Association between oral nutrition and inflammation after intestinal transplantation.

Intestinal transplantation (Itx) can be a life-saving treatment for certain patient populations, including those patients with intestinal failure (IF) who develop life-threatening complications due to the use of parenteral nutrition (PN). Most patients who have undergone Itx are eventually able to tolerate a full oral diet. However, little guidance or consensus exists regarding optimizing the specific components of an oral diet for Itx patients, including macronutrients, micronutrients and dietary patterns. While oral dietary prescriptions have moved to the forefront of primary and preventive care, this movement has yet to occur across the field of organ transplantation. Evidence to date points to the role of systemic chronic inflammation (SCI) in a wide variety of chronic diseases as well as post-transplant graft dysfunction. This review will discuss current trends in oral nutrition for Itx patients and also offer novel insights into nutritional management techniques that may help to decrease SCI and chronic disease risk as well as optimize graft function.

Normothermic Preservation of the Intestinal Allograft.

Intestinal allotransplantation was first described in the 1960s and successfully performed in the 1980s. Since that time, less progress has been made in the preservation of the allograft before transplantation and static cold storage remains the current standard. Normothermic machine perfusion represents an opportunity to simultaneously preserve, assess, and recondition the organ for transplantation and improve the procurement radius for allografts. The substantial progress made in the field during the last 60 years, coupled with the success of the preclinical animal model of machine perfusion-preserved intestinal transplantation, suggest we are approaching the point of clinical application.

Indications for Intestinal Transplantation.

Outcomes for patients with chronic intestinal failure have improved with organization of experts into multidisciplinary teams delivering care in intestinal rehabilitation programs. There have been improvements in understanding of intestinal failure complications as well as development of newer therapies that have amplified the improvements in survival. In spite of this encouraging trend, patients who fail PN are often referred too late for intestinal transplantation. The author proposes a more rational framework that might allow earlier identification of intestinal failure patients at risk for PN-failure, who could appropriately be considered earlier for intestinal transplantation with improvements in overall outcomes.

Abdominal Wall Closure in Intestinal and Multivisceral Transplantation: A State-Of-The-Art Review of Vascularized Abdominal Wall and Nonvascularized Rectus Fascia Transplantation.

Failure to close the abdomen after intestinal or multivisceral transplantation (Tx) remains a frequently occurring problem. Two attractive reconstruction methods, especially in large abdominal wall defects, are full-thickness abdominal wall vascularized composite allograft (AW-VCA) and nonvascularized rectus fascia (NVRF) Tx. This review compares surgical technique, immunology, integration, clinical experience, and indications of both techniques. In AW-VCA Tx, vascular anastomosis is required and the graft undergoes hypotrophy post-Tx. Furthermore, it has immunologic benefits and good clinical outcome. NVRF Tx is an easy technique without the need for vascular anastomosis. Moreover, a rapid integration and neovascularization occurs with excellent clinical outcome.

Intestinal Transplantation: Include the Spleen with Intestinal Graft?

The traditional procedure for multivisceral transplant (MVT) is to transplant the stomach, pancreas, intestine, and liver en bloc. During surgery, the native spleen is routinely removed from the recipient, and it usually creates more space in the abdomen to insert the allogeneic graft. Thus, recipients often become asplenic after MVT. Considering all of the risks and benefits, we advocate that temporary transplant of the donor spleen could be the best option for MVT recipients; it could potentially reduce the rate of intestinal allograft rejection without increasing the risk for graft-versus-host disease.

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. The question as to whether to reestablish intestinal continuity, and thus not require a stoma is vexed. However, data and experience would suggest this can be safely done with good functional results.

Should a Stoma Be Used After Intestinal Transplant.

As we all acknowledge benefits of ostomies, they can come with significant morbidity, quality of life issues, and major complications, especially during reversal procedures. In recent years, we have started to observe that similar graft and patient survival can be achieved without ostomies in certain cases. This observation and practice adopted in a few large-volume transplant centers opened a new discussion about the necessity of ostomies in intestinal transplantation. There is still more time and randomized studies will be needed to better understand and analyze the risk/benefits of "No-ostomy" approach in intestinal transplantation.

Abdominal Organ Transplantation: Noteworthy Literature in 2023.

This review highlights noteworthy literature published in 2023 and pertinent to anesthesiologists and critical care physicians caring for patients undergoing abdominal organ transplantation. We feature 9 studies from 593 peer-reviewed papers on pancreatic transplantation, 3 from 194 on intestinal transplantation, and 28 from over 4513 on kidney transplantation. The liver transplantation section includes a special focus on 20 studies from 5666 clinical trial publications. We explore a broad range of topics, including donor management, perioperative recipient management, and innovative pharmacologic and mechanical interventions tested for the improvement of patient and graft outcomes and survival.

Updates in induction immunosuppression regimens for intestinal transplantation.

Intestinal allografts are the most immunologically complex and carry the highest risk of rejection among solid organ transplantation, necessitating complex immunosuppressive management. We evaluated the latest information regarding induction immunosuppression, with an emphasis on established, novel, and emergent therapies. We also reviewed classic and novel induction immunosuppression strategies for highly sensitized recipients. Comparable progress has been made in intestinal transplantation clinical outcomes since the implementation of induction strategies. This review shows a clear diversity of induction protocols can be observed across different centers. The field of intestinal transplantation is still in its early stages, which is further complicated by the limited number of institutions capable of intestinal transplantation and their geographical variation, which further hinders the development of adequately powered studies in comparison to other organs. As the implementation of institution-specific induction protocols becomes more refined and results are disseminated, future research efforts should be directed towards the development of efficacious induction strategies.

Tolerance in intestinal transplantation.

Intestinal transplantation (ITx) is highly immunogenic, resulting in the need for high levels of immunosuppression, with frequent complications along with high rejection rates. Tolerance induction would provide a solution to these limitations. Detailed studies of alloreactive T cell clones as well as multiparameter flow cytometry in the graft and peripheral tissues have provided evidence for several tolerance mechanisms that occur spontaneously following ITx, which might provide targets for further interventions. These include the frequent occurrence of macrochimerism and engraftment in the recipient bone marrow of donor hematopoietic stem and progenitor cells carried in the allograft. These phenomena are seen most frequently in recipients of multivisceral transplants and are associated with reduced rejection rates. They reflect powerful graft-vs-host responses that enter the peripheral lymphoid system and bone marrow after expanding within and emigrating from the allograft. Several mechanisms of tolerance that may result from this lymphohematopoietic graft-vs-host response are discussed. Transcriptional profiling in quiescent allografts reveals tolerization of pre-existing host-vs-graft-reactive T cells that enter the allograft mucosa and become tissue-resident memory cells. Dissection of the pathways driving and maintaining this tolerant tissue-resident state among donor-reactive T cells will allow controlled tolerance induction through specific therapeutic approaches.

Clinical outcomes of intestinal transplant recipients receiving maintenance basiliximab, sublingual tacrolimus and prednisone: A case series.

INTRODUCTION: Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1-year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone. METHODS: A retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information. RESULTS: A total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4-28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4-13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2-13.2) ng/mL; month 6: 8.4 (7.6-9.6) ng/mL; and month 12: 8.8 (6.2-9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year. CONCLUSION: The combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.

History of clinical intestinal transplantation.

The intestines have been considered the "forbidden organ" for years, and intestinal failure became the last organ failure recognized as such in the medical field. The impossibility of providing adequate nutritional support, turned these patients into recipients of just palliative comfort. In the 1960's, parenteral nutrition appeared as the most reasonable replacement therapy, but the initial success obtained with clinical kidney, heart, liver, lung and pancreas transplantation served as background to explore intestinal transplantation. The first clinical report of an isolated intestinal transplant was done by Richard Lillihei in 1967; in 1983, Thomas Starzl, performed the first multi visceral transplant, and in 1990, David Grant performed the first combined liver-intestinal transplant in an adult recipient in Canada. Since then, advances in immunosuppressive therapies and surgical innovations have allowed not only a continuous increase in indications, but also a worldwide application of all procedures, bringing clinical intestinal transplantation to reality. In this historical account, the most important contributions have been summarized, thus describing the steady progress, expansion and novelties developed over the last 56 years, since the first attempt. Clinical intestinal transplantation remains a complex and evolving field; ongoing research and technological advancements will continue shaping its future.

Current approaches for risk assessment of intestinal transplant patients: A view from the histocompatibility laboratory.

Despite its recent decline in volumes, intestinal transplantation remains an important option for patients with irreversible intestinal failures. The long-term outcome of an intestinal transplant has stagnated. The major cause of graft loss is rejection, resulting from mismatches in human leukocyte antigens (HLA) and the presence of antibodies to mismatched donor-specific HLA antigens (DSA). Literature has reported that DSAs, either preformed before transplantation or developed de novo after transplantation, are harmful to intestinal grafts, especially for those without combined liver grafts. A comprehensive assessment of DSA by the histocompatibility laboratory is critical for successful intestinal transplantation and its long-term survival. This paper briefly reviews the history and current status of different methods for detecting DSA and their clinical applications in intestinal transplantation. The focus is on applying different antibody assays to manage immunologically challenging intestinal transplant patients before and after transplantation. A clinical case is presented to illustrate the complexity of HLA tests and the necessity of multiple assays. The review of risk assessment by the histocompatibility laboratory also highlights the need for close interaction between the laboratory and the intestinal transplant program.

OPTN/SRTR 2022 Annual Data Report: Intestine.

Intestine remains the least frequently transplanted solid organ, although the survival and quality-of-life benefits of transplant to individuals with irreversible intestinal failure have been well demonstrated. The trend seen over the past 15 years of fewer listings and fewer transplants appears to be continuing, most noticeably in infants, children, and adolescents. There were only 146 additions to the intestine waiting list in 2022, and the proportion of adult candidates continues to increase, so that now 61% of the intestine waiting list are adult candidates. There has been little change in the distribution by sex, race and ethnicity, or primary diagnosis on the waiting list, or for those receiving transplant. The transplant rate for adults has decreased to 55.6 transplants per 100 patient-years, but the pediatric transplant rate remains relatively stable at 22.8 transplants per 100 patient-years. The decrease in transplant rates for adults is primarily the result of falling rates for those listed for combined intestine-liver, and this is reflected in the pretransplant mortality rates, which are twice as high for candidates in need of both organs compared with those listed for intestine alone. Overall, intestine transplant numbers decreased to a total of 82 intestine transplants in 2022, only one above the lowest ever value of 81 in 2019. No major changes were seen in the immunosuppression protocols, with most recipients having induction therapy and tacrolimus-based maintenance. Graft failure rates appear to have improved at 1, 3, and 5 years for intestine without liver, but this is not seen for combined intestine-liver. Graft and patient survival are better for pediatric recipients compared with adult recipients for both liver-inclusive and liver-exclusive transplant. Rates of posttransplant lymphoproliferative disorder are higher for recipients of intestine without liver.

Excess waitlist mortality among candidates for multivisceral liver-intestine transplant in acuity circle allocation.

Candidates for multivisceral transplant (MVT) have experienced decreased access to transplant in recent years. Using Organ Procurement and Transplantation Network data, transplant and waiting list outcomes for MVT (ie, liver-intestine, liver-intestine-pancreas, and liver-intestine-kidney-pancreas) candidates listed between February 4, 2018, and February 3, 2022, were analyzed, including model for end-stage liver disease/pediatric end-stage liver disease and exception scores by era (before and after acuity circle [AC] implementation on February 4, 2020) and age group (pediatric and adult). Of 284 MVT waitlist registrations (45.6% pediatric), fewer had exception points at listing post-AC compared to pre-AC (10.0% vs 19.1%), and they were less likely to receive transplant (19.1% vs 35.9% at 90 days; 35.7% vs 57.2% at 1 year). Of 177 MVT recipients, exception points at transplant were more common post-AC compared to pre-AC (30.8% vs 20.2%). Postpolicy, adult MVT candidates were more likely to be removed due to death/too sick compared with liver-alone candidates (13.5% vs 5.6% at 90 days; 24.2% vs 9.8% at 1 year), whereas no excess waitlist mortality was observed among pediatric MVT candidates. Under current allocation policy, multivisceral candidates experience inferior waitlist outcomes compared with liver-alone candidates. Clarification of guidance around submission and approval of multivisceral exception requests may help improve their access to transplantation and achieve equity between multivisceral and liver-alone candidates on the liver transplant waiting list.

Timing and Complications of Intestinal Ostomy Takedown After Intestinal and Multivisceral Transplantation.

BACKGROUND: Ileostomies are typically created at the time of intestinal and multivisceral transplantation to assist in graft monitoring with endoscopy and biopsies. Often, these ostomies are reversed with a takedown procedure once there is stable graft function, but data are limited on associated complications of the takedown procedure for patients with intestinal transplants. METHODS: To assess complications associated with takedowns in this patient population, we performed a retrospective analysis of patients who had an intestinal transplant with elective ostomy takedown after transplant. No prisoners were used in the study and this manuscript is in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: A total of 16 patients, 10 isolated patients with intestinal transplants and 6 patients with multivisceral transplants, were included in the study, and takedown occurred at a mean of (236.8 ± 117.1) days after transplant. Of the 16 patients, 5 patients (31%) had uncomplicated courses after takedown with no infection, no rejection, and no hospital readmission within 3 months of takedown. The rest of the patients (69%) developed either infection or rejection within 3 months of takedown, and 1 patient died of infection after ileostomy takedown. CONCLUSION: This case series highlights the high risk of complications after ileostomy takedown for patients with intestinal transplants and contributes to the growing debate regarding the role of ileostomy creation and reversal in patients with intestinal transplants.

Endoscopic Surveillance of the Intestinal Allograft: Recommendations From the Intestinal Rehabilitation and Transplant Association Working Group.

Intestinal transplant (ITx) rejection lacks a reliable noninvasive biomarker and rejection surveillance relies on serial endoscopies and mucosal biopsies followed by histologic assessment. Endoscopic biopsies are also essential for identifying other ITx-related complications such as infectious, allergic, and inflammatory graft enteritis as well as post-transplant lymphoproliferative disease or graft versus host disease. In spite of its central role in ITx, published guidelines on endoscopy and biopsy are lacking and significant variability between centers in terms of timing and technical performance exists. Therefore, an international expert group convened and discussed several aspects related to the surveillance endoscopy after ITx with the aim to summarize and standardize its practice. This article summarizes these considerations on endoscopic ITx monitoring and highlights practices of surveillance and for-cause endoscopy, biopsy techniques, pathologic evaluation, potential risks and complications, outsourcing, and less-invasive monitoring techniques.

Innovative surgical techniques in the intestine and multivisceral transplant.

PURPOSE OF REVIEW: This timely review delves into the evolution of multivisceral transplantation (MVT) over the past six decades underscoring how advancements in surgical techniques and immunosuppression have driven transformation, to provide insight into the historical development of MVT, shedding light on its journey from experimentation to a valuable clinical approach. RECENT FINDINGS: The review presents contemporary enhancements in surgical methods within the context of intestinal transplantation. The versatility of MVT is emphasized, accommodating diverse organ combinations and techniques. Both isolated intestinal transplantation (IIT) and MVT have seen expanded indications, driven by improved parenteral nutrition, transplantation outcomes, and surgical innovations. Surgical techniques are tailored based on graft type, with various approaches for isolated transplantation. Preservation strategies and ostomy techniques are also covered, along with graft assessment advancements involving donor-specific antibodies. SUMMARY: This review's findings underscore the remarkable evolution of MVT from experimental origins to a comprehensive clinical practice. The progress in surgical techniques and immunosuppression has broadened the spectrum of patients who can benefit from intestinal transplant, including both IIT and MVT. The expansion of indications offers hope to patients with complex gastrointestinal disorders. The detection of donor-specific antibodies in graft assessment advances diagnostic accuracy, ultimately improving patient outcomes.

Nutrition support considerations in pediatric small bowel transplantation.

Enteral autonomy is the primary goal of intestinal failure therapy. Intestinal transplantation (ITx) is an option when enteral autonomy cannot be achieved and management complications become life-threatening. The purpose of this review is to summarize existing medical literature related to nutrition requirements, nutrition status, and nutrition support after pediatric ITx. Achieving or maintaining adequate growth after intestinal transplant in children can be challenging because of episodes of rejection that require the use of corticosteroids, occurrences of infection that require a reduction or discontinuation of enteral or parenteral support, and fat malabsorption caused by impaired lymphatic circulation. Nutrient requirements should be assessed and modified regularly based on nutrition status, growth, ventilatory status, wound healing, and the presence of complications. Parenteral nutrition (PN) should be initiated as a continuous infusion early postoperatively. Enteral support should be initiated after evidence of graft bowel function and in the absence of clinical complications. Foods high in simple carbohydrates should be limited, as consumption may result in osmotic diarrhea. Short-term use of a fat-free diet followed by a low-fat diet may reduce the risk of the development of chylous ascites. Micronutrient deficiencies and food allergies are common occurrences after pediatric ITx. Enteral/oral vitamin and mineral supplementation may be required after PN is weaned. Nutrition management of children after ITx can be challenging for all members of the healthcare team. Anthropometric parameters and micronutrient status should be monitored regularly so that interventions to promote growth and prevent or reverse nutrient deficiencies can be implemented promptly.

Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation.

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.