Growing experience of surgical gut rehabilitation: essential role in the management of gut failure in adult patients.

PURPOSE OF REVIEW: With the inherent therapeutic limitations of gut transplantation, the concept of surgical gut rehabilitation was introduced to restore nutritional autonomy in pediatric patients. With favorable outcomes in these young patients, there has been increasing interest in the applicability of gut rehabilitative surgery to a growing population of adults with gut failure due to various etiologies. We aim to review the current status of surgical gut rehabilitation for adult gut failure patients in the era of multidisciplinary gut rehabilitation and transplantation. RECENT FINDINGS: Indications for surgical gut rehabilitation have been gradually expanding, with gut failure after bariatric surgery recently added. Serial transverse enteroplasty (STEP) has been used with favorable outcomes in adult patients, including those with intrinsic intestinal disease. Autologous gut reconstruction (AGR) is the most frequently used surgical rehabilitative method; its outcome is further improved with conjunctive use of bowel lengthening and enterocyte growth factor as a part of comprehensive gut rehabilitation. SUMMARY: Accumulated experiences have validated the efficacy of gut rehabilitation for survival, nutritional autonomy, and quality of life in adults with gut failure of various etiology. Further progress is expected with growing experience around the world.

Blockade or deficiency of PD-L1 expression in intestinal allograft accelerates graft tissue injury in mice.

The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by severe cellular infiltrations, massive destruction of villi, and increased crypt apoptosis in the graft. Interestingly, PD-L1-/- allografts were more severely rejected than wild-type allografts, but the presence or absence of PD-L1 in recipients did not affect the degree of allograft injury. PD-L1-/- allografts showed increased infiltrating Ly6G+ and CD11b+ cells in lamina propria on day 4, whereas the degree of CD4+ or CD8+ T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1-/- allografts had increased mRNA expressions of Cxcr2, S100a8/9, Nox1, IL1rL1, IL1r2, and Nos2 in the lamina propria cells on day 4. Taken together, study results suggest that PD-L1 expression in the intestinal allograft, but not in the recipient, plays a critical role in mitigating allograft tissue damage in the early phase after transplantation. The PD-1/PD-L1 interaction may contribute to immune regulation of the intestinal allograft via the innate immune system.

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.

Five Hundred Patients With Gut Malrotation: Thirty Years of Experience With the Introduction of a New Surgical Procedure.

OBJECTIVES: Define clinical spectrum and long-term outcomes of gut malrotation. With new insights, an innovative procedure was introduced and predictive models were established. METHODS: Over 30-years, 500 patients were managed at 2 institutions. Of these, 274 (55%) were children at time of diagnosis. At referral, 204 (41%) patients suffered midgut-loss and the remaining 296 (59%) had intact gut with a wide range of digestive symptoms. With midgut-loss, 189 (93%) patients underwent surgery with gut transplantation in 174 (92%) including 16 of 31 (16%) who had autologous gut reconstruction. Ladd's procedure was documented in 192 (38%) patients with recurrent or de novo volvulus in 41 (21%). For 80 patients with disabling gastrointestinal symptoms, gut malrotation correction (GMC) surgery "Kareem's procedure" was offered with completion of the 270° embryonic counterclockwise-rotation, reversal of vascular-inversion, and fixation of mesenteric-attachments. Concomitant colonic dysmotility was observed in 25 (31%) patients. RESULTS: The cumulative risk of midgut-loss increased with volvulus, prematurity, gastroschisis, and intestinal atresia whereas reduced with Ladd's and increasing age. Transplant cumulative survival was 63% at 10-years and 54% at 20-years with best outcome among infants and liver-containing allografts. Autologous gut reconstruction achieved 78% and GMC had 100% 10-year survival. Ladd's was associated with 21% recurrent/de novo volvulus and worsening (P > 0.05) of the preoperative National Institute of Health patient-reported outcomes measurement information system gastrointestinal symptom scales. GMC significantly (P ≤ 0.001) improved all of the symptomatology domains with no technical complications or development of volvulus. GMC improved quality of life with restored nutritional autonomy (P < 0.0001) and daily activities (P < 0.0001). CONCLUSIONS: Gut malrotation is a clinicopathologic syndrome affecting all ages. The introduced herein definitive correction procedure is safe, effective, and easy to perform. Accordingly, the current standard of care practice should be redefined in this orphan population.

Disease recurrence after gut transplantation.

PURPOSE OF REVIEW: Despite three decades of clinical experience, this article is the first to comprehensively address disease recurrence after gut transplantation. Pertinent scientific literature is reviewed and management strategies are discussed with new insights into advances in gut pathobiology and human genetics. RECENT FINDINGS: With growing experience and new perspectives in the field of gut transplantation, the topic of disease recurrence continues to evolve. The clinicopathologic spectrum and diagnostic criteria are better defined in milieu of the nature of the primary disease. In addition to neoplastic disorders, disease recurrence is suspected in patients with pretransplant Crohn's disease, gut dysmotility, hypercoagulability and metabolic syndrome. There has also been an increased awareness of the potential de-novo development of various disorders in the transplanted organs. For conventionally unresectable gastrointestinal and abdominal malignancies, ex-vivo excision and autotransplantation are advocated, particularly for the nonallotransplant candidates. SUMMARY: Similar to other solid organ and cell transplantations, disease recurrence has been suspected following gut transplantation. Despite current lack of conclusive diagnostic criteria, recurrence of certain mucosal and neuromuscular disorders has been recently described in a large single-centre series with an overall incidence of 7%. Disease recurrence was also observed in recipients with pretransplant hypercoagulability and morbid obesity with respective incidences of 4 and 24%. As expected, tumour recurrence is largely determined by type, extent and biologic behaviour of the primary neoplasm. With the exception of high-grade aggressive malignancy, disease recurrence is still of academic interest with no significant impact on overall short and long-term outcome.

Management of Five Hundred Patients With Gut Failure at a Single Center: Surgical Innovation Versus Transplantation With a Novel Predictive Model.

OBJECTIVE(S): To define the evolving role of integrative surgical management including transplantation for patients gut failure (GF). METHODS: A total of 500 patients with total parenteral nutrition-dependent catastrophic and chronic GF were referred for surgical intervention particularly transplantation and comprised the study population. With a mean age of 45 ±â€Š17 years, 477 (95%) were adults and 23 (5%) were children. Management strategy was guided by clinical status, splanchnic organ functions, anatomy of residual gut, and cause of GF. Surgery was performed in 462 (92%) patients and 38 (8%) continued medical treatment. Definitive autologous gut reconstruction (AGR) was achievable in 378 (82%), primary transplant in 42 (9%), and AGR followed by transplant in 42 (9%). The 84 transplant recipients received 94 allografts; 67 (71%) liver-free and 27 (29%) liver-contained. The 420 AGR patients received a total of 790 reconstructive and remodeling procedures including primary reconstruction, interposition alimentary-conduits, intestinal/colonic lengthening, and reductive/decompressive surgery. Glucagon-like peptide-2 was used in 17 patients. RESULTS: Overall patient survival was 86% at 1-year and 68% at 5-years with restored nutritional autonomy (RNA) in 63% and 78%, respectively. Surgery achieved a 5-year survival of 70% with 82% RNA. AGR achieved better long-term survival and transplantation better (P = 0.03) re-established nutritional autonomy. Both AGR and transplant were cost effective and quality of life better improved after AGR. A model to predict RNA after AGR was developed computing anatomy of reconstructed gut, total parenteral nutrition requirements, cause of GF, and serum bilirubin. CONCLUSIONS: Surgical integration is an effective management strategy for GF. Further progress is foreseen with the herein-described novel techniques and established RNA predictive model.

Total pancreaticoduodenectomy with autologous islet transplantation 14 years after liver-contained composite visceral transplantation.

Chronic pancreatitis (CP) is a severely disabling disorder with potential detrimental effects on quality of life, gut function, and glucose homeostasis. Disease progression often results in irreversible morphological and functional abnormalities with development of chronic pain, mechanical obstruction, and pancreatic insufficiency. Along with comprehensive medical management, the concept of total pancreatectomy and islet autotransplantation (TP-AIT) was introduced 40 years ago for patients with intractable pain and preserved beta-cell function. With anticipated technical difficulties, total excision of the inflamed-disfigured gland is expected to alleviate the incapacitating visceral pain and correct other associated abdominal pathology. With retrieval of sufficient islet-cell mass, the autologous transplant procedure has the potential to maintain an euglycemic state without exogenous insulin requirement. The reported herein case of CP-induced recalcitrant pain and foregut obstruction is exceptional because of the technical challenges in performing native pancreaticoduodenectomy in close proximity to the composite visceral allograft with complex vascular and gut reconstructions. Equally novel is transplanting the auto-islets in the liver-contained visceral allograft. Despite intravenous nutrition shortly after birth, liver transplantation at age 13, retransplantation with liver-contained visceral allograft at age 17 and TP-AIT at age 31, the 38-year-old recipient is currently pain free with full nutritional autonomy and normal glucose homeostasis.

Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients.

Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal and multivisceral transplant (ITx) recipient survival. We investigated the role of myeloid-derived suppressor cells (MDSCs) in ITx. We identified MDSCs as CD33+ CD11b+ lineage(CD3/CD56/CD19)- HLA-DR-/low cells with 3 subsets, CD14- CD15- (e-MDSCs), CD14+ CD15- (M-MDSCs), and CD14- CD15+ (PMN-MDSCs), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs after ITx; among MDSC subsets, M-MDSC numbers were maintained at a high level after 2 months post ITx. The MDSC numbers decreased in ITx recipients with ACR. MDSC numbers were positively correlated with serum interleukin (IL)-6 levels and the glucocorticoid administration index. IL-6 and methylprednisolone enhanced the differentiation of bone marrow cells to MDSCs in vitro. M-MDSCs and e-MDSCs expressed CCR1, -2, and -3; e-MDSCs and PMN-MDSCs expressed CXCR2; and intestinal grafts expressed the corresponding chemokine ligands after ITx. Of note, the percentage of MDSCs among intestinal mucosal CD45+ cells increased after ITx. A novel in vitro assay demonstrated that MDSCs suppressed donor-reactive T cell-mediated destruction of donor intestinal epithelial organoids. Taken together, our results suggest that MDSCs accumulate in the recipient PBMCs and the grafted intestinal mucosa in ITx, and may regulate ACR.

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion.

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.

Imaging of Intestinal and Multivisceral Transplantation.

Intestinal transplantation has evolved from its experimental origins in the mid-20th century to its status today as an established treatment option for patients with end-stage intestinal failure who cannot be sustained with total parenteral nutrition. The most common source of intestinal failure in both adults and children is short-bowel syndrome, but a host of other disease processes can lead to this common end-point. The development of intestinal transplantation has presented multiple hurdles for the transplant community, including technical challenges, immunologic pitfalls, and infectious complications. Despite these hurdles, the success rate has climbed over the past decades owing to achievements that include improved surgical techniques, new immunosuppressive regimens, and more effective strategies for posttransplant surveillance and management. Nearly 2800 intestinal transplants have been performed worldwide, and current patient and graft survival rates are now comparable to those of other types of solid organ transplantations. As their population continues to increase, it will be increasingly likely that intestinal-transplant patients will seek imaging at sites other than transplant centers. Therefore, it is important that diagnostic and interventional radiologists be familiar with the procedure, its common variations, and the spectrum of postoperative complications. In this article, the authors provide an overview of intestinal transplantation, including the indications, variations, expected postoperative anatomy, and range of potential complications. ©RSNA, 2018.

Autologous Reconstruction and Visceral Transplantation for Management of Patients With Gut Failure After Bariatric Surgery: 20 Years of Experience.

OBJECTIVE: Bariatric surgery (BS) is currently the most effective treatment for severe obesity. However, these weight loss procedures may result in the development of gut failure (GF) with the need for total parenteral nutrition (TPN). This retrospective study is the first to address the anatomic and functional spectrum of BS-associated GF with innovative surgical modalities to restore gut function. METHODS: Over 2 decades, 1500 adults with GF were referred with history of BS in 142 (9%). Of these, 131 (92%) were evaluated and received multidisciplinary care. GF was due to catastrophic gut loss (Type-I, 42%), technical complications (Type-II, 33%), and dysfunctional syndromes (Type-III, 25%). Primary bariatric procedures were malabsorptive (5%), restrictive (19%), and combined (76%). TPN duration ranged from 2 to 252 months. RESULTS: Restorative surgery was performed in 116 (89%) patients with utilization of visceral transplantation as a rescue therapy in 23 (20%). With a total of 317 surgical procedures, 198 (62%) were autologous reconstructions; 88 (44%) foregut, 100 (51%) midgut, and 10 (5%) hindgut. An interposition alimentary conduit was used in 7 (6%) patients. Reversal of BS was indicated in 84 (72%) and intestinal lengthening was required in 10 (9%). Cumulative patient survival was 96% at 1 year, 84% at 5 years, and 72% at 15 years. Nutritional autonomy was restored in 83% of current survivors with persistence or relapse of obesity in 23%. CONCLUSIONS: GF is a rare but serious life-threatening complication after BS. Successful outcome is achievable with comprehensive management, including reconstructive surgery and visceral transplantation.

Radiologic features of pancreatic and biliary complications following composite visceral transplantation.

Small bowel transplantation is a surgical technique reserved for patients with end-stage intestinal failure. Despite its inherent technical difficulties, it has emerged as the standard of care for these patients. This article reviews the background and different surgical techniques for this procedure and then fully describes the spectrum of imaging findings of pancreatic and biliary complications, which have a prevalence of up to 17%, after this procedure based on 23-year single-center experience. The pancreaticobiliary complications encountered in our experience and discussed in this article include: ampullary stenosis, biliary cast, choledocholithiasis, bile leak, recurrent cholangitis, acute pancreatitis, chronic pancreatitis, and pancreatic duct fistula. Familiarity with the broad spectrum of PB complications and their variable manifestations will help radiologists to accurately diagnose these complications which have relatively high morbidity and mortality in these immune-compromised patients.

Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model.

INTRODUCTION: Normothermic machine perfusion (NMP) is an emerging preservation modality that holds the potential to prevent the injury associated with low temperature and to promote organ repair that follows ischemic cell damage. While several animal studies have showed its superiority over cold storage (CS), minimal studies in the literature have focused on safety, feasibility, and reliability of this technology, which represent key factors in its implementation into clinical practice. The aim of the present study is to report safety and performance data on NMP of DCD porcine livers. MATERIALS AND METHODS: After 60 minutes of warm ischemia time, 20 pig livers were preserved using either NMP (n = 15; physiologic perfusion temperature) or CS group (n = 5) for a preservation time of 10 hours. Livers were then tested on a transplant simulation model for 24 hours. Machine safety was assessed by measuring system failure events, the ability to monitor perfusion parameters, sterility, and vessel integrity. The ability of the machine to preserve injured organs was assessed by liver function tests, hemodynamic parameters, and histology. RESULTS: No system failures were recorded. Target hemodynamic parameters were easily achieved and vascular complications were not encountered. Liver function parameters as well as histology showed significant differences between the 2 groups, with NMP livers showing preserved liver function and histological architecture, while CS livers presenting postreperfusion parameters consistent with unrecoverable cell injury. CONCLUSION: Our study shows that NMP is safe, reliable, and provides superior graft preservation compared to CS in our DCD porcine model.

Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers.

The effects of normothermic machine perfusion (NMP) on the postreperfusion hemodynamics and extrahepatic biliary duct histology of donation after cardiac death (DCD) livers after transplantation have not been addressed thoroughly and represent the objective of this study. Ten livers (5 per group) with 60 minutes of warm ischemia were preserved via cold storage (CS) or sanguineous NMP for 10 hours, and then they were reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, the arterial and portal vein flows were stable in the NMP group during the entire reperfusion simulation, whereas they decreased dramatically in the CS group after 16 hours of reperfusion (P < 0.05); these findings were consistent with severe parenchymal injury. Similarly, significant differences existed between the CS and NMP groups with respect to the release of hepatocellular enzymes, the volume of bile produced, and the levels of enzymes released into bile (P < 0.05). According to histology, CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhaging, denudated biliary epithelium, and submucosal bile duct necrosis, whereas NMP livers showed very mild injury to the liver parenchyma and biliary architecture. Most importantly, Ki-67 staining in extrahepatic bile ducts showed biliary epithelial regeneration. In conclusion, our findings advance the knowledge of the postreperfusion events that characterize DCD livers and suggest NMP as a beneficial preservation modality that is able to improve biliary regeneration after a major ischemic event and may prevent the development of ischemic cholangiopathy in the setting of clinical transplantation.

Minimal effect of bortezomib in reducing anti-pig antibodies in human leukocyte antigen-sensitized patients: a pilot study.

BACKGROUND: Bortezomib, a proteasome inhibitor used to treat multiple myeloma, has been administered (± plasma exchange ± intravenous immunoglobulin [IVIg]) in attempts to reduce antibodies against human leukocyte antigens (HLA) in sensitized patients undergoing organ transplantation. To our knowledge, bortezomib has not been investigated for its effect on natural anti-pig antibodies. If bortezomib could reduce the production of anti-pig antibodies, this would likely be beneficial to the outcome of pig organ grafts in primates. METHODS: Nine patients received bortezomib either to reduce anti-HLA antibody levels before organ allotransplantation or to treat antibody-mediated rejection. Patients at the Mayo Clinic (Group 1; n = 4) received bortezomib alone, whereas at the UPMC (Group 2; n = 5), this was combined with plasmaphereses ± IVIg in some cases. Anti-pig IgM and IgG levels against wild-type (WT) and α1,3-galactosyltransferase gene knockout (GTKO) pig aortic endothelial cells (flow cytometry-relative mean fluorescence intensity) and anti-Gal IgM and IgG (ELISA-OD480 nm ) were measured pre- and post-bortezomib therapy. RESULTS: Mean anti-pig IgM levels were 11.2 (WT) and 1.9 (GTKO) pre-bortezomib treatment and 9.4 (WT: P = 0.02) and 1.7 (GTKO: P = 0.33) post-bortezomib treatment, respectively. Mean anti-pig IgG levels were 4.3 (WT) and 1.5 (GTKO) pre-bortezomib treatment and 3.6 (WT: P = 0.21) and 1.4 (GTKO: P = 0.20) post-bortezomib treatment, respectively. Mean anti-Gal IgM and IgG levels were 0.7 and 1.1, respectively, pre-treatment, and 0.6 (P = 0.03) and 1.1 (NS), respectively, post-treatment. When the data were analyzed in Groups 1 and 2 separately, there were no significant differences between the pre- and post-bortezomib levels of anti-pig, anti-non-Gal, or anti-Gal IgM or IgG. CONCLUSIONS: From this limited study, we conclude that bortezomib might reduce anti-Gal IgM levels in primates, but, in this respect alone, is unlikely to have any significant effect on the outcome of GTKO pig organ transplantation.

Intestinal transplantation: review of operative techniques.

The improvement of outcomes in intestinal transplantation (ITx) over the last two decades has been made possible through standardization in surgical techniques, improvements in immunosuppressive and induction protocols, and post-operative patient care. From a surgical technical point of view, all different types of small bowel containing transplants can be categorized into three main prototypes, including isolated small bowel, liver-small bowel, and multivisceral transplantations. In this review, we describe these three main prototypes and discuss the most important technical modifications of each type, as well as donor and recipient procedures, and highlight the more recent operative technical topics of discussion in the literature.

A natural tetrahydropyrimidine, ectoine, ameliorates ischemia reperfusion injury after intestinal transplantation in rats.

BACKGROUND/AIMS: Ischemia reperfusion (I/R) injury after small bowel transplantation leads to inflammatory reactions and loss of structural integrity with subsequent graft contractile dysfunction in the early postoperative phase. The natural tetrahydropyrimidine ectoine (1-,4-,5-,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid; THP) protects the ileal mucosa and muscularis against effects of I/R injury in an experimental model of isolated graft reperfusion. The effects of THP treatment were evaluated in an established experimental intestinal transplant model. METHODS: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (6 h cold ischemia time). Perioperative THP treatment (intraluminal/intravascular) groups were compared to vehicle-treated animals (after 3 and 24 h) and non-transplanted controls (n = 5/group). Park's score defined the effects of I/R injury. The infiltration of neutrophils, monocytes and macrophages, mRNA expression of IL-6 and TNF-α, serum levels of IL-6 and NO and smooth muscle contractility were evaluated. RESULTS: Improved graft outcome after intraluminal and intravascular THP treatment was defined by considerably ameliorated neutrophil infiltration and less histological signs of I/R injury (p ≤ 0.05). In the presence of THP, mRNA expression of IL-6 and TNF-α and IL-6 and NO serum levels were reduced and smooth muscle function was improved. CONCLUSION: THP treatment offers protection against the effects of I/R injury in intestinal transplantation in vivo, however, only as supplementary treatment option.

Role of tissue expanders in patients with loss of abdominal domain awaiting intestinal transplantation.

Abdominal closure is a complex surgical problem in intestinal transplant recipients with loss of abdominal domain, as graft exposure results in profound morbidity. Although intraoperative coverage techniques have been described, this is the first report of preoperative abdominal wall augmentation using tissue expanders in patients awaiting intestinal transplantation. We report on five patients who received a total of twelve tissue expanders as a means to increase abdominal surface area. Each patient had a compromised abdominal wall (multiple prior operations, enterocutaneous fistulae, subcutaneous abscesses, stomas) with loss of domain and was identified as high risk for an open abdomen post-transplant. Cross-sectional imaging and dimensional analysis were performed to quantify the effect of the expanders on total abdominal and intraperitoneal cavity volumes. The overall mean increase in total abdominal volume was 958 cm(3) with a mean expander volume of 896.5 cc. Two expanders were removed in the first patient due to infection, but after protocol modification, there were no further infections. Three patients eventually underwent small bowel transplantation with complete graft coverage. In our preliminary experience, abdominal tissue expander placement is a safe, feasible, and well-tolerated method to increase subcutaneous domain and facilitate graft coverage in patients undergoing intestinal transplantation.