John S. Bynon

Surgical treatment of diabetes mellitus with pancreas transplantation.

ObjectiveThe authors compared results and morbidity in insulin-dependent diabetes mellitus (IDDM) patients undergoing preemptive pancreas transplantation (PTx) either before dialysis or before the need for a kidney transplant with IDDM patients undergoing conventional combined pancreas-kidney transplantation (PKT) after the initiation of dialysis therapy. Summary Background DataCombined PKT has become accepted generally as the best treatment option in carefully selected IDDM patients who either are dependent on dialysis or for whom dialysis is imminent. With improving results, the timing of PKT relative to the degree of nephropathy is evolving. However, it is not well established that the advantages of preemptive PTx can be achieved without incurring a detrimental effect on graft function or survival. MethodsOver a 4-year study period, data on the following 3 recipient groups were collected prospective and analyzed retrospectively: 1) 38 IDDM patients undergoing combined PKT while on dialysis (PKT:D);2) 44 IDDM patients undergoing preemptive PKT before dialysis (PKT:ND); and 3) 20 IDDM patients undergoing solitary PTx. All patients underwent whole organ PTx with bladder drainage and were treated with quadruple immunosuppression. ResultsActuarial 1-year patient survival is 100%, 98%, and 93%, respectively. One-year actuarial PTx survival (insulin-independence) is 92%, 95%, and 78%, respectively. The incidence of rejection, infection, operative complications, readmissions, and total hospital days was similar in the three groups. Long-term renal and pancreas allograft function and quality of life were similarly comparable. Rehabilitation potential favored the solitary PTx and PKT:ND groups. ConclusionsPreemptive PKT or solitary PTx performed earlier in the course of diabetes is associated with good results, facilitated rehabilitation, and may prevent further diabetic complications.

Two-dose daclizumab induction therapy in 209 liver transplants: a single-center analysis.

Background. Patient and graft survival after liver transplantation are adversely affected by early posttransplant renal dysfunction. Therefore, our immunosuppressive strategies should be as “renal sparing” as possible. This is the largest published series to date using daclizumab induction therapy in a renal-sparing regimen. Methods. This is a retrospective, nonrandomized study comparing 209 adult liver transplants with daclizumab induction to 115 transplants with no induction. Results. Patient and graft survival were similar, despite higher pretransplant acuity of illness and older age in the induction group. Acute rejection within the first 6 months occurred less commonly in the induction group (25.4% vs. 39.1%, P=0.01), despite significantly delayed initiation and lower doses of a calcineurin inhibitor. Mycophenolate mofetil was used more commonly in induction patients, but the efficacy of daclizumab in preventing rejection was independent of this. Patients with a pretransplant creatinine concentration 1.5 mg/dL or less had less rejection if they received induction. Renal function worsened in noninduction patients but showed sustained improvement throughout follow-up in induction patients with a pretransplant creatinine concentration greater than 1.5 mg/dL. Induction therapy provided better rejection prophylaxis among those requiring temporary calcineurin inhibitor cessation because of renal dysfunction. The incidences of histologic hepatitis C recurrence and cytomegalovirus infection were similar in each group. Conclusions. Liver recipients with and without pretransplant renal dysfunction have less acute rejection with daclizumab induction therapy. This is not associated with an increased risk of over-immunosuppression. Sustained renal improvement in recipients with pretransplant renal dysfunction is possible with daclizumab induction.

Viral prophylaxis in combined pancreas-kidney transplant recipients

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

Multimodality treatment for patients with hepatocellular carcinoma: analysis of prognostic factors in a single Western institution series.

There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including ortbotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham from January 1990 through December 1999. Clinicopathologic and treatment factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or lV tumors. The median follow-up for survivors was 22 months. The l-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial l-, 3-, and S-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.

Retrograde Flushing of Living Donor Renal Allografts Via The Renal Vein: A Simple, Effective Technique

Background Prograde flushing (PF) of living donor renal allografts with preservation solution via the renal artery or arteries is standard practice. PF may be difficult and potentially injurious to the donor kidney, especially in grafts with small or multiple arteries. In this report, we present our experience with retrograde flushing (RF) of 7 living donor kidneys via the renal vein. Methods Retrospective review of 7 consecutive living donor renal transplants performed using the RF technique was performed. The 7 preceding living donor renal transplants performed using the standard arterial PF technique served as a control group. Results All 7 recipients of RF kidneys experienced immediate graft function. At postoperative days 3 and 30, there was no difference in estimated glomerular filtration rate between the RF study group and PF controls. Conclusions The RF technique is simple and safe, with results equivalent to the PF technique. The RF technique may be especially useful after recovering kidneys with small and/or multiple arteries.

IMPROVED OUTCOMES IN CADAVERIC RENAL ALLOGRAFTS WITH PULSATILE PRESERVATION.

BACKGROUND Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation pulsatile perfusion (PP) versus cold storage (CS) is debated. METHODS Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( < or = 20 min, 21-40 min, or > 40 min) and total ischemic time (TIT) ( < or > or = 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. RESULTS There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). CONCLUSIONS Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.