The first stents designed for use in the biliary tree and

Imaging and Advanced Technology Michael B. Wallace, Section Editor Expandable Gastrointestinal Stents TODD H. BARON Department of Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, Minnesota The first stents designed for use in the biliary tree and the esophagus were composed of rigid plastic. Selfexpandable metal biliary stents (SEMS) became commercially available in the United States approximately 15 years ago, followed several years later by esophageal SEMS. Self-expandable plastic stents (SEPS) for esophageal use are now available. The last areas for stent development were gastroduodenal and colonic (Figure 1). SEMS were initially developed without a coating (uncovered), but a variety of coverings and modifications have been introduced. In this article, the latest technology of self-expandable stents within the gastrointestinal tract are reviewed. Basic Concepts SEMS are composed of a variety of metals and are marketed and designed specifically for esophagus, biliary, duodenal, and colonic sites. 1 The stents vary based on type of alloy, lattice width, configuration, degree of shortening with, lengths and diameters, presence of a covering, and delivery systems. The tissue response to covered stents is well-established. 1 Uncovered SEMS imbed into the stricture and surrounding tissue so that over time they become deeply integrated and nonremovable (Figure 2). Covered SEMS were developed to combat tumor ingrowth and to close fistulae. However, the covering also prevents imbedding in the tissue so that covered SEMS can be removed and have the potential to be used in benign disease. Unfortunately, with this removability comes an increased risk of migration, because tissue anchoring does not occur. One self-expandable plastic stent (Polyflex, Boston Scientific, Natick, MA) has been developed and is available for esophageal use. This stent does not imbed into the tissue and is approved by the US Food and Drug Administration (FDA) for benign disease and removability. Selfexpandable stents may be placed endoscopically with or without the assistance of fluoroscopy or under fluoroscopic guidance alone by interventional radiologists. Esophageal Stents Esophageal stents provide palliation of dysphagia and closure of tracheoesophageal fistulae (Figure 3). 2 Comparative studies have shown that SEMS have lower insertion complications compared with rigid esophageal stents. Uncovered, partially covered, completely covered SEMS, and one SEPS are available (Table 1; Figure 4). Covered SEMS have prolonged patency in malignant disease compared with uncovered SEMS because of the prevention of tumor ingrowth through the interstices of the stent. 2 Small- and large-diameter stents are available for placement into the proximal and distal esophagus, respectively. One SEMS with an anti-reflux valve is FDA-approved for placement across the gastroesophageal junction to reduce gastroesophageal reflux and potential aspiration of gastric contents (Figure 4). 2 Only the SEPS is approved for benign disease at the time of this report. Fully covered SEMS have promise for treatment of benign disease and results from outside the United States confirm their removability. 3 Biliary Stents Plastic biliary stents were introduced almost 30 years ago for relief of biliary obstruction. Although larger diameters provide longer patency, the diameter is limited by the size of the endoscope channel. Plastic biliary stents invariably occlude owing to bacterial biofilm and reflux of duodenal contents. Expandable biliary SEMS were designed to overcome the limitation of endoscope channel size to allow an increase in luminal stent diameter, thereby prolonging stent patency. 1 Comparative studies have shown a significant prolongation of patency over traditional plastic stents for palliation of malignant biliary obstruction. As for the esophagus, a variety of FDAapproved SEMS are available for palliation of malignant biliary obstruction (Table 2); none are currently approved for benign disease. Three covered SEMS are available and designed to prolong stent patency over uncovered SEMS by preventing tumor ingrowth (Figure 5). However, data from comparative studies have not conclusively shown a significant improvement in stent patency. In addition, 2007 by the AGA Institute 0016-5085/07/$32.00 doi:10.1053/j.gastro.2007.09.056 GASTROENTEROLOGY 2007;133:1407 1411

Figure 3. Closure of tracheoesophageal fistula. Endoscopic view: Immediately after placement of covered stent. Figure 1. Illustration of SEMS throughout the GI tract. covered biliary SEMS have a higher migration rate and possibly an increased risk of cholecystitis. 4,5 Although not approved for benign disease, there are reports of placing covered SEMS for treatment of benign strictures and postoperative biliary leaks 6 ; the SEMS are removed after resolution of the underlying pathology. At present, drug-eluting stents are not available, although preliminary studies have shown that paclitaxel inhibits proliferation of cell lines responsible for metal stent obstruction and may have a role in drug-eluting stents. 7 Results from animal studies have shown the feasibility of placing expandable biodegradable biliary stents for management of bile duct leaks 8 and human studies using these devices in benign disease are awaited. Gastroduodenal Stents Expandable stents provide palliation of malignant gastric outlet obstruction (Figure 6). 9 Two uncovered SEMS are FDA-approved for this indication (Table 3). The most recently available SEMS have smooth, rounded edges that theoretically reduce injury to the small bowel mucosa. The delivery systems of these SEMS are small enough to pass through the working channel of therapeutic endoscopes such that stents can be deployed as far distally as the endoscope can be passed, including through double-balloon endoscopes. They are not used for benign disease because of lack of removability. Figure 2. Illustration of stent embedment in the luminal wall over time from left to right. The top of the illustration represents the lumen. Note the stent imbeds deeply into the wall. Figure 4. A variety of covered esophageal stents. Far left is a windsock anti-reflux stent. 1408

Table 1. FDA-Approved Expandable Esophageal Stents Materials Deployment diameter Features Boston Scientific Ultraflex NG Covered Nitinol 18 mm, proximal flange 23 mm; 23 mm, proximal flange 28 mm Ultraflex NG Uncovered Nitinol 18 mm, proximal flare; 23 mm Wallstent II Elgiloy (Cobalt- Chromium- Nickel) 20 mm midportion; 28 mm flared ends Polyflex Polyester/silicone 16 mm, proximal flare 20 mm; 18 mm, proximal flare 23 mm; 21 mm, proximal flare 25 mm Cook Endoscopy Z-Stent Fully Covered Stainless steel 18 mm center; 25 mm flared ends Z-stent Uncoated Flange Stainless steel 18 mm midportion; 25 mm flared ends Z-stent with Dua Anti-reflux valve Stainless steel 18 mm midportion; 25 mm flared ends Alveolus Alimaxx-E Nitinol 18 mm midportion, 22 mm midportion (flared ends, proximal end 5 mm larger and distal end 3 mm larger) Available in distal or proximal release system; 48% 54% foreshortening during deployment Available in distal or proximal release; 48% 54% foreshortening during deployment Reconstrainable; bare metal wires at ends of stent; 28% foreshortening during deployment Approved for removability; 36% 41% foreshortening during deployment No foreshortening during deployment Portion of flanges uncovered; no foreshortening Windsock on distal end to prevent gastroesophageal reflux when placed across gastroesophageal junction; no foreshortening Completely covered (internally lined); no foreshortening Colonic Stents Expandable colonic SEMS are used for relief of malignant colonic obstruction in 2 ways: palliation and preoperatively as a bridge to surgery to allow a subsequent 1-stage operation. 9 When used in the latter situation, the stent is removed when the tumor is resected. Four FDA-approved SEMS are available (Table 3). Two of these have delivery systems that are small enough to pass through the channel of the endoscope. Therefore, these SEMS can be placed as far proximally as the endoscope can be passed, including into the right colon and ileum. All FDA-approved colonic SEMS are uncovered because of the extremely high rate of migration when partially covered SEMS are used in the colon. Although there are few data regarding the use of colonic SEMS in benign disease, uncovered stents have been used as a bridge to surgery in patients with acute colonic Table 2. FDA-Approved Expandable Biliary Stents Manufacturer/stent Material Cell design Covered stent available Shortening (%) Reconstrainable Conmed/Flexxus Nitinol Open No 1 No Boston Scientific/Wallstent Elgiloy (cobaltchromium-nickel) Closed Yes, ends 40 Yes uncovered Boston Scientific/Wallflex Nitinol Closed Yes, fully 40 Yes covered Cook Endoscopy/Zilver Nitinol Open No 0 No W. L. Gore & Associates/ Viabil Nitinol Open Yes (only available as covered) 0 No 1409

Figure 6. Fluoroscopic view of covered duodenal stent duodenum immediately after placement. Figure 5. Endoscopic view of covered biliary stent exiting the bile duct into the duodenum immediately after placement. obstruction. 10 Their lack of removability is not a concern because they are removed at the time of surgery with the diseased bowel. Occasional cases in which a removable covered colonic stent was placed with resolution of a benign stricture have been reported. 11 Summary A variety of self-expandable stents are available for use within the gastrointestinal tract and biliary system. Nearly all of these are approved for management of malignant disease. Placement of expandable stents for benign conditions is becoming more common; however, improvements in stent designs are needed to prevent migration while maintaining removability. References 1. Baron TH. Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 2001; 344:1681 1687. 2. Papachristou GI, Baron TH. Use of stents in benign and malignant esophageal disease. Rev Gastroenterol Disord 2007;7:74 88. 3. Yoon CJ, Shin JH, Song HY, et al. Removal of retrievable esophageal and gastrointestinal stents: experience in 113 patients. AJR Am J Roentgenol 2004;183:1437 1444. 4. Fumex F, Coumaros D, Napoleon B, et al; Societe Francaise d Endoscopie Digestive. Similar performance but higher cholecystitis rate with covered biliary stents: results from a prospective multicenter evaluation. Endoscopy 2006;38:787 792. Table 3. FDA-Approved Expandable Duodenal and Colonic Stents Materials Deployed Diameters Features Boston Scientific Ultraflex Precision Colonic Nitinol 25 mm (proximal flare 30 mm) Non-TTS; nonreconstrainable; 23% foreshortening Wallstent Enteral Elgiloy (cobalt-chromium-nickel) 20 mm; 22 mm TTS delivery; reconstrainable; 39% 49% foreshortening during Wallflex Enteral Duodenal Nitinol 22 mm body, 27 mm proximal flare TTS delivery; reconstrainable; 30% 38% foreshortening during Wallflex Enteral Colonic Nitinol 25 mm body, 30 mm proximal flare; 22 mm body, 27 mm proximal flare TTS delivery; reconstrainable; 30% 38% foreshortening during Cook Endoscopy Colonic Z-stent Stainless steel 25 mm Non-TTS; no foreshortening TTS, through-the-scope. 1410

5. Leung J, Rahim N. The role of covered self-expandable metallic stents in malignant biliary strictures. Gastrointest Endosc 2006; 63:1001 1003. 6. Kahaleh M, Sundaram V, Condron SL, et al. Temporary placement of covered self-expandable metallic stents in patients with biliary leak: midterm evaluation of a pilot study. Gastrointest Endosc 2007;66:52 59. 7. Kalinowski M, Alfke H, Kleb B, et al. Paclitaxel inhibits proliferation of cell lines responsible for metal stent obstruction: possible topical application in malignant bile duct obstructions. Invest Radiol 2002;37:399 404. 8. Laukkarinen J, Nordback I, Mikkonen J, et al. A novel biodegradable biliary stent in the endoscopic treatment of cystic-duct leakage after cholecystectomy. Gastrointest Endosc 2007;65:1063 1068. 9. Simmons DT, Baron TH. Technology insight: Enteral stenting and new technology. Nat Clin Pract Gastroenterol Hepatol 2005;2: 365 374. 10. Small AJ, Young-Fadok TM, Baron TH. Expandable metal stent placement for benign colorectal obstruction: outcomes for 23 cases. Surg Endosc 2007;Aug 18; [Epub ahead of print]. 11. Seo TS, Song HY, Sung KB, et al. A benign colorectal stricture: treatment with a retrievable expandable nitinol stent. Cardiovasc Intervent Radiol 2003;26:181 183. Address requests for reprints to: Todd H. Baron, MD, 200 First Street SW, Charlton 8, Rochester, Minnesota 55905. e-mail: baron.todd@ mayo.edu; fax: (507) 266-3939. Research support by Boston Scientific and further support from Speaker s bureau Cook, ConMed and Consultant ConMed, Alveolus, Cook. 1411