- Breast Cancer
- Cancer Control
- Diagnostics and Screening
- Gastrointestinal Oncology
- Genitourinary Cancers
- Geriatric Oncology
- Gynecological Oncology
- Head, Neck and Thyroid Cancers
- Hematological Malignancies
- Infection in Hematology
- Lung Cancer
- Neurological Oncology
- Patient Care
- Pediatric Oncology
- Platelets, Hemostasis and Thrombosis
- Red Blood Cells
- Supportive Oncology
Transcatheter Arterial Chemoembolisation for the Treatment of Hepatocellular Carcinoma
US Oncology Review, 2005;1(1):52-4
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer worldwide, and its incidence is constantly increasing.1,2 There are 13,000–19,000 cases per year in the US and 350,000 to one million cases per year worldwide.3–5 Chronic hepatitis C (HCV) infection and improved survival of patients with cirrhosis seem to account for most of this rising incidence.6
Treatment is dependent on disease status, including size and number of lesions, patient’s hepatic reserve and other co-morbidities. Partial hepatic resection with adequate margins and liver transplantation are potentially curative surgical options for selected patients. However, only 30–40% of patients with HCC qualify for surgery, leaving the rest to pursue non-surgical palliative options.7 In this direction, innovative local ablative therapies for HCC have recently shown great progress and promising results. Among them, transcatheter arterial chemoembolisation is a minimally invasive approach for the palliative treatment of unresectable HCC that constantly evolves, in terms of utilized drugs, embolic materials, technical, and technological advances.
Citation US Oncology Review, 2005;1(1):52-4
This article outlines the current status of this imageguided intervention for treatment of HCC and introduces some new concepts and advances in the era of minimally invasive therapy of HCC.
The technique of transcatheter arterial chemoembolisation (TACE) exploits HCC preferential blood supply from the hepatic artery to deliver the anti-tumor therapy, while sparing the surrounding liver parenchyma.8,9 Since TACE was introduced as a palliative treatment in patients with unresectable HCC, it has become one of the most common procedures in interventional radiology. Currently, chemoembolisation is the preferred treatment for unresectable HCC.10–12 TACE is also employed as an adjunctive therapy to liver resection or as a bridge to liver transplantation, as well as prior to radiofrequency ablation (RFA).13–17
TACE involves the injection of chemotherapeutic agents, with or without lipiodol and embolic agents, into the branch of the hepatic artery that feeds the tumor.18 Contraindications to this technique are constantly reviewed.The absence of hepatopedal blood flow (portal vein thrombosis), the presence of encephalopathy and biliary obstruction are currently re-evaluated as absolute contraindications, whereas relative contraindications include a variety of other factors, such as:
• serum bilirubin >2mg/dL;
• lactate dehydrogenase >425U/L;
• aspartate aminotransferase >100U/L;
• tumor burden involving >50% of the liver;
• cardiac or renal insufficiency;
• recent variceal bleeding; or
• significant thrombocytopenia.
- Bosch F X, Ribes J, Diaz M, Cleries R,“Primary liver cancer: worldwide incidence and trends”, Gastroenterology (2004);127 (5 Suppl 1): pp. S5–S16.
- Parkin D M, Bray F, Ferlay J, Pisani P, “Estimating the world cancer burden: Globocan 2000”, Int. J. Cancer (2001); 94 (2): pp. 153–156.
- Landis S H, Murray T, Bolden S,Wingo P A,“Cancer statistics, 1999”, CA Cancer J. Clin. (1999);49 (1): pp. 8–31, 1.
- El-Serag H B, Mason A C, “Rising incidence of hepatocellular carcinoma in the United States”, N. Engl. J. Med. (1999);340 (10): pp. 745–750.
- Cha C, DeMatteo R P, Blumgart L H, “Surgery and ablative therapy for hepatocellular carcinoma”, J. Clin. Gastroenterol. (2002);35 (5 Suppl 2): pp. S130–S137.
- El-Serag H B, Mason A C, “Risk factors for the rising rates of primary liver cancer in the United States”, Arch. Intern. Med. (2000);160 (21): pp. 3,227–3,230.
- Okuda K,“Hepatocellular carcinoma”, J. Hepatol. (2000);32 (1 Suppl): pp. 225–237.
- Yamada R, Nakatsuka H, Nakamura K, Sato M, Itami M, Kobayashi N, et al., “Hepatic artery embolization in 32 patients with unresectable hepatoma”, Osaka City Med. J. (1980);26 (2): pp. 81–96.
- Yamada R, Sato M, Kawabata M, Nakatsuka H, Nakamura K,Takashima S, “Hepatic artery embolization in 120 patients with unresectable hepatoma”, Radiology (1983);148 (2): pp. 397–401.
- Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire,“A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma”, N. Engl. J. Med. (1995);332 (19): pp. 1,256–1,261.
- Lo C M, Ngan H, Tso W K, Liu C L, Lam C M, Poon R T, et al., “Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma”, Hepatology (2002);35 (5): pp. 1,164–1,171.
- Llovet J M, Real M I, 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 (9319): pp. 1,734–1,739.
- Aoki T, Imamura H, Hasegawa K, Matsukura A, Sano K, Sugawara Y, et al.,“Sequential preoperative arterial and portal venous embolizations in patients with hepatocellular carcinoma”, Arch. Surg. (2004);139 (7): pp. 766–774.
- Llovet J M, Burroughs A, Bruix J, “Hepatocellular carcinoma”, Lancet (2003);362 (9399): pp. 1,907–1,917.
- Llovet J M,“Treatment of Hepatocellular Carcinoma”, Curr.Treat. Options Gastroenterol. (2004);7 (6): pp. 431–441.
- Arii S,Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M, et al.,“Results of surgical and nonsurgical treatment for smallsized hepatocellular carcinomas: a retrospective and nationwide survey in Japan, The Liver Cancer Study Group of Japan”, Hepatology (2000);32 (6): pp. 1,224–1,229.
- Livraghi T, Meloni F, Morabito A,Vettori C, “Multimodal image-guided tailored therapy of early and intermediate hepatocellular carcinoma: long-term survival in the experience of a single radiologic referral center”, Liver Transpl. (2004);10 (2 Suppl 1): pp. S98–106.
- Geschwind J F,“Chemoembolization for hepatocellular carcinoma: where does the truth lie?”, J.Vasc. Interv. Radiol. (2002);13 (10): pp. 991–994.
- Bruix J, Sala M, Llovet J M, “Chemoembolization for hepatocellular carcinoma”, Gastroenterology (2004), 127 (5 Suppl 1): pp. S179–188.
- Xiong Z P,Yang S R, Liang Z Y, Xiao E H,Yu X P, Zhou S K, et al., “Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma”, Hepatobiliary Pancreat Dis. Int. (2004);3 (3): pp. 386–390.
- Kobayashi N, Ishii M, Ueno Y, Kisara N, Chida N, Iwasaki T, et al., “Co-expression of Bcl-2 protein and vascular endothelial growth factor in hepatocellular carcinomas treated by chemoembolization”, Liver (1999);19 (1): pp. 25–31.
- Jaeger H J, Mehring U M, Castaneda F, Hasse F, Blumhardt G, Loehlein D, et al., “Sequential transarterial chemoembolization for unresectable advanced hepatocellular carcinoma”, Cardiovasc. Intervent. Radiol. (1996);19 (6): pp. 388–396.
- Geschwind J F, Ramsey D E, van der Wal B C, Kobeiter H, Juluru K, Hartnell G G, et al., “Transcatheter arterial chemoembolization of liver tumours: effects of embolization protocol on injectable volume of chemotherapy and subsequent arterial patency”, Cardiovasc. Intervent. Radiol. (2003);26 (2): pp. 111–117.
- Therasse P,Arbuck S G, Eisenhauer E A,Wanders J, Kaplan R S, Rubinstein L, et al.,“New guidelines to evaluate the response to treatment in solid tumours. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada”, J. Natl. Cancer Inst. (2000);92 (3): pp. 205–216.
- Tsuchida Y, Therasse P, “Response evaluation criteria in solid tumours (RECIST): new guidelines”, Med. Pediatr. Oncol. (2001);37 (1): pp. 1–3.
- Murakami T, Nakamura H, Hori S,Tomoda K, Mitani T, Nakanishi K, et al., “Detection of viable tumor cells in hepatocellular carcinoma following transcatheter arterial chemoembolization with iodized oil, Pathologic correlation with dynamic turbo-FLASH MR imaging with Gd-DTPA”, Acta. Radiol. (1993);34 (4): pp. 399–403.
- Castrucci M, Sironi S, De Cobelli F, Salvioni M, Del Maschio A, “Plain and gadolinium-DTPA-enhanced MR imaging of hepatocellular carcinoma treated with transarterial chemoembolization”, Abdom. Imaging (1996);21 (6): pp. 488–494.
- Bartolozzi C, Lencioni R, Caramella D, Mazzeo S, Ciancia E M, “Treatment of hepatocellular carcinoma with percutaneous ethanol injection: evaluation with contrast-enhanced MR imaging”, AJR Am. J. Roentgenol. (1994);162 (4): pp. 827–831.
- Kamel I R, Bluemke D A, Ramsey D, Abusedera M, Torbenson M, Eng J, et al., “Role of diffusion-weighted imaging in estimating tumor necrosis after chemoembolization of hepatocellular carcinoma”, AJR Am. J. Roentgenol. (2003);181 (3): pp. 708–710.
- Lim H K, Han J K, “Hepatocellular carcinoma: evaluation of therapeutic response to interventional procedures”, Abdom. Imaging (2002);27 (2): pp. 168–179.
- Takayasu K,Arii S, Matsuo N,Yoshikawa M, Ryu M,Takasaki K, et al.,“Comparison of CT findings with resected specimens after chemoembolization with iodized oil for hepatocellular carcinoma”, AJR Am. J. Roentgenol. (2000);175 (3): pp. 699–704.
- Bruix J, Llovet J M, Castells A, Montana X, Bru C,Ayuso M C, et al.,“Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution”, Hepatology (1998);27 (6): pp. 1,578–1,583.
- Simonetti R G, Liberati A, Angiolini C, Pagliaro L,“Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials”, Ann. Oncol. (1997);8 (2): pp. 117–136.
- Qian J,Truebenbach J, Graepler F, Pereira P, Huppert P, Eul T, et al.,“Application of poly-lactide-co-glycolide-microspheres in the transarterial chemoembolization in an animal model of hepatocellular carcinoma”, World J. Gastroenterol. (2003);9 (1): pp. 94–98.
- Constantin M, Fundueanu G, Bortolotti F, Cortesi R, Ascenzi P, Menegatti E, “Preparation and characterisation of poly(vinyl alcohol)/cyclodextrin microspheres as matrix for inclusion and separation of drugs”, Int. J. Pharm. (2004);285 (1-2): pp. 87–96.
- Vallee J N, Lo D, Guillevin R, Reb P, Adem C, Chiras J, “In vitro study of the compatibility of tris-acryl gelatin microspheres with various chemotherapeutic agents”, J.Vasc. Interv. Radiol. (2003);14 (5): pp. 621–628.
- Fujiwara K, Hayakawa K, Nagata Y, Hiraoka M, Nakamura T, Shimizu Y, et al., “Experimental embolization of rabbit renal arteries to compare the effects of poly L-lactic acid microspheres with and without epirubicin release against Intra-arterial injection of epirubicin”, Cardiovasc. Intervent. Radiol. (2000);23 (3): pp. 218–223.
- Geschwind J F, Khwaja A, Hong K,“New Intra-arterial drug delivery system: Pharmacokinetics and tumor response in an animal model of liver cancer”, In: 2005 ASCO Annual Meeting; (2005); Orlando, Florida; 2005.
- Geschwind J-F H, Ko Y H,Torbenson M S, Magee C, Pedersen P L, “Novel Therapy for Liver Cancer: Direct Intra-arterial Injection of a Potent Inhibitor of ATP Production”, Cancer Res. (2002);62 (14): pp. 3,909–3,913.
- Geschwind J F, Georgiades C S, Ko Y H, Pedersen P L, “Recently elucidated energy catabolism pathways provide opportunities for novel treatments in hepatocellular carcinoma”, Expert Rev. Anticancer Ther. (2004);4 (3): pp. 449–457.
- Gwak G-Y,Yoon J-H, Kim K M, Lee H-S, Chung J W, Gores G J,“Hypoxia stimulates proliferation of human hepatoma cells through the induction of hexokinase II expression”, Journal of Hepatology (2005);42 (3): p. 358.
- Leist M, Single B, Castoldi A F, Kuhnle S, Nicotera P,“Intracellular Adenosine Triphosphate (ATP) Concentration:A Switch in the Decision Between Apoptosis and Necrosis”, J. Exp. Med. (1997);185 (8): pp. 1,481–1,486.
- Xu R-h, Pelicano H, Zhou Y, Carew J S, Feng L, Bhalla K N, et al.,“Inhibition of Glycolysis in Cancer Cells:A Novel Strategy to Overcome Drug Resistance Associated with Mitochondrial Respiratory Defect and Hypoxia”, Cancer Res. (2005);65 (2): pp. 613–621.
- Liapi E H K, Georgiades C S, Geschwind J F, “Three-dimensional rotational angiography (3D-RA): introduction of an adjunctive tool for successful transarterial chemoembolization”, J.Vasc. Interv. Radiol. (2005);in press.