Enzalutamide Prior to Radium-223 Is Associated with Better Overall Survival in Metastatic Castration-Resistant Prostate Cancer Patients Compared to Abiraterone-A Retrospective Study.

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003-0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.

The EXPANDER-1 trial: introduction of the novel Urocross™ Expander System for treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH).

PURPOSE: To demonstrate the safety and feasibility of the Urocross Expander System (formerly branded as XFLO Expander System), an implantable nitinol tissue expander to trea t patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Men of 50 years or older were eligible to participate in the international, prospective, three-arm, open-label EXPANDER-1 trial if they had a prostate volume between 30 and 80 cc, prostatic urethra length between 20 and 60/80 mm, international prostate symptom score (IPSS) > 13, peak urinary flow (Qmax) < 12 mL/s, post-void residual (PVR) urine volume < 250 mL and quality of life (QoL) score ≥ 3. Patients had pre-assigned implant indwell times (1, 6, and 12 months for Arm-1, Arm-2 and Arm-3 respectively) with follow-up through 6 months (Arm-1) and 3 years (Arm-2 and Arm-3) post-retrieval. RESULTS: Outcome from treated subjects with their 6-month post-retrieval will be presented in this manuscript, as data collection from longer-term follow-up is ongoing. As of May 24, 2021, 39 and 22 men (mean age: 65), respectively, had implants successfully deployed and retrieved without any complications. No cases of implant encrustation were observed. Device- and procedure-related adverse events were predominantly mild to moderate in severity. Three SAEs were reported. Only one patient required catheterization post-implant for more than three days. Improvements in clinical parameters such as IPSS, QoL, PVR and Qmax as well as sexual function were observed. CONCLUSIONS: Preliminary results demonstrate that the Urocross Expander System is a feasible and safe procedure for treating BPH/LUTS. A strong signal of efficacy justifies further evaluation of this PRostatic Urethral Expansion (PURE) procedure. Negative features of earlier generations of prostatic implants such as biocompatibility, migrations and encrustation have possibly been overcome.

Relationships of multiple metals exposure, global DNA methylation, and urothelial carcinoma in central Taiwan.

The relationship between heavy metal exposure and human health has been investigated mostly for individual metals, failing to consider their potential interactions. In this study, we assessed the joint effects of multiple metals using generalized weighted quantile sum (WQS) regression on the risk of urothelial carcinoma (UC). Also, we performed mediation analysis to evaluate the mediator %5-MedC in DNA involved in the mechanism of urothelial carcinogenesis. We conducted a hospital-based case-control study of 355 UC patients and 710 controls, where diagnosis of UC was histologically confirmed. All data were collected from face-to-face interviews and medical records. Also, we measured six metals and 8-OHdG in urine samples along with %5-MedC in peripheral blood. Ni and Pb levels increased with UC risk in single-pollutant analysis using traditional logistic regression, and similar results were obtained in multi-pollutant analysis, where all metals analyzed were considered. In WQS analysis, the weights of Ni (27%), Pb (20%), Cr (18%), and Co (16%) predominated in the metal mixture index. WQS score and UC risk showed odds ratios of 1.65 (95%CI: 1.26, 2.15) and 1.43 (95%CI: 1.00, 2.05) for a linear and non-linear relationship, respectively. Finally, we did not observe a natural indirect effect of %5-MedC in DNA; however, a marginal effect of WQS score and natural direct effect were still found after considering a natural indirect effect. In conclusion, positive associations between WQS scores and increased risk of UC were observed. Interactions of multiple metals should be considered in assessing human health risk.

A double-blind, randomized, placebo-controlled, parallel study to evaluate the efficacy and safety of imidafenacin in patients with overactive bladder in Taiwan.

OBJECTIVE: This study evaluated the efficacy and safety of imidafenacin 0.1 mg twice daily vs placebo for Taiwanese patients with overactive bladder (OAB) after a 12-week oral administration. METHODS: This randomized, double-blind, placebo-controlled, two-arm, parallel-group, prospective study enrolled 118 patients across 11 study sites in Taiwan. Subjects were randomized to imidafenacin or placebo in a 2:1 ratio and entered the 12-week treatment period. At the subsequent visits, efficacy outcome measures and safety assessments were collected for analysis. The primary efficacy outcome was the change in the mean number of micturitions per day. Secondary endpoints included mean changes from baseline in urgency episodes and urge incontinence episodes per day and mean volume voided per micturition. Safety outcomes were also collected and compared between groups. RESULTS: A total of 78 and 40 patients were allocated to the imidafenacin and placebo groups, respectively. Among them, 100 patients (imidafenacin, 65 and placebo, 35) completed the trial. Compared with placebo, imidafenacin was significantly better at reducing the number of micturitions per day (-1.29 ± 2.23 vs -0.46 ± 3.49, P = .0171) and reducing the mean number of urge incontinence episodes (-0.15 ± 0.52 vs 0.04 ± 0.50, P = .0386) at week 12. Adverse events were reported in 35 subjects (44.9%) and 16 (40%) in the imidafenacin and placebo groups, including constipation (n = 3, 4), dry mouth (n = 11, 2), and urinary tract infection (n = 7, 4), respectively. One patient in the imidafenacin group had mild dysuria. CONCLUSION: Imidafenacin demonstrated efficacy and safety in the treatment of OAB in Taiwanese patients.

Increased risk of prostatitis in male patients with depression.

Objectives: To investigate whether male patients with depression are at an increased risk of prostatitis.Methods: We used a universal insurance claims database in Taiwan from 2000 to 2010 to identify patients with newly diagnosed depression (n = 13,019) (depression cohort) and those without depression (n = 53,026) (comparison cohort). Both cohorts were matched by age and index year of depression incidence. Hazard ratios of prostatitis were calculated by multivariable Cox proportional hazard models.Results: The incidence of prostatitis demonstrated a 2-fold increase in the depression cohort in comparison with that observed in the non-depression cohort, with an adjusted hazard ratio of 1.70 after adjustment for age, occupation, urbanisation level, potential comorbidity and medication. Furthermore, patients with depression, relative to the non-depression cohort, were 1.85-fold more likely to develop acute prostatitis, 1.76-fold more likely to develop chronic prostatitis and 1.63-fold more likely to develop unspecific prostatitis. Major associations still existed; even those stratified by age, occupation, urbanisation level and comorbidity all showed greater increased risks of prostatitis in the depression cohort than in the non-depression cohort.Conclusions: Depression can be an independent factor associated with the increased risk of prostatitis for men. The incidence of chronic prostatitis is greater than that of acute prostatitis. Close surveillance for UTI and depression treatment and lifestyle intervention should be considered for men with high risk for prostatitis. The mechanism associated with the development of prostatitis in men with depression requires further study. In addition, the mechanism of prostatitis may need comprehensive investigation.

Prostate Health Index (PHI) improves prostate cancer detection at initial biopsy in Taiwanese men with PSA 4-10 ng/mL.

In this study, we aimed to validate the Prostate Health Index (PHI) for the detection of prostate cancer (PCa). We prospectively enrolled patients aged 50-75 years with a serum prostate specific antigen (PSA) level of 4-10 ng/mL undergoing transrectal biopsy of the prostate between April 2016 and May 2017. The primary outcome was the diagnostic performance of various PSA derivatives (total PSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI) to predict PCa. The secondary outcome was comparisons of PSA derivatives between patients with a Gleason score (GS) ≤6 and GS ≥7. PCa was diagnosed in 36 of 154 (23.4%) patients, and 26 (16.9%) had a GS ≥7. The areas under the receiver operating characteristic curves were significantly greater in %p 2PSA and PHI than in PSA (0.76 vs. 0.57, p = 0.015 and 0.77 vs. 0.57, p = 0.004, respectively). Patients with a GS ≥7PCa had marginally higher %p2PSA and PHI than those with a GS of 6 (17.8 vs. 12.73, p = 0.06; 46.58 vs. 31.55, p = 0.05). At a PHI cutoff value of 29.6, the sensitivity and specificity were 77.8% and 67.8% in detecting PCa, respectively. In addition, 57.1% of the patients avoided an unnecessary biopsy, while three patients (1.9%) with GS 7 PCa were missed. In conclusion, the ability of %p2PSA and PHI to predict prostate biopsy outcome was better than that of PSA and %fPSA in the initial biopsy in Taiwanese men with serum PSA between 4 and 10 ng/mL.

Increased risk of anxiety among patients with urolithiasis: A nationwide population-based cohort study.

OBJECTIVES: To investigate whether patients with urolithiasis are at an increased risk of anxiety and depression. METHODS: We used universal insurance claims data in Taiwan from 2000 to 2011 to identify patients with newly diagnosed urolithiasis (n = 32 617) and those without urolithiasis (n = 130 465). Incidences, hazard ratios, and incidence rate ratios of anxiety and depression were determined in both cohorts in terms of baseline demographic characteristics and comorbidities until December 2011. RESULTS: The urolithiasis cohort yielded a higher incidence of anxiety (11.9 vs 6.91 per 1000 person-years) with an adjusted hazard ratio of 1.5 (95% confidence interval 1.42-1.57) than the non-urolithiasis cohort. The urolithiasis cohort also showed a higher incidence of depression (5.79 vs 3.95 per 1000 person-years) with an adjusted hazard ratio of 1.26 (95% confidence interval 1.18-1.35) than the non-urolithiasis cohort. Regardless of the patients' baseline comorbidities, patients with urolithiasis showed a higher incidence rate ratio of anxiety and depression than those without urolithiasis (with no comorbidities: adjusted hazard ratio 1.62, 95% confidence interval 1.49-1.76] for anxiety and adjusted hazard ratio 1.37, 95% confidence interval 1.23-1.54 for depression). CONCLUSION: Urolithiasis is recurrent, and significantly associated with anxiety and depression. Therefore, urologists should diagnose patients suspected with this disease and provide proper medical care.

Associations of cyclooxygenase 2 polymorphic genotypes with bladder cancer risk in Taiwan.

AIM: Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in southwestern Taiwan. However, the genetic contribution to its etiology is not well-understood. The aim of this study is to evaluate the association of cyclooxygenase 2 (Cox-2) polymorphic genotypes with Taiwan bladder cancer patients. MATERIALS AND METHODS: Six polymorphic variants of Cox-2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same amount of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method. RESULTS: Among the six polymorphic sites examined, only the Cox-2 promoter G-765C (rs20417) genotypes were positively associated with bladder cancer risk (p=0.0102). Individuals with the Cox-2 -765GC genotypes were associated with higher prostate cancer risk than those with -765GG. CONCLUSION: Our findings provide evidence that the C allele of Cox-2 promoter G-765C may be associated with the overexpression of COX-2 during bladder cancer development and may be a useful marker for the early detection of bladder cancer.

Significant association of caveolin-1 (CAV1) genotypes with upper urothelial tract cancer.

AIM: Upper urothelial tract cancer is unusually of high incidence in Taiwan and it is valuable to study the specificity of this disease in Taiwan and compare the corresponding findings with those of Western countries. In the literature, it has been reported that single nucleotide variation of caveolin-1 gene (CAV1) plays an important role in risk of several types of cancer, such as hepatoma, leukemia, nasopharyngeal carcinoma, oral, breast, bladder and prostate cancer, but we are not aware of any reports on upper urothelial tract cancer. The aim of this study was to evaluate the association of six polymorphic genotypes of CAV1 with upper urothelial tract cancer within a Taiwanese population. MATERIALS AND METHODS: A total of 218 patients with upper urothelial tract cancer and 580 healthy controls in central Taiwan were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for six CAV1 polymorphic genotypes, C521A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992), and their association with upper urothelial tract cancer susceptibility was examined. RESULTS: The distribution of genotypes of CAV1 rs3807987 and rs7804372 were significantly different between cancer patient and control groups (p=0.0188 and 0.0090, respectively), while those for CAV1 rs1997623, rs12672038, rs3757733 and rs3807992 were not significant (p>0.05). The haplotype analysis of the two polymorphic genotypes showed that compared with the GG/AT, and GG/AA haplotypes of CAV1 rs3807987/rs7804372, those carrying GG/TT, AG/TT and AA/TT variants have a significantly increased risk of upper urothelial tract cancer (odds ratio=1.61, 1.50 and 2.67, 95% confidence interval=1.05-2.47, 1.18-1.90, and 1.37-5.18, respectively). On the contrary, other haplotype variants conferred non-significant elevated risk. CONCLUSION: Our results suggest that individual and combined CAV1 rs3807987/rs7804372 genotypes are involved in predisposition to upper urothelial tract cancer in the Taiwanese population.

Remote monitoring of videourodynamics using smart phone and free instant messaging software.

AIMS: To evaluate the feasibility of using smart phones plus free instant messaging software for remote monitoring of videourodynamics. METHODS: From November 2011 to October 2012, 85 females with voiding disorders were enrolled for videourodynamic tests. The patients were assigned to videourodynamics remotely monitored by the attending physician by using iPhone/iPad and Skype (group 1) and videourodynamics with the attending physician present (group 2). The procedural time and videourodynamic qualities, assessed by the frequency of adherence to the modified Sullivan criteria, in each group were recorded and compared. RESULTS: There were 44 and 41 patients in group 1 and group 2, respectively. The mean procedural time was comparable between group 1 and group 2 (56.3 vs. 54.4 min, P = 0.25). The frequencies of adherence to the modified Sullivan criteria were similar in each group. CONCLUSIONS: The qualities of videourodynamics under the attending physician's remote or direct monitoring were both appropriate. Based on the convenience of Internet, the popularity of smart phones and the intention to make the urologists use their time more efficiently, our study provides remote monitoring as an alternative way for performing videourodynamics.

The role of XRCC6 T-991C functional polymorphism in renal cell carcinoma.

BACKGROUND: The DNA non-homologous end-joining repair gene XRCC6 (Ku70) plays a key role in both the DNA double-strand break (DSB) repair and cell cycle arrest. Defects in DSB repair capacity can lead to genomic instability. We hypothesized that a variant in the XRCC6 gene was associated with susceptibility to renal cell carcinoma (RCC). MATERIALS AND METHODS: In a hospital-based case-control study of 92 patients with RCC and 580 cancer-free controls, the frequency matched by age and sex, the associations of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter A-31G (rs132770), and intron 3 (rs132774) polymorphisms with RCC risk were investigated in a Taiwanese population. At the same time, 30 adjacent renal tissue samples were tested to estimate the XRCC6 mRNA expression by real-time quantitative reverse transcription. RESULTS: Compared with the TT genotype, the TC genotype had a significantly increased risk of RCC [adjusted odds ratio=2.24, 95% confidence interval=1.25-4.08, p=0.0175]. The in vivo mRNA expression in renal tissues revealed a statistically significant lower XRCC6 mRNA expression in samples with TC/CC genotypes compared to those with the TT genotype (p=0.0039). CONCLUSION: These evidence suggests that the XRCC6 T-991C genotype together with its mRNA expression are involved in the etiology of RCC and may be a marker for susceptibility to RCC in the population of Taiwan.

Association of DNA double-strand break gene XRCC6 genotypes and lung cancer in Taiwan.

AIM: The DNA repair gene X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) is thought to play an important role in the repair of DNA double-strand breaks. It is known that defects in double-strand break repair capacity can lead to irreversible genomic instability. However, the association of polymorphic variants of XRCC6 with lung cancer susceptibility has never been reported. In this hospital-based case-control study, the association of XRCC6 promoter T-991C (rs5751129), promoter G-57C (rs2267437), promoter G-31A (rs132770), and intron 3 (rs132774) polymorphisms with lung cancer risk in a Taiwanese population, was studied. MATERIALS AND METHODS: In total, 358 patients with lung cancer and 716 healthy controls recruited from the China Medical Hospital in Taiwan were genotyped. RESULTS: The results showed that there were significant differences between lung cancer and control groups in the distribution of their genotypic (p=3.7×10(-4)) and allelic frequency (p=2.7×10(-5)) in the XRCC6 promoter T-991C polymorphism. Individuals who carried at least one C allele (TC or CC) had a 2.03-fold increased odds ratio of developing lung cancer compared to those who carried the wild-type TT genotype (95% conference internal=1.42-2.91, p=0.0001). For the other three polymorphisms, there was no difference between the case and control groups in the distribution of either genotypic or allelic frequency. CONCLUSION: In conclusion, the XRCC6 promoter T-991C, but not the promoter C-57G, promoter G-31A or intron 3, is associated with lung cancer susceptibility.

Outcome Measurement of Overactive Bladder.

Overactive bladder (OAB) is a common disease. The diagnosis of OAB is based on its symptoms without physiological markers of disease activity. Frequently used assessment methods for OAB include frequency volume chart; urodynamic studies; patient-reported outcomes questionnaires, such as the Overactive Bladder Questionnaire, King's Health Questionnaire, patient perception of bladder conditions; and OAB symptom score. The severity of OAB and degree of improvement after treatment can be obtained by comprehensive evaluation. However, a consensus of which evaluations should be used to define the severity of OAB is still lacking. We expect a proper OAB assessment with universal acceptance in the future.