Search

Of 109 cyclosporine-treated cadaveric renal allograft recipients, 45 were free of acute rejection in the first 4 weeks after transplantation. Eleven of 45 (24%) subsequently had delayed, biopsy-proven first rejection episodes 34-61 days after grafting, often after discharge from the hospital. Delayed rejectors had significantly higher plasma creatinine levels at all times during the first posttransplant month than 34 nonrejectors. Trough serum cyclosporine levels were similar in the two groups, although by the 4th week oral cyclosporine dose was significantly lower in the delayed rejection group. Two-thirds of those patients who had serum creatinine levels greater than or equal to 260 mumol/l at 2 weeks and greater than or equal to 225 mumol/l at 3 weeks had a delayed acute rejection episode. Renal transplant recipients treated with cyclosporine who have serum creatinine levels at or above these levels should be aggressively worked up and closely followed for the development of delayed acute rejection.

Because absorption of cyclosporine (CyA) given orally immediately after liver transplantation is unreliable, the drug is usually given intravenously until external biliary drainage is discontinued. Intravenous CyA, however, is associated with serious side effects, making its use potentially hazardous. We report the results of a new strategy in which we used oral CyA exclusively and refed bile to enhance oral CyA absorption. Thirty-two liver transplant recipients with indwelling T tubes were studied. All were given sequential quadruple drug immunosuppression with antilymphoblast globulin, azathioprine, and steroids. Oral CyA and refeeding of bile was started when renal function was stable. By the second posttransplant week, satisfactory CyA levels were achieved, and antilymphoblast globulin therapy was stopped. There were significant associations between oral CyA dose and CyA level and between quantity of refed bile and CyA level (p less than 0.001). CyA dose and quantity of bile refed were covariates, however, and in multiple regression analysis, only the quantity of refed bile was significant (p = 0.001). CyA levels did not correlate with rejection. The incidence of rejection was 63%. At a mean follow-up of 9 months, 28/32 (88%) patients were alive, and actuarial 1-year patient survival was 84%. Current graft and renal function are excellent (serum bilirubin, 1.0 +/- 0.1 mg/dl; serum creatinine, 1.2 +/- 0.1 mg/dl). We conclude that intravenous CyA can be avoided in virtually all liver-transplant recipients by administration of oral CyA with bile in the early posttransplant period.

The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced by some centers, it may be important to administer exogenous insulin in the postoperative period to provide islet rest. Using a porcine pancreas transplant model that simulates clinical transplantation, we studied 2 groups: 1 group (n = 8) received constant insulin infusion for 7 days after transplantation; the control group (n = 5) received vehicle only. The islets in the insulin infusion group were rested as evidenced by a significantly decreased mean C-peptide level (0.27 +/- 0.04 ng/ml) as compared to the control group (0.66 +/- 0.08 ng/ml) (P less than 0.05). After insulin infusion was discontinued, intravenous glucose tolerance testing found insulin, C-peptide and glucagon responses were not different between groups. Glucose clearance was also comparable; K values were -1.79 and -1.60 in the insulin infusion and control groups, respectively. In conclusion, islet rest by insulin infusion for 7 postoperative days did not improve subsequent pancreas transplant endocrine function.

Using a retrospective analysis we compared 79 recipients of cadaveric renal allografts who were treated with cyclosporine as the sole initial immunosuppressant and 29 concurrent transplant recipients treated with conventional immunosuppressants. The cyclosporine-treated group had a slightly higher actuarial patient survival at four years (86 per cent v. 76 per cent). Actuarial graft survival at four years was 70 per cent in the cyclosporine group, as compared with 62 per cent in the conventionally immunosuppressed group. The incidence of acute rejection episodes was 62.1 per cent in the former and 65.5 per cent in the latter. Nephrotoxicity was managed either by reduction of the dose of cyclosporine or by conversion to conventional immunosuppression. Monitoring of trough serum levels of cyclosporine facilitated its administration. Serum creatinine levels have been higher in cyclosporine-treated patients with functioning grafts, but graft deterioration has not occurred after more than three years. Cyclosporine provides adequate immunosuppression for patients with renal allografts. At four years, the rates of patient and graft survival remain superior to those with conventional immunosuppression. In 41 per cent of patients the use of steroids was completely avoided. The longer-term results of this powerful immunosuppressive agent are not yet known.

Liver transplantation is a highly successful therapy for liver diseases that were previously debilitating and often fatal within a few months. One-year actuarial patient survival for our first 162 patients is 74.7%. Our results have improved since the inception of the program despite the fact that the indications have been extended to higher risk patients such as those with fulminating hepatitis or thrombosed portal veins. The prognosis following transplantation for each specific indication needs to be defined, especially for hepatitis, alcoholic cirrhosis and individual cancers. We believe that a more conservative approach to immunosuppression, close attention to intravenous and enteral nutrition, and aggressive treatment of complications (including prompt reoperation when indicated) have been important improvements in our management practices.

Hepatic artery complications after liver transplantation are uncommon, but represent an important cause of morbidity and mortality. In addition, these complications tax an already limited supply of donor organs because of the frequent need for retransplantation in this group of patients. In this study, we examined the incidence of hepatic arterial anomalies in donors and recipients of orthotopic liver transplants, focusing on the techniques that are available for hepatic arterial reconstruction and on the occurrence of hepatic arterial complications. A total of 77 liver transplants were carried out in 68 patients. Standard recipient anatomy was present in 60 of 68 patients (88%). Anomalous vessels were identified in eight patients (12%), including six cases of replaced right hepatic artery (9%) and two cases of replaced left hepatic artery (3%). Donor liver arterial anatomy was standard in 62 cases (80%). Anomalous arterial supply was identified in 15 of 77 donor livers (20%), including replaced left hepatic artery in nine (12%) and replaced right hepatic artery in six (8%). A variety of methods were used to manage the anomalous vessels. There was one hepatic artery pseudoaneurysm, three cases of hepatic artery thrombosis (4%), and one patient developed a dissection of the native celiac axis. In primary transplants, utilization of the recipient's proper hepatic artery was associated with a significantly higher risk of hepatic artery thrombosis (P less than 0.04) when compared with the common hepatic artery or the branch patch technique. Use of a Carrel patch on the donor artery was associated with a significantly reduced incidence of hepatic artery thrombosis (P less than 0.0003). For retransplantation, it is recommended that a more proximal recipient anastomotic site be chosen. An innovative method is described that provides increased length of the donor arterial supply without the use of an arterial graft.

Many authors advocate mandatory surgical exploration for all patients with penetrating neck trauma, while other maintain that with careful diagnostic evaluation some patients safely can be spared an operation. From our hospitals, 65 cases of penetrating neck trauma were reviewed, 27 of which showed no mortality without operation. Surgical exploration of the neck showing no injury added $1,930 to the cost of hospitalization. Review of the surgical literature discloses that mortalities reported by authors advocating selective and mandatory exploration are similar. The incidence of missed significant injury is low among patients observed selectively. A management algorithm for the diagnostic evaluation and treatment of patients with penetrating neck trauma is advocated. All stable patients should undergo four-vessel angiography. Studies of the cervical esophagus may be performed. Patients with entirely normal diagnostic evaluations may be observed safely, sparing unnecesary operation.

In this report recent experience with renal transplantation in 43 children who were 17 days to 16 years old was reviewed. One-year patient survival rate was 98%, and overall one-year graft survival rate was 68%. One-year graft survival rate was 73% for cyclosporine-treated patients and 78% for recipients of related donor kidneys. A subpopulation of patients affected with renal insufficiency since infancy was analyzed separately to evaluate the prognosis of these patients, who have previously been reported to be a high risk for permanent neurologic, developmental, and growth retardation. All 16 such patients underwent transplantation. Gross motor delay that was noted in 31% of patients before surgery resolved in all patients after transplantation. No evidence of severe developmental delay was noted after transplant and seven of 11 patients with successful transplants had evidence of catch-up growth. Overall renal transplantation is a safe and effective procedure for children with renal failure, and even the patients at highest risk for growth and developmental failure caused by renal insufficiency show potential for rehabilitation after transplantation.

Transplantation of the pancreaticoduodenal allograft (PDA) has recently been advocated as a technique that is superior to the use of the segmental allograft. However, the effect of simple cold storage preservation on the PDA has not been studied. We investigated the effect of 24 and 4 hours of cold storage in Eurocollins solution on porcine PDA function after transplantation in pancreatectomized pigs. A regimen of cyclosporine and prednisone was used, which prevented rejection for at least 28 days after transplantation. Cold storage preservation for 24 hours uniformly resulted in PDA failure. Compared with recipients of immediately transplanted PDA, recipients of PDA cold stored for 4 hours had marked plasma hyperamylasemia (10,000 U/L versus 1932 U/L), relative glucose intolerance (K value -2.15 versus -2.66), hypoinsulinemia (peak immunoreactive insulin 11.0 microU/ml versus 34.7 microU/ml), and an abnormal pattern of insulin secretion as demonstrated with intravenous glucose tolerance testing. There was also a higher incidence of technical complications in the group transplanted with cold-stored PDAs. Our results suggest that there is a detrimental effect on porcine PDA function after only 4 hours of cold storage in Eurocollins solution.

Orthotopic liver transplantation has been performed for a growing range of liver-based inborn errors of metabolism. Previous authors have documented that liver transplantation can reverse the coagulation defect of hemophilia A. In this article we report total correction of factor IX deficiency in a patient with hemophilia B and blood product-related liver disease. Intraoperative bleeding was not excessive, and the donor liver produced normal amounts of factor IX immediately.

A mathematical technique known as deconvolutional analysis was used to provide a critical and previously missing element in the computations required to quantitate hepatic function scintigraphically. This computer-assisted technique allowed for the determination of the time required, in minutes, of a labeled bilirubin analog (99mTc-disofenin) to enter the liver via blood and exit via bile. This interval was referred to as the mean transit time (MTT). The critical process provided for by deconvolution is the mathematical simulation of a bolus injection of tracer directly into the afferent blood supply of the liver. The raw data required for this simulation are obtained from the intravenous injection of labeled disofenin, a member of the HIDA family of radiopharmaceuticals. In this study, we perform experiments which document that the simulation process itself is accurate. We then calculate the MTT under a variety of experimental conditions involving progressive hepatic ischemia/reperfusion injury and correlate these results with the results of simultaneously performed BSP determinations and hepatic histology. The experimental group with the most pronounced histologic findings (necrosis, vacuolization, disorganization of hepatic cords) also have the most prolonged MTT and BSP half-life. However, both quantitative imaging and BSP testing are able to identify milder degrees of hepatic ischemic injury not reflected in the histologic evaluation. Quantitative imaging with deconvolutional analysis is a technique easily adaptable to the standard nuclear medicine minicomputer. It provides rapid results and appears to be a sensitive monitor of hepatic functional disturbances resulting from ischemia and reperfusion.

Oxygen free radicals are mediators of tissue injury and catalase is an enzyme which is involved in limiting this process. We examined peripheral blood catalase activity (PBCA) to assess its value as a marker in detecting tissue injury related to renal allograft rejection. Thirty-one consecutive recipients of kidney (n = 29) or simultaneous kidney/pancreas (n = 2) transplants and 10 normal volunteers were studied. Catalase activity, measured by the disk-flotation method, was expressed as Sigma units X 10(-3)/ml (SU/ml) of whole blood. Normal PBCA was determined to be greater than 76 SU/ml. Twenty-nine episodes of renal allograft rejection (diagnosed by clinical criteria +/- biopsy [79%]) were observed in 26 patients. PBCA (mean +/- SEM) was found to be low (64 +/- 1 SU/ml) in 28/29 episodes (chi 2 = 46.3, P less than 0.001), and the decrease (at least two consecutive daily catalase values less than 76 SU/ml) occurred 2 days prior to the clinical/biopsy diagnosis of rejection in 26/28 episodes. The sensitivity of PBCA as a discriminant of rejection was 97%, specificity was 96%, and test accuracy was 96%. PBCA less than 50 SU/ml on two or more occasions occurred in five cases and transplant nephrectomy was required in four of these because of uncontrollable rejection. Nine episodes of cyclosporine nephrotoxicity occurred in 7 patients and none of these episodes was associated with a decreased PBCA. Our data suggest that decreased PBCA is a sensitive and specific indicator of renal allograft rejection. PBCA remains normal during episodes of cyclosporine nephrotoxicity and therefore provides a rapid and inexpensive discriminant from allograft rejection.

Few noninvasive methods are available to diagnose complications following liver transplantation. Hepatobiliary scintigraphy can differentiate rejection from primary biliary complications such as obstruction or extravasation in patients with nonspecific clinical findings such as fever and rising liver function studies. In the following case report, an unexpected biliary leak from a recipient accessory hepatic duct was demonstrated by [99mTc] DISIDA scintigraphy following liver transplantation.