Low-intensity extracorporeal shock wave therapy in the treatment of erectile dysfunction. Diagnostic and therapeutic options — a literature review

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a modern therapeutic option for erectile dysfunction (ED). The European Association of Urology (EAU) has classified it as a first-line treatment for ED. The use of Li-ESWT is recommended in appropriately informed patients with mild erectile dysfunction (EF). The recommendations include the use of LI-ESWT for patients who respond poorly to drug therapy and those who, for individual reasons, are unable or unwilling to use vasoactive substances. It is worth noting that the level of recommendation is described as weak (insufficient evidence of efficacy, indicating the need for further research). The mechanism of action of Li-ESWT is not well understood, but it is known that it affects the formation of new blood vessels, promotes quantitative and qualitative improvement of vascular endothelial cells, and increases the production of nitric oxide (has a nutritional effect, generating congestion). Improvement of erectile function in people undergoing Li-ESWT was noted in patients with vascular ED, and importantly, studies are underway to apply this form of therapy to other etiopathogenesis of ED. Li-ESWT results in an improvement in EF as measured by the International Index of Erectile Function (IIEF), an increase in the average Erectile Hardness Score (EHS), and an improvement in quality of sexual life; however, the level of increase remains clinically unsatisfactory. The efficacy of Li-ESWT has been confirmed in studies in patients with the most advanced vascular ED. Importantly, there were no side effects both during and after therapy and the improvement in EF was sustained long-term (up to 2 years). The advantages of Li-ESWT therapy are associated with the removal of the cause of vasogenic ED, which transfers into improved sexual performance, allows patients to regain spontaneity of intercourse and prompts wider use of this innovative therapy.Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a modern therapeutic option for erectile dysfunction (ED). The European Association of Urology (EAU) has classified it as a first-line treatment for ED. The use of Li-ESWT is recommended in appropriately informed patients with mild erectile dysfunction (EF). The recommendations include the use of LI-ESWT for patients who respond poorly to drug therapy and those who, for individual reasons, are unable or unwilling to use vasoactive substances. It is worth noting that the level of recommendation is described as weak (insufficient evidence of efficacy, indicating the need for further research). The mechanism of action of Li-ESWT is not well understood, but it is known that it affects the formation of new blood vessels, promotes quantitative and qualitative improvement of vascular endothelial cells, and increases the production of nitric oxide (has a nutritional effect, generating congestion). Improvement of erectile function in people undergoing Li-ESWT was noted in patients with vascular ED, and importantly, studies are underway to apply this form of therapy to other etiopathogenesis of ED. Li-ESWT results in an improvement in EF as measured by the International Index of Erectile Function (IIEF), an increase in the average Erectile Hardness Score (EHS), and an improvement in quality of sexual life; however, the level of increase remains clinically unsatisfactory. The efficacy of Li-ESWT has been confirmed in studies in patients with the most advanced vascular ED. Importantly, there were no side effects both during and after therapy and the improvement in EF was sustained long-term (up to 2 years). The advantages of Li-ESWT therapy are associated with the removal of the cause of vasogenic ED, which transfers into improved sexual performance, allows patients to regain spontaneity of intercourse and prompts wider use of this innovative therapy

Clinical Relevance of Circulating Tumor Cells in Prostate Cancer Management

Given the low specificity of the routinely used biomarker prostate-specific antigen, circulating tumor cell (CTC) enumeration seems to be particularly useful in the monitoring of prostate cancer. In this review, we focused on a few aspects of CTC enumeration in prostate malignancies: prognostic value in metastatic and non-metastatic tumors, role in the monitoring of treatment outcomes, use as a surrogate marker for survival, and other applications, mostly for research purposes. CTC enumeration, without a doubt, offers an attractive perspective in the management of prostate cancer. However, the vast majority of available data about the role of CTC in this malignancy originate from randomized studies of anticancer agents and do not necessarily translate into real-world clinical practice. Further, most studies on the application of CTC in prostate cancer patients were limited to advanced stages of this malignancy. Meanwhile, the role of CTC in the early stages of prostate cancer, in which some patients may present with occult disseminated disease, is still relatively poorly understood, and should thus be studied extensively. Other obstacles in the widespread application of CTC enumeration in routine clinical practice include considerable discrepancies in the number of cells determined with various commercially available systems

Expression of pre-selected TMEMs with predicted ER localization as potential classifiers of ccRCC tumors

BACKGROUND: VHL inactivation is the most established molecular characteristic of clear cell renal cell carcinoma (ccRCC), with only a few additional genes implicated in development of this kidney tumor. In recently published ccRCC gene expression meta-analysis study we identified a number of deregulated genes with limited information available concerning their biological role, represented by gene transcripts belonging to transmembrane proteins family (TMEMs). TMEMs are predicted to be components of cellular membranes, such as mitochondrial membranes, ER, lysosomes and Golgi apparatus. Interestingly, the function of majority of TMEMs remains unclear. Here, we analyzed expression of ten TMEM genes in the context of ccRCC progression and development, and characterized these proteins bioinformatically. METHODS: The expression of ten TMEMs (RTP3, SLC35G2, TMEM30B, TMEM45A, TMEM45B, TMEM61, TMEM72, TMEM116, TMEM207 and TMEM213) was measured by qPCR. T-test, Pearson correlation, univariate and multivariate logistic and Cox regression were used in statistical analysis. The topology of studied proteins was predicted with Metaserver, together with PSORTII, Pfam and Localizome tools. RESULTS: We observed significant deregulation of expression of 10 analyzed TMEMs in ccRCC tumors. Cluster analysis of expression data suggested the down-regulation of all tested TMEMs to be a descriptor of the most advanced tumors. Logistic and Cox regression potentially linked TMEM expression to clinical parameters such as: metastasis, Fuhrman grade and overall survival. Topology predictions classified majority of analyzed TMEMs as type 3 and type 1 transmembrane proteins, with predicted localization mainly in ER. CONCLUSIONS: The massive down-regulation of expression of TMEM family members suggests their importance in the pathogenesis of ccRCC and the bioinformatic analysis of TMEM topology implies a significant involvement of ER proteins in ccRCC pathology

Analysis of Circulating Tumor Cells in Patients with Non-Metastatic High-Risk Prostate Cancer before and after Radiotherapy Using Three Different Enumeration Assays

The characterization of circulating tumor cells (CTCs) can lead to a promising strategy for monitoring residual or relapsing prostate cancer (PCa) after local therapy. The aim of this study was to compare three innovative technologies for CTC enumeration in 131 high-risk patients with PCa, before and after radiotherapy, combined with androgen deprivation. The CTC number was tested using the FDA-cleared CellSearch® system, the dual fluoro-EPISPOT assay that only detects functional CTCs, and the in vivo CellCollector® technology. The highest percentage of CTC-positive patients was detected with the CellCollector® (48%) and dual fluoro-EPISPOT (42%) assays, while the CellSearch® system presented the lowest rate (14%). Although the concordance among methods was only 23%, the cumulative positivity rate was 79%. A matched-pair analysis of the samples before, and after, treatment suggested a trend toward a decrease in CTC count after treatment with all methods. CTC tended to be positivity correlated with age for the fluoro-EPISPOT assay and with PSA level from the data of three assays. Combining different CTC assays improved CTC detection rates in patients with non-metastatic high-risk PCa before and after treatment. Our findings do not support the hypothesis that radiotherapy leads to cancer cell release in the circulation

Circulating Tumor Cells as a Marker of Disseminated Disease in Patients with Newly Diagnosed High-Risk Prostate Cancer

The aim of this study was to investigate whether the enumeration of circulating tumor cells (CTCs) in blood can differentiate between true localized and metastatic prostate cancer. A cross-sectional study of 104 prostate cancer patients with newly diagnosed high-risk prostate cancer was conducted. In total, 19 patients presented metastatic disease and 85 were diagnosed with localized disease. Analyses included intergroup comparison of CTC counts, determined using the CellSearch® system, EPISPOT assay and GILUPI CellCollector®, and ROC analysis verifying the accuracy of CTC count as a maker of disseminated prostate cancer. The vast majority (94.7%) of patients with advanced-stage cancer tested positively for CTCs in at least one of the assays. However, significantly higher CTC counts were determined with the CellSearch® system compared to EPISPOT assay and GILUPI CellCollector®. Identification of ≥4 CTCs with the CellSearch® system was the most accurate predictor of metastatic disease (sensitivity 0.500; specificity 0.900; AUC (95% CI) 0.760 (0.613–0.908). Furthermore, we tried to create a model to enhance the specificity and sensitivity of metastatic prediction with CTC counts by incorporating patient’s clinical data, including PSA serum levels, Gleason score and clinical stage. The composite biomarker panel achieved the following performance: sensitivity, 0.611; specificity, 0.971; AUC (95% CI), 0.901 (0.810–0.993). Thus, although the sensitivity of CTC detection needs to be further increased, our findings suggest that high CTC counts might contribute to the identification of high-risk prostate cancer patients with occult metastases at the time of diagnosis