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INTRODUCTION AND OBJECTIVE:Non–muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous; thus many patients fail to respond to treatment and relapse. Here, we identified a molecular signa...

INTRODUCTION AND OBJECTIVES:on-muscle-invasive BC (NMIBC) is a malignant disease characterized by high recurrence and progression rates, which constitutes significant challenge. At present, urinary...

The appropriate management for asymptomatic renal stones remains unclear. We assessed the natural history and progression rate of such stones and identified clinical factors associated with an increased risk of stone related events.We retrospectively reviewed the medical records of 201 male and 146 female patients with asymptomatic renal stones. It was recommended that patients be followed every 6 months. Mean followup was 31 months (range 6 to 180). Patients were divided into 2 groups by stone related events, including spontaneous stone passage, flank pain, stone growth or the need for intervention during followup.Spontaneous passage occurred in 101 patients (29.1%). Of the patients 186 (53.6%) and 161 (46.4%) did and did not have stone related events, respectively. Of the whole cohort 85 patients (24.5%) required intervention but only 4.6% needed surgery. At 19 months after diagnosis 50% of the patients had a symptom. Those with stone related events were more likely to be younger (mean ± SD age 46.6 ± 12.7 vs 49.3 ± 12.6 years) and male, and have a stone history (p = 0.047, 0.017 and 0.014, respectively). Male gender significantly decreased the probability of freedom from stone related events (log rank test p = 0.0135) and it was an independent predictor of stone related events (HR 1.521, p = 0.009). Younger patients, and those with smaller stones and no stone growth were more likely to experience spontaneous passage and less likely to undergo intervention (each p0.05).Asymptomatic renal stones can be followed safely but long-term followup is necessary. Periodic followup and early intervention should be recommended in patients with risk factors.

INTRODUCTION AND OBJECTIVES: Recently, a proteomic study of sera from patients with bladder cancer identified S100A8 and S100A9 as tumor-associated proteins. The present cross-sectional study investigates whether calprotectin, the heterodimer of S100A8/ S100A9 may serve as a urinary biomarker for the detection of urothelial bladder cancer. METHODS: Urinary calprotectin concentrations were assessed in a population of 181 subjects including 46 cases of bladder cancer. 41 cases of renal cell cancer, 54 cases of prostate cancer, and 40 healthy subjects served as control. Acute kidney injury, urinary tract infection, previous BCG-treatment and secondary transurethral resection of the bladder tumor were defined as exclusion criteria. Assessment was performed by ELISA and immunohistochemistry detecting calprotectin. RESULTS: Mean calprotectin concentrations (ng/ml) were significantly higher in patients with bladder cancer than in healthy controls (522.3 vs. 51.0, p < 0.001), renal cell cancer (90.4, p < 0.001), and prostate cancer (71.8, p < 0.001). In urothelial carcinoma prominent immunostaining occurred in a subset of tumor cells and in infiltrating myeloid cells. Receiver operating characteristic (ROC) analysis provided an AUC of 0.87 for the differentiation of bladder cancer and healthy control. A cut-off value of 140 ng/ml (determined by Youden’s index) resulted in sensitivity and specificity values of 80,4% and 92,5%. Low grade tumors were associated with significantly lower calprotectin concentrations than high grade tumors (351.9 vs. 1635 ng/ml, p 1⁄4 0.004). CONCLUSIONS: Urothelial malignancies are associated with highly increased concentrations of calprotecin in the urine. In absence of renal failure and pyuria, calprotectin constitutes a promising biomarker for the detection of bladder cancer.

of the PC away from normal renal parenchyma) is classically used for familial Renal Cell Carcinoma (RCC) but has not been widely adopted for sporadic RCC. We investigate whether tumor histology predicts the presence, thickness, and extension of tumor through the PC, potentially identifying tumors best suited for a TE nephron-sparing approach. METHODS: Twenty-five consecutive total or partial nephrectomies for pT1 clear cell, papillary, chromophobe, and oncocytoma were included (N 100 total tumors). Specimens were reviewed for numerous pathological features including stage, grade, lympho-vascular invasion, as well as characteristics of PC such as capsular presence/ absence, mean thickness, continuity, and tumor capsule invasion (TCI). PC parameters (thinnest, thickest and mean) were calculated from multiple measurements using an ocular micrometer, rounded to the nearest tenth of a millimeter. RESULTS: Tumor sizes in each group were similar. PC was complete in: papillary (n 21, 84%), clear cell (n 19, 76%), chromophobe (n 7, 28%), and oncocytoma (n 1, 4%); present but incomplete in oncocytoma (n 14, 56%), chromophobe (n 11, 44%), clear cell (n 6, 24%), and papillary (n 2, 8%); and absent in oncocytoma (n 10, 40%), chromophobe (n 7, 28%), papillary(n 2, 8%), and clear cell (0%). TCI was seen in 30% of papillary and only 8% of clear cell (p-value 0.006) PC. When present, mean thickness of the PC was significantly thicker for clear cell (0.8mm) when compared to the other tumors (papillary and chromophobe 0.6mm and oncocytoma 0.3mm). Multivariate logistic regression demonstrated only tumor type to be significantly associated with TCI (p-value 0.046, OR 10.3 (95%CI)). CONCLUSIONS: In pT1 renal tumors, PC appears predictable based on tumor histology. The PC is likely to be absent or incomplete in renal oncocytoma and chromophobe. Papillary RCC demonstrates the highest % of TCI which could predict higher surgical margin rates during TE surgery. Clear cell RCC possesses the thickest, most complete tumor capsule with minimal TCI and may be best suited for TE partial nephrectomy.

INTRODUCTION AND OBJECTIVES: This study aimed to identify the value of RUNX3 methylation in normal adjacent urothelium of the patients with non-muscle invasive bladder cancer NMIBC). METHODS: Fifty-five tumor tissues and normal donor-matched adjacent tissues from patients underwent transurethral resection (TUR) were selected. RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RESULTS: Methylation rate of RUNX3 in normal adjacent urothelium was 47.3%. Promoter methylation occurred frequently in both pathologically normal urothelium and tumor samples from NMIBC patients, and correlated with the transition from normal to bladder tumor (P 0.020). Methylation in normal adjacent urothelium was associated with tumor number (P 0.022) and progression (P 0.035). KaplanMeier estimates revealed that RUNX3 methylation of normal urothelium was associated with significant differences in time to progression (P 0.017) in NMIBC. Multivariate Cox regression analysis showed that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P 0.042] was an independent predictor of recurrence. CONCLUSIONS: In patients with NMIBC after TUR, RUNX3 methylation in normal adjacent urotehlium predict the disease progression exactly.

INTRODUCTION AND OBJECTIVES: Aberrant methylation of promoter CpG islands is known to be a major inactivation mechanism of the tumor suppressor and tumor-related genes. Ras association domain family 1A (RASSF1A) promotor hypermethylation has been shown to be associated with bladder cancer (BC), but the exact prognostic effects of RASSF1A remain to be elusive. The aim of the present study was to investigate the effect of RASSF1A methylation status as a prognostic marker in BC tissues. METHODS: Primary BC tissues were obtained from 301 patients whose tumors comprised 186 non-muscle invasive bladder cancers (NMIBC) and 115 muscle invasive bladder cancers (MIBC). The association between the hypermethylation of RASSF1A and clinicopathological characteristics of enrolled patients was analyzed using methylation specific polymerase chain reaction. The prognostic significance of the RASSF1A was evaluated by Kaplan-Meier and multivariate Cox regression model. RESULTS: Promoter hypermethylation of RASSF1A was present in 33.6% of BC and occurred more frequently in MIBC (46.1%) than in NMIBC (25.8%) (P 0.001). Methylation was associated with high tumor stage (P 0.026), high grade (P 0.001) and progression (P 0.039), when compared with tumors without methylation in NMIBC. Among the patients with recurrence in NMINC, Kaplan-Meier estimates revealed significant differences in time to progression according to the RASSF1 gene methylation status (P 0.002). Multivariate Cox regression analysis revealed that methylation of RASSF1A (hazards ratio: 15.592, P 0.001) was an independent predictor of cnacer progression in the patients with recurred NMIBC. CONCLUSIONS: It is very difficult to predict the prognosis and to select the optimal treatment modality in recurred NMIBC patients. Identification of RASSF1A methylation status as a prognosticator for predicting progression in patients with recurred NMIBC might be useful in a clinical setting.