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Objective . The primary objective of this study is to address the reconstruction time challenge in magnetic particle imaging (MPI) by introducing a novel approach named SNR-peak-based frequency selection (SPFS). The focus is on improving spatial resolution without compromising reconstruction speed, thereby enhancing the clinical potential of MPI for real-time imaging. Approach . To overcome the trade-off between reconstruction time and spatial resolution in MPI, the researchers propose SPFS as an innovative frequency selection method. Unlike conventional SNR-based selection, SPFS prioritizes frequencies with signal-to-noise ratio (SNR) peaks that capture crucial system matrix information. This adaptability to varying quantities of selected frequencies enhances versatility in the reconstruction process. The study compares the spatial resolution of MPI reconstruction using both SNR-based and SPFS frequency selection methods, utilizing simulated and real device data. Main results. The research findings demonstrate that the SPFS approach substantially improves image resolution in MPI, especially when dealing with a limited number of frequency components. By focusing on SNR peaks associated with critical system matrix information, SPFS mitigates the spatial resolution degradation observed in conventional SNR-based selection methods. The study validates the effectiveness of SPFS through the assessment of MPI reconstruction spatial resolution using both simulated and real device data, highlighting its potential to address a critical limitation in the field. Significance. The introduction of SPFS represents a significant breakthrough in MPI technology. The method not only accelerates reconstruction time but also enhances spatial resolution, thus expanding the clinical potential of MPI for various applications. The improved real-time imaging capabilities of MPI, facilitated by SPFS, hold promise for advancements in drug delivery, plaque assessment, tumor treatment, cerebral perfusion evaluation, immunotherapy guidance, and in vivo cell tracking., (© 2024 Institute of Physics and Engineering in Medicine.)

Introduction: In recent years advances have been made in the microsurgical treatment of congenital or acquired central lymphatic lesions. While acquired lesions can result from any surgery or trauma of the central lymphatic system, congenital lymphatic lesions can have a variety of manifestations, ranging from singular thoracic duct abnormalities to complex multifocal malformations. Both conditions may cause recurrent chylous effusions and downstream lymphatic congestion depending on the anatomical location of the thoracic duct lesion and are associated with an increased mortality due to the permanent loss of protein and fluid., Methods: We present a case series of eleven patients undergoing central lymphatic reconstruction, consisting of one patient with a cervical iatrogenic thoracic duct lesion and eleven patients with different congenital thoracic duct lesions or thrombotic occlusions., Results: Anastomosis of the thoracic duct and a nearby vein was performed on different anatomical levels depending on the underlying central lymphatic pathology. Cervical ( n  = 4), thoracic ( n  = 1) or abdominal access ( n  = 5) was used for central lymphatic reconstruction with promising results. In 9 patients a postoperative benefit with varying degrees of symptom regression was reported., Conclusion: The presented case series illustrates the current rapid advances in the field of central microsurgical reconstruction of lymphatic lesions alongside the relevant literature., Competing Interests: NL acts as scientific advisor and consultant for Medical Microinstruments (MMI). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Weinzierl, Grünherz, Puippe, Gnannt, von Reibnitz, Giovanoli, Vetter, Möhrlen, Wildgruber, Müller, Pieper, Gutschow and Lindenblatt.)

Purpose: Transarterial chemoembolization (TACE) has become the standard of care for the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, current clinical practice guidelines lack consensus on the best selection of a specific TACE technique. This study aims to compare safety, tumor response, and progression-free survival (PFS) of conventional TACE (cTACE), drug-eluting bead TACE (DEB-TACE), and degradable starch microsphere TACE (DSM-TACE)., Methods: This retrospective study included n = 192 patients with HCC who underwent first TACE with unbiased follow-up at 4-6 weeks at our center between 2008 and 2021. Eligibility for TACE was BCLC intermediate stage B, bridging/down-staging (B/D) to liver transplantation (LT), or any other stage when patients were not suitable for resection, LT, local ablation, or systemic therapy. Patients were grouped into three cohorts (n = 45 cTACE, n = 84 DEB-TACE, n = 63 DSM-TACE), and further categorized by TACE indication (B/D or palliative). Liver function and adverse events, response assessed by the modified response evaluation criteria in solid tumors (mRECIST) 4-6 weeks post-TACE and PFS were analyzed., Results: There were no significant differences in age, gender distribution, BCLC stage, or etiology of liver disease among the three TACE groups, even in the B/D or palliative subgroups. DEB-TACE induced slight increases in bilirubin in the palliative subgroup and in lactate dehydrogenase in the entire cohort 4-6 weeks post-TACE, and more adverse events in the palliative subgroup. DEB-TACE and DSM-TACE showed significantly higher disease control rates (complete and partial response, stable disease) compared to cTACE, especially in the B/D setting (p < 0.05). There was no significant difference in PFS between the groups [median PFS (months): cTACE, 10.0 vs. DEB, 7.0 vs. DSM, 10.0; p = 0.436]., Conclusion: Our study provides valuable perspectives in the decision-making for a specific TACE technique: DEB-TACE and DSM-TACE showed improved tumor response. DEB-TACE showed a prolonged impact on liver function and more side effects, so patients with impaired liver function should be more strictly selected, especially in the palliative subgroup., (© 2024. The Author(s).)

Background and Purpose: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC)., Materials and Methods: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years., Results: Proliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively)., Conclusion: Increased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome., Competing Interests: Declaration of competing interest The work of Shraga Nahum Goldberg was supported by the Israeli Science Foundation [grant number 904/2020]. All the other authors do not have to declare conflict of interests., (Copyright © 2024. Published by Elsevier Inc.)

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).)

A neonatal female patient exhibited a congenital intricate vascular malformation affecting the liver, encompassing anomalies in the arterial, venous, and portal venous systems and notably including an aneurysm within the portal vein. The management strategy involved a staged endovascular approach, initially using retrograde embolization via the venous outflow tract. Subsequently, transarterial embolization was performed to address complications associated with pulmonary and portal hypertension., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Fibro-adipose vascular anomaly (FAVA) is characterized by intramuscular vascular malformation with secondary overgrowth of further mesenchymal elements, particularly fibro-adipose tissue. A rare disease complicated by nonspecific, overlapping clinical and imaging features, FAVA is often misdiagnosed, causing a dilemma in its diagnostic and therapeutical management. We present a case of FAVA of the lower extremity., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen-activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification., Methods and Results: This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen-activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty-five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V-Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen-activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3-4: RAS , 9/13 versus non- RAS , 3/11) and more frequent progression after treatment ( RAS , 10/13 versus non- RAS , 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19)., Conclusions: This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

Purpose: To evaluate the benefit of a contrast-enhanced computed tomography (CT) radiomics-based model for predicting response and survival in patients with colorectal liver metastases treated with transarterial Yttrium-90 radioembolization (TARE)., Materials and Methods: Fifty-one patients who underwent TARE were included in this single-center retrospective study. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 3-month follow-up. Patients were stratified as responders (complete/partial response and stable disease, n = 24) or non-responders (progressive disease, n = 27). Radiomic features (RF) were extracted from pre-TARE CT after segmentation of the liver tumor volume. A model was built based on a radiomic signature consisting of reliable RFs that allowed classification of response using multivariate logistic regression. Patients were assigned to high- or low-risk groups for disease progression after TARE according to a cutoff defined in the model. Kaplan-Meier analysis was performed to analyze survival between high- and low-risk groups., Results: Two independent RF [Energy, Maximal Correlation Coefficient (MCC)], reflecting tumor heterogeneity, discriminated well between responders and non-responders. In particular, patients with higher magnitude of voxel values in an image (Energy), and texture complexity (MCC), were more likely to fail TARE. For predicting treatment response, the area under the receiver operating characteristic curve of the radiomics-based model was 0.75 (95% CI 0.48-1). The high-risk group had a shorter overall survival than the low-risk group (3.4 vs. 6.4 months, p < 0.001)., Conclusion: Our CT radiomics model may predict the response and survival outcome by quantifying tumor heterogeneity in patients treated with TARE for colorectal liver metastases., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Objective: To investigate the effects of simultaneous cortisol cosecretion (CCS) on body composition in computed tomography (CT)-imaging and metabolic parameters in patients with primary aldosteronism (PA) with the objective of facilitating early detection., Design: Retrospective cohort study., Patients: Forty-seven patients with PA and CCS confirmed by 1-mg dexamethasone suppression test (DST) with a cutoff of ≥1.8 µg/dL were compared with PA patients with excluded CCS (non-CCS, n = 47) matched by age and sex., Methods: Segmentation of the fat compartments and muscle area at the third lumbar region was performed on non-contrast-enhanced CT images with dedicated segmentation software. Additionally, liver, spleen, pancreas and muscle attenuation were compared between the two groups., Results: Mean cortisol after DST was 1.2 µg/dL (33.1 nmol/L) in the non-CCS group and 3.2 µg/dL (88.3 nmol/L) in the CCS group with mild autonomous cortisol excess (MACE). No difference in total, visceral and subcutaneous fat volumes was observed between the CCS and non-CCS group (p = .7, .6 and .8, respectively). However, a multivariable regression analysis revealed a significant correlation between total serum cholesterol and results of serum cortisol after 1-mg DST (p = .026). Classification of the patients based on visible lesion on CT and PA-lateralization via adrenal venous sampling also did not show any significant differences in body composition., Conclusion: MACE in PA patients does not translate into body composition changes on CT-imaging. Therefore, early detection of concurrent CCS in PA is currently only attainable through biochemical tests. Further investigation of the long-term clinical adverse effects of MACE in PA is necessary., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Objective . Imaging of superparamagnetic iron oxide nanoparticles based on their non-linear response to alternating magnetic fields shows promise for imaging cells and vasculature in healthy and diseased tissue. Such imaging can be achieved through x-space reconstruction typically along a unidirectional Cartesian trajectory, which rapidly convolutes the particle distribution with a 'anisotropic blurring' point spread function (PSF), leading to images with anisotropic resolution. Approach . Here we propose combining the time domine-system matrix and x-space reconstruction methods into a forward model, where the output of the forward model is the PSF-blurred x-space reconstructed image. We then treat the blur as an inverse problem solved by Kaczmarz iteration. Main results . After we have proposed the method optimization, the normal resolution of simulation and device images has been increased from 3.5 mm and 5.25 mm to 1.5 mm and 3.25 mm, which has reached the level in the tangential resolution. Quantitative indicators of image quality such as PSNR and SSIM have also been greatly improved. Significance . Simulation and imaging of real phantoms indicate that our approach provides better isotropic resolution and image quality than the x-space method alone or other methods for removing PSF blur. Using our proposed method to optimize the image quality of x-space reconstructed images using unidirectional Cartesian trajectories, it will promote the clinical application of MPI in the future., (© 2024 Institute of Physics and Engineering in Medicine.)

Purpose: To describe a novel ultrasound-guided technique for percutaneous radiofrequency ablation of vascular malformations-the "moving shot technique.", Methods: Preliminary observational cohort study, conducted from June 1, 2019, to January 31, 2021, including all consecutive patients diagnosed with vascular malformations who were treated with ultrasound-guided radiofrequency ablation using the moving shot technique. Only patients who had undergone at least one unsuccessful previous treatment were included (sclerotherapy with ethanol/aethoxysklerol or embolization/surgery)., Results: Eight patients with a median age of 22 years (interquartile range, 13-31) were included. Patients had different vascular malformations consisting of 1 arteriovenous malformation, 4 venous malformations, and 1 each a mixed venous-lymphatic malformation, a glomuvenous malformation and a FAVA (fibroadipose vascular anomaly). Malformations were located at the limbs in 5 patients (62.5%), the subcutaneous/intramuscular tissue of the body in 2 patients (25%) and at the chin in 1 patient (12.5%). Clinical symptoms were pain in 8 patients (100%), swelling in 6 patients (75%), and partial immobility in 4 patients (50%). All patients showed an improvement of clinical symptoms after treatment with 7 (87.5%) being completely asymptomatic and 1 (12.5%) showing improvement of immobility and pain. No procedural complications, such as nerve damage or skin burns occurred., Conclusion: The moving shot technique using ultrasonography-guided radiofrequency ablation is a promising technique for the interventional treatment of vascular malformations and should be validated in multicenter-approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sporns, Psychogios, Blackham, Zech, Wildgruber and Takes.)

Background: Sinistral, or left-sided, portal hypertension (SPH) is a rare cause of upper gastrointestinal (GI) hemorrhage resulting from obstruction of the splenic vein. Venous drainage from the spleen via collaterals can result in venous hemorrhage into both the retroperitoneal and intra-abdominal spaces due to increased venous blood pressure in peripancreatic and gastroduodenal vasculature. SPH can occur secondary to pancreatitis with thrombosis of the splenic vein. Another possible cause is the surgical ligation of the splenic vein as part of pancreaticoduodenectomy (PD). Although splenectomy has been traditionally considered as the treatment of choice to relieve venous hypertension, individual concepts for each patient have to be developed. Considering the venous collateral drainage pathways, a comprehensive approach involving surgical, endoscopic, and interventional radiology interventions may be necessary to address the underlying cause of variceal bleeding. Among these approaches, splenic artery embolization (SAE) has demonstrated efficacy in mitigating the adverse effects associated with elevated venous outflow pressure., Summary: This review summarizes key imaging findings in SPH patients after PD and highlights the potential of minimally invasive embolization for curative treatment of variceal hemorrhage., Key Messages: (i) SPH is a potential consequence after major pancreas surgery. (ii) Collateral flow can lead to life-threatening abdominal bleeding. (iii) Depending on the origin and localization of the bleeding, a dedicated management is required, frequently involving interventional radiology techniques., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking., Materials and Methods: A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses., Results: LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter &gt;5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS., Conclusion: iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC., (© 2024 S. Karger AG, Basel.)

Background & Aims: Herein we used data derived from the SORAMIC trial to explore the predictive value of systemic inflammatory markers (neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib monotherapy or the combination of selective internal radiation therapy (SIRT)/sorafenib., Methods: Patients randomized to sorafenib monotherapy or SIRT/sorafenib within the per-protocol population of the SORAMIC trial were evaluated in this exploratory post hoc analysis. The median baseline values of NLR and PLR were used as cut-off values to describe subgroups. Kaplan-Meier curves with log-rank tests were used to evaluate median survival in the sorafenib and SIRT/sorafenib arms in each subgroup. Multivariable Cox regression analysis was applied to eliminate the effect of confounding factors., Results: A total of 275 patients with a median overall survival of 12.4 months were included in this analysis. The median NLR value of the cohort was 2.77 and the median PLR was 26.5. There was no significant difference in overall survival between the sorafenib and SIRT/sorafenib arms in patients with low NLR ( p  = 0.72) and PLR ( p  = 0.35) values. In patients with high NLR values, there was no statistically significant difference in median overall survival between SIRT/sorafenib and sorafenib cohorts (12.1 vs . 9.2 months, p  = 0.21). In patients with high PLR values, overall survival in the SIRT/sorafenib arm was significantly longer than in the sorafenib arm (15.9 vs . 11.0 months, p  = 0.029). This significant difference was preserved in the multivariable analysis (SIRT/sorafenib arm: hazard ratio 0.65, 95% CI 0.44-0.96, p  = 0.03) incorporating age, Child-Pugh grade, and alpha-fetoprotein levels., Conclusions: PLR is a potential predictive factor of benefit from additional SIRT in patients with HCC receiving sorafenib therapy. The potential predictive value of PLR should be further evaluated in future trials., Impact and Implications: Systemic therapies are the mainstay of treatment in patients with hepatocellular carcinoma at advanced stages. However, not all patients respond well to these treatments. In our analysis, using blood test parameters showing systemic inflammation status, we were able to identify patients who would benefit more from combined treatment with a locoregional treatment of radioembolization (or selective internal radiation therapy)., Competing Interests: Osman Öcal: Honoraria: Bayer. Max Seidensticker: Personal fees: Bayer, Sirtex. Najib Ben Khaled: Travel expenses: EISAI. Lecture honoraria: Falk Foundation and Astra Zeneca. Maciej Pech: Grants: Sirtex, Bayer; Personal fees: Sirtex. Bruno Sangro: Consultancy fees: Adaptimmune, Astra Zeneca, Bayer, BMS, Boston Scientific, BTG, Eisai, Eli Lilly, H3 Biomedicine, Ipsen, Novartis, Merck, Roche, Sirtex Medical and Terumo. Speaker fees: Astra Zeneca, Bayer, BMS, BTG, Eli Lilly, Ipsen, Novartis, Merck, Roche, Sirtex Medical and Terumo. Grants (to Institution): BMS and Sirtex Medical. Jens Ricke: Grants: Sirtex, Bayer; Personal fees: Sirtex, Bayer. Moritz Wildgruber: Speaker fees: Sirtex. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Purpose: To investigate the prognostic value of computed tomography (CT) derived imaging biomarkers in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and develop a predictive nomogram model., Patients and Methods: This retrospective study included 178 patients with histopathologically confirmed HCC who underwent liver transplantation between 2007 and 2021 at the two academic liver centers. We evaluated dedicated imaging features from baseline multiphase contrast-enhanced CT supplemented by several clinical findings and laboratory parameters. Time-to-recurrence was estimated by Kaplan-Meier analysis. Univariable Cox proportional hazard regression and multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent prognostic factors for recurrence. A nomogram model was then built based on the independent factors selected through LASSO regression, to predict the probabilities of HCC recurrence at one, three, and five years., Results: The rate of HCC recurrence after LT was 17.4% (31 of 178). The LASSO analysis revealed six independent predictors associated with an elevated risk of tumor recurrence. These predictors included the presence of peritumoral enhancement, the presence of over three tumor lesions, the largest tumor diameter greater than 3 cm, serum alpha-fetoprotein (AFP) levels exceeding 400 ng/mL, and the presence of a tumor capsule. Conversely, a history of bridging therapies was found to be correlated with a reduced risk of HCC recurrence. In addition, Kaplan-Meier curves showed patients with irregular margin, satellite nodules, or small lesions displayed shorter time-to-recurrence. Our nomogram demonstrated good performance, yielding a C-index of 0.835 and AUC values of 0.86, 0.88, and 0.85 for the predictions of 1-year, 3-year, and 5-year TTR, respectively., Conclusion: Imaging parameters derived from baseline contrast-enhanced CT showing malignant behavior and aggressive growth patterns, along with serum AFP and history of bridging therapies, show potential as biomarkers for predicting HCC recurrence after transplantation., Competing Interests: Prof. Dr. Enrico De Toni reports personal fees from AstraZeneca, Bayer, BMS, EISAI, Eli Lilly & Co, MSD, Mallinckrodt, Omega, Pfizer, IPSEN, Terumo and Roche; grants from Arqule, AstraZeneca, BMS, Bayer, Celsion and Roche, personal fees from BMS and Falk, Eli Lilly, and Roche, during the conduct of the study. Prof. Dr. Christian Lange reports personal fees, non-financial support from AbbVie, personal fees from AstraZeneca, Falk, CSL Behring, Boston Scientific, Eisai, Roche, Norgine, Shionogi, Sobi, outside the submitted work. Prof. Dr. Max Seidensticker reports personal fees from Bayer, during the conduct of the study; grants, personal fees from Sirtex medical, personal fees from Cook Medical, Siemens Healthineers, Balt, Astra Zeneca, LIAM; grants from Bayer, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Hoang et al.)

Background: Portal vein embolization (PVE) is used to induce remnant liver hypertrophy prior to major hepatectomy. The purpose of this study was to evaluate the predictive value of baseline computed tomography (CT) data for future remnant liver (FRL) hypertrophy after PVE., Methods: In this retrospective study, all consecutive patients undergoing right-sided PVE with or without hepatic vein embolization between 2018 and 2021 were included. CT volumetry was performed before and after PVE to assess standardized FRL volume (sFRLV). Radiomic features were extracted from baseline CT after segmenting liver (without tumor), spleen and bone marrow. For selecting features that allow classification of response (hypertrophy ≥ 1.33), a stepwise dimension reduction was performed. Logistic regression models were fitted and selected features were tested for their predictive value. Decision curve analysis was performed on the test dataset., Results: A total of 53 patients with liver tumor were included in this study. sFRLV increased significantly after PVE, with a mean hypertrophy of FRL of 1.5 ± 0.3-fold. sFRLV hypertrophy ≥ 1.33 was reached in 35 (66%) patients. Three independent radiomic features, i.e. liver-, spleen- and bone marrow-associated, differentiated well between responders and non-responders. A logistic regression model revealed the highest accuracy (area under the curve 0.875) for the prediction of response, with sensitivity of 1.0 and specificity of 0.5. Decision curve analysis revealed a positive net benefit when applying the model., Conclusions: This proof-of-concept study provides first evidence of a potential predictive value of baseline multi-organ radiomics CT data for FRL hypertrophy after PVE., (© 2023. The Author(s).)

Background: Primary lymphoma of the central nervous system (PCNSL) encompasses a variety of lymphoma subtypes, with the majority being diffuse large B-cell lymphomas, which require aggressive systemic treatment. In contrast, low-grade lymphomas are reported infrequently and are mostly limited to dural manifestations. Very rarely, parenchymal low-grade PCNSL is diagnosed, and the cases documented in the literature show a wide variety of treatment approaches., Methods: We screened all cases of PCNSL treated at our department (a tertiary hematooncology and neurooncology center) in the last 15 years and conducted a comprehensive literature research in the PubMed database., Results: Overall, two cases of low-grade primary parenchymal PCNSL treated with irradiation were identified. The dose prescriptions ranged from 30.6 to 36 Gy for the involved site, with sparing of the hippocampal structures. Both patients had an excellent response to the treatment with a mean follow-up of 20 months. No clinical or radiological signs of treatment toxicity were detected., Conclusions: Our analysis corroborates the results from the literature and demonstrates that parenchymal low-grade PCNSL shows a good response to localized radiation treatment, enabling a favorable outcome while avoiding long-term treatment toxicity.

Introduction: Patients with Fontan palliation are susceptible to congestive hepatopathy and Fontan-associated liver disease (FALD) because of hemodynamic changes. The staging of liver fibrosis involves various methods, including invasive biopsy. Transjugular liver biopsy (TJLB) offers a less invasive alternative, enhancing liver disease surveillance in routine cardiac catheterization. We detail the technical aspects, share initial outcomes, and discuss existing literature., Methods/results: During routine follow-up cardiac catheterization indicated by hemodynamic or clinical alterations, four patients aged between 16 and 26 years with univentricular Fontan circulation and three patients with biventricular circulation underwent TJLB during routine surveillance catheterization. The examinations were performed under conscious sedation and local anesthesia without general anesthesia. Jugular access was obtained at the site of liver localization, and a 5 F multipurpose catheter was inserted into the liver veins. After hand angiography to delineate the local hepatic venous anatomy, an exchange wire was used to place the bioptome, and three consecutive biopsies were performed. There were no complications, especially perforation or bleeding. The technical success rate was 100%, with all obtained samples appropriate for histopathological diagnostics. The total additional procedure time was less than 20 min., Conclusion: TJLB is an attractive alternative method for obtaining liver specimens in the scope of FALD care. We believe that it should be performed during routine hemodynamic evaluations in Fontan patients and can be performed safely with very low additional time expenditure. As the biopsy site is intravascular, the risk of external bleeding or hematoma is significantly reduced despite the high intrahepatic pressures and the usually impaired coagulation profile in these patients. Based on our initial experience and the lower complication rates compared with other techniques, TJLB should be considered a standard approach in these patients and used more often during the long-term follow-up of Fontan patients. It can be performed in the same setting whenever a hemodynamic assessment of patients with congenital heart defects is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mandilaras, Meyer, Mühlberg, Braun, Haas, Jakob, Dalla Pozza, Wildgruber and Fischer.)

Purpose: The role of microRNA-146a (miR-146a) in defining the tumor immune microenvironment (TIME) is well established. The aim of this study was to evaluate circulating miR-146a as an early prognostic marker of 90 Y-radioembolization ( 90 Y-RE) in metastatic liver cancer and to assess the correlation between circulating miR-146a and TIME cellular composition in distant, yet untreated metastases., Methods: Twenty-one patients with bilobar liver lesions from gastro-intestinal cancer underwent lobar 90 Y-RE. Biopsy of contralateral lobe abscopal tumors was acquired at the onset of a second treatment session at a median of 21 days after initial RE, immediately prior to ablation therapy of the contralateral lobe tumor. miR-146a was measured by RT-qPCR in plasma collected 24 h before (T1) and 48 h after (T2) initial unilobar 90 Y-RE. The level of miR-146a was correlated with the infiltration of CD4 + , CD8 + , FoxP3 T cells, CD163 + M2 macrophages and immune-exhausted T cells in the abscopal tumor tissue acquired before the second treatment session., Results: Plasma samples collected at T2 showed a higher concentration of miR-146a with respect to T1 in 43% of the patients (p = 0.002). In these patients, tumors revealed a pro-tumorigenic immune composition with enrichment of Tim3 + immune exhausted cells (p = 0.021), in combination with a higher infiltration of CD163 + M2 macrophages and a lower infiltration of CD8 + T cells. Patients with a higher level of miR-146a after 90 Y-RE showed a trend to shorter OS (p = 0.055)., Conclusion: miR-146a may represent a novel prognostic biomarker for 90 Y-radioembolization in metastatic liver cancer., (© 2023. The Author(s).)

Purpose: To investigate the role of microRNA-21 (miR21) in radiofrequency (RF) ablation-induced tumor growth and whether miR21 inhibition suppresses tumorigenesis., Material and Methods: Standardized liver RF ablation was applied to 35 C57/BL6 mice. miR21 and target proteins pSTAT3, PDCD4, and PTEN were assayed 3 hours, 24 hours, and 3 days after ablation. Next, 53 Balb/c and 44 C57BL/6 mice received Antago-miR21 or scrambled Antago-nc control, followed by intrasplenic injection of 10,000 CT26 or MC38 colorectal tumor cells, respectively. Hepatic RF ablation or sham ablation was performed 24 hours later. Metastases were quantified and tumor microvascular density (MVD) and cellular proliferation were assessed at 14 or 21 days after the procedures, respectively., Results: RF ablation significantly increased miR21 levels in plasma and hepatic tissue at 3 and 24 hours as well as target proteins at 3 days after ablation (P < .05, all comparisons). RF ablation nearly doubled tumor growth (CT26, 2.0 SD ± 1.0 fold change [fc]; MC38, 1.9 SD ± 0.9 fc) and increased MVD (CT26, 1.9 SD ± 1.0 fc; MC38, 1.5 ± 0.5 fc) and cellular proliferation (CT26, 1.7 SD ± 0.7 fc; MC38, 1.4 SD ± 0.5 fc) compared with sham ablation (P < .05, all comparisons). RF ablation-induced tumor growth was suppressed when Antago-miR21 was administered (CT26, 1.0 SD ± 0.7 fc; MC38, 0.9 SD ± 0.4 fc) (P < .01, both comparisons). Likewise, Antago-miR21 decreased MVD (CT26, 1.0 SD ± 0.3 fc; MC38, 1.0 SD ± 0.2 fc) and cellular proliferation (CT26, 0.9 SD ± 0.3 fc; MC38, 0.8 SD ± 0.3 fc) compared with baseline (P < .05, all comparisons)., Conclusions: RF ablation upregulates protumorigenic miR21, which subsequently influences downstream tumor-promoting protein pathways. This effect can potentially be suppressed by specific inhibition of miR21, rendering this microRNA a pivotal and targetable driver of tumorigenesis after hepatic thermal ablation., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

The purpose of this study is to evaluate the technical and clinical outcome of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary leakage. All patients who underwent ultrasound-assisted PTBD between January 2017 and December 2021 due to biliary leakage with nondilated biliary systems were retrospectively evaluated for periprocedural characteristics, medical indications, technical success (successful placement of drainage catheter), clinical success (resolved leak without additional procedures), fluoroscopy time, procedure duration, and clinical outcomes. 74 patients with a mean age of 64.1 ± 15.1 years were identified. Surgery was the most common etiology of biliary leak with 93.2% of the cases. PTBD had a 91.8% (68/74) technical success rate and an 80.8% clinical success rate. The mean procedure and fluoroscopy duration were 43.5 and 18.6 minutes. Age > 65 years (P = .027) and left-sided drainage (P = .034) were significant risk factors of clinical failure. Procedure-related major complications were 2 bleedings from the liver and 1 bleeding from an intercostal artery (major complication rate 4%). PTBD is a feasible, safe, and effective treatment option in patients with biliary leakage with low complication rates., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To characterize the artifacts of an 18-gauge coaxial nickel-titanium needle using a balanced steady-state free precession sequence in magnetic resonance imaging-guided interventions at 3.0 tesla., Methods: The influence of flip angle (FA), bandwidth, matrix, slice thickness (ST), and read-out direction on needle artifact behavior was investigated for different intervention angles (IA). Artifact diameters were rated at predefined positions. Subgroup differences were assessed using Bonferroni-corrected non-parametric tests and correlations between continuous variables were expressed using the Bravais-Pearson coefficient. Interrater reliability was quantified using intraclass correlation coefficients (ICCs), and a contrast-enhanced target lesion to non-enhanced muscle tissue contrast ratio was quantified., Results: The artifact diameters decreased with an increase in FA for all IAs ( P < 0.001) and with an increase in ST for IAs of 45°-90° (all P < 0.05). Tip artifacts occurred at low IAs (0°-45°) and gradually increased in size with a decrease in IA ( P = 0.022). The interrater reliability was high (ICC: 0.994-0.999). The contrast-enhanced target lesion to non-enhanced muscle tissue contrast ratio presented positive correlations with increasing FAs and matrices ( P < 0.001; P = 0.003) and a negative correlation with increasing STs ( P = 0.007)., Conclusion: To minimize needle artifacts, it is recommended to use FAs of 40°-60°, a ST of >7 mm, and, if possible, an IA of 45°-60°. The visibility of the target lesion and the needle's artifact behavior must be weighed up against each other when choosing the ST, while higher FAs (40°-60°) and matrices (224 × 224/256 × 256) are associated with low artifacts and sufficient lesion visibility., Competing Interests: The authors declared no conflicts of interest.

Background: Acute intracranial large vessel occlusion (LVO) is an important cause of morbidity and mortality among children; however, unlike in adults, no clinical trial has investigated the benefit of mechanical thrombectomy (MT) in pediatric LVO. Thus, MT remains an off-label procedure for pediatric stroke., Purpose: To investigate the efficacy and safety of MT in pediatric LVO., Methods: A systematic literature search was conducted in Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, and Cochrane Central Register of Clinical Trials databases. Studies reporting safety and efficacy outcomes for endovascular treatment of pediatric LVO were included. Data regarding recanalization, functional outcome, symptomatic intracranial hemorrhage (sICH), and mortality were extracted from the included studies. Functional outcome was assessed with the modified Rankin scale (mRS). A fixed or random-effects model was used to calculate pooled event rates and 95% confidence intervals (CI)., Results: In this study 11 studies comprising 215 patients were included. The successful recanalization rate was 90.3% (95% CI = 85.77-95.11%), and complete recanalization was achieved in 52.7% (95% CI = 45.09-61.62%) of the cases. The favorable (mRS = 0-2) and excellent (mRS = 0-1) outcome rates were 83.3% (95% CI = 73.54-94.50%) and 59.5% (95% CI = 44.24-80.06%), respectively. The overall sICH prevalence was 0.59% (95% CI = 0-3.30%) and mortality rate was 3.2% (95% CI = 0.55-7.38%)., Conclusion: In our meta-analysis, MT demonstrated a promising safety and efficacy profile for pediatric patients, with consistently high efficacy outcomes and low complication rates. Our results support the utilization of MT in pediatric LVOs; however, prospective studies are still needed to further establish the role of pediatric MT as a first-line treatment strategy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Biomarkers are essential to implement personalized therapies in cancer treatment options. As primary liver tumors are increasing and treatment is coupled to liver function and activation of systemic cells of the immune system, we investigated blood-based cells for their ability to predict response to local ablative therapy., Methods: We analyzed peripheral blood cells in 20 patients with primary liver cancer at baseline and following brachytherapy. In addition to platelets, leukocytes, lymphocytes, monocytes, neutrophils and most common ratios PLR, LMR, NMR and NLR, we investigated T cell and NKT cell populations of 11 responders and 9 non-responders using flow cytometry., Results: We have found a peripheral blood cell signature that differed significantly between responders and non-responders treated with interstitial brachytherapy (IBT). At baseline, non-responders featured higher numbers of platelets, monocytes and neutrophils, a higher platelet-to-lymphocyte ratio and an increase in the NKT cell population with a concurrent reduction in CD16 + NKT cells. Simultaneously, a lower percentage of CD4 + T cells was present in non-responders, as also reflected in a lower CD4/8 ratio. CD45RO + memory cells were lower in both, CD4 + and CD8 + T cell populations whereas PD-1 + T cells were only present in the CD4 + T cell population., Conclusion: Baseline blood-based cell signature may function as a biomarker to predict response following brachytherapy in primary liver cancer., (© 2023. The Author(s).)

Purpose: The purpose of the study was to investigate outcome after pediatric transjugular intrahepatic portosystemic shunt (TIPS) with respect to survival MATERIAL AND METHODS: After searching for studies on TIPS in children in Ovid, Medline, Embase, Scopus and Cochrane published between 2000 and 2022, individual patient data were retrieved from five retrospective cohorts. Overall survival (OS) and transplant-free survival (TFS) were calculated using Kaplan-Meier analysis and log-rank test and compared to the indication (ascites vs. variceal bleeding) as well as to the level of obstruction (pre-hepatic vs. hepatic vs. post-hepatic). Additionally, TIPS patency was analyzed., Results: n = 135 pediatric patients were included in the final analysis. Indication for pediatric TIPS creation was heterogeneous among the included studies. TIPS patency decreased from 6 to 24 months, subsequent pediatric liver transplantation was performed in 22/135 (16.3%) of cases. The presence of ascites was related with poorer TFS (HR 2.3, p = 0.023), while variceal bleeding was not associated with impaired survival. Analysis of the level of obstruction (pre-hepatic, hepatic and post-hepatic) failed to prove significantly reduced OS for post-hepatic obstruction (HR 3.2, p = 0.092) and TFS (HR 1.3, p = 0.057). There was no difference in OS and TFS according to age at time of TIPS placement., Conclusions: The presence of ascites associates with impaired survival after TIPS in children, with no differences in survival according to the age of the child. Interventional shunt procedures can be considered feasible for all ages., Level of Evidence: Level 2a., (© 2023. The Author(s).)

Purpose: To perform radiofrequency (RF) ablation of hepatocellular carcinoma (HCC) and to assess serological and histopathological markers of tumorigenesis in distant untreated tumors to determine whether these were associated with unfavorable outcomes such as early relapse and increased biological aggressiveness., Materials and Methods: The study cohort comprised 13 patients from a prospective single-arm study. All patients underwent 2 ablation sessions of multifocal HCC nodules 14 days apart. Core biopsy samples of untreated tumors were acquired at baseline and at the time of the second ablation session. Samples were stained immunohistochemically with Ki-67 (proliferation) and CD34 (microvasculature). Blood plasma was obtained at baseline and 2 days after the initial ablation session and analyzed for hepatocyte growth factor (HGF), vascular endothelial growth factor C, and angiopoietin-2 using an enzyme-linked immunosorbent assay. The clinical follow-up period ranged from 7 to 25 months. Patients were stratified as responders (complete remission or limited and delayed recurrence at >6 months; n = 6) or nonresponders (any recurrence within 6 months or >3 new tumors or any new tumor of >3 cm thereafter; n = 7)., Results: In 3 of 7 nonresponders, the Ki-67 index markedly increased in untreated tumors, whereas Ki-67 was stable in all responders. Microvascular density strongly increased in a single nonresponder only. HGF and angiopoietin-2 increased by >30% in 3 of 7 and 4 of 7 nonresponders, respectively, whereas they were stable or decreased in responders. Overall, ≥2 biomarkers were elevated in 6 of 7 (85.7%) nonresponders, whereas 4 of 6 responders demonstrated no increased biomarker and 2 patients demonstrated increase in 1 biomarker only (P = .002)., Conclusions: RF ablation of HCC can produce protumorigenic factors that induce effects in distant untreated tumors. These may potentially function as biomarkers of clinical outcome., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy., Methods: Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated. For simultaneous analysis of different metabolites, multiparametric CEST-MRI with calculation of asymmetric magnetization transfer ratio (MTR asym ) at 1.2 to 2.0 ppm for glucose-weighted, 2.0 ppm for creatine-weighted and 3.2 to 3.6 ppm for amide proton transfer- (APT-) weighted CEST contrast was conducted. Ex vivo validation of MRI results was achieved by 1 H nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry imaging with laser postionization and immunohistochemistry., Results: During tumor progression, the two tumor models showed divergent trends for all examined CEST contrasts: While glucose- and APT-weighted CEST contrast decreased and creatine-weighted CEST contrast increased over time in the 4T1 model, 67NR tumors exhibited increased glucose- and APT-weighted CEST contrast during disease progression, accompanied by decreased creatine-weighted CEST contrast. Already three days after treatment initiation, CEST contrasts captured response to ICI therapy in both tumor models., Conclusion: Multiparametric CEST-MRI enables non-invasive assessment of metabolic signatures of the TME, allowing both for estimation of the degree of tumor malignancy and for assessment of early response to immune checkpoint inhibition., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: The aim of this study was to investigate an integrated diagnostics approach for prediction of the source of aldosterone overproduction in primary hyperaldosteronism (PA)., Methods: 269 patients from the prospective German Conn Registry with PA were included in this study. After segmentation of adrenal glands in native CT images, radiomic features were calculated. The study population consisted of a training (n = 215) and a validation (n = 54) cohort. The k = 25 best radiomic features, selected using maximum-relevance minimum-redundancy (MRMR) feature selection, were used to train a baseline random forest model to predict the result of AVS from imaging alone. In a second step, clinical parameters were integrated. Model performance was assessed via area under the receiver operating characteristic curve (ROC AUC). Permutation feature importance was used to assess the predictive value of selected features., Results: Radiomics features alone allowed only for moderate discrimination of the location of aldosterone overproduction with a ROC AUC of 0.57 for unilateral left (UL), 0.61 for unilateral right (UR), and 0.50 for bilateral (BI) aldosterone overproduction (total 0.56, 95% CI: 0.45-0.65). Integration of clinical parameters into the model substantially improved ROC AUC values (0.61 UL, 0.68 UR, and 0.73 for BI, total 0.67, 95% CI: 0.57-0.77). According to permutation feature importance, lowest potassium value at baseline and saline infusion test (SIT) were the two most important features., Conclusion: Integration of clinical parameters into a radiomics machine learning model improves prediction of the source of aldosterone overproduction and subtyping in patients with PA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mansour, Mittermeier, Walter, Schachtner, Rudolph, Erber, Schmidt, Heinrich, Bruedgam, Tschaidse, Nowotny, Bidlingmaier, Kunz, Adolf, Ricke, Reincke, Reisch, Wildgruber and Ingrisch.)

Purpose: The purpose of this study was to assess the efficacy of transarterial embolization in COVID-19 patients with an arterial bleeding and to investigate differences between various patient groups concerning survival., Method: We retrospectively reviewed COVID-19 patients undergoing transarterial embolization due to an arterial bleeding in a multicenter study from April 2020 to July 2022 and analyzed the technical success of embolization and survival rate. 30-day survival between various patient groups was analyzed. The Chi- square test and Fisher's exact test were used for testing association between the categorical variables., Results: 53 COVID-19 patients (age: 57.3 ± 14.3 years, 37 male) received 66 angiographies due to an arterial bleeding. The initial embolization was technically successful in 98.1% (52/53). In 20.8% (11/53) of patients, additional embolization was necessary due to a new arterial bleeding. A majority of 58.5% (31/53) had a severe course of COVID-19 infection necessitating ECMO-therapy and 86.8% (46/53) of patients received anticoagulation. 30-day survival rate in patients with ECMO-therapy was significantly lower than without ECMO-therapy (45.2% vs. 86.4%, p = 0.004). Patients with anticoagulation did not have a lower 30-day survival rate than without anticoagulation (58.7% vs. 85.7%, p = 0.23). COVID-19 patients with ECMO-therapy developed more frequently a re-bleeding after embolization than non-ECMO-patients (32.3% vs. 4.5%, p = 0.02)., Conclusions: Transarterial embolization is a feasible, safe, and effective procedure in COVID-19 patients with arterial bleeding. ECMO-patients have a lower 30-day survival rate than non-ECMO-patients and have an increased risk for re-bleeding. Treatment with anticoagulation could not be identified as a risk factor for higher mortality., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: Prognostic biomarkers identifying patients with early tumor progression after local ablative therapy remain an unmet clinical need. The aim of this study was to investigate circulating miR-21 and miR-210 levels as prognostic biomarkers of HCC treated by CT-guided high-dose rate brachytherapy (HDR-BT)., Materials and Methods: 24 consecutive HCC patients (BCLC A and B) treated with CT-guided HDR-BT (1 × 15 Gy) were included in this prospective IRB-approved study. RT-PCR was performed to quantify miR-21 and miR-210 levels in blood samples acquired prior to and 2 d after HDR-BT. Follow-up imaging (contrast-enhanced liver MRI and whole-body CT) was performed in 3 months follow-up intervals. Therapy response was assessed with patients classified as either responders or non-responders (12 each). Responders were defined as having no local or diffuse systemic progression within 6 months and no diffuse systemic progression exceeding 3 nodules/nodule diameter > 3 cm from 6 months to 2 years. Non-responders had recurrence within 6 months and/or tumor progression with > 3 nodules or individual lesion diameter > 3 cm or extrahepatic disease within two years, respectively. Biostatistics included parametric and non-parametric testing (Mann-Whitney-U-test), as well as Kaplan-Meier curve construction., Results: The responder group demonstrated significantly decreasing miR-21 values 2 d post therapy compared to non-responders (median miR-21 2 -ΔΔCт : responders 0.73 [IQR 0.34], non-responders 1.53 [IQR 1.48]; p = 0.0102). miR-210 did not show any significant difference between responders and non-responders (median miR-210 2 -ΔΔCт : responders 0.74 [IQR 0.45], non-responders 0.99 [IQR 1.13]; p = 0.8399). Kaplan-Meier curves demonstrated significantly shorter time to systemic progression for increased miR-21 (p = 0.0095) but not miR-210 (p = 0.7412), with events accumulating > 1 year post therapy in non-responders (median time to systemic progression 397 days)., Conclusion: Increasing circulating miR-21 levels are associated with poor response and shorter time to systemic progression in HDR-BT-treated HCC. This proof-of-concept study provides a basis for further investigation of miR-21 as a prognostic biomarker and potential stratifier in future clinical trials of interventional oncology therapies., Trial Registration: In this monocentric clinical study, we analyzed prospectively acquired data of 24 patients from the "ESTIMATE" patient cohort (Studiennummer: DRKS00010587, Deutsches Register Klinischer Studien). Ethical approval was provided by the ethics committee "Ethikkommission bei der LMU München" (reference number "17-346") on June 20, 2017 and August 26, 2020., (© 2023. The Author(s).)

Background: Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy., Methods: Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry., Results: Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage., Conclusion: DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy., (© 2023. The Author(s).)

Variations in vascular wall shear stress are often presumed to result in the formation of atherosclerotic lesions at specific arterial regions, where continuous laminar flow is disturbed. The influences of altered blood flow dynamics and oscillations on the integrity of endothelial cells and the endothelial layer have been extensively studied in vitro and in vivo. Under pathological conditions, the Arg-Gly-Asp (RGD) motif binding integrin α v β 3 has been identified as a relevant target, as it induces endothelial cell activation. Animal models for in vivo imaging of endothelial dysfunction (ED) mainly rely on genetically modified knockout models that develop endothelial damage and atherosclerotic plaques upon hypercholesterolemia (ApoE -/- and LDLR -/- ), thereby depicting late-stage pathophysiology. The visualization of early ED, however, remains a challenge. Therefore, a carotid artery cuff model of low and oscillating shear stress was applied in CD-1 wild-type mice, which should be able to show the effects of altered shear stress on a healthy endothelium, thus revealing alterations in early ED. Multispectral optoacoustic tomography (MSOT) was assessed as a non-invasive and highly sensitive imaging technique for the detection of an intravenously injected RGD-mimetic fluorescent probe in a longitudinal (2-12 weeks) study after surgical cuff intervention of the right common carotid artery (RCCA). Images were analyzed concerning the signal distribution upstream and downstream of the implanted cuff, as well as on the contralateral side as a control. Subsequent histological analysis was applied to delineate the distribution of relevant factors within the carotid vessel walls. Analysis revealed a significantly enhanced fluorescent signal intensity in the RCCA upstream of the cuff compared to the contralateral healthy side and the downstream region at all time points post-surgery. The most obvious differences were recorded at 6 and 8 weeks after implantation. Immunohistochemistry revealed a high degree of α v -positivity in this region of the RCCA, but not in the left common carotid artery (LCCA) or downstream of the cuff. In addition, macrophages could be detected by CD68 immunohistochemistry in the RCCA, showing ongoing inflammatory processes. In conclusion, MSOT is capable of delineating alterations in endothelial cell integrity in vivo in the applied model of early ED, where an elevated expression of integrin α v β 3 was detected within vascular structures.

Background and Objectives: Perfusion imaging can identify adult patients with salvageable brain tissue who would benefit from thrombectomy in later time windows. The feasibility of obtaining hyperacute perfusion sequences in pediatric stroke is unknown. The aim of this study was to determine whether contrast perfusion imaging delayed time to treatment and to assess perfusion profiles in children with large vessel occlusion stroke., Methods: The Save ChildS retrospective cohort study (January 2000-December 2018) enrolled children (1 month-18 years) with stroke who underwent thrombectomy from 27 European and U.S. stroke centers. This secondary analysis included patients with anterior circulation occlusion and available imaging for direct review by the neuroimaging core laboratory. Between-group comparisons were performed using the Wilcoxon rank-sum exact test for continuous variables or Fisher exact test for binary variables. Given the small number of patients, evaluation of perfusion imaging parameters was performed descriptively only., Results: Of 33 patients with available neuroimaging, 15 (45.4%) underwent perfusion (CT perfusion n = 6; MR perfusion n = 9); all were technically adequate. The median time from onset to recanalization did not differ between groups {4 hours (interquartile range [IQR] 4-7.5) perfusion+; 3.4 hours (IQR 2.5-6.5) perfusion-, p = 0.158}. Target mismatch criteria were met by 10/15 (66.7%) patients and did not correlate with reperfusion status or functional outcome. The hypoperfusion intensity ratio (HIR) was favorable in 11/15 patients and correlated with older age but not NIHSS, time to recanalization, or stroke etiology. Favorable HIR was associated with better functional outcome at 6 months (Pediatric Stroke Outcome Measure 1.0 [IQR 0.5-2.0] vs 2.0 [1.5-3.0], p = 0.026) and modified Rankin Scale 1.0 [0-1] vs 2.0 [1.5-3.5], p = 0.048) in this small sample., Discussion: Automated perfusion imaging is feasible to obtain acutely in children and does not delay time to recanalization. Larger prospective studies are needed to determine biomarkers of favorable outcome in pediatric ischemic stroke and to establish core and penumbral thresholds in children., (© 2022 American Academy of Neurology.)

Background: The inflammatory tumor microenvironment (TME) is formed by various immune cells, being closely associated with tumorigenesis. Especially, the interaction between tumor-infiltrating T-cells and macrophages has a crucial impact on tumor progression and metastatic spread. The purpose of this study was to investigate whether oscillating-gradient diffusion-weighted MRI (OGSE-DWI) enables a cell size-based discrimination between different cell populations of the TME., Methods: Sine-shaped OGSE-DWI was combined with the Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) approach to measure microscale diffusion distances, here relating to cell sizes. The accuracy of IMPULSED-derived cell radii was evaluated using in vitro spheroid models, consisting of either pure cancer cells, macrophages, or T-cells. Subsequently, in vivo experiments aimed to assess changes within the TME and its specific immune cell composition in syngeneic murine breast cancer models with divergent degrees of malignancy (4T1, 67NR) during tumor progression, clodronate liposome-mediated depletion of macrophages, and immune checkpoint inhibitor (ICI) treatment. Ex vivo analysis of IMPULSED-derived cell radii was conducted by immunohistochemical wheat germ agglutinin staining of cell membranes, while intratumoral immune cell composition was analyzed by CD3 and F4/80 co-staining., Results: OGSE-DWI detected mean cell radii of 8.8±1.3 µm for 4T1, 8.2±1.4 µm for 67NR, 13.0±1.7 for macrophage, and 3.8±1.8 µm for T-cell spheroids. While T-cell infiltration during progression of 4T1 tumors was observed by decreasing mean cell radii from 9.7±1.0 to 5.0±1.5 µm, increasing amount of intratumoral macrophages during progression of 67NR tumors resulted in increasing mean cell radii from 8.9±1.2 to 12.5±1.1 µm. After macrophage depletion, mean cell radii decreased from 6.3±1.7 to 4.4±0.5 µm. T-cell infiltration after ICI treatment was captured by decreasing mean cell radii in both tumor models, with more pronounced effects in the 67NR tumor model., Conclusions: OGSE-DWI provides a versatile tool for non-invasive profiling of the inflammatory TME by assessing the dominating cell type T-cells or macrophages., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The aim of this project is the sustainable implementation of a vascular anomalies (VA) program in Tanzania., Materials and Methods: In 2021 the first interdisciplinary VA program was initiated at Muhimbili National Hospital (MNH), Dar Es Salaam, Tanzania in a stepwise approach. During the planning phase the clinical need for minimally-invasive therapies of VAs and the preexisting structures were assessed by the local Interventional Radiology (IR) team at MNH. During the initiation phase, an IR team from two German VA centers joined the interdisciplinary team at MNH for clinical workup, image-guided procedures and follow-up. VA patients were recruited from existing patient records or seen at clinics as de novo presentations following nationwide advertisement. In the post-processing phase joined online conferences for follow-up and support in management of new patients were established. Further follow-up was supported by attending providers from other established VA centers, traveling to bolster the primary operators of MNH., Results: The first interdisciplinary VA program was successfully launched in Tanzania. Minimally-invasive treatments were successfully trained, by performing ultrasound-guided sclerotherapy with polidocanol and bleomycin in twelve patients with slow-flow malformations, one endovascular embolization of a high-flow malformation, and medical treatment of an aggressive infantile hemangioma. Regular online follow-up presentations have been initiated. Follow-up evaluation and required treatment was sustained when appropriate., Conclusion: The presented "hands-on" training set the ground for the first interdisciplinary VA program in Tanzania. This framework is expected to establish comprehensive and sustainable care of patients with VAs in East Africa and can serve as a blueprint for other sites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Puhr-Westerheide, Masthoff, Shah, Krechel, Shemwetta, Naif, Ukweh, Abdul, Sarkar, Baraka, Malecela, Lekasio, Rajab, Mungia, Sianga, Manji, Mbuguje, Khoncarly, Minja, Laage Gaupp and Wildgruber.)

Background: Venous malformations tend to retain their slow-flow behavior, even in progressive disease or regression following therapy., Objective: The aim of this study is to analyze the development of acquired hemodynamic relevant arterio-venous fistulae in patients with slow-flow malformations., Methods: This study is a retrospective analysis based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies. Patients with venous malformations and development of secondary arterio-venous fistulae were included. Indications for therapy of the vascular malformation were based on patients' symptoms and complications. The following endpoints were of clinical interest and were assessed: origin of development of arteriovenous fistula, development of secondary comorbidities as a result of the vascular malformation. For analysis we focused on descriptive statistics., Results: Out of 1213 consecutive patients with vascular malformations, in 6 patients perfusion changed from slow flow to arterio-venous fast-flow patterns. Four patients developed the fistula after local trauma in the area of the malformation, the other 2 patients developed the fistula due to progression of the disease and recurrent thrombophlebitis. These 2 patients had no trauma or interventions at the time of arterio-venous fistula development., Conclusions: Acquired arterio-venous fast-flow fistula in patients with slow flow vascular malformation is very rare and might be a result of local trauma or the progression of the disease with recurrent thrombophlebitis. Specific evidence-based treatment options for these patients do not exist.

Purpose: Arteriovenous malformations (AVMs) as rare diseases are diagnostically and therapeutically challenging. Due to the limited evidence regarding treatment outcome, prospective data are needed on how different treatment regimens affect outcome. The aims of this prospective trial are to determine effectiveness, safety, and clinical outcome of multimodal treatment in patients with extracranial AVMs., Materials and Methods: After clinical and magnetic resonance imaging (MRI)-based diagnosis and informed consent, 146 patients (> 4 years and < 70 years) undergoing multimodal therapy in tertiary care vascular anomalies centers will be included in this prospective observational trial. Treatment options include conservative management, medical therapy, minimally invasive image-guided procedures (embolization, sclerotherapy) and surgery as well as combinations of the latter. The primary outcome is the patient-reported QoL 6 months after completion of treatment using the short form-36 health survey version 2 (SF-36v2) and the corresponding short form-10 health survey (SF-10) for children. In addition, clinical presentation (physician-reported signs), MRI imaging (radiological assessment of devascularization), recurrence rate, and therapeutic safety will be analyzed. Further follow-up will be performed after 12, 24, and 36 months. Moreover, liquid biopsies are being obtained from peripheral blood at multiple time points to investigate potential biomarkers for therapy response and disease progression., Discussion: The APOLLON trial is a prospective, multicenter, observational open-label trial with unequal study groups to generate prospective evidence for multimodal treatment of AVMs. A multicenter design with the potential to assess larger populations will provide an increased understanding of multimodal therapy outcome in this orphan disease., Trial Registration: German Clinical Trials Register (identification number: DRKS00021019) https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00021019 ., (© 2022. The Author(s).)

Objectives: To evaluate the safety and outcome of image-guided sclerotherapy for treating venous malformations (VMs) of the face., Materials and Methods: A multicenter cohort of 68 patients with VMs primarily affecting the face was retrospectively investigated. In total, 142 image-guided sclerotherapies were performed using gelified ethanol and/or polidocanol. Clinical and imaging findings were assessed to evaluate clinical response, lesion size reduction, and complication rates. Sub-analyses of complication rates depending on type and injected volume of the sclerosant as well as of pediatric versus adult patient groups were conducted., Results: Mean number of procedures per patient was 2.1 (±1.7) and mean follow-up consisted of 8.7 months (±6.8 months). Clinical response ( n = 58) revealed a partial relief of symptoms in 70.7% (41/58), 13/58 patients (22.4%) presented symptom-free while only 4/58 patients (6.9%) reported no improvement. Post-treatment imaging ( n = 52) revealed an overall objective response rate of 86.5% (45/52). The total complication rate was 10.6% (15/142) including 4.2% (7/142) major complications, mostly (14/15, 93.3%) resolved by conservative means. In one case, a mild facial palsy persisted over time. The complication rate in the gelified ethanol subgroup was significantly higher compared to polidocanol and to the combination of both sclerosants (23.5 vs. 6.0 vs. 8.3%, p = 0.01). No significant differences in complications between the pediatric and the adult subgroup were observed (12.1 vs. 9.2%, p = 0.57). Clinical response did not correlate with lesion size reduction on magnetic resonance imaging (MRI)., Conclusion: Image-guided sclerotherapy is effective for treating VMs of the face. Clinical response is not necessarily associated with size reduction on imaging. Despite the complex anatomy of this location, the procedures are safe for both adults and children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schmidt, Masthoff, Goldann, Brill, Sporns, Segger, Schulze-Zachau, Takes, Köhler, Deniz, Öcal, Mansour, Ümütlü, Shemwetta, Baraka, Mbuguje, Naif, Ukweh, Seidensticker, Ricke, Gebauer, Wohlgemuth and Wildgruber.)

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a molecularly heterogeneous tumor entity with no clinically established imaging biomarkers. We hypothesize that tumor morphology and physiology, including vascularity and perfusion, show variations that can be detected by differences in contrast agent (CA) accumulation measured non-invasively. This work seeks to establish imaging biomarkers for tumor stratification and therapy response monitoring in PDAC, based on this hypothesis., Methods and Materials: Regional CA accumulation in PDAC was correlated with tumor vascularization, stroma content, and tumor cellularity in murine and human subjects. Changes in CA distribution in response to gemcitabine (GEM) were monitored longitudinally with computed tomography (CT) Hounsfield Units ratio (HUr) of tumor to the aorta or with magnetic resonance imaging (MRI) ΔR 1 area under the curve at 60 s tumor-to-muscle ratio (AUC60r). Tissue analyses were performed on co-registered samples, including endothelial cell proliferation and cisplatin tissue deposition as a surrogate of chemotherapy delivery., Results: Tumor cell poor, stroma-rich regions exhibited high CA accumulation both in human (meanHUr 0.64 vs. 0.34, p < 0.001) and mouse PDAC (meanAUC60r 2.0 vs. 1.1, p < 0.001). Compared to the baseline, in vivo CA accumulation decreased specifically in response to GEM treatment in a subset of human (HUr -18%) and mouse (AUC60r -36%) tumors. Ex vivo analyses of mPDAC showed reduced cisplatin delivery (GEM: 0.92 ± 0.5 mg/g, vs. vehicle: 3.1 ± 1.5 mg/g, p = 0.004) and diminished endothelial cell proliferation (GEM: 22.3% vs. vehicle: 30.9%, p = 0.002) upon GEM administration., Conclusion: In PDAC, CA accumulation, which is related to tumor vascularization and perfusion, inversely correlates with tumor cellularity. The standard of care GEM treatment results in decreased CA accumulation, which impedes drug delivery. Further investigation is warranted into potentially detrimental effects of GEM in combinatorial therapy regimens., (© 2022. The Author(s).)

In cirrhotic patients with hepatocellular carcinoma (HCC), right-sided radioembolization (RE) with Yttrium-90-loaded microspheres is an established palliative therapy and can be considered a "curative intention" treatment when aiming for sequential tumor resection. To become surgical candidate, hypertrophy of the left liver lobe to > 40% (future liver remnant, FLR) is mandatory, which can develop after RE. The amount of radiation-induced shrinkage of the right lobe and compensatory hypertrophy of the left lobe is difficult for clinicians to predict. This study aimed to utilize machine learning to predict left lobe liver hypertrophy in patients with HCC and cirrhosis scheduled for right lobe RE, with external validation. The results revealed that machine learning can accurately predict relative and absolute volume changes of the left liver lobe after right lobe RE. This prediction algorithm could help to estimate the chances of conversion from palliative RE to curative major hepatectomy following significant FLR hypertrophy., (© 2022. The Author(s).)

Objective: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach., Methods: The highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy., Results: Significant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher K trans values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower K trans values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90 th percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models., Conclusions: Multiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gerwing, Hoffmann, Kronenberg, Hansen, Masthoff, Helfen, Geyer, Wachsmuth, Höltke, Maus, Hoerr, Krähling, Hiddeßen, Heindel, Karst, Kimm, Schinner, Eisenblätter, Faber and Wildgruber.)

Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients' response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kimm, Kästle, Stechele, Öcal, Richter, Ümütlü, Schinner, Öcal, Salvermoser, Alunni-Fabbroni, Seidensticker, Goldberg, Ricke and Wildgruber.)

Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16-34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1-4), with a median of 49 mg (range, 8-75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3-13), median tumor volumes decreased by 59% (interquartile range, 40-71%) and T2 signal intensity decreased by 36% (interquartile range, 19-55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3-4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs.

PURPOSE This study aimed to evaluate the safety and outcome of image-guided embolization for treating arteriovenous malformations (AVMs) of the hand using ethylene-vinyl alcohol copolymer (EVOH). METHODS A retrospective, multicenter cohort of 15 patients with AVMs of the hand treated with 35 imageguided embolotherapies using EVOH was investigated. Clinical history, symptomatology, and imaging findings were assessed to evaluate clinical outcome (symptom-free, partial relief of pain, no improvement of pain, and clinical progression despite embolization), lesion devascularization (total, 100%; near-total, 90%-99%; substantial, 70%-90%; partial, 30%-70%; and failure, 0%-30%), and peri- and postprocedural complication rates (major complications classified according to CIRSE guidelines). Substratification analysis was performed with respect to the involvement of different anatomical compartments and the injected volume of the embolic agent. RESULTS Patients were treated for pain (93.3%), skin ulceration (46.7%), and local bleeding (33.3%). The mean number of embolotherapies was 2.3 (±1.1) in 3 patients, a planned surgical resection was conducted after embolization. Clinical outcome after a median follow-up of 18 months revealed an overall response of 11/15 patients (73.3%). Imaging at last follow-up revealed 70%- 99% reduced vascularization in 12/15 patients (80%) including 2 patients (13.3%) with a neartotal devascularization of 90%-99%. Peri- and postprocedural complications occurred in 8.5% and 31.5%, respectively, including 17.1% major complications, in 1 case requiring a previously unplanned resection. Involvement of the finger was associated with increased rates of persistent symptoms compared to the other groups (P=.049). No significant difference between the embolic agent volume injected and complication rates was found (P=.372). CONCLUSION Image-guided embolization using EVOH-based liquid embolic agents is effective for treating AVMs of the hand in the mid-term.

Purpose: SORAMIC is a randomized controlled trial in patients with advanced hepatocellular carcinoma (HCC) undergoing sorafenib ± selective internal radiation therapy (SIRT). We investigated the value of extracellular vesicle (EV)-based proteomics for treatment response prediction., Experimental Design: The analysis population comprised 25 patients receiving SIRT+sorafenib and 20 patients receiving sorafenib alone. Patients were classified as responders or nonresponders based on changes in AFP and imaging or overall survival. Proteomic analysis was performed on plasma EVs by LC/MS, followed by bioinformatics analysis. Clinical relevance of candidate EV proteins was validated by survival and receiver-operating characteristic analysis with bootstrap internal sampling validation. Origin of circulating EV was explored by IHC staining of liver and tumor tissues and transcriptomics of blood cells., Results: Proteomic analysis identified 56 and 27 EV proteins that were differentially expressed in plasma EVs between responders and nonresponders receiving SIRT+sorafenib and sorafenib alone, respectively. High EV-GPX3/ACTR3 and low EV-ARHGAP1 were identified as candidate biomarkers at baseline from the 13 responders to SIRT+sorafenib with statistically significant AUC = 1 for all and bootstrap P values 2.23 × 10-5, 2.22 × 10-5, and 2.23 × 10-5, respectively. These patients showed reduced abundance of EV-VPS13A and EV-KALRN 6 to 9 weeks after combined treatment with significant AUC and bootstrap P values. In reverse, low GPX3 and high ARHGAP1 demonstrated better response to sorafenib monotherapy with AUC = 0.9697 and 0.9192 as well as bootstrap P values 8.34 × 10-5 and 7.98 × 10-4, respectively. HCC tumor was the likely origin of circulating EVs., Conclusions: In this exploratory study, EV-based proteomics predicted response to SIRT+sorafenib and sorafenib-only treatment in patients with advanced HCC of metabolic origin., (©2022 The Authors; Published by the American Association for Cancer Research.)

We report the case of an 11-year-old girl with difficultly speaking and a history of singular, self-limiting oral bleeding. Clinical and radiological examination in the emergency room showed a vascularized tumor of the base of the tongue, which almost completely occluded the oropharynx. After complex anesthesiologic preparation and endoluminal embolization, the tumor was safely removed by transoral laser microsurgery. Histology revealed a rare benign schwannoma of the oropharynx. Further clinical examinations and genetic screening were recommended., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: To evaluate the safety and outcome of image-guided embolotherapy of extracranial arteriovenous malformations (AVMs) primarily affecting the face., Materials and Methods: A multicenter cohort of 28 patients presenting with AVMs primarily affecting the face was retrospectively investigated. Fifty image-guided embolotherapies were performed, mostly using ethylene-vinyl alcohol copolymer-based embolic agents. Clinical and imaging findings were assessed to evaluate response during follow-up (symptom-free, partial relief of symptoms, no improvement, and progression despite embolization), lesion devascularization (total, 100%; substantial, 76-99%; partial, 51-75%; failure, < 50%; and progression), and complication rates (classified according to the CIRSE guidelines). Sub-analyses regarding clinical outcome (n = 24) were performed comparing patients with (n = 12) or without (n = 12) subsequent surgical resection after embolotherapy., Results: The median number of embolotherapy sessions was 2.0 (range, 1-4). Clinical outcome after a mean follow-up of 12.4 months (± 13.3; n = 24) revealed a therapy response in 21/24 patients (87.5%). Imaging showed total devascularization in 14/24 patients (58.3%), including the 12 patients with subsequent surgery and 2 additional patients with embolotherapy only. Substantial devascularization (76-99%) was assessed in 7/24 patients (29.2%), and partial devascularization (51-75%) in 3/24 patients (12.5%). Complications occurred during/after 12/50 procedures (24.0%), including 18.0% major complications. Patients with subsequent surgical resections were more often symptom-free at the last follow-up compared to the group having undergone embolotherapy only (p = 0.006)., Conclusion: Image-guided embolotherapy is safe and effective for treating extracranial AVMs of the face. Subsequent surgical resections after embolization may substantially improve patients' clinical outcome, emphasizing the need for multimodal therapeutic concepts., Level of Evidence: Level 4, Retrospective study., (© 2022. The Author(s).)

Prediction of response to percutaneous sclerotherapy in patients with venous malformations (VM) is currently not possible with baseline clinical or imaging characteristics. This prospective single-center study aimed to predict treatment outcome of percutaneous sclerotherapy as measured by quality of life (QoL) by using radiomic analysis of diffusion-weighted (dw) magnetic resonance imaging (MRI) before and after first percutaneous sclerotherapy. In all patients ( n = 16) pre-interventional (PRE-) and delta (DELTA-) radiomic features (RF) were extracted from dw-MRI before and after first percutaneous sclerotherapy with ethanol gel or polidocanol foam, while QoL was assessed using the Toronto Extremity Salvage Score (TESS) and the 36-Item Short Form Survey (SF-36) health questionnaire. For selecting features that allow differentiation of clinical response, a stepwise dimension reduction was performed. Logistic regression models were fitted and selected PRE-/DELTA-RF were tested for their predictive value. QoL improved significantly after percutaneous sclerotherapy. While no common baseline patient characteristics were able to predict response to percutaneous sclerotherapy, the radiomics signature of VMs (independent PRE/DELTA-RF) revealed high potential for the prediction of clinical response after percutaneous sclerotherapy. This proof-of-concept study provides first evidence on the potential predictive value of (delta) radiomic analysis from diffusion-weighted MRI for Quality-of-Life outcome after percutaneous sclerotherapy in patients with venous malformations.