Search

Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation.Extracorporeal liver perfusion (ECLP) has been proposed as a method of “bridging” such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure.

Intestinal transplantation has become an accepted therapy for short bowel syndrome and other types of intestinal failure. In order to assess digestive capabilities and feeding practices in a group of 22 pediatric patients after intestinal transplantation, we assessed mucosal disaccharidase activities and assimilation of total dietary lipid and vitamin E. Twelve of the patients had undergone contemporaneous liver transplantation.

The relationship between central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) and serum sodium changes in the setting of orthotopic liver trans plantation (OLT) is examined. Postmortem examination of 14 patients with end-stage liver disease who under went liver transplantation revealed CPM in four, of which three also had EPM. A retrospective review of clinical and laboratory data was performed on all patients. There were marked perioperative rises (21–32 mEq/L) in the serum sodium concentration in all four patients who developed myelinolysis. In contrast, the largest increase in sodium in patients without demyelination was 16 mEq/L. We conclude that perioperative rises in the serum sodium concentration increase the risk of myelinolysis. CPM and EPM should be considered if the patient develops mental status changes or focal neurological deficits several days after OLT.

We report on the efficacy and safety of FK506 tacrolimus compared with a cyclosporine CsAbased immunosuppressive regimen after 1 year of treatment in pediatric liver allograft recipients < 12 years participating in a multicenter U.S. randomized trial. Patients received either FK506 or CsA as primary immunosuppression following a first ABOcompatible liver transplant. Intravenous FK506 was initiated at 0.1 mgkg per day, followed by oral FK506 beginning at 0.3 mgkg per day. The dose was adjusted to maintain plasma trough levels of 0.52.0 ngml. The CsA group was treated according to each center's usual protocol. Both groups received the same initial doses of corticosteroids. All rejection episodes were biopsyproven and a standardized algorithm was adopted for the treatment of rejection. Thirty patients were randomized to the FK506 group and 20 to the CsA group. After twelve months of followup 20 patients remained in the FK506 group and 13 in the CsA group. Patient survivals were 80 and graft survival 70 in the FK506 group compared with 81 and 71 respectively, in the CsA group. 48 of the FK506 group remained rejectionfree compared with 21 of the CsA group, and 79 of FK506treated patients did not require OKT3 compared with 68 of CsA treated patients. The cumulative corticosteroid dose was less at each time point throughout the first year in the FK506 group. The incidence of serious and minor infections was similar in both groups. Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major toxicities reported. Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. There was no difference in mean serum creatinine at 12 months between the two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compared with a 30 incidence in the CsA group. In conclusion, compared with CsA, there is a trend toward less rejection in FK506treated pediatric allograft recipients, while both drugs have a similar spectrum of side effects.

Hepatic artery thrombosis is a dreadful complication of orthotopic liver transplantation. It should be suspected in cases of fulminant liver failure, delayed bile leak, or intermittent sepsis of unknown cause after liver transplantation. Accurate diagnosis is assisted by ultrasound and computerized tomography scans, but usually requires arteriography. Prompt retransplantation is required in most of the cases.

A persistent problem in orthotopic liver transplantation (OLT) is primary nonfunction (PNF) of the hepatic allograft. In most instances the cause of the failure is unknown. In an attempt to minimize these graft failure, modifications in the procurement and operative procedure have been investigated. One change in the procedure at the University of Nebraska Medical Center has been the monitoring of the temperature of the fluid in the back table bath during preparation of the donor liver. Our initial procedure involved creating an ice slurry of lactated Ringer's solution and ice slush in which the donor liver was then prepared. The temperature of this ice slurry was retrospectively found to be from –3°C to –1°C (group I). In this group there was a higher-than-expected incidence of PNF. To investigate whether the temperature of the back table bath influenced the incidence of PNF, beginning with transplant No. 42 the preparation of the back table bath was modified. The bath was created by adding a small amount of PlasmaLyte slush to 2 L of PlasmaLyte (group II). The temperature of the bath was maintained at 2–4°C. Data were collected on 100 consecutive liver transplants. All transplants were performed using standard techniques, the operation for the two groups differing only as described above. Transaminase levels were followed as an index of the allograft function and were expected to begin to normalize within 2–3 days after transplantation. While both groups display this trend, transaminase levels in group II were significantly lower postoperatively than group I levels (P<0.05). Preoperative values were similar. There were 7 PNFs in group I; 0 in group.

Twelve dogs had transplantation of almost the entire small intestine in the orthotopic location; immunosuppression was with cyclosporine and prednisone. Half the dogs had survival of at least one month, and a third lived for at least four months. Two of the animals are still living after 550 and 555 days. Maintenance of nutrition, and absorption of D-xylose and fat were better than in control animals with an iatrogenic short gut syndrome, but distinctly worse than that of normal dogs.

The introduction of UW solution into clinical transplantation has permitted extended cold storage preservation of the liver. Over a 46-month period, we have performed 308 orthotopic liver transplants (268 primary, 42 retransplants) in 266 recipients. Our experience is divided into cold-storage preservation in Eurocollins (163 transplants in 140 recipients) and UW (145 transplants in 131 recipients) solutions. Donor and recipient factors were comparable between the two groups. The use of UW solution has permitted an increase in the mean preservation time from 5.2±1.0 [EC] to 12.8±4.3 [UW] hr (P0.001). The mean total operating time was reduced but intraoperative blood loss was unchanged with UW preservation. The number of transplants performed during the daytime hours has increased dramatically (21.5 [EC] vs. 71 [UW], P0.001). The incidence of primary nonfunction, hepatic artery thrombosis, 1-month graft survival, and early retransplantation were similar in the 2 groups. Initial allograft function as determined by bile production, histology, and clinical assessment were likewise similar. Mean serum bilirubin, transaminase, and prothrombin levels were virtually identical by 5 days post-transplant.

In an effort to determine the total one-year cost of liver transplantation, the underlying drivers of that cost, and any cost differences between alternative immunosuppressive regimens, an analysis was performed comparing the average one-year posttransplant charges of 322 patients participating in the “U.S. Multi-center Prospective Randomized Trial Comparing FK-506 to Cyclosporine in Liver Transplantation.” Total one-year inpatient charges including all readmissions were examined. Professional fees and outpatient charges were excluded. Costs for tacrolimus drug and blood assays were assumed to be equal to those in the CsA group. For patients completing the study, the tacrolimus group had an average length of stay and average one-year cost seven days (P.06) and 19,290 (P.05) lower than the CsA group. The difference in rejection profiles between the two arms seems to largely account for the lower costs. The tacrolimus arm consistently had fewer patients in the more severe rejection groups. Increased incidence and severity of rejection were directly related to higher average lengths of stay and costs of transplantation (P<.001). Tacrolimus immunosuppression during the first year after liver transplantation is more cost-effective than CsA in achieving similar patient and graft survival rates. Differing incidence and severity of rejection can dramatically affect the first-year cost of liver transplantation.

Although combined pancreas-kidney transplantation (PKT) has become a valid treatment option for selected type I diabetics, the timing of PKT relative to the degree of nephropathy remains controversial. We analyzed results and morbidity in 30 type I diabetics undergoing PKT after starting dialysis (PKT:D) versus 31 type I diabetics undergoing PKT prior to dialysis (PKT:ND). The two groups were similar with the respect to age, duration and severity of diabetes, gender, race, preservation time, retransplants, sensitization, HLA-match-ing, and CMV status. The mean preoperative serum creatinine was higher in the PKT:D group (9.9 ± 3.4 vs. 3.9 ± 1.9 mg/dl PKT:ND, P<0.01). All patients were managed with quadruple immunosuppression with OKT3 induction. Actuarial patient survival is 100 (PKT:D) and 96.8 (PKT:ND). Renal and pancreas allograft survival are 97 and 93, respectively, in both groups. The incidence of rejection, infection, operative complications, reflux pancreatitis, and total hospital days was similar in both groups. Long-term renal and pancreas allograft function and quality of life were likewise comparable. No adverse coagulation or immuno-logic effects were noted in the PKT:ND group. Rehabilitation potential favored the PKT:ND group.

Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas-kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6 patient survival (1 cardiovascular death), 97.1 kidney graft survival, and 94.2 pancreas graft survival. Thirty-three evaluated patients (24.1) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n=12) and pancreas graft survival after PTA is 83.3 and 50, respectively. Our conclusion is that a multidisciplinary

During a 38-month period, we studied 320 liver transplants in 283 recipients (202 adults, 81 children). CMV disease was documented in 85 patients (30.0). The major risk factor for CMV disease was primary CMV exposure (transplanting a seropositive allograft into a seronegative recipient). A total of 42 patients (14.8) had primary CMV exposure. Twenty-one patients were historical controls, while the next 21 received prophylaxis for CMV infection in a nonrandomized trial of consecutive study groups. The regimen of prophylaxis consisted of intravenous immune globulin (IgG; 0.5 g/kg) at weekly intervals for 6 weeks and acyclovir for 3 months. CMV prophylaxis resulted in a dramatic reduction in the incidence of CMV disease (71.4 vs. 23.8, P<0.01). All cases of CMV were treated with intravenous ganciclovir (5 mg/kg b.i.d. for 14 days), with 5 patients in the control group developing recurrent CMV disease (33.3 relapse). In the 16 patients receiving prophylaxis who did not develop CMV disease, all developed positive CMV-IgG titers with the passive administration of IgG. However, none developed any evidence of CMV infection or viral shedding as assessed by IgM titers and surveillance viral cultures. Four deaths occurred (all control patients), but none were related to CMV disease. Overall patient and graft survivals after primary CMV exposure were 90.5 and 82.2, respectively, after a mean follow-up of 14 months. Conclusion: Primary CMV exposure is a major risk factor for CMV disease in liver transplant recipients. Intravenous IgG plus acyclovir is safe and effective in preventing CMV infection and disease in this setting. Because of the scarcity of donor organs, we do not advocate protective matching to avoid primary CMV exposure but rather recommend prophylaxis to prevent CMV disease in this high-risk group.

Hepatic artery thrombosis is a continuing source of morbidity and mortality following orthotopic liver transplantation. The cornerstone of therapy has been urgent retransplantation that is limited by organ availability. For this reason we developed a policy of urgent revascularization for allograft rescue.

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2).

The most common application of small bowel transplantation is for the patient with parenteral nutrition-induced liver failure. In this setting, the small intestine is transplanted simultaneously with the liver. We identified three technical problems that we believe contributed to complications in our first eight patients. First, pancreaticoduodenectomy was challenging in the infant donor. Second, the bowel graft was prone to volvulus around the skeletonized donor portal vein. Third, in the pediatric recipient, use of the donor bowel for Roux-en-Y biliary reconstruction was associated with biliary leaks in the early postoperative period. Our surgical technique of liver/small bowel (L/SB) transplantation has evolved since our early experience in 1990. Modifications in the L/SB operation, reported briefly in 1996 and 1997, have led to easier graft preparation and have reduced the incidence of technical complications.

The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection.

Cyclosporine is a potent immunosuppressive drug, which has doserelated nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Longterm survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twentynine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity.

We have developed a donor operation that incorporates en bloc removal of the liver and intestine with a limited surgical resection in vivo. Over the past 18 months, we have used the following technique for the retrieval and preparation of seven isolated small intestinal allografts. The donor operation and bench preparation can be divided into three phases. During the first phase, the small intestine is removed with the liver, pancreas, and an aortic segment. In the second phase performed ex vivo, the donor liver can be separated from the specimen. The third phase involves additional bench dissection to yield an isolated intestinal allograft. The principle advantage of this technique is that it reduces potential liver injury by minimizing the surgical dissection required in vivo. Also, dividing the liver from the intestine ex vivo allows the organs to be separated in a bloodless field under controlled conditions that may be especially important when two different surgical teams are involved.