Intestinal Transplantation Research Articles

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

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. 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. 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. 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.

Nursing Points for the Treatment of Children with Autism Spectrum Disorders through Endoscopic Intestinal Transplantation via Colonic Route and Washing Microbiota Transplantation

Nursing Points for the Treatment of Children with Autism Spectrum Disorders through Endoscopic Intestinal Transplantation via Colonic Route and Washing Microbiota Transplantation

Approach to Congenital Diarrhea and Enteropathies (CODEs).

Congenital diarrhea and enteropathies (CODEs) constitute a group of rare genetic disorders characterized by severe diarrhea and malabsorption in the neonatal period or early infancy. Timely diagnosis and treatment is essential to prevent life-threatening complications, including dehydration, electrolyte imbalance, and malnutrition. This review offers a simplified approach to the diagnosis of CODEs, with a specific focus on microvillus inclusion disease (MVID), congenital tufting enteropathy (CTE), congenital chloride diarrhea (CLD), and congenital sodium diarrhea (CSD).Patients with CODEs typically present with severe watery or occasionally bloody diarrhea, steatorrhea, dehydration, poor growth, and developmental delay. Therefore, it is crucial to thoroughly evaluate infants with diarrhea to rule out infectious, allergic, or anatomical causes before considering CODEs as the underlying etiology. Diagnostic investigations for CODEs encompass various modalities, including stool tests, blood tests, immunological studies, endoscopy and biopsies for histology and electron microscopy, and next-generation sequencing (NGS). NGS plays a pivotal role in identifying the genetic mutations responsible for CODEs.Treatment options for CODEs are limited, often relying on total parenteral nutrition for hydration and nutritional support. In severe cases, intestinal transplantation may be considered. The long-term prognosis varies among specific CODEs, with some patients experiencing ongoing intestinal failure and associated complications. In conclusion, the early recognition and accurate diagnosis of CODEs are of paramount importance for implementing appropriate management strategies. Further research and advancements in genetic testing hold promise for enhancing diagnostic accuracy and exploring potential targeted therapies for these rare genetic disorders.

The role of intestinal microbiota and microbial metabolites in the development of functional constipation

The main link in the pathogenesis of functional constipation (FC) with slow intestinal transit is a decrease in the motor function of the colon. Data from experimental and clinical studies indicate that the gut microbiota is involved in the regulation of colonic motility through various mechanisms. At the same time, the study of the molecular processes underlying the influence of the intestinal microbiota and its metabolites on the motor function of the colon is at an early stage. The review analyzes the literature on the role of intestinal microbiota in the development of FD, presents data on the mechanisms of action of various microbial metabolites on the motor and secretory function of the colon, and briefly describes new approaches to the treatment of FD based on modulating the composition of the intestinal microflora. FZ is accompanied by specific changes in the composition of the intestinal microbiota, and in recent years, researchers have established cause-and-effect relationships between certain enterotypes and the development of FZ. To date, the main microbial metabolites have been identified that have a stimulating or inhibitory effect on propulsive peristalsis, as well as on the intensity of secretion of anions and water by colonocytes. Approaches to optimizing the composition of the microbiota in FZ are based on the use of pro- and prebiotics, antibiotics, as well as the use of intestinal microbiota transplantation. A deeper understanding of the molecular mechanisms mediating the influence of the microbiota and its metabolites on colonic motor function may serve as the basis for the development of new approaches to the treatment of FZ.

Intestinal Autotransplantation for Locally Advanced or Locally Recurrent Colon Cancer Invading SMA

Objective: To examine the outcomes of intestinal autotransplantation (IATx) in patients with locally advanced or recurrent colon cancer (LACC or LRCC) invading the superior mesenteric artery (SMA). Background: SMA Involvement in LACC or LRCC is deemed unresectable and is associated with a poor prognosis. Combined extended resections of multiple organs together with SMA, followed by IATx may offer favorable clinical outcomes. However, data on its safety and efficacy are scarce. Design: This retrospective cohort study included patients undergoing IATx between May 2018 and December 2022 in intestinal transplant programs at two university-affiliated hospitals in China. Patients with LACC or LRCC concomitantly with SMA contact of more than 180° were included. Patients with a locoregional peritoneal, pelvic, or distal metastasis were excluded. Results: Ten patients underwent either IATx combined with pancreaticoduodenectomy (n=8) or IATx alone (n=2). Eight patients (80%) were male, and the median age was 55 years (range, 32 – 71 y). The Kaplan-Meier estimates for recurrence-free survival and overall survival at 3 years after IATx were 68% and 80%, respectively. No perioperative deaths occurred. All ten patients experienced postoperative complications including Clavien-Dindo grade I (n=1), grade II (n=4), grade IIIa (n=1), grade IIIb (n=3) and grade IVa (n=1), which comprised acute venous thromboses, upper gastrointestinal hemorrhage, anastomotic leak, gastropareses and significant pleural effusions. With an average follow-up of 23.9 months, eight patients (80%) were currently alive without evidence of disease. Conclusion: Extended resection for LACC or LRCC invading SMA can be performed safely and is associated with prolonged survival.

Plasticity of intragraft alloreactive T cell clones in human gut correlates with transplant outcomes.

The site of transition between tissue-resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity, and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single-cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells were mainly distributed to TRM, effector T (Teff)/TRM, and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to Teff/TRM clusters in association with rejection. By integrating pre- and post-transplantation (Tx) mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in the human gut, providing novel insight into TRM biology.

Nutrition care for the adult post-intestinal transplant patient.

Intestinal transplantation has emerged as an accepted treatment choice for individuals experiencing irreversible intestinal failure. This treatment is particularly relevant for those who are not candidates or have poor response to autologous gut reconstruction or trophic hormone therapy, and who can no longer be sustained on parenteral nutrition. One of the main goals of transplant is to eliminate the need for parenteral support and its associated complications, while safely restoring complete nutrition autonomy. An intestinal transplant is a complex process that goes beyond merely replacing the intestines to provide nourishment and ceasing parenteral support. It requires an integrated management approach in the pretransplant and posttransplant setting, and high-quality nutrition treatment is one of the cornerstones leading to favorable outcomes and long-term management. Since the outset of intestinal transplant in the early 2000s, there is observed improvement of achieving nutrition autonomy sooner in the initial posttransplant phase; however, the development of nutrition complications in the chronic posttransplant period remains a long-term risk. This review delineates the decision-making process and clinical protocols used to nutritionally manage and monitor pre- and post-intestine transplant patients.

Application of enzyme-linked immunosorbent assay to detect antimicrobial peptides in human intestinal lumen

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and β-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.

The impact of colonic allograft inclusion on intestinal transplantation outcomes: Results from UNOS/OPTN database analysis.

Outcomes of intestinal transplantation with colon allograft (ICTx) remain controversial. We aimed to assess the outcomes of ICTx in comparison to intestinal transplantation without colon (ITx) using the UNOS/OPTN registry database. We retrospectively reviewed 2612 patients who received primary intestinal transplants from 1998 to 2020. The rates of acute rejection (AR) within 6 months after transplant were compared between ICTx and ITx. Risk factors of 6-month AR were examined using logistic regression model by era. Furthermore, conditional graft survival was analyzed to determine long-term outcomes of ICTx. Of 2612 recipients, 506 (19.4%) received ICTx. Graft and patient survival in ICTx recipients were comparable to those in ITx recipients. White ICTx recipients had a higher incidence of AR within 6 months compared to ITx during the entire study period (p=.002), colonic inclusion did not increase the risk of 6-month AR in the past decade. ICTx recipients who experienced 6-month AR had worse graft and patient survival compared to those who did not (p<.001 and p=.004, respectively). Among patients who did not develop 6-month AR, Cox proportional hazard model analysis revealed that colonic inclusion was independently associated with improved conditional graft survival. In the recent transplant era, colonic inclusion is no longer associated with a heightened risk of 6-month AR and may provide better long-term survival compared to ITx when AR is absent. Risk adjustment for rejection and proper immunosuppressive therapy are crucial to maximize the benefits of colonic inclusion.

Nutritional outcomes following intestinal transplant: Preliminary findings from the Cambridge intestinal transplantation unit

Nutritional outcomes following intestinal transplant: Preliminary findings from the Cambridge intestinal transplantation unit

Fallo intestinal crónico secundario a síndrome de intestino corto: papel actual de la cirugía, la rehabilitación médica y el trasplante intestinal. Informe evolutivo a 16 años de manejo multidisciplinario

decades, medical treatments and surgical procedures have been incorporated, developed and improved under the name intestinal rehabilitation. When performed by multi- and interdisciplinary teams, these treatments have high success rates. Objective: The aim of present study is to describe the 16-year outcomes in the management of patients with CIF secondary to short bowel syndrome (SBS) and the role of surgery, medical rehabilitation, and transplantation. Material and methods: We conducted a retrospective analysis on a prospective database of patients treated with chronic intestinal failure due to SBS between February 2006 and March 2022. Results: A total of 492 patients (368 adults (Group A) and 124 pediatric patients (Group B)] were included. Group A: 111 patients underwent autologous gastrointestinal reconstruction surgery (AGIRS), 16 were treated with semisynthetic glucagon-like peptide-2 (sGLP2); 83% achieved rehabilitation, with 77% survival at 10 years; 6.8% (17 patients) required intestinal transplantation (ITx), with 89% independence from parenteral nutrition (PN) at 1 year and post-ITx survival of 29% at 10 years. Group B: 18 patients underwent AGIRS; 9 underwent serial transverse enteroplasty (STEP); and 6 received sGLP2; 52% were rehabilitated, with 69% survival at 10 years; 28 patients received ITx, with 69% independence from PN at 1 year and 39% survival at 10 years. Conclusion: These results highlight the central role of surgery and medical rehabilitation in the recovery of intestinal function.

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

Loss of α-smooth muscle actin immunostaining is not a useful marker for functional impairment: a comparison from patients with and without small bowel motility disorder

Abstract Introduction/Objective Prior studies have reported the loss α-smooth muscle actin (α-SMA) immunostaining in the inner circular layer of the muscularis propria in small bowel motility disorder cases, but this remains controversial with conflicting data. In this study we aimed to characterize the immunoreactivity of α-SMA expression in the muscularis propria of the small intestine, specifically jejunum, in patients with and without small bowel motility disorder. Methods/Case Report A total of 28 samples of transmural proximal jejunum biopsies from adult patients with small bowel motility disorder by manometric and/or radiologic testing and 47 control tissues were evaluated. The controls were full thickness, longitudinal tissue sections from segmental resections performed due to trauma from gunshot wound (n= 30), multi-visceral transplant for neoplasms (n= 4), liver failure with concurrent portal vein thrombosis (n= 9), and isolated intestinal transplant for Crohn disease (n= 4). Immunostaining for α-SMA was performed with appropriate controls to confirm the presence of staining in the circular and longitudinal muscle layers of the muscularis propria in each sample and recorded as retained or diminished. Results (if a Case Study enter NA) In the small bowel motility disorder and control cases, 43% (12/28) and 62% (29/47) of the cases showed no or minimal α-SMA expression in the inner circular layer with peripheral accentuation (p = 0.113), respectively. The remaining small bowel motility disorder cases (16/28, 57%) and the control group (18/47, 38%) showed retained expression of α-SMA in both layers of the muscularis propria. Conclusion Loss or diminished α-SMA expression in the inner circular layer of muscularis propria is present in similar frequency in cases with and without small bowel motility disorder and does not correlate with impairment of function.

Breast Cancer and Intestinal Microbiota Transplantation

Breast cancer has been studied relating it to the intestinal microbiota and its own microbiota. Giving a primary role to the dysbiosis that occurs in both the mammary gland and the intestine. Likewise, metabolic processes and immunological eventualities have been considered as determining factors; By the way, many of them are determined by the intestinal microbiota itself, which is given the deserved name of endocrine gland, because it acts at a distance, and it is not only the super-organ or the new organ, but the multiple studies have generated this honorable new consideration. We break down breast cancer, in order to determine the usefulness of the Intestinal Microbiota Transplant and we observe the importance of Resilience in the Intestinal Microbiota. The clinical significance of Dysbiosis, both breast and intestinal, in the genesis of the condition is emphasized and the importance, which it has, is given to Apoptosis. Generally, the pattern of the breast microbiota, in descending order, is: Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. The breast microbiota can be used as a potential biomarker. The importance of the different axes that influence the process are analyzed, such as the Gut-microbiota-brain Axis, the breast-brain axis, the cancer-microbiome-gut axis and the cancer-microbiota-immunity axis. It is pointed out how chemo and radiotherapy affect the intestinal microbiota and breast cancer, as well as antibiotics. Finally, the effect of biotics and Fecal Microbiota Transplant are determined.

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.

Hypoglycemic Effect of Trichosanthes pericarpium to Type 2 Model Diabetic Mice via Intestinal Bacteria Transplantation.

The treatment of diabetes with plant ingredients such as in Traditional Chinese Medicine (TCM) is an alternative to classical chemotherapy. This study aims to explore the hypoglycemic effect of Trichosanthes pericarpium powder (TP) and intestinal bacteria transplantation in type 2 diabetic mice. The relationship between intestinal bacteria transplantation and improvement in insulin resistance was also investigated. The polyphenols and terpenoids in the TP were identified by LC-MS/MS. Streptozotocin was used to induce a mouse model of type 2 diabetes. Diabetic mice were treated with different doses of TP and the intestinal bacteria obtained from the high-dose TP group for four weeks. As a result, FBG levels were found to be significantly reduced in diabetic mice, weight gain and organ enlargement were alleviated, and insulin resistance was significantly improved. TP administration also improved the disorder in intestinal bacteria in diabetic mice. Besides, TP can increase the liver AMPK, SIRT1, GLUT1, and GLUT4 gene expression, while down-regulated PEPCK and G6Pase gene expression suggest a potential mechanism for hypoglycemia in diabetic mice. Oral administration of Trichosanthes pericarpium powder in the treatment of diabetes may be achieved by restoring hepatic function, improving insulin resistance, and the dynamic balance of intestinal bacteria.

Adherence to recommended vaccination policies for pre- and post-solid organ transplantation patients: A national questionnaire survey in Japan

BackgroundPre-transplant vaccination is recommended for patients undergoing solid organ transplantation (SOT). While appropriate vaccination protocols are implemented at some facilities, transplantation is sometimes performed with inadequate preoperative vaccine management. Vaccination rates vary across facilities, but those of SOT centers in Japan have never been investigated. This study aimed to conduct a nationwide questionnaire survey to assess pre- and post-transplant vaccination policies among SOT facilities in Japan. MethodsThe survey was conducted from September to November 2022. All registered (n = 221) solid organ (namely, the lungs, liver, kidneys, pancreas, heart, and small intestine) transplant facilities were asked to complete a web-based survey. ResultsThe survey response rate was 70.2 %. Live and inactivated vaccines were recommended at 64.9 % and 68.9 % of the responding facilities, respectively. The following vaccines were incorporated into the vaccination protocols of facilities: pneumococcal vaccine, 31.7 % (13-valent pneumococcal conjugate vaccine) and 65.4 % (23-valent pneumococcal polysaccharide vaccine); hepatitis B virus vaccine, 67.3 %; severe acute respiratory syndrome coronavirus 2 vaccine, 73.1 %; influenza vaccine, 73.1 %; and zoster vaccines, 23.1 %. The reasons for unresponsiveness to vaccinations included inadequate time before transplantation (60.3 %), cost burden (41.1 %), high number of vaccinations (21.9 %), no recognition of the need for vaccination (17.9 %), and the requirement to explain the need for vaccination (15.2 %). ConclusionsOur study revealed gaps in vaccination practices across nationwide facilities in Japan. The findings indicate the importance of promoting scheduled efficiency and encouraging the national health system to reduce vaccine costs with the support of public subsidies.

Comparison of the effects of normothermic machine perfusion and cold storage preservation on porcine intestinal allograft regenerative potential and viability

Intestinal transplantation (IT) is the final treatment option for intestinal failure. Static cold storage (CS) is the standard preservation method used for intestinal allografts. However, CS and subsequent transplantation induce ischemia-reperfusion injury (IRI). Severe IRI impairs epithelial barrier function, including loss of intestinal stem cells (ISC), critical to epithelial regeneration. Normothermic machine perfusion (NMP) preservation of kidney and liver allografts minimizes CS-associated IRI; however, it has not been used clinically for IT. We hypothesized that intestine NMP would induce less epithelial injury and better protect the intestine’s regenerative ability when compared with CS. Full-length porcine jejunum and ileum were procured, stored at 4 °C, or perfused at 34 °C for 6 hours (T6), and transplanted. Histology was assessed following procurement (T0), T6, and 1 hour after reperfusion. Real-time quantitative reverse transcription polymerase chain reaction, immunofluorescence, and crypt culture measured ISC viability and proliferative potential. A greater number of NMP-preserved intestine recipients survived posttransplant, which correlated with significantly decreased tissue injury following 1-hour reperfusion in NMP compared with CS samples. Additionally, ISC gene expression, spheroid area, and cellular proliferation were significantly increased in NMP-T6 compared with CS-T6 intestine. NMP appears to reduce IRI and improve graft regeneration with improved ISC viability and proliferation.

Sustained elimination of parenteral support in adult patients with under 60 cm of small intestine: A case series.

Patients with short bowel syndrome (SBS) are often managed by expert multidisciplinary teams. One of the main goals in the management of SBS is the weaning of parenteral support (PS). Weaning of PS removes the risks associated with long-term central line placement and eliminates the need for intestinal transplant. Whereas several papers detail the ongoing care and management of patients with SBS who are dependent on PS, there are few reports discussing the successful weaning of PS in this patient population. We present five case studies examining weaning of PS in adult patients with <60-cm small bowel and partial or full colon who were enrolled in a multidisciplinary adult intestinal rehabilitation program. The case studies demonstrate weaning can occur >2 years after initial assessment and enrollment in an expert program. The ability of the program to focus on individualized care and frequent patient communication is key to PS weaning in patients with SBS.

Idiopathic Ileal Ulceration After Intestinal Transplantation.

Idiopathic ileal ulceration after intestinal transplantation (ITx) has been discussed infrequently and has an uncertain natural history and relation to graft rejection. Herein, we review our experience with this pathology. We retrospectively reviewed 225 ITx in 217 patients with minimum 1 y graft survival. Routine graft endoscopy was conducted up to twice weekly within the first 90 d after ITx, gradually decreasing to once yearly. Risks for ulceration over time were evaluated using Cox regression. Of 93 (41%) patients with ulcers, 50 were found within 90 d after ITx mostly via ileoscopy; delayed healing after biopsy appeared causal in the majority. Of the remaining 43 patients with ulcers found >90 d after ITx, 36 were after ileostomy closure. Multivariable modeling demonstrated within 90-d ulcer associations with increasing patient age (hazard ratio [HR], 1.027; P < 0.001) and loop ileostomy (versus Santulli ileostomy; HR, 0.271; P < 0.001). For ulcers appearing after ileostomy closure, their sole association was with absence of graft colon (HR, 7.232; P < 0.001). For ulcers requiring extended anti-microbial and anti-inflammatory therapy, associations included de novo donor-specific antibodies (HR, 3.222; P < 0.007) and nucleotide oligomerization domain mutations (HR, 2.772; P < 0.016). Whole-cohort post-ITx ulceration was not associated with either graft rejection (P = 0.161) or graft failure (P = 0.410). Idiopathic ulceration after ITx is relatively common but has little independent influence on outcome; risks include ileostomy construction, colon-free ITx, immunologic mutation, and donor sensitization.