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We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 ± 1.9 days in the Neoral group vs 7.8 ± 4.9 days in the Sandimmune group (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13 %) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60 %) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early posttransplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year posttransplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24 % in these 59 patients compared to our historical experience of 70 % using Sandimmune.

Cytomegalovirus (CMV) remains the most important infection in the renal transplant recipient. Few data are available that provide guidance for approaches that seek to reduce the reactivation of latent disease after transplantation. To test the efficacy of polyimmune gammaglobulin in kidney and kidney/pancreas transplantation, consenting recipients with serologic evidence of previous CMV disease were randomized to receive i.v. polyimmune gammaglobulin (500 mg/kg) within 3 days of transplant with 250 mg/kg at weeks 1, 2, 4, and 6 or no prophylaxis. Both groups received identical induction and rejection immunosuppressive therapy. Polyimmune gammaglobulin prophylaxis reduced CMV reactivation infections. The incidence of reactivation infections was half in patients receiving Nashville/rabbit antithymocyte serum (N/R-ATS) compared with those receiving monoclonal anti-CD-3 therapy. Patients receiving polyimmune gammaglobulin along with N/R-ATS had an incidence of infection of only 10%. Reactivation infections were twice as common in patients who had primary nonfunction and nearly three times as common in patients with acute rejection. Both risk factors were associated with longer anti-T-cell therapy. Polyimmune gammaglobulin prophylaxis should be considered in transplant patients with previous CMV exposure who will be receiving prolonged anti-T-cell therapy because of acute rejection or primary nonfunction.

Attempts at improving anastomoses have included the development of stapling techniques. Our purpose was to evaluate arcuate-legged clipped versus standard sutured anastomoses of the hepatic artery (HA), portal vein (PV), and bile duct in a porcine liver transplantation model. Two groups of pigs were studied intraoperatively and 1 day after liver transplantation. A control group underwent sutured anastomosis of PV and HA with polypropylene and of bile duct with polydioxanone (n = 8). An experimental group underwent anastomoses with arcuate-legged clips (n = 8). We analyzed the time to perform anastomosis and flows before and at various time points after anastomosis. In addition, patency and histology of the anastomoses were evaluated 1 day after operation, including a fibrin-thrombosis score, medial injury, and inflammation score. Times to complete HA and PV anastomoses were not different between clipped and sutured groups. However, the time was shorter to complete bile duct anastomosis with clips than with sutures (6.3 +/- 1.1 minutes and 13.3 +/- 2.0 minutes, respectively). Flows through HA anastomoses were not different between groups, but flow through the PV was higher in clipped compared with sutured anastomosis (P = 0.06). Patency was 100 per cent with no leaks for all three anastomoses in both groups. Histologic data were similar between vascular anastomotic groups. Sutured bile duct anastomoses revealed mild smooth muscle injury in 75 per cent whereas clipped bile duct anastomoses displayed no smooth muscle injury. We conclude that arcuate-legged clipped anastomosis represents a viable option to sutured anastomoses of the PV, HA, and bile duct anastomoses. Bile duct anastomoses were completed in less than half the time and with less tissue damage documented histologically.

Following primary liver transplantation, immunosuppressive efficacy of Neoral and Prograf was similar and superior to that of Sandimmune. Rejection incidence was statistically increased with Sandimmune therapy. Incidence of hypertension, posttransplant diabetes mellitus, and infectious complications was not statistically different. Although early compromise in renal function was associated with Sandimmune, Neoral, and Prograf immunosuppression, no progressive renal dysfunction was identified.

Healthcare reform has mandated scrutiny of the fiscal aspects of patient care as well as medical outcomes. Therefore, we reviewed our experience with 50 liver transplant recipients from a multidisciplinary collaborative transplant team. From February 1991 to July 1994, of 175 patients referred, 75 were formally evaluated for transplantation; 56 (76%) of these patients were accepted for transplantation; 50 patients underwent 53 transplants. Operative mortality of 6 per cent, retransplantation rate of 6 per cent, 6-month actuarial survival of 88 per cent, 1-year survival of 86 per cent, and the 2 and 3-year survival of 83 per cent were unchanged over time. Quality of life evaluated by the Karnofsky Performance Status was a mean of 55 pretransplant, 72 at 3 months, 79 at 6 months, 84 at 1 year, 88 at 2 years, and 95 at 3 years, demonstrating improved general health and functional rehabilitation after transplantation. Psychosocial Adjustment to Illness Scale scores demonstrated significant improvement following transplantation, improving most dramatically in the vocation environment, domestic environment, and sexual relationship domains. Postoperative length of stay has declined with an average of 28 days in 1991, 22 days in 1992, 19 days in 1993, and 14 days in 1994. Average total hospital, organ procurement, and physician charges for the transplantation hospitalization was $165,000. Average 91-92 hospital charges were $154,000 and were reduced in 93-95 to $103,000 (P.05). We found that charges and length of stay decreased over time, while the outcome and quality of patient care was maintained. We believe the collaborative practice, case management, and revised patient care protocols are responsible.

We report on two cases of infiltrative renal tumor developing in two kidney transplant recipients from a single cadaveric donor source. Interestingly, while this is only the second case of a de novo renal allograft tumor, both were morphologically infiltrative. The fact that both tumors were infiltrative may be secondary to immunosuppression therapy. While computed tomography (CT) evaluation of suspected renal pathology provides excellent anatomical detail, renal transplant recipients are initially evaluated using ultrasound and renal scintigraphy to avoid contrast reagents which could further impair renal function, as well as to reduce the image procedure cost and the patient radiation dose. Unfortunately, infiltrative tumors may be isoechoic on ultrasound, providing a confusing or conflicting report when compared to scintigraphic findings. This case report is significant radiographically because the original neoplasm was initially detected using technetium-99m-labeled mercaptoacetyltriglycine (99mTc-MAG3) scintigraphy and was not appreciated by sonographic studies, even retrospectively. This case demonstrates the usefulness of 99mTc-MAG3 scintigraphy to follow-up evaluations of renal transplants by providing detailed anatomical information as well as functional analysis of the kidney.

Colonic complications after renal transplantation are uncommon but have a high mortality rate. Some have recommended colonic screening in patients over 50 years of age prior to transplantation to lessen the impact of colonic diverticular disease. We report our 9-year experience of colonic screening for diverticular disease in potential recipients over the age of 50 and compare these results to the overall colonic complication rate in the same time period. From 1981-1990, 1186 renal transplants in 1019 patients were performed, during which time all potential recipients over the age of 50 yr were required to undergo colon evaluation prior to transplantation. Twenty cases of diverticular disease were found with more than a quarter of the cases in patients with adult polycystic disease. All underwent renal transplantation without a pre-transplant colectomy, and none had post transplant symptomatic colon disease. During that same time period a total of 14 colonic complications requiring surgical intervention were encountered with a mortality rate of 40%. Acute diverticulitis occurred in 5 patients, all of whom were over 50 yr of age, on low-dose immunosuppression, and in most cases it occurred remotely after transplantation. Colonic dysplasia/neoplasia also occurred remotely after transplantation in 2 patients over the age of 50. Cytomegalovirus (CMV) colitis was the next most common complication, accounting for 3 cases. This complication, which occurred in younger patients, was associated with high-dose steroid immunosuppression and had a high mortality rate, in spite of surgical intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of race upon renal allograft survival is controversial. Between 1981 and 1987, at Vanderbilt University Medical Center, 448 patients (75 black, 373 white) received azathioprine, 3 mg/kg daily; prednisone, 30 mg daily; and intravenous antithymocyte sera, 0.2 mL/kg/day for 14 days, after transplantation. Prednisone doses were decreased gradually to 10 mg daily within 6 months of transplantation. Azathioprine was maintained at doses of 2 to 3 mg/kg/daily; lower doses were administered if significant myelosuppression occurred. One-year graft survival was 72% and 85% among black and white recipients, respectively (P less than .01). Two hundred thirty-six patients have been treated with azathioprine (3 mg/kg initially tapered during the first week to 1.5 to 2 mg/kg); prednisone, 30 mg daily; and cyclosporine, 10 mg/kg per day. Cyclosporine therapy was begun after recipient serum creatinine levels had decreased below 3 mg/dL. Before therapy was initiated and until levels of cyclosporine were maintained between 150 and 200 ng/mL (whole blood), antithymocyte serum was administered. This immunosuppressive protocol resulted in 1-year graft survival of 90% and 87% in black and white recipients, respectively. Not only was graft loss markedly reduced, but the interracial difference noted before the use of cyclosporine was no longer evident. The type of immunosuppressive therapy used clearly affected 1-year allograft survival among black recipients. The combination of azathioprine, cyclosporine, and prednisone resulted in improved graft survival overall, but had the most significant effect among blacks.

Immunosuppressive efficacy of Neoral and Prograf following primary hepatic transplantation was comparable. Incidence of rejection episodes, infectious complications, hypertension, and postoperative diabetes mellitus was comparable. Although clinical use of both immunosuppressants was associated with early compromise in renal function, no progressive renal dysfunction was observed.

The advent of potent immunosuppressive drugs to prevent rejection has led to a phenomenal improvement in renal transplant results increasing spectacularly the number of transplant recipients to arrive in the transplant clinic who remain for many years. This has engendered a series of questions about the most appropriate cyclosporine dosing for these patients that prevents rejection while avoiding toxicity. Three separate issues were analyzed: the most appropriate combination strategy with cyclosporine as a base "double" or "triple" therapy; the possibility of conversion from regimens containing cyclosporine to those devoid of it; and the optimal cyclosporine dose for a maintenance regimen. A meta-analysis of seven individual prospective and randomized trials of double versus triple therapy encompassing 1,080 patients revealed no statistical difference between the two regimens in terms of graft survival at 1 or 5 yr, patient survival, the rejection rate per patient, or the infection rate. In an analysis of 17 separate studies in which conversion away from cyclosporine was attempted, in 629 individuals with 702 individuals left on cyclosporine as controls, a significant risk of acute rejection (P0.001) was found in the withdrawn group without evidence of improved graft survival. Certain factors such as previous rejection, race, and degree of reactivity predicted even more rejection in the withdrawn group. Analyzing six separate studies of renal transplant recipients maintained on cyclosporine for up to 5 yr with renal functional stability, one can conclude that a dose of approximately 4.0 mg/kg per day is optimal. Because of variant pharmacokinetics or concomitant medicines, blood levels can confirm a therapeutic concentration with this target dose.(ABSTRACT TRUNCATED AT 250 WORDS)

The site at which the vasomotor effects of cyclosporine are associated with acute nephrotoxicity appears to be the afferent arteriole. Proposed mechanisms mediating these effects include sympathetic nerve stimulation, disruption of the balance between vasodilating and vasoconstricting prostaglandins, hypersensitivity to vasoactive peptides, and endothelin release. These mechanisms mediate cyclosporine-associated intrarenal vasoconstriction, yet the causal relationship between these changes and the obliterative vasculopathy seen in association with chronic progressive renal allograft dysfunction is uncertain. Histologic findings seen in chronic progressive renal dysfunction are nonspecific and cannot be correlated solely with cyclosporine use. Retrospective studies analyzing both aggregate serial serum creatinine and reciprocal creatinine determinations did not report a pattern of progressive attrition consequent to toxic nephropathy. Prospective studies with serial GFR determinations with various reference substances found no progressive deterioration in allograft function. Both the retrospective and prospective studies indicate that the attrition of renal allograft function associated with cyclosporine use reflect the chronic effects of immunologic injury. Renal function in extrarenal transplant recipients immunosuppressed with cyclosporine can be characterized by an initial decline in native renal function followed by subsequent stabilization beyond the first 6 months. There does not appear to be an inordinate rate of progression to ESRD.

A new operative procedure for the preservation of pancreatic fragments is introduced ("intestinalization") in which vascularized fragments are placed inside a jejunal pouch. This step is done to manage all secretions, lymph and potential debris coming from the pancreas; to maintain the primary portal drainage of insulin; to avoid vascular operations, and to keep the fragment in a denervated state and still preserve its endocrine function to prevent diabetes. The procedure was compared with conventional end to end pancreaticojejunostomy. Sixteen dogs were studied. Group 1 consisted of four dogs that had intestinalization of the pancreatic tail. Group 2 is made up of eight dogs that had complete resection of the remaining duodenal portion of the gland as well as intestinalization of the pancreatic tail. Group 3 consisted of four dogs that had end to end pancreaticojejunostomy to the isolated tail and complete resection of the duodenal portion of the gland as those dogs in group 2. No dog became diabetic during the time of observation (up to one year)--fasting glucose levels and K values in glucose tolerance tests remained normal. Insulin peak values at ten minutes were lower postoperatively. However, return to fasting levels occurred equally fast postoperatively. There was no difference among the groups. The most important morphologic finding in the intestinalized fragments was a firm capsule surrounding the tissue after two weeks. Exocrine atrophy was present in both groups 2 and 3 after one year. No reinnervation of intestinalized pancreas was seen. Intestinalization may offer an alternative to pancreatic resection especially when heterotopic autotransplantation is considered.

Die hohe Morbiditat und Mortalitat resezierender Eingriffe am Pankreas werden bedingt durch Insuffizienz der pankreatodigestiven Anastomose (1), durch Pankreatitiden mit Nekrosenbildung (1, 2) sowie durch Entgleisung des Glucosestoffwechsels in folge des Verlustes der Inselzellen (2, 3). Eine Operationsmethode ist somit erforderlich, die eine Insuffizienz der Anastomose unmoglich macht, eventuell entstehende Pankreasnekrosen drainiert, gleichzeitig das verbleibende Organ denerviert und dessen endokrine Funktion nicht beeintrachtigt.

Pancreatitis was induced in the opossum by occluding the common bile duct above or below the entrance of the pancreatic duct. The common channel theory was tested by evaluating the effect of preligation of the pancreatic duct to prevent the reflux of bile after ligation of the distal common duct. The severity of the disease was determined by histologic grading of the degree of pancreatic tissue necrosis. Serum amylase, lipase, and calcium were determined. Concomitant obstruction of the biliary and pancreatic ducts produced severe necrotizing pancreatitis whether or not bile reflux was present. Pancreatic ductal obstruction alone was associated with acinar atrophy and mild interstitial pancreatitis. Biliary obstruction alone above the entrance of the pancreatic duct resulted in marked hyperemia of the gland but without histologic evidence of pancreatic inflammation. A positive bacterial culture of the pancreas was obtained in only four of 36 opossums in a distribution to suggest random contamination. There was an inverse correlation between calcium levels and the degree of tissue necrosis. This study demonstrates that biliary obstruction rather than bile reflux into the pancreas is a requisite for the pathogenesis of severe biliary pancreatitis in this model.