DT-diaphorase and cytochrome B5 reductase in human lung and breast tumours.

The level of expression of enzymes that can activate or detoxify bioreductive agents within tumours has emerged as an important feature in the development of these anti-tumour compounds. The levels of two such reductase enzymes have been determined in 19 human non-small-cell lung tumours and 20 human breast tumours, together with the corresponding normal tissue. DT-diaphorase (DTD) enzyme levels (both expression and activity) were determined in these samples. Cytochrome b5 reductase (Cytb5R) activity was also assessed. With the exception of six patients, the levels of DTD activity were below 45 nmol min(-1) mg(-1) in the normal tissues assayed. DTD tumour activity was extremely variable, distinguishing two different groups of patients, one with DTD activity above 79 nmol min(-1) mg(-1) and the other with levels that were in the same range as found for the normal tissues. In 53% of the lung tumour samples, DTD activity was increased with respect to the normal tissue by a factor of 2.4-90.3 (range 79-965 nmol min[-1] mg[-1]). In 70% of the breast tumour samples, DTD activity was over 80 nmol min(-1) mg(-1) (range 83-267 nmol min[-1] mg[-1]). DTD expression measured by Western blot correlated well with the enzyme activity measured in both tumour and normal tissues. The levels of the other reductase enzyme, Cytb5R, were not as variable as those for DTD, being in the same range in both tumour and normal tissue or slightly higher in the normal tissues. The heterogeneous nature of DTD activity and expression reinforces the need to measure enzyme levels in individual patients before therapy with DTD-activated bioreductive drugs.     

Open Versus Endovascular Repair of Abdominal Aortic Aneurysms: What Does Each Really Cost?

Endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) has emerged as an alternative to open repair (OR). The aim of this study was to compare the clinical outcomes and specific costs of these procedures since commercialization.A retrospective analysis of 119 consecutive infrarenal AAA repaired via an EVAR or an OR between July 2000 and September 2001 was performed. Patient charts were reviewed. Diagnostic-related group (DRG) classification and payer mix were identified. The hospital cost accounting system was accessed to obtain actual variable direct cost (AVDC) for the two groups. Percentages of the mean AVDC for the two groups were compared in the following cost categories: graft, operating room, radiology procedures and supplies, pharmacy, respiratory therapy, clinical laboratories, surgical floor, and monitored unit. Hospital profit margins were determined. Fifty-five patients underwent EVAR and 64 patients underwent OR. Mean aneurysm size was 5.5Â cm (EVAR) and 6.1Â cm (OR). Mean intensive care unit (ICU) stay was 0.09 days for EVAR vs. 3.5 days for OR (p < 0.05). Mean length of stay (LOS) was 1.96 days for EVAR vs. 7.3 days for OR (p < 0.05). Reimbursement was based on DRG 110, 47.3% in the EVAR and 79.7% in the OR group (p < 0.05), and DRG 111, 50.9% in the EVAR group and 12.5% in the OR group (p < 0.05). The payer mix showed no significant differences between the two groups. Mean AVDC for EVAR was 1.74 times that of OR. Significant differences in the distribution of costs were found in the following: graft costs (58% vs. 6.3%, p < 0.05), radiology procedures and supplies (3.9% vs. 0.1%, p < 0.05), pharmacy (1.9% vs. 10.5%, p < 0.05), and monitored unit (7.3% vs. 24.65%, p < 0.05) comparing EVAR vs. OR, respectively. Median cost of an endovascular graft was 22.4 times that of the standard graft for OR. Average hospital profit margins for an EVAR case was 49.5% vs. 88.6% for OR. Despite significant differences in monitored unit utilization, pharmacy services, and respiratory therapy services by the OR group, the cost of EVAR is appreciably more expensive. Furthermore, increased DRG reimbursement, and decreased ICU use and LOS do not compensate for the cost of EVAR. The main cost of EVAR is the cost of the graft itself. Hospital profit margins are acceptable with both the EVAR and OR procedures at this time; however, with proposed reductions in reimbursement, the ability to cover the cost of this new technology may be threatened.     

A comparative study of strains of salmonella isolated from irrigation waters, vegetables and human infections

A total of 181 samples of irrigation water from the farmlands of Granada were examined for the presence of Salmonella spp. At the same time 849 samples of the crops from these farmlands and of vegetables sold in city market-places were studied. Sampling was done regularly over the period of study which ran from March 1981 to February 1983. Isolates from these sources were compared with 93 salmonellas isolated from human pathological material at various hospitals of the city of Granada from 1979-80, and again from 1981-3. The most commonly isolated serotypes of human origin were S. typhimurium and S. enteritidis. In irrigation waters and in crops, S. typhimurium, S. kapemba, S. london and S. blockley were found to be the most common. The results indicate a close relationship between the isolates from the irrigation waters and those from the vegetables, but their relationship to prevalent human infections is less clear.     

Less efficacy with alternating regimen as adjuvant chemotherapy in stage II node-positive breast cancer: results at 8 years (Pronacam 85).

A randomized trial to compare adjuvant treatment with an alternating regimen with conventional chemotherapy was performed. A total of 589 node-positive patients were included and stratified according to number of positive nodes (N1-3 and N > 4) and menopausal status. Premenopausal N1-3 patients were randomized to cyclophosphamide, methotrexate and fluorouracil (CMF) or CMF/4''-epirubicin, cyclophosphamide (EC), post-menopausal N1-3 patients to fluorouracil, 4 epirubicin, cyclophosphamide (FEC) or CMF/EC and pre- and post-menopausal patients with N > or = 4 to fluorouracil, 4'' epirubicin, cyclophosphamide, methotrexate, prednisone (FECMP) or CMF/EC. In premenopausal patients, CMF was superior to CMF/EC in terms of disease-free survival (DFS) (65% vs 45%, P = 0.0149) and survival (72.3% vs 50.2%, P = 0.0220) whereas, for N > or = 4 patients, differences between FECMP and CMF/EC did not achieve statistical significance (DFS 35% vs 26.2%; survival 50% vs 38.1%, P = NS). For post-menopausal patients, FEC was superior to CMF/EC in DFS (58.6% vs 36.8%, P = 0.0215) and survival (66.2% vs 46%, P = 0.0155). In post-menopausal patients with N > 4, differences favouring CMF/EC were significant in DFS (40.4% vs 22%, P = 0.0371) but not in survival (47.4% vs 32.2%, P = 0.1185). Alternating regimens did not offer better results in premenopausal and post-menopausal N1-3 patients. Results regarding post-menopausal N > 4 women require further confirmation.     

Cytosolic levels of TFF1/pS2 in breast cancer: their relationship with clinical–pathological parameters and their prognostic significance

Summary Background The Trefoil Factor 1 (TFF1/pS2), a peptide consisting of 60 amino acids, is the most abundant estrogen-induced messenger RNA present in MCF-7 breast cancer cells. The objective of this work was to evaluate the cytosolic TFF1 content in breast carcinomas, its possible relationship with different clinical–pathological parameters, and its potential prognostic significance and predictive value. Methods Cytosolic TFF1 levels were examined by immunoradiometric assay in 1031 patients with invasive breast cancer. The median follow-up period was of 50 months. Results There was a wide variability of cytosolic TFF1 levels in tumors (0.9–743.2 ng/mg protein). Statistical analysis showed that TFF1 levels were significantly higher in premenopausal patients (p=0.001), as well as in tumors showing any of the following characteristics: good differentiation (p=0.0001), ER and PgR positivity (p=0.0001 and p=0.001, respectively), diploidy (p=0.045) and a high S-phase fraction (p=0.001). In addition, the presence of high intratumoral TFF1 levels (cut-off: 2 ng/mg protein) was independently associated with a shorter overall survival in the group of patients as a whole (p=0.001) as well as in the subgroup with node-negative breast cancer (p=0.0004). Likewise, high intratumoral TFF1 levels were associated with a more prolonged overall survival in patients who received adjuvant tamoxifen (p=0.004). Conclusions In breast cancer patients, intratumoral TFF1 levels are associated with a better clinical outcome, especially in those with node-negative tumors. In addition, TFF1 levels have a low but significant predictive value in regards to response to adjuvant therapy with tamoxifen.