The effect of surgery on monocyte function.

The effect of surgery and anaesthesia in relation to tumour spread and the development of sepsis is discussed and also in relation to the host's defence mechanisms. The structure and function of the monocyte-macrophage and its central role in natural and acquired immunity is elaborated. The methods of assessing monocyte function are critically evaluated and techniques of measuring migration, phagocytosis, chemi1uminescence and determining the whole blood monocyte count are described. Monocyte function was determined in normal subjects and before and after surgery in patients with benign disease and with colorectal cancer. Prior to surgery patients with colorectal tumours tended to have impaired monocyte migration, and increased phagocytosis, chemiluminescence and whole blood counts; serum from these patients also impaired migration both by an effect on the cells and on the chemotactic solution. Whereas surgery resulted in functional alterations considered to be beneficial in patients with benign disease, certain deleterious effects were found after surgery for malignancy: there was some further impairment of migration; serum further inhibited migration and reduced the capacity of a standard chemotactic solution; serum prevented the anticipated increase in chemiluminescence; finally total opsonic activity was decreased. Levamisole, an immunostimulating agent was administered prior to surgery with a view to enhancing monocyte migration, which is a fundamental property of the monocyte. Although encouraging results were seen in the pre-operative increase of migration from the poor migratory responses observed in some patients with tumours, the post-operative fall was not altered by levamisole. Other post-operative aspects of monocyte function were also unaffected by levamisole. The implications of these results are discussed in the context of previous findings on the effect of surgery on host immunity with particular reference to the fixed macrophages of the reticuloendothelial system

RECIST response classification for each CT scan comparing SDV and original data (numbers relate to CT scans not patients).

*<p>No scan result available in the respective data set.</p

Treatment effectiveness analysis results – comparison of data sets.

*<p>HR >1 indicates a benefit to experimental treatment.</p>1<p>Discrepancy in number of deaths between SDV and original data is due to the identification of 29 additional dates of death (all dates occurred before the censoring date used in this comparison) following source data verification. These patients were censored in the ‘original’ analysis using date of last follow-up.</p>2<p>Date of progression missing for one patient (id 113).</p>3<p>Date of progression is before date of randomisation for one patient (id 468).</p

Response analysis comparing SDV and original data (numbers relate to patients).

*<p>OR >1 indicates a benefit to experimental treatment.</p

Baseline discrepancies between SDV and original data.

*<p>Four ineligible patients were not identified as ineligible by SDV.</p

Kaplan Meier curves comparing SDV and original data: Progression Free Survival.

<p>Kaplan Meier curves comparing SDV and original data: Progression Free Survival.</p

Date of death discrepancies between SDV and original data.

<p>Date of death discrepancies between SDV and original data.</p

Patients with discrepancy in number of Serious Adverse Events.

<p>Patients with discrepancy in number of Serious Adverse Events.</p

Clinical-pathological parameters of pancreatic cancer patients.

*<p> Logrank <i>P</i>-value for the differences in survival.</p>†<p> Median survival upper limit not calculable due to insufficient number of events.</p

Multivariate Cox regression analysis for the effect of mutations on survival in malignant exocrine cancer patients.

*<p> Hazard ratio and corresponding P-value for effect of mutations on survival calculated after adjusting with gender, age, TNM status, tumor differentiation grade and histology.</p