Prognostic Factors for Mortality in Acute Mesenteric Ischemia.

Postoperative mortality in patients undergoing surgical and/or interventional treatment for acute mesenteric ischemia (AMI) has remained an unsolved problem in recent decades. Here, we investigated clinical predictors of postoperative mortality in a large European cohort of patients undergoing treatment for AMI. In total, 179 patients who underwent surgical and/or interventional treatment for AMI between 2009 and 2021 at our institution were included in this analysis. Associations between postoperative mortality and various clinical variables were assessed using univariate and multivariable binary logistic regression analysis. Most of the patients were diagnosed with arterial ischemia (AI; n = 104), while venous ischemia (VI; n = 21) and non-occlusive mesenteric ischemia (NOMI; n = 54) were present in a subset of patients. Overall inhouse mortality was 55.9% (100/179). Multivariable analyses identified leukocytes (HR = 1.08; p = 0.008), lactate (HR = 1.25; p = 0.01), bilirubin (HR = 2.05; p = 0.045), creatinine (HR = 1.48; p = 0.039), etiology (AI, VI or NOMI; p = 0.038) and portomesenteric vein gas (PMVG; HR = 23.02; p = 0.012) as independent predictors of postoperative mortality. In a subanalysis excluding patients with fatal prognosis at the first surgical exploration (n = 24), leukocytes (HR = 1.09; p = 0.004), lactate (HR = 1.27; p = 0.003), etiology (AI, VI or NOMI; p = 0.006), PMVG (HR = 17.02; p = 0.018) and intraoperative FFP transfusion (HR = 4.4; p = 0.025) were determined as independent predictors of postoperative mortality. Further, the risk of fatal outcome changed disproportionally with increased preoperative lactate values. The clinical outcome of patients with AMI was determined using a combination of pre- and intraoperative clinical and radiological characteristics. Serum lactate appears to be of major clinical importance as the risk of fatal outcome increases significantly with higher lactate values

Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection

Simple Summary: Hepatocellular carcinoma remains a leading cause of cancer-related death and the most common primary hepatic malignancy in the Western hemisphere. Previous research found that angiogenesis-related cytokines and elevated levels of interleukin 8 and vascular endothelial growth factor (VEGF) shorten the expected time of survival. Moreover, factors of tumor angiogenesis- and hypoxia-driven signaling pathways are already associated with worse outcome in disease-free survival in several tumor entities. Our study investigates the prognosis of hepatocellular carcinoma patients based on a selection of ten different single-nucleotide polymorphisms from angiogenesis, carcinogenesis, and hypoxia pathways. Our study with 127 patients found supporting evidence that polymorphisms in angiogenesis-associated pathways corelate with disease-free survival and clinical outcome in patients with hepatocellular carcinoma. Abstract: Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)-restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of "high-expression" variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients' individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery

New Frontiers in Organ Preservation and Hepatoprotection

This editorial aims to summarize the 13 scientific articles published in the Special Issue entitled “New Frontiers in Organ Preservation and Hepatoprotection” [...

Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches

The Benefits of Fibrinolysis Combined with Venous Systemic Oxygen Persufflation (VSOP) in a Rat Model of Donation after Circulatory Death and Orthotopic Liver Transplantation

Organ shortage has led to the increasing utilization of livers retrieved from donors after circulatory death (DCD). These pre-damaged organs are susceptible to further warm ischemia and exhibit minimal tolerance for cold storage. The aim was thus to examine the effects of fibrinolysis combined with Venous Systemic Oxygen Persufflation (VSOP) on the preservation of DCD livers in vivo. Livers of male Lewis rats were explanted after 45 min of warm ischemia, cold-stored for 18 h, and transplanted into a recipient animal. Livers were left untreated or underwent either VSOP or fibrinolysis via Streptokinase (SK) or received combined SK and VSOP. Combined treatment exhibited improved microvascular flow at 168 h (p = 0.0009) and elevated microperfusion velocity at 24 h post-transplantation (p = 0.0007). Combination treatment demonstrated increased portal venous flow (PVF) at 3 and 24 h post-transplantation (p = 0.0004, p < 0.0001), although SK and VSOP analogously achieved increases at 24 h (p = 0.0036, p = 0.0051). Enzyme release was decreased for combination treatment (p = 0.0002, p = 0.0223) and lactate dehydrogenase (LDH) measurements were lower at 24 h post-transplantation (p = 0.0287). Further supporting findings have been obtained in terms of serum cytokine levels and in the alterations of endothelial injury markers. The combination treatment of SK + VSOP might provide improved organ integrity and viability and may therefore warrant further investigation as a potential therapeutic approach in the clinical setting of DCD

Systematic Review on Characteristics and Reporting Quality of Animal Studies in Liver Regeneration Triggered by Portal Vein Occlusion and Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy:Adherence to the ARRIVE Guidelines

Background: Portal vein occlusion and associating liver partition and portal vein ligation for staged hepatectomy techniques are in the spotlight of oncological liver surgery. Research involving animal models is indispensable to study the mechanisms of liver regeneration. Inaccurate reporting acts as a significant barrier during the correct interpretation of preclinical findings. Hence, we performed a systematic review to evaluate the status quo of the reporting standards and to assess the potential factors influencing reporting in animal studies, which are focusing on portal vein occlusion and/or associating liver partition and portal vein ligation for staged hepatectomy techniques. Materials and methods: A systematic review was performed in the PubMed and Ovid MEDLINE databases. Baseline study characteristics were recorded, and quality assessment was performed using the Animals in Research: Reporting in vivo Experiments (ARRIVE) checklist. Results: A total of 107 research articles were included for the comprehensive assessment. In the subgroup analysis, newer reports and studies from the post-ARRIVE era, and reports from Europe were all associated with significantly higher ARRIVE scores (P <0.05). Univariable regression analysis confirmed these factors as predictors of higher reporting quality. However, in the multivariable analysis, only publishing in the post-ARRIVE era has been found as single independent predictor of higher reporting standards (P = 0.028 post-ARRIVE total score 75th percentile; P = 0.000 post-ARRIVE total score median). Conclusions: Although an improving trend has been observed in reporting quality over the past years, this effect was clearly insufficient. Our results emphasize the need for further measures to improve the methodical quality at all levels of planning, execution, and reporting of preclinical studies in liver regeneration research. (C) 2018 Elsevier Inc. All rights reserved

Prognostic evaluation of HCC patients undergoing surgical resection:an analysis of 8 different staging systems

Purpose No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. Methods Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) chi(2) (homogeneity), linear trend (LT) chi(2) (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. Results Liver resection for HCC was performed in 160 patients. Median OS was 39 months (95% confidence interval (CI): 32-46 months) and median RFS was 26 months (95% CI: 16-34 months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR chi(2) 30.08, LT chi(2) 13.90, AIC 455.27) and CLIP (LR chi(2) 28.65, LT chi(2) 18.95, AIC 460.07) being the best performing staging systems. Conclusions ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery