Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study

Lipiodol injection is a useful method for detecting liver tumors, especially hepatocellular carcinoma (HCC). We therefore prepared and tested a new emulsion of lipiodol containing epirubicin andcis-diamminedichloroplatinum (CDDP), drugs that are very effective against HCC. This CDDP-epirubicin-lipiodol suspension (CELS) was injected into 18 HCC patients via a celiac angiographic catheter. In 11 of these patients, CELS was followed by transcatheter arterial embolization (TAE) therapy. Clinical and pharmacological investigations were performed in all 18 patients, and the following results were obtained. CELS is pharmacologicall and chemically stable, and both the results of the dissolution test and the serum levels of these two drugs indicate that slow release can be obtained. After the injection of CELS, serum levels of AFP and PIVKA-II decreased immediately, and no fatal clinical side effects were encountered. Although no statistically significant difference was observed, the survival (Kaplan-Meier method) of patients injected with CELS in the presence or absence of TAE therapy can be estimated to be much longer than that of patients receiving CDDP-lipiodol suspension injection in the presence (16 patients) or absence (6 patients) of TAE therapy. A combination of CELS injection and TAE therapy might be effective and useful for the treatment of HCC.Presented at the Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 February 1991     

Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma

The long-term effects of Lipiodol-transcatheter arterial embolization (Lp-TAE) combined with cisplatin (CDDP) or doxorubicin (ADM) on unresectable hepatocellular carcinoma (HCC) were analyzed. Eighty-four consecutive patients with unresectable HCC were treated with TAE. Of the 84, 38 patients were treated with CDDP-Lp-TAE (CDDP group), whereas the remaining 46 patients were treated with ADM-Lp-TAE (ADM group). No significant difference in characteristics of patients and tumors was noted between the groups. CDDP (50 mg) or ADM (20-50 mg) was administered with Lp followed by embolization of the feeding arteries using gelatin sponge particles. The mean number of TAE treatments was 3.3 in the CDDP group and 1.9 in the ADM group (p < 0.01). The 5-year overall survival rates of the CDDP group and the ADM group were 19% and 6%, respectively. The overall survival rate of the CDDP group was significantly higher than that of the ADM group (p < 0.05). No serious side effects were observed in either group. CDDP-Lp-TAE improved the prognosis of unresectable HCC compared with ADM-Lp-TAE, which may be attributable to the fact that CDDP-Lp-TAE treatment could be repeated more times than ADM-Lp-TAE.     

Transarterial "pile-up" infusion therapy of cisplatin and lipiodol emulsion in hepatic malignancies without TAE (transcatheter arterial embolization)]

We developed a modified transcatheter arterial infusion method using anticancer agents to treat hepatic malignancies; intermittent injections of iodized oil, lipiodol, containing adriamycin or epirubicin during the arterial infusion of cisplatin (75-200 mg/body) in order to achieve a higher concentration and longer retention of these anticancer agents in the tumor tissue. Fourteen patients with hepatocellular carcinoma (HCC) and five patients with metastatic liver cancer were treated with this "pile-up" arterial infusion therapy by anticancer agents without gelatin sponge TAE. In HCC patients, 50% or greater reduction in tumor size was obtained in 7 of 14 patients (50%). Serum AFP levels decreased by more than 75% in 6 of 7 patients in whom pretreatment serum levels of AFP were more than 200 ng/ml. The one-year and two-year survival rates were estimated at 55% and 27.5%, respectively, by the Kaplan-Meier method. Significant reduction in tumor size was not observed in 5 cases with metastatic liver cancer. Concerning the adverse effects, alimentary symptoms and fever were noted for a few days in many cases, but they were temporary and tolerable in almost all of the patients. Severe adverse changes in laboratory data were not observed. Thus this "pile-up" infusion therapy of anticancer agents without TAE may be a useful therapy for HCC.     

A randomized trial of intrahepatic arterial infusion of 4′-epidoxorubicin with Lipiodol versus 4′-epidoxorubicin alone in the treatment of hepatocellular carcinoma

We conducted a prospective randomized trial to evaluate the efficacy of Lipiodol in intrahepatic arterial infusion chemotherapy for patients with hepatocellular carcinoma (HCC). A total of 38 patients with unresectable HCCs and underlying cirrhosis were entered in this trial, and 36 of them were evaluable. Every 4 weeks, 17 patients received 70 mg of 4-epidoxorubicin (epirubicin) alone (group A), whereas 19 patients received a Lipiodol emulsion containing the same dose of epirubicin (group B) through the hepatic artery. A tumor response (CR+PR) was observed in 12% of group A patients and in 42% of group B patients. The group B patients showed a significantly higher response rate than the group A patients. There was a tendency for an increased duration of survival (P=0.09) in the group B patients. These results suggested that the infusion of the Lipiodol emulsion with epirubicin was more effective than epirubicin alone for the treatment of these patients with HCC.Work presented at the Third International Symposium on Treatment of Liver Cancer, Scoul, Korea, 12–13 February 1993     

Non-surgical (medical) treatment of hepatocellular carcinoma (HCC)

Choice of treatment for HCC depends mainly on the size of tumor and patient's liver function because more than 80% of HCC patients are associated with liver cirrhosis. Percutaneous ethanol injection therapy (PEIT), transcatheter arterial embolization (TAE) and intraarterial infusion chemotherapy are, at present, commonly used treatments for HCC in Japan. PEIT is a safe and reliable treatment, in which absolute ethanol is injected to the tumor through a fine needle under US guide. PEIT is indicated for tumors of small size, which can not be removed surgically. The survival rate of PEIT for small liver cancer, less than 2 cm in diameter, is similar with the one of surgically removed cases. TAE is indicated for advanced HCC. Chemoembolization with Lipiodol is commonly used with good result. After TAE has been often performed, the survival rate of HCC patients was dramatically increased. In future, TAE combined with percutaneous transhepatic portal embolization or PEIT would be applied more often to obtain complete destruction of the lesion for advanced HCC. Intraarterial infusion chemotherapy is indicated for advanced HCC, in which TAE can not be performed. MMC, ADM and CDDP are commonly used anti-cancer drugs. Recently frequent infusion of these drugs has become possible by using implantable reservoir with good result. We have performed chemosensitivity test by SRCA for HCC specimens obtained by biopsy using a fine needle.     

A case report of successful transcatheter arterial embolization therapy for osseous metastasis of hepatocellular carcinoma

A 74-year-old man was admitted to our hospital with a chief complaint of severe local pain of the hip joint. Radiological findings showed a metastasized lesion on the left side of the pelvic wall originated from hepatocellular carcinoma (HCC) in the anterior segment of the liver. Transcatheter arterial embolization (TAE) therapy using epirubicin, Lipiodol and Spongel was successfully performed twice for primary HCC, and four times for osseous metastasis of HCC. After TAE therapy, the size of the metastasized lesion decreased with relief of pain, and an improvement in performance status of 4 to 2 was achieved. In conclusion, TAE therapy is thought to be very useful in the treatment of osseous metastasis of HCC with severe local pain.     

Assessment of therapeutic effects of cisplatin-phosphatidyl-choline-lipiodol (CPL) suspension for hepatocellular carcinoma]

Sixty-three patients with unresectable hepatocellular carcinoma (HCC) were treated with cisplatin-phosphatidyl-choline-Lipiodol (CPL) suspension. Partial response (PR) and minor response (MR) were obtained in 3 of 14 cases (21.4%) by one shot therapy, and in 13 of 43 cases (30.2%) by TAE therapy. AFP decreased in 11 of 15 patients (73.3%) by one shot therapy, and in 32 of 33 patients (97%) by TAE therapy. PIVKA II also decreased. The one-year survival rate was 74% in TAE therapy, and 52% in one shot therapy. The two-year survival rate was 53% in TAE therapy, and 28% in one shot therapy. Nausea, vomiting and fever were noted in most cases as adverse effects, but they were slight. The concentration of free-CDDP in the peripheral venous blood was lower and continued longer than that of CDDP on the market. These results suggest that CPL was useful as an anticancer agent for arterial chemotherapy or TAE therapy for unresectable HCC.     

A phase II trial of transcatheter arterial infusion chemotherapy with an epirubicin-Lipiodol emulsion for advanced hepatocellular carcinoma refractory to transcatheter arterial embolization

Introduction Transcatheter arterial embolization (TAE) has been recognized as an effective palliative treatment option for advanced hepatocellular carcinoma (HCC). However, no effective alternative treatments for TAE-refractory HCC have yet been established. The aim of this study was to evaluate the antitumor activity and toxicity of transcatheter arterial infusion chemotherapy using an epirubicin-Lipiodol emulsion in patients with TAE-refractory HCC. Methods Patients with TAE-refractory HCC were enrolled. A dose of 60 mg/m² epirubicin emulsified in Lipiodol and contrast medium was administered from the feeding artery of the HCC. Treatment was repeated every 4 to 12 weeks if there was no evidence of tumor progression or unacceptable toxicity. Results Twenty patients were enrolled in this trial. The median number of treatment courses was 1 (range 1–4). Among the enrolled patients, one (5%) achieved a partial response, and three (15%) showed a minor response. Five (25%) patients had no change and 11 (55%) showed progressive disease. The median survival time, 1-year survival rate and median progression-free survival time for the patients as a whole were 12.4 months, 52.6%, and 1.1 months, respectively. The main grade 3 and 4 toxicities were leukocytopenia (35%), neutropenia (65%), thrombocytopenia (30%), and elevations of the aspartate aminotransferase (45%) and alanine aminotransferase (35%) levels. These toxicities were generally brief and reversible. Conclusion Transcatheter arterial infusion chemotherapy with an epirubicin-Lipiodol emulsion appears to have only modest activity with moderate toxicity for treatment of patients with TAE-refractory HCC. These findings do not support its use in practice, and further studies with the same regimen in patients with TAE-refractory HCC are not recommended.     

Targeted Chemotherapy for Unresectable Primary and Metastatic Liver Cancer

In targeted chemotherapy, Lipiodol Ultrafluid was used as a carrier of anticancer drugs; these combinations were termed oily anticancer agents. Arterial injection therapy with these oily anticancer agents was performed in 330 patients with unresecrable hepatocellular carcinoma (HCC) and 110 patients with unresectable metastatic liver cancer. The alpha-fetoprotein (AFP) level decreased in 178 of 186 AFP-positive patients with HCC. Tumor size was reduced in 256 of 269 evaluable patients with HCC. The treatment seemed to prolong survival and in 193 HCC patients who were good candidates for therapy (those without Child C liver cirrhosis, without tumor occupying all four segments of the liver, or without extrahepatic spread) the 1-, 2-, and 5-year survival rates were 85, 52, and 34% respectively. In the 110 patients with metastatic liver cancer, the carcinoembryonic antigen level and tumor size were reduced. The 1-, 2-, and 5-year survival rates of these 110 patients were 61, 32, and 22% respectively.     

Arterial chemotherapy and transcatheter arterial embolization therapy for non-resectable hepatocellular carcinoma

An assessment was made on the therapeutic effects of arterial chemotherapy and transcatheter arterial embolization (TAE) therapy on 378 cases with non-resectable hepatocellular carcinoma (HCC). For the 191 cases who had undergone arterial chemotherapy, 22% had a 1-year survival rate, 8.9% survived for 2 years, and 4.0% for 3 years. Of these, for the 128 cases who were compatible with our criteria for patient selection, the three survival rates were 31.4%, 12.2% and 5.9% respectively. However, for the other 63 cases, who were incompatible with our criteria, the 1-year survival rate was 1.6% and it was worse for the cases who had received supportive care alone. For the cases who had undergone arterial chemotherapy, the highest survival rates were obtained by the alternate administration of different anticancer agents, and the three survival rates were 39.0%, 13.1% and 4.9% respectively. For the 187 cases who had undergone TAE therapy, the 1-year survival rate was 66.2%, the 2-year survival rate 36.5%, and the 3-year survival rate 21.9%. For the 124 cases with a tumor progression rate of less than 20% in the liver (E1), the survival rates were 77.8%, 50.1% and 30.8% respectively. The peripheral venous drug concentrations of mitomycin C and adriamycin were lower, but were maintained for a longer period in TAE therapy than in arterial chemotherapy. These results suggest that consideration of the criteria for patient selection and the alternate administration of anticancer agents are necessary in arterial chemotherapy, and that the best therapeutic effects can be obtained by TAE therapy combined with chemotherapy for cases of non-resectable HCC because of the chemotherapeutic and ischemic effects on the tumors.     

Effect of arterial administration of a high-molecular weight antitumor agent, styrene maleic acid neocarzinostatin, in embolization-resistant liver cancer

Background. Hepatocellular carcinoma often shows a resistance to transcatheter arterial embolization in the course of therapy repetition. Methods. Forty-four of 103 consecutive patients with hepatocellular carcinoma showing a resistance to repeated embolization therapy were treated with intra-arterial injection of the high-molecular weight antitumor agent styrene-maleic acid neocarzinostatin (Zinostatin) mixed with Lipiodol (group A). The remaining 59 patients received repeated embolization with epirubicin given in the same way (group B). Results. In group A, computerized tomography scans 3 months after the therapy showed "complete" accumulation of Lipiodol in 2 patients (4.5%), and "good" accumulation (50%–99%) in 11 (25.0%); 10%–49% accumulation was shown in 12 patients (41.9%), and less than 10% in 19 patients (32.6%). In group B, 1 patient (1.7%) showed complete accumulation, 4 (6.8%) showed "good" accumulation, 10 (16.9%) showed 10%–49% accumulation, and 44 (74.6%) showed less than 10%. Multivariate logistic regression analysis showed that factors affecting Lipiodol accumulation after therapy included tumor multiplicity (P < 0.0001), use of Zinostatin (P = 0.010), and decompensation of cirrhosis (P = 0.049). In the 44 patients with Zinostatin injection, tumor size was the only factor affecting Lipiodol accumulation. Survival rates in groups A and B were 70.4% and 45.8%, respectively, at the end of the first year, 36.8% and 17.3% at the end of the second year, and 24.5% and 13.0% at the end of the third year (P = 0.0087). Conclusion. Intra-arterial Zinostatin injection therapy increased the Lipiodol accumulation rate and the survival rate in patients with embolization-resistant HCC, and the best candidates for the treatment were patients with smaller liver cancer of 50 mm. Received: March 23, 1998 / Accepted: November 24, 1998     

Chemoembolization therapy of hepatocellular carcinoma-antitumor effect and side effect

Chemoembolization therapy with arterial injection of a mixture of various anticancer agents (CDDP, ADR, MMC) and Lipiodol along with gelfoam particles was carried out on 158 cases of hepatocellular carcinoma between January 1985 and July 1987. In two groups using CDDP the tumor regressed 50% or more in higher percentage than in the groups without CDDP. The antitumor effect was more significant in the group using CDDP and ADR than in the group using CDDP alone. No significant side effect was noted in any case.     

Clinical study of the effect of cisplatin therapy in unresectable hepatocellular carcinoma

Twenty-one cases of unresectable hepatocellular carcinoma (HCC), including 15 cases receiving intravenous infusion of CDDP in addition to transcatheter arterial embolization (TAE), and 6 cases receiving intraarterial infusion of CDDP in combination with sodium thiosulfate rescue (STS rescue) were studied. In the 15 cases given intravenous infusion therapy with TAE, favorable effects were observed in 33.3% of patients, and the 50% survival period was 22.5 months. In the 6 cases given intraarterial infusion, favorable effects were obtained in 66.6% of patients, but the 50% survival period was 2 months. The side effects observed most frequently were nausea and vomiting. All the other side effects observed were not so severe. These results suggest that intravenous CDDP infusion in addition to TAE is favorable, producing a life-prolongation effect.     

Assessment of chemoembolization therapy for primary liver cancer using a stabilized Adriamycin-lipiodol suspension

We formulated a new lipiodol-Adriamycin suspension (ADM/lipiodol, 50 mg/10 ml) that remained stable for 48 h (half-life, 25±3 days). In five cases of hepatocellular carcinoma (HCC) resected after intra-arterial infusion of this agent, the ADM concentration in the tumor was quite high and the tumor necrosis rate was more than 80% on histological examination. Over a 5-year period, 180 patients with unresectable HCC underwent transcatheter arterial embolization therapy (TAE) in the presence or absence of this agent. The regimens consisted of suspension injection alone (A,n=54), suspension injection+TAE using gelatin sponge (B,n=29), TAE followed by suspension injection (C,n=34), and TAE alone (D,n=63). The estimated 1-year survival values determined for patients treated with these regimens were 70%, 73%, 43%, and 39% respectively, and the corresponding 3-year survival values were 27%, 31%, 15%, and 10%. The survival achieved using suspension injection was thus superior to that obtained using conventional TAE, and combined therapy with suspension injection followed by TAE seemed to enhance survival, although there were some biases in tumor size and in the stage of tumor progression. For patients with tumors measuring 5 cm or more in diameter, the survival obtained using regimen A was lower than that achieved using regimen D, but the combination of TAE and suspension injection improved the 1-year survival value obtained using regimen D from 34% to 52%. For patients with tumors measuring less than 5 cm in diameter, the survival achieved using regimen A was markedly better than that obtained using regimen D, although no difference was found between the survival value achieved using regimen A and that obtained using regimens B and C. On the basis of these results, our newly formulated ADM-lipiodol suspension was surmised to be effective by itself against relatively small HCC tumors, whereas it enhanced the efficacy of conventional TAE in large lesions.Presented at the Second International Symposium on Treatment of Liver Cancer, Taipei, 3–4 February 1991     

Styrene maleic acid neocarzinostatin-transcatheter embolization for hepatocellular carcinoma--third report

To evaluate the effect of styrene maleic neocarzinostatin-transcatheter arterial embolization (SMANCS-TAE), 40 patients with unresectable hepatocellular carcinoma (HCC) of hypervascular radiological feature, associated with liver cirrhosis (LC), 18 in clinical stage 2 and 20 in stage 3, were treated by SMANCS-TAE. SMANCS with Lipiodol and then gelatin sponge particles were injected into the artery branch supplying HCC using selective catheterization, and its effect was evaluated by computed tomography (CT) Grade. In patients with Grade III or less (Lipiodol accumulation < 99% in the entire tumor) after the first course of therapy, SMANCS-TAE or arterial injection of SMANCS-Lipiodol was performed once or twice more. Consequently, 32 of 40 patients (80%) obtained Grade IV (100% Lipiodol accumulation in the entire tumor) after from once to thrice (median, 1.6 courses). Grade IV was maintained in 26 of 32 patients, and non-recurrence was found 16 of 40 (40%) at the primary tumor to the time at last of follow up. Severe side effects were not noted except in 10 cases with narrowness of hepatic artery and cases of 2 biloma in patients undergoing therapy two or more times. The 1-, 2-, 3-, and 5-year survival rate was 85, 64, 35, and 26%, respectively. No significant difference was noted in the survival rate between clinical stage 2 and 3 liver cirrhosis (LC). But the survival rate of patients who continued to exhibit Grade IV at the primary tumor was significantly better than in those exhibiting Grade III or less (96, 68, 56, and 43% vs 64, 29, 0, and 0%, respectively; p < 0.01). In conclusion, the HCC patients, even those with decompensated LC, who obtained and maintained Grade IV after SMANCS-TAE could reduce the courses of treatment without severe side effects and survived longer. SMANCS-TAE might be useful for the good quality of life of HCC patients.     

TACE versus TAE as therapy for hepatocellular carcinoma

Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.     

TACE versus TAE as therapy for hepatocellular carcinoma

Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.     

Repeated arterial infusion chemotherapy for inoperable hepatocellular carcinoma using implantable drug delivery system]

We performed a clinical evaluation of repeated arterial infusion chemotherapy using an implantable drug delivery system for 41 patients with inoperable hepatocellular carcinoma (HCC). About half of our patients could not undergo transcatheter arterial embolization (TAE) because of extreme tumor extension and/or accompanying advanced cirrhosis. In most patients we implanted a 5 Fr. catheter non-surgically and connected it to an implanted injection port through a subcutaneous tunnel. The treatment schedule was weekly or biweekly intrahepatic one-shot administration of mitomycin C, adriamycin, 5-fluorouracil and epirubicin. The response rate (CR + PR) was 24.4%. The median survival period was 401.1 days. The 6 month, 1-year and 2-year survival rates were 73%, 48% and 24%, respectively. There were no severe side effects nor complications. The implantable drug delivery system will contribute not only to improved therapeutic efficacy for inoperable HCC but also improve the quality of life for patients.     

海藻酸钠微球在肝动脉化疗栓塞治疗中晚期原发性肝癌中的疗效研究

目的 比较海藻酸钠(KMG)微球和明胶海绵颗粒在肝动脉化疗栓塞中的栓塞效能、疗效,并探讨栓塞效能和疗效间的关系.方法 接受KMG微球及明胶海绵颗粒栓塞的同质中晚期肝癌患者各50例,分别为实验组和对照组,比较两组患者的栓塞效能(术后1个月瘤灶的碘油沉积率)以及栓塞疗效,并比较栓塞效能与疗效间的关系.结果 术后第一个月的碘油沉积率实验组和对照组分别为(81.32±13.322)%和(50.78±19.723)%;差别有统计学意义.2年肝内肿瘤进展率实验组和对照组分别为48%和68%;差异有统计学意义;无进展生存率实验组和对照组分别为46%和26%,有统计学意义.实验组和对照组1年和2年生存率分别82%,72%和60%,38%;差异有统计学意义.实验组和对照组1、2年肝外肿瘤进展率分别2%,4%和20%,30%,有统计学意义.1年肝内肿瘤进展及1年无进展生存率,两组比较无差别.实验组和对照组1年生存率分别为82.2%和33.3%;差异有统计学意义,而无进展生存率分别为74.0%和30.4%;P=0.009,且1年肝内肿瘤进展率分比为4.1%和29.6%;P<0.001,肝外肿瘤进展率实验组和对照组分别为0.31%vs 35.5%;P<0.001.结论 KMG微球治疗应用于肝动脉化疗栓塞术中治疗原发性肝癌安全,患者耐受良好;作为栓塞剂,较之明胶海绵颗粒,能取得更优的近期以及远期疗效. 肿瘤灶中碘油的沉积率作为栓塞效果的指标,碘油沉积率较高的肝癌患者其预后往往更优于乏碘油沉积的肝癌患者.     

Multimodality treatment for patients with hepatocellular carcinoma: a single institution retrospective series.

BACKGROUND: The main therapeutic options for hepatocellular carcinoma (HCC) are hepatic resection, transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT) and regional chemotherapy (RC). METHODS: This study retrospectively examined the results of primary treatment of 600 patients with hepatocellular carcinoma selected according to the treatment guidelines of our facility and the results of various combination therapies for recurrent cases. The selection criteria of therapeutic options included the number and size of tumours and hepatic function. RESULTS: The selected primary treatment was hepatic resection for 53.7% of the cases, TAE for 31.5%, PEIT for 8.2% and RC for 6.6%,. The treatment for post-resection recurrence was TAE alone for 62.4% of the cases, TAE + RC for 4.0%, PEIT for 15.2%, TAE + PEIT alone for 4.8%, RC for 8.0% and hepatic resection for 5.6%. The treatment for post-TAE recurrence was TAE alone for 83% of the cases, TAE + PEIT for 9%, TAE + RC for 3%, RC alone for 3% and PEIT alone for 2%. For post-PEIT, therapy was PEIT alone for 71.4% of the cases and PEIT + TAE for 28.6%. For post-RC, RC alone was used for 92.5% and RC + PEIT for 7.5%. The cumulative 3 and 5-year survival rates were 84.4% and 70.6%, respectively for stage I; 61.5% and 48.6% for stage II; 52.7% and 20.5% for stage III; and 22.8% and 17.1% for stage IVA. The cumulative 5 and 7-year survival rates after the primary treatments were 52.% and 40.1%, respectively, for hepatic resection; 46.5% and 38.7%, for TAE; 49.6% and 33.1% for PEIT; and 16.7% and 8.3% for RC. CONCLUSIONS: To improve the treatment results for HCC, early detection is essential and various modalities of treatments in combination should be used for recurrence after primary treatment.