Development Of A Swine Model For Benign Biliary Stenosis By Endoscopic Application Of Intraluminal Electrothermal Injury And In Vivo Study Of A Novel Biodegradable Biliary Stent

ObjectiveThe purpose of the study is to develop a swine benign biliary stricture model using adiathermic sheath by endoscopic application of intraluminal electrothermal injury, evaluateits feasibility and investigate an effective and safe energy dose. Furthermore, a newbiodegradable stent is inserted to the injured bile duct and evaluate its safety andeffectiveness of the biliary stent for resolving benign biliary stenosis.MethodsPartⅠ:12healthy Ba-ma miniature swine were randomly divided into three groups:low, medium and high energy group. A diathermic sheath was inserted into the lowersection of the common bile duct in the animals, and then electrocautery was applied to thecommon bile ducts with various energy doses. Cholangiography and liver function testswere repeated at every7-day interval. Record the time of biliary stricture (≤50%baselinediameter of the common bile duct) formation and compare the success rates of benignbiliary stenosis between each group. The animals of each group were sacrificed anddissected1month after the endoscopic electrothermal injury and the common bile ductswere excised for histopathologic analysis.PartⅡ:10animals were selected and divided into fast absorbing stents group andmedium absorbing stents group according to the degradation rates of biliary stents(Archimedes biodegradable biliary stents,2mm or3.2mm in diameter,2-3weeks for fast absorbing stents to begin to degrade and3-6weeks for medium absorbing stents). Biliarydilatation was implemented with a10Fr biliary dilatation catheter to the five BBS modelsin partⅠ, then a biodegradable stent was inserted to the injured bile duct and as two-stagestents group. Modeling using the same method and immediately placed an Archimedesbiliary stent, as one-stage stents group (n=5). Cholangiography and liver function testswere repeated at7-day intervals to observe the degree of stent degradation and theeffectiveness of stenting (ERC imaging and anatomy confirmed that luminal diameter wasmore than50%of the original diameter). The pigs were sacrificed and the bile ducts wereobtained for histopathologic evaluation1,2and3months after stenting.ResultsPartⅠ: In the low energy group (20w*20s), the bile duct stenosis was not found intwo animals (50%) and pathological examination showed mild inflammatory cellinfiltration in the common bile duct. In the medium energy group (30w*20s), all animals(n=4) had biliary stenosis, accompanied with moderately elevated serum bilirubin but nototally bile duct obstruction1month after operation. Tissue examination showed significantepithelial cells proliferation accompanied with a large number of chronic inflammatorycells infiltration. In high energy group (40w*20s), biliary stenosis formation wereconfirmed in all4experimental pigs by endoscopic cholangiography. Totally biliaryobstruction was found in2cases and one of them died at22days. An autopsy revealed bileduct perforation which was tightly wrapped by around organizations, bile leakage andsevere adhesion. Pathological examination revealed that bile duct mucosa became necrosis,submucosal collagen fibers largely proliferated and arranged densely and haphazardly.There was no significant difference (P=0.10) in the success rate of benign biliary stenosisamong three groups according to the predetermined standards. However, the stenosis gradeof medium or high energy group was higher than that in the low energy group (P＜0.05).PartⅡ: Ten biodegradable stents were successfully implanted into the bile ducts ofall10pigs,5for one-stage and5for two-stage, with no significant operational difficulties.Stent migration occurred in one pig and stent fracture occurred in two pigs, which all had performance of bile duct obstruction. The remaining stents (n=7) were all graduallydegraded and the degradation rate was consistent with the label. They had no significantadverse reactions such as bile duct obstruction. The total efficiency for treatment of BBSwith stenting was70%(7/10). Pathological examination revealed a small amount of bileduct mucosa became necrosis and a lot of mixed inflammatory cells infiltration one monthafter stenting. Epithelial cells and submucosal glands were significantly hyperplasia withthe chronic inflammatory cells decreased2months later. In3months, mucosal lesionswere basically repaired. Submucosal glands were hyperplasia, extracellular collagen fibersw e r e o v e r-d e p o s i t i o n, a n d s o m e o f t h e m b e c a m e h y a l i n i z a t i o n.Conclusion1. The method of endoscopic application of intraluminal electrothermal injury with adiathermic sheath to develop a swine BBS model was effective and convenient, themedium energy settings (30w*20s) was more reliable and secure and the average time ofbile duct stenosis formation was2weeks.2. Archimedes biodegradable stent had a certain effect in prevention and treatment ofBBS, the degradation rate of the stent was consistent with that in vitro study. However, thestent design still needs further improvement and perfection.