Current Opinion in Organ Transplantation最新文献

Purpose of review: Pancreas and islet transplantation face critical organ shortage challenges, with many potential grafts discarded due to concerns about consequences of ischemia-reperfusion injury, particularly from donation after circulatory death (DCD) donors. Static cold storage remains standard practice but has significant limitations. Novel preservation technologies may improve transplant outcomes, donor selection and even expand the donor pool.

Recent findings: Normothermic regional perfusion in DCD donors has increased pancreas utilization with promising one-year graft survival comparable to donation after brain-death (DBD) donors. Hypothermic machine perfusion maintains tissue integrity and shows promising preclinical results. Oxygenated hypothermic machine perfusion successfully restores tissue adenosine triphosphate (ATP) levels without notable tissue injury. Normothermic machine perfusion, despite challenges, offers potential for viability assessment and resuscitation.

Summary: Advanced preservation technologies provide platforms for assessment, reconditioning, and therapeutic interventions for pancreas grafts. Clinical translation requires consensus on perfusion parameters and perfusate composition optimized for pancreatic preservation. Future developments should focus on implementing sensitive and specific assessment methods, including beta-cell specific biomarkers, to confidently select and utilize marginal pancreas grafts for transplantation.

Purpose of review: Pancreas retransplantation (PRT) remains a topic of debate due to the increased risks involved and advancements in diabetes mellitus management.

Recent findings: The majority of PRT are pancreas after kidney (PAK) transplants, typically performed when a primary simultaneous pancreas-kidney (SPK) transplant results in pancreas graft failure while the kidney graft remains functioning. Over the past few decades, the number of PRT procedures has declined, mirroring the decrease in PAK transplant activity. Technical or late immunological loss of the initial pancreas is associated with better PRT outcomes, whereas early immunological failure and sensitization predict poor post-PRT outcome.

Summary: Several critical factors must be considered when evaluating PRT, including the cause and timing of primary pancreas graft failure, as well as the recipient's surgical and immunological profile. PRT outcomes should be interpreted with caution, as most primary pancreas transplants (PT) are SPK, whereas the majority of PRT are solitary PT. When comparing only primary solitary PT to PRT, the outcomes are similar, particularly when performed in high-volume centers.

Purpose of review: In recent years, rates of pancreas transplantation have remained stagnant in part due to increasingly stringent donor criteria. Compared to other abdominal organs, the use of extended criteria grafts in pancreas transplantation, including donation after cardiac death (DCD) donors, remains limited. The purpose of this review is to highlight recent work in the field of pancreas and islet preservation.

Recent findings: Emerging preclinical and clinical data support the use of machine perfusion, both normothermic and hypothermic, as a mechanism by which to assess graft viability in an ex-situ circulation system prior to transplantation. Similarly, as normothermic regional perfusion (NRP) gains popularity, it will have significant implications on the potential organ pool for pancreas transplantation. Finally, recent advancements in cryoprotective agent composition as well as cooling and rewarming technologies have great potential to facilitate subzero preservation of pancreata and islets for long-term storage.

Summary: Broad scaling of newer preservation techniques for pancreas and islet transplantation will require overcoming challenges, including optimizing protocols, ensuring cost-effectiveness, and translation of experimental techniques to the clinical setting. Nevertheless, these strategies for pancreas procurement and preservation may facilitate increased use of marginal grafts and increase the donor pool.

Purpose of review: Numerous donor risk factors have been identified as contributing to poor outcomes and posttransplant complications following pancreas transplantation; however, recipient risk factors have received less attention and study. A thorough evaluation of recipient factors, that is, careful patient selection and/or prehabilitation, is essential for improving patient and graft survival rates. This review synthesizes recent studies on recipient-related risk factors and explores potential strategies to optimize transplant outcomes.

Recent findings: Traditional recipient risk factors include advanced age, cardiovascular disease, and peripheral vascular disease. Recipient risk factors can be categorized as either preoperative or immediate postoperative. Emerging studies have investigated additional preoperative recipient risk factors in pancreas transplantation, such as socioeconomic factors including education level and insurance status, frailty, donor-recipient sex mismatch, donor-recipient size mismatch, obesity, hypoalbuminemia, and donor-specific antibody (DSA). Immediate postoperative risk factors that have been newly examined include hospital stays, kidney delayed graft function (DGF), weight gain, orthostatic hypotension, de-novo DSA (dnDSA), and posttransplant diabetes mellitus (PTDM).A recently published Pancreas Transplantation Outcome Predictions (PTOP) tool incorporating both donor and recipient characteristics may offer a holistic model and provide longer-term outcome predictions, but remains to be validated. Still, the field would benefit from a universally standardized and consistently implemented tool for guiding patient selection and testing prehabilitation strategies.

Summary: This article provides a comprehensive, up-to-date analysis of recently studied recipient-related risk factors and a novel tool for risk assessment.

Purpose of review: The purpose of this review is to provide a comprehensive analysis of the current literature on pediatric donors for pancreas transplantation, with a focus on donor selection, clinical outcomes and surgical approaches. This review aims to highlight the feasibility and challenges of utilizing pediatric donors, assess the impact of donor and recipient selection criteria on outcomes, and explore innovations in surgical techniques.

Recent findings: Numerous retrospective studies show that pediatric donors yield outcomes comparable to those from adult donors. Despite challenges posed by small caliber vessels and donor-recipient size mismatches, favorable long-term outcomes, including high rates of insulin independence and stable graft function have been reported, even in cases where initial concerns about low islet mass existed. Complications such as thrombosis, pancreatitis, and ischemia-reperfusion injury remain risks, but improved anticoagulation protocols and perioperative management have significantly mitigated them. Surgical innovations, such as en-bloc transplantation with kidneys and refined vascular anastomosis techniques may minimize thrombotic and graft loss complications.

Summary: Pediatric donors are a viable option for pancreas transplantation, with outcomes matching those from adult donors, when properly selected and managed. Advances in surgical techniques and perioperative care have improved utilization and success rates.

Purpose of review: Normothermic regional perfusion (NRP) is a novel technique developed to improve organ utilization and recipient outcomes following donation after circulatory death (DCD). NRP has revolutionized DCD liver transplant by extending donor criteria and reducing the incidence of ischemic cholangiopathy (IC) and other complications in recipients. However, there is significant geographic and center-specific variation in NRP use and practices. This review collates practices from pioneering NRP centers across the globe regarding donor selection criteria, NRP techniques, organ viability monitoring, and other key areas to help guide the continued growth of NRP liver transplantation.

Recent findings: DCD livers recovered using NRP have consistently demonstrated excellent outcomes, with IC and patient and graft survival rates approaching those seen with grafts from donation after brain death donors. Recently, transplant centers have been working to increase the DCD donor pool by relaxing limits on donor quality, reconsidering organ viability markers, and combining NRP with ex situ machine perfusion technologies.

Summary: NRP is a powerful organ recovery technology transforming the practice of DCD liver transplantation. Current evidence suggests that organ utilization could be further expanded using NRP recovery, with excellent clinical outcomes reported by centers using less stringent donor and organ viability criteria.

Purpose of review: Primary and secondary liver cancers are frequently unresectable at the time of diagnosis. Historically, these patients were treated with palliative therapy and no hope for curative resection. While liver transplant has been the standard of care for unresectable hepatocellular carcinoma (HCC), its indications have expanded to other oncologic indications based on promising data from select centers. This review focuses on the utilization of liver transplant for HCC, cholangiocarcinoma, and colorectal liver metastasis.

Recent findings: In the realm of HCC, immunotherapy is an emerging treatment that has the potential for use in the advanced and neoadjuvant setting. It can benefit patients by downstaging them to resectable or transplantable disease burden. Regarding cholangiocarcinoma, better molecular profiling and targeted therapies have benefited patients, and ongoing studies in the United States and internationally will help further delineate the patients with cholangiocarcinoma who benefit from transplantation. Finally, there is emerging evidence that liver transplant for colorectal liver metastases can be safe and effective. While there is promising data showing survival benefit of liver transplantation (LT) for CRLM, standardized guidelines and recommendations in coordination with multidisciplinary oncology teams will be essential for establishing best practices.

Summary: Similar to the evolution of LT becoming the standard of care for well selected patients with HCC, the evolution of the role for LT for other hepatobiliary malignancies is quickly progressing as centers in Europe, Asia, and North America gain experience and develop protocols for selected patients with favorable tumor biology. Optimal oncology treatment requires multidisciplinary tumor board and case-by-case approaches which are essential for providing these patients with the best chance at optimal survival.

Purpose of review: To explore the emerging use of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) patients eligible for liver transplantation (LT), particularly as bridging and downstaging therapies. This review also addresses the clinical challenges of integrating ICIs into transplant protocols, including graft rejection, immune-related toxicities, and gaps in evidence.

Recent findings: ICIs have shown potential as bridging and downstaging therapies before LT, with multicentric studies reporting 75.6% successful downstaging, 85% 3-year post-LT survival, and 7.2% rejection-related mortality. A washout interval >94 days and older age have been identified as protective factors against allograft rejection. Combining locoregional therapies with ICIs has proven effective in the EMERALD-1 and LEAP-012 trials, which demonstrated improved progression-free survival (15.0 and 14.6 months, respectively) with ICI-TACE combinations. Similarly, the STAR-FIT phase II trial, combining TACE, SBRT, and avelumab, showed a 42% complete response rate and 12% conversion to curative therapy. Toxicity and rejection risk remain major challenges.

Summary: ICIs represent a promising tool for expanding transplant eligibility in HCC, but their integration into LT pathways remains complex. Safety concerns, particularly regarding timing and immune modulation, require careful evaluation. Prospective studies and biomarker development are needed to guide clinical decision-making. Novel therapies such as CAR-T cells may offer more targeted approaches in the future.

Purpose of review: Pediatric liver transplant waitlist mortality remains disproportionately high, particularly among infants under one year old. Despite the success of split liver transplantation (SLT) in improving pediatric access to transplants, its utilization remains limited. This review examines barriers to SLT adoption, explores the impact of pediatric-focused allocation policies, and evaluates the potential of machine perfusion technology in expanding the pediatric donor pool.

Recent findings: Studies have demonstrated that SLT outcomes are comparable to whole graft transplants when performed at experienced centers. However, logistical challenges, technical expertise, and policy limitations hinder its widespread adoption. Countries with pediatric-prioritized allocation and mandatory SLT policies, such as Italy and the United Kingdom, have significantly reduced pediatric waitlist mortality. Additionally, machine perfusion technology has emerged as a promising solution, allowing for ex vivo graft splitting and reducing ischemic injury, which may enhance graft utilization.

Summary: A multifaceted approach is necessary to improve pediatric liver transplant outcomes, including stronger pediatric-first allocation policies, SLT training expansion, and integration of machine perfusion technologies. Implementing these strategies in the United States could significantly reduce pediatric waitlist mortality without negatively impacting adult transplant candidates.

Purpose of review: We provide a review on the incidence, consequences, and management of obesity in patients before and after pancreas transplant.

Recent findings: Obesity is common in patients with both type 1 and type 2 diabetes. Obesity at the time of pancreas transplant is associated with worse graft and patient survival, while weight gain after transplant is associated with insulin resistance and posttransplant diabetes. Currently, lifestyle interventions are the backbone of obesity management and can improve insulin sensitivity, but result in only modest weight loss. Metabolic and bariatric surgery (MBS) offers the potential for substantial and durable weight loss. Laparoscopic sleeve gastrectomy is the procedure of choice and can be performed safely both before and after pancreas transplant. Antiobesity medications (AOMs) may also be effective, but concerns remain regarding determine the safety and efficacy when used in pancreas transplant recipients. More evidence is needed to guide the use of AOMs and MBS in pancreas transplant recipients.

Summary: Lifestyle interventions, MBS, and AOMs each have a role in managing obesity after pancreas transplantation. In light of limited evidence and unique challenges in pancreas transplant patients, obesity management in pancreas transplant patients requires an individualized approach that leverages multidisciplinary expertise.