risk of mortality, whereas male patients do not seem to be affected by the level of TINs. These results suggest that women appear to have a better prognosis than men in advanced gastric carcinoma. Gender differences in some host defense mechanisms and particularly in neutrophil function may be responsible for this event. Confirmation of these findings would give valuable insights about host reaction to gastric cancer growth and, ultimately, possibly would have implications regarding the identification of low-risk patients who could be spared adjuvant therapy.
The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse. © 2001 Cancer Research Campaign http://www.bjcancer.com
The evolution of gastric moderate and severe dysplasia was examined in a prospective multicenter study. One-hundred-and-nine of 141 patients with the endoscopic-bioptic diagnosis of moderate or severe dysplasia had an adequate follow-up and were included into the study. After revision of the initial slides by a gastrointestinal pathologist, 57 patients whose lesions did not meet the histological criteria for dysplasia were excluded, being reclassified as hyperplastic or metaplastic lesions (group 2). The 52 patients with confirmed moderate or severe dysplasia (group 1) were followed up for at least six months or underwent surgery for confirmed dysplasia or cancer. Thirty-two cancers were found in group 1 (33% in patients with moderate and 81% in patients with severe dysplasia). Among them, about half (n = 17) were early gastric cancers. Neither severe dysplasia nor cancer were found during the follow-up in group 2. Mean follow-up time was 13 months in group 1 and 16 months in group 2. Our results indicate that: 1) Confirmed moderate dysplasia shows a high risk of cancer development and requires strict bioptic follow-up; 2) Surgery is indicated in confirmed severe gastric dysplasia seen in the early detection of gastric cancer.
The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen þ tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage 450% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (Po0.01 and o0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l À1 onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, Po0.05) and 13.0 g/dl À1 (81.0 vs 57.6%, Po0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels p13 g dl À1 showed a lower treatmentinduced reduction in Ki67 expression (Po0.04) and a higher Ki67 expression at postoperative evaluation (Po0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism.
Prospective studies have shown a relationship between hyperinsulinaemia, an indirect index of insulin resistance, and IHD in men with normal glucose tolerance. In NIDDM this association is less clear possibly due to the poor significance of insulin and C-peptide concentrations as an index of insulin resistance. Therefore, only a direct measurement of insulin sensitivity could clarify the possible relationship between insulin resistance and IHD in NIDDM. We have evaluated insulin sensitivity, by means of an ITT, and some risk factors for IHD in 72 men with NIDDM, 36 with and 36 without IHD, attending our out-patient Diabetic Clinic. The two groups were of similar age, duration of diabetes, glycaemic control and body composition. Subjects with IHD were more insulin resistant (K(ITT) index 2.45 +/- 0.18 vs 3.12 +/- 0.13% per min, in patients with and without IHD, respectively, p < 0.004), had higher total (p = 0.011) and LDL serum cholesterol levels (p = 0.010) and greater prevalence of hypertension (p = 0.001) compared to subjects without IHD. Using step-wise logistic regression analysis, insulin resistance (odds ratio 2.57, 95% CI 1.87-3.28, p = 0.008), hypertension (odds ratio 8.17, 95% CI 6.86-9.48, p = 0.002), total serum cholesterol levels (odds ratio 1.02, 95% CI 1.005-1.035, p = 0.015) and BMI (0.79, 95% CI 0.67-0.97, p = 0.049) were independently associated with IHD. After adjustment for age and duration of diabetes, only insulin sensitivity was directly related to the age of onset of IHD, independently from other clinical and metabolic parameters (p < 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)
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