On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein
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ORIGINAL SCIENTIFIC REPORT WITH VIDEO
On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein Yoshiharu Kono1 • Takeaki Ishizawa1,2 • Norihiro Kokudo1 • Yugo Kuriki3 • Ryu J. Iwatate4 • Mako Kamiya4,5 • Yasuteru Urano3,4,6 • Akiko Kumagai7 • Hiroshi Kurokawa7 • Atsushi Miyawaki7 Kiyoshi Hasegawa1
•
Accepted: 28 August 2020 Ó The Author(s) 2020
Abstract Background Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established. Method Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (n = 22) or liver transplantation (n = 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 lM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging. Results The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939, p \ 0.001; direct bilirubin: rs = 0.929, p \ 0.001). Approximate time required for bilirubin measurements with UnaG was 15 min, whereas it took about 40 min with the conventional method at a hospital laboratory. Following administration of UnaG on hepatic surfaces, the fluorescence imaging identified bile leaks not only on the resected specimens but also in the abdominal cavity of the swine hepatectomy models. Conclusion Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00268-020-05774-x) contains supplementary material, which is available to authorized users. & Atsushi Miyawaki [email protected] & Kiyoshi Hasegawa [email protected] 1
Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan
2
Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
3
Laboratory of Chemistry and Biology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
4
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
5
Japan Science and Technology Agency, PRESTO, Saitama, Japan
6
Japan Agency for Medical Research and Development, CREST, Tokyo, Japan
7
Laboratory for Cell Function Dynamics, RIKEN Centre for Brain Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
123
World J Surg
Abbreviations FI Fluorescence intensity ICG Indocyanine green IDB Indirect bilirubin TB Total bilirubi
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