Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2020; 26(46): 7312-7324
Published online Dec 14, 2020. doi: 10.3748/wjg.v26.i46.7312
Extrahepatic bile duct reconstruction in pigs with heterogenous animal-derived artificial bile ducts: A preliminary experience
Hao Shang, Jian-Ping Zeng, Si-Yuan Wang, Ying Xiao, Jiang-Hui Yang, Shao-Qing Yu, Xiang-Chen Liu, Nan Jiang, Xia-Li Shi, Shuo Jin
Hao Shang, Jian-Ping Zeng, Si-Yuan Wang, Shao-Qing Yu, Xiang-Chen Liu, Shuo Jin, Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102200, China
Ying Xiao, Jiang-Hui Yang, Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102200, China
Nan Jiang, Institute for Precision Medicine Tsinghua University, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
Xia-Li Shi, Department of Anesthesiology and Operation, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Author contributions: Shang H and Zeng JP contributed equally to this work; Shang H, Zeng JP and Jin S designed the study; Shang H, Zeng JP, Yu SQ, Liu XC, Jiang N, Shi XL and Jin S carried out the study; Xiao Y and Yang JH performed the pathological analysis; Zeng JP and Wang SY collected and analyzed the data; Shang H and Jin S wrote the manuscript.
Supported by the Beijing Natural Science Foundation, No. 7194338.
Institutional review board statement: The study was reviewed and approved by the Local Ethics Committee of Beijing Tsinghua Changgung Hospital (Beijing, China) (permit No. 2016-KY-GJ-10).
Institutional animal care and use committee statement: All the experiments were conducted in compliance with the NIH Guidelines and the Animal Research Protocol of Experimental Animal Center of Beijing Tsinghua Changgung Hospital.
Conflict-of-interest statement: All authors declare no conflicts of interest related to this work.
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:
Corresponding author: Shuo Jin, MD, PhD, Attending Doctor, Department of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing 102200, China.
Received: August 27, 2020
Peer-review started: August 27, 2020
First decision: September 30, 2020
Revised: October 6, 2020
Accepted: November 2, 2020
Article in press: November 2, 2020
Published online: December 14, 2020
Research background

Several approaches have been explored to address extrahepatic biliary duct injury (BDI). The high incidence of complications affects postoperative recovery. Animal-derived artificial bile duct (ada-BD), a nonimmunogenic scaffold, could replace the defect via providing good physiological conditions for the regeneration of autologous bile duct structures without changing the original anatomical and physiologic conditions.

Research motivation

To assess the safety and feasibility of a novel animal derived material for treating extrahepatic BDI in pigs.

Research objectives

To evaluate and confirm the long-term feasibility of a novel heterogenous ada-BD for treating extrahepatic BDI.

Research methods

Eight pigs were randomly divided into two groups. Surgery was performed to develop a bile duct injury and repair model via a 2 cm long novel heterogenous ada-BD to repair an approximately 2 cm segmental defect of various parts of the common bile duct (CBD) for all pigs. Group A received ada-BD-to-duodenum anastomosis to repair the distal CBD defect, and group B received ada-BD-to-CBD anastomosis to repair the intermedial CBD defect. The endpoint for observation was 6 mo (group A) and 12 mo (group B) after the operation.

Research results

All experimental animals survived until the endpoints for observation. The liver function was almost regular. Histologic analysis indicated a marked biliary epithelial layer covering the neo-bile duct and regeneration of the submucosal connective tissue and smooth muscle without significant signs of immune rejection. In comparison, the submucosal connective tissue was more regular and thicker in group B than in group A, and there was superior integrity of the regeneration of the biliary epithelial layer. Despite the advantages of the regeneration of the bile duct smooth muscle observed in group A, the effect on the patency of the ada-BD grafts in group B was not confirmed by macroscopic assessment and cholangiography.

Research conclusions

Repairing a CBD defect with an ada-BD appears to be a feasible and safe approach. A large sample study is needed to confirm the durability and safety of these preliminary results.

Research perspectives

Ada-BD showed a high similarity between the bovine ureter and bile duct. The decellularized bovine ureter provided an optimal pathophysiological condition and a novel material to avoid immunological rejection. All the encouraging results bring a new hope for bile duct repairment.