The economic efficiency of amlodipine in the treatment of coronary atherosclerosis--an analysis based on the PREVENT study

Background: High health service expenditure on the one hand, and the politically declared objective of stability of statutory contributions and restriction of public funds on the other hand, have been central points of the political and social discussion for several years. The over-proportional increase in health service expenditure is obvious, compared to the increase in the costs of living. Patients and Methods: Cost-effectiveness of amlodipine in the treatment of coronary atherosclerosis was analysed by applying the results of the PREVENT study to the Swiss health system. Results: Calculation of effectiveness shows an additional life expectancy of 0.083 years in the amlodipine cohort compared to the placebo cohort, over an observation period of 3 years. The cost-effectiveness of amlodipine treatment is approximately CHF 14,650 per life-year gained. Conclusion: The administration of the calcium antagonist amlodipine in CHD patients is cost-effective.     

Clinical and histopathological correlations of fecal calprotectin release in colorectal carcinoma

AIM:To determine calprotectin release before and after colorectal cancer operation and compare it to tumor and histopathological parameters.METHODS:The study was performed on patients with diagnosed colorectal cancer admitted for operation.Calprotectin was measured in a single stool sample before and three months after the operation using an enzymelinked immunosorbent assay(ELISA).Calprotectin levels greater than or equal to 50μg/g were considered positive.The compliance for collecting stool samples was assessed and the value of calprotectin was correlated to tumor and histopathological parameters of intra-and peri-tumoral inflammation.Surgical specimens were fixed in neutral buffered formalin and stained with hematoxylin and eosin.Staging was performed according to the Dukes classification system and the 7th edition tumor node metastasis classification system.Intra-and peri-tumoral inflammation was graded according to the Klintrup criteria.Immunohistochemical quantification was performed for MPO,CD45R0,TIA-1,CD3,CD4,CD8,CD57,and granzyme B.Statistical significance was measured using Wilcoxon signed rank test,Kruskal Wallis test and Spearman’s rank correlation coefficient as appropriate.RESULTS:Between March 2009 and May 2011,80 patients with colorectal cancer(46 men and 34 women,with mean age of 71±11.7 years old)were enrolled in the study.Twenty-six patients had rectal carcinoma,29 had left-side tumors,23 had right-side tumors,and2 had bilateral carcinoma.In total,71.2%of the patients had increased levels of calprotectin before the operation(median 205μg/g,range 50-2405μg/g)and experienced a significant decrease three months after the operation(46μg/g,range 10-384μg/g,P<0001).The compliance for collecting stool samples was 89.5%.Patients with T3 and T4 tumors had significantly higher values than those with T1 and T2 cancers(P=0.022).For all other tumor parameters(N,M,G,L,V,Pn)and location,no significant difference in calprotectin concentration was found.Furthermore,the calprotectin levels and histological grading of both peri-and intra-tumoral inflammation was not correlated.Additional testing with specific markers for lymphocytes and neutrophils also revealed no statistically significant correlation.CONCLUSION:Fecal calprotectin decreases significantly after colorectal cancer operation.Its value depends exclusively on the individual T-stage,but not on other tumor or histopathological parameters.     

High throughput sequencing reveals high specificity of TNFAIP3 mutations in ocular adnexal marginal zone B-cell lymphomas

The majority of ocular adnexal (OA) lymphomas (OAL) are extranodal marginal zone lymphomas (MZL). First high throughput sequencing (HTS) studies on OA-MZL showed inconsistent results and the distribution of mutations in reactive lymphoid lesions of this anatomic region has not yet been sufficiently addressed. We characterized OAL and lymphoid lesions of the OA by targeted HTS. The study included 34 OA-MZL, 11 chronic conjunctivitis, five mature small cell B-cell lymphomas spreading to the OA, five diseases with increase of IgG4+ plasma cells, three Burkitt lymphomas (BL), three diffuse large B-cell lymphomas (DLBCL), three mantle cell lymphomas, three idiopathic orbital inflammations/orbital pseudo tumors (PT), and three OA lymphoid hyperplasia. All cases were negative for Chlamydia. The mutational number was highest in BL and lowest in PT. The most commonly (and exclusively) mutated gene in OA-MZL was TNFAIP3 (10 of 34 cases). Altogether, 20 out of 34 patients harbored mutually exclusive mutations of either TNFAIP3, BCL10, MYD88, ATM, BRAF, or NFKBIE, or nonexclusive mutations of IRF8, TNFRSF14, KLHL6, and TBL1XR1, all encoding for NK-κB pathway compounds or regulators. Thirteen patients (38%) had, to a great part, mutually exclusive mutations of chromatin modifier-encoding genes: KMT2D, CREBBP, BCL7A, DNMT3A, EP300, or HIST1H1E. Only four patients harbored co-occurring mutations of genes encoding for NK-κB compounds and chromatin modifiers. Finally, PTEN, KMT2D, PRDM1, and HIST1H2BK mutations were observable in reactive lymphoid lesions too, while such instances were devoid of NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes. In conclusion, 80% of OA-MZL display mutations of either NK-κB compounds or chromatin modifiers. Lymphoid lesions of the OA bearing NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes highly likely represent lymphomas.     

Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl-2 and Bcl-xL antisense treatment

Our study was designed to investigate the role of the anti-apoptotic proteins Bcl-2 and Bcl-xL in the chemoresistance of cells derived from malignant pleural mesothelioma. First, we determined the basal expression levels of Bcl-2 and Bcl-xL in mesothelioma cells and examined the effect of their downregulation by antisense oligonucleotides. Bcl-xL mRNA and protein could be readily detected in mesothelioma cell lines, whereas only low levels of Bcl-2 mRNA and protein were found. Preferential downregulation of either Bcl-xL alone or of Bcl-xL and Bcl-2 simultaneously was achieved by treatment with antisense oligonucleotides 4259 and 4625, respectively, whereas the expression of other apoptosis-relevant genes remained unaffected. Treatment with oligonucleotides 4259 or 4625 lowered the apoptosis threshold in ZL34 mesothelioma cells, as indicated by an increase in cell death accompanied by increased caspase-3-like activity, a decrease of the mitochondrial transmembrane potential and the cleavage of procaspase-7 and ICAD. In addition to the direct induction of apoptosis, antisense treatment sensitized ZL34 cells to the cytostatic effect of cisplatin and gemcitabine, with the combination of 4625 and cisplatin being the most effective. Our results demonstrate that Bcl-2 and Bcl-xL antisense treatment facilitates apoptosis in mesothelioma cells and suggest the use of Bcl-2/Bcl-xL bispecific antisense treatment in combination with cisplatin or gemcitabine for therapy of malignant pleural mesothelioma.     

Interdisciplinary evidence-based recommendations for the follow-up of testicular germ cell cancer patients

Over the last years, clear treatment recommendations for patients with testicular cancer have been published. This has led to significant improvements in outcome and survival. Moreover, active surveillance has become a cornerstone in the management of clinical stage I seminomatous and non-seminomatous germ cell tumors. On the other hand, the existing recommendations for the follow-up of testis cancer patients are unclear and differ widely. Follow-up recommendations in this young patient population have to be as evidence based as possible, feasible in order to ensure adherence, and must not be harmful. Therefore, attention has to be paid to the negative impact of unnecessary radiation exposure. Recently, new evidence became available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging at follow-up, and the risks of excessive radiation due to imaging, and in particular that of computed tomography (CT) scans. This article summarizes the recommendations for follow-up of testicular cancer patients of an interdisciplinary multinational working group consisting of urologists, medical oncologists, and radiation oncologists.     

Patients with low prostate-specific antigen levels (< or =4 ng/ml) would benefit from a twelve-core biopsy protocol for prostate cancer detection

INTRODUCTION: Prostate biopsy protocols using twelve cores rather than the standard six cores have consistently shown improved prostate cancer detection rates. The aim of our study was to evaluate whether the improved rate of prostate cancer detection in patients with low prostate-specific antigen levels warrants the standardization of a twelve-core biopsy protocol in this group. PATIENTS AND METHODS: The clinical and pathological records from 241 patients treated between 2000 and 2003 were evaluated, and the impact of a twelve-core biopsy protocol on the prostate cancer detection rate relative to prostate-specific antigen levels compared to the standardized six-core biopsies was analyzed. RESULTS: Prostate cancer was detected in 34% (81/241) of the patients who underwent transrectal ultrasound-guided biopsy. An additional 23.5% (19/81) of the carcinomas were diagnosed using the twelve-core biopsy protocol, and 84.2% (16/19) of these fulfilled the clinical significance criterion developed by Epstein and coworkers (see text). Interestingly, the greatest increase was found in the patient group with prostate-specific antigen levels < or =4 ng/ml. CONCLUSIONS: Patients with low prostate-specific antigen levels (< or =4 ng/ml) would benefit from the standardized use of a twelve-core biopsy protocol using peripheral cores.