Partially Covered Metal Stents Efficacy in Biliary Drainage of Malignant Extrahepatic Biliary Obstruction (METARSI): a multicenter randomized controlled trial

Aims The primary aim of this randomized trial was to compare stent patency in unresectable malignant biliary stricture after placement of partially covered metallic stent (PC-SEMS) vs uncovered metal stent (U-SEMS). Secondary aims were to evaluate the stents performance in terms of migration rate, patient survival in the absence of stent dysfunction, the incidence of early (within 7 days) or late (30 days) complications with these different stents types

Methods Prospective multicenter randomized controlled and “non-profit” clinical trial. After determining the inclusion and exclusion criteria, a second investigator acceded the proper randomization list during the procedure. After stent placement (T0), biliary drainage was considered effective reaching bilirubin level less than 2 mg/dl (T1).

Subsequently, patients were divided into two groups based on the possibility of oncological treatment:

- in patients who were not resectable and cannot be treated with chemotherapy (UNFIT group), follow-up included blood tests and telephone/outpatient evaluation at 3, 9 and 12 months±3 weeks (T2);

- in unresectable patients undergoing neo-adjuvant or palliative chemotherapy (FIT group) the follow-up included blood tests and telephone/outpatient evaluation at 3, 6, 9 and 12 months±3 weeks (T2).

Results Between March 2021 and February 2023, 256 patients were randomized to receive an uncovered (n. 124) or a partially covered (n. 132) SEMS. Stent placement was successful in all enrolled patients.All the inserted stents were 10 mm in diameter. Within 7 days after stent insertion, two patients developed moderate pancreatitis resolved with medical treatment. Eight patients developed cholangitis: 4 patients in the PC-SEMS group were treated with antibiotic therapy alone, while 4 patients (2 in PC-SEMS and 2 in U-SEMS group), required an endoscopic re-intervention to insert a coaxial biliary plastic stent. Cholecystitis developed in two patients from the PC-SEMS group and required a second ERCP to remove the first stent and insert a new one.Late stent dysfunction occurred in 24 cases (12 patients in both groups). Tumor ingrowth with or without biliary sludge impaction was registered in 22 cases; Median time to late stent obstruction was 270 days (IQR 95-273) in the USEMS group and 193 days (IQR, 111-273) in the PC- SEMS group (p-value 0.78).

Conclusions In conclusion our study showed no differences in terms of efficacy and safety between U-SEMS and PC-SEMS. To optimize stents performance, the development of devices that prevent migration, incomplete expansion, biofilm formation and tumor ingrowth are required [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29]

 

MissingLinkText

Conflicts of Interest

Authors do not have any conflict of interest to disclose.

• References

• 1 Singh A, Gelrud A, Agarwal B.. Biliary strictures: diagnostic considerations and approach. Gastroenterol Rep (Oxf) 2015; 3: 22-31 [PMID: 25355800
• 2 Elmunzer BJ, Maranki JL, Gómez V, Tavakkoli A, Sauer BG, Limketkai BN, Brennan EA, Attridge EM, Brigham TJ, Wang AY.. ACG Clinical Guideline: Diagnosis and Management of Biliary Strictures. Am J Gastroenterol 2023; 118: 405-426 [PMID: 36863037
• 3 Tanisaka Y, Mizuide M, Fujita A, Ogawa T, Katsuda H, Saito Y, Miyaguchi K, Jinushi R, Terada R, Nakano Y, Tashima T, Mashimo Y, Ryozawa S.. Current Status of Endoscopic Biliary Drainage in Patients with Distal Malignant Biliary Obstruction. J Clin Med 2021; 10: 4619 [PMID: 34640637
• 4 Kapoor BS, Mauri G, Lorenz JM.. Management of Biliary Strictures: State-of-the-Art Review. Radiology 2018; 289: 590-603 [PMID: 30351249
• 5 Abraham NS, Barkun JS, Barkun AN.. Palliation of malignant biliary obstruction: a prospective trial examining impact on quality of life. Gastrointest Endosc 2002; 56: 835-841 [PMID: 12447294
• 6 Nakai Y, Isayama H, Wang H, Rerknimitr R, Khor C, Yasuda I, Kogure H, Moon JH, Lau J, Lakhtakia S, Ratanachu-ek T, Seo DW, Lee DK, Makmun D, Dy F, Liao W, Draganov PV, Almadi M, Irisawa A, Katanuma A, Kitano M, Ryozawa S, Fujisawa T, Wallace MB, Itoi T, Devereaux B.. International consensus statements for endoscopic management of distal biliary stricture. J Gastroenterol Hepatol 2020; 35: 967-979 [PMID: 31802537
• 7 Dumonceau J-M, Tringali A, Papanikolaou IS, Blero D, Mangiavillano B, Schmidt A, Vanbiervliet G, Costamagna G, Devière J, García-Cano J, Gyökeres T, Hassan C, Prat F, Siersema PD, van Hooft JE.. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated October 2017. Endoscopy 2018; 50: 910-930 [PMID: 30086596
• 8 Moss AC, Morris E, Leyden J, MacMathuna P.. Do the benefits of metal stents justify the costs? A systematic review and meta-analysis of trials comparing endoscopic stents for malignant biliary obstruction. Eur J Gastroenterol Hepatol 2007; 19: 1119-1124 [PMID: 17998839
• 9 Glazer ES, Hornbrook MC, Krouse RS.. A meta-analysis of randomized trials: immediate stent placement vs. surgical bypass in the palliative management of malignant biliary obstruction. J Pain Symptom Manage 2014; 47: 307-314 [PMID: 23830531
• 10 Zheng B, Wang X, Ma B, Tian J, Jiang L, Yang K.. Endoscopic stenting versus gastrojejunostomy for palliation of malignant gastric outlet obstruction. Dig Endosc 2012; 24: 71-78 [PMID: 22348830
• 11 Bliss LA, Eskander MF, Kent TS, Watkins AA, de Geus SWL, Storino A, Ng SC, Callery MP, Moser AJ, Tseng JF.. Early surgical bypass versus endoscopic stent placement in pancreatic cancer. HPB (Oxford) 2016; 18: 671-677 [PMID: 27485061
• 12 Jang S, Stevens T, Parsi MA, Bhatt A, Kichler A, Vargo JJ.. Superiority of Self-Expandable Metallic Stents Over Plastic Stents in Treatment of Malignant Distal Biliary Strictures. Clin Gastroenterol Hepatol 2022; 20: e182-e195 [PMID: 33346140
• 13 Chen M-Y, Lin J-W, Zhu H-P, Zhang B, Jiang G-Y, Yan P-J, Cai X-J.. Covered Stents versus Uncovered Stents for Unresectable Malignant Biliary Strictures: A Meta-Analysis. Biomed Res Int 2016; 2016: 6408067 [PMID: 27051667
• 14 Yang Z, Wu Q, Wang F, Ye X, Qi X, Fan D.. A systematic review and meta-analysis of randomized trials and prospective studies comparing covered and bare self-expandable metal stents for the treatment of malignant obstruction in the digestive tract. Int J Med Sci 2013; 10: 825-835 [PMID: 23794946
• 15 Yokota Y, Fukasawa M, Takano S, Kadokura M, Shindo H, Takahashi E, Hirose S, Kawakami S, Fukasawa Y, Sato T, Enomoto N.. Partially covered metal stents have longer patency than uncovered and fully covered metal stents in the management of distal malignant biliary obstruction: a retrospective study BMC Gastroenterol. 2017; 17 [PMID: 29020933.
• 16 Outcome of both-bare type nitinol metal stents in distal biliary malignant obstruction: A post-market clinical follow-up study | Gastrointestinal Tract. (e-pub ahead of print 22 September 2023).
• 17 Isayama H, Hamada T, Yasuda I, Itoi T, Ryozawa S, Nakai Y, Kogure H, Koike K.. TOKYO criteria 2014 for transpapillary biliary stenting. Dig Endosc 2015; 27: 259-264 [PMID: 25209944
• 18 Li J, Li T, Sun P, Yu Q, Wang K, Chang W, Song Z, Zheng Q.. Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis. PLoS One 2016; 11: e0149066 [PMID: 26859673
• 19 Almadi MA, Barkun AN, Martel M.. No benefit of covered vs uncovered self-expandable metal stents in patients with malignant distal biliary obstruction: a meta-analysis. Clin Gastroenterol Hepatol 2013; 11: 27-37.e1 [PMID: 23103324
• 20 Park DH, Kim M-H, Choi JS, Lee SS, Seo DW, Kim JH, Han J, Kim JC, Choi EK, Lee SK.. Covered versus uncovered wallstent for malignant extrahepatic biliary obstruction: a cohort comparative analysis. Clin Gastroenterol Hepatol 2006; 4: 790-796 [PMID: 16716757
• 21 Elshimi E, Morad W, Elshaarawy O, Attia A.. Optimization of biliary drainage in inoperable distal malignant strictures. World J Gastrointest Endosc 2020; 12: 285-296 [PMID: 32994859
• 22 Yang MJ, Kim JH, Yoo BM, Hwang JC, Yoo JH, Lee KS, Kang JK, Kim SS, Lim SG, Shin SJ, Cheong JY, Lee KM, Lee KJ, Cho SW.. Partially covered versus uncovered self-expandable nitinol stents with anti-migration properties for the palliation of malignant distal biliary obstruction: A randomized controlled trial. Scand J Gastroenterol 2015; 50: 1490-1499 [PMID: 26133200
• 23 Kim JY, Ko GB, Lee TH, Park S-H, Lee YN, Cho YS, Jung Y, Chung I-K, Choi HJ, Cha S-W, Moon JH, Cho YD, Kim S-J.. Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction. Gut Liver 2017; 11: 440-446 [PMID: 28208003
• 24 Costamagna G, Tringali A, Reddy DN, Devière J, Bruno M, Ponchon T, Neuhaus H, Mutignani M, Rao GV, Lakhtakia S, Le Moine O, Fockens P, Rauws EA, Lepilliez V, Schumacher B, Seelhoff A, Carr-Locke D.. A new partially covered nitinol stent for palliative treatment of malignant bile duct obstruction: a multicenter single-arm prospective study. Endoscopy 2011; 43: 317-324 [PMID: 21360423
• 25 Sakai Y, Tsuyuguchi T, Hirata N, Sugiyama H, Shimura K, Nakaji S, Shiratori T, Fujimoto T, Tsuchiya S, Mikami S, Yokosuka O.. Long-term outcome of the WallFlex partially covered stent for unresectable malignant biliary obstruction: a multicenter single-arm prospective study. Hepatogastroenterology 2013; 60: 1854-1860 [PMID: 24088309
• 26 Soderlund C, Linder S, Bergenzaun PE, Grape T, Hakansson H-O, Kilander A, Lindell G, Ljungman M, Ohlin B, Nielsen J, Rudberg C, Stotzer P-O, Svartholm E, Toth E, Frozanpor F.. Nitinol versus steel partially covered self-expandable metal stent for malignant distal biliary obstruction: a randomized trial. Endoscopy 2014; 46: 941-948 [PMID: 25321620
• 27 Conio M, Mangiavillano B, Caruso A, Filiberti RA, Baron TH, De Luca L, Signorelli S, Crespi M, Marini M, Ravelli P, Conigliaro R, De Ceglie A.. Covered versus uncovered self-expandable metal stent for palliation of primary malignant extrahepatic biliary strictures: a randomized multicenter study. Gastrointest Endosc 2018; 88: 283-291.e3 [PMID: 29653120
• 28 Suksai N, Kamalaporn P, Chirnaksorn S, Siriyotha S.. Factors associated with patency of self-expandable metal stents in malignant biliary obstruction. BMC Gastroenterol 2023; 23: 392 [PMID: 37964198
• 29 Saleem A, Leggett CL, Murad MH, Baron TH.. Meta-analysis of randomized trials comparing the patency of covered and uncovered self-expandable metal stents for palliation of distal malignant bile duct obstruction. Gastrointest Endosc 2011; 74: 321-327.e1–3 [PMID: 21683354

Publication History

Article published online:
27 March 2025