Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31⁺ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects. Graphical abstract Mechanical stress increases VEGF expression in endothelial AVM cells, possibly causing the VEGF upregulation in the microenvironment of AVM cells. The resulting RAS/RAF/MEK/ERK signaling in leads to progression of fast-flow malformations. The monoclonal VEGF-A antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. Sporadically occurring slow-flow malformations (LMs, VMs) have mutations in TEK or PIK3CA. TEK encodes the endothelial receptor tyrosine kinase TIE2. Sporadic extracranial fast-flow malformations (AVMs) show mutations in KRAS, BRAF and MAP2K1, which encodes the dual specificity mitogen-activated protein kinase MEK1. Combined targeting of the molecular causes of the disease could be key to achieve symptom control and reduce lesion growth. Orange: gain-of-function; Blue, circled with orange: enhanced signaling.

Purpose Assessment of intraoperative quantitative shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions (FLLs) during liver surgery using postoperative histopathological results as the gold standard. Materials and Methods US data of 79 consecutive patients with 98 FLLs who underwent liver surgery between 08/2015 – 06/2017 were prospectively acquired and retrospectively analyzed. Multifrequency linear/T-shaped probes (6 – 9 MHz) were used to store cine loops of at least 5 s and images of B-mode, SWE and CEUS. The first CEUS loop was continuously documented over 1 min. in each case. Quantitative SWE analysis of FLLs was performed by placing 5 regions of interest to measure shear wave speed (m/s) and stiffness (kPa). CEUS was evaluated during the arterial, portal venous and late phase after i. v. bolus injections of 2.4 – 10 ml sulfur hexafluoride microbubbles. Postoperative histopathology after tumor resection or intraoperative biopsy was obtained to confirm findings of SWE and CEUS. Results Of 98 FLLs in 79 patients (mean age: 58 years sd ± 12y) 88 were malignant and 10 were benign ranging from 0.69 to 15.2 cm in size (mean: 2.8 cm, sd ± 2.25 cm). SWE characterized 73/88 FLLs correctly as malignant and 7/10 as benign using a cut-off value of 2.5 m/s/21.3 kPa (p < 0.0005). The sensitivity was 83 %, specificity 70 %, accuracy 82 %. CEUS could correctly identify 86/88 malignant and 8/10 benign FLLs. The sensitivity was 98 %, specificity 80 %, accuracy 96 %. SWE could correctly identify 2 malignant FLLs which CEUS falsely characterized as benign. Conclusion Intraoperative CEUS and SWE are excellent tools for the highly accurate visualization, characterization and malignancy assessment of hepatic tumors during liver surgery.

Therapy options for ruptured Achilles tendons need to take into account the right balance of timing, amount and intensity of loading to ensure a sufficient biomechanical resilience of the healing tendon on the one hand, and to enable an adequate tensile stimulus on the other hand. However, biomechanical data of human Achilles tendons after rupture during the separate healing stages are unknown. Shear wave elastography is an ultrasound technique that measures material elastic properties non-invasively, and was proven to have a very good correlation to biomechanical studies. Taking advantage of this technology, 12 patients who suffered from an acute Achilles tendon rupture were acquired and monitored through the course of one year after rupture. Nine of these patients were treated non-operatively and were included for the analysis of biomechanical behaviour. A significant increase of material elastic properties was observed within the first six weeks after trauma (up to 80% of baseline value), where it reached a plateau phase. A second significant increase occurred three to six months after injury. This pilot study suggests a time correlation of biomechanical properties with the biological healing phases of tendon tissue. In the reparative phase, a substantial amount of biomechanical resilience is restored already, but the final stage of biomechanical stability is reached in the maturation phase. These findings can potentially be implemented into treatment and aftercare protocols.

AIM: Aim of this study was to firstly describe reproducible, objective perfusion parameters of contrast-enhanced ultrasound (CEUS) kinetics of parathyroid gland adenoma (PA) using perfusion analysis software (VueBox® , Bracco, Italy). Thereby the eff

AIM: To evaluate the Efficacy of intraoperative contrast enhanced ultrasound (Io-CEUS) for assessment of radiofrequency ablation (RFA) during liver tumor surgery. MATERIAL AND METHODS: Retrospective analyis was performed on 18 patients who underwent