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Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.

This review provides a thorough overview of contemporary treatment strategies for complex renal calculi, including large-volume stones, stones with increased hardness and greater number, or stones with abnormal anatomy. The development of tailored treatment plans for stone removal is essential for treatment success. A literature search was conducted on PubMed using the Keyword “complex renal calculi” along with “percutaneous nephrolithotomy (PCNL),” “retrograde intrarenal surgery (RIRS),” “endoscopic combined intrarenal surgery (ECIRS),” “stone free rate,” and “complications.” Based on the findings, the use of “minimally invasive PCNL,” “multiple-tract PCNL,” “staged RIRS,” and “ECIRS” is proposed in addition to the traditional PCNL suggested using the European Association of Urology guidelines. Renal calculi in patients with solitary kidneys or who underwent kidney transplants are considered to be complex, and treatment options that allow preservation of their remaining renal function should be considered.

Abstract Background The study aimed to investigate the association between socioeconomic status and severity of oral epithelial dysplasia (OED) using current data from the Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). Methods This retrospective analysis was conducted in the Department of Oral and Maxillofacial Surgery at a general hospital in Taipei, Taiwan. A total of 134 participants were analysed from a previous study database of 150 patients. The inclusion criteria included age > 20 years and a history of either tobacco or betel nut use. Background information, including para-habits such as betel and tobacco use, was analysed using the Pearson chi-square (χ2) test; furthermore, the correlation of background information with OED severity was investigated using logistic regression (mild or moderate/severe). Results High school education level (P

Abstract To compare perioperative circulating tumor cells (CTC) in primary upper tract urothelial carcinoma (UTUC) patients who underwent hand-assisted retroperitoneoscopic nephroureterectomy (HANU) or robotic-assisted nephroureterectomy (RANU). A total of 29 patients received RANU (n = 10) or HANU (n = 19). Peripheral blood samples were collected before, 24 h after surgery (POh24) and on postoperative day 28 (POD28). The demographic and pathologic data are similar in both groups. RANU had a longer operative time (p = 0.031), less bleeding volume (p = 0.004), and comparable pain sore (p = 0.169). The mean CTC numbers before surgery (2.4 vs. 2.3, p = 0.482), POh24 (2.4 vs. 1.9, p = 0.668) and POD28 (0.5 vs. 0.6, p = 0.280) were not significant different among groups. The amount of CTCs in both groups decreased and reached similar level on POD28. No significant difference of overall and intravesical recurrence rate between the two approaches. In comparison to RANU, more surgical manipulation does not affect tumor cell translocation into the bloodstream in UTUC patients who received HANU. However, a longer follow-up would be needed for the final comparison of tumor recurrence.

Background: Wilms' tumor (nephroblastoma) is the most common solid primary renal malignancy in children but extremely rare in adult population. We report the clinical presentation and therapeutic results of our adult Wilms' tumor patients and review the previous literatures about diagnosis and treatments. Methods: A retrospective review was carried out to investigate the patients with adult Wilms' tumor at the Tri-Service General Hospital during a 35-year period (1980–2014). Seven patients ≥16 years old (one female and six males; median age at the time of diagnosis of 24 years; range: 21–48 years) were staged according to the National Wilms' Tumor Study staging system as follows: three patients had Stage II disease, two patients had Stage III disease, and two patients had Stage IV disease. All statistical values were represented as mean ± standard deviation. All tests were two-sided, with P < 0.05 considered statistically significant. All statistical analyses were carried out using SPSS software (IBM, Armonk, NY, USA). Results: The most common clinical presentation is flank pain (57%) followed by palpable mass (43%). Only one patient presented with gross hematuria. Four patients underwent renal arteriography, which all disclosed irregular, tortuous vessel pattern with faint tumor stain. All patients underwent radical nephrectomy (one – hand-assisted laparoscopic nephrectomy and six – open transperitoneal nephrectomy). Two patients developed lung metastases after radical surgery. Six patients received multimodal therapy, including surgery, chemotherapy, and radiation therapy. The mean disease-free survival is 81 months. The 3- and 5-year survival rates are 83% and 71% separately. Conclusions: Selective renal arteriography could provide a valuable diagnostic hint in adult Wilms' tumor. Using multimodality therapy, improved prognosis could be achieved.

Abstract Enzalutamide (ENZ) is an important drug used to treat castration-resistant prostate cancer (CRPC), which inhibits androgen receptor (AR) signaling. Previous study showed that 3,3′-diindolylmethane (DIM) is an AR antagonist that also inhibits Wnt signaling and epithelial-mesenchymal transition (EMT). To investigate whether combined treatment with ENZ and DIM can overcome ENZ resistance by regulating Wnt signaling to inhibit AR signaling and EMT in ENZ-resistant prostate cancer cells, 22Rv1 cells were cultured in normal medium and treated with ENZ, DIM, and DIM with ENZ. Exposure of ENZ-resistant cells to both DIM and ENZ significantly inhibited cell proliferation without cytotoxicity and invasion in comparison with the control. DIM significantly increased the E-cadherin expression and inhibited the expressions of Vimentin and Fibronectin, subsequently inhibiting EMT. Co-treatment with ENZ and DIM significantly increased the expressions of GSK3β and APC and decreased the β-catenin protein expression, causing inhibition of Wnt signaling and AR expression, it also significantly decreased the AR-v7 expression and down-regulated AR signaling. Via suppression of Wnt and AR signaling, co-treatment increased the E-cadherin and decreased the Vimentin and Fibronectin RNA and protein expressions, then inhibited EMT. Co-treatment with DIM and ENZ regulated Wnt signaling to reduce not only the AR expression, but also the AR-v7 expression, indicating suppression of EMT that inhibits cancer cell proliferation, invasion and migration to ameliorate ENZ resistance.

This study aimed to explore the existence of circulating tumor cells (CTCs) in patients with muscle-invasive bladder cancer (MIBC) and their predictive potential for response to neoadjuvant chemotherapy (NAC). From 33 blood samples of MIBC patients, CTCs were isolated by cell surface markers and enriched by the IsoFlux™ device, followed by morphological and immunofluorescent identification. CTCs were detected at baseline in all samples. Immunofluorescence confirmed the tumor origin. MIBC patients were stratified by NAC response into the disease control (DC) and progressive disease (PD) groups. In the DC group, the number of CTCs decreased significantly after four courses of NAC (p < 0.0001). CTC counts in 7.5 mL after four NAC cycles were highly correlated with postoperative pathological T stage (p < 0.0001). Our study demonstrated that CTCs might represent a valuable predictive marker for NAC response in MIBC. CTC detection in MIBC patients could allow early arrangement of radical cystectomy for NAC non-responders to prevent disease progression while receiving the NAC courses.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose solution was performed. After 1 week, we conducted a urodynamic test, bladder staining, and ECM-related gene expression analysis to examine the treatment’s efficacy. We found that dextrose treatment could recover the instability of the bladder, reduce frequent urination, and improve the glycosaminoglycan layer regeneration and the bladder wall thickness along with a significant intense expression of CD44 receptors. Furthermore, we enrolled 29 IC/BPS patients with previous hyaluronic acid/Botox treatment for more than 6 months with remained unchanged condition. In this study, they received intravesical injections of 10% dextrose solution followed by assessments for up to 12 weeks. Patient characteristics and a 3-day voiding diary before treatment were recorded. Patient responses were examined using IC/BPS-related questionnaires. Moreover, expressions of growth factors and cytokines were analyzed. The results demonstrated that dextrose prolotherapy in patients with IC/BPS reduced the frequency of treatment over time, with the mean number of treatments being 3.03 ± 1.52, and significantly reduced the incidence of nocturia and questionnaire scores associated with symptoms. Dextrose prolotherapy significantly enhanced EGF level and, in contrast, reduced the level of HGF, PIGF-1, and VEGF-D after several weeks following treatment. The cytokine analysis showed that the expressions of IL-12p70 and IL-10 were significantly up-regulated after dextrose prolotherapy in IC/BPS patients. The levels of most growth factors and cytokines in IC/BPS patients had no significant difference and showed a similar tendency as time progressed when compared to healthy controls. Overall, the alteration of growth factors and cytokines exhibited safe treatment and potential stimulation of tissue remodeling. In summary, our study demonstrated that dextrose prolotherapy is a promising treatment strategy for IC/BPS disease management.

Bladder cancer is one of the most prevailing cancers worldwide. Although treatments for urothelial carcinoma have improved, the rate of recurrence observed in the clinic is still high. The aim of this study was to evaluate whether cholesterol biosynthesis is involved in the effect of Farnesoid X Receptor (FXR) on bladder cancers. FXR overexpression contributed to activation of 5′ AMP-activated protein kinase (AMPK) and decreased cholesterol levels. FXR overexpression reduced cholesterol biosynthesis and secretion by downregulating Sterol Regulatory Element Binding Protein 2 (SREBP2) and 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR) expression. In addition, an AMPK inhibitor, dorsomorphin, reversed the inhibition of migration, invasion and angiogenesis by FXR overexpression. In a metastatic xenograft animal study, FXR overexpression suppressed bladder cancer lung metastasis by decreasing matrix metalloproteinase-2 (MMP2), SREBP2 and HMGCR expression. Moreover, FXR overexpression combined with atorvastatin treatment further enhanced the downregulation of the migratory, adhesive, invasive and angiogenic properties in human urothelial carcinoma. In clinical observations, statin administration was associated with better survival rates of early-stage bladder cancer patients. Our results may provide guidance for improving therapeutic strategies for the treatment of urothelial carcinoma.

(1) Background: Bladder cancer is a malignant tumor mainly caused by exposure to environmental chemicals, with a high recurrence rate. NR1H4, also known as Farnesoid X Receptor (FXR), acts as a nuclear receptor that can be activated by binding with bile acids, and FXR is highly correlated with the progression of cancers. The aim of this study was to verify the role of FXR in bladder cancer cells. (2) Methods: A FXR overexpressed system was established to investigate the effect of cell viability, migration, adhesion, and angiogenesis in low-grade TSGH8301 and high-grade T24 cells. (3) Results: After FXR overexpression, the ability of migration, adhesion, invasion and angiogenesis of bladder cancer cells declined significantly. Focal adhesive complex, MMP2, MMP9, and angiogenic-related proteins were decreased, while FXR was overexpressed in bladder cancer cells. Moreover, FXR overexpression reduced vascular endothelial growth factor mRNA and protein expression and secretion in bladder cancer cells. After treatment with the proteosome inhibitor MG132, the migration, adhesion and angiogenesis caused by FXR overexpression were all reversed in bladder cancer cells. (4) Conclusions: These results may provide evidence on the role of FXR in bladder cancer, and thus may improve the therapeutic efficacy of urothelial carcinoma in the future.

Screening for oral potentially malignant disorders (OPMDs) with dysplasia in high-risk groups is suggested in countries with a high prevalence of the disorders. This study aimed to compare the accuracy of diagnoses of OPMDs with dysplasia made by a primary examiner (general dental clinician) and a specialist (oral and maxillofacial surgeon) using the current Taiwanese Nationwide Oral Mucosal Screening Program (TNOMSP). A total of 134 high-risk participants were enrolled for oral mucosal screening via the TNOMSP. A primary examiner and a specialist examined each participant. Mucosal biopsies were obtained and subjected to histopathological analysis. The OPMD most frequently diagnosed by the primary examiner was thin homogeneous leukoplakia (48/134; 35.8%), and in 39/134 participants (29.1%) the diagnosis was uncertain, but abnormalities were suggested. The OPMDs most frequently diagnosed by the specialist were erythroleukoplakia (23/134; 17.2%) and thin homogeneous leukoplakia (21/134; 15.7%), and 51/134 participants (38.1%) were diagnosed with other diseases. Via histopathology, 70/134 participants (52.3%) were diagnosed with dysplasia, and 58/134 (43.3%) were diagnosed with benign conditions. The specialist's diagnoses exhibited a higher specificity, positive predictive value, and accuracy than the primary examiners. A specialist using the current TNOMSP for high-risk participants diagnosed OPMDs with dysplasia more accurately than a primary examiner. Early diagnosis of high-risk OPMDs is crucial in countries with a high prevalence of the disorders. Proficient examination via the current TNOMSP by trained clinician is effective for the management of OPMDs with dysplasia.

Among herbal medicines, magnolia bark extract, particularly its components honokiol (Hono) and magnolol (Mag), has been widely documented to have antineoplastic properties. The present study aimed to evaluate the synergism of Hono and Mag in bladder cancer therapy both in vitro and in vivo. Treatment with Mag alone at concentrations up to 80 μM failed to have an antiproliferative effect. In contrast, the combination of Hono and Mag at 40 μM decreased viability, caused cell cycle arrest and enhanced the proportion of Annexin V/7AAD-positive cells. Moreover, Mag with Hono at 40 μM induced caspase 3-dependent apoptosis and autophagy. Neither Hono nor Mag alone had an anti-migratory effect on bladder cancer cells. In contrast, Hono and Mag at 20 μM inhibited the motility of TSGH8301 and T24 cells in wound-healing and Transwell assays. The above phenomena were further confirmed by decreased phosphorylated focal adhesion kinase (p-FAK), p-paxillin, integrin β1, and integrin β3 protein levels. In a nude mouse xenograft model, Mag/Hono administration preferentially retarded T24 tumor progression, which was consistent with the results of cellular experiments. Current findings suggest Hono and Mag treatment as a potential anticancer therapy for both low- and high-grade urothelial carcinoma.

Ketamine was first synthesized as a clinical medicine for anesthesia in 1970. It has been used as a recreational drug because of its low cost and hallucination effect in the past decade. Part of ketamine abusers may experience ketamine-related cystitis (KC) and suffer from lower urinary tract symptoms, including urinary frequency, urgency, and severe bladder pain. As the disease progression, a contracted bladder, petechial hemorrhage of the bladder mucosa, and ureteral stricture with hydronephrosis may occur. The pathophysiology of KC is still uncertain, although several hypotheses have been raised. Cessation of ketamine abuse is critical for the management of KC to prevent progressive disease, and effective treatment has not been established. Research has provided some theoretical bases for developing in vitro experiments, animal models, and clinical trials. This review summarized evidence of molecular mechanisms of KC and potential treatment strategies for KC. Further basic and clinical studies will help us better understand the mechanism and develop an effective treatment for KC.

Background: Endoscopic combined intrarenal surgery (ECIRS) adds ureteroscopic vision to percutaneous nephrolithotomy (PCNL), which can be helpful when dealing with complex renal stones. Yet, there is still no consensus on the superiority of ECIRS. We aimed to critically analyze the available evidence of studies comparing efficacy, safety, bleeding risk, and efficiency of ECIRS and PCNL. Methods: We searched for studies comparing efficacy (initial and final stone-free rate), safety (postoperative fever, overall and severe complications), efficiency (operative time and hospital stay) and bleeding risk between ECIRS and PCNL. Meta-analysis was performed. Results: Seven studies (919 patients) were identified. ECIRS provided a significantly higher initial stone-free rate, higher final stone-free rate, lower overall complications, lower severe complications, and lower rate of requiring blood transfusion. There was no difference between the two groups in terms of postoperative fever, hemoglobin drop, operative time, and hospital stay. In the subgroup analysis, both minimally invasive and conventional ECIRS were associated with a higher stone-free rate and lower complication outcomes. Conclusions: When treating complex renal stones, ECIRS has a better stone-free rate, fewer complications, and requires fewer blood transfusions compared with PCNL. Subgroups either with minimally invasive or conventional intervention showed a consistent trend.

Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin βA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.

Bladder cancer (BC) has a high recurrence rate worldwide. The aim of this study was to evaluate the role of fatty acid binding protein 6 (FABP6) in proliferation and migration in human bladder cancer cells. Cell growth was confirmed by MTT and colony formation assay. Western blotting was used to explore protein expressions. Wound healing and Transwell assays were performed to evaluate the migration ability. A xenograft animal model with subcutaneous implantation of BC cells was generated to confirm the tumor progression. Knockdown of FABP6 reduced cell growth in low-grade TSGH-8301 and high-grade T24 cells. Cell cycle blockade was observed with the decrease of CDK2, CDK4, and Ki67 levels in FABP6-knockdown BC cells. Interestingly, knockdown of FBAP6 led to downregulation of autophagic markers and activation of AKT-mTOR signaling. The application of PI3K/AKT inhibitor decreased cell viability mediated by FABP6-knockdown additionally. Moreover, FABP6-knockdown reduced peroxisome proliferator-activated receptor γ and retinoid X receptor α levels but increased p-p65 expression. Knockdown of FABP6 also inhibited BC cell motility with focal adhesive complex reduction. Finally, shFABP6 combined with cisplatin suppressed tumor growth in vivo. These results provide evidence that FABP6 may be a potential target in BC cells progression.

Background: In this study, we aimed to identify the association between chronic periodontal disease (CPD) and erectile dysfunction (ED) in a large young population. Patients and Methods: Totally 2191 male participants aged 18–28 years attended the Army Training Center in Taiwan between August 2012 and May 2013. All 1932 included participants filled in the International Index of Erectile Function-5 (IIEF-5) questionnaire and received a comprehensive dental examination to classify whether CPD. Results: There was a statistically significant correlation between the presence of ED and CPD (P < 0.001). Multivariate logistic regression analysis indicated that men with CPD were 1.6 (95% confidence interval = 1.280–2.009, P < 0.001) times more likely to have ED than men without CPD after adjusting confounders. Conclusion: This study demonstrates a link between ED and CPD, and it may be attributed to a combination of psychogenic and organic etiologies, such as systemic inflammation, oxidative stress, and endothelial dysfunction. This study highlights the significance of oral health, which may take a role in sexual function, even in young males. In clinical practice, more comprehensive management strategies to address participants with ED and CPD need to be investigated.

Perirenal hematoma after extracorporeal shock wave lithotripsy (ESWL) is an unusual but underdiagnosed complication. Most hematomas are asymptomatic, but severe complications are possible, which may require intervention such as a blood transfusion. We present the case of a 41-year-old Asian man suffering from a symptomatic huge perirenal/subcapsular hematoma with scrotal hematoma after ESWL; we reviewed the literature and examined the possible risk factors and treatments. This case was a very rare presentation of hematoma extension into the scrotum region from an ipsilateral perirenal hemorrhage caused by shock wave lithotripsy treatment.

Clinical bladder tumor histological analysis shows that high expression of S1PR1 is associated with poor patient prognosis. However, there are no studies that describe the underlying mechanism. To investigate the relative distribution and actual function of S1PR1 in bladder tumors, we analyzed multiple clinical databases in combination with tumor purity and immune cell infiltration simulations, as well as databases of well-defined histological phenotypes of bladder cancer, and single-cell sequencing of adjacent normal tissues and bladder tumors, and further compared them with bladder cancer cell lines. The results showed that S1PR1 expression was generally higher in normal tissues than in bladder cancer tissues, and its distribution was mainly in endothelial cells or immune cells. The association between high S1PR1 expression and poor prognosis may be due to tumor invasion of adjacent normal tissues, where highly expressed S1PR1 may affect prognostic interpretation. The effect of S1PR1 itself on cancer cells was associated with cell adhesion, and in bladder cancer cells, S1PR1 expression was negatively correlated with cell motility. Moreover, the use of FTY-720 will cause an increased metastatic ability of bladder cancer cells. In conclusion, we suggest that the use of S1PR1-specific inhibition as a synergistic treatment requires more observation and consideration.

Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α-treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α-treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α-treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC.

We aimed to explore the associations between different lipid profiles and semen quality in a large-scale general male population. Sperm concentration, total sperm motility, progressive motility, and normal sperm morphology of total 7601 participants were recorded. The association of these semen parameters with the triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein of serum lipid profiles was analyzed. Sperm concentration was statistically positively correlated with triglyceride and very low-density lipoprotein (adjusted P = 0.001 and P = 0.005, respectively). Total sperm motility and progressive motility were statistically increased with increasing low-density lipoprotein and cholesterol levels (both adjusted P = 0.008 and P < 0.001, respectively). The similar J-shaped associations (high-low-low-high) were noted between individual lipid profile and normal sperm morphology, especially low-density lipoprotein and cholesterol with statistical significance (adjusted P = 0.017 and P = 0.021, respectively). The prevalence of abnormal total sperm motility and progressive motility was decreased in participants with high levels of cholesterol (P = 0.008 and P = 0.019, respectively), and the reverse J-shaped associations (low-high-high-low) were noted between high-density lipoprotein, triglyceride, very low-density lipoprotein, and the prevalence of abnormal normal sperm morphology (P = 0.010, P = 0.037, and P = 0.025, respectively). A high cholesterol level was associated with better sperm motility. Similar J-shaped associations were noted between all lipid profiles and normal sperm morphology; meanwhile, the reverse J-shaped trends were identified between them and abnormal normal sperm morphology prevalence.

Objective: The aim of this study was to evaluate the therapeutic response and complications of high-intensity focused ultrasound for patients with localized prostate cancer. Materials and Methods: We evaluated the clinical outcomes of 29 patients who received high-intensity focused ultrasound as first-line treatment for localized prostate cancer at our hospital from October 2010 to March 2016. Biochemical recurrence was defined, according to the Stuttgart definition of biochemical failure, as the prostate-specific antigen nadir plus 1.2 ng/mL. Prostate-specific antigen levels and complications were recorded during regular follow-up. Results: The mean follow-up period was 24.6 months. Six patients experienced biochemical recurrence (20.68%). Disease progression was noted in six patients (20.68%), and salvage therapy was performed in these patients. The 24.6-month cancer-specific survival rate was 100%. No severe complications were reported. Conclusion: High-intensity focused ultrasound is an alternative therapy for patients with localized prostate cancer. In combination with preceding transurethral resection of the prostate, this treatment shows promise in disease control with a low complication rate in short-term follow-up.

Background. A multicenter, randomized, open-label, parallel group, pilot, 52-week study in Asian countries that assessed the renal function, efficacy, and safety of reduced-exposure versus standard-exposure prolonged-release tacrolimus (PR-T) in adult kidney transplant recipients (KTRs). Methods. Posttransplantation, KTRs received PR-T from weeks 0 to 4 (initial dose, 0.2–0.3 mg/kg; target trough level, 6–10 ng/mL). At week 4, KTRs were randomized (1:1) to receive reduced-exposure PR-T (target 4–6 ng/mL, weeks 4–12; 3–5 ng/mL, weeks 12–52) or standard-exposure PR-T (target: 6–10 ng/mL, weeks 4–52). Primary end point: estimated glomerular filtration rate (eGFR) over 52 weeks. Secondary end points (week 52) included creatinine clearance, serum creatinine, graft/patient survival, biopsy-confirmed acute rejection (AR), composite of graft loss/patient death/biopsy-confirmed AR, and steroid-resistant AR. Treatment-emergent adverse events were recorded. Results. Sixty-six KTRs received PR-T (reduced-exposure, n = 32; standard-exposure, n = 34) and were analyzed. After per-protocol dose adjustment, mean ± standard deviation tacrolimus trough level was lower with reduced- versus standard-exposure PR-T (week 52, 4.5 ± 1.1 ng/mL vs 8.0 ± 2.2 ng/mL). In the reduced- versus standard-exposure group, eGFR was similar at weeks 8 to 52 (overall least-square mean difference, –2.82; 95% confidence interval, −7.91 to 2.27; P = 0.272). At week 52, there was no significant difference in creatinine clearance (P = 0.375) or serum creatinine (P = 0.547) between groups. All grafts/patients survived, no steroid-resistant AR was reported, and 4 and 3 patients had AR in reduced- and standard-exposure groups, respectively. Drug-related treatment-emergent adverse events were reported in 34.4% and 38.2% of patients, respectively. Conclusions. Reducing exposure to PR-T resulted in a clinically acceptable short-term safety profile and was generally as effective as standard tacrolimus exposure for Asian patients.

Background: The aim of this study was to examine the utility of the vascular ring connector (VRC) and compare the clinical outcomes to conventional suture technique in the operation for acute type A aortic dissection (AAAD). Methods: We retrospectively enrolled 64 consecutive patients (mean age 57.4 ± 12.7 years, range 24-82 years) with AAAD who underwent emergent surgery in our institution from September 2010 to November 2014. Patients were divided into VRC group (55 patients) and conventional suture group (nine patients) based on the use of VRC during the operation. The preoperative characteristics, operative variables, and postoperative outcomes were collected and analyzed. Results: Male patients predominated in both groups. The mean times of cardiopulmonary bypass and aortic cross-clamp were 200.1 ± 99.9 and 193.6 ± 54.7 min (P = 0.425) and 107.5 ± 56.2 and 112.3 ± 40.8 min (P = 0.404) in the VRC group and suture group, respectively. There were more blood transfusions within 24 h (1513.3 ± 949.2 vs. 841.8 ± 801.1 ml) and more mediastinal drainage amount (1314.4 ± 650.3 ml vs. 942.1 ± 527.2 ml) in the suture group than in the VRC group. In the VRC group, 36.3% of patients did not require blood transfusion. Moreover, the pumping time and cardiac ischemic times were longer in the one-VRC group than in the two-VRC group. Operative mortality did not differ between the two groups (10.9% in VRC and 11.1% in suture group, P = 0.985). No dislodgement of VRC during or after operation and no bleeding from sutureless anastomosis site were noted. Conclusion: Use of VRC is associated with equivalent operative mortality and morbidity compared to suture group in patients with AAAD undergoing an emergent operation. This study demonstrates the clinical safety and efficacy of VRC in reducing the need of blood transfusion within 24 h and mediastinal drainage within 72 h. However, further randomized studies and long-term surveillance of the use of VRC in AAAD are still mandatory.

Objective: Based on the TAX 327 Phase III trial, docetaxel (DTX)-based chemotherapy is the standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). However, some heterogeneity is observed in clinical practice. The present study aimed to evaluate the outcomes of a weekly low-dose DTX regimen, which is clinical practice at our institution, and to compare it with the standard triweekly DTX use in the TAX 327 trial. Materials and methods: We reviewed the charts of all mCRPC patients treated with DTX 30 mg/m2 weekly on Days 1 and 8 of a 3-week cycle and prednisolone 5 mg twice daily between January 2006 and February 2014 in our hospital. Results: In the first-line setting, 19 patients with mCRPC received weekly DTX chemotherapy. The median four cycles of treatment were given in our cohort. The median follow-up period from the start of chemotherapy was 27.9 months (range 5.4–67.2months). The prostate-specific antigen (PSA) response rate was 47.3%, and the median overall survival was 15.8 months (range 1.2–34.5 months). The main toxicities were anemia (57%), fatigue (26%), and neuropathy (10%). Two patients had different Grade 3 to 4 adverse events (neutropenia and anemia). Our results revealed initial PSA 12 months) of response to primary hormone therapy, rechallenge, and a higher accumulation dose of DTX were associated with good prognosis. Conclusion: For Taiwanese mCRPC patients, weekly DTX 30 mg/m2 is an efficient regimen for disease control with relatively low Grade 3 or 4 hematological adverse effects. The proper treatment duration of DTX therapy for mCRPC in Taiwanese patients is still uncertain, so further research is needed.

Hyperphosphatemia is a serious complication in chronic kidney disease (CKD) that occurs due to insufficient excretion of phosphorus during failure of renal function. Both CKD and an excessive phosphorus intake have been reported to increase oxidative stress and result in poor male fertility, but little is known about the reproductive function of the CKD under a poorly controlled phosphate intake. Eight-week-old C57BL/6 mice (n = 66) were randomly divided into four groups: a sham operation group received a chow diet as control (SC group, n = 14), CKD-induced mice received a chow diet (CKDC group, n = 16), control mice received a high phosphorus (HP) diet (SP group, n = 16), and CKD-induced mice received a HP diet (CKDP group, n = 20). CKD was induced by performing a 5/6 nephrectomy. The chow diet contained 0.6% phosphorus, while the HP diet contained 2% phosphorus. Impaired testicular function and semen quality found in the CKD model may result from increased oxidative stress, causing apoptosis and inflammation. The HP diet aggravated the negative effects of testicular damage in the CKD-induced mice.

The aim of this study was to investigate the effects of metformin supplementation on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice with high-fat and high-cholesterol diet-induced obesity. Forty male C57BL/6 mice were fed a normal diet (NC group, n = 10) or a high-fat and high-cholesterol diet (HFC group, n = 30) for 24 weeks, and mice randomly chosen from the HFC group were later treated with metformin for the final 8 weeks of HFC feeding (HFC + Met group, n = 15). Compared with the HFC group, the obese mice supplemented with metformin exhibited improved blood cholesterol, glucose and insulin resistance. The HFC group diminishes in the sperm motility and normal sperm morphology, while the poorer maturity of testicular spermatogenesis was improved by metformin treatment. The HFC group exhibited a higher estradiol level and a lower 17β-HSD protein expression. Further analyses showed that metformin treatment increased the activities of superoxide dismutase, catalase and glutathione peroxidase and reduced lipid peroxidation. Nevertheless, both the HFC and HFC + Met groups exhibited increased expressions of apoptosis and inflammation proteins in the testis. Metformin treatment ameliorated obesity-induced poor testicular spermatogenesis and semen quality through increasing the testosterone level and antioxidant capacity.

A 71-year-old man presented with spondylodiscitis with epidural and psoas muscle abscesses following transrectal ultrasound (TRUS)-guided prostate biopsy. These rare complications were detected by computed tomography of the abdomen and magnetic resonance imaging of the lumbar spine. The patient was successfully treated with antibiotics and underwent neurosurgery. Awareness of presentations such as backache and weakness of the lower limbs after prostate biopsy is important as these symptoms are usually mistaken for bone or muscle problems and often not recognized as being related to infection.

Objective: There are currently no practical guidelines regarding recurrent or complex urethral strictures in Taiwan. Furthermore a specific urological reconstruction center focusing on urethroplasties in this area is currently unavailable. In this study we aim to share the experience of our institute according to an algorithm for this disease entity. Materials and methods: From December 2007 to October 2013, adult males with complex urethral strictures were enrolled. Six different surgical techniques were used for treatment. Clinical features and outcomes were analyzed through a retrospective chart review. Results: The mean age was 39 years, with a mean follow-up period of 42 months (range, 5–76 months). An average of three sessions of previous treatments was noted. The overall primary success, requiring no further intervention, was 46%. Permanent failure occurred in one patient (2.6%). The primary success for urethroplasty in distal, penile, bulbar, posterior urethra, and in stricture with hypospadias was 100%, 40%, 83%, 29%, and 60%, respectively. From the perspective of procedure type, anterior anastomotic urethroplasty (80%) and skin-based flaps (75%) resulted in the highest success rate. Following anterior or posterior buccal mucosal graft-augmented urethroplasties, 40% of patients received additional short-term dilatations or urethrotomies. Conclusion: Complex urethral strictures can be managed by a variety of surgical techniques according to specific stricture locations. However, a careful postoperative follow-up for recurrences is mandatory, since ∼40% of patients undergoing buccal mucosal graft-augmented urethroplasties were expected to have additional procedures after the index urethroplasty.

Introduction: Long-term ketamine abuse may cause variable lower urinary tract symptoms (LUTS) and severe cystitis. The clinical features of ketamine-associated cystitis (KC) are very similar to bladder pain syndrome/interstitial cystitis (BPS/IC). Intravesical administration of hyaluronic acid (HA) is one of the regimens for treating BPS/IC. In this study, we aim to investigate whether intravesical HA therapy may improve the LUTS of patients with KC. Materials and methods: Four female patients and one male patient with KC who failed oral medications were enrolled in this study. HA (Cystistat) at a dose of 40 mg in a volume of 50 mL of phosphate-buffered saline was injected into the bladder on a weekly basis for 6 weeks and then monthly for a further 3 months. Response to therapy was evaluated by the visual analog scale (VAS) for pain, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), and Interstitial Cystitis Problem Index (ICPI). Treatment efficacy was assessed by comparing the pretreatment and posttreatment mean scores of the five questionnaires using the paired t test. Results: The mean age of the patients was 22 ± 1.5 years. The mean duration of ketamine abuse was 68 ± 16.7 months. After intravesical HA therapy for 4 weeks, statistically significant mean decreases in VAS (from 7 to 4.4, p = 0.03), IPSS voiding subscore (from 16.2 to 11.6, p = 0.017), and ICSI (from 16.4 to 13.6, p = 0.016) questionnaire scores were seen. However, only ICSI constantly reduced after 4 weeks of treatment. Conclusion: Intravesical HA therapy may have short-term benefits for improving bladder pain and voiding symptoms in patients with KC.

Extragastrointestinal stromal tumors (EGISTs) originate from several anatomic sites, except the digestive system. We describe an early prostatic EGIST case with lower urinary tract symptoms and a palpable lesion on digital examination. The patient received transrectal ultrasonography-guided biopsy of the prostate, and the pathological finding demonstrated positive staining for DOG-1 and CD117. Treatment included only imatinib, which shrank the tumor and led to complete remission. Because of enlarged prostate volume with tumor progression, the initial common manifestations are lower urinary tract symptoms. Surgical resection is the recommended management, particularly in bulky lesions. However, imatinib still plays an important role in long-term therapy. We also review the associated reported cases of prostatic EGISTs.

Objective: Despite an earlier detection of prostate cancer (Pca) is promising, pathologically advanced disease still exists in 40–52% of cases. We present a retrospective study of adjuvant radiotherapy (ART) in adverse pathological tumor characteristics of PCa, and analyze the optimal time for ART. Materials and methods: From 2004 to 2012, we identified 53 men with adverse pathological characteristics of PCa receiving early [< 3 months after radical prostatectomy (RP), n=42] or delayed (3–12 months after RP, n=11) ART after RP. The adverse pathological characteristics of PCa were defined as positive surgical margins, extracapsular extension, seminal-vesicle invasion, or detectable prostate-specific antigen after RP. The primary-outcome collection includes 5-year biochemical-free survival (BCFS), PCa-specific mortality, bone-related events, salvage-hormonal-therapy utilization, and intervention for urethral stricture. Results: There was no PCa-specific mortality in the 5-year follow-up. When compared with the delayed ART in men with adverse pathological characteristics of PCa, early ART was associated with the trend to improve the 5-year BCFS (89% vs. 73%; p=0.1) and less salvage hormonal therapy (45% vs. 54%; p=0.29). The delayed ART is associated with the trend of fewer urethral strictures (9% vs. 14 %; p=0.32). But, there was no significant difference between both groups. Conclusion: Compared with the delayed ART, early ART for adverse pathological tumor characteristics of PCa seems to have the trend in improvement in the 5-year BCFS and metastasis-free survival. Because of our limited case number, a prospective study with more cases to confirm the effect of ART is needed.

Whether sexual function is affected by circumcision is a subject of considerable debate among advocate and opponent opinions. We analyzed the sexual function of young men, and the differences between those who were uncircumcised and circumcised, in Taiwan. A total of 506 patients who received circumcision between January 2009 and March 2011 at the urology department in our center were enrolled. Before circumcision, the patients' sexual performances were evaluated using the International Index of Erectile Function-5 (IIEF-5), and the Brief Male Sexual Function Inventory (BMSFI) questionnaires. They were evaluated using the questionnaires again, after a postoperative interval of 90 days. Furthermore, intravaginal ejaculation latency times (IELT) of the patients were also measured. The IELT and scores in five main domains of the BMSFI, and IIEF, before and after circumcision, were analyzed. A total of 442 patients were available for follow up. The mean age was 25.14 ± 4.46 years (range = 19–35 years). The differences in the BMSFI scores were statistically significant (p

Renal cell carcinoma (RCC) is a common aggressive genitourinary tract tumor and in which distant metastases eventually develop. It is known to have potential to metastasize to almost any site, but metastatic RCC to the duodenum is extremely rare. We discuss a 57-year-old male patient who had undergone a right radical nephrectomy 12 years previously and free of disease for RCC presented with a 3-days history of shortness of breath, fatigue, dyspepsia, black tarry stools, and generalized weakness. The diagnosis made from the biopsy specimens on upper gastrointestinal panendoscopy study was metastatic RCC in the duodenum. He underwent the surgical exploration for pancreaticoduodenectomy subsequently. He had an uneventful recovery with Sutent (Sunitinib malate) was used after surgery for adjuvant target therapy and there was no evidence of recurrence 6 months after the procedure.

Excellent wound dressing is essential for effective wound repair and regeneration. However, natural polymeric skin substitutes often lack mechanical strength and hydrophilicity. One way to overcome this limitation is to use biodegradable polymers with high mechanical strength and low skin-irritation induction in wet environments. Bacterial cellulose (BC) is an attractive polymer for medical applications; unlike synthetic polymers, it is biodegradable and renewable and has a strong affinity for materials containing hydroxyl groups. Therefore, we conjugated it with resveratrol (RSV), which has a 4′-hydroxyl group and exhibits good biocompatibility and no cytotoxicity. We synthesized BC scaffolds with immobilized RSV and characterized the resulting BC/RSV scaffold with scanning electron microscopy and Fourier-transform infrared spectroscopy. We found that RSV was released from the BC in vitro after ~10 min, and immunofluorescence staining showed that BC was highly biocompatible and regenerated epithelia. Additionally, Masson’s trichrome staining showed that the scaffolds preserved the normal collagen-bundling pattern and induced re-epithelialization in defective rat epidermis. These results indicated that RSV-conjugated BC created a biocompatible environment for stem cell attachment and growth and promoted epithelial regeneration during wound healing.

We present a case of a healthy 43-year-old man who experienced right lower abdominal mass with gastrointestinal upset for 6 months. A series of imaging studies revealed a large lobulated cyst in the right pelvis and retroperitoneum. Because of the persistent symptom, surgical intervention was performed to remove the cystic lesion. The final pathology report demonstrated a large seminal vesicle cyst with agenesis of kidney. It is compatible with the diagnosis of Zinner's syndrome. However, right lower abdominal mass is a rare manifestation of this syndrome. This case reminds us a unique differential diagnosis of a right lower abdominal mass.

Background: To offer an easily produced and cost-effective specimen retrieval bag that can be used to reduce the cost of laparoscopic surgery. Methods: From January 2005 to October 2009, 135 patients underwent laparoscopic surgery for adrenalectomy or prostatectomy, during which a homemade specimen retrieval bag was used. The retrieval bag was produced from a large sterile surgical glove, 2-0 nylon thread, and 1-0 RB-1 needle Vicryl thread. A purse-string suture at the opening of the bag was made using the nylon thread, and the bottom of the bag was double-tied using the tail of the Vicryl thread. The bag was introduced into the peritoneal cavity via a 12-mm port, and the specimen was enclosed with the use of two laparoscopic instruments. The bag was then extracted by extending the port incisional wound. Results: We used a homemade retrieval bag to extract specimens from 110 patients who underwent robot-assisted laparoscopic radical prostatectomy and 25 patients who underwent laparoscopic adrenalectomy. The procedure was performed safely, and no bags were broken. No complications were observed after the operations such as wound infection, ileus, or intestinal adhesion. In our experience, our homemade endobag can be easily used by surgeons to extract specimens from the abdominal cavity. The total cost of hospitalization was also reduced for the patients. Conclusion: The homemade specimen retrieval bag is cost-effective and useful for the retrieval of intact specimens. It is also easy to make and safe to use.

Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.

Previous studies investigated the impacts of a partial nephrectomy (PN) or radical nephrectomy (RN) on cardiovascular events and death. However, the association between the type of nephrectomy (PN vs. RN) and cardiovascular disease is still equivocal. This retrospective cohort study aimed to compare the risk of coronary heart disease (CHD) between patients who underwent a PN and those who underwent an RN. We used data from the Taiwan Longitudinal Health Insurance Database 2005. In total, 60 patients who underwent a PN and 545 patients who underwent an RN were included. Each patient was tracked for 1-, 2-, 3-, and 5-year periods to identify those who were subsequently diagnosed with CHD. Cox proportional hazard regression analyses were used to calculate hazard ratios (HRs) for CHD during 1-, 2-, 3-, and 5-year follow-up periods between these two cohorts. For the 1-year follow-up period, the adjusted HR was 0.39 (95% CI: 0.05~2.90, p = 0.355) for patients who underwent a PN compared to those who underwent an RN. Additionally, the adjusted HRs of CHD in patients who underwent a PN for 2-, 3- and 5-year follow-up periods were 1.40 (95% CI: 0.62~3.16, p = 0.417), 1.09 (95% CI: 0.52~2.31, p = 0.814), and 1.02 (95% CI: 0.48~2.18, p = 0.961), respectively, compared to those who underwent an RN. We concluded that there was no significant difference in the risk of CHD between patients who underwent a PN and those who underwent an RN.