Cystoscopy is considered the gold standard for the clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it may compromise patients' compliance and account for the failure in detecting recurrent BC in some patients. In this paper, we investigated the role of urinary metabonomics in the diagnosis of human BC. Gas chromatography/time-of-flight mass spectrometry was applied for the urinary metabolic profiling of 24 BC patients and 51 non-BC controls. The acquired data were analyzed using multivariate principal component analysis followed by orthogonal partial least-squares discriminant analysis (OPLS-DA). Model validity was verified using permutation tests and receiver operating characteristic (ROC) analysis. BC patients were clearly distinguished from non-BC subjects based on their global urinary metabolic profiles (OPLS-DA, 4 latent variables, R(2)X = 0.420, R(2)Y = 0.912 and Q(2) (cumulative) = 0.245; ROC AUC of 0.90; 15 marker metabolites). One-hundred percent sensitivity in detecting BC was observed using urinary metabonomics versus 33% sensitivity achieved by urinary cytology. Additionally, urinary metabonomics exhibited potential in the staging and grading of bladder tumors. In summary, urinary metabonomics is amenable for the noninvasive diagnosis of human BC.

Cystoscopy is the gold standard clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it compromises patients' compliance toward surveillance screening and challenges the detection of recurrent BC. Therefore, the development of a noninvasive method for the diagnosis and surveillance of BC and the elucidation of BC progression become pertinent. In this study, urine samples from 38 BC patients and 61 non-BC controls were subjected to urinary metabotyping using two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS). Subsequent to data preprocessing and chemometric analysis, the orthogonal partial least-squares discriminant analysis (OPLS-DA, R2X=0.278, R2Y=0.904 and Q2Y (cumulative)=0.398) model was validated using permutation tests and receiver operating characteristic (ROC) analysis. Marker metabolites were further screened from the OPLS-DA model using statistical tests. GC×GC-TOFMS urinary metabotyping demonstrated 100% specificity and 71% sensitivity in detecting BC, while 100% specificity and 46% sensitivity were observed via cytology. In addition, the model revealed 46 metabolites that characterize human BC. Among the perturbed metabolic pathways, our clinical finding on the alteration of the tryptophan-quinolinic metabolic axis in BC suggested the potential roles of kynurenine in the malignancy and therapy of BC. In conclusion, global urinary metabotyping holds potential for the noninvasive diagnosis and surveillance of BC in clinics. In addition, perturbed metabolic pathways gleaned from urinary metabotyping shed new and established insights on the biology of human BC.

SUMMARY Intravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients’ urine. This study concerns the production of IL‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, tumour necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ) and soluble ICAM‐1 (sICAM‐1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL‐1β, IL‐2, IL‐6, IL‐8, IL‐10, TNF‐α, IFN‐γ and sICAM‐1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL‐6, IL‐8 and IL‐10) could be detected after the first instillation, whilst others (e.g. IL‐2 and IFN‐γ) were not detected until after the third or fourth instillation. Interestingly, IL‐4 was not detected, perhaps suggesting a differential effect on Th2‐like responses. Some patients produced particularly elevated or non‐detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought t o be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data.

This meta-analysis evaluated the efficacy and safety of periprostatic nerve block (PPNB) and intrarectal local anesthestic (IRLA) gel in alleviating pain during prostate biopsy. Electronic databases MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE were searched to identify all randomized controlled trials comparing PPNB with periprostatic placebo injection, no injection or with IRLA. Studies for inclusion were identified and extracted by two authors independently. The main outcome measure was patients' assessment of mean pain scores on a 10-point scale at the end of the biopsy procedure. Secondary outcomes were complications and adverse events. Continuous data from the trials were combined by calculating the weighted mean difference (WMD) with its 95% confidence interval. In total, 25 studies met the inclusion criteria. Twenty studies involving 1685 patients compared PPNB with either no anesthesia or with placebo injection controls, showing a significant reduction in pain score in the anesthetic group (WMD À2.09, 95% CI À2.44 to À1.75, Po0.00001). Five studies with 466 patients compared IRLA and control. Although IRLA was associated with pain reduction, the effect size was not statistically significant (WMD À0.22, 95% CI À0.56 to 0.12). Six studies with 872 patients compared PPNB with IRLA, showing a significant pain reduction in the former group (WMD À1.53, 95% CI À2.67 to À0.39, P ¼ 0.008). No trials reported an increase in complications in the treatment arms. In conclusion, the evidence from randomized controlled trials shows that local anesthetic given as a PPNB, but not as an intrarectal instillation, is effective and safe in alleviating pain from transrectal ultrasound biopsy of the prostate.