Clinical performance and utility of a NNMT-based urine test for bladder cancer.

BACKGROUND: Bladder cancer (BC) represents the most common neoplasm of the urinary tract. Although cystoscopy and urine cytology represent the gold standard methods to monitor BC, both procedures have limitations. Therefore, the identification of reliable biomarkers for early and noninvasive detection of BC is urgently required. METHODS: In this study, we analyzed nicotinamide N-methyltransferase (NNMT) expression in urine samples from 55 BC patients and 107 controls, using real-time polymerase chain reaction (PCR). Receiver operating characteristic (ROC) analysis was used to identify the best cutoff value to discriminate BC patients from healthy donors, and to evaluate the diagnostic accuracy of a urine-based NNMT test. RESULTS: The results demonstrated that urinary NNMT expression was significantly (p<0.05) higher in BC patients. Moreover, a significant (p<0.05) inverse correlation was found between NNMT expression and histological grade. The ROC analysis revealed that a ΔCq of 13.3 was the best cutoff value, since it was associated with the highest combination of sensitivity and specificity. Moreover, the area under the curve (AUC) value was 0.913 (p<0.05), indicating the excellent diagnostic accuracy of a urine-based NNMT test. CONCLUSIONS: Our data indicate that NNMT is a promising biomarker that could be used to support the early and noninvasive diagnosis of BC.

Safety and efficacy of percutaneous nephrolithotomy in the Galdakao - Modified Supine Valdivia position: A prospective analysis.

OBJECTIVE: Aim of the present study was to evaluate the safety and efficacy of Percutaneous Nephrolithotomy (PCNL) in the Galdakao- Modified Supine Valdivia (GMSV) position in order to predict operative time, stone-free rate and onset of complications taking into account comorbidity, stone-related parameters and anatomic upper urinary tract abnormalities. MATERIAL AND METHODS: A prospective evaluation of patients who underwent to PCNL in GMSV position for renal stones > 2 cm, from January 2009 to February 2015 was performed. According to the technique, upper urinary tract abnormalities, stone chemical and morphological characteristics, and patients' history were matched with operative outcome, in terms of stone-free, intervention time and incidence of perioperative complications. RESULTS: Seventy-two cases were collected; mean operative time was 105 minutes (DS 41): staghorn stones and the presence of comorbidity resulted statistically significant variables. The complication-rate resulted in line with data showed in literature: hyperpyrexia and hemorrhage were the more frequently complications found. The overall stone-free was reached in 48 patients (67%), and it was influenced by patients' anatomic abnormalities. CONCLUSIONS: In the treatment of renal stones, PCNL may be a safe and effective choice; nevertheless, patients' anatomic abnormalities or staghorn-stones may influence the outcomes. Thus, a prospective study with a larger population is needed to verify our outcomes.

The role of intraoperative ultrasound in small renal mass robotic enucleation.

INTRODUCTION: As a result of the growing evidence on tumor radical resection in literature, simple enucleation has become one of the best techniques associated to robotic surgery in the treatment of renal neoplasia, as it guarantees minimal invasiveness and the maximum sparing of renal tissue, facilitating the use of reduced or zero ischemia techniques during resection. The use of a robotic ultrasound probe represents a useful tool to detect and define tumor location, especially in poorly exophytic small renal mass. MATERIALS AND METHODS: A total of 22 robotic enucleations were performed on < 3 cm renal neoplasias (PADUA score 18 Pz 6/7 e 4 Pz 8) using a 12-5 MHz robotic ultrasound probe (BK Drop-In 8826). RESULTS: Once kidney had been isolated from the adipose capsule at the site of the neoplasia (2), the exact position of the lesion could be easily identified in all cases (22/22), even for mostly endophytic lesions, thanks to the insertion of the ultrasound probe through the assistant port. Images were produced and visualized by the surgeon using the TilePro feature of the DaVinci surgical system for producing a picture-in-picture image on the console screen. The margins of resection were then marked with cautery, thus allowing for speedy anatomical dissection. This reduced the time of ischemia to 8 min (6-13) and facilitated the enucleation technique when performed without clamping the renal peduncle (6/22). No complications due to the use of the ultrasound probe were observed. CONCLUSIONS: The use of an intraoperative robotic ultrasound probe has allowed for easier identification of small, mostly endophytic neoplasias, better anatomical approach, shorter ischemic time, reduced risk of pseudocapsule rupture during dissection, and easier enucleation in cases performed without clamping. It is noteworthy that the use of intraoperative ultrasound probe allows mental reconstruction of the tumor through an accurate 3D vision of the hidden field during surgical dissection.

Upregulation of tissue and urinary nicotinamide N-methyltransferase in bladder cancer: potential for the development of a urine-based diagnostic test.

Carcinoma of the bladder is one of the most common urologic malignancies occurring worldwide. Diagnosis and monitoring of bladder urothelial carcinoma (UC) are based on cystoscopy and urinary cytology. However, these diagnostic methods still have some limitations, mainly related to invasive nature and lack of sensitivity. New reliable and non-invasive biomarkers for bladder cancer detection are therefore required. To explore the involvement of enzymes of drug metabolism in bladder cancer, in the present study, we analyzed the gene expression profiles of tumor and normal looking tissues obtained from the same patient by cDNA macroarray. The enzyme nicotinamide N-methyltransferase (NNMT) was identified as a highly expressed gene in bladder cancer. RT-PCR, Real-Time PCR, Western blot analysis, and catalytic activity assay, performed on a large cohort of patients with bladder UC, confirmed NNMT upregulation. NNMT mRNA and protein levels were also determined in urine specimens obtained from patients with bladder UC and healthy subjects. We found that NNMT expression levels were significantly higher in patients with bladder tumor compared to controls that showed very low or undetectable amounts of NNMT transcript and protein. Our results indicate that a marked NNMT increase is a peculiar feature of bladder UC and suggest the potential suitability of urine NNMT expression levels determination for early and non-invasive diagnosis of bladder cancer.