follow-up. Fifty recipients from 1987-92 met these criteria. Records were reviewed for graft survival, graft function, readmissions, and medical complications. Psychosocial adjustment and quality of life were assessed using the SCL-90-R and SIP surveys, respectively. Patient, kidney, and pancreas survivals were 94%, 86%, and 85% at five years (Kaplan-Meier), with a mean follow-up of 4.3 years. The 3 deaths were due to 2 sudden arrests at home (presumed to be cardiac events) and 1 episode of sepsis. Other graft losses were due to rejection, except for one case of sepsis. The remaining patients are normoglycemic (glucose 92 +/- 23 mg/dl) and have a creatinine of 1.8 +/- 0.6 mg/dl. Mortality after the first year was 0.9%/year. Estimated kidney and pancreas half-lives were 15 +/- 2 and 23 +/- 7 years, respectively. Hospitalization, acute rejection, graft pancreatitis, dehydration, and severe infections all decreased dramatically after the first year. While CMV was the most common infection in the first year, foot infections predominated thereafter. Retinal hemorrhage was infrequent. Sudden death (presumably cardiac) was the chief cause of mortality, while peripheral vascular disease resulted in several amputations. Fractures were common, suggesting the need for increased attention to bone demineralization. Psychosocial and quality of life evaluations were within normal limits. In conclusion, most complications specifically related to transplantation occur in the first year, but underlying disease renders these patients susceptible to a variety of cardiovascular, bone, and other disorders.

Twelve patients who experienced steroid-resistant rejection after primary liver transplantation while receiving cyclosporine-based therapy were converted to tacrolimus without receiving OKT3 or additional steroids. The indications for conversion were ongoing biopsy-confirmed rejection. All patients had received one course of high-dose intravenous steroids, which failed to reverse the rejection episode. No other antirejection therapy was given. Tacrolimus was initiated to reverse rejection and for maintenance therapy. The tacrolimus target level was 15-20 ng/ml (whole blood, IMX). All 12 patients had rapid reversal of the rejection episode and did not experience recurrent rejection (mean follow-up: 8.2 +/- 1.2 months). The mean bilirubin level dropped from 6.1 mg/dl at the initiation of tacrolimus therapy to 4.4 mg/dl by day 7 of therapy, 2.5 mg/dl by day 14, and 1.5 mg/dl by day 21 (P < 0.003). Serum glutamic pyruvic transaminase demonstrated a similar response. The serum creatinine level was unchanged at 1.5 mg/dl. No major adverse reactions were noted in this group of patients. Patient and graft survival rates were 100%. Four of the eight patients with a follow-up of >4 months are no longer receiving steroid therapy. Tacrolimus is effective as the primary therapy for the treatment of steroid-resistant rejection and provides a rapid and sustained biochemical response. Patients with mild to moderate rejection may be safely converted from cyclosporine to tacrolimus without an additional steroid bolus or OKT3 therapy. Early "preemptive" conversion to tacrolimus prior to the use of additional steroids or OKT3 may decrease overall rejection therapy requirements. This approach has promise for improved graft survival and fewer infectious and immunologic complications.