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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.

The last three decades witnessed continual evolution of the organ allocation strategy. The Organ Procurement and Transplant Network (OPTN) primary goals were to promote patient access to transplantation and improve equity among single and multi-organ candidates. Other intended objectives were to optimize donor use and maximize transplant utility. These relentless efforts were commanded by the OPTN 'Final Rule' and directed by different scientific and legislative allied committees (1).

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 ± 17 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.

The successful development of multivisceral and composite visceral transplantation is among the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathologic conditions. The outcome has markedly improved over the last 3 decades owing to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.

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.

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.

The successful development of multivisceral and composite visceral transplantation is among the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathologic conditions. The outcome has markedly improved over the last 3 decades owing to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.

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.

Small bowel transplant is an acceptable procedure for intractable Crohn’s disease (CD). Some case reports and small series describe the apparent recurrence of CD in the transplanted bowel. This commentary discusses evidence in favor of and against this alleged recurrence and argues that a molecular characterization is needed to prove or disprove that inflammation emerging in the transplanted bowel is a true recurrence of the original CD.

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.

Background: Recipients requiring kidney-enbloc visceral allograft often face challenges during transplantation. We report a case with a unique technique of urinary diversion in enbloc liver-intestine-kidney transplantation for irradiation enteritis and cystitis. Methods: The patient is a 65 year-old man with Crohn's disease and history of anal adenocarcinoma treated with abdominoperineal resection and adjuvant chemo- and radiotherapy. Case will be presented with pictures and/ or video. Results: The patient developed gut failure due to short gut and multiple bowel obstructions secondary to radiation enteritis. Urinary incontinence developed after irradiation caused frequent urinary tract infection leading to kidney failure. He was listed for combined liver-intestine-kidney transplantation and received en-bloc allograft from a 35 year-old male brain-dead donor. During evisceration of native organs, frozen abdomen was encountered and subtotal enterectomy leaving 30 cm of jejunum was performed. Urinary bladder was rock hard with no augmentation, unacceptable to implant the allograft ureter. Arterial inflow was established with an aortic conduit between the native and allograft infra-renal aorta. The native jejunum was transected at 10 cm and the proximal segment was connected to allograft jejunum to establish the continuity of alimentary tracts. The distal 20 cm of native jejunum was anastomosed to allograft ureter for urinary diversion Postoperative course was unremarkable with adequate urinary output and allograft functions. The patient was well rehabilitated in hospital due to lack of safe rehabilitative facilities during COVID pandemic and discharged home on post-operative day 47. Conclusion: Combined kidney and visceral transplantation in the setting of irradiated bladder requires pre-operative planning of urinary reconstruction with several options. When native intestine is available and not damaged from original disease, urinary diversion using the native jejunum is the safest option amongst others including cystoplasty and urinary diversion using allograft ileum.

Introduction: Coronavirus disease 2019 (COVID-19) outbreak posed unique challenges for immunosuppressed patients. Little is known about the clinical course and immunosuppression management of this novel infection in intestinal transplant recipients. Methods: We experienced 6 adult intestinal transplant recipients who had a positive swab test of COVID-19 and symptoms. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. Results: Median age was 53 years (range 30-71). They had 3 liver-free composite allografts, 2 isolated intestine, and 1 intestine-kidney with median time from transplant of 8 years (range 4-12). Maintenance immunosuppressive therapy was tacrolimus/steroid in 4, and tacrolimus monotherapy in 2 patients. The most common symptom was cough (n=5) followed by fever (n=3) and dyspnea (n=3). All had ground glass opacities on computed tomography. Four patients were admitted to our institution but two were managed at local hospital due to difficulty of transportation. Immunosuppression therapy was never suspended and was reduced for one patient. Pharmacological therapy consisted in remdesivir and steroids for 4 recipients (67%) associated with convalescent plasma in 2 cases (33%) plus tocilizumab in 1 case (17%), and steroids for 2 patients (33%) associated with convalescent plasma in 1 case (17%). Two patients required intubation for acute respiratory distress syndrome. One patient received antibiotics for superimposed bacterial pneumonia. Mean white blood cells and lymphocyte count were 4.72±0.6 k/uL and 0.96±0.65 k/uL at presentation, respectively. Mean D-Dimer, C-reactive protein and ferritin were 740±160 ng/ml, 4.1±5 mg/dl and 249±149 ng/ml, respectively at presentation, with a peak of 1255±785 mg/ml, 10.9±8 mg/dl and 630±318 ng/ml, respectively. No significant changes were noted in liver and renal function. Before discharge, all patients underwent ileoscopy and allograft biopsies with no evidence of inflammation/rejection. Mean hospital stay was 36±21 days. Death occurred in 2 patients (33%) who were managed at local hospital. No recurrence was noted with mean follow up of 90 days. Conclusions: We treated intestinal transplant recipients symptomatic for COVID-19 without immunosuppression interruption. No increased inflammation or rejection was noted in the intestinal grafts. Aggressive treatment of COVID-19 infection should be granted under expertise of intestinal transplant and transplant infectious disease team.

Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1-3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.

Despite recent therapeutic advances, patients with Crohn's disease (CD) continue to experience high recurrence with cumulative structural damage and ultimate loss of nutritional autonomy. With short bowel syndrome, strictures, and enteric fistulae being the underlying pathology, CD is the second common indication for home parenteral nutrition (HPN). With development of intestinal failure, nutritional management including HPN is required as a rescue therapy. Unfortunately, some patients do not escape the HPN-associated complications. Therefore, the concept of gut rehabilitation has evolved as part of the algorithmic management of these patients, with transplantation being the ultimate life-saving therapy. With type 2 intestinal failure, comprehensive rehabilitative measures including nutritional care, pharmacologic manipulation, autologous reconstruction, and bowel lengthening is often successful, particularly in patients with quiescent disease. With type 3 intestinal failure, transplantation is the only life-saving treatment for patients with HPN failure and intractable disease. With CD being the second common indication for transplantation in adults, survival outcome continues to improve because of surgical innovation, novel immunosuppression, and better postoperative care. Despite being a rescue therapy, the procedure has achieved survival rates similar to other solid organs, and comparable to those who continue to receive HPN therapy. With similar technical, immunologic, and infectious complications, survival is similar in the CD and non-CD recipients. Full nutritional autonomy is achievable in most survivors with better quality of life and long-term cost-effectiveness. CD recurrence is rare with no impact on graft function. Further progress is anticipated with new insights into the pathogenesis of CD and mechanisms of transplant tolerance.

The utilization of normothermic machine perfusion (NMP) may be an effective strategy to resuscitate livers from donation after circulatory death (DCD). There is no consensus regarding the efficacy of different perfusates on graft and bile duct viability. The aim of this study was to compare, in an NMP porcine DCD model, the preservation potential of three different perfusates. Twenty porcine livers with 60 min of warm ischemia were separated into four preservation groups: cold storage (CS), NMP with Steen solution (Steen; XVIVO Perfusion Inc., Denver, CO), Steen plus red blood cells (RBCs), or whole blood (WB). All livers were preserved for 10 h and reperfused to simulate transplantation for 24 h. During preservation, the NMP with Steen group presented the highest hepatocellular injury. At reperfusion, the CS group had the lowest bile production and the worst hepatocellular injury compared with all other groups, followed by NMP with Steen; the Steen plus RBC and WB groups presented the best functional and hepatocellular injury outcomes, with WB livers showing lower aspartate aminotransferase release and a trend toward better results for most parameters. Based on our results, a perfusate that contains an oxygen carrier is most effective in a model of NMP porcine DCD livers compared with Steen solution. Specifically, WB-perfused livers showed a trend toward better outcomes compared with Steen plus RBCs.

The successful development of intestinal and multivisceral transplantation is one of the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathology. The outcome has markedly improved over the last three decades due to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.

The surgical management of gastrointestinal failure continues to evolve with major advances in the fields of intestinal transplantation and gut rehabilitation [1–3]. The recent significant improvement in the therapeutic efficacy of intestinal and multivisceral transplantation has elevated the level of such a challenging procedure to permanently reside in a respected place in the surgical armamentarium [3–7]. In parallel, the concept of gut rehabilitation was introduced and has recently evolved, utilizing novel autologous reconstructive procedures [2]. In addition, distinctive small bowel lengthening techniques were implemented to enhance the natural adaptation process in patients with short bowel syndrome (SBS) [1, 2, 8, 9].

Intestinal transplantation (ITX) constitutes a salvage treatment for irreversible intestinal failure and failure of parenteral nutrition. Chronic rejection (CR) remains the key obstacle for long-term intestinal graft survival but the pathomechanisms are incompletely understood. This study systematically reviews experimental models addressing CR after ITX in order to summarize current knowledge on CR pathogenesis and identify promising experimental strategies. A systematic literature search was conducted in line with the PRISMA guidelines, and 68 out of 677 articles qualified for the final analysis. The average methodological quality of the studies was suboptimal with 7 out of 11 points as assessed by a modified Oxford Centre for Evidence-Based Medicine score. Histology of the chronically rejected graft was almost universally integrated as outcome parameter but we found significant heterogeneity in utilized transplant techniques, organ preservation, immunosuppression and time points of CR-assessment. Several studies identified cellular and humoral immunologic mechanisms in chronic intestinal rejection. Yet, neither preventive nor therapeutic strategies against CR have been successfully introduced into human intestinal transplantation highlighting the persistent need for optimized experimental models. In this review, we aim to improve the translational value of forthcoming investigations on CR by discussing the experimental status quo and potential innovative approaches.

The successful development of multivisceral and composite visceral transplantation is among the milestones in the recent history of human organ transplantation. All types of gastrointestinal transplantation have evolved to be the standard of care for patients with gut failure and complex abdominal pathologic conditions. The outcome has markedly improved over the last 3 decades owing to technical innovation, novel immunosuppression, and better postoperative care. Recent data documented significant improvement in the long-term therapeutic indices of all types of visceral transplantation close to that achieved with thoracic and solid abdominal organs.

The multivisceral transplantation is indicated for patients with intestinal failure who can no longer be maintained on total parenteral nutrition (TPN). Some of the significant challenges that the field has faced include associated massive lymphoid tissue, high antigenicity, and microbial colonization of the gut. However, with innovative surgical techniques, novel immunosuppressive therapies, and improved postoperative care, multivisceral transplantation has progressed significantly with much improved outcomes. This chapter focuses on the 50-year history and evolution of intestinal and multivisceral transplantation with special reference to nomenclature, indications, surgical techniques, management strategies, and therapeutic efficacy.

In the 1990s, the introduction of visceral transplantation fuelled interest in other innovative therapeutic modalities for gut rehabilitation. Ethanol lock and omega-3 lipid formulations were introduced to reduce the risks associated with total parenteral nutrition (TPN). Autologous surgical reconstruction and bowel lengthening have been increasingly utilized for patients with complex abdominal pathology and short-bowel syndrome. Glucagon-like peptide 2 analogue, along with growth hormone, are available to enhance gut adaptation and achieve nutritional autonomy. Intestinal transplantation continues to be limited to a rescue therapy for patients with TPN failure. Nonetheless, survival outcomes have substantially improved with advances in surgical techniques, immunosuppressive strategies and postoperative management. Furthermore, both nutritional autonomy and quality of life can be restored for more than two decades in most survivors, with social support and inclusion of the liver being favourable predictors of long-term outcome. One of the current challenges is the discovery of biomarkers to diagnose early rejection and further improve liver-free allograft survival. Currently, chronic rejection with persistence of preformed and development of de novo donor-specific antibodies is a major barrier to long-term graft function; this issue might be overcome with innovative immunological and tolerogenic strategies. This Review discusses advances in the field of gut rehabilitation, including intestinal transplantation, and highlights future challenges. With the growing interest in individualized medicine and the value of health care, a novel management algorithm is proposed to optimize patient care through an integrated multidisciplinary team approach.

BACKGROUND Fusarium spp. infections have become an emerging and lethal threat to the immunocompromised patient population, especially those with neutropenia. Recently there have been increased reports in solid organ transplant recipients. Presentation is commonly as soft tissue infections several months post-transplant. With high morbidity and mortality, efficacious antifungal therapy is essential. This remains challenging with limited data and no established clinical breakpoints defined. CASE REPORT We report on a modified multi-visceral transplant patient that developed a Fusarium infection only 7 weeks post-transplant in the native hard palate and esophagus, without any soft tissue lesions, which persisted despite aggressive combination treatment with amphotericin B lipid complex and voriconazole. CONCLUSIONS Fusarium spp. infection in solid organ transplant is a significant challenge without clear diagnostic clinical indicators of infection, or specific time of onset, in addition to possible emergence of a more aggressive drug-resistant strain.

Recent advances in immunosuppressive regimens have decreased acute cellular rejection (ACR) rates and improved intestinal 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-MDSC), CD14(+)CD15(−) (M-MDSC), and CD14(−)CD15(+) (PMN-MDSC), in peripheral blood mononuclear cells (PBMCs) and mononuclear cells in the grafted intestinal mucosa. Total MDSC numbers increased in PBMCs following ITx; among MDSC subsets, M-MDSC numbers were maintained at high level after 2 months following ITx. The MDSC numbers decreased in ITx recipients suffering from ACR. MDSC numbers were positively correlated with serum IL-6 levels and the glucocorticoid administration index. IL-6 and methylprednisolone enhanced the differentiation of bone marrow cells (BMCs) 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 following 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.

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 to3 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.

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.

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.

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.