Tumoural activation of TLR3-SLIT2 axis in endothelium drives metastasis.

Blood vessels support tumours by providing nutrients and oxygen, while also acting as conduits for the dissemination of cancer1. Here we use mouse models of breast and lung cancer to investigate whether endothelial cells also have active 'instructive' roles in the dissemination of cancer. We purified genetically tagged endothelial ribosomes and their associated transcripts from highly and poorly metastatic tumours. Deep sequencing revealed that metastatic tumours induced expression of the axon-guidance gene Slit2 in endothelium, establishing differential expression between the endothelial (high Slit2 expression) and tumoural (low Slit2 expression) compartments. Endothelial-derived SLIT2 protein and its receptor ROBO1 promoted the migration of cancer cells towards endothelial cells and intravasation. Deleting endothelial Slit2 suppressed metastatic dissemination in mouse models of breast and lung cancer. Conversely, deletion of tumoural Slit2 enhanced metastatic progression. We identified double-stranded RNA derived from tumour cells as an upstream signal that induces expression of endothelial SLIT2 by acting on the RNA-sensing receptor TLR3. Accordingly, a set of endogenous retroviral element RNAs were upregulated in metastatic cells and detected extracellularly. Thus, cancer cells co-opt innate RNA sensing to induce a chemotactic signalling pathway in endothelium that drives intravasation and metastasis. These findings reveal that endothelial cells have a direct instructive role in driving metastatic dissemination, and demonstrate that a single gene (Slit2) can promote or suppress cancer progression depending on its cellular source.

[Robot-assisted Microsurgery for Autologous Breast Reconstruction - Robotic Breast Reconstruction]. / Roboter-assistierte Mikrochirurgie zur autologen Brustrekonstruktion.

BACKGROUND: With the introduction of novel surgical robots and surgical microscopes for the special needs of open microsurgery, the concept of robotic-assisted microsurgery is gaining popularity. While initial preclinical studies indicate a steep learning curve, favourable ergonomics and improved precision, albeit with an increased operating time, data on the clinical application of the new systems is still limited. This study describes our first clinical experience with robotic-assisted autologous breast reconstruction and outlines the opportunities and limitations of the approach. PATIENTS AND METHODS: Our retrospective data analysis included a total of 28 patients who underwent unilateral robotic-assisted autologous breast reconstruction between July 2022 and August 2023. We applied a combined approach using the Symani Surgical System together with the RoboticScope. Descriptive evaluation of patient characteristics, surgical data and complications was performed. RESULTS: Average patient age was 54.3±11.1 years and average BMI was 26.5±3.5 kg/m2. Twenty-six patients received a DIEP flap and 2 patients received a PAP flap, the flaps being connected to the internal mammary artery in 22 cases, to a perforator of the internal mammary artery in 5 cases, and to a branch of the thoracodorsal artery in one case. The average incision-suture time was 267±89 min, with an average ischaemia time of 86±20 min and duration of the arterial anastomosis of 29±12 min. In two cases, immediate intraoperative anastomosis revision was performed, but no flap loss occurred. CONCLUSION: The results of this study demonstrate the safe feasibility of robot-assisted autologous breast reconstruction using a combination of Symani and RoboticScope. In the future, special attention should be paid to minimally invasive techniques of flap harvest and connecting vessel preparation.

Ideal suturing technique for robot-assisted microsurgical anastomoses.

The development of novel robotic devices specifically designed for open microsurgery leads to increasing applications in reconstructive procedures. While initial studies revealed improved precision and surgical ergonomics upon robotic assistance, surgical time was consistently observed to be increased. This study compares two robotic suturing techniques using the Symani Surgical System and RoboticScope in a preclinical setting, to further leverage the benefits of novel robotic devices in microsurgery. Six experienced microsurgeons performed three microvascular anastomoses with a "steady-thread" suturing technique and a "switch-thread" technique on 1.0-mm-diameter artificial silicone vessels. Time for anastomosis and participant's satisfaction with the techniques and robotic setup were recorded. Anastomosis quality and microsurgical skills were assessed using the Anastomosis Lapse Index and Structured Assessment of Microsurgery Skills. Lastly, technical error messages and thread ruptures were quantified. Knot tying was significantly faster and evaluated significantly better by participants using the steady-thread technique (4.11 ± 0.85 vs. 6.40 ± 1.83 min per anastomosis). Moreover, microsurgical skills were rated significantly better using this technique, while both techniques consistently led to high levels of anastomosis quality (2.61 ± 1.21 vs. 3.0 ± 1.29 errors per anastomosis). In contrast, the switch-thread technique was associated with more technical error messages in total (14 vs. 12) and twice as many unintended thread ruptures per anastomosis (1.0 ± 0.88 vs. 0.5 ± 0.69). This study provides evidence for the enhanced performance of a steady-thread suturing technique, which is suggested to be applied upon robot-assisted microsurgical procedures for optimized efficiency.

Preclinical Performance of the Combined Application of Two Robotic Systems in Microsurgery: A Two-center Study.

Background: Recent advancements in the development of robotic devices increasingly draw the attention toward the concept of robotic microsurgery, as several systems tailored to open microsurgery are being introduced. This study describes the combined application of a novel microsurgical robot, the Symani, with a novel robotic microscope, the RoboticScope, for the performance of microvascular anastomoses in a two-center preclinical trial. Methods: Six novices, residents, and experienced microsurgeons (n = 18) performed five anastomoses on 1.0-mm-diameter silicone vessels with a conventional versus combined robotic approach, resulting in 180 anastomoses. Microsurgical performance was evaluated, analyzing surgical time, subjective satisfaction with the anastomosis and robotic setup, anastomosis quality using the anastomosis lapse index score, microsurgical skills using the Structured Assessment of Microsurgery Skills score, and surgical ergonomics using the Rapid Entire Body Assessment score. Results: All participants significantly improved their performance during the trial and quickly adapted to the novel systems. Surgical time significantly decreased, whereas satisfaction with the anastomosis and setup improved over time. The use of robotic systems was associated with fewer microsurgical errors and enhanced anastomosis quality. Especially novices demonstrated accelerated skill acquisition upon robotic assistance compared with conventional microsurgery. Moreover, upper extremity positioning was significantly improved. Overall, the robotic approach was subjectively preferred by participants. Conclusions: The concept of robotic microsurgery holds great potential to improve precision and ergonomics in microsurgery. This two-center trial provides promising evidence for a steep learning curve upon introduction of robotic microsurgery systems, suggesting further pursuit of their clinical integration.