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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.

Fifteen patients with Laennec's cirrhosis underwent orthotopic liver transplantation between 1963 and the end of 1979. The first eight patients died perioperatively or within two months, but four of the next seven patients had long survival; three are still alive after 11 to 14 years. After the introduction of cyclosporine therapy, 41 more patients with alcoholic cirrhosis were treated with liver transplantation from 1980 to June 1987. The one-year survival is 73.2%, and, after one to three years, 28 (68%) of the recipients are living. Of the 35 patients in the combined old and new series who lived for six months or longer, only two returned to alcohol abuse. Social and vocational rehabilitation has been the rule in these recipients who were selected primarily because of urgency of need, because they or their families insisted on treatment, and because they and their families thereby committed themselves to long-standing programs of alcoholism care.

A tension mucocele was created in three hepatic homografts by ligating a low-lying cystic duct during transplant cholecystectomy and by incorporating its outflow end into the anastomosis of the common hepatic duct to the recipient common duct or Roux limb of jejunum. The consequent complication of obstruction of the biliary tract that necessitated reoperation and excision of the mucocele in all three patients can be avoided by the simple expedient of completely removing the cystic duct when feasible or providing egress to the secretion of the cystic duct as described.

From March 1980 to July 1987, 1000 patients with various end-stage liver diseases received orthotopic liver transplants. Of the 1000 patients, three hundred two had definite histories of bleeding from esophageal varices before transplantation. There were 287 patients with nonalcoholic liver diseases and 15 patients with alcoholic cirrhosis. All patients had very poor liver function, which was the main indication for liver transplantation. One- through 5-year actuarial survival rates of the 302 patients were 79%, 74%, 71%, 71%, and 71%, respectively. These survival rates are far better than those obtained with other available modes of treatment for bleeding varices when liver disease is advanced. Long-term sclerotherapy is the treatment of primary choice for bleeding varices. Patients in whom sclerotherapy fails should be considered for liver transplantation unless clear contraindications exist.

The purpose of this study was to clarify the effect of orthotopic liver transplantation on hypersplenism. In a 1-year period from July 1, 1986 to June 30, 1987, 196 adult patients underwent 233 orthotopic liver transplantations. Of the 58 patients with hypersplenism who were analyzed in this study, hypersplenism was more commonly associated with postnecrotic cirrhosis than other kinds of liver disease (55.3% (47/85) vs. 14.5% (11/76); p less than 0.001). Postoperative platelet counts were statistically higher than preoperative values (p less than 0.05). The latest platelet counts were more than 100,000/mm3 in 53 patients (91.4%). Of the eight patients whose preoperative and postoperative spleen volumes could be compared, all showed the reduction in the spleen size (p less than 0.02). We conclude that orthotopic liver transplantation, which is a radical surgical procedure for portal hypertension, reverses hypersplenism.

Aplastic anemia developed in 9 of 32 patients (28 percent) undergoing orthotopic liver transplantation for acute non-A, non-B hepatitis, at one to seven weeks after the procedure. No patient previously had evidence of hematologic dysfunction or conditions known to be associated with aplastic anemia. No other cases of aplastic anemia were identified among 1463 patients undergoing liver transplantation for all other indications at the four centers participating in the study (chi-square = 415, P less than 0.001; 95 percent confidence interval for the incidence of aplastic anemia after transplantation for non-A, non-B hepatitis, 13 to 44 percent, vs. 0.00 to 0.13 percent for all other indications). The operative and postoperative treatment of these patients was not otherwise different, indicating that the aplastic anemia was a complication of the hepatitis, not of the transplantation procedure. Four of the nine patients died of complications due to infections. Three of the surviving patients have been followed for less than six months, one for one year, and one for two years. The two patients followed the longest have recovered marrow function to an appreciable degree, and two of the others have evidence of early recovery. We conclude that patients undergoing orthotopic liver transplantation for non-A, non-B hepatitis are at a high risk for the development of aplastic anemia.

Liver transplantation has become an extraordinarily valuable and useful operation, but one that is not perfect and that has not been exploited to anything like its full potential. Better immunosuppression may become available soon as exemplified by developments with the Japanese drug, FK506. Improved preservation with the UW solution is already here. With these advantages, liver transplantation is certain to become far more widely used than at any time in the past. Examples were cited of innovative approaches using liver transplantation for the treatment of hepatic malignancies.

From January 1, 1986 to July 30, 1988, 530 consecutive cadaver kidney transplantations were performed with patient selection by a point system that took into account time awaiting an organ, donor-recipient matching, degree of presensitization, and some less important factors. The effect of the system was to diminish judgmental factors in case selection which in the past, had probably operated to the disadvantage of "undesirable" potential recipients, including older ones. Primary 1-year graft survival (74%) and graft survival after retransplantation (71%) were lower than in the earlier time. However, the results with triple-drug therapy using CsA, AZA and P demonstrated 88% 1-year graft survival for primary graft recipients and 74% in highly sensitized patients, with comparable patient mortality. These latter observations provide some assurance that the concepts of equitable access and efficient utilization of a scarce resource are not mutually exclusive.

New and exciting advances in renal transplantation are continuously being made, and the horizons for organ transplantation are bright and open. This article reviews only a few of the newer advances that will allow renal transplantation to become even more widespread and successful. The important and exciting implications for extrarenal organ transplantation are immediately evident.

Eight hundred and sixty kidney transplants were performed at the University of Pittsburgh over a 3.75-year period between January 1, 1986 and October 19, 1989. Recipient selection was by means of a computerized point system designed to allocate organs equitably. Ninety-three percent 1-year patient survival and 74% 1-year graft survival were obtained in the overall group; 80% 1-year graft survival was obtained in patients receiving immunosuppression with CsA, azathioprine, and prednisone. These data serve as a measure of what can be achieved with an equitably based allocation system and can serve as a basis of comparison with other allocation protocols or new immunosuppressive regimens.

In the Pittsburgh series of 1,000 orthotopic liver transplants (OLTx), from January 1981 to July 1987, the indication for transplantation in five patients consisted of unresectable hepatic metastases arising from endocrine tumors of gastrointestinal origin: glucagonoma, two patients; carcinoid, two, and gastrinoma, one patient. Three patients underwent resection of the primary tumor (two distal pancreatectomies and one ileal resection) at the time of the hepatic transplantation. All patients underwent extensive nodal dissection. Three of the five patients are alive with no evidence of residual disease after a median follow-up study of 12 months. Hepatic transplantation broadens the concept of radical excision of tumor and may be considered as a potential therapeutic approach for some highly selected instances of unresectable hepatic metastases arising from endocrine tumors of the intestine and pancreas.

The purpose of this study was to define parameters which could be predictive of hepatic artery thrombosis, which continues to be a major complicating factor in pediatric liver transplantation. The hepatic blood flow of 14 pediatric liver patients (15 grafts) who weighed less than 15 kg was measured electromagnetically during orthotopic liver transplantation. The results of blood flow determination and the clinical data in 7 patients (8 grafts) who developed hepatic artery thrombosis were compared with those of 7 control patients. All patients with a hepatic arterial flow of less than 60 ml/min developed hepatic artery thrombosis (4/8 vs. 0/7; p < 0.05), and the patients with hepatic artery thrombosis exhibited higher total hepatic and portal vein flow per 100 gram of liver tissue (262 vs. 136 ml/min; p < 0.001 and 222 vs. 80 ml/min; p < 0.025, respectively) as well as longer cold preservation time (384 vs. 326 min; p < 0.025). The results of our study suggest that hepatic arterial flows of less than 60 ml/min are critical for the development of hepatic artery thrombosis, and that portal venous overflow and increased preservation times may contribute to the development of hepatic artery thrombosis.

Hepatic artery thrombosis has been a grave complication after liver transplantation. The diagnosis, when suspected, must be confirmed, since retransplantation has to be considered promptly. In a few cases, recovery with good function of the dearterialized graft has been seen.

Mycotic aneurysm at the site of a Carrel patch arterial anastomosis occurred in four patients who had undergone whole pancreas transplantation 2.5 to 14.5 months previously. In all patients, the graft had been removed, leaving the Carrel patch on the iliac artery. The aneurysms ruptured into the intestine or the extraperitoneal space. The ruptures were sudden and life-threatening in three of four cases. This diagnosis must be suspected in patients with a history of pancreas transplantation in the immediate or distant past if they present with unexplained hypotension, cardiac arrest, or gastrointestinal tract bleeding.

Ninety liver transplantations were performed in 81 patients. Plasma endotoxin was measured preoperatively, at the end of the anhepatic phase, and on postoperative days 1, 3, and 7. The presence of high endotoxin levels preoperatively and at the end of the anhepatic period was associated with graft failure and a high mortality. Patients with primary nonfunction of their transplants typically had severe endotoxemia. Endotoxemia could be a cause rather than an effect of perioperative complications and graft loss.

Experience with the use of Orthoclone OKT3 monoclonal antibody for the treatment of acute cellular rejection in a series of 130 human orthotopic liver transplantations is reviewed. Treatment was highly effective in reversing rejection, in reducing the rate of retransplantation, and in lowering patient mortality. OKT3 was also useful for cyclosporine sparing in patients with poor renal function, hypertension, or CNS toxicity. There was a significant incidence of opportunistic infection associated with the use of OKT3.

Results of liver transplantation have dramatically improved since the introduction of cyclosporine. Most deaths occur within the first 3 postoperative months. Morbidity and mortality can be minimized by early diagnosis and aggressive management of postoperative surgical complications.

In 313 consecutive recipients of 393 orthotopic liver grafts, there were 51 (16.3%) and nine (2.9%) patients who had pre-existing portal vein and inferior vena cava abnormalities, respectively. These abnormalities required adjustments in the transplant operation and were a source of morbidity and mortality. The incidence of thrombosis of the reconstructed portal vein was 1.8%. Only three (0.8%) vena caval thromboses were seen after 393 liver replacements. Venous stenoses or disruptions were rare. Six women with the Budd-Chiari syndrome had liver replacement. Although this disorder is a veno-occlusive disease, five of the recipients achieved prolonged survival, only one had recurrence of disease, and three are alive after 2-6 years.

The results of 219 orthotopic human liver transplants performed during 1985 at the University of Pittsburgh were reviewed to determine whether donor parameters could be used to predict the quality of early graft function. Multivariate discriminant analysis demonstrated that traditional parameters of donor assessment are unreliable predictors of poor graft function. Furthermore, 56% of the donors considered poor by conservative selection criteria produced livers with good early posttransplant function. Survival of recipients of primary allografts from donors rated poor was no different than survival of recipients of allografts from donors rated good.

Liver transplantation is now the preferred treatment for many diseases leading to end-stage liver disease. Transplantation for cancer has been disappointing and there is a significant recurrence rate after transplantation in hepatitis B-virus carriers. Additional strategies will have to be developed if we are to improve the results of transplantation for these patients. The role of immunological factors in liver transplantation continues to reveal significant differences from their role in renal transplantation and will continue to be an interesting area of study for years to come.