Dolly Martin

Clinical Intestinal Transplantation: A Decade of Experience at a Single Center

ObjectiveTo 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 DataWith 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. MethodsDuring 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 (cyclophos-phamide 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. ResultsThe 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. ConclusionThe 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.

Logistics and Technique for Procurement of Intestinal, Pancreatic, and Hepatic Grafts From the Same Donor

ObjectiveTo assess a technique for simultaneous recovery of the intestine, pancreas, and liver from the same donor. Summary Background DataWith the more frequent use of pancreatic and intestinal transplantation, a procurement procedure is needed that permits retrieval of both organs as well as the liver from the same cadaveric donor for transplantation to different recipients. It is believed by many procurement officers and surgeons, however, that this objective is not technically feasible. MethodsA technique for simultaneous recovery of the intestine, pancreas, and liver was used in 13 multiorgan cadaver donors during a 26-month period, with transplantation of the organs to 33 recipients. The intestine was removed from 11 donors separately and in continuity with the pancreas in the other 2. Six additional pancreases were excised and transplanted separately. Thirteen livers were retrieved, one of which was discarded because of steahorrhea. Ten of the remaining 12 livers were transplanted intact; the other 2 were split in situ and used as reduced-size hepatic allografts in four recipients. ResultsNone of the 11 intestinal, 6 pancreatic, 2 intestinal–pancreatic, or 14 whole or partial liver allografts sustained serious ischemic injury or were lost as a result of technical complications. One liver recipient died 25 months after surgery of recurrent C virus hepatitis. The other 32 recipients had adequate allograft function with a mean follow-up of 8 months. ConclusionIt was possible using the described technique to retrieve intestine, pancreas, and liver allografts safely from the same donor and to transplant these organs to different 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.”

The efficacy of daclizumab for intestinal transplantation: preliminary report

We previously identified rejection as the most significant risk factor for intestinal allograft survival.1 The reported efficacy of daclizumab (Zenapax. Hoffman-LaRoche) prophylaxis with solid organ transplantation2 triggered its use at our center as induction therapy for intestinal transplantation.

Pediatric intestinal retransplantation: techniques, management, and outcomes.

Background. Intestinal retransplantation (Re-ITx) has historically been associated with high morbidity and mortality. Methods. The outcomes of all children receiving Re-ITx between 1990 and 2007 at our center were reviewed. Results. One hundred seventy-two children received primary intestinal grafts. Fourteen children (8.1%) were retransplanted with 15 grafts. Causes of graft failure were acute cellular rejection (ACR, n=4), liver failure (n=2), chronic rejection (n=3), posttransplant lymphoproliferative disorder (n=1), graft dysmotility or dysfunction (n=3), ACR with severe infection (n=1), and arterial graft aneurysm (n=1). Initial transplants were isolated bowel in nine, liver-bowel in five, and one multivisceral. The mean time of initial graft survival was 34.2 months. Re-ITx was with isolated bowel in two, liver-bowel in four, and multivisceral in nine (four with kidney). Initial immunosuppression was Tac-Pred based in nine and rabbit antithymocyte globulin-Tac based in six cases. Re-ITx was carried out under Tac-Pred in six, rabbit antithymocyte globulin-Tac in eight, and alemtuzumab monoclonal anti-CD52 antibody in one. Ten (71.4%) patients are alive with functioning grafts at a mean current follow-up time of 55.9 months. Four patients died from posttransplant lymphoproliferative disorder, severe ACR, fungal sepsis, and bleeding from pseudoaneurysm, respectively, at a mean time of 5.7 months post-Re-ITx. All surviving patients weaned-off total parenteral nutrition at a median time of 32 days and 90% are off intravenous fluids. Conclusions. Improved long-term survival and outcome in pediatric Re-ITx may be attributed to improvements in initial immunosuppression protocols, technical modifications, proper timing, and improved infectious disease monitoring. Careful patient selection and posttransplant management are essential for successful long-term outcome.

Histopathologic characteristics of human intestine allograft acute rejection in patients pretreated with thymoglobulin or alemtuzumab.

BACKGROUND:We report herein the histopathologic characteristics of human intestine allograft acute rejection in a consecutive series of 48 patients receiving small bowel transplantations and treated with a preconditioning protocol between July 4, 2001 and January 31, 2004.METHODS:Recipient pretreatment was with an IV infusion of 5–10 mg/kg thymoglobulin or 30–60 mg of alemtuzumab (Campath 1H) over several hours prior to revascularization. Postoperative treatment was limited to tacrolimus (target 12-h trough level 10–15 ng/mL) unless additional drugs were needed to treat breakthrough rejection.RESULTS:A total of 3,497 biopsies of the allograft jejunum and/or ileum were obtained. A recently validated histological grading schema was prospectively utilized to grade acute rejection. A total of 116 acute rejection episodes were diagnosed (48 indeterminate, 36 mild, 11 moderate, and 21 severe). Several unique histopathologic features of allograft acute rejection were observed in the pretreated patients. First, scattered lamina propria neutrophilic inflammation often precedes the onset of acute rejection. Second, acute rejection is often associated with more prominent eosinophils in lamina propria or eosinophilic cryptitis. Third, certain acute rejection episodes are characterized by absence of crypts with intact surface villous epithelium. Finally, the mucosal damage associated with moderate or severe acute rejection can completely recover after additional immunosuppressive treatment.CONCLUSION:This study describes several characteristic histopathologic features of allograft small bowel acute rejection associated with thymoglobulin or alemtuzumab preconditioning. Recognition of these unique histopathologic features will enable accurate diagnosis and ensure successful weaning of immunosuppressive drugs.

Intestinal transplantation for patients with short gut syndrome and hypercoagulable states

Intestinal transplantation has become a life-saving procedure for patients with irreversible intestinal failure who can no longer be maintained on total parenteral nutrition (TPN).1 This is the first report to address the management policy and efficacy of intestinal transplantation as a rescue therapy for patients with intestinal failure and visceral vascular thrombosis.

Intestinal Transplantation in Children

This review summarizes the outcomes and known adverse effects of current immunosuppression strategies in use in pediatric intestinal transplantation. Intestinal transplantation has evolved from an experimental therapy to a highly successful treatment for children with intestinal failure who have complications with total parenteral nutrition. Because of continued success with intestinal transplantation over the past decade, the focus of clinicians and researchers is shifting from short-term patient survival to optimizing long-term outcomes.Current 5-year patient and graft survival rates after intestinal transplantation are 58% and 40%, respectively, in the US; single centers have reported nearly 80% patient and 60% graft survival rates at 5 years. The immunosuppression strategy in intestinal transplantation includes a tacrolimus-based regimen, usually in conjunction with an antibody induction therapy such as rabbit-antithymocyte globulin, interleukin-2 receptor antagonists, or alemtuzumab. The use of these immunosuppressive regimens, along with improved medical and surgical care, has contributed significantly toward improved outcomes. Optimization of post-transplant immunosuppression strategies to reduce adverse effects while minimizing acute and chronic graft rejection is a strong clinical and research focus.

Endoscopic evaluation of small intestine transplant grafts.

Background The management of small bowel transplantation is unique because signs of rejection can be obtained visually by endoscopy. The aim of this study was to evaluate the accuracy of endoscopic appearance in assessing histologic evidence of acute cellular rejection (ACR). Methods Endoscopies were performed in 66 asymptomatic “surveillance” small bowel transplant recipients and 71 symptomatic recipients from a single center. For surveillance patients, 125 ileoscopies were performed to collect 590 biopsies, and for the symptomatic group, 229 ileoscopies and jejunoscopies were conducted to obtain 434 biopsies. Results The sensitivity and specificity of endoscopic visualization in detecting ACR was 50% and 91.5% for the surveillance group and 43% and 67% for the symptomatic patients. In surveillance, visual impression alone would have missed three cases of moderate and no cases of severe ACR, whereas in the symptomatic group, visual inspection alone would have missed 20 cases of moderate ACR, and findings from visual inspection of the chimney were normal in 55% of cases with proximal ACR. However, chimney biopsy was generally representative of biopsy findings in the proximal graft but would have missed moderate to severe rejection in three patients (1%). In a subset of 23 endoscopies, zoom endoscopy did not improve visual discrimination. The only complication was a biopsy-related non–life-threatening bleed. Conclusions In symptomatic patients, visual inspection detected all cases of severe rejection but would have missed patients with early readily treatable rejection and thus making biopsy mandatory in clinical practice. Our results support the current practice of ileoscopic biopsy alone for graft surveillance in asymptomatic patients.

INTESTINAL TRANSPLANTATION FOR END STAGE CROHN'S DISEASE

was >12% (vs. 3% in the base case). When the model length was decreased to 1or 2-years, the IFX strategy dominated, but at all other model lengths, surgery dominated. CONCLUSION(S): Our model, which included complications of both surgery and IFX, suggested that for patients who are failing maximal non-biologic medical therapy for chronic ulcerative colitis, IFX therapy is a cost-effective short-term strategy, while surgery is the cost-effective long-term strategy. Given the sensitivity of our model to discounting of future health states, patient perceptions of treatments for ulcerative colitis are a vital part of the decision-making process in this population.