Outcomes of Portosystemic Shunts in Children with and without Liver Transplantation.

Purpose: Limited data exist regarding outcome and morbidity associated with portosystemic shunts in the pediatric transplant population. Our study assesses the outcomes of pediatric patients who underwent a portosystemic shunt procedure, both with and without liver transplantation (LT). Methods: This study retrospectively reviewed the medical records of pediatric patients aged 0-19 years who underwent shunt placement between 2003 and 2017 at a tertiary care center. The analysis included cases of shunt placement with or without LT. Results: A total of 13 pediatric patients were included in the study with median age of 8.8 years. Among the cases, 11 out of 13 (84.6%) underwent splenorenal shunt, 1 (7.7%) underwent a mesocaval shunt, and another 1 (7.7%) underwent a Modified Rex (mesoportal) shunt. Additionally, 5 out of 13 (38.5%) patients had LT, with 4 out of 5 (80.0%) receiving the transplant before shunt placement, and 1 out of 5 (20.0%) receiving it after shunt placement. Gastrointestinal bleeding resulting from portal hypertension was the indication in all cases. A total of 10 complications were reported in 5 patients; the most common complication was anemia in 3 (23.1%) patients. At the most recent follow-up visit, the shunts were functional without encephalopathy, and no deaths were reported. Conclusion: Shunt placement plays a crucial role in the management of patients with portal hypertension. Our study demonstrates favorable long-term outcomes in pediatric patients who underwent shunt placement. Long term shunt outcomes were similar and unremarkable in patients with LT and without LT.

Current Advances in Graft-versus-host Disease After Intestinal Transplantation.

Graft-versus-host disease (GvHD) remains a potentially fatal complication following intestinal transplant (ITx). Over the past decade, advances in the understanding of the pathophysiology of this complex immunological phenomenon have led to the reassessment of the host systemic immune response and have created a gateway for novel preventive and therapeutic strategies. Although sufficient evidence dictates the use of corticosteroids as a first-line option, the treatment for refractory disease remains contentious and lacks a standardized therapeutic approach. Timely diagnosis remains crucial, and the advent of chimerism detection and immunological biomarkers have transformed the identification, prognostication, and potential for survival after GvHD in ITx. The objectives of the following review aim to discuss the clinical and diagnostic features, pathophysiology, advances in immune biomarkers, as well as therapeutic opportunities in the prevention and treatment of GvHD in ITx.

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.

Idiopathic Ileal Ulceration After Intestinal Transplantation.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Effects of Teduglutide on Diarrhea in Pediatric Patients with Short Bowel Syndrome-Associated Intestinal Failure.

OBJECTIVES: This post-hoc analysis evaluated the effect of teduglutide treatment on diarrhea in patients with short bowel syndrome-associated intestinal failure (SBS-IF). METHODS: Data from 2 open-label, multicenter, phase 3 pediatric SBS-IF clinical trials of teduglutide (NCT01952080 and NCT02682381) were pooled where possible. The primary objective was to evaluate the change in stool consistency, frequency, and volume from baseline to weeks 12 and 24 of treatment in patients who received any teduglutide dose from both studies ("total teduglutide"). Safety assessments included gastrointestinal adverse event reporting. RESULTS: Overall, 101 patients were analyzed. Among the total teduglutide group (n = 87), there were significant changes from baseline to weeks 12 and 24 in mean (standard error) Bristol Stool Form Scale (BSFS) score [-1.8 (0.26; P < 0.0001) and -2.2 (0.27; P < 0.0001), respectively], parenteral nutrition and/or intravenous fluid (PN/IV) volume [-16.9 (1.7; P < 0.0001) and -20.1 (2.3; P < 0.0001) mL/kg/day, respectively], and enteral nutrition volume [9.2 (1.7; P < 0.0001) and 9.6 (2.3; P = 0.0002) mL/kg/day, respectively]. Among patients in the standard of care group (n = 14) there were numerical changes in BSFS score, and enteral nutrition volume at weeks 12 and 24; significant changes in PN/IV volume [-6.9 (1.5) mL/kg/day; P = 0.0041] were observed at 24 weeks, but not at 12 weeks. CONCLUSION: In this post-hoc analysis, short-term treatment with teduglutide was associated with improved stool consistency, as well as trends towards reductions in PN/IV requirements and advancements in enteral nutrition volume in children with SBS-IF. Further research assessing the impact of patient-level factors on stool characteristics when using teduglutide is warranted.

Mismatch epitope load predicts de novo-DSA-free survival in pediatric liver transplantation.

BACKGROUND: Our knowledge of de novo anti-HLA donor-specific antibodies (dnDSA) in liver transplantation continues to be defined. We hypothesized that differences of HLA-DR/DQ mismatches can improve precision in alloimmune risk categorization and be applied to tailor immunosuppression. METHODS: A retrospective chart review of 244 pediatric patients consecutively transplanted at our center between 2003 and 2019 was performed to identify patients tested for dnDSA. Records were queried for: demographics, pre-transplant diagnosis, biopsy-proven T-cell-mediated rejection (TCMR), radiology proven biliary complications, tacrolimus trough levels, dnDSA characteristics, and HLA typing. The eplet mismatch analyses were performed using HLAMatchmaker™ 3.1. All statistical analyses were conducted using R software version 3.40. RESULTS: There were 99 dnDSA-negative patients and 73 dnDSA-positive patients (n = 70 against class II and n = 3 against class I and II). ROC analysis identified optimal cutoff of eplet mismatch load for dnDSA and defined risk groups for an alloimmune outcome. Kaplan-Meier curves and log-rank tests showed high eplet mismatch load was associated with shorter dnDSA-free survival (log-rank p = .001). Multivariable Cox regression models showed that tacrolimus coefficient of variation and tacrolimus mean levels were significantly associated with dnDSA-free survival (p < .001 and p = .036). Fisher's exact test showed that dnDSA was associated with an increased likelihood of TCMR (OR 14.94; 95% CI 3.65 - 61.19; p < .001). Patients without TCMR were more likely to have dnDSA to HLA-DQ7 and less likely to have dnDSA to HLA-DQ2 (p = .03, p = .080). CONCLUSIONS: Mismatched epitope load predicts dnDSA-free survival in pediatric liver transplant, while dnDSA specificity may determine alloimmune outcome.

Graft Versus Host Disease After Intestinal Transplantation: A Single-center Experience.

BACKGROUND: Graft versus host disease (GVHD) is an uncommon but highly morbid complication of intestinal transplantation (ITx). In this study, we reviewed our 17-y experience with GVHD focusing on factors predicting GVHD occurrence and survival. METHODS: Retrospective review of 271 patients who received 1 or more ITx since program inception in 2003 with survival analysis using Cox proportional hazard modeling. RESULTS: Of 271 patients, 28 developed GHVD 34 (18-66) d after ITx presenting with rash or rash with fever in 26, rectosigmoid disease in 1, and hemolysis in 1; other sites, mainly rectosigmoid colon, were involved in 13. Initial skin biopsy demonstrated classic findings in 6, compatible findings in 14, and no abnormalities in 2. Additional sites of GVHD later emerged in 14. Of the 28 patients, 16 died largely from sepsis, the only independent hazard for death (hazard ratio [HR], 37.4181; P = 0.0008). Significant (P < 0.0500) independent hazards for occurrence of GVHD in adults were pre-ITx functional intestinal failure (IF) (HR, 15.2448) and non-IF diagnosis (HR, 20.9952) and early post-ITx sirolimus therapy (HR, 0.0956); independent hazards in children were non-IF diagnosis (HR, 4.3990), retransplantation (HR, 4.6401), donor:recipient age ratio (HR, 7.3190), and graft colon omission (HR, 0.1886). Variant transplant operation was not an independent GVHD hazard. CONCLUSIONS: Initial diagnosis of GVHD after ITx remains largely clinical, supported but not often confirmed by skin biopsy. Although GVHD risk is mainly recipient-driven, changes in donor selection and immunosuppression practice may reduce incidence and improve survival.

Operational tolerance in intestinal transplantation.

By presenting the first case report of true operational tolerance in an intestinal transplant patient, we aim to demonstrate that tolerance is possible in a field that has been hampered by suboptimal outcomes. Although operational tolerance has been achieved in liver and kidney transplantation, and some intestinal transplant patients have been able to decrease immunosuppression, this is the first instance of true operational tolerance after complete cessation of immunosuppression. A patient received a deceased-donor small intestinal and colon allograft with standard immunosuppressive treatment, achieving excellent graft function after overcoming a graft-versus-host-disease episode 5 months posttransplant. Four years later, against medical advice, the patient discontinued all immunosuppression. During follow-up visits 2 and 3 years after cessation of immunosuppression, the patient exhibited normal graft function with full enteral autonomy and without histological or endoscopic signs of rejection. Mechanistic analysis demonstrated immune competence against third party antigen, with in vitro evidence of donor-specific hyporesponsiveness in the absence of donor macrochimerism. This proof of principle case can stimulate future mechanistic studies on diagnostic and therapeutic strategies, for example, cellular therapy trials, that can lead to minimization or elimination of immunosuppression and, it is hoped, help revitalize the field of intestinal transplantation.

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure: Pooled Analysis of 4 Clinical Studies.

BACKGROUND: This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). METHODS: Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. RESULTS: Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. CONCLUSION: Based on integrated data from 4 clinical studies, including long-term follow-up for ≤161 weeks, teduglutide had a safety profile consistent with the individual core pediatric studies and as expected for pediatric patients with SBS-IF who never received teduglutide. The most frequent AEs reflected treatment with teduglutide, complications of the underlying disease, and typical childhood illnesses.

Factors Associated With 5- and 10-Year Survival After Intestinal Transplantation in Infants and Children.

OBJECTIVES: Intestinal transplantation is an option for permanent intestinal failure with parenteral nutrition intolerance. We sought to determine long-term intestinal graft survival in pediatric patients at our center and to identify factors influencing survival. METHODS: Retrospective chart review of 86 patients transplanted between 2003 and 2013, targeting potential explanatory variables related to demographics, perioperative factors, and postoperative complications. RESULTS: Intestinal graft survival was 71% and 65% after 5 and 10 years, respectively. Five-year graft survival was attained in 79% of patients with a history of anatomic intestinal failure compared with 45% with functional intestinal failure (P = 0.0055). Compared with nonsurvival, 5-year graft survival was also associated with reduced incidences of graft-versus-host disease (2% vs 16%, P = 0.0237), post-transplant lymphoproliferative disorder (3% vs 24%, P = 0.0067), and de novo donor-specific antibodies (19% vs 57%, P = 0.0451) plus a lower donor-recipient weight ratio (median 0.727 vs 0.923, P = 0.0316). Factors not associated with 5-year intestinal graft survival included graft rejection of any severity and inclusion of a liver graft. Factors associated with graft survival at 10 years were similar to those at 5 years. CONCLUSIONS: In our experience, outcomes in pediatric intestinal transplantation have improved substantially for anatomic but not functional intestinal failure. Graft survival depends on avoidance of severe infectious and immunological complications including GVHD, whereas inclusion of a liver graft provides no obvious survival benefit. Reduced success with functional intestinal failure may reflect inherently increased susceptibility to complications in this group.

Human norovirus targets enteroendocrine epithelial cells in the small intestine.

Human noroviruses are a major cause of diarrheal illness, but pathogenesis is poorly understood. Here, we investigate the cellular tropism of norovirus in specimens from four immunocompromised patients. Abundant norovirus antigen and RNA are detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. Negative-sense viral RNA, a marker of active viral replication, is found predominantly in intestinal epithelial cells, with chromogranin A-positive enteroendocrine cells (EECs) identified as a permissive cell type in this patient. These findings are consistent with the detection of norovirus-positive EECs in the other three immunocompromised patients. Investigation of the signaling pathways induced in EECs that mediate communication between the gut and brain may clarify mechanisms of pathogenesis and lead to the development of in vitro model systems in which to evaluate norovirus vaccines and treatment.

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study.

BACKGROUND: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). METHODS: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24. RESULTS: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. CONCLUSION: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

New Insights Into the Indications for Intestinal Transplantation: Consensus in the Year 2019.

In 2001, a Statement was published that described indications for intestinal transplantation in patients with intestinal failure expected to require parenteral nutrition indefinitely. Since 2001, advances in the management of intestinal failure including transplantation and patient survival, both on extended parenteral nutrition and after transplantation, have improved, leading to a reduction in the number of intestinal transplants worldwide from a peak of 270 per year in 2008 to 149 per year in 2017. These changes suggest that the original 2001 Statement requires reassessment. All patients with permanent intestinal failure should be managed by dedicated multidisciplinary intestinal rehabilitation teams. Under care of these teams, patients should be considered for intestinal transplantation in the event of progressive intestinal failure-associated liver disease, progressive loss of central vein access, and repeated life-threatening central venous catheter-associated infections requiring critical care. Additional indications for transplantation include large desmoid tumors and other intra-abdominal tumors with reasonable expectation of posttransplant cure, extensive mesenteric vein thrombosis and intestinal infarction, total intestinal aganglionosis, and nonrecoverable congenital secretory diarrhea. Quality of life typically improves after successful intestinal transplantation and may support the decision to proceed with transplantation when other indications are present. However, the requirement for life-long immunosuppression and its associated side effects preclude intestinal transplantation if motivated only by an expectation of improved quality of life. Increasing experience with intestinal transplantation and critical appraisal of transplant outcomes including graft survival and patient quality of life together with potential advances in immunosuppression can be expected to influence transplant practices in the future.

Tandem Orthotopic Living Donor Liver Transplantation Followed by Same Donor Haploidentical Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency.

BACKGROUND: An 11-year-old girl with dedicator of cytokinesis 8 (DOCK8) deficiency was proposed for potentially curative hematopoietic stem cell transplantation (HSCT), the donor being her haploidentical mother. However, end-stage liver disease caused by chronic Cryptosporidium infection required liver transplantation before HSCT. METHODS: Consequently, a staged approach of a sequential liver transplant followed by a HSCT was planned with her mother as the donor for both liver and HSCT. RESULTS: The patient successfully underwent a left-lobe orthotopic liver transplant; however, she developed a biliary leak delaying the HSCT. Notably, the recipient demonstrated 3% donor lymphocyte chimerism in her peripheral blood immediately before HSCT. Haploidentical-related donor HSCT performed 2 months after liver transplantation was complicated by the development of acyclovir-resistant herpes simplex virus viremia, primary graft failure, and sinusoidal obstruction syndrome. The patient died from sinusoidal obstruction syndrome-associated multiorgan failure with Candida sepsis on day +40 following HSCT. CONCLUSIONS: We discuss the many considerations inherent to planning for HSCT preceded by liver transplant in patients with primary immunodeficiencies, including the role of prolonged immunosuppression and the risk of infection before immune reconstitution. We also discuss the implications of potential recipient sensitization against donor stem cells precipitated by exposure of the recipient to the donor lymphocytes from the transplanted organ.

Long-term survival in visceral transplant recipients in the new era: A single-center experience.

There is a paucity of data on long-term outcomes following visceral transplantation in the contemporary era. This is a single-center retrospective analysis of all visceral allograft recipients who underwent transplant between November 2003 and December 2013 with at least 3-year follow-up data. Clinical data from a prospectively maintained database were used to assess outcomes including patient and graft survival. Of 174 recipients, 90 were adults and 84 were pediatric patients. Types of visceral transplants were isolated intestinal transplant (56.3%), combined liver-intestinal transplant (25.3%), multivisceral transplant (16.1%), and modified multivisceral transplant (2.3%). Three-, 5-, and 10-year overall patient survival was 69.5%, 66%, and 63%, respectively, while 3-, 5-, and 10-year overall graft survival was 67%, 62%, and 61%, respectively. In multivariable analysis, significant predictors of survival included pediatric recipient (P = .001), donor/recipient weight ratio <0.9 (P = .008), no episodes of severe acute rejection (P = .021), cold ischemia time <8 hours (P = .014), and shorter hospital stay (P = .0001). In conclusion, visceral transplantation remains a good option for treatment of end-stage intestinal failure with parenteral nutritional complications. Proper graft selection, shorter cold ischemia time, and improvement of immunosuppression regimens could significantly improve the long-term survival.

Fecal pancreatic elastase-1 in the evaluation of pancreatic function after pediatric intestinal transplantation.

Fat malabsorption is common after SBT. To identify whether anatomic variant transplants differ in occurrence of exocrine pancreatic insufficiency that could contribute to fat malabsorption, we measured FPE repeatedly in 54 recipients of a SBT, ages 6.2 to 320 months. FPE determination most distant from SBT was 6.1 years. Of the 54, 39% received an isolated intestinal graft (native pancreas only), 48% received an en bloc liver-intestinal-pancreas graft (native and graft pancreas), and 13% received a multivisceral graft (graft pancreas only). Initial FPE was normal (>200 µg/g) in 15 of the 54 at a median of 22 (11-61) days after SBT. Recipients of a liver-intestine-pancreas transplant were more likely to have normal FPE within 30 days after SBT than were isolated intestinal or multivisceral transplant recipients (47%, 19%, and 0%, respectively, P = .049). Of the remaining 39 patients, 34 eventually demonstrated a normal FPE at a median of 168 (31-943) days after SBT. Type of SBT did not influence the likelihood of achieving a normal FPE level or time when it occurred. Five (9%) patients failed to achieve normal FPE, including 3 who died within 2 years after SBT. In conclusion, possessing both graft and native pancreas as in transplantation of an en bloc liver-intestinal-pancreas graft facilitates early normalization of FPE that eventually occurs in most patients irrespective of transplant type. Failure to recover normal pancreatic function may be associated with severe post-transplant complications.

Visceral transplantation in patients with intestinal-failure associated liver disease: Evolving indications, graft selection, and outcomes.

Intestinal failure (IF)-associated liver disease (IFALD) is widely recognized as a lethal complication of long-term parenteral nutrition. The pathophysiology of IFALD is poorly understood but appears to be multifactorial and related to the inflammatory state in the patient with IF. Visceral transplant for IFALD includes variants of intestine, liver, or combined liver-intestine allografts. Graft selection for an individual patient depends on the etiology of IF, abdominal and vascular anatomy, severity of IFALD, and potential for intestinal rehabilitation. The past decade has witnessed dramatic improvement in the management of IFALD, principally due to improved lipid emulsion formulations and the multidisciplinary care of the patient with IF. As the recognition and treatment of IFALD continue to improve, the requirement of liver-inclusive visceral grafts appears to be decreasing, representing a paradigm shift in the care of the patient with IF. This review highlights the current indications, graft selection, and outcomes of visceral transplantation for IFALD.

The use of vascular homografts in pediatric small bowel transplantation: Single-center experience over a decade.

Intestinal transplantation in children has evolved with more isolated small intestine transplants being performed compared to combined liver-intestine transplants. Consequently, surgical techniques have changed, frequently requiring the use of vascular homografts of small caliber to revascularize the isolated small intestine, the impact of which on outcomes is unknown. Among 106 pediatric intestine and multivisceral transplants performed at our center since 2003, 33 recipients of an isolated small intestine graft were included in this study. Outcome parameters were thrombotic complications, graft, and patient survival. A total of 29 of 33 (87.9%) patients required arterial and/or venous homografts from the same donor, mainly iliac or carotid artery and iliac or innominate vein, respectively (donor's median age 1.1 years [2 months to 23 years], median weight 10 kg [14.7-48.5]). Post-transplant, there were three acute arterial homograft thromboses and one venous thrombosis resulting in two peri-operative graft salvages and two graft losses. Three of four thromboses occurred in patients with primary hypercoagulable state, including the two graft losses. Overall, at a median of 4.1 years (1-10.2) from transplant, 29 of 33 (88%) patients are alive with 26 of 33 (79%) functioning grafts. The procurement of intact, size-matched donor vessels and the management of effective post-transplant anticoagulation are critical.

Meeting Report of the XIV International Small Bowel Transplant Symposium: Summary of Presentations, Workshops, and Debates From a Comprehensive Meeting on Intestinal Failure, Rehabilitation, and Transplantation, Buenos Aires, Argentina, June 10-13, 2015.

The 2015 meeting of the Intestinal Transplant Association was held in Buenos Aires, Argentina. This was the 14th International Small Bowel Transplant Symposium, and it was the first meeting organized as a joint venture of the Transplantation Society, the Intestinal Transplant Association, and the Argentinean Transplant Society (Sociedad Argentina de Trasplantes). Innovative aspects of the classic meeting format included workshops sessions, debates, and multicenter studies. This report highlights the most prominent scientific contributions and results of the first such symposium in a Latin American country.

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation.

FV is primarily produced in the liver, and congenital FV deficiency is a disorder with an incidence of one in 1 million. Standard care is to treat severe bleeding phenotypes with FFP as there is no recombinant or plasma-derived FV concentrate. We present a case of a neonate with known severe FV deficiency diagnosed after prolonged bleeding after circumcision who represented at age 2 months with a large left intraparenchymal hemorrhage. His bleed was treated with FFP, platelet transfusion, recombinant VIIa, and emergent evacuation. He was maintained on plasma infusions but was unable to space his infusions beyond 48 hours. Liver transplantation was considered as a definitive treatment for this condition. While awaiting a suitable liver, his FV trough levels occasionally dropped below 5%, and he suffered from a second acute intracranial bleed. He received an orthotopic liver transplant at age 5 months, resulting in correction of his FV levels. He has not required any plasma infusions post-transplantation and has had no further bleeding episodes. Liver transplantation should be considered as definitive treatment early in the course for patients with severe FV deficiency and first time life-threatening bleed.