Byers W. Shaw

REVERSIBILITY OF LYMPHOMAS AND LYMPHOPROLIFERATIVE LESIONS DEVELOPING UNDER CYCLOSPORIN-STEROID THERAPY

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms.

Intraoperative Changes in Blood Coagulation and Thrombelastographic Monitoring in Liver Transplantation

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and an-hepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30–60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrornbelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors.

Venous bypass in clinical liver transplantation.

A venous bypass technique (BP) that does not require the use of systemic anticoagulation is used routinely at our institution in all adult patients during the anhepatic phase of liver transplantation (LT). Complete cardiopulmonary profiles were obtained in a subset of 28 consecutive cases. During the anhepatic phase while on bypass, mean arterial pressure, central venous pressure, and pulmonary arterial wedge pressure were maintained at prehepatectomy levels. Oxygen consumption fell secondary to a decrease in temperature and the removal of the liver. Consequently, cardiac index fell without an increase in arterial-venous O2 content difference, reflecting adequate tissue oxygenation. Compared with 63 patients in a previous series given LT without bypass (NBP), the 57 total BP patients experienced better postoperative renal function (p < 0.001), required less blood use during surgery (p < 0.01), and had better survival 30 days after LT. The equivalency of 90-day survival in these groups results from the lack of effect of BP on the long-term survival of patients considered at high risk for metabolic reasons. BP patients at high risk for technical considerations, however, survived LT whereas NBP patients did not. BP offers other advantages important in establishing LT as a service-oriented procedure.

Role of liver transplantation in cancer therapy.

Fifty-four patients underwent total hepatectomy and liver replacement in the presence of a primary liver malignancy. In 13 recipients in whom the hepatic tumors were incidental to some other endstage liver disease, recurrence was not seen and 12 of the 13 patients are alive after 4 months to 15 1/2 years. In contrast, tumors recurred in 3 of every 4 patients who received liver replacement primarily because of hepatic malignancies that could not be resected by conventional techniques of subtotal hepatectomy and who lived for at least 2 months after transplantation. The most encouraging results were in patients with the fibrolamellar hepatocellular carcinomas that grow slowly and metastasize late, but even with this lesion, the recurrence rate was 57%. In future trials, additional effective anticancer therapy will be needed to improve the results of liver transplantation for primary liver malignancy, but what an improved strategy should be has not yet been defined.

Vascular complications after orthotopic liver transplantation

Over a 57-month period, we performed 430 orthotopic liver transplants in 372 patients. A total of 38 vascular complications were identified including hepatic artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n = 5). A number of potential risk factors for the development of vascular thrombosis were evaluated with only children, weight less than 10 kg, and cold ischemia time found to be significant. The clinical presentation included fulminant hepatic failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex ultrasonography was diagnostic in nearly all cases. Therapeutic modalities included revascularization, revascularization followed by retransplantation, retransplantation alone, and observation. Five cases of hepatic artery rupture occurred in four patients. Infectious arteritis was present in four patients. The 6-month actuarial survival in patients with vascular complications was 70%. Early diagnosis is critical for graft salvage, with surgical intervention the mainstay of therapy.

Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era

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.

OUTCOMES OF 385 ADULT-TO-ADULT LIVING DONOR LIVER TRANSPLANT RECIPIENTS: A REPORT FROM THE A2ALL CONSORTIUM

Objective:The objective of this study was to characterize the patient population with respect to patient selection, assess surgical morbidity and graft failures, and analyze the contribution of perioperative clinical factors to recipient outcome in adult living donor liver transplantation (ALDLT). Summary Background Data:Previous reports have been center-specific or from large databases lacking detailed variables. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) represents the first detailed North American multicenter report of recipient risk and outcome aiming to characterize variables predictive of graft failure. Methods:Three hundred eighty-five ALDLT recipients transplanted at 9 centers were studied with analysis of over 35 donor, recipient, intraoperative, and postoperative variables. Cox regression models were used to examine the relationship of variables to the risk of graft failure. Results:Ninety-day and 1-year graft survival were 87% and 81%, respectively. Fifty-one (13.2%) grafts failed in the first 90 days. The most common causes of graft failure were vascular thrombosis, primary nonfunction, and sepsis. Biliary complications were common (30% early, 11% late). Older recipient age and length of cold ischemia were significant predictors of graft failure. Center experience greater than 20 ALDLT was associated with a significantly lower risk of graft failure. Recipient Model for End-stage Liver Disease score and graft size were not significant predictors. Conclusions:This multicenter A2ALL experience provides evidence that ALDLT is a viable option for liver replacement. Older recipient age and prolonged cold ischemia time increase the risk of graft failure. Outcomes improve with increasing center experience.

Experience with 150 liver resections

One hundred fifty liver resections were performed with an operative mortality rate of 4%. Indications for liver resections were 43 primary liver malignancies, 43 metastatic liver tumors, and 64 benign liver diseases. The 3-year actuarial survival rate after treatment of primary liver malignancy was 56%, and that after treatment of metastatic liver tumors was 66%. All but one of 59 patients with benign disease who survived operation were alive without development of late symptoms or complications.

HEART-LIVER TRANSPLANTATION IN A PATIENT WITH FAMILIAL HYPERCHOLESTEROLAEMIA

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.

FUNGAL INFECTIONS IN LIVER TRANSPLANT RECIPIENTS

Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P<0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P<0.05) and antibiotics (P<0.05), longer transplant operative time (P<0.02), longer posttransplant operative time (P<0.01), duration of antibiotic use after transplant surgery (P<0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P<0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P<0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious nonfungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P<0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P=0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.