SummaryPost-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 posttransplantation neoplasms.
The difficulties in consistently prolonging survival after orthotopic liver transplantation have been documented by us 1 and by Calne. 2 In this report we describe a new trial of orthotopic liver transplantation in 14 patients who were scheduled to be treated with cyclosporin A and prednisone. Two patients died during the operation. Ten (83 per cent) of the 12 patients who survived surgery and received the drugs are living after eight to 14½ months; another lived for a year, before dying of a recurrence of cholangiocarcinoma.Although longer follow-up periods and more case studies will be required to establish the safety and effectiveness of this form of therapy, the exceptionally encouraging early results seem attributable to the use of cyclosporin A in combination with low doses of steroids for immunosuppression. The first use of cyclosporin A in liver transplantation was reported by Calne et al. 3 MethodsFourteen patients (age range, eight to 41 years) were accepted for the pilot trial. Liver replacement was attempted between March 10 and September 28, 1980. Two patients who were scheduled to be treated with cyclosporin A plus prednisone died during operation. One bled to death from a laceration of the portal vein, and the other received a homograft too large to permit the abdomen to be closed. Thus only 12 patients were treated with immunosuppression. TransplantationThe general techniques used in these operations have been previously described. 1,4 Seven of the 14 livers were removed during operations in cities other than Denver (75 to 2000 miles [120 to 3200 km] away). All 14 livers were preserved with Collins' solution, as described by Benichou et al. 5 Ischemia lasted from 1½ to 10½ hours. Biliary-tract reconstruction was performed through duct-to-duct, gallbladder-to-jejunal-Roux-limb, and common-duct-toRoux-limb anastomosis, in that order of frequency. Selection of Recipients and DonorsOf the 12 patients who survived the operation, three had chronic aggressive hepatitis and three had the Budd-Chiari syndrome. The following diseases were present in one patient each: primary biliary cirrhosis, secondary biliary cirrhosis, sclerosing cholangitis, hepatoma, Byler's NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript disease, and intrahepatic atresia. Of the two patients who died during operation, one had sclerosing cholangitis and the other had secondary biliary cirrhosis (caused by a gunshot wound to the hepatic hilum).Each donor was blood-group compatible with each respective recipient. There were no positive T-cell or B-cell cytotoxic cross matches at warm temperatures. In the 12 surviving patients, mismatches at the A and B loci averaged 3.3±0.7 (S.D.) and matches averaged 0.6±0.5. The number of matching DR loci ranged from 0 to 1 (mean, 0.4). ImmunosuppressionCyclosporin A treatment was started on the day of operation (17.5 mg per kilogram of body weight per day, given intramuscularly or by mouth). After six to eight weeks the doses were reduced to 10 mg per kilogram per day or le...
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Insulin, glucagon, and insulin/glucagon mixtures have been infused for four days into the left portal vein of dogs after portacaval shunt. In the left but not the right liver lobes, insulin alone reduced atrophy, preserved hepatocyte ultrastructure, and trebled cell renewal. Glucagon alone had no effect. In small doses, glucagon did not potentiate the action of insulin and in large doses it may have reduced the insulin benefit. These studies explain the development of the previously mysterious Eck fistula syndrome, provide clues about in-vivo cell growth control by hormones, and suggest new lines of inquiry about the pathogenesis and/or treatment of several human disease processes.
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