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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.

We have previously shown that immediately after liver transplantation (LT) the porcine recipient exhibits elevated plasma glucagon, increased fractional synthetic rate (FSR) of fibrinogen, and decreased FSR of fixed or structural liver proteins. The purpose of this study was to evaluate the effect of nutritional and hormonal supplementation on these observations 24 h after LT. Two groups of nine pigs were studied 1 day after LT using radioisotopic and arteriovenous difference techniques. A control group underwent LT with saline infusion and a supplemented group underwent LT with infusion of glucose, amino acids (6 and 1.06 mg/kg. min, respectively), and intraportal insulin (0.6 mU/kg. min) and glucagon (1.3 ng/kg. min). Primed constant infusions of [3H]leucine were used to determine leucine flux, an estimate of whole body protein breakdown, and fractional synthetic rates (FSR). The following changes were noted with supplementation: elevated plasma insulin (6 +/- 1 versus 29 +/- 4 microU/ml, control versus supplemented, respectively, P < 0.05), decreased glucagon to normal levels (323 +/- 65 versus 102 +/- 12 pg/ml, P < 0.05), decreased fibrinogen FSR (108 +/- 15 versus 70 +/- 6%/day, P < 0.025), and increased fixed liver protein FSR (8 +/- 1 versus 13 +/- 2%/day, P < 0.05, respectively). Albumin FSR was unaltered by supplementation (8 +/- 2 versus 6 +/- 1%/day, respectively). Nutritional and hormonal supplementation immediately after LT restored the measured protein synthesis in the allograft to near normal levels 1 day after transplantation., (Copyright 1999 Academic Press.)

Background: The liver is one of the principal organs responsible for the uptake and release of amino acids in the body. The ability of the transplanted liver to clear plasma amino acids is associated with a functioning allograft. However, clinical assessment is limited by the inability to access the portal vein postoperatively. Therefore, using a porcine liver transplant model, we examined (1) the plasma levels of amino acids presented to the new hepatic allograft and (2) the capacity of the new allograft to clear these amino acids from the circulation., Materials and Methods: Two groups of commercially bred pigs were studied: a control group (n = 8) underwent laparotomy and a transplanted group (n = 6) underwent orthotopic liver transplantation (LT) using veno-venous bypass. All pigs had catheters placed in the carotid artery and portal and hepatic veins and ultrasonic transit time flow probes placed around the hepatic artery and portal vein. Plasma profiles of 23 amino acids were analyzed by high-pressure liquid chromatography. Hepatic balances of amino acids, using arteriovenous difference techniques coupled with hepatic blood flows, were also analyzed on postoperative day 1., Results: Neither portal vein blood flow (703 +/- 74 ml/min vs 666 +/- 82 ml/min) nor hepatic artery blood flow (322 +/- 43 ml/min vs 209 +/- 59 ml/min) was significantly different between the control and the transplanted groups, respectively. The transplanted group had significantly increased plasma levels of alanine (135 +/- 13 mumol/l vs 382 +/- 72 mumol/l), hydroxyproline (30 +/- 5 mumol/l vs 60 +/- 9 mumol/l), methionine (25 +/- 2 mumol/l vs 55 +/- 10 mumol/l), ornithine (36 +/- 5 mumol/l vs 141 +/- 33 mumol/l), phenylalanine (84 +/- 5 mumol/l vs 120 +/- 12 mumol/l), threonine (75 +/- 9 mumol/l vs 159 +/- 27 mumol/l), and tryptophan (17 +/- 2 mumol/l vs 31 +/- 4 mumol/l). The transplanted group also had significantly decreased plasma levels of isoleucine (122 +/- 12 mumol/l vs 85 +/- 8 mumol/l) and taurine (71 +/- 7 mumol/l vs 35 +/- 7 mumol/l). These individual amino acid changes were not accompanied by impairment in the net hepatic amino acid balance or the hepatic fractional extraction of amino acids between the two groups., Conclusion: These results suggest that the circumstances associated with liver transplantation alter the fasting amino acid profile immediately postoperatively. However, liver transplantation does not impair the normal hepatic allograft uptake of most plasma amino acids. Thus, the changes observed in the circulating levels of amino acids may represent alterations in nonhepatic production and/or utilization. Furthermore, altered plasma amino acid profiles following liver transplantation are not necessarily indicative of impaired hepatic allograft amino acid metabolism.

Hemodialysis vascular access-related hospitalizations account for more than 20% of United States end-stage renal disease (ESRD) hospitalizations, with an annual cost approximating $675 million. Limiting access-related costs while delivering similar degrees of quality care thus would enhance alternative utilization of ESRD funding. We implemented a vascular access care pathway emphasizing coordinated patient evaluation and outpatient surgery to determine whether such an intervention affected outcomes associated with vascular access surgery. Data examining hospitalization and vascular access surgery charges, complications, and patient satisfaction (determined by questionnaire) were analyzed, comparing patients who underwent vascular access surgery in 1994 and 1995 as inpatients (non-care pathway patients) and patients who underwent vascular access surgery via the care pathway in 1995. Inpatient days declined in 1995 (1994: 582 days; 1995: 85 days; P < 0.03) and the average charges per patient for the care pathway cohort were significantly less than charges per patient in 1994 and charges for non-care pathway patients in 1995 (1994 patients: $10,524 +/- $5,209; 1995 non-care pathway patients: $11,196 +/- $5,806; 1995 care pathway patients: $4,686 +/- $2,912/patient; P < 0.02). Incidence rates for major (life-threatening) complications were not significantly different between 1994 patients and care pathway patients in 1995. However, the 1995 non-care pathway patients had a higher incidence of major complications (15.4%). Forty-seven repeat access procedures were performed in 29 patients in 1994 versus 35 repeat access procedures in 22 care pathway patients in 1995, and 12 repeat access procedures were performed in eight non-care pathway patients in 1995. Finally, a majority of the patients entered into the care pathway who responded to a survey stated that they were satisfied with access surgery via the care pathway. These data suggest that a vascular access care pathway can reduce hospital days and costs while achieving acceptable outcomes for access surgery.

These studies were undertaken to evaluate the mechanisms for changes in plasma insulin and glucagon levels observed post-liver transplantation. Two groups of pigs were studied: a control group (n = 8) underwent laparotomy and catheter placement in the carotid artery and portal and hepatic veins. Hepatic blood flow was measured by ultrasonic flow probes placed around the hepatic artery and portal vein. An experimental group (n = 8) underwent orthotopic liver transplantation and similar instrumentation. On Day 1 after surgery, an estimate of insulin and glucagon secretion and hepatic extraction was determined using arteriovenous difference techniques. Serum assays were performed for markers of hepatic and renal function. Plasma insulin levels of the transplanted pigs were higher in the carotid artery (4 +/- 1 microU/ml vs 7 +/- 1 microU/ml), but not in the hepatic vein (5 +/- 1 microU/ml vs 7 +/- 1 microU/ml) and in the portal vein (10 +/- 2 microU/ml vs 12 +/- 2 microU/ml). Arterial plasma C-peptide was significantly greater in the transplanted group (0.23 +/- 0.02 ng/ml vs 0.42 +/- 0.03 ng/ml); however, the molar ratio of C-peptide and insulin was not different between the two groups (3.6 +/- 0.9 vs 3.4 +/- 0.4). Plasma glucagon levels of the transplanted pigs were significantly elevated in the carotid artery (111 +/- 11 pg/ml vs 323 +/- 65 pg/ml), portal vein (221 +/- 27 pg/ml vs 495 +/- 69 pg/ml), and hepatic vein (142 +/- 15 pg/ml vs 395 +/- 58 pg/ml). The estimate of pancreatic secretion of insulin (115 +/- 28 microU/kg.min) vs 71 +/- 21 microU/kg.min) and glucagon (2.0 +/- 0.4 ng/kg.min vs 2.7 +/- 0.7 ng/kg.min) and the fractional hepatic extraction rate of insulin (35 +/- 8% vs 32 +/- 5%) were not different between the two groups. However, the hepatic fractional extraction rate of glucagon was significantly decreased in the transplanted group (25 +/- 5% vs 11 +/- 3%). Therefore, the hyperglucagonemia observed 24 hr following liver transplantation is partly due to reduced hepatic fractional extraction of glucagon while the hyperinsulinemia is mainly due to the nonhepatic clearance of insulin. We speculate that decreased renal function may contribute to the hyperinsulinemia, elevated C-peptide concentrations, and hyperglucagonemia.

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.

This cross-over study compared the pharmacokinetic parameters obtained from cyclosporine (CsA) concentration-time profiles after administration of the corn oil-based soft gel cap (CsA-GC) with those with the microemulsion (CsA-ME) gel cap. Neither the fasting state nor the coadministration of a low- or high-fat breakfast affected the pharmacokinetics of CsA presented in either formulation. Comparisons of the three sets of pharmacokinetic parameters--namely, after fasting or after low-fat or after high-fat diets--demonstrated the CsA-ME formulation to display greater intraindividual reproducibility of the C0 and C12 trough levels (TLs), Cmax, tmax, and area under the concentration-time curve (AUC) than the CsA-GC formulation. Although the degree of interindividual variation in AUC, Cmax and tmax after CsA-ME administration was slightly, but significantly, less than after CsA-GC administration, there was no difference between the two formulations in terms of the customarily monitored C0 or C12 TL values. CsA-ME showed higher correlation coefficients of drug exposure (AUC) with C12 than CsA-GC (0.910 versus 0.712). However, CsA-ME administration resulted in only modest improvement over CsA-GC administration in the relationships between drug dose and C0, C12, or AUC--namely, 0.645 versus 0.496, 0.611 versus 0.517, and 0.700 versus 0.501, respectively. Correlation analysis between individual timed samples and AUC determinations revealed that CsA-ME requires significantly less frequent blood monitoring for prediction of total drug exposure than does CsA-GC. Although the clinical utility of this reproducible pharmacokinetic behavior remains to be demonstrated in the de novo transplant setting, the markedly reduced intraindividual variation produced by administration of CsA-ME will likely improve the accuracy of pretransplant prediction of, and reduce the frequency of subsequent adjustments in, CsA doses.

Background and Methods: The safety of long-term immunosuppression with cyclosporine in renal-transplant recipients is not well understood. This drug may cause a progressive toxic nephropathy, but it also preserves renal function because it prevents rejection. To determine the effect of cyclosporine on renal function and graft rejection, we conducted a retrospective analysis of data on 1663 renal-transplant recipients at six centers., Results: The rate of graft survival was 78 percent (median follow-up, 36 months). Grafts were was lost in 279 patients (17 percent), mostly because of acute rejection (68 patients) or chronic graft dysfunction that was unresponsive to a reduction in the dose of cyclosporine (125 patients); 92 patients died with functioning grafts. The median change in the serum creatinine concentration in all patients after transplantation was less than 0.001 mg per deciliter per month (< 0.09 mumol per liter per month). Patients who had episodes of rejection had decreased rates of long-term graft function and survival. Eight percent of patients with functioning grafts at one year had first episodes of rejection more than one year after transplantation. These late first rejections were associated with noncompliance with therapy (in 34 percent), blood cyclosporine concentrations that were marginally lower than those of patients who had no episodes of rejection, and a low rate of successful reversal of rejection (77 percent, vs. 97 percent in patients with rejection during the first year; P < 0.001)., Conclusions: The majority of renal-transplant patients tolerate long-term cyclosporine therapy without evidence of progressive toxic nephropathy. Graft failure is most often due to rejection.

Disseminated histoplasmosis occasionally involves the kidney, but the infection usually does not cause either urinary symptoms or a decrease in renal function. We present a case of disseminated histoplasmosis in a renal transplant recipient who presented with urinary obstruction in the allograft from a sloughed renal papilla infected with the fungus. At the same time the patient had chronic meningitis from Histoplasma capsulatum. The literature on renal involvement with histoplasmosis is reviewed.

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 (P < 0.001) 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)

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)

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.

Three renal transplant recipients were studied who developed the hemolytic uremic syndrome (HUS) during cyclosporine (CsA) immunosuppression. All patients displayed characteristic findings including normocytic, normochromic anemia, thrombocytopenia, erythrocyte morphologic abnormalities, increased numbers of reticulocytes, bone marrow hyperplasia, and renal failure. The clinical studies support the diagnosis of an extrinsic hemolytic process. Renal biopsy specimens demonstrated fibrin deposition and glomerular thrombosis. The renal failure was not responsive to antirejection therapy. The first patient was converted to azathioprine and consequently had a gradual improvement in renal function. Failure to convert the second patient resulted in adequate immunosuppression and subsequent graft loss. The third patient's improvement corresponded with a moderate CsA dose reduction. The occurrence of HUS in these patients represents a de novo presentation after CsA immunosuppression. An analysis of these cases indicates that CsA should be discontinued if HUS persists after moderate dose reduction.

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.

Intestinalization, a new method of pancreatic preservation in which vascularized pancreatic fragments are placed inside a jejunal pouch, has been tested for its effectiveness in the prevention of shock and death due to segmental pancreatitis. Intestinalization of the fragment resulted in the survival of eight of nine animals (89 percent) in which recovery was uneventful, whereas animals with pancreatitis in situ or in a mobilized fragment without intestinalization had a mortality rate of 100 percent within 2 days. We conclude that intestinalization ameliorates the outcome of hemorrhagic pancreatitis in the pancreatic fragment by effectively draining toxic products. The procedure may also be useful in pancreatic transplantation since no reintervention is necessary if graft failure or rejection occurs because the pancreas is accessible by endoscopy.