Modified three-layer vesicourethral reconstruction in robot-assisted radical prostatectomy can change cystography pattern and improve early recovery of continence.

BACKGROUND AND OBJECTIVES: To determine early continence outcomes after three-layer vesicourethral reconstruction during robot-assisted radical prostatectomy (RARP) and the role of postoperative cystography pattern. METHODS: Between May 2015 and January 2019, a total of 170 consecutive patients with localized prostate cancer who underwent RARP, were divided into one- and three-layer groups based on the method of vesicourethral reconstruction. Continent status, preoperative, intraoperative, postoperative, clinicopathological variables, and cystography parameters were analyzed. The patients were followed up for at least 12 months. RESULTS: Of the 170 consecutive patients, 85 with one-layer vesicourethral anastomosis, and 85 with three-layer reconstruction. The continence rates immediately after catheter removal, 4, 12, and 24 weeks after RARP were 47.1%, 75.3%, 92.9%, and 98.8% in the three-layer group; compared to 15.3%, 60%, 78.8%, and 90.6% in the one-layer group, respectively. In the multivariate analysis, three-layer reconstruction was the only independent variable with a 42% risk reduction of postprostatectomy incontinence (hazard ratio (HR): 0.58, 95% confidence interval (CI) = 0.42-0.80, p = 0.001). Cystography in the three-layer group revealed less anastomotic leakage, less sharp bladder neck angle, and higher bladder neck level category. CONCLUSIONS: Three-layer anatomical reconstruction demonstrated promising early continence outcomes, and postoperative cystography revealed a specific pattern more associated with continence.

Risk of major adverse cardiovascular events among second-line hormonal therapy for metastatic castration-resistant prostate cancer: A real-world evidence study.

BACKGROUND: To evaluate the possible major adverse cardiovascular events (MACE) associated with second-line hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We performed a population-based real-world cohort study of 4962 prostate cancer patients between 2014 and 2017 utilizing the Chang Gung Research Database of Taiwan. The second-line hormonal therapies included enzalutamide and abiraterone acetate. The outcomes of interest were MACE, including acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF) events that resulted in hospitalization. Cox proportional-hazards models with inverse probability of treatment weighting (IPTW) with propensity scores were used. RESULTS: After IPTW, 288 patients were prescribed second-line hormonal therapy and 1575 received first-line androgen-deprivation therapy (ADT). Of all patients diagnosed with MACE, the event rates were 2.92% in the second-line hormonal group and 2.22% in the first-line ADT group. The mean follow-up period was 9.52 months for the second-line hormonal group. Patients who received second-line hormonal therapy exhibited a significantly increased risk for MACE (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 2.03-4.89), ACS (HR: 4.94; 95% CI: 2.36-10.33), and HF (HR: 2.83; 95% CI: 1.53-5.25), compared with the first-line ADT group, but a similar risk for IS was observed in both groups (HR: 1.70; 95% CI: 0.95-3.04). CONCLUSIONS: The real-world evidence study revealed increased risks for MACE in mCRPC patients receiving second-line hormonal therapy.

Wild coral oocytes are more amenable to low temperature preservation than cultured counterparts.

Few studies have examined the biochemical differences between cultured and wild coral after undergoing low-temperature preservation. The present study aimed to explore the differences in the biochemical characteristics of cultured and wild coral cells and oocytes (Echinopora gemmacea and Oxypora lacera) in cryopreservation conditions. Wild and cultured coral cells were extracted and subjected to freezing experiments involving multiple types and concentrations of cryoprotectant, and the oocytes from the cultured and wild corals were subjected to chilling experiments. Cultured and wild coral cells exhibited no significant differences in viability or cell density after cryopreservation, whereas the oocytes from the cultured corals E. gemmacea and O. lacera exhibited lower chilling tolerance compared with their wild counterparts. Significant differences were observed between the oocytes from the cultured and wild corals after low-temperature preservation, particularly in their metabolic activity and vital status, which could be possibly attributed to food consumption and environmental factors. The study provides a foundation for research promoting the technological development of artificial coral propagation and cryopreservation.

Long-term use of valproic acid reduced mortality in bipolar disorder patients in a Taiwanese population: An association analysis using the national health insurance research database (NHIRD).

OBJECTIVE: Valproic acid (VPA) is used for the treatment of epilepsy and bipolar disorder (BD). The aims of this study was to examine that long-term VPA use affects mortality in BD patients. METHODS: Association analysis was conducted using the National Health Insurance Research Database (NHIRD) of Taiwan. The long-term VPA use group was selected as patients treated with VPA for BD who used VPA only. The control group consisted of BD patients who were not treated with VPA or lithium. The lithium use group consisted by BD patients used lithium only was also joined the analysis. The cofactors included age (>65 years), sex and the Charlson Comorbidity Index. RESULTS: The hazard ratio (HR) of mortality for the VPA group was 0.83 (95% confidence interval (CI), (0.70-0.99); P = 0.04) and the result of lithium group did not reach statistical significance. Furthermore only the duration> 3 years subgroup had a significantly lower incidence of mortality than the control group, with an HR of 0.54 (95% CI, (0.42-0.70); P < 0.001) and 0.58 (95% CI, (0.38, 0.89); P = 0.013 in VPA and lithium groups, respectively. The effect of VPA treatment in terms of reducing the risk of mortality was evidenced only in the male population and the <65 years subgroup (HR: 0.75; 95% CI, (0.59-0.95), and 0.78; 95% CI, (0.64-0.96), respectively). The major limitation of this study was that the causes of death of the expired subjects were not available. CONCLUSION: Long-term VPA use decreases the risk of mortality in BD patients, especially in the male population and those aged <65 years.

Expression and function role of DNA methyltransferase 1 in human bladder cancer.

BACKGROUND: The identification of potential tumor markers will help improve therapeutic planning and patient management. Therefore, the aim of this study was to highlight the role of DNA methyltransferase 1 (DNMT1) in bladder cancer. METHODS: A total of 50 samples of nonmalignant urothelium, 65 of muscle-invasive bladder cancers, 15 of distant metastasis, and 50 of nonmuscle-invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments investigating changes in tumor behavior, treatment response, and related signaling in bladder cancer. RESULTS: The incidence of nuclear DNMT1 immunoreactivity in the bladder cancer specimens (45%) was significantly higher than in nonmalignant urothelium (15%, P = .0005), and the incidence in cancer was positively linked to clinical stage (24% in ≤T1 vs 55% in T2-T4, P = .0007). The staining of DNMT1 was also significantly linked to lower complete response rates (P = .0014) and reduced survival rates (P = .000). By in vitro and in vivo experiments, DNMT1 silencing vector reduced tumor growth and attenuated treatment resistance in bladder cancer cells. Less epithelial-mesenchymal transition, less invasion, and slower tumor growth were noted in cancer cells with inhibited DNMT1. Furthermore, the epidermal growth factor receptor-mediated phosphatidylinositol 3'-kinase-protein kinase B pathway might be the mechanism underlying the effects of DNMT1 on bladder cancer. CONCLUSIONS: DNMT1 could be a significant clinical predictor for stage and treatment response of bladder cancer. Moreover, targeting this enzyme could be a promising strategy for treating bladder cancer, as evidenced by inhibited tumor growth and enhanced radiosensitivity.

Ultralow-Threshold Continuous-Wave Room-Temperature Crystal-Fiber/Nanoperovskite Hybrid Lasers for All-Optical Photonic Integration.

Continuous-wave (CW) room-temperature (RT) laser operation with low energy consumption is an ultimate goal for electrically driven lasers. A monolithically integrated perovskite laser in a chip-level fiber scheme is ideal. However, because of the well-recognized air and thermal instabilities of perovskites, laser action in a perovskite has mostly been limited to either pulsed or cryogenic-temperature operations. Most CW laser operations at RT have had poor durability. Here, crystal fibers that have robust and high-heat-load nature are shown to be the key to enabling the first demonstration of ultralow-threshold CW RT laser action in a compact, monolithic, and inexpensive crystal fiber/nanoperovskite hybrid architecture that is directly pumped with a 405 nm diode laser. Purcell-enhanced light-matter coupling between the atomically smooth fiber microcavity and the perovskite nanocrystallites gain medium enables a high Q (≈1500) and a high ß (0.31). This 762 nm laser outperforms previously reported structures with a record-low threshold of 132 nW and an optical-to-optical slope conversion efficiency of 2.93%, and it delivers a stable output for CW and RT operation. These results represent a significant advancement toward monolithic all-optical integration.

Second-line Hormonal Therapy for the Management of Metastatic Castration-resistant Prostate Cancer: a Real-World Data Study Using a Claims Database.

We evaluated the efficacy of second-line hormonal therapy for treatment of metastatic castration-resistant prostate cancer (mCRPC) in a real-world retrospective study. We conducted a population-based real-world cohort study of 258 mCRPC patients between 2014 and 2018 using the Chang Gung Research Database (CGRD) of Taiwan. The second-line hormonal therapy included abiraterone acetate and enzalutamide. The clinical efficacy outcomes were overall survival (OS) and prostate-specific antigen (PSA) doubling time. The median PSA level was also assessed. In total, 223 mCRPC patients who underwent second-line hormonal therapy met all of the inclusion and exclusion criteria for this study. Among them, 65 (29.1%) patients were in the PSA response group and 158 (70.9%) were in the non-response group. The median age was 72.9 years. The median OS was 12.3 months (range: 9.9-19.9 months) and 9.6 months (range: 5.3-15.9 months) in the response and non-response groups, respectively, and the respective PSA doubling times were 9.0 months (range: 4.4-11.6 months) and 3.9 months (range: 2.2-9.1 months), with a median follow-up period of 10.5 months. A significantly longer median OS was seen in the PSA response group. This real-world database study demonstrated that clinical outcomes of second-line hormonal therapy were better in patients with a PSA response. Further studies are warranted to achieve a better understanding of second-line hormonal therapy for mCRPC in Asian populations.

The Potential Effect of Different Doses of Ionizing Radiation on Genes and Disease.

AIM: The chromosomal aberrations induced by radiation appear about nonrandomly distributed across the whole genome. Previous studies have shown that chromosomes with high DNA content are less frequently involved in the formation of symmetrical translocations and dicentric chromosomes than expected, whereas smaller chromosomes are more frequently involved. We hypothesized that these translocation regions are linked to radiation sensitivity. MATERIALS AND METHODS: We investigated the frequencies of chromosome translocations induced by radiation exposure and adjusted the results according to chromosome length. We specifically analyzed whole blood samples from 3 participants. The samples were irradiated using 60Co at doses of 0.5, 1, 2.5, and 5 Gy. Traditional Giemsa-trypsin-Wright band staining was performed to identify the translocations in the chromosomes, and results were compared with microarray data generated in our previous study. RESULTS: Our analysis indicated that chromosomes 9q were the most sensitive to translocations after various doses of radiation, and such translocations occurred in the euchromatin region. Chromosomes 1, 9, 15, and 17 were more sensitive to radiation doses of 0.5 Gy. This observation could be useful when selecting sensitive reference chromosomes in the low-dose region. The results of expression profiling analysis for radiation-sensitive regions were similar to those of chromosome translocation analysis. CONCLUSION: This study shows that some chromosomes or genomic regions are more sensitive to alteration by radiation exposure.

Long-term use of valproic acid and the prevalence of cancers in bipolar disorder patients in a Taiwanese population: An association analysis using the National Health Insurance Research Database (NHIRD).

BACKGROUND: Epigenetic events play a major role in the carcinogenesis of many cancers. A retrospective cohort study had been performed to evaluate the effects of exposure to the anticonvulsant agent valproic acid (VPA), a histone deacetylase inhibitor, on the risk of developing cancers. METHODS: The study was based on the 1998 through 2009 National Health Insurance Research Database (NHIRD), provided by the Taiwan National Health Research Institute. Patients with a diagnosis of bipolar disorder (ICD-9-CM codes 296.0, 296.1, 296.4-8) from 1998 to 2009 were identified. VPA and lithium were the primary index drugs. Patients treated with anticonvulsants who did not use VPA or lithium were selected as the control group. Competing risk regression analysis were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) reflecting the association between use of VPA and cancer incidence. RESULTS: The cancer incidence of bipolar disorder patients treated with VPA was no significant difference than treated with lithium and other anticonvulsants. In subgroup analysis, VPA associated to higher risk of genitourinary cancer in the duration < 1 year group (HR: 3.49; 95%CI: 1.04, 11.67). No significant differences in other cancers incidence in any duration of VPA treatment. LIMITATIONS: The cancer prevalence in selected bipolar disorder patients was still low. The sample size was not enough for some types of cancer. CONCLUSIONS: A role of VPA in cancer prevention was not found in this study. An increased subgroup risk of genitourinary cancer was observed.

Surgical technique to achieve high durability of flexible ureteroscopes: A single hospital experience.

BACKGROUND: To describe a novel operative technique resulting in extended durability and improved ease of use of current flexible ureteroscopes (FURS). A surgical method employing a modified technique of using an Olympus digital flexible URF-V ureteroscope was developed. METHODS: We retrospectively studied 546 patients who underwent retrograde intrarenal surgery (RIRS) using this modified approach performed by a single surgeon at our hospital, and investigated the outcome and durability of the ureteroscope. RESULTS: Through the study period, the URF-V ureteroscope required repair five times in total. During factory maintenance, distal working channel damage was noted twice, and outer bending rubber damage was noted once. The most recent two repairs were required due to laser penetration. Despite the damage and repairs, the deflection system was almost entirely intact after high-frequency use. The durability of FURS determines the efficacy of RIRS for renal stones. CONCLUSION: In this report, we described our modified upside-down technique for manipulation of FURS under unequal dual deflection in order to preserve the deflection apparatus, which yielded a greatly prolonged durability. Additionally, the use of mimic drive turning decreased the time needed to train urologists.

Significance of IL-6 in the transition of hormone-resistant prostate cancer and the induction of myeloid-derived suppressor cells.

Hormone-resistant (HR) prostate cancers are highly aggressive and respond poorly to treatment. A better understanding of the molecular mechanisms involved in HR should lead to more rational approaches to therapy. The role of IL-6/STAT3 signaling in the transition of HR with aggressive tumor behavior and its possible link with myeloid-derived suppressor cells (MDSCs) were identified. In the present study, murine prostate cancer cell line (TRAMP-C1) and a hormone-resistant cell sub-line (TRAMP-HR) were used. Changes in tumor growth, invasion ability, and the responsible pathway were investigated in vitro and in vivo. We also examined the role of IL-6 in HR tumor progression and the recruitment of MDSCs. As seen in both in vitro and in vivo experiments, HR had aggressive tumor growth compared to TRAMP-C1. From mRNA and protein analysis, a higher expression of IL-6 associated with a more activated STAT3 was noted in HR tumor. When IL-6 signaling in prostate cancer was blocked, aggressive tumor behavior could be overcome. The underlying changes included decreased cell proliferation, less epithelial-mesenchymal transition, and decreased STAT3 activation. In addition to tumor progression, circulating IL-6 levels were significantly correlated with MDSC recruitment in vivo. Inhibition of IL-6 abrogated the recruitment of MDSCs in tumor- bearing mice, associated with slower tumor growth and attenuated angiogenesis. In conclusion, altered IL-6/STAT3 signaling is crucial in HR transition, aggressive behavior, and MDSC recruitment. These findings provide evidence for therapeutically targeting IL-6 signaling in prostate cancer.

Ectonucleotide pyrophosphatase/phosphodiesterase 1 K173Q polymorphism is associated with diabetic nephropathy in the Taiwanese population.

Diabetic nephropathy is the leading cause of end-stage renal disease in the world. The cause of diabetic nephropathy seems to be multifactorial, and about one-third of patients with diabetes eventually develop this complication. The gene encoding ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is a candidate susceptibility gene for obesity and type 2 diabetes. We assessed rs1044498 (K173Q) located in the ENPP1 gene for association with diabetes nephropathy among 201 diabetic subjects without nephropathy and 215 diabetic subjects with nephropathy in the Taiwanese population. The single-nucleotide polymorphism (SNP) rs1044S498 in ENPP1 was associated with diabetes nephropathy in our study subjects. The AC+CC genotype of the rs1044498 SNP was a risk factor for the development of nephropathy in diabetic patients. Further, the AC+CC genotype of rs1044498 was a genetic risk factor in obese (defined by waist circumference) diabetic patients, but not in nonobese diabetic patients. We confirmed the association between the rs1044498 SNP in ENPP1 and diabetic nephropathy, especially among obese diabetic patients, in the Taiwanese population.

Primary testicular actinomycosis mimicking metastatic tumor.

We report a rare case of right primary testicular actinomycosis presenting as multiple testicular lesions mimicking a metastatic tumor in a 71-year-old patient with gastric adenocarcinoma. Preoperative diagnosis is difficult. The enlarged and inflamed testis was removed by orchiectomy and testicular actinomycosis was diagnosed after pathological examination. The patient had not received any further antibiotic prescription and there was no recurrent or other site involvement after orchiectomy. We illustrate this case, though it is rare, to alert pathologists and clinicians to the possible occurrence of primary testicular actinomycosis mimicking metastatic lesions in a cancer patient. To diagnose, extensive sampling of the tissue specimens may be needed. We also reviewed the published literature and found that the treatment of choice for testicular actinomycosis was orchiectomy. The usage of penicillin after orchiectomy does not seem to affect the outcomes of the disease.

A randomized trial comparing intravesical instillations of mitoxantrone and doxorubicin in patients with superficial bladder cancer.

BACKGROUND: This randomized trial was conducted to compare the efficacy and side effects of intravesical mitoxantrone instillation with those of doxorubicin in superficial bladder cancer following transurethral resection. METHODS: Sixty-three patients were randomized into mitoxantrone and doxorubicin groups. Most of the patients enrolled were elderly people (mean age, 71 years). The instilled doses of doxorubicin and mitoxantrone were 30 and 14 mg, respectively. Disease recurrence and side effects were compared using Fisher's exact test. The interval to recurrence was shown by Kaplan-Meier survivorship curves, and the log-rank test was used to compare the time to recurrence. RESULTS: The median follow-up period was 36 months. Thirty-three patients received mitoxantrone, whereas 30 patients used doxorubicin. The recurrence rate in the doxorubicin group was 30% (95% CI: 19.8%-38.8%), while it was 27.3% (95% CI: 17.5%-36.8%) in the mitoxantrone group. The median recurrence-free survival in the mitoxantrone group and in the doxorubicin group was 22 and 20 months, respectively (p=0.580). Higher recurrence rates were found for Grade III and multiple primary tumors. There was no significant difference in response rates (p=0.784). The incidence of side effects was 20% in the doxorubicin group and 21.2% in the mitoxantrone group. However, the difference was not significant (p>0.99). CONCLUSIONS: The results revealed that the efficacy and side effects of mitoxantrone were similar to those of doxorubicin. Especially for patients with pulmonary tuberculosis or aged patients with primary bladder tumors, mitoxantrone and doxorubicin may be the tolerable and effective intravesical agents.