Viability and biocompatibility of an adhesive system for intrarenal embedding and endoscopic removal of small residual fragments in minimally-invasive stone treatment in an in vivo pig model
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To evaluate the viability and biocompatibility of a novel, patented bioadhesive system for intrarenal embedding and retrieval of residual fragments after endoscopic lithotripsy. Complete stone clearance via active removal of residual fragments (RF) after intracorporeal laser lithotripsy may be time-consuming and fail in many cases. Therefore, the novel adhesive has been developed and evaluated for the first time in an in vivo pig model in the present work.
Four female domestic pigs underwent flexible ureteroscopy (RIRS) or percutaneous nephrolithotomy (PNL) under general anesthesia (8 kidneys, 4 × RIRS, 4 × PNL) evaluating the bioadhesive system. Interventions: RIRS without adhesive system (sham procedure, kidney I); 3 × RIRS using the bioadhesive system (kidneys II–IV); and 4 × PNL using the bioadhesive system (V–VIII). We endoscopically inserted standardized human stone probes followed by comminution using Ho:YAG lithotripsy. The bioadhesive (kidney II–VIII) was then applied and the adhesive-stone fragment complex extracted. After nephrectomy, all kidneys were evaluated by two independent, blinded pathologists. Endpoints were the procedure’s safety and adhesive system’s biocompatibility.
We observed no substantial toxic effects. We were able to embed and remove 80–90% of fragments. However, because of the pig’s hampering pyelocaliceal anatomy, a quantified, proportional assessment of the embedded fragments was compromised.
For the first time, we demonstrated the proven feasibility and safety of this novel bioadhesive system for embedding and endoscopically removing small RF in conjunction with a lack of organ toxicity in vivo.
KeywordsMeSH Terms of the US National Library of Medicine Kidney calculi/therapy Urolithiasis/therapy Ureteroscopy/instrumentation Ureteroscopy/methods Ureteroscopy/therapy
Retrograde intrarenal surgery/flexible ureteroscopy
Shock wave lithotripsy
Ureteral access sheath
This work was funded by research grant 031A387 from the Federal Ministry of Education and Research of Germany (GO-Bio program). We would like to thank Michaela von Aichberger for illustration of Fig. 1. All authors have made a significant contribution to the findings and methods in this paper. All authors have read and approved the final draft. The work has not already been published and has not been submitted simultaneously to any other journal. The corresponding author takes on the aforementioned responsibilities.
SH: protocol/project development, performed surgery, data collection and management, data analysis, manuscript, and figure writing/editing. KR: protocol/project development and developed chemical composition. IG: protocol/project development and developed chemical composition. JH: performed anesthesia. MS: performed histopathologic examination. PB: performed histopathologic examination. UW: data analysis and supervision. MS: protocol/project development, manuscript writing/editing, and supervision. AM: protocol/project development, performed surgery, manuscript, and figure writing/editing, supervision.
Compliance with ethical standards
Conflict of interest
Ulrich Wetterauer: advisory board, DR. KADE Pharmazeutische Fabrik GmbH, Berlin, Germany (unrelated to the presented work). Martin Schoenthaler: consultant contract with Schoelly GmbH, Denzlingen, Germany and NeoTract Inc., Pleasanton, U.S.A. (both unrelated to the present work). Arkadiusz Miernik: consultant contract with Schoelly GmbH, Denzlingen, Germany (unrelated to the present work). In addition, Martin Schoenthaler, Arkadiusz Miernik, Ingo Grunwald, and Katharina Richter hold the patents AU002013387207A1, CA000002910164A1, CN000105283140A, EP000002988682A1, EP000002796101B1, EP000002796101A1, KR102016004322A, US020160074561A1, and WO002014173468A1 all issued to the Albert Ludwig University of Freiburg and the Fraunhofer Society for the Advancement of Applied Research and covering the technology of the novel bioadhesive system reported in this study. None of the other authors has any conflict of interest or financial ties to disclose.
Animal studies were approved by the local governmental review board for animal studies and performed in accordance with current EU regulations (2017/63/EU). The study was approved by our local ethics committee and was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave their informed consent to provide stone material prior to their inclusion in the study. Number 296/15, Ethics Committee of the University Medical Center Freiburg. Animal Welfare Committee’s of the University of Freiburg: registration no: G-15/147 German Clinical Trial Register ID: DRKS00010243 (approved WHO primary register).
Sources of financial support
Research grant from the Germany Ministry of Education and Research BMBF (031A387) and own institutional funding, IRB approved protocol number: 296/15 leading ethics committee: Ethik-Kommission der Albert-Ludwigs-Universität Freiburg, Germany.
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