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Comparison of puncture deviation and puncture duration between computed tomography (CT)- and C-arm CT (CACT)-guided puncture performed by residents in training (RiT).In a cohort of 25 RiTs enrolled in a research training program either CT- or CACT-guided puncture was performed on a phantom. Prior to the experiments, the RiT's level of training, experience playing a musical instrument, video games, and ball sports, and self-assessed manual skills and spatial skills were recorded. Each RiT performed two punctures. The first puncture was performed with a transaxial or single angulated needle path and the second with a single or double angulated needle path. Puncture deviation and puncture duration were compared between the procedures and were correlated with the self-assessments.RiTs in both the CT guidance and CACT guidance groups did not differ with respect to radiologic experience (p = 1), angiographic experience (p = 0.415), and number of ultrasound-guided puncture procedures (p = 0.483), CT-guided puncture procedures (p = 0.934), and CACT-guided puncture procedures (p = 0.466). The puncture duration was significantly longer with CT guidance (without navigation tool) than with CACT guidance with navigation software (p 0.001). There was no significant difference in the puncture duration between the first and second puncture using CT guidance (p = 0.719). However, in the case of CACT, the second puncture was significantly faster (p = 0.006). Puncture deviations were not different between CT-guided and CACT-guided puncture (p = 0.337) and between the first and second puncture of CT-guided and CACT-guided puncture (CT: p = 0.130; CACT: p = 0.391). The self-assessment of manual skills did not correlate with puncture deviation (p = 0.059) and puncture duration (p = 0.158). The self-assessed spatial skills correlated positively with puncture deviation (p = 0.011) but not with puncture duration (p = 0.541).The RiTs achieved a puncture deviation that was clinically adequate with respect to their level of training and did not differ between CT-guided and CACT-guided puncture. The puncture duration was shorter when using CACT. CACT guidance with navigation software support has a potentially steeper learning curve. Spatial skills might accelerate the learning of image-guided puncture.· The CT-guided and CACT-guided puncture experience of the RiTs selected as part of the program "Researchers for the Future" of the German Roentgen Society was adequate with respect to the level of training.. · Despite the lower collective experience of the RiTs with CACT-guided puncture with navigation software assistance, the learning curve regarding CACT-guided puncture may be faster compared to the CT-guided puncture technique.. · If the needle path is complex, CACT guidance with navigation software assistance might have an advantage over CT guidance..· Meine TC, Hinrichs JB, Werncke T et al. Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. Fortschr Röntgenstr 2022; 194: 272 - 280.ZIEL: Vergleich der Punktionsabweichung und -dauer zwischen Computertomografie (CT) – und C-Arm-CT (CACT) -gesteuertem Punktionsverfahren bei Anwendung durch Assistenzärzte in Weiterbildung (AiW).In einer Kohorte von 25 AiW, die Teil einer wissenschaftlichen Förderung waren, wurden entweder CT- oder CACT-gesteuerte Punktionen an einem Phantom durchgeführt. Vor Beginn wurden der Weiterbildungsstand, die Erfahrung mit Spielen eines Musikinstruments, mit Videospielen und mit Ballsportarten und die Selbsteinschätzung von manueller Geschicklichkeit und räumlichem Denkvermögen abgefragt. Jede/r AiW führte 2 Punktionen durch, wobei die 1. Punktion mit einem transaxialen bzw. einfach angulierten Nadelpfad und die 2. Punktion mit einem einfach bzw. doppelt angulierten Nadelpfad erfolgte. Punktionsabweichung und -dauer wurden zwischen den Verfahren verglichen und mit den Selbsteinschätzungen korreliert.Die beiden Gruppen der AiW zeigten keine Unterschiede in der Erfahrung in der Radiologie (p = 1), in der Angiografie (p = 0.415) und in der Anzahl bereits durchgeführter Punktionen gesteuert durch Ultraschall (p = 0,483), CT (p = 0,934) und CACT (p = 0,466). In der CT (ohne Navigationssoftware) war die Punktionsdauer signifikant länger als mit der CACT-Bildsteuerung mit Navigationssoftware (p 0,001). Bei der Punktionsdauer zeigten sich keine signifikanten Unterschiede zwischen der 1. und 2. Punktion im CT (p = 0,719), während die 2. Punktion mit CACT schneller durchgeführt werden konnte (p = 0,006). Die Punktionsabweichung war weder signifikant zwischen CT- und CACT-Bildsteuerung (p = 0,337), noch zwischen der 1. und 2. Punktion der jeweiligen Verfahren (CT: p = 0,130; CACT: p = 0,391). Die Selbsteinschätzung der manuellen Geschicklichkeit korrelierte nicht mit der Punktionsabweichung (p = 0,059) und -dauer (p = 0,158). Das subjektive räumliche Denkvermögen zeigte eine moderate positive Korrelation zur Punktionsabweichung (p = 0,011), aber nicht zur -dauer (p = 0,541).Die AiW erreichten eine dem Ausbildungsstand entsprechende, klinisch adäquate Punktionsabweichung unter CT- und CACT-Bildsteuerung. Die CACT-gesteuerten Punktionen mit Unterstützung durch Navigationssoftware wurden schneller durchgeführt, und auch die Lernkurve war mit CACT-Bildsteuerung steiler. Räumliches Denkvermögen kann möglicherweise das Erlernen bildgesteuerter Punktionen beschleunigen.· Die Erfahrung mit Punktionen war in einer Gruppe von AiW, die im Rahmen des Programms der Deutschen Röntgengesellschaft e. V. „Forscher-für-die-Zukunft“ ausgesucht wurden, dem Weiterbildungsstand entsprechend.. · Trotz kollektiv geringerer Erfahrung der radiologischen AiW mit der CACT-gesteuerten Punktion mit Navigationssoftwareunterstützung ist die Lernkurve gegenüber der einfachen CT-Punktion möglicherweise steiler.. · Bei schwierigen Punktionswegen könnte die CACT-Bildsteuerung mit Softwareunterstützung einen Vorteil in der Durchführung gegenüber der konventionellen CT-Bildsteuerung haben..· Meine TC, Hinrichs JB, Werncke T et al. Phantom study for comparison between computed tomography- and C-Arm computed tomography-guided puncture applied by residents in radiology. Fortschr Röntgenstr 2022; 194: 272 – 280.

Purpose Extracellular vesicles, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators of intercellular communication. The purpose of this study was to assess the distribution of extracellular vesicles from highly malignant breast cancer and their subsequent effect on the immune cell infiltrate in target organs of metastasis. Procedures Extracellular vesicles were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthy BALB/c mice. The purity of the isolate was verified by electron microscopy and western blotting. Extracellular vesicles were additionally subjected to proteome analysis. After labeling with the fluorescent dye DiR, extracellular vesicles were injected into healthy BALB/c mice and their in vivo distribution was assessed using fluorescence reflectance imaging (FRI). Following ex vivo imaging of the organs, lung tissue samples were analyzed for extracellular vesicle-mediated changes of myeloid cells and T cell numbers, using flow cytometry. Proteome analysis revealed major differences in the cargo of tumor cell–derived versus extracellular vesicles from healthy serum. Results In contrast to control extracellular vesicles, DiR-labeled extracellular vesicles from tumor cells preferentially accumulated in lung, liver, and spine. Subsequent flow cytometry of the immune cell composition of lung tissue samples revealed an increase of cytotoxic CD8+ T cells and a decrease of CD4+ T-helper cells as well as an increase in mature macrophages in response to tumor cell EV. Conclusions In conclusion, distribution of tumor cell–derived extracellular vesicles follows a specific pattern and can be monitored, using dedicated imaging. Extracellular vesicles alter the immune cell composition in target organs of metastasis, using a specific proteome cargo.

About 40% of non‐small lung cancer (NSCLC) patients have metastatic disease at the time of diagnosis. However, metastatic NSCLC in the biliary duct system is extremely rare. A high proportion of patients with acute liver failure due to advanced NSCLC do not receive any treatment due to organ dysfunction or poor performance status. Here, we report a case of successful treatment with chemoimmunotherapy in a young woman with obstructive jaundice and acute hepatic failure due to multiple intrahepatic bile duct metastases. Key points Significant findings of the study Chemotherapy in NSCLC patients with liver failure is a therapeutic challenge. Acute hepatic failure are often exclusion criteria for therapy of NSCLC. Some reports showed a benefit of ICIs plus chemotherapy for NSCLC with liver metastases. What this study adds Combination of ICIs and chemotherapy is effective and safe in critically ill patients with lung cancer and impaired liver function., We report a case of successful treatment with chemimmunotherapy in a young woman with obstructive jaundice and acute hepatic failure due to multiple intrahepatic bile duct metastases of NSCLC.

Objective Stand-alone minimally invasive approaches for the surgical management of spinal dumbbell tumors carry the risk of incomplete resections and impaired hemostasis. More-extensive approaches require subsequent instrumentation with metal artifacts impairing follow-up imaging. Here, we present a technical note on percutaneous instrumentation using carbon fiber–reinforced polyether ether ketone (CFR-PEEK) hardware combined with a minimally invasive posterolateral approach for tumor resection. Methods We present a Technical Note and according case series of 7 patients with dumbbell tumors in the lumbar and thoracolumbar spine operated on between 2017 and 2020. CFR-PEEK pedicle screws and rods were inserted percutaneously. Afterwards, a dedicated self-standing retractor for posterolateral approaches was connected to the screws. Following a unilateral facetectomy, the tumor was resected in a microsurgical fashion. Clinical data are reported with respect to the Preferred Reporting Of CasE Series in Surgery (PROCESS) guidelines. Results Four patients presented with de novo tumors. Three patients were treated for residual tumor mass after previous surgeries. Gross total resection was achieved in all 7 cases, as demonstrated by early postoperative magnetic resonance imaging. Histopathology demonstrated 5 World Health Organization grade I schwannomas, 1 grade II hemangiopericytoma, and 1 cavernous hemangioma. No postoperative complications were observed. CFR-PEEK hardware allowed unambiguous visualization of the resection cavity on follow-up imaging. Conclusions Resection of dumbbell tumors via a minimally invasive posterolateral approach and instrumentation with CFR-PEEK hardware allows maximal and safe resection. Due to lack of major metal artifacts, carbon fiber hardware improves the interpretation of follow-up imaging as well as planning of radiation if required for tumor recurrence.

Objective To evaluate the effectiveness of interventional therapy in acute, non-malignant, non-cirrhotic portal vein thrombosis. Methods We present a retrospective study of eight consecutive patients who presented with an acute non-malignant, non-cirrhotic portal vein thrombosis and were treated by mechanical recanalization using an escalating scheme including local aspiration, thrombolysis, rheolysis and the implantation of transjugular intrahepatic portosystemic shunt or other visceral stents. Results Recanalization rates applying the escalating scheme were good, with a success rate of 75%. However, major complications occurred in 50% of patients, mostly due to bleeding at the percutaneous access site, and minor complications in 12.5% of patients. Conclusion Interventional therapy is effective in acute portal vein thrombosis, but should only be performed at specialized centers and based on an individual treatment decision.

Owing to improvements in our understanding of the biological principles of tumour initiation and progression, a wide variety of novel targeted therapies have been developed. Developments in biomedical imaging, however, have not kept pace with these improvements and are still mainly designed to determine lesion size alone, which is reflected in the Response Evaluation Criteria in Solid Tumors (RECIST). Imaging approaches currently used for the evaluation of treatment responses in patients with solid tumours, therefore, often fail to detect successful responses to novel targeted agents and might even falsely suggest disease progression, a scenario known as pseudoprogression. The ability to differentiate between responders and nonresponders early in the course of treatment is essential to allowing the early adjustment of treatment regimens. Various imaging approaches targeting a single dedicated tumour feature, as described in the hallmarks of cancer, have been successful in preclinical investigations, and some have been evaluated in pilot clinical trials. However, these approaches have largely not been implemented in clinical practice. In this Review, we describe current biomedical imaging approaches used to monitor responses to treatment in patients receiving novel targeted therapies, including a summary of the most promising future approaches and how these might improve clinical practice. The development of more-targeted cancer therapies has not been matched by more-targeted imaging methods. This discrepancy has, in some scenarios, resulted in inaccurate assessments of the effects of novel therapies. In this Review, the authors describe potential novel imaging approaches that could be adopted to enable improvements in imaging-based monitoring of treatment responses and resistance.

Germ cell tumors (GCTs) are the most frequent malignancy in male patients between 15 and 45 years of age. Cisplatin-based chemotherapy shows excellent cure rates, but patients with cisplatin-resistant GCTs have a poor prognosis. Nintedanib (BIBF 1120, Vargatef) inhibits the receptor classes vascular endothelial growth factor receptor, platelet derived growth factor receptor, and fibroblast growth factor receptor, and has shown activity against many tumors, as well as in idiopathic lung fibrosis and bleomycin-induced lung injury. Here, we investigated the antineoplastic and antiangiogenic properties of nintedanib in cisplatin-resistant and cisplatin-sensitive GCT cells, both alone and in combination with classical cytotoxic agents such as cisplatin, etoposide, and bleomycin. The half-maximal inhibitory concentration (IC50) of nintedanib was 4.5 ± 0.43 μmol/l, 3.1 ± 0.45 μmol/l, and 3.6 ± 0.33 μmol/l in cisplatin-sensitive NTERA2, 2102Ep, and NCCIT cells, whereas the IC50 doses of the cisplatin-resistant counterparts were 6.6 ± 0.37 μmol/l (NTERA2-R), 4.5 ± 0.83 μmol/l (2102Ep-R), and 6.1 ± 0.41 μmol/l (NCCIT-R), respectively. Single treatment with nintedanib induced apoptosis and resulted in a sustained reduction in the capacity of colony formation in both cisplatin-sensitive and cisplatin-resistant GCT cells. Cell cycle analysis showed that nintedanib induced a strong G0/G1-phase arrest in all investigated cell lines. Combination treatment with cisplatin did not result in additive, synergistic, or antagonistic effects. The in-vivo activity was studied using the chorioallantoic membrane assay and indicated the antiangiogenic potency of nintedanib with markedly reduced microvessel density. Topical treatment of inoculated tumor plaques resulted in a significant reduction of the tumor size. This indicates that nintedanib might be a promising substance in the treatment of GCT.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. Results: MTD was 3 mg/m2 tTF-NGR/day &times, 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t1/2(terminal) of 8 to 9 h without accumulation in daily administrations. Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.

Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.