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The authors assessed the impact of severe hepatic impairment on the disposition of fingolimod--a sphingosine-1-phosphate receptor immunomodulator primarily metabolized by CYP4F2--in 6 patients and 6 matched healthy controls who received a single 5-mg oral dose. Compared with healthy controls, severe hepatic-impaired subjects had a doubled area under the concentration time curve (AUC) and 50% prolonged elimination half-life but a similar peak blood concentration. When these data were combined with those from a previous study in mild and moderate hepatic-impaired subjects, there were significant positive correlations between fingolimod AUC versus bilirubin (r = 0.683) and prothrombin time (r = 0.777) and a significant negative correlation versus albumin (r = 0.578), confirming the importance of liver function for fingolimod clearance. For patients with severe hepatic impairment (Child-Pugh class C), a standard first dose of fingolimod could be given followed by a maintenance dose that is reduced by half from the normal maintenance dose. [ABSTRACT FROM AUTHOR]

Biliary anastomotic strictures after liver transplantation are a major source of morbidity and graft failure; however, repeated endoscopic therapy has shown variable long-term success rates. Thus the aim of this prospective case series was to evaluate the safety and efficacy of using paclitaxel-eluting balloons in 13 patients requiring treatment for symptomatic anastomotic strictures following liver transplantation. Sustained clinical success-defined as no need for further endoscopic intervention for at least 6 months - was achieved in 12 /13 patients (92 %). One, two, and three interventions were required in 9 (69 %), 1, and 2 patients, respectively (mean number of sessions was 1.46). Mean (± SD) bilirubin level dropped from 6.8 (± 4.1) mg/dL to 1.4 (± 0.9) mg/dL. These promising results justify carrying out a randomized comparative trial to confirm this innovative approach. [ABSTRACT FROM AUTHOR]

Competing Interests: Die Übersicht über die Interessenkonflikte der Autorinnen und Autoren sind im Leitlinienreport veröffentlicht.

In Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human ATP7B knock-out intestinal cells to their respective wild-type controls. We observed gastrointestinal (GI) inflammation in patients, rats and mice lacking ATP7B. Mitochondrial alterations and increased intestinal leakage were observed in WD rats, Atp7b -/- mice and human ATP7B KO Caco-2 cells. Proteome analyses of intestinal WD homogenates revealed profound alterations of energy and lipid metabolism. The intestinal damage in WD animals and human ATP7B KO cells did not correlate with absolute Cu elevations, but likely reflects intracellular Cu mislocalization. Importantly, Cu depletion by the high-affinity Cu chelator methanobactin (MB) restored enterocyte mitochondria, epithelial integrity, and resolved gut inflammation in WD rats and human WD enterocytes, plausibly via autophagy-related mechanisms. Thus, we report here before largely unrecognized intestinal damage in WD, occurring early on and comprising metabolic and structural tissue damage, mitochondrial dysfunction, and compromised intestinal barrier integrity and inflammation, that can be resolved by high-affinity Cu chelation treatment., Competing Interests: Declaration of competing interest HZ is scientific consultant for ArborMed Co. Ltd. GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); European Research CouncilAdvanced Investigator Award (ERC-2021-ADG, ICD-Cancer, Grant No. 101052444), European Union Horizon 2020 Projects Oncobiome, Prevalung (grant No. 101095604) and Crimson; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology ANR-18-IDEX-0001; a Cancer Research ASPIRE Award from the Mark Foundation; the RHUs Immunolife and LUCA-pi; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union, the European Research Council or any other granting authority. Neither the European Union nor any other granting authority can be held responsible for them., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bulevirtide (BLV) is approved for the treatment of chronic hepatitis D (CHD). Because only limited long-term experience has been reported, we aimed to evaluate the efficacy and safety of BLV treatment in patients with advanced chronic liver disease (ACLD). We performed a retrospective analysis of patients with CHD who received BLV 2 mg/day for >12 months at a tertiary center. Virological response (VR) was defined as a reduction in hepatitis delta virus-ribonucleic acid (HDV-RNA) ≥2 log 10 from baseline or HDV-RNA negativity and biochemical response (BR) as gender-specific normalization of transaminases. We identified 14 patients (9 men, 5 women; median age of 48 years; interquartile range (IQR) of 37-55), of whom 12 (86%) had suggested or assumed ACLD according to Baveno VI criteria. The median duration of BLV treatment was 26 months (IQR 17-27). During treatment, the mean HDV-RNA level decreased from log 10 5.58 IU/ml to levels between log 10 2.19 IU/ml and log 10 3.19 IU/ml. HDV-RNA negativity was achieved in up to 63% after 24 months. VR and BR were 86% and 43% after 12 months, 90% and 60% after 18 months, 75% and 75% after 24 months, and 100% and 50% after 30 months, respectively. Two nonpersisting viral breakthroughs were observed after 24 months of treatment. The Child Pugh score and model of end-stage liver disease (MELD) scores remained stable or improved in 12 patients (86%). Only one patient developed hepatic decompensation after 24 months of treatment with ascites requiring large-volume paracentesis which was not associated with viral breakthrough, portal vein thrombosis, or hepatocellular carcinoma. Treatment with BLV beyond one year is effective and safe for patients with CHD and ACLD. Liver function remained stable or improved during treatment in the vast majority of patients, and only one case of hepatic decompensation occurred during a median follow-up of 26 months., Competing Interests: Christoph Schramm received fee for advisory service for Gilead Science GmbH, Germany. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Ayaz Sapuk et al.)

Background: Imaging-based assessment of sarcopenia is a well-validated prognostic tool for patients with chronic liver disease. However, little is known about its value in patients with primary sclerosing cholangitis (PSC). This cross-sectional study aimed to investigate the predictive value of the cross-sectional imaging-based skeletal muscle index (SMI) for transplant-free survival (TFS) in patients with PSC., Methods: A total of 95 patients with PSC who underwent abdominal cross-sectional imaging between 2008 and 2022 were included in this retrospective study. SMI was measured at the third lumbar vertebra level (L3-SMI). The cut-off values to define sarcopenia were < 50 cm²/m² in male patients and < 39 cm²/m² in female patients. The primary outcome of this study was TFS, which was defined as survival without liver transplantation or death from any cause., Results: Our study indicates that L3-SMI sarcopenia impairs TFS in patients with PSC (5-year TFS: 33.9% vs. 83.3%, p = 0.001, log-rank test). L3-SMI sarcopenia was independently associated with reduced TFS via multivariate Cox regression analysis (HR = 2.749; p = 0.028). Body mass index reduction > 10% at 12 months, which is used as MELD standard exception (SE) criterion in Eurotransplant (in Germany only until September 2023), was not significantly associated with TFS in the multivariate Cox regression analysis (HR = 1.417; p = 0.330). Substitution of BMI reduction with L3-SMI in the German SE criteria improved the predictive accuracy of TFS compared to the established SE criteria (multivariable Cox regression analysis: HR = 4.007, p < 0.001 vs. HR = 1.691, p = 0.141)., Conclusion: Imaging-based diagnosis of sarcopenia via L3-SMI is associated with a low TFS in patients with PSC and may provide additional benefits as a prognostic factor in patient selection for liver transplantation., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is a common complication of chronic liver diseases and remains a relevant cause of cancer-related mortality worldwide. The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) as a risk factor for hepatocarcinogenesis is on the rise. Early detection of HCC has been crucial in improving the survival outcomes of patients with metabolic dysfunction-associated steatohepatitis (MASH), even in the absence of cirrhosis. Understanding how hepatocarcinogenesis develops in MASH is increasingly becoming a current research focus. Additive risk factors such as type 2 diabetes mellitus (T2DM), genetic polymorphisms, and intestinal microbiota may have specific impacts. Pathophysiological and epidemiological associations between MASH and HCC will be discussed in this review. We will additionally review the available tumor therapies concerning their efficacy in MASH-associated HCC treatment.

Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development., Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database., Results: Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1 , COL1A1 , COL1A2 , THBS2 , COL3A1 , COL5A1 , APOE , SPP1 , and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1 , COL1A2 , THBS2 , COL3A1 , COL5A1 , and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells., Conclusion: Our findings suggest that the identified hub genes, particularly BGN , FN1 , COL1A2 , THBS2 , COL3A1 , and COL5A1 , play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients.

Background & Aims: Hepatitis B surface antigen (HBsAg) drives hepatocarcinogenesis. Factors and mechanisms involved in this progression remain poorly defined, hindering the development of effective therapeutic strategies. Therefore, the mechanisms involved in the HBsAg-induced transformation of normal liver into hepatocellular carcinoma (HCC) were investigated., Methods: Hemizygous Tg(Alb1HBV)44Bri/J mice were examined for HBsAg-induced carcinogenic events. Gene set-enrichment analysis identified significant signatures in HBsAg-transgenic mice that correlated with endoplasmic reticulum (ER) stress, unfolded protein response, autophagy and proliferation. These events were investigated by western blotting, immunohistochemical and immunocytochemical staining in 2-, 8- and 12-month-old HBsAg-transgenic mice. The results were verified in HBsAg-overexpressing Hepa1-6 cells and validated in human HBV-related HCC samples., Results: Increased BiP expression in HBsAg-transgenic mice indicated induction of the unfolded protein response. In addition, early-phase autophagy was enhanced (increased BECN1 and LC3B) and late-phase autophagy blocked (increased p62) in HBsAg-transgenic mice. Finally, HBsAg altered lysosomal acidification via ATF4- and ATF6-mediated downregulation of lysosome-associated membrane protein 2 (LAMP2) expression. In patients, HBV-related HCC and adjacent tissues showed increased BiP, p62 and downregulated LAMP2 compared to uninfected controls. In vitro, the use of ER stress inhibitors reversed the HBsAg-related suppression of LAMP2. Furthermore, HBsAg promoted hepatocellular proliferation as indicated by Ki67, cleaved caspase-3 and AFP staining in paraffin-embedded liver sections from HBsAg-transgenic mice. These results were further verified by colony formation assays in HBsAg-expressing Hepa1-6 cells. Interestingly, inhibition of ER stress in HBsAg-overexpressing Hepa1-6 cells suppressed HBsAg-mediated cell proliferation., Conclusions: These data showed that HBsAg directly induces ER stress, impairs autophagy and promotes proliferation, thereby driving hepatocarcinogenesis. In addition, this study expanded the understanding of HBsAg-mediated intracellular events in carcinogenesis., Impact and Implications: Factors and mechanisms involved in hepatocarcinogenesis driven by hepatitis B surface antigen (HBsAg) are poorly defined, hindering the development of effective therapeutic strategies. This study showed that HBsAg-induced endoplasmic reticulum stress suppressed LAMP2, thereby mediating autophagic injury. The present data suggest that restoring LAMP2 function in chronic HBV infection may have both antiviral and anti-cancer effects. This study has provided insights into the role of HBsAg-mediated intracellular events in carcinogenesis and thereby has relevance for future drug development., Competing Interests: Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Authors.)

Background: The role of early treatment response for patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with concurrent chemo-radiotherapy (cCRT) is unclear. The study aims to investigate the predictive value of response to induction chemotherapy (iCX) and the correlation with pattern of failure (PoF)., Materials and Methods: Patients with LA-NSCLC treated with cCRT were included for analyses (n = 276). Target delineations were registered from radiotherapy planning PET/CT to diagnostic PET/CT, in between which patients received iCX. Volume, sphericity, and SUVpeak were extracted from each scan. First site of failure was categorised as loco-regional (LR), distant (DM), or simultaneous LR+M (LR+M). Fine and Gray models for PoF were performed: a baseline model (including performance status (PS), stage, and histology), an image model for squamous cell carcinoma (SCC), and an image model for non-SCC. Parameters included PS, volume (VOL) of tumour, VOL of lymph nodes, ΔVOL, sphericity, SUVpeak, ΔSUVpeak, and oligometastatic disease., Results: Median follow-up was 7.6 years. SCC had higher sub-distribution hazard ratio (sHR) for LRF (sHR = 2.771 [1.577:4.87], p < 0.01) and decreased sHR for DM (sHR = 0.247 [0.125:0.485], p  <  0.01). For both image models, high diagnostic SUVpeak increased risk of LRF (sHR = 1.059 [1.05:1.106], p < 0.01 for SCC, sHR = 1.12 [1.03:1.21], p < 0.01 for non-SCC). Patients with SCC and less decrease in VOL had higher sHR for DM (sHR = 1.025[1.001:1.048] pr. % increase, p = 0.038)., Conclusion: Poor response in disease volume was correlated with higher sHR of DM for SCC, no other clear correlation of response and PoF was observed. Histology significantly correlated with PoF with SCC prone to LRF and non-SCC prone to DM as first site of failure. High SUVpeak at diagnosis increased the risk of LRF for both histologies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Hepatitis B virus (HBV)-transgenic mice exhibit competent innate immunity and are therefore an ideal model for considering intrinsic or cell-based mechanisms in HBV pathophysiology. A highly replicative model that has been little used, let alone characterized, is the Tg1.4HBV-s-rec strain derived from cross breeding of HBV-transgenic mouse models that either accumulate (Alb/HBs, Tg[Alb1-HBV]Bri44) or lack (Tg1.4HBV-s-mut) the hepatitis B surface antigen (HBsAg). Tg1.4HBV-s-rec hepatocytes secreted HBsAg, Hepatitis B extracellular antigen (HBeAg) and produced HBV virions. Transmission electron microscopy visualised viral particles (Tg1.4HBV-s-rec), nuclear capsid formations (Tg1.4HBV-s-mut and Tg1.4HBV-s-rec) and endoplasmic reticulum malformations (Alb/HBs). Viral replication in Tg1.4HBV-s-rec and Tg1.4HBV-s-mut differed in HBsAg expression and interestingly in the distribution of HBV core antigen (HBcAg) and HBV × protein. While in Tg1.4HBV-s-mut hepatocytes, the HBcAg was located in the cytoplasm, in Tg1.4HBV-s-rec hepatocytes, the HBcAg appeared in the nuclei, suggesting a more productive replication. Finally, Tg1.4HBV-s-rec mice showed symptoms of mild hepatitis, with reduced liver function and elevated serum transaminases, which appeared to be related to natural killer T cell activation. In conclusion, the study of Alb/HBs, Tg1.4HBV-s-mut and their F1 progeny provides a powerful tool to elucidate HBV pathophysiology, especially in the early HBeAg-positive phases of chronic infection and chronic hepatitis., (© 2023. The Author(s).)

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis. Numerous studies have investigated the dynamics of HEV infection markers, but the most suitable marker for diagnosing ongoing or recent HEV infection remains to be determined. Recent evidence suggests that serum antigen testing is superior to serum IgM and RNA quantification. Moreover, it has been found that infected individuals excrete HEV antigen in significant quantities through urine. To address this question, we conducted a longitudinal analysis involving 16 patients with acute or chronic HEV infection in an area where genotype 3 HEV is prevalent. Our findings indicate that the diagnostic and monitoring capabilities of antigen testing for HEV infection can be further enhanced by measuring it in urine. Additionally, we were able to demonstrate that this enhancement is likely due to the presence of HEV-reactive IgG in blood plasma, which hampers efficient detection of HEV antigen through sandwich ELISA. In conclusion, urine-based antigen testing appears to be superior to measuring anti-HEV antibodies or viral RNA for diagnosing suspected HEV infection and monitoring ongoing infections.

Background: Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the most frequent histological subtypes of non-small cell lung cancer (NSCLC). The aim of this study was to investigate how patients with AC and SCC benefit from image-guided adaptive radiotherapy (ART) with tumour match., Material and Methods: Consecutive patients diagnosed with AC or SCC of the lung treated with definitive chemo-radiotherapy before and after the implementation of ART and tumour match were retrospectively included for analyses. Data collection included baseline patient and treatment characteristics in addition to clinical data on radiation pneumonitis (RP), failure, and survival. Patients were divided into four categories based on their histology and treatment before ( n  = 173 [89 AC and 84 SCC]) and after implementation of ART ( n  = 240 [141 AC and 99 SCC])., Results: Median follow-up was 5.7 years for AC and 6.3 years for SCC. Mean lung dose decreased for both histologies with ART, whereas mean heart dose only decreased for patients with AC. Incidences of grade 3 and 5 RP decreased for both histologies with ART. Loco-regional failure (LRF) rates decreased significantly for patients with SCC after ART ( p  = .04), no significant difference was observed for AC. Overall survival (OS) increased significantly for SCC after ART ( p  < .01): the 2-year OS increased from 31.0% (95% confidence interval [CI] [22.5-42.6]) to 54.5% (95% CI [45.6-65.3]). No significant effect on OS was observed for patients with AC., Conclusion: ART and tumour match in the radiotherapeutic treatment of patients with locally advanced NSCLC primarily led to decreased LRF and improved OS for patients with SCC.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (CU), and rarely with Crohn's disease (CD). Various long-term analyses show different rates of cancer and the need for orthotopic liver transplantation (OLT) in patients with isolated PSC and with concomitant IBD, respectively. However, data on the detailed course of PSC with or without IBD are limited. We aimed to analyze the clinical disease course of PSC patients without IBD compared to PSC patients with UC and CD, respectively. A retrospective data analysis of patients with isolated PSC (n = 41) and of patients with concomitant IBD (n = 115) was performed. In detail, PSC disease characteristics including occurrence of dominant stenoses, liver cirrhosis, OLT and malignancy, as well as the temporal course of PSC activity and disease progression, were analyzed. A multivariable Cox regression model and a Fine-Gray competing risk model were further used for the independent risk factor analysis of cirrhosis development and OLT. Patients with isolated PSC were significantly older at first diagnosis than patients with PSC-IBD (39 vs. 28 years, p = 0.02). A detailed analysis of the course of PSC revealed a faster PSC progression after initial diagnosis in isolated PSC patients compared to PSC-IBD including significantly earlier diagnosis of dominant stenoses (29 vs. 74 months, p = 0.021) and faster progression to liver cirrhosis (38 vs. 103 months, p = 0.027). Patients with isolated PSC have a higher risk of developing cirrhosis than patients with PSC-IBD (Gray's test p = 0.03). OLT was more frequently performed in male patients with isolated PSC compared to males with coincident IBD (48% (n = 13) vs. 33% (n = 25), p = 0.003). Colorectal carcinoma was significantly more often diagnosed in patients with PSC-IBD than in isolated PSC (8.7% vs. 0%, p = 0.042). Patients with isolated PSC seem to have a different clinical course of disease than PSC patients with concomitant IBD characterized by a more pro-fibrotic disease course with earlier onset of liver cirrhosis and dominant stenosis but with less malignancy. These data may be interpreted as either a more progressive disease course of isolated PSC or a later diagnosis of the disease at an advanced disease stage. The different clinical courses of PSC and the underlying mechanisms of the gut-liver axis need further attention.

Background: Acute-on-chronic liver failure (ACLF) mostly occurs when there is an acute insult to the liver in patients with pre-existing liver disease, and it is characterized by a high mortality rate. Various therapeutic approaches have been used thus far, with orthotopic liver transplantation being the only definitive cure. Clinical trials and meta-analyses have investigated the use of granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow-derived stem cells. Some studies have suggested that G-CSF may have a significant role in the management and survival of patients with ACLF. However, the results are conflicting, and the efficacy of G-CSF still needs to be confirmed., Aim: The aim was to assess the efficacy of G-CSF in patients with ACLF., Methods: Electronic databases were searched until May 2023 for randomized controlled trials investigating the use of G-CSF in adult patients with ACLF. Outcome measures were the effects of G-CSF on overall survival, changes in liver disease severity scores, complications of cirrhosis, other G-CSF-related adverse effects, and all-cause mortality. The study's protocol has been registered with Prospero (CRD42023420273)., Results: Five double-blind randomized controlled trials involving a total of 421 participants met the inclusion criteria. The use of G-CSF demonstrated a significant effect on overall survival (HR 0.63, 95% CI 0.41 to 0.95, and I 2 48%), leading to a decreased mortality (LogOR-0.97, 95% CI -1.57 to -0.37, and I 2 37.6%) and improved Model for End-Stage Liver Disease (MELD) scores (SMD -0.87, 95% CI -1.62 to -0.13, and I 2 87.3%). There was no correlation between the improvement of the Child-Pugh score and the use of G-CSF(SMD -2.47, 95% CI -5.78 to 0.83, and I 2 98.1%). The incidence of complications of cirrhosis did not decrease significantly with G-CSF treatment (rate ratio 0.51, 95% CI 0.26 to 1.01, and I 2 90%). A qualitative synthesis showed that the use of G-CSF is safe., Conclusions: The administration of G-CSF has demonstrated a positive impact on overall survival, liver function, and the MELD score. The presence of heterogeneity in the included studies prohibits conclusive recommendations.

Background: Pulmonary metastasectomy (PM) is a widely accepted surgical procedure. This study aims to investigate postoperative morbidity and mortality after PM and develop a score to predict high-risk patients., Methods: We retrospectively investigated all patients undergoing a PM in our institution from November 2012 to January 2023. Complications were defined as the diagnosis of any new disease after the PM up to 30 days after the operation., Results: 1284 patients were identified. At least one complication occurred in 145 patients (11.29%). Only one patient died during the hospital stay. Preoperative cardiovascular comorbidities (OR: 2.99, 95% CI: 1.412-3.744, p = 0.01), major lung resections (OR: 2.727, 95% CI: 1.678-4.431, p < 0.01), repeated pulmonary metastasectomy (OR: 1.759, 95% CI: 1.040-2.976, p = 0.03) and open thoracotomy (OR: 0.621, 95% CI: 0.415-0.930, p = 0.02) were identified as independent factors for postoperative complications. Based on the above independent factors for postoperative morbidity, the Essen score was developed (overall correct classification: 94.6%, ROC-Analysis: 0.828, 95% CI: 0.795-0.903)., Conclusion: PM is a safe surgical procedure with acceptable morbidity and low mortality. The aim of the Essen score is to identify patients that are associated with risk for postoperative complications after PM.

Recommended treatment options for advanced-stage hepatocellular carcinoma (HCC) include systemic therapy (ST) and trans-arterial radioembolization (TARE) with Yttrium-90 (Y90). Before the approval of immune-checkpoint inhibitors, a similar safety profile was reported for TARE and ST with tyrosine kinase inhibitors (TKI). However, whole-liver treatment and underlying cirrhosis were identified as risk factors for potentially lethal radioembolization-induced liver disease (REILD). Therefore, the safety and efficacy of TARE and ST with atezolizumab/bevacizumab were compared in patients with advanced HCC involving at least both liver lobes in a retrospective real-world cohort. In total, 74 patients with new or recurrent advanced-stage HCC (BCLC stage B/C) were included if treated with either bilobar TARE (n = 33) or systemic combination therapy with atezolizumab plus bevacizumab (n = 41). Most patients had compensated liver function (90.5% were classified as Child-Pugh Score A, 73% as ALBI Grade 1) at baseline. Although not significant, patients treated with ST showed a more prolonged overall survival than those treated with Y90 TARE (7.1 months vs. 13.0 months, p = 0.07). While a similar disease control rate could be achieved with bilobar TARE and atezolizumab/bevacizumab, in the TARE group, overall survival was curtailed by the occurrence of REILD. In patients with underlying liver cirrhosis, the liver function at baseline was a predictor for REILD.