Preclinical evaluation of endoscopic placement of a steroid-eluting metal stent in an in vivo porcine benign biliary stricture model

Abstract

Treatment of benign biliary strictures (BBS) using fully covered self-expandable metal stents (FCSEMS) has a high success rate, but recurrence can occur. Corticosteroids may be useful based on their anti-fibrotic and anti-inflammatory effects. We investigated the safety and efficacy of corticosteroid-eluting FCSEMS in an animal model. BBSs were created by radiofrequency ablation in 12 mini-pigs. Four weeks later, FCSEMS coated with 0 mg (control), 15 mg (steroid 1 × group), or 30 mg (steroid 2 × group) triamcinolone were inserted endoscopically. The in vitro drug release assay revealed that the optimal stent had 15 mg of triamcinolone and a hydrophilic membrane. No transmural necrosis or perforation occurred in any animal. Fibrous wall thickness tended to decrease macroscopically and microscopically in a triamcinolone dose-dependent manner (control vs. steroid 2 × group: 773.1 vs. 468.5 µm, P = 0.037). Thickness also decreased over time in the steroid 2 × group (3 days vs. 4 weeks: 907.9 vs. 468.5 µm, P = 0.025). Blood parameters tended to improve after stent insertion. In a porcine BBS model, steroid-eluting FCSEMS showed potential as a safe and effective treatment modality to reduce fibrotic tissue. Studies are required to confirm their safety and efficacy in humans with refractory BBS.

Feasibility and safety of a novel 3D-printed biodegradable biliary stent in an in vivo porcine model: a preliminary study

“…Therefore, although there was a difference in fibrosis thickness between the control and stent groups in our study, the degree of fibrosis in the stent group was minimal. Furthermore, according to previous studies 29 , 30 , mild inflammation and fibrosis in the porcine bile duct that did not cause problems such as biliary obstruction or leakage were interpreted as acceptable in terms of safety and feasibility.…”

“…Although there have been no studies on the fracture rate of biodegradable biliary stents, in a previous human study using PDO stents 28 , 25% of patients developed mild cholangitis during stent indwelling. Siiki et al reported that degradation and rupture of the stent may cause intermittent obstruction of bile flow, resulting in acute cholangitis 29 . However, blockage of the large bile duct with stent fragments or stone formation may be a minor complication, as most cases can be resolved with endoscopic procedures.…”

Triamcinolone acetonide alleviates benign biliary stricture by ameliorating biliary fibrosis and inflammation

“…Our primary goal was to uncover the molecular mechanisms responsible for the anti-fibrotic and anti-inflammatory effects of corticosteroids on gallbladder mucosa. To explore these mechanisms of corticosteroid-eluting stents in a BBS pig model ( 9 ), we conducted a comprehensive analysis, including IHC, ELISA, real-time PCR, and transcriptome analysis, to assess alterations in factors related to fibrosis and inflammation, at both the protein and RNA levels. Our data directly showed that as the concentration of TA increased, there was a significant reduction in fibrosis-related signaling, highlighting a dose-dependent increase in the anti-fibrotic effects of TA.…”

“…In our previous study, we assessed the therapeutic impact of a newly developed drug-eluting metal stent, incorporating corticosteroids, triamcinolone acetonide (TA), known for their anti-fibrotic and anti-inflammatory properties ( 9 ). This evaluation was conducted using a BBS pig model.…”

Relationship between postoperative biliary stricture and clinical characteristics of patients with benign and malignant biliary diseases.

“…In terms of imaging manifestations, magnetic resonance cholangiopancreatography (MRCP), computed tomography (CT), B-ultrasound, T-tube radiography, choledochoscopy, duodenoscopy and other imaging examinations and endoscopy have played an important role in the diagnosis and differential diagnosis of postoperative biliary stenosis [ 8 – 10 ]. Due to the persistence of stenosis, secondary surgery under endoscopy, direct vision or endoscopy is often required, which not only increases the pain of patients, but also wastes medical resources [ 11 , 12 ].…”