Intestinal Transplant for Hirschsprung's Disease: Stoma for Life or Not?

Hirschsprung's disease is a dysmotility disease caused by lack of ganglion cells in the bowel wall that can affect varying lengths of the intestine. In extreme circumstances, there can be little remaining ganglionated bowel, and the patient becomes dependent on parental nutrition (PN) for survival. Intestinal transplant has been utilized to salvage these patients suffering terminal complications of PN.

Operational tolerance after intestine re-transplantation in childhood and immunological correlates. Case report and review.

Background: Operational tolerance after retransplantation of the intestine has never been reported.

Purpose: To two recently described intestine transplant recipients with operational tolerance, we now add a third.

Methods: Review of case record and immunological testing to confirm donor-specific hyporesponsiveness in multiple immune cell compartments.

Pediatric intestinal transplantation.

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960's, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.

Long-term outcomes of intestinal transplantation from donors aged under 1 year.

Background: The aim of the study was to analyze the long-term outcomes of transplants utilizing ITx donors <1 year and to compare these results with older donors.

Methods: Between January 2007 and December 2019, the primary ITx donors in the Children's Hospital of Pittsburgh of UPMC were retrospectively reviewed. Short- and long-term outcomes of recipients receiving a deceased donor organ from donors <1 year were compared with those found in all other recipients.

Multidrug-resistant organisms: A significant cause of severe sepsis in pediatric intestinal and multi-visceral transplantation.

Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric intestinal (ITx) and multi-visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015.

Twenty Years of Gut Transplantation for Chronic Intestinal Pseudo-obstruction: Technical Innovation, Long-term Outcome, Quality of Life, and Disease Recurrence.

Objective: To define long-term outcome, predictors of survival, and risk of disease recurrence after gut transplantation (GT) in patients with chronic intestinal pseudo-obstruction (CIPO).

Background: GT has been increasingly used to rescue patients with CIPO with end-stage disease and home parenteral nutrition (HPN)-associated complications. However, long-term outcome including quality of life and risk of disease recurrence has yet to be fully defined.

Severe Sepsis in Pediatric Liver Transplant Patients: The Emergence of Multidrug-Resistant Organisms.

Objectives: To describe characteristics of liver transplant patients with severe sepsis in the PICU.

Design: Retrospective descriptive analysis.

Setting: Tertiary children's hospital PICU.

Pediatric Intestinal Transplantation.

Pediatric intestinal transplantation has moved from the theoretic to an actual therapy for children with irreversible intestinal failure who are suffering from complications of total parenteral nutrition. Owing to significant advancement in the management of intestinal failure and prevention of parenteral nutrition-related complications that have led to reduction in incidence of parenteral nutrition-associated liver disease and have improved intestinal adaptation, the indications for intestinal transplantation are evolving. Long-term outcomes have improved, but challenges in long-term graft function owing to chronic rejection and immunosuppressant-related complications remain the major opportunities for improvement.

Long-term outcomes and predictors in pediatric liver retransplantation.

Historically, 9-29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed.

Long-term survival, nutritional autonomy, and quality of life after intestinal and multivisceral transplantation.

Objective: To assess long-term survival, graft function, and health-related quality of life (QOL) after visceral transplantation.

Background: Despite continual improvement in early survival, the long-term therapeutic efficacy of visceral transplantation has yet to be defined.

Methods: A prospective cross-sectional study was performed on 227 visceral allograft recipients who survived beyond the 5-year milestone.

A decade of experience with a single dose of rabbit antithymocyte globulin or alemtuzumab pretreatment for intestinal and multivisceral transplantation.

In 2001, we hypothesized that recipient pretreatment with a single-dose of an anti-lymphoid depleting agent followed by tacrolimus monotherapy could promote alloengraftment with minimal long-term immunosuppression. As of November 2010, the protocol was applied to 175 adults: 46 (26%) received rATG (5 mg/kg) and 129 (74%) received alemtuzumab (30 mg). Targeted 12-hour tacrolimus trough levels were 10-15 ng/mL followed by attempts of spaced-dose reduction in selected patients.

Allospecific CD154 + T-cytotoxic memory cells as potential surrogate for rejection risk in pediatric intestine transplantation.

Clinical end-points dictate large trial enrollments and exclude children with the rare intestine transplant procedure (ITx), who experience higher drug-related morbidity. We evaluate the novel rejection-risk parameter, allo-(antigen)-specific CD154 + TcMs (i) as surrogates for ACR using Prentice's criteria, (ii) for association with immunosuppression targets to determine Fleming's surrogate end-point designation, and (iii) as time-to-event end-point in a simulated comparison of alemtuzumab (NCT#01208337, n = 14) and rabbit anti-human thymocyte globulin (rATG, n = 16) among 30 children with ITx. CD154 + TcM were measured in MLR before, and at 1-60 and 61-200 days after ITx (NCT#01163578).

Current status of pediatric intestinal failure, rehabilitation, and transplantation: summary of a colloquium.

An international symposium convened September 9-11, 2010, in Chicago to present the state of the art and science of the multidisciplinary care of intestinal failure in children. Medical and surgical management of the child with intestinal failure was presented with a focus on the importance of multidisciplinary intestinal failure management. Issues of timing of referral and benefit risk analysis for intestine "rehabilitation" and transplant were presented.

Modified multivisceral transplantation with spleen-preserving pancreaticoduodenectomy for patients with familial adenomatous polyposis "Gardner's Syndrome".

Background: Liver-sparing "modified" multivisceral transplantation (MMVTx) has recently been more used for patients with diffuse gastrointestinal disorders and preserved hepatic functions. Evisceration techniques with preservation of native spleen were also introduced to reduce risk of posttransplant lymphoproliferative disorders. This study focuses on the indications of MMVTx for patients with familial adenomatous polyposis (FAP) and the technical feasibility of performing spleen-preserving pancreaticoduodenectomy (SPPD).

NOD2 gene polymorphism rs2066844 associates with need for combined liver-intestine transplantation in children with short-gut syndrome.

Objectives: The nucleotide-binding oligomerization protein 2 (NOD2) gene single nucleotide polymorphisms (SNPs) associated with Crohn's disease were recently associated with severe rejection after small-bowel transplantation (SBTx). The purpose of this study was to re-test this association and explore whether deficient innate immunity suggested by the NOD2 SNPs predisposes to intestine failure requiring isolated SBTx or combined liver-intestine failure requiring combined liver-SBTx (LSBTx).

Methods: Archived DNA from 85 children with primary isolated SBTx or LSBTx was genotyped with Taqman biallelic discrimination assays.

Abernethy malformation complicated by hepatopulmonary syndrome and a liver mass successfully treated by liver transplantation.

A seven-yr-old boy presented with persistent oxygen requirement following a respiratory infection. Physical exam was remarkable for orthodeoxia and digital clubbing. Laboratory evaluation showed elevated A-a oxygen gradient of 48 mmHg and mildly elevated transaminases.

Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges.

Objective: To assess the evolution of visceral transplantation in the milieu of surgical technical modifications, new immunosuppressive protocols, and other management strategies.

Summary Background Data: With the clinical feasibility of intestinal and multivisceral transplantation in 1990, multifaceted innovative tactics were required to improve outcome and increase procedural practicality.

Methods: Divided into 3 eras, 453 patients received 500 visceral transplants.

Pyridoxal-5'-phosphate deficiency after intestinal and multivisceral transplantation.

Background: Successful intestinal transplantation is measured by the achievement of clinical nutritional autonomy (CNA). However, the ability of the graft to maintain normal micronutrient levels including vitamins has yet to be thoroughly evaluated.

Objective: After an initial clinical observation of isolated cases of pyridoxal-5'-phosphate (PLP) deficiency, this prospective study was designed to address the incidence of, risk factors for, and management of PLP deficiency in adult intestinal transplant recipients.

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.

Intestinal transplantation under tacrolimus monotherapy after perioperative lymphoid depletion with rabbit anti-thymocyte globulin (thymoglobulin).

Modifications in the timing and dosage of immunosuppression can ameliorate the morbidity and mortality that has prevented widespread use of intestinal transplantation (ITx) in children. Thirty-six patients receiving ITx, aged 5 months to 20 years were given 2-3 mg(kg of rabbit anti-thymocyte globulin (rATG, thymoglobulin) just before ITx, and 2-3 mg(kg postoperatively (total 5 mg(kg). Twice daily doses of tacrolimus (TAC) were begun enterally within 24 h after graft reperfusion with reduction of dose quantity or frequency after 3 months.

Evolutionary experience with immunosuppression in pediatric intestinal transplantation.

Background/purpose: Intestinal transplantation has developed to become the standard of care for patients with irreversible intestinal failure who are not responding to total parenteral nutrition. Once considered experimental, it has taken time and much effort for the procedure to become a clinical reality, with final acceptance primarily because of the vastly improved outcomes. Advances and novel modifications in immunosuppression have been at the forefront of these improvements.

Carcinoma of donor origin after liver-intestine transplantation in a child.

Tumor-related complications after intestinal transplantation in children have been principally EBV driven post-transplant disorders. We describe the clinical course of a child, with a diagnosis of microvillus inclusion disease who received a liver and intestine allograft at the age of 9 months. His postoperative course was significant for multiple episodes of acute intestinal allograft rejection and eventually the development of post-transplant lymphoproliferative disorder (PTLD), which resolved.

Sclerosing peritonitis after intestinal transplantation in children.

Long-term graft dysfunction and/or graft loss after intestinal transplantation (ITx) is a significant concern. Sclerosing peritonitis (SP) is a manifestation of chronic allograft failure and its presence may also include classic arterial obliterative arteriopathy (OA) as in chronic rejection. We describe the clinical presentation and management of SP occurring after ITx in children.