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Abstract: The aim of the study was to evaluate the long-term survival of patients with invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the metastatic behavior of these two disease entities. Originally, all consecutive patients with pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area served by the Tampere University Hospital and their matched IDC controls were identified and re-evaluated histopathologically in this follow-up study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and survival were collected until the end of year 2009. Statistical analyses including Kaplan–Meier method, log-rank test, Fisher's exact test and Cox regression analysis were performed with the PASW Statistics 18.0 computer program. P-values of <0.05 were considered statistically significant. Within the mean follow-up time of 10.04 years, locoregional recurrences were significantly more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in the total number of distant recurrences or bilaterality were observed. However, when the first distant recurrence sites were studied, ILC patients had significantly less lung metastases (p = 0.04), but more skin metastases (p = 0.04). During the whole follow-up period IDCs metastasized significantly more frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were more common among ILCs (p = 0.02). Although the known favorable prognostic factors (hormone receptor positivity, low grade, low s-phase) were more common for the ILCs, the disease-free survival, the overall survival and the survival after recurrence did not differ between the groups. However, the Cox-regression model showed significantly worse survival for ILCs after adjusting for age, TNM-status, grade and ER-positivity (p = 0.004). In conclusion, ILC and IDC differ in respect for visceral metastases. Despite the known favorable prognostic factors and originally favorable survival, patients with lobular histology appear to have a worse survival in the multivariate analysis after a prolonged follow-up. [Copyright &y& Elsevier]

Abstract: Objectives: We reviewed the use of negative pressure wound treatment (NPWT) for problematic wounds. Methods: A systematic literature review was undertaken to assess the effectiveness and safety of NPWT. Randomized controlled trials (RCTs) assessing NPWT were included. Results: A total of 14 RCTs were included. Trials included patients with pressure wounds (2), post-traumatic wounds (3), diabetic foot ulcers (4) and miscellaneous chronic ulcers (5). In all trials NPWT was at least as effective and in some cases more effective than the control treatment. Most evidence supports the effectiveness of NPWT on chronic leg ulcers and posttraumatic ulcers. NPWT appears to be a safe treatment, and serious adverse events have been rarely reported. Only two trials were classified as high quality studies, whereas the remaining were classified as having poor internal validity. Conclusions: Reliable evidence on the effectiveness of NPWT is scarce. Tentative evidence indicates that the effectiveness of NPWT is at least as good as or better than current local treatment for wounds. The need for large high-quality randomised studies is apparent. [Copyright &y& Elsevier]

Summary: Mechanisms of prostate cancer progression during hormonal therapy and the pathobiologic consequences of androgen receptor (AR) gene amplification are inadequately known. To further investigate the hypothesis that AR gene amplification is associated with increased cell proliferation, we analyzed 123 paraffin-embedded prostate cancer specimens from men who experienced tumor relapse during androgen withdrawal therapy. We used fluorescence in situ hybridization to quantify AR gene copy number and Ki-67 immunohistochemistry to determine cell proliferation. One third of the tumors showed AR gene amplification. Among tumors with AR amplification, the mean cell proliferation rate was 19.8 (SD, 12.3; 95% confidence interval [CI], 15.4-24.1), whereas it was 13.0 (SD, 15.9; 95% CI, 9.1-16.8) in tumors without amplification (P = .032). In the best fitting logistic regression model, only proliferation remained significant (P = .040). When the median Ki-67 labeling index (6.7%) of all tumors was used as a cutoff point, the tumors with AR amplification were more frequently highly proliferating than tumors with no amplification (P = .010; odds ratio, 3.4; 95% CI, 1.4-8.3). Our results imply that progression of prostate cancer during androgen withdrawal therapy is associated with AR gene amplification and increased cell proliferation rate in one third of tumors. We suggest that AR gene amplification is an important molecular mechanism underlying the increase in proliferation rate of a substantial fraction of recurrent prostate carcinomas. However, efforts should be targeted to develop prostate cancer cell lines to study causal relationships between AR gene amplification and various biologic variables. [Copyright &y& Elsevier]

Background: Experimental studies have shown that activation of bradykinin B2 receptor is one of the most important triggers of ischemic preconditioning. However, the effect of exogenous administration of bradykinin in cardiac surgery is not yet known. The present prospective randomized study was designed to investigate the effect of bradykinin pretreatment in patients undergoing elective coronary artery bypass surgery.Methods: Forty-one patients with multiple-vessel coronary artery disease and stable angina, admitted for the first time for elective coronary artery bypass surgery, were randomized into control or bradykinin (BK) groups. Patients in the BK group received bradykinin infusion for 7 minutes (total dose 25 μg) before the initiation of cardiopulmonary bypass. Perioperative cardiac specific troponin I (cTnI) and creatine kinase cardiac isoenzyme (CKMB) release and hemodynamics were recorded.Results: Bradykinin infusion caused acute decrease of blood pressure in most of the cases and the mean minimum mean blood pressure during bradykinin infusion was 72.7% of the original mean blood pressure (MBP) level (74.7 ± 7.9 vs 54.4 ± 12.1 mm Hg, p < 0.01). There were no differences in baseline levels of cTnI and CKMB between the groups. The postoperative cTnI levels were lower than 10 ng/mL in most patients in both groups (18 in the BK group and 15 in the control group). There was no difference in cTnI between the groups. However, patients who received bradykinin released significantly less CKMB than did the controls postoperatively (6 hours, BK, 22.1 ± 9.5 vs control, 23.6 ± 12.7 U/L; 12 hours, BK, 19.4 ± 12.4 vs control, 28.7 ± 23.8 U/L; 24 hours, BK, 21.5 ± 14.7 vs control, 35.5 ± 28.9 U/L; 48 hours, BK, 14.4 ± 7.5 vs control, 23.5 ± 13.6 U/L; analysis of variance [ANOVA] for repeated measurement, p = 0.036). Maximum CKMB was also lower in the BK group (22.4 ± 14.4 vs 37.7 ± 27.5 U/L, p = 0.044). There was no significant difference between the groups in any of the hemodynamic variables.Conclusions: Exogenous bradykinin infusion showed weak cardioprotective effect in the low-risk patients undergoing coronary artery bypass surgery but the dose used in the study caused acute decrease of systemic blood pressure. [Copyright &y& Elsevier]