Biopsy-directed immunosuppression following hepatic transplantation in man.

Patients undergoing orthotopic hepatic transplantation were studied with routinely available liver function studies and serial hepatic biopsies. Rejection was diagnosed only if confirmed histologically. Cyclosporine and a rapidly decreasing dose of corticosteroids were used for immunosuppression. Hepatic dysfunction suggesting rejection was seen in 22 instances, but acute rejection was diagnosed histologically in only 6 patients. The liver function studies used in these patients did not accurately distinguish rejection from other causes of hepatic dysfunction. We conclude that liver biopsy as performed in these patients is an accurate and safe means of assessing the adequacy of immunosuppression and minimizing the use of high dose corticosteroids.

Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts.

Transplantation of kidneys from older donors is being advocated to expand the organ donor pool. However, the prevalence of atherosclerosis and age-induced renal structural alterations account for the variable function of allografts procured from these older donors. Pretransplant biopsies are sometimes used to evaluate kidneys from older donors, but to date there are no defined criteria correlating the extent of structural alterations in these kidneys to subsequent function. We investigated the effect of glomerulosclerosis, a marker for nephrosclerosis, on graft outcome. Sixty-five baseline biopsies of kidney allografts were retrospectively analyzed to identify a referent point of glomerulosclerosis that correlated with inferior graft outcome. Age and death from nontraumatic cerebrovascular injuries were the main correlates for donor glomerulosclerosis (P < 0.001). Allografts with poor function at 6 months defined as serum creatinine > 2.5 mg/dl (n = 13) or nephrectomy (n = 4) had a mean of 20% glomerulosclerosis at the time of implantation compared with only 2% sclerosis in allografts with good function (P < 0.05). Delayed graft function occurred in 22% and 33% of recipients with no glomerulosclerosis and those with less than 20% glomerulosclerosis, respectively. In contrast, patients receiving kidneys with > 20% sclerosis had an 87% incidence of delayed function (P < 0.05). Moreover, graft loss occurred in 7% of recipients of kidneys with less than 20% sclerosis and in 38% of recipients with > 20% sclerosis (P < 0.04). Measurements of serum creatinine in the donors did not distinguish the different degrees of glomerulosclerosis found on biopsy. Our data indicate that donor glomerulosclerosis greater than 20% increases the risk of delayed graft function and poor outcome of transplanted kidneys. Therefore, we advocate the use of routine biopsies of kidneys from older (> 50 yrs) donors and those donors with nontraumatic cerebrovascular accidents, despite seemingly normal preprocurement serum creatinine.

Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole.

Metabolism of cyclosporine is reduced by ketoconazole binding to the monooxygenase responsible for cyclosporine degradation. This isozyme of cytochrome P450, along with other similar monooxygenases, is involved in the regulation of the synthesis and degradation of important metabolic pathways of cholesterol. Monooxygenases throughout these pathways are inhibited by ketoconazole binding causing a decreased metabolism of calcitriol, bile acids, and steroid hormones, and can thereby potentiate altered lipid metabolism, bone metabolism, and weight status of transplant recipients. A group of renal transplant recipients taking ketoconazole (n=25) was compared with a matched cohort not receiving ketoconazole for metabolic changes during the first six months posttransplantation. Lower LDL cholesterol levels were seen in the ketoconazole group (109 +/- 8 mg/dl) than the no ketoconazole group (140 +/- 8 mg/dl) at one month but this difference was not sustained at six months. More bone loss occurred in the ketoconazole group as demonstrated by significant changes in bone density as well as a greater urinary appearance of bone collagen crosslink, deoxy-pyridinoline (29 +/- 4 nmol dpd/mmol creatinine and 18 +/- 4 at six months for the ketoconazole group versus the no ketoconazole group, respectively, P<0.05). Weight gain changes were different between the ketoconazole group and no ketoconazole group (6.4 +/- 1.4 kg versus 5.0 +/- 1.3 kg) at six months and an increased rate of weight gain over time in the ketoconazole group (0.02 kg/day at one month versus 0.05 kg/day at six months, P<0.007). Effectiveness of ketoconazole inhibition of cyclosporine is valuable, but inhibition of other metabolic pathways should be evaluated as well.

Ruptured hepatic adenoma. A spectrum of presentation and treatment.

Six cases of ruptured hepatic adenoma treated in our medical center were reviewed with attention directed toward presenting symptomatology and methods of treatment. These patients, five women who were long-term users of oral contraceptives and one man who had never taken steroid medication, presented with right upper quadrant abdominal pain of variable degree and duration. The cardiovascular status of these patients was also variable, ranging from a normal blood pressure, which allowed an orderly workup, and planned resection of the tumor to hypovolemic shock requiring emergency laparotomy for control of hemorrhage. The extent of surgery depended on the location and the number of adenomas, with the goal being to resect the adenoma and control hemorrhage while preserving as much normal liver parenchyma as possible. The treatment of choice in this disease is resection of the tumor with a margin of normal liver parenchyma. In those cases in which that is not practical, resectional debridement has proven to be an effective alternative.

Portal vein obstruction in patients requiring hepatic resection or transplantation.

Four patients with chronic portal vein occlusion (or near occlusion) who required major hepatic resection or transplantation are described. In each case, portal vein patency was restored, and objective evidence of long-term patency is presented in three patients. These patients demonstrate the feasibility of restoring and indefinitely maintaining portal venous flow coincident to major hepatic surgery.

Autotransfusion in hepatic transplantation.

Hepatic transplantation is often accompanied by a large volume of intraoperative blood loss which may place extraordinary transfusion demands on a community blood bank. In an effort to conserve blood bank resources, intraoperative autotransfusion has recently been used in our adult patients undergoing orthotopic hepatic transplantation. A group of seven patients receiving autotransfusion was studied and compared to another group of five patients who did not receive autotransfusion. In spite of receiving more blood during the transplant procedure, the autotransfusion group required a mean of 7.9 units less banked blood. Post-transplant transfusion requirements and bleeding complications were similar in both groups. Hematocrit and total bilirubin were not adversely affected, while transient elevation of BUN and serum creatinine appeared to be unrelated to the salvage process. This procedure was found to be safe and cost-effective, while conserving blood bank resources.

Survival following hepatic transplantation in the cyclosporine era.

In a series of 50 consecutive patients receiving 55 hepatic transplants, the 6-month survival was 76 per cent. Mortality was considerably higher in patients with complications of advanced liver failure (56%) than in patients that were not hospital-confined preceding the transplant procedure (10%). The causes of death were related primarily to technical errors, and uncommonly caused by rejection or uncontrollable infection. This striking change in the cause of death occurring in the cyclosporine era results from the use of more specific immunosuppression and close scrutiny of the allograft with frequent hepatic biopsy. Both of these principles diminish the reliance on high-dose corticosteroid therapy, and therefore promote wound healing and resistance to fatal infection.

Liver transplantation with cyclosporine and low-dose corticosteroids.

Twenty consecutive patients receiving 21 hepatic transplants were treated with cyclosporine and low-dose corticosteroids. Survival was 80 per cent at 30 days, 75 per cent at 6 months, and 65% in the 6-17 months follow-up period. Compared with earlier series, this improved survival using cyclosporine results from fewer infectious and sound healing complications. Reliance on hepatic biopsy to confirm the diagnosis of rejection may also reduce the corticosteroid exposure and help diminish the complications of excessive immunosuppression.

Hepaticopancreaticogastroduodenectomy with transplantation for metastatic islet cell carcinoma in childhood.

Symptomatic islet cell carcinoma of the pancreas with liver metastasis, a rare tumor cured only by complete resection, was unresponsive to chemotherapy and was treated with hepaticopancreaticogastroduodenectomy en bloc resection with transplantation in an 11-year-old girl. This radical surgery in conjunction with adjuvant chemotherapy and interstitial and external beam irradiation has resulted in symptomatic relief and no evidence of disease at 15 months posttransplant.

Social structure of collared peccaries (Pecari tajacu): does relatedness matter?

Relatedness is considered an important factor in shaping social structure as the association among kin might facilitate cooperation via inclusive fitness benefits. We addressed here the influence of relatedness on the social structure of a Neotropical ungulate, the collared peccary (Pecari tajacu). As peccaries are highly social and cooperative, live in stable cohesive herds and show certain degree of female philopatry and high mean relatedness within herds, we hypothesized that kin would be spatially closer and display more amicable and less agonistic interactions than non-kin. We recorded spatial association patterns and rates of interactions of two captive groups. Pairwise relatedness was calculated based on microsatellite data. As predicted, we found that kin were spatially closer than non-kin, which suggests that relatedness is a good predictor of spatial association in peccaries. However, relatedness did not predict the rates of social interactions. Although our results indirectly indicate some role of sex, age and familiarity, further studies are needed to clarify the factors that shape the rates of interactions in collared peccaries. This article is part of a Special Issue entitled: Neotropical Behaviour.