Comparison of Transrectal Prostate Biopsy Results with Histology of Transurethral Resection of the Prostate in Men Undergoing High-Intensity Focused Ultrasound

Introduction: The aim of our study was to evaluate the significance of transurethral resection of the prostate (TURP) to detect prostate cancer (PCa). A comparison was performed of the TURP specimens of patients undergoing high-intensity focused ultrasound (HIFU) with the core biopsies. Materials and Methods: TURP before undergoing HIFU therapy was performed in 106 patients without neoadjuvant treatment. The resected tissue was subjected to histopathological evaluation and compared to the histological results of transrectal prostate biopsy. Results: Cancer was detected in the resected tissue of 69 patients (65%). A positive correlation of the amount of resected tissue and detection of PCa could be demonstrated in a multivariate analysis. Conclusions: With a rate of 65% PCa detected by TURP, our data provide evidence that TURP might be suitable to detect PCa in a small group of selected patients with continuously rising PSA levels and several negative biopsies. On the other hand, these data underline/reinforce the necessity to treat the whole gland using modern treatment modalities such as HIFU and cryotherapy

Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

Metastatic renal cell carcinoma (RCC) seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK) cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells

Clinical studies applying cytokineinduced killer cells for the treatment of renal cell carcinoma

Metastatic renal cell carcinoma (RCC) seems to be resistant to conventional chemo-and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK) cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells

Alterations of Global Histone H3K9 and H3K27 Methylation Levels in Bladder Cancer

Background: Epigenetic alterations, including histone modifications, play an important role during carcinogenesis. This study was designed to systematically investigate histone H3K9 and H3K27 methylation levels in bladder cancer (BCa) tissue. Methods:A tissue microarray with urothelial BCa (150 non-muscle-invasive BCa, NMIBC; 121 muscle-invasive BCa, MIBC; 31 metastatic BCa, MET) and normal urothelium (29, CTRL) specimen was used to determine the global levels of H3K9 and H3K27 mono-, di- and tri-methylation. Results: Global levels of H3K9 and H3K27 methylation were significantly higher in CTRL than in BCa, and levels in NMIBC were higher compared to MIBC. Histone nnethylation levels of MET resembled MIBC. We observed furthermore a correlation of histone nnethylation levels with pT stage (H3K9me1, H3K9me2, H3K9me3, H3K27me1, H3K27me3) and grade (H3K9nne2, H3K9me3, H3K27nne1) in NMIBC. H3K9me1, H3K9me3, H3K27me1 and H3K27me3 levels were also correlated with pT stage in MIBC. Histone modifications were not associated with recurrence-free or cancer-specific survival. Conclusions: Global histone H3K9 and H3K27 nnethylation levels are altered in BCa. (C) 2014 S. Karger AG, Base

Therapeutic response and side effects of repeated radioligand therapy with 177Lu- PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer

Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with (177)Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64–82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17–2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients

Left Ventricular Diastolic Function in Subjects Conceived through Assisted Reproductive Technologies

Subjects conceived through assisted reproductive technologies (ART) potentially suffer from impaired left ventricular (LV) function due to premature vascular aging. This study aimed to evaluate whether subtle differences in LV diastolic function can be observed echocardiographically between young ART subjects and their spontaneously conceived peers. The echocardiographic assessment included the measurement of LV dimensions, mitral inflow velocities, and myocardial velocity at early diastole (E’, cm/s) at the LV wall and the interventricular septum (IVS). An average from E/E’LV and E/E’IVS (E/E’AVG) was derived. In total, 66 ART subjects and 83 controls (12.85 ± 5.80 years vs. 13.25 ± 5.89 years, p = 0.677) were included. The ART subjects demonstrated a significantly lower E’LV (19.29 ± 3.29 cm/s vs. 20.67 ± 3.78 cm/s, p = 0.020) compared to their spontaneously conceived peers. Study participants of ≥ 10 years of age displayed a significantly higher E/E’AVG (6.50 ± 0.97 vs. 6.05 ± 0.99, p = 0.035) within the ART cohort. The results of this study demonstrate a significantly lower LV diastolic function in the ART subjects. However, no significant changes in LV diastolic function were observed between the two groups when the results were adjusted for age, birth weight percentile, and gestational age. Those ART subjects born preterm might have an elevated risk of developing LV diastolic alterations and could therefore profit from close echocardiographic monitoring

Vascular Health of Females with History of Assisted Reproductive Technology

The use of assisted reproductive technologies (ART) for the treatment of infertility is gaining popularity. Limited data on the overall vascular health of females with history of ART are available. This pilot study aimed to investigate the overall vascular health of females with history of ART compared to individuals who conceived spontaneously. The assessment of overall vascular health included the measurement of brachial blood pressure, central blood pressure, and pulse wave velocity, as well as the evaluation of the arterial stiffness and carotid intima-media thickness (cIMT) of the common carotid arteries. Conventional blood lipids including lipoprotein a (Lp(a)) were also determined. In total, 45 females with history of ART and 52 females who conceived spontaneously were included (mean age: 47.72 ± 5.96 years vs. 46.84 ± 7.43 years, p = 0.525). An initial comparison revealed a significantly higher prevalence of elevated Lp(a) in ART females (p = 0.011). However, after multiple comparison correction, the significant result disappeared (p = 0.132). Within the cohort of ART females, no significantly higher cardiovascular risk was detected regarding vascular function. The potentially higher prevalence of elevated Lp(a) in ART females must be further investigated in future studies, as it might contribute to the impaired reproductive process in this cohort

Vascular Health in Adults Born After Using Assisted Reproductive Technologies

An increasing number of children are conceived by assisted reproductive technologies (ART). Several studies indicated vascular alterations in ART children. However, limited data is available within the adult ART population. Therefore, this study investigated the overall vascular health of young ART adults in comparison to spontaneously conceived peers. In total, 16 ART subjects and 22 spontaneously conceived peers (22.06 +/- 2.21 years vs. 22.00 +/- 2.14 years, p = 0.194) were enrolled for the assessment of endothelial function, brachial blood pressure, central blood pressure, pulse wave velocity, carotid intima-media thickness, and blood lipids. No significant differences in vascular function were detected between the in vitro fertilization subgroup (n = 9), the intracytoplasmic sperm injection subgroup (n = 7) and spontaneously conceived peers. This pilot study suggests an unimpaired vascular function in young ART adults. In the future, multi-centric studies with a greater sample size are required to confirm the results of the current study and enable precise cardiovascular risk stratification of the adult ART population

Subjects Conceived through Assisted Reproductive Technologies Display Normal Arterial Stiffness

Multiple studies reported signs of vascular dysfunction in subjects conceived through assisted reproductive technologies (ART). The assessment of arterial stiffness in this cohort seems beneficial for risk stratification. Regional arterial stiffness of the abdominal aorta (AAO) and the common carotid arteries (CCA) was evaluated sonographically using two-dimensional speckle tracking in subjects conceived through ART and spontaneously conceived peers. Global arterial stiffness was assessed utilizing an oscillometric blood pressure device. The cohorts of 67 ART subjects and 86 spontaneously conceived peers (11.31 (8.10–18.20) years vs. 11.85 (8.72–18.27) years, p = 0.43) did not differ significantly in parameters of regional and global arterial stiffness. In the sub-analysis of study participants ≥10 years of age, markers of arterial stiffness did not display significant differences between both groups. However, a higher tendency of brachial systolic blood pressure was demonstrated in the ART cohort compared to the control group (120.18 ± 9.57 mmHg vs. 116.55 ± 8.05 mmHg, p = 0.050). The present study displayed no significant differences in arterial stiffness between ART subjects and spontaneously conceived peers. Moreover, this study suggests that arterial stiffness does not elevate more profoundly in ART subjects with increasing age. Further studies are required for a more detailed cardiovascular risk stratification of the ART cohort