State of pediatric liver transplantation in the United States and achieving zero wait list mortality with ideal outcomes: A statement from the Starzl Network for Excellence in Pediatric Transplant Surgeon's Working Group.

BACKGROUND: Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized. METHODS: Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face. RESULTS: A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant. CONCLUSIONS: Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.

Liver transplantation in pediatric patients: twenty years of experience at the University of Wisconsin.

Developments in surgical technique, immunosuppression, organ procurement and preservation, and patient selection criteria have resulted in improved long-term patient and graft survival after pediatric liver transplantation. In this study, we examined the results of 196 liver transplants performed in 155 pediatric patients at University of Wisconsin Children's Hospital. Patients were divided into two groups according to age at the time of liver transplant. Infants under 12 months of age comprised Group 1 (n=74) and children from one to 18 yr comprised Group 2 (n=122). Outcomes for whole, reduced-size, and split liver transplantation were compared in infants and children. Biliary atresia was the most common indication in both groups. Patients underwent 128 whole size, 50 reduced size, and 18 split liver transplants. Forty-one retransplantations were performed in 14 infants (18.9%) and in 27 children (22.1%). One hundred eleven patients (56.6%) had one or more rejection episode [37 infants (50.0%) and 74 children (60.6%)]. Thirty-nine patients (19.8%) developed CMV infections, 42 (21.4%) developed EBV infections, and 14 developed PTLD (six infants and eight children). Thirty-six patients (18.3%) developed HAT. Seven patients (4.5%) developed malignancy (one infant and six children). Out of 155 patients, 33 (21.3%) died during the study period. The most common etiology of mortality included central nervous system pathology (n=7; 4.5%), sepsis (n=6; 3.8%), and cardiac causes (n=6; 3.8%). One-, five-, and 10-yr actuarial patient survival was 86, 79, and 74% in infants and 90, 83 and 80% in children. Graft survival at one, five, and 10 yr was 77, 73 and 71% in infants and 88, 81 and 78% in children, respectively. Despite its technical challenges, the outcomes of liver transplantation in pediatric patients with end-stage liver disease are excellent and result in significant long-term patient and graft survival.

Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation.

BACKGROUND: An increase in the incidence of autoimmune diseases has been described in patients receiving alemtuzumab. METHODS: To determine whether induction with alemtuzumab increases recurrence of glomerular disease, we performed a retrospective study in 443 patients with biopsy-proven glomerular diseases undergoing kidney transplantation. Patients receiving alemtuzumab (n=161) were compared with those receiving interleukin (IL)-2-receptor antagonists (n=217) or antithymocyte globulin (n=64). RESULTS: Biopsy-proven glomerular disease recurrence was similar in patients induced with alemtuzumab or IL-2 receptor antagonists. Patients receiving antithymocyte antibody had a lower recurrence rate than patients treated with other induction agents, with borderline significance (hazard ratio [HR] 0.13, 95% confidence interval [95% CI] 0.02-0.98, P=0.047). Patients with systemic lupus treated with alemtuzumab had a similar re-emergence of autoreactive antibodies to patients treated with other agents. Recurrent disease increased the risk of allograft failure (HR 2.36, 95% CI 1.28-4.32, P=0.0056). The development of acute rejection and the use of deceased (vs. living) donor kidneys were also significant factors influencing graft survival. A greater risk of mortality was detected in those patients with recurrent glomerular disease (HR 3.76, 95% CI 1.37-10.35, P=0.01), whereas increased age at transplantation (HR 1.05) and the use of deceased (vs. living) donor kidneys (HR 3.20) also increased mortality. No specific induction agent significantly affected graft loss or mortality when using adjusted or unadjusted hazard ratios. CONCLUSIONS: In this retrospective analysis, induction with alemtuzumab did not increase the rate of re-emergence of autoantibodies or biopsy-proven recurrence of glomerular disease. A slight reduction in the incidence of recurrence was observed in patients treated with thymoglobulin, yet this observation can only be validated in a prospective randomized trial.

Maintaining urine production and early allograft function during laparoscopic donor nephrectomy.

OBJECTIVES: Intraoperative oliguria and its impact on early postoperative allograft function have been expressed as potential concerns of laparoscopic kidney donation. We evaluated our ability to maintain adequate diuresis during laparoscopic donor nephrectomy and its potential impact on early graft function compared with open donation. METHODS: We performed a retrospective review of 98 laparoscopic and 80 open donor nephrectomies from 1999 to 2002. All laparoscopic donors received infusions of mannitol (grams of mannitol equaled patient weight in kilograms) and dopamine (2 to 3.0 microg/kg/min) throughout the pneumoperitoneum. All open donors received a single dose of mannitol (12.5 g). Multiple donor variables were compared, including operative time, estimated blood loss, intraoperative fluid administration (in milliliters per kilogram per hour), intraoperative urine production (milliliters per kilogram per hour), and change in creatinine at discharge. The postoperative recipient data were compared, including initial 24-hour urine output, 1-week creatinine level, 1-month creatinine level, and need for postoperative hemodialysis. RESULTS: No significant differences were noted in the donor groups with respect to age, weight, intraoperative fluid administration, or change in creatinine at discharge. The mean operative urine production was greater in the laparoscopic group at 5.22 mL/kg/hr than in the open group at 2.43 mL/kg/hr (P = 0.0001). The mean estimated blood loss was significantly lower (P = 0.0001) for the laparoscopic donors (106.7 mL) than for the open donors (184.7 mL). No significant differences were seen among the recipient groups. CONCLUSIONS: The use of mannitol and dopamine infusions during laparoscopic donor nephrectomy provided superior intraoperative urine production in the donor and equivalent early graft function in the recipient compared with the open approach.

Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long-term outcomes.

OBJECTIVE: The outcomes of simultaneous pancreas-kidney (SPK) transplantation with donor organs procured from donation after cardiac death (DCD) are compared with transplants performed with donor organs recovered from donation after brain death (DBD). SUMMARY BACKGROUND DATA: Concerns exist regarding the utilization of pancreata obtained from DCD donors. While it is known that DCD kidneys will have a higher rate of DGF, long-term functional graft survival data for DCD pancreata have not been reported. METHODS: A retrospective review of all DCD SPK transplants performed at a single center was undertaken. RESULTS: Patient, pancreas, and kidney survival at 5 years were similar between DCD and DBD organs. Pancreas function and outcomes were indistinguishable between the 2 modes of procurement. As expected, the DCD kidneys had an elevated rate of DGF, which had no significant long-term clinical impact. CONCLUSION: SPK transplantation using selected DCD donors is a safe and viable method to expand the organ pool for transplantation.

Donation after cardiac death: the University of Wisconsin experience with liver transplantation.

OBJECTIVE: To determine whether the outcomes of liver transplantation (LTx) from donation after cardiac death (DCD) donors are equivalent to those from donation after brain death (DBD) donors. SUMMARY BACKGROUND DATA: Because of the significant donor organ shortage, more transplant centers are using livers recovered from DCD donors. However, long-term, single-center outcomes of liver transplantation from DCD donors are limited. METHODS: From January 1, 1993, to July 31, 2002, 553 liver transplants were performed from DBD donors and 36 were performed from DCD donors. Differences in event rates between the groups were compared with Kaplan-Meier estimates and the log-rank test. Differences in proportion and differences of means between the groups were compared with Fisher exact test and the Wilcoxon rank sum test, respectively. RESULTS: Mean warm ischemic time at recovery in the DCD group was 17.8 +/- 10.6 minutes. The overall rate of biliary strictures was greater in the DCD group at 1 year (33% versus 10%) and 3 years (37% versus 12%; P = 0.0001). The incidence of hepatic artery thrombosis, portal vein stenosis/thrombosis, ischemic-type biliary stricture (ITBS), and primary nonfunction were similar between groups. However, the incidence of both hepatic artery stenosis (16.6% versus 5.4%; P = 0.001) and hepatic abscess and biloma formation (16.7% versus 8.3%; P = 0.04) were greater in the DCD group. Trends toward worse patient and graft survival and increased incidence of ITBS were seen in DCD donors greater than 40 years compared with DCD donors less than 40 years. Overall patient survival at 1 year (DCD, 80%; versus DBD, 91%) and 3 years (DCD, 68%; versus DBD, 84%) was significantly less in the DCD group (P = 0.002). Similarly, graft survival at 1 year (DCD, 67%; versus DBD, 86%) and 3 years (DCD, 56%; versus DBD, 80%) were significantly less in the DCD group (P = 0.0001). CONCLUSIONS: Despite similar rates of primary nonfunction, LTx after controlled DCD resulted in worse patient and graft survival compared with LTx after DBD and increased incidence of biliary complications and hepatic artery stenosis. However, overall results of LTx after controlled DCD are encouraging; and with careful donor and recipient selection, LTx after DCD may successfully increase the donor liver pool.

Liver transplantation for HELLP syndrome.

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a rare complication of pregnancy that is associated with preeclampsia and may result in rupture of the liver. Although there have been case reports of liver transplantation for HELLP syndrome, the outcomes of transplantation for this rare indication have not been reported. Furthermore, the optimal management of complicated HELLP syndrome and indications for liver transplantation are unclear. Our objective was to review the national experience with liver transplantation for HELLP syndrome and to develop a comprehensive algorithm for the management of liver complications of HELLP syndrome, including indications for transplantation. A recent case from our institution is reported and the literature is reviewed. The results of liver transplantation for HELLP syndrome were analyzed from the United Network for Organ Sharing database. Between October 1987 and November 2003 there have been 8 deceased donor liver transplants performed for complications related to HELLP syndrome. As of the most recent follow-up, 6 of the 8 patients are alive, with both deaths occurring within 1 month of transplantation, and 2 patients have required retransplantation. This review supports that good results can be obtained with liver transplantation for patients with complicated HELLP syndrome that have either ongoing, uncontrolled hemorrhage or liver necrosis and failure. Patients with complicated HELLP syndrome are best managed at a center with expertise in liver transplantation.

Superior long-term results of simultaneous pancreas-kidney transplantation from pediatric donors.

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.

Campath-1H in renal transplantation: The University of Wisconsin experience.

BACKGROUND: Immune cell depletion is known to prevent renal allograft rejection and injury. We evaluated the humanized monoclonal antibody Campath-1H (alemtuzumab; ILEX Oncology, San Antonio, Texas) in renal transplant recipients for its safety and efficacy in preventing rejection when used in combination with a calcineurin inhibitor, mycophenolate mofetil, and low-dose steroid therapy. METHODS: One hundred twenty-six consecutive renal allograft recipients received 2 doses of Campath-1H antibody on days 0 and 1. Outcomes were compared to patients who received an anti-CD25 antibody (n=799), Thymoglobulin (n=160), or other antibody treatment (n=156) in combination with a calcineurin inhibitor, mycophenolate mofetil, and higher dose steroids. RESULTS: The Campath-1H group overall experienced less rejection than the other 3 groups (P=.037). Patients with delayed graft function experienced less rejection with Campath-1H than control groups (P=.0096) and improved graft survival (P=.0119). There was no difference in infection or malignancies between the 4 groups. CONCLUSIONS: Campath-1H was well tolerated in renal transplant patients and led to significant reductions in incidence of rejection. Patients with delayed graft function experienced significantly improved graft survival.

Donation after cardiac death: the University of Wisconsin experience.

OBJECTIVES: The objective of this analysis was to compare the results of transplantation of livers, pancreases, kidneys, and lungs from donation after cardiac death (DCD) donors to organs transplanted from donation after brain death (DBD) donors. METHODS: From January 1984 through July 2000, outcomes of 382 DCD kidneys were compared to 1,089 kidneys (SPK) transplants and 36 liver transplants from DCD donors were compared to 455 SPK and 510 liver transplants from DBD donors. Likewise, 31 simultaneous pancreas-kidneys transplants from DBD donors. RESULTS: The rate of delayed graft function (DGF) was higher in kidneys transplanted from DCD donors (27.5% versus 21.3%, p=0.01). Likewise, discharge creatinines were higher in recipients of DCD kidneys (1.9 mg/dL versus 1.7 mg/dL, p=0.001). There was no difference in 10-year graft survival between DCD and DBD recipients (45.0% versus 48.0%, p=0.054). No difference in 5-year pancreatic and renal allograft survival was seen after SPK from DCD or DBD donors. After liver transplantation, biliary strictures were higher in recipients of DCD livers (13.9% versus 8.0%, p=0.03). Likewise, 3-year patient and graft survivals were lower for recipients of DCD livers (65.8% versus 84.9%, p=0.01; and 58.6% versus 76.9%, p=0.006). CONCLUSIONS: This large experience with transplantation from DCD donors demonstrates that similar patient and graft survivals can be expected when compared to recipients of organs from DBD donors.

Donation after cardiac death: the university of wisconsin experience with renal transplantation.

Owing to the shortage of organ donors, there is renewed interest in donation after cardiac death (DCD), formerly referred to as nonheart-beating donation. From January 1984 until August 2000, 382 renal transplants were performed from DCD donors. These were compared with 1089 renal transplants performed from donation after brain death (DBD) donors. The mean warm ischemic time in DCD donors was 16.5 min. There was no statistical difference in cold ischemic time, rate of primary nonfunction, or graft loss in the first 30 days after transplantation. The rate of delayed graft function (DGF) was higher for DCD donors (27.5% vs. 21.3%; p = 0.016) and discharge creatinine was higher in DCD donors (1.92 mg/dL vs. 1.71 mg/dL; p = 0.001). There was no statistical difference in the 5-, 10-, or 15-year allograft survival when DCD donors were compared with DBD donors (64.8%, 44.8%, 27.8% vs. 71.3%, 48.3%, 33.8%; p = 0.054). Likewise, no statistical difference in the rate of technical complications was seen. Our long-term data indicate that the results of renal transplantation from DCD donors are equivalent to long-term allograft survival from DBD donors despite an increase in the rate of DGF. Organ procurement organizations, transplant centers, and hospitals should work to expand the implementation of DCD policies.

Liver transplantation for biliary atresia: 19-year, single-center experience.

OBJECTIVES: In this study, we describe our 19-year experience with liver transplantation as the definitive treatment for congenital biliary atresia. MATERIALS AND METHODS: We performed a retrospective study of 115 liver transplants from 1984 to 2003 in 85 patients with congenital biliary atresia. We determined the impact of era of transplantation (1984-1993 and 1994-2003), recipient age (< 1 and > 1), prior portoenterostomy, and type of surgery (whole-, reduced-, and split-liver transplant) on the outcome of the transplant. RESULTS: Overall long-term survival is 83%. Survival is greater in the more-recent era. No impact of age or prior portoenterostomy on survival was seen. Split-liver grafts showed superior graft survival, whereas reduced-liver transplants had the worst overall graft survival. CONCLUSIONS: Our results confirm that long-term patient survival after liver transplantation for congenital biliary atresia is excellent. When required, partial liver grafts provide excellent long-term outcome.

Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study.

Campath-1H, an anti-CD52 monoclonal antibody, was used as induction therapy (40 mg i.v. total dose) in 29 primary human renal transplants, and the patients were maintained on rapamycin monotherapy (levels 8-15 ng/mL) post-transplant. Campath-1H profoundly depletes lymphocytes long-term and more transiently depletes B cells and monocytes. All patients are alive and well at 3-29 months of follow up. One graft was lost because of rejection. There have been no systemic infections and no malignancies. Eight of 29 patients have experienced rejection, which was successfully treated in seven of eight patients. Five of these patients had pathological evidence of a humoral component of their rejection. Seven of the 29 patients were converted to standard triple therapy on account of rejection. Rapamycin was generally well tolerated in that there were no significant wound-healing problems; two lymphoceles required surgical drainage; and most patients were treated with a lipid-lowering agent. Flow crossmatch testing post-transplant revealed evidence of alloantibody in two patients tested with previous combined cellular and humoral rejection. Biopsies have shown no chronic allograft nephropathy to date. In view of the relatively high incidence of early humoral rejection, we plan to modify the immunosuppressive regimen in subsequent pilot studies. This clinical trial provides insight into the use of Campath-1H induction in combination with rapamycin maintenance monotherapy.

Long-term outcomes in simultaneous pancreas-kidney transplantation: lessons relearned.

We analyzed 752 simultaneous pancreas kidney transplants performed at the University of Wisconsin from December 1985-February 2003. Patient survival rates at 5 and 10 years were 88% and 77%. The 5- and 10-year pancreas survival rates were 78% and 61% and the corresponding kidney survival rates were 80% and 59%. In this limited retrospective analysis of outcomes after simultaneous pancreas-kidney transplantation, the importance of donor selection is re-emphasized. Donor age and donor BMI significantly impact on graft and recipient survival. Furthermore, complications following SPK transplantation negatively impact on outcomes.

Liver transplantation at the University of Wisconsin.

Liver transplantation remains the only definitive therapy for patients with decompensated liver disease. Significant advances over the past 20 years in surgical technique, immunosuppressive agents, patient selection, and infection prophylaxis and treatment have led to improved patient and graft survival. The success of liver transplantation coupled with expanding indications has resulted in a marked shortage of donor organs. Our approach at the University of Wisconsin to address the shortage of liver allografts is to maximize organ donation and recovery, include the use of liver allografts from donation after cardiac death, the use of split liver transplant, and the use of living-donor liver transplant when necessary. Split-liver transplantation is an effective technique to expand the number of organs available for transplantation. Continued improvements in organ preservation remain a priority to maximize outcomes, especially when the use of marginal donors or split-liver transplantation is planned. Recipient selection criteria have been expanded to include older recipients as well as previous recipients of multiple allografts. Over time it has become clear that less intensive immunosuppression is required since many patients can be maintained on tacrolimus monotherapy. We remain committed to a continued evaluation of donor and recipient factors in order to maximize outcomes of liver transplantation, as well as a critical appraisal of current and newer immunosuppressive agents and their effects on long-term outcome and recurrent disease.

Survival surgery: removal of the spleen or thymus.

Although for most experiments lymphoid tissue is removed from the freshly sacrificed animal, there are several circumstances which require the surgical removal, under anesthesia, of either the thymus or spleen, and the recovery of the animal for further investigation. This unit describes survival surgery for removal of the adult spleen as well as the adult and neonatal thymus of the mouse.