Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette–Guérin (BCG) therapy. Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared. Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively;p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien– Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001). Conclusions Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted.

Purpose: We developed immune checkpoint molecules to target recombinant dendritic cells (DCs) and verified their anti-tumor efficacy and immune response against prostate cancer. Materials and Methods: DCs were generated from mononuclear cells in the tibia and femur bone marrow of mice. We knocked down the programmed death ligand 1 (PD-L1) on monocyte-derived DCs through siRNA PD-L1. Cell surface antigens were immune fluorescently stained through flow cytometry to analyze cultured cell phenotypes. Furthermore, we evaluated the efficacy of monocyte-derived DCs and recombinant DCs in a prostate cancer mouse model with subcutaneous TRAMP-C1 cells. Lastly, DC-induced mixed lymphocyte and lymphocyte-only proliferations were compared to determine cultured DCs’ function. Results: Compared to the control group, siRNA PD-L1 therapeutic DC-treated mice exhibited significantly inhibited tumor volume and increased tumor cell apoptosis. Remarkably, this treatment substantially augmented interferon-gamma and interleukin-2 production by stimulating T-cells in an allogeneic mixed lymphocyte reaction. Moreover, we demonstrated that PD-L1 gene silencing improved cell proliferation and cytokine production. Conclusions We developed monocyte-derived DCs transfected with PD-L1 siRNA from mouse bone marrow. Our study highlights that PD-L1 inhibition in DCs increases antigen-specific immune responses, corroborating previous immunotherapy methodology findings regarding castration-resistant prostate cancer.

The development of lab-on-a-chip technology based on microfluidics has been used from diagnostic test to drug screening in biomedical science. Lab-on-a-chip technology is also being expanded to the concept of an organ-on-a-chip with the development of cell biology and biocompatible material development. In addition, artificial intelligence (AI) has brought dramatic changes over the past few years in science, industry, defense, science and healthcare. AI-generated output is beginning to prove comparable or even superior to that of human experts. Lab-on-a-chip technology in specific microfluidic devices can overcome the above bottlenecks as a platform for building and implementing AI in a large-scale, cost-effective, high-throughput, automated and multiplexed manner. This platform, high-throughput imaging, becomes an important tool because it can generate high-content information which are too complex to analyze with conventional computational tools. In addition to the capabilities of a data provider, lab-on-a-chip technology can also be leveraged to enable AI developed for the accurate identification, characterization, classification and prediction of objects in heterogeneous samples. AI will provide quantitative and qualitative analysis results close to human in the urology field with lab-on-a-chip.

Clear cell renal cell carcinoma (ccRCC) is a disease with a wide variety of clinical progressions such as the rate of disease progression or the degree of metastasis. About 30% of ccRCC patients suffer from metastatic diseases, and about 30% develop metastasis after diagnosis. In the case of metastatic RCC, early prediction of the disease is important because of the poor prognosis, but ccRCC-specific molecular markers for clinical use are not available yet. As an alternative, liquid biopsy, which can find molecules released from tumor tissues in circulating blood and obtain information on metastatic dissemination and recurrence of ccRCC, is emerging. In this article, we will introduce molecules such as cell free DNA, cell free RNA, protein, and exosomes available as circulating biomarkers for liquid biopsy. We will also introduce some promising technologies that can compensate for the limitations of liquid biopsy.

Purpose: Although Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is the most widely used bladder cancer immunotherapy, innate immune responses involving antimicrobial peptides (AMPs) cause BCG failure. Here, we developed genetically modified recombinant BCG (rBCG) strains which escape AMPs and evaluate the efficacy and effects of rBCG. Materials and Methods: We constructed rBCG strains expressing Streptococcal inhibitor of complement (Sic), which confers resistance to human α-defensin-1 and cathelicidin, and d-alanyl carrier protein ligase (dltA), which confers resistance to cationic AMPs. Sic and dltA were separately cloned into the pMV306 plasmid and introduced into BCG via electroporation. The efficacy of the Sic and dltA gene electroporation into BCG was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The internalization rates and anticancer effects of the rBCG strains containing Sic (rBCG-Sic) and dltA (rBCG-dltA) was evaluated by the orthotopic bladder cancer mouse model. Results: The cycle quantification (Cq) values of rBCG-Sic (y=-4.8823x+13.645, R2=0.9996) and rBCG-dltA (y=-5.438x+11.641, R2=0.9995) were inverse correlations to the amount of Sic and dltA genes dose dependently. The mean introduction proportions of Sic and dltA genes into BCG by electroporation were 22.2%, 27.5% and showed constant efficacy. In the orthotopic bladder cancer mouse model, the relative internalization number of rBCG-Sic, and rBCG-dltA into bladder cell in mouse bladder were higher than that of BCG and the tumor volume at rBCG-Sic were lower than at BCG and rBCG-dltA at 11, 14 and 18 days. Conclusions Our results showed that constructed rBCG-Sic and rBCG-dltA by electroporation and the rBCG-Sic and rBCG-dltA can effectively escape BCG-stimulated AMPs, and significantly improved immunotherapeutic tools to treat bladder cancer in orthotopic bladder cancer mouse model.

To systematically review relevant literature on efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced and metastatic urothelial cell cancer (UCC), renal cell cancer (RCC), and prostate cancer. In platinum pretreated UCC, efficacy of pembrolizumab was superior to chemotherapy, with longer median overall survival (OS; 10.3 months vs. 7.4 months), a higher objective response rate (ORR; 21.1% vs. 11.4%, p=0.001), and a lower adverse event rate (60.9% vs. 90.2%). Three randomized controlled trials (RCTs) assessed the safety and efficacy of nivolumab in advanced RCC. The median OS (25.0 months vs. 19.6 months) and the ORR (25% vs. 5%) were higher in patients treated with nivolumab compared with second-line everolimus. In patients with metastatic castration-resistant prostate cancer, 2 RCTs were identified, which did not show significant benefits for ipilimumab over placebo. In UCC and RCC, there was no conclusive association between programmed cell death receptor ligand 1 (PD-L1) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment, respectively. Therefore, in metastatic UCC and RCC, pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus, respectively. No beneficial effect of ipilimumab was observed in prostate cancer patients. PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome.
Carcinoma, Renal Cell ; Cell Death ; Drug Therapy ; Everolimus ; Humans ; Immunotherapy ; Platinum ; Prostatic Neoplasms ; Treatment Outcome ; Urologic Neoplasms

STUDY DESIGN: Case report. OBJECTIVES: To report the effectiveness of open reduction and internal (screw) fixation treatment performed to treat dislocation of the first coccygeal vertebra. SUMMARY OF LITERATURE REVIEW: Most treatment methods for coccygeal dislocation were conservative treatment for acute coccygodynia and coccygectomy for chronic coccygodynia. MATERIALS AND METHODS: A 18-year-old female presented with severe coccygodynia due to a fall down the stairs. Computed tomography showed dislocation of the first coccygeal vertebra. We performed open reduction and internal fixation with a 4.0-mm shortthread cancellous screw with a washer, with no additional procedure for bone union. RESULTS: Union was achieved 10 weeks postoperatively. CONCLUSIONS: Open reduction and internal (screw) fixation can be a useful method for coccygeal vertebra dislocation.
Adolescent ; Dislocations* ; Female ; Humans ; Methods ; Spine*

Seasonal variation in urinary stone presentation is well described in the literature. However, previous studies have some limitations. To explore overall cumulative exposure-response and the heterogeneity in the relationships between daily meteorological factors and urolithiasis incidence in 6 major Korean cities, we analyzed data on 687,833 urolithiasis patients from 2009 to 2013 for 6 large cities in Korea: Seoul, Incheon, Daejeon, Gwangju, Daegu, and Busan. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of mean daily urolithiasis incidence (MDUI) associated with mean daily meteorological factors, including the cumulative RR for a 20-day period. The estimated location-specific associations were then pooled using multivariate meta-regression models. A positive association was confirmed between MDUI and mean daily temperature (MDT), and a negative association was shown between MDUI and mean daily relative humidity (MDRH) in all cities. The lag effect was within 5 days. The multivariate Cochran Q test for heterogeneity at MDT was 12.35 (P = 0.136), and the related I2 statistic accounted for 35.2% of the variability. Additionally, the Cochran Q test for heterogeneity and I2 statistic at MDHR were 26.73 (P value = 0.148) and 24.7% of variability in the total group. Association was confirmed between daily temperature, relative humidity and urolithiasis incidence, and the differences in urolithiasis incidence might have been partially attributable to the different frequencies and the ranges in temperature and humidity between cities in Korea.
Busan ; Daegu ; Gwangju ; Humans ; Humidity ; Incheon ; Incidence ; Korea* ; Meteorological Concepts ; Population Characteristics ; Seasons ; Seoul ; Urinary Calculi ; Urolithiasis*

About 80% of Bladder cancer is non muscle invasive bladder cancer (NMIBC). Despite of appropriate therapy, a lot of NMIBC recur as a superficial tumor or progress to muscle invasive disease. Several studies about prognostic factors of recurrence and progression have reported a single risk factor variously according to each study. These efforts were developed to predict the risk by scoring system and large-scale studies had been conducted. These studies had limitations that their patients did not receive BCG (bacillus Calmette-Guerin) immunotherapy, immediate intravesical chemotherapy, second-look TUR (transurethral resection) in high-risk group. Through studies to date, patients with NMIBC have showed heterogenous prognosis and a more sophisticated scoring system can give personalized treatment and exact prediction.
Drug Therapy ; Humans ; Immunotherapy ; Mycobacterium bovis ; Prognosis ; Recurrence* ; Research Design ; Risk Factors ; Urinary Bladder Neoplasms ; Urinary Bladder*