Structural changes of the intravesical ureter in children with vesicoureteral reflux-does ischemia have a role?

PURPOSE: Previous studies have revealed structural and metabolic changes in the distal most ureter, impairing its contractile properties, and, thus, having a role in the pathogenesis of vesicoureteral reflux. Musculature and nerves are replaced by interstitial collagen, while matrix degrading enzymes are over expressed. We investigated the microvessel architecture of the ureterovesical junction to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS: Ureteral endings were obtained from 28 children during antireflux surgery. Ureteral tissue from 14 age matched autopsy specimens served as control. Routine histological paraffin embedded sections were immunostained, detecting CD31 as an endothelial marker as well as vascular endothelial growth factor. Microvessel density and vascular endothelial growth factor expression were investigated based on computer assisted high power field magnification analyses. The t test and the Spearman rho test were applied for statistical evaluation. RESULTS: Overall, microvessel density was significantly reduced in cases of vesicoureteral reflux. While reflux grade and age were not correlated with microvessel density, it was particularly decreased in regions lacking smooth musculature. Vascular endothelial growth factor was observed in smooth muscle, endothelial and connective tissue cells. Additionally, cellular vascular endothelial growth factor expression was markedly abridged in cases of vesicoureteral reflux compared to healthy controls. CONCLUSIONS: Overall microperfusion is supposed to be impaired, leading to tissue ischemia due to reduction of vascular endothelial growth factor expression and subsequent microvessel density. Diminished ureteral perfusion is likely to induce and support smooth muscle dysfunction as well as subsequent extracellular matrix remodeling, including increased collagen deposition. These ongoing functional and structural alterations may further deteriorate the active valve mechanism of the ureterovesical junction, causing vesicoureteral reflux.

[Ultrasound contrast agents and prostate cancer]. / Ultraschallkontrastmittel und Prostatakarzinom.

Prostatic carcinoma is the most frequent malignant disease in men and associated with very high mortality. The diagnostic work-up of prostatic carcinoma is based on tests to determine the level of prostate-specific antigen (PSA), digital rectal examination, and transrectal sonography. Due to diagnostic limitations, ultrasound-guided prostate biopsy is the method of choice for diagnosis of prostatic carcinoma. New imaging technologies allow detection of prostatic carcinoma, thus facilitating removal of specific biopsy specimens from these regions. Introduction of ultrasound contrast agents ("echo signal enhancers") significantly increased the diagnostic potential of this method, making it possible to visualize tumor vascularization.

Vascular damage induced by type 2 diabetes mellitus as a risk factor for benign prostatic hyperplasia.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the relationship between benign prostatic hyperplasia (BPH) and arteriosclerosis shown in a model of type 2 diabetes in a trans-sectional population study using contrast-enhanced colour Doppler ultrasound for exact assessment of prostatic blood flow. METHODS: Contrast-enhanced transrectal colour Doppler ultrasound was performed using a microbubble-based ultrasound enhancer SonoVue for evaluating prostate vascularity (transitional zone [TZ] and peripheral zone [PZ]) in diabetic BPH patients, non-diabetic BPH patients and healthy subjects. Computer-assisted quantification of colour pixel intensity (CPI) was used to objectively evaluate the prostate vascularity. Resistive index measurements were obtained in the TZ and the PZ. Findings were compared between these three groups. RESULTS: TZ-CPI was significantly lower in diabetic patients than in non-diabetic BPH men (p=0.001), whereas the CPI of the PZ showed no difference between these two groups (p=0.978). TZ-CPI of patients with diabetic and non-diabetic BPH were significantly lower than in controls (p<0.001), but no difference was found between diabetic and healthy patients in the PZ (p=0.022) and borderline significance was seen when comparing patients of the BPH group with the control patients (p=0.019). Resistive index values of the TZ in diabetic patients showed significantly higher values (p<0.001) than the BPH and control groups. CONCLUSIONS/INTERPRETATION: The significantly lower CPI and higher resistive index values of the TZ in diabetic patients compared with patients with non-diabetic BPH and healthy subjects indicate considerable vascular damage in the TZ of these patients. Diabetic vascular damage may cause hypoxia and may contribute to the pathogenesis of BPH.

Characteristics of prostate cancers detected at low PSA levels.

BACKGROUND: When age-referenced PSA levels as recommended by Oesterling et al.1 were used as a biopsy criterion, only 25% of the cancers detected in a population based PSA Screening Project were organ-confined. This observation led to the decision to use low PSA levels as the sole indication for biopsy. Since 1995 age-referenced PSA levels of 1.25-3.25 ng/ml have been used in combination with a percentage free PSA cutoff of 18%. This PSA cutoff reduction led to a statistically significant migration to lower pathological stages with a decreased prostate cancer mortality in the years 1996-2001. However, concerns have been raised that screening with low PSA levels may detect clinically insignificant cancers. MATERIALS AND METHODS: We evaluated prostate cancer patients with low PSA levels in terms of heterogeneity, clinical significance, multifocality, and tumor biology including ploidy and proliferation index. RESULTS: Concerning heterogeneity the Gleason score of the needle biopsy failed to predict the Gleason score of the radical prostatectomy specimen in nearly 40% of prostate cancer patients; regarding multifocality 65% of patients with low PSA levels showed multifocal lesions and 36% exhibited tetraploid DNA distribution; more than 50% of tetraploid tumors were found in patients with tumor volumes of less than 0.5 cm(3). Ploidy correlated with the Ki-67 proliferation index, but not with tumor volume. CONCLUSIONS: These results demonstrate that small prostate cancers with low PSA levels and low tumor volumes exhibit all features of prostate cancers with higher tumor volumes and show the characteristics of malignant cancers, i.e., multifocality, tetraploidy, and high proliferative activity.

[The value of ultrasound (US) in the diagnosis of prostate cancer]. / Sonographie des Prostatakarzinoms. Derzeitiger Stand und Zukunftsperspektiven.

The value of ultrasound (US) in the diagnosis of prostate cancer has increased in importance in the past decade, which is mainly related due to the increasing incidence of prostate cancer, the most common malignancy in men. The value of conventional gray-scale US for prostate cancer detection has been extensively investigated. The introduction of US contrast agents has dramatically changed the role of US for prostate cancer detection. Advances in US techniques were introduced to further increase the role of US contrast agents. Although most of these advances in US techniques, which use the interaction of the contrast agent with the transmitted US waves are very sensitive for the detection of microbubbles, are mostly unexplored, in particular for prostate applications. First reports of contrast-enhanced US investigations of blood flow of the prostate have shown that contrast-enhanced US adds important information to the conventional US technique. We present a critical evaluation of the current status of transrectal US imaging for prostate cancer detection. Furthermore, we give background information on US contrast agents and imaging modalities. Early results of contrast-enhanced US suggest the feasibility of the use of US contrast agents to enhance US imaging of the prostate. The application of US contrast agents for the detection and clinical staging of prostate cancer is promising. However, future clinical trials will be needed to determine the promise of contrast-enhanced US of the prostate evolves into clinical application.

Malignant melanoma in spouses.

A study of three married couples where both spouses developed malignant melanoma was undertaken at the New York University-Bellevue Medical Center melanoma registry. An upper bound was calculated for the number of spouses expected to develop melanoma, along with the origin of the disease and its relation to nation-wide rates of incidence. The observed number was six times greater than the bound.