Is there an indication for adjuvant or neoadjuvant systemic therapy in prostate cancer?

In the meantime prostate cancer has become the most common malignancy in the male population. Due to the shift in age at the time of first diagnosis in favour of younger men with a high life expectancy and a maximum of physical and sexual activity it would be desirable to have neoadjuvant or adjuvant therapy concepts at hand which lead to an improvement of therapeutic success. So far the results of studies for adjuvant and neoadjuvant hormonal ablation therapy concepts have not led to a clear therapeutic reference. Only before radiation therapy is neoadjuvant hormonal ablation a standard part of therapy at most centres. Existing data for chemotherapeutic concepts are limited to androgen-independent advanced prostate cancer. An international study using docetaxel as an adjuvant drug is currently being performed, but the results are not yet available.     

Proapoptotische Antikörper als neue Tumortherapeutika

To convert the concept already successful in mice into clinical practice and commercialize it, a human anti-CD95-antibody must be produced. In a second step experiments must be performed on various normal healthy cells and tissues to determine whether these human anti-CD95-antibodies administered in very low doses have any effect on human cells (particularly hepatocytes) or at least cause only minimal side effects. If these studies yield positive results, then clinical trials can be conducted in which increasing doses are given to exclude an acute hepatotoxic effect and then the effect exerted by the antibody in combination with irradiation on tumor growth can be investigated.The advantage of this concept lies in the fact that systemic stimulus (low doses of anti-CD95-antibodies) is highly intensified by local radiotherapy and only then initiates cell death. Since the anti-CD95-antibodies trigger apoptosis primarily in tumor endothelia, this approach could be employed not only for prostate cancer and melanomas, which have already been tested, but also for many other tumors.     

Mineral loss during etching of enamel lesions

This study was aimed at determining the amount of mineral removed from incipient enamel lesions during acid etching. The rationale being that fissures which are scheduled for sealing will often have undetected demineralized regions. Lesions were formed in bovine enamel specimens using either an acidified gelatine gel or a lactate buffer containing methane hydroxy diphosphonate. Different parts of each lesion were acid-etched either for a 1- or for a 2-min period in 36% H3PO4 or served as control. Mineral content profiles were recorded on thin sections using computerized microradiography to determine the mineral loss resulting from acid etching. The results show that during etching a layer at the outer surface is removed completely. The thickness of this layer was greater for lesions when compared with sound enamel and depended on the lesion characteristics (porosity and fluoride content). The amount of mineral removed from the deeper layers of the lesion was very small; and in the innermost part of the lesions the mineral profiles of the control and acid-etched areas coincide. These observations indicate that the effect of etching is essentially restricted to a thin outer layer, irrespective of the porosity of the underlying tissue. Although the thickness of the etched-off layer was different between the two types of lesions, these findings were made for both types studied. In practical terms this implies that etching of enamel lesions does not cause an excessive mineral loss throughout the lesion.     

Dialysis efficacy during acetate-free biofiltration

Background. Acetate-free biofiltration (AFB) is a haemodiafiltration technique based on continuous post-dilution infusion of a sterile isotonic bicarbonate solution. We performed a long-term randomized prospective trial to compare dialysis efficacy and metabolic control of AFB versus bicarbonate haemodialysis (HD). Methods. The AFB group consisted of 11 and the HD group of nine patients, matched for age, sex and urea reduction rate. Biochemical parameters were obtained every 3 months for 1 year (haemoglobin, calcium, phosphate, urea, pre- and post-dialysis bicarbonate, and parathormone (PTH)) and medication was updated. Efficacy of dialysis calculated by KT/V using the dialysate sampling method was determined every 3 months. In AFB patients, the infusion rate of bicarbonate solution was adjusted individually to obtain bicarbonate values of ⩾22 mmol/l before dialysis and ⩽32 mmol/l after dialysis. In the HD group, bicarbonate was added as oral medication to match these bicarbonate concentrations. Statistical analysis was performed using ANOVA for repeated measurements. Results. Pre-dialysis serum bicarbonate levels had risen to the same extent in both groups at the end of the study period (AFB from 21.8 to 26.1 mmol/l, P<0.001, and HD from 20.8 to 24.9 mmol/l, P<0.001). Post-dialysis bicarbonate level was higher in the AFB than in the HD group (P<0.01). Calcium and phosphate levels remained stable in both groups. PTH increased in both groups (AFB from 10.6 to 23.7 pmol/l, and HD from 24.6 to 32.8 pmol/l), with a significant rise only in the AFB patients (P<0.013). Finally, haemoglobin levels and erythropoietin dosage did not change in either group. No significant differences between the two groups were observed. Conclusions. Acidosis was better corrected in AFB without the need for oral supplementation of bicarbonate. However, neither serum calcium nor phosphate levels changed. The observed increase in PTH in the AFB group remains to be clarified. Dialysis efficacy, measured as KT/V, improved during AFB.     

Stellenwert der systemische Chemotherapie des Harnblasenkarzinoms

Almost half of the patients with muscle invasive disease already habor at the time of their first diagnosis occult or distant metastases. Systemic disease has a poor prognosis with a long term survival of less than 10%. The administration of systemic chemotherapy aims to improve the course of locally advanced or metastatic disease. A survival benefit of 5% for patients receiving neoadjuvant and 9–11% using adjuvant chemotherapy is in the first scenario minimal, in the adjuvant setting to be noteworthy. The MVAC-schedule and the Gemcitabine/Cisplatin-combination chemotherapy have to be regarded as standard for induction chemotherapy. However, the 5-year survival rates with 15 or 13% are disappointing. Thus, prognostic factors gain importance since with their consideration significant differences in survival rates can be found. Hope is provided by a novel class of substances, the target-specific drugs, which selectively interfere with the cascade of steps involved in tumorigenesis.     

A randomized trial of alcohol 70% versus alcoholic iodine 2% in skin disinfection before insertion of peripheral infusion catheters

Skin disinfection before insertion of peripheral infusion catheters is standard practice, but a comparison in effectiveness of the two most widely used disinfectants is lacking. We compared alcohol 70% and alcoholic iodine 2% in a prospective randomized trial. Data from 109 patients on a pulmonary ward were analysed. Phlebitis occurred six times in the alcohol group and 12 times in the iodine group. This relative risk reduction of 53% failed to reach significance (P = 0·18). The power of the study, however, was only 0·55, meaning a 45% chance of missing a true difference. As countless catheters are inserted each year, a small difference in phlebitis rate could save discomfort to many patients. Thus, a larger trial seems warranted. The addition of theophylline to the prednisone infusion resulted in a significantly higher phlebitis rate: 27·3 versus 9·2% (P = 0·03).     

Matrix metalloproteinase‐7 as a marker of metastasis and predictor of poor survival in bladder cancer

Matrix metalloproteinases (MMPs) play an important role in tumor progression and metastasis. Here, we investigated the prognostic relevance of MMP‐7 in urinary bladder cancer. MMP‐7 gene expression was measured in tissue samples of 101 patients using quantitative real‐time PCR. Circulating MMP‐7 serum levels of 98 individuals (79 patients and 19 controls) were analyzed by enzyme‐linked immunosorbent assay. The results were compared with the clinical follow‐up data, performing Kaplan–Meier log‐rank test as well as univariate and multivariate Cox analysis. In representative cases, immunohistochemical analysis for MMP‐7 was performed. We detected significantly elevated MMP‐7 levels both in tissue and serum samples of patients with metastatic disease (P = 0.001 and P = 0.002). Multivariate analysis revealed that high MMP‐7 tissue expression and serum concentration are stage‐ and grade‐independent predictors of both metastasis‐free (hazard ratio [HR] = 3.80, 95% confidence interval [CI], 1.29–11.23, P = 0.016, and HR = 2.53, 95% CI, 1.01–6.37, P = 0.048) and disease‐specific survival (HR = 1.89, 95% CI, 1.00–3.55, P = 0.050 and HR = 1.95, 95% CI, 1.03–3.71, P = 0.041). Based on these findings, we conclude that MMP‐7 is a promising marker to detect present and to predict future metastasis. Serum MMP‐7 analysis provides information about the risk of metastasis before surgery which could help to optimize therapeutic procedures. Furthermore, high MMP‐7 tissue and/or serum levels could identify patients most likely to benefit from early adjuvant chemotherapy. (Cancer Sci 2010; 101: 1300–1308)     

Resolution problems in echocardiology: a source of interpretation errors.

Resolution is the ability of the echocardiographic system to distinguish closely lying structures. This is usually defined in two directions: laterally (lateral resolution) and in depth (axial resolution). With use of short ultrasonic pulses, axial resolution is not a major problem. By far the more important problem is the limited lateral resolution that results from the finite beam width of current ultrasonic devices. This results in the display of echoes that originate from off-axis structures. How these off-axis or "spurious echoes" affect the display is a function of the way the echographic information is handled. In conventional M-mode tracings, spurious echoes are displayed at a site where there is no directly corresponding anatomic structure, whereas with two-dimensional imaging, these echoes may result in important distortions of structures. The underlying principles are illustrated by a clinical experiment wherein the ball of a Starr-Edwards mitral valve prosthesis serves as a target of known shape and dimensions. These data are used to elucidate some of the problems and potential errors encountered in the interpretation of clinical M-mode recordings of the aorta, mitral valve and the left ventricular endocardium as well as their cross-sectional analysis. They also explain the present limitations of quantification of left ventricular performance from cross-sectional images.