Biomarkers in lower urinary tract symptoms/overactive bladder: a critical overview.

PURPOSE OF REVIEW: Biomarkers constitute objectively measurable characteristics that can be evaluated as indicators of physiological and pathogenic processes and might be used as diagnostic, prognostic or predictive tools in clinical care. This review examines the availability of biomarkers to treat the dynamic and complex symptoms of overactive bladder (OAB). RECENT FINDINGS: OAB biomarkers may contribute to reveal the origin of storage symptoms in otherwise healthy individuals. The research encompassing the changes that occur in the bladder or in the peripheral (and central) nervous system might be determined through blood or urinary molecules (neurotrophins, ATP, prostaglandins, C-reactive protein and cytokines) or the measurement of events occurring in the bladder wall (bladder wall or detrusor wall thickness, oxyhemoglobin and deoxyhemoglobin concentration). These biomarkers might contribute to a better understanding of the pathophysiologic mechanisms underlying OAB. SUMMARY: The word biomarker to name all the parameters described above, from bladder wall thickness to urinary molecules, has been introduced to call the attention to a field wherein objective noninvasive parameters were nonexistent. OAB treatment based on a biomarker, in comparison to the treatment based on a diagnosis made from a careful history and exclusion of urinary tract infection, is not supported by current literature.

Cell-based therapy for the deficient urinary sphincter.

When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.

Incidental prostate cancer at radical cystoprostatectomy: implications for apex-sparing surgery.

OBJECTIVE: To analyse retrospectively the clinicopathological features of incidental prostate cancer in patients undergoing radical cystoprostatovesiculectomy (RCP) for invasive bladder cancer, as recent studies suggest that prostatic apex-sparing surgery in patients undergoing RCP improves urinary continence and erectile function after surgery, but in those with incidental prostate cancer, leaving the apical region endangers the oncological outcome. PATIENTS AND METHODS: From 2004 to 2007, at our institution, 95 men had RCP for invasive bladder cancer. We reviewed their clinicopathological variables, especially apical involvement, and the course of prostate-specific antigen (PSA) levels before and after surgery. We compared clinically significant and insignificant prostate cancers. RESULTS: Of the 95 patients, 26 had incidental prostate cancer (mean age 68 years, range 53-80) on definitive histological examination. The mean (sd, range) preoperative PSA level in all 26 men was 3.6 (0.8, 0.2-14) ng/mL, but six of the 26 patients had preoperative PSA levels of >4 ng/mL and one other had suspicious findings on a digital rectal examination. Involvement of the apex was histologically confirmed in seven of the 26 patients (27%), including four with significant prostate cancer (P = 0.039). Preoperative PSA levels did not differ significantly between the seven patients with significant and 19 with insignificant prostate cancer, but seven patients with apical involvement had significantly higher PSA levels before RCP than the 19 who did not (P < 0.04). PSA levels after RCP remained below the limit of detection in all patients over a mean (range) follow-up 14.3 (3-32) months. CONCLUSION: In our series, preserving the apex of the prostate to decrease morbidity after RCP carried a 7.3% risk (seven of 95 patients) of leaving significant cancer in the residual prostatic tissue. No preoperative clinical value could exclude apical involvement. Therefore, our findings stress the oncological need for a careful and complete excision of the prostate during RCP.

Treatment outcomes and resource use of patients with neurogenic detrusor overactivity receiving botulinum toxin A (BOTOX) therapy in Germany.

PURPOSE: To evaluate treatment outcomes and resource consumption of patients with neurogenic detrusor overactivity (NDO) before and after botulinum toxin A (Botox) therapy in Germany. METHODS: In a multi-center, cross-sectional, retrospective cohort study, data of patients with NDO 12 months before and after the first Botox therapy were analyzed. RESULTS: 214 patients (mean age 38 +/- 14.8 years, 145 male, 69 female) with NDO due to spinal cord injury (81%); myelomeningocele (14%), or Multiple Sclerosis (5%) from seven hospitals were included. Mean interval between treatments was 8 months. Following treatment, mean maximum detrusor pressure, maximum cystometric capacity and detrusor compliance improved significantly. Prior to Botox therapy, 68% reported urinary tract infections (UTI), 63% had incontinence episodes, and 58% used incontinence aids. These numbers decreased significantly (p < 0.05) after treatment to 28, 33, and 28%, respectively. In patients using incontinence aids, mean costs per patient decreased from 2euro to 1euro per day, whereas the mean cost of drugs to treat UTIs per patient decreased from 163euro to 80euro per year, respectively. CONCLUSION: This is the first study demonstrating the clinical usefulness of Botox therapy in clinical practice. Successful treatment resulted in lower costs for NDO associated morbidity due to less need for incontinence aids and UTI medication.

Human Mesenchymal Stromal Cells from Different Sources Diverge in Their Expression of Cell Surface Proteins and Display Distinct Differentiation Patterns.

When germ-free cell cultures became a laboratory routine, hopes were high for using this novel technology for treatment of diseases or replacement of cells in patients suffering from injury, inflammation, or cancer or even refreshing cells in the elderly. Today, more than 50 years after the first successful bone marrow transplantation, clinical application of hematopoietic stem cells is a routine procedure, saving the lives of many every day. However, transplanting other than hematopoietic stem and progenitor cells is still limited to a few applications, and it mainly applies to mesenchymal stromal cells (MSCs) isolated from bone marrow. But research progressed and different trials explore the clinical potential of human MSCs isolated from bone marrow but also from other tissues including adipose tissue. Recently, MSCs isolated from bone marrow (bmMSCs) were shown to be a blend of distinct cells and MSCs isolated from different tissues show besides some common features also some significant differences. This includes the expression of distinct antigens on subsets of MSCs, which was utilized recently to define and separate functionally different subsets from bulk MSCs. We therefore briefly discuss differences found in subsets of human bmMSCs and in MSCs isolated from some other sources and touch upon how this could be utilized for cell-based therapies.

Towards a Treatment of Stress Urinary Incontinence: Application of Mesenchymal Stromal Cells for Regeneration of the Sphincter Muscle.

Stress urinary incontinence is a significant social, medical, and economic problem. It is caused, at least in part, by degeneration of the sphincter muscle controlling the tightness of the urinary bladder. This muscular degeneration is characterized by a loss of muscle cells and a surplus of a fibrous connective tissue. In Western countries approximately 15% of all females and 10% of males are affected. The incidence is significantly higher among senior citizens, and more than 25% of the elderly suffer from incontinence. When other therapies, such as physical exercise, pharmacological intervention, or electrophysiological stimulation of the sphincter fail to improve the patient's conditions, a cell-based therapy may improve the function of the sphincter muscle. Here, we briefly summarize current knowledge on stem cells suitable for therapy of urinary incontinence: mesenchymal stromal cells, urine-derived stem cells, and muscle-derived satellite cells. In addition, we report on ways to improve techniques for surgical navigation, injection of cells in the sphincter muscle, sensors for evaluation of post-treatment therapeutic outcome, and perspectives derived from recent pre-clinical studies.

Labelling and tracking of human mesenchymal stromal cells in preclinical studies and large animal models of degenerative diseases.

Success of stem cell therapies were reported in different medical disciplines, including haematology, rheumatology, orthopaedic surgery, traumatology, and others. Currently, more than 4000 clinical trials using stem cells have been completed or are underway, among which 378 investigated or are at present investigating mesenchymal stromal cells (MSCs). The majority of clinical trials using stem- or progenitor- cells, including hematopoietic stem cells and MSCs, target the immune system. However, therapies based on MSCs are increasingly implemented to treat symptoms in which failure of the resident stem cells in situ, or malfunction of tissues or structures are not associated with immune cells or inflammation, but instead are associated with mechanical or metabolic stress, ageing, developmental or acquired malformations, and other causes. To proceed further in the development of stem cell therapies as a safe and effective treatment for surgical and other medical specialities, the behaviour of MSCs implanted in preclinical models and their impact on the site of application need to be explored in detail. Depending on the pre-clinical model employed, tracking of labelled stem cells in live animals makes an enormous difference for exploration of the mechanisms and kinetics involved in MSC-mediated tissue regeneration. Here we review (pre-)clinically applicable key methods to label human MSCs for short and long-term observations in small and large animal models.