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Luisa Gluth, Crista Ochsenfarth, Phuong Nam Viet Pham, Jan M. Wischermann, Thomas Komanek, Florian Bernhard Gerhard Roghmann, Ulrich Frey

• Anesthetics have been shown to alter tumor progression and seem to influence surgical cancer outcome. Circulating extracellular vesicles as mediators of intercellular communication are involved in cancer progression and may be influenced by anesthetics. In this prospective, randomized study, effects of anesthetics on extracellular vesicles and associated micro-RNAs in bladder cancer patients undergoing radical cystectomy were tested. Extracellular vesicles from 51 patients at four perioperative time points receiving Propofol or Sevoflurane were extracted with polymer-based methods and quantified with a nanoparticle-tracking analysis. Vesicle-associated micro-RNAs were analyzed with a real-time polymerase chain reaction using array cards and single assays for tumor-associated miR-21-5p, miR-15a-5p, miR-17-5p and miR-451a. Plasma extracellular vesicle concentration (suture: fold change (fc) in Propofol at 4.1 \(\pm\) 3.9 vs. Sevoflurane at 0.8 \(\pm\) 0.5; p = 0.003) and associated miRNAs increased significantly (+30% post induction, +9% 30 Min surgery) in the Propofol group. Tumor-associated miRNAs increased during surgery in both groups (fc in miR-21-5p: 24.3 \(\pm\) 10.2, \(\it p\) = 0.029; fc in miR-15a-5p: 9.7 \(\pm\) 3.8, \(\it p\) = 0.027; fc in miR-17-5p: 5.4 \(\pm\) 1.7, \(\it p\) = 0.014), whereas antitumor miR-451a increased in the Propofol group only (fc: 2.5 \(\pm\) 0.6 vs. 1.0 \(\pm\) 0.2; \(\it p\) = 0.022). Anesthetics influence extracellular vesicles and associated micro-RNAs of bladder cancer patients during surgery. Increased expression of antitumor micro-RNA may be an explanatory approach for decreased tumor cell viability after Propofol.