Effect of drug-eluting metal stents in benign esophageal stricture: an in vivo animal study

Background and study aims: The aim of this study in canines was to investigate the effectiveness and safety of self-expandable metal stents, which were coated with paclitaxel to minimize the tissue response.

Materials and methods: 14 dogs (5 – 10 kg) were randomly allocated to two groups. Drug-eluting stents (DES, n = 7) or nondrug-eluting stents (non-DES, n = 7) were endoscopically inserted and fixed in the esophagus of healthy dogs. Every 2 weeks, for a maximum period of 8 weeks, an endoscopic examination was performed to evaluate the status of stent insertion, the grade of tissue hyperplasia, and mucosal change at both ends of the stent.

Results: One case of stent migration was observed after 4 weeks in the non-DES group. In this group, tissue reaction and hyperplasia remained for more than 4 weeks after stent insertion. By contrast, an endoscopic examination of the surrounding esophageal mucosa in the DES group showed very little tissue reaction, and the stent was easily separated from the esophageal tissue.

Conclusion: Although further studies are required to confirm our results, we suggest that these newly designed DES may provide an alternative tool to manage refractory benign esophageal stricture.

References

• 1 Shah J N. Benign refractory esophageal strictures: widening the endoscopist’s role.  Gastrointest Endosc. 2006;  63 164-167
• 2 Lew R J, Kochman M L. A review of endoscopic methods of esophageal dilation.  J Clin Gastroenterol. 2002;  35 117-126
• 3 Said A, Brust D J, Gaumnitz E A. et al . Predictors of early recurrence of benign esophageal strictures.  Am J Gastroenterol. 2003;  98 1252-1256
• 4 Song H Y, Park S I, Do Y S. et al . Expandable metallic stent placement in patients with benign esophageal strictures: results of long-term follow-up.  Radiology. 1997;  203 131-136
• 5 Fiorini A, Fleischer D, Valero J. et al . Self-expandable metal coil stents in the treatment of benign esophageal strictures refractory to conventional therapy: a case series.  Gastrointest Endosc. 2000;  52 259-262
• 6 Evrard S, Le Moine O, Lazaraki G. et al . Self-expanding plastic stents for benign esophageal lesions.  Gastrointest Endosc. 2004;  60 894-900
• 7 Repici A, Conio M, De Angelis C. et al . Temporary placement of an expandable polyester silicone-covered stent for treatment of refractory benign esophageal strictures.  Gastrointest Endosc. 2004;  60 513-519
• 8 Fry S W, Fleischer D E. Management of a refractory benign esophageal stricture with a new biodegradable stent.  Gastrointest Endosc. 1997;  45 179-182
• 9 Tanaka T, Takahashi M, Nitta N. et al . Newly developed biodegradable stents for benign gastrointestinal tract stenoses: a preliminary clinical trial.  Digestion. 2006;  74 199-205
• 10 Jung I S. Development of newly designed fully covered self-expandible metal stent for the treatment of refractory benign esophageal stricture and evaluation of its tissue response in dogs [dissertation]. Asan; Soon Chun Hyang University 2007
• 11 Lee D H. Drug-eluting stent in gastrointestinal disease.  Korean J Gastroenterol. 2007;  49 294-299
• 12 Lee D K, Kim H S, Kim K S. et al . The effect on porcine bile duct of a metallic stent covered with a paclitaxel-incorporated membrane.  Gastrointest Endosc. 2005;  61 296-301
• 13 Baron T H, Burqart L J, Pochron N L. An internally covered (lined) self-expanding metal esophageal stent: tissue response in a porcine model.  Gastrointest Endosc. 2006;  65 263-267
• 14 Little A G, Naunbeim K S, Ferguson M K. et al . Surgical management of esophageal strictures.  Ann Thorac Surg. 1988;  45 144-147
• 15 Yim H B, Jacobson B C, Saltzman J R. et al . Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction.  Gastrointest Endosc. 2001;  53 329-332
• 16 Domschke W, Foerster E C, Matek W. et al . Self-expanding mesh stent for esophageal cancer stenosis.  Endoscopy. 1990;  22 134-136
• 17 Kozarek R A, Ball T J, Patterson D J. Metallic self-expanding stent application in the upper gastrointestinal tract: caveats and concerns.  Gastrointest Endosc. 1992;  38 1-6
• 18 Maetani I, Ogawa S, Hoshi H. et al . Self-expanding metal stents for palliative treatment of malignant biliary and duodenal stenoses.  Endoscopy. 1994;  26 701-704
• 19 Feretis C, Benakis P, Dimopoulos C. et al . Palliation of malignant gastric outlet obstruction with self-expanding metal stents.  Endoscopy. 1996;  28 225-228
• 20 Pinto I T. Malignant gastric and duodenal stenosis: palliation by peroral implantation of a self-expanding metallic stent.  Cardiovasc Intervent Radiol. 1997;  20 431-434
• 21 Venu R P, Pastika B J, Kini M. et al . Self-expandable metal stents for malignant gastric outlet obstruction: a modified technique.  Endoscopy. 1998;  30 553-558
• 22 Yates 3rd M R, Morgan D E, Baron T H. Palliation of malignant gastric and small intestinal strictures with self-expandable metal stents.  Endoscopy. 1998;  30 266-272
• 23 Soetikno R M, Lichtenstein D R, Vandervoort J. et al . Palliation of malignant gastric outlet obstruction using an endoscopically placed Wallstent.  Gastrointest Endosc. 1998;  47 267-270
• 24 Seo Y S, Park J J, Kim B G. et al . Segmental amputation of esophagus with bronchial-wall rupture during removal of a stent for benign esophageal stricture.  Gastrointest Endosc. 2006;  64 141-143
• 25 Nam D S, Lee W K. Development of polymer coating method for stable stent coating using chemical bond between metal surface and polymer.  J Kor Pharm Sci. 2007;  37 7-14
• 26 Lee K B, Chun H J, Kim Y B. et al . Mechanical characterization of self-expandable esophageal metal stents.  Korean J Gastrointest Endosc. 2001;  23 61-68
• 27 Parness J, Horwitz S B. Taxol binds to polymerized tubulin in vitro.  J Cell Biol. 1981;  91 479-487
• 28 Roussel E, Belanger M M, Couet J. G2/M blockade by paclitaxel induces caveolin-1 expression in A549 lung cancer cells: caveolin-1 as a marker of cytotoxicity.  Anticancer Drugs. 2004;  15 961-967
• 29 Torres K, Horwitz S B. Mechanisms of Taxol-induced cell death are concentration dependent.  Cancer Res. 1998;  58 3620-3626
• 30 Fan W. Possible mechanism of paclitaxel-induced apoptosis.  Biochem Pharmacol. 1999;  57 1215-1221
• 31 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
• 32 Rowinsky E K, Donehower R C. Paclitaxel (taxol).  N Engl J Med. 1995;  332 1004-1014
• 33 Dhanikula A B, Panchagnula R. Localized paclitaxel delivery.  Int J Pharm. 1999;  183 85-100
• 34 Mani G, Feldman M D, Patel D. et al . Coronary stents: a materials perspective.  Biomaterials. 2007;  28 1689-1710