Darlene Koritsky

Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges.

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.

Nutrition and Quality of Life Following Small Intestinal Transplantation

BACKGROUND:The outcome from small bowel transplantation (SBTx) has improved progressively over the past decade raising questions as to whether indications should be broadened from those currently followed based on “TPN (total parenteral nutrition) failure.”OBJECTIVE AND METHODS:To assess current outcome, we studied the effect of transplantation on nutritional autonomy, organ function, and quality of life (QoL) measured by a validated self-administered questionnaire containing 26 domains and 130 questions, for a minimum of 12 months in a cohort of 46 consecutively transplanted patients between June 2003 and July 2004. The majority of transplanted patients (76%) had intestinal failure because of extreme short bowel, the remainder having either chronic pseudo-obstruction or porto-mesenteric vein thrombosis (PMVT). All but the PMVT patients were dependent on home TPN (HPN) (median 2, range 0–25 yr) and had developed serious recurrent infective complications with (25%) or without central vein thrombosis and liver failure. Sixty-one percent received a liver in addition to a small intestine.RESULTS:Follow-up was for a mean of 21 (range 12–36) months. Five patients died, two with chronic graft rejection. All the remaining patients have graft survival with an average of 1.2 (range 0–5) episodes of acute rejection. All patients were weaned from TPN by a median of 18 days (range 1–117 days) and from tube feeding by day 69 (range 22–272 days). There was a significant improvement in overall assessment of QoL and in 13 of 26 of the specific domains examined.CONCLUSION:Our results confirm the claim that a new era has dawned for SBTx, such that, with continued progress, it can potentially become an alternative to HPN for the management of permanent intestinal failure, rather than a last-chance treatment for “TPN failure.”

Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks.

Background. Early experience with intestinal and multivisceral transplantation was plagued with high risk of rejection and posttransplant lymphoproliferative disorders (PTLD). To improve outcome, innovative management and immunosuppressant strategies were sequentially evolved. Methods. With initiation of the program in 1990, serial monitoring of Epstein-Barr-Viral load was introduced in 1994 with adoption of preemptive antiviral therapy. In 1995, cyclophosphamide or daclizumab induction was added to the tacrolimus-steroid-based multiple drug immunosuppressions. Such a conventional approach was replaced in 2001 with a novel immunosuppressive protocol consisting of recipient pretreatment with a single dose of rabbit antithymocyte globulin or alemtuzumab and posttransplant tacrolimus monotherapy. Results. With a total of 395 consecutive primary recipients, de novo malignancy(s) developed in 61 (15%) patients, with PTLD in 52 (13%), and nonlymphoid cancer (NLC) in 13 (3.2%). Malignancy was donor driven in 3 (4.6%) recipients and associated with graft-versus-host disease in 7 (11.4%). Children were at a significantly higher risk (P<0.001) of PTLD, and adults were more vulnerable (P=0.01) to NLC. With multivariate analyses, type of immunosuppression, recipient age, splenectomy, and treatment of rejection were significant PTLD risk factors. Conclusions. Despite pretransplant lymphoid depletion, preemptive antiviral therapy and minimization of posttransplant immunosuppression significantly reduced PTLD morbidity (P=0.0001) and mortality (P=0.001) with no impact on NLC. Patient survival was also improved (P=0.0001) with 91% at 1 year and 75% at 5 years.

Therapeutic Efficacy of Intestinal and Multivisceral Transplantation: Survival and Nutrition Outcome

The clinical introduction of intestinal transplantation has added a new dimension and offered a valid therapeutic option for patients with irreversible intestinal failure. In the year 2000, the Center for Medicare & Medicaid Services (CMS) recognized intestinal, combined liver-intestinal, and multivisceral transplantation as the standard of care for patients with irreversible intestinal and parenteral nutrition (PN) failure. Accordingly, the indications for the procedure are currently limited to those who develop life-threatening PN complications. However, a recent improvement in survival similar to other solid organ transplant recipients should justify lifting the current restricted criteria, and the procedure should be considered before the development of PN failure. Equally important is the awareness of the recent evolution in nutrition management and outcome after transplantation. Early and progressive enteral feeding using a complex polymeric formula is safe and effective after successful transplantation. Full nutrition autonomy is universally achievable among most intestinal and multivisceral recipients, with enjoyment of unrestricted oral diet. Such a therapeutic benefit is commonly maintained among long-term survivors, with full rehabilitation and restoration of quality of life.

Gut rehabilitation and intestinal transplantation

The field of short bowel syndrome and gastrointestinal failure has recently evolved, particularly after the clinical introduction of intestinal and multivisceral transplantation. For nearly three decades, the management of short bowel syndrome was limited to the natural adaptation process and lifelong intravenous supplementation. However, recent clinical availability of intestinal transplantation as an alternative to total parenteral nutrition, has fueled the field with relentless efforts to enhance intestinal adaptation and gut rehabilitation with the achievement of full nutritional autonomy. Intestinal and multivisceral transplantation has added new dimensions as a creative therapy to short bowel syndrome patients, as well as those with extensive abdominal pathology that could not be treated with conventional methods. With continuous improvement in the survival outcome, the procedure has become more widely applicable and commonly utilized, with more than 65 intestinal transplant centers worldwide. With the procedure currently showing improvement in therapeutic indices, including cost effectiveness and quality of life, we believe intestinal and multivisceral transplantation should promptly be offered to short bowel syndrome patients who fail conventional rehabilitation as well as those with complex abdominal pathology.