A comparison of the sensitivities of contrast and isotope voiding cystourethrograms for the detection of pancreas transplant bladder leaks.
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Biomedical subjects
Publications and source records attributed to J D Pirsch.
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After a decade of rapid development, SPK transplantation has become routine at our center. There are several developments responsible for the current high level of success: UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications. The critical modifications in surgical technique have included the avoidance of systemic heparinization, complete mobilization of the iliac vein for a tension-free anastomosis between an unmodified donor portal vein and the recipient iliac vein, oversewing of the revised duodenal staple lines and meticulous hemostasis. The most important recent improvement in immunosuppression is the use of mycophenolate mofetil, which has dramatically reduced rejection. Finally, PDC leaks, the principal and potentially most devastating complication of SPK transplantation, are rapidly diagnosed and treated expeditiously.
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.
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Orthotopic liver transplantation has become the treatment of choice for most children and infants with end-stage liver disease. The purpose of this retrospective study was to examine the results of 100 consecutive liver transplants performed in infants and children at a single institution. During an 8-year study period (July 1984 to December 1992), 100 pediatric liver transplants were performed in 76 patients. Thirty-four patients (44.7%) were infants (mean age, 7.0 months; mean weight, 6.1 kg), and 42 (55.3%) were children (mean age, 8.2 years; mean weight, 30.6 kg). There were 36 reduced-size liver transplants (RLT) and 64 whole-size transplants (WLT). Eight infants (23.5%) and 10 children (20.7%) required retransplantation. After transplantation, 71% of the patients had one or more rejection episodes, 66% had one or more infections, 17.1% had biliary complications, and 39.4% required one or more reoperations. There were 17 deaths. The actuarial 8-year survival rate for the patients with biliary atresia was 82.3%; for all infants in this series, it was 77.6%. No difference in patient survival was noted when RLT was compared with WLT. The overall 8-year actuarial patient survival rate for infants and children was 77.3%.
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To date one of the major dilemmas in clinical pancreas transplantation is the lack of a reliable indicator for pancreas rejection. In a consecutive series of 52 patients undergoing simultaneous pancreas and kidney (SPK) transplantation with bladder drainage technique between October 1991 and December 1992 a new test using serial levels of serum human anodal trypsinogen (HAT) was evaluated for its efficacy to detect pancreas rejection. Postoperative baseline levels of HAT were compared to peak HAT values at time of rejection. HAT profiles at time of rejection were calculated and compared to profiles of urinary amylase, serum amylase, fasting blood sugar and serum creatinine. In this series one year patient survival was 97%, graft survival of the pancreas 86% and of the kidney 90%. In 71% of the patients at least one rejection episode occurred. At time of kidney-biopsy proven rejection with a concurrent serum creatinine rise a significant HAT level rise to more than 1000 ng/ml was observed from baseline levels of 200 ng/ml (P < 0.001) indicating kidney and pancreas rejection (73%). Urinary amylase levels decreased in the majority of rejection episodes at the same time from baseline levels to less than 20,000 U/l. In 25% of the rejection episodes a significant serum creatinine rise was observed without a HAT rise or urinary amylase decrease indicating kidney-only rejection, while in 2% a urinary amylase decrease and simultaneous HAT also was observed with a negative kidney biopsy indicating pancreas-only rejection. We feel that increase in HAT levels significantly correlates with pancreas rejection. After SPK, determination of HAT is an additional helpful non-invasive test. In pancreas transplantation alone HAT can be a useful indicator to detect rejection and facilitate timing of a pancreas biopsy and initiation of antirejection treatment.
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)
Current immunosuppressive protocols have significantly decreased graft loss to acute rejection but have had no effect on graft loss to chronic rejection. Recently, attention has been focused on the prevention and management of chronic rejection. Centers must come to a uniform definition of this phenomenon so that studies can be compared. It is believed that the definition should include both a typical clinical course and a definitive biopsy. For kidney transplant recipients, the major risk factor for the development of chronic rejection appears to be a previous acute rejection episode. Other important risk factors include low-dose maintenance immunosuppression and previous infection. Noncompliance probably plays a role in some patients. For extrarenal transplant recipients, chronic rejection has been associated with cytomegalovirus infection and/or HLA-DR matching. Immunoregulatory processes posttransplant may modify or attenuate the development of chronic rejection. Large, prospective clinical studies are required to further elucidate risk factors and to determine the effect of intervention.
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1. LURD transplants were associated with excellent one-year graft survival of 92%. This survival was superior to that for cadaver transplants performed during the same period. 2. High-risk groups for LURDs are children (age < 18 years) and repeat transplant recipients. Both groups were associated with significantly decreased graft survival. 3. The effects of HLA matching and donor-specific transfusions are not significant. 4. Because of the critical shortage of donor organs and the increasing waiting time for renal transplantation, the use of LURDs can be recommended as a means to expand the number of available organs.
BACKGROUND: Although liver transplantation offers definitive treatment for portal hypertension with end-stage liver failure, surgical portosystemic shunts avoid the risks of transplantation and immunosuppressive therapy, and transjugular intrahepatic portosystemic shunt (TIPS) creates a portosystemic shunt with minimal operative risk. The appropriate applications of these modalities are discussed. METHODS: All adults undergoing primary liver transplantation alone (PLT, n = 265), PLT after TIPS (n = 34), PLT after surgical shunts (n = 12), surgical shunt alone (n = 13), TIPS alone (n = 35), or surgical shunt after PLT (n = 5) served as the basis of this study. RESULTS: In contrast to surgical shunts before PLT, TIPS before PLT increased the 1-year graft survival. Surgical shunts alone were done in 18 patients with normal or near normal liver function with 100% survival. TIPS alone offered effective symptomatic relief to most patients, all of whom were judged not to be surgical candidates. CONCLUSIONS: TIPS, surgical shunts, and liver transplantation each have a logical role in management of portal hypertension. Surgical candidates with Child's B or C liver failure should be treated with liver transplantation, and TIPS offers effective treatment for nonsurgical candidates. Surgical shunts can be performed with excellent results in patients with Child's A liver disease. Portal vein occlusion with normal liver function can be successfully treated with surgical shunts.
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In summary, we feel that excellent 5-year patient and graft survival results can be obtained using SPK transplantation with bladder drainage technique. Despite the good results, a significant morbidity with prolonged hospitalization is seen after pancreas transplantation. This increased morbidity is due to infectious complications, rejection and urological complications. As a result of the popularity of bladder drainage, the complications after pancreas transplantation have shifted from intraabdominal to urological. Enteric conversion after SPK transplantation is the treatment of choice for chronic hematuria and a duodenal segment leak. In our hands this method appeared to be a safe and reliable procedure with a low complication rate. Enteric conversion should be considered in early leaks after failure of one attempt to suture repair the anastomotic site. In larger leaks or late leaks, it is advisable to perform an immediate enteric conversion. With the considerations above one might ask why enteric conversion is not our current primary choice for the initial transplant procedure. We have, however, noted a higher incidence of postoperative intraabdominal septic complications as well as mycotic aneurysms at the arterial suture line in a small series of 16 primarily enterically drained pancreas transplants. We also fear that the leakage rate after primary duodenoenteric drainage could be higher because of significant edema after transplantation in the preserved duodenal segment. We doubt, therefore, that the primary anastomosis with the bowel is as safe as one performed during enteric conversion when preservation injury has been resolved. At that point the patient is in stable condition and on significantly lower doses of immunosuppression than at the time of transplantation. This study demonstrates that urological complications constitute a major part of the morbidity after SPK transplantation. Despite this fact, appropriate treatment including enteric conversion can resolve most of the complications and prevent long-term morbidity or even graft loss.
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Calcium channel blockers have immunomodulating effects in vitro and may be effective in preventing cyclosporine nephrotoxicity. We studied the effect of verapamil following renal transplantation on the incidence of rejection and cyclosporine nephrotoxicity in a double-blind, placebo-controlled trial. Patients were randomly assigned to placebo (n = 28) or verapamil (n = 32) at doses of 80 mg twice a day. There was no difference in the incidence of rejection or cyclosporine toxicity in the two study arms. Recipients randomized to verapamil had lower mean cyclosporine doses at all intervals during a 1-year follow-up. Although cyclosporine doses were lower in the placebo group, the mean cyclosporine levels were equivalent in the two groups. Recipients in the verapamil-treated group had a higher mean serum creatinine at the end of the study--1.7 mg/dL versus 1.4 mg/dL in the placebo group. Actual 1-year graft survival was 89% for the placebo recipients versus 91% in the verapamil-treatment group. When compared with placebo, the concomitant use of low-dose verapamil results in lower cyclosporine doses but equivalent cyclosporine blood levels. Reduction in the incidence of rejection or cyclosporine nephrotoxicity were not observed.
OBJECTIVE: The urological complications of 210 patients who underwent simultaneous pancreas-kidney (SPK) transplantation over a 7-year period were reviewed. SUMMARY BACKGROUND DATA: Worldwide, bladder drainage has become the accepted method of exocrine drainage after pancreas transplantation. With the increasing use of bladder drainage, the surgical post-transplant complications have shifted from intra-abdominal complications to urological complications. METHODS: Two hundred ten diabetic patients received SPK transplants with bladder drainage. A retrospective review was conducted to analyze the incidence, type, and management of urological complications. RESULTS: The most frequent urological complications were hematuria, leak from the duodenal segment, recurrent urinary tract infections, urethritis, and ureteral stricture and disruption. Complications related to the renal transplant included ureteral stricture and leaks, as well as lymphoceles. CONCLUSIONS: Despite the high incidence of urological complications, 5-year actuarial patient and graft survival are excellent. Only one graft and one patient were lost secondary to urological complications.