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Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept®S) in a Swine Model

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Abstract

Background

This study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model.

Methods

In four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed.

Results

Hepatic arterial embolization using DSMs was technically successful in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 ± 6.1 min (range, 26–39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis.

Conclusion

Temporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study.

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References

  1. Murata S, Mine T, Ueda T, Nakazawa K, Onozawa S, Yasui D, Kumita S (2013) Transcatheter arterial chemoembolization based on hepatic hemodynamics for hepatocellular carcinoma. Sci World J 2013:479805

  2. de Baere T, Deschamps F (2011) Arterial therapies of colorectal cancer metastases to the liver. Abdom Imaging 36(6):661–670

    Article  PubMed  Google Scholar 

  3. Goin JE, Salem R, Carr BI, Dancey JE, Soulen MC, Geschwind JF et al (2005) Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities. J Vasc Interv Radiol 16:205–213

    Article  PubMed  Google Scholar 

  4. Salem R, Lewandowski RJ, Atassi B, Gordon SC, Gates VL, Barakat O et al (2005) Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol 16:1627–1639

    Article  PubMed  Google Scholar 

  5. Lencioni R, Petruzzi P, Crocetti L (2013) Chemoembolization of hepatocellular carcinoma. Semin Intervent Radiol 30:3–11

    Article  PubMed Central  PubMed  Google Scholar 

  6. Sueyoshi E, Hayashida T, Sakamoto I, Uetani M (2010) Vascular complications of hepatic artery after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. AJR Am J Roentgenol 195(1):245–252

    Article  PubMed  Google Scholar 

  7. Wiggermann P, Wohlgemuth WA, Heibl M, Vasilj A, Loss M, Schreyer AG, Stroszczynski C, Jung EM (2013) Dynamic evaluation and quantification of microvascularization during degradable starch microspheres transarterial chemoembolisation (DSM-TACE) of HCC lesions using contrast enhanced ultrasound (CEUS): a feasibility study. Clin Hemorheol Microcirc 53(4):337–348

    CAS  PubMed  Google Scholar 

  8. Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146(6):873–887

    Article  CAS  PubMed  Google Scholar 

  9. Nishiofuku H, Tanaka T, Matsuoka M, Otsuji T, Anai H, Sueyoshi S, Inaba Y, Koyama F, Sho M, Nakajima Y, Kichikawa K (2013) Transcatheter arterial chemoembolization using cisplatin powder mixed with degradable starch microspheres for colorectal liver metastases after FOLFOX failure: results of a phase I/II study. J Vasc Interv Radiol 24(1):56–65

    Article  PubMed  Google Scholar 

  10. Murata S, Tajima H, Ichikawa K, Onozawa S, Wang J, Kumita S, Nomura K (2008) Oily chemoembolization combined with degradable starch microspheres for HCC with cirrhosis. Hepatogastroenterology 55(84):1041–1046

    PubMed  Google Scholar 

  11. Meyer C, Pieper CC, Ezziddin S, Wilhelm KE, Schild HH, Ahmadzadehfar H (2014) Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours. Eur J Nucl Med Mol Imaging 41(2):231–237

    Article  CAS  PubMed  Google Scholar 

  12. Wang J, Murata S, Kumazaki T (2006) Liver microcirculation after hepatic artery embolization with degradable starch microspheres in vivo. World J Gastroenterol 12:4214–4218

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Forsberg JO (1978) Transient blood flow reduction induced by intra-arterial injection of degradable starch microspheres: experiments on rats. Acta Chir Scand 144:275–281

    CAS  PubMed  Google Scholar 

  14. Yamasaki T, Hamabe S, Saeki I, Harima Y, Yamaguchi Y, Uchida K, Terai S, Sakaida I (2011) A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial. J Gastroenterol 46(3):359–366

    Article  CAS  PubMed  Google Scholar 

  15. Pohlen U, Buhr HJ, Berger G, Ritz JP, Holmer C (2012) Hepatic arterial infusion (HAI) with PEGylated liposomes containing 5-FU improves tumor control of liver metastases in a rat model. Invest New Drugs 30:927–935

    Article  CAS  PubMed  Google Scholar 

  16. Chang D, Jenkins SA, Grime SJ, Nott DM, Cooke T (1996) Increasing hepatic arterial flow to hypovascular hepatic tumours using degradable starch microspheres. Br J Cancer 73(8):961–965

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Ritz JP, Lehmann K, Isbert C, Roggan A, Germer CT, Buhr HJ (2005) Effectivity of laser-induced thermotherapy: in vivo comparison of arterial microembolization and complete hepatic inflow occlusion. Lasers Surg Med 36(3):238–244

    Article  PubMed  Google Scholar 

  18. Ritz JP, Lehmann KS, Zurbuchen U, Wacker F, Brehm F, Isbert C, Germer CT, Buhr HJ, Holmer C (2007) Improving laser-induced thermotherapy of liver metastases: effects of arterial microembolization and complete blood flow occlusion. Eur J Surg Oncol 33(5):608–615

    Article  PubMed  Google Scholar 

  19. Monbaliu D, Crabbé T, Roskams T, Fevery J, Verwaest C, Pirenne J (2005) Livers from non–heart-beating donors tolerate short periods of warm ischemia. Transplantation 79(9):1226–1230

    Article  PubMed  Google Scholar 

  20. Wiggermann P, Heibl M, Niessen C, Muller-Wille R, Gossmann H, Uller W et al (2012) Degradable starch microspheres transarterial chemoembolisation (DSM-TACE) of HCC: dynamic contrast-enhanced ultrasonography (DCE-US) based evaluation of therapeutic efficacy using a novel perfusion software. Clin Hemorheol Microcirc 52:123–129

    CAS  PubMed  Google Scholar 

  21. Tanabe T, Fujii S (2000) Investigation of basal levels of blood biochemistry in swine. Annual Report of Kyoto City Institute of Health and Environmental Sciences, vol 66. Kyōto-shi: Dō Kenkyūjo, Kyoto, Japan, pp 89–96

  22. Latimer KS, Mahaffey EA, Prasse KW (2003) Duncan and Prasse’s veterinary laboratory medicine: clinical pathology, 4th edn. Wiley-Blackwell, Ames

    Google Scholar 

  23. Yipintsoi T, Dobbs WA Jr, Scanlon PD, Knopp TJ, Bassingthwaighte JB (1973) Regional distribution of diffusible tracers and carbonized microspheres in the left ventricle of isolated dog hearts. Circ Res 33(5):573–587

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Domenech RJ, Hoffman JI, Noble MI, Saunders KB, Henson JR, Subijanto S (1969) Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs. Circ Res 25(5):581–596

    Article  CAS  PubMed  Google Scholar 

  25. Bastian P, Bartkowski R, Köhler H, Kissel T (1998) Chemo-embolization of experimental liver metastases: part I. distribution of biodegradable microspheres of different sizes in an animal model for the locoregional therapy. Eur J Pharm Biopharm 46(3):243–254

    Article  CAS  PubMed  Google Scholar 

  26. Yamada T, Nakamura K, Matsuo R, Murata K, Usuki N, Kaminou T, Tsubakimoto M, Manabe T, Takashima S, Nakatsuka H et al (1988) Experimental and clinical studies on degradable starch microspheres (DSM) in the treatment of hepatic neoplasms. Gan To Kagaku Ryoho 15(8 Pt 2):2617–2620

    CAS  PubMed  Google Scholar 

  27. Furuse J, Ishii H, Satake M, Onaya H, Nose H, Mikami S, Sakai H, Mera K, Maru Y, Yoshino M (2003) Pilot study of transcatheter arterial chemoembolization with degradable starch microspheres in patients with hepatocellular carcinoma. Am J Clin Oncol 26(2):159–164

    Article  CAS  PubMed  Google Scholar 

  28. Kan Z, Madoff DC (2008) Liver anatomy: microcirculation of the liver. Semin Intervent Radiol 25(2):77–85

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of interest

Claus C. Pieper, Carsten Meyer, Brigitte Vollmar, Karlheinz Hauenstein, Hans H. Schild, and Kai E. Wilhelm have no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Claus C. Pieper, Carsten Meyer & Hans H. Schild

  2. Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, 18057, Rostock, Germany

    Brigitte Vollmar

  3. Department of Diagnostic and Interventional Radiology, University of Rostock, Schillingallee 35, 18057, Rostock, Germany

    Karlheinz Hauenstein

  4. Evangelische Kliniken Bonn, Johanniter Hospital, Johanniterstraße 3-5, 53113, Bonn, Germany

    Kai E. Wilhelm

Authors
  1. Claus C. Pieper
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  2. Carsten Meyer
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Correspondence to Claus C. Pieper.

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Pieper, C.C., Meyer, C., Vollmar, B. et al. Temporary Arterial Embolization of Liver Parenchyma with Degradable Starch Microspheres (EmboCept®S) in a Swine Model. Cardiovasc Intervent Radiol 38, 435–441 (2015). https://doi.org/10.1007/s00270-014-0966-2

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  • DOI: https://doi.org/10.1007/s00270-014-0966-2

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