Blood supply and drug delivery to primary and secondary human liver cancers studied with in vivo bromodeoxyuridine labeling.

BACKGROUND: Because bromodeoxyuridine (BrdU) is incorporated into DNA synthesizing (S-phase) cells, the blood supply of liver tumors can be traced by injecting BrdU into either the hepatic artery or portal vein. It also is possible to study the delivery of anti-cancer drugs acting during S-phase when they are injected by these routes. The blood supply of and drug delivery to liver tumors were examined using BrdU in patients with 19 metastatic liver cancers and 8 hepatocellular carcinomas. METHODS: At the time of hepatic resection, 200 mg of BrdU was injected by the various routes or 200 mg of BrdU suspended in 2 ml of a lipid contrast medium was injected into the hepatic artery by a reported method 2 weeks before hepatectomy. The liver tumors resected were stained immunohistochemically with an avidin-biotin-peroxidase complex method using anti-BrdU monoclonal antibody. RESULTS: BrdU injected into the hepatic artery or portal vein was incorporated into the metastatic liver tumor. After intraarterial infusion BrdU suspension, the delivery of BrdU was enhanced. The nuclei of hepatocellular carcinomas that received BrdU from the hepatic artery or portal vein incorporated BrdU. CONCLUSIONS: Metastatic liver cancers had both arterial and portal blood supplies. Hepatocellular carcinomas also had, not only an arterial, but also a portal blood supply. In both primary and secondary hepatic cancers, the delivery of anti-cancer agents acting during S-phase using the lipid contrast medium administration method was excellent.

[Clinical study of the drug delivery in metastatic liver cancer using bromodeoxyuridine].

As the model of an anti-cancer agent acting at DNA synthesizing phase, BrdU was infused for metastatic liver cancers into the portal vein and/or the hepatic artery. After administration, the liver tumors were resected, and immunohistochemical staining was performed using anti-BrdU monoclonal antibody. Two of 6 portal group tumors were stained. All 4 arterial and 3 arterio-portal group tumors were stained. Therefore, it was proved that metastatic liver tumors had both arterial and portal blood supply. But areas to which BrdU was delivered were only peripheral, and the inmost area was 2 mm from the tumor surface. After the intra-arterial infusion of BrdU suspended in lipiodol, the delivery of BrdU was highly enhanced and 4 of 6 tumors were stained even to the deepest areas. However, one tumor of which the major part was necrotic and one tumor which produced mutin were not stained at all. It was interesting that after intra-arterial administration of BrdU suspended in lipiodol, BrdU was also found in the cytoplasm of normal liver cells.

[Trans-arterial embolization or transarterial infusion of anti-cancer drugs suspended in a lipid contrast medium against unresectable metastatic liver cancer].

We had 84 patients with unresectable metastatic liver cancer from May, 1980 to December 1987 in the National Matsudo Hospital. Eighteen of them had no treatment; 26 of them had serial transarterial embolization (TAE) with or without infusion of anti-cancer drug dispersed in lipiodol; 7 of them had only serial trans-arterial infusion (L-TAI) of an anticancer drug suspended in lipiodol. A significant survival advantage of patients with TAE or L-TAI was noted when compared with no treatment, but there was no difference between the survival rate of patients with TAE and L-TAI. There were some 82 patients with unresectable metastatic liver cancer from October 1984 to March 1988 in Kyto Prefectural University of Medicine Hospital. Thirteen of them had L-TAI using one anti-cancer drug (one-drug group); 8 of them had L-TAI using two drugs (two-drug group); 22 of them had L-TAI with three drugs (three-drug group). The survival rate of the three-drug group was superior to the one- and two-drug groups. It was concluded that TAE was not necessary for metastatic liver cancer, but L-TAI must be undertaken, because combined cancer chemotherapy enhanced the effect of L-TAI.