[Outcome of TAE for hepatocellular carcinoma: comparative study of SMANCS-TAE and non-SMANCS/LpTAE].

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of SMANCS/lipiodol mixture was retrospectively compared to TAE with intraarterial infusion of epirubicin/lipiodol mixture in initial treatment of 54 patients with unresected hepatocellular carcinoma. The therapeutic effects were evaluated by the rate of tumor necrosis after the initial procedure and the cumulative survival rate. Eighteen patients were treated with SMANCS, and 36 patients were treated with epirubicin. There was no significant difference in patient background between the two groups; the hepatic functional reserve was not seriously disturbed in most of the patients, and multiple hepatic lesions were seen in half the patients. Complete tumor necrosis assessed by the imaging of dynamic CT one month after TAE was seen in approximately 40% of the cases in each group. Local recurrence was seen in half the patients after assessment of complete tumor necrosis within one year in both groups. There was no significant difference in survival period. There was also no significant difference of the frequency and degree of the side effects. In conclusion, no distinct difference of outcome was found in the two groups in this comparative study. Further studies in many cases over a longer period will be needed to elucidate the effects of SMANCS in TAE.

Immunohistochemical study of expression and cellular localization of the multidrug resistance gene product P-glycoprotein in primary liver carcinoma.

BACKGROUND: Expression and cellular localization of the multidrug resistance gene product P-glycoprotein, which plays an important role in multidrug resistance to cancer chemotherapy, were immunohistochemically studied in paraffin sections from 55 patients with primary liver carcinoma. METHODS: Tumor samples from 43 patients with hepatocellular carcinoma (HCC) and from 12 with cholangiocellular carcinoma (CCC) were obtained at autopsy or at surgical resection. Immunohistochemical study was performed by the avidin-biotin-peroxidase technique using monoclonal antibody JSB-1 directed against P-glycoprotein. RESULTS: Anti-P-glycoprotein immunostaining was observed in 67.4% of cases with HCC and in 66.7% of cases with CCC. When P-glycoprotein was detected in HCC, it was localized on the contact surface among tumor cells regardless of histologic type and on the cellular surface facing the blood space in the trabecular type and on the luminal surface in the pseudoglandular type. In CCC, relatively weak immunoreactivity for P-glycoprotein was localized in the cytoplasm of tumor cell both in glandular and nonglandular types, and stronger immunoreactivity was sometimes seen on the luminal surface of glandular type. The incidence of expression of P-glycoprotein was not influenced by previous cancer chemotherapy both in HCC and CCC. In the trabecular type of HCC, however, all cases with P-glycoprotein expression on the cellular surface facing the blood space were from the patients treated with antitumor agents. CONCLUSIONS: Resistance to cancer chemotherapy in primary liver carcinoma results from P-glycoprotein protein expression.

[The present status of chemotherapy for hepatocellular carcinoma].

In general, chemotherapy does not play an essential role in hepatocellular carcinoma (HCC) because of the low sensitivity to antitumor agents in cancer cells. Additionally, the vast majority of patients with HCC have chronic liver disease, notably cirrhosis, so it is virtually impossible to administer a large amount of antitumor agents. In fact, chemotherapy plays an important part in multimodal treatment for HCC. Whenever chemotherapy is used for patients in the advanced stage, it should be aimed to improve prognosis without impairment of their quality of life. Regarding prognostic factors of chemotherapy for unresectable patients, both reserved hepatic function and tumor advancement are important. Intra-arterial infusion chemotherapy using MMC, ADM, CDDP and/or 5-FU via hepatic artery is appropriately used to improve the therapeutic efficacy. The response rate by one shot injection seems to be approximately 10-20% in general. Although it is not clear which medicine and means of administration are most effective, oral administration is used as a subsidiary treatment for HCC in general. In order to enhance the efficacy of antitumor agents, various drug delivery systems including selective enhancement of tumor blood flow with angiotensin II and drug carriers such as Lipiodol have been applied. Recently, totally implantable arterial access devices have been used for intermittent intra-arterial infusion chemotherapy. It seems to make life easier for the treated patients. Further trials are planned to develop new modes of chemotherapy such as overcoming multidrug resistance by calcium antagonists.

[Intra-arterial infusion chemotherapy: clinical applications and current status of therapeutic effects on various malignant tumors].

Intra-arterial infusion chemotherapy for various malignant tumors in order to improve the antitumor effects and to diminish the side effects has been performed in general since the 1950's. Numerous reports have shown favourable therapeutic effects followed by the development of the new anticancer agents. Although in recent years application of intra-arterial administration of anticancer agents alone has been limited to such target tumors as liver cancer because of application of mechanical arterial embolization using gelatin sponge cubes, attempts have been made to enhance the antitumor effect. In order to improve targeting and stagnancy of anticancer agents in the tumor area, drug delivery systems involving arrangement of the hemodynamics of the tumor area (balloon-occluded arterial infusion therapy, administration with vasoconstrictive agents such as noradrenaline or angiotensin II and/or as administration with various drug carriers (microcapsules, lipiodol, albumin microspheres, Degradable Starch Microspheres, liposomes, etc.) have been prepared and made available for clinical use with various tumors. Furthermore, development of totally implantable equipment of intra-arterial use for not only continuous infusion but one-shot injection of anticancer agents contributes to the treatment of patients longer and more frequently with less trouble. In the future intra-arterial infusion chemotherapy will have an important role for treatment of various malignant tumors, especially as one part of multimodal treatments, although the pharmacokinetics should be more fully-studied.