Multivisceral Recipients Research Articles

Modifications in Abdominal Wall Graft Retrieval: When the Donor Closure Is Not Guaranteed

Twenty percent of intestinal transplant recipients will require a surgical alternative to conventional primary abdominal wall closure. Abdominal wall transplant is adevelopingtechnique that is increasingly performed for this purpose in isolated intestinal or multivisceral recipients; however, adequate closure of the donor is paramount while simultaneously obtaining a large enough graft. The aim of this study is to describe alternative surgical techniques for closure of the donor in cases in which abdominal wall graft extraction hinders subsequent donor abdominal closure. We describe the cases of 2 young donors in whom intestinal extraction was not carried out and in whom wall closure was not feasible, following standard techniques after abdominal wall graft extraction. We performed 2 different procedures to obtain adequate closure. 1. Hemifascia and hemiabdominal wall graft extraction: It is an option when the recipients require an extension of the abdominal aponeurosis yet have enough skin to guarantee skin closure. The perfusion of both epigastric arteries is needed. The remaining cutaneous half is used for closing the donor's abdomen.2. Hemiabdominal wall graft extraction: Full-thickness abdominal wall is harvested from the donor, selecting the most vascularized half. It is an alternative for recipients who need a skin implant in addition to an aponeurosis extension. This option should be used for recipients who do not require a large fascial graft but do require a significant cutaneous graft. The nontransplanted half of full-thickness abdominal wall is used for donor closure. Abdominal wall transplant allows forexpansion of the abdominal cavity in organ recipients and reduces the risk of compartmental syndrome and subsequent ischemia. However, the donor wall defect must be considered. The choice of donation technique was based on the magnitude of the defect in the donor as well as the size of defect to be covered in the recipient while ensuring a tight and complete closure of the donor's abdomen. Abdominal wall graft extraction can be performed using nonconventional techniques that account for the extension and type of coverage needed by the recipient while guaranteeing proper closure of the donor.

317.7: qPCR Based Immunotherapy in Intestinal Transplant Recipients and Candidates

Introduction: Inflammatory bowel disease (IBD) in intestinal transplantation (ITx) recipients and candidates is a complication that may be the result of an immune dysregulation due to the immunosuppression or the underlying disease. Conventional treatment of IBD, including corticosteroids and immunotherapy with monoclonal antibodies, uses to be effective, but in some patients the inflammation is refractory to the treatment. The aim of the study was to determine the intestinal mucosa cytokine expression in order to establish the optimal therapy in two multivisceral recipients and two ITx candidates with persistent enteritis. Methods: Two multivisceral recipients with episodes of ulcerative enteritis refractory to corticosteroids and infliximab treatment were studied, as well as, two ITx candidates with intestinal failure and inflammatory colitis and enteropathy, respectively. Mucosal biopsies were taken from affected and healthy areas and frozen in RNAlater until RNA extraction. Expression of cytokine genes which are targeted by approved drugs (IL1B, IL6, IL12p70, IL17A, IL23 and TNF) was determined by qPCR. Gene expression was calculated as 2-ΔCt using GAPDH as endogenous control. Results: ITx recipients (Patients 1 and 2): both patients (13 and 14 years old males) developed in the late posttransplant ulcerative ileitis and ulcerative colitis respectively. They were initially treated with metilprednisolone without achieving endoscopic improvement. Graft cytokine expression in pre-treatment biopsies of healthy and inflamed area was carried out, both of them showing a significant increase of IL6, correlating with high IL6 plasmatic levels (Figure 1A and 1B). Tocilizumab was then administered every two weeks, getting the clinical resolution in two months.ITx candidates: Patient 3 was a 5 years old male with trichohepatoenteric syndrome, showing ulcerative colitis. He was tread with corticosteroids without endoscopic or clinical improvement. Intestine cytokine expression in pre-treatment biopsies was carried out objectifying elevated IL1 and IL6 levels, so he was treated with Tocilizumab achieving great healing of the colitis (Figure 1C). Patient 4 was a 1 year old male suffering from autoinflammatory disorder with a mutation in mevalonate kinase gene, having enteropathy. He was empirically treated with Infliximab with initial improvement, but having a deterioration afterwards. Intestine cytokine expression in pre-treatment biopsies showed elevated IL1, IL6 and TNF levels (Figure 1D). He was treated with Anakinra without clinical improvement, changing for Adalimumab achieving clinical resolution. Conclusions: In the context of mucosal inflammation, the analysis of intragraft cytokine expression by qPCR is a useful and affordable tool to guide the treatment in a personalized way, showing a high effectiveness of the therapy.

317.8: Antibody-Removal Therapies in Pediatric Intestinal and Multivisceral Recipients: Why, When and How? A Single-Center Experience

317.8: Antibody-Removal Therapies in Pediatric Intestinal and Multivisceral Recipients: Why, When and How? A Single-Center Experience

276. SARS-CoV-2 Infection in Solid Organ Transplant Candidates and Recipients at Texas Children’s Hospital: A Retrospective Review

BackgroundTexas Children’s Hospital (TCH) is the largest pediatric solid organ transplant (SOT) program in the US, performing heart, kidney, liver, and lung transplants. Limited data exists about SARS-CoV-2 infection (COVID-19) in the pediatric SOT populations. We evaluated the impact of COVID-19 in a cohort of PCR positive SOT candidates and recipients. We hypothesized that COVID-19 would more severely impact SOT recipients compared to transplant candidates. MethodsPatients with SOT or transplant candidates at TCH with a positive SARS-CoV-2 RT-PCR test since March 1, 2020 to April 12, 2021 were included in the cohort. Retrospective medical record review was performed, and descriptive statistics were used. ResultsA total of 103 SOT patients were identified, 13 candidates and 90 recipients. Of the SOT candidates, there were 1 heart, 3 kidney, and 9 liver transplant candidates. The SOT recipient cohort included 33 heart, 6 lung, 20 kidney, 33 liver and 2 multi-visceral recipients. A significant difference in age was observed between candidates and recipients with candidates being younger with median age of 4.5 years as opposed to recipient’s median age of 12.8 years (p=0.0003). The majority of patients, 70 of 101 (69%), were symptomatic. Most common symptoms reported were fever in 34/70 (49%), cough in 31/70 (44%), and headache in 19/70 (27%). A higher percentage of candidates (31%, 4 of 13) were hospitalized for acute COVID-19 infection compared to (17%, 15 of 90) of recipients. A transplant candidate who ultimately died from underlying illness and COVID-19 was the only patient in the cohort who required mechanical ventilation. More deaths (2/13, 15%) occurred in transplant candidates with COVID-19 compared to transplant recipients with COVID-19 (1/90, 1%, p=0.04); however, 2 of the deaths occurred after recovery from acute COVID-19 illness.ConclusionOur study suggests that pediatric candidates who are actively listed for transplant with underlying conditions have more severe acute COVID-19 illness than pediatric SOT recipients despite their immunosuppression based on the higher mortality observed in the transplant candidates. Prospective studies are needed to better understand which specific patients are at increased risk for mortality from COVID-19.Disclosures Leanne Petters, MSN, APRN, CPNP-AC, Pfizer (Scientific Research Study Investigator) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB) Elizabeth A. Moulton, MD, PhD, Pfizer (Scientific Research Study Investigator)

P.136: Impact of Insulin Therapy in Pancreas Transplantation Donors on Graft Outcomes: An Analysis of the OPTN/UNOS Database

Introduction: Hyperglycemia requiring insulin treatment is frequent in critically ill patients and potential pancreas donors. Information on the impact of donor insulin use on pancreas outcomes is scarce. Thus, we explored the influence of donor insulin use on recipient and pancreas graft survival. Methods: Retrospective study with 12841 pancreas recipients (either simultaneous pancreas-kidney, pancreas after kidney or pancreas alone) from the OPTN/UNOS registry performed between 2000 and 2017. Multivisceral recipients other than simultaneous pancreas-kidney, those transplants from a donor < 30 kg and recipients with diabetes other than type 1 or 2 were excluded. Insulin donor requirements were defined as the need for any dose of insulin within 24 hours prior to donation. A Propensity Score (Inverse Probability of Treatment Weighting) approach was performed. Results: A total of 7765 (60%) patients received a pancreas from a donor with insulin requirements. After inverse probability of treatment weighting on donor and recipient covariates, pancreas graft survival (death-censored) at 1 year was similar between those who received an insulin-requiring donor and the remaining (89% vs 89%, P > 0.05), as well as at 5 and 10 years (78% and 69% vs 79% and 70%, respectively, P = 0.35)(Figure). Donor insulin therapy was not associated neither with an increased risk of recipient death (HR 0.94 [95% CI 0.85–1.04], P = 0.26), pancreas graft failure (HR 1.06 [95% CI 0.98–1.16], P = 0.15) nor any post-transplant complication (HR 1.11 [95% CI 0.98–1.24], P = 0.06). Discussion/Conclusions: Insulin requirements in a potential pancreas donor is not associated, per se, with an impaired pancreas graft and patient survival. Thus, donors who require insulin therapy may be suitable for pancreas transplantation.The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the OPTN or the U.S. Government.

P-68: The Degree of Post-transplant Hypomagnesaemia Seen in Multivisceral Recipients Cannot be Explained Solely by the use of PPI or Immunosuppression

P-68: The Degree of Post-transplant Hypomagnesaemia Seen in Multivisceral Recipients Cannot be Explained Solely by the use of PPI or Immunosuppression

PE-13: Ulcerative Enteritis Succesfully Treated with Tocilizumab in Two Multivisceral Recipients: Personalized Therapy Based in Intragraft Gene Expression

PE-13: Ulcerative Enteritis Succesfully Treated with Tocilizumab in Two Multivisceral Recipients: Personalized Therapy Based in Intragraft Gene Expression

Variability of Pneumocystis jirovecii prophylaxis use among pediatric solid organ transplant providers.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis after pediatric solid organ transplant (SOT) is routinely recommended, but practice varies. Online survey was sent in 2018 to 707 members of the International Pediatric Transplant Association. A total of 105 responded, representing 47 institutions in 18 countries consisting of transplant physicians (66%), transplant surgeons (19%), nurse practitioners (6%), infectious disease physicians (5%), or pharmacists (4%). PJP prophylaxis was reported by 88%, while 12% did not routinely give prophylaxis. The majority not using PJP prophylaxis performed renal transplants (67%) citing low incidence of PJP (62%). Trimethoprim/sulfamethoxazole was first-line agent (95%). PJP prophylaxis for 4-6months was the most frequent duration following kidney (48%, 27/56), liver (42%, 13/31), and heart (40%, 10/25) transplant. Abdominal multivisceral providers equally gave 10-12months (47%) or lifelong (47%); most lung transplant providers gave lifelong prophylaxis (85%). Across all organs, 21% provided lifetime prophylaxis. After completion of prophylaxis, 32% do not restart for any reason; majority of the rest would restart for treatment of acute graft rejection. 83% reported no PJP cases in the prior 12months; 14% reporting 1-5 infections. Only 3% reported a case of PJP infection on prophylaxis; none in SOT. PJP prophylaxis is routinely provided to pediatric SOT patients though practice and duration vary by center and organ type. Durations of 4-6months were most common for renal, liver, and heart transplant recipients, while 10-12months or lifelong prophylaxis were commonly reported for abdominal multivisceral recipients and most lung transplant recipients are given lifelong prophylaxis.

P1.15: Paediatric domino liver transplant following multivisceral transplant (liver-inclusive) with splenic preservation – A case report

Introduction:A multivisceral transplant followed by domino implantation of the resected liver to another patient was first reported by Tzakis in 1999. Since then there has not been much development in this technique and its implications for both recipients. We present a paediatric multivisceral transplantation with native spleen preservation followed by the use of the recipient’s liver as a domino graft for another child. Patients and Methods:Multivisceral donor: 3 year old boy with hypoxic brain damage, blood group O+, weight 14kg. Multivisceral recipient: 7 year old boy, blood group A+, weight 24 kg, with severe intestinal failure (Neuropathic intestinal dysmotility). No enteral feed and 24-h PN, with persistent central line infections. Listed for multivisceral transplant seeking immunological advantage. At transplant, normal native liver (mild portal fibrosis at biopsy) preserved for domino transplant. Splenic artery and left gastric artery were preserved. Pancreas removed leaving splenic vein. Spleno-caval shunt performed preserving native spleen. Native liver perfused with UW solution and stored. Multiorgan graft implanted (liver, stomach, duodenum, pancreas, small bowel and right haemicolon). CIT: 10h. Domino liver recipient: 3 year old boy, blood group: A+, weight 12 kg, with cholestatic liver disease. Domino liver transplant (graft weight: 484 g, CIT: 10h, duct-to-duct anastomosis). Results:Multivisceral recipient had bowel obstruction (day 3 post-transplant) that required laparotomy. No acute cellular rejection and no serious infections post-operatively. Stoma reversed at 5 m. He remains on enteral feeding and PN support due to rapid bowel transit. The domino liver recipient had acute cellular rejection (day 8 post-transplant). Anastomotic biliary stricture corrected with biliary reconstruction (6 m post-transplant). Conclusion:A liver-inclusive intestinal transplant seems to give an immunological advantage to the recipient by decreasing rejection episodes but make them vulnerable to lethal infections (Wu & Cruz, 2018), which is maybe worsened by native splenectomy at transplantation. Preserving the native spleen may reduce the incidence of PTLD, GVHD and risk of infections. The above case could be a better option than a modified multivisceral transplantation and using the multivisceral recipient’s liver as a domino graft will decrease the impact on the donor pool. More cases are required to establish the advantages of these surgical techniques.

Prospective Analysis of EBV+ PTLD in a Multi-Center Study of Pediatric Transplant Recipients

Post-transplant lymphoproliferative disorder (PTLD) remains a serious problem in the pediatric transplant population. The Clinical Trials of Organ Transplantation in Children (CTOT-C)-06 is an NIH-sponsored multi-institutional study intended to identify viral and immune biomarkers of Epstein-Barr virus (EBV)-associated PTLD. The laboratory studies are ongoing and herein we describe the enrolled and transplanted population to date. Enrollment began in August, 2014 and will continue until August, 2018. At the conclusion of the study all subjects will have a minimum of one year and a maximum of four years of follow-up post-transplant. As of November, 2017 there were 784 pediatric subjects enrolled and 687 children (53% male; 47% female) have received a transplant (50% liver, 22% heart, 22% kidney, 6% small intestine or multi-visceral). The mean age at transplant was 6.4 years (range 0-21 years) and 57% were EBV+, while 35% were EBV- and 8% had unknown EBV status. Of the EBV- subjects, 23% seroconverted during the study period. To date, 17 subjects (6 male, 11 female) have been diagnosed with EBV+ PTLD for an overall incidence of 2.5% (heart, n=5; kidney, n=5; liver, n=5; multivisceral, n=2). The incidence of EBV+ PTLD by organ transplanted was 3.3% in heart, 3.3% in kidney, 1.5% in liver, and 10% in multivisceral. The overall mean time post-transplant of EBV+ PTLD diagnosis was 18.9 months (range 1.7-43.9 months). The mean time post-transplant of EBV+ PTLD diagnosis by organ was 25.9 months in heart recipients, 17.8 months in kidney recipients, 19.6 months in liver recipients and 2.8 months in multivisceral recipients. Eight of the 17 patients diagnosed with EBV+ PTLD received induction medication and 10 were EBV-seronegative at transplantation. The anatomic location of disease was nodal (n=8), tonsillar (n=1) and extranodal (n=8). In summary, we report on the first large prospective US-based multi-center study on EBV+ PTLD in the era of modern immunosuppression and heightened surveillance for EB, and observe a continued incidence of EBV+ PTLD in pediatric transplant recipients. NIH 1UO1AI104342.

Hospitalizations for Respiratory Syncytial Virus and Vaccine-Preventable Infections in the First 2 Years After Pediatric Liver Transplant

To examine in liver transplant recipients at centers participating in the Pediatric Health Information System dataset the number of hospitalizations for respiratory syncytial virus (RSV) and vaccine-preventable infections (VPIs) in the first 2 years after transplantation, morbidity and mortality associated with these hospitalizations, and costs associated with these hospitalizations. A retrospective cohort study of patients <18 years of age who underwent liver transplantation at a Pediatric Health Information System center between January 1, 2004, and December 31, 2012. Hospitalizations for RSV/VPIs during the first 2 years post-transplant were ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Data were collected on clinical care, outcomes, and costs during these hospitalizations. There were 2554 liver transplant recipients identified; 415 patients (16.3%) had 544 cases of RSV/VPIs. RSV, rotavirus, and influenza were the most common infections resulting in hospitalization. Ninety-two patients (3.6%) had RSV/VPI during their transplant hospitalization. Transplant hospitalizations complicated by RSV/VPI were longer (44 days vs. 21 days; P < .001), had higher rejection rates (37% vs. 26%; P = .02), and were more expensive ($259 697 vs. $190 860; P < .001). Multivariate analyses identified age <2 years at transplant (P < .001) and multivisceral recipient (P = .04) as predictors of a hospitalization for RSV. VPIs occurred in 1 of 6 liver transplant recipients in the first 2 years post-transplant, a significantly higher rate than in the general pediatric population. These hospitalizations had substantial morbidity, mortality, and costs, demonstrating the importance of vaccinating patients before transplantation.

Pediatric solid organ transplant recipients: transition to home and chronic illness care.

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post-discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care.

Lymphoproliferative Disorders and De Novo Malignancies in Intestinal and Multivisceral Recipients: Improved Outcomes With New Outlooks

Lymphoproliferative Disorders and De Novo Malignancies in Intestinal and Multivisceral Recipients: Improved Outcomes With New Outlooks

Lymphoproliferative Disorders and De Novo Malignancies in Intestinal and Multivisceral Recipients: Improved Outcomes With New Outlooks

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

Five Hundred Intestinal and Multivisceral Transplantations at a Single Center

To assess the evolution of visceral transplantation in the milieu of surgical technical modifications, new immunosuppressive protocols, and other management strategies. With the clinical feasibility of intestinal and multivisceral transplantation in 1990, multifaceted innovative tactics were required to improve outcome and increase procedural practicality. Divided into 3 eras, 453 patients received 500 visceral transplants. The primary used immunosuppression was tacrolimus-steroid-only during Era I (5/90–5/94), adjunct induction with multiple drug therapy during Era II (1/95–6/01), and recipient pretreatment with tacrolimus monotherapy during Era III (7/01–11/08). During Era II/III, donor bone marrow was given (n = 79), intestine was ex vivo irradiated (n = 44), and Epstein-Barr-Virus (EBV)/cytomegalovirus (CMV) loads were monitored. Actuarial patient survival was 85% at 1-year, 61% at 5-years, 42% at 10-years, and 35% at 15-years with respective graft survival of 80%, 50%, 33%, and 29%. With a 10% retransplantation rate, second/third graft survival was 69% at 1-year and 47% at 5-years. The best outcome was with intestine-liver allografts. Era III rabbit antithymocyte globulin or alemtuzumab pretreatment-based strategy was associated with significant (P < 0.0001) improvement in outcome with 1- and 5-year patient survival of 92% and 70%. Survival has greatly improved over time as management strategies evolved. The current results clearly justify elevating the procedure level to that of other abdominal organs with the privilege to permanently reside in a respected place in the surgical armamentarium. Meanwhile, innovative tactics are still required to conquer long-term hazards of chronic rejection of liver-free allografts and infection of multivisceral recipients.

Emerging role of donor-specific anti–human leukocyte antigen antibody determination for clinical management after solid organ transplantation

Preformed and de novo donor-specific HLA antibodies (DSA) have been associated with allograft dysfunction and failure. The application of solid-phase methods have increased the sensitivity and specificity of antibody detection; however the clinical significance of these DSA is under evaluation. In the present study, we summarize six cases (four renal transplant recipients, one multivisceral recipient, and one heart-and-lung transplant recipient) to illustrate the role of the histocompatibility laboratory in providing the most comprehensive workup to assess the risk of graft dysfunction associated with antibody-mediated rejection (AMR). These cases illustrate the potential risk assessment for AMR in various situations: (1) in patients exhibiting low levels of DSA pretransplantation; (2) protocol immunosuppression minimization during stepwise weaning; and (3) desensitization protocols. Furthermore, increased sensitivity of DSA determination is indicated for the interpretation of focal C4d and its clinical significance. The clinical relevance of monitoring for circulating DSA with solid-phase single-antigen assays is also discussed. These cases exemplify the rationale for all patients to be monitored for DSA post-transplantation, with the frequency adjusted based on the individual risk for AMR.

Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance

Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post-transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single-dose of Thymoglobulin (rATG) or Campath-1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic-guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.

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

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

Transplantation of the Spleen

To describe the effect of the splenic allograft in human multivisceral transplantation. We performed transplants of the spleen as part of a multivisceral graft in an attempt to decrease both the risk of infection from an asplenic state and the risk of rejection by a possible tolerogenic effect. To our knowledge, this is the first report of human splenic transplantation in a large series. All primary multivisceral recipients who received a donor spleen (N = 60) were compared with those who did not receive a spleen (N = 81). Thirty-five of 60 (58%) are alive in the spleen group, and 39 of 81 (48%) are alive in control group (P = 0.98). In univariate analysis, splenic recipients showed superiority in freedom-from-any rejection (P = 0.02) and freedom-from-moderate or severe rejection (P = 0.007). No significant differences were observed in analyses of infectious complications between the spleen and control groups. Both platelet and leukocyte counts became normal in splenic patients, whereas these counts were significantly increased in nonsplenic recipients. Observed incidence of graft versus host disease (GVHD) was 8.25% (5 of 60) in the spleen group and 6.2% (5 of 81) in the control group (P = 0.70). Increased incidence of autoimmune hemolysis was observed in the spleen group. Allograft spleen can be transplanted within a multivisceral graft without significantly increasing the risk of GVHD. The allogenic spleen seems to show a protective effect on small bowel rejection. Further investigation with longitudinal follow-up is required to precisely determine the immunologic and hematologic effects of the allograft spleen.

Clostridium difficile Colitis in Solid Organ Transplantation—A Single-Center Experience

Clostridium difficile (CD) is one of the most common causes of diarrhea in solid organ transplantation (SOT). Between 1996 and 2005, a total of 2474 solid organ transplants were performed at our institution, of which 43 patients developed CD-associated diarrhea. There were 3 lung, 3 heart, 20 liver, 8 kidney-pancreas, 6 kidney, 1 composite tissue, and 2 multivisceral recipients. Onset of CD infection ranged from 5 to 2453 days posttransplant. All patients presented with abdominal pain and watery diarrhea. Toxins A and B were detected using rapid immunoassay or enzyme immunoassay. Treatment consisted of reduction of immunosuppression, fluid and electrolyte replacement, metronidazole (n=20), oral vancomycin (n=20), and a combination of metronidazole and vancomycin (n=2). Toxic megacolon was seen in five patients. Two of them had colonoscopic decompression, and the remaining three required colonic resection. One of these patients died due to multiorgan failure after cured CD enteritis. The remaining patients were discharged with well-functioning grafts and all are currently alive. CD colitis was a rare complication prior to 2000; 38 of the 43 cases occurred thereafter. We conclude that CD colitis represents a severe complication following SOT. Recently, a dramatic increase in the incidence of this complication has been observed. The development of life-threatening toxic megacolon must be considered in solid organ recipients.