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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.

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.)

Purpose of Review: Sensitization to human leukocyte antigens (HLAs) limits access to potential donors and contributes to inferior graft survival after transplantation. In this article, we will review the effects of HLA-specific antibodies on intestinal transplant outcomes, and discuss considerations in the monitoring and treatment of anti-HLA antibodies., Recent Findings: Only a handful of studies has investigated the effects of donor-specific anti-HLA antibodies (DSAs) on intestinal allograft outcomes. Most have reported associations between DSA presence and rejection-related graft failure. The evolution of antibody detection methods and improvements in crossmatch testing have allowed for a systematic approach to the broadly sensitized transplant candidate, and facilitated the identification of compatible organ donors. The virtual crossmatch can be used to aid in organ allocation and avoid transplantation across preformed DSA. However, much remains unknown about the mechanisms of antibody-mediated injury in the intestinal graft, and the effectiveness of current therapies against DSA has yet to be established., Summary: On the basis of available data, we will provide recommendations for the testing and management of DSA among intestinal transplant recipients. The precise management protocol should be tailored to each individual based on immunologic risk as well as clinical status.

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.

As of September 19, 2014, 2441 cases of intestinal transplantation have been performed in 46 centers (2400 deceased, 41 living). Eight centers did more than 100 transplants. Annual case numbers peaked in 2007 (N = 198) and steadily decreased to 109 cases in 2013. Short gut syndrome (68%) and functional bowel problems (15%) are two major indications for intestinal transplantation. The 3 major types of transplants involving the intestine include: isolated intestine transplant (I); simultaneous intestine, liver, and pancreas transplant (I+L+P); and, combined intestine and liver (I+L) transplant. Graft survival has significantly improved in recent years, mainly due to improved first year graft survival. The 1-, 5-, and 10-year graft survivals were: 74%, 42%,and 26%, respectively (I); 70%, 50%, and 40%, respectively (I+L+P); and 61%, 46%, and 40%, respectively (I+L). The longest graft survivals for I, l+L+P, and l+L were 19 years, 16 years, and 23 years, respectively. Steroids, Thymoglobulin, and rituximab are 3 major induction agents used in recent years. Prograf, steroids, and Cellcept are 3 major maintenance agents. Induction recipients (68% of all patients) had a significantly lower acute rejection rate than nonrecipients before discharge (60% versus 75%, p < 0.001). Most of the patients received 2 (53%) or 3 (25%) maintenance immunosuppressants. Acute rejection episodes were usually treated with one (60%) or two agents (27%). Steroids were most commonly used (50-60%). OKT3 has been replaced with antithymocyte globulin (since 1999) and rituximab (since 2006). During 1990-2000, 94% (N = 445) of patients received ABO identical intestinal transplants, while 6% (N = 29) received ABO compatible transplants. ABO identical transplant recipients had a significantly higher 5-year graft survival rate than ABO compatible recipients (39% versus 21%, p < 0.0001). In recent years (2001- 2012), more patients received ABO compatible (N = 188, 11%) than in the early decade (p < 0.01). 5-year graft survival rates of ABO compatible transplants were lower than those of ABO identical transplants. However, the difference did not reach statistical significance (46% versus 49%, p = 0.07). The effect of ABO compatibility on graft outcome was further confirmed by Cox Analysis. ABO incompatible transplants are still rarely performed (N = 4) in intestine. In conclusion, annual case numbers of intestinal transplants have been decreasing, regardless of improved graft survival. ABO compatible intestinal transplants previously had a significantly lower graft survival rate than ABO identical transplants. However, the graft survival difference became less significant in recent years, possibly due to, or at least partly due to the use of new immunosuppressive agents.

Intestinal transplantation is a viable treatment strategy for patients with irreversible intestinal failure for whom parenteral nutrition is no longer an option. Although improvements have been made in short-term post-transplant survival outcomes, long-term allograft loss, mainly to acute or chronic rejection, remains a major obstacle to successful transplantation. In all types of solid organ transplants, there is increasing evidence that antibodies directed against human leukocyte antigens, and in particular donor-specific antibodies (DSA), contribute to acute and chronic rejection as well as allograft loss. In this single-center review of intestinal transplant recipients, we report that the presence of pretransplant circulating DSA and the de novo induction of DSA posttransplant are both associated with increased risks of allograft loss. Although the cumulative incidence of acute rejection was not significantly affected by the presence of DSA, the power of this single-center study may be limited. Prospective, multicenter studies are needed to further elucidate the role of DSA in intestinal transplant recipients. In the published literature, there is a clear link between the presence of pre-formed DSA and early injury to the mucosal vasculature of the allograft. Two groups have reported an association between pretransplant DSA and the frequency of acute rejection episodes and subsequent graft loss. Similarly, studies investigating the effects of de novo DSA have demonstrated a relationship between the presence of post-transplant circulating antibodies and the occurrence of acute rejection and the risk of allograft failure. The use of a liver-containing graft appears to facilitate the clearance of pre-formed antibodies and prevents the de novo induction of post-transplant antibodies. The most recent report stated that the de novo induction of DSA is concurrently accompanied by signs or rejection, such that the detection of circulating antibodies may signify impending graft injury, and supports the potential utility of DSA as a non-invasive biomarker for rejection in intestinal transplantation.