Tumour size and vascular invasion predict distant metastasis in stage I breast cancer. Grade distinguishes early and late metastasis.

BACKGROUND: Recent Dutch guidelines recommend adjuvant systemic treatment (AST) for women with high grade stage I breast carcinoma > or =1 cm. High grade is defined as Bloom and Richardson grade 3 (B&R3), Nottingham modification, or mitotic activity (MAI) > or =10/1.59 mm2. AIMS: To investigate the validity of these histological prognostic factors as the exclusive defining criteria. MATERIALS/METHODS: Fifty patients with stage I breast carcinoma who developed distant metastases and 50 matched controls without metastasis were studied; none had received AST. RESULTS: Cases more often had tumours > or =1 cm (p = 0,019), B&R3 tumours (p = 0.059), grade 3 nuclei (p = 0.005), and vascular invasion (p = 0.007). No differences were found for MAI > or =10 (p = 0.46). In multivariate analysis, the only significant variables were vascular invasion and tumour size (odds ratios: 8.21 and 5.35, respectively). In a separate analysis, the 50 cases were divided into 25 patients with early and 25 with late metastasis. Those with early metastasis more often had B&R3 tumours (p = 0.009) and grade 3 nuclei (p = 0.006). No differences were found for tumours > or =1 cm, vessel invasion, or MAI > or =10. Using the present Dutch guidelines for AST, based on B&R3, 20 cases and 11 controls would have received AST. Based on MAI > or =10, 14 cases and 11 controls would have received AST. CONCLUSIONS: Tumour size and vessel invasion are the best prognostic factors for disease free survival in patients with stage I breast cancer. Dutch selection criteria for AST for these patients need to be improved. Some prognostic factors are time dependent, making their use as selection criteria for AST more complicated.

Hospital volume and post-operative mortality after resection for gastric cancer.

AIMS: In low-volume hospitals, expertise in gastric surgery is difficult to maintain because of the decreasing incidence of gastric cancer and the fall of surgery for ulcer disease. We evaluated the prognostic impact of hospital volume on post-operative mortality (POM) in a consecutive series of 1978 patients. METHODS: Information on patients undergoing resection for gastric cancer in the period 1987-97 was retrieved from the Rotterdam Cancer Registry. The relationship between hospital volume and POM was analysed by logistic regression, adjusting for other prognostic factors. RESULTS: POM was 7.9% on average but varied between the 22 hospitals from 3.1% to 15.1% (P=0.15). Hospital volume had no prognostic influence (P=0.74). Prognostic factors were age (70-79 years odds ratio (OR)=3.8, 80+ years OR=6.0), sex (male OR=1.7), stage (IV OR=1.8) and (partial) gastrectomy for cardia cancers (OR=2.0). CONCLUSION: Variation in POM between hospitals was large but not related to hospital volume. For cardia cancer, POM rates were lower after oesophagogastrectomy.

Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin 1 production by Staphylococcus aureus in both logarithmic and stationary phases of growth.

Production of exotoxins by staphylococci and streptococci may lead to the development of toxic shock syndrome (TSS). Because clindamycin inhibits exotoxin production, its use has been advocated for the treatment of TSS. However, the bacteriostatic action of clindamycin might be a disadvantage for the treatment of overwhelming infections. We investigated the effects of flucloxacillin and gentamicin on exotoxin production, because incubation with these antibiotics combines bactericidal action with protein synthesis inhibition. Staphylococcus aureus during the logarithmic and stationary phases of growth was incubated with either clindamycin, flucloxacillin, or a combination of flucloxacillin and gentamicin at concentrations of 2 or 10 times the MIC. In logarithmic-phase cultures clindamycin had a static effect on bacterial growth. After incubation with flucloxacillin, either alone or in combination with gentamicin, a rapid and large reduction in the number of viable bacteria was demonstrated. In stationary-phase cultures none of the antibiotics significantly changed the number of viable bacteria. TSS toxin 1 (TSST-1) production during logarithmic-phase growth was inhibited by > or =95% by all antibiotics. In stationary-phase cultures, clindamycin, flucloxacillin, and the combination of flucloxacillin and gentamicin inhibited TSST-1 production by 95, 30, and 75%, respectively, compared with the level of exotoxin production in the controls. The present results indicate that clindamycin inhibits TSST-1 production and exerts bacteriostatic activity in both bacterial growth phases. Because the combination of flucloxacillin and gentamicin combines the inhibition of exotoxin production with high bactericidal activity at least in logarithmic-phase cultures, it should be considered an alternative to clindamycin for the treatment of exotoxin-mediated diseases, especially in patients with overwhelming infections.