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(Radiology. 2000;215:123-128.)
© RSNA, 2000

Vascular and Interventional Radiology

Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma in Patients with Cirrhosis: Evaluation of Damage to Nontumorous Liver Tissue-Long-term Prospective Study1

Eugenio Caturelli, MD, Domenico A. Siena, MD, Saverio Fusilli, BSc, Maria Rosaria Villani, MD, Giuseppe Schiavone, MD, Michele Nardella, MD, Silverio Balzano, MD and Francesco Florio, MD

1 From the Division of Gastroenterology (E.C., D.A.S., M.R.V., G.S.), the Department of Anatomy and Histopathology (S.F.), and the Angiography Service, Department of Diagnostic Imaging (M.N., S.B., F.F.), Ospedale "Casa Sollievo della Sofferenza" IRCCS, I-71013 San Giovanni Rotondo, Foggia, Italy. Received March 10, 1999; revision requested May 21; revision received July 2; accepted July 26. Address reprint requests to E.C.


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To evaluate damage to cirrhotic liver tissue after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).

MATERIALS AND METHODS: TACE was performed in 111 patients with HCC that involved less than 30% of the liver. Baseline liver function was evaluated with Child-Pugh scores and other indicators. Eighty-two patients had Child-Pugh class A disease, 27 had class B disease, and two had class C disease. All patients underwent chemotherapy followed by gelatin sponge particle embolization in the proper ("complete" embolization; n = 69) or right or left main ("partial" embolization; n = 42) hepatic artery. Liver function was assessed 4 months later, and 95 patients underwent a second TACE (complete embolization in 57, partial in 38). Liver function was again assessed 4 months later in 60 patients.

RESULTS: No patient died. Child-Pugh scores increased in all patients from a mean 5.96 to 6.28 (not significant) and 6.51 (P = .05) after first and second TACEs, respectively. In patients with class A disease, scores increased from a mean 5.37 to 5.73 (P = .01) and 5.89 (P = .001) after first and second TACEs, respectively; in patients with class B disease, scores changed from a mean of 7.48 to 7.67 and 7.30 after first and second TACEs, respectively (not significant).

CONCLUSION: TACE does not induce significant long-term worsening of liver function in patients with class A or B cirrhosis.

Index terms: Hepatic arteries, therapeutic embolization, 952.1264, 952.1266 • Liver, cirrhosis, 761.794 • Liver neoplasms, 761.323 • Liver neoplasms, chemotherapeutic infusion, 761.1266


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms in the world, with an estimated incidence of 250,000 to 1 million new cases per year (1). This cancer is more frequent in some African and Asian regions and less frequent in Western countries (2), where it often is complicated by liver cirrhosis (3,4). Overall, HCC is associated with cirrhosis in 70%–90% of cases (4,5).

The presence and degree of cirrhosis, which directly influence liver function, can greatly affect the ability to perform surgical treatment (6), the intrahepatic recurrence and new growth of HCC (7,8), and, ultimately, survival (9). The prognosis in untreated patients is poor, with a median survival of less than 6 months after diagnosis (10). Surgical resection currently is considered to be the only curative treatment for HCC (11), but only a small number of patients can undergo such treatment. In the majority of cases, HCC is inoperable due to tumor extension, severely impaired hepatic functional reserve, or both. In these latter cases, the role of orthotopic liver transplantation is still a subject of debate (12,13).

In patients who are unsuitable candidates for surgery, local ablation therapies (eg, percutaneous injection of ethanol, hot saline solution, or acetic acid or radio-frequency interstitial thermal ablation) appear to be valid mainly for treatment of single neoplastic lesions smaller than 3–4 cm in diameter (14,15). Transcatheter arterial chemoembolization (TACE) has been widely used in cases of inoperable HCC during the past 15 years. Although the therapeutic effectiveness of this procedure is controversial, one can still affirm that TACE "is currently the mainstay of nonsurgical treatments for HCC" (16), because other systemic therapies (eg, treatment with tamoxifen citrate) have proved to be ineffective (17).

Severe hepatic dysfunction, as quantified with the Child-Pugh score has long been considered to be a contraindication to TACE (18,19), not only because of the possibility of severe complications following the procedure but also because of the poor prognosis despite treatment in patients with Child-Pugh class C disease (20,21).

Although TACE has been widely used in patients with cirrhosis, few authors have reported extensively on the effect of the procedure on liver function (20,22), and we are aware of only three studies (19,23,24) in which the damage caused by TACE to nontumorous liver tissue was estimated. To our knowledge, there are no reported data from large series about the long-term effects of TACE on hepatic functional reserve; moreover, the degree of liver impairment that would be predictive of the degree of liver dysfunction after TACE has not been ascertained. Likewise, it is not known if there are any limitations to the performance of TACE with regard to patient age. Furthermore, to our knowledge, the role of embolization in inducing long-term worsening of liver function in patients without portal venous obstruction has not been evaluated.

In the present study, we prospectively evaluated the long-term nontumorous hepatic tissue damage caused by TACE in a series of 171 procedures performed in 111 patients with HCC and cirrhosis. The roles of age and preexistent hepatic functional reserve and the results of embolization also were assessed.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
TACE was performed because of otherwise untreatable HCC in 111 consecutive patients with cirrhosis, including 98 men and 13 women (mean age, 65 years; range, 43–83 years). The cause of cirrhosis was hepatitis infection in 98 patients (hepatitis B in nine, hepatitis C in 89), alcohol related in four, and both hepatitis C and alcohol related in nine.

The diagnosis of HCC was determined with findings from ultrasonographically (US) guided fine-needle biopsy in 91 patients and with the combination of a serum {alpha}1-fetoprotein level that is diagnostic for HCC (>200 ng/mL [>200 µg/L]) and detection of a focal hepatic lesion at US in 20 patients. No patient had HCC nodules that involved more than 30% of the liver, as determined at US. Portal venous thrombosis was excluded prior to TACE by means of Doppler US.

Baseline evaluation of liver function included determination of the Child-Pugh score (25) and serum levels of aspartate aminotransferase, alanine aminotransferase, cholesterol, fibrinogen, and cholinesterase. The Child-Pugh score is determined on the basis of albumin and total bilirubin levels in serum, prothrombin time, and presence and degree of ascites and hepatic encephalopathy. The Child-Pugh class of disease was A (score, 5–6) in 82 patients, B (score, 7–9) in 27, and C (score, 10–15) in two.

Our institutional review board did not require approval, because the procedures were performed for clinical reasons. Informed consent was obtained from all patients after the nature and purpose of the TACE procedure had been fully explained.

Coaxial microcatheters were used in about 10% of the procedures when a substenotic or tortuous hepatic artery was present. No adjunctive medication was administered to the patients to prevent arterial spasm. Intraarterial chemotherapy was performed with injection of 10–12 mL of iodized oil (Lipiodol Ultra Fluide; Laboratoire Guerbet, Roissy, France) mixed with an emulsion of 40 mg of doxorubicin hydrochloride in the proper hepatic artery. All patients then underwent embolization: In 69 patients, the proper hepatic artery was embolized because of bilobar spread of HCC nodules; in the other 42 patients, only the main left (15 patients) or right (27 patients) hepatic artery was embolized, rather than one or more branches. Embolization was performed by means of a mixture of iopamidol (Iopamiro 300; Bracco, Milan, Italy) and 1-mm-diameter absorbable gelatin sponge particles (Spongostan; Ferrosan, Søborg, Denmark).

After the TACE procedure, the patients recovered with 20–24 hours bed rest. After this time, compression of the femoral artery, which had been used as an access for administration of medication, was removed. During the first 6 hours after TACE, patients underwent hourly clinical evaluation (abdominal examination and measurements of pulse rate, arterial blood pressure, and body temperature). At 4–6 hours after TACE, a white blood cell count was performed if the patient was febrile. On the morning after TACE, a routine hematologic check was performed in all patients; if severe abdominal pain or fever persisted, patients underwent abdominal US to help exclude complications such as liver abscess, peritoneal effusion, or portal venous thrombosis. Patients usually were discharged 2 days after the TACE procedure, subsequent to a further clinical examination.

After 1 month, a computed tomographic (CT) scan of the liver was obtained to facilitate assessment of the intralesional deposition of iodized oil. A positive finding was an indication for performance of repeat TACE. In seven patients, an avascular pattern of HCC lesions (already documented at angiography) indicated that iodized oil was not deposited in lesions: These patients were excluded from further TACE procedures.

After 4 months, liver function tests in all 111 patients were again performed to evaluate hepatic functional reserve. Of these, 95 patients underwent a second TACE with the same procedure as in the first TACE. Sixteen patients (nine with Child-Pugh class A disease, five with class B disease, and two with class C disease) did not undergo a second TACE because of refusal (two patients), an avascular pattern of HCC lesions (seven patients), development of portal venous thrombosis (four patients), or stenosis of the common hepatic artery (three patients). Of the 95 patients who underwent a second TACE, 57 underwent embolization of the proper hepatic artery, and 38 underwent embolization of a main branch (left hepatic artery in 13, right hepatic artery in 25).

Sixty patients who underwent a second TACE could be completely evaluated with liver function tests and liver CT scans obtained 4 months later, before a third TACE procedure. Of these 60 patients, 35 had undergone embolization of the proper hepatic artery and 25 had undergone embolization of a main branch (left hepatic artery in nine, right hepatic artery in 16). A third TACE was not performed in 35 patients (27 with Child-Pugh class A disease, eight with class B disease) because (a) complete necrosis of HCC nodules was achieved after second TACE (three patients), (b) refusal (16 patients), (c) development of portal venous thrombosis (eight patients), or (d) stenosis of the common or proper hepatic artery (eight patients).

A total of 171 TACE procedures (111 first TACEs, 60 second TACEs) were considered for the final analysis because consequences of the procedures could be completely evaluated after 4 months. Statistical consultation ensured use of the appropriate statistical analysis. The Kruskal-Wallis test was used on the basis of differences between baseline and posttreatment values, to eliminate biologic variability.


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
No patient died due to TACE in our series, and none had acute liver failure. Severe post-TACE syndrome (defined as presentation with nausea and vomiting, high fever, and/or abdominal pain necessitating analgesics) occurred after 27 (15.8%) of 171 TACE procedures. Two major complications occurred in two patients (both with Child-Pugh class A disease) after the first TACE: a subdiaphragmatic abscess (successfully treated by means of percutaneous drainage) and a pulmonary oil embolism (medically treated).

For all 171 TACE procedures, the Child-Pugh score increased from a mean baseline value (± SD) of 5.96 ± 1.19 to 6.28 ± 1.49 at 4 months after the first TACE and to 6.51 ± 1.57 at 4 months after the second TACE (Fig 1). Only the difference between baseline scores and those determined after the second TACE approached significance (P = .05).



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  		Figure 1. Bar graph shows mean values of Child-Pugh scores at baseline (before first TACE) in 111 patients, at 4 months after first TACE in 111 patients, and at 4 months after second TACE in 60 patients. Eighty-two patients had Child-Pugh class A disease, 27 had class B disease, and two had class C disease. Differences were found in all patients between baseline scores and those obtained after second TACE (P = .05) and in patients with class A disease between baseline scores and those obtained after first TACE (P = .01) and after second TACE (P = .001).

 
For the 82 patients with Child-Pugh class A disease, the score was significantly increased from a mean baseline value of 5.37 ± 1.28 to a value of 5.73 ± 1.44 at 4 months after the first TACE (P = .01) and to a value of 5.89 ± 1.37 at 4 months after the second TACE (P = .001) (Fig 1). The difference between scores obtained after the first TACE and those obtained after the second TACE was not significant. For the 27 patients with Child-Pugh class B disease, the mean Child-Pugh score did not change significantly after treatment. The baseline score was 7.48 ± 1.09 before treatment, 7.67 ± 1.20 at 4 months after the first TACE, and 7.30 ± 1.61 at 4 months after the second TACE (Fig 1).

No patient with class A disease was reclassified as having class B disease, and no patient with class B disease was reclassified as having class C disease after either the first or the second TACE. No patient, despite slight fluctuations in Child-Pugh score, experienced important long-term (8 months) worsening of his or her clinical status.

Of the other five parameters of liver function we considered, three—serum levels of aspartate aminotransferase, cholesterol, fibrinogen, and cholinesterase—showed no significant variation from baseline values after the first and the second TACE procedures (Figs 2, 3). Serum alanine aminotransferase level showed an increase that approached significance (P = .05) from a baseline level of 92.3 ± 59.81 to 113.0 ± 70.1 at 4 months after second TACE (Fig 3).



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  		Figure 2. Bar graph shows mean serum levels of cholesterol (CHOL) and fibrinogen (FIBR) in all 111 patients at baseline, at 4 months after first TACE, and at 4 months after second TACE. No significant differences were found.

 


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  		Figure 3. Bar graph shows mean serum levels of cholinesterase (CHE), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in all 111 patients at baseline, at 4 months after first TACE, and at 4 months after second TACE. The only difference that approached significance was between alanine aminotransferase levels at baseline and those after second TACE (P = .05).

 
No significant variation between pre- and posttreatment Child-Pugh scores was found when comparing patients older with those younger than 65 years. The lack of influence of age on determining deterioration of liver function after TACE was also confirmed with results after stratification according to Child-Pugh class A or class B disease.

Embolization of the proper hepatic artery did not cause a significant long-term variation in Child-Pugh score, as compared with the score after embolization of only one branch of the hepatic artery. The lack of influence of "complete" embolization on deterioration of nontumorous liver tissue function was evident in the 60 patients who underwent two TACE procedures, including those who underwent embolization of the proper hepatic artery. The results after stratification according to Child-Pugh class A and class B disease in patients who underwent embolization of the proper hepatic artery showed no role for pretreatment hepatic functional reserve in determination of post-TACE impairment of liver function.

During the 8 months of this study, no patient showed progression of HCC that involved more than 30% of the liver. Growth of HCC, therefore, was excluded as a factor in determining hepatic functional reserve.


   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
TACE is the most widely used therapy in patients with HCC who are considered to be unsuitable candidates for surgery (16). Such a treatment makes use of the hypervascular nature of HCC (26): Antineoplastic agents are directly injected into the hepatic artery, allowing high intratumoral concentrations of drugs and thereby reducing systemic side effects. The mixture of chemotherapeutic agents and iodized oil is almost completely retained in neoplastic nodules (27) and can remain in HCC tissue for a long time (28). Subsequent mechanical embolization of the artery feeding the neoplasm causes ischemic damage to the tumor (29) and prolongs the duration of the effects of chemotherapeutic agents. Among the various proposed schedules of treatment, the most effective is the one that combines endoarterial injection of antineoplastic agents (eg, epirubicin hydrochloride, cisplatin, mitomycin C, doxorubicin hydrochloride, floxuridine) mixed with iodized oil and embolization of the feeding artery with gelatin sponge material or a steel coil (9,21,29–31). The use of a coil is inappropriate when multiple treatments are planned.

The authors of many nonrandomized trials (20,21,29,30,32–34) have reported the positive effect of TACE on the decrease in tumor size, as well as prolongation of survival with good quality of life. Other authors (8,18) have reported that TACE is clinically useful only in patients with small HCC and preserved liver function. Such results indicate that TACE should be considered not only the best possible therapeutic approach in patients with advanced HCC but also a step to take before surgical resection or liver transplantation (34,35). Some authors (36) have also proposed that TACE be combined with percutaneous ethanol injection in the treatment of large HCC.

These favorable data have not been universally confirmed, however, and three randomized trials (37–39) did not result in a significant prolongation of survival after TACE when compared with survival after no treatment. Bruix et al, who initially observed a marked antitumoral effect by using a single session of transarterial embolization without associated chemotherapy (29) subsequently did not find improvement in survival after use of the same procedure (40).

The discrepancies in results among the numerous randomized and nonrandomized trials are mainly dependent on the extreme heterogeneity of either the enrolled patients or the methods used for TACE or transarterial embolization. In some important controlled studies (37,38), more than half of enrolled patients had advanced cirrhosis and/or extensive neoplastic disease. Despite the need for randomized controlled trials on this issue, few such studies have been published in the literature, and even fewer are suitable for meta-analysis (41). The crucial issue with respect to the feasibility of randomized controlled studies will always be the ethical acceptability of a trial with a study arm in which patients are not treated (such patients would hypothetically be young, have good hepatic compensation despite cirrhosis, and have two nodules of well-differentiated HCC).

For evaluation of the effectiveness of TACE, a main point is the number of TACE procedures performed in the same patient. Longer survival seems to be related to multiple TACE sessions (21,29,30,42). TACE sometimes induces an immediate worsening of hepatic dysfunction, with increases in jaundice, serum levels of aminotransferases, and ascites or development of hepatic encephalopathy (19,20). Some of these phenomena may be due to tumor lysis and liver cell necrosis. These adverse effects usually are transient, and liver function returns to its initial status or to normal within 2–3 weeks (20,23,24). Even in patients with advanced HCC but with Child-Pugh class A or B cirrhosis, immediate hepatic dysfunction after TACE disappears in about 4 weeks, which is the time necessary for liver regeneration. These side effects of TACE usually are less frequent and less marked after repeat procedures.

Some authors (9,19,21,29,31) have reported irreversible deterioration of liver function or even acute liver failure in patients who have undergone TACE, especially if a severe impairment in functional reserve (Child-Pugh advanced class B or C) existed prior to treatment. Although the possible impairment of liver function is a critical point in decision making about the feasibility of TACE, there are few studies in the literature in which the effects of TACE on hepatic function have been adequately reported (20,22), and we know of only three (19,23,24) in which the negative effects of TACE on nontumorous liver tissue were evaluated. Of these, one study (23) included assessment of hepatic functional reserve after 15 TACE procedures by using the maximal removal rate of indocyanine green; liver damage immediately after TACE was evident in half the patients. In another study (24), the degree of damage to nontumorous liver tissue due to TACE was assessed by measuring serum levels of fructose-1-phosphate aldolase in 17 patients; major liver damage immediately after TACE was found in all patients, with liver function returning to normal values within 10 days. In the only study of which we are aware with a large series of patients (n = 152), Chung et al (19) assessed liver function but evaluated the Child-Pugh score 1 week after TACE. Chung et al identified precise factors that predisposed patients for early complications after TACE; these factors included major portal venous obstruction, biliary obstruction, previous biliary surgery, hepatic arterial occlusion after multiple TACE procedures, excessive amount of iodized oil injected, nonselective embolization, and, above all, impaired hepatic functional reserve.

There has been speculation about the possible cause of liver damage due to TACE. Owing to selective uptake of the mixture of antineoplastic drugs and iodized oil by tumorous tissue, the possible adverse effects of TACE on nontumorous liver tissue are unlikely to be related to such administration alone. Moreover, it has been found in experimental animal models (27) that even large amounts of iodized oil (0.5–2.0 mL per kilogram body weight) can be tolerated. On the other hand, nonselective embolization can damage tissues other than neoplastic nodules, and the blockage of hepatic arterial flow adversely affects nontumorous liver tissue. Although it has been demonstrated that hepatic arterial embolization with gelatin sponge particles does not cause important damage to liver function in experimental animals (27) and humans with preserved hepatic functional reserve (43), there is no doubt that the most serious complication of TACE—namely, acute liver failure—almost always follows hepatic arterial embolization (44). Hepatic insufficiency after TACE is much more likely to occur in patients with portal venous obstruction (19,43,44), and this confirms the major role of ischemic rather than toxic damage in determining the cause of liver failure in these patients (24).

In our study, we performed TACE in patients with Child-Pugh class A or class B disease and a patent portal venous system. In such a selected population, embolization (which was never superselective and in more than half the patients involved both branches of the main hepatic artery) did not constitute a further risk factor for the development of liver failure after TACE, regardless of the Child-Pugh class. Overall, the increases in Child-Pugh scores after a second TACE only approached significance in comparison with baseline scores, without important variations in the patients' clinical status. Surprisingly, damage to nontumorous liver tissue caused by TACE, although slight, was more evident in patients with class A disease than in those with class B disease; however, all patients with class A disease maintained their initial class 4 months after the second TACE procedure. These data suggest that repeat TACE does not influence long-term hepatic functional reserve, which confirms the results of Bronowicki et al (20) and Bruix et al (29).

To our knowledge, there are no published data concerning the feasibility of TACE in older patients. Of interest, patient age in our series had no effect on nontumorous liver function. On the basis of these results, it can be argued that there is no age limitation for TACE in patients with Child-Pugh class A or B cirrhosis.

In conclusion, we can affirm that TACE produced only slight and clinically negligible long-term impairment of liver function in patients with Child-Pugh class A or B cirrhosis and no portal venous obstruction. Such an effect seems to be unrelated to patient age, site of embolization (proper hepatic artery or one main hepatic artery branch), and repeat treatment.


   Footnotes
 
Abbreviations: HCC = hepatocellular carcinoma TACE = transcatheter arterial chemoembolization

Author contributions: Guarantor of integrity of entire study, E.C.; study concepts, D.A.S., S.F.; study design, E.C., S.F., M.R.V.; definition of intellectual content, E.C., D.A.S.; literature research, M.R.V., G.S.; clinical studies, E.C., D.A.S., M.N., S.B., F.F.; data acquisition, M.R.V., G.S.; data analysis, S.F.; statistical analysis, S.F.; manuscript preparation, E.C., M.R.V.; manuscript editing, E.C., M.R.V., F.F.; manuscript review, M.N., S.B.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Rustgui VK. Epidemiology of hepatocellular carcinoma. Gastroenterol Clin North Am 1987; 16:545-551.
  2. Muir C, Waterhouse J, Mack T, et al. Cancer incidence in five continents Vol 5. Lyon, France: International Agency for Research on Cancer, 1987; 88.
  3. Zamann SN, Johnson PJ, Williams R. Silent cirrhosis in patients with hepatocellular carcinoma. Cancer 1990; 65:1607-1610.[Medline]
  4. Simonetti GR, Liberati A, Angiolini C, Pagliaro L. Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol 1997; 8:117-136.[Abstract/Free Full Text]
  5. Okuda K. Hepatocellular carcinoma: recent progress. Hepatology 1992; 15:948-955.[Medline]
  6. Dusheiko GM, Hobbs KEF, Dick R, Burroughs AK. Treatment of small hepatocellular carcinomas. Lancet 1992; 340:285-288.[Medline]
  7. Ikeda K, Saitoh S, Koida I, et al. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcholic cirrhosis. Hepatology 1993; 18:47-53.[Medline]
  8. Adachi E, Maeda T, Matsumata T, et al. Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology 1995; 108:768-775.[Medline]
  9. Hatanaka Y, Yamashita Y, Takahashi M, et al. Unresectable hepatocellular carcinoma: analysis of prognostic factors in transcatheter management. Radiology 1995; 195:747-752.[Abstract/Free Full Text]
  10. Levin B, Amos C. Therapy of unresectable hepatocellular carcinoma. N Engl J Med 1995; 332:1294-1296.[Free Full Text]
  11. Tsuzuki T, Sugioka A, Ueda M, et al. Hepatic resection for hepatocellular carcinoma. Surgery 1990; 107:511-520.[Medline]
  12. Iwatsuki S, Starzl TE, Sheahan DG, et al. Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg 1991; 214:221-229.[Medline]
  13. Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver transplantation versus resection for hepatocellular carcinoma in cirrhosis. Ann Surg 1993; 218:145-251.[Medline]
  14. Livraghi T, Giorgio A, Marin G, et al. Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. Radiology 1995; 197:101-108.[Abstract/Free Full Text]
  15. Rossi S, Buscarini E, Garbagnati F, et al. Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode. AJR Am J Roentgenol 1998; 170:1015-1022.[Abstract/Free Full Text]
  16. Okada S. Transcatheter arterial embolization for advanced hepatocellular carcinoma: the controversy continues (editorial). Hepatology 1998; 27:1743-1744.[Medline]
  17. Cancer Liver Italian Program (CLIP) Group. Tamoxifen in treatment of hepatocellular carcinoma: a randomised controlled trial. Lancet 1998; 352:17-20.[Medline]
  18. Ryder SD, Rizzi PM, Metivier E, Karani J, Williams R. Chemoembolization with lipiodol and doxorubicin: applicability in British patients with hepatocellular carcinoma. Gut 1996; 38:125-128.[Abstract/Free Full Text]
  19. Chung JW, Park JH, Han JK, et al. Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996; 198:33-40.[Abstract/Free Full Text]
  20. Bronowicki JP, Vetter D, Dumas F, et al. Transcatheter oily chemoembolization for hepatocellular carcinoma: a 4-year study of 127 French patients. Cancer 1994; 74:16-24.[Medline]
  21. Farinati F, De Maria N, Marafin C, et al. Unresectable hepatocellular carcinoma in cirrhosis. Dig Dis Sci 1996; 14:2332-2339.
  22. Liaw YF, Lin DY. Transcatheter hepatic arterial embolization in the treatment of hepatocellular carcinoma. Hepatogastroenterology 1990; 37:484-488.[Medline]
  23. Miyoshi S, Minami Y, Kawata S, et al. Changes in hepatic functional reserve after transcatheter embolization of hepatocellular carcinoma. J Hepatol 1988; 6:332-336.[Medline]
  24. Khan KN, Nakata K, Kusumoto Y, et al. Evaluation of nontumorous tissue damage by transcatheter arterial embolization for hepatocellular carcinoma. Cancer Res 1991; 51:5667-5671.[Abstract/Free Full Text]
  25. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni ME, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60:646-649.[Medline]
  26. Matsui O, Kadoya M, Kameyama T, et al. Benign and malignant nodules in cirrhotic livers: distinction based on blood supply. Radiology 1991; 178:493-497.[Abstract/Free Full Text]
  27. Kan Z, Sato M, Ivancev K, et al. Distribution and effect of iodized poppyseed oil in the liver after hepatic artery embolization: experimental study in several animal species. Radiology 1993; 186:861-866.[Abstract/Free Full Text]
  28. Roul JL, Bourguet P, Bretagne JF, et al. Hepatic artery injection of I-131–labeled lipiodol. I. Biodistribution study results in patients with hepatocellular carcinoma and liver metastases. Radiology 1988; 168:541-545.[Abstract/Free Full Text]
  29. Bruix J, Castells A, Montanya X, et al. Phase II study of transarterial embolization in European patients with hepatocellular carcinoma: need for controlled trials. Hepatology 1994; 20:643-650.[Medline]
  30. Ikeda K, Kumada H, Saitoh S, Arase Y, Chayama K. Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. Cancer 1991; 68:2150-2154.[Medline]
  31. Bronowicki JP, Boudjema K, Chone L, et al. Comparison of resection, liver transplantation and transcatheter oily chemoembolization in the treatment of hepatocellular carcinoma. J Hepatology 1996; 24:293-300.[Medline]
  32. Lin DY, Liaw YF, Lee TY, Lai CM. Hepatic arterial embolization in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Gastroenterology 1988; 94:453-456.[Medline]
  33. Yamashita Y, Takahashi M, Koga Y, et al. Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion. Cancer 1991; 67:385-391.[Medline]
  34. Harada T, Matsuo K, Inoue T, Tamesue S, Inoue T, Nakamura H. Is preoperative hepatic arterial chemoembolization safe and effective for hepatocellular carcinoma?. Ann Surg 1996; 224:4-9.[Medline]
  35. Yu YQ, Xu DB, Zhou XD, Lu JZ, Tang ZY, Mack P. Experience with liver resection after hepatic arterial chemoembolization for hepatocellular carcinoma. Cancer 1993; 71:62-65.[Medline]
  36. Bartolozzi 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; 197:812-818.[Abstract/Free Full Text]
  37. Pelletier G, Roche A, Olivier I, et al. A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J Hepatol 1990; 11:181-184.[Medline]
  38. Madden MV, Krige JEJ, Bailey S, et al. Randomized trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma. Gut 1993; 34:1598-1600.[Abstract/Free Full Text]
  39. Groupe D'Etude et de Traitement du Carcinome Hépatocellulaire. A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Eng J Med 1995; 11:1256-1261.
  40. Bruix J, Llovet JM, Castells A, 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; 27:1578-1583.[Medline]
  41. Simonetti RG, Liberati A, Angiolini C, Pagliaro L. Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials. Ann Oncol 1997; 8:117-136.
  42. Kanematsu T, Matsumata T, Shirabe K, et al. A comparative study of hepatic resection and trascatheter arterial embolization for the treatment of primary hepatocellular carcinoma. Cancer 1993; 71:2181-2186.[Medline]
  43. Yamada R, Sato M, Kayabata M, et al. Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 1983; 148:397-401.[Abstract/Free Full Text]
  44. Yamashita Y, Torashima M, Oguni T, et al. Liver parenchymal changes after transcatheter arterial embolization therapy for hepatoma: CT evaluation. Abdom Imaging 1993; 18:352-356.[Medline]



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