Predictive role of ureteral wall thickness and patient characteristics in endoscopic treatment outcomes for ureteral stricture disease following stone surgery.

PURPOSE: To evaluate the role of certain radiological parameters and patient characteristics in predicting the success of endoscopic treatment in ureteral stricture disease. METHODS: Fifty one adult patients with ureteral stricture disease (< 1 cm) after developing due to upper ureteral stones with ureteroscopic laser disintegration were included and in addition to stone and patient parameters, radiological parameters including ureteral wall thickness (UWT) at the impacted stone site were also measured on computed tomography (CT) images. Patients were divided into two groups: Group 1: Patients with endoscopic treatment success and Group 2: Patients with endoscopic treatment failure. The possible relationship between the UWT values and other radiological parameter was comparatively evaluated. RESULTS: Mean UWT value assessed at the treated stone site was significantly higher in cases unresponsive to endoscopic treatment with values of 2.77 ± 1.03 mm and 4.25 ± 1.32 mm in Group 1 and 2 respectively. A cut off value 3.55 mm for UWT was found to be highly predictive for endoscopic treatment failure. CONCLUSIONS: Our current results indicated that assessment of UWT value at the obstructing stone could be helpful enough to predict the likelihood of failure following endoscopic management of strictures with high sensitivity and specificity. Evaluation of this particular parameter could let the endourologists to look for more rational treatment alternatives with necessary measures taken on time.

Confirmation of negative urine culture status after appropriate antibiotic treatment prior to endourological stone procedures: Is it really necessary?

To evaluate the necessity of confirmation for a negative urine culture test outcome after an appropriate antibiotic regimen for urinary tract infection (UTI) prior to endoscopic stone removal procedures. 170 cases receiving an appropriate antibiotic treatment for culture proven UTI based on test outcomes before endoscopic stone removal were evaluated in two groups: Group 1 (n = 85) Patients in whom a second urine culture test was performed to ensure "negative urine culture" status prior to the procedures after receiving antibiotic therapy and Group 2 (n = 85). Patients receiving the same antibiotic therapy without any additional urine culture test before the procedures. Cases were comparatively evaluated with respect to the statistical significance of post-operative infective complications (fever, sepsis), duration of hospital stay and readmission rates during early post-operative period. Our findings demonstrated no significant difference regarding the rate of infective complications (presence of fever, incidence of septic findings), hospitalization period and readmission rates between the two groups. Although the presence of a negative urine status has been confirmed by urine culture test in group 1 cases, no additional urine culture test was performed with this aim in group 2 cases (negative urine culture was confirmed only with urinalysis) and the outcomes regarding the infective problems were found to be similiar. Our current findings indicate that a second urine culture test may not be a "must" if the patients receive an appropriate antibiotic regimen based on the sensitivity test outcomes for a reasonable time period.

Metabolic Syndrome is Associated with Prostate Cancer Diagnosed on Biopsy but not the Gleason Score and the Number of Cancer-Positive Cores: A Prospective Controlled Study.

OBJECTIVE: We aimed to investigate the association between metabolic syndrome (MetS) and prostate cancer (PCa) in patients undergoing prostate biopsy. MATERIALS AND METHODS: Between January 2018 and December 2022, MetS was investigated according to Adult Treatment Panel III (ATP III) criteria in men who underwent prostate biopsy with transrectal ultrasound (TRUS). Clinicopathological factors such as, digital rectal examination (DRE), prostate-specific antigen (PSA), prostate volume, waist circumference, body mass index (BMI), age, blood pressure, testosterone, lipid profiles, fasting blood glucose level, C-reactive protein (CRP) and MetS were analyzed. RESULTS: A total of 908 men underwent biopsies, of which 492 (51.5%) had MetS according to ATP III criteria. The number of patients diagnosed with PCa in biopsy was 270 (29.7%). PCa cases were significantly older, with a lower prostate volume and a higher PSA value and higher blood pressure compared to patients without PCa (p < 0.001). 146 of 416 (35.0%) patients with MetS had PCa while 124 of 492 (25.2%) patients without MetS had PCa (p < 0.001). Out of 270 patients with PCa, 174 (64.4%) had Gleason score <7 and 96 (35.6%) had Gleason score ≥7. In patients with a Gleason score ≥7, PSA, DRE(+) and core positive number were significantly higher compared to patients with Gleason score <7, while glycemia and high-density lipoprotein (HDL) cholesterol levels were significantly lower (p < 0.001). Multivariate analysis showed that age, PSA, positive DRE, prostate volume (p < 0.001), diastolic blood pressure, CRP and MetS were the only independent parameters associated with a higher risk of cancer on biopsy (p < 0.05). CONCLUSIONS: Our findings show that MetS is associated with PCa diagnosed on biopsy but not with the Gleason score and the number of cancer-positive cores. However, these results should be confirmed by larger, multicenter and prospective studies.

A New Promising Pathway in Aggressive Prostate Cancer: Treg/mir-let8c/lin28b.

PURPOSE: The progress of prostate cancer entails complex contemporaneous tumor developmental events in diverse stages that they are still yet to be clarified. miRNAs might accompany to balance between regulatory and cytotoxic T cells in tumors. Here, we investigated miRNAs and Regulatory T cell (Treg) marker FOXP3 expressions within prostate cancer spectrum. METHODS: Thirty-eight prostate cancer patients enrolled within two groups to the study as having Gleason Score ≤ 7 (Group-1) and ≥ 8 (Group-2) that compared to 19 benign prostate hyperplasia controls. Twelve miRNAs expressions were analyzed by real time PCR from paraffin-embedded prostate tissue samples. Correlations between serum PSA levels, immunohistochemical staining of CD3, CD4, FOXP3 and miRNA expressions were analyzed. RESULTS: In our study, hsa-let7c-3p significantly 1,52 (p=0.018) and 1,84 (p=0.0095) fold down- regulated whereas, miR-141-3p was significantly 2,36 (p=0.0006) and 2,24 (p=0.001) fold upregulated in the prostate cancer patients compared to benign prostate hyperplasia in group 1 and 2, respectively. Only CD4 (p=0.004) and PSA (p<0.001) have statistically significant differences among groups when compared to benign prostate hyperplasia. miR-143-p, miR-221-3p, hsa-let7c-3p and miR-17-3p expressions were significantly correlated with regulatory T cell marker FOXP3 expression. CONCLUSIONS: For the first time, we reported significantly altered expression levels of miRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143, miR17) and correlations between Treg marker FOXP3 in the aggressive prostate cancer patients suggesting that prostate cancer progression might be under the regulation of crosstalk between Tregs and miRNAs.

Ear atresia: Is there a role of apoptosis-regulating miRNAs?

OBJECTIVE: The molecular events underlying ear development involve numerous regulatory molecules; however, the role of microRNAs (miRNAs) has not been explored in patients with ear atresia. Here, we aimed to investigate the expressions of 20-22 nucleotide noncoding RNAs. METHODS: We selected 12 miRNAs that function to control post-transcriptional gene expression in different pathways, including apoptosis, angiogenesis, and chondrogenesis. The altered miRNA expressions were analyzed by real-time PCR from serum samples of 7 patients with ear atresia and 8 controls. RESULTS: We found that the expression of apoptosis-regulating miRNAs was significantly downregulated in patients with ear atresia. TThe expressions of miR126, miR146a, miR222, and miR21 were significantly decreased by 76.2-(p=0.041), 61.8-(p=0.000), 30.5-(p=0.009), and 71.21-fold (p=0.042), respectively, compared with controls. CONCLUSION: Abnormal ear development in ear atresia patients, could possibly be due to the reduced expression of apoptosis regulating miRNAs. Changes in the regulation of tumor protein p53 (TP53), p53 upregulated modulator of apoptosis (PUMA), Fas cell surface death receptor (FAS), FAS ligand (FasL), and phosphatase and tensin homolog (PTEN) directly or within the apoptosis-related cascades may play important roles during development, particularly in the external ear. This is the first report to present the possible association between apoptosis-regulating miRNAs and ear atresia/microtia.

Selective Inhibition of Parallel DNA Damage Response Pathways Optimizes Radiosensitization of Glioblastoma Stem-like Cells.

Glioblastoma is the most common form of primary brain tumor in adults and is essentially incurable. Despite aggressive treatment regimens centered on radiotherapy, tumor recurrence is inevitable and is thought to be driven by glioblastoma stem-like cells (GSC) that are highly radioresistant. DNA damage response pathways are key determinants of radiosensitivity but the extent to which these overlapping and parallel signaling components contribute to GSC radioresistance is unclear. Using a panel of primary patient-derived glioblastoma cell lines, we confirmed by clonogenic survival assays that GSCs were significantly more radioresistant than paired tumor bulk populations. DNA damage response targets ATM, ATR, CHK1, and PARP1 were upregulated in GSCs, and CHK1 was preferentially activated following irradiation. Consequently, GSCs exhibit rapid G2-M cell-cycle checkpoint activation and enhanced DNA repair. Inhibition of CHK1 or ATR successfully abrogated G2-M checkpoint function, leading to increased mitotic catastrophe and a modest increase in radiation sensitivity. Inhibition of ATM had dual effects on cell-cycle checkpoint regulation and DNA repair that were associated with greater radiosensitizing effects on GSCs than inhibition of CHK1, ATR, or PARP alone. Combined inhibition of PARP and ATR resulted in a profound radiosensitization of GSCs, which was of greater magnitude than in bulk populations and also exceeded the effect of ATM inhibition. These data demonstrate that multiple, parallel DNA damage signaling pathways contribute to GSC radioresistance and that combined inhibition of cell-cycle checkpoint and DNA repair targets provides the most effective means to overcome radioresistance of GSC.