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Effectiveness of Transarterial Embolization in Treatment of Symptomatic Hepatic Hemangiomas: Systematic Review and Meta-analysis

CardioVascular and Interventional Radiology volume 44, pages 80–91 (2021)Cite this article

Abstract

Purpose

To evaluate the current evidence for the effectiveness of transarterial embolization (TAE) in treatment of symptomatic hepatic hemangiomas.

Materials and Methods

A systematic literature review was conducted in PubMed, CINAHL and Scopus databases to identify studies of hepatic hemangiomas treated with transarterial embolization. Main outcome was defined as the mean difference between pre- and post-TAE hemangioma diameters. Treatment agents were categorized as Lipiodol based [bleomycin (L + BE), pingyangmycin (L + PYG) or ethanol (L + ethanol)] and non-Lipiodol based (polyvinyl-alcohol-only). Conventional random-effect meta-analysis technique was applied to analyze data.

Results

Of 3080 initially inspected publications, 21 studies were included in the meta-analysis comprising of 1450 patients with total of 1871 hemangiomas (36.2% male, mean age: 46.3 ± 3.6 years). One hundred and twenty-six, 1666, 41 and 38 lesions were treated with L + BE, L + PYG, L + ethanol and PVA, respectively. Median follow-up time after embolization was 12 months. Lipiodol-based treatments showed significant effect in reducing hemangioma size after TAE compared to PVA (P < 0.001). Pooled diameter reduction (cm) (95% confidence interval) was − 4.37( − 5.32, − 3.42), − 4.70( − 5.70, − 3.71), − 0.93( − 2.02, 0.16) for overall TAE treatment, Lipiodol-based and non-Lipiodol-based treatments, respectively. Main complications included post-embolization syndrome and transient liver enzyme elevation (pooled incidence for Lipiodol-based and non-Lipiodol-based techniques: 36% and 33%; and 37% and 0, respectively). No fatal complications were reported. Symptomatic improvement was reported in 63.3%–100% of the cases with majority of studies (15/21) reporting improvement in all cases (pooled response rate: 98%).

Conclusions

Transarterial embolization with bleomycin, pingyangmycin or ethanol in combination with Lipiodol is safe and associated with reduced size of hemangiomas resulting in symptoms alleviation.

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References

  1. Akhlaghpoor S, Torkian P, Golzarian J. Transarterial bleomycin–lipiodol embolization (b/le) for symptomatic giant hepatic hemangioma. CardioVasc Interv Radiol. 2018;41(11):1674–82.

    Article  Google Scholar 

  2. Bennett JM, Reich SD. Drugs five years later: bleomycin. Ann Intern Med. 1979;90(6):945–8.

    Article  CAS  PubMed  Google Scholar 

  3. Blackburn H, West S. Management of postembolization syndrome following hepatic transarterial chemoembolization for primary or metastatic liver cancer. Cancer Nurs. 2016;39(5):E1–8.

    Article  PubMed  Google Scholar 

  4. Bozkaya H, Cinar C, Besir FH, Parildar M, Oran I. Minimally invasive treatment of giant haemangiomas of the liver: embolisation with bleomycin. Cardiovasc Intervent Radiol. 2014;37(1):101–7.

    Article  PubMed  Google Scholar 

  5. Bozkaya H, Cinar C, Ünalp ÖV, Parildar M, Oran I. Unusual treatment of Kasabach-Merritt syndrome secondary to hepatic hemangioma: embolization with bleomycin. Wien Klin Wochenschr. 2015;127(11–12):488–90.

    Article  CAS  PubMed  Google Scholar 

  6. Duxbury MS, Garden OJ. Giant haemangioma of the liver: observation or resection? Digestive surgery. 2010;27(1):7–11.

    Article  PubMed  Google Scholar 

  7. Fan SL, Tong XQ, Wang J, Song L. Transarterial embolization for treatment of giant hepatic hemangiomas: an analysis of 46 cases. World Chin J Dig. 2013;21(20):1925–30.

    Article  Google Scholar 

  8. Filippiadis DK, Binkert C, Pellerin O, Hoffmann RT, Krajina A, Pereira PL. Cirse quality assurance document and standards for classification of complications: the cirse classification system. Cardiovasc Intervent Radiol. 2017;40(8):1141–6.

    Article  CAS  PubMed  Google Scholar 

  9. Firouznia K, Ghanaati H, Alavian SM, et al. Management of liver hemangioma using trans-catheter arterial embolization. Hepat. Mon. 2014;14(2):e25788.

    PubMed  PubMed Central  Google Scholar 

  10. Gao J, Ding X, Ke S, et al. Radiofrequency ablation in the treatment of large hepatic hemangiomas: a comparison of multitined and internally cooled electrodes. J Clin Gastroenterol. 2014;48(6):540–7.

    Article  CAS  PubMed  Google Scholar 

  11. Gao J, Ke S, Ding X-m, Zhou Y-m, Qian X-j, Sun W-b. Radiofrequency ablation for large hepatic hemangiomas: initial experience and lessons. Surgery. 2013;153(1):78–85.

    Article  PubMed  Google Scholar 

  12. Giavroglou C, Economou H, Ioannidis I. Arterial embolization of giant hepatic hemangiomas. Cardiovasc Intervent Radiol. 2003;26(1):92–6.

    Article  PubMed  Google Scholar 

  13. Hanks B, Suhocki P, DeLong D, et al. The efficacy and tolerability of transarterial chemo-embolization (TACE) compared with transarterial embolization (TAE) for patients with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2008;26(15_suppl):4595.

    Article  Google Scholar 

  14. He Y, Lan Y, Liu Y, et al. Pingyangmycin and bleomycin share the same cytotoxicity pathway. Molecules. 2016;21(7):862.

    Article  PubMed Central  CAS  Google Scholar 

  15. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions Version 5.1.0 [updated March 2011]. The cochrane collaboration. 2011.

  16. Ho H-Y, Wu T-H, Yu M-C, Lee W-C, Chao T-C, Chen M-F. Surgical management of giant hepatic hemangiomas: complications and review of the literature. Chang Gung Med J. 2012;35(1):70–8.

    PubMed  Google Scholar 

  17. Huang Y-D, Li P, Tong X, et al. Effects of bleomycin A5 on caspase-3, P53, bcl-2 expression and telomerase activity in vascular endothelial cells. Indian J Pharmacol. 2015;47(1):55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jiang XY, Xu K. The middle-long term effect of TAE with pingyangmycin-lipiodol emulsion for hepatic hemangioma. J Intervent Radiol. 2012;21(1):31–4.

    Google Scholar 

  19. Jin H. A preliminary approach to pathological and biochemical changes of the lungs injured by domestic pingyangmycinum. Zhonghua bing li xue za zhi = Chinese J Pathol. 1992;21(5):278–80.

    CAS  Google Scholar 

  20. Kirnap M, Boyvat F, Boyacioglu S, Hilmioglu F, Moray G, Haberal M. The effect of bleomycin embolization on symptomatic improvement and hemangioma size among patients with giant liver hemangiomas. Intl J Surg. 2018;12:12–6.

    Google Scholar 

  21. Lerner SM, Hiatt JR, Salamandra J, et al. Giant cavernous liver hemangiomas: effect of operative approach on outcome. Arch Surg. 2004;139(8):818–23.

    Article  PubMed  Google Scholar 

  22. Li HW, Chen DJ, He MJ, Lian H, Wang GY. Transcatheter arterial embolization and regional injection to treat the cavernous hemangioma of liver. Chin J Intervent Imaging Ther. 2007;4(3):192–5.

    CAS  Google Scholar 

  23. Li Y, Jia Y, Li S, et al. Transarterial chemoembolization of giant liver haemangioma: a multi-center study with 836 cases. Cell Biochem Biophys. 2015;73(2):469–72.

    Article  CAS  PubMed  Google Scholar 

  24. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS medicine. 2009;6(7):e1000100.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Luo Q, Zhao F. How to use bleomycin A5 for infantile maxillofacial haemangiomas: clinical evaluation of 82 consecutive cases. J Cranio-Maxillofac Surg. 2011;39(7):482–6.

    Article  Google Scholar 

  26. Malagari K, Alexopoulou E, Dourakis S, et al. Transarterial embolization of giant liver hemangiomas associated with Kasabach-Merritt syndrome: a case report. Acta Radiol. 2007;48(6):608–12.

    Article  CAS  PubMed  Google Scholar 

  27. Millis JM. Molina DC What is the best surgical method of addressing hepatic hemangiomas? difficult decisions in hepatobiliary and pancreatic surgery. Cham: Springer; 2016. p. 25–37.

    Book  Google Scholar 

  28. Park SY, Tak WY, Jung MK, et al. Symptomatic-enlarging hepatic hemangiomas are effectively treated by percutaneous ultrasonography-guided radiofrequency ablation. J Hepatol. 2011;54(3):559–65.

    Article  PubMed  Google Scholar 

  29. Phan SH, Kunkel SL. Lung cytokine production in bleomycin-induced pulmonary fibrosis. Exp Lung Res. 1992;18(1):29–43.

    Article  CAS  PubMed  Google Scholar 

  30. Season W, Wang W, Chen J, Wang G, Pay L, Wu J. Pingyangmycin iodized oil emulsion plus gelatin sponge particles embolization of hepatic hemangioma study of the efficacy of treatment intervention. Med J Chin Peoples Liberation Army. 2015;40(6):513–4.

    Google Scholar 

  31. Shin SW. The current practice of transarterial chemoembolization for the treatment of hepatocellular carcinoma. Korean J Radiol. 2009;10(5):425–34.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Singh RK, Kapoor S, Sahni P, Chattopadhyay TK. Giant haemangioma of the liver: is enucleation better than resection? Ann R Coll Surg Engl. 2007;89(5):490–3.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Srivastava D, Gandhi D, Seith A, Pande G, Sahni P. Transcatheter arterial embolization in the treatment of symptomatic cavernous hemangiomas of the liver: a prospective study. Abdom Imaging. 2001;26(5):510–4.

    Article  CAS  PubMed  Google Scholar 

  34. Srivastava DN, Gandhi D, Seith A, Pande GK, Sahni P. Transcatheter arterial embolization in the treatment of symptomatic cavernous hemangiomas of the liver: A prospective study. Abdom Imaging. 2001;26(5):510–4.

    Article  CAS  PubMed  Google Scholar 

  35. Suh JS, Shin KH, Na JB, Won JY, Hahn SB. Venous malformations: sclerotherapy with a mixture of ethanol and lipiodol. Cardiovasc Intervent Radiol. 1997;20(4):268–73.

    Article  CAS  PubMed  Google Scholar 

  36. Sullivan GM. Irb 101. J Grad Med Educ. 2011;3(1):5–6.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sun JH, Nie CH, Zhang YL, et al. Transcatheter arterial embolization alone for giant hepatic hemangioma. PLoS ONE. 2015;10(8):e0135158.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Szejnfeld D, Nunes TF, Fornazari VAV, et al. Transcatheter arterial embolization for unresectable symptomatic giant hepatic hemangiomas: single-center experience using a lipiodol-ethanol mixture. Radiol Bras. 2015;48(3):154–7.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tian JL, Du YH, Luo J, Li CL, Zhang LY. Changes of liver function and lesion size after transcatheter arterial chemoembolization of hepatic hemangiomas. Chin J Intervent Imaging Ther. 2010;7(3):273–7.

    Google Scholar 

  40. Toro A, Mahfouz A-E, Ardiri A, et al. What is changing in indications and treatment of hepatic hemangiomas. Ann Hepatol. 2014;13(4):327–39.

    Article  PubMed  Google Scholar 

  41. Vaidya S, Tozer KR, Chen J. An overview of embolic agents. Semin Intervent Radiol. 2008;25(3):204–15.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Wahab MA, El Nakeeb A, Ali MA, et al. Surgical management of giant hepatic hemangioma: single center’s experience with 144 patients. J Gastrointest Surg. 2018;22(5):849–58.

    Article  PubMed  Google Scholar 

  43. Wang BT, Liu ZY, Zhang JM. Interventional embolotherapy in treatment of liver hemangioma. Chin J Med Imaging Technol. 2014;30(4):549–51.

    Google Scholar 

  44. Wang JB, An X, Wang H, et al. Transcatheter arterial embolization with the mixture of ethanol and lipiodol for the treatment of hepatic cavernous hemangiomas. J Intervent Radiol. 2010;19(5):358–60.

    Google Scholar 

  45. Wang S, Gao J, Yang M, et al. Intratumoral coagulation by radiofrequency ablation facilitated the laparoscopic resection of giant hepatic hemangioma: a surgical technique report of two cases. Oncotarget. 2017;8(31):52006.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Yamamoto T, Kawarada Y, Yano T, Noguchi T, Mizumoto R. Spontaneous rupture of hemangioma of the liver: treatment with transcatheter hepatic arterial embolization. Am J Gastroenterol. 1991;86(11):1645–9.

    CAS  PubMed  Google Scholar 

  47. Yue H, Qian J, Elner VM, et al. Treatment of orbital vascular malformations with intralesional injection of pingyangmycin. Br J Ophthalmol. 2013;97(6):739–45.

    Article  PubMed  Google Scholar 

  48. Zeng Q, Li Y, Chen Y, Ouyang Y, He X, Zhang H. Gigantic cavernous hemangioma of the liver treated by intra-arterial embolization with pingyangmycin-lipiodol emulsion: a multi-center study. Cardiovasc Intervent Radiol. 2004;27(5):481–5.

    Article  PubMed  Google Scholar 

  49. Zhang AZ, Cui Y, Yang CM. Observation of superselectively hepatic artery embolization treatment with pingyangmycin lipiodol emulsion for patients with liver cavernous hemangioma. Chin J Cancer Prev Treat. 2009;16(17):1349–50.

    Google Scholar 

  50. Zhang H, Zhao XJ. Mid-long term clinical effects of the 110 °C pingyangmycin-lipiodol chemoembolization for the treatment of liver hemangiomas. Chin J Intervent Imaging Ther. 2015;12(1):34–8.

    CAS  Google Scholar 

  51. Zhang W, Chen G, Ren JG, Zhao YF. Bleomycin induces endothelial mesenchymal transition through activation of mTOR pathway: a possible mechanism contributing to the sclerotherapy of venous malformations. Br J Pharmacol. 2013;170(6):1210–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang X, Xiong B, Yao Q, Zheng CS. Transcatheter arterial sclerotic embolization for the treatment of giant hepatic cavernous hemangioma: Analysis of the effectiveness and the safety. J Intervent Radiol. 2015;24(11):992–5.

    Google Scholar 

  53. Zhang X, Yan L, Li B, et al. Comparison of laparoscopic radiofrequency ablation versus open resection in the treatment of symptomatic-enlarging hepatic hemangiomas: a prospective study. Surg Endosc. 2016;30(2):756–63.

    Article  PubMed  Google Scholar 

  54. Zheng JW, Yang XJ, Wang YA, He Y, Ye WM, Zhang ZY. Intralesional injection of Pingyangmycin for vascular malformations in oral and maxillofacial regions: an evaluation of 297 consecutive patients. Oral Oncol. 2009;45(10):872–6.

    Article  CAS  PubMed  Google Scholar 

  55. Zhu K, Cao JM. Transcatheter selective hepatic arteriography combined with embolization therapy for the treatment of hepatic hemangiomas. J Intervent Radiol. 2010;19(12):985–7.

    Google Scholar 

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Acknowledgement

We appreciate Dr. Mehdi Yaseri’s assistance with meta-analysis.

Funding

This study was not supported by any funding.

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Authors and Affiliations

  1. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Pooya Torkian

  2. Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Jianjun Li

  3. Dotter Department of Interventional Radiology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97239, USA

    Jianjun Li, John A. Kaufman & Younes Jahangiri

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  1. Pooya Torkian
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Correspondence to Younes Jahangiri.

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Torkian, P., Li, J., Kaufman, J.A. et al. Effectiveness of Transarterial Embolization in Treatment of Symptomatic Hepatic Hemangiomas: Systematic Review and Meta-analysis. Cardiovasc Intervent Radiol 44, 80–91 (2021). https://doi.org/10.1007/s00270-020-02611-5

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  • DOI: https://doi.org/10.1007/s00270-020-02611-5

Keywords

  • Hepatic hemangioma
  • Transarterial embolization
  • Lipiodol
  • Bleomycin
  • Pingyangmycin