The vascularisation of Brown-Pearce carcinoma implanted in rabbit liver.

Abstract

THE vasculature of tumours has been extensively studied by a variety of techniques, but interest has largely centred upon pure morphology. It is only recently that evidence has emerged for the existence of a special haemodynamic state peculiar to neoplastic growth and possibly of fundamental biological significance.The work of Young, Lumsden andStalker (1950), andShivas (1959) showing the existence of a capillary and venous hypertension in Brown-Pearce carcinoma has prompted this study of its vascularisation-in liver, to determine whether it conforms to the fairly clearly defined pattern of preferential supply from the hepatic artery. The concept of neoplastic haemodynamics confers a new importance upon the positive results obtained, and the findings of earlier workers must be re-examined.The present study utilised an injection technique with neoprene latex, which possesses good power of penetration of the microcirculation (Lieb, 1940) and produces a three-dimensional cast easily studied under the dissecting microscope. MATERIAL AND METHODSHealthy rabbits of mixed strains, aged 6-8 months, and weighing 2-3 kilogrammes, were used. Under nembutal anaesthesia, supplemented with ether as necessary, laparotomy was performed through a short upper midline incision and fresh fragments of Brown-Pearce carcinoma from a donor animal were implanted into the liver parenchyma using standard lumbar puncture needles. The operation was performed on 20 animals which were killed at intervals varying from 10 to 21 days after inoculation. Where a visible or palpable tumour was present the liver was removed after identification of the portal vein and hepatic artery, and perfused with normal saline through portex cannulae at pressures approximating to the normal in the living animal (130 mm. Hg in the hepatic artery, 15 cm. water in the portal vein). When the effluent from the hepatic vein ran consistently clear, coloured neoprene latex was injected under similar pressures. The cast was then fixed in a bath of concentrated hydrochloric acid for 48 hours, with a change of acid at 24 hours. Fat was then cleared by washing in 2-ethoxy-ethanol for 24 hours, and the casts were stored in distilled water with a crystal of thymol to prevent the growth of fungus. The importance ofusing fresh neoprene latex cannot be too strongly stressed, as prolonged storage undoubtedly diminishes the powers of penetration of the latex. RESULTSTumour growth was obtained in 8 of the 20 animals. Four livers were perfused through the portal vein, 1 through the hepatic artery and 3 through both vessels simultaneously using different colours of neoprene. The findings are summarised in Table I.

Tumour angiogenesis factor (TAF) in human and animal tumours

“…Similarly, tumourinduced blood vessels have been reported to be imperfectly formed and often consist merely of endothelial tubes, without any surrounding coats of muscle or connective tissue, unlike vessels arising in normal tissues (Ide et a / . , 1939;Algire and Chalkley, 1945; Delorme e l a/., 1965; Goodall et a!., 1965; Warren and Shubik, 1966;Shivas and Gillespie, 1969; Folkman rt a!., 1971 ; Le Serve and Hellman, 1972; Eddy and Casarett, 1973 ; Friedman et a/., 1974). The fact that many newlyformed blood vessels are evident 48 h after exposure to TAF indicates that vascular proliferation must start very soon.…”

Diabetes and Growth of Tumour Transplants

“…It is indeed remarkable how much this idea has been overlooked. The work of Shivas and Gillespie (1969) also stated that transplantable tumours in the liver might have different arterial patterns in them, but they did not specify to which type of tumour these vasculature changes referred. Ackerman and Lien (1969) tried to differentiate quantitatively the absorption of radio-active substances into tumours when given intra-arterially or intra-portally, comparing the absorption in normal tissue, thus introducing the term " tumour liver tissue ratio ", in order to assess the nature of the tumour.…”