Rakesh Sindhi

OBJECTIVE: To assess the evolution of visceral transplantation in the milieu of surgical technical modifications, new immunosuppressive protocols, and other management strategies. SUMMARY BACKGROUND DATA: With the clinical feasibility of intestinal and multivisceral transplantation in 1990, multifaceted innovative tactics were required to improve outcome and increase procedural practicality. METHODS: Divided into 3 eras, 453 patients received 500 visceral transplants. The primary used immunosuppression was tacrolimus-steroid-only during Era I (5/90–5/94), adjunct induction with multiple drug therapy during Era II (1/95–6/01), and recipient pretreatment with tacrolimus monotherapy during Era III (7/01–11/08). During Era II/III, donor bone marrow was given (n = 79), intestine was ex vivo irradiated (n = 44), and Epstein-Barr-Virus (EBV)/cytomegalovirus (CMV) loads were monitored. RESULTS: Actuarial patient survival was 85% at 1-year, 61% at 5-years, 42% at 10-years, and 35% at 15-years with respective graft survival of 80%, 50%, 33%, and 29%. With a 10% retransplantation rate, second/third graft survival was 69% at 1-year and 47% at 5-years. The best outcome was with intestine-liver allografts. Era III rabbit antithymocyte globulin or alemtuzumab pretreatment-based strategy was associated with significant (P < 0.0001) improvement in outcome with 1- and 5-year patient survival of 92% and 70%. CONCLUSION: Survival has greatly improved over time as management strategies evolved. The current results clearly justify elevating the procedure level to that of other abdominal organs with the privilege to permanently reside in a respected place in the surgical armamentarium. Meanwhile, innovative tactics are still required to conquer long-term hazards of chronic rejection of liver-free allografts and infection of multivisceral recipients.

OBJECTIVE: To assess the long-term efficacy of intestinal transplantation under tacrolimus-based immunosuppression and the therapeutic benefit of newly developed adjunct immunosuppressants and management strategies. SUMMARY BACKGROUND DATA: With the advent of tacrolimus in 1990, transplantation of the intestine began to emerge as therapy for intestinal failure. However, a high risk of rejection, with the consequent need for acute and chronic high-dose immunosuppression, has inhibited its widespread application. METHODS: During an 11-year period, divided into two segments by a 1-year moratorium in 1994, 155 patients received 165 intestinal allografts under immunosuppression based on tacrolimus and prednisone: 65 intestine alone, 75 liver and intestine, and 25 multivisceral. For the transplantations since the moratorium (n = 99), an adjunct immunosuppressant (cyclophosphamide or daclizumab) was used for 74 transplantations, adjunct donor bone marrow was given in 39, and the intestine of 11 allografts was irradiated with a single dose of 750 cGy. RESULTS: The actuarial survival rate for the total population was 75% at 1 year, 54% at 5 years, and 42% at 10 years. Recipients of liver plus intestine had the best long-term prognosis and the lowest risk of graft loss from rejection (P =.001). Since 1994, survival rates have improved. Techniques for early detection of Epstein-Barr and cytomegaloviral infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, and most recently allograft irradiation may have contributed to the better results. CONCLUSION: The survival rates after intestinal transplantation have cumulatively improved during the past decade. With the management strategies currently under evaluation, intestinal transplant procedures have the potential to become the standard of care for patients with end-stage intestinal failure.

OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD.

In Brief Objective: To assess long-term survival, graft function, and health-related quality of life (QOL) after visceral transplantation. Background: Despite continual improvement in early survival, the long-term therapeutic efficacy of visceral transplantation has yet to be defined. Methods: A prospective cross-sectional study was performed on 227 visceral allograft recipients who survived beyond the 5-year milestone. Clinical data were used to assess outcome including graft function and long-term survival predictors. The socioeconomic milestones and QOL measures were assessed by clinical evaluation, professional consultation, and validated QOL inventory. Results: Of 376 recipients, 227 survived beyond 5 years, with conditional survival of 75% at 10 years and 61% at 15 years. With a mean follow-up of 10 ± 4 years, 177 (92 adults, 85 children) are alive, with 118 (67%) recipients 18 years or older. Nonfunctional social support and noninclusion of the liver in the visceral allograft are the most significant survival risk factors. Nutritional autonomy was achievable in 160 (90%) survivors, with current serum albumin level of 3.7 ± 0.5 gm/dL and body mass index of 25 ± 6 kg/m2. Despite coexistence or development of neuropsychiatric disorders, most survivors were reintegrated to society with self-sustained socioeconomic status. In parallel, most of the psychological, emotional, and social QOL measures significantly (P < 0.05) improved after transplantation. Current morbidities with potential impact on global health included dysmotility (59%), hypertension (37%), osteoporosis (22%), and diabetes (11%), with significantly (P < 0.05) higher incidence among adult recipients. Conclusions: With new tactics to further improve long-term survival including social support measures, visceral transplantation has achieved excellent nutritional autonomy and good QOL. Three metrics were used to assess long-term therapeutic efficacy of visceral transplantation. With new tactics to further improve long-term survival including social support measures, the procedure has achieved excellent nutritional autonomy with good quality of life. Early consideration for gut rehabilitation with autologous bowel reconstructive or transplant surgery is recommended, particularly in the pediatric population, to reduce the risk of life-long neuropsychiatric disorders.