Search

Transcatheter arterial chemoembolization (TACE) is widely performed in 32% of the patients with unresectable hepatocellular carcinoma (HCC) at initial diagnosis and in 58% of those with recurrent HCC in Japan. However, the patient population which undergoes TACE is heterogeneous, and thus the 3-year survival rate varies from 26 to 47%. The selection criteria for TACE is 2-3 tumors3 cm or 4 or more tumors in patients with liver damage A/B (corresponding well to Child-Pugh class A/B) and absence of vascular invasion and extrahepatic spread, as proposed by Japanese guidelines. The 3-year survival rate of TACE for patients with 2-3 tumors3 cm or 4 or more tumors was 55 and 46%, respectively, in Child-Pugh A and 30 and 22%, respectively, in class B. These outcomes could help to understand the various results of TACE in different backgrounds in the East and West. Recently, TACE with calibrated drug-eluting beads loaded with doxorubicin showed a similar tumor response and radioembolization with yttrium-90 microspheres demonstrated a similar median survival compared with conventional TACE. Based on these results, the combination of TACE and novel molecular targeted agents can be used to elucidate the synergic effect on survival.

Of 15,681 patients with hepatocellular carcinoma (HCC), 30% underwent transcatheter arterial chemoembolization with lipiodol (Lip-TACE) including infusion chemotherapy with lipiodol (Lip-TAI) for the initial treatment, and 58% underwent it for recurrent HCC according to the latest biannual report of the Liver Cancer Study Group of Japan (LCSGJ). Superselective Lip-TACE is considered to be indispensable to maximize the therapeutic effect (TE) and to minimize injury to the non-cancerous liver. The local recurrence rate of a single session Lip-TACE for HCC ≤5 cm in diameter ranged from 33 to 38% at 3 years. A pathologic study using resected specimens of 26 HCCs treated by Lip-TACE showed that the mean necrosis rates and frequency of complete necrosis in three groups, small (≤3 cm, n = 6 HCCs), medium (3.1–5 cm, n = 10), and large size (≧5.1 cm, n = 10) were 95, 87.1%; 68.4, 66.7%; 30, 0%, respectively. Namely, the smaller the tumor size, the higher the TE. However, Lip-TAI showed no correlation between TEs and tumor size. A comparative study between the pathologically proven necrosis rate on the maximum cut surface of the lesion and radiologic necrosis estimated by CT showed a significantly good correlation when the lipiodol-retained area was presumed necrotic, but a poor correlation when it was presumed a viable one. No correlation was seen between the pathologic necrosis rate and the decreased rate of the lesion treated by Lip-TACE assessed by WHO criteria. The modified version of the assessment criteria of the TE of treatment for liver cancer was proposed by the LCSGJ in 2009, using a 4-grade treatment effect with two factors of tumor necrosis and tumor regression.

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3–4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19–45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.

Transcatheter arterial chemoembolization (TACE) is widely performed in 32% of patients with unresectable hepatocellular carcinoma (HCC) at initial diagnosis and in 58% of those with recurrent HCC in Japan. However, the patient population which undergoes TACE is heterogeneous, and thus the 3-year survival rate varies from 26 to 47%. The selection criteria for TACE is 2-3 tumors >3 cm or 4 or more tumors in patients with liver damage A/B (corresponding well to Child-Pugh class A/B) and absence of vascular invasion and extrahepatic spread, as proposed by Japanese guidelines. The 3-year survival rate of TACE for patients with 2-3 tumors >3 cm or 4 or more tumors was 55 and 46%, respectively, in Child-Pugh A and 30 and 22%, respectively, in class B. These outcomes could help in understanding the various results of TACE in different backgrounds in the East and West. Recently, TACE with calibrated drug-eluting beads loaded with doxorubicin showed a similar tumor response and radioembolization with yttrium-90 microspheres demonstrated a similar median survival compared with conventional TACE. Based on these results, the combination of TACE and novel molecular targeted agents can be used to elucidate the synergic effect on survival.

Background: The Liver Cancer Study Group of Japan has designated early hepatocellular carcinoma (HCC) a clinically early-stage HCC corresponding to a high-grade dysplastic nodule as proposed by the International Working Party. Methods: The majority of resected early HCCs were demonstrated as having hypo- or isoattenuation in the arterial and delayed phases of dynamic CT. Results: Only 5% of early HCCs were hyperattenuated on dynamic CT, whereas 94% of advanced small HCC were hyperattenuated. CT arterial portography (CTAP) showed that 66% of early HCCs were hypo- and 34% were isoattenuated. CT hepatic arteriography (CTHA) demonstrated that 55% of them were hypo-, 30% were iso- and the remaining 15% were hyperattenuated. Conclusions: These findings suggest that most early HCCs receive equal or decreased blood supply from both portal and arterial blood flow compared with surrounding hepatic parenchyma. In contrast, 97% of small advanced HCCs were hypoattenuated on CTAP, and 93% were hyperattenuated on CTHA. For nodule-in-nodule type HCC, the central portion of the lesion was hyperattenuating and the peripheral portion was hypoattenuating in the arterial phase of dynamic CT, and both areas became hypoattenuated in the delayed phase. Sixty hypoattenuating nodular lesions in chronic liver disease were followed periodically with helical CT. Thirty-six (60%) of them developed to the hyperattenuating type (attenuation conversion), 21 were unchanged, and 3 disappeared spontaneously. The hyper-in-hypo-attenuating lesions showed rapid progression to entirely enhanced lesions, i.e. overt HCC. Dynamic CT is recommended as one of the low-invasive imaging modalities to follow the hypoattenuating nodules and to determine the optimal treatment with careful attention being given to intratumoral attenuation conversion.

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). Thirty HCC patients underwent transcatheter arterial injection of 4 mg SMANCS-lipiodol emulsion. Their responses were evaluated by computed tomography 1 month after treatment. Complete response (CR) was defined as disappearance or 100% necrosis of all tumors. Partial response (PR) was defined as ≧50% reduction and/or ≧50% necrosis. We regarded the lipiodol accumulation in tumors as being necrotic. CR and PR were observed in 8 patients (27%) and 4 patients (13%), respectively, and the overall response rate (CR + PR/all patients) was 40% (12/30). Of 12 patients whose serum α-fetoprotein levels had been more than 200 ng/ml before treatment, 5 patients (42%) showed more than 50% reduction in this level within 1 month after treatment. Toxicity was quite acceptable, although grade 4 toxicity (WHO) was observed as liver dysfunction in 1 patient. Transarterial chemotherapy with SMANCS, which is well tolerated, appears to have moderate antitumor effect in patients with HCC.