Yu-Hsiang Lin

Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells

Growth differentiation factor-15 (GDF15), a member of the TGF-β superfamily, affects tumor biology of certain cancers, but remains poorly understood in bladder cancer cells. This study determined the expression, regulation, function, and potential downstream target genes of GDF15 in bladder carcinoma cells. The transitional papilloma carcionoma cells (RT4) expressed higher levels of GDF15 as compared with the bladder carcinoma cells (HT1376 and T24). Treatments of recombinant human GDF15 (rhGDF15) reduced the proliferations of HT1376 and T24 cells. Expression of GDF15 was upregulated via DNA demethylation and p53. The cell proliferation, invasion, and tumorigenesis were reduced in ectopic overexpression of GDF15, while enhanced in GDF15 knockdown. The expressions of mammary serine protease inhibitor (MASPIN) and N-myc downstream-regulated family genes (NDRG1, NDRG2, and NDRG3) were upregulated by GDF15 overexpressions and rhGDF15 treatments in bladder carcinoma cells. GDF15 knockdown induced epithelial-mesenchymal transition (EMT) and F-actin polarization in HT1376 cells. Our results suggest that enhanced expressions of MASPIN and N-myc downstream-regulated family genes and the modulation of EMT may account for the inhibitory functions of GDF15 in the cell proliferation, invasion, and tumorigenesis of bladder carcinoma cells. The GDF15 should be considered as a tumor suppressor in human bladder carcinoma cells.

Prostate-derived ets factor represses tumorigenesis and modulates epithelial-to-mesenchymal transition in bladder carcinoma cells

Prostate-derived Ets (E-twenty six) factor (PDEF), an epithelium-specific member of the Ets family of transcription factors, has been shown to play a role in suppressing the development of many epithelium-derived cancers such as prostate and breast cancer. It is not clear, however, whether PDEF is involved in the development or progression of bladder cancer. In a comparison between normal urothelium and bladder tumor tissue, we identified significant decreases of PDEF in the tumor tissue. Further, the immunohistochemistry assays indicated a significantly higher immunostaining of PDEF in low-grade bladder tumors. Additionally, the highly differentiated transitional-cell bladder carcinoma RT-4 cells expressed significantly more PDEF levels than the bladder carcinoma HT1376 and the T24 cells. Ectopic overexpression of PDEF attenuated proliferation, invasion, and tumorigenesis of bladder carcinoma cells in vitro and in vivo. PDEF enhanced the expression levels of mammary serine protease inhibitor (MASPIN), N-myc downstream regulated gene 1 (NDRG1), KAI1, and B-cell translocation gene 2 (BTG2). PDEF modulated epithelial-mesenchymal-transition (EMT) by upregulating E-cadherin expression and downregulating the expression of N-cadherin, SNAIL, SLUG, and vimentin, leading to lower migration and invasion abilities of bladder carcinoma cells. Filamentous actin (F-actin) polarization and remodeling were observed in PDEF-knockdown RT-4 cells. Our results suggest that PDEF gene expression is associated with the extent of bladder neoplasia and PDEF modulated the expressions of EMT-related genes. The induction of BTG2, NDRG1, MASPIN, and KAI1 gene expressions by PDEF may explain the inhibitory functions of PDEF on the proliferation, invasion, and tumorigenesis in bladder carcinoma cells.

Prostatectomy using different lasers for the treatment of benign prostate hyperplasia in aging males

Purpose Endoscopic lasers have become a treatment option for benign prostate hyperplasia (BPH). The study reported here sought to elucidate the benefits and drawbacks of different laser systems in the treatment of patients with BPH. Methods The study enrolled 741 patients diagnosed with lower urinary tract symptoms secondary to BPH during the period January 2005 to December 2011. The techniques used in the study were photoselective vaporization of the prostate, thulium laser prostatectomy, and diode laser prostatectomy. Patients were assigned to one of three groups according to the type of laser treatment they received. Outcomes were evaluated using the International Prostate Symptom Score (IPSS), quality of life, maximal urinary flow rate, post-voiding residual urine volume, and prostate-specific antigen (PSA) level. Results The baseline characteristics of patients who received diode laser prostatectomy show a significant elevated risk and high American Society of Anesthesiology score (P=0.001). Operative time and catheter removal time differed significantly between the three groups (P=0.001). No cases were converted to transurethral resection of the prostate intraoperatively due to bleeding (P=0.142). Among the three groups, there were no significant differences in maximal flow rate, lower post-void residual urine, and postoperative PSA level during the entire follow-up period (P<0.05). Further, no significant differences in postoperative IPSS, quality of life, or bladder neck contracture (P=0.23) were observed. However, a significant difference was observed with regard to prolonged use of Foley catheters and prolonged hospital stay among patients in the diode laser group (P=0.001). Conclusion Laser prostatectomies are effective in dealing with lower urinary tract symptoms. Early subjective functional results (maximal flow rate, IPSS, and post-void residual urine) appeared the same as those obtained following laser prostatectomy. Thus, it appears that lasers are safe and effective as long as the patients are carefully selected for treatment.

Use of the SF-36 quality of life scale to assess the effect of pelvic floor muscle exercise on aging males who received transurethral prostate surgery

Purpose We used the Short Form (SF)-36® Health Survey scale to assess the effect of pelvic floor muscle exercise (PFE) on aging males who received transurethral resection of the prostate (TUR-P). Methods From April 2010 to December 2010, a total of 66 patients who underwent TUR-P were enrolled in this study. They were randomized into two groups (with 33 patients in each group) – an experimental group who performed postoperative PFE every day and a control group. Data, including the International Prostate Symptom Score (IPSS), uroflowmetry study, and the SF-36 quality of life measure, were collected before the operation, and at 1, 4, 8, and 12 weeks after the operation. We analyzed the differences between the two groups with respect to their IPSS scores, maximal urinary flow rate, residual urine amount, and life quality. Results A total of 61 patients (experimental group: 32 patients, and control group: 29 patients) completed this study. We found that at 12 weeks postop, patients who performed PFE every day had a better maximal urinary flow rate (16.41 ± 6.20 vs 12.41 ± 7.28 mL/min) (P = 0.026) compared with patients in the control group. The experimental group had a much greater decrease in IPSS score (P < 0.001). As for the SF-36 scale, the experimental group had higher scores than did the control group on both the physiological domain (54.86 vs 49.86) (P = 0.029) and the psychological domain (61.88 vs 52.69) (P = 0.005). However, there were no significant differences with respect to the postvoiding residual urine between the two groups (57.24 ± 52.95 vs 64.68 ± 50.63 mL) (P = 0.618). Conclusion Compared with the control group, patients who performed PFE for 12 weeks after TUR-P showed improvement in their maximal urinary flow rate and lower urinary tract symptoms, and had a better quality of life. The immediate initiation of PFE is suggested for patients who undergo TUR-P.

Prostatic urethral angle might be a predictor of treatment efficacy of α-blockers in men with lower urinary tract symptoms

Purpose We investigated the association of the prostatic urethral angle (PUA) with peak urinary flow rate (Qmax) and the severity of lower urinary tract symptoms (LUTS) on the aging male. We also evaluated the effect of the PUA on the treatment efficacy of tamsulosin on men with LUTS. Materials and methods The records were obtained from a prospective database for first-visit male patients with LUTS in the outpatient department of our institution. These patients underwent a detailed physical examination and taking of medical history. A transrectal ultrasound was performed on these patients. The prostate size, length of intravesical prostatic protrusion (IPP), PUA, and International Prostate Symptom Score (IPSS) of the patients were evaluated. Uroflowmetry and a bladder scan for residual urine were also performed on every patient. Tamsulosin 0.2 mg per day was prescribed. The IPSS and uroflowmetry were reevaluated after they had received treatment for 3 months. Results A total of 178 patients were included, and 149 of them completed this cohort study. The mean PUA was 48.32°±13.74°. The mean prostate volume was 39.19±20.87 mL, and the mean IPP was 5.67±7.85 mm. On multivariate linear regression analysis, the PUA was independently associated with the IPSS (P<0.001), Qmax (P=0.004), post-treatment IPSS change (P=0.032), and post-treatment Qmax change (P<0.001). However, the prostate volume and IPP were not associated with these clinical items. Conclusion The PUA is significantly associated with Qmax and IPSS in men with LUTS. The PUA is also inversely correlated with changes in Qmax and IPSS after tamsulosin treatment. Namely, the PUA might be a predictor for the treatment efficacy of α-blockers in aging men with LUTS.

The safety and efficacy of aspirin intake in photoselective vaporization laser treatment of benign prostate hyperplasia.

Endoscopic surgical treatment has become an option to treat benign prostate hyperplasia. We evaluated the safety and effectiveness of photoselective vaporization of the prostate (PVP) in patients. We evaluated preoperative and perioperative parameters, functional outcomes, and adverse events up to 12 months postoperatively of patients on oral anticoagulation therapy undergoing PVP, and compared the results with patients who did not take anticoagulation therapy. A total of 89 patients who received photoselective vaporization laser for benign prostate hyperplasia from May 2006 to February 2011 in our hospital were enrolled in our study. The patients were divided into two groups based on whether or not they were taking oral aspirin; 23 (25.8%) patients were taking aspirin derivatives (aspirin group), and 66 (74.2%) were not taking aspirin derivatives (control group). The mean prostate volume (58.8 mL vs 51 mL; P = 0.16) and mean energy consumption (235,268 J vs 289,793 J; P = 0.097) were comparable between the aspirin group and control group. The average postoperative results of hemoglobin were 13.4 mg/ dL for the aspirin group versus 13.9 mg/dL for the control group (P = 0.327). A significantly higher maximum flow rates and 80% improved post-void residual urine were noted during the followup. Postoperatively all variable showed significant improvement starting at month 1 of followup and remained improved for the 12 month followup. Postoperative complications were low and comparable between groups. PVP was characterized by excellent hemostatic properties and a very low intraoperative complication rate, even in the patients who were taking aspirin. On the basis of our perioperative results, we recommend PVP as a safe and effective procedure for patients with symptomatic benign prostate hyperplasia when taking an aspirin derivative.

A comparison of androgen deprivation therapy versus surgical castration for patients with advanced prostatic carcinoma

Aim:To examine the outcomes of patients with advanced prostate carcinoma who underwent medical or surgical castration.Methods:A hundred twenty one consecutive cases of patients with advanced prostate carcinoma who underwent medical or surgical castration between 2001 and 2006 were retrospectively reviewed. Associations between clinical outcomes and prognostic scoring factors were determined based on the Reijke study. In the surgical and medical castration groups, the impact on the prostate-specific antigen (PSA) normalization rate, the rebound rate and the disease-free survival rate were evaluated. The mean follow-up was 36.1 months.Results:In the initial 12 months, there were no statistical differences in the PSA normalization rate and the PSA rebound rate between the two groups. However, the PSA rebound rate after the 12th month (20.90% vs 40.74%, P=0.0175) and the 18th month PSA normalization rate (59.70% vs 37.04%, P=0.0217) differed significantly between the two groups, and these differences were maintained to the end of the study. When comparing patients grouped according to Reijke prognosis scores, there was no difference between medical and surgical castration for the good prognosis group. However, among the patients given a poor prognosis, surgical castration was superior in terms of the PSA normalization rate, the PSA rebound rate, the tumor progression-free survival rate (P<0.001) and the overall survival rate (P<0.001).Conclusion:Advanced prostate carcinoma patients with poor pretreatment prognosis scores should undergo surgical castration rather than medical castration for better PSA rebound rates and overall survival.

Risk factors associated with ineligibility of adjuvant cisplatin-based chemotherapy after nephroureterectomy.

Purpose Radical nephroureterectomy (RNU) is a standard treatment for upper urinary tract urothelial carcinoma. However, RNU can result in decreased renal function and cannot be treated with adjuvant chemotherapy. We performed a risk group stratification analysis to determine the preoperative factors that are predictive of diminished renal function after RNU. Materials and methods We retrospectively evaluated the medical records of all patients who underwent nephroureterectomy for upper urinary tract urothelial carcinoma at the Chang Gung Memorial Hospital from 2001 to 2008. We analyzed the association between perioperative glomerular filtration rate and preoperative parameters including cancer characteristics, serum creatinine level, and kidney size measured on computed tomographic images. Results A total of 242 patients fulfilled the inclusion criteria. The average decrease in renal function 1 month after RNU was 19.7%. Using 60 mL/min/1.73 m2 as the eligibility cutoff for cisplatin-based chemotherapy, 42.1% of the population was eligible prior to nephroureterectomy, whereas following surgery only 15.2% remained eligible. Using a cutoff of 45 mL/min/1.73 m2, 59.9% of the cohort was eligible for fractionated cisplatin dosing preoperatively, whereas only 32.6% remained above the cutoff postoperatively. The most significant predictors of poor postoperative renal function were body mass index >25 kg/m2, age >65 years, contralateral kidney length less than 10 cm, and absence of ipsilateral hydronephrosis. Conclusion Our results suggest that older age, higher body mass index, smaller contralateral renal length, and absence of ipsilateral hydronephrosis are predictive of decreased renal function after RNU.

Transurethral resection of the prostate achieves favorable outcomes in stroke patients with symptomatic benign prostate hyperplasia

Abstract Objectives: To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure. Methods: This retrospective cohort study analyzed claims data collected during the period of 1997–2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared. Results: Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT

Is diabetes mellitus associated with clinical outcomes in aging males treated with transurethral resection of prostate for bladder outlet obstruction: implications from Taiwan Nationwide Population-Based Cohort Study

659,000, NT