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ABSTRACT: 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.
Transplantation 09/2012; 94(7):757-762. · 4.00 Impact Factor
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ABSTRACT: 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.
Paediatric Drugs 06/2011; 13(3):149-59. · 1.79 Impact Factor
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George V. Mazariegos,
Kyle Soltys,
Geoffrey Bond,
Alin Girnita,
Zurab Machaidze,
Ronald Jaffe,
Michael Green, Dolly Martin,
Adriana Zeevi,
Robert Squires,
Graciela Perez,
Kareem Abu-Elmagd,
Rakesh Sindhi
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ABSTRACT: 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.
Transplantation 12/2008; 86(12):1777-1782. · 4.00 Impact Factor
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ABSTRACT: 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."
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.
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.
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 American Journal of Gastroenterology 06/2007; 102(5):1093-100. · 7.28 Impact Factor
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ABSTRACT: 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."
The American Journal of Gastroenterology 04/2007; 102(5):1093-1100. · 7.28 Impact Factor
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ABSTRACT: 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.
Recipient pretreatment was with an i.v. 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.
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.
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.
The American Journal of Gastroenterology 08/2006; 101(7):1617-24. · 7.28 Impact Factor
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Adriana Zeevi,
Judith A Britz,
Carol A Bentlejewski,
David Guaspari,
Wu Tong,
Geoff Bond,
Noriko Murase,
Clyde Harris,
Marsha Zak, Dolly Martin,
Diane R Post,
Richard J Kowalski,
Kareem Abu Elmagd
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ABSTRACT: Long term use of immunosuppressants impacts the cardiovascular system and increases the risk of infection and malignancy. To effectively reduce immunosuppression in a transplant recipient a tool is needed to directly monitor the level of immune function. The Cylex(R) Immune Cell Function Assay, approved by the FDA for the assessment of cell-mediated immunity, shows promise as an objective measure of a transplant recipient's immune function. In a blinded retrospective study, the immune function was compared to clinical courses and histological examinations of biopsies of 20 small bowel transplant recipients during periods of immunosuppressant tapering. Eight patients with no major adverse events or changes of immunosuppressive therapy had moderate to low immune function and were categorized as immunologically and clinically stable. Twelve patients displaying strong immune responses were immunologically and clinically volatile requiring addition of steroids and or OKT3. Results validate the clinical utility of the Cylex Immune Cell Function Assay as an objective tool for assessing immune function. By evaluating immune function, physicians now can identify those patients who are candidates for minimization of immunosuppressant therapy, manage the timing and rate of immunosuppressant weaning and be forewarned of increased patient risk.
Transplant Immunology 11/2005; 15(1):17-24. · 1.46 Impact Factor
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Kareem Abu-Elmagd,
Jorge Reyes,
Geoffrey Bond,
George Mazariegos,
Tong Wu,
Noriko Murase,
Rakesh Sindhi, Dolly Martin,
Joanne Colangelo,
Marsha Zak,
Douglas Janson,
Mohamed Ezzelarab,
Igor Dvorchik,
Maria Parizhskaya,
Melvin Deutsch,
Anthony Demetris,
John Fung,
Thomas E Starzl
Annals of Surgery 10/2001; · 7.49 Impact Factor
