Progress of Downstaging Therapy in Treating Hepatocellular Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HUANGZhi-ping , ZHANGPeng , WANGWen-tao ,  YANLü-nan

Department of Liver. Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

YANLü-nan, Email: yanlunan_688@163.com

Keywords：

Hepatocellular carcinoma; Downstaging therapy; Molecular target therapy; Liver transplantation; Liver resection

DOI：

10.7507/1007-9424.20140219

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summary the progress and status of downstaging therapy in treating hepatocellular carcinoma. Methods The related literatures were reviewed and analyzed by searching PubMed and MEDLINE. Results Although the clinical prognosis of advanced hepatocellular carcinoma was poor, the liver resection or liver transplantation after downstaging therapy could significantly improve the prognosis of patients. However, differences were existed if different downstaging therapies and selections of standard were used. Conclusion To improve the prognosis of patients with advanced hepatocellular carcinoma, the downstaging therapy should be ingeniously selected based on the situation of the patients.

Citation： HUANGZhi-ping, ZHANGPeng, WANGWen-tao, YANLü-nan. Progress of Downstaging Therapy in Treating Hepatocellular Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(7): 910-915. doi: 10.7507/1007-9424.20140219 Copy

1.	European Association For The Study Of The Liver1;European Organisation For Research And Treatment Of Cancer. EASLEORTC clinical practice guidelines:management of hepatocellular carcinoma[J]. J Hepatol, 2012, 56(4):908-943.
2.	戴朝六, 赵阳.原发性肝癌的综合治疗[J].中国普外基础与临床杂志, 2014, 21(2):133-137.
3.	El-Serag HB, Rudolph KL. Hepatocellular carcinoma:epidemiology and molecular carcinogenesis[J]. Gastroenterology, 2007, 132(7):2557-2576.
4.	Merican I, Guan R, Amarapuka D, et al. Chronic hepatitis B virus infection in Asian countries[J]. J Gastroenterol Hepatol, 2000, 15(12):1356-1361.
5.	Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma:the BCLC staging classification[J]. Semin Liver Dis, 1999, 19(3):329-338.
6.	Lau WY, Lai EC. Salvage surgery following downstaging of unresectable hepatocellular carcinoma--a strategy to increase resectability[J]. Ann Surg Oncol, 2007, 14(12):3301-3309.
7.	Alves RC, Alves D, Guz B, et al. Advanced hepatocellular carcinoma. Review of targeted molecular drugs[J]. Ann Hepatol, 2011, 10(1):21-27.
8.	Lau WY, Ho SK, Yu SC, et al. Salvage surgery following downstaging of unresectable hepatocellular carcinoma[J]. Ann Surg, 2004, 240(2):299-305.
9.	Lai EC, Lau WY. The continuing challenge of hepatic cancer in Asia[J]. Surgeon, 2005, 3(3):210-215.
10.	Borie F, Bouvier AM, Herrero A, et al. Treatment and prognosis of hepatocellular carcinoma:a population based study in France[J]. J Surg Oncol, 2008, 98(7):505-509.
11.	Toso C, Kneteman NM, James Shapiro AM, et al. The estimated number of patients with hepatocellular carcinoma selected for liver transplantation using expanded selection criteria[J]. Transpl Int, 2009, 22(9):869-875.
12.	Toso C, Mentha G, Kneteman NM, et al. The place of downstaging for hepatocellular carcinoma[J]. J Hepatol, 2010, 52(6): 930-936.
13.	Yao FY, Breitenstein S, Broelsch CE, et al. Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma?[J]. Liver Transplant, 2011, 17(S2):S109-S116.
14.	Tang ZY, Zhou XD, Ma ZC, et al. Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma[J]. HBPD Int, 2004, 3(4):495-498.
15.	Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. New Engl J Med, 1996, 334(11):693-700.
16.	Hanje AJ, Yao FY. Current approach to down-staging of hepatocellular carcinoma prior to liver transplantation[J]. Curr Opin Organ Tran, 2008, 13(3):234-240.
17.	Shi XJ, Jin X, Wang MQ, et al. Effect of resection following downstaging of unresectable hepatocelluar carcinoma by transcatheter arterial chemoembolization[J]. Chinese Med J(Engl), 2012, 125(2):197-202.
18.	金鑫, 史宪杰, 王茂强, 等.大肝癌58例患者经肝动脉插管化疗栓塞降期治疗体会[J].中华医学杂志, 2012, 91(14): 950-955.
19.	Kermiche-Rahali S, Di Fiore A, Drieux F, et al. Complete pathological regression of hepatocellular carcinoma with portal vein thrombosis treated with sorafenib[J]. World J Surg Oncol, 2013, 11(1):171.
20.	Kulik LM, Atassi B, Van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere^®) treatment of unresectable hepatocellular carcinoma:Downstaging to resection, RFA and bridge to transplantation[J]. J Surg Oncol, 2006, 94(7):572-586.
21.	Bruix J, Sherman M. Management of hepatocellular carcinoma: an update[J]. Hepatology, 2011, 53(3):1020-1022.
22.	Memon K, Lewandowski RJ, Riaz A, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma[J]. Recent Results Cancer Res, 2013, 190:207-224.
23.	Ibrahim SM, Kulik L, Baker T, et al. Treating and downstaging hepatocellular carcinoma in the caudate lobe with Yttrium-90 radioembolization[J]. Cardiovasc Inter Rad, 2012, 35(5):1094-1101.
24.	Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization[J]. Am J Transplant, 2009, 9(8):1920-1928.
25.	Khalaf H, Alsuhaibani H, Al-Sugair A, et al. Use of Yttrium-90 microsphere radioembolization of hepatocellular carcinoma as downstaging and bridge before liver transplantation:a case report[J]. Transplant Proc, 2010, 42(3):994-998.
26.	Majno PE, Adam R, Bismuth H, et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis[J]. Ann Surg, 1997, 226(6):688-703.
27.	WHO handbook for reporting results of cancer treatment[R]. Geneva (Switzerland):World Health Organization Offset Publication, 1979:No. 48.
28.	Graziadei IW, Sandmueller H, Waldenberger P, et al. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome[J]. Liver Transplant, 2003, 9(6):557-563.
29.	Otto G, Herber S, Heise M, et al. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma[J]. Liver Transplant, 2006, 12(8):1260-1267.
30.	Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors[J]. J Natl Cancer Inst, 2000, 92(3):205-216.
31.	Millonig G, Graziadei IW, Freund MC, et al. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma[J]. Liver Transplant, 2007, 13(2):272-279.
32.	Chapman WC, Doyle MBM, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation[J]. Ann Surg, 2008, 248(4):617-625.
33.	De Luna W, Sze DY, Ahmed A, et al. Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation[J]. Am J Transplant, 2009, 9(5):1158-1168.
34.	Di Benedetto F, Tarantino G, Montalti R, et al. Laparoscopic radiofrequency ablation in the caudate lobe for hepatocellular carcinoma before liver transplantation[J]. J Laparoendosc Adv Surg Tech A, 2012, 22(4):400-402.
35.	Zanus G, Boetto R, Gringeri E, et al. Microwave thermal ablation for hepatocarcinoma:six liver transplantation cases[J]. Transplant Proc, 2011, 43(4):1091-1094.
36.	Yu CY, Ou HY, Huang TL, et al. Hepatocellular carcinoma downstaging in liver transplantation[J]. Transplant Proc, 2012, 44(2):412-414.
37.	Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma:expansion of the tumor size limits does not adversely impact survival[J]. Hepatology, 2001, 33(6): 1394-1403.
38.	Yao FY, Kerlan RK, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation:An intention-to-treat analysis[J]. Hepatology, 2008, 48(3):819-827.
39.	Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma:results of down-staging in patients initially outside the Milan selection criteria[J]. Am J Transplant, 2008, 8(12):2547-2557.
40.	Lei JY, Yan LN. Comparison between living donor liver transplantation recipients who met the Milan and UCSF criteria after successful downstaging therapies[J]. J Gastrointest Surg, 2012, 16(11):2120-2125.
41.	Izumi N. Recent advances of radiofrequency ablation for early hepatocellular carcinoma[J]. J Gastroen Hepatol, 2011, 26(Suppl 1):115-122.
42.	de Baère T, Risse O, Kuoch V, et al. Adverse events during radiofrequency treatment of 582 hepatic tumors[J]. Am J Roentgenol, 2003, 181(3):695-700.
43.	Choi D, Lim HK, Kim MJ, et al. Liver abscess after percutaneous radiofrequency ablation for hepatocellular carcinomas:frequency and risk factors[J]. Am J Roentgenol, 2005, 184(6): 1860-1867.
44.	Elias D, Di Pietroantonio D, Gachot B, et al. Liver abscess after radiofrequency ablation of tumors in patients with a biliary tract procedure[J]. Gastroenterol Clin Biol, 2006, 30(6-7):823-827.
45.	Jansen MC, van Duijnhoven FH, van Hillegersberg R, et al. Adverse effects of radiofrequency ablation of liver tumours in the Netherlands[J]. Brit J Surg, 2005, 92(10):1248-1254.
46.	Llovet JM, Vilana R, Brú C, et al. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma[J]. Hepatology, 2001, 33(5):1124-1129.
47.	Latteri F, Sandonato L, Di Marco V, et al. Seeding after radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis:a prospective study[J]. Digest Liver Dis, 2008, 40(8): 684-689.
48.	Sun Z, Li G, Ai X, et al. Hepatic and biliary damage after transarterial chemoembolization for malignant hepatic tumors:incidence, diagnosis, treatment, outcome and mechanism[J]. Crit Rev Oncol Hematol, 2011, 79(2):164-174.
49.	Buijs M, Vossen JA, Frangakis C, et al. Nonresectable Hepatocellular carcinoma:long-term toxicity in patients treated with transarterial chemoembolization--single-center experience1[J]. Radiology, 2008, 249(1):346-354.
50.	Lu W, Li YH, Yu ZJ, et al. A comparative study of damage to liver function after TACE with use of low-dose versus conventionaldose of anticancer drugs in hepatocellular carcinoma[J]. Hepatogastroenterology, 2007, 54(77):1499-1502.
51.	Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma[J]. Hepatology, 2002, 35(5):1164-1171.
52.	Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics[J]. J Hepato, 2007, 46(3):474-481.
53.	Kim MH, Choi MS, Choi YS, et al. Clinical features of liver abscess developed after radiofrequency ablation and transarterial chemoembolization for hepatocellular carcinoma[J]. Korean J Hepato, 2006, 12(1):55-64.
54.	Xia J, Ren Z, Ye S, et al. Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer[J]. Eur J Radiol, 2006, 59(3):407-412.
55.	Tarazov PG, Polysalov VN, Prozorovskij KV, et al. Ischemic complications of transcatheter arterial chemoembolization in liver malignancies[J]. Acta Radiol, 2000, 41(2):156-160.
56.	Park WK, Chang JC, Lee HZ, et al. A case of resection of biloma with hepatocellular carcinoma after embolization[J]. Taehan Kan Hakhoe Chi, 2002, 8(3):331-335.
57.	Sakamoto I, Iwanaga S, Nagaoki K, et al. Intrahepatic biloma formation (bile duct necrosis) after transcatheter arterial chemoembolization[J]. Am J Roentgenol, 2003, 181(1):79-87.
58.	Sergio A, Cristofori C, Cardin R, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness[J]. Am J Gastroenterol, 2008, 103(4):914-921.
59.	Nowak AK, Chow PKH, Findlay M. Systemic therapy for advanced hepatocellular carcinoma:a review[J]. Eur J Cancer, 2004, 40(10):1474-1484.

1. European Association For The Study Of The Liver1;European Organisation For Research And Treatment Of Cancer. EASLEORTC clinical practice guidelines:management of hepatocellular carcinoma[J]. J Hepatol, 2012, 56(4):908-943.
2. 戴朝六, 赵阳.原发性肝癌的综合治疗[J].中国普外基础与临床杂志, 2014, 21(2):133-137.
3. El-Serag HB, Rudolph KL. Hepatocellular carcinoma:epidemiology and molecular carcinogenesis[J]. Gastroenterology, 2007, 132(7):2557-2576.
4. Merican I, Guan R, Amarapuka D, et al. Chronic hepatitis B virus infection in Asian countries[J]. J Gastroenterol Hepatol, 2000, 15(12):1356-1361.
5. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma:the BCLC staging classification[J]. Semin Liver Dis, 1999, 19(3):329-338.
6. Lau WY, Lai EC. Salvage surgery following downstaging of unresectable hepatocellular carcinoma--a strategy to increase resectability[J]. Ann Surg Oncol, 2007, 14(12):3301-3309.
7. Alves RC, Alves D, Guz B, et al. Advanced hepatocellular carcinoma. Review of targeted molecular drugs[J]. Ann Hepatol, 2011, 10(1):21-27.
8. Lau WY, Ho SK, Yu SC, et al. Salvage surgery following downstaging of unresectable hepatocellular carcinoma[J]. Ann Surg, 2004, 240(2):299-305.
9. Lai EC, Lau WY. The continuing challenge of hepatic cancer in Asia[J]. Surgeon, 2005, 3(3):210-215.
10. Borie F, Bouvier AM, Herrero A, et al. Treatment and prognosis of hepatocellular carcinoma:a population based study in France[J]. J Surg Oncol, 2008, 98(7):505-509.
11. Toso C, Kneteman NM, James Shapiro AM, et al. The estimated number of patients with hepatocellular carcinoma selected for liver transplantation using expanded selection criteria[J]. Transpl Int, 2009, 22(9):869-875.
12. Toso C, Mentha G, Kneteman NM, et al. The place of downstaging for hepatocellular carcinoma[J]. J Hepatol, 2010, 52(6): 930-936.
13. Yao FY, Breitenstein S, Broelsch CE, et al. Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma?[J]. Liver Transplant, 2011, 17(S2):S109-S116.
14. Tang ZY, Zhou XD, Ma ZC, et al. Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma[J]. HBPD Int, 2004, 3(4):495-498.
15. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis[J]. New Engl J Med, 1996, 334(11):693-700.
16. Hanje AJ, Yao FY. Current approach to down-staging of hepatocellular carcinoma prior to liver transplantation[J]. Curr Opin Organ Tran, 2008, 13(3):234-240.
17. Shi XJ, Jin X, Wang MQ, et al. Effect of resection following downstaging of unresectable hepatocelluar carcinoma by transcatheter arterial chemoembolization[J]. Chinese Med J(Engl), 2012, 125(2):197-202.
18. 金鑫, 史宪杰, 王茂强, 等.大肝癌58例患者经肝动脉插管化疗栓塞降期治疗体会[J].中华医学杂志, 2012, 91(14): 950-955.
19. Kermiche-Rahali S, Di Fiore A, Drieux F, et al. Complete pathological regression of hepatocellular carcinoma with portal vein thrombosis treated with sorafenib[J]. World J Surg Oncol, 2013, 11(1):171.
20. Kulik LM, Atassi B, Van Holsbeeck L, et al. Yttrium-90 microspheres (TheraSphere^®) treatment of unresectable hepatocellular carcinoma:Downstaging to resection, RFA and bridge to transplantation[J]. J Surg Oncol, 2006, 94(7):572-586.
21. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update[J]. Hepatology, 2011, 53(3):1020-1022.
22. Memon K, Lewandowski RJ, Riaz A, et al. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma[J]. Recent Results Cancer Res, 2013, 190:207-224.
23. Ibrahim SM, Kulik L, Baker T, et al. Treating and downstaging hepatocellular carcinoma in the caudate lobe with Yttrium-90 radioembolization[J]. Cardiovasc Inter Rad, 2012, 35(5):1094-1101.
24. Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization[J]. Am J Transplant, 2009, 9(8):1920-1928.
25. Khalaf H, Alsuhaibani H, Al-Sugair A, et al. Use of Yttrium-90 microsphere radioembolization of hepatocellular carcinoma as downstaging and bridge before liver transplantation:a case report[J]. Transplant Proc, 2010, 42(3):994-998.
26. Majno PE, Adam R, Bismuth H, et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis[J]. Ann Surg, 1997, 226(6):688-703.
27. WHO handbook for reporting results of cancer treatment[R]. Geneva (Switzerland):World Health Organization Offset Publication, 1979:No. 48.
28. Graziadei IW, Sandmueller H, Waldenberger P, et al. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome[J]. Liver Transplant, 2003, 9(6):557-563.
29. Otto G, Herber S, Heise M, et al. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma[J]. Liver Transplant, 2006, 12(8):1260-1267.
30. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors[J]. J Natl Cancer Inst, 2000, 92(3):205-216.
31. Millonig G, Graziadei IW, Freund MC, et al. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma[J]. Liver Transplant, 2007, 13(2):272-279.
32. Chapman WC, Doyle MBM, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation[J]. Ann Surg, 2008, 248(4):617-625.
33. De Luna W, Sze DY, Ahmed A, et al. Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation[J]. Am J Transplant, 2009, 9(5):1158-1168.
34. Di Benedetto F, Tarantino G, Montalti R, et al. Laparoscopic radiofrequency ablation in the caudate lobe for hepatocellular carcinoma before liver transplantation[J]. J Laparoendosc Adv Surg Tech A, 2012, 22(4):400-402.
35. Zanus G, Boetto R, Gringeri E, et al. Microwave thermal ablation for hepatocarcinoma:six liver transplantation cases[J]. Transplant Proc, 2011, 43(4):1091-1094.
36. Yu CY, Ou HY, Huang TL, et al. Hepatocellular carcinoma downstaging in liver transplantation[J]. Transplant Proc, 2012, 44(2):412-414.
37. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma:expansion of the tumor size limits does not adversely impact survival[J]. Hepatology, 2001, 33(6): 1394-1403.
38. Yao FY, Kerlan RK, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation:An intention-to-treat analysis[J]. Hepatology, 2008, 48(3):819-827.
39. Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma:results of down-staging in patients initially outside the Milan selection criteria[J]. Am J Transplant, 2008, 8(12):2547-2557.
40. Lei JY, Yan LN. Comparison between living donor liver transplantation recipients who met the Milan and UCSF criteria after successful downstaging therapies[J]. J Gastrointest Surg, 2012, 16(11):2120-2125.
41. Izumi N. Recent advances of radiofrequency ablation for early hepatocellular carcinoma[J]. J Gastroen Hepatol, 2011, 26(Suppl 1):115-122.
42. de Baère T, Risse O, Kuoch V, et al. Adverse events during radiofrequency treatment of 582 hepatic tumors[J]. Am J Roentgenol, 2003, 181(3):695-700.
43. Choi D, Lim HK, Kim MJ, et al. Liver abscess after percutaneous radiofrequency ablation for hepatocellular carcinomas:frequency and risk factors[J]. Am J Roentgenol, 2005, 184(6): 1860-1867.
44. Elias D, Di Pietroantonio D, Gachot B, et al. Liver abscess after radiofrequency ablation of tumors in patients with a biliary tract procedure[J]. Gastroenterol Clin Biol, 2006, 30(6-7):823-827.
45. Jansen MC, van Duijnhoven FH, van Hillegersberg R, et al. Adverse effects of radiofrequency ablation of liver tumours in the Netherlands[J]. Brit J Surg, 2005, 92(10):1248-1254.
46. Llovet JM, Vilana R, Brú C, et al. Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma[J]. Hepatology, 2001, 33(5):1124-1129.
47. Latteri F, Sandonato L, Di Marco V, et al. Seeding after radiofrequency ablation of hepatocellular carcinoma in patients with cirrhosis:a prospective study[J]. Digest Liver Dis, 2008, 40(8): 684-689.
48. Sun Z, Li G, Ai X, et al. Hepatic and biliary damage after transarterial chemoembolization for malignant hepatic tumors:incidence, diagnosis, treatment, outcome and mechanism[J]. Crit Rev Oncol Hematol, 2011, 79(2):164-174.
49. Buijs M, Vossen JA, Frangakis C, et al. Nonresectable Hepatocellular carcinoma:long-term toxicity in patients treated with transarterial chemoembolization--single-center experience1[J]. Radiology, 2008, 249(1):346-354.
50. Lu W, Li YH, Yu ZJ, et al. A comparative study of damage to liver function after TACE with use of low-dose versus conventionaldose of anticancer drugs in hepatocellular carcinoma[J]. Hepatogastroenterology, 2007, 54(77):1499-1502.
51. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma[J]. Hepatology, 2002, 35(5):1164-1171.
52. Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads:efficacy and doxorubicin pharmacokinetics[J]. J Hepato, 2007, 46(3):474-481.
53. Kim MH, Choi MS, Choi YS, et al. Clinical features of liver abscess developed after radiofrequency ablation and transarterial chemoembolization for hepatocellular carcinoma[J]. Korean J Hepato, 2006, 12(1):55-64.
54. Xia J, Ren Z, Ye S, et al. Study of severe and rare complications of transarterial chemoembolization (TACE) for liver cancer[J]. Eur J Radiol, 2006, 59(3):407-412.
55. Tarazov PG, Polysalov VN, Prozorovskij KV, et al. Ischemic complications of transcatheter arterial chemoembolization in liver malignancies[J]. Acta Radiol, 2000, 41(2):156-160.
56. Park WK, Chang JC, Lee HZ, et al. A case of resection of biloma with hepatocellular carcinoma after embolization[J]. Taehan Kan Hakhoe Chi, 2002, 8(3):331-335.
57. Sakamoto I, Iwanaga S, Nagaoki K, et al. Intrahepatic biloma formation (bile duct necrosis) after transcatheter arterial chemoembolization[J]. Am J Roentgenol, 2003, 181(1):79-87.
58. Sergio A, Cristofori C, Cardin R, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness[J]. Am J Gastroenterol, 2008, 103(4):914-921.
59. Nowak AK, Chow PKH, Findlay M. Systemic therapy for advanced hepatocellular carcinoma:a review[J]. Eur J Cancer, 2004, 40(10):1474-1484.

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