Value of Immunological Biomarkers in Early Prediction of Bacillus Calmette-Guerin Failure in High-Risk Non-muscle-invasive Bladder Cancer

Objectives To investigate the predictive value of different immunological markers on treatment outcomes after bacillus Calmette-Guerin (BCG) induction in high-risk non-muscle-invasive bladder cancer (NMIBC). Patients and Methods Patients who underwent transurethral resection of bladder tumors for NMIBC were assessed for study eligibility. Urine and blood samples were taken from patients at baseline (immediately before the first dose of induction). Urine samples were evaluated for interleukin (IL)-6, IL-8, IL-10, IL-11, and interferon- γ by solid-phase enzyme-linked immunosorbent assay (ELISA). Blood samples were evaluated for epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) using quantitative reverse transcriptase-polymerase chain reaction analysis. Each marker was assessed in relation to tumor recurrence. Results Between June 2016 and December 2019, 160 patients were included. Tumor recurrence occurred in 47 (29.38%) patients over a median (IQR) follow-up of 24 (12: 49) months. Using univariate analysis, the following urinary cytokines were associated with higher recurrence: urinary IL-6, 8, 10, 11, and interferon-γ. Also, serum EGFR and HER2 were associated with higher recurrence. On multivariate Cox regression analysis, significant variables include HER2 [HR (95%CI): 2.675 (1.367-5.233), p= 0.004], and IL-11 [HR (95%CI): 0.889 (0.825-0.957), p= 0.002]. Conclusions Serum HER2 and urinary IL-11 could be applied in clinical practice to predict BCG failure in patients with high-risk NMIBC, so those patients could be offered other modalities (radical cystectomy) early with better survival. Further studies are recommended to establish their exact role

Predictors of Success after Extracorporeal Shock Wave Lithotripsy (ESWL) for Renal Calculi Between 20-30 mm: A Multivariate Analysis Model

The first-line management of renal stones between 20-30 mm remains controversial. The Extracorporeal Shock Wave Lithotripsy (ESWL) stone-free rates for such patient groups vary widely. The purpose of this study was to define factors that have a significant impact on the stone-free rate after ESWL in such controversial groups. Between January 1990 and January 2004, 594 patients with renal stones 20-30 mm in length underwent ESWL monotherapy. Stone surface area was measured for all stones. The results of treatment were evaluated after 3 months of follow-up. The stone-free rate was correlated with stone and patient characteristics using the Chi-square test; factors found to be significant were further analyzed using multivariate analysis. Repeat ESWL was needed in 56.9% of cases. Post-ESWL complications occurred in 5% of cases and post-ESWL secondary procedures were required in 5.9%. At 3-month follow-up, the overall stone-free rate was 77.2%. Using the Chi-square test, stone surface area, location, number, radiological renal picture, and congenital renal anomalies had a significant impact on the stone-free rate. Multivariate analysis excluded radiological renal picture from the logistic regression model while other factors maintained their statistically significant effect on success rate, indicating that they were independent predictors. A regression analysis model was designed to estimate the probability of stone-free status after ESWL. The sensitivity of the model was 97.4%, the specificity 90%, and the overall accuracy 95.6%. Stone surface area, location, number, and congenital renal anomalies are prognostic predictors determining stone clearance after ESWL of renal calculi of 20-30 mm. High probability of stone clearance is obtained with single stone ≤400 mm 2 located in renal pelvis with no congenital anomalies. Our regression model can predict the probability of the success of ESWL in such controversial groups and can define patients who would need other treatment modality

Could the bulbar urethral end location on the cystourethrogram predict the outcome after posterior urethroplasty for pelvic fracture urethral injury?

ABSTRACTObjectives To identify cystourethrogram (CUG) findings that independently predict the outcome of posterior urethroplasty (PU) following pelvic fracture urethral injury (PFUI).Methods Findings of CUG included the location of the proximal end of the bulbar urethra in zones A (superficial) or B (deep) according to its relationship with the pubic arch. Others included the presence of pelvic arch fracture, bladder neck, and posterior urethral appearance. The primary outcome was the need for reintervention either endoscopically or by redo urethroplasty. Independent predictors were modeled using a logistic regression model and a nomogram was constructed and internally validated using 100-bootstrap resampling. Time-to-event analysis was performed to validate the results.Results A total of 196 procedures in 158 patients were analyzed. The success rate was 83.7% with 32 (16.3%) procedures requiring direct vision internal urethrotomy, urethroplasty, or both in 13 (6.6%), 12 (6.1%), and 7 (3.6%) patients, respectively. On multivariate analysis, bulbar urethral end located at zone B (odds ratio [OR]: 3.1; 95% confidence interval [CI]: 1.1–8.5; p = 0.02), pubic arch fracture (OR: 3.9; 95%CI: 1.5–9.7; p = 0.003), and previous urethroplasty (OR: 4.2; 95% CI: 1.8–10.1; p = 0.001) were independent predictors. The same predictors were significant in the time-to-event analysis. The nomogram discrimination was 77.3% and 75% in the current data and after validation.Conclusions The location of the proximal end of the bulbar urethra and redo urethroplasty could predict the need for reintervention after PU for PFUI. The nomogram could be used preoperatively for patient counseling and procedure planning

Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma

Background Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma. Methods A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil-to-lymphocyte ratio were evaluated. Results The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non–muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors. Conclusions Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression

Identification of Epigenetic Interactions between miRNA and Gene Expression as Potential Prognostic Markers in Bladder Cancer

Purpose: To identify the role of a set of microRNAs and their target genes and protein expression levels in the pathogenesis of bladder cancer with a muscular invasion (T2–T4) and non-muscular invasion (T1). Methods: In 157 patients, bladder specimen was examined for the expression of a set of miRNAs including let-7a-5p, miRNA-449a-5p, miRNA-145-3P, miRNA-124-3P, miRNA-138-5p, and miRNA-23a-5p and their targeted genes; β-catenin, WNT7A, IRS2, FZD4, SOS1, HDAC1, HDAC2, HIF1α, and PTEN using the qRT-PCR technique. The prognostic effect of miRNAs and their targeted genes on cancer-specific survival (CSS) was evaluated in pT2–pT4 stages. Results: pT1 was found in 40 patients while pT2–4 was found in 117 patients. The expression of let-7a-5P, miR-124-3P, miR-449a-5P, and miR-138-5P significantly decreased in pT2–4 compared with pT1 (p p p = 0.31). Higher expression levels of WNT7A, β-catenin, IRS2, FZD4, and SOS1 genes were observed in pT2–pT4 compared with pT1, whereas HDAC1, HDAC2, HIF1α, and PTEN genes were downregulated in pT2–pT4 compared with pT1. Lower CSS was significantly associated with lower expression of let-7a-5P, miR-124-3P, miR-449a-5P, and miR-138-5P. Higher expression of β-catenin, FZD4, IRS2, WNT7a, and SOS1 was significantly associated with worse CSS. In contrast, lower levels of HDAC1, HDAC2, HIF1α, and PTEN were associated with lower CSS. Conclusion: Our results support let-7a-5P, miR-124-3P, miR-138-5P, and their target genes can be developed as accurate biomarkers for prognosis in bladder cancer with a muscular invasion