A histopathological study of 703 surgical specimens from patients with adenocarcinoma of the rectum revealed invasion of veins by primary growth in almost 52 per cent. Follow-up studies on the patients showed that the corrected 5-year survival rate was significantly worse and liver metastases developed more frequently when venous invasion was present. Invasion of extramural veins was particularly significant whereas spread confined to intramural veins was less important. Invasion of large (thick-walled) veins was of greater consequence than invasion of small (thin-walled) veins and spread into thick-walled extramural veins had the greatest adverse influence of all. Venous spread of tumour takes place in parallel with local spread as measured by the Dukes' stage but exerts an influence on prognosis independent of the Dukes' stage. Similarly, vein invasion parallels the number of lymph node metastases but appears to exert an independent influence on prognosis. Observation of venous spread provides a precise assessment of the likely behaviour of rectal carcinoma and supplements, but does not replace indices such as the Dukes' stage or the number of lymph node metastases in routine use. The implications for surgical technique and management are discussed.

Histopathological material from operation specimens of rectal adenocarcinoma was reviewed and invasion of veins identified in 51.9% of 703 cases. The extent of venous invasion, thickness of the walls of invaded veins and various other histological features were examined in detail. By follow-up studies recurrence rates, incidence of distant metastases and corrected 5-year survival rates were obtained; correlation with the histopathological results showed that invasion of extramural and thick-walled veins is associated with a poor prognosis independent of the degree of differentiation of the adenocarcinoma. Prognosis is not significantly related to the presence of necrosis of intravenous tumour and a clearly defined stroma in the intravenous growth all appear to exert a protective influence on patient survival. Whereas permeation of capillaries in vein walls, the presence of loose clumps of tumour cells in veins and direct contact between tumour cells and venous blood appear to adversely affect survival. Venous invasion is shown to be related to local invasiveness of rectal carcinoma. Suggested modes of venous spread and interaction with host tissues are proposed, with implications for general attitudes to the spread of cancer and metastasis.

1Steady-state serum phenytoin concentrations were measured in adult epileptic patients receiving a maintenance dose of phenytoin (300 mg daily). 2 Serum phenytoin concentration showed a positive correlation with age. 3 Serum phenytoin concentration showed a negative correlation with body weight and with height. Multiple correlation analysis indicated that body weight influenced the concentration to a much greater degree than height. 4 When corrected for body weight and height, the serum phenytoin concentrations in women were lower than those in men, although the difference was not statistically significant. 5 Although each of these factors contributes to the interindividual variation in serum phenytoin concentrations, the contribution of each is small. Other factors, such as genetic differences and the' effect of saturation kinetics, are much more important in determining steady-state concentrations. Adjusting the dose according to the age, weight and height of a patient would achieve only a marginal improvement in therapy.

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