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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 18F-fluorodeoxyglucose (FDG) that has been shown to have significant implications in the clinical oncology setting. Across various solid tumor malignancies, including lung cancer, head and neck cancer, breast cancer, esophageal cancer, and colorectal cancer, the current literature has demonstrated an association between MTV and various clinical outcomes. MTV may be used in conjunction with several existing and established clinical parameters to help inform risk stratification and treatment strategies and predict outcomes in cancer. Optimizing such volumetric parameters is paramount for advancing efforts to advance cancer care for our patients. While such advancements are made, it is important to investigate and address the limitations of MTV, including variability in terms of measurement methods, a lack of standardized cut-off values, and the impact of inherent tumor heterogeneity. Despite these limitations, which can precipitate challenges in standardization, MTV as a prognostic factor has great potential and opens an avenue for the future integration of technology into an image-based precision medicine model of care for cancer patients. This article serves as a narrative review and explores the utility and limitations of PET-MTV in various settings of solid-organ malignancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Liver transplantation (LT) is a key treatment for liver cancers by reducing tumor burden and improving liver function. While LT offers significant improvement in survival, cancer recurrence rates remain high. Ischemia-reperfusion injury (IRI) caused by mitochondria dysfunction drives tumor recurrence by creating a favorable pro-inflammatory microenvironment. Therefore, strategies that decrease IRI may also decrease cancer recurrence following LT. Machine perfusion techniques are increasingly used in routine clinical practice of LT with improved post-transplant outcomes. Normothermic (NMP) and hypothermic oxygenated machine perfusion (HOPE) provide oxygen to ischemic tissues, and impact IRI and potential cancer recurrence through different mechanisms. This article discussed the link between IRI-associated inflammation and tumor recurrence after LT and examined the role of machine perfusion as a strategy to mitigate the risk of cancer recurrence. Upfront NMP ("ischemia free organ transplantation") and end-ischemic HOPE were shown to reduce hepatocellular carcinoma recurrence in retrospective studies. Liver transplantation (LT) is a key treatment for primary and secondary liver cancers, reducing tumor burden with concurrent improvement of liver function. While significant improvement in survival is noted with LT, cancer recurrence rates remain high. Mitochondrial dysfunction caused by ischemia-reperfusion injury (IRI) is known to drive tumor recurrence by creating a favorable microenvironment rich in pro-inflammatory and angiogenic factors. Therefore, strategies that decrease reperfusion injury and mitochondrial dysfunction may also decrease cancer recurrence following LT. Machine perfusion techniques are increasingly used in routine clinical practice of LT with improved post-transplant outcomes and increased use of marginal grafts. Normothermic (NMP) and hypothermic oxygenated machine perfusion (HOPE) provide oxygen to ischemic tissues, and impact IRI and potential cancer recurrence through different mechanisms. This article discussed the link between IRI-associated inflammation and tumor recurrence after LT. The current literature was screened for the role of machine perfusion as a strategy to mitigate the risk of cancer recurrence. Upfront NMP ("ischemia free organ transplantation") and end-ischemic HOPE were shown to reduce hepatocellular carcinoma recurrence in retrospective studies. Three prospective randomized controlled trials are ongoing in Europe to provide robust evidence on the impact of HOPE on cancer recurrence in LT. [ABSTRACT FROM AUTHOR]

Simple Summary: Ischemia-reperfusion injury (IRI) is the source of significant graft inflammation in liver transplantation. Such injuries can lead to increased recurrence of both benign and malignant diseases of the biliary tree after transplant. Herein, we review the mechanisms and risk factors for the link between IRI and biliary recurrence, as well as evidence for strategies to mitigate this damage. Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue's ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted. [ABSTRACT FROM AUTHOR]

The comparison of outcomes in liver transplantation (LT) is hampered by using clinically nonrelevant surrogate endpoints and considerable variability in reported relevant posttransplant outcomes. Such variability stems from nonstandard outcome measures across studies, variable definitions of the same complication, and different timing of reporting. The Clavien-Dindo classification was established to improve the rigor of outcome reporting but is nonspecific to an intervention, and there are unsolved dilemmas specifically related to LT. Core outcome sets (COSs) have been used in other specialties to standardize outcomes research, but have not been defined for LT. Thus, we use the 5 major benchmarking studies published to date to define a 10-measure COS for LT using previously validated metrics. We further provide standard definitions for each of the 10 measures that may be used in international research on the topic. These definitions also include standard time points for recording to facilitate between-study comparisons and future meta-analysis. These 10 outcomes are paired with 3 validated, procedure-independent metrics, including the Clavien-Dindo Classification and the Comprehensive Complications Index. The Clavien scale and Comprehensive Complications Index are specifically reviewed to enhance their utility in LT, and their use, along with the COS, is explored. We encourage future studies to employ this COS along with the Clavien-Dindo grading system and Comprehensive Complications Index to improve the reproducibility and generalizability of research concerning LT., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Retinal pigment epithelium (RPE) dysfunction due to accumulation of reactive oxygen species and oxidative damage is a key event in the development of age-related macular degeneration (AMD). Here, we examine the therapeutic potential of ZLN005, a selective PGC-1 α transcriptional regulator, in protecting RPE from cytotoxic oxidative damage. Gene expression analysis on ARPE-19 cells treated with ZLN005 shows robust upregulation of PGC-1 α and its associated transcription factors, antioxidant enzymes, and mitochondrial genes. Energetic profiling shows that ZLN005 treatment enhances RPE mitochondrial function by increasing basal and maximal respiration rates, and spare respiratory capacity. In addition, ZLN005 robustly protects ARPE-19 cells from cell death caused by H 2 O 2 , ox-LDL, and NaIO 3 without exhibiting any cytotoxicity under basal conditions. ZLN005 protection against H 2 O 2 -mediated cell death was lost in PGC-1 α -silenced cells. Our data indicates that ZLN005 efficiently protects RPE cells from oxidative damage through selective induction of PGC-1 α and its target antioxidant enzymes. ZLN005 may serve as a novel therapeutic agent for retinal diseases associated with RPE dystrophies.