Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.

Five-year survival data were obtained in 97 percent or 1105 of 1140 new patients with histologically confirmed colorectal adenocarcinoma during a 12-month period in 1981 and 1982, as part of a large comprehensive population-based study of colorectal cancer incidence, etiology, and survival, The Melbourne Colorectal Cancer Study. Fifteen percent of patients were Dukes' A stage, 32 percent were Dukes' B, 25 percent were Dukes' C, and 29 percent were Dukes' D. At five years after diagnosis, the observed survival rate was 36 percent and the adjusted rate was 42 percent. Dukes' staging was a highly discriminating factor in survival (P less than 0.001). Survival rates were better in women than in men and better for patients with colon cancer than for patients with rectal cancer. Survival by Dukes' staging was not affected by colon subsite or by the tumor being the first and single tumor, metachronous tumor, or synchronous tumor. The survival of younger patients was better for Dukes' stages A, B, and C, and worse for Dukes' D. Survival was worse in the presence of bowel perforation in Dukes' C and D stages. Within Dukes' D (incurable cases), survival was best in the absence of hepatic metastases, slightly worse when only hepatic metastases were present, and poorest in the presence of both hepatic and extrahepatic metastases. Statistical modeling of survival determinants other than staging indicated that cell differentiation had the largest effect (survival decreasing with poor cell differentiation), followed by site (survival worse for rectal cancer than colon cancer), then age (survival better for younger patients), while bowel perforation had the smallest effect on survival.