A Comprehensive Analysis of Immune Response in Patients with Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Bladder carcinoma has elevated morbimortality due to its high recurrence and progression in localized disease. A better understanding of the role of the tumor microenvironment in carcinogenesis and response to treatment is needed. METHODS: Peripheral blood and samples of urothelial bladder cancer and adjacent healthy urothelial tissue were collected from 41 patients and stratified in low- and high-grade urothelial bladder cancer, excluding muscular infiltration or carcinoma in situ. Mononuclear cells were isolated and labeled for flow cytometry analysis with antibodies aimed at identifying specific subpopulations within T lymphocytes, myeloid cells and NK cells. RESULTS: In peripheral blood and tumor samples, we detected different percentages of CD4+ and CD8+ lymphocytes, monocyte and myeloid-derived suppressor cells, as well as differential expression of activation- and exhaustion-related markers. Conversely, only a significant increase in bladder total monocytes was found when comparing bladder and tumor samples. Interestingly, we identified specific markers differentially expressed in the peripheral blood of patients with different outcomes. CONCLUSION: The analysis of host immune response in patients with NMIBC may help to identify specific markers that allow optimizing therapy and patient follow-up. Further investigation is needed to establish a strong predictive model.

Genitourinary tract symptoms in patients admitted with COVID-19: Exploring changes in frequency by determinants and pandemic waves.

Background: Urothelial cells exhibit increased expression of angiotensin-converting enzyme-2 receptor, which is the binding site of severe acute respiratory syndrome coronavirus 2 to cells. The frequency and distribution of genitourinary tract symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19) is unknown. Objective: We explored trends in genitourinary tract symptoms by gender and each of six pandemic waves in patients admitted for COVID-19, and related them with severity, death and length of hospitalization. Design Setting and Participants: A retrospective study took place in our institution of COVID-19 admitted patients. Only patients with RT-PCR or antigen test confirmed SARS-CoV-2 infection were included. Demographic, clinical, and genitourinary symptoms were explored. Outcome Measurements and Statistical Analysis: COVID-19 patients with genitourinary tract symptoms were compared with those without. Statistical comparisons were conducted by parametric and nonparametric tests for quantitative variables, and χ 2 test for qualitative variables. Results and limitations: Out of a total of 4,661 COVID-19 patients, genitourinary symptoms were found in 21,1%. These symptoms were more frequent in patients admitted for longer than 30 days, except for urinary incontinence (UI) and erectile dysfunction (ED). Acute kidney injury (AKI) and urinary tract infections (UTI) had a higher presence in the 5th (16.7%; 12.8% respectively) and 3rd wave (13.3%; 12.6% respectively). Genitourinary symptoms were higher for those patients admitted in critical care units. Frequency of AKI, UI, UTI and acute urinary retention (AUR) were higher for patients who were finally deceased (26.2%; 3.5%; 13.6% and 3.6% respectively). Conclusions: A high frequency of genitourinary symptoms in patients admitted for COVID-19 was observed, whose frequency and distribution varied according to pandemic waves. Specific genitourinary conditions were associated with worse outcomes and poorer prognosis.

Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression.

Bladder cancer is the second most frequent malignancy of the urinary tract after prostate cancer. Current diagnostic techniques, such as cystoscopy and biopsies are highly invasive and accompanied of undesirable side effects. Moreover, there are no suitable biomarkers for relapse or progression prognosis. We analysed whether the specific composition of microRNAs (miRNAs) and proteins of extracellular vesicles (EVs) that urothelial tumour cells of bladder mucosa release into the urine, could reflect their pathologic condition. For this purpose, urinary EVs were isolated and their protein and miRNA composition evaluated in healthy donors and low or high-grade bladder cancer patients. Using a microarray platform containing probes for 851 human miRNAs we found 26 deregulated miRNAs in high-grade bladder cancer urine EVs, from which 23 were downregulated and 3 upregulated. Real-time PCR analysis pointed to miR-375 as a biomarker for high-grade bladder cancer while miR-146a could identify low-grade patients. Finally, several protein markers were also deregulated in EVs from tumour patients. Our data suggest that the presence of ApoB in the 100,000 pellet is a clear marker for malignancy.

Bilateral obstructive uropathy secondary to giant periureteral diverticulum.

Bladder diverticula are herniations of the mucosa through the fibers of the bladder muscle connected by necks of variable amplitude. They are often asymptomatic, although they may lead to complications that require a surgical therapeutic approach. We report the case of a patient with bilateral obstructive uropathy secondary to a giant periureteral diverticulum that was treated by diverticulectomy and reimplantation of the left ureter in the bladder.

Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer.

OBJECTIVE: To analyze the correlation between circulating tumor cell (CTC) levels and clinicopathologic parameters (prostate-specific antigen level, Gleason score, and TNM stage) in patients with metastatic hormone-sensitive prostate cancer (PCa) and to establish its prognostic value in overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: A prospective, 3-arm study was performed that included 30 patients with localized PCa; 30 patients with metastatic PCa, and 30 healthy volunteers. A single 7.5-mL peripheral blood sample was taken. The CTCs were isolated using an immunomagnetic method based on the CellSearch system. Kendall's tau and Spearman's rho coefficients of correlation were used. The multivariate Cox regression model addressed OS and PFS. RESULTS: The median follow-up was 42.9 months (interquartile range 27.14-49.5). A significant positive correlation was demonstrated between the CTC level and all tumor burden markers (prostate-specific antigen and T, N, and M stage; P <.001), except for Gleason score (tau = 0.16). A cutoff of ≥ 4 CTCs/7.5 mL was chosen to distinguish patients with a poor prognosis. These patients had a significantly shorter median OS and PFS (24 vs 45 months and 7 vs 44 months, respectively; P <.001). As the CTC level increased, the OS and PFS decreased. The risk of mortality and progression for the patients with ≥ 4 CTCs was 4.1 (P = .029) and 8.5 (P <.001) times greater. Multivariate analyses indicated that a CTC of ≥4 was an independent prognostic factor for PFS (hazard ratio 5.9, P <.005). CONCLUSION: The CTC count in peripheral blood could provide a method of staging PCa correctly and be of value when assessing the prognosis of metastatic hormone-sensitive PCa.