Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population.

OBJECTIVE: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. METHODS: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. RESULTS: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively (p = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively (p = 0.002). CONCLUSION: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.

Resiniferatoxin for treatment of lifelong premature ejaculation: a preliminary study.

OBJECTIVES: To evaluate the efficacy of resiniferatoxin in the treatment of patients with lifelong premature ejaculation. METHODS: A total of 41 outpatients (mean age 26.14 ± 4 years) with premature ejaculation completed the present study. They were randomly separated into the resiniferatoxin group and the placebo group. The resiniferatoxin group included 11 patients with redundant prepuce and 10 patients without redundant prepuce, whereas the placebo group contained 10 patients with redundant prepuce and 10 patients without. For the treatment, the glans were respectively soaked in 30 mL of resiniferatoxin with a concentration of 100 nmol/L or 10% alcohol solution for 30 min before sexual intercourse. Clinical efficacy was assessed by using the Chinese Index of Sexual Function for Premature Ejaculation-5 and the intravaginal ejaculation latency time before or 4 weeks after the treatment. The side-effects were also evaluated. RESULTS: In the resiniferatoxin group, the effective rate of patients with redundant prepuce was 63.6%, and both the intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5 significantly increased (P < 0.05). However, the effective rate of patients without redundant prepuce was 20%, and there were no significant changes of their intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5 before and after the resiniferatoxin treatment (P > 0.05). The total effective rate of patients treated with resiniferatoxin was 42.9%. In the placebo group, the effective rate of patients with or without redundant prepuce was 20% and 10%, respectively. The total effective rate of patients treated with placebo was 15%, and there were no significant changes of their intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5 before and after the placebo treatment (P > 0.05). The side-effects included a slight burning sensation for the glans penis and dysuria. CONCLUSIONS: These preliminary results show that resiniferatoxin might be suitable for treating patients with lifelong premature ejaculation and particularly those with redundant prepuce.

Overactive bladder symptom score to evaluate efficacy of solifenacin for the treatment of overactive bladder symptoms.

BACKGROUND: Overactive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB. METHODS: This was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated. RESULTS: At baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy. CONCLUSIONS: We showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Prostatic Schistosoma japonicum with atypical immunophenotyping of individual glandular tubes: a case report and review of the literature.

There are few cases of prostatic schistosomiasis. Here we report a case of Schistosoma japonicum of the prostate, in which the immunophenotyping of individual glandular tubes was atypical. Whether the S. japonicum infection contributed to the lesion or not is unknown. We suspect the lesion was a sign of early precancerous hyperplasia. Follow-up of this patient may give clues about the relationship between schistosomiasis and prostate cancer. This is the first case report of prostatic S. japonicum in the English literatures. A review of the literature is carried out.

[Progress in home uroflowmetry in evaluation of lower urinary tract symptoms in patients].

Uroflowmetry is the most widely used non-invasive urodynamic tool for most patients with suspected lower urinary tract dysfunction. Home uroflowmetry can produce multiple representative flow readings in adequate privacy condition when patients feel a normal desire. Because of its advantages of decreasing variability, describing circadian rhythms and combating problems inherent to clinic-based measurements, it can improve diagnostic accuracy and predictive value. Further studies are required to confirm quantitative data of patient's preferences and to measure cost-benefit of home uroflowmetry.

Ketamine-associated urinary tract dysfunction: an underrecognized clinical entity.

INTRODUCTION: The use of ketamine as a recreational drug is on the increase among young adults attending clubs and parties. Recreational ketamine users have anecdotally reported increased lower urinary tract symptoms while using the substance. METHODS: We describe the severe lower urinary tract symptoms experienced in 6 patients with chronic recreational ketamine use. We obtained a detailed history and physical examination along with further investigation to identify a relationship between recreational ketamine use and these symptoms. RESULTS: The urine cultures were sterile in all cases. Intravenous urography was performed in 3 patients and demonstrated bilateral upper ureteric narrow, mild bilateral hydronephrosis and contracted bladder urodynamic studies showed detrusor instability with urinary leakage when the bladder was filled to a capacity of 30- 50 ml. Cystoscopy revealed a small capacity bladder with erythematous lesions throughout the bladder. Bladder biopsies were performed in 3 patients and showed up as chronic cystitis. Ketamine cessation along with intravesical sodium hyaluronate solution appeared to provide some symptomatic relief. CONCLUSION: Ketamine-associated urinary tract dysfunction appears to be a relatively new clinical phenomenon. The pathological mechanism of ketamine-associated urinary tract dysfunction is unknown and current management strategies are ketamine cessation along with intravesical sodium hyaluronate solution.

Lower urinary tract destruction due to ketamine: a report of 4 cases and review of literature.

Four young ketamine abusers with lower urinary tract symptoms presented to regional hospitals in Shenzhen, China. Investigations demonstrated contracted bladders and other urinary tract abnormalities. There have been few reports of similar findings in ketamine abusers in the Chinese mainland. We followed up each patient for 1.5 years and their individual treatment strategies are also discussed.

[Abnormal expression and significance of MIR-184 in human renal carcinoma].

OBJECTIVE: To explore the role of microRNA-184(MIR-184) in the development of renal cell carcinoma(RCC). METHODS: The expressions of MIR-184 in 51 patients with RCC Investigated, normal adjacent tissues (ADTs) matched by fluorescence quantitative PCR technology (RT-qPCR) and the correlations analyzed between MIR-184 expression and the age, gender and clinical stage of RCC patients. RESULTS: The average expression of MIR-184 in RCC was -14.664 6 ± 5.362 4, while that in ADTs was -10.408 7 ± 3.482 7(P<0.01). Bounded with the MIR-184 expression in RCC, patients were divided into lower-expression group and higher-expression group. Meanwhile, the RCC patients were divided into three groups according to the age, gender and clinical stage of the patients. Chi-square statistical analysis showed that the expression level of MIR-184 was not significantly correlated with the patient's age, gender and clinical stage (respectively: P>0.03, P>0.99, P>0.03). CONCLUSION: MIR-184 in RCC was significantly lower than that in ADTs, which may have potential significance in the occurrence and development of RCC.

[Age-specific reference ranges for prostate specific antigen in 16 222 Chinese men].

OBJECTIVE: To investigate the PSA level of 16 222 asymptematic men in Shenzhen who came from different areas of China, in order to find out the PSA levels of Chinese men. METHODS: Serum samples of 16 222 men who came to Peking University Shenzhen Hospital for health examination were collected, all of whom had no symptoms. Their serum PSA levels were measured with MEIA with ILMA instrument. RESULTS: The mean PSA level of the 16 222 men in our research was 0.986 µg/L, and the standard deviation was 1.190. The 95% percentile was 2.375 µg/L. Of all the cases ,the 95% percentile of 15 498 was lower than 2.5 µg/L, about 95.472%;that of 699 was between 2.5-10.0 µg/L, about 4.306%;And if took 4.0 µg/L as reference value,that of 15 948 cases was below 4.0 µg/L, about 98.244%;that of 249 was between 4.0-10.0 µg/L, about 1.534%;That of only 36 cases was greater than 10.0 µg/L, about 0.222%;The 95% percentiles of the different age groups were: 10-19 years 0-1.067 µg/L;20-29 years 0-1.818 µg/L;30-39 years 0-1.914 µg/L;40-49 years 0-2.001 µg/L;50-59 years 0-2.900 µg/L;60-69 years 0-5.862 µg/L;70-79 years 0-8.536 µg/L;elder than 80 years 0-12.869 µg/L;There were statistic differences between thedifferent age groups. CONCLUSION: Our data demonstrate that the mean value of PSA levels of Chinese men is 0.986 µg/L at present stage, and the 95% percentile is 2.375 g/L. Our PSA levels of each age group are different from Oesterling's reference values which are commonly accepted in the world. The PSA level of Chinese men who are under 60 years is lower than that of Euramericans, while the PSA level of Chinese men who are above 60 years is higher than that of Euramericans. This shows that for the men who are under 60 the reference value should be 2.5 µg/L, while for the men who are above 60, we could still use 4 µg/L as reference value.

[Comparison of new portable home electronic uroflowmeter with Laborie uroflowmeter].

OBJECTIVE: To design a new portable home electronic uroflowmeter and compare it with traditional methods. METHODS: The system consists of collectors, urine conducting apparatus, intelligent cell phone, wireless network communication technology, computer analysis and drawing, and data storage technology, etc., and can automatically collect voiding information from patients with lower urinary tract symptoms(LUTS) Through Bluetooth, the voiding information was sent to the patient's intelligent cell phone from the collector, then stored directly by intelligent cell phone and wirelessly transmitted to the workstation in hospital. The system was primarily tested with regard to accuracy of measurement of the voided volume. Multiple doses with known volume were introduced in the system and Laborie uroflowmeter. Furthermore, 38 outpatients who had LUTS were tested simultaneously with the system and Laborie uroflowmeter. The statistical method for assessing agreement between the two methods of clinical measurement was Bland-Altman analysis. Among the subjects, there were 22 male patients and 16 female patients, ranging from 21 to 37 years old, with an average age of 25.5 years, of whom, 19 were tested once and 19 patients twice, equaling to 57 tests. RESULTS: The system could accurately collect and analyze voiding time, uroflowmetry, voided volume, and automatically provide uroflowmetry parameters. The measurement error of 100, 200, 300, 500 and 800 mL is less than 5%. 12.28%, 5.26% and 3.51% of the Qmax, Qave and voided volume points were beyond the 95% limits of agreement. The maximum absolute values of the Qmax, Qave and voided volume difference were 0.38 mL/s, 0.70 mL/s and 2.90 mL, respectively.They agreed with the recommendation of Standardization International Continence Society. CONCLUSION: The new portable home electronic uroflowmeter has good agreement with Laborie uroflowmeter,and is a new LUTS monitoring system integrated with correct, reliable, real-time, convenient and easy-managing advantages. It is as noninvasive and reliable as traditional methods, and its portable feature facilitates application out of hospitals. It can also record voiding diaries.

[Ketamine-associated urinary tract damage].

Ketamine is widely used as an anesthetic during surgical procedures in both animals and humans. As its unique effects of inducing the dissociative hallucinatory,vivid dreams, out-of-body experiences, and delirium, it has diverted from legitimate uses to the illicit drug market, and abusing ketamine has become a serious social problem. The abusers may use ketamine alone or mixe it with other drugs to get an intense pleasure. There are case reports from all over the world in recent years that abusing ketamine may induce severe lower urinary tract symptoms (LUTS), and a variety of anatomical and functional lesions can be found in the urinary tract if further examinations are administrated. There is no universally recognized treatment protocols for this syndrome. Ketamine cessation or even reduction is the most effective treatment to prevent deterioration of the urinary tract, and intravesical instillation of hyaluranic acid (cystitstat) and oral pentosan polysulphate (elmiron) may take effect. The pathogenesis of ketamine-associated urinary tract destruction is unclear, and further study is needed.

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder.

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.

MicroRNA expression signatures of bladder cancer revealed by deep sequencing.

BACKGROUND: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression. They are aberrantly expressed in many types of cancers. In this study, we determined the genome-wide miRNA profiles in bladder urothelial carcinoma by deep sequencing. METHODOLOGY/PRINCIPAL FINDINGS: We detected 656 differentially expressed known human miRNAs and miRNA antisense sequences (miRNA*s) in nine bladder urothelial carcinoma patients by deep sequencing. Many miRNAs and miRNA*s were significantly upregulated or downregulated in bladder urothelial carcinoma compared to matched histologically normal urothelium. hsa-miR-96 was the most significantly upregulated miRNA and hsa-miR-490-5p was the most significantly downregulated one. Upregulated miRNAs were more common than downregulated ones. The hsa-miR-183, hsa-miR-200b ∼ 429, hsa-miR-200c ∼ 141 and hsa-miR-17 ∼ 92 clusters were significantly upregulated. The hsa-miR-143 ∼ 145 cluster was significantly downregulated. hsa-miR-182, hsa-miR-183, hsa-miR-200a, hsa-miR-143 and hsa-miR-195 were evaluated by Real-Time qPCR in a total of fifty-one bladder urothelial carcinoma patients. They were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium (p < 0.001 for each miRNA). CONCLUSIONS/SIGNIFICANCE: To date, this is the first study to determine genome-wide miRNA expression patterns in human bladder urothelial carcinoma by deep sequencing. We found that a collection of miRNAs were aberrantly expressed in bladder urothelial carcinoma compared to matched histologically normal urothelium, suggesting that they might play roles as oncogenes or tumor suppressors in the development and/or progression of this cancer. Our data provide novel insights into cancer biology.

[Development of remote wireless mobile voiding diary and a report of its objective voiding in 20 young people].

OBJECTIVE: To find out the data of the micturitions in healthy young people with the remote & mobile voiding diary monitoring system. METHODS: Twenty healthy young people were studied and ten of them were female. The ages ranged from 22 to 35 years (the mean age: 27.4 years). The females were 22-33 years old (the mean age: 26.4 years ) and the males 24-35 years old (the mean age: 28.4 years). With the remote & mobile voiding diary monitoring system, their voiding information was collected. Through bluetooth, the voiding information was sent to the patient's intelligent cell phone from the collector, then stored directly by intelligent cell phone and wirelessly transmitted to the workstation in the hospital. All of them completed the voiding diaries for 7 days and the data were analyzed. RESULTS: The average micturition of the young healthy people was 5.6 times (3.4-7.4) per 24 hours,in which 5.3 (3.4-7.3) times were in the daytime and 0.3 (0-1.3)times in the night. The functional voiding volume was 318 mL (66-642 mL). The mean voiding volume in 24 hours was 1 724 mL (1152-2 415 mL), in which 1 289 mL (786-2 039 mL) was in the daytime and 435 mL (292-805 mL) in the night. The mean drinking volume was 1 022 mL (453-1 721 mL) in the daytime and 7 mL (0-43 mL) in the night. The nocturia index (Ni) was 1.03, the nocturnal polyuria index (NPi) 26%, and the nocturnal bladder capacity index (NBCi) 0.27. CONCLUSION: The remote & mobile voiding diary monitoring system can help us get the objective voiding information from young health people for the first time. It is reliable, maneuverable and can be widely used in clinical diagnosis.

[Advances in clinical study of nocturia].

Nocturia is one of the most common reasons for interrupted sleep in general adult population. The condition affects both men and women, with an incidence that increases dramatically with age. Nocturia has a negative impact on quality of life, affecting both morbidity and mortality. International Continence Society (ICS) issued a report of terminology standardization in 2002, in which nocturia is defined as waking during the night at least once to urinate. Nocturia is a common complaint in elderly population. Although most cases of nocturia are assumed to be caused by urologic problems, the interacting effects of aging and sleep on renal and urinary function, in fact, cause nocturia in the elderly. Effective diagnosis of the condition is dependent on a clear understanding of its underlying etiology. Multiple factors may cause nocturia, such as behavioral or environmental factors and pathologic conditions. In general, the causes of nocturia fall into three categories: diurnal polyuria, nocturnal polyuria, and low bladder capacity. Careful evaluation of medications and underlying medical conditions is essential for the proper management of nocturia. A voiding diary is necessary to diagnose the syndrome of nocturnal polyuria, which is a common cause of nocturia. Addressing any underlying conditions that contribute to nocturia is the first step in treating the condition. Lifestyle and behavioral changes may provide benefit in some individuals, but for many cases, pharmacotherapy is the best option. Antimuscarinic agents are first-line therapies for overactive bladder and are often used in the management of nocturia. Current treatment options also include desmopressin, a synthetic analog of arginine vasopressin, which can increase urinary osmolality and decrease total urinary volume. The desmopressin therefore increases the length of time until the first nocturnal void and decreases the number of nocturnal voids, the NUV voided, and the percentage of urine voided at night.

UPK3A: a promising novel urinary marker for the detection of bladder cancer.

OBJECTIVES: Current methods for reliable detection of bladder cancer have some limitations. Finding better noninvasive methods for detection of bladder cancer is an important topic in urology. We want to evaluate prospectively the early detection power of human uroplakin 3 A (UPK3A) for bladder cancer. METHODS: Urine samples were obtained from 32 healthy volunteers, 44 patients with benign urological disorders and 122 patients with bladder cancer. The urine UPK3A levels were quantified by enzyme-linked immunosorbent assay. All the samples were also tested with NMP22 test and cytology examination. RESULTS: The urinary UPK3A levels are uniformly elevated in bladder cancer patients than in those of normal volunteers and patients with benign urological disorders, and the differences in the mean urinary UPK3A levels of bladder cancer patients and those of normal individuals or benign urological disorders are statistically significant (P <.01). The receiver operating characteristic (ROC) curve of UPK3A showed an excellent area under the ROC curve of 0.907. In this study, the optimal combination of sensitivity and specificity were determined as 83% and 83%, for a cut-off value of absorbance unit 0.0685, respectively. The sensitivity of urine UPK3A, NMP22, and cytology for detecting bladder cancer were 83%, 58%, and 64%, respectively, whereas specificity was 83%, 75%, and 82%, respectively. CONCLUSIONS: We conclude that individuals with bladder cancer have higher UPK3A values. Our data suggest that urine measurement of UPK3A is a sensitive marker for the detection of bladder cancer. However, it needs further studies in larger cohorts.

Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma.

BACKGROUND: With the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology. METHODOLOGY: The expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients. PRINCIPAL FINDINGS: A total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e.g., cell cycle and apoptosis pathways) and cell communication (e.g., focal adhesion and ECM-receptor interaction) were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of ∼50 ccRCC patients. CONCLUSIONS: Our study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC.