Search

The history of intestinal transplantation can be traced back to the turn of the twentieth century. Although advancements have been made, the intestine still presents a greater challenge to transplantation than does that of other solid organs, experiencing higher rates of graft rejection and lower long-term survival. Increasingly, intestinal re-transplantation (re-ITx) is seen as a viable option and is now the fourth most common indication for ITx. Changes to immunosuppression protocols, technical modifications, and infectious disease monitoring have contributed to improved outcomes. The authors review the literature on re-ITx in regard to the history, management considerations, and future directions., Competing Interests: Disclosure The authors declare that they have no relevant or material financial interests that relate to the research described in this paper., (Published by Elsevier Inc.)

The role of angiotensin II type-1 receptor (AT1R) antibodies in intestinal transplantation (ITx) is unclear. The aims were 1) to identify the prevalence of AT1R antibodies in pediatric ITx, compared to pediatric intestinal failure (IF), and 2) to determine whether AT1R antibodies were associated with graft dysfunction. 46 serum samples from 25 ITx patients (3 isolated ITx, 22 liver-inclusive ITx) were collected during routine visits >6 months apart and during episodes of graft dysfunction as a result of infectious enteritis or rejection. For comparison, samples were collected from 7 IF control patients. AT1R antibodies were considered positive for levels >17 U/mL. The median (range) AT1R antibody level for ITx patients was 40.0 U/mL (7.2-40.0), compared to 7.0 U/mL (5.7-40.0) for IF patients (p = .02). There was a trend toward higher prevalence of AT1R antibodies in ITx compared with IF patients (68% versus 29%, p = .09). Among ITx patients, the prevalence of AT1R antibodies was not different between periods of active graft dysfunction and normal health (83% versus 67%, p = .31). For 16 patients with >2 samples, AT1R antibodies remained positive in 67% cases, developed in 14% cases, disappeared in 10% cases, and remained negative in 10% cases. The changes in AT1R antibodies did not correlate with de/sensitizing events. This is the first study of AT1R antibodies in pediatric ITx. AT1R antibodies are highly prevalent after ITx and may be triggered by immune activation associated with the transplant. However, their pathogenicity and clinical utility remain in question., (© 2021 Wiley Periodicals LLC.)

Background: Temporary ileostomy during intestinal transplantation (ITx) is the standard technique for allograft monitoring. A detailed analysis of the ITx ileostomy has never been reported., Methods: A retrospective review of a single-center ITx database was performed. The analysis was divided into ileostomy formation and takedown episodes., Results: One hundred thirty-five grafts underwent ileostomy formation, and 79 underwent ileostomy takedown. Median age at ITx was 7.7 years and weight was 23 kg. Allograft types were intestine (22%), liver/intestine (55%), multivisceral (16%), and modified multivisceral (7%). Sixty-four percent had 1-stage ITx, whereas 36% required 2-staged ITx. Final ileostomy types were end (20%), loop (10%), distal blowhole (59%), and proximal blowhole (11%). Ileostomy formation: Thirty-one grafts had complications (23%), including prolapse (26%), ischemia (16%), and parastomal hernia (19%). Twelve required surgical revision. There were no significant differences in graft type, ileostomy type, survival, and ileostomy takedown rate between grafts with and without complications. Colon inclusive grafts had higher complication rates (P = 0.002). Ileostomy takedown: Ileostomy takedown occurred at a median of 422 days post-ITx. Twenty-five complications occurred after 22 takedowns (28%), including small bowel obstruction (27%) and abscess (18%). Fifteen grafts required surgical correction. Recipients with complications had longer hospital stay (17 versus 9 d; P = 0.001) than those without complications. Graft type, ileostomy type, and survival were not different., Conclusions: The first of its kind analysis of the surgical ileostomy after ITx reveals that most recipients can undergo successful ileostomy formation/takedown, complication rates are significant but within an acceptable range, and complications do not affect survival. This study demonstrates that the routine use of transplant ostomies remains an acceptable practice after ITx. However, true analysis of risk and benefit will require a randomized control trial.

Immunophenotyping of peripheral blood mononuclear cells has been shown to be a useful, non-invasive method of predicting acute cellular rejection (ACR) following intestinal transplantation (ITx). Our objectives were to characterize differences in the T cell immunophenotype of ITx recipients in peripheral blood samples (1) collected late versus early after ITx and (1) associated with episodes of ACR and infectious enteritis. An IRB-approved, cross-sectional study of ITx recipients was performed. Peripheral blood samples were collected during normal visits and episodes of allograft dysfunction. A total of 38 patients were included in the analysis: 31 ITx recipients (87% liver-inclusive allografts) and 7 intestinal failure control patients. Of the ITx patients, 26 patients were pediatric patients (<21 years). A total of 70 samples were analyzed from ITx recipients, including 51 during normal visits and 19 during episodes of allograft dysfunction (median of 2 samples per patient; range of 1-6 samples per patient). In the late (n = 32) versus early post-ITx (n = 19) normal samples, there was a significantly higher percentage of central memory CD4 T cells (p = .001). In the ACR (n = 5) versus infectious enteritis (n = 14) samples, there was a higher percentage of CD8 T cells expressing HLA-DR (p = .002), CD57 (p < .001), and KLRG1 (p < .001) and a higher percentage of CD4 T cells expressing CD57 (p = .03). Additional studies are needed with larger cohorts to validate these changes in the T cell immunophenotype. Further elucidating T cell immunophenotypes in ITx will lead to a better understanding of immune mechanisms of allograft dysfunction, identification of potential biomarkers in ITx, and optimized selection of immunosuppressive therapies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Post-transplant lymphoproliferative disease (PTLD) has the highest incidence following intestinal transplantation (ITx). Our center has seen a recent increase in PTLD. Our aim was to review a single-center PTLD experience with a focus on clinical characteristics and outcomes. We completed a retrospective review of biopsy-proven PTLD cases using a prospectively maintained database of 115 ITx recipients transplanted between 1991 and 2014. Nineteen (17%) ITx recipients developed 25 PTLD cases during a median follow-up time of 6.4 (1.6-14.6) years. The incidence of early PTLD was 6% (n = 7). There was a trend toward increased risk of PTLD in children compared with adults (P = .11) and a significantly increased risk of PTLD in re-ITx compared with primary ITx recipients (P = .03). Most PTLD cases were diagnosed between 2010 and 2014 (n = 14). All early PTLD cases were EBV+ on in situ hybridization. Overall graft and patient survival are 68% and 74%, respectively. Second episodes of PTLD were diagnosed in 43% of surviving pediatric patients. Our program has a low incidence of early PTLD with overall excellent graft and patient survival following diagnosis. However, we have also seen a rising incidence of late PTLD. The cause of the increase is unknown as no major changes in immunosuppression protocols have occurred since 1999., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Rejection remains the leading cause of allograft loss, and a major barrier to improving long-term outcomes after intestinal transplantation. Our aim is to define the prevalence and investigate the role of donor-specific antibody (DSA) on intestinal graft outcomes., Methods: The study includes 109 transplants performed in 95 recipients at a single center. Patients were screened for DSA pretransplant, monitored regularly posttransplant and when clinically indicated using the single-antigen bead Luminex assay. Standard induction immunosuppression was with interleukin-2 receptor antagonists, and antithymocyte globulin in high-risk recipients. Maintenance regimens were tacrolimus-based., Results: Pretransplant DSA was detected in 12 (11%) recipients with 50% continuing to have circulating antibodies posttransplant. An additional 24 (25%) patients developed de novo DSA, and of these, 71% had persistent antibodies. Recipients with preformed DSA demonstrated elevated risks of early graft failure, whereas those with de novo DSA experienced accelerated graft loss once DSA was detected, reaching a 28% failure rate within 2 years. HLA-DQ mismatch is a significant risk factor for de novo DSA emergence, whereas the persistence of antibodies is predicted by DSA strength and specificity. Although inclusion of the liver in the intestinal allograft imparts an immunological advantage against rejection-related graft loss, this protective effect was lost among recipients with persistent DSA., Conclusions: The presence of DSA is associated with inferior graft outcomes among intestinal transplant recipients. An enhanced understanding of the mechanisms by which DSA causes allograft injury, and effective strategies targeting humoral immune reactivity are needed to improve long-term intestinal graft outcomes.

Objectives: Biopsies remain the criterion standard in the diagnosis of intestinal transplant (ITx) rejection, and gastrointestinal endoscopy plays a pivotal role in patient management. Herein, we describe a single-center 23-year endoscopic experience in pediatric ITx recipients., Methods: A retrospective review of endoscopy and pathology reports of all ITx recipients <18 years old transplanted between 1991 and 2013 was performed with the aim of describing the procedural indications, findings, and complications., Results: A total of 1770 endoscopic procedures within 1014 sessions were performed. A combination of esophagogastroduodenoscopy and ileoscopy was the most common procedure (36%). Increased stool output (35%) and surveillance endoscopy (32%) were the most common indications. A total of 162 episodes of biopsy-proven rejection were diagnosed. The first episode of rejection occurred at a median of 1 month after ITx. Of histology-proven rejections, 45% had normal-appearing endoscopies. The rate of procedural complications, including but not limited to bleeding and perforation, was 1.8%., Conclusions: Endoscopy with biopsy plays a significant role in the care of ITx recipients. Multiple procedures are required for graft surveillance, diagnosis of rejection, subsequent treatment, and follow-up of therapy. The gross endoscopic appearance, particularly in mild to moderate acute cellular rejection, does not correlate well with histology. Complex anatomy, complication rates that are higher than patients with non-ITx pediatric endoscopy, and timely histologic interpretation by experienced pathologists are reasons that these procedures should be performed at centers accustomed to caring for ITx recipients. The field would benefit from the development of a noninvasive biomarker to reliably and efficiently detect rejection.

Pregnancy after solid organ transplantation is becoming more common, with the largest recorded numbers in renal and liver transplant recipients. Intestinal transplantation is relatively new compared to other solid organs, and reports of successful pregnancy are far less frequent. All pregnancies reported to date in intestinal transplant recipients have been in women with stable graft function. The case reported here involves the first reported successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and dependence on both transplant immunosuppression and parenteral nutrition (PN) at the time of conception. Pregnancy was unplanned and unexpected in the setting of chronic illness and menstrual irregularities, discovered incidentally on abdominal ultrasound at approximately 18 weeks' gestation. Rapamune was held, tacrolimus continued, and PN adjusted to maintain consistent weight gain. A healthy female infant was delivered vaginally at term. Medical complications during pregnancy included anemia and need for tunneled catheter replacements. Ascites and edema were improved from baseline, with recurrence of large volume ascites shortly after delivery. Successful pregnancy is possible in the setting of transplant immunosuppression, chronic intestinal graft dysfunction, and long-term PN requirement, but close monitoring is required to ensure the health of mother and child., (Copyright © 2015 Elsevier Inc. All rights reserved.)