New biological prognostic predictors have been studied; however, some factors have limited clinical application due to tissue-specific expression and high cost. There is the need for a promising predictive factor that is simple to detect and that is closely linked to oncological outcomes in patients with urothelial bladder cancer (BC) who have undergone radical cystectomy (RC). Therefore, we investigated the clinical prognostic value of the preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) on oncological outcomes in patients with urothelial BC after RC. We retrospectively evaluated clinicopathological data of 118 patients with non-metastatic urothelial BC after RC between 2008 and 2013 at a single center. The association between the De Ritis ratio and clinicopathological findings was assessed. The potential prognostic value of the De Ritis ratio was analyzed using the Kaplan-Meier method, and multivariate Cox analyses were performed to identify the independent predictors of metastasis-free survival, cancer-specific survival, and overall survival. According to the receiver operating curve of the De Ritis ratio for metastasis, we stratified the patients into 2 groups using a threshold of 1.3. A high De Ritis ratio was more likely to be associated with old age and the female sex. Kaplan-Meier estimates revealed that patients with a high De Ritis ratio had inferior metastasis-free survival, cancer-specific survival, and overall survival outcomes (P = 0.012, 0.024, and 0.022, respectively). Multivariate analysis revealed that a high De Ritis ratio was an independent prognostic factor for metastasis (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.161–4.914; P = 0.018), cancer-related death (HR, 2.755; 95% CI, 1.214–6.249; P = 0.015), and overall death (HR, 2.761; 95% CI, 1.257–6.067; P = 0.011). An elevated De Ritis ratio was significantly associated with worse prognosis in patients who underwent RC for urothelial BC. This ratio might further improve the predictive accuracy for prognosis in BC.

We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

Interstitial cystitis (IC) is a chronic intractable disease. Recently, the potential application of stem cell (SC) therapy was suggested for IC management. This study aimed to establish an optimal SC source and verify the efficacy and safety of SC injection therapy in an IC rat model. After IC animal model induction, urine-derived stem cells (USCs), adipose tissue-derived stem cells (ADSCs), bone marrow-derived stem cells (BMSCs) and amniotic fluid-derived stem cells (AFSCs) were injected into the bladder submucosa. The following parameters were analysed: 1) functional improvement of bladder via cystometry, 2) histological changes and 3) inflammatory gene expression and regenerative potential of damaged bladder tissues. Additionally, an optimal method for SC introduction in terms of effective bladder regeneration was analysed. Intercontraction interval was significantly increased and inflammatory reactions and fibrotic changes were decreased in all of the SC-injected groups than in the control group. PCR analysis revealed that inflammatory gene expression significantly decreased in the USC-treated group than in the other groups. To confirm the optimal SC injection route in the IC rat model, group was divided according to the following criteria: 1) direction of SC injection into the bladder submucosa, 2) injection via tail vein, 3) transurethral instillation. In each analysis, the groups in which SCs were injected into the bladder submucosa showed significantly longer intercontraction interval, better morphologic regeneration and inhibition of bladder inflammatory reaction compared with the other groups. Regardless of the cell source, human tissue-derived mesenchymal SCs regenerated damaged bladder tissue, promoted functional recovery and inhibited inflammatory cell accumulation in an IC rat model; particularly, USC had the highest inhibitory effect on inflammation. Additionally, direct USC injection into the bladder submucosa was expected to have the best therapeutic effect, which will be an important factor for clinical applications in the future.

Bladder cancer is a common global cancer with a high percentage of metastases and high mortality rate. Thus, it is necessary to identify new biomarkers that can be helpful in diagnosis. Pyruvate dehydrogenase kinase 4 (PDK4) belongs to the PDK family and plays an important role in glucose utilization in living organisms. In the present study, we evaluated the role of PDK4 in bladder cancer and its related protein changes. First, we observed elevated PDK4 expression in high-grade bladder cancers. To screen for changes in PDK4-related proteins in bladder cancer, we performed a comparative proteomic analysis using PDK4 knockdown cells. In bladder cancer cell lines, PDK4 silencing resulted in a lower rate of cell migration and invasion. In addition, a PDK4 knockdown xenograft model showed reduced bladder cancer growth in nude mice. Based on our results, PDK4 plays a critical role in the metastasis and growth of bladder cancer cells through changes in ERK, SRC, and JNK.

Bladder cancer, one of the most frequently diagnosed cancers worldwide, is associated with high morbidity and mortality and a poor prognosis. The bladder cancer types include 1) non-muscle invasive bladder cancer (NMIBC) and 2) muscle invasive bladder cancer (MIBC). Metastases and chemoresistance in MIBC patients are the leading causes of the high death rate. c-Jun N-terminal kinase (JNK) is an important factor for the undifferentiated state of cancer cells. JNK belongs to the mitogen-activated protein kinases (MAPKs) family; it is activated by various extracellular stimuli, such as stress, radiation, and growth factors and mediates diverse cellular functions, such as apoptosis, autophagy, proliferation, invasion, and migration by mediating AKT (Ak strain transforming), ATG (Autophagy related), mTOR (Mammalian target of rapamycin), and caspases 3, 8, and 9. This review describes the JNK-related functions, mechanisms, and signaling in bladder cancer.

Fluoroscopy is usually required during retrograde intrarenal surgery (RIRS). Although fluoroscopy is considered necessary for effective and safe RIRS, there is growing awareness regarding radiation exposure risk to patients and surgeons. We conducted a multicenter-based, randomized, controlled trial to compare the safety and effectiveness of radiation-free (RF) RIRS with radiation-usage (RU) RIRS for kidney stone management. From August 2020 to April 2022, patients with a unilateral kidney stone (≤20 mm) eligible for RIRS were prospectively enrolled in 5 tertiary medical centers after randomization and divided into the RF and RU groups. RIRS was performed using a flexible ureteroscope with a holmium:YAG laser. The primary end point of this study was the success rate, defined as complete stone-free or residual fragments with asymptomatic kidney stones ≤ 3 mm. The secondary end point of this study was ascertaining the safety of RF RIRS. The success rates were analyzed using a noninferiority test. Of the 140 consecutive randomized participants, 128 patients completed this study (RF: 63; RU: 65). The success rates (78% vs 80%, P = .8) were not significantly different between the groups. The rate of high-grade (grade 2-4) ureter injury was not significantly higher in the RF group compared to the RU group (RF = 3 [4.8%] vs RU = 2 [3.1%], P = .6). In RF RIRS, the success rate was noninferior compared to RU RIRS (the difference was 2.2% [95% CI, 0.16-0.12]). This study demonstrated that the surgical outcomes of RF RIRS were noninferior to RU RIRS.