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Nitroglycerine use in transcatheter arterial (chemo)embolization in patients with hepatocellular carcinoma and dual-energy CT assessment of Lipiodol retention

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Abstract

Objectives

To investigate whether the addition of nitroglycerine to transcatheter arterial (chemo)embolization (TAE/TACE) can increase the delivery and effectiveness of TAE/TACE in patients with hepatocellular carcinoma (HCC) by dual-energy CT.

Methods

HCC patients (BCLC stage A or B) were randomized to (n = 51) or not to (n = 50) receive nitroglycerine and an emulsion of Lipiodol with or without doxorubicin, followed by embolization with Gelfoam pledgets. Dual-energy CT was performed pre- and 1 to 3 months post-embolization to assess changes in tumour diameter and Lipiodol levels in tumours.

Results

Median tumour diameter decreased from baseline in both groups with and without nitroglycerine (7.11 % vs. 12.5 %, respectively), and was statistically significant in the group receiving nitroglycerine (P = 0.023). There was no difference between the two groups in disease response (P = 0.237). The concentration and percentage of Lipiodol retained in tumours were significantly greater in patients treated with nitroglycerine compared to those without (median concentration 15.05 mg/mL vs. 4.40 mg/mL, respectively, P < 0.001; median percentage 82.01 % vs. 36.75 %, respectively, P < 0.001).

Conclusions

Nitroglycerine increased delivery of the Lipiodol emulsion via TAE/TACE to HCC tumours with significant tumour reduction. Dual-energy CT can accurately quantify the amount of Lipiodol deposited in tumours.

Key Points

• Nitroglycerine improves delivery of tumour-targeted therapy via enhanced permeability and retention.

• In hepatocellular carcinoma, nitroglycerine added to TAE/TACE showed greater tumour reduction.

• Dual-energy CT can reliably quantify the amount of Lipiodol in TAE/TACE.

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References

  1. Bosch FX, Ribes J, Díaz M, Cléries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:S5–S16

    Article  PubMed  Google Scholar 

  2. Thomas MB, Jaffe D, Choti MM et al (2010) Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting. J Clin Oncol 28:3994–4005

    Article  PubMed  Google Scholar 

  3. National Cancer Institute (2011) Adult primary liver cancer treatment (PDQ®) health profession version. http://www.cancer.gov/cancertopics/types/liver. Accessed 5 Nov 2011

  4. Rougier P, Mitry, Barbare JC, Taieb J (2007) Hepatocellular carcinoma (HCC): an update. Semin Oncol 34:S12–S20

    Article  PubMed  CAS  Google Scholar 

  5. Ramsey DE, Kernagis LY, Soulen MC, Geschwind JF (2002) Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 13:S211–S221

    Article  PubMed  Google Scholar 

  6. Lencioni R (2010) Loco-regional treatment of hepatocellular carcinoma in the era of molecular targeted therapies. Oncology 78:107–112

    Article  PubMed  Google Scholar 

  7. Konno T, Maeda H, Iwai K et al (1983) Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report. Eur J Cancer Clin Oncol 19:1053–1065

    Article  PubMed  CAS  Google Scholar 

  8. Konno T, Maeda H, Iwai K et al (1984) Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium. Cancer 54:2367–2374

    Article  PubMed  CAS  Google Scholar 

  9. Jinno K, Moriwaki S, Tanada M et al (1992) Clinicopathological study on combination therapy consisting of arterial infusion of lipiodol-dissolved SMANCS and transcatheter arterial embolization for hepatocellular carcinoma. Cancer Chemother Pharmacol 31:S7–S12

    Article  PubMed  Google Scholar 

  10. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392

    PubMed  CAS  Google Scholar 

  11. Maeda H, Sawa T, Konno T (2001) Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 74:47–61

    Article  PubMed  CAS  Google Scholar 

  12. Maeda H (2001) SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy. Adv Drug Deliv Rev 46:169–185

    Article  PubMed  CAS  Google Scholar 

  13. Nagamitsu A, Greish K, Maeda H (2009) Elevating blood pressure as a strategy to increase tumor-targeted delivery of macromolecular drug SMANCS: cases of advanced solid tumors. Jpn J Clin Oncol 9:756–766

    Article  Google Scholar 

  14. Maeda H, Noguchi Y, Sato K, Akaike T (1994) Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor. Jpn J Cancer Res 85:331–334

    Article  PubMed  CAS  Google Scholar 

  15. Wu J, Akaike T, Maeda H (1998) Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger. Cancer Res 58:159–165

    PubMed  CAS  Google Scholar 

  16. Seki T, Fang J, Maeda H (2009) Enhanced delivery of macromolecular antitumor drugs to tumors by nitroglycerin application. Cancer Sci 100:2426–2430

    Article  PubMed  CAS  Google Scholar 

  17. Stoeckelhuber BM, Suttmann I, Stoeckelhuber M, Kueffer G (2003) Comparison of the vasodilating effect of nitroglycerin, verapamil, and tolazoline in hand angiography. J Vasc Interv Radiol 14:749–754

    Article  PubMed  Google Scholar 

  18. Bilbao R, Bustos M, Alzuguren P, Pajares et al (2000) A blood-tumor barrier limits gene transfer to experimental liver cancer: the effect of vasoactive compounds. Gene Ther 7:1824–1832

    Article  PubMed  CAS  Google Scholar 

  19. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63:136–151

    Article  PubMed  CAS  Google Scholar 

  20. Pleguezuelo M, Marelli L, Misseri M et al (2008) TACE versus TAE as therapy for hepatocellular carcinoma. Expert Rev Anticancer Ther 8:1623–1641

    Article  PubMed  CAS  Google Scholar 

  21. Graser A, Johnson TR, Chandarana H, Macari M (2009) Dual energy CT: preliminary observations and potential clinical applications in the abdomen. Eur Radiol 19:13–23

    Article  PubMed  Google Scholar 

  22. Zhang LJ, Peng J, Wu SY et al (2010) Liver virtual non-enhanced CT with dual-source, dual-energy CT: a preliminary study. Eur Radiol 20:2257–2264

    Article  PubMed  Google Scholar 

  23. Oliveri RS, Wetterslev J, Gluud C (2011) Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 16:CD004787

    Google Scholar 

  24. Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25

    Article  PubMed  Google Scholar 

  25. Marelli L, Shusang V, Buscombe JR et al (2009) Transarterial injection of (131)I-lipiodol, compared with chemoembolization, in the treatment of unresectable hepatocellular cancer. J Nucl Med 50:871–877

    Article  PubMed  CAS  Google Scholar 

  26. Hou YC, Janczuk A, Wang PG (1999) Current trends in the development of nitric oxide donors. Curr Pharm Des 5:417–441

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Diagnostic Radiology, National Cheng-Kung University Hospital, No. 138 Sheng Li Road, Tainan, Taiwan, 704, Republic of China

    Yi-Sheng Liu, Ming-Tsung Chuang, Yi-Shan Tsai & Hong-Ming Tsai

  2. Liver Cancer Collaborative Oncology Group (LCCOG), National Cheng-Kung University Hospital, No. 138 Sheng Li Road, Tainan, Taiwan, 704, Republic of China

    Yi-Sheng Liu, Hong-Ming Tsai & Xi-Zhang Lin

  3. Department of Internal Medicine, National Cheng-Kung University Hospital, No. 138 Sheng Li Road, Tainan, Taiwan, 704, Republic of China

    Xi-Zhang Lin

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  1. Yi-Sheng Liu
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  2. Ming-Tsung Chuang
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  3. Yi-Shan Tsai
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  4. Hong-Ming Tsai
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Correspondence to Xi-Zhang Lin.

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Liu, YS., Chuang, MT., Tsai, YS. et al. Nitroglycerine use in transcatheter arterial (chemo)embolization in patients with hepatocellular carcinoma and dual-energy CT assessment of Lipiodol retention. Eur Radiol 22, 2193–2200 (2012). https://doi.org/10.1007/s00330-012-2484-4

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  • DOI: https://doi.org/10.1007/s00330-012-2484-4

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