From critical care to organ preservation: the potential role of hemadsorption in transplantation-a narrative review.

Background And Objective: Hemadsorption, a therapeutic modality traditionally used to mitigate cytokine storm in critically ill patients and is now being tested in other medical fields including organ transplantation, especially for organs from extended criteria donors. Such organs are susceptible to ischemia-reperfusion injury (IRI) during transplantation, which is known to release a cascade of innate immune mediators including damage-associated molecular patterns (DAMPs) and cytokines during reperfusion and ultimately leading to graft dysfunction based on the metabolic injury. To address this challenge, early studies have integrated hemadsorption filters into organ perfusion circuits, such as normothermic regional perfusion (NRP) in donors and machine perfusion (MP) of grafts, with the aim to reduce inflammation and improve organ viability.

Hypothermic Oxygenated Perfusion Versus Static Cold Storage in Transplantation of Extended Criteria Liver Grafts: A Systematic Review and Meta-Analysis.

Background: The use of extended criteria donor livers (ECD) is becoming more routine in many transplant centers. These organs have higher risks for complications; however, hypothermic-oxygenated perfusion (HOPE) was found to improve outcomes, including graft survival. We aim to assess the effect of HOPE on different types of ECD liver grafts.

Use of Histotripsy to Rapidly Relieve Biliary Obstruction in a Patient With Recurrent Hilar Cholangiocarcinoma.

Hilar cholangiocarcinoma (HCCA) is a rare, aggressive cancer often diagnosed at an unresectable stage. Patients commonly require systemic therapy and biliary stenting to manage symptoms and maintain liver function. Histotripsy is a novel, non-invasive, mechanical ablation technique recently FDA-approved for liver tumors.

Distant Tumor Response in the Pelvis After Histotripsy of a Metastatic Sarcoma of the Liver in a Patient With Differentiated Liposarcoma.

Dedifferentiated liposarcoma with leiomyosarcomatous differentiation is a rare, aggressive subtype of soft tissue sarcoma with limited treatment options. Histotripsy is a novel, non-invasive, non-thermal ablative therapy that uses focused ultrasound to induce mechanical tissue destruction through acoustic cavitation. We report a case of a 72-year-old female with metastatic dedifferentiated liposarcoma who underwent histotripsy for 2 large hepatic metastases after progression on other therapies.

Reducing percutaneous cholecystostomy for acute calculous cholecystitis: A multisite quality improvement initiative.

Background: Laparoscopic cholecystectomy is the gold standard for treating acute calculous cholecystitis, whereas percutaneous cholecystostomy is typically reserved for patients at prohibitive surgical risk, given its greater complication rates. This multisite quality improvement initiative aimed to reduce the use of percutaneous cholecystostomy in patients at acceptable risk for surgery.

Methods: In October 2023, a multidisciplinary team implemented an acute calculous cholecystitis care pathway across 8 teaching hospitals.

A New Era of Decision-making in Liver Transplantation: A Prospective Validation and Cost-effectiveness Analysis of FMN-guided Liver Viability Assessment During Normothermic Machine Perfusion.

Objectives: Flavin mononucleotide (FMN), a marker of mitochondrial complex 1 injury, has not yet been validated for its predictive value of outcomes and economic impact.

Background: Normothermic machine perfusion (NMP) is the only ex situ perfusion technique currently approved for liver transplantation in the United States. Optimal graft viability assessment on this approach remains controversial.

Optical Spectroscopic Detection of Mitochondrial Biomarkers (FMN and NADH) for Hypothermic Oxygenated Machine Perfusion: A Comparative Study in Different Perfusion Media.

Ex situ machine perfusion has emerged as a pivotal technique for organ preservation and pre-transplant viability assessment, where the real-time monitoring of mitochondrial biomarkers-flavin mononucleotide (FMN) and nicotinamide adenine dinucleotide (NADH)-could significantly mitigate ischemia-reperfusion injury risks. This study develops a non-invasive optical method combining fluorescence and UV-visible spectrophotometry to quantify FMN and NADH in hypothermic oxygenated perfusion media. Calibration curves revealed linear responses for both biomarkers in absorption and fluorescence (FMN: λ = 445 nm, λ = 530-540 nm; NADH: λ = 340 nm, λ = 465 nm) at concentrations < 100 μg mL.

Re-emergence of early liver transplant access for hepatocellular carcinoma in the era of normothermic machine perfusion.

Background: Since the Food and Drug Administration (FDA) approval of normothermic machine perfusion (NMP) in September 2021, liver transplantation (LT) numbers dramatically increased with shortened waitlist times. This is generally a positive trend. However, this might allow candidates with hepatocellular carcinoma (HCC) in the United States to receive LT without exception scores, for whom expedited transplant might not be ultimately beneficial.

Mechanisms and Management of Graft In- and Out-flow in Liver Transplantation: A Narrative Review of the Literature and Guide for Interventional Management.

Background And Aims: Management of the dual vascular supply of liver grafts in liver transplantation (LT) is increasingly recognized as crucial to achieving adequate graft function. We aim to review how the relationship between graft in-flow and out-flow affects graft function, and how surgeons can manage graft function within the context of liver hemodynamic autoregulation. This includes mechanisms of such autoregulation including the hepatic artery buffer response (HABR), and the impact of porto-systemic circulatory changes on graft inflow.

Circulating Tumor DNA in Primary and Secondary Liver Cancers: A Comprehensive Review.

Similar to many other cancer types, liver malignancies pose the common challenges of late detection of primary tumors and recurrences. Liquid biopsies, which assess the presence of circulating tumor DNA, have emerged as a novel, non-invasive clinical tool for diagnostic and surveillance purposes. This review represents an introductory and comprehensive overview of the current circulating tumor DNA (ctDNA) literature relevant to primary and secondary liver malignancies.

Upper limit of normothermic machine preservation of liver grafts from donation after circulatory death yet to be defined.

Background: The normothermic machine perfusion pump (NMPP) could shape the future of transplantation. Providing optimization, NMPP attenuates ischemic insult while replenishing energy. An understanding of machine perfusion time (MPT) impact and potential clinical benefits is paramount and necessitates exploration.

Quantifying Flavin mononucleotide: an internationally validated methodological approach for enhanced decision making in organ transplantation.

Background: Increasing donor risk, particularly in liver transplantation, where organs are often marginal, has made dynamic organ preservation techniques and viability assessment essential to safely improve organ quality and increase utilisation. However, existing viability parameters are based on routine clinical assessment in patients with acute liver failure, trauma, or liver resections. These parameters often do not correlate with clinically relevant post-transplant outcomes.

Transforming Transplant Oversight: Enhancing Combined Cardiothoracic Surgery and Liver Transplantation With Normothermic Machine Perfusion.

Background: Simultaneous cardiothoracic surgery and liver transplantation (LT) is a high-risk procedure associated with high mortality and morbidity rates. The use of normothermic machine perfusion (NMP) allows graft quality enhancement, assessment of liver viability, and logistics optimization, expanding the donor pool and reducing organ discard rate. We share our institution's experience with simultaneous cardiothoracic surgery and LT, using NMP for liver graft preservation and viability assessment.

Out of Sequence Allocation in Liver Transplantation: A Poorly Used Tool to Improve Organ Utilization.

Significance: We evaluated the impact of OOS on organ utilization and also what factors impact the decision to employ OOS.

Background: Deceased donor liver allocation typically follows a ranked match-run of potential recipients. Organ procurement organizations (OPOs) may deviate from liver transplant standardized allocation using "out-of-sequence" (OOS) matches.

Histotripsy of Liver Tumors: Patient Selection, Ethical Discussions, and How We Do It.

Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options.

Elderly Ages in Liver Transplantation: Are Older Donors Really Higher Risk?

Background: There is currently a supply and demand mismatch in liver transplantation, with more patients needing transplants than grafts available. The use of older donors is one potential way of expanding access to viable grafts. No national study has yet reported on outcomes of liver transplants with donors ≥70 y.

Programmatic Normothermic Machine Perfusion and Association with Liver Transplant Waitlist Outcomes for Patients with Lower Model for End-Stage Liver Disease Score.

Background: Normothermic machine perfusion (NMP) may enhance the use of extended criteria donor livers which might impact waitlist outcomes. Its impact on patients with low Model for End-Stage Liver Disease (MELD) scores, who generally face longer waitlist times, has not been studied. This study aimed to assess the impact of NMP on waitlist and post liver transplantation (LT) outcomes accounting for MELD allocation preference.

Expanding Indications in Transplant Oncology.

Liver transplantation is aptly described as the only curative treatment for cirrhosis and cirrhosis with co-morbid hepatocellular carcinoma (HCC). Its utility in the management of various other primary and secondary liver cancers is gaining traction rapidly, with more thorough assessments on broader populations continuing to emerge. Most prominently, this includes colorectal cancer liver metastasis (CRLM), cholangiocarcinoma (CCA), neuroendocrine tumors (NETs), and more.

Bridging therapy with histotripsy prior to liver transplantation for hepatocellular carcinoma: a first case report.

Background: Histotripsy is a novel, non-invasive, non-ionizing, and non-thermal ablation technique that disrupts tumors using acoustic cavitation. We report the first use of Histotripsy as bridging therapy prior to liver transplant for hepatocellular carcinoma (HCC) treated with histotripsy.

Case Presentation: A 59-year-old woman presented with Metabolic-Associated Steatotic Liver Disease (MASLD) cirrhosis (labMELD = 14), hepatic encephalopathy, and a single 2 cm OPTN V lesion in the left lateral segment consistent with HCC.

The first international experience with histotripsy: a safety analysis of 230 cases.

Background: Histotripsy is a novel, noninvasive, nonionizing, and nonthermal approach that uses focused ultrasound waves to treat liver tumors. This technology received a de novo Food and Drug Administration grant in late 2023. This study aimed to provide the first report on post-trial real-world clinical safety data.

PET-Assessed Metabolic Tumor Volume Across the Spectrum of Solid-Organ Malignancies: A Review of the Literature.

Solid-organ malignancies represent a significant disease burden and remain one of the leading causes of death globally. In the past few decades, the rapid evolution of imaging modalities has shifted the paradigm towards image-based precision medicine, especially in the care of patients with solid-organ malignancies. Metabolic tumor volume (MTV) is one such semi-quantitative parameter obtained from positron emission tomography (PET) imaging with F-fluorodeoxyglucose (FDG) that has been shown to have significant implications in the clinical oncology setting.

Sequence of Chemotherapy May Not Impact Survival After Resection of Pancreatic Tail Adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) of the body/tail is notably different than PDAC in the head of the pancreas. Surgery plus chemotherapy is known to improve outcomes for all PDAC. The sequence of this therapy is well studied in head cancers yet has never been evaluated systematically in relation to distal pancreatectomy (DP).