Massimo Asolati

Outcome at 3 Years with a Prednisone-Free Maintenance Regimen: A Single-Center Experience with 349 Kidney Transplant Recipients

Historically, late steroid withdrawal after kidney transplants has been associated with an increased rejection rate. Recently, low rejection rates have been reported for recipients treated with complete avoidance or rapid elimination of steroids. However, follow‐up has been short. We herein report on 3‐year outcome in recipients whose prednisone was rapidly eliminated and who were maintained on a steroid‐free regimen. From 10/1/1999 through 5/1/2003, 349 recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone.

Chronic rejection: the next major challenge for pancreas transplant recipients.

Objective. With newer immunosuppressive agents, acute rejection and graft loss resulting from acute rejection have become less common for pancreas transplant recipients. As long-term graft survival rates have improved, an increasing number of grafts are being lost to chronic rejection (CR). We studied the incidence of CR and identified risk factors. Methods. We retrospectively analyzed all cadaver pancreas transplants performed at the University of Minnesota between June 19, 1994, and December 31, 2002. We determined the causes of graft loss, the incidence of graft loss to CR and, using multivariate techniques, the major risk factors for CR. Results. A total of 914 cadaver pancreas transplants were performed in the following three categories: simultaneous pancreas-kidney (SPK) (n=321), pancreas after kidney (PAK) (n=389), and pancreas transplant alone (PTA) (n=204). The mean recipient age was 41.3 years and the mean donor age was 30.1 years. Of the 914 pancreas grafts, 643 (70.3%) continue to function (mean length of follow-up, 39 months). The most common cause of graft loss was technical failure, accounting for 118 (12.9%) of the failed grafts. The second most common cause was CR, accounting for 80 (8.8%) of the failed grafts. The incidence of graft loss to CR was highest for PTA (n=23 [11.3%]) and PAK (n=45 [11.6%]) recipients and lowest for SPK recipients (n=12 [3.7%]) (P =0.002). By multivariate analysis, the most significant risk factors for graft loss to CR were a previous episode of acute rejection (relative risk [RR]=4.41, P <0.0001), an isolated (vs. simultaneous) transplant (PAK or PTA [vs. SPK], RR=3.02, P =0.002), cytomegalovirus infection posttransplant (RR=2.41, P =0.001), a retransplant (versus primary transplant) (RR=2.27, P =0.004), and one or two (vs. zero) antigen mismatches at the B loci (RR=1.68, P =0.04). Conclusions. As short-term pancreas transplant results improve and as isolated (PAK or PTA) pancreas transplants gain in popularity, CR will become increasingly common as a cause of pancreas graft loss.

Living Related Segmental Bowel Transplantation: From Experimental to Standardized Procedure

Introduction:Living donor bowel transplantation has recently emerged as a valuable alternative to cadaver bowel transplant. We herein present our single-center experience with this procedure. Materials and Methods:From April 1998 to October 2004, 12 living donor intestinal transplants were performed in 11 patients (7 males, 4 females; average age, 26 years). Four of the patients were children under 5 years. A segment of distal ileum 150 to 180 cm long in pediatric recipients and 200 cm long in adult was used. The immunosuppressive protocol consisted of induction with thymoglobulin and maintenance with tacrolimus with or without mycophenolate mofetil and steroids. Results:All donors recovered well and did not experience any early or late complications. The overall 1- and 3-year patient survival was 82% with a graft survival of 75%. In the last 8 patients, transplanted after January 2000, the 1-year patient and graft survival has been 100% and 88%, respectively. The median hospital stay was 36 days (range, 13–290 days). During the first year after transplant only, the patient who received a totally mismatched graft experienced one episode of rejection (8%). All the surviving patients are currently supported by enteral diet without fluid requirements. Conclusions:Living donor bowel transplantation is a valuable strategy in the treatment of irreversible intestinal failure. The results have improved over the years thanks to increased experience of the team.

Successful ABO-incompatible pediatric liver transplantation utilizing standard immunosuppression with selective postoperative plasmapheresis

Transplanting blood group A, B, or O (ABO)‐incompatible (ABO‐I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO‐I liver grafts—regardless of recipient age—have comparable long‐term survival (mean follow‐up of 3.25 yr) with ABO‐compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One‐year actuarial patient survival for ABO‐matched grafts vs. ABO‐I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO‐I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO‐compatible group. There were no vascular complications and 2 biliary strictures in the ABO‐I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO‐I grafts in a more elective setting associated with split and living donor liver transplants. Liver Transpl 12:972–978, 2006.

Rapid Discontinuation of Prednisone in Higher-risk Kidney Transplant Recipients

Prednisone-minimization protocols have been successful in low-risk recipients. We report on the use of a protocol incorporating rapid discontinuation of prednisone in a cohort of kidney transplant recipients (n = 79) at increased immunologic risk. Our data suggests that such recipients should not be excluded from prednisone-minimization protocols.

Outcomes of laparoscopic and open colectomy at academic centers.

BACKGROUND Laparoscopic techniques have emerged as a suitable approach for colon resection. This study determined and compared the outcomes of patients undergoing laparoscopic or open colectomy at United States academic centers. METHODS Using ICD-9-CM codes, we obtained data from the University HealthSystem Consortium database for 50,443 patients who underwent open (n = 47,090; 94%) or laparoscopic (n = 3,353; 6%) colectomy during a 5-year period (2002 to 2006). Outcomes studied included length of stay (LOS), costs, in-hospital morbidity and risk-adjusted mortality rates. RESULTS Mean LOS (open = 11 days and laparoscopic = 7 days) was significantly shorter and mean costs (open =

Intrasplenic hepatocyte allotransplantation in dalmatian dogs with and without cyclosporine immunosuppression

23,000 and laparoscopic =

Long-term outcome of a prospective trial of steroid withdrawal after kidney transplantation

17,000) significantly fewer with the laparoscopic approach. The overall in-hospital morbidity rate was significantly lower with laparoscopic colectomy (open = 33% and laparoscopic = 24%). The risk-adjusted mortality ratio was comparable between groups (open = .9 and laparoscopic = .7). COMMENTS Despite the major biases inherent in this retrospective review of the University Health System Consortium, which favors the use of laparoscopic colectomy by United States academic surgeons, laparoscopic colectomy offers the potential of significantly shorter LOS, fewer costs, lower in-hospital morbidity rates, and comparable risk-adjusted mortality rates compared with open colectomy. Laparoscopic colectomy is as safe as the open approach.

Low infectious complications in segmental living related small bowel transplantation in adults

Hepatocyte allotransplantation has been performed successfully in several small animal models for the amelioration of inborn metabolic errors. Before a human clinical trial of hepatocyte allotransplantation can be attempted, preliminary experience in a large animal model is needed. We transplanted isolated mongrel hepatocytes into the spleen of dalmatians in the attempt to cure their inborn error of uric acid metabolism. Of 10 dalmatian recipients, two that received 9-10 x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes and were randomized either to no treatment or to oral cyclosporine (CsA). Levels of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the four nonimmunosuppressed dalmatians, a reproducible average reduction in urinary uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline within 14 days. In the CsA-immunosuppressed dalmatians, the average decline in UUAEx was 30%. The partial correction of the metabolic defect persisted for an average of 25 days in three immunosuppressed dogs, whereas in one dog, the partial correction lasted for over 90 days. No change in UUAEx was observed in two dalmatians that underwent sham laparotomy and intrasplenic injection of saline solution; CsA given alone to dalmatians did not modify UUAEx. We conclude that the dalmatian dog is a valuable large animal model for studies of the role of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.

Medical and surgical treatment of neonatal hemochromatosis: single center experience.

BACKGROUND Steroid withdrawal (SW) after kidney transplantation is desirable to avoid associated serious side effects. We studied the long-term outcome of a group of kidney transplant recipients who underwent SW. METHODS Between 1991 and 1993, kidney transplant recipients (N = 12) who had posttransplantation diabetes were entered in a prospective trial of SW. These patients were compared with a demographically similar comparison cohort (N = 66). End points of the study were patient and graft survival, incidence of late acute and chronic rejection, and changes in diabetes management. RESULTS Previously published data from the SW group at 15 months of follow-up indicated improvement in diabetes control without any adverse effect on patient or graft actuarial survival. At long-term follow-up (mean, 56 months) the improvement in diabetes management was not detectable. The incidence of late acute rejection in SW and cohort groups was 42% and 8%, respectively (P = .006). Likewise, the incidence of chronic rejection in the SW versus cohort group was 42% and 12%, respectively (P = .014). CONCLUSIONS Although SW appeared to be successful initially, our long-term data indicate that SW significantly increases the risk of late acute rejection and chronic rejection episodes without benefits in posttransplantation diabetes management. Steroid withdrawal in patients with posttransplantation diabetes should be approached with caution.