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Abstract The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/β-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/β-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.

PurposeTo evaluate the prognostic impact of the lowest level of tumor location for upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).Materials and methodsData were collected from patients with UTUC treated with RNU (01/2005- 06/2020) at a single center in Taiwan. Patients were stratified by the lowest level of tumor location into three groups: renal pelvis only (RPO), above upper ureter (AUU), and below upper ureter (BUU). We compared characteristics between groups and examined the association of the lowest level of tumor involvement with intravesical recurrence (IVR), systemic metastasis (SM), and cancer-specific mortality (CSM).ResultsOverall, 1239 patients (542 RPO, 260 AUU, 437 BUU) were enrolled. Concurrent bladder cancer, multifocality, tumor architecture, lymphovascular invasion, carcinoma in situ, and variant histology were significantly different across different tumor locations. BUU had worse five-year intravesical recurrence (IVR), systemic metastasis (SM) and cancer-specific mortality (CSM) (p < 0.001, p = 0.056 and p = 0.13, respectively). In multivariable models, the lowest level of tumor involvement was an independent predictor of IVR (AUU hazard ratio (HR) = 1.52, p = 0.007; BUU HR = 1.75, p < 0.001), but only BUU was an independent predictor of SM (HR = 1.61, p = < 0.001) and CSM (HR = 1.51, p = 0.008).ConclusionThe lowest level of tumor involvement in UTUC, especially BUU, was associated with a higher risk of IVR, SM and CSM. Assessment of the lowest level of tumor involvement after RNU may help identify patients who require more intensive follow-up.

Abstract Background Prostate biopsy remains the gold standard approach to verify prostate cancer diagnosis. Transrectal (TR) biopsy is a regular modality, while transperineal (TP) biopsy is an alternative for the patients who display persistently high levels of prostate-specific antigen (PSA) and thus have to undergo repeat biopsy. This study aimed to compare the cancer detection rates between TR and TP approaches and assess the post-bioptic complications of the two procedures. Besides, the feasibility of performing TP biopsies under local anesthesia was also evaluated. Methods A total of 238 outpatient visits meeting the criteria for prostate cancer biopsy were enrolled for this study. They were divided into two groups: the TP group (n = 130) consists of patients destined to undergo local anesthetic TP biopsy; and the TR group (n = 108) contained those who received TR biopsy as comparison. Age, PSA level, digital rectal exam (DRE) finding, prostate volume, and biopsy core number were used as the parameters of the multivariable analyses. The comparable items included cancer detection rate, complication rate, admission rate and visual analog scale (VAS) score. Results The cancer detection rates between TP and TR groups were quite comparable (45% v.s. 49%) (p = 0.492). However, the TP group, as compared to the TR group, had significantly lower incidence of infection-related complications (except epididymitis and prostatitis) that commonly occur after biopsies. None of the patients in the TP group were hospitalized due to the post-bioptic complications, whereas there was still a minor portion of those in the TR group (7.4%) requiring hospitalization after biopsy. Medians (25–75% quartiles) of visual analog scale (VAS) were 3 [3, 4] and 4 [3–5] respectively for the TP and TR procedures under local anesthesia, but no statistical significance existed between them (p = 0.085). Conclusions Patients receiving TP biopsy are less likely to manifest infection-related complications. Therefore, TP biopsy is a more feasible local anesthetic approach for prostate cancer detection if there are concerns for infectious complications and/or the risk of general anesthesia.

Abstract Background Physicians doubt percutaneous nephrostomy (PCN) insertion on cancer related hydronephrosis patients causes tumor seeding and worse cancer control. In this article, we attempted to determine if preoperative PCN alters cancer control in upper tract urothelial cancer (UTUC) patients. Methods Retrospective analysis of UTUC patients in a single center from 2005 to 2015. Exclusion criteria included lymph node metastasis, and patients underwent perioperative adjuvant chemotherapy or radiotherapy. There were 664 patients in this analysis, with clinico-pathological data being collected retrospectively for Cox-regression statistical analysis. Outcomes were measured by local recurrence, distant metastasis and cancer-specific death with Kaplan-Meier curves. Results There were respectively 25 and 639 UTUC cancers in the preoperative PCN and non-PCN insertion groups with mean follow-up duration of 37.9 and 48.6 months, respectively. The preoperative PCN group consisted of 17 patients (68%) with tumor located in the ureter, while the PCN-negative group included 236 patients (36%) with tumor located in the ureter being statistically significant. These two groups were comparable in gender, age, follow-up duration, tumor stage, and pathological features of the UTUC. As for the cancer control in the PCN group, 4(16%), 1(4%) and 1(4%) had local recurrence, distant metastasis and cancer-specific death respectively; in the non-PCN group, 101(15.8%), 96(15%) and 72(11.2%) exhibited local recurrence, distant metastasis and cancer-specific death respectively. Statistical analysis showed no difference in oncologic outcomes between these two groups.(p = 0.804, 0.201 and 0.254). Conclusions Preoperative percutaneous nephrostomy on upper-tract urothelial cancer poses little risk on tumor seeding and could be considered as part of treatment strategy if renal function preservation is needed.

Abstract The impact of tumor infiltrating lymphocytes (TILs) on survival was confirmed in various cancer types. Our study aims to investigate the prognostic role of TILs on survival in patients with metastatic urothelial carcinoma (mUC) receiving platinum based chemotherapy. Patients who were diagnosed to have pathologically proved mUC between 1997 and 2016 and received palliative chemotherapy with platinum based regimen were recruited into our study. Kaplan-Meier curves and Cox regression analysis were constructed for overall survival (OS). A total of 259 mUC patients were enrolled into our study with median age 63 years and median follow-up visit 13.5 months. Of these patients, 179 (69%) had intense TILs and 80 (31%) had non-intense TILs. The median OS were 15.7 vs. 6.7 months (P =

Objective: This study aims to evaluate the operative efficacy and safety of the GreenLight 180-W XPS laser system in comparison to the GreenLight 120-W HPS system used by a single experienced surgeon for the treatment of bladder outlet obstruction caused by an enlarged prostate. Materials and methods: We retrospectively compared the patients undergoing GreenLight 180-W XPS (September 2014–September 2015) and GreenLight 120-W HPS (August 2008–September 2009) for lower urinary tract symptoms secondary to benign prostatic hyperplasia by a single experienced surgeon. The patient baseline characteristics, perioperative parameters, and complications were recorded. Prostate size and prostate-specific antigen were also assessed. Functional parameters, including International Prostate Symptom Score, maximum uroflow rate, postvoid residual, and quality of life score, were analyzed in different follow-up periods. Results: A total of 130 patients (65 in the HPS and 65 in the XPS group) were included in this study. Intraoperative lasing time was significantly shorter in the XPS group, but the postoperative length of catheterization and hospital stay were comparable in both groups. The number of fibers used during vaporization was significantly less, and only one case required two fibers for prostate vaporization in the XPS group (p=0.03). During the follow-up period, there was statistically significant improvement compared with baseline in all functional parameters in each group. However, no significant difference was observed in these parameters between the two groups. The mean percentages of prostate volume reduction were 57% and 41% and those of prostate-specific antigen reduction were 60% and 49%, respectively, in the XPS and HPS groups. Complications were comparable between the two groups. Conclusion: The 180-W XPS system displays a shorter lasing time, less laser fiber use, more volume reduction, and a comparable safety profile in comparison with the 120-W HPS system for the treatment of bladder outlet obstruction caused by an enlarged prostate.

Preserving renal function and controlling oncological outcomes are pertinent when managing renal neoplasms. Cryoablation is the recommended treatment only for clinical T1a stage renal tumour. Here, we compared the outcomes of robot-assisted laparoscopic partial nephrectomy (RaPN) and laparoscopic cryoablation (LCA) in the treatment of patients with localised T1-T2 renal tumours. Overall, 86 patients who received RaPN and 78 patients underwent LCA were included in this study. The intraoperative, postoperative, and oncological outcomes in the LCA group were non-inferior to the RaPN group. Moreover, LCA demonstrated shorter operative time (267.45 ± 104.53 min vs. 138.56 ± 45.28 min, p < 0.001), lower blood loss (300.56 ± 360.73 mL vs. 30.73 ± 50.31 mL, p < 0.001), and slight renal function deterioration because of the reduced invasiveness, without compromising on the oncological outcomes.

This study was conducted to determine the efficacy of switching therapy with a second-line luteinizing hormone–releasing hormone (LHRH) analogue after prostate-specific antigen (PSA) progression for advanced prostate cancer. We enrolled 200 patients, from December 2005 to September 2013, with nodal positive, metastatic prostate cancer or disease progression after definite treatment receiving continuous LHRH analogue therapy with monthly depot leuprorelin(sc) acetate 3.75 mg/vial (LA) or goserelin acetate(sc) 3.6 mg/vial (GA). If the patients had castration-resistant prostate cancer, the treatment choice of switching therapy (from LA to GA or from GA to LA) prior to starting chemotherapy was given. The LH, testosterone level, and PSA change were recorded. The records showed that there were 127 patients receiving LA as initial ADT therapy, whereas the other 73 patients were in GA therapy. A total of 92 patients received LHRH analogue switching therapy (54 patients switched from LA to GA and 38 switched from GA to LA). The effect of LH and testosterone reduction prior to and after switching therapy was comparable between the two groups, and increased PSA level after 3 months of treatment was seen in both groups (median PSA: 15.7–67.7 ng/mL in the LA to GA group; 15.2–71.4 ng/mL in the GA to LA group). This study concluded that switching therapy for patients with PSA progression after ADT has no efficacy of further PSA response.

To determine the optimal number of cycles of docetaxel for metastatic castration-resistant prostate cancer, we retrospectively collected 73 patients receiving varying numbers of docetaxel plus prednisolone and analyzed the clinical outcomes including overall survival, prostate-specific antigen (PSA) response, and adverse events. The study included 33 patients receiving ≤ 10 cycles of docetaxel and 40 patients receiving > 10 cycles. Patients receiving > 10 cycles were younger than those who received ≤ 10 cycles. There was no statistical significant difference in overall survival between the two groups (log-rank test, p = 0.75). Adverse effects were more common among patients receiving ≥ 10 cycles of treatment. A PSA flare-up was observed among six patients (8.2%); the median duration of the PSA surge was 3 weeks (range, 3–12 weeks). The overall survival rates in patients with PSA flare-up were comparable with the patients having PSA response. We concluded that at least four cycles of docetaxel should be administered in metastatic castration-resistant prostate cancer patients in order not to cease treatment prematurely from potentially beneficial chemotherapy. However, administering > 10 cycles does not result in any further improvement in survival and is associated with more adverse effects.

Galectin-1 (GAL1) is a β-galactoside-binding protein involved in multiple aspects of tumorigenesis. However, the biological role of GAL1 in upper tract urothelial carcinoma (UTUC) has not been entirely understood. Herein, we investigated the oncological effects of GAL1 expression in tumor specimens and identified related gene alterations through molecular analysis of GAL1. Clinical parameter data and tumor specimens were collected from 86 patients with pT3N0M0 UTUC who had undergone radical nephroureterectomy. We analyzed the difference in survival by using Kaplan−Meier analyses and Cox proportional regression models and in GAL1 expression by using immunohistochemical (IHC) methods. Public genomic data from the Cancer Genome Atlas (TCGA) and GSE32894 data sets were analyzed for comparison. Using four urothelial carcinoma (UC) cell lines (BFTC-909, T24, RT4, and J82) as in vitro models, we evaluated the functions of GAL1 in UC cell growth, invasiveness, and migration and its role in downstream signaling pathways. The study population was classified into two groups, GAL1-high (n = 35) and GAL1-low (GAL1 n = 51), according to IHC interpretation. Univariate analysis revealed that high GAL1 expression was significantly associated with poor recurrence-free survival (RFS; p = 0.028) and low cancer-specific survival (CSS; p = 0.025). Multivariate analysis revealed that GAL1-high was an independent predictive factor for RFS (hazard ratio (HR) 2.43; 95% confidence interval (CI) 1.17−5.05, p = 0.018) and CSS (HR 4.04; 95% CI 1.25−13.03, p = 0.019). In vitro studies revealed that GAL1 knockdown significantly reduced migration and invasiveness in UTUC (BFTC-909) and bladder cancer cells (T24). GAL1 knockdown significantly reduced protein levels of matrix metalloproteinase-2 (MMP-2) and MMP-9, which increased tissue inhibitor of metalloproteinase-1 (TIMP-1) and promoted epithelial−mesenchymal transition (EMT). Through gene expression microarray analysis of GAL1 vector and GAL1-KD cells, we identified multiple significant signaling pathways including p53, Forkhead box O (FOXO), and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT). We validated microarray results through immunoblotting, thus proving that downregulation of GAL1 reduced focal adhesion kinase (FAK), p-PI3K, p-AKT, and p-mTOR expression. We concluded that GAL1 expression was highly related to oncological survival in patients with locally advanced UTUC. GAL1 promoted UC invasion and metastasis by activating the FAK/PI3K/AKT/mTOR pathway.

Background: Previous studies demonstrated that GC (gemcitabine and cisplatin) provided a similar survival advantage as M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for urothelial carcinoma of the bladder (UCB), and had a better safety profile and improved tolerability. However, no clinical clues in selection of first-line chemotherapy regimen were suggested. This study aims to determine whether different sites of metastasis and chemotherapy regimens affected the prognosis of patients with metastatic UCB. Methods: Patients with metastatic UCB were retrospectively reviewed. Data on clinical characteristics, progression free survival (PFS), overall survival (OS), overall response rate (ORR) and complete response (CR) rate were analyzed. Results: Between 2000 and 2012, a total of 76 patients with metastatic UCB were enrolled. The median age was 64.5 years and the median follow-up period was 13.6 months. Of these patients, 37 had lymph node-only metastasis (LOM) and 39 had non-LOM. The median survival was significantly longer for UCB patients with LOM. The median PFS was 10.0 months for LOM and 4.3 months for non-LOM (P = < 0.01), while the median OS was 16.9 months for LOM and 10.5 months for non-LOM (P = < 0.01). The ORR and CR rate were both significantly higher in patients with LOM than in those with non-LOM. Subgroup analysis suggested that UCB patients with LOM treated with M-VAC had a better survival. The median PFS was 16.4 months in the M-VAC group and 8.7 months in the GC group (P = 0.08), while the median OS was 23.1 months in the M-VAC group and 16.0 months in the GC group (P = 0.03). The CR rate remained significant. Conclusions: UCB patients with LOM, especially those treated with M-VAC, had better survival outcomes and greater CR rate than those with non-LOM. However, the sample size of this study was quite small and analyzed on a retrospective basis. Further prospective randomized studies are warranted.

We developed a novel inflammation-based model (NPS), which consisted of a neutrophil to lymphocyte ratio (NLR) and platelet count (PC), for assessing the prognostic role in patients with metastatic urothelial carcinoma (UC).We performed a retrospective analysis of patients with metastatic UC who underwent systemic chemotherapy between January 1997 and December 2014 in Kaohsiung Chang Gung Memorial Hospital. The defined cutoff values for the NLR and PC were 3.0 and 400 × 103/μL, respectively. Patients were scored 1 for either an elevated NLR or PC, and 0 otherwise. The NPS was calculated by summing the scores, ranging from 0 to 2. The primary endpoint was overall survival (OS) by using Kaplan-Meier analysis. Multivariate Cox regression analysis was used to identify the independent prognostic factors for OS.In total, 256 metastatic UC patients were enrolled. Univariate analysis revealed that patients with either a high NLR or PC had a significantly shorter survival rate compared with those with a low NLR (P = .001) or PC (P < .0001). The median OS in patients with NPS 0, 1, and 2 was 19.0, 12.8, and 9.3 months, respectively (P < .0001). Multivariate analysis revealed that NPS, along with the histologic variant, liver metastasis, age, and white cell count, was an independent factor facilitating OS prediction (hazard ratio 1.64, 95% confidence interval 1.20-2.24, P = .002).The NLR and PC are independent prognostic factors for OS in patients with metastatic UC. The NPS model has excellent discriminant ability for OS.

Xp11.2 translocation renal cell carcinoma (RCC) is rare and predominantly found in children and young adults. Because of the property of overexpressed transcription factor E3 (TFE3) fusion protein, immunohistochemical (IHC) staining with TFE3 antibody makes an excellent diagnostic tool. This study analyzed preliminary experiences of eight Xp11.2 translocation RCCs in our institution between 2007 and 2012. In four males and four females with a mean age of 28.4 years. Xp11.2 translocation RCCs were diagnosed. TFE3 IHC stain was positive in all tumor specimens. As the initial presentation, four patients suffered from abdominal pain, three cases had gross hematuria, and one case had hemoptysis caused by existing lung metastasis. The tumor was located in the right kidney (75%) with mean diameter of 5.85 ± 2.64 cm. Three cases (38%, 3/8) presented with lymph node metastasis at the time of diagnosis. In five cases (63%, 5/8), the initial diagnosis was Stage III and IV. Treatment included open surgery (one partial nephrectomy and five radical nephrectomies), cryoablation, immunotherapy, and target therapy. The mean follow-up time was 32 months. One patient died after 23.4 months of follow-up. The application of TFE3 IHC stain will improve the diagnostic accuracy for detecting XP11.2 translocation renal cell carcinoma. Surgery or cryoablation both had excellent prognosis in early stages. Although the disease is believed to be indolent, an increasingly aggressive clinical course should be kept in mind, especially for children and young adults.

The prevalence of upper tract urothelial carcinoma (UTUC) in Taiwan is relatively higher than thatin Western countries. Aristolochic acid (AA), which is widely used in traditional Chinese herbology, is now recognized to be one of the carcinogens for UTUC. Numerous UTUC patients have chronic kidney diseases or end-stage renal diseases; however, little literature hasreported on theoncogenic pathway of AA-related UTUC. The aim of our study was to identify the potential target treatment for AA-related UTUC. Here, we established an AA pre-exposure followed bya 3-methylcholanthrene (MCA) stimulus tumorigenic cell model. We not only demonstrated that AA pre-exposure MCA stimulus tumorigenic cells have more behaviors of cell migration and invasion by enhancing the metalloproteinases (MMP) activity, which is compatible with clinical findings of AA-related UTUC, but we also validated that AA pre-exposure MCA stimulus tumorigeniccells could be activated through the mitogen-activated protein kinases (MAPK) pathway. We further dissected the route of the MAPK pathway and found that the p38 and extracellular signal regulated kinases (ERK) sub-pathways might play essential roles in AA pre-exposure urothelial cancer cell lines. This consequence was also corroborated with a tissue study in AA-exposed patients.

Advanced upper urinary tract urothelial carcinoma (UTUC) is often associated with poor oncologic outcomes. The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) protein, belongs to the SPARC-related family of matricellular proteins. Much literature has been published describing the role of SPARCL1 in the prognosis many cancers. In this study, methylated promoter regions in high-grade and high-stage upper urinary urothelial tumours compared with normal urothelium were analyzed and revealed that SPARCL1 was the most significantly hypermethylated gene in UTUC tissues. Then we prospectively collected UTUC samples and adjacent normal urothelium for pyrosequencing validation, identifying significant CpG site methylation in UTUC tissues. In addition, SPARCL1 RNA levels were significantly lower in UTUC samples. Multivariate Cox regression analysis from 78 patients with solitary renal pelvic or ureteral pT3N0M0 urothelial carcinomas revealed that only negative SPARCL1 expression and nonpapillary tumour architecture were independently associated with systemic recurrence (p = 0.011 and 0.008, respectively). In vitro studies revealed that the behaviour of BFTC-909 cells was less aggressive and more sensitive to radiation or chemotherapy after SPARCL1 overexpression. Thus, SPARCL1 could be considered as a prognostic marker and help decision-making in clinical practice.

Artificial urinary sphincter (AUS) is the gold standard treatment for urinary incontinence owing to sphincter incompetence. We reviewed our experience in AUS implantation. From 1995 to 2009, 19 patients underwent 25 AUS implantations performed by a single surgeon. The cause of incontinence was sphincter incompetence, which was secondary to prostate surgery, neurogenic bladder, radiation, and post-traumatic urethral lesion. Twenty-three prostheses were placed in the bulbar urethra for male patients: 11 AUS cuffs were placed through the perineal approach and 12 through the penoscrotal approach. Two procedures were applied over the bladder neck for the female patients. Through a retrospective review of charts, continence and complications were analyzed. The mean follow-up time was 50.0 ± 42.9 months (range: 2–146 months). There were 16 successful surgeries (64%), and these patients were free from the need for a pad. In eight surgeries (32%), the devices were removed due to infection, while one implantation (4%) was unsuccessful due to perforation into the bulbar urethra. There was a statistically significant difference (p = 0.024) in failure rates between patients who received radiotherapy (100%) and other patients (22.7%). There was no statistically significant difference in dry and revision rates (p > 0.05) between the perineal and penoscrotal approach. Accordingly, over half of the patients with total incontinence benefitted from AUS implantation. In consideration of the high failure rate for patients receiving radiotherapy, caution should be exercised in the use of implantation. Secondary implantation has a satisfactory success rate in selected patients. The same success rate was noted for both perineal and penoscrotal approaches.

To assess the effect of alfuzosin (XATRAL) 10 mg once daily on sexual function in men with moderate to severe lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), patients with suggestive symptomatic BPH, an International Prostate Symptom Score (IPSS) >8 (range of scores, 0–35), and sexual attempts at least once per month were enrolled. All patients received alfuzosin 10 mg once daily for 24 weeks and were asked to complete the IPSS test and Male Sexual Health Questionnaire at weeks 0 (baseline), 1, 4, 12, and 24. Other assessments included the International Index of Erectile Function—five-item version (range of scores: 5–25), as well as onset of action and peak urinary flow rate (Qmax). From September 2006 to May 2008, 279 patients were enrolled from nine centers in Taiwan. At 24 weeks, alfuzosin effectively improved LUTS and quality of life, as demonstrated by a reduction in the IPSS total score (17.3 vs. 9.9, p

Adrenal myelolipoma is a rare, nonfunctioning, and benign tumor. We report our experience of surgically treated patients from a single institute and review the literature. Six patients (three men and three women) were diagnosed and received surgical intervention. A retrospective analysis was done by reviewing medical records. In our series, three patients were diagnosed incidentally and the others were discovered due to symptoms. All received surgery, including laparoscopic adrenalectomy. There was no recurrence. In the literature review, right adrenal gland was dominant and the prevalent age was from the fourth to sixth decades. The most common symptoms were abdominal and flank pain. Adrenal myelolipoma is uncommon and easily confused with malignancy when of large size (≥6 cm). Surgery may be reserved for symptomatic cases and those lesions that cannot reliably be diagnosed. Large tumors (≥6 cm) can be excised surgically or laparoscopically.

To present single institution open-label experience with intravesical liposomes (LPs), a mucosal protective agent, in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) and to assess the safety and efficacy on IC/PBS symptoms. A total of 17 symptomatic IC/PBS patients were treated with intravesical LPs (80 mg/40 mL distilled water) once a week for 4 weeks (n=12) or twice a week treatment for 4 weeks (n=5). The primary outcome was the change in the O’Leary-Sant Symptom/Problem score and O’Leary-Sant total Score from baseline to Week 4 and Week 8. Other outcome measurements included the changes in pain scale, urgency scale, voiding log, and patient global assessment. Both weekly and biweekly LP instillation regiments were well tolerated. The incidence of urinary incontinence, retention, or unanticipated adverse changes was not noted at any dose either during the treatment or at the 4-week follow-up. The O’Leary-Sant Symptom/Problem score, O’Leary-Sant total Score, and pain score were significantly improved from baseline at both dose regimens with added benefit with the biweekly regimen. Intravesical LPs treatment is safe and its efficacy has sustained duration. Furthermore large-scale, placebo-controlled studies are warranted to assess the efficacy for this promising new treatment for IC/PBS.

Objective: We evaluated the efficacy and outcome of laser photoselective vaporization of prostate (PVP) in patients with voiding difficulty due to prostatic obstruction induced by advanced prostate cancer (PC). Methods: We retrospectively studied the records of 13 patients with advanced PC and prostatic obstruction with a mean prostate volume of 65.0 ml. All of the 13 patients received PVP between 2006 and 2010 due to the symptoms of voiding difficulty or acute urinary retention (AUR; N = 10) refractory to medical treatment. Perioperative safety and functional results were evaluated. Results: Lasering time ranged from 24 to 20 minutes (mean 67 ± 26), during which 66–423 KJ (mean 172 ± 95) of laser energy was delivered. All patients could resume voiding function with a mean catheterization time of 3.0 days. Conclusions: Our preliminary results suggest that PVP is a safe and effective procedure for relieving prostatic obstruction without intraoperative blood transfusion, water intoxication, or other complications in patients with advanced prostate cancer.

PurposeThis study investigated the prognostic role of histopathological variants in patients with advanced urothelial carcinoma (UC) who were treated with systemic chemotherapy.Materials and methodsWe conducted a retrospective analysis of patients with unresectable and/or metastatic UC who underwent systemic chemotherapy between January 1997 and December 2013 in Kaohsiung Chang Gung Memorial Hospital. Histopathological types were categorized as pure UC (PUC) and variants of UC (VUC). The overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier analyses and Cox proportional regression models.ResultsA total of 206 patients were enrolled; 53 of the patients (25.7%) had histopathological variants. The most common variant was squamous differentiation (68%). Compared with patients with PUC, patients with VUC significantly exhibited upper urinary tract origin (75% vs 52%, P = .008), chronic renal insufficiency (40% vs 23%, P = .03), and carboplatin-based chemotherapy (28% vs 10%, P = .003). According to univariate analysis, the median OS for PUC patients was significantly higher than that for VUC patients (15.9 vs 11.3 months, P = .007). The median PFS for patients who received first-line chemotherapy was 6.1 and 3.8 months for PUC patients and VUC patients, respectively (P = .004). Multivariate analysis revealed that VUC (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.16-2.40, P = .006), an age ≤ 60 years (HR 0.70, 95% CI 0.49-0.99, P = .045) and presence of visceral metastasis (HR 1.54, 95% CI 1.11-2.13, P = .009) were independent factors facilitating OS prediction.ConclusionsThe presence of histopathological variants indicates poor survival outcomes in patients with metastatic UC. Accordingly, VUC should be integrated into and considered an independent factor in a predictive model of survival.

The involvement of microRNAs (miRNAs) in cancer development and their potential as prognostic biomarkers are becoming increasingly known. However, the signature of miRNAs and their regulatory roles in tumorigenesis of upper tract urothelial carcinoma (UTUC) remain to be elucidated. This study aimed to profile the miRNA expression pattern in UTUC tumor tissues and identify candidate miRNAs with prognostic and/or therapeutic functions. Methods and Results: We collected 22 UTUC tissue and adjacent normal tissues samples from patients who underwent nephroureterectomy. The miRNAs signatures of three selected UTUC samples using next-generation sequencing showed that miR-30a-5p was significantly downregulated in UTUC tumors compared to adjacent normal tissues. The differentially-expressed miRNAs were specifically validated by quantitative real-time polymerase chain reaction. In addition, the miRNA expression signatures were analyzed with the transcriptome profile characterized by microarray. Further in vitro studies indicated that overexpression of miR-30a-5p significantly suppressed proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in cultured BFTC-909 UTUC cells. As a potential target gene of miR-30a-5p in the tight junction pathway suggested by the pathway enrichment analysis, the reduced expression of tight junction protein claudin-5 in UTUC cells was demonstrated to be upregulated by miR-30a-5p genetic delivery. Conclusions: Taken together, our findings demonstrated that miR-30a-5p inhibits proliferation, metastasis, and EMT, and upregulates the expression of tight junction claudin-5 in UTUC cells. Thus, miR-30a-5p may provide a promising therapeutic strategy for UTUC treatment.

PurposeTo study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome.Materials and methodsFemale Wistar rats were fed a fructose-rich diet (60%) or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs) were divided into a group with normal detrusor function or detrusor overactivity (DO). Acidic adenosine triphosphate (ATP) solution (5mM, pH 3.3) was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting.ResultsCompared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X(3), and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups.ConclusionsAlterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X(3), and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.

Purpose: Conventional transurethral resection of bladder tumors (cTURBT) has been the main technique for treating visible bladder tumor for decades. However, the reported rate of detrusor muscle presence in cTURBT specimen was lower than 80%, which is associated with imprecise staging and poor prognosis. Here, we present a retrospective analysis to compare the detrusor muscle detection rate and outcomes between en bloc resection of bladder tumor (ERBT) and cTURBT. Materials and Methods: Between January 2016 and December 2019, a total of 150 procedures performed by single surgeon in single institute were reviewed in this study. Of these procedures, 41 (27.3%) were ERBT and 109 (72.6%) were cTURBT. The two techniques were compared for pathological detrusor muscle detection, history of upper tract urothelial cancer, number of tumor lesions, histopathological grading and staging, time of operation, and time of catheterization and hospitalization. Results: The muscularis propria detection rate was statistically significantly higher in the ERBT group than in the cTURBT group (82.9% vs. 43.1%, P < 0.0001). The multivariate analysis showed resection method as an independent factor of detrusor muscle presentation (P < 0.0001). The mean Foley catheter indwelling and hospitalization days were longer in the ERBT group but were only 1 day longer than in the cTURBT group. Conclusions: ERBT significantly increases the muscularis propria detection rate than cTURBT. ERBT can provide more accurate cancer staging and contribute to proper decision-making. This study strengthens ERBT as a feasible and promising management of bladder cancer.