Role of Transcatheter Intra-arterial Therapies for Hepatocellular Carcinoma
2014; Elsevier BV; Volume: 4; Linguagem: Inglês
10.1016/j.jceh.2014.03.048
ISSN2213-3453
AutoresShashi Bala Paul, Hanish Sharma,
Tópico(s)Liver Disease Diagnosis and Treatment
ResumoTranscatheter intra-arterial therapies play a vital role in treatment of HCC due to the unique tumor vasculature. Evolution of techniques and newer efficacious modalities of tumor destruction have made these techniques popular. Various types of intra-arterial therapeutic options are currently available. These constitute: bland embolization, trans-arterial chemotherapy, trans-arterial chemo embolization with or without drug-eluting beads and trans-arterial radio embolization, which are elaborated in this review. Transcatheter intra-arterial therapies play a vital role in treatment of HCC due to the unique tumor vasculature. Evolution of techniques and newer efficacious modalities of tumor destruction have made these techniques popular. Various types of intra-arterial therapeutic options are currently available. These constitute: bland embolization, trans-arterial chemotherapy, trans-arterial chemo embolization with or without drug-eluting beads and trans-arterial radio embolization, which are elaborated in this review. Transcatheter intra-arterial therapies are widely used loco-regional palliative therapies for the management of intermediate and relatively advanced stage of hepatocellular carcinoma (HCC).1Yumoto Y. Jinno K. Tokuyama K. et al.Hepatocellular carcinoma detected by iodized oil.Radiology. 1985; 154: 19-24Crossref PubMed Google Scholar, 2Konno T. Maeda H. Iwai K. et al.Effect of arterial administration of high-moleculan- weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma.Eur J Cancer Clin Oncol. 1983; 19: 1053-1065Abstract Full Text PDF PubMed Google Scholar, 3Ohishi H. Uchida H. Yoshimura H. et al.Hepatocellular carcinoma detected by iodized oil: use of anticancer agents.Radiology. 1985; 154: 25-29Crossref PubMed Google Scholar, 4Takayasu K. Shima Y. Muramatsu Y. et al.Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents.Radiology. 1987; 163: 345-351Crossref PubMed Google Scholar This is largely so because, the majority of the patients present with advanced disease at the outset and this precludes the use of curative treatment options.5Paul S.B. Manjunatha Y.C. Acharya S.K. Palliative treatment in advanced hepatocellular carcinoma: has it made any difference?.Trop Gastroenterol. 2009; 30: 125-134PubMed Google Scholar The current article expands on the consensus guidelines discussed and drafted at the INASL task force on hepatocellular carcinoma convened at Puri from February 7,8 2013. Last decade has witnessed important developments in practised intra-arterial therapies. These constitute-bland embolization, trans-arterial chemotherapy, trans-arterial chemoembolization with or without drug-eluting beads and trans-arterial radioembolization.6Lewandowski R.J. Geschwind J.F. Liapi E. Salem R. Transcatheter intraarterial. therapies: rationale and overview.Radiology. 2011; 259: 641-657Crossref PubMed Scopus (42) Google Scholar All these types of intra-arterial options have a common goal of producing local tumor destruction but the mechanism of achieving this goal varies. The liver has a dual blood supply. The dominant supply (about 75%–80%) is from the portal vein while the remaining 20%–25% is supplied by the hepatic artery. During carcinogenesis, HCC becomes increasingly "arterialized" and the hepatic artery becomes its sole supplier resulting in neo-angiogenesis.7Markowitz J. The hepatic artery.Surg Gynecol Obstet. 1952; 95: 644-646PubMed Google Scholar This fact is utilized by the different intra-arterial therapies for administering cytotoxic drugs/embolizing agents to the tumor through its feeding hepatic artery leading to local tumor destruction and sparing the normal liver parenchyma. Trans-arterial embolization was introduced in the 1950s.7Markowitz J. The hepatic artery.Surg Gynecol Obstet. 1952; 95: 644-646PubMed Google Scholar Embolization can be categorized into bland embolization (TAE), trans-arterial chemoembolization (TACE) and trans-arterial radiotherapy (TART). TAE produces terminal arterial blockade resulting in ischemia and cytotoxic damage to the tumor. TACE refers to a combination of the delivery of chemotherapy followed by embolization of the feeding arterial supply producing twin advantages of action. TART uses internal radiation for destroying the tumor(s) followed by concomitant embolization of the feeding artery.8Llovet J.M. Burroughs A. Bruix J. Hepatocellular carcinoma.Lancet. 2003; 362: 1907-1917Abstract Full Text Full Text PDF PubMed Scopus (2293) Google Scholar Embolization aims at occluding the arterial supply of the malignant liver tumor using embolizing agents producing tumor hypoxia and resultant tumor necrosis. Two types of embolizing agents are in use-temporary embolizing agents like gelatin sponge (available as particles, cubes, pellets or powder form), autologous blood clot and degradable starch microspheres, and the permanent or semi-permanent types like polyvinyl alcohol (PVA particles) and steel coils.9Marelli L. Stigliano R. Triantos C. et al.Trans-arterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Interv Radiol. 2007; 30: 6-25Crossref PubMed Scopus (335) Google Scholar Gelatin sponge is the most commonly used temporary embolizing material, which is 1–2 mm in diameter. Recanalization of the embolized artery generally takes place within 2 weeks.10Coldwell D.M. Stokes K.R. Yakes W.F. Embolotherapy: agents, clinical applications, and techniques.Radiographics. 1994; 14: 623-643Crossref PubMed Google Scholar, 11Chung J.W. Transcatheter arterial chemoembolization of hepatocellular carcinoma.Hepatogastroenterology. 1998; 45: 1236-1241PubMed Google Scholar PVA particles produce distal arterial obstruction due to their smaller size and cause semi permanent/permanent occlusion. Hence, in HCC they are mainly used as a second line agent for embolizing the collaterals formed as a consequence to repeated embolization with other agents. No consensus exists on the most effective embolizing agent. TAE has been previously used as an effective treatment for unresectable HCC. The survival benefit12Maluccio M.A. Covey A.M. Porat L.B. et al.Transcatheter arterial embolization with only particles for the treatment of unresectable hepatocellular carcinoma.J Vasc Interv Radiol. 2008; 19: 862-869Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar and marked anti tumoral effect13Llovet J.M. Real M.I. Montana X. et al.Arterial embolisation or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial.Lancet. 2002; 359: 1734-1739Abstract Full Text Full Text PDF PubMed Scopus (1492) Google Scholar, 14Bruix J. Llovet J.M. Castells A. et al.Trans-arterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.Hepatology. 1998; 27: 1578-1583Crossref PubMed Scopus (403) Google Scholar, 15Llovet J.M. Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.Hepatology. 2003; 37: 429-442Crossref PubMed Scopus (1352) Google Scholar on patients of unresectable HCC have been reported in many studies. A recent study showed a median survival of 21 months with the 1-, 2- and 3-year survival rates of 66%, 46% and 33% respectively.12Maluccio M.A. Covey A.M. Porat L.B. et al.Transcatheter arterial embolization with only particles for the treatment of unresectable hepatocellular carcinoma.J Vasc Interv Radiol. 2008; 19: 862-869Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar On comparing outcomes of TAE with TACE, a large meta-analysis (3 RCTs, 412 patients) demonstrated no survival difference between the two techniques9Marelli L. Stigliano R. Triantos C. et al.Trans-arterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Interv Radiol. 2007; 30: 6-25Crossref PubMed Scopus (335) Google Scholar However, another study found that compared to TAE, TACE significantly prolonged progression free survival and time to progression, but not the overall survival.16Morse M.A. Hanks B.A. Suhocki P. et al.Improved time to progression for trans-arterial chemoembolization compared with trans-arterial embolization for patients with unresectable hepatocellular carcinoma.Clin Colorectal Cancer. 2012 Sep; 11: 185-190Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Thus, though TAE is reported as efficacious, the ultimate outcome with TACE is better. Hence TAE is no longer recommended currently in the era when the procedure of TACE is available. TACE is a twin procedure of super-selective trans-arterial delivery of the chemotherapeutic agents through the feeding hepatic artery of the tumor followed by administration of the embolizing agents. (Figure 1) This provides a dual attack on the tumor, firstly by producing cytotoxic damage within the tumor by high concentration of the chemotherapeutic drugs and secondly by additional embolization which prevents the washout of the chemotherapeutic drugs from the tumor causing prolonged retention within the tumor site resulting in ischemic necrosis and enhanced tumor destruction. TACE was introduced in the late 1970s and since then this technique has come a long way.17Yamada R. Sato M. Kawabata M. Nakatsuka H. Nakamura K. Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma.Radiology. 1983; 148: 397-401Crossref PubMed Google Scholar, 18Yamada R. Nakatsuka H. Nakamura K. et al.Hepatic artery embolization in 32 patients with unresectable hepatoma.Osaka City Med J. 1980; 26: 81-96PubMed Google Scholar TACE is considered as the primary therapeutic option for unresectable HCC.5Paul S.B. Manjunatha Y.C. Acharya S.K. Palliative treatment in advanced hepatocellular carcinoma: has it made any difference?.Trop Gastroenterol. 2009; 30: 125-134PubMed Google Scholar, 19Takayasu K. Arii S. Ikai I. et al.Prospective cohort study of trans-arterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients.Gastroenterology. 2006; 131: 461-469Abstract Full Text Full Text PDF PubMed Scopus (370) Google Scholar A number of expert guidelines have commented on suitable candidates for TACE.20Kudo M. Izumi N. Kokudo N. HCC Expert Panel of Japan Society of Hepatology et al.Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan society of hepatology (JSH) 2010 updated version.Dig Dis. 2011; 29: 339-364Crossref PubMed Scopus (114) Google Scholar, 21European Association for The Study of The Liver European Organisation for Research and Treatment of Cancer EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2012 Apr; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 22Bruix J. Sherman M. Management of hepatocellular carcinoma. An update AASLD practice guidelines.Hepatology. 2010; 0: 1-35Google Scholar The ideal candidates are patients of HCC with multi-nodular tumors with preserved liver function (Child-Pugh class A or B), without vascular invasion or extra-hepatic spread.14Bruix J. Llovet J.M. Castells A. et al.Trans-arterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.Hepatology. 1998; 27: 1578-1583Crossref PubMed Scopus (403) Google Scholar, 23Bruix J. Sala M. Llovet J.M. Chemoembolization for hepatocellular carcinoma.Gastroenterology. 2004; 127: S179-S188Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar These have been staged as BCLC B and C (with normal main portal vein) based on the Barcelona clinic liver cancer (BCLC) staging.24Cillo U. Vitale A. Grigoletto F. et al.Prospective validation of the barcelona clinic liver Cancer staging system.J Hepatol. 2006; 44: 723-731Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar TACE may also be offered to patients with inoperable small tumors (BCLC stage A), which are not amenable for local ablation due to technical limitations.25Omata M. Laurentius L.A. Ryosuke T. et al.Asian Pacific Association for the Study of the liver consensus recommendations on hepatocellular carcinoma.Hepatlogy Int. 2010; 4: 439-474Crossref PubMed Scopus (166) Google Scholar It is also used as adjuvant therapy or as a means of down-staging the disease before liver transplantation, but whether these approaches provide ultimate survival benefit remains unclear26Chua T.C. Liauw W. Saxena A. et al.Systematic review of neoadjuvant trans-arterial chemoembolization for resectable hepatocellular carcinoma.Liver Int. 2010; 30: 166-174Crossref PubMed Scopus (21) Google Scholar, 27Gerundi G.E. Neri D. Merenda R. et al.Role of trans-arterial chemoembolization before liver resection for hepatocarcinoma.Liver Transpl. 2000; 6: 619-626Crossref PubMed Google Scholar, 28Zhou J.P. Zhou W.P. Fu S.Y. Shan Y.F. Yao X.P. Wu M.C. Influence of preoperative transcatheter arterial chemoembolization on liver function in patients with resectable large hepatocellular carcinoma.Gandan Waike Zazhi. 2003; 11: 256-258Google Scholar, 29Stockland A.H. Walser E.M. Paz-Fumagalli R. McKinney J.M. May G.R. Preoperative chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: influence of emergent versus elective procedures on patient survival and tumor recurrence rate.Cardiovasc Interv Radiol. 2007; 30: 888-893Crossref PubMed Scopus (10) Google Scholar Stringent selection criteria for TACE should be followed for favorable outcomes. Liver functional reserve is a crucial component and patients with Child-Pugh A or B7 without ascites should be encouraged, whilst those with Child-Pugh C status should be excluded since the ischemic insult can lead to severe adverse events.30Groupe d'Etude et de Traitement du Carcinome HépatocellulaireA comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma.N Engl J Med. 1995; 332: 1256-1261PubMed Google Scholar Contraindications of TACE are general contraindications to any intra-arterial procedure, allergic reaction to contrast media, pregnancy, poor liver function, presence of hepatofugal blood flow, main portal vein thrombosis, extra-hepatic metastases, WHO performance status more than 2 and end stage tumoral disease (Okuda III)10Coldwell D.M. Stokes K.R. Yakes W.F. Embolotherapy: agents, clinical applications, and techniques.Radiographics. 1994; 14: 623-643Crossref PubMed Google Scholar Patients with thrombosis of the main portal vein (PVT) are considered a contraindication for TACE. This is due to the risk of aggravating hepatic insufficiency resulting from ischemia causing worst outcomes.23Bruix J. Sala M. Llovet J.M. Chemoembolization for hepatocellular carcinoma.Gastroenterology. 2004; 127: S179-S188Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar However, some contradictory results of survival benefit have been reported31Lo C.M. Ngan H. Tso W.K. et al.Randomized controlled trial of trans-arterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology. 2002; 35: 1164-1171Crossref PubMed Scopus (1168) Google Scholar, 32Kim K.M. Kim J.H. Park I.S. et al.Reappraisal of repeated trans-arterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion.J Gastroenterol Hepatol. 2009; 24: 806-814Crossref PubMed Scopus (38) Google Scholar, 33Luo J. Guo R.P. Lai E.C.H. et al.Trans-arterial chemoembolization for unresectable hepatocellular carcinoma with Portal vein tumor thrombosis: a prospective comparative study.Ann Surg Oncol. 2011; 18: 413-420Crossref PubMed Scopus (52) Google Scholar, 34De Lope C.R. Tremosini S. Forner A. Reig M. Bruix J. Management of HCC.J Hepatol. 2012; 56: S75-S87Abstract Full Text PDF PubMed Scopus (113) Google Scholar PVT should therefore not be considered as an absolute contraindication for TACE in patients with preserved liver function.32Kim K.M. Kim J.H. Park I.S. et al.Reappraisal of repeated trans-arterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion.J Gastroenterol Hepatol. 2009; 24: 806-814Crossref PubMed Scopus (38) Google Scholar, 33Luo J. Guo R.P. Lai E.C.H. et al.Trans-arterial chemoembolization for unresectable hepatocellular carcinoma with Portal vein tumor thrombosis: a prospective comparative study.Ann Surg Oncol. 2011; 18: 413-420Crossref PubMed Scopus (52) Google Scholar, 35Shi M. Chen J.A. Lin X.J. et al.Trans-arterial chemoembolization as initial treatment for unresectable hepatocellular carcinoma in southern China.World J Gastroenterol. 2010; 16: 264-269Crossref PubMed Scopus (23) Google Scholar Better estimates of risk stratification in individual patients are needed. No standardized protocol exists with regard to the choice of chemotherapeutic agent, dosage, dilution and the rate of injection.36European Association for Study of Liver European Organisation for Research and treatment of Cancer.Eur J Cancer. 2012; 48: 599-641Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Doxorubicin, mitomycin and cisplatin are the common chemotherapeutic drugs used alone or in combination. Irrespective of the choice of the chemotherapeutic drug used, an emulsion of the drug is prepared with an iodized oil called lipiodol, which acts as a carrier and increases the intratumoral retention of the drugs causing a prolonged effect.37Raoul J.L. Heresbach D. Bretagne J.F. et al.Chemoembolization of hepatocellular carcinomas: a study of the biodistribution and pharmacokinetics of doxorubicin.Cancer. 1992; 70: 585-590Crossref PubMed Scopus (105) Google Scholar, 38Nakamura H. Hashimoto T. Oi H. Sawada S. Transcatheter oily chemoembolization of hepatocellular carcinoma.Radiology. 1989; 170: 783-786Crossref PubMed Google Scholar Use of single or multiple chemotherapeutic drugs have been undertaken in the procedure of TACE.39Lee J. Park J.O. Kim W.S. et al.Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma.Cancer Chemother Pharmacol. 2004; 54: 385-390Crossref PubMed Scopus (47) Google Scholar, 40Bobbio-Pallavicini E. Porta C. Moroni M. et al.Epirubicin and etoposide combination chemotherapy to treat hepatocellular carcinoma patients: a phase II study.Eur J Cancer. 1997; 33: 1784-1788Abstract Full Text PDF PubMed Scopus (48) Google Scholar A recent three arm randomized trial has shown better response with less number of treatment sessions with the use of multiple drugs in TACE and with drug eluding beads as compared to TACE undertaken with a single drug.41Petruzzi N.J. Frangos A.J. Fenkel J.M. et al.Single-center comparison of three chemoembolization Regimens for hepatocellular carcinoma.J Vasc Interv Radiol. 2013; 24: 266-273Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar No standard embolizing agent, quantity or guidelines for re-treatment strategy have been recommended for TACE. More intense regimes of repeating TACE every 2 months has been shown to induce liver failure in high proportion of cases.27Gerundi G.E. Neri D. Merenda R. et al.Role of trans-arterial chemoembolization before liver resection for hepatocarcinoma.Liver Transpl. 2000; 6: 619-626Crossref PubMed Google Scholar A number of factors have been correlated with effective post TACE response viz; tumor diameter less than 5 cm, less than 50% replacement of liver by tumor tissue and unilobar tumor. Other prognostic factors include the alpha feto protein [AFP] level, differentiation of HCC, number of tumor nodules, portal vein thrombosis, presence of tumor capsule, and degree of lipiodol retention post-procedure.14Bruix J. Llovet J.M. Castells A. et al.Trans-arterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution.Hepatology. 1998; 27: 1578-1583Crossref PubMed Scopus (403) Google Scholar, 16Morse M.A. Hanks B.A. Suhocki P. et al.Improved time to progression for trans-arterial chemoembolization compared with trans-arterial embolization for patients with unresectable hepatocellular carcinoma.Clin Colorectal Cancer. 2012 Sep; 11: 185-190Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 17Yamada R. Sato M. Kawabata M. Nakatsuka H. Nakamura K. Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma.Radiology. 1983; 148: 397-401Crossref PubMed Google Scholar, 21European Association for The Study of The Liver European Organisation for Research and Treatment of Cancer EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2012 Apr; 56: 908-943Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 31Lo C.M. Ngan H. Tso W.K. et al.Randomized controlled trial of trans-arterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.Hepatology. 2002; 35: 1164-1171Crossref PubMed Scopus (1168) Google Scholar, 42Georgiades C.S. Hong K. D'Angelo M. Geschwind J.F. Safety and efficacy of trans-arterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis.J Vasc Interv Radiol. 2005; 16: 1653-1659Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar Large tumors with poor baseline liver function, have shown least benefit from TACE. TACE has been successfully used in combination with various modalities for the treatment of relatively large tumors depicting better survival rates.43Yau T. Chan P. Epstein R. Poon R.T. Management of advanced hepatocellular carcinoma in the era of targeted therapy.Liver Int. 2009; 29: 10-17Crossref PubMed Scopus (33) Google Scholar, 44Bartolozzi C. Lencioni R. Caramella D. et al.Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization.Radiology. 1995; 197: 812-818Crossref PubMed Google Scholar, 45Narvaez-Lugo J. Cáceres W.W. Toro D.H. et al.Transcatheter arterial chemoembolization and percutaneous ethanol injection for hepatocellular carcinoma: a retrospective review of the veterans affairs Caribbean healthcare system.Cancer Control. 2008; 15: 80-85PubMed Google Scholar, 46Xu Z.M. Wang J.H. Zhen Z.J. Chen H.W. Cui W.Z. Percutaneous radiofrequency ablation combined with transcatheter arterial chemoembolization and percutaneous ethanol injection for recurrent small hepatocellular carcinoma.Nan Fang Yi Ke Da Xue XueBao. 2006; 26: 1626-1628PubMed Google Scholar Commonly tried combination modalities with improved results are, percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), laser ablation (LA), oral chemotherapy and targeted therapy.47Seror O. N'Kontchou G. Haddar D. et al.Large infiltrative hepatocellular carcinomas: treatment with percutaneous intraarterial ethanol injection alone or in combination with conventional percutaneous ethanol injection.Radiology. 2005; 234: 299-309Crossref PubMed Scopus (18) Google Scholar, 48Decaens T. Roudot-Thoraval F. Bresson-Hadni S. et al.Impact of pretransplantation trans-arterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma.Liver Transpl. 2005; 11: 767-775Crossref PubMed Scopus (134) Google Scholar, 49Graziadei I.W. 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.Liver Transpl. 2003; 9: 557-563Crossref PubMed Scopus (266) Google Scholar, 50Yamakado K. Nakatsuka A. Ohmori S. et al.Radiofrequency ablation combined with chemoembolization in hepatocellular carcinoma: treatment response based on tumor size and morphology.J Vasc Interv Radiol. 2002; 13: 1225-1232Abstract Full Text Full Text PDF PubMed Google Scholar, 51Pacella C.M. Bizzarri G. Cecconi P. et al.Hepatocellular carcinoma: long-term results of combined treatment with laser thermal ablation and transcatheter arterial chemoembolization.Radiology. 2001; 219: 669-678Crossref PubMed Google Scholar, 52Graf H. Jüngst C. Straub G. et al.Chemoembolization combined with pravastatin improves survival in patients with hepatocellular carcinoma.Digestion. 2008; 78: 34-38Crossref PubMed Scopus (27) Google Scholar Repeated sessions of TACE can be used for downsizing the tumor and subsequently making the patient suitable for ablation. Complete response has been achieved in 90% of the large tumors subjected to repeated sessions of TACE followed by LA.53Zangos S. Eichler K. Balzer J.O. et al.Large-sized hepatocellular carcinoma (HCC): a neoadjuvant treatment protocol with repetitive trans-arterial chemoembolization (TACE) before percutaneous MR-guided laser-induced thermotherapy (LITT).Eur Radiol. 2007; 17: 553-563Crossref PubMed Scopus (16) Google Scholar, 54Vogl T.J. Mack M.G. Balzer J.O. et al.Liver metastases: neoadjuvant downsizing with trans-arterial chemoembolization before laser-induced thermotherapy.Radiology. 2003; 229: 457-464Crossref PubMed Scopus (71) Google Scholar Similar superior results have been achieved with combination with PEI, and RFA.55Kim S.K. Lim H.K. Kim Y.H. et al.Hepatocellular carcinoma treated with radiofrequency ablation: spectrum of imaging findings.RadioGraphics. 2003; 23: 107-121Crossref PubMed Google Scholar Better quality of life scores have also been shown in patients treated with TACE with RFA than those treated with TACE alone.56Wang Y.B. Chen M.H. Yan K. Yang W. Dai Y. Yin S.S. Quality of life after radiofrequency ablation combined with transcatheter arterial chemoembolization for hepatocellular carcinoma: comparison with transcatheter arterial chemoembolization alone.Qual Life Res. 2007; 16: 389-397Crossref PubMed Scopus (30) Google Scholar Combination of TACE and oral chemotherapeutic drug, sorafenib too is being tried with promising results.57Bai W. Wang Y.J. Zhao Y. et al.Sorafenib in combination with trans-arterial chemoembolization improves survival of unresectable hepatocellular carcinoma: a propensity-score matching study.J Dig Dis. 2013; 14: 181-190Crossref PubMed Scopus (7) Google Scholar TACE has multiple roles as a palliative treatment. TACE when performed prior to hepatic resection in patients with large tumors, produces reduction in tumor volume. It is safe, efficacious with high rates of pathological response.23Bruix J. Sala M. Llovet J.M. Chemoembolization for hepatocellular carcinoma.Gastroenterology. 2004; 127: S179-S188Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar It destroys remnant cancer cells, decreases recurrence rate and prolongs survival.9Marelli L. Stigliano R. Triantos C. et al.Trans-arterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Interv Radiol. 2007; 30: 6-25Crossref PubMed Scopus (335) Google Scholar, 24Cillo U. Vitale A. Grigoletto F. et al.Prospective validation of the barcelona clinic liver Cancer staging system.J Hepatol. 2006; 44: 723-731Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar On the contrary, decreasing survival rates have also been reported, possibly due to hepatic and immunological damage occurring with TACE.25Omata M. Laurentius L.A. Ryosuke T. et al.Asian Pacific Association for the Study of the liver consensus recommendations on hepatocellular carcinoma.Hepatlogy Int. 2010; 4: 439-474Crossref PubMed Scopus (166) Google Scholar Role of TACE as an adjuvant therapy thus remains quite controversial. TACE has also been used as adjuvant therapy for preventing postoperative recurrence. Cases where intrahepatic recurrence occurs following resection, TACE is successfully used as a palliative therapy. TACE also has a role to play in HCC patients planned for orthotopic liver transplant (OLT). It provides a dual benefit - controlling tumor growth as well as producing tumor necrosis. This results in reduced chances of tumor dissemination during surgery. Moreover, down staging of the disease can be achieved making these patients suitable for OLT. TACE is thus the commonly used bridging modality in transplant patients. However, despite achieving tumor down staging, no significant advantage in survival and recurrence rate has been shown in the patients following OLT.26Chua T.C. Liauw W. Saxena A. et al.Systematic review of neoadjuvant trans-arterial chemoembolization for resectable hepatocellular carcinoma.Liver Int. 2010; 30: 166-174Crossref PubMed Scopus (21) Google Scholar Criteria for the success and failure of TACE relate to the technique and outcome of the procedure. Additionally superselective TACE with an attempt to deliver the drug very close to the tumor has a better outcome than whole-liver or lobar TACE. This minimizes embolization of non-targeted normal liver parenchyma.9Marelli L. Stigliano R. Triantos C. et al.Trans-arterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies.Cardiovasc Interv Radiol. 2007; 30: 6-25Crossref PubMed Scopus (335) Google Scholar, 58Iwazawa J. Ohue S. Mitani T. et al.Identifying feeding arteries during tace of hepatic tumors: comparison of c-arm ct and digital subtraction angiography.AJR. 2009 apr; 192: 1057-1063Crossref PubMed Scopus (40) Google Scholar Superselective cannulation of the extra hepatic arterial feeders is even further difficult to negotiate because of the unusually long, tortuous and
Referência(s)