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PurposeTo differentiate subtypes of hepatocellular adenoma (HCA) based on enhancement characteristics in gadoxetic acid (Gd-EOB) magnetic resonance imaging (MRI).Materials and methodsForty-eight patients with 79 histopathologically proven HCAs who underwent Gd-EOB-enhanced MRI were enrolled (standard of reference: surgical resection). Two blinded radiologists performed quantitative measurements (lesion-to-liver enhancement) and evaluated qualitative imaging features. Inter-reader variability was tested. Advanced texture analysis was used to evaluate lesion heterogeneity three-dimensionally.ResultsOverall, there were 19 (24%) hepatocyte nuclear factor (HNF)-1a-mutated (HHCAs), 37 (47%) inflammatory (IHCAs), 5 (6.5%) b-catenin-activated (bHCA), and 18 (22.5%) unclassified (UHCAs) adenomas. In the hepatobiliary phase (HBP), 49.5% (39/79) of all adenomas were rated as hypointense and 50.5% (40/79) as significantly enhancing (defined as > 25% intralesional GD-EOB uptake). 82.5% (33/40) of significantly enhancing adenomas were IHCAs, while only 4% (1/40) were in the HHCA subgroup (p < 0.001). When Gd-EOB uptake behavior was considered in conjunction with established MRI features (binary regression model), the area under the curve (AUC) increased from 0.785 to 0.953 for differentiation of IHCA (atoll sign + hyperintensity), from 0.859 to 0.903 for bHCA (scar + hyperintensity), and from 0.899 to 0.957 for HHCA (steatosis + hypointensity). Three-dimensional region of interest (3D ROI) analysis showed significantly increased voxel heterogeneity for IHCAs (p = 0.038).ConclusionGd-EOB MRI is of added value for subtype differentiation of HCAs and reliably identifies the typical heterogeneous HBP uptake of IHCAs. Diagnostic accuracy can be improved significantly by the combined analysis of established morphologic MR appearances and intralesional Gd-EOB uptake.Key Points•Gd-EOB-enhanced MRI is of added value for subtype differentiation of HCA.•IHCA and HHCA can be identified reliably based on their typical Gd-EOB uptake patterns, and accuracy increases significantly when additionally taking established MR appearances into account.•The small numbers of bHCAs and UHCAs remain the source of diagnostic uncertainty.

BackgroundWhile laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy.MethodsWe here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias.ResultsOne hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien–Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B–C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable.ConclusionsWe propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.

BackgroundWhile minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches.MethodsClinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses.ResultsOut of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien–Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery.ConclusionsWe propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most patients present with advanced or metastatic HCC at diagnosis and face a dismal prognosis. Tyrosine kinases are the gold standard treatment for this disease but yield limited survival benefits. Immune checkpoint inhibitors that augment adaptive immunity have been tested in HCC. Complex interactions between tumor cells, lymphocytes and the tumor environment determine the efficacy of such immunotherapies. Innate immune mechanisms – known drivers of liver disease progression in pre-HCC conditions such as fibrosis or cirrhosis – may either support or counteract tumor-related immune activation. In this review, we will highlight current concepts of the role of the innate immune system in hepatocarcinogenesis and discuss their relevance for translation into clinics.

Ischemia-reperfusion injury (IRI) constitutes a significant source of morbidity and mortality after orthotopic liver transplantation (OLT). The allograft is metabolically impaired during warm and cold ischemia and is further damaged by a paradox reperfusion injury after revascularization and reoxygenation. Short-term and long-term complications including post-reperfusion syndrome, delayed graft function, and immune activation have been associated with IRI. Due to the current critical organ shortage, extended criteria grafts are increasingly considered for transplantation, however, with an elevated risk to develop significant features of IRI. In recent years, ex vivo machine perfusion (MP) of the donor liver has witnessed significant advancements. Here, we describe the concept of hypothermic (oxygenated) machine perfusion (HMP/HOPE) approaches and highlight which allografts may benefit from this technology. This review also summarizes clinical applications and the main aspects of ongoing randomized controlled trials on hypothermic perfusion. The mechanistic aspects of IRI and hypothermic MP—which include tissue energy replenishment, optimization of mitochondrial function, and the reduction of oxidative and inflammatory damage following reperfusion—will be comprehensively discussed within the context of current preclinical and clinical evidence. Finally, we highlight novel trends and future perspectives in the field of hypothermic MP in the context of recent findings of basic and translational research.

IntroductionThe aim of this study was to develop a reliable objective structured assessment of technical skills (OSATS) score for linear-stapled, hand-sewn closure of enterotomy intestinal anastomoses (A-OSATS).Materials and methodsThe Delphi methodology was used to create a traditional and weighted A-OSATS score highlighting the more important steps for patient outcomes according to an international expert consensus. Minimally invasive novices, intermediates, and experts were asked to perform a minimally invasive linear-stapled intestinal anastomosis with hand-sewn closure of the enterotomy in a live animal model either laparoscopically or robot-assisted. Video recordings were scored by two blinded raters assessing intrarater and interrater reliability and discriminative abilities between novices (n = 8), intermediates (n = 24), and experts (n = 8).ResultsThe Delphi process included 18 international experts and was successfully completed after 4 rounds. A total of 4 relevant main steps as well as 15 substeps were identified and a definition of each substep was provided. A maximum of 75 points could be reached in the unweighted A-OSATS score and 170 points in the weighted A-OSATS score respectively. A total of 41 anastomoses were evaluated. Excellent intrarater (r = 0.807–0.988, p < 0.001) and interrater (intraclass correlation coefficient = 0.923–0.924, p < 0.001) reliability was demonstrated. Both versions of the A-OSATS correlated well with the general OSATS and discriminated between novices, intermediates, and experts defined by their OSATS global rating scale.ConclusionWith the weighted and unweighted A-OSATS score, we propose a new reliable standard to assess the creation of minimally invasive linear-stapled, hand-sewn anastomoses based on an international expert consensus. Validity evidence in live animal models is provided in this study. Future research should focus on assessing whether the weighted A-OSATS exceeds the predictive capabilities of patient outcomes of the unweighted A-OSATS and provide further validity evidence on using the score on different anastomotic techniques in humans.

The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC—especially hypervascular HCC lesions—in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.

BackgroundAlthough Bismuth-Corlette (BC) type 4 perihilar cholangiocarcinoma (pCCA) is no longer considered a contraindication for curative surgery, few data are available from Western series to indicate the outcomes for these patients. This study aimed to compare the short- and long-term outcomes for patients with BC type 4 versus BC types 2 and 3 pCCA undergoing surgical resection using a multi-institutional international database.MethodsUni- and multivariable analyses of patients undergoing surgery at 20 Western centers for BC types 2 and 3 pCCA and BC type 4 pCCA.ResultsAmong 1138 pCCA patients included in the study, 826 (73%) had BC type 2 or 3 disease and 312 (27%) had type 4 disease. The two groups demonstrated significant differences in terms of clinicopathologic characteristics (i.e., portal vein embolization, extended hepatectomy, and positive margin). The incidence of severe complications was 46% for the BC types 2 and 3 patients and 51% for the BC type 4 patients (p = 0.1). Moreover, the 90-day mortality was 13% for the BC types 2 and 3 patients and 12% for the BC type 4 patients (p = 0.57). Lymph-node metastasis (N1; hazard-ratio [HR], 1.62), positive margins (R1; HR, 1.36), perineural invasion (HR, 1.53), and poor grade of differentiation (HR, 1.25) were predictors of survival (all p ≤0.004), but BC type was not associated with prognosis. Among the N0 and R0 patients, the 5-year overall survival was 43% for the patients with BC types 2 and 3 pCCA and 41% for those with BC type 4 pCCA (p = 0.60).ConclusionsIn this analysis of a large Western multi-institutional cohort, resection was shown to be an acceptable curative treatment option for selected patients with BC type 4 pCCA although a more technically challenging surgical approach was required.

IntroductionHepatocellular adenomas (HCAs) are solid liver tumours that are usually found incidentally during routine medical check-ups. Multiple modifiable and non-modifiable factors constitute a risk for the malignant transformation of HCAs to hepatocellular carcinoma (HCC), which has emerged to be one of the fastest growing causes of cancer-related mortality globally. This study protocol for a planned systematic review and meta-analysis documents the methodological approach to identify risk factors and their risk estimates for the transformation from HCA to HCC.Methods and analysisTwo independent reviewers will systematically search and extract data from studies in patients of all ages published between January 1970 and June 2021 on PubMed, MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Scopus Web of Science, Ovid, The Cochrane Hepatobiliary Group Controlled Trials Register and The Cochrane Central Register of Controlled Trials by using an a priori defined search strategy. Study quality will be rated with the National Institute of Health quality assessment tools. Disagreements will be resolved by consensus with a third independent reviewer. The primary outcome will be the odds ratio (OR) of developing HCC in patients with prediagnosed HCA depending on the exposure to risk factors. HCC diagnosis must be inferred based on imaging techniques or pathology. We will use R V.4.0.2 to conduct meta-analyses and generate pooled ORs based on random effects models. Results will be presented as forest plots. Cochran’s Q and I2 test will be performed to assess heterogeneity between included studies. Funnel plots and Egger’s weighted regression will be used to evaluate publication bias.Ethics and disseminationNo ethical approval is required as we will use and analyse data from previously published studies in which informed consent was obtained. The results will be disseminated in a peer-reviewed journal on completion.PROSPERO registration numberCRD42020206578.