Diagnostic value of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 pathway in transitional cell carcinoma of the bladder.

Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase (MMP)-9, and NGAL/MMP-9 complex have been evaluated as diagnostic markers of several cancers, but results for bladder cancer are scanty. We evaluated these proteins in urine and serum of 89 patients with histologically confirmed bladder cancer and 119 cancer-free controls from a case-control study. Urinary concentrations were standardized on creatinine level. The performance of these proteins as cancer biomarkers was evaluated through the receiver operating characteristic (ROC) analysis. Urinary level of NGAL, MMP-9, and NGAL/MMP-9 complex was higher in current smokers, whereas no impact of dietary habits was observed. After adjusting for tobacco smoking, urinary concentration of MMP-9 was independently associated with cancer invasiveness, grading, and histological subtype, with elevated concentrations among T2-T4 and non-papillary bladder cancers. Conversely, NGAL and NGAL/MMP-9 complex were significantly higher in non-papillary than in papillary subtype. The pattern was less clear in serum, but correlation between urinary and serum concentration was poor, especially for Ta/is-T1 tumors. The ROC analysis confirmed that MMP-9 was the best marker (area under the ROC curve (AUC) = 0.68). Performances were much greater for muscle-invasive bladder cancers (AUC = 0.90), with elevated negative predictive values (97 %). The present study suggests that NGAL/MMP-9 pathway is associated with an aggressive phenotype of bladder cancer. The elevated negative predictive value of MMP-9 and NGAL/MMP-9 complex makes them candidate markers of exclusion test for bladder cancer. These proteins may be integrated in the surveillance of bladder cancer, thus diminishing patients' discomfort and improving compliance.

Histopathological characteristics of microfocal prostate cancer detected during systematic prostate biopsy.

OBJECTIVE: To evaluate the prevalence of adverse pathological features and the percentage of multifocal and/or bilateral disease in a series of patients who underwent radical prostatectomy (RP) for unique, microfocal prostate cancer (miPCa) detected on prostate biopsy in the pre-active surveillance (AS) era. PATIENTS AND METHODS: In this retrospective, multi-institutional study, we analysed the clinical records of 131 consecutive patients who underwent either retropubic or robot-assisted RP for miPCa at two referral centres from January 2000 to December 2011. miPCa was defined as a neoplastic lesion present in ≤10% of core with biopsy Gleason score not applicable or biopsy Gleason score 6. RESULTS: There were 17 (13%) pT3-4 prostate cancers and a single case (0.8%) of pN+ tumour. Moreover, 31 (24.1%) patients had a Gleason score of >6 in the RP specimen. Therefore, unfavourable pathological features (pT3-4/N+ and/or Gleason score >6) were present in 40 (30.5%) patients. The median (interquartile range) prostate-specific antigen (PSA) density was 0.11 (0.09-0.17) and 0.16 (0.11-0.24) ng/mL/mL in patients with favourable and unfavourable pathological characteristics, respectively (P = 0.003). The receiver operating characteristic curve had an area under the curve value of 0.67 (95% confidence interval 0.56-0.77) for PSA density to predict the risk of unfavourable pathological features. CONCLUSION: Patients with miPCa who are candidates for an AS protocol should be adequately informed that in ≈30% of cases the cancer might be locally advanced and/or with a Gleason score of >6. Those unfavourable pathological characteristics could be predicted by the PSA density value. Further studies should investigate the role of a more extensive biopsy sampling to reduce the risk of under-staging and/or under-grading in patients with an initial diagnosis of miPCa.

Retrograde transureteral approach: a safe and efficient treatment for recurrent cystine renal stones.

Most patients presenting cystinuria require multiple urological procedures during their lifetime. In this kind of patients the availability of minimally invasive procedure represents an advantage of minimizing the cumulative morbidity of several repeated treatments. Herein we report our experience using ureterorenoscopy (URS) for the treatment of recurrent renal cystine stones. From 2003 to 2007, 10 patients (4 males and 6 females) with one or multiple recurrent renal cystine stones underwent URS. Overall, 21 procedures have been performed. Mean maximum diameter of stones was 11.2 mm (range 5-30 mm). Either 8-9.5 F semirigid or 7.9 F flexible ureteroscopes were used. In 6 cases, stones were removed using a basket; in 9 procedures laser lithotripsy with flexible scope was performed; in 6 cases renal calculi were pulled down in the ureter using flexible instrument and then shattered with laser introduced by semirigid instrument. Stone-free status was defined as the absence of any residual fragment. A complete stone clearance was obtained in 15 out of 21 procedures (71%). In 5 cases (24%) significant residual fragments occurred; in the remaining case (5%) URS was ineffective. In 5 out of these unsuccessful procedures, stone clearance was obtained with auxiliary treatments. The last patient has not been treated yet. No major complications occurred as a result of the procedures. URS offers excellent advantages in case of recurrent hard calculi such as cystine stones. Minimally invasive procedures allow satisfactory outcomes, improving patients' quality of life.

Role of transperineal six-core prostate biopsy in patients with prostate-specific antigen level greater than 10 ng/mL and abnormal digital rectal examination findings.

OBJECTIVES: To define whether six-core biopsies still have a role in patients presenting with prostate-specific antigen (PSA) levels greater than 10 ng/mL and abnormal digital rectal examination (DRE) findings. Recent studies have suggested that the six-core biopsy is inadequate for the diagnosis of prostate cancer; however, it remains controversial whether an increased number of cores is justified in all patients. METHODS: From June 2002 to February 2005, 122 (18.8%) of 650 patients underwent prostate biopsy because of a PSA level greater than 10 ng/mL and abnormal DRE findings. All patients underwent transperineal ultrasound-guided prostate biopsy in a standardized fashion: a six-core biopsy was performed first, followed by six additional cores during the same session, four in the peripheral and two in the transition zone. RESULTS: The detection rate in patients with a PSA level greater than 10 ng/mL and abnormal DRE findings was 72.1% (88 of 122) and 75.4% (92 of 122) using the 6-core and 12-core biopsy, respectively. One case of tumor was missed by the six-core biopsy among patients with a PSA level greater than 15 ng/mL and abnormal DRE findings. No cases of tumor were missed by six-core biopsy in the group with a PSA level greater than 20 ng/mL and abnormal DRE findings. CONCLUSIONS: Six-core biopsy provided a similar cancer detection rate compared with 12-core biopsy in patients with PSA levels greater than 10 ng/mL and abnormal DRE findings. An initial approach with 6-core biopsy is reasonable in patients with a PSA level greater than 10 ng/mL and abnormal DRE findings and is advocated in those with PSA greater than 20 ng/mL and abnormal DRE findings.