2-Methyl-9-hydroxyellipticine (MHE) added to tumoral hepatocyte cultures (400 ng MHE/ml medium) is responsible for a cytostatic effect. This decrease of cellular proliferation and of DNA synthesis is accompanied by an increase of intracellular free spermidine levels. We could not attribute this result to a deviation of this polyamine metabolism. These increased concentrations of free spermidine are connected to a decrease of the amount of nuclear bound polyamines, mainly joined with the RNA fraction. Thus, the cytostatic effect observed with this drug might be related to a decrease in the amount of spermidine connected to RNA; therefore, its intercalating effect is only indirectly responsible for the cellular proliferation decrease.

Three hundred and twenty five implantable catheters (PAC) were used in the treatment of 319 patients with neoplastic disease in 21 French centers. Two hundred and sixty three were inserted in central venous position, 43 in hepatic artery and 11 were intraportal. There were no failures at the time of insertion nor any deaths imputable to the method. Whilst the mean duration of use was 182 days, 72 catheters remain patent after one year of use or more. The risk of obstruction is 3,6% : 1,5% for I.V. sites and 13,9% in intra-arterial because internal caliber are smaller. There were 2,4%, of cases of skin leakage or necrosis and sepsis rate was 2,7%, more frequent er after percutaneous insertion. These result justify the use of this device in long term chemotherapy.

Vindesine, a vinblastine derivative, was evaluated in 36 patients with malignant tumours of the buccal cavity previously untreated. Vindesine was used (1) pre-operatively, in short, weekly intravenous courses for 1 to 3 weeks and (2) prior to radiotherapy of inoperable tumours, in prolonged treatments, either by bolus i.v. injections with vein washing weekly or, in case of failure, by continuous i.v. infusion over 5 days. In the first group major responses were obtained in 22.2% of the cases. In the second group only 1 of 18 patients responded to weekly injections, whereas 3 out of 10 patients responded to continuous infusion (including one complete remission), showing that this mode of administration was more effective than bolus injections. Toxic reactions to the drug are discussed. Venous damage was the predominant complication of continuous infusion.

A series of 15 cases of hepatic metastases of unknown etiology is reported. All patients had a needle biopsy of the liver. The search for primary tumor was restricted to only those tumors requiring specific therapeutic protocols. Patients received intravenous chemotherapy in accordance with histopathological classification. This chemotherapy induced objective improvement in 46 percent of cases. The average survival of responding patients is about 16 months. Three patients had complete remissions and underwent a second laparotomy with excision of necrotic lesions in one case and installation of a catheter for endarterial hepatic chemotherapy in another. The investigators propose a diagnostic and therapeutic protocol for such patients.

This technique of anti-cancer treatment of hepatic cancers has a twofold interest: it delivers local chemotherapy in direct contact with the tumours and it allows repeated access to the blood supply of the liver without the need for surgery. This second point is particularly emphasized in the form of a technical description of the method of approach to the hepatic arterial system, which is as non-aggressive as possible and which allows permanent vascular access. This study, which required close collaboration between the departments of Vascular Radiology, Radiotherapy and Surgery, was initially considered as a feasibility study of a technique enabling the simple use of implantable vascular access sites.

Discontinuous daily ambulatory intra-arterial chemotherapy using a needle access chamber implanted subcutaneously was achieved for treatment of nonresectable isolated hepatic metastases. This original approach is a compromise between the uncomfortable exterior catheter and the exorbitant cost of a pump implant. Phase I study (6 cases) brought out the technical problems involved in this method. Phase II study (presently 11 cases) of only primary colonic or rectal tumor metastases treated with 5-fluorouracil and mitomycin C was undertaken. The preliminary results of this small series yields 64 percent objective improvement for which 55 percent are complete remissions.

314 patients with liver metastases were admitted to the Department of Surgery. University of Angers, from 1963 to 1983. The primary sites include tumors of the colon and rectum (129 patients), pancreas (74 patients), stomach (51 patients), extrahepatic bile ducts (38 patients), esophagus (7 patients), small intestine (4 patients), ovaries (4 patients), kidney (3 patients) and 4 malignant melanomas. Surgical management of liver metastases was hepatectomy (23 cases) or wedge resection (4 cases) when metastases were solitary or multiple but unilateral, selective (2 patients), total (4 patients), temporary (4 patients), desarterialization or regional intraarterial chimiotherapy (12 patients) were performed for non resectable metastases. Most of the resections (22 cases) were done for apparently solitary metastases from colorectal cancer, while a palliative treatment was utilized for some hypervascular deposits from renal, ovarian and endocrine primary tumors. The operative mortality rate was 4 per cent (2 of 49 patients): one right, and one left hepatectomies. Nine patients survived more than 2 years after liver resection, two lived more than 4 years; the longest survival (62 months) occurred after plurisegmentectomies for carcinoid metastases. The results of palliative surgery were deceptive, 14 patients died within one year, 2 patients survived 2 years, and 1 patient had a 68 months survival after liver desarterialization for carcinoid metastases. We conclude that an agressive surgical approach in the treatment of solitary or multiple resectable liver metastases is based upon several tenets. The primary tumor, when the site is the colon or the rectum preferendly must be well differentiated, Dukes B class, especially with no evidence of extrahepatic metastases.(ABSTRACT TRUNCATED AT 250 WORDS)