Angiotensin alteration of drug uptake in an experimental model of hepatic metastases.

To evaluate the use of angiotensin-II (A-II) as a means of improving results with intra-arterial infusions of hepatic tumors, 32 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine [( 3H]FUDR) was administered via peripheral ear vein in 9 control rabbits (iv), via the hepatic artery in 12 rabbits (HA), and following a constant infusion of A-II in the remaining 11 rabbits (HA/A-II). Biopsies of tumor and normal hepatic parenchyma were taken and tissue levels of FUDR measured. Hepatic artery infusions, both with and without A-II, resulted in a significantly greater tumor uptake of FUDR than the iv infusions (P less than 0.001). More importantly, the tumor/liver ratio of FUDR uptake was significantly greater in the HA/A-II group (3.40) than that in the HA without A-II (0.98) group (P less than 0.001). This difference is due to the decreased FUDR uptake by normal hepatic parenchyma in rabbits undergoing A-II infusion; tumor drug uptake is similar for both groups. We conclude that the addition of angiotensin II to hepatic artery infusional chemotherapy significantly improves the tumor/liver ratio of drug uptake in this experimental model of hepatic metastases.

Total gastrectomy in the treatment of advanced gastric cancer.

To assess the role of total gastrectomy in the treatment of advanced gastric cancer, we reviewed the records of 27 patients who underwent the procedure from 1979 to 1988. Operative mortality was 4 percent (1 of 27), and postoperative morbidity occurred in 48 percent of the patients. Twenty-five of 26 patients were tolerating solid food at the time of discharge; 21 were able to maintain oral alimentation until just prior to their death. Median survival following the operation was 15 months (range: 2 to 110 months), with a 62 percent absolute 1-year survival rate and a 38 percent 2-year survival rate. On the basis of these results, we conclude that in patients with advanced gastric carcinoma, total gastrectomy with Roux-Y esophagojejunostomy can be performed with an acceptable morbidity and mortality, provides significant palliation by restoring the patient's ability to eat, and should be performed when technically feasible, even in the presence of gross residual disease.

Value of measuring hormone receptor levels of regional metastatic carcinoma of the breast.

To assess the value of measuring the estrogen- and progesterone-receptor content of metastatic nodal disease, 38 women with node-positive breast cancer were prospectively evaluated. Receptor content of the primary tumor and a pathologically confirmed positive node were measured simultaneously using a dual-isotope, dextran-coated, charcoal-binding assay. A receptor content of greater than or equal to 10 fmol/mg of cytosol protein was considered positive for both the estrogen-receptor and progesterone-receptor assays. Overall concordance between the primary tumors and the nodal metastases was 82% (31/38 patients) for the estrogen-receptor measurements and 84% (31/37 patients) for the progesterone-receptor measurements. Paired receptor levels were significantly correlated: r = .745 for the estrogen-receptor measurements and r = .805 for the progesterone-receptor measurements. Despite this correlation, 6 (25%) of 24 patients with an estrogen receptor-positive primary tumor had an estrogen receptor-negative nodal metastasis. Four (20%) of 20 patients with a progesterone receptor-positive primary tumor had a progesterone receptor-negative nodal metastasis. Six (24%) of 25 patients with tumors labeled as hormonally sensitive on the basis of the receptor content of the primary tumor had receptor-negative nodal disease. In reflecting the hormonal status of the more aggressive elements of the primary tumor, receptor levels of metastatic nodes may provide more useful information than the levels of the primary tumor as a guideline for further therapy.

Hepatic artery versus portal vein and systemic infusion of fluorodeoxyuridine of rabbit VX-2 hepatic implants.

To compare the efficacy of regional and systemic infusions of hepatic tumors, and to correlate this with tumor perfusion, 29 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine (H3-FUDR) and technetium-99m-labeled macroaggregated albumin (Tc 99m-MAA) were infused through the hepatic artery, portal vein, and peripheral vein. Hepatic artery infusion resulted in a significantly improved tumor-to-liver ratio of FUDR uptake (p less than 0.001). The increased tumor uptake correlated with a two-fold increase in tumor arterial blood flow as compared with normal liver demonstrated by the MAA infusion. We conclude that infusional therapy is superior to both portal vein and systemic infusions. Portal vein infusion results in no uptake of drug by the tumor. Hepatic artery scintigraphy with MAA may be useful in selecting appropriate patients for this type of therapy.