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Drug-eluting stent in malignant biliary obstruction

Abstract

Introduction

In unresectable malignant bile duct obstruction, endoscopic stent insertion is the treatment of choice. However, the current stent allows only mechanical palliation of the obstruction, and has no anti-tumor effect. Currently, in the vascular field, the drug-eluting stent (DES) is very highly favored.

Material and methods

The requirements for a DES in a non-vascular tract, such as the bile duct, are far different from those of a DES to be used in the vascular tract. The non-vascular DES must suppress tumor proliferation as well as mucosal hyperplasia. For example, the non-vascular stent might be covered with a membrane that gradually releases a chemo-agent. We do not have much experience with DES in the bile duct. Nonetheless, we are continuously testing many anti-tumor agents in animal and human studies.

Conclusion

We expect and hope DES will work effectively for tumor cells in diverse ways and, more importantly, will prolong stent patency and the patients’ survival periods. But considerable investigation and a clinical study of DES will be required to achieve these goals.

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References

  1. Machan L, Jessurun L, Hunter W, Arsenault L. Angiogenesis inhibitor-coated metallic stents in the porcine bile duct: prevention of benign reactive overgrowth. Radiology. 1995;197(Suppl 1):241.

    Google Scholar 

  2. Machan L, Hunter W. Angiogenesis inhibition as a means to prevent stent overgrowth. J Vasc Interv Radiol. 1997;8(Suppl 1):198–9.

    Google Scholar 

  3. Manifold DK, Cowling M, Maynard N, Machan L, Mason R, Adam A. Paclitaxel coated stents in oesophageal adenocarcinoma. Cardiovasc Intervent Radiol. 1998;21:S129.

    Article  Google Scholar 

  4. Mezawa S, Homma H, Sato T, Doi T, Miyanishi K, Takada K, et al. A study of carboplatin-coated tube for the unresectable cholangiocarcinoma. Hepatology. 2000;32:916.

    PubMed  Article  CAS  Google Scholar 

  5. Lee DH, Kang SG, Jeong S, Yoon CJ, Choi JA, Byun JN, et al. Local delivery system of immune modulating drug for unresectable adenocarcinoma: in vitro experimental study and in vivo animal study. Cardiovascular and inter. Cardiovasc Intervent Radiol. 2006;29:832–7.

    PubMed  Article  Google Scholar 

  6. Uehara K, Ichida T, Sugahara S, Ishikawa T, Yamagiwa S, Yoshida Y, et al. Systemic administration of liposome-encapsulated OK-432 prolongs the survival of rats with hepatocellular carcinoma through the induction of IFN-gamma-producing hepatic lymphocytes. J Gastroenterol Hepatol. 2002;17:81–90.

    PubMed  Article  CAS  Google Scholar 

  7. Okamoto M, Oshikawa T, Tano T, Ohe G, Furuichi S, Nishikawa H, et al. Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432. J Natl Cancer Inst. 2003;95:316–26.

    PubMed  CAS  Article  Google Scholar 

  8. Nakahara S, Tsunoda T, Baba T, Asabe S, Tahara H. Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce cytotoxic T lymphocytes specific to tumor refection peptide. Cancer Res. 2003;63:4112–8.

    PubMed  CAS  Google Scholar 

  9. Takahashi K, Harauchi D, Kimura S, Saito S, Monden Y. OK-432 develops CTL and LAK activity in mononuclear cells from regional lymph nodes of lung cancer patients. Int J Immunopharmacol. 1998;20:375–88.

    PubMed  Article  CAS  Google Scholar 

  10. Oshikawa T, Okamoto M, Ohe G, Furuichi S, Nishikawa H, Ahmed S, et al. Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation, by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of KO-432: comparison between the TS-2-binding and TS-2-unbinding fraction. Int Immunopharmacol. 2003;3:643–55.

    PubMed  Article  CAS  Google Scholar 

  11. Nishikido M, Kiyohara T, Koga S, Shindo K, Matsuya F, Saito Y, et al. OK-432-induced killer cell activity: potential method for monitoring immunological complications after renal transplantation. Nephrol Dial Transplant. 2001;16:2067–71.

    PubMed  Article  CAS  Google Scholar 

  12. Itoh T, Ueda Y, Okugawa K, Fujiwara H, Fuji N, Yamashita T, et al. Streptococcal preparation OK-432 promotes functional maturation of human monocyte-derived dendritic cells. Cancer Immunol Immunother. 2003;52:207–14.

    PubMed  CAS  Google Scholar 

  13. Lee DK, Kim HS, Kim KS, Lee WJ, Kim HK, Won YH, et al. The effect on porcine bile duct of a metallic stent covered with a paclitaxel-incorporated membrane. Gastrointest Endosc. 2005;61:296–301.

    PubMed  Article  Google Scholar 

  14. Suk KT, Kim JW, Kim HS, Baik SK, Oh SJ, Lee SJ, et al. Human application of a metallic stent covered with a paclitaxel-incorporated membrane for malignant biliary obstruction: multicenter pilot study. Gastrointest Endosc. 2007;66:798–803.

    PubMed  Article  Google Scholar 

  15. Lee DH. Drug-eluting stent in gastrointestinal disease. Korean J Gastroenterol. 2007;49:294–9.

    PubMed  Google Scholar 

  16. Mani G, Feldman MD, Patel D, Agrawal CM. Coronary stents: a materials perspective. Biomaterials. 2007;28:1689–710.

    PubMed  Article  CAS  Google Scholar 

  17. Machan L. Clinical experience and applications of drug-eluting stents in the noncoronary vascular, bile duct and esophagus. Adv Drug Deliv Rev. 2006;58:447–62.

    PubMed  Article  CAS  Google Scholar 

  18. Rowinsky EK, Donehover RC. Paclitaxel (Taxol). N Engl J Med. 1995;332:1004–14.

    PubMed  Article  CAS  Google Scholar 

  19. Kalinowski M, Alfke H, Kleb B, Durfeld F, Joachim Wagner H. 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.

    PubMed  Article  CAS  Google Scholar 

  20. Dhanikula AB, Panchagnula R. Localized paclitaxel delivery. Int J Pharm. 1999;183:85–100.

    PubMed  Article  CAS  Google Scholar 

  21. Wassef W, Syred I. Designer stents: are we there yet? Gastrointest Endosc. 2007;66:804–8.

    PubMed  Article  Google Scholar 

  22. Folkman J, Hochberg M. Self-regulation of growth in three dimensions. J Exp Med. 1973;138:745–53.

    PubMed  Article  CAS  Google Scholar 

  23. Hunter WL, Burt HM, Machan L. Local delivery of chemotherapy: a supplement to existing cancer treatments. A case for surgical pastes and coated stents. Adv Drug Deliv Rev. 1997;26:199–207.

    PubMed  Article  CAS  Google Scholar 

  24. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery. J Controlled Release. 2001;70:157–67.

    Article  Google Scholar 

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Acknowledgments

The author thanks Professor D. H. Lee (Department of Internal Medicine, Inha University, Incheon, Korea) and Professor K. Na (Division of Biosciences and Technology, Catholic University, Bucheon, Korea) for their assistance in preparing this manuscript.

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Correspondence to Dong Ki Lee.

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Lee, D.K. Drug-eluting stent in malignant biliary obstruction. J Hepatobiliary Pancreat Surg 16, 628–632 (2009). https://doi.org/10.1007/s00534-009-0135-1

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  • DOI: https://doi.org/10.1007/s00534-009-0135-1

Keywords

  • Drug-eluting stent
  • Malignant biliary obstruction
  • Cholangiocarcinoma