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With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs . 31.7%, in SCS group ( p  =  0.05 ). Primary non-function was 3.3% for SCS-L vs . 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs .344 U/L, p  =  0.007 ). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT.

Background Metabolic reprogramming is a well-known marker of cancer, and it represents an early event during hepatocellular carcinoma (HCC) development. The recent approval of several molecular targeted agents has revolutionized the management of advanced HCC patients. Nevertheless, the lack of circulating biomarkers still affects patient stratification to tailored treatments. In this context, there is an urgent need for biomarkers to aid treatment choice and for novel and more effective therapeutic combinations to avoid the development of drug-resistant phenotypes. This study aims to prove the involvement of miR-494 in metabolic reprogramming of HCC, to identify novel miRNA-based therapeutic combinations and to evaluate miR-494 potential as a circulating biomarker. Methods Bioinformatics analysis identified miR-494 metabolic targets. QPCR analysis of glucose 6-phosphatase catalytic subunit (G6pc) was performed in HCC patients and preclinical models. Functional analysis and metabolic assays assessed G6pc targeting and miR-494 involvement in metabolic changes, mitochondrial dysfunction, and ROS production in HCC cells. Live-imaging analysis evaluated the effects of miR-494/G6pc axis in cell growth of HCC cells under stressful conditions. Circulating miR-494 levels were assayed in sorafenib-treated HCC patients and DEN-HCC rats. Results MiR-494 induced the metabolic shift of HCC cells toward a glycolytic phenotype through G6pc targeting and HIF-1A pathway activation. MiR-494/G6pc axis played an active role in metabolic plasticity of cancer cells, leading to glycogen and lipid droplets accumulation that favored cell survival under harsh environmental conditions. High miR-494 serum levels associated with sorafenib resistance in preclinical models and in a preliminary cohort of HCC patients. An enhanced anticancer effect was observed for treatment combinations between antagomiR-494 and sorafenib or 2-deoxy-glucose in HCC cells. Conclusions MiR-494/G6pc axis is critical for the metabolic rewiring of cancer cells and associates with poor prognosis. MiR-494 deserves attention as a candidate biomarker of likelihood of response to sorafenib to be tested in future validation studies. MiR-494 represents a promising therapeutic target for combination strategies with sorafenib or metabolic interference molecules for the treatment of HCC patients who are ineligible for immunotherapy.

The rising prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Hepatocellular Carcinoma in the elderly population has increased the demand for liver transplantation (LT) in patients over 70 years. Advanced age, however, is still considered an independent risk factor. This study aims to evaluate post-transplant oucomes in patients aged over 70 years, traditionally viewed as an age limit for transplant. We retrospectively analyzed 584 LT recipients (36 aged ≥70, 548 aged <70). Viral cirrhosis was more frequent in the younger group (36.1% vs. 13.1%), while MASLD was more common in those over 70 (25% vs. 13.1%) (p = 0.013). Model for End-Stage Liver Disease (MELD) scores were lower in patients over 70 (13, IQR 9–17) compared to the younger group (15, IQR 10–23) (p = 0.032). Propensity score matching (3:1 ratio, without replacement) was performed based on MELD and cirrhosis etiology. After matching, no significant differences were found in postoperative outcomes, overall survival, or graft survival. Our findings demonstrate that carefully selected patients over 70 can achieve post-transplant outcomes comparable to younger patients. Advanced age alone should not be considered an absolute contraindication; instead, a comprehensive, multidimensional assessment is essential to identify suitable candidates.

Background For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. Methods All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009–2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). Results The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. Conclusions The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.

The burden of post-operative complications of patients undergoing liver resection for hepatocellular carcinoma (HCC) is a cause of morbidity and mortality. Recently, sarcopenia has been reported to influence the outcome of patients with cirrhosis. We aimed to assess factors associated with sarcopenia and its prognostic role in liver surgery candidates. We included all patients with compensated advanced chronic liver disease (cACLD) undergoing liver resection for primary HCC consecutively referred to the University of Bologna from 2014 to 2019 with an available preoperative abdominal CT-scan performed within the previous three months. A total of 159 patients were included. The median age was 68 years, and 80.5% of the patients were male. Sarcopenia was present in 82 patients (51.6%). Age and body mass index (BMI) were associated with the presence of sarcopenia at multivariate analysis. Thirteen (8.2%) patients developed major complications and 14 (8.9%) presented PHLF grade B-C. The model for end-stage liver disease score was associated with the development of major complications, whereas cACLD presence, thrombocytopenia, portal hypertension (PH), Child-Pugh score and Albumin-Bilirubin score were found to be predictors of clinically significative PHLF. The rate of major complications was 11.8% in sarcopenic patients with cACLD compared with no complications (0%) in patients without sarcopenia and cACLD (p = 0.032). The rate of major complications was significantly higher in patients with (16.3%) vs. patients without (0%) sarcopenia (p = 0.012) in patients with PH. In conclusion, sarcopenia, which is associated with age and BMI, may improve the risk stratification of post-hepatectomy major complications in patients with cACLD and PH.

Background The aim of the study was to evaluate perioperative outcomes and to evaluate factors influencing rative morbidity and adoption of minimally invasive technique in 1-team (1-T) versus two teams (2-T) management of synchronous colorectal liver metastases. Methods Within four referral centers, a group of 234 patients treated in 1-T centers was identified and compared with a group of 253 patients treated in 2-T. A nonparametric bootstrap process was applied to the original cohorts of 1-T group and 2-T group as a resampling method to obtain bootstrapped cohorts (155 patients per group). Results 33.5% of patients in 1-T boot group and 38.1% in the 2-T boot group were operated by laparoscopic approach. Multivariate analysis revealed that approach to primary tumor (laparoscopic or open) and intraoperative blood loss were independent prognostic factors for morbidity. Team approach did not show any significant correlation with incidence of postoperative complications nor with choice for laparoscopic approach. Conclusion The optimization of team strategy for patients with SCRLM is not solely based on the adoption of a 1-T or 2-T approach, but should instead be based on the implementation of a standard protocol for management of these patients.

Background: The Italian Score for Organ Allocation (ISO), a transplant benefit oriented allocation system, was introduced in Italy in 2016. The main objective of this study is to identify risk factors for Drop-Out in hepatocellular (HCC) patients enlisted for LT before (Pre-ISO Era) and after ISO (ISO Era) introduction, while the secondary objective is to evaluate the survival results. Methods: CIFs for liver transplantation and Drop-Out were estimated and compared between eras. Factors associated with Drop-Out were identified through multivariable competing risks regression. Survival results were compared using the log-rank test. Results: Between 2011 and 2020, 410 patients with HCC were listed for LT. We observed 103 vs. 217 LT and 49 vs. 41 Drop-Outs (p < 0.001) during the Pre-ISO and ISO Era, respectively. In the multivariable analysis, ISO ([sHR] 0.43; 95%CI 0.28–0.66, p < 0.001) and Alcoholic Cirrhosis ([sHR] 0.27, 95%CI 0.11–0.70; p = 0.007) were revealed to be protective factors for Drop-Out. One year after listing, the CI for Drop-Out decreased from 13.2% to 6.2% (p = 0.02). Despite no differences observed in post-LT survival, a significant difference in the intention-to-treat survival from enlisting was found (p = 0.0019). Conclusions: Among other factors, ISO results were protective for the Drop-Out risk in HCC patients awaiting LT, with a benefit in ITT-OS survival.

In recent years, Transcranial Color Doppler (TCCD) has gained increasing recognition as a non-invasive neuromonitoring tool. However, there remains a strong tendency to view arterial TCCD as the ‘stethoscope for the brain,’ while the assessment of cerebral venous flow is still underrepresented in clinical protocols. This review aims to explore the emerging role of venous TCCD, particularly when combined with Internal Jugular Vein (IJV) ultrasound, in evaluating cerebral venous outflow in both critically ill and surgical patients. We conducted a narrative review of e-Pub articles from PubMed, MEDLINE, and Scopus, on the pathophysiological factors that impair cerebral venous drainage and their clinical implications in surgical and critical care settings. Based on this evidence, we developed two procedural algorithms that integrate established knowledge of cerebral venous hemodynamics with common clinical conditions affecting venous outflow, including internal jugular central venous catheter placement, mechanical ventilation, and pneumoperitoneum. The algorithms emphasize systematic monitoring of cerebral venous drainage, including assessment of internal jugular vein morphology and Rosenthal’s vein flow, to guide procedural optimization and minimize potential neurological complications. They were informed by validated frameworks, such as the RaCeVa protocol, and are illustrated through two representative clinical case scenarios. Cerebral venous congestion can be induced by multiple established risk factors, including mechanical ventilation, cardiovascular disease, elevated intra-abdominal pressure, the Trendelenburg position, and central venous catheterization. In selected patients, real-time venous TCCD monitoring, combined with IJV assessment, allows early detection of cerebral venous outflow impairment and guides timely hemodynamic and procedural adjustments in both surgical settings and critical care contexts. Venous TCCD neuromonitoring may help prevent intracranial hypertension and its consequent neurological complications. It can guide clinical decisions during procedures that may compromise cerebral venous drainage, such as mechanical ventilation, the placement of large-bore central venous catheters, or laparoscopic and robot-assisted surgeries. Further studies are warranted to validate this strategy and better define its role in specific high-risk clinical scenarios.

Background It remains unclear whether hepatectomy for hepatocellular carcinoma should be performed as an anatomic resection (AR) or a nonanatomic resection (NAR). Because no randomized controlled trials are currently available on this topic, a meta-regression analysis was performed on available observational studies to control for confounding variables. Methods A systematic review of studies published from 1990 to 2011 in the PubMed and Embase databases was performed. Patient and disease-free survival (DFS), postoperative mortality, and morbidity were considered as outcomes. Results are expressed as relative risk (RR) or weighted mean differences with 95 % of confidence interval. Results Eighteen observational studies involving 9,036 patients were analyzed: 4,012 were in the AR group and 5,024 in the NAR group. Meta-analysis suggested that AR provided better 5-year patient survival (RR 1.14; P  = 0.001) and DFS than NAR (RR 1.38; P  = 0.001). However, patients in the NAR group were characterized by a higher prevalence of cirrhosis (RR 1.27; P  = 0.010), more advanced hepatic dysfunction (RR 0.90 for Child-Pugh class A; P  = 0.001) and smaller tumor size (weighted mean difference 0.36 cm; P  < 0.001) compared with patients in the AR group. Meta-regression analysis showed that the different proportion of cirrhosis in the NAR group significantly affected both 5-year patient survival (RR 1.28; P  = 0.016) and DFS (RR 1.74; P  = 0.022). Tumor size only slightly affected DFS (RR 1.72; P  = 0.076). Postoperative mortality and morbidity were unaffected ( P  > 0.05 in all cases). Conclusions Patient survival and DFS after AR seem to be superior to NAR because the worse liver function reserve in the NAR group significantly affects prognosis.