Study of the Apoptotic Effect in Patients with Urological versus Gynaecological Chronic Pelvic Pain.

The objective is to observe if it could be possible to use the apoptosis test to distinguish different aetiologies in chronic pelvic pain syndrome (CPPS). A prospective study was done, 106 patients, 57 had previously been diagnosed with urological chronic pelvic pain (UCPP)/interstitial cystitis (IC) and 49 patients with gynaecological chronic pelvic pain (GCPP). Neoplastic cells cultures were exposed to the urine of patients with UCPP/IC and patients with GCPP. The urine ability to provoque apoptosis on them was analysed. The apoptosis degree was measured by quantifying the percentage of cells in phase subG0, determined by a flow cytometry analysis. It is observed that the cell cultures exposed to urine of patients with UCPP had a significantly higher sub-G1 peak and G2 phase than those of the cells exposed to urine from patient's GCPP. The average values of apoptosis in patients with UCPP were significantly higher to that obtained in -patients having GCPP. With the apoptosis tests having a value >10%, it is considered as positive as well. This means that when we are faced with a patient who has UCPP or non-bladder chronic pelvic pain, the probability of having an UCPP increases by 45% when the apoptosis test is positive for a value >10%. Urine from patients with UCPP has significantly higher apoptotic effect over than the effect produced by urine from patients with GCPP. The apoptosis test could be useful as an illness biomarker.

Detection of prostate cancer using a voltammetric electronic tongue.

A simple method based on the multivariate analysis of data from urine using an electronic voltammetric tongue is used to detect patients with prostate cancer. A sensitivity of 91% and a specificity of 73% were obtained to distinguish the urine from cancer patients and the urine from non-cancer patients.

Towards the potential use of (1)H NMR spectroscopy in urine samples for prostate cancer detection.

A simple method based in multivariate analysis of (1)H NMR spectra profiles of urine samples can be used to detect patients with prostate cancer.

Enhancing Prostate Tumor Biobanking Reliability with Improved Sampling Technique and Histological Characterization.

Acquiring fresh and well-characterized tumor tissue samples is critical for conducting high-quality "omics" studies. However, it can be particularly challenging in the context of prostate cancer (PC) due to the unique nature of this organ and the high heterogeneity associated with this tumor. On the other hand, histopathologically characterizing samples before their storage without causing significant tissue alterations is also an intriguing challenge. In this context, we present a new method for acquiring, mapping, characterizing, and micro-dissecting resected prostate tissue based on anatomopathological criteria. Unlike previously published protocols, this method reduces the time required for histopathological analysis of the prostate specimen without compromising its structure, which is crucial for assessing surgical margins. Furthermore, it enables the delineation and micro-macro dissection of fresh prostate tissue samples, with a focus on histological tumor areas defined by pathological criteria such as Gleason score, precursor lesions (high-grade prostatic intraepithelial neoplasia - PIN), and inflammatory lesions (prostatitis). These samples are then stored in a Biobank for subsequent research analyses.

New bladder cancer non-invasive surveillance method based on voltammetric electronic tongue measurement of urine.

Bladder cancer (BC) is the sixth leading cause of death by cancer. Depending on the invasiveness of tumors, patients with BC will undergo surgery and surveillance lifelong, owing the high rate of recurrence and progression. In this context, the development of strategies to support non-invasive BC diagnosis is focusing attention. Voltammetric electronic tongue (VET) has been demonstrated to be of use in the analysis of biofluids. Here, we present the implementation of a VET to study 207 urines to discriminate BC and non-BC for diagnosis and surveillance to detect recurrences. Special attention has been paid to the experimental setup to improve reproducibility in the measurements. PLSDA analysis together with variable selection provided a model with high sensitivity, specificity, and area under the ROC curve AUC (0.844, 0.882, and 0.917, respectively). These results pave the way for the development of non-invasive low-cost and easy-to-use strategies to support BC diagnosis and follow-up.

Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer.

Bladder cancer (BC) represents a clinical, social, and economic challenge due to tumor-intrinsic characteristics, limitations of diagnostic techniques and a lack of personalized treatments. In the last decade, the use of liquid biopsy has grown as a non-invasive approach to characterize tumors. Moreover, the emergence of omics has increased our knowledge of cancer biology and identified critical BC biomarkers. The rewiring between epigenetics and metabolism has been closely linked to tumor phenotype. Chromatin remodelers interact with each other to control gene silencing in BC, but also with stress-inducible factors or oncogenic signaling cascades to regulate metabolic reprogramming towards glycolysis, the pentose phosphate pathway, and lipogenesis. Concurrently, one-carbon metabolism supplies methyl groups to histone and DNA methyltransferases, leading to the hypermethylation and silencing of suppressor genes in BC. Conversely, α-KG and acetyl-CoA enhance the activity of histone demethylases and acetyl transferases, increasing gene expression, while succinate and fumarate have an inhibitory role. This review is the first to analyze the interplay between epigenome, metabolome and cell signaling pathways in BC, and shows how their regulation contributes to tumor development and progression. Moreover, it summarizes non-invasive biomarkers that could be applied in clinical practice to improve diagnosis, monitoring, prognosis and the therapeutic options in BC.

Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer.

Patients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of pre-neoplastic lesions and carcinomas in situ (CIS), invasiveness, and high costs. This work aims to identify a urinary metabolomic signature of recurrence by proton Nuclear Magnetic Resonance (1H NMR) spectroscopy for the follow-up of NMIBC patients. To do this, changes in the urinary metabolome before and after transurethral resection (TUR) of tumors are analyzed and a Partial Least Square Discriminant Analysis (PLS-DA) model is developed. The usefulness of this discriminant model for the detection of tumor recurrences is assessed using a cohort of patients undergoing monitoring. The trajectories of the metabolomic profile in the follow-up period provide a negative predictive value of 92.7% in the sample classification. Pathway analyses show taurine, alanine, aspartate, glutamate, and phenylalanine perturbed metabolism associated with NMIBC. These results highlight the potential of 1H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach.

Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer.

Metabolism reprogramming is considered a hallmark of cancer. The study of bladder cancer (BC) metabolism could be the key to developing new strategies for diagnosis and therapy. This work aimed to identify tissue and urinary metabolic signatures as biomarkers of BC and get further insight into BC tumor biology through the study of gene-metabolite networks and the integration of metabolomics and transcriptomics data. BC and control tissue samples (n = 44) from the same patients were analyzed by High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance and microarrays techniques. Besides, urinary profiling study (n = 35) was performed in the same patients to identify a metabolomic profile, linked with BC tissue hallmarks, as a potential non-invasive approach for BC diagnosis. The metabolic profile allowed for the classification of BC tissue samples with a sensitivity and specificity of 100%. The most discriminant metabolites for BC tissue samples reflected alterations in amino acids, glutathione, and taurine metabolic pathways. Transcriptomic data supported metabolomic results and revealed a predominant downregulation of metabolic genes belonging to phosphorylative oxidation, tricarboxylic acid cycle, and amino acid metabolism. The urinary profiling study showed a relation with taurine and other amino acids perturbed pathways observed in BC tissue samples, and classified BC from non-tumor urine samples with good sensitivities (91%) and specificities (77%). This urinary profile could be used as a non-invasive tool for BC diagnosis and follow-up.

Model selection for within-batch effect correction in UPLC-MS metabolomics using quality control - Support vector regression.

Ultra performance liquid chromatography - mass spectrometry (UPLC-MS) is increasingly being used for untargeted metabolomics in biomedical research. Complex matrices and a large number of samples per analytical batch lead to gradual changes in the instrumental response (i.e. within-batch effects) that reduce the repeatability and reproducibility and limit the power to detect biological responses. A strategy for within-batch effect correction based on the use of quality control (QC) samples and Support Vector Regression (QC-SVRC) with a radial basis function kernel was recently proposed. QC-SVRC requires the optimization of three hyperparameters that determine the accuracy of the within-batch effects elimination: the tolerance threshold (ε), the penalty term (C) and the kernel width (γ). This work compares three widely used strategies for QC-SVRC hyperparameter optimization (grid search, random search and particle swarm optimization) using a UPLC-MS data set containing 193 urine injections as model example. Results show that QC-SVRC is robust to hyperparameter selection and that a pre-selection of C and ε, followed by optimization of γ is competitive in terms of accuracy, precision and number of function evaluations with full grid analysis, random search and particle swarm optimization. The QC-SVRC optimization procedure can be regarded as a useful non-parametric tool for efficiently complementing alternative approaches such as QC-robust splines correction (RSC).

Risk Model for Prostate Cancer Using Environmental and Genetic Factors in the Spanish Multi-Case-Control (MCC) Study.

Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model.

Efficacy and tolerability of fesoterodine in older and younger subjects with overactive bladder.

OBJECTIVES: To assess the effect of age on fesoterodine efficacy and tolerability in subjects with an overactive bladder. METHODS: The data from 2 randomized, 12-week studies of 1681 subjects treated with fesoterodine 4 or 8 mg or placebo were pooled and stratified by age. The subjects completed 3-day bladder diaries at baseline and weeks 2 and 12, the King's Health Questionnaire at baseline and week 12, and the Treatment Benefit Scale at week 12. RESULTS: Of the subjects aged <65 years, fesoterodine 4 and 8 mg was associated with statistically significant improvements in the diary variables at week 12 versus placebo. Greater improvement in urgency urinary incontinence was seen with fesoterodine 8 mg versus 4 mg. For those aged ≥65 to <75 years, fesoterodine 4 and 8 mg significantly improved all diary variables, except for the mean voided volume and micturition frequency, respectively, [corrected] versus placebo. In subjects aged ≥75 years, fesoterodine 8 mg significantly improved all diary variables, except for mean voided volume, versus placebo. No significant improvements were observed with fesoterodine 4 mg versus placebo. Fesoterodine significantly improved several King's Health Questionnaire domains versus placebo in all age groups. Fesoterodine 4 mg did not significantly improve any domains in subjects aged ≥75 years. In all age groups, the treatment response rates were significantly greater with both fesoterodine doses versus placebo. Dry mouth and constipation occurred more frequently in subjects aged ≥75 years receiving fesoterodine 8 mg than in those receiving fesoterodine 4 mg or placebo, although the discontinuation rates because of dry mouth and constipation were not increased. CONCLUSIONS: Fesoterodine 4 and 8 mg effectively treated overactive bladder symptoms in subjects aged <75 years. Fesoterodine 8 mg was effective in subjects aged ≥75 years.

Manejo quirúrgico de la endometriosis vésico-ureteral y sus complicaciones / Surgical management of deep endometriosis

La endometriosis ureteral es una infrecuente localización de endometriosis profunda, que puede condicionar una grave disminución de la función renal de forma silenciosa. Se presenta el caso de una paciente con fibrosis peritoneal secundaria a endometriosis profunda, cuya inespecífica sintomatologia conllevó un retraso diagnóstico, permitiendo el desarrollo de hidronefrosis. Es necesario descartar la presencia de endometriosis profunda en mujeres en edad fértil con hidronefrosis de etiología desconocida.

Deep endometriosis rarely entails ureteral involvement. It may be responsible of asymptomatic loss of renal function. A 35-year-old woman, gravida 1, para 1, was managed for peritoneal fibrosis due to deep infiltrating endometriosis. The nonspecific symptoms let a delayed diagnosis and a subsequent hydronephrosis. It must be excluded the existence of deep endometriosis in women of childbearing age with hydronephrosis of unknown etiology.