New development of transarterial immunoembolization (TIE) for therapy of hepatocellular carcinoma with intrahepatic metastases

Abstract

The prognosis of patients with multiple hepatocellular carcinoma (HCC) remains disappointing. In this study, we devised a new therapeutic modality for HCC consisting of transarterial immunoembolization (TIE) using OK-432 and fibrinogen and then analyzed the preliminary results. In the first series, we applied the treatment to 19 patients with advanced HCC who had proved to be insensitive to several previous conventional treatments. In all, 14 patients (74%) with unresected HCC have currently survived for between 2 and 16 months after TIE. The remaining 5 patients died at 17, 14, 8, 7, and 4 months after TIE. The serum levels of tumor markers decreased in all of the patients, and a marked reduction in tumor size was observed in six patients after TIE. A high fever occurred in all cases, and abdominal pain and loss of appetite were also observed after TIE. However, deterioration of liver function was negligible. After confirmation of the safety of this method, we started a second study series in which this TIE treatment was selected as the first choice. Six patients have been treated to date. All patients in this group underwent hepatic resection at 6-48 days following TIE. Histological examination of the resected specimens following TIE showed massive infiltration of mononuclear cells around tumor cell nests and lytic necrosis as well as coagulation necrosis of the main tumor and the intrahepatic metastases. In conclusion, our results indicate that TIE may be a safe and promising therapy for patients with HCC.

Liposome‐encapsulated OK‐432 specifically and sustainedly induces hepatic natural killer cells and intermediate T cell receptor cells

“… 28 Kanai et al reported that transarterial immunoembolization with OK‐432 and fibrinogen was effective, but caused fever in 100% of the patients treated. 29 If OK‐Lipo is used in place of unencapsulated OK‐432, systemic side effects, such as fever, will be lessened because there is little extravasation of the drug.…”

Effect of Transarterial Immunoembolization as Preoperative Treatment for Hepatocellular Carcinoma

“…OK432, a penicillin-killed and lyophilized preparation of a low-virulence strain of Streptococcus pyogenes that was developed by Okamoto et al, is successfully used as an immunotherapeutic agent in malignancies by polarizing the T-cell response to a helper T-cell 1 (Th1)dominant state [16][17][18] . Preliminary studies have shown that transarterial immunoembolization (TIE), in which a mixture of OK-432, fibrinogen, and thrombin is injected into the hepatic artery before clotting via a catheter introduced by the Seldinger technique, has a tumoricidal effect against hepatocellular carcinoma 19,20) . In these reports, the beneficial effects of TIE were evident not only for inoperable patients but also for patients with resectable tumors as a preoperative therapy 19,20) .…”

Transarterial chemoembolization alone and in combination with other therapies: a comparative study in an animal HCC model

“…In addition, mitomycin can eliminate the suppressor cells or suppressor factor in the blood or effusion, resulting in augmented anticancer activity of OK-432-activated immunopotentiating cells, especially T-cells [31,32]. It was also proven by histological examination that transarterial immunoembolization (TIE) seems to be more effective than conventional TAE for the therapy of extracapsular invasion and prevention of intrahepatic metastases in humans [14,33]. Okuno et al found that hepatic infusion of IL-2 can increase the permeability of the hepatic endothelium, resulting in an increase of hepatic extraction of antitumor agents [34].…”