Effective diagnosis and surveillance of Bladder Cancer (BCa) is currently challenged by detection methods that are of poor sensitivity, particularly for low-grade tumors, resulting in unnecessary invasive procedures and economic burden. We performed HR-MAS NMR-based global metabolomic profiling and applied unsupervised principal component analysis (PCA) and hierarchical clustering performed on NMR dataset of bladder derived tissues and identified metabolic signatures that differentiate BCa from benign disease. A partial least-square discriminant analysis (PLS-DA) model (leave-one-out cross-validation) was used as diagnostic model to distinguish benign and BCa tissues. Receiver operating characteristic curve generated either from PC1 loadings of PCA or from predicted Y-values resulted in an area under curve of 0.97. Relative quantification of more than fifteen tissue metabolites derived from HR-MAS NMR showed significant differences (P < 0.001) between benign and BCa samples. Noticeably, striking metabolic signatures were observed even for early stage BCa tissues (Ta-T1) demonstrating the sensitivity in detecting BCa. With the goal of cross-validating metabolic signatures derived from HR-MAS NMR, we utilized the same tissue samples to analyze eight metabolites through gas chromatography-mass spectrometry (GC-MS)-targeted analysis, which undoubtedly complements HR-MAS NMR derived metabolomic information. Cross-validation through GC-MS clearly demonstrates the utility of straightforward, non-destructive and rapid HR-MAS NMR technique for clinical diagnosis of BCa with even greater sensitivity. In addition to its utility as a diagnostic tool, these studies will lead to a better understanding of aberrant metabolic pathways in cancer as well as the design and implementation of personalized cancer therapy through metabolic modulation.

OBJECTIVES To better understand the risk of short-term complications associated with perioperative intravesical mitomycin-C (MMC) therapy for patients undergoing endoscopic management of non-muscle invasive bladder cancer (NMIBC). METHODS AND MATERIALS Using an institutional database of patients with bladder cancer, we performed a retrospective case-control study of patients receiving perioperative MMC after tumor resection (2008–2012). MMC cases were matched by clinical stage to controls receiving endoscopic resection alone. Demographic information, clinicopathologic details and outcomes were compared between groups. Outcomes of interest included overall, genitourinary (GU) and major complications. Chi-square tests and multivariable logistic regression were used to evaluate associations between patient characteristics, clinical factors, exposure to MMC and outcomes of interest. RESULTS One-hundred sixteen patients treated with MMC were matched to 116 controls. Patients receiving MMC were younger (p=0.04) and more likely to have invasive disease (i.e., T1 or greater) (23% vs. 15%, p=0.02). Complications were more frequent among patients who were treated with MMC (34.5% vs. 19.8%, OR 2.89, 95% CI 1.43–5.81). The most common complication among MMC patients that required medical management was dysuria (17%). Major complications were more common among MMC patients (5.2% vs. 0.9%), but this difference did not reach statistical significance (p=0.11). CONCLUSIONS Use of MMC is associated with a greater odds of complications compared to controls. Patients should be counseled regarding both the benefits and potential risks of perioperative intravesical MMC. Continued research is required to understand the safety implications associated with the use of perioperative, intravesical MMC.

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