Normothermic liver perfusion derived extracellular vesicles have concentration-dependent immunoregulatory properties.

Extracellular vesicles (EVs) are major contributors to immunological responses following solid organ transplantation. Donor derived EVs are best known for their role in transplant rejection through transferring donor major histocompatibility complex proteins to recipient antigen presenting cells, a phenomenon known as ‛cross-decoration'. In contrast, donor liver-derived EVs are associated with organ tolerance in small animal models.

Nodular regenerative hyperplasia and liver transplantation: a systematic review.

Nodular regenerative hyperplasia (NRH) is a primary disease of the liver that may cause noncirrhotic portal hypertension. Common causes include autoimmune, hematologic, immune deficiency, and myeloproliferative disorders. Given the limited data regarding the development of NRH in contemporary immunosuppressive protocols and the occurrence of NRH post-liver transplantation, we systematically reviewed NRH as it pertains to liver transplantation.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients.

Premalignant Lesions in the Kidney Transplant Candidate.

End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population.

Analysis of >15 000 Solid Organ Transplant Recipients Reveals Nonanal Genitourinary HPV-related Disease as Highest Risk Predictor for Anal Squamous Intraepithelial Lesions/Anal Cancer.

Background: Solid organ transplantation is a risk predictor for virally-mediated anal squamous intraepithelial lesions and cancer (anal disease). Precancerous squamous intraepithelial lesions can be detected by screening, and treatment may prevent cancer progression. Screening recommendations are not well defined.

Detrimental impact of early biopsy-proven rejection in liver transplantation.

Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long-term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first-time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy-proven acute cellular rejection (EBPR) within the first 90 days post-transplant and compared outcomes between the groups.

Five Critical Gene-Based Biomarkers With Optimal Performance for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most fatal cancers in the world. There is an urgent need to understand the molecular background of HCC to facilitate the identification of biomarkers and discover effective therapeutic targets. Published transcriptomic studies have reported a large number of genes that are individually significant for HCC.

CD8 T Cells Target Antigen Cross-Presented by Bone Marrow Derived Cells to Induce Bystander Rejection of Grafts Lacking the Cognate Peptide-MHC.

CD8 T cells play a key role in cancer immunotherapy and allograft rejection. However, it is not clear how they kill cells and tissues that do not have the agonist peptide-major histocompatibility complex (MHC) on their surface, as in the settings of MHC class I deficient tumors and indirect rejection of MHC-mismatched transplants. CD8 T cells might respond to agonist antigen cross-presented on hematopoietic cells, leading to a "bystander" rejection.

Blood products and liver transplantation: A strategy to balance optimal preparation with effective blood stewardship.

Background: Unanticipated transfusion requirements during liver transplantation can delay lifesaving intraoperative resuscitation and strain blood bank resources. Risk-stratified preoperative blood preparation can mitigate these deleterious outcomes.

Study Design And Methods: A two-tiered blood preparation protocol for liver transplantation was retrospectively evaluated.

The Immunological Effect of Oxygen Carriers on Normothermic Liver Perfusion.

Introduction: Normothermic liver perfusion (NEVLP) is an organ preservation method that allows liver graft functional assessment prior to transplantation. One key component of normothermic perfusion solution is an oxygen carrier to provide oxygen to the liver to sustain metabolic activities. Oxygen carriers such as red blood cells (RBCs) or hemoglobin-based oxygen carriers have an unknown effect on the liver-resident immune cells during NEVLP.

Post-pancreatic transplant enteric leaks: The role of the salvage operation.

Enteric drainage in pancreas transplantation is complicated by an enteric leak in 5%-8%, frequently necessitating pancreatectomy. Pancreatic salvage outcomes are not well studied. Risk factors for enteric leak were examined and outcomes of attempted graft salvage were compared to immediate pancreatectomy.

Liver Transplantation for Hepatocellular Carcinoma With Bile Duct Tumor-Associated Thrombi: A Systematic Review and Pooled Analysis.

Introduction: The significance of bile duct tumor-associated thrombi in patients undergoing transplantation for hepatocellular carcinoma (HCC) is controversial. Therefore, we performed a systematic review of the literature with pooled analysis to investigate the impact of biliary invasion on HCC recurrence and patient survival.

Methods: Of 1,584 references screened, eight were included for analysis.

RNA sequencing analysis of hepatocellular carcinoma identified oxidative phosphorylation as a major pathologic feature.

Dysregulation of expression of functional genes and pathways plays critical roles in the etiology and progression of hepatocellular carcinoma (HCC). Next generation-based RNA sequencing (RNA-seq) offers unparalleled power to comprehensively characterize HCC at the whole transcriptome level. In this study, 17 fresh-frozen HCC samples with paired non-neoplastic liver tissue from Caucasian patients undergoing liver resection or transplantation were used for RNA-seq analysis.

Single-cell RNA sequencing distinguishes dendritic cell subsets in the rat, allowing advanced characterization of the effects of FMS-like tyrosine kinase 3 ligand.

Tissue-resident dendritic cells (DCs) are essential for immunological homeostasis and hold promise for a variety of therapeutic interventions. The rare nature of tissue-resident DCs and their suboptimal description in the lab rat model has limited their characterization. To address this limitation, FMS-like tyrosine kinase 3 ligand (FLT3L) has been utilized to expand these population in vitro and in vivo for investigative or therapeutic purposes.

Clinician and patient attitudes toward use of organs from hepatitis C viremic donors and their impact on acceptance: A contemporary review.

Background: The use of Hepatitis C (HCV) NAT positive allografts remains unusual and is clustered at few centers. We conducted a contemporary literature review to assess whether patient and clinician attitudes toward viremic organs impact acceptance.

Methods: Databases including PubMed, MEDLINE, and SCOPUS databases were reviewed to identify studies focused on evaluating patient and provider perceptions of HCV NAT positive organ use within the DAA era (January 2015-April 2021).

Interleukin-10 and Transforming Growth Factor-β Cytokines Decrease Immune Activation During Normothermic Ex Vivo Machine Perfusion of the Rat Liver.

Normothermic ex vivo liver perfusion (NEVLP) is a novel system for organ preservation that may improve over static cold storage clinically and offers the chance for graft modification prior to transplantation. Although recent studies have shown the presence of inflammatory molecules during perfusion, none have yet shown the effects of NEVLP on liver-resident immune cell activation. We investigated the effects of NEVLP on liver-resident immune cell activation and assessed the ability of anti-inflammatory cytokines interleukin 10 (IL10) and transforming growth factor β (TGF-β) to improve organ function and reduce immune activation during perfusion.

Predicting the Safe Use of Deceased After Circulatory Death Liver Allografts in Primary Sclerosing Cholangitis.

Objectives: The use of deceased after circulatory death liver allografts in patients with primary sclerosing cholangitis is controversial, given the increased risk of graft complications in patients with primary sclerosing cholangitis. We hypothesized that transplant of deceased after circulatory death livers into recipients with primary sclerosing cholangitis when appropriately selected using the UK deceased after circulatory death scoring system is not associated with increased graft failure and mortality.

Materials And Methods: We analyzed 99 229 transplants (between January 2001 and December 2018) from the Organ Procurement and Transplantation Network database.

Immunological organ modification during Ex Vivo machine perfusion: The future of organ acceptance.

Ex vivo machine perfusion (EVMP) has gained revitalized interest in recent years due to the increasing use of marginal organs which poorly tolerate the standard preservation method static cold storage (SCS). EVMP improves on SCS in a number of ways, most notably by the potential for reconditioning of the donor organ prior to transplantation without the ethical concerns associated with organ modulation before procurement. Immunomodulatory therapies administered during EVMP can influence innate and adaptive immune responses to reduce production of inflammatory molecules and polarize tissue-resident immune cells to a regulatory phenotype.

Complex Ureteral Reconstruction in Kidney Transplantation.

Objectives: Despite advances in surgical techniques and organ preservation, transplant ureteric strictures remain a common complication in kidney transplantation. A variety of endourological and surgical techniques have been utilized; however, there is a lack of consensus on the optimal modality in dealing with these complex cases.

Materials And Methods: We present challenging ureteral reconstruction cases after failed attempts at ureteral dilatation, failed conventional open repairs, and/or with bladder dysfunction.

Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

Background: Pharmaceuticals to inhibit mammalian target of rapamycin (mTOR) protein, which plays an integral role in T cell survival and function, have been used to prevent complications associated with organ transplantation. Although studies have individually shown that resveratrol can inhibit mTOR and that inhibiting mTOR leads to attenuated immune function, no studies to date have examined these two functions conjointly under one study. Therefore, we hypothesize that resveratrol will decrease mTOR activation and expression as well as attenuate stimulated T cell activation and proliferation in peripheral blood mononuclear cells (PBMC).

Pre-transplant bariatric surgery is associated with increased fungal infection after liver transplant.

Aim: The impact of pre-transplant (pre-TXP) bariatric surgery (BS) on outcomes after liver transplant (LTX) has not been completely elucidated. Roux-en Y gastric bypass (RYGB) is one of the most common BS procedures. The primary objective of this study was to identify the risk of infection in LTX recipients with pre-TXP RYGB.