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   Table of Contents - Current issue
March-April 2019
Volume 30 | Issue 2
Page Nos. 45-90

Online since Thursday, March 28, 2019

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Bladder cancer in Taiwan p. 45
Stephen Shei-Dei Yang
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Autophagy modulation by dysregulated micrornas in human bladder cancer p. 46
Ji-Fan Lin, Po-Chun Chen, Thomas I-Sheng Hwang
The catabolic process of autophagy is an essential cellular function that directs the breakdown and recycling of cellular macromolecules. Increased autophagy causes various cancers, mainly bladder cancer (BC), to survive under microenvironmental stress and promotes cancer cell growth and aggressiveness. Cancer cells with rapid proliferation require a high basal level of autophagy to deal with the increased metabolic rate that generates reactive oxygen species, misfolded proteins, and damaged organelles. The regulation of autophagy by a class of small noncoding microRNAs (miRNAs) in human cancer has been discovered in recent years. In BC, a high basal level of autophagy plays critical roles in cancer survival and resistance to chemotherapy. Some studies have suggested that miRNAs participate in regulating these functions. In this review, we focused on recent key findings in the study of dysregulated miRNAs and their involvement in the regulation of autophagy in BC.
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Bladder calculi in Taiwan p. 53
Chun-Yo Laih, Chao-Hsiang Chang, Wen-Chi Chen
In Taiwan, the reported admission rate for bladder calculi was 7.5% of all patients with urolithiasis. The admission rate for bladder calculi was 12.9/100,000 in 2010, with elderly males constituting 91.8% of these patients. Pediatric bladder calculi are rare in Taiwan with a reported prevalence of only 0.047%. There are four possible causes of secondary bladder calculi, namely bladder outlet obstruction (BOO), neurogenic bladder, intravesical foreign bodies, and renal transplant. The biggest reported bladder stone in Taiwan was approximately 7 cm × 4.8 cm in size, with a weight of 320 g. Several pathogenic factors contribute to the formation of bladder calculi, including intravesical foreign bodies, BOO, neurogenic bladder, and metabolic abnormalities. Contemporary treatment of bladder calculi includes endoscopic cystolithotripsy or cystolitholapaxy with laser or LithoClast lithotripters. Some studies from Taiwan have reported that bladder calculi may increase the risk of cancer. An association between bladder calculi and chronic kidney disease has been reported in serial reports. In conclusion, most bladder calculi can be treated by endoscopic surgery and attention to associated comorbidities is warranted.
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Suppression of quercetin-induced autophagy enhances cytotoxicity through elevating apoptotic cell death in human bladder cancer cells p. 58
Te-Fu Tsai, Thomas I-Sheng Hwang, Ji-Fan Lin, Hung-En Chen, Shan-Che Yang, Yi-Chia Lin, Kuang-Yu Chou
Objective: Quercetin, a natural dietary compound, has been demonstrated with antitumor activities against several types of cancers by disrupting cell cycle and inducing apoptotic cell death. However, human bladder cancer cells such as 5637 and T24 cells expressing mutant p53 are resistant to a 24 hrs quercetin treatment. In this study, the anticancer effect of quercetin was evaluated in these bladder cancer cells. Materials and Methods: The bladder cancer cells treated with quercetin were subjected to evaluated cell apoptosis by caspase activity, TUNEL assay and cell viability assay. The cell autophagy was assessed by detecting procession of LC3-II autophagic marker protein. Results: After 48 and 72 hrs of incubation, quercetin was found to be significantly effective in inhibiting proliferation of 5637 and T24 cells in a dose-dependent manner. Quercetin treatment increased the caspase 3/7 activities, percentage of subG0/G1 cells, and DNA fragmentation, indicating an induced apoptotic cell death. Pretreatment of a pan-caspase inhibitor, Z-VAD-FMK, attenuated the quercetin-decreased cell viability, suggesting that the cytotoxicity caused by quercetin mainly via apoptotic cell death. We also found that quercetin induced autophagy, as evidenced by the increased processing of LC3-II, a specific marker of autophagy. The disruption of autophagic flux by using bafilomycin A1, an autophagy inhibitor, caused significant accumulation of cellular p62 and LC3-II. In addition, the pretreatment of autophagy inhibitors, Baf A1 and chloroquine, strongly augmented apoptosis in 5637 and T24 cells, indicating the suppression of quercetin-induced autophagy enhanced apoptosis. Furthermore, the decreased cell viability and increased LC3-II processing were attenuated in quercetin-treated cells which pretreated with a reactive oxygen species (ROS) scavenger, N-acetyl cystine (NAC) suggested that quercetin-induced cytotoxicity and autophagy were initiated by the generation of ROS. Conclusion: This study proposes that combined treatment of autophagy inhibitor which sensitizes cells to quercetin treatment may be a better therapeutic approach to reduce bladder cancer cells proliferation.
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Efficacy of bladder instillations with mitomycin or bacillus Calmette–Guérin in patients with T1 high-grade bladder cancer: Experience from a single center p. 67
Li-Wen Chang, Sheng-Chun Hung, Jian-Ri Li, Chuan-Shu Chen, Cheng-Kuang Yang, Chen-Li Cheng, Yen-Chuan Ou, Hao-Chung Ho, Kun-Yuan Chiu, Chao-Hsiang Chang, Shian-Shiang Wang
Objectives: To evaluate the efficacy of instillations with mitomycin C (MMC) or bacillus Calmette–Guérin (BCG) in patients with T1 high-grade bladder cancer (BC). Patients and Methods: From 2007 to 2015, 186 patients admitted to Taichung Veteran General Hospital with new diagnosis of T1 high-grade BC receive transurethral resection of the bladder tumor (TURBT) and 6 weekly adjuvant instillation following. Histological stage followed the WHO grading system. End point evaluation was recurrence and progression to muscle invasive BC. Results: A total of 118 patients received 6 weekly intravesical instillation chemotherapy with MMC and 68 with BCG. Above all, 93 patients received immediate intravesical MMC after TURBT. The mean follow-up period was 46.78 ± 19.05 months in the MMC group versus 50.13 ± 24.18 months in the BCG group (P = 0.512). The BCG group showed better outcomes with longer 5-year recurrence-free survivals (64.6% vs. 50.0%, P of log rank = 0.008*) and progression-free survivals (94.1% vs. 87.3%, P of log rank = 0.023*). The treatment efficacy of BCG in comparison to MMC was further adjusted in uni-multivariate analysis model (recurrence: Hazard ratio [HR] =0.511, 95% confidence interval [CI] = 0.304–0.858, P= 0.011*; progression: HR = 0.216, 95% CI = 0.068–0.683, P= 0.009*). We also explore smoker, multiple lesions, and tumor diameter >3 cm to be risk factors for recurrence. Conclusions: For patients with T1 high-grade nonmuscle invasive BC, the adjuvant therapy with BCG, as opposed to MMC, resulted in better outcomes based on recurrence and progression with tolerable complications. For immediate single instillations, in comparison, the efficacy was lower in preventing tumor recurrence and progression in the current stage.
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Differentiating tower from bell curves in smooth continuous uroflowmetry curves of healthy adolescents p. 74
Stephen Shei-Dei Yang, Shang-Jen Chang
Introduction: The definition of each uroflow pattern is vague, and therefore, interpreting uroflowmetry curves is associated with low inter-rater agreement. The aim of the study is to evaluate whether subjective or objective parameters could better differentiate tower from bell curves. Materials and Methods: Uroflow curves of community healthy adolescents with smooth continuous curves and minimal fluctuations within optimal bladder volume were independent reviewed by two experienced pediatric urodynamists and classified as bell or tower. The objective parameters generated from uroflow curves including Franco-Yang (F-Y) index (≧80) and angle at peak flow rate (A_Qmax ≧80°) were also used to differentiate tower from bell. The participants were asked to complete dysfunctional voiding symptom score (10 items, score 0–3). Results: A total of 287 adolescents with a mean age of 15.3 ± 1.7 years were enrolled and 150 curves were eligible for analysis. The inter-rater agreement was low (kappa = 0.27). Adolescents with uroflow curves classified as tower though F-Y index and A_Qmax were associated with higher urgency score than those with bell curves. However, adolescents with the tower curves defined by interpreters did not have higher urgency scores. Conclusions: Objective classification of tower curves with may be more reliable than subjective classification by the urodynamists. However, a significant proportion of participants with tower curves did not have urgency symptoms.
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The effect of treatment timing and urinary drainage on the outcome of urinary tuberculosis p. 79
Tsu-Feng Lin, Wun-Rong Lin, Marcelo Chen, Huang-Kuang Chang, Wen-Chou Lin, Wei-Kung Tsai, Stone Yang, Allen W Chiu
Background: Urinary tuberculosis (TB) has a variety of clinical manifestations and is a diagnostic challenge for urologists. Delayed treatment can lead to loss of renal function and structural destruction. In this study, we analyzed the relationship between the timing of treatment and outcomes in patients with urinary TB. Methods: We performed a retrospective chart review of all patients with urinary TB from 1978 to 2016 at our hospital and analyzed the patients' symptoms, diagnostic methods, imaging studies, time to diagnosis, treatment methods, and follow-up. Results: Twenty-one patients (median age: 49 years) had urinary TB, of whom 18 had hydronephrosis and hydroureter. No bilateral renal involvement was noted. The median duration from symptom onset to anti-TB treatment was 78.5 days. There was no significant relationship between symptom-to-treatment time and posttreatment changes in renal function (Pearson's r = 0.103, P > 0.05); however, the symptom-to-treatment time was linearly associated with pre- and posttreatment hydronephrosis grade (Pearson's r = 0.667, P= 0.03, and r = 0.710, P= 0.007, respectively). In multivariate analysis, the symptom-to-treatment time was found to be an independent predictor of improvements in hydronephrosis but was not associated with renal function change. Of nine patients with upper urinary tract drainage, hydronephrosis improved in three and was stable in five patients. Of 12 patients without drainage, four experienced renal loss. Conclusion: Urinary TB has vague clinical manifestations and is prone to a delayed diagnosis. Early diagnosis and prompt internal ureteral stenting may prevent renal loss in certain patients.
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Commentary from readers: Penile fracture management p. 84
Beuy Joob, Viroj Wiwanitkit
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Re: A tertiary center experience of fracture penis – A clinical diagnosis p. 85
Lalit Kumar, MC Arya
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Transcaval ureter: A rare embryological anomaly of inferior vena cava causing obstructive uropathy p. 86
Mukesh Chandra Arya, Mayank Baid, Rahul Tiwari, Vivek Vasudeo, Abhiyutthan Singh
Transcaval ureter is a rare condition caused by abnormality in the embryogenesis of the inferior vena cava (IVC). It results from a segmental duplication of the IVC which creates a venous ring that encircles the right ureter. Here, we report a case of a 42-year-old female who presented to us with a history of right flank pain for 2 years. Ultrasonography, intravenous urogram, and contrast-enhanced computed tomography (CECT) scan of the abdomen suggested it to be a retrocaval ureter. On exploration, contrary to the report of imaging, the ureter was found to transverse in between two segments of IVC and thus on table, a diagnosis of the right transcaval ureter as the cause of obstruction was made. The patient underwent segmental ureteral resection followed by ureteroureterostomy. Follow-up CECT scan was done to document two segments of IVC and thus confirm our intraoperative finding.
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Cme test p. 89

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