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Andreas G. Tzakis - One of the best experts on this subject based on the ideXlab platform.
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Intestinal and Multivisceral Transplantation at the University of Miami.
Clinical transplants, 2009Co-Authors: Gennaro Selvaggi, Seigo Nishida, Eddie Island, Akin Tekin, David Levi, Debbie Weppler, Jang Moon, Andreas G. TzakisAbstract:At the University of Miami Liver and GI Transplant Program, over 300 intestinal transplant procedures were performed in the last 15 years in adult and pediatric recipients. Good patient and graft survival rates are now achievable. Rejection remains the complication that is most difficult to prevent and manage. Induction with antilymphocyte agents, followed by maintenance with tacrolimus, is the preferred immunosuppression protocol at our center. We have expanded the use of Multivisceral Transplantation in pediatric recipients with short gut and significant liver dysfunction from parenteral nutrition. We also advocate the use of large intestine as part of the intestinal graft as well as inclusion of the spleen in Multivisceral grafts, which in our experience can be safely accomplished. The future of intestinal Transplantation lies in the use of noninvasive markers of intestinal rejection, and continued refinements in immunosuppression protocols.
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Analysis of acute and chronic rejection in multiple organ allografts from reTransplantation and autopsy cases of Multivisceral Transplantation
Transplantation, 2008Co-Authors: Hidenori Takahashi, Tomoaki Kato, Seigo Nishida, Gennaro Selvaggi, Eddie Island, David Levi, Victor Delacruz, Debbie Weppler, Jang I. Moon, Andreas G. TzakisAbstract:Background.Small intestinal allografts in Multivisceral Transplantation are felt to be more susceptible to acute cellular rejection (ACR) and chronic rejection (CR) when compared with other allografts although there is little direct evidence for this impression.Methods.A total of 48 cases of multipl
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Intestinal and Multivisceral Transplantation: future perspectives.
Frontiers in bioscience : a journal and virtual library, 2007Co-Authors: Gennaro Selvaggi, Andreas G. TzakisAbstract:The field of intestinal Transplantation has experienced a progressive increase in patient and graft survival over the last few years, leading to a parallel increase in the number of programs performing such type of surgical procedures. Indications for intestinal transplant include irreversible intestinal failure, compounded by potential life-threatening complications such as loss of intravenous access, liver failure or multiple episodes of infections. The type of graft that is required is highly individualized according to the patient's original diagnosis and status. Presence of short gut syndrome alone is indication for isolated intestinal transplant; liver failure mandates the use of a liver graft (liver-intestine or Multivisceral transplant); intestinal dysmotility disorders with intact liver function require the use of a modified Multivisceral graft. Most of the current immunosuppression protocols consist in induction immunosuppression and maintenance doses of tacrolimus. Rejection and infectious complications remain the most common causes of morbidity and mortality; it is therefore essential to closely monitor the intestinal graft to prevent such occurrences. Future developments include: the use of non-invasive markers of rejection; a refinement in surgical techniques; development of advanced immunosuppression protocols; expansion of living related transplant and Multivisceral Transplantation in selected patients.
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Transplantation of the Spleen: Effect of Splenic Allograft in Human Multivisceral Transplantation
Annals of surgery, 2007Co-Authors: Tomoaki Kato, Andreas G. Tzakis, André Ibrahim David, Gennaro Selvaggi, Hidenori Takahashi, Jeffrey J Gaynor, James M. Mathew, Rolando Garcia-morales, E. Hernandez, Seigo NishidaAbstract:The spleen is the largest single secondary lymphoid organ and a vital site of the reticuloendothelial system. As such, this organ plays a major role in both adaptive and innate immune responses. Healthy individuals that have undergone posttraumatic splenectomy have long-term impairment of humoral and cellular immunity.1 Specifically, these patients are extremely susceptible to encapsulated bacteria infection from Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B and similar organisms.1 The polysaccharide capsules of these bacteria elicit a T-cell independent immune response that depends on the function of the spleen’s marginal B cells.2 Splenectomized patients have diminished responses to such antigens.3 In children less than 5 years of age, the risk of overwhelming postsplenectomy sepsis may be increased 60- to 100-fold compared with children who have not had a splenectomy.4 Multivisceral Transplantation (MVT) has been successfully performed in adults and children with intestinal and liver failure,5,6 with the results having improved dramatically in recent years.5,6 The traditional procedure for MVT is to transplant the stomach, pancreas, intestine, and liver en bloc. The spleen of the recipient is removed during the procedure, leaving MVT recipients in an asplenic state. Because of the concern of an increased risk of sepsis with an asplenic state, we have included the allograft spleen as part of the Multivisceral graft since 2001. In animal models, donor splenic Transplantation is known to induce donor-specific tolerance.7–13 Sporadic cases of splenic Transplantation in humans have been reported in the past,8–27 as part of a pancreas transplant or in an attempt to treat hematological disorders. No previous literature is available on the effect of human splenic allograft for tolerogenicity. In this manuscript, we evaluate and compare our experience of Multivisceral transplant recipients who did and did not receive a splenic allograft to elucidate the effect of this donor-derived lymphoid organ in human Transplantation.
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intestinal and Multivisceral Transplantation in children
Annals of Surgery, 2006Co-Authors: Tomoaki Kato, Andreas G. Tzakis, Werviston Defaria, André Ibrahim David, Gennaro Selvaggi, Jeffrey J Gaynor, Alessandro Bussotti, J I Moon, Takehisa Ueno, S SantiagoAbstract:Objective: To describe a single-center experience of pediatric intestinal Transplantation (Itx) and to provide an overview of the children who underwent this procedure along with their outcomes. Background Data: Pediatric Itx presents multiple challenges because of the very young ages at which patients require Transplantation and their higher susceptibility to infectious complications. Methods: We have performed 141 Itx in 123 children with a median age of 1.37 years. Primary grafts included isolated intestine (n = 28), liver and intestine (n = 27), Multivisceral (n = 61), and Multivisceral without the liver (n = 7). Two protocol modifications were introduced in 1998: daclizumab induction and frequent rejection surveillance. In 2001, indications for Multivisceral Transplantation were expanded, and induction with Campath-lH was introduced. Results: Actuarial patient survival at 1 and 3 years for group 1 (January 1994 to December 1997, n = 25), group 2 (January 1998 to March 2001, n = 29), group 3a (April 2001 to present, daclizumab, n = 51), and group 3b (April 2001 to present, Campath-lH, n = 18) was 44%/32%, 52%/38%, 83%/60%, and 44%/44%, respectively (P = 0.0003 in favor of group 3a). Severe rejection implied a dismal prognosis (65% mortality at 6 months). Observed incidence of severe rejection in groups 1, 2, 3a, and 3b was 32%, 24%, 14%, and 11%, respectively. In multivariable analysis, use of a Multivisceral (with or without liver) transplant (P = 0.002), induction with daclizumab (P = 0.005), patient at home prior to transplant (P = 0.007), and age at transplant ≥ 1 year (P = 0.02) favorably influenced patient survival. Multivisceral transplant was protective with respect to the mortality rate due to rejection, while an older age at transplant was associated with both a lower incidence rate of developing respiratory infection and lower risk of mortality following the respiratory infection. Survivors are off parenteral nutrition and have demonstrated significant growth catch-up. Conclusions: Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.
Tomoaki Kato - One of the best experts on this subject based on the ideXlab platform.
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Intestinal/Multivisceral Transplantation
Pediatric Critical Care Medicine, 2014Co-Authors: Gwenn E. Mclaughlin, Tomoaki KatoAbstract:Intestinal/Multivisceral Transplantation has evolved from an experimental procedure to the treatment of choice for patients with irreversible intestinal failure and serious complications related to long-term parenteral nutrition. Children who are likely to suffer permanent intestinal failure and benefit from intestinal Transplantation include those with a remaining small bowel length of less than 30–40 cm, absence of the ileocecal valve, colonic resection and malabsorptive syndromes. Indications for transplant include frequent severe bouts of catheter associated sepsis, threatened loss of vascular access and the development of liver cirrhosis from cholestasis. Children who are more likely to experience cholestasis from total parenteral nutrition include those who experience persistent hyperbilirubinemia (greater than 6 mg/dl despite enteral nutrition), those with recurrent sepsis and/or bacterial overgrowth and those with minimal tolerance of any enteral feeds in the first few months post resection. The 1 year survival rate after intestinal Transplantation has markedly improved over the last several years but long term survival rates have remained unchanged. The improved short term survival rates have led to an increased prevalence of this patient population in intensive care units. Management of intestinal and Multivisceral transplant recipients is uniquely challenging because of complications arising from the high incidence of transplant rejection and its treatment. In the ICU, the complexity of medical care for the transplant recipient requires a multidisciplinary approach with coordination by an intensivist in collaboration with the transplant surgeon, gastroenterologist, and other specialists.
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Analysis of acute and chronic rejection in multiple organ allografts from reTransplantation and autopsy cases of Multivisceral Transplantation
Transplantation, 2008Co-Authors: Hidenori Takahashi, Tomoaki Kato, Seigo Nishida, Gennaro Selvaggi, Eddie Island, David Levi, Victor Delacruz, Debbie Weppler, Jang I. Moon, Andreas G. TzakisAbstract:Background.Small intestinal allografts in Multivisceral Transplantation are felt to be more susceptible to acute cellular rejection (ACR) and chronic rejection (CR) when compared with other allografts although there is little direct evidence for this impression.Methods.A total of 48 cases of multipl
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Transplantation of the Spleen: Effect of Splenic Allograft in Human Multivisceral Transplantation
Annals of surgery, 2007Co-Authors: Tomoaki Kato, Andreas G. Tzakis, André Ibrahim David, Gennaro Selvaggi, Hidenori Takahashi, Jeffrey J Gaynor, James M. Mathew, Rolando Garcia-morales, E. Hernandez, Seigo NishidaAbstract:The spleen is the largest single secondary lymphoid organ and a vital site of the reticuloendothelial system. As such, this organ plays a major role in both adaptive and innate immune responses. Healthy individuals that have undergone posttraumatic splenectomy have long-term impairment of humoral and cellular immunity.1 Specifically, these patients are extremely susceptible to encapsulated bacteria infection from Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B and similar organisms.1 The polysaccharide capsules of these bacteria elicit a T-cell independent immune response that depends on the function of the spleen’s marginal B cells.2 Splenectomized patients have diminished responses to such antigens.3 In children less than 5 years of age, the risk of overwhelming postsplenectomy sepsis may be increased 60- to 100-fold compared with children who have not had a splenectomy.4 Multivisceral Transplantation (MVT) has been successfully performed in adults and children with intestinal and liver failure,5,6 with the results having improved dramatically in recent years.5,6 The traditional procedure for MVT is to transplant the stomach, pancreas, intestine, and liver en bloc. The spleen of the recipient is removed during the procedure, leaving MVT recipients in an asplenic state. Because of the concern of an increased risk of sepsis with an asplenic state, we have included the allograft spleen as part of the Multivisceral graft since 2001. In animal models, donor splenic Transplantation is known to induce donor-specific tolerance.7–13 Sporadic cases of splenic Transplantation in humans have been reported in the past,8–27 as part of a pancreas transplant or in an attempt to treat hematological disorders. No previous literature is available on the effect of human splenic allograft for tolerogenicity. In this manuscript, we evaluate and compare our experience of Multivisceral transplant recipients who did and did not receive a splenic allograft to elucidate the effect of this donor-derived lymphoid organ in human Transplantation.
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intestinal and Multivisceral Transplantation in children
Annals of Surgery, 2006Co-Authors: Tomoaki Kato, Andreas G. Tzakis, Werviston Defaria, André Ibrahim David, Gennaro Selvaggi, Jeffrey J Gaynor, Alessandro Bussotti, J I Moon, Takehisa Ueno, S SantiagoAbstract:Objective: To describe a single-center experience of pediatric intestinal Transplantation (Itx) and to provide an overview of the children who underwent this procedure along with their outcomes. Background Data: Pediatric Itx presents multiple challenges because of the very young ages at which patients require Transplantation and their higher susceptibility to infectious complications. Methods: We have performed 141 Itx in 123 children with a median age of 1.37 years. Primary grafts included isolated intestine (n = 28), liver and intestine (n = 27), Multivisceral (n = 61), and Multivisceral without the liver (n = 7). Two protocol modifications were introduced in 1998: daclizumab induction and frequent rejection surveillance. In 2001, indications for Multivisceral Transplantation were expanded, and induction with Campath-lH was introduced. Results: Actuarial patient survival at 1 and 3 years for group 1 (January 1994 to December 1997, n = 25), group 2 (January 1998 to March 2001, n = 29), group 3a (April 2001 to present, daclizumab, n = 51), and group 3b (April 2001 to present, Campath-lH, n = 18) was 44%/32%, 52%/38%, 83%/60%, and 44%/44%, respectively (P = 0.0003 in favor of group 3a). Severe rejection implied a dismal prognosis (65% mortality at 6 months). Observed incidence of severe rejection in groups 1, 2, 3a, and 3b was 32%, 24%, 14%, and 11%, respectively. In multivariable analysis, use of a Multivisceral (with or without liver) transplant (P = 0.002), induction with daclizumab (P = 0.005), patient at home prior to transplant (P = 0.007), and age at transplant ≥ 1 year (P = 0.02) favorably influenced patient survival. Multivisceral transplant was protective with respect to the mortality rate due to rejection, while an older age at transplant was associated with both a lower incidence rate of developing respiratory infection and lower risk of mortality following the respiratory infection. Survivors are off parenteral nutrition and have demonstrated significant growth catch-up. Conclusions: Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.
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Inclusion of spleen in pediatric Multivisceral Transplantation.
Transplantation proceedings, 2006Co-Authors: Tomoaki Kato, John F. Thompson, Seigo Nishida, Juan Madariaga, Gary Kleiner, André Ibrahim David, Gennaro Selvaggi, Phillip Ruiz, Andreas G. TzakisAbstract:Abstract Inclusion of the donor spleen may be beneficial for small children who receive Multivisceral Transplantation (MVT) because asplenia is associated with increased risk of bacterial sepsis. Beginning in 2003, the spleen was transplanted together with Multivisceral Transplantation in 17 children under daclizumab induction (spleen group). The results were compared to 23 children who received Multivisceral Transplantation without the spleen (control group) with the same immunosuppression regimen. Median age of 17 patients who received a spleen was 0.80 years (range 0.54–1.66). Platelet counts at 30 and 60 days posttransplant were significantly lower in the spleen group (average values: day 30: 399,000 vs 636,000, P = .015; day 60: 413,000 vs 622,000, P = .0056). WBC counts at 30 and 60 days posttransplant were also decreased in the spleen group but the difference was not statistically significant. Median rejection-free survival was 205 days in the spleen group and 101 days in the control group ( P = NS). Median length of hospital stay was 39 days in the spleen group and 61 days in the control group. With a median follow-up of 398 days (spleen group) and 1232 days (control group), 3 of 17 (17%) in the spleen group developed graft versus host disease (GVHD), whereas 1 of 23 (4.5%) in control group did ( P = NS). In one patient in each group, GVHD was fatal. No patient developed posttransplant lymphoproliferative disorder (PTLD) in the spleen group, whereas 4 of 23 (17%) in the control group developed PTLD. One-year patient survival was 84% in the spleen group and 86% in the control group. Recipients of the spleen as part of a Multivisceral graft had significantly lower platelet counts. Rejection-free survival may be prolonged, but the risk of GVHD may be increased.
Rodrigo Vianna - One of the best experts on this subject based on the ideXlab platform.
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Pancreas Transplantation in the setting of Multivisceral Transplantation
Transplantation Bioengineering and Regeneration of the Endocrine Pancreas, 2020Co-Authors: Mahmoud Morsi, Gaetano Ciancio, Javier Gonzalez, Ahmed Farag, Rodrigo ViannaAbstract:Abstract The pancreas transplant as a part of Multivisceral or multiorgan Transplantation has always been approached with caution because of graft pancreatitis, rejection, or technical complications. The Multivisceral Transplantation is a complicated process, starting from the recipient, the donor selection, the indications, the contraindications, and the postoperative management. Intestinal transplant recipients generally require more profound immunosuppression than patients receiving other solid organs because of the higher immunogenicity of the intestine. Unlike the early years of intestinal Transplantation, when technical challenges and vascular events were likely to cause graft loss and patient mortality, the current most common causes of allograft dysfunction are infection and graft rejection. Unlike the early years of intestinal Transplantation, when technical challenges and vascular events were likely to cause graft loss and patient mortality, the current most common causes of allograft dysfunction are infection and graft rejection.
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Neoadjuvant peptide receptor radionuclide therapy and modified Multivisceral Transplantation for an advanced small intestinal neuroendocrine neoplasm: an updated case report.
Innovative surgical sciences, 2017Co-Authors: Ashley K. Clift, Rodrigo Vianna, Henk Giele, Srikanth Reddy, R. Macedo, Adil Al-nahhas, Harpreet Wasan, Gabriel Gondolesi, Peter J. Friend, Anil VaidyaAbstract:Small intestinal neuroendocrine neoplasms (SI-NEN) frequently metastasise to regional lymph nodes, and surgery is the mainstay of therapy for such patients. However, despite the possible use of advanced surgical techniques, the resection of both primary and locoregional diseases is not always attainable. Intestinal and Multivisceral Transplantation has been performed in a small number of patients with conventionally nonresectable, slow-growing tumours threatening the mesenteric root but has remained controversial. The use of donor skin in "sentinel flaps" in Transplantation theoretically offers advantages in tailoring immunosuppression and monitoring for rejection. We represent (with extended follow-up) the first case of a patient with inoperable extensive mesenteric metastases from SI-NEN, who underwent neoadjuvant peptide receptor radionuclide therapy before a modified Multivisceral transplant with a concomitant vascularised sentinel forearm flap. At 48 months after Transplantation, our patient remained at full physical activity with no evidence of disease recurrence on either tumour biochemistry or radiological imaging.
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Modified liver-free Multivisceral Transplantation for a metastatic small bowel neuroendocrine tumor: a case report.
Transplantation proceedings, 2015Co-Authors: A. Frilling, Henk Giele, Georgios Vrakas, Srikanth Reddy, R. Macedo, Adil Al-nahhas, Harpreet Wasan, Ashley K. Clift, Gabriel Gondolesi, Rodrigo ViannaAbstract:Neuroendocrine tumors originating from the small bowel frequently metastasize to the lymph nodes and/or liver. Although surgical extirpation of the primary tumor and locoregional metastases epitomizes the management of patients with such tumors, this is not always possible with conventional surgical techniques. Nonresectable, slow-growing tumors involving the mesenteric root represent a generally accepted indication for deceased donor intestinal and Multivisceral Transplantation. Furthermore, vascularized sentinel forearm flaps offer opportunities for monitoring graft rejection and tailoring immunosuppression regimens. Here, we report the first documented case of modified liver-free Multivisceral Transplantation preceded by neoadjuvant 177-lutetium peptide receptor radionuclide therapy in a patient with a small bowel neuroendocrine tumor and extensive lymph node metastases in the mesenterium. At a follow-up of 21 months the patient is biochemically and radiologically disease-free.
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Multivisceral Transplantation: Where Do We Stand?
Clinics in liver disease, 2014Co-Authors: Kalyan Ram Bhamidimarri, Thiago Beduschi, Rodrigo ViannaAbstract:Intestinal Transplantation is the definitive therapy for patients with irreversible intestinal failure and can be combined with Transplantation of other abdominal organs, such as stomach, spleen, and pancreas with or without liver. There is an increasing trend in the volume of intestinal and Multivisceral Transplantation in the past few decades and there is also increasing trend in patient and graft survival primarily due to improved patient selection, advances in immunosuppression, and improved perioperative management. This review summarizes the various key elements in patient selection, types of grafts, and updates in the perioperative management involved in Multivisceral Transplantation.
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Multivisceral Transplantation: Expanding Indications and Improving Outcomes
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2012Co-Authors: Richard S. Mangus, Chandrashekhar A. Kubal, A. Joseph Tector, Jonathan A. Fridell, Rodrigo ViannaAbstract:Introduction Multivisceral Transplantation includes the simultaneous Transplantation of multiple abdominal viscera including the stomach, duodenum, pancreas, and small intestine, with (Multivisceral transplant, MVT) or without the liver (modified MVT, MMVT). This study reviews the changing indications and outcomes for this procedure over a 7-year period at a university medical center.
Richard S. Mangus - One of the best experts on this subject based on the ideXlab platform.
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cytomegalovirus infection after intestinal Multivisceral Transplantation a single center experience with 210 cases
Transplantation, 2016Co-Authors: Shunji Nagai, Chandrashekhar A. Kubal, Richard S. Mangus, Jonathan A. Fridell, Eve Anderson, Burcin Ekser, Joseph A TectorAbstract:BACKGROUND Cytomegalovirus (CMV) infection is the most prevalent infectious complication after solid organ Transplantation, and recipients of isolated intestinal Transplantation (IIT)/Multivisceral Transplantation (MVT) are among those at the highest risk. Limited clinical data exist regarding CMV infection after IIT/MVT. The aim of this study is to analyze risk factors for posttransplant CMV infection and to assess the efficacy and validity of our prophylaxis and treatment regimens in intestinal Transplantation. METHODS Medical records of 210 IIT/MVT patients were retrospectively reviewed. Posttransplant CMV prophylaxis regimen consisted of ganciclovir followed by 1 year of valganciclovir. The addition of CMV immunoglobulin (CMVIG) was decided according to donor/recipient CMV serostatus (D/R). All results of CMV PCR and/or pp65 antigenemia, and pathological reports were reviewed. Time to the incidence of CMV infection (viremia and/or tissue invasive disease) and risk factors for CMV infection were investigated. RESULTS CMV infection was observed in 34 of 210 (16%) with a median onset of 347 days. Rejection was significantly associated with CMV infection (P = 0.01, odds ratio = 2.61). In the high-risk serostatus group (D+/R-), prophylactic CMVIG and induction with high-dose rabbit antithymocyte globulin (>10 mg/kg) were associated with a lower CMV infection rate on univariate analysis. The CMVIG remained to be an independent factor on multivariate analysis (P = 0.04, hazard ratio = 0.93/dose). Mortality associated with CMV infection occurred in 4, and CMV infection adversely affected patient survival (P = 0.001, hazard ratio = 2.71). CONCLUSIONS Prophylaxis with CMVIG and appropriate induction with rabbit antithymocyte globulin may be important to reduce CMV infection in high-risk serostatus group (D+/R-).
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Multivisceral Transplantation to Treat Advanced Neuroendocrine Tumors in Gastrointestinal Tract: Experience at a Single Transplantation Center
American Journal of Clinical Pathology, 2015Co-Authors: Jingmei Lin, Richard S. Mangus, Michael G. House, Oscar W. CummingsAbstract:Neuroendocrine tumor (NET) originating in gastrointestinal tract (GI) frequently metastasizes to lymph nodes and the liver. Rare cases of Multivisceral Transplantation (MVT) to manage widespread GI NET have been reported. We studied 11 patients who received MVT for advanced GI NET, including clinicopathological features of TNM stage, Ki67, mitosis, and the …
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post transplant persistent lymphopenia is a strong predictor of late survival in isolated intestine and Multivisceral Transplantation
Transplant International, 2015Co-Authors: Shunji Nagai, Chandrashekhar A. Kubal, Richard S. Mangus, Jonathan A. Fridell, Eve Anderson, Burcin Ekser, Tracy Burch, Joseph A TectorAbstract:Absolute lymphocyte count (ALC) has been identified as a prognostic factor in liver Transplantation. We hypothesized that a lower ALC may be linked to poor outcomes in isolated intestinal/Multivisceral Transplantation (IIT/MVT). The aim of this study was to investigate the prognostic impact of ALC in IIT/MVT. A total 141 IIT/MVT patients were eligible for the study. Post-transplant ALCs (at 3, 6, and 12 months) were evaluated, and prognostic impact of trend of ALC during the first year was investigated. Of these 141 patients, 108 patients survived in the first year (1-year survivors). One-year survivors were categorized according to post-transplant ALC at each time point. When ALC was decreased throughout the first year (post-transplant persistent lymphopenia: <500/μl at 3, 6, and 12 months), patient survival (P < 0.001, hazard ratio = 5.09) and graft survival (P < 0.001, hazard ratio = 5.15) after the first year was significantly worse, and this remained to be an independent risk factor. Negative impact of persistent lymphopenia on patient and graft survival was significant regardless of type of intestinal graft. Infection leading to mortality occurred more frequently in the persistent lymphopenia group (43% vs. 24%). Trend of post-transplant ALC may be a strong predictive marker for long-term outcome in 1-year survivors after IIT/MVT.
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prospective monitoring of donor specific anti hla antibodies after intestine Multivisceral Transplantation significance of de novo antibodies
Transplantation, 2015Co-Authors: Chandrashekhar A. Kubal, Richard S. Mangus, Jonathan A. Fridell, Romil Saxena, Andrew L Lobashevsky, Nancy Higgins, A. Joseph TectorAbstract:BACKGROUND Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/Multivisceral Transplantation. METHODS In 79 intestine/Multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after Transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR). RESULTS Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liver-excluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibody-mediated rejection was diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy. CONCLUSIONS De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusing mechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.
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Intestine and Multivisceral Transplantation: Current Status and Future Directions
Current Gastroenterology Reports, 2015Co-Authors: Chandrashekhar A. Kubal, Richard S. Mangus, A. Joseph TectorAbstract:Intestinal failure and associated parenteral nutrition-induced liver failure cause significant morbidity, mortality, and health care burden. Intestine Transplantation is now considered to be the standard of care in patients with intestinal failure who fail intestinal rehabilitation. Intestinal failure-associated liver disease is an important sequela of intestinal failure, caused by parenteral lipids, requiring simultaneous liver-intestine transplant. Lipid minimization and, in recent years, the emergence of fish oil-based lipid emulsions have been shown to reverse parenteral nutrition-associated hyperbilirubinemia, but not fibrosis. Significant progress in surgical techniques and immunosuppression has led to improved outcomes after intestine Transplantation. Intestine in varying combination with liver, stomach, and pancreas, also referred to as Multivisceral Transplantation, is performed for patients with intestinal failure along with liver disease, surgical abdominal catastrophes, neuroendocrine and slow-growing tumors, and complete portomesenteric thrombosis with cirrhosis of the liver. Although acute and chronic rejection are major problems, long-term survivors have excellent quality of life and remain free of parenteral nutrition.
Seigo Nishida - One of the best experts on this subject based on the ideXlab platform.
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association between donor specific antibodies and acute rejection and resolution in small bowel and Multivisceral Transplantation
Transplantation, 2011Co-Authors: Hsin Lin Tsai, Seigo Nishida, Ignacio Gonzalezpinto, P Tryphonopoulos, E Island, Jei Wen Chang, Gennaro SelvaggiAbstract:BACKGROUND: Donor-specific antibodies (DSA) are associated with acute kidney graft rejection, but their role in small bowel/Multivisceral allograft remains unclear. We carried out a prospective study to understand the impact of DSA in the setting of intestinal allograft rejection. METHODS: Thirteen patients (15 grafts) were serially evaluated for DSA levels pre- and posttransplant. DSA was determined by Luminex and the results were interpreted as fluorescence intensity (FI), with FI more than 3000 considered positive. RESULTS: The clinical rejection episodes in allografts were significantly associated with the presence of DSA (P=0.041).We obtained 291 biopsy samples from graft ileum and date-matched DSA assay reports. Sixty-three (21.65%) of the biopsies showed acute rejection. The appearance of DSA were preformed (n=5, anti-human leukocyte antigen class II=3, anti-class I and II=2), de novo (n=4, 15.25±4.72 days after Transplantation, anti-class II=1, and anti-class I and II=3) and never (n=6). Among the 63 biopsies, 30(47.6%) had significant correlations with positive DSA (kappa=0.30, P<0.001) and manifested severe rejection grade (P=0.009). CONCLUSIONS: In this cohort of small bowel/Multivisceral Transplantation patients, there was a high incidence of DSA. The presence of DSA should alert the clinical team of a higher risk of rejection, and reduction of the FI is clinically associated with resolution. Serial endoscopy guided biopsies combined with simultaneous DSA measurement in postintestinal Transplantation follow-up is an effective means of screening for cellular and humoral-based forms of acute rejection.
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Intestinal and Multivisceral Transplantation at the University of Miami.
Clinical transplants, 2009Co-Authors: Gennaro Selvaggi, Seigo Nishida, Eddie Island, Akin Tekin, David Levi, Debbie Weppler, Jang Moon, Andreas G. TzakisAbstract:At the University of Miami Liver and GI Transplant Program, over 300 intestinal transplant procedures were performed in the last 15 years in adult and pediatric recipients. Good patient and graft survival rates are now achievable. Rejection remains the complication that is most difficult to prevent and manage. Induction with antilymphocyte agents, followed by maintenance with tacrolimus, is the preferred immunosuppression protocol at our center. We have expanded the use of Multivisceral Transplantation in pediatric recipients with short gut and significant liver dysfunction from parenteral nutrition. We also advocate the use of large intestine as part of the intestinal graft as well as inclusion of the spleen in Multivisceral grafts, which in our experience can be safely accomplished. The future of intestinal Transplantation lies in the use of noninvasive markers of intestinal rejection, and continued refinements in immunosuppression protocols.
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Analysis of acute and chronic rejection in multiple organ allografts from reTransplantation and autopsy cases of Multivisceral Transplantation
Transplantation, 2008Co-Authors: Hidenori Takahashi, Tomoaki Kato, Seigo Nishida, Gennaro Selvaggi, Eddie Island, David Levi, Victor Delacruz, Debbie Weppler, Jang I. Moon, Andreas G. TzakisAbstract:Background.Small intestinal allografts in Multivisceral Transplantation are felt to be more susceptible to acute cellular rejection (ACR) and chronic rejection (CR) when compared with other allografts although there is little direct evidence for this impression.Methods.A total of 48 cases of multipl
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Transplantation of the Spleen: Effect of Splenic Allograft in Human Multivisceral Transplantation
Annals of surgery, 2007Co-Authors: Tomoaki Kato, Andreas G. Tzakis, André Ibrahim David, Gennaro Selvaggi, Hidenori Takahashi, Jeffrey J Gaynor, James M. Mathew, Rolando Garcia-morales, E. Hernandez, Seigo NishidaAbstract:The spleen is the largest single secondary lymphoid organ and a vital site of the reticuloendothelial system. As such, this organ plays a major role in both adaptive and innate immune responses. Healthy individuals that have undergone posttraumatic splenectomy have long-term impairment of humoral and cellular immunity.1 Specifically, these patients are extremely susceptible to encapsulated bacteria infection from Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B and similar organisms.1 The polysaccharide capsules of these bacteria elicit a T-cell independent immune response that depends on the function of the spleen’s marginal B cells.2 Splenectomized patients have diminished responses to such antigens.3 In children less than 5 years of age, the risk of overwhelming postsplenectomy sepsis may be increased 60- to 100-fold compared with children who have not had a splenectomy.4 Multivisceral Transplantation (MVT) has been successfully performed in adults and children with intestinal and liver failure,5,6 with the results having improved dramatically in recent years.5,6 The traditional procedure for MVT is to transplant the stomach, pancreas, intestine, and liver en bloc. The spleen of the recipient is removed during the procedure, leaving MVT recipients in an asplenic state. Because of the concern of an increased risk of sepsis with an asplenic state, we have included the allograft spleen as part of the Multivisceral graft since 2001. In animal models, donor splenic Transplantation is known to induce donor-specific tolerance.7–13 Sporadic cases of splenic Transplantation in humans have been reported in the past,8–27 as part of a pancreas transplant or in an attempt to treat hematological disorders. No previous literature is available on the effect of human splenic allograft for tolerogenicity. In this manuscript, we evaluate and compare our experience of Multivisceral transplant recipients who did and did not receive a splenic allograft to elucidate the effect of this donor-derived lymphoid organ in human Transplantation.
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Inclusion of spleen in pediatric Multivisceral Transplantation.
Transplantation proceedings, 2006Co-Authors: Tomoaki Kato, John F. Thompson, Seigo Nishida, Juan Madariaga, Gary Kleiner, André Ibrahim David, Gennaro Selvaggi, Phillip Ruiz, Andreas G. TzakisAbstract:Abstract Inclusion of the donor spleen may be beneficial for small children who receive Multivisceral Transplantation (MVT) because asplenia is associated with increased risk of bacterial sepsis. Beginning in 2003, the spleen was transplanted together with Multivisceral Transplantation in 17 children under daclizumab induction (spleen group). The results were compared to 23 children who received Multivisceral Transplantation without the spleen (control group) with the same immunosuppression regimen. Median age of 17 patients who received a spleen was 0.80 years (range 0.54–1.66). Platelet counts at 30 and 60 days posttransplant were significantly lower in the spleen group (average values: day 30: 399,000 vs 636,000, P = .015; day 60: 413,000 vs 622,000, P = .0056). WBC counts at 30 and 60 days posttransplant were also decreased in the spleen group but the difference was not statistically significant. Median rejection-free survival was 205 days in the spleen group and 101 days in the control group ( P = NS). Median length of hospital stay was 39 days in the spleen group and 61 days in the control group. With a median follow-up of 398 days (spleen group) and 1232 days (control group), 3 of 17 (17%) in the spleen group developed graft versus host disease (GVHD), whereas 1 of 23 (4.5%) in control group did ( P = NS). In one patient in each group, GVHD was fatal. No patient developed posttransplant lymphoproliferative disorder (PTLD) in the spleen group, whereas 4 of 23 (17%) in the control group developed PTLD. One-year patient survival was 84% in the spleen group and 86% in the control group. Recipients of the spleen as part of a Multivisceral graft had significantly lower platelet counts. Rejection-free survival may be prolonged, but the risk of GVHD may be increased.
