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ranscatheter Arterial Chemoembolization:urrent Technique and Future Promise

leni Liapi, MD, Christos C. Georgiades, MD, PhD, Kelvin Hong, MD, andean-Francois H. Geschwind, MD

Transarterial chemoembolization is the mainstay of catheter based interventional oncologictherapies. This article describes the history of the procedure, selection of appropriatecandidates, technical aspects of procedure performance, results, complications, and ap-propriate follow-up. In addition, the limitations and challenges of the procedure are out-lined. Finally, the reader is introduced to novel and promising techniques and devices thathold future promise for transarterial therapy of malignancies.Tech Vasc Interventional Rad 10:2-11 © 2007 Elsevier Inc. All rights reserved.

KEYWORDS transcatheter arterial chemoembolization, liver cancer, technique

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ranscatheter arterial chemoembolization (TACE) has sig-nificantly contributed to the evolution of interventional

adiology, as it proficiently represents the novel group ofinimally invasive catheter-directed oncologic therapies.ased on the initial observation that most hepatic malignant

esions receive their blood supply by the hepatic artery,ACE may effectively deliver highly concentrated doses ofhemotherapy to the tumor bed, whereas sparing the sur-ounding hepatic parenchyma.1,2

In practice, despite its promising concept of design, TACEas not proved to be as effective and potent as in theory.mong several challenging obstacles that have not yet beenxceeded, is the heterogeneity of chemotherapeutic agentsmployed and the several variations in the application of theechnique. This disparity hinders the conduct of systematiceta-analyses or the design of randomized trials that wouldemonstrate a clear survival benefit.3 Despite controversynd diversity, TACE has gained wide acceptance over the past0 years and is currently considered as the mainstay therapyor unresectable primary and metastatic liver cancer.4,5 In thisrticle, we attempt to review the technical and clinical part ofhe procedure, as well as current results, effectiveness, anduture potential of TACE.

rom the Russell H. Morgan Department of Radiology and RadiologicalScience, Division of Cardiovascular and Interventional Radiology, TheJohns Hopkins Hospital, Baltimore, MD.

ddress reprint requests to Jean-Francois H. Geschwind, MD, AssociateProfessor of Radiology, Surgery, and Oncology, Director, Cardiovascularand Interventional Radiology, Section Chief, Interventional Radiology,Director, Interventional Radiology Research, The Johns Hopkins Hospi-

ltal, Baltimore, MD 21287. E-mail: jfg@jhmi.edu.

1089-2516/07/$-see front matter © 2007 Elsevier Inc. All rights reserved.doi:10.1053/j.tvir.2007.08.008

rief History andeview of Underlyingechanisms for Tumor Damage

ACE was introduced in 1977 by Dr. Yamada, who firstxploited hepatocellular carcinoma’s preferential bloodupply from the hepatic artery to deliver antitumor ther-py, without damaging the surrounding liver paren-hyma.1,2 A decade later, the observation that the injectionf lipiodol, an iodinated ester derived from poppy-seedil, can be selectively up-taken and retained by primaryepatocellular carcinoma (HCC) and hepatic metastases ofolonic and neuroendocrine tumors, led to the establish-ent of this compound as an important part of the in-

ected chemotherapeutic cocktail.6-8 Moreover, lipiodolas found to effectively engage the chemotherapeutic

gents, whereas leading to dual embolization and tumorecrosis.Theoretically, embolization of the feeding vessel causes

schemia of the tumor, and when combined with chemother-py, results in tumor necrosis. Despite this promising obser-ation, only 44% of large treated lesions demonstrate exten-ive necrosis in pathology, leading to further questioning ofhe true mechanism of producing tumor necrosis.9 Recenttudies have shown that tumor ischemia and hypoxia up-egulate several molecular factors, such as the vascularndothelial growth factor (VEGF), and hypoxia inducibleactor-1 (HIF-1), thereby preventing cell apoptosis andtimulating tumor growth.10,11 These novel observationseed to be further tested in the clinical setting so as toemonstrate the role of possible interactions between hyp-xia and the effect of embolization during a chemoembo-

ization procedure.

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Transcatheter arterial chemoembolization 3

atient Selectionnd Indications for TACEowadays, chemoembolization is the preferred treatment fornresectable HCC.12-14 Despite the recently encouraging in-ention-to-treat studies, TACE is still considered a palliativeption. TACE is also employed as an adjunctive therapy toiver resection or as a bridge to liver transplantation, as well asefore radiofrequency ablation.15-19 Promising results haveeen recently demonstrated with unresectable cholangiocar-inoma treated with chemoembolization.20 Chemoemboliza-ion has also successfully been employed for patients witharcinoid tumor, pancreatic islet tumor and sarcoma meta-tatic to the liver, whereas the efficacy of TACE in patientsith colorectal metastases is less established. Promising re-

ults have been recently demonstrated with unresectableholangiocarcinoma treated with chemoembolization.20

Not every patient with unresectable primary or metastaticiver tumor may benefit from chemoembolization. One impor-ant aspect in the selection of patients is the presence of adequateiver function. In patients with advanced liver disease, treat-

ent-induced liver failure may offset the antitumoral effect orurvival benefit of the intervention. Predictors of outcome areelated to tumor burden (tumor size, vascular invasion, and AFPevels), liver functional impairment (Child-Pugh, bilirubin, as-ites), performance status (Karnofsky index, ECOG), and re-ponse to treatment. Thus, the best candidates are patients withreserved liver function and asymptomatic lesions without vas-ular invasion or extrahepatic spread.

ontraindications for TACEbsolute contraindications for TACE such as absence ofepatopedal blood flow and presence of encephalopathy andiliary obstruction have been recently reclassified as relativenes. Several articles have demonstrated little negative im-act on hepatic function in cases of portal vein tumoralhrombosis and chemoembolization can be safely performedf hepatopedal collateral flow is present.21,22 In such cases, auperselective approach as well as an adjustment of the che-otherapeutic dosage may minimize liver damage.Current absolute contraindications for TACE now include

umor resectability, intractable systemic infection, and extensiveepatic disease (Child-Pugh C). Relative contraindications in-lude a variety of other factors including, but not limited to:erum bilirubin �2 mg/dL, lactate dehydrogenase �425 U/L,spartate aminotransferase �100 U/L, tumor burden involvingore than 50% of the liver, presence of extrahepatic metastases,oor performance status, cardiac or renal insufficiency, ascites,ecent variceal bleeding, or significant thrombocytopenia, in-ractable arteriovenous fistula, surgical portocaval anastomosis,evere portal vein thrombosis, and tumor invasion to IVC andight atrium. Table 1 summarizes the list of absolute and relativeontraindications for TACE.

atient Preparationefore TACE all patients should undergo a gadolinium-en-anced magnetic resonance imaging (MRI) study of the liver,

referably with perfusion/diffusion sequences. This will de- b

ineate the extent and viability of tumor and serve as a base-ine study to plan future treatment. A dual phase MRI oromputed tomography (CT) are also acceptable but the ad-ition of the diffusion sequences may demonstrate and quan-ify tumor necrosis.23 In addition to information regardingumor viability, cross-sectional imaging may add valuablenformation regarding its vascular supply. For example, theresence of portal vein thrombosis and/or variant vascularnatomy may alter the embolization part of the procedure oreduce the procedure time and contrast load.

Patients are premedicated depending on the tumor histol-gy, renal function, and prior surgical and medical history.atients whose sphincter of Oddi function have been elimi-ated, that is, hepatojejunostomy, sphincterotomy patients,r patients with percutaneous or internal biliary stents, are atigh risk for developing a hepatic abscess after TACE. Strin-ent 24-hour bowel preparation and intravenous administra-ion of broad-spectrum intravenous antibiotics before therocedure all but eliminate this possibility. Because the pro-edure is performed under conscious sedation, an 8-hourPO status is required.

echnical Considerationslthough many different chemoembolization protocols haveeen used in the past, the combination of some chemotherapeu-ic agents and a vehicle such as lipiodol constitutes the basis ofost procedures. Single drug therapies or combinations of

gents have been used. The most widely used single chemother-peutic agent is doxorubicin and the combination of cisplatin,oxorubicin, and mitomycin C is the most common drug com-ination infused. The issue of how selectively the catheterhould be placed (lobar or segmental) during chemoemboliza-ion remains controversial. Nonocclusive and occlusive tech-iques have been described.24 Improved tumor response haseen shown when chemoembolization can be repeated multipleimes with maintenance of long-term arterial patency.25,26 Sev-ral types of embolic agents have been utilized in conjunctionith lipiodol for chemoembolization, including gelfoam pow-er and pledgets, polyvinyl alcohol, starch and glass micro-pheres, or embospheres.24 The gelatin sponges cause only tem-orary thrombosis lasting about 2 weeks, whereas polyvinyllcohol and embospheres create a more permanent effect.

Following, we describe the Johns Hopkins Hospital proto-ol, which consists of segmental or subsegmental chemoem-

able 1 Contraindications for TACE

bsolute1. Tumor respectability2. Extensive intractable infection3. Extensive liver disease

elative1. Borderline liver function2. Total bilirubin >4 mg/dL3. Portal vein thrombosis4. Uncorrectable coagulopathy5. Poor general health6. Significant arterio-venous shunting through the tumor7. Encephalopathy

olization with use of the triple chemotherapeutic cocktail of

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oxorubicin, mytomicin, and cisplatin with lipiodol, fol-owed by the injection of embospheres.

echniquefter a treatment plan is formulated and written, informedonsent is obtained the patient is brought to the interven-ional radiology suite, placed on the fluoroscopy table supinend both groins are prepared in a sterile fashion. After vol-me loading with normal saline and administration of con-cious sedation, the single-wall Seldinger technique with an8-gauge needle is used to access the right common femoralrtery. A 5-French vascular sheath is then placed into thertery over a 0.035 glide wire. Under fluoroscopic guidance,5-French catheter (Simmons-1 or Cobra) is then used to

elect the superior mesenteric artery (SMA) and the celiacxis.

A prolonged angiogram of the SMA is performed, which isarried well into the portal venous phase. This allows con-urrent assessment of any variant vessels to the liver (acces-

ory or replaced hepatic artery), retrograde flow though theastroduodenal artery (GDA), and visualization and identifi-ation of a patient portal vein (Fig 1A-C and 2A-C). A celiacngiogram adequately demonstrates hepatic branch anat-my, possible presence of replaced left hepatic artery, orther variant arteries. If possible, the right inferior phrenicrtery should be interrogated to exclude malignant parasiti-ation of blood flow. It is necessary that the injection ratessed should balance adequate opacification of the targetedessels without unnecessary reflux of contrast material intohe aorta or other vessels proximal to the injection site. Overhe guide wire, the 5-French catheter is next advancednto the desired hepatic artery branch. Depending on tumorocation, a selective hepatic arteriogram demonstrates theumor “blush” (Fig 3A-C). Special attention should be paid tohe falciform, phrenic, right, or accessory gastric arteries,upraduodenal, retroduodenal, retroportal, and cystic arter-es, to avoid nontarget embolization. The catheter should bedvanced beyond the gastroduodenal artery. In difficult casesith complex vascular anatomy, the utilization of three-di-

Figure 1 (A-C) DSA A-P views of the superior mesenteric artery,celiac axis and selective accessory right hepatic artery in a 55-year-old male patient with multiple neuroendocrine metastases to theliver, treated with TACE. (A) Accessory right hepatic artery arisingoff the superior mesenteric artery, supplying multiple lesions. (B)DSA of the celiac axis demonstrates the presence of a right hepaticartery. (C) Selective angiogram of the accessory right hepatic artery,showing multiple hypervascular lesions.

Transcatheter arterial chemoembolization 5

Figure 2 (A-D) DSA A-P views of the celiac axis, SMA, and right hepatic artery of 71-year-old male patient with HCC.(A) DSA view of the celiac axis, showing occlusion of the common hepatic artery. (B) DSA view of the SMA shows ahypertrophied pancreatoduodenal arcade and GDA, communicating with the proper hepatic artery. (C) Selective DSAview of the pancreatoduodenal arcade, GDA, and right hepatic artery. The tip of the 5 French glide Cobra catheter is inthe SMA and secured at the origin of the inferior pancreatoduodenal artery. (D) Successful engagement of the right

hepatic artery with a 3 French microcatheter.

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ensional rotational angiography may help in minimizingrocedure risks or complications and lead a more effective

esion targeting.27

Visualization of reversal of flow can be demonstrated by aicrocatheter injection with relatively high injection rates. It

s also important to identify any arteriovenous shunting pat-erns, which have been reported to occur in 31 to 63% ofases between second-order branches.28 In such cases, directmbolization of recognized shunts, even in the setting ofortal vein thrombosis, followed by chemoembolization mayrove effective (Figs 4A, B).After this initial visceral vascular evaluation has been per-

ormed, the vessel of interest targeting the specific tumor beds subsequently accessed. A solution containing cisplatin00 mg, doxorubicin 50 mg, and mitomycin C 10 mg in a 1:1o 2:1 mixture with ethiodol is subsequently injected, untiltasis is achieved. Then, 5 to 10 mL of intra-arterial lidocaines injected for immediate analgesia and to diminish postpro-edural symptoms. This is followed by injection of 1 to 2 mL ofixture containing embosphere particles (100-500 �m in size),

uspended in 1:1 ratio in contrast medium. The embolizationndpoint is not artery occlusion, but reduction in arterial inflow,or prevention of quick chemotherapy washout. Closure of fem-ral artery access can be achieved with use of a closure devicehen no standard contraindication prevailed after the perfor-ance of common femoral arteriography. A recent study onatients treated with TACE, showed that repetitive use of a col-

agen plug closure device after each procedure, does not impose D

atients to further risks.29 Table 2 shows the list of items used inur angiography suites for each procedure.

ecoveryfter proper hemostasis is achieved, the patient is placed onatient controlled analgesia (PCA) pump, intravenous hydra-ion and sent to the floor. Frequent vital signs monitoring isnly required for the 4-hour postprocedure period afterhich routine nursing checks are adequate. PRN medication

hould include (in addition to the morphine or fentanylCA), antinausea and additional pain medication for break-hrough pain. After the initial observation period, the patients encouraged to ambulate under supervision. The use of alosure device can reduce the observation period to 2 hours.s soon as the patient ambulates, the Foley catheter (if oneas placed) is removed and orally intake is advanced as tol-

rated. When the patient is ambulatory, a noncontrast CT ofhe abdomen is obtained to document the distribution ofipiodol and the degree of lipiodol uptake by the tumor.

ollow-up and Evaluationf Response to Treatment

or maximum benefit, patients should be advised to returnor a follow-up clinical visit 4 to 6 weeks after treatment.

igure 3 (A-C) DSA A-P views of the celiac axis, left hepatic artery,nd final lipiodol deposition after TACE in a 67-year-old male pa-ient with a single left-lobe HCC lesion. (A) DSA view of the celiacxis demonstrates classic anatomy. (B) DSA view of the left hepaticrtery demonstrates a hypervascular lesion. (C) Snapshot afterACE demonstrates lipiodol deposition in the treated lesion.

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uring this visit, liver function tests, as well as a perfusion-

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Transcatheter arterial chemoembolization 7

iffusion MRI scan of the liver is performed. The decision toetreat is based on the combination of imaging and laboratoryndings as well as the patient’s performance status.According to the World Health Organization (WHO) and

he Response Evaluation Criteria in Solid Tumors (RECIST),eduction in tumor size is the optimal outcome of every che-oembolization.30,31 Additionally, tumor enhancement onT or MRI delineate viability, as enhancing portions of the

umor are presumed to be viable whereas the nonenhancingnes are presumed necrotic.32-34 However, the presence ofipiodol on CT scans after chemoembolization may obscureumor enhancement and make image interpretation moreifficult. Perfusion-diffusion MRI can successfully overcomehis obstacle, as lipiodol does not obscure gadolinium en-ancement and measurement of increased free water contentithin the tumor translates into cancerous cell death.23 Fur-

hermore, diffusion MRI may prove more useful in the earlyosttreatment period after TACE, when tumors are not ex-ected to change in size despite the fact that they may beonviable (Fig 5).35,36

Lack of satisfactory response after one session of TACE

Figure 4 (A, B) DSA A-P views of the aorta and left hepat(left lobe lesion shown here) and intratumoral arterioshowing a hypervascular left lobe lesion, with early opportal venous shunting. (B) After successful gelfoam eengagement of the left hepatic artery shows no further c

able 2 List of Materials Used in an Angiography Suite for ahemoembolization Procedure

Items

5 Fr vascular sheathBentson wires5 Fr pigtail catheters5 Fr Simmons 1 catheters, glide0.35 Terumo glide wires3 Fr microcatheters (ie, Renegade)Microcatheter wires (ie, Transcend)

sChemotherapy resistant three way stop cocks

oes not predict eventual response and repeated treatmentsargeting the same lesion are sometimes necessary to be per-ormed. The emergence of any contraindications to TACEetween consecutive procedures precludes re-treatment;hus, before each procedure, the relevant laboratory valueshould be obtained and the patient re-evaluated.

omplications and Side EffectsACE has been reported to be frequently complicated byain, fever, nausea, fatigue, and elevated transaminases, com-only referred to as the postembolization syndrome. These

ymptoms are usually self-limited, are more common in caseshere large tumors are treated. In selected cases, carefulostoperative monitoring is required to differentiate postem-olization syndrome from other, more serious, complica-ions, such as liver abscess, gallbladder infarction, and septi-emia.

Complications resulting from nontarget embolization in-lude necrosis in undesirable arterial beds, such as the cysticrtery and gastrointestinal, cutaneous, and phrenic capillaryeds. Hepatic arterial pseudoaneurysm formation or arterialtenosis may occur after difficult or inelegant catheter manip-lations. Liver failure and hepatorenal syndrome are more

ikely to occur in debilitated patients with advanced diseasend those with impaired liver function or compromised por-al flow; in such individuals, it is important to weigh theossible complications of the procedure against its potentialenefits. Other uncommon problems after TACE include

schemic cholecystitis, pulmonary or cerebral embolization,ypothyroidism, or the development of a pleural effusion.able 3 summarizes a list of most commonly encountered

y in a 50-year-old male with history of multifocal HCCl venous communication. (A) DSA view of the aorta,ion of the portal vein, revealing an impressive arterio-ation of the arterio-portal venous shunting, selectivenication. TACE was safely performed thereafter.

ic arter-portaacificatmboliz

ide effects and complications of TACE.

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urvival Benefithe median survival of patients with inoperable HCC is 4 tomonths (which can be extended with maximal supportive

are to approximately 10 months). Despite that chemoembo-ization had early in its course proved to reduce tumorrowth, initial large randomized trials failed to demonstrate aurvival advantage.37-39 However, in 2002, two randomizedontrolled trials published showed a survival advantage forACE in selected patients with preserved liver function andupportive maintenance.13,14 A meta-analysis that includedeven randomized trials of arterial embolization for unre-ectable hepatocellular carcinoma provided further sup-ort of the efficacy of TACE.16 Compared with controleither conservative treatment or less favorable therapy,uch as intravenous 5-fluorouracil), there was a statisti-ally significant improvement in 2-year survival with arte-ial chemoembolization (odds ratio 0.53, 95% confidencenterval 0.32-0.89).16 TACE showed a median survival of

ore than 2 years and, although rarely, converted some pa-ients into operable candidates.

There is less experience with TACE in the treatment ofepatic metastases.40 Several studies have an excellent symp-omatic and biologic complete response rate of 70 to 73% ofatients with metastatic carcinoid treated with chemoembo-

ization.41 The efficacy of TACE in other groups, such asatients with colorectal metastasis, is less established.42

uture Promiseesearch activity on chemoembolization can be divided into

hree distinct areas that correspond to the three major ele-ents of the procedure: advancements in chemotherapeutic

gents, embolic agents, and embolization technique.Advances in the knowledge of the molecular and hepatic

Figure 5 (A-G) A 53-year-old female with a history of me(portal venous phase) showing a hypervascular lesion me(diffusion weighted imaging) corresponding to the lesiondemonstrates hypervascularity in segments 7 and 8. (D)mixture, showing good lipiodol deposition in the targegood lipiodol deposition in the targeted area. (F) MRIshowing a wedge-shaped area, corresponding to the targlesion (favorable response). Note that, according to the Rin size, measuring 4.4 � 5.6 cm. (G) MRI scan of the livea predominantly hyperintense wedge-shaped area, wi

able 3 Complications of TACE

Complication

ostembolization syndrome (pain, fever, nausea, fatigue, andleucocytosis)

iver abscessallbladder infarctionepticemia

rreversible liver failureepatorenal syndromeulmonary oil embolizationerebral embolization

(favorable response), compared with the baseline ADC value o

umorigenesis have led to the development of novel cyto-tatic agents that may interact on some disrupted pathways,nhibit angiogenesis, and limit chemotherapeutic dose-re-ated toxicity. Phase I/II/III studies are currently testinghether antiangiogenesis agents, inhibitors of growth-factor-

ignaling and cell cycle enzymes, nonspecific growth inhibi-ory agents, specific antagonists of HCC tumor markers, andnti-inflammatory agents, may have a potential impact on thereatment of liver cancer.43 The combination of these emerg-ng agents with chemoembolization seems challenging, as theeduction in the formation of new vessels may combinedith the high-intratumoral cytotoxic chemotherapeutic con-

entrations that are achieved during TACE. BevacizumabAvastin, Genentech Inc, San Francisco, CA), a humanizedonoclonal antibody that binds vascular endothelial growth

actor (VEGF) and prevents its interaction to receptors on theurface of endothelial cells, has been recently added to theriple chemoembolization cocktail for patients with primarynd metastatic liver cancer. A recent pilot study, in selectedCC patients undergoing TACE who additionally received

ntravenous bevacizumab, showed encouraging results withood drug tolerance and prolonged disease control.44 Twohase II trials, evaluating the safety and efficacy of the com-ination of bevacizumab with TACE, are currently recruitingatients with primary and metastatic unresectable liver can-er.45,46 3-Bromopyruvate (3-BrPa) is another example of arug disrupting a metabolic pathway, which has been re-ently tested via transcatheter infusion. 3-BrPa is a hexoki-ase II specific inhibitor, which potently abolishes cell ATProduction via the inhibition of glycolysis.3 Preliminary stud-

es on the rabbit VX2 liver tumor model with direct intrarterialnfusion of 3-BrPa showed complete tumor destruction, withoutffecting the surrounding normal liver parenchyma.3,43 Theechanism of resistance of normal cells against 3-BrPa hasot yet been clarified, though it might be related to the dif-erent levels of hexokinase II expression between normal andalignant cells.47 Recombinant adenoviral vectors, such as

hose expressing recombinant b-galactosidase or human he-atocyte growth factor, soaked in gelatin sponge pledgets,ave been recently tested for transcatheter delivery in ca-ines.48

Despite that extensive research is available on hepatic em-olization, the precise effect of embolization on tumor cellsemains largely undefined. In fact, recent data suggest thatypoxia, generated by arterial embolization, may activateeveral genes, including vascular endothelial growth factorVEGF) and hexokinase II, therefore leading to compensa-

carcinoid to the liver. (A) Baseline MRI scan of the liverg 1.8 cm in segment 8. (B) Baseline MRI scan of the liveribed in (A). (C) DSA A-P view of the right hepatic arteryspot image after the injection of the chemoembolizationa. (E) CT scan of the liver, 1 day after TACE, showingthe liver (portal venous phase), 1 month after TACE,

ea, with a 75% decrease in enhancement of the targetedand WHO criteria, the targeted area has now increasedsion weighted imaging), 1 month after TACE, showing

increased apparent diffusion coefficient (ADC) value

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ory angiogenesis and tumor growth.49 Similar simple obser-ations have also confirmed the angiogenesis theory by theormation of early revascularization after proximal and tem-orary embolization induced with gelfoam.50 It seems thatcclusion of more peripheral vessels generates a nearly com-lete tumor necrosis, favoring for distal embolization. Spher-

cal embolic agents allow for accurate calibration, optimalnd complete geometric vessel occlusion and therefore, maylay an important role in achieving distal occlusion. More-ver, drug-loaded (doxorubicin or irinotecan-loaded) micro-pheres have recently been developed for intra-arterial injec-ion.51 Doxorubicin-eluting beads (DC Bead for loading byhe physician and PRECISION Bead preloaded with doxoru-icin, Biocompatibles UK Ltd, Surrey, UK) were initiallyested on the rabbit Vx-2 tumor model and demonstratedonsistent drug release over time with excellent tumor con-rol.51 Clinical studies are currently in progress and initialesults seem to be rather encouraging. Irinotecan-elutingeads for metastatic colon cancer are also under develop-ent.52

Currently, there is no consensus on how selective (lobarersus segmental) chemoembolization should be. Many in-erventional radiologists prefer to treat one lobe of the liver atach treatment session, regardless of the extent or number ofumors, whereas others may choose a more selective ap-roach. Despite that longer survival seems to be related toultiple TACE sessions, further research is required to assess

he effectiveness of long-term arterial patency.53 Time-to-re-reat is also a subject of debate. Some centers prefer to treatatients at fixed timing, whereas others on disease progres-ion after the initial response. In our institution, decision toe-treat is made based on imaging and clinical assessment ofumor response. Appointments for imaging and clinical eval-ation though are scheduled within a fixed interval of timefter each treatment.

onclusionhemoembolization is currently routinely performed inany institutions throughout the world. Despite that, stan-ardization of the technique is essential for the conduct of

arge prospective randomized trials and meta-analyses, thisay prove difficult to achieve, as there is no consensus re-

arding the chemotherapeutic agents, embolic materials, andmbolization technique or re-treatment approach. Althoughomogeneity and consistency may boost the effectiveness ofhe procedure, research in other areas, such as the applica-ion of combination therapies or further employment of genend molecular therapies, may also give new dimensions tohis locoregional therapy.

eferences1. Yamada R, Nakatsuka H, Nakamura K, et al: Hepatic artery emboliza-

tion in 32 patients with unresectable hepatoma. Osaka City Med J26:81-96, 1980

2. Yamada R, Sato M, Kawabata M, et al: Hepatic artery embolization in120 patients with unresectable hepatoma. Radiology 148:397-401,1983

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1. Kobayashi N, Ishii M, Ueno Y, et al: Co-expression of Bcl-2 protein andvascular endothelial growth factor in hepatocellular carcinomas treatedby chemoembolization. Liver 19:25-31, 1999

2. Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire: Acomparison of lipiodol chemoembolization and conservative treatmentfor unresectable hepatocellular carcinoma. N Engl J Med 332:1256-1261, 1995

3. Lo CM, Ngan H, Tso WK, et al: Randomized controlled trial of transar-terial lipiodol chemoembolization for unresectable hepatocellular car-cinoma. Hepatology 35:1164-1171, 2002

4. Llovet JM, Real MI, Montana X, et al: Arterial embolisation or chemo-embolisation versus symptomatic treatment in patients with unresect-able hepatocellular carcinoma: A randomised controlled trial. Lancet359:1734-1739, 2002

5. Aoki T, Imamura H, Hasegawa K, et al: Sequential preoperative arterialand portal venous embolizations in patients with hepatocellular carci-noma. Arch Surg 139:766-774, 2004

6. Llovet JM, Burroughs A, Bruix J: Hepatocellular carcinoma. Lancet362:1907-1917, 2003

7. Llovet JM: Treatment of hepatocellular carcinoma. Curr Treat OptionsGastroenterol 7:431-441, 2004

8. Arii S, Yamaoka Y, Futagawa S, et al: Results of surgical and nonsurgicaltreatment for small-sized hepatocellular carcinomas: A retrospectiveand nationwide survey in Japan. The Liver Cancer Study Group ofJapan. Hepatology 32:1224-1229, 2000

9. Livraghi T, Meloni F, Morabito A, et al: Multimodal image-guidedtailored therapy of early and intermediate hepatocellular carcinoma:Long-term survival in the experience of a single radiologic referralcenter. Liver Transpl 10:S98-S106, 2004

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