Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2020; 26(31): 4589-4606
Published online Aug 21, 2020. doi: 10.3748/wjg.v26.i31.4589
Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma
Jing-Bo Xiao, Jun-Yong Weng, Yang-Yang Hu, Gui-Long Deng, Xin-Jian Wan
Jing-Bo Xiao, Yang-Yang Hu, Xin-Jian Wan, Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
Jing-Bo Xiao, Hospitalist and Internal Medicine Inpatient Department, Shanghai Jiahui International Hospital, Shanghai 200233, China
Jun-Yong Weng, Gui-Long Deng, Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China
Xin-Jian Wan, Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
Author contributions: Wan XJ conceived the study; Xiao JB mainly carried out the experiments and wrote the manuscript; Weng JY, Hu YY assisted in performing experiments; Deng GL performed the surgical procedures; Wan XJ supervised the study and revised the article.
Supported by the National Natural Science Foundation of China, No. 81870452 and No. 81470904; Science and Technology Development Funds of Shanghai of China, No. 16411952400.
Institutional review board statement: This study was approved by the Ethics Committee of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine.
Institutional animal care and use committee statement: All experimental procedures were approved by the Animal Care and Use Committee of Shanghai General Hospital, Shanghai Jiaotong University School of Medicine.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xin-Jian Wan, MD, Chief Doctor, Department of Gastroenterology and Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, No. 650 Xinsongjiang Road, Shanghai 201620, China. xinjian_wan_shsl@163.com
Received: June 3, 2020
Peer-review started: June 3, 2020
First decision: June 18, 2020
Revised: June 30, 2020
Accepted: July 30, 2020
Article in press: July 30, 2020
Published online: August 21, 2020
Processing time: 78 Days and 7.6 Hours
ARTICLE HIGHLIGHTS
Research background

Currently, extrahepatic cholangiocarcinoma (ECC) is rarely curable and associated with a poor prognosis. Effective endoscopic management is fundamental for ECC at an unresectable stage; however, the current biliary stents used clinically have shown no antitumor effect and are associated with high failure rates due to reocclusion after stent implantation.

Research motivation

DES is a new therapeutic concept for the management of ECC and may realize a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis. However, there have been only limited studies thus far, and all of them were only single-drug-loaded stents with a simple design and unsatisfactory efficacy. Our study was motivated by the need to develop a novel DES that can improve palliative endoscopic management for ECC. In addition, we have accumulated rich experience with sodium cholate and disodium ethylene diamine tetraacetic acid-eluting stents for the dissolution of bile duct stones in our previous studies, which aided in our current study.

Research objectives

Our study aimed to develop a novel DES coated with gemcitabine (GEM) and cisplatin (CIS)-loaded PLCL nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct locally to inhibit tumor growth and reduce systemic toxicity.

Research methods

In our study, four different DESs were manufactured by the mixed electrospinning method, namely, bare-loaded, single-drug-loaded (GEM or CIS), and dual-drug-loaded (GEM and CIS) stents, with four drug-loading ratios (5%, 10%, 15%, and 20%). The drug release property, antitumor activity in the ECC cell line and mouse xenograft model, and biocompatibility in the normal porcine bile duct were evaluated to confirm the feasibility and efficacy of this novel DES for ECC.

Research results

We identified 10% as the appropriate drug-loading ratio based on the drug release property and inhibition efficiency. Further investigation indicated that these drug-loaded nanofilms exert ideal antitumor activity and good biosecurity.

Research conclusion

This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and exerts potent antitumor activity in vitro and in vivo. Therefore, it might be considered an alternative strategy for the palliative therapy of ECC patients.

Research perspectives

Future studies comparing DESs and conventional systemic chemotherapy may provide more reliable evidence for the preclinical evaluation of this novel stent for the management of ECC. With development and progress in multidisciplinary therapy for cancer, it is also worth investigating the benefit of replacing systemic chemotherapy with DESs together with targeted therapy and immunotherapy in the future.