THE ABSENCE OF AUTONOMIC PERIVASCULAR NERVES IN HUMAN COLORECTAL LIVER METASTASES

The peptidergic/aminergic innervation of normal liver and tumour blood vessels was investigated in order to determine vascular control with a view to improving the efficacy of hepatic arterial cytotoxic infusio n in the treatment of colorectal liver metastases. Selected areas of l iver metastases and macroscopically normal liver from resection specim ens (n=13) were studied using light microscope immunohistochemistry fo r the presence of protein gene product 9.5 (PGP), vasoactive intestina l polypeptide (VIP), neuropeptide Y (NPY), calcitonin gene-related pep tide (CGRP), substance P (SP) and tyrosine hydroxylase (TH). The ultra structure of blood vessels supplying liver metastases and their periva scular innervation were also examined by transmission electron microsc opy. In the normal liver, perivascular immunoreactive nerve fibres con taining PGP, NPY and TH were observed around the interlobular blood ve ssels and along the sinusoids and the central vein of the hepatic lobu le. The greatest density of immunoreactive nerve fibres was seen for P GP, followed (in decreasing order) by NPY and TH. VIP, SP and CGRP imm unoreactivity was observed only in nerve bundles associated with the l arge interlobular blood vessels. In contrast, no perivascular immunore active nerves were observed in colorectal liver metastases. Electron m icroscopy confirmed the absence of perivascular nerves in liver metast ases. In addition, it showed that the walls of these blood vessels wer e composed of a layer of endothelial cells surrounded by an incomplete or, very rarely in the periphery of the tumour, a complete, layer of synthetic phenotype of smooth muscle-like cells. These results imply t hat the blood vessels supplying liver metastases are bereft of normal neuronal regulation; whether there is a role for endothelial cell cont rol of blood Bow in these vessels is not yet known.