Search

Introduction: Posthepatectomy liver failure (PHLF) remains the main reason for short-term mortality after liver surgery. APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), score and the liver function maximum capacity test (LiMAx) are both established preoperative (preop) liver function tests. The aim of this study was to compare both tests for their predictive potential for clinically significant PHLF grade B and C (B+C)., Materials and Methods: 352 patients were included from 4 European centers. Patients had available preop APRI+ALBI scores and LiMAx results. Predictive potential for PHLF, PHLF B+C and 90-day mortality was compared using receiver operating characteristic (ROC) curve analysis and calculation of the area under the curve (AUC). Published cutoffs of ≥ -2.46 for APRI+ALBI and of <315 for LiMAx were assessed using chi-squared test., Results: APRI+ALBI showed superior predictive potential for PHLF B+C (N = 34; AUC = 0.766), PHLF grade C (N = 20; AUC = 0.782) and 90-day mortality (N = 15; AUC = 0.750). When comparing the established cutoffs of both tests, APRI+ALBI outperformed LiMAx in prediction of PHLF B+C (APRI+ALBI ≥2.46: Positive predictive value (PPV) = 19%, negative predictive value (NPV) = 97%; LiMAx <315: PPV = 3%, NPV = 90%) and 90-day mortality (APRI+ALBI ≥2.46: PPV = 12%, NPV = 99%; LiMAx <315: PPV = 0%, NPV = 94%) CONCLUSION: In our analysis, APRI+ALBI outperformed LiMAx measurement in the preop prediction of PHLF B+C and postoperative mortality, at a fraction of the costs, manual labor and invasiveness., Competing Interests: Declaration of competing interest Patrick Starlinger was involved in the development of a freely available smartphone-first application (TELLAPRIALBI, https://tellaprialbi.howto.health), all other authors have no conflict of interest to declare., (© 2024 Published by Elsevier Ltd.)

Background & Aims: Surgical resection of the cancerous tissue represents one of the few curative treatment options for neoplastic liver disease. Such partial hepatectomy (PHx) induces hepatocyte hyperplasia, which restores liver function. PHx is associated with bacterial translocation, leading to an immediate immune response involving neutrophils and macrophages, which are indispensable for the priming phase of liver regeneration. Additionally, PHx induces longer-lasting intrahepatic apoptosis. Herein, we investigated the effect of apoptotic extracellular vesicles (aEVs) on neutrophil function and their role in this later phase of liver regeneration., Methods: A total of 124 patients undergoing PHx were included in this study. Blood levels of the apoptosis marker caspase-cleaved cytokeratin-18 (M30) and circulating aEVs were analyzed preoperatively and on the first and fifth postoperative days. Additionally, the in vitro effects of aEVs on the secretome, phenotype and functions of neutrophils were investigated., Results: Circulating aEVs increased at the first postoperative day and were associated with higher concentrations of M30, which was only observed in patients with complete liver recovery. Efferocytosis of aEVs by neutrophils induced an activated phenotype (CD11b high CD16 high CD66b high CD62L low ); however, classical inflammatory responses such as NETosis, respiratory burst, degranulation, or secretion of pro-inflammatory cytokines were not observed. Instead, efferocytosing neutrophils released various growth factors including fibroblast growth factor-2 and hepatocyte growth factor (HGF). Accordingly, we observed an increase of HGF-positive neutrophils after PHx and a correlation of plasma HGF with M30 levels., Conclusions: These data suggest that the clearance of PHx-induced aEVs leads to a population of non-inflammatory but regenerative neutrophils, which may support human liver regeneration., Lay Summary: In this study, we show that the surgical removal of a diseased part of the liver triggers a specific type of programmed cell death in the residual liver tissue. This results in the release of vesicles from dying cells into the blood, where they are cleared by circulating immune cells. These respond by secreting hepatocyte growth factors that could potentially support the regeneration of the liver remnant., Competing Interests: Conflict of interests Thomas Hammond is employed by and is a shareholder in AstraZeneca. All other authors declare no conflicts. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Micro-metastatic growth is considered the main source of early cancer recurrence. Nutritional and microenvironmental components are increasingly recognized to play a significant role in the liver. We explored the predictive potential of preoperative plasma metabolites for postoperative disease recurrence in colorectal cancer liver metastasis (CRCLM) patients., Methods: All included patients (n = 71) had undergone R0 liver resection for colorectal cancer liver metastasis in the years between 2012 and 2018. Preoperative blood samples were collected and assessed for 180 metabolites using a preconfigured mass-spectrometry kit (Biocrates Absolute IDQ p180 kit). Postoperative disease-free (DFS) and overall survival (OS) were prospectively recorded. Patients that recurred within 6 months after surgery were defined as "high-risk" and, subsequently, a three-metabolite model was created which can assess DFS in our collective., Results: Multiple lysophosphatidylcholines (lysoPCs) and phosphatidylcholines (PCs) significantly predicted disease recurrence within 6 months (strongest: PC aa C36:1 AUC = 0.83, p = 0.003, PC ae C34:0 AUC = 0.83, p = 0.004 and lysoPC a C18:1 AUC = 0.8, p = 0.006). High-risk patients had a median DFS of 183 days versus 522 days in low-risk population (p = 0.016, HR = 1.98 95% CI 1.16-4.35) with a 6 months recurrence rate of 47.6% versus 4.7%, outperforming routine predictors of oncological outcome., Conclusion: Circulating metabolites identified CRCLM patients at highest risk for 6 months disease recurrence after surgery. Our data also suggests that circulating metabolites might play a significant pathophysiological role in micro-metastatic growth and concomitant early tumor recurrences after liver resection. However, the clinical applicability and performance of this proposed metabolomic concept needs to be independently validated in future studies., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)