Impact of laparotomy and liver resection on the peritoneal concentrations of fibroblast growth factor 2, vascular endothelial growth factor and hepatocyte growth factor.

PURPOSE: Some data have suggested that major surgery is associated with the post-operative growth of residual tumour masses but the mechanism of this is unknown. This study was designed to determine the relationship between intraperitoneal (IP) cytokine levels, and laparotomy in benign and malignant settings. METHODS: Intraperitoneal fluid specimens were obtained at the start and at the end of laparotomy in patients with benign conditions (n=10) and in others undergoing resection of hepatic metastases from colorectal cancer (n=10). Using ELISA the concentration of the angiogenic cytokines, HGF, VEGF-A, VEGF-C, VEGF-D and FGF-2 was determined. RESULTS: The data show that in 16 of 20 patients there was a significant increase (P=0.006) in the IP concentration of hepatocyte growth factor (HGF) but not in the other growth factors by the end of the operation. The mean increase in HGF concentration was 821.5 pg/ml (95% CI: 11.0-6,426.0). Neither the groups (malignant and non-malignant) nor the length of operation correlated with greater or lesser increases in HGF. CONCLUSION: The observation that the increase in HGF occurred in both the cancer and non-cancer groups suggests that it is the surgery rather than the disease that is associated with the increased cytokine concentration. As HGF is a potent endothelial, epithelial and mesenchymal mitogen the data highlight HGF as a potential target for anti-cancer treatments in the peri-operative period. However, investigators should closely monitor wound healing as this may be compromised by this new class of drugs.

A falling HbA1c is not necessarily an indicator of improving diabetes control.

The finding of a very low haemoglobin A1c (HbA1c) (1.4%) in a diabetic patient with fairly high plasma glucose levels prompted haematological investigations, which revealed auto-immune haemolysis and a Hb concentration of 7.7 g/L. Following treatment, both Hb and HbA1c concentrations increased roughly in parallel until, 4 months later, Hb was 13.8 g/L, HbA1c 5.2% and plasma glucose was 6.8 mmol/L. This case illustrates that a falling HbA1c cannot always be attributed to improving glucose control in diabetic patients.

Age does not influence levels of HbA1c in normal subject.

To resolve whether haemoglobin A1c(HbA1c) levels in normal subjects increase with age, we measured HbA1c in 399 patients undergoing routine oral glucose tolerance test (OGTT). The OGTT results categorized the patients into 127 normal, 94 impaired glucose tolerance (IGT) and 178 diabetic. None of these groups showed a significant correlation between HbA1c and age and we cannot, therefore, see a need for age-specific reference ranges for HbA1c. Some of the confusion in the literature may have arisen from less rigorous categorization of subjects than we used, resulting in the inclusion of some individuals with IGT or diabetes in the 'normal' groups of other studies. The prevalence of such abnormality would be expected to be greater amongst older subjects, falsely suggesting a correlation between HbA1c and age, and we were able to demonstrate this with our own data when insufficiently rigorous criteria were applied for the selection of normal subjects.

The relative merits of haemoglobin A1c and fasting plasma glucose as first-line diagnostic tests for diabetes mellitus in non-pregnant subjects.

HbA1c was measured by high-performance ion-exchange chromatography in 401 non-pregnant patients undergoing oral glucose tolerance tests (OGTT). All those with HbA1c>6.2% (reference range 3.8-5.5%) had diabetic OGTT (sensitivity 41%, specificity 100%). Although a fasting plasma glucose (FPG) cut-off > or =7.0 mmol l(-1), as recommended by the American Diabetes Association (ADA), had greater sensitivity (78%), false positives (12%) limited its usefulness, so more diagnostic confidence could be placed in a positive HbA1c. In agreement with the ADA, we found FPG gave only slightly lower diabetes prevalence than the OGTT, but this masked a significant number of individual discrepancies (false positives and negatives) cancelling out each other. The new ADA category of impaired fasting glucose did not correlate well with impaired glucose tolerance. HbA1c is insufficiently sensitive as a direct substitute for the OGTT. A third of subjects diabetic on OGTT had normal HbA1c values, so it cannot exclude diabetes as currently defined, but HbA1c screening could make sufficient positive diagnoses to reduce our non-pregnant OGTTs by one-fifth. If a 'risk threshold' for diabetic complications could be applied to HbA1c, it could replace the OGTT as a more pragmatic diagnostic/prognostic test.

Fasting plasma glucose as a diagnostic indicator of diabetes mellitus.

Among 233 patients referred for glucose tolerance test (GTT), 36.4% of 129 non-pregnant subjects were classified as diabetic, compared with only 2.9% of 104 pregnant subjects. Preliminary screening using a fasting plasma glucose upper cut-off of 7.0 mmol/l, above which the subject was classified as diabetic and a lower one of 4.4 mmol/l, below which he or she was considered normal, would have eliminated the need for 30% of GTTs and positively identified 60% of the diabetics in the non-pregnant group. Only one patient would have been significantly misclassified, possibly owing to inadequate fasting. However, little benefit would result from applying an upper cut-off to low-prevalence populations such as the pregnant group. Like other recent surveys, this study suggests that World Health Organisation diagnostic figures for fasting plasma glucose could be revised downwards to 7.0 mmol/l. Conversely, to be fairly certain that an individual is not diabetic, fasting plasma glucose must be below about 4.4 mmol/l.