Journal: European Urology Focus

Abbreviation

Eur Urol Focus

Publisher

Elsevier

Journal Volumes

ISSN

2405-4569

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2020 - 20213
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Publications 1 - 3 of 3
  • Assessment of Electrospun and Ultra-lightweight Polypropylene Meshes in the Sheep Model for Vaginal Surgery
    Item type: Journal Article
    Hympanova, Lucie; Rynkevic, Rita; Román, Sabiniano; et al. (2020)
    European Urology Focus
    Background There is an urgent need to develop better materials to provide anatomical support to the pelvic floor without compromising its function. Objective Our aim was to assess outcomes after simulated vaginal prolapse repair in a sheep model using three different materials: (1) ultra-lightweight polypropylene (PP) non-degradable textile (Restorelle) mesh, (2) electrospun biodegradable ureidopyrimidinone-polycarbonate (UPy-PC), and (3) electrospun non-degradable polyurethane (PU) mesh in comparison with simulated native tissue repair (NTR). These implants may reduce implant-related complications and avoid vaginal function loss. Design, setting, and participants A controlled trial was performed involving 48 ewes that underwent NTR or mesh repair with PP, UPy-PC, or PU meshes (n = 12/group). Explants were examined 60 and 180 d (six per group) post-implantation. Intervention Posterior rectovaginal dissection, NTR, or mesh repair. Outcome measurements and statistical analysis Implant-related complications, vaginal contractility, compliance, and host response were assessed. Power calculation and analysis of variance testing were used to enable comparison between the four groups. Results There were no visible implant-related complications. None of the implants compromised vaginal wall contractility, and passive biomechanical properties were similar to those after NTR. Shrinkage over the surgery area was around 35% for NTR and all mesh-augmented repairs. All materials were integrated well with similar connective tissue composition, vascularization, and innervation. The inflammatory response was mild with electrospun implants, inducing both more macrophages yet with relatively more type 2 macrophages present at an early stage than the PP mesh. Conclusions Three very different materials were all well tolerated in the sheep vagina. Biomechanical findings were similar for all mesh-augmented repair and NTR. Constructs induced slightly different mid-term inflammatory profiles. Patient summary Product innovation is needed to reduce implant-related complications. We tested two novel implants, electrospun and an ultra-lightweight polypropylene textile mesh, in a physiologically relevant model for vaginal surgery. All gave encouraging outcomes.
  • Bacteriophages: a Panacea in Neuro-Urology?
    Item type: Review Article
    Leitner, Lorenz; Kessler, Thomas M.; Klumpp, Jochen (2020)
    European Urology Focus
  • Tracing Clonal Dynamics Reveals that Two- and Three-dimensional Patient-derived Cell Models Capture Tumor Heterogeneity of Clear Cell Renal Cell Carcinoma
    Item type: Journal Article
    Bolck, Hella A.; Corrò, Claudia; Kahraman, Abdullah; et al. (2021)
    European Urology Focus
    Background Extensive DNA sequencing has led to an unprecedented view of the diversity of individual genomes and their evolution among patients with clear cell renal cell carcinoma (ccRCC). Objective To understand subclonal architecture and dynamics of patient-derived two-dimensional (2D) and three-dimensional (3D) ccRCC models in vitro, in order to determine whether they mirror ccRCC inter- and intratumor heterogeneity. Design, setting, and participants We have established a comprehensive platform of living renal cancer cell models from ccRCC surgical specimens. Outcome measurements and statistical analysis We confirmed the concordance of 2D and 3D patient-derived cell (PDC) models with the original tumor tissue in terms of histology, biomarker expression, cancer driver mutations, and copy number alterations. We addressed inter- and intrapatient heterogeneity by analyzing clonal dynamics during serial passaging. Results and limitations In-depth genetic characterization verified the presence of heterogeneous cell populations, and revealed a high degree of similarity between subclonal compositions of monolayer and organoid cell cultures and the corresponding parental ccRCCs. Clonal dynamics were evident during serial passaging of cells in vitro, suggesting that PDC cultures can offer insights into evolutionary potential and treatment susceptibility of ccRCC subclones in vivo. Proof-of-concept drug profiling using selected ccRCC-targeted therapy agents highlighted patient-specific vulnerabilities in PDC models that could not be anticipated by interrogating commercially available cell lines. Conclusions We demonstrate that PDC models mirror inter- and intratumor heterogeneity of ccRCC in vitro. Based on our findings, we envision that the use of these models will advance our understanding of the trajectories that cause genetic diversity and their consequences for treatment on an individual level. Patient summary In this study, we developed two- and three-dimensional patient-derived models from clear cell renal cell carcinoma (ccRCC) as “mini-tumors in a dish.” We show that these cell models retain important features of the human ccRCCs such as the profound tumor heterogeneity, thus highlighting their importance for cancer research and precision medicine.
Publications 1 - 3 of 3