Intestinal Transplantation Research Articles

245.4: Living donor intestinal transplantation: Two decades of experience in China.

245.4: Living donor intestinal transplantation: Two decades of experience in China.

245.7: Outcomes of intestinal transplant in a single large adult centre.

245.7: Outcomes of intestinal transplant in a single large adult centre.

P.403: Donor-recipient lymphocyte turnover kinetics is affected by immunosuppressive treatment in a model of intestinal transplantation acute cellular rejection.

P.403: Donor-recipient lymphocyte turnover kinetics is affected by immunosuppressive treatment in a model of intestinal transplantation acute cellular rejection.

416.1: Immune profiling of donor and recipient γδ T cells after human intestinal transplantation reveals their roles in lymphohematopoietic graft-versus-host responses and graft rejection.

416.1: Immune profiling of donor and recipient γδ T cells after human intestinal transplantation reveals their roles in lymphohematopoietic graft-versus-host responses and graft rejection.

245.8: Shiraz Transplant Center; leader of the intestinal transplant in the Middle East; challenges and opportunities.

245.8: Shiraz Transplant Center; leader of the intestinal transplant in the Middle East; challenges and opportunities.

Deceased donor non-composite split liver and intestinal transplantation for children.

Children with intestinal failure suffer liver damage associated with parenteral nutrition: a condition known as intestinal failure-associated liver disease (IFALD), which requires transplantation of both liver and intestine. In many countries, simultaneous transplantation of these two organs is performed using grafts from a deceased donor, but there have been no such cases in Japan, and the details of the procedure are not clear. Recently, we performed simultaneous split liver and intestinal transplantation in two premature infants with IFALD, using organs from identical deceased donors and achieved good results. These are the first two cases of this procedure being performed in Japan. We report these cases and discuss the important aspects of the surgical and perioperative management.

Current Status of Chronic Intestinal Failure Management in Adults.

Chronic intestinal failure (CIF) is a heterogeneous disease that affects pediatric and adult populations worldwide and requires complex multidisciplinary management. In recent years, many advances in intravenous supplementation support, surgical techniques, pharmacological management, and intestinal transplants have been published. Based on these advances, international societies have published multiple recommendations and guidelines for the management of these patients. The purpose of this paper is to show the differences that currently exist between the recommendations (ideal life) and the experiences published by different programs around the world. A review of the literature in PubMed from 1980 to 2024 was carried out using the following terms: intestinal failure, CIF, home parenteral nutrition, short bowel syndrome, chronic intestinal pseudo-obstruction, intestinal transplant, enterohormones, and glucagon-like peptide-2. There is a difference between what is recommended in the guidelines and consensus and what is applied in real life. Most of the world's countries are not able to offer all of the steps needed to treat this pathology. The development of cooperative networks between countries is necessary to ensure access to comprehensive treatment for most patients on all continents, but especially in low-income countries.

Posttransplant inflammatory bowel disease after successful solid organ transplantation: Not out of the woods yet.

Gastrointestinal symptoms can occur following pediatric solid organ transplantation (SOT), and a subset of children will develop chronic inflammatory bowel disease (IBD) posttransplant. The goal of this study was to characterize patients who developed IBD following SOT, their treatment modalities, and clinical course. A retrospective review was performed of electronic medical records of patients 0-18 years of age who underwent heart, kidney, liver, or intestinal transplantation at our center from January 2009 to April 2019. Patients who developed IBD were included in the final analysis. Demographics, symptoms, and clinical information were recorded. Endoscopic and histologic data and initial and current medications were noted for each patient. Outcomes of interest included phenotype at the time of IBD diagnosis, surgical interventions for IBD, and clinical trajectory at last median follow-up. Eight patients with IBD after heart (n = 3, 37.5%), kidney (n = 2, 25.0%), liver (n = 1, 12.5%), intestinal (n = 1, 12.5%), or multivisceral (heart and kidney, n = 1, 12.5%) transplants were included. Before IBD diagnosis, most patients developed diarrhea (n = 5, 62.5%) and abdominal pain (n = 5, 62.5%). Abnormal endoscopic findings were most common in the colon. Patients were started on medications including 5-aminosalicylates, steroids, and azathioprine. Two patients required biologic therapy and were receiving vedolizumab at last follow-up. Some patients required adjustment of immune suppression. Posttransplant IBD can occur following SOT. Patients exhibit inflammatory, nonstricturing disease though one patient experienced fistulizing disease. Complications are uncommon and many patients enter remission with 5-aminosalicylates alone, though some require adjustment in primary immune suppression.

Prognostic factors for pediatric patients with severe intestinal motility disorders: a single institution's experience.

To identify the prognostic factors for pediatric severe intestinal motility disorder (IMD). We reviewed the medical records of patients with severe IMD, who required total parenteral nutrition (TPN) for ≥ 60days at our institution between April, 1984 and March, 2023, examining their characteristics to identify prognostic factors. The types of IMD in the 14 patients enrolled in this study were as follows: isolated hypoganglionosis (IHG, n = 6), extensive aganglionosis (EAG: n = 6), and chronic idiopathic intestinal pseudo-obstruction (CIIP, n = 2). There was no significant difference in mortality among the three types of severe IMD. Weaning-off TPN and the use of the colon were not significant prognostic factors, but cholestasis was a significant prognostic factor (p = 0.005). There was a high mortality rate (50%), with the major causes of death being intestinal failure-associated liver disease (IFALD) following hepatic failure, and catheter-related blood stream infection (CRBSI). One IHG patient underwent small bowel transplantation but died of acute rejection. Severe IMD is still associated with a high mortality rate and cholestasis predicts the prognosis. Thus, preventing or improving IFALD and CRBSI caused by long-term TPN is important for reducing the mortality rate.

Bacillus coagulans restores pathogen-induced intestinal dysfunction via acetate-FFAR2-NF-κB-MLCK-MLC axis in Apostichopus japonicus.

Skin ulceration syndrome (SUS) is currently the main disease threatening Apostichopus japonicus aquaculture due to its higher mortality rate and infectivity, which is caused by Vibrio splendidus. Our previous studies have demonstrated that SUS is accompanied by intestinal microbiota (IM) dysbiosis, alteration of short-chain fatty acids (SCFAs) content and the damage to the intestinal barrier. However, the mediating effect of IM on intestine dysfunction is largely unknown. Herein, we conducted comprehensive intestinal microbiota transplantation (IMT) to explore the link between IM and SUS development. Furthermore, we isolated and identified a Bacillus coagulans strain with an ability to produce acetic acid from both healthy individual and SUS individual with IM from healthy donors. We found that dysbiotic IM and intestinal barrier function in SUS recipients A. japonicus could be restored by IM from healthy donors. The B. coagulans strain could restore IM community and intestinal barrier function. Consistently, acetate supply also restores intestinal homeostasis of SUS-diseased and V. splendidus-infected A. japonicus. Mechanically, acetate was found to specifically bind to its receptor-free fatty acid receptor 2 (FFAR2) to mediate IM structure community and intestinal barrier function. Knockdown of FFAR2 by transfection of specific FFAR2 siRNA could hamper acetate-mediated intestinal homeostasis in vivo. Furthermore, we confirmed that acetate/FFAR2 could inhibit V. splendidus-activated NF-κB-MLCK-MLC signaling pathway to restore intestinal epithelium integrity and upregulated the expression of ZO-1 and Occludin. Our findings provide the first evidence that B. coagulans restores pathogen-induced intestinal barrier dysfunction via acetate/FFAR2-NF-κB-MLCK-MLC axis, which provides new insights into the control and prevention of SUS outbreak from an ecological perspective.IMPORTANCESkin ulceration syndrome (SUS) as a main disease in Apostichopus japonicus aquaculture has severely restricted the developmental A. japonicus aquaculture industry. Intestinal microbiota (IM) has been studied extensively due to its immunomodulatory properties. Short-chain fatty acids (SCFAs) as an essential signal molecule for microbial regulation of host health also have attracted wide attention. Therefore, it is beneficial to explore the link between IM and SUS for prevention and control of SUS. In the study, the contribution of IM to SUS development has been examined. Additionally, our research further validated the restoration of SCFAs on intestinal barrier dysfunction caused by SUS via isolating SCFAs-producing bacteria. Notably, this restoration might be achieved by inhibition of NF-κB-MLCK-MLC signal pathway, which could be activated by V. splendidus. These findings may have important implications for exploration of the role of IM in SUS occurrence and provide insight into the SUS treatment.

Transition from pediatric to adult care in patients with chronic intestinal failure on home parenteral nutrition: How to do it right?

BackgroundLife expectancy of children with chronic intestinal failure (CIF) on home parenteral nutrition has greatly improved. Children are now able to grow into adulthood which requires transfer from pediatric to adult health care. A guideline for structured transition is lacking and the demand for a more standardized care for this patient group is necessary. Therefore, we investigated the perceptions of health care professionals from various disciplines working in this specific field, concerning effective interventions regarding transition to adult health care. AimTo create a standardized protocol which provides practical guidance for health care professionals in order to bridge the gap between pediatric and adult health care and to facilitate successful transition of children with chronic intestinal failure. MethodsA survey consisting of 20 interventions for transition was sent out to members of the Intestinal Failure working group of European Reference Network for Rare Inherited Congenital (gastrointestinal and digestive) Anomalies (ERNICA) and the Network of Intestinal Failure and Intestinal Transplant in Europe (NITE) group - European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) healthcare professionals in 48 medical centers in various countries. Next to 20 interventions, an open-ended question to fill in any other suggestion with respect to most effective intervention was included. Interventions scoring higher than 80% by the participants were included in the protocol. Interventions scoring between 50% and 80% and other own suggestions were discussed during a consensus meeting and included when consensus, defined as unanimous agreement, was reached. Interventions scoring as effective by < 50% of participants were excluded directly. ResultsA total of 80 healthcare professionals from 33 medical centers (participation rate 69%) participated. The protocol consisted of modifiable components expected to be targets of interventions. The most important key outcomes of the survey were: 1) assessment of patient’s transition readiness and provision of knowledge to the patient by the pediatric team, 2) involvement of parents in the transition process, and 3) collaboration between the pediatric and adult chronic intestinal failure team. In addition it is advised that the transition process should start 1 to 2 years before transfer. A nurse specialist working in both services should form a bridge. All interventions must be tailor-made and based on the maturity of the patient. ConclusionThis study provides a protocol describing transition of children with chronic intestinal failure from pediatric to adult care. This international protocol will serve as practical guidance for pediatric chronic intestinal failure which will provide a more structured, optimal transition process. It is advised to use this protocol as a formal checklist that can be placed in the patient’s chart to review and track the transition process by CIF team members. Future research investigating transition readiness of CIF patients is needed.

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24h in University of Wisconsin (UW) solution containing MSC-CM with 50-100kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

Indications and successes of intestinal transplantation in children in the 21st century: A retrospective cohort study

AimsTo report the results and successes of intestinal transplantation (ITx) in the most active European centres, to emphasize that, although it is a difficult procedure, it should remain a therapeutic option for children with total, definitive and complicated intestinal failure when intestinal rehabilitation fails. MethodsWe retrospectively collected data about all patients less than 18 receiving an ITx from 2010 to 2022 in 8 centres, and outcomes in July 2022. ResultsITx was performed in 155 patients, median age 6.9 years, in 45% for short bowel syndromes, 22% congenital enteropathies, 25% motility disorders, and 15% re-transplantations. Indications were multiple in most patients, intestinal failure-associated liver disease in half. The graft was in 70% liver-containing. At last follow up 64% were alive, weaned from parenteral nutrition, for 7.9 years ; 27% had died and the graft was removed in 8%, mostly early after ITx. DiscussionITx, despite its difficulties, can give a future to children with complicated intestinal failure. It should be considered among the therapeutic options offered to patients with a predicted survival rate lower than that after ITx. Patients should be early discussed within multidisciplinary teams in ITx centres, to avoid severe complications impacting the results of ITx, or even to avoid ITx.

Evaluation of pediatric patients for intestinal transplantation in the modern era.

To review recent evaluations of pediatric patients with intestinal failure (IF) for intestinal transplantation (ITx), waiting list decisions, and outcomes of patients listed and not listed for ITx at our center. Retrospective chart review of 97 patients evaluated for ITx from January 2014 to December 2021 including data from referring institutions and protocol laboratory testing, body imaging, endoscopy, and liver biopsy in selected cases. Survival analysis used Kaplan-Meier estimates and Cox proportional hazards regression. Patients were referred almost entirely from outside institutions, one-third because of intestinal failure-associated liver disease (IFALD), two-thirds because of repeated infective and non-IFALD complications under minimally successful intestinal rehabilitation, and a single patient because of lost central vein access. The majority had short bowel syndrome (SBS). Waiting list placement was offered to 67 (69%) patients, 40 of whom for IFALD. The IFALD group was generally younger and more likely to have SBS, have received more parenteral nutrition, have demonstrated more evidence of chronic inflammation and have inferior kidney function compared to those offered ITx for non-IFALD complications and those not listed. ITx was performed in 53 patients. Superior postevaluation survival was independently associated with higher serum creatinine (hazard ratio [HR] 15.410, p = 014), whereas inferior postevaluation survival was associated with ITx (HR 0.515, p = 0.035) and higher serum fibrinogen (HR 0.994, p = 0.005). Despite recent improvements in IF management, IFALD remains a prominent reason for ITx referral. Complications of IF inherent to ITx candidacy influence postevaluation and post-ITx survival.

Advances in Intestinal Transplantation, Part I

Advances in Intestinal Transplantation, Part I

National adult small intestine transplant (NASIT) forum: a unique, multidisciplinary team meeting for patients being considered for intestinal transplant in the UK

National adult small intestine transplant (NASIT) forum: a unique, multidisciplinary team meeting for patients being considered for intestinal transplant in the UK

Nutritional status of intestinal transplant recipients: one year follow-up data from a UK adult transplant centre

Nutritional status of intestinal transplant recipients: one year follow-up data from a UK adult transplant centre

Survival in patients on home parenteral nutrition is non-inferior to patients with other indications for intestinal transplant

Survival in patients on home parenteral nutrition is non-inferior to patients with other indications for intestinal transplant

Nutritional outcomes following multi-visceral transplant: preliminary findings from the Cambridge intestinal transplantation unit

Nutritional outcomes following multi-visceral transplant: preliminary findings from the Cambridge intestinal transplantation unit

Impact of Recipient and Donor Body Mass Index on Survival Outcomes After Intestinal Transplantation: A United Network for Organ Sharing Database Analysis.

BACKGROUND Long-term patient survival after intestinal transplantation (IT) remains low compared with other organ transplants despite years of advancement in clinical experience. While patients with extremely high or low body mass index (BMI) are often considered ineligible for IT, the impact of BMI on post-transplant IT survival remains understudied. MATERIAL AND METHODS Using the United Network for Organ Sharing Standard Transplant database, we conducted a retrospective cohort study on patients who underwent IT between April 11, 1994, and September 29, 2021. We assessed the association of recipient and donor BMI at transplant with post-transplant mortality using Kaplan-Meier survival curves and univariate and multivariate Cox regression analyses. RESULTS A total of 1541 patients were included in our final sample. Of these patients, 806 were females (52.5%) and most were in the normal-weight BMI subgroup (54.2%). Obese class II (mean; 36.8±10.92 years) and underweight patients (mean; 37.6±13.37 years) were significantly younger than patients in other BMI categories. The adjusted multivariate model demonstrated an increased risk of mortality in underweight IT recipients compared to normal-weight IT recipients (aHR=1.25, 95% confidence interval [CI], 1.02-1.54; P=0.032).There was no significant association between donor BMI categories and survival in IT recipients. CONCLUSIONS Recipient BMI below normal is associated with an increased risk of mortality after intestinal transplantation and represents a potentially modifiable patient characteristic to improve survival outcomes.