Perfusate Liver Arginase 1 Levels After End-Ischemic Machine Perfusion Are Associated with Early Allograft Dysfunction.

: The rising use of liver grafts from donation after circulatory death (DCD) has been enabled by advances in normothermic regional perfusion (NRP) and machine perfusion (MP) technologies. We aimed to identify predictive biomarkers in DCD grafts subjected to NRP, followed by randomization to either normothermic machine perfusion (NMP) or dual hypothermic oxygenated perfusion (D-HOPE). : Among 57 DCD donors, 32 liver grafts were transplanted, and recipients were monitored for one week post-transplant.

Sequential Normothermic Regional Perfusion and End-ischemic Ex Situ Machine Perfusion Allow the Safe Use of Very Old DCD Donors in Liver Transplantation.

Background: In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach.

Concomitant training in robotic and laparoscopic liver resections of low-to-intermediate difficulty score: a retrospective analysis of the learning curve.

In the setting of minimally invasive liver surgery (MILS), training in robotic liver resections (RLR) usually follows previous experience in laparoscopic liver resections (LLR). The aim of our study was to assess the learning curve of RLR in case of concomitant training with LLR. We analyzed consecutive RLRs and LLRs by a surgeon trained simultaneously in both techniques (Surg1); while a second surgeon trained only in LLRs was used as control (Surg2).

Immunohistochemical Study of Airways Fibrous Remodeling in Smoking Mice.

The fibrotic remodeling in chronic obstructive pulmonary disease (COPD) is held responsible for narrowing of small airways and thus for disease progression. Oxidant damage and cell senescence factors are recently involved in airways fibrotic remodeling. Unfortunately, we have no indications on their sequential expression at anatomical sites in which fibrotic remodeling develops in smoking subjects.

First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy.

Robotic versus laparoscopic liver resections: propensity-matched comparison of two-center experience.

Background: The advantages of the robotic approach in minimally invasive liver surgery (MILS) are still debated. This study compares the short-term outcomes between laparoscopic (LLR) and robotic (RLR) liver resections in propensity score matched cohorts.

Methods: Data regarding minimally invasive liver resections in two liver surgery units were retrospectively reviewed.

A narrative review of intrahepatic cholangiocarcinoma: a surgical curative option.

Background And Objective: Cholangiocarcinoma (CCA) is the second commonest primary liver malignancy. Nowadays, the only available treatment with curative intent of intrahepatic cholangiocarcinoma (iCCA) is surgical resection, with a 5-year overall survival (OS) of 25-40%. However, recurrence rate remains high.

FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells.

Replication stress (RS) is a leading cause of genome instability and cancer development. A substantial source of endogenous RS originates from the encounter between the transcription and replication machineries operating on the same DNA template. This occurs predominantly under specific contexts, such as oncogene activation, metabolic stress, or a deficiency in proteins that specifically act to prevent or resolve those transcription-replication conflicts (TRCs).

The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres.

Background: As literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead.

Methods: Data of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated.

Characterization of Chromosomal Instability in Glioblastoma.

Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system (CNS). The poor prognosis of GBM due to resistance to therapy has been associated with high chromosomal instability (CIN). Replication stress is a major cause of CIN that manifests as chromosome rearrangements, fragility, and breaks, including those cytologically expressed within specific chromosome regions named common fragile sites (CFSs).

Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation.

Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT.

Implementing a robotic liver resection program does not always require prior laparoscopic experience.

Background: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program.

Methods: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs.

Genome (in)stability at tandem repeats.

Repeat sequences account for over half of the human genome and represent a significant source of variation that underlies physiological and pathological states. Yet, their study has been hindered due to limitations in short-reads sequencing technology and difficulties in assembly. A important category of repetitive DNA in the human genome is comprised of tandem repeats (TRs), where repetitive units are arranged in a head-to-tail pattern.

Centromeres under Pressure: Evolutionary Innovation in Conflict with Conserved Function.

Centromeres are essential genetic elements that enable spindle microtubule attachment for chromosome segregation during mitosis and meiosis. While this function is preserved across species, centromeres display an array of dynamic features, including: (1) rapidly evolving DNA; (2) wide evolutionary diversity in size, shape and organization; (3) evidence of mutational processes to generate homogenized repetitive arrays that characterize centromeres in several species; (4) tolerance to changes in position, as in the case of neocentromeres; and (5) intrinsic fragility derived by sequence composition and secondary DNA structures. Centromere drive underlies rapid centromere DNA evolution due to the "selfish" pursuit to bias meiotic transmission and promote the propagation of stronger centromeres.

The Role of Salvage Transplantation in Patients Initially Treated With Open Versus Minimally Invasive Liver Surgery: An Intention-to-Treat Analysis.

Despite gaining wide consensus in the management of hepatocellular carcinoma (HCC), minimally invasive liver surgery (MILS) has been poorly investigated for its role in the setting of salvage liver transplantation (SLT). A multicenter retrospective analysis was carried out in 6 Italian centers on 211 patients with HCC who were initially resected with open (n = 167) versus MILS (n = 44) and eventually wait-listed for SLT. The secondary endpoint was identification of risk factors for posttransplant death and tumor recurrence.

Impaired Replication Timing Promotes Tissue-Specific Expression of Common Fragile Sites.

Common fragile sites (CFSs) are particularly vulnerable regions of the genome that become visible as breaks, gaps, or constrictions on metaphase chromosomes when cells are under replicative stress. Impairment in DNA replication, late replication timing, enrichment of A/T nucleotides that tend to form secondary structures, the paucity of active or inducible replication origins, the generation of R-loops, and the collision between replication and transcription machineries on particularly long genes are some of the reported characteristics of CFSs that may contribute to their tissue-specific fragility. Here, we validated the induction of two CFSs previously found in the human fetal lung fibroblast line, Medical Research Council strain (MRC-5), in another cell line derived from the same fetal tissue, Institute for Medical Research-90 cells (IMR-90).

Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study.

Several risk factors for ischaemic-type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donor's decade (<60 yo; 60-69 yo; 70-79 yo and ≥80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL.

Ongoing Lung Inflammation and Disease Progression in Mice after Smoking Cessation: Beneficial Effects of Formyl-Peptide Receptor Blockade.

The most important risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoking. Until now, smoking cessation (SC) is the only treatment effective in slowing down the progression of the disease. However, in many cases SC may only relieve the airflow obstruction and inflammatory response.

Salvage of an Octogenarian Liver Graft Using Normothermic Perfusion: A Case Report.

Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor.