4D flow MRI-guided treatment of portal-hypertensive complications in a patient with multiple extrahepatic arterioportal shunts.

Portal hypertension is the underlying reason for complications like ascites or gastrointestinal varices in end-stage liver disease. On rare occasions, portal hypertension may be caused by extrahepatic arterioportal shunts. This report illustrates an outstanding case of extrahepatic arterioportal shunting as an uncommon cause of TIPS-refractory portal hypertension. Four-dimensional flow magnetic resonance imaging (4D flow MRI) is a novel non-invasive technique that enables the visualization of complex vascular disorders but has not been put into daily clinical practice in hepatology. In this case, 4D flow MRI enabled the visualization of three abdominal arterioportal shunts as the reason for TIPS-refractory portal hypertension. The quantification of individual shunt flow rates by 4D flow MRI guided our treatment strategy consisting of embolization during interventional angiography and surgical resection of all three arterioportal shunts. In conclusion, this case highlights the usefulness of 4D flow MRI for evaluating shunt flow in cases of complex vascular disorders and portal-hypertensive complications, thus helping to guide therapeutic decisions and monitoring the therapeutic success.

Infectious complications of radiologically placed upper arm ports: A single center analysis.

OBJECTIVES: Infections are common complications in venous access ports. The presented analysis aimed to investigate the incidence, microbiological spectrum, and acquired resistances of pathogens in upper arm port associated infections to provide a decision aid in the choice of therapy. MATERIALS AND METHODS: In total, 2667 implantations and 608 explantations were performed at a high-volume tertiary medical center between 2015 and 2019. In cases with infectious complications (n = 131, 4.9%), procedural conditions and results of microbiological testing were reviewed retrospectively. RESULTS: Of 131 port associated infections (median dwell time 103 days, interquartile range 41-260), 49 (37.4%) were port pocket infections (PPI) and 82 (62.6%) were catheter infections (CI). Infectious complications occurred more often after implantation in inpatients compared to outpatients (P < 0.01). PPI were mainly caused by Staphylococcus aureus (S. aureus, 48.3%) and coagulase-negative staphylococci (CoNS, 31.0%). Other gram-positive and gram-negative species were encountered in 13.8% and 6.9%, respectively. CI were caused less frequently by S. aureus (8.6%) than CoNS (39.7%). Other gram-positive and gram-negative strains were isolated in 8.6% and 31.0%, respectively. Candida species were seen in 12.1% of CI. An acquired antibiotic resistance was detected in 36.0% of all significant isolates, occurring especially in CoNS (68.3%) and gram-negative species (24.0%). CONCLUSIONS: Staphylococci comprised the largest group of pathogens in upper arm port associated infections. However, gram-negative strains and Candida species should also be considered as a cause of infection in CI. Due to the frequent detection of potential biofilm-forming pathogens, port explantation is an important therapeutic measure, especially in severely ill patients. Acquired resistances must be anticipated when choosing an empiric antibiotic treatment.

CIRSE Standards of Practice on Bronchial Artery Embolisation.

This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing bronchial artery embolisation to effectively treat haemoptysis. It has been developed by an expert writing group established by the CIRSE Standards of Practice Committee.

Radiation dose reduction during adrenal vein sampling using a new angiographic imaging technology.

To compare the patient radiation doses during angiographic selective adrenal vein sampling (AVS) before and after an imaging technology upgrade. In this retrospective single-center-study, cumulative air kerma (AK), cumulative dose area product (DAP), fluoroscopy time and contrast agent dosage were recorded from 70 patients during AVS. 35 procedures were performed before and 35 after an imaging processing technology upgrade. Mean values were calculated and compared using an unpaired student's t-test. DSA image quality was assessed independently by two blinded readers using a four-point Likert scale (1 = poor; 4 = excellent) and compared using Wilcoxon signed-rank test. After the technology upgrade we observed a significant reduction of 35% in AK (1.7 ± 0.7 vs. 1.1 ± 0.7 Gy, p = 0.01) and a significant reduction of 28% in DAP (235.1 ± 113 vs. 170.1 ± 94 Gy*cm2, p = 0.01) in comparison to procedures before the upgrade. There were no significant differences between the number of exposure frames (143 ± 86 vs. 132 ± 61 frames, p = 0.53), fluoroscopy time (42 ± 23 vs. 36 ± 18 min, p = 0.22), or the amount of contrast medium used (179.5 ± 84 vs. 198.1 ± 109 ml, p = 0.41). There was also no significant difference regarding image quality (3 (2-4) vs. 3 (2-4), p = 0.67). The angiographic imaging technology upgrade significantly decreases the radiation dose during adrenal vein sampling without increasing time of fluoroscopy or contrast volume and without compromising image quality.

Sequential Systemic Treatment in Advanced Hepatocellular Carcinoma Is Able to Prolong Median Survival to More than 3 Years in a Selected Real-World Cohort.

INTRODUCTION: The number of efficacious systemic agents for advanced hepatocellular carcinoma (HCC) has rapidly increased over the past 3 years. However, guidance for optimal sequential systemic treatment in patients with advanced disease and experience with outcome and safety profiles are lacking. OBJECTIVE: We aimed to assess efficacy and tolerability of sequential systemic therapy of advanced HCC. METHODS: Our single-center study prospectively followed 14 patients who received multiple, sequential systemic therapies after progression or intolerance to sorafenib. Endpoints were overall and progression-free survival (OS, PFS), objective response rate (ORR), and treatment-emergent adverse events (TEAE). RESULTS: Patients had well-compensated liver function and good performance status at start of each systemic therapy. Agents included sorafenib (n = 14), regorafenib (n = 10), immunotherapy with nivolumab or pembrolizumab (n = 10), lenvatinib (n = 3), ramucirumab (n = 2), and others, with a median of 3 lines of systemic therapy per patient. Median OS was 37.4 months from initiation of first-line therapy with sorafenib. PFS and ORR for sorafenib, regorafenib, and immunotherapy were 6.6, 5.3, and 6.6 months, and 15.4, 11.1, and 22.2%, respectively. TEAE were frequent (46-80%), but mostly manageable during tyrosine kinase inhibitor therapy and without the need for termination in most patients. However, TEAE due to immunotherapy (60%) led to cessation of treatment in 40% of the patients. CONCLUSIONS: Sequential systemic therapy is able to prolong median OS in selected patients with advanced HCC to more than 3 years. TEAE are frequent, but manageable, and the quality of adverse events depends on the respective agent. Further investigation of potential predictive biomarkers for treatment allocation is needed.

Pulmonary blood volume estimation in mice by magnetic particle imaging and magnetic resonance imaging.

This methodical work describes the measurement and calculation of pulmonary blood volume in mice based on two imaging techniques namely by using magnetic particle imaging (MPI) and cardiac magnetic resonance imaging (MRI). Besides its feasibility aspects that may influence quantitative analysis are studied. Eight FVB mice underwent cardiac MRI to determine stroke volumes and anatomic MRI as morphological reference for functional MPI data. Arrival time analyses of boli of 1 µl of 1 M superparamagnetic tracer were performed by MPI. Pulmonary transit time of the bolus was determined by measurements in the right and left ventricles. Pulmonary blood volume was calculated out of stroke volume, pulmonary transit time and RR-interval length including a maximal error analysis. Cardiac stroke volume was 31.7 µl ± 2.3 µl with an ejection fraction of 71% ± 6%. A sharp contrast bolus profile was observed by MPI allowing subdividing the first pass into three distinct phases: tracer arrival in the right ventricle, pulmonary vasculature, and left ventricle. The bolus full width at half maximum was 578 ms ± 144 ms in the right ventricle and 1042 ms ± 150 ms in the left ventricle. Analysis of pulmonary transit time revealed 745 ms ± 81 ms. Mean RR-interval length was 133 ms ± 12 ms. Pulmonary blood volume resulted in 177 µl ± 27 µl with a mean maximal error limit of 27 µl. Non-invasive assessment of the pulmonary blood volume in mice was feasible. This technique can be of specific value for evaluation of pulmonary hemodynamics in mouse models of cardiac dysfunction or pulmonary disease. Pulmonary blood volume can complement cardiac functional parameters as a further hemodynamic parameter.

Efficiency of Percutaneous Stent Angioplasty in Renal Artery Stenosis - 15 Years of Experience at a Single Center.

PURPOSE: To determine the therapeutic efficiency of percutaneous revascularization in renal artery stenosis (RAS), as well as the role of comprehensive factors such as patient selection and degree of artery stenosis, on clinical outcome. METHODS AND MATERIALS: 101 patients with hemodynamically relevant RAS underwent percutaneous angioplasty (PTA). 65.7 % were male (mean age: 64 years; range: 18-84). The clinical data was retrospectively analyzed. The serum creatinine (Cr), glomerular filtration rate (GFR), and blood pressure (BP) levels pre- and postprocedural, between 6 months and 1 year, were retrospectively collected and statistically analyzed. RESULTS: Follow-up data was available in 34 (33.7 %) and 28 patients (27.7 %) for Cr and MAP, respectively. A significant drop in mean arterial pressure (MAP) was observed on follow-up (mean -5.27 mmHg). Higher baseline Cr and MAP values showed a more pronounced drop in the follow-up (Cr: p 0.002; difference to baseline -0.25 mg/dL, 95 %CI:-0.36, -0.07 and BP p < 0.001; diff. to baseline -0.72 mmHg; 95 %CI: -1.4, -0.40). There was no association between comorbidities, gender, and degree of stenosis with renal and BP outcome. No significant improvement in renal function was observed on follow-up (mean Cr drop: -0.015 mg/dL). The age group 51-60 years showed a significant improvement in BP (p 0.030; diff. to baseline -19.2 mmHg; 95 %CI: -34, -4.3). There was a slight reduction in antihypertensive medication following angioplasty (0.2 fewer). Minor complications were recorded in five procedures (4.9 %). CONCLUSION: Percutaneous renal artery revascularization in the presence of atherosclerotic RAS is a safe procedure associated with a significant drop in post-procedural BP. No significant improvement in renal function was observed. Further prospective studies focused on patient selection are necessary. KEY POINTS: · Percutaneous stent angioplasty in renal artery stenosis is associated with a significant improvement in post-procedural blood pressure control.. · There is no improvement in renal function after percutaneous stent angioplasty for renal artery stenosis (RAS).. · Percutaneous stent angioplasty is a safe procedure.. CITATION FORMAT: · Guerreiro H, Avanesov M, Dinnies S et al. Efficiency of Percutaneous Stent Angioplasty in Renal Artery Stenosis - 15 Years of Experience at a Single Center. Fortschr Röntgenstr 2021; 193: 298 - 304.

Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation.

In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation.

Smart chest X-ray worklist prioritization using artificial intelligence: a clinical workflow simulation.

OBJECTIVE: The aim is to evaluate whether smart worklist prioritization by artificial intelligence (AI) can optimize the radiology workflow and reduce report turnaround times (RTATs) for critical findings in chest radiographs (CXRs). Furthermore, we investigate a method to counteract the effect of false negative predictions by AI-resulting in an extremely and dangerously long RTAT, as CXRs are sorted to the end of the worklist. METHODS: We developed a simulation framework that models the current workflow at a university hospital by incorporating hospital-specific CXR generation rates and reporting rates and pathology distribution. Using this, we simulated the standard worklist processing "first-in, first-out" (FIFO) and compared it with a worklist prioritization based on urgency. Examination prioritization was performed by the AI, classifying eight different pathological findings ranked in descending order of urgency: pneumothorax, pleural effusion, infiltrate, congestion, atelectasis, cardiomegaly, mass, and foreign object. Furthermore, we introduced an upper limit for the maximum waiting time, after which the highest urgency is assigned to the examination. RESULTS: The average RTAT for all critical findings was significantly reduced in all prioritization simulations compared to the FIFO simulation (e.g., pneumothorax: 35.6 min vs. 80.1 min; p < 0.0001), while the maximum RTAT for most findings increased at the same time (e.g., pneumothorax: 1293 min vs 890 min; p < 0.0001). Our "upper limit" substantially reduced the maximum RTAT in all classes (e.g., pneumothorax: 979 min vs. 1293 min/1178 min; p < 0.0001). CONCLUSION: Our simulations demonstrate that smart worklist prioritization by AI can reduce the average RTAT for critical findings in CXRs while maintaining a small maximum RTAT as FIFO. KEY POINTS: • Development of a realistic clinical workflow simulator based on empirical data from a hospital allowed precise assessment of smart worklist prioritization using artificial intelligence. • Employing a smart worklist prioritization without a threshold for maximum waiting time runs the risk of false negative predictions of the artificial intelligence greatly increasing the report turnaround time. • Use of a state-of-the-art convolution neural network can reduce the average report turnaround time almost to the upper limit of a perfect classification algorithm (e.g., pneumothorax: 35.6 min vs. 30.4 min).

Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype.

BACKGROUND: The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cells (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features, both on the recurrence after curative resection and on clinical outcome, remains unknown. To address this, we investigated the spatial heterogeneity of CSC-features with the aim of identifying the unique HCC patient subgroups amenable to adjuvant treatment. METHODS: We designed a tissue microarray (TMA) from patients who had received liver resection between 2011 and 2017. Tumor specimens were sampled at multiple locations (n = 3-8). EpCAM-positivity was assessed for intensity and proportion by applying a score dividing three groups: (i) negative (E-/-); (ii) heterogeneous (E-/+); and (iii) homogeneous (E+/+). The groups were further analysed with regard to time-to-recurrence (TTR) and recurrence-free-survival (RFS). RESULTS: We included 314 tumor spots from 69 patients (76.8% male, median age 66, liver cirrhosis/fibrosis 75.8%). The risk factors were alcohol abuse (26.2%), NASH (13.1%), HBV (15.5%), HCV (17.9%) and others (27.4%), representative of a typical Western cohort. E+/+ patients experienced significantly shorter TTR and RFS compared to E+/- and E-/- patients (TTR 5 vs. 19 months, p = 0.022; RFS 5 vs. 14 vs. 21 months, p = 0.016). Only homogeneous EpCAM-positivity correlated with higher AFP levels (> 400 ng/ml, p = 0.031). CONCLUSIONS: Spatial heterogeneity of EpCAM-expression was markedly present in the cohort. Of note, only homogeneous EpCAM-expression correlated significantly with early recurrence, whereas heterogeneous EpCAM-expression was associated with clinical endpoints comparable to EpCAM-negativity. We identified a unique HCC subtype associated with a high risk of tumor recurrence.

Targeting the Mutational Landscape of Bystander Cells: Drug-Promoted Blood Cancer From High-Prevalence Pre-neoplasias in Patients on BRAF Inhibitors.

Drug-promoted cancers are increasingly recognized as a serious clinical problem in patients receiving BRAF inhibitory treatment. Here we report on a patient with BRAF mutant hairy cell leukemia and monoclonal B-cell lymphocytosis (MBL), who responded durably to BRAF/MEK inhibitors (BRAFi/MEKi) but experienced transformation of a RAS mutant MBL to chronic lymphocytic leukemia (CLL) with accelerated nodal progression. Hypothesizing that BRAFi triggered excessive MEK-ERK signaling in the MBL/CLL clone via the CRAF/RAS complex as previously described for BRAFi-induced cancers, BRAFi was discontinued inducing a rapid remission of the CLL on MEKi alone. Liquid biopsy monitoring showed a continuous increase of the MBL/CLL clone from the start of BRAFi/MEKi treatment followed by a rapid decline upon BRAFi withdrawal. Next-generation sequencing of a cohort of patients with MBL and monoclonal gammopathy of unclear significance (MGUS) revealed that almost one third of these cases harbored RAS mutations. In view of the population frequency of lymphatic pre-malignant conditions and the prevalence of RAS mutations in such cases, vigilant surveillance remains critical in patients treated with BRAF inhibitors.

Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1.

Hepatic amebiasis, predominantly occurring in men, is a focal destruction of the liver due to the invading protozoan Entamoeba histolytica. Classical monocytes as well as testosterone are identified to have important functions for the development of hepatic amebiasis in mice, but a link between testosterone and monocytes has not been identified. Here we show that testosterone treatment induces proinflammatory responses in human and mouse classical monocytes. When treated with 5α-dihydrotestosterone, a strong androgen receptor ligand, human classical monocytes increase CXCL1 production in the presence of Entamoeba histolytica antigens. Moreover, plasma testosterone levels of individuals undergoing transgender procedure correlate positively with the TNF and CXCL1 secretion from their cultured peripheral blood mononuclear cells following lipopolysaccharide stimulation. Finally, testosterone substitution of castrated male mice increases the frequency of TNF/CXCL1-producing classical monocytes during hepatic amebiasis, supporting the hypothesis that the effects of androgens may contribute to an increased risk of developing monocyte-mediated pathologies.

Treatment Lines in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the second most lethal malignancy worldwide. In the Western world, HCC predominantly develops in patients with liver cirrhosis. Therefore, application of locoregional interventions and systemic agents should be based on an interdisciplinary evaluation, most importantly, taking the functional liver reserve into account. This review summarizes current treatment lines and novel strategies in the management of HCC. For the most part, randomized controlled trials and large meta-analyses are reported, with an emphasis on systemic therapies. SUMMARY: In patients with limited hepatic disease and sufficient liver function, resection and local ablation are the most frequently employed curative locoregional therapies. Due to recurrence rates of up to 70% within 5 years and in patients with compromised liver function not amenable to these local modalities, liver transplantation remains superior in terms of tumor control and long-term survival. However, its applicability is limited because of the increasing gap between available donor organs and patients on the waiting list. Transarterial chemoembolization is commonly employed to bridge patients to transplantation and also serves as standard of care for patients not suitable for other local therapies. Recently, various phase 3 trials have reported a clinical benefit for the tyrosine kinase inhibitors lenvatinib, regorafenib, and cabozantinib in HCC. In addition, ramucirumab, an angiostatic antibody, also improves survival in second-line systemic therapy. This opens new avenues in the sequential application of treatment lines, and thus early response assessment is necessary to fully utilize the clinical impact of locoregional therapies and systemic therapies and to shift patients to further treatment lines before hepatic deterioration. KEY MESSAGES: Clinical decision-making in hepatocellular carcinoma is based on an interdisciplinary evaluation. Liver transplantation should always be considered as long-term curative treatment option, especially in T2 patients. In palliative treatment, early response assessment is required to advance patients to the next treatment line before decompensation.

Liver infiltrating T cells regulate bile acid metabolism in experimental cholangitis.

BACKGROUND & AIMS: T cells are central mediators of liver inflammation and represent potential treatment targets in cholestatic liver disease. Whereas emerging evidence shows that bile acids (BAs) affect T cell function, the role of T cells for the regulation of BA metabolism is unknown. In order to understand this interplay, we investigated the influence of T cells on BA metabolism in a novel mouse model of cholangitis. METHODS: Mdr2-/- mice were crossed with transgenic K14-OVAp mice, which express an MHC class I restricted ovalbumin peptide on biliary epithelial cells (Mdr2-/-xK14-OVAp). T cell-mediated cholangitis was induced by the adoptive transfer of antigen-specific CD8+ T cells. BA levels were quantified using a targeted liquid chromatography-mass spectrometry-based approach. RESULTS: T cell-induced cholangitis resulted in reduced levels of unconjugated BAs in the liver and significantly increased serum and hepatic levels of conjugated BAs. Genes responsible for BA synthesis and uptake were downregulated and expression of the bile salt export pump was increased. The transferred antigen-specific CD8+ T cells alone were able to induce these changes, as demonstrated using Mdr2-/-xK14-OVAp recipient mice on the Rag1-/- background. Mechanistically, we showed by depletion experiments that alterations in BA metabolism were partly mediated by the proinflammatory cytokines TNF and IFN-γ in an FXR-dependent manner, a process that in vitro required cell contact between T cells and hepatocytes. CONCLUSION: Whereas it is known that BA metabolism is dysregulated in sepsis and related conditions, we have shown that T cells are able to control the synthesis and metabolism of BAs, a process which depends on TNF and IFN-γ. Understanding the effect of lymphocytes on BA metabolism will help in the design of combined treatment strategies for cholestatic liver diseases. LAY SUMMARY: Dysregulation of bile acid metabolism and T cells can contribute to the development of cholangiopathies. Before targeting T cells for the treatment of cholangiopathies, it should be determined whether they exert protective effects on bile acid metabolism. Herein, we demonstrate that T cell-induced cholangitis resulted in decreased levels of harmful unconjugated bile acids. T cells were able to directly control synthesis and metabolism of bile acids, a process which was dependent on the proinflammatory cytokines TNF and IFN-γ. Understanding the effect of lymphocytes on bile acid metabolism will help in the design of combined treatment strategies for cholestatic liver diseases.

Transjugular Intrahepatic Portosystemic Shunt: A Possible Risk Factor for Direct-Acting Antiviral Treatment Failure in Patients With Hepatitis C?

Direct-acting antiviral (DAA) therapies have revolutionized the treatment of chronic hepatitis C virus infection, achieving sustained virological response (SVR) rates of >90% even in patients with advanced liver cirrhosis. Having observed an unusual case of repeated DAA therapy failures in a patient with a transjugular intrahepatic portosystemic shunt (TIPS), we assessed a possible association between prior TIPS placement and DAA failure. A structured search of our clinical database revealed 10 patients who had received DAA therapy after TIPS placement. At the time of therapy, most patients (8; 80%) presented with a Child-Pugh score B, and the following DAA regimens were used: sofosbuvir/ledipasvir ± ribavirin (5 patients), sofosbuvir/daclatasvir ± ribavirin (3), sofosbuvir/velpatasvir (2), and sofosbuvir/velpatasvir/voxilaprevir (1). In total, 5 patients (50%) achieved an SVR, whereas a virological relapse occurred in the other half of the cases, including 2 patients with multiple relapses. In this patient cohort, SVR rates were unusually low for all regimens: sofosbuvir/ledipasvir ± ribavirin, 3/5 (60%); sofosbuvir/daclatasvir ± ribavirin, 2/3 (66%); sofosbuvir/velpatasvir, 0/2 (0%); and sofosbuvir/velpatasvir/voxilaprevir, 0/1 (0%), and patients with a TIPS made up a relevant proportion of DAA failures in patients with cirrhosis at our center: sofosbuvir/ledipasvir, 2/18 (11%); sofosbuvir/daclatasvir, 1/4 (25%); sofosbuvir/velpatasvir, 2/3 (66%); and sofosbuvir/velpatasvir/voxilaprevir, 1/1 (100%). Conclusion: We observed a high rate of virological relapse in patients with a TIPS who received DAA treatment and therefore postulate that TIPS placement may be a possible risk factor for DAA failure due to the profound hemodynamic changes evoked by the intervention. Longer treatment duration or addition of ribavirin might be warranted in these patients.

Patient radiation dose in percutaneous biliary interventions: recommendations for DRLs on the basis of a multicentre study.

OBJECTIVE: Percutaneous biliary interventions (PBIs) can be associated with a high patient radiation dose, which can be reduced when national diagnostic reference levels (DRLs) are kept in mind. The aim of this multicentre study was to investigate patient radiation exposure in different percutaneous biliary interventions, in order to recommend national DRLs. METHODS: A questionnaire asking for the dose area product (DAP) and the fluoroscopy time (FT) in different PBIs with ultrasound- or fluoroscopy-guided bile duct punctures was sent to 200 advanced care hospitals. Recommended national DRLs are set at the 75th percentile of all DAPs. RESULTS: Twenty-three facilities (9 interventional radiology depts. and 14 gastroenterology depts.) returned the questionnaire (12%). Five hundred sixty-five PBIs with 19 different interventions were included in the analysis. DAPs (range 4-21,510 cGy·cm2) and FTs (range 0.07-180.33 min) varied substantially depending on the centre and type of PBI. The DAPs of initial PBIs were significantly (p < 0.0001) higher (median 2162 cGy·cm2) than those of follow-up PBIs (median 464 cGy·cm2). There was no significant difference between initial PBIs with ultrasound-guided bile duct puncture (2162 cGy·cm2) and initial PBIs with fluoroscopy-guided bile duct puncture (2132 cGy·cm2) (p = 0.85). FT varied substantially (0.07-180.33 min). CONCLUSIONS: DAPs and FTs in percutaneous biliary interventions showed substantial variations depending on the centre and the type of PBI. PBI with US-guided bile duct puncture did not reduce DAP, when compared to PBI with fluoroscopy-guided bile duct puncture. National DRLs of 4300 cGy·cm2 for initial PBIs and 1400 cGy·cm2 for follow-up PBIs are recommended. KEY POINTS: • DAPs and FTs in percutaneous biliary interventions showed substantial variations depending on the centre and the type of PBI. • PBI with US-guided bile duct puncture did not reduce DAP when compared to PBI with fluoroscopy-guided bile duct puncture. • DRLs of 4300 cGy·cm2for initial PBIs (establishing a transhepatic tract) and 1400 cGy·cm2for follow-up PBIs (transhepatic tract already established) are recommended.

Ascites control by TIPS is more successful in patients with a lower paracentesis frequency and is associated with improved survival.

BACKGROUND & AIMS: Refractory ascites is the main reason for the implantation of a transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis, but ascites control by TIPS fails in a relevant proportion of cases. Here, we investigated whether routine parameters pre-TIPS can predict persistent ascites after TIPS implantation and whether persistent ascites predicts long-term clinical outcome. METHODS: A detailed retrospective analysis of 128 patients receiving expanded polytetrafluoroethylene-covered stents for the treatment of refractory ascites was performed. Persistent ascites post-TIPS was defined as the prolonged need for paracentesis >3 months after TIPS. The influence of demographics, laboratory results, pre-TIPS heart and liver ultrasound results, and invasive hemodynamic parameters on persistent ascites was evaluated by univariable and multivariable logistic regression. Predictors of the composite endpoint liver transplantation/death were analyzed using a multivariable Cox regression. RESULTS: Ascites control post-TIPS was achieved in 95/128 patients (74%), whereas ascites remained persistent in 33/128 cases (26%). On multivariable analysis, a lower paracentesis frequency pre-TIPS (odds ratio 1.672; 95% CI 1.253-2.355) and lower baseline creatinine levels (odds ratio 2.640; CI 1.201-6.607) were associated with ascites control. Patients with persistent ascites post-TIPS had and impaired transplant-free survival (median 10.0 vs. 25.8 months), for which persistent ascites was the only independent predictor (hazard ratio 5.654; CI 3.019-10.59). CONCLUSION: TIPS-placement in patients with lower paracentesis frequency and creatinine levels is associated with superior ascites control. Thus, TIPS implantation should be considered in moderate decompensation and not as a last resort. Persistent ascites post-TIPS seems to be the only predictor of liver transplantation and death. LAY SUMMARY: The insertion of a transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites should be considered in patients with moderate decompensation and not as a last resort, as lower paracentesis frequency and creatinine levels pre-TIPS are associated with superior ascites control. In turn, failure to control ascites seems to be the only predictor of liver transplantation and death.

Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2-/- mice.

Multi drug resistance protein 2 knockout mice (Mdr2-/-) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, tumour development, and DNA damage in Mdr2-/- mice. HO-1 was induced by intraperitoneal injection of cobalt protoporphyrin IX (CoPP) twice weekly for 9 consecutive weeks. Immediately after HO-1 induction, liver function improved and infiltration of CD4+ and CD8+ T cells was reduced. Furthermore, we observed increased p38 activation with concomitant reduction of Cyclin D1 expression in aged Mdr2-/- mice. Long-term effects of HO-1 induction included increased CD8+ T cell infiltration as well as delayed and reduced tumour growth in one-year-old animals. Unexpectedly, DNA double-strand breaks were detected predominantly in macrophages of 65-week-old Mdr2-/- mice, while DNA damage was reduced in response to early HO-1 induction in vivo and in vitro. Overall, early induction of HO-1 in Mdr2-/- mice had a beneficial short-term effect on liver function and reduced hepatic T cell accumulation. Long-term effects of early HO-1 induction were increased CD8+ T cell numbers, decreased proliferation as wells as reduced DNA damage in liver macrophages of aged animals, accompanied by delayed and reduced tumour growth.