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.

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.

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.

[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.

[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.

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.