BMC Urology - Latest articles

ProCOC: The prostate cancer outcomes cohort study

2008-06-17

Background: Despite intensive research over the last several decades on prostate cancer, many questions particularly those concerning early diagnosis and the choice of optimal treatment for each individual patient, still remain unanswered. The goal of treating patients with localized prostate cancer is a curative one and includes minimizing adverse effects to preserve an adequate quality of life. Better understanding on how the quality of life is affected depending on the treatment modality would assist patients in deciding which treatment to choose; furthermore, the development of prognostic biomarkers that indicate the future course of the illness is a promising approach with potential and the focus of much attention. These questions can be addressed in the context of a cohort study.Methods/DesignThis is a prospective, multi-center cohort study within the canton of Zurich, Switzerland. We will include patients with newly diagnosed localized prostate cancer independently of treatment finally chosen. We will acquire clinical data including quality of life and lifestyle, prostate tissue specimen as well as further biological samples (blood and urine) before, during and after treatment for setup of a bio-bank. Assessment of these data and samples in the follow up will be done during routine controls. Study duration will be at least ten years. Influence of treatment on morbidity and mortality, including changes in quality of life, will be identified and an evaluation of biomarkers will be performed. Further we intend to set up a bio-bank containing blood and urine samples providing research of various natures around prostate cancer in the future.DiscussionWe presume that this study will provide answers to pertinent questions concerning prognosis and outcomes of men with localised prostate cancer.

Optimized haemostasis in nephron-sparing surgery using small-intestine submucosa

2008-04-29

Background: The indications for nephron-sparing surgery are expanding constantly. One major contributing fact for this development is the improvement of haemostatic techniques following excision of the tumor. Nevertheless, postoperative bleeding complications still occur. To prevent this, we prospectively studied the effect of application of small-intestine submucosa (SIS) over the renal defect. Methods: We performed 55 nephron-sparing surgeries applying SIS between 08/03 and 10/06 in 53 pts. (mean age: 59 yrs., range 29 – 79 yrs.). After resection of the renal tumor and application of a haemostyptic agent, we used SIS to secure and apply compression on the defect. Results: The final pathology revealed clear-cell and papillary carcinoma, papillary adenoma, oncocytoma, and angiomyolipoma in 39 (70.9%), 6 (10.9), 1 (1.8%), 2 (3.6%) and 7 (12.7%) patients, respectively. The 45 malignant lesions (81.8%) were classified as pT1a and pT1b in 35 (77.8%) and 10 (22.2%) patients, respectively. The median tumor size was 4.5 cm (range: 1.3 – 13 cm). The median operating time was 186 min (range: 90 – 260 min). 18 (32.7%) procedures were performed without ischemia. 23 (41.8%) and 14 (25.5%) cases were operated in in-situ cold and warm ischemia, respectively. The median intraoperative blood loss was 730 cc (range: 100 – 2500 cc). No open operative revision was indicated due to postoperative bleeding complications. Furthermore, there was no necessity to substitute persistent blood loss from the drains postoperatively. No urinoma occurred. Conclusion: SIS is a highly effective and easy-to-use instrument for preventing postoperative bleeding and urinary fistula complications in nephron-sparing surgery.

Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

2008-04-23

Background: Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC) in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods: Flat panel detector-based cone beam computed tomography (FPDCT) was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT). Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1) protein expression. Results: Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071) and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.). Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion: FPDCT allows longitudinal monitoring of exophytic tumor growth in the UPII-SV40T model of BC that bypasses need for chemical carcinogens, which confound analysis of androgen effects. Androgens increase tumor cell growth in vitro and in vivo and decrease TSP1 expression, possibly explaining the therapeutic effect of castration. This effect may, in part, explain gender differences in BC incidence and implies anti-androgenic therapies may be effective in preventing and treating BC.

Sutureless prepuceplasty with wound healing by second intention: An alternative surgical approach in children's phimosis treatment

Efstratios Christianakis — 2008-03-04

Background: A new technique for the treatment of children's phimosis is presented that minimizes the repairing time, the postoperative complications and maintains the physical foreskin appearance intact. Methods: Eightyseven children with phimosis were treated with this new developed technique, between 2003 and 2005. Sutureless prepuceplasty creates a permanent surgical extension of the close prepuce. Stretching and retraction of phimotic foreskin reveals a tight prepuce ring that is cutting in its dorsal surface longitudinally. Rarely triple symmetric incisions in the preputial outlet are necessary. The foreskin is loose and moves absolutely free in bilateral courses. The wounds are healing by second intention. Antisepsis, steroids and Elicina cream, (which contains allantoin, collagen, elastin, glycolic acid and vitamins A, D, and E) should apply daily, for twenty to thirty days. Results: The foreskin is moving in centripetal or efferent courses absolutely loosely, painlessly and bloodlessly. The mean time of follow-up was 27 months (one to four years). No complications were observed. Conclusion: Sutureless prepuceplasty may present an acceptable alternative in children's phimosis reconstruction.

Antimicrobial peptides of the Cecropin-family show potent antitumor activity against bladder cancer cells

2008-03-03

Background: This study evaluated the cytotoxic and antiproliferative efficacy of two well-characterized members of the Cecropin-family of antimicrobial peptides against bladder tumor cells and benign fibroblasts. Methods: The antiproliferative and cytotoxic potential of the Cecropins A and B was quantified by colorimetric WST-1-, BrdU- and LDH-assays in four bladder cancer cell lines as well as in murine and human fibroblast cell lines. IC50 values were assessed by logarithmic extrapolation, representing the concentration at which cell viability was reduced by 50%. Scanning electron microscopy (SEM) was performed to visualize the morphological changes induced by Cecropin A and B in bladder tumor cells and fibroblasts. Results: Cecropin A and B inhibit bladder cancer cell proliferation and viability in a dose-dependent fashion. The average IC50 values of Cecropin A and B against all bladder cancer cell lines ranged between 73.29 μg/ml and 220.05 μg/ml. In contrast, benign fibroblasts were significantly less or not at all susceptible to Cecropin A and B. Both Cecropins induced an increase in LDH release from bladder tumor cells whereas benign fibroblasts were not affected. SEM demonstrated lethal membrane disruption in bladder cancer cells as opposed to fibroblasts. Conclusion: Cecropin A and B exert selective cytotoxic and antiproliferative efficacy in bladder cancer cells while sparing targets of benign murine or human fibroblast origin. Both peptides may offer novel therapeutic strategies for the treatment of bladder cancer with limited cytotoxic effects on benign cells.

Study of the response of the penile corporal tissue and cavernosus muscles to micturition

Ahmed Shafik, Ismail A Shafik, Olfat El Sibai and Ali A Shafik — 2008-03-02

Background: The reaction of the corpora cavernosa (CC), the corpus spongiosum (CS), the bulbocavernosus (BCM) and ischiocavernosus (ICM) muscles to passage of urine through the urethra during micturition is not known. We investigated the hypothesis that the passage of urine through the urethra stimulates the corporal tissue and cavernosus muscles. Methods: In 30 healthy men (mean age 42.8 ± 11.7 years), the electromyographic activity (EMG) of the CC, CS, BCM, and ICM were recorded before and during micturition, and on interruption of and straining during micturition. These tests were repeated after individual anesthetization of urethra, corporal tissue, and cavernosus muscles. Results: During micturition, the slow wave variables (frequency, amplitude, conduction velocity) of the CC and CS decreased while the motor unit action potentials of the BCM and ICM increased; these EMG changes were mild and returned to the basal values on interruption or termination of micturition. Micturition after individual anesthetization of urethra, corporal tissue and cavernosal muscles did not effect significant EMG changes in these structures, while saline administration produced changes similar to those occurring before saline administration. Conclusion: The decrease of sinusoidal and increase of cavernosus muscles' EMG activity during micturition apparently denotes sinusoidal relaxation and cavernosus muscles contraction. Sinusoidal muscle relaxation and cavernosus muscles contraction upon micturition are suggested to be mediated through a 'urethro-corporocavernosal reflex'. These sinusoidal and cavernosus muscle changes appear to produce a mild degree of penile tumescence and stretch which might assist in urinary flow during micturition.

CT scanning for diagnosing blunt ureteral and ureteropelvic junction injuries

Sarah J Ortega, Fernado S Netto, Paul Hamilton, Peter Chu and Homer C Tien — 2008-02-07

Background: Blunt ureteral and ureteropelvic (UPJ) injuries are extremely rare and very difficult to diagnose. Many of these injuries are missed by the initial trauma evaluation. Methods: Trauma registry data was used to identify all blunt trauma patients with ureteral or UPJ injuries, from 1 April 2001 to 30 November 2006. Demographics, injury information and outcomes were determined. Chart review was then performed to record initial clinical and all CT findings. Results: Eight patients had ureteral or UPJ injuries. Subtle findings such as perinephric stranding and hematomas, and low density retroperitoneal fluid were evident on all initial scans, and prompted delayed excretory scans in 7/8 cases. As a result, ureteral and UPJ injuries were diagnosed immediately for these seven patients. These findings were initially missed in the eighth patient because significant associated visceral findings mandated emergency laparotomy. All ureteral and UPJ injuries have completely healed except for the case with the delay in diagnosis. Conclusion: Most blunt ureteral and UPJ injuries can be identified if delayed excretory CT scans are performed based on initial CT findings of perinephric stranding and hematomas, or the finding of low density retroperitoneal fluid.

Duloxetine versus placebo for the treatment of women with stress predominant urinary incontinence in Taiwan: a double-blind, randomized, placebo-controlled trial

2008-01-25

Background: This manuscript compares the efficacy and safety of duloxetine with placebo in Taiwanese women with SUI. Methods: Taiwanese women with SUI were were randomly assigned to placebo (n = 61) or duloxetine 80 mg/day (n = 60) in this double-blind, 8-week, placebo-controlled study. Outcome variables included: incontinence episode frequency (IEF), Incontinence Quality of Life questionnaire (I-QOL) scores, and Patient Global Impression of Improvement rating (PGI-I). Results: Decrease in IEF was significantly greater in duloxetine-treated than placebo-treated women (69.98% vs 42.56%, P < .001). No treatment differences in I-QOL scores were significant. There were significant differences in PGI-I rating. Treatment-emergent adverse events (TEAEs) were experienced by more duloxetine-treated than placebo-treated women (80.0% vs 44.3%; P < .001). Discontinuations due to adverse events were significantly greater for duloxetine-treated than placebo-treated women (26.7% vs 6.6%; P = .003). Conclusion: Data provide evidence for the safety and efficacy of duloxetine for the treatment for Taiwanese women with SUI.Trial RegistrationClinicalTrials.gov Identifier: NCT00475358

Factorial validity and internal consistency of the PRAFAB questionnaire in women with stress urinary incontinence

2008-01-24

Background: To investigate the factor structure, dimensionality and construct validity of the (5-item) PRAFAB questionnaire score in women with stress urinary incontinence (stress UI). Methods: A cross validation study design was used in a cohort of 279 patients who were randomly divided into Sample A or B. Sample A was used for preliminary exploratory factor analyses with promax rotation. Sample B provided an independent sample for confirming the premeditated and proposed factor structure and item retention. Internal consistency, item-total and subscale correlations were determined to assess the dimensionality. Construct validity was assessed by comparing factor-based scale means by clinical characteristics based on known relationships. Results: Factor analyses resulted in a two-factor structure or subscales: items related to 'leakage severity' (protection, amount and frequency) and items related to its 'perceived symptom impact' or consequences of stress UI on the patient's life (adjustment and body (or self) image). The patterns of the factor loadings were fairly identical for both study samples. The two constructed subscales demonstrated adequate internal consistency with Cronbach's alphas in a range of 0.78 and 0.84 respectively. Scale scores differed by clinical characteristics according to the expectations and supported the construct validity of the scales. Conclusion: The findings suggest a two-factorial structure of the PRAFAB questionnaire. Furthermore the results confirmed the internal consistency and construct validity as demonstrated in our previous study. The best description of the factorial structure of the PRAFAB questionnaire was given by a two-factor solution, measuring the stress UI leakage severity items and the perceived symptom impact items. Future research will be necessary to replicate these findings in different settings, type of UI and non-white women and men.

The urologic epithelial stem cell database (UESC) – a web tool for cell type-specific gene expression and immunohistochemistry images of the prostate and bladder

2007-12-11

Background: Public databases are crucial for analysis of high-dimensional gene and protein expression data. The Urologic Epithelial Stem Cells (UESC) database http://scgap.systemsbiology.net/ is a public database that contains gene and protein information for the major cell types of the prostate, prostate cancer cell lines, and a cancer cell type isolated from a primary tumor. Similarly, such information is available for urinary bladder cell types.DescriptionTwo major data types were archived in the database, protein abundance localization data from immunohistochemistry images, and transcript abundance data principally from DNA microarray analysis. Data results were organized in modules that were made to operate independently but built upon a core functionality. Gene array data and immunostaining images for human and mouse prostate and bladder were made available for interrogation. Data analysis capabilities include: (1) CD (cluster designation) cell surface protein data. For each cluster designation molecule, a data summary allows easy retrieval of images (at multiple magnifications). (2) Microarray data. Single gene or batch search can be initiated with Affymetrix Probeset ID, Gene Name, or Accession Number together with options of coalescing probesets and/or replicates. Conclusion: Databases are invaluable for biomedical research, and their utility depends on data quality and user friendliness. UESC provides for database queries and tools to examine cell type-specific gene expression (normal vs. cancer), whereas most other databases contain only whole tissue expression datasets. The UESC database provides a valuable tool in the analysis of differential gene expression in prostate cancer genes in cancer progression.