Skip to main content
Top
Published in: World Journal of Surgery 12/2020

Open Access 01-12-2020 | Liver Transplantation | Original Scientific Report with Video

On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein

Authors: Yoshiharu Kono, Takeaki Ishizawa, Norihiro Kokudo, Yugo Kuriki, Ryu J. Iwatate, Mako Kamiya, Yasuteru Urano, Akiko Kumagai, Hiroshi Kurokawa, Atsushi Miyawaki, Kiyoshi Hasegawa

Published in: World Journal of Surgery | Issue 12/2020

Login to get access

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 µM 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.
Appendix
Available only for authorised users
Literature
2.
go back to reference Capussotti L, Ferrero A, Viganò L et al (2006) Bile leakage and liver resection: where is the risk? Arch Surg 141:690–4 discussion 695CrossRefPubMed Capussotti L, Ferrero A, Viganò L et al (2006) Bile leakage and liver resection: where is the risk? Arch Surg 141:690–4 discussion 695CrossRefPubMed
3.
go back to reference Ishizawa T, Hasegawa K, Aoki T et al (2008) Neither multiple tumours nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 34:1908–1916CrossRef Ishizawa T, Hasegawa K, Aoki T et al (2008) Neither multiple tumours nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 34:1908–1916CrossRef
4.
go back to reference Yamazaki S, Takayama T, Moriguchi M et al (2012) Criteria for drain removal following liver resection. Br J Surg 99:1584–1590CrossRefPubMed Yamazaki S, Takayama T, Moriguchi M et al (2012) Criteria for drain removal following liver resection. Br J Surg 99:1584–1590CrossRefPubMed
5.
go back to reference Ishizawa T, Zuker NB, Conrad C et al (2014) Using a 'no drain' policy in 342 laparoscopic hepatectomies: which factors predict failure? HPB (Oxford) 16:494–499CrossRef Ishizawa T, Zuker NB, Conrad C et al (2014) Using a 'no drain' policy in 342 laparoscopic hepatectomies: which factors predict failure? HPB (Oxford) 16:494–499CrossRef
7.
go back to reference Ichida A, Hasegawa K, Takayama T et al (2016) Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection. Br J Surg 103:1795–1803CrossRefPubMed Ichida A, Hasegawa K, Takayama T et al (2016) Randomized clinical trial comparing two vessel-sealing devices with crush clamping during liver transection. Br J Surg 103:1795–1803CrossRefPubMed
8.
go back to reference Brauer DG, Nywening TM, Jaques DP et al (2016) Operative site drainage after hepatectomy: a propensity score matched analysis using the American College of Surgeons NSQIP targeted hepatectomy database. J Am Coll Surg 223:774–83.e2CrossRefPubMedPubMedCentral Brauer DG, Nywening TM, Jaques DP et al (2016) Operative site drainage after hepatectomy: a propensity score matched analysis using the American College of Surgeons NSQIP targeted hepatectomy database. J Am Coll Surg 223:774–83.e2CrossRefPubMedPubMedCentral
9.
go back to reference Yeo CJ, Cameron JL, Sohn TA et al (1990s) Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 226:248–257CrossRefPubMedPubMedCentral Yeo CJ, Cameron JL, Sohn TA et al (1990s) Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 226:248–257CrossRefPubMedPubMedCentral
10.
11.
12.
go back to reference Liu CL, Fan ST, Lo CM et al (2004) Abdominal drainage after hepatic resection is contraindicated in patients with chronic liver diseases. Ann Surg 239:194–201CrossRefPubMedPubMedCentral Liu CL, Fan ST, Lo CM et al (2004) Abdominal drainage after hepatic resection is contraindicated in patients with chronic liver diseases. Ann Surg 239:194–201CrossRefPubMedPubMedCentral
13.
go back to reference Sun HC, Qin LX, Lu L et al (2006) Randomized clinical trial of the effects of abdominal drainage after elective hepatectomy using the crushing clamp method. Br J Surg 93:422–426CrossRefPubMed Sun HC, Qin LX, Lu L et al (2006) Randomized clinical trial of the effects of abdominal drainage after elective hepatectomy using the crushing clamp method. Br J Surg 93:422–426CrossRefPubMed
14.
go back to reference Ishizawa T, Hasegawa K, Kokudo N et al (2009) Risk factors and management of ascites after liver resection to treat hepatocellular carcinoma. Arch Surg 144:46–51CrossRefPubMed Ishizawa T, Hasegawa K, Kokudo N et al (2009) Risk factors and management of ascites after liver resection to treat hepatocellular carcinoma. Arch Surg 144:46–51CrossRefPubMed
15.
go back to reference Ichida A, Kono Y, Sato M et al (2020) Timing for removing prophylactic drains after liver resection: an evaluation of drain removal on the third and first postoperative days. Ann Transl Med 8(7):454CrossRefPubMedPubMedCentral Ichida A, Kono Y, Sato M et al (2020) Timing for removing prophylactic drains after liver resection: an evaluation of drain removal on the third and first postoperative days. Ann Transl Med 8(7):454CrossRefPubMedPubMedCentral
16.
go back to reference Koch M, Garden OJ, Padbury R et al (2011) Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery 149:680–688CrossRefPubMed Koch M, Garden OJ, Padbury R et al (2011) Bile leakage after hepatobiliary and pancreatic surgery: a definition and grading of severity by the International Study Group of Liver Surgery. Surgery 149:680–688CrossRefPubMed
17.
go back to reference Lo SF, Doumas BT (2011) The status of bilirubin measurements in US laboratories: why is accuracy elusive? Semin Perinatol. 35(3):141–7CrossRefPubMed Lo SF, Doumas BT (2011) The status of bilirubin measurements in US laboratories: why is accuracy elusive? Semin Perinatol. 35(3):141–7CrossRefPubMed
18.
go back to reference Kumagai A, Ando R, Miyatake H et al (2013) A bilirubin-inducible fluorescent protein from eel muscle. Cell 153:1602–1611CrossRefPubMed Kumagai A, Ando R, Miyatake H et al (2013) A bilirubin-inducible fluorescent protein from eel muscle. Cell 153:1602–1611CrossRefPubMed
19.
20.
go back to reference Yamashita S, Sakabe M, Ishizawa T et al (2013) Visualization of the leakage of pancreatic juice using a chymotrypsin-activated fluorescent probe. Br J Surg 100:1220–1228CrossRefPubMed Yamashita S, Sakabe M, Ishizawa T et al (2013) Visualization of the leakage of pancreatic juice using a chymotrypsin-activated fluorescent probe. Br J Surg 100:1220–1228CrossRefPubMed
21.
go back to reference Mori K, Ishizawa T, Yamashita S et al (2015) Intraoperative visualization of pancreatic juice leaking from the pancreatic stump in a swine model. Gastroenterology 149:1334–1336CrossRefPubMed Mori K, Ishizawa T, Yamashita S et al (2015) Intraoperative visualization of pancreatic juice leaking from the pancreatic stump in a swine model. Gastroenterology 149:1334–1336CrossRefPubMed
22.
go back to reference Ishizawa T, Bandai Y, Ijichi M et al (2010) Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy. Br J Surg 97:1369–1377CrossRefPubMed Ishizawa T, Bandai Y, Ijichi M et al (2010) Fluorescent cholangiography illuminating the biliary tree during laparoscopic cholecystectomy. Br J Surg 97:1369–1377CrossRefPubMed
23.
go back to reference Kaibori M, Ishizaki M, Matsui K et al (2011) Intraoperative indocyanine green fluorescent imaging for prevention of bile leakage after hepatic resection. Surgery 150:91–98CrossRefPubMed Kaibori M, Ishizaki M, Matsui K et al (2011) Intraoperative indocyanine green fluorescent imaging for prevention of bile leakage after hepatic resection. Surgery 150:91–98CrossRefPubMed
24.
go back to reference Terasawa M, Ishizawa T, Mise Y et al (2017) Applications of fusion fluorescence imaging using indocyanine green in laparoscopic hepatectomy. Surg Endosc 31:5111–5118CrossRefPubMed Terasawa M, Ishizawa T, Mise Y et al (2017) Applications of fusion fluorescence imaging using indocyanine green in laparoscopic hepatectomy. Surg Endosc 31:5111–5118CrossRefPubMed
Metadata
Title
On-Site Monitoring of Postoperative Bile Leakage Using Bilirubin-Inducible Fluorescent Protein
Authors
Yoshiharu Kono
Takeaki Ishizawa
Norihiro Kokudo
Yugo Kuriki
Ryu J. Iwatate
Mako Kamiya
Yasuteru Urano
Akiko Kumagai
Hiroshi Kurokawa
Atsushi Miyawaki
Kiyoshi Hasegawa
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
World Journal of Surgery / Issue 12/2020
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-020-05774-x

Other articles of this Issue 12/2020

World Journal of Surgery 12/2020 Go to the issue