Jeremiah G. Turcotte

Randomized controlled trial of hand-assisted laparoscopic versus open surgical, live donor nephrectomy

BACKGROUND Laparoscopic live donor nephrectomy for renal transplantation is being performed in increasing numbers with the goals of broadening organ supply while minimizing pain and duration of convalescence for donors. Relative advantages in terms of recovery provided by laparoscopy over standard open surgery have not been rigorously assessed. We hypothesized that laparoscopic as compared with open surgical live donor nephrectomy provides briefer, less intense, and more complete convalescence. METHODS Of 105 volunteer, adult, potential living-renal donors interested in the laparoscopic approach, 70 were randomly assigned to undergo either hand-assisted laparoscopic or open surgical live donor nephrectomy at a single referral center. Objective data and subjective recovery information obtained with telephone interviews and validated questionnaires administered 2 weeks, 6 weeks, and 6-12 months postoperatively were compared between the 23 laparoscopic and 27 open surgical patients. RESULTS There was 47% less analgesic use (P=0.004), 35% shorter hospital stay (P=0.0001), 33% more rapid return to nonstrenuous activity (P=0.006), 23% sooner return to work (P=0.037), and 73% less pain 6 weeks postoperatively (P=0.004) in the laparoscopy group. Laparoscopic patients experienced complete recovery sooner (P=0.032) and had fewer long-term residual effects (P=0.0015). CONCLUSIONS Laparoscopic donor nephrectomy is associated with a briefer, less intense, and more complete convalescence compared with the open surgical approach.

Long‐term survival after liver transplantation in children with metabolic disorders

Abstract: Background: Liver transplantation for inherited metabolic disorders aims to save the patients life when the disorder is expected to progress to organ failure, and to cure the underlying metabolic defect. Methods: We retrospectively analyzed 146 pediatric liver transplants (28 metabolic; 118 non‐metabolic) performed between 1986 and 2000. Results: Twenty‐eight transplants were performed in 24 children with metabolic disease (8 females; 16 males; age range 3 months to 17 yr). Indications included α−1‐antitrypsin deficiency (n = 8), two cases each of hyperoxaluria type 1, Wilsons disease, hereditary tyrosinemia type I, citrullinemia, methylmalonic acidemia, and one case each of propionic acidemia, Crigler–Najjar syndrome type I, neonatal hemachromatosis, hemophilia B, Niemann–Pick disease type B, and cystic fibrosis. Eighteen transplants were whole organ grafts and 10 were lobar or segmental. Auxiliary liver transplants were performed in two patients and three received combined liver‐kidney transplants. There were three deaths from sepsis, two from chronic rejection, and one from fulminant hepatitis. Seven of 10 patients currently of school age are within 1 yr of expected grade and three who had pretransplant developmental delay have remained in special education. Actuarial survival rates at 5 and 10 yr are 78% and 68%, respectively, with mean follow‐up in excess of 5 yr. These results compare favorably to 100 pediatric patients transplanted for non‐metabolic etiologies (65% and 61%, respectively) (p= NS). Conclusions: Pediatric liver transplantation for metabolic disorders results in excellent clinical and biochemical outcome with long survival and excellent quality of life for most recipients.

The hepatic artery in liver transplantation.

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 recipients 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.

BREAST FEEDING AND MATERNAL-DONOR RENAL ALLOGRAFTS: POSSIBLY THE ORIGINAL DONOR-SPECIFIC TRANSFUSION

Large numbers of maternal lymphocytes are present in breast milk. We asked whether exposure of an infant to maternal lymphocytes during the process of breast feeding would have an effect on the subsequent reactivity of a patient to a maternal-donor related renal transplant. We studied the posttransplant course of 55 patients who had received a primary maternal-donor transplant. Twenty-seven recipients had been breastfed during infancy and 28 recipients had not been breast-fed. A history of breast feeding was associated with a more favorable posttransplant course as measured by the percentage of patients who had no rejection episodes during the first posttransplant year (P ≶ .006). The one-year graft function rate for breast-fed recipients was 82%; this was statistically significantly better than the 57% measured for non-breast-fed recipients (P ≶ .05). Statistical significance of differences between groups was not attained when results were evaluated over a five-year interval. A difference between breastfed and non-breast-fed recipients was not apparent when we evaluated a somewhat smaller group of patients who had received a paternal donor transplant. From these observations we conclude that the process of breast feeding during infancy may result in a measurable immunologic benefit to the recipient of a subsequent maternal-donor related renal transplant.

A prospective controlled trial of cold-storage versus machine-perfusion preservation in cadaveric renal transplantation.

A prospective controlled study was carried out in 60 consecutive cadaver renal donors comparing cold storage to pulsatile machine-perfusion preservation. Each donor served as its own control, by allocating one of the kidneys to each of the two preservation methods. There were 51 evaluable pairs of kidneys. Recipient age, panel-reactive antibody level, history of prior renal transplant, and immunosuppressive regimen were similar in the two preservation groups. Almost all recipients were treated with cyclosporine, and over 50% received antilymphoblast globulin. Total cold ischemic time was 1262 +/- 387 min in the machine-perfused group and 1309 +/- 426 min in the cold-storage group (P = NS). Prolonged ischemia (greater than 24 hr) occurred in 31% of machine-perfused and 22% of cold-stored kidneys (P = NS). Post-operative serum creatinine levels at 1, 7, and 30 days posttransplant were similar in both groups. Dialysis requirements were also similar, with 21 recipients of machine-perfused kidneys (41%) requiring at least one dialysis treatment compared to 16 patients (31%) in the cold-stored group (P = NS); the mean number of dialysis treatments required was 3.14 +/- 1.46 and 3.06 +/- 1.29, respectively (P = NS). Long ischemic time (greater than 24 hr) was associated with a higher rate of dialysis requirement in both groups, but in neither case did this achieve statistical significance. The distribution of graft losses within the first 30 days was similar in both groups, and the incidence of preservation-related graft failure was not significantly different. These results demonstrate that, in the cyclosporine era, machine perfusion offers no significant advantages over cold storage for cadaver renal preservation. Because machine perfusion is considerably more expensive and cold storage is simpler and facilitates the logistics of organ sharing, we recommend simple hypothermic storage of renal allografts as the preservation method of choice.

Corticosteroid withdrawal after liver transplantation

BACKGROUND Long-term side effects of corticosteroids (CSs) result in > major morbidity for recipients of orthotopic liver transplants (OLT). We instituted a program of CS withdrawal among OLT recipients to quantify the contribution of CS to adverse clinical sequelae and to determine whether long-term CS administration is necessary to avoid rejection. METHODS Recipients who had normal allograft function on CS, cyclosporine, and azathioprine more than 1 year after OLT were offered CS withdrawal during 12 to 22 weeks. Patients underwent routine clinical monitoring and laboratory studies. Continuous variables were compared by paired t test analysis. RESULTS CSs were discontinued in 51 recipients; 45 (88%) of 51 patients remain steroid-free after a mean follow-up of 13.8 months (range, 4 to 36). CS therapy was reinstituted in 6 patients who had abnormal transaminase levels during routine follow-up. Among the patients who remain off CS, there were no significant changes in blood pressure, transaminase, alkaline phosphatase, bilirubin, or glucose levels during the study period. Mean number of blood pressure medications decreased from 0.7 +/- 0.1 to 0.4 +/- 0.1 (p = 0.007). Cholesterol decreased from 217 +/- 8 mg/dl on CS to 204 +/- 9 mg/dl at 1 month (p = 0.0001), 183 +/- 10 mg/dl at 3 months (p = 0.0001), 198 +/- 8 mg/dl at 6 months (p = 0.04), 213 +/- 11 mg/dl at 12 months (p = 0.01), 209 mg/dl +/- 16 at 18 months (p = 0.02), and 183 +/- 19 mg/dl at 24 months (p = 0.2) off CS. Weight loss occurred in 88% of patients and averaged 9.5 pounds. CONCLUSIONS CS therapy can be successfully withdrawn without precipitating rejection in liver transplant recipients who have stable graft function 1 year after OLT. The incidence and severity of hypertension and hypercholesterolemia are reduced in patients whose CSs have been withdrawn.

Immunosuppression with medroxyprogesterone acetate.

A potent synthetic progestin, medroxyprogesterone acetate (MPG), was evaluated for immunosuppressive activity. The survival of dogs with renal allografts was significantly prolonged and serum creatinine was decreased in animals treated with large doses of MPG. Survival of dogs with renal allografts which received both medroxyprogesterone and azathioprine was markedly prolonged when compared with animals receiving azathioprine alone. In rabbits receiving MPG alone, skin allografts survived 1.7 to 2.8 times longer than controls. The primary humoral antibody response of rabbits to bovine γ-globulin was also suppressed. The influence of MPG on peripheral leukocyte count and the histology of lymph nodes, spleen, and thymus was studied in clogs. Although probably not as potent an immunosuppressive agent, as azathioprine or corticosteroids, MPG may be useful in humans because of its low toxicity.

Extra Vesical Ureteroneocystostomy in Renal Transplantation

From October 1970 to January 1986, 808 patients underwent renal transplant ureteroneocystostomy by an extravesical technique. Complications related to the anastomosis and/or ureter were reviewed. There were 23 total complications, for an over-all urological complication rate of 2.8 per cent. Of these complications 17 were related to the ureteroneocystostomy, for an anastomotic complication rate of 2.1 per cent. Complications were almost universally repaired by another operation. Two patients died and 1 lost the allograft because of urological complications.

Extra Vesical Ureteroneocystostomy in 170 Renal Transplant Patients

Urinary tract reconstitution was done in 170 consecutive renal transplant patients, using an extravesical ureteronecystostomy. The urologic complication rate was 8.5 per cent but complications associated directly with the anastomosis occurred in only 5 per cent of the cases. There have been no anastomotic complications in the last 104 transplants. Vesicoureteral reflux occurred in 20 per cent of 50 patients surveyed. Death in 2 cases and loss of the kidney in 1 were associated with urologic complications.

Progression of Diabetic Retionopathy after Pancreas Transplantation

The progression of diabetic retinopathy after combined pancreatic and kidney transplantation was studied in eight patients for 12 to 49 months. Four patients who had rapid pancreatic graft failure constituted a control group for comparison with four patients who retained functioning grafts. Using Fishers exact probability test, the authors found no posttransplantation difference between the two groups in visual acuity lost, severity of diabetic macular edema, extent of capillary closure, progression of preretinal gliosis, development of disc or preretinal neovascularization, or worsening of the severity of the retinopathy. Achievement of normoglycemia by pancreatic transplantation is not effective in halting the progression of diabetic retinopathy in patients who already have severe diabetic microangiopathy joined the current follow-up.