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Simultaneous Injection of Autologous Mononuclear Cells with TACE in HCC Patients; Preliminary Study

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Abstract

Background

The discovery of the pluripotent stem cells made the prospect of cell therapy and tissue regeneration a clinical reality, especially with the evidence of contribution of the stem cells of bone marrow origin in hepatic regeneration. Infusion of bone marrow stem cells before trans-arterial chemoembolization may help to increase liver volume and consequently increase hepatic reserve in patients with HCC, and this may improve the outcome of this procedure.

Materials and Methods

Four Child B class patients with unresectable hepatocellular carcinoma treated by transarterial chemoembolization were injected with autologous bone marrow mononuclear layer containing stem cell in the hepatic artery feeding the contralateral lobe of the liver in the same session, follow-up of the patients was done by doing liver profile and CT liver volumetry before the surgery and 3 months later.

Results

We observed that patients receiving stem cell therapy simultaneously with TACE had shown a significant improvement in biological and volumetric parameters of liver function compared to those historically reported of patients receiving TACE only who usually shows deterioration of liver parameters.

Conclusion

BMC infusion into the hepatic artery synchronized with TACE for patients with chronic liver disease complicated with HCC is safe, feasible, and demonstrated an improvement in both biological and radiological volumetric parameters.

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References

  1. Cha C, DeMatteo RP, Blumgart LH. Surgery and ablative therapy for hepatocellular carcinoma. J Clin Gastroenterol. 2002;35(5 Suppl 2):S130–7.

    PubMed  Google Scholar 

  2. Jemel A et al. Cancer statistics. CA Cancer J Clin. 2006;56(2):106–30.

    Google Scholar 

  3. Alsowmely AM, Hodgson HJ. Non-surgical treatment of hepatocellular carcinoma. Aliment Pharmacol Ther. 2002;16:1–15.

    CAS  PubMed  Google Scholar 

  4. Chen MS, Li JQ, Zhang YQ, Lu LX, Zhang WZ, Yuan YF, et al. High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma. World J Gastroenterol. 2002;8:74–8.

    PubMed  Google Scholar 

  5. Li L, Wu PH, Li JQ, Zhang WZ, Lin HG, Zhang YQ. Segmental transcatheter arterial embolization for primary hepatocellular carcinoma. World J Gastroenterol. 1998;4:511–12.

    PubMed  Google Scholar 

  6. Huo TI, Huang YH, Wu JC, Lee PC, Chang FY, Lee SD. Survival benefit of cirrhotic patients with hepatocellular carcinoma treated by percutaneous ethanol injection as a salvage therapy. Scand J Gastroenterol. 2002;37:350–5.

    PubMed  Google Scholar 

  7. Teratani T, Ishikawa T, Shiratori Y, Shiina S, Yoshida H, Imamura M, et al. Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy using percutaneous ethanol injection therapy. Cancer. 2002;95:816–23.

    CAS  PubMed  Google Scholar 

  8. Jiang HC, Liu LX, Piao DX, Xu J, Zheng M, Zhu AL, et al. Clinical short-term results of radiofrequency ablation in liver cancers. World J Gastroenterol. 2002;8:624–30.

    PubMed  Google Scholar 

  9. Allgaier HP, Galandi D, Zuber I, Blum HE. Radiofrequency thermal ablation of hepatocellular carcinoma. Dig Dis. 2001;19:301–10.

    CAS  PubMed  Google Scholar 

  10. Vogl TJ, Mack MG, Roggan A, Straub R, Eichler KC, Muller PK, et al. Internally cooled power laser for MR-guided interstitial laser-induced thermotherapy of liver lesions: initial clinical results. Radiology. 1998;209:381–5.

    CAS  PubMed  Google Scholar 

  11. Pacella CM, Bizzarri G, Cecconi P, Caspani B, Magnolfi F, Bianchini A, et al. Hepatocellular carcinoma: long-term results of combined treatment with laser thermal ablation and transcatheter arterial chemoembolization. Radiology. 2001;219:669–78.

    CAS  PubMed  Google Scholar 

  12. Itamoto T, Katayama K, Fukuda S, Fukuda T, Yano M, Nakahara H, et al. Percutaneous microwave coagulation therapy for primary or recurrent hepatocellular carcinoma: long-term results. Hepatogastroenterology. 2001;48:1401–5.

    CAS  PubMed  Google Scholar 

  13. Seki T, Tamai T, Nakagawa T, Imamura M, Nishimura A, Yamashiki N, et al. Combination therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation therapy for hepatocellular carcinoma. Cancer. 2000;89:1245–51.

    CAS  PubMed  Google Scholar 

  14. Dominguez J, Rafecas A, Torras J, Fabregat J, Guardiola J, Jaurrieta Qian J, et al. Combined interventional therapies of HCC. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer. 2000;88:50–7.

    PubMed  Google Scholar 

  15. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.

    PubMed  Google Scholar 

  16. Vogl TJ, Trapp M, Schroeder H, Mack M, Schuster A, Schmitt J, et al. Transarterial chemoembolization for hepatocellular carcinoma: volumetric and morphologic CT criteria for assessment of prognosis and therapeutic success—results from a liver transplantation center. Radiology. 2000;214:349–57.

    CAS  PubMed  Google Scholar 

  17. Bartolozzi C, Lencioni R, Caramella D, Vignali C, Cioni R, Mazzeo S, et al. Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology. 1995;197:812–18.

    CAS  PubMed  Google Scholar 

  18. Janis and Friends, Hepatitis C Support web site, Liver Cancer 2008.

  19. Biselli M, Andreone P, Gramenzi A, Trevisani F, Cursaro C, Rossi C, et al. Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case controlled study. Clin Gastroenterol Hepatol. 2005;3(9):918–25.

    PubMed  Google Scholar 

  20. National Institutes of Health. Clinical trials. Transcatheter arterial chemoembolization. http://www.clinicaltrials.gov/. Accessed 17 December 2007.

  21. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Hepatobiliary cancers. 2008. http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. Accessed 17 December 2007.

  22. Yamada T, Alpers DH, Lane L, Owyang C, Powell DW, editors. Textbook of gastroenterology. 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2003 May 1. Chapter 118.

  23. HAYES Medical Technology Directory™. Chemoembolization for Primary Liver Cancer. Lansdale, PA: HAYES, Inc.; ©2003 Winifred S. Hayes, Inc. Originally published Jul 12, 2002. Update Search Apr 9, 2007.

  24. Libbrecht L, Desmet V, Van Damme B, Roskams T. The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells. J Hepatol. 2000;33:76–84.

    CAS  PubMed  Google Scholar 

  25. Almeida-Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED. Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood. 2004;104:2582–90.

    CAS  PubMed  Google Scholar 

  26. Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40:1304–11.

    PubMed  Google Scholar 

  27. am Esch 2nd JS, Knoefel WT, Klein M, Ghodsizad A, Fürst G, Poll LW, et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells. 2005;23(4):463–70.

    PubMed  Google Scholar 

  28. Zhu AX, Duda DG, Sahani DV, Jain RK. Development of sunitinib in hepatocellular carcinoma: rationale, early clinical experience, and correlative studies. Cancer J 2009; 15(4): 263–68

    Google Scholar 

  29. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    PubMed  Google Scholar 

  30. Sacco R, Bertini M, Petruzzi P, Bertoni M, Bargellini I, Bresci G, et al. Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: a cohort study. World J Gastroenterol. 2009;15(15):1843–8.

    PubMed  Google Scholar 

  31. Hao MZ, Chen Q, Lin HL, Wu H, Chen Q-Z, Li J-C, Zheng J-X, Ye Y-B. Comparison of intra-arterial chemotherapy with gemcitabine or floxuridine followed by TACE with oxaliplatine. Hepatitis Monthly 2009; 9(4): 253–60

    Google Scholar 

  32. Fürst G, Schulte am Esch J, Poll LW, Hosch SB, Fritz LB, Klein M, et al. Portal vein embolization and autologous CD133+ bone marrow stem cells for liver regeneration: initial experience. Radiology. 2007;243:171–9.

    PubMed  Google Scholar 

  33. Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131:461–9.

    CAS  PubMed  Google Scholar 

  34. Huo T-I, Huang Y-H, Wu J-C, Lee P-C, Chang F-Y, Lee S-D. Induction of complete tumor necrosis may reduce intrahepatic metastasis and prolong survival in patients with hepatocellular carcinoma undergoing locoregional therapy: a prospective study. Ann Oncol. 2004;15(5):775–80.

    PubMed  Google Scholar 

  35. Chan AO, Yuen MF, Hui CK, et al. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer. 2002;94(6):1747–52.

    PubMed  Google Scholar 

  36. Fujii H, Hirose T, Oe S, et al. Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice. J Hepatol. 2002;36:653–9.

    CAS  PubMed  Google Scholar 

  37. Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 2000;31:235–40.

    CAS  PubMed  Google Scholar 

  38. De Silvestro G, Vicarioto M, Donadel C, et al. Mobilization of peripheral blood hematopoietic stem cells following liver resection surgery. Hepatogastroenterology. 2004;51:805–10.

    PubMed  Google Scholar 

  39. Forbes SJ, Vig P, Poulsom R, et al. Bone marrow-derived liver stem cells: their therapeutic potential. Gastroenterology. 2002;123:654–5.

    PubMed  Google Scholar 

  40. Ghodsizad A, Klein H-M, Borowski A, et al. Intraoperative isolation and processing of bone marrow derived stem cell. Cytotherapie. 2004;6:523–6.

    CAS  Google Scholar 

  41. Gehling UM, Willems M, Schlagner K, et al. Partial hepatectomy induces mobilization of a distinct population of progenitor cells in healthy liver donors. J Hepatol. 2004;40:19.

    Google Scholar 

  42. Wang X, Ge S, McNamara G, et al. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood. 2003;101:4201–8.

    CAS  PubMed  Google Scholar 

  43. Sakaida I. Autologous bone marrow cell infusion therapy for liver cirrhosis. J Gastroenterol Hepatol 2008; 23(9): 1349–53

    Google Scholar 

  44. Kallis YN, Alison MR, Forbes SJ. Bone marrow stem cells and liver disease. Gut 2007;56: 716–24

    Google Scholar 

  45. Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 1995;16(4):557–64.

    CAS  PubMed  Google Scholar 

  46. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol. 2000;18(2):307–16.

    CAS  PubMed  Google Scholar 

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Correspondence to Alaa Ismail.

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Ismail, A., AlDorry, A., Shaker, M. et al. Simultaneous Injection of Autologous Mononuclear Cells with TACE in HCC Patients; Preliminary Study. J Gastrointest Canc 42, 11–19 (2011). https://doi.org/10.1007/s12029-010-9218-0

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