Complement Component 1, s Subcomponent Overexpression is an Independent Poor Prognostic Indicator in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder.

PURPOSE: Urothelial carcinoma of the urinary bladder and upper tract is prevalent. By subjecting a documented transcriptome data set of urothelial carcinoma of bladder (GSE31684) to data mining and focusing on genes linked to peptidase activity (GO:0008233), we recognized C1S as the most significantly upregulated gene related to an advanced tumor status and metastasis. We subsequently analyzed the association of both C1S mRNA and its encoded protein expression with the clinical and pathological significance. MATERIALS AND METHODS: We used real-time reverse transcription polymerase chain reaction to detect C1S transcription levels in 20 cases each of urothelial carcinoma of bladder and upper tract. An immunohistochemical stain was conducted to determine C1s protein expression levels in patients with urothelial carcinoma of upper tract (n = 340) and urinary bladder (n = 295). Furthermore, we examined the correlation of C1s expression with clinicopathological characteristics, disease-specific survival, and metastasis-free survival. RESULTS: C1S transcription levels were significantly high in patients with advanced-stage tumors of both groups (all P < .05). Immunohistochemical analysis revealed that C1s expression levels were significantly associated with adverse clinicopathological parameters in both groups of urothelial carcinoma (all P < .05). C1s overexpression predicted poor disease-specific and metastasis-free survival rates for both urothelial carcinoma groups in the univariate analysis, and it was also an independent prognostic factor in the multivariate analysis (all P < .05). CONCLUSIONS: C1s may play a pivotal role in urothelial carcinoma progress and can represent a vital prognostic marker and a promising new therapeutic target in urothelial carcinoma.

SPOCK1 Overexpression Confers a Poor Prognosis in Urothelial Carcinoma.

PURPOSE: The majority deaths of cancer patients are related to metastasis, thus genes associated with cell motility interest us. SPOCK1 was elected by data mining and serial evaluation. In addition, SPOCK1 has been reported to be highly expressed in different human cancers and been related to adverse outcomes. Therefore, we validate its prognostic significance in urothelial carcinoma (UC). MATERIALS AND METHODS: Real-time RT-PCR assay was used to detect SPOCK1 transcript level in 27 urinary tract urothelial carcinoma (UTUC) and 27 urinary bladder urothelial carcinoma (UBUC) samples. Immunohistochemistry evaluated by H-score determined SPOCK1 expressions in 340 UTUCs and 295 UBUCs. The transcript and protein expression were correlated with clinicopathological features. Further evaluations of the prognostic significance of SPOCK1 for disease-specific survival (DSS) and metastasis-free survival (MeFS) were analyzed. RESULTS: The expressions of SPOCK1 in UC were higher than those in normal urothelium by immunohistochemistry. The statistical analysis of clinicopathologic characteristics and immunohistochemistry showed that the higher expression of SPOCK1 was correlated to pT status (P<0.001), lymph node metastasis (UTUC, P=0.006; UBUC, P=0.033), higher histological grade (UTUC, P<0.001; UBUC, P<0.001), vascular invasion (UTUC, P<0.001; UBUC, P<0.001), perineurial invasion (UTUC, P<0.001; UBUC, P=0.001) and frequent mitosis (UTUC, P<0.001; UBUC, P=0.001). The prognosis of SPOCK1 of UC showed high SPOCK1 expression had significantly worse DSS and MeFS. CONCLUSIONS: The investigation demonstrated that the higher expression of SPOCK1 correlates with a poor prognosis in UC.

BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

AIMS: Amino acid biosynthesis is one of the cardinal events of carcinogenesis that has not been investigated in urothelial carcinoma (UC). By data-mining a published transcriptomic database of UCs of urinary bladder (UBUCs) (GSE31684), we identified branched-chain amino acid transaminase 1 (BCAT1) as the most significantly stepwise up-regulated gene during tumour progression among those associated with the amino acid biosynthetic process (GO:0008652). Accordingly, we analysed BCAT1 transcript and protein expression with their clinicopathological significance. METHODS AND RESULTS: We used real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect BCAT1 transcript levels in 20 UCs of upper tract (UTUCs) and 20 UBUCs, respectively. Immunohistochemical study was performed to determine BCAT1 protein expression in 340 UTUCs and 295 UBUCs. Higher BCAT1 transcript levels were associated with higher pT status in both groups (P < 0.05). BCAT1 protein overexpression was also associated significantly with adverse clinicopathological features, e.g. advanced pT stage, nodal metastasis, high pathological grade, etc. (P < 0.05). BCAT1 overexpression predicted worse disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (P ≤ 0.001). CONCLUSION: BCAT1 overexpression is associated with advanced tumour status, and implies adverse clinical outcomes of UCs, suggesting that its role in tumour progression could serve as a prognostic biomarker and a novel therapeutic target in UC.

Noncontrast computed tomography can predict the outcome of shockwave lithotripsy via accurate stone measurement and abdominal fat distribution determination.

Urolithiasis is a common disease of the urinary system. Extracorporeal shockwave lithotripsy (SWL) has become one of the standard treatments for renal and ureteral stones; however, the success rates range widely and failure of stone disintegration may cause additional outlay, alternative procedures, and even complications. We used the data available from noncontrast abdominal computed tomography (NCCT) to evaluate the impact of stone parameters and abdominal fat distribution on calculus-free rates following SWL. We retrospectively reviewed 328 patients who had urinary stones and had undergone SWL from August 2012 to August 2013. All of them received pre-SWL NCCT; 1 month after SWL, radiography was arranged to evaluate the condition of the fragments. These patients were classified into stone-free group and residual stone group. Unenhanced computed tomography variables, including stone attenuation, abdominal fat area, and skin-to-stone distance (SSD) were analyzed. In all, 197 (60%) were classified as stone-free and 132 (40%) as having residual stone. The mean ages were 49.35 ± 13.22 years and 55.32 ± 13.52 years, respectively. On univariate analysis, age, stone size, stone surface area, stone attenuation, SSD, total fat area (TFA), abdominal circumference, serum creatinine, and the severity of hydronephrosis revealed statistical significance between these two groups. From multivariate logistic regression analysis, the independent parameters impacting SWL outcomes were stone size, stone attenuation, TFA, and serum creatinine. [Adjusted odds ratios and (95% confidence intervals): 9.49 (3.72-24.20), 2.25 (1.22-4.14), 2.20 (1.10-4.40), and 2.89 (1.35-6.21) respectively, all p < 0.05]. In the present study, stone size, stone attenuation, TFA and serum creatinine were four independent predictors for stone-free rates after SWL. These findings suggest that pretreatment NCCT may predict the outcomes after SWL. Consequently, we can use these predictors for selecting the optimal treatment for patients with urinary stones.

Effects of supraphysiological testosterone treatment and orchiectomy on ischemia/reperfusion-induced bladder dysfunction in male rabbits.

INTRODUCTION: The roles of testosterone and orchiectomy on male bladder subjected to ischemic/reperfusion (I/R) injuries received little attention. To fill this gap, the present study intended to examine testosterone and orchiectomy effects on male rabbits subjected to I/R damages. AIM: To elucidate the effects of testosterone and orchiectomy on contractile response, bladder morphology, interstitial fibrosis, and oxidative stress in male rabbit bladder subjected to I/R surgery. METHODS: Male New Zealand rabbits were distributed into five groups as follows: Group 1 received sham surgical procedure. In group 2, I/R surgery was performed. In group 3, testosterone (100 µg/kg/day) was intramuscularly injected prior to I/R surgery. In group 4, orchiectomy was performed prior to I/R surgery. In group 5, orchiectomy was performed with subsequent testosterone administration, followed by I/R surgery. All the rabbits were euthanized 7 days after I/R. Comparative studies were analyzed to elucidate the effects of testosterone and orchiectomy on bladder dysfunction subjected to I/R injuries. MAIN OUTCOME MEASURES: Bladder contractile function was evaluated. Masson's trichrome staining and immunohistochemical studies were performed to evaluate bladder morphology and intramural nerve terminals. Western blotting was examined to investigate the expressions of fibrosis and oxidative stress markers. RESULTS: I/R surgery significantly decreased bladder contractility in response to various stimulations with and without testosterone treatment. I/R damages decreased bladder nerve density with and without testosterone. The expressions of fibrosis and oxidative stress-related proteins were increased by I/R injuries with or without testosterone treatment. Testosterone depletion significantly decreased the expressions of transforming growth factor-ß and fibronectin expressions after I/R injury. Supraphysiological testosterone treatment after orchiectomy greatly increased the expressions of these fibrosis proteins; however, orchiectomy alone ameliorated I/R injuries. CONCLUSIONS: Testosterone treatment or orchiectomy affected I/R-induced bladder damages in male rabbits. Orchiectomy decreased the level of fibrosis and oxidative stress markers and increased neurofilament densities. Supraphysiological exogenous testosterone administration after orchiectomy further exacerbated such detrimental effects of I/R.

Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis.

OBJECTIVES: We have reported previously that the TP53 codon72 polymorphism (rs1042522) is associated with the incidence and invasiveness of bladder cancer in a Han Chinese population. Using an enlarged sample, we investigated the role of rs1042522 and of tagSNPs that were predicted to be in linkage disequilibrium with codon72 in relation to the incidence, invasiveness, and prognosis of bladder cancer. METHODS AND MATERIALS: A sample of 201 patients and 311 controls without cancer were genotyped for 5 tagSNPs using tetra-primer ARMS and/or an allele-specific PCR technique. RESULTS: The genotyped data were analyzed using Haploview 4.2, and a 10,000-permutation test showed that the rs9895829G allele (P = 0.003) and the rs1788227C allele (P = 0.027) were both associated with the incidence of bladder cancer. With respect to haplotype associations, after the data were adjusted for age, the haplotypes GTT (P = 0.001) and GGTC (P < 0.001) were correlated with a low incidence of bladder cancer. In contrast, none of the TP53 haplotypes were associated significantly with high tumor grade or muscle invasiveness. On the basis of Cox regression analysis, haplotype CGCC and invasiveness were associated with cancer-related death. Structural equation modeling showed that haplotypes GGCC and CGCC played opposing roles with respect to bladder cancer-related death; haplotype GGCC was a protective factor, whereas haplotype CGCC was a risk factor. CONCLUSIONS: The TP53 codon72 polymorphism appears to play a crucial role in determining the association between TP53 haplotype and the incidence and prognosis of bladder cancer. Further functional assays to confirm whether these TP53 haplotypic variants interact with the proteins N-Myc and NDRG is necessary.

Sexual dysfunction in women with ketamine cystitis: a case-control study.

OBJECTIVE: • To conduct a case-control study evaluating clinical symptom severity and sexual dysfunction in women with ketamine cystitis (KC). PATIENTS AND METHODS: • In total, 29 patients with KC and 27 controls completed the symptoms survey. • Participants completed a visual pelvic pain analogue scale, an O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index questionnaire, a Female Sexual Function Index, and a short form of the Chinese Health Questionnaire-12. RESULTS: • Both the Interstitial Cystitis Symptom Index and Interstitial Cystitis Problem Index scores were significantly higher in patients with KC compared to controls (P < 0.001). • The prevalence of sexual dysfunction was high in patients with KC. • There was a difference in total adjusted Female Sexual Function Index scores between the patients with KC and controls: mean (sd) total Female Sexual Function Index score 17.65 (6.15) for KC cases vs 25.87 (4.16) for controls (P < 0.001). • Except for the sexual desire domain of female sexual dysfunction, patients with KC scored lower on all domains compared to controls. • There was no significant difference between patients with KC and controls with respect to mental health as evaluated by the Chinese Health Questionnaire-12. CONCLUSIONS: • Sexual dysfunction and KC symptoms severely impacted on quality of life. • Mental health had no significant difference between patients with KC and controls.

p53 codon 72 polymorphism as a progression index for bladder cancer.

The aim of this study was to calculate the positive predictive value (PPV) and negative predictive value (NPV) to determine whether p53 codon 72 can be used as a bladder cancer management index. Ninety-six patients diagnosed with bladed cancer and two control groups of 427 randomly sampled community participants and 142 non-cancerous individuals without a prior history of cancer were enrolled. After preliminary analysis, the convergent validity resulted in 96 patients from this study and 129 patients from our previous study. Results showed that these two groups were of the same population, and could be merged into one case group. Logistic regression showed that the Pro/Pro genotype was not statistically significantly associated with bladder cancer incidence using each sample set after adjustment by age and gender. Moreover, the Pro/Pro genotype was not associated with high-grade tumors (P=0.078), but was highly correlated to muscle-invasive tumors (P=0.002). Pro/Pro genotype carriers were estimated to have a 3.36-fold higher risk to develop invasive tumors compared to non-carriers. The NPV of the Pro/Pro genotype for invasive tumors was 88.00%, and the PPV was 31.91%. By Cox regression analysis, high-grade tumors were associated with recurrence (P=0.020, OR=1.83), whereas invasive tumors were associated with cancer-related death (P<0.001, OR=2.87). p53 codon 72 polymorphism is associated with bladder cancer progression rather than incidence and prognosis. The Pro/Pro genotype in p53 codon 72 polymorphism shows a high NPV for bladder cancer progression, thus, it can be used clinically as a progression index in bladder cancer management.

p53 codon 72 polymorphism was associated with vulnerability, progression, but not prognosis of bladder cancer in a Taiwanese population: an implication of structural equation modeling to manage the risks of bladder cancer.

INTRODUCTION: p53 codon 72 polymorphism has been reported to be associated with bladder cancer incidence, progression and prognosis, but the association is still under debate. A tentative model was constructed to evaluate the association between p53 codon 72 polymorphism and bladder cancer. SUBJECTS AND METHODS: In this study, a total of 554 participants were enrolled. The genotyping was carried out using PCR-RFLP and DNA direct sequencing. RESULTS: The genotype distribution of p53 codon 72 polymorphism was significantly different between bladder cancer patients and controls (p = 0.039). In logistic regression, diagnostic age and genotype Pro/Pro were the risk factors for developing an invasive tumor. A 4.526-fold risk was estimated for the patients with Pro/Pro genotype as opposed to non-Pro/Pro genotype to develop invasive tumors. However, the extent of p53 codon 72 polymorphism did not predict bladder cancer prognosis. CONCLUSIONS: A conceptual mode was constructed; in addition, the moderating and mediating analysis was also carried out in a structural equation model to resolve possible confounding effects. Taken together, p53 codon 72 polymorphism may be associated with bladder cancer incidence and progression, but not prognosis. Further study is needed to evaluate the usefulness of the constructed model in risk assessment.

TP53 codon 72 Gene Polymorphism Paradox in Associated with Various Carcinoma Incidences, Invasiveness and Chemotherapy Responses.

TP53 is the most common mutated gene in human cancers. Approximately half of all human malignancies exhibit TP53 mutations. The TP53 codon 72 polymorphism is a single-nucleotide polymorphism (SNP) in exon 4, resulting in the expression of either arginine (CGC) or proline (CCC) residues. In this article, we review literatures published in MEDLINE, and attempt to describe how these two polymorphic variants of TP53 are functionally distinct, and how they influence cancer vulnerability and response to chemotherapy. The Arg72 variant has been shown to be more likely to induce apoptosis than the Pro72 variant, due to its ability to localize itself to mitochondria and trigger the release of cytochrome c into the cytosol. However, the influence of the TP53 codon 72 polymorphism on the risk of developing various cancers, and their progression remains inconclusive because there has been no sustained evidence supporting a crucial role for the codon 72 variant in cancer therapy till now. We hypothesize that TP53 gene might not only be involved in cell cycle control and the apoptosis induction response to DNA damage, but may also modulate individual cancer risk, and that this may correlate with the biofunctions of the two codon 72 variants. Additionally, latent factors might function synergistically with codon 72 variants to confer susceptibility to cancer development, progression, prognosis, and therapeutic responsiveness. Further etiological investigations are essential to reveal the association of and interaction between genetic and environmental factors in relation to carcinogenesis.

Mutation of the p53 tumor suppressor gene in transitional cell carcinoma of the urinary tract in Taiwan.

Early detection of a mutated p53 gene is thought to provide useful information in a wide range of human tumors. The aim of this study was to identify the role of the p53 gene in transitional cell carcinoma of the urinary tract. From March 1992 to July 2003, 75 patients (54 men and 21 women) with a mean age of 66.85 years and pathologically diagnosed transitional cell carcinoma were enrolled in this study. Fifty-eight patients had bladder cancer, eight had ureteral cancer, and nine had renal-pelvic cancer. Rapid screening for mutation of the p53 gene was performed using polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and sequencing analysis. Primer sets were designed to amplify fragments within exons 4, 5, 6, 7, and 8 of the p53 gene. Pathology classified 37 tumors as low grade and 38 as high grade. Tumor stage was pT1 or less in 29 patients and at least pT2 in 46 patients. Of the 75 patients in this study, 47 (62.7%) had a p53 mutation. Of the patients with a p53 mutation, 33 (70.2%) had invasive tumors. Invasive tumors were associated with p53 mutation (p < 0.05). Noted in 20 patients (26.7%), exon 4 was the most common site of the mutation. Of the patients with exon 4 mutations, 15 (75%) had invasive tumors and nine (45%) had high-grade tumors. Additionally, among the 20 patients with a common polymorphism at codon 72, 16 (80%) had invasive tumors and 14 (70%) had high-grade tumors. In this study, 62.7% of patients with transitional cell carcinoma had a p53 mutation, suggesting that the p53 gene mutation may be used as a marker of transitional cell carcinoma. Invasive tumors are more likely to have a p53 gene mutation. A simple analysis of the p53 gene using PCR/SSCP is suitable for screening for p53 abnormalities in transitional cell carcinoma. The relationship between cancer risk and the codon 72 polymorphism of exon 4 needs further investigation.

Acute necrotizing ureteritis with obstructive uropathy following instillation of silver nitrate in chyluria: a case report.

Chyluria occurs as a result of communication between the lymphatics and the renal pelvis. It is believed that instillation of silver nitrate into the renal pelvis is a safe, minimally invasive and effective treatment for chyluria. We report an unusual complication of acute necrotizing ureteritis following instillation of silver nitrate in a case of chyluria. It resolved completely with non-surgical intervention. The diagnosis and management of chyluria is discussed, with a brief review of the literature.

Spontaneous dissecting aneurysm of the renal artery: a case report.

Primary dissecting aneurysms of the renal artery are exceedingly rare. The triad of flank pain, hematuria, and hypertension of acute onset in the absence of urinary obstruction should suggest this rare condition. We report a case of spontaneous dissecting aneurysm of the renal artery treated using conservative medical treatment. The diagnosis, therapeutic management, and outcome are discussed.