Early endoscopic primary realignment decreases stricture formation and reduces medical costs in traumatic complete posterior urethral disruption in a 2-year follow-up.

BACKGROUND: There are presently several options for the management of posterior urethral disruption. However, these options remain controversial for several reasons. Thus, this medical issue has been continuously investigated. METHODS: From 1991 to 2001, 22 patients with complete posterior urethral disruption out of 720 urethral injury cases were retrospectively reviewed using strict criteria. The 22 cases were grouped into two different management groups, the endoscopic early realignment (ER) group and the delayed urethrotomy (DU) group. The frequency of optic internal urethrotomy for urethral strictures and individual medical costs were evaluated over a two-year period. RESULTS: The ER group had a mean frequency of 1.3 ± 0.82 urethrotomies in the first year and 1.8 ± 1.23 over two years while the DU group had a significantly higher urethrotomy frequency, 2.5 ± 1.35 in the first year and 4.1 ± 1.91 over two years. The costs for the DU group were 50% higher than the ER group at the end of second year. CONCLUSION: An early endoscopic realignment operation saved up to NT 36,000 (New Taiwan Dollars) in costs with an average of 2.3 fewer further urethrotomy procedures in each case during the 2-year follow-up period. Therefore, early urethral realignment for traumatic complete posterior urethral disruption should be encouraged to prevent intractable urethral stricture and lower medical costs.

Identification of genetic alterations in upper urinary tract urothelial carcinoma in end-stage renal disease patients.

Clinical presentations of end-stage renal disease (ESRD) patients on dialysis with upper urinary tract urothelial carcinoma (UUT-UC) are different from those with normal renal function. The pathogenesis remains unknown. We investigated the pathogenetic influence of chromosomal aberrations in patient on dialysis with UUT-UC. The chromosomal aberrations of UUT-UC specimens from seven dialysis patients were assessed by conventional comparative genomic hybridization (cCGH). Subsequently, we further investigated 20 cases by whole genome and fine-tiling oligonucleotide array-based CGH to demonstrate gains and losses, and compared with the clinicopathologic background. The chromosomal aberrations in UUT-UC specimens from dialysis patients were more complex than in bladder urothelial carcinoma (B-UC). Our data showed that gains at 5p, 7, 19q, and losses at 4q, 9p, and 15q are common in UUT-UC of ESRD patients. Gains in regions associated with DNA repair genes were noted in this study. High-stage and high-grade tumors displayed more copy number variants. In addition, female ESRD patients with UUT-UC had more frequent chromosomal aberrations than their male counterparts. In conclusion, unique chromosomal aberrations were indentified in UUT-UC in ESRD patients.

Combretastatin A-4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model.

BACKGROUND AND PURPOSE: Bladder cancer is a highly recurrent cancer after intravesical therapy, so new drugs are needed to treat this cancer. Hence, we investigated the anti-cancer activity of combretastatin A-4 (CA-4), an anti-tubulin agent, in human bladder cancer cells and in a murine orthotopic bladder tumour model. EXPERIMENTAL APPROACH: Cytotoxicity of CA-4 was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, propidium iodide (PI) staining assay and clonogenic survival assay. In vivo microtubule assembly assay, cell cycle analyses, Western blot and cell migration assay were used to study the mechanism of CA-4. The effect of intravesical CA-4 therapy on the development of tumours was studied in the murine orthotopic bladder tumour model. KEY RESULTS: CA-4 inhibited microtubule polymerization in vivo. Cytotoxic IC(50) values of CA-4 in human bladder cancer cells were below 4 nM. Analyses of cell-cycle distribution showed CA-4 obviously induced G(2)-M phase arrest with sub-G(1) formation. The analyses of apoptosis showed that CA-4 induced caspase-3 activation and decreased BubR1 and Bub3 in cancer cells. In addition to apoptosis, CA-4 was also found to induce the formation of multinucleated cells. CA-4 had a significantly reduced cell migration in vitro. Importantly, the in vivo study revealed that intravesical CA-4 therapy retarded the development of murine bladder tumours. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that CA-4 kills bladder cancer cells by inducing apoptosis and mitotic catastrophe. It inhibited cell migration in vitro and tumour growth in vivo. Hence, CA-4 intravesical therapy could provide another strategy for treating superficial bladder cancers.

Coronary phenotypes in patients with erectile dysfunction and silent ischemic heart disease: a pilot study.

INTRODUCTION: Accumulated evidence shows that erectile dysfunction (ED) may be a precursor of coronary artery disease (CAD). AIMS: The purpose of this study was to explore the differences in coronary phenotypes between patients with ED and patients with angina pectoris. METHODS: The study enrolled 30 ED patients (study group) and 120 age-matched angina patients who had no ED (control group). All patients had angiographically documented CAD. MAIN OUTCOME MEASURES: The differences in demographic characteristics, biochemical profiles and coronary characteristics between the study and control groups were compared. RESULTS: Diabetes mellitus (DM) and obesity defined by body mass index were more common in the study group than in the control group. The mean number of lesions and mean number of vessels with evidence of CAD were significantly different between the study and control groups (2.3 ± 0.1 vs. 2.2 ± 0.1, P < 0.001; 2.0 ± 0.2 vs. 1.8 ± 0.1, P < 0.001). The distribution of vessel involvement was similar between the groups, except for more common involvement of the ramus in the study group. There were no differences in distribution of lesion sites between the two groups. The control group had a higher percentage of type A stenotic lesions than the study group (16.3% vs. 2.9%, P = 0.004). Significant differences were also observed in type C lesions (52.9% in study group vs. 38.0% in control group, P = 0.026). Fewer calcified, irregular, and bifurcated lesions were present in the study group compared to control. CONCLUSIONS: This study documented coronary phenotypes in ED patients without symptomatic CAD. Although the artery size hypothesis and ED had well been thought to be a precursor of CAD, the severity of coronary lesions in these patients was not more benign than that observed in angina pectoris patients who have no ED.

4'-Chloro-3,5-dihydroxystilbene, a resveratrol derivative, induces lung cancer cell death.

AIM: To examine the antitumor effect of 4'-chloro-3,5-dihydroxystilbene, a resveratrol derivative, on lung adenocarcinoma A549 cells. METHODS: The cytotoxic IC(50) was determined by direct cell counting. Flow cytometry, monodansylcadaverine (MDC) staining, transfection, Western blot and a proteasome activity assay were used to study the cellular mechanism of 4'-chloro-3,5-dihydroxystilbene. A xenograft nude mouse model was used to analyze the antitumor effect in vivo. RESULTS: 4'-Chloro-3,5-dihydroxystilbene induced a rapid and persistent increase in the intracellular reactive oxygen species in the cells, but the cell death could not be inhibited by two antioxidant agents. The derivative caused sub-G(1) formation, a decrease in the mitochondria membrane potential and poly (ADP-ribose) polymerase degradation, and the caspase inhibitor Z-VAD-FMK could partially prevent cell death. It also induced a significant increase in intracellular acidic vacuoles, LC3-II formation and intracellular GFP-LC3 aggregation. An autophagic inhibitor partially reversed cell death. Additionally, 4'-chloro-3,5-dihydroxystilbene induced the accumulation of ubiquitinated conjugates and inhibited proteasome activity in cells. In an in vivo study, 4'-chloro-3,5-dihydroxystilbene retarded tumor growth in nude mice. CONCLUSION: These data suggest that the resveratrol derivative 4'-chloro-3,5-dihydroxystilbene could be developed as an anti-tumor compound.

Independent determinants of coronary artery disease in erectile dysfunction patients.

INTRODUCTION: There is growing evidence of a link between erectile dysfunction (ED) and coronary artery disease (CAD). AIMS: The purpose of this study was to explore the independent determinants of CAD in ED outpatients. METHODS: This study enrolled 243 patients, ranging in age from 21 to 81 years old, suffering from ED as diagnosed by the International Index of Erectile Function (IIEF) scores. All patients underwent exercise stress tests or thallium-201 single-photon emission computed tomography perfusion imagings. Based on examination results, patients were divided into study (22 patients with a positive finding) and control groups (221 patients with a negative finding). MAIN OUTCOME MEASURES: The differences of demographic characteristics, biochemical profiles, pro-inflammatory and inflammatory markers, and echocardiographic characteristics between study and control group were compared. RESULTS: The age, presence of DM and current smoking status were significant high in the study group. A significant lower high-density lipoprotein (HDL) cholesterol level, a higher percentage of HDL cholesterol level < 40 mg/dL, and a higher apo-lipoprotein B/A1, high sensitive C-reactive protein (hs-CRP) and homocysteine found in the study group. The Framingham cardiac risk scores, the ratio of mitral inflow velocity to early diastolic velocity in the annulus derived by tissue Doppler imaging (E/Et), the ratio of E/Et > or = 15, the value of carotid intima-media thickness (IMT), and IMT > or = 1 mm were higher in study group than in the control group. In stepwise multiple logistic regression analysis, a high waist-to-hip ratio (WHR), high IMT, high E/Et, hs-CRP levels, LDL cholesterol > or = 130 mg/dL, smoking status, and the presence of DM and metabolic syndrome (MS) were independent determinants of CAD in ED patients. CONCLUSIONS: This study first shows the independent determinants of CAD in ED outpatients. This novel finding may improve the screening of low-risk ED patients for CAD.

The inhibitory effect of Gynostemma pentaphyllum on MCP-1 and type I procollagen expression in rat hepatic stellate cells.

AIM OF THE STUDY: Gynostemma pentaphyllum is a popular folk medicine that has been used for treatment of hepatitis in Asia. Our previous study demonstrates that Gynostemma pentaphyllum n-butanol extract inhibits the onset and improves the recovery of CCl(4)-induced liver fibrogenesis in rats and inhibits PDGF-induced rat hepatic stellate cells (HSCs) proliferation. In this study, the effect of Gynostemma pentaphyllum extract on cytokines and type I procollagen expression was analyzed. MATERIALS AND METHODS: Rat HSCs were treated with PDGF, Gynostemma pentaphyllum n-butanol extract, RP-18-Gyp fraction, rapamycin or vehicle. Rat cytokine antibody array chip or ELISA kit was used for cytokines detection. Intracellular protein expression was detected by Western blotting, mRNA expression was analyzed by RT-PCR. RESULTS: RP-18-Gyp fraction is the more purified gypenosides fraction from Gynostemma pentaphyllum n-butanol extract. In cell proliferation, the inhibitory effect of 200 microg/ml RP-18-Gyp fraction is similar to 500 microg/ml Gynostemma pentaphyllum n-butanol extract. Furthermore, both of them have the ability of decreasing monocyte chemoattractant protein-1 (MCP-1) mRNA expression and protein release and inhibiting type I procollagen protein expression. CONCLUSIONS: Both of Gynostemma pentaphyllum n-butanol extract and its more purified RP-18-Gyp fraction have the biological activities in the inhibition of cell proliferation, MCP-1 release and type I procollagen expression in rat HSCs. These data could provide the evidence to support for the traditional use of Gynostemma pentaphyllum in hepatitis.

Characterization of immunological activities of peanut stilbenoids, arachidin-1, piceatannol, and resveratrol on lipopolysaccharide-induced inflammation of RAW 264.7 macrophages.

Biological activities of peanut stilbenoids, mainly resveratrol and its derivatives, have attracted increased attention and interest because of peanut being a potent producer and a dietary channel to convey these polyphenols to the human body. As arachidin-1 and piceatannol are structurally close to resveratrol, it is worthy to investigate their immunological activities on inhibition of lipopolysaccharide (LPS)-induced production of PGE2 and NO and mediation of the related transcription factors (NF-kappaB and C/EBP) of RAW 264.7 macrophage cells. Productions of PGE2 and NO were inhibited by all the test stilbenoids in a dose-dependent manner while gene and protein expressions of COX-2 and iNOS were not inhibited. As shown by NF-kappaB-driven luciferase assay, LPS-induced NF-kappaB activities were also reduced by the stilbenoids. In further, when these stilbenoids were subjected to monitoring their inhibitory effectiveness on LPS-induced transcription factor expressions of C/EBPdelta and C/EBPbeta, only C/EBPdelta expressions were reduced. Thus, these stilbenoids were effective in inhibition of PGE2- or NO-mediated inflammation and NF-kappaB- or C/EBPdelta-mediated inflammatory gene expression. In comparison, the highest inhibitory activity on LPS-induced PGE2/NO production, C/EBPdelta gene expression, and NF-kappaB activation was piceatannol which was followed in order by arachidin-1 and resveratrol. The observed anti-inflammatory activities of these peanut stilbenoids are of merit in further consideration for nutraceutical applications.

Modified bowel preparation to reduce infection after prostate biopsy.

BACKGROUND: Infectious complications after ultrasound guided prostate biopsy are an important issue of concern. We found a higher infection rate with traditional bowel preparation, the phosphate enema, for prostate biopsy and so we modified our technique. In addition, we tried to assess the efficacy of this modified method for aged patients in an agricultural area who have poor compliance or inaccuracy when self-administering bowel preparations. METHODS: Between April 2002 and May 2005, all patients who received prostate biopsy were reviewed retrospectively. Exclusion criteria included patients who had an indwelling Foley catheter, symptomatic urinary tract infection or suspected prostatitis before prostate biopsy. Group I consisted of patients who self-administered a phosphate enema at home. Group II had a phosphate enema combined with povidone-iodine administered by a doctor at the hospital. All patients took oral fluoroquinolone (500 mg) twice daily for a period of one day before the procedure. Both groups received trimethoprim (160 mg) with sulfamethoxazole (800 mg) twice daily for three days after the biopsy. Postoperative infection was defined as an oral temperature higher than 37.7 centigrade or any episodes of chills with painful digital rectal examination. RESULTS: There were 65 patients in Group I and 157 patients in Group II. Within Group I, six patients (9.23%) were found to have a symptomatic infection with leukocytosis or chills; none were found in Group II. Between Group I and II, different bowel preparation was the only parameter shown to have statistical significance on the infection rate. CONCLUSIONS: Bowel preparation before prostate biopsy is not standardized among urologists. Phosphate enema with povidone-iodine administered at the hospital is an effective way to reduce the infection rate for agricultural people who have poor compliance or inaccuracy when self-administering bowel preparations.

A decade of recurrent cystitis in a woman due to a giant vesical calculus.

A 50-year-old woman suffering from recurrent cystitis for one decade developed a 660-g stone in her bladder. Abdominal plain radiography showed a huge stone shadow measuring 12 x 9 x 8 cm in size.

Clinical observations of the effect of antidiuretic hormone on nocturia in elderly men.

OBJECTIVE: To evaluate the effect of desmopressin on nocturia, based on patients' subjective scoring of nocturia, as desmopressin is widely used to treat nocturnal enuresis and nocturnal polyuria. PATIENTS AND METHODS: We investigated a specific subgroup of 28 men with benign prostate obstruction and nocturia who were treated with desmopressin. Patients with nocturnal polyuria were excluded. All the patients were refractory to treatment with antimuscarinics or anticholinergics, e.g. oxybutynin, tolterodine, and propantheline bromide. We assessed the effect of desmopressin using a quantitative nocturia score and analysed its synergistic effect with alpha-blockers. RESULTS: The mean frequency of nocturia was 6.1 before desmopressin and most (86%) patients had an improvement in nocturia within 1-12 weeks of treatment with desmopressin. There was a 43% reduction in nocturia after using desmopressin (P < 0.001). The correlation coefficient between the number of nocturnal voids and the reduction in nocturia after treatment with desmopressin was 0.756, indicating that the more severe the nocturia, the more effective was desmopressin. CONCLUSIONS: Desmopressin is effective for refractory nocturia in elderly men with no nocturnal polyuria, and has limited side-effects.

Therapeutic options for proximal ureter stone: extracorporeal shock wave lithotripsy versus semirigid ureterorenoscope with holmium:yttrium-aluminum-garnet laser lithotripsy.

OBJECTIVES: To compare the safety and cost-effectiveness of ureterorenoscopic holmium:yttrium-aluminum-garnet (YAG) laser lithotripsy (URSL) with extracorporeal shock wave lithotripsy (ESWL) for proximal ureteral stones. METHODS: This investigation assessed 220 patients with upper ureteral stones. Those in the ESWL group were treated on an outpatient basis using the Medispec Econolith 2000 (Medispec, Germantown, MD) under intravenous sedation. URSL was performed with a 6/7.5F semirigid tapered ureterorenoscope and holmium:YAG laser under spinal anesthesia on an inpatient basis. A successful outcome was defined as the patient being stone free on radiography 1 month after treatment. The stone size, success rate, postoperative complications, and cost were evaluated in each group. RESULTS: A total of 220 patients were enrolled in this study. Hematuria and flank pain were the most common complaints in each group. The mean stone burden +/- SD was 58.7 +/- 3.1 mm2 in the ESWL group and 108.4 +/- 10.0 mm2 in the URSL group (P = 0.000). The accessibility of the semirigid ureterorenoscope for upper ureteral stones was 98.1% (101 of 103), and the stone-free rate achieved after one treatment was 83.2% (84 of 101). The initial stone-free rate of in situ ESWL was 63.9% (76 of 119). Significantly, the initial stone-free rate of the URSL group was superior to that of the ESWL group (P = 0.001). The average cost in the URSL group appeared to be lower than that in the ESWL group (P = 0.000). CONCLUSIONS: The results of this study have demonstrated that URSL achieved excellent results for upper ureter calculi. In terms of cost and effectiveness, this procedure should be the first-line therapy for proximal ureter stones.

Comparison between extracorporeal shock wave lithotripsy and semirigid ureterorenoscope with holmium:YAG laser lithotripsy for treating large proximal ureteral stones.

PURPOSE: Management of large impacted upper ureteral calculi remains challenging for urologists. These calculi are frequently associated with obstructive uropathy and deteriorated renal function. Extracorporeal shock wave lithotripsy (SWL) is the least invasive treatment but its success rate is decreased for large impacted upper ureteral calculi. According to the American Urological Association guidelines on ureteral stones published in 1997, the appropriateness of ureteroscopy decreases when stone size exceeds 1 cm. However, the application of advanced ureteroscopy and techniques has increased the success rate of treating proximal ureter calculi. In this study we compared the safety and efficacy of ureterorenoscopic holmium:YAG laser lithotripsy (URSL) with SWL for large impacted proximal ureteral stones. MATERIALS AND METHODS: This study evaluated 82 patients with large impacted upper ureteral stones. Two patients were excluded from study owing to conversion to open surgery. SWL and URSL were performed in 41 and 39 patients, respectively. Those in the SWL group were treated on an outpatient basis with Medispec Econolith 2000 (Medispec, Germantown, Maryland) under intravenous sedation. The URSL was performed with a 6/7.5Fr semirigid tapered ureterorenoscope and holmium:YAG laser with the patient under spinal anesthesia on an inpatient basis. Successful outcome was defined as the patient being stone-free on radiography 1 month after treatment. Stone size, success rate, postoperative complications and cost were analyzed in each group. RESULTS: A total of 80 patients were enrolled in this study. Hematuria and flank pain were the most common complaints in each group. Mean stone size +/- SD was 1.28 +/- 0.04 cm in the SWL group and 1.51 +/- 0.05 cm in URSL group (p = 0.0009). Accessibility of the semirigid ureterorenoscope for impacted upper ureteral stones was 95.1% (39 of 41) and the stone-free rate achieved after 1 sitting was 92% (36 of 39). The initial stone-free rate of in situ SWL was 61% (25 of 41). Notably, the initial stone-free rate in the URSL group was better than that of the SWL group (p = 0.003). The efficiency quotient was 0.53 for URSL and 0.59 for SWL. The average cost in the URSL group appears to be lower than in the SWL group. Both groups were free of major complications. CONCLUSIONS: This study demonstrated that URSL achieved excellent results for upper ureteral calculi greater than 1 cm. Thus, this procedure should be considered first line therapy for large proximal ureteral stones.

Different treatment strategies for end stage renal disease in patients with transitional cell carcinoma.

PURPOSE: Transitional cell carcinoma is the most common urinary tract cancer in Taiwanese patients on dialysis. It is a unique finding compared within Western countries. Due to this geographic difference and a higher recurrence rate a more extensive operation and aggressive followup protocols should be refined for these patients on dialysis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with transitional cell carcinoma who had end stage renal disease and underwent hemodialysis. Records were reviewed for hemodialysis duration, initial tumor location, tumor grade, stage, operative method, operative complication and final surgical status. Tumor grade and stage was determined by the WHO and proposed Jewett systems. Six patient groups were classified according to final surgical status for comparative analysis. RESULTS: A total of 30 patients were included in this study. Painless gross hematuria and urethral bloody discharge were the most common complaints. Tumor in 25 of the 30 cases was high grade and all were early stage. Of the patients 11 (36.7%) had undergone bilateral nephroureterectomy and radical cystectomy in as a 1 or multiple step procedure. Six patients (20%) had undergone bilateral nephroureterectomy at 1 or 2 sequential operations. Seven of the 13 patients (53.8%) in whom low urinary tract transitional cell carcinoma was initially treated with transurethral resection unfortunately had recurrent transitional cell carcinoma of the upper urinary tract. Ten of the 14 patients (71.4%) with upper urinary tract transitional cell carcinoma who underwent nephroureterectomy and bladder cuff excision had subsequent transitional cell carcinoma within the bladder. CONCLUSIONS: Patients with transitional cell carcinoma on dialysis had a higher recurrence rate in the upper urinary tract than patients not on dialysis. Most cases were at an early stage but with high grade tumor behavior. In 11 patients (36.7%) total exenteration of the urinary tract except the urethra was eventually done. The final bilateral nephroureterectomy rate was 56.7%. Since the rate of total exenteration and bilateral nephrectomy was abnormally high at such a short followup, 1-step bilateral nephroureterectomy and radical cystectomy are a recommended treatment for patients with transitional cell carcinoma on dialysis.