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.

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.

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.

Multidrug-resistant Klebsiella Pneumoniae Infection Led to Resection of the Graft in a Small Bowel Transplant Recipient: A Case Report and Review of the Literature.

BACKGROUND: Infection due to multidrug-resistant Klebsiella pneumoniae is a common cause of graft resection after small bowel transplantation. We report a failed case in which the intestinal graft was resected 18 days after the operation due to postoperative infection with multidrug-resistant K pneumoniae and a literature review of other common causes of small bowel transplantation failure have been reported. METHODS: A female, 29 years of age, underwent partial living small bowel transplantation for short bowel syndrome. After the operation, the patient was infected with multidrug-resistant K pneumoniae, even though various anti-infective regimens were employed. It further developed into sepsis and disseminated into intravascular coagulation, leading to exfoliation and necrosis of the intestinal mucosa. Finally, the intestinal graft had to be resected to save the patient's life. RESULTS: Multidrug-resistant K pneumoniae infection often affects the biological function of intestinal grafts and can even lead to necrosis. Other common causes of failure, including postoperative infection, rejection, post-transplantation lymphoproliferative disorder, graft-vs-host disease, surgical complications, and other related diseases, were also discussed throughout the literature review. CONCLUSIONS: Pathogenesis due to diverse and interrelated factors makes the survival of intestinal allografts a great challenge. Therefore, only by fully understanding and mastering the common causes of surgical failure can the success rate of small bowel transplantation be effectively improved.

A new stage of experimental surgery for organoid based intestinal regeneration - A review of organoid research and recent advance.

Small intestinal transplantation has emerged as an essential treatment for intestinal failure, but its relatively high graft rejection rate and mortality rate when compared to those of other transplanted organs has led to difficulties in post-transplantation treatment management. The recently-developed technique of creating organoids from somatic stem cells has created a challenging opportunity to develop a treatment that involves the creation of a substitute small intestine using autologous cells instead of transplanting another individual's small intestines. The remaining partial large intestine is then used as a segmental graft, and autologous small intestinal organoid transplantation is conducted on its epithelium in order to create a pedunculated hybrid graft. This is a new surgical technique for interposing with the original ileocecal region. The hybrid large intestine acquires both the lymphatic vessels that are involved in nutrient absorption and the original peristaltic function of the large intestine.This lecture touches upon the history of the development of organoid medicine, after which an introduction is provided of the revolutionary surgical technique in which a functional small intestine is created by regenerating autologous cells.The content here was introduced in a special lecture (online) at the 29th Congress of the Experimental Surgical Session of the Hungarian Surgical Society (Host: Dr. Norbert Nemeth, 9/9/2022, Budapest).

Twenty Years of Abdominal Wall Allotransplantation: A Systematic Review of the Short- and Long-Term Outcomes.

BACKGROUND: Abdominal wall allotransplantation following intestinal and multivisceral transplant procedures has proven to be successful in achieving adequate closure in patients in whom other techniques have proven inadequate. Thus far, the focus of these abdominal wall allotransplants has been on graft and overall patient survival following surgery and the implementation of immunosuppression. The purpose of this study was to review the outcomes of abdominal wall allotransplantation reported in the literature. METHODS: The PubMed database was queried, and 2595 articles were found. Search criteria used were "abdominal wall transplant" and "abdominal wall allotransplant." Of these, eight met inclusion/exclusion criteria. RESULTS: In the present study, eight publications were identified reporting abdominal wall allotransplants, for a total of 38 full-thickness abdominal wall allotransplantations performed worldwide. All studies reported abdominal wall allotransplantation in combination with visceral organ allotransplantation. Abdominal wall allotransplantations reported thus far have been nonneurotized. Abdominal wall allotransplantations have proven to be beneficial both in terms of abdominal wall closure and acting as a sentinel marker for rejection for underlying visceral organ allotransplantation. The success of abdominal wall allotransplants and their long-term survival has introduced the question of functionality and long-term durability. Cadaveric studies have shown that it is possible to neurotize abdominal wall allotransplants, and future direction toward neurotized abdominal wall allotransplantation requires tools to assess functional outcomes of these transplants. CONCLUSIONS: Abdominal wall allotransplantation is an important reconstructive option when abdominal wall closure is challenging and should be considered in combination with visceral organ allotransplantations. There may be potential benefit in neurotizing the abdominal wall allotransplant for functional use, and future studies should aim to include functional outcomes.

25 Years of a Standardized Technique for Living Donor Intestinal Transplantation: A Systematic Review.

A safe, reproducible and standardized surgical technique for intestinal procurement and transplantation from a living donor (LD) was introduced in 1997 and has been used in the majority of cases since. The key principles are: 1. procurement of 180-200 cm of distal ileum in adults (about 60-150 cm in pediatric recipients depending on age and weight) on a vascular pedicle comprising the LD ileocolic vessels or terminal branches of the superior mesenteric vessels, 2. the terminal ileum (30-40 cm of the most distal ileum), the ileocecal valve and the cecum remain with the donor to not interfere with B12-absorption and bowel transit time, 3. systemic venous drainage with anastomoses between the LD ileocolic vessels and the recipient's infrarenal aorta and vena cava, and 4. restoration of recipient bowel continuity through proximal anastomosis and distal graft ileostomy for biopsy access and graft monitoring. Recipients of a successful LD intestinal transplant become total parenteral nutrition (TPN)-independent within a few weeks posttransplant. LD vs deceased donor (DD) intestinal transplants can be performed in a more timely fashion. Hence, LD (in contrast to DD) intestinal transplants are also pre-emptive procedures in patients with advanced, but still reversible, TPN-induced liver disease and help reduce the wait-list mortality for combined DD intestinal and liver transplants. Life-saving combined LD intestinal and liver transplants, albeit rare, have also been successfully performed either simultaneously or subsequently. There have been no reported deaths or major complications of living intestinal donors. A better metabolic profile has been reported in some donors post-donation. In total, 85 documented LD intestinal transplants have been performed worldwide at over 20 different transplant centers in 12 different countries. In about 70 transplants, the standardized technique was used. There has been no difference in outcome between LD vs DD intestinal transplants. Long-term studies have shown that > 10 year of graft function is not uncommon. Since the introduction of the standardized surgical technique, LD intestinal transplantation has evolved from an experimental to an established and standardized procedure.

Current review on the role of ileostomy following intestinal transplantation.

PURPOSE OF REVIEW: This review describes the historical rationale for ostomy creation at the time of intestinal transplantation (ITx), examines the utility of endoscopy in graft monitoring, details the limitations and potential complications of endoscopy in this patient population, highlights preliminary reports of ITx without surveillance biopsy or stoma formation, and emphasizes the importance of novel biomarkers for graft monitoring. Data will be discussed from contemporary publications in the field, as well as the Intestinal Transplant Registry. RECENT FINDINGS: Significant improvements have been made in early outcomes following ITx, yet long-term survival remains challenged by rejection. Although endoscopy and biopsy are the gold-standard for graft monitoring, some centers have performed ITx recently without surveillance endoscopy or stoma formation with similar success. Others have touted the need for less-invasive, timely and accurate biomarkers as essential to help improve results. SUMMARY: The review provides a thorough overview of the emerging debate in the field of ITx regarding the importance of surveillance endoscopy and stoma formation in ITx recipients.

Update on immunosuppressive strategies in intestinal transplantation.

PURPOSE OF REVIEW: The intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to low volume of transplants and few centers with experience, there is paucity of evidence-based, standardized, and effective therapeutic regimens. We herein review the most recent data about immunosuppression, focusing on novel and emerging therapies. RECENT FINDINGS: Recent data are moving the field toward increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mammalian target of rapamycin inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for tumor necrosis factor-α inhibition, α4ß7 integrin inhibition, microbiome modulation, desensitization protocols, and tolerance induction strategies. We also highlight emerging novel therapies for GVHD, especially the promising role of Janus kinase inhibition. SUMMARY: New insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.

Closing the abdomen: update on the current surgical toolkit.

PURPOSE OF REVIEW: Achieving abdominal wall closure after intestinal transplantation (ITx) is one of the crucial surgical challenges. This problem is present in 25-50% of all transplants due to reduction in abdominal domain, fistulae and extensive adhesions due to previous surgeries. Failure to achieve closure is an independent risk factor for mortality and graft loss. The aim of this paper is to summarize the current options to achieve this. RECENT FINDINGS: Successful closure of the abdomen requires a tension-free repair. Primary closure of the fascia can be reinforced with synthetic or biological mesh. For more complex fascial defects bridging mesh, nonvascularised or vascularised rectus fascia can be utilised. If all components of the abdominal wall are affected, then a full-thickness abdominal wall transplantation may be necessary. SUMMARY: A variety of successful techniques have been described by different groups to enable abdominal wall closure after ITx. Emerging developments in preoperative imaging, reconstructive surgery and immunology have expanded the surgical toolkit available. Crucial is a tailor-made approach whereby patients with expected closure issues are identified prior to surgery and the simplest technique is chosen.

Evaluating the diagnostic value of zoom endoscopic surveillance compared to routine biopsy after intestinal transplantation.

BACKGROUND: After intestinal transplantation, close allograft monitoring especially during the early postoperative period is crucial since the intestine is a highly immunogenic organ. Current protocols are based on endoscopic and histologic examination with the latter one being linked to the risk of bleeding and perforation. AIMS: Evaluation of the diagnostic value of endoscopy utilizing magnification to predict acute cellular rejection compared to routine allograft biopsies. METHODS: Fourteen patients underwent the protocol with longitudinal zoom endoscopic and histological graft monitoring during the first year after transplantation. The intestinal mucosa was analyzed during endoscopy utilizing the SASAKI score while a minimum of two biopsies were taken during each examination. A new graduation of severity for acute cellular rejection based on the findings of the SASAKI score is established. RESULTS: Endoscopic findings of 385 examinations and more than 1000 intestinal allograft biopsies were analyzed. A total of 7 acute cellular rejection episodes in 6/14 patients occurred. Allograft endoscopy was able to diagnose ACR with a sensitivity of 76% and a specificity of 82%. CONCLUSIONS: Our results will be critical for refining protocols for allograft monitoring after intestinal transplantation thus paving the way towards less invasive measures.

Experimental study to assess the impact of vasopressors administered during maintenance of the brain-dead donation in the quality of the intestinal graft.

BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01). CONCLUSION: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.

BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3 + counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3 + mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE ( p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver ( p ˂ 0.01). CONCLUSION: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.

Renal revascularization by a pedicled intestinal segment wrapping the kidney: a new method for kidney revascularization.

BACKGROUND: Renal artery stenosis is caused by a heterogeneous group of diseases, including atherosclerosis and fibromuscular dysplasia, which can be treated medically, via endovascular techniques, or by open revascularization; however, satisfactory and effective results are not always obtained. We aimed to assess the possibility of renal revascularization by a pedicled intestinal segment wrapping the kidney. METHODS: Five dogs were operated on at three steps. At the first step, laparotomy was performed, and the right kidney was released. Subsequently, an 8-10 cm segment of jejunum was separated longitudinally, and mucosectomy was done. This intestinal patch wrapped up the kidney. After eight weeks, the kidney and the intestinal patch were analyzed, and the renal artery was ligated. After four weeks, the kidney and the intestinal patch were sent for pathological evaluation. RESULTS: At the 12th week of evaluation, no evidence of abscess formation or collection was seen. All kidneys had a normal color, consistency, and size. All renal cells were alive, and neither atrophy nor necrosis was seen. Glomerulus and tubules were intact, and no inflammatory change was visible. Furthermore, thick wall vasculature was inspected in a fibromuscular tissue, rising from the intestinal flap toward the kidney. One of the dogs expired due to peritonitis and sepsis in the fifth week. CONCLUSION: In our study, indirect perfusion of the kidney by an intestinal patch was achieved successfully. This represents new hope in patients suffering from chronic renal failure who underwent former medical and surgical interventions with undesirable results.

Describing universal Strongyloides serologic screening among pediatric intestinal and liver transplant recipients.

BACKGROUND: Strongyloides spp hyperinfections are a worldwide phenomenon that proves fatal for solid organ transplant recipients. Screening protocols to guide prophylaxis management vary institution to institution from universal to epidemiology driven. Our institution initiated a universal screening protocol regardless of travel history and exposure to ensure no cases were missed. METHODS: In this study, we describe the outcomes of three Strongyloides sero-positive children whom underwent intestinal or liver transplantation and the experience of universal screening at a tertiary care county hospital in South Florida. RESULTS: Among the 66 intestine and liver pediatric transplant recipients who were screened for Strongyloides antibodies, only three were identified to be sero-positive via the screening mechanism. Two of three had significant epidemiology risk factors. None of the patients reviewed were found to have developed hyperinfection. However, reflecting on the experience represented by our series of pediatric patients, the risk of any complication related to Strongyloides status appears low. Even among this South Florida population whom come from or travel to endemic regions are in contact with sero-positive individuals, very few illustrate sero-positivity. CONCLUSION: While institutions continue to analyze the cost-benefit of universal testing vs. universal prophylaxis vs. targeted screening, the decision must encompass the patient population, rolling cumulative incidence, and morbidity and mortality related to this disease.

Primary effusion lymphoma occurring in the setting of transplanted patients: a systematic review of a rare, life-threatening post-transplantation occurrence.

BACKGROUND: Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed. METHODS: We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms "primary effusion lymphoma" and "post-transplant". RESULTS: Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted. CONCLUSIONS: Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.

Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation.

In humans receiving intestinal transplantation (ITx), long-term multilineage blood chimerism often develops. Donor T cell macrochimerism (≥4%) frequently occurs without graft-versus-host disease (GVHD) and is associated with reduced rejection. Here we demonstrate that patients with macrochimerism had high graft-versus-host (GvH) to host-versus-graft (HvG) T cell clonal ratios in their allografts. These GvH clones entered the circulation, where their peak levels were associated with declines in HvG clones early after transplant, suggesting that GvH reactions may contribute to chimerism and control HvG responses without causing GVHD. Consistently, donor-derived T cells, including GvH clones, and CD34+ hematopoietic stem and progenitor cells (HSPCs) were simultaneously detected in the recipients' BM more than 100 days after transplant. Individual GvH clones appeared in ileal mucosa or PBMCs before detection in recipient BM, consistent with an intestinal mucosal origin, where donor GvH-reactive T cells expanded early upon entry of recipient APCs into the graft. These results, combined with cytotoxic single-cell transcriptional profiles of donor T cells in recipient BM, suggest that tissue-resident GvH-reactive donor T cells migrated into the recipient circulation and BM, where they destroyed recipient hematopoietic cells through cytolytic effector functions and promoted engraftment of graft-derived HSPCs that maintain chimerism. These mechanisms suggest an approach to achieving intestinal allograft tolerance.

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. METHODS: Fifty-five patients with CIPO, 23 (42%) children and 32 (58%) adults, underwent GT and were prospectively studied. All patients suffered gut failure, received HPN, and experienced life-threatening complications. The 55 patients received 62 allografts; 43 (67%) liver-free and 19 (33%) liver-contained with 7 (13%) retransplants. Hindgut reconstruction was adopted in 1993 and preservation of native spleen was introduced in 1999. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 41 (75%). RESULTS: Patient survival was 89% at 1 year and 69% at 5 years with respective graft survival of 87% and 56%. Retransplantation was successful in 86%. Adults experienced better patient (P = 0.23) and graft (P = 0.08) survival with lower incidence of post-transplant lymphoproliferative disorder (P = 0.09) and graft versus host disease (P = 0.002). Antilymphocyte pretreatment improved overall patient (P = 0.005) and graft (P = 0.069) survival. The initially restored nutritional autonomy was sustainable in 23 (70%) of 33 long-term survivors with improved quality of life. The remaining 10 recipients required reinstitution of HPN due to allograft enterectomy (n = 3) or gut dysfunction (n = 7). Disease recurrence was highly suspected in 4 (7%) recipients. CONCLUSIONS: GT is life-saving for patients with end-stage CIPO and HPN-associated complications. Long-term survival is achievable with better quality of life and low risk of disease recurrence.

Cost-effectiveness of Intestinal Transplantation Compared to Parenteral Nutrition in Adults.

BACKGROUND: Intestinal transplantation (ITx) is the most expensive abdominal organ transplant. Detailed studies about exact costs and cost-effectiveness compared to home parenteral nutrition (HPN) therapy in chronic intestinal failure are lacking. The aim is to provide an in-depth analysis of ITx costs and evaluate cost-effectiveness compared to HPN. METHODS: To calculate costs before and after ITx, costs were analyzed in 12 adult patients. To calculate the costs of patients with uncomplicated chronic intestinal failure, 28 adults, stable HPN patients were studied. Total costs including surgery, admissions, diagnostics, HPN therapy, medication, and ambulatory care were included. Median (range) costs are given. RESULTS: Costs before ITx were €69 160 (€60 682-90 891) in year 2, and €104 146 (€83 854-186 412) in year 1. After ITx, costs were €172 133 (€122 483-351 407) in the 1st year, €40 619 (€3905-113 154) in the 2nd year, and dropped to €15 743 (€4408-138 906) in the 3rd year. In stable HPN patients, the costs were €83 402 (€35 364-169 146) in the 1st year, €70 945 (€31 955-117 913) in the 2nd year, and stabilized to €60 242 (€29 161-238 136) in the 3rd year. CONCLUSIONS: ITx, although initially very expensive, is cost-effective compared to HPN in adults by year 4, and cost-saving by year 5.

Trisomy 3, a sole recurrent cytogenetic abnormality in pediatric polymorphic post-transplant lymphoproliferative disorder (PTLD).

Trisomy 3 has been previously reported in association with T-cell lymphomas and less commonly in different types of non-Hodgkin B-cell lymphomas. Trisomy 3 has also been reported in two cases of pediatric post-transplant lymphoproliferative disorder (PTLD). We present comprehensive clinicopathologic review of two pediatric patients with cardiac and liver/intestinal allografts that developed polymorphic PTLD characterized by trisomy 3. Both patients had Epstein-Barr virus (EBV) viremia and EBV was positive in tissue by EBER in situ hybridization. Using karyotype analysis and fluorescence in situ hybridization, we identified trisomy 3 in both patients. Both patients responded to treatment and are now free of the PTLD. Trisomy 3, an uncommon cytogenetic finding in pediatric polymorphic PTLD, may be a recurrent cytogenetic aberration if confirmed in a larger study of pediatric PTLDs. Further clinical follow up might help stratify significance of trisomy 3 as a prognostic factor.

Evaluation of transplantation sites for human intestinal organoids.

Our group has developed two transplantation models for the engraftment of Human Intestinal Organoids (HIOs): the renal subcapsular space (RSS) and the mesentery each with specific benefits for study. While engraftment at both sites generates laminated intestinal structures, a direct comparison between models has not yet been performed. Embryonic stem cells were differentiated into HIOs, as previously described. HIOs from the same batch were transplanted on the same day into either the RSS or mesentery. 10 weeks were allowed for engraftment and differentiation, at which time they were harvested and assessed. Metrics for comparison included: mortality, engraftment rate, gross size, number and grade of lumens, and expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism. Mortality was significantly increased when undergoing mesentery transplantation, however engraftment was significantly higher. Graft sizes were similar between groups. Morphometric parameters were similar between groups, however m-tHIOs presented with significantly fewer lumens than k-tHIO. Transcript and protein level expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism were similar between groups. Transplantation into both sites yields viable tissue of similar quality based on our assessments with enhanced engraftment and a dominant lumen for uniform study benefiting the mesenteric site and survival benefiting RSS.