Bowel Transplantation

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Enrico Benedetti - One of the best experts on this subject based on the ideXlab platform.

  • Segmental Living-Related Small Bowel Transplantation
    Abdominal Solid Organ Transplantation, 2020
    Co-Authors: Ivo Tzvetanov, Giuseppe D’amico, Enrico Benedetti
    Abstract:

    Small Bowel Transplantation (SBT) has provided effective therapy for the patients with chronic, irreversible intestinal failure affected by life-threatening complications of total parenteral nutrition [1].

  • living related segmental Bowel Transplantation from experimental to standardized procedure
    Annals of Surgery, 2006
    Co-Authors: Enrico Benedetti, Mark J Holterman, Massimo Asolati, Stefano Di Domenico, Jose Oberholzer, Howard Sankary, Herand Abcarian, Giuliano Testa
    Abstract:

    Introduction: Living donor Bowel Transplantation has recently emerged as a valuable alternative to cadaver Bowel transplant. We herein present our single-center experience with this procedure.

  • combined living donor liver small Bowel Transplantation
    Transplantation, 2005
    Co-Authors: Giuliano Testa, Mark J Holterman, Herand Abcarian, Eunice John, Susan Kecskes, Enrico Benedetti
    Abstract:

    : We are reporting the first known case of sequential combined living donor liver/small Bowel Transplantation (LDL/SBT). A 2-year-old boy born with gastroschisis and intestinal malrotation lost his entire small Bowel and colon shortly after birth. He underwent a living donor small Bowel transplant at 1 year of age that was lost 4 months after implantation for posttransplant lymphoproliferative disease (PTLD). He recovered from PTLD but developed total parenteral nutrition (TPN)-induced liver failure. He received a combined left lateral liver and terminal ileum transplant that we chose to perform sequentially due to the presence of preformed antibodies against his mother's tissues. The mother had no complications and a cumulative hospital stay of 7 days. At 9 months postsurgery, the patient is on full enteral nutrition and has suffered neither technical complications nor rejection. The technique described here is reproducible and makes combined living donor LDL/SBT an alternative to combined cadaveric liver-small Bowel transplant.

  • Combined living donor liver/small Bowel Transplantation.
    Transplantation, 2005
    Co-Authors: Giuliano Testa, Mark J Holterman, Herand Abcarian, Eunice John, Susan Kecskes, Enrico Benedetti
    Abstract:

    : We are reporting the first known case of sequential combined living donor liver/small Bowel Transplantation (LDL/SBT). A 2-year-old boy born with gastroschisis and intestinal malrotation lost his entire small Bowel and colon shortly after birth. He underwent a living donor small Bowel transplant at 1 year of age that was lost 4 months after implantation for posttransplant lymphoproliferative disease (PTLD). He recovered from PTLD but developed total parenteral nutrition (TPN)-induced liver failure. He received a combined left lateral liver and terminal ileum transplant that we chose to perform sequentially due to the presence of preformed antibodies against his mother's tissues. The mother had no complications and a cumulative hospital stay of 7 days. At 9 months postsurgery, the patient is on full enteral nutrition and has suffered neither technical complications nor rejection. The technique described here is reproducible and makes combined living donor LDL/SBT an alternative to combined cadaveric liver-small Bowel transplant.

  • segmental living related small Bowel Transplantation in adults
    Journal of Gastrointestinal Surgery, 2001
    Co-Authors: Luca Cicalese, Herand Abcarian, Cristiana Rastellini, Pierpaolo Sileri, Enrico Benedetti
    Abstract:

    The advent of small Bowel Transplantation has provided selected patients with chronic intestinal irreversible failure with a physiologic alternative to total parenteral nutrition. Recently a standardized technique for living related small Bowel Transplantation (LR-SBTx) has been developed. Three patients with short Bowel syndrome underwent LR-SBTx at our institution. All donors were ABO compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm of ileum was harvested and transplanted with its vascular pedicle constituted by the ileocolic artery and vein. The grafts were transplanted with a short cold and warm ischemia time. The immunosuppression regimen consisted of oral FK-506, prednisone, and intravenous induction with atgam. Serial biopsies of the intestinal grafts were performed to evaluate rejection or viral infections. The postoperative course was uneventful for all donors. All of the recipients are currently alive and well. Two of three patients are off total parenteral nutrition and tolerating an oral diet with no limitations on daily activity. In the third patient, the graft was removed 6 weeks after Transplantation. At the time of enterectomy, no technical or immunologic complications were documented. Absorption tests for D-xylose and fecal fat studies were performed showing functional adaptation of the segmental graft. All biopsies were negative for acute rejection. A well-matched segmentai ileal graft from a living donor can provide complete rehabilitation for patients with short Bowel syndrome. Our initial experience suggests that the risk of acute rejection and infection is greatly reduced compared to cadaveric Bowel Transplantation. Further clinical application of this procedure is warranted.

Betsy C Herold - One of the best experts on this subject based on the ideXlab platform.

  • first case of toxoplasmosis following small Bowel Transplantation and systematic review of tissue invasive toxoplasmosis following noncardiac solid organ Transplantation
    Transplantation, 2006
    Co-Authors: Andrew L Campbell, Margret S Magid, Gabriel Gondolesi, Cindy L Goldberg, Carolina Rumbo, Betsy C Herold
    Abstract:

    Background. Toxoplasmosis prophylaxis is standard following heart and heart lung Transplantation, when an increased risk of allograft transmitted Toxoplasma is well-recognized. In contrast, prophylaxis and routine serologic evaluation of donors and recipients for Toxoplasma in noncardiac solid organ Transplantation (SOT) is not recommended. We report the first case of disseminated toxoplasmosis following small Bowel Transplantation, presumably transmitted via the transplanted intestine and systematically review reported cases of toxoplasmosis in noncardiac SOT recipients to determine if current guidelines should be reconsidered. Methods. Systematic MEDLINE review was performed for tissue invasive toxoplasmosis in noncardiac SOT recipients and analysis of clinical features, serologic status, and treatment regimens with respect to mortality. Results. Fifty-two cases of toxoplasmosis in noncardiac SOT recipients were identified. Eighty-six percent developed disease within 90 days of Transplantation. Presentation was nonspecific and consisted of fever (77%), respiratory distress (29%), neurologic manifestations (29%), and bone marrow suppression (26%). Multivariate analyses demonstrated that localized disease (odds ratio [OR]=37.36, 95% CI 1.85–754.85), treatment received (OR=1.814, 95% CI 1.193–3.480) and donor and recipient serostatus (OR=1.39, 95% CI 1.068–1.815) were predictors of survival. High-risk recipients (donor seropositive/recipient seronegative) developed disease earlier (16 days vs. 31 days P=0.002) and were less likely to survive (OR=0.14, 95% CI 0.03–0.69) than standard-risk recipients. Conclusions. Toxoplasmosis is recognized following noncardiac SOT. Reduction of morbidity and mortality necessitates knowledge of donor and recipient Toxoplasma serostatus, prophylaxis, early diagnosis, and treatment. The findings support a reconsideration of preTransplantation evaluation and prophylaxis strategies in SOT recipients.

  • adenovirus infection in pediatric small Bowel Transplantation recipients
    Transplantation, 2003
    Co-Authors: Rebecca J Pinchoff, Stuart S Kaufman, Margret S Magid, Dean D Erdman, Gabriel Gondolesi, Meryl H Mendelson, Kliti Tane, Stephen G Jenkins, Thomas M Fishbein, Betsy C Herold
    Abstract:

    Background. The purpose of this study was to determine the prevalence of adenoviral infection in pediatric small Bowel Transplantation (SBT) recipients, examine risk factors for progression to histologic disease, and examine the impact of adenovirus on outcome. Methods. Beginning in July 2000, all SBT recipients had viral cultures for adenovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) obtained routinely during graft biopsies. The medical records were retrospectively reviewed for frequency and site of viral culture, types and doses of immunosuppressive drugs, episodes of rejection, histology of allograft biopsies, and other infections. Adenoviral isolates were typed by polymerase chain reaction and type-specific neutralization assays. Results. All 14 SBT recipients who met enrollment criteria had evidence of adenoviral infection (intestinal graft, 13; liver graft, 1). Eight of 14 developed histologic disease with identifiable adenoviral intranuclear inclusions. In contrast, CMV enteritis was identified in only one patient, who subsequently also developed adenoviral disease. No other viruses were detected. Adenoviral cultures were first positive within 30 days of transplant in nine. Patients with histologic disease were more likely than those without to have received intensive corticosteroid therapy (P<0.007), had virus isolated from more than one site (P=0.03), and had persistent positive cultures (P<0.01). Conclusions. Adenovirus was commonly isolated from children undergoing intestinal Transplantation. Progression to disease may be associated with more intensive immunosuppressive therapy and inability to clear virus.

Kareem Abuelmagd - One of the best experts on this subject based on the ideXlab platform.

  • pediatric small Bowel Transplantation
    Seminars in Pediatric Surgery, 2010
    Co-Authors: Navdeep Nayyar, George V Mazariegos, Sarangarajan Ranganathan, Kyle Soltys, Geoffrey Bond, Ronald Jaffe, Anita Nucci, Beverly Kosmach, Robert H Squires, Kareem Abuelmagd
    Abstract:

    The multivisceral liver-intestine-pancreas-stomach allograft was first described by Starzl nearly 50 years ago. Since then, over 1000 children have received small Bowel Transplantation (SBTx), alone or with the liver and other organs, for refractory short gut syndrome (SGS) because of a variety of congenital conditions. In 2001, SBTx was approved as definitive therapy for SGS by Medicare. Currently, 1- and 5-year graft survival routinely exceeds 90% and 80%, respectively. The expected outcomes also include freedom from parenteral nutrition, normalization of growth parameters, and quality of life. However, recurrent rejection, complications of high-dose immunosuppression, or chronic rejection, which is more likely to occur after SBTx without a liver graft, account for differences between early and late survival. Future efforts aimed at overcoming such challenges include preventing SBTx through early referral to comprehensive SGS management programs and understanding why the liver protects the small Bowel allograft from rejection. Finally, inflammatory mechanisms, which predispose the highly immunogenic small Bowel allograft to a protracted risk of resistant rejection must be elucidated, in order to ensure durable success.

  • elevated myeloid plasmacytoid dendritic cell ratio associates with early acute cellular rejection in pediatric small Bowel Transplantation
    Transplantation, 2010
    Co-Authors: Ankit Gupta, Kareem Abuelmagd, Chethan Ashokkumar, Mylarappa Ningappa, Brandon W Higgs, Sara Snyder, Matthew Johnson, Adriana Zeevi, Angus W Thomson, George V Mazariegos
    Abstract:

    Background. Acute cellular rejection affects more than 60% of children after small Bowel Transplantation (SBTx). Dendritic cells (DCs) are potent antigen-presenting cells, modulate immune responses to gut microbes, and may serve as markers of rejection-prone small Bowel Transplantation (SBTx). Methods. Myeloid CD11c + DC (MDC), which may have inflammatory functions, and plasmacytoid CD123 + DC (PDC), which may have tolerogenic potential, were measured by flow cytometric analysis, longitudinally (pretransplant, and at days 1 to 60, 61 to 200 posttransplant) in 23 children after SBTx. All children received cadaveric allografts with rabbit anti-human thymocyte globulin induction and steroid-free tacrolimus maintenance therapy. Rejectors were those children (n= 16), who experienced biopsy-proven acute cellular rejection within 60 days of SBTx. Results. Of 69 maximum possible observations, 62 were available for analysis. Among rejectors, a significantly higher MDC:PDC ratio (P=0.004) was associated with numerically higher MDC counts and significantly lower PDC frequencies (P=0.017) during the 1- to 60-day time period, compared with nonrejectors. Logistic regression analysis, leave-one-out cross-validation, and receiver operating characteristic analysis revealed that MDC:PDC ratio more than or equal to 1.52 was associated with rejector status with sensitivity/specificity of 86/67% during the 1 - to 60-day risk period for early SBTx rejection. Repeated measures analysis showed a significantly higher MDC:PDC ratio (P=0.043, F-test) among rejectors, compared with nonrejectors in cumulative data for pre-SBTx and 1- to 60-day time points. No correlation was seen between DC subsets and tacrolimus blood concentration at any time point. Conclusions. We conclude that an elevated MDC:PDC ratio associates with early small Bowel allograft rejection and may, therefore, identify at-risk recipients in the clinic.

  • allospecific cd154 t cells identify rejection prone recipients after pediatric small Bowel Transplantation
    Surgery, 2009
    Co-Authors: Chethan Ashokkumar, George V Mazariegos, Kyle Soltys, Ankit Gupta, Mylarappa Ningappa, Brandon W Higgs, Tamara Fazzolare, Lisa Remaley, Geoffrey J Bond, Kareem Abuelmagd
    Abstract:

    Background Up to 70% of children with small Bowel Transplantation (SBTx) experience acute cellular rejection (ACR). Allospecific CD154+ T cells predict liver ACR in children in a novel, 16-hour mixed leukocyte response (MLR) assay, but remain untested in SBTx. Methods The expression of CD154 was measured in 4 subsets—naive (N) and memory (M) CD154+ T-helper (Th) and T-cytotoxic (Tc) cells (ie, CD154+ ThN, CD154+ ThM, CD154+ TcN, and CD154+ TcM, respectively)—in the MLR of single blood samples obtained from 32 children with SBTx within 60 days of SBTx biopsy. Children showing ACR in these biopsies were termed Rejectors. The ratio of donor-induced to third-party–induced CD154+ T cells was called the immunoreactivity index (IR). We hypothesized that IR >1 denoted increased donor-specific alloreactivity and increased risk of rejection; in contrast, IR Results Rejectors showed significantly greater numbers of donor-specific CD154+ T-cell subsets. Logistic regression analysis and leave-one-out cross validation followed by receiver operating characteristic analysis showed that, among the 4 subsets, IR ≥1.23 for CD154+ TcM identified Rejectors with a sensitivity and specificity of 93% and 88%. Also, a significant negative correlation was observed between CD154 expression and CTLA4 expression in allospecific Tc (Spearman's rho = –0.616, P = .006) but not in Th. Conclusion Allospecific CD154+ TcM identify rejection-prone children with SBTx.

Christoph Troppmann - One of the best experts on this subject based on the ideXlab platform.

  • Combined Liver—Total Bowel Transplantation Has No Immunologic Advantage Over Total Bowel Transplantation Alone: A Prospective Study in a Porcine Model
    Archives of Surgery, 1997
    Co-Authors: Rainer W G Gruessner, Enrico Benedetti, Raouf E. Nakhleh, Jacques Pirenne, Kumar G. Belani, David S. Beebe, Richard J. Carr, Christoph Troppmann, Angelika C. Gruessner
    Abstract:

    Background: Rejection remains a major obstacle to successful Bowel Transplantation in humans. It has been suggested that a simultaneous liver transplant would shield the Bowel graft from immunologic attack, but the liver shortage would be aggravated. In a preclinical model, we studied the influence of simultaneous liver grafting by comparing the incidence of early Bowel rejection after combined liver—total (small- and large-) Bowel transplants vs total Bowel transplants alone. Methods: We assessed the incidence of early posttransplant rejection, graft-vs-host disease, and infection after combined liver—total Bowel transplants (group 1, n=10) and total Bowel transplants alone (group 2, n=9) in outbred Yorkshire Landrace pigs. Liver and Bowel grafts were transplanted orthotopically with portal vein drainage after recipient hepatectomy (group 1) and total enterectomy (groups 1 and 2). Posttransplant immunosuppression was performed with intravenous tacrolimus (whole blood levels, 15 to 30 ng/mL) and prednisolone. In groups 1 and 2, Bowel biopsy specimens from the ileostomy were obtained daily. In group 1, liver biopsy specimens were obtained weekly. Rejection was graded according to a 4-point scoring system (none, mild, moderate, and severe). Results: Overall graft survival at days 7, 14, and 21 was 89%, 44%, and 11%, respectively, in group 1 vs 100%, 100%, and 86%, respectively, in group 2 (P Conclusions: Simultaneous liver grafting did not further reduce the incidence of early Bowel rejection or graft-vs-host disease when compared with total Bowel transplants alone. Based on the results of this preclinical study, simultaneous liver grafting is not indicated for patients with short-Bowel syndrome and normal liver function. Arch Surg. 1997;132:1077-1085

  • a prospective study of fk506 versus csa and pig atg in a porcine model of small Bowel Transplantation
    Transplantation, 1995
    Co-Authors: Rainer W G Gruessner, Enrico Benedetti, Raouf E. Nakhleh, Jacques Pirenne, Angelika C. Gruessner, Jonathan P Fryer, Carlos G Fasola, David L Dunn, Ihor Bekersky, Christoph Troppmann
    Abstract:

    Rejection remains a major barrier to successful Bowel Transplantation, and immunosuppressive protocols are far from standardized. In 88 nonrelated outbred pigs, we compared the effects of two immunosuppressive regimens-one with FK506, the other with cyclosporine (CsA) and pig antithymocyte globulin (ATG)-on incidence and severity of rejection in the early, critical posttransplant period. Group A (n=14) was nonimmunosuppressed (controls). Group B (n=17) received pig ATG (10 mg/kg/day ×10 days), CsA (3 mg/kg/day), prednisolone (2 mg/kg/day), and azathioprine (2.5 mg/kg/day); predisolone and azathioprine were each reduced by 50% at 8 and 15 days posttransplant. Trough CsA whole-blood concentrations were ≥400 ng/ml for the first 7 days, ≥200 ng/ml thereafter. Group C (n=13) received FK506 (0.2 mg/kg/day) and prednisolone (2 mg/kg/day); prednisolone was reduced by 50% at 8 and 15 days. FK506 whole-blood concentrations were ≥20 ng/ml. All immunosuppression in groups B and C was given intravenously. We performed orthotopic small Bowel transplants with systemic venous drainage. Recipient Bowel was resected distal to the second portion of the duodenum and proximal to the rectum at transplant; Bowel continuity was restored by duodenojejunostomy; ileostomy was created distally to allow access for daily biopsies. We graded interstitial and vascular rejection separately, according to a scoring system (no, mild, moderate, and severe rejection). Rejection-free graft survivals at 7, 14, and 21 days posttransplant were 38%, 19%, and 0% n group A; 93%, 93%, and 62% in group B; and 100%, 91%, and 82% in group C (P<0.001). Comparing rejection in the immunosuppressed groups, group C (FK506) had a stronger tendency toward rejection than group B (CsA-ATY); significant differences between groups B and C were, however, noted only on individual days posttransplant, not over time. The death rate due to irreversible rejection was not significantly different in groups B and C (P=0.8), but was significantly better in both of these immunosuppressed groups than in group A (P<0.001). Pig survival was significantly longer in group C than in B (P=0.001) due to a lower infection rate in group C. Posttransplant serum interleukin 2 and 7 levels did not correlate with rejection grades. Graft-versus-host reaction was noted only in the skin in 29% of group A, 73% of group B, and 77% of group C pigs; liver and native Bowel were not involved. We concluse that high-dose intravenous immunosuppressive regimens-whether FK506 or CsA-ATG-can effectively prevent moderate and severe interstitial rejection in the early period after Bowel Transplantation

Herand Abcarian - One of the best experts on this subject based on the ideXlab platform.

  • living related segmental Bowel Transplantation from experimental to standardized procedure
    Annals of Surgery, 2006
    Co-Authors: Enrico Benedetti, Mark J Holterman, Massimo Asolati, Stefano Di Domenico, Jose Oberholzer, Howard Sankary, Herand Abcarian, Giuliano Testa
    Abstract:

    Introduction: Living donor Bowel Transplantation has recently emerged as a valuable alternative to cadaver Bowel transplant. We herein present our single-center experience with this procedure.

  • combined living donor liver small Bowel Transplantation
    Transplantation, 2005
    Co-Authors: Giuliano Testa, Mark J Holterman, Herand Abcarian, Eunice John, Susan Kecskes, Enrico Benedetti
    Abstract:

    : We are reporting the first known case of sequential combined living donor liver/small Bowel Transplantation (LDL/SBT). A 2-year-old boy born with gastroschisis and intestinal malrotation lost his entire small Bowel and colon shortly after birth. He underwent a living donor small Bowel transplant at 1 year of age that was lost 4 months after implantation for posttransplant lymphoproliferative disease (PTLD). He recovered from PTLD but developed total parenteral nutrition (TPN)-induced liver failure. He received a combined left lateral liver and terminal ileum transplant that we chose to perform sequentially due to the presence of preformed antibodies against his mother's tissues. The mother had no complications and a cumulative hospital stay of 7 days. At 9 months postsurgery, the patient is on full enteral nutrition and has suffered neither technical complications nor rejection. The technique described here is reproducible and makes combined living donor LDL/SBT an alternative to combined cadaveric liver-small Bowel transplant.

  • Combined living donor liver/small Bowel Transplantation.
    Transplantation, 2005
    Co-Authors: Giuliano Testa, Mark J Holterman, Herand Abcarian, Eunice John, Susan Kecskes, Enrico Benedetti
    Abstract:

    : We are reporting the first known case of sequential combined living donor liver/small Bowel Transplantation (LDL/SBT). A 2-year-old boy born with gastroschisis and intestinal malrotation lost his entire small Bowel and colon shortly after birth. He underwent a living donor small Bowel transplant at 1 year of age that was lost 4 months after implantation for posttransplant lymphoproliferative disease (PTLD). He recovered from PTLD but developed total parenteral nutrition (TPN)-induced liver failure. He received a combined left lateral liver and terminal ileum transplant that we chose to perform sequentially due to the presence of preformed antibodies against his mother's tissues. The mother had no complications and a cumulative hospital stay of 7 days. At 9 months postsurgery, the patient is on full enteral nutrition and has suffered neither technical complications nor rejection. The technique described here is reproducible and makes combined living donor LDL/SBT an alternative to combined cadaveric liver-small Bowel transplant.

  • segmental living related small Bowel Transplantation in adults
    Journal of Gastrointestinal Surgery, 2001
    Co-Authors: Luca Cicalese, Herand Abcarian, Cristiana Rastellini, Pierpaolo Sileri, Enrico Benedetti
    Abstract:

    The advent of small Bowel Transplantation has provided selected patients with chronic intestinal irreversible failure with a physiologic alternative to total parenteral nutrition. Recently a standardized technique for living related small Bowel Transplantation (LR-SBTx) has been developed. Three patients with short Bowel syndrome underwent LR-SBTx at our institution. All donors were ABO compatible with a good human leukocyte antigen match. A segment of 180 to 200 cm of ileum was harvested and transplanted with its vascular pedicle constituted by the ileocolic artery and vein. The grafts were transplanted with a short cold and warm ischemia time. The immunosuppression regimen consisted of oral FK-506, prednisone, and intravenous induction with atgam. Serial biopsies of the intestinal grafts were performed to evaluate rejection or viral infections. The postoperative course was uneventful for all donors. All of the recipients are currently alive and well. Two of three patients are off total parenteral nutrition and tolerating an oral diet with no limitations on daily activity. In the third patient, the graft was removed 6 weeks after Transplantation. At the time of enterectomy, no technical or immunologic complications were documented. Absorption tests for D-xylose and fecal fat studies were performed showing functional adaptation of the segmental graft. All biopsies were negative for acute rejection. A well-matched segmentai ileal graft from a living donor can provide complete rehabilitation for patients with short Bowel syndrome. Our initial experience suggests that the risk of acute rejection and infection is greatly reduced compared to cadaveric Bowel Transplantation. Further clinical application of this procedure is warranted.