Conservative management for postprostatectomy urinary incontinence

BACKGROUND: Urinary incontinence is common after radical prostatectomy and can also occur in some circumstances after transurethral resection of the prostate (TURP). Conservative management includes pelvic floor muscle training with or without biofeedback, electrical stimulation, extra-corporeal magnetic innervation (ExMI), compression devices (penile clamps), lifestyle changes, or a combination of methods.   OBJECTIVES: To determine the effectiveness of conservative management for urinary incontinence up to 12 months after transurethral, suprapubic, laparoscopic, radical retropubic or perineal prostatectomy, including any single conservative therapy or any combination of conservative therapies.  SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register (5 February 2014), CENTRAL (2014, Issue 1), EMBASE (January 2010 to Week 3 2014), CINAHL (January 1982 to 18 January 2014), ClinicalTrials.gov and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (both searched 29 January 2014), and the reference lists of relevant articles.  SELECTION CRITERIA: Randomised or quasi-randomised controlled trials evaluating conservative interventions for urinary continence in men after prostatectomy.  DATA COLLECTION AND ANALYSIS: Two or more review authors assessed the methodological quality of the trials and abstracted data. We tried to contact several authors of included studies to obtain extra information.  MAIN RESULTS: Fifty trials met the inclusion criteria, 45 in men after radical prostatectomy, four trials after TURP and one trial after either operation. The trials included 4717 men of whom 2736 had an active conservative intervention. There was considerable variation in the interventions, populations and outcome measures. Data were not available for many of the pre-stated outcomes. Men's symptoms improved over time irrespective of management.There was no evidence from eight trials that pelvic floor muscle training with or without biofeedback was better than control for men who had urinary incontinence up to 12 months after radical prostatectomy; the quality of the evidence was judged to be moderate (for example 57% with urinary incontinence in the intervention group versus 62% in the control group, risk ratio (RR) for incontinence after 12 months 0.85, 95% confidence interval (CI) 0.60 to 1.22). One large multi-centre trial of one-to-one therapy showed no difference in any urinary or quality of life outcome measures and had narrow CIs. It seems unlikely that men benefit from one-to-one PFMT therapy after TURP. Individual small trials provided data to suggest that electrical stimulation, external magnetic innervation, or combinations of treatments might be beneficial but the evidence was limited. Amongst trials of conservative treatment for all men after radical prostatectomy, aimed at both treatment and prevention, there was moderate evidence of an overall benefit from pelvic floor muscle training versus control management in terms of reduction of urinary incontinence (for example 10% with urinary incontinence after one year in the intervention groups versus 32% in the control groups, RR for urinary incontinence 0.32, 95% CI 0.20 to 0.51). However, this finding was not supported by other data from pad tests. The findings should be treated with caution because the risk of bias assessment showed methodological limitations. Men in one trial were more satisfied with one type of external compression device, which had the lowest urine loss, compared to two others or no treatment. The effect of other conservative interventions such as lifestyle changes remained undetermined as no trials involving these interventions were identified.  AUTHORS' CONCLUSIONS: The value of the various approaches to conservative management of postprostatectomy incontinence after radical prostatectomy remains uncertain. The evidence is conflicting and therefore rigorous, adequately powered randomised controlled trials (RCTs) which abide by the principles and recommendations of the CONSORT statement are still needed to obtain a definitive answer. The trials should be robustly designed to answer specific well constructed research questions and include outcomes which are important from the patient's perspective in decision making and are also relevant to the healthcare professionals. Long-term incontinence may be managed by an external penile clamp, but there are safety problems

Quantifying the natural history of post-radical prostatectomy incontinence using objective pad test data

BACKGROUND: Urinary incontinence (UI) following radical prostatectomy is a well-recognized risk of the surgery. In most patients post-operative UI improves over time. To date, there is limited objective, quantitative data on the natural history of the resolution of post-prostatectomy UI. The purpose of this study was to define the natural history of post radical prostatectomy incontinence using an objective quantitative tool, the 1-hour standard pad test. METHODS: 203 consecutive patients underwent radical prostatectomy by a single surgeon between 03/98 & 08/03. A standardized 1-hour pad test was administered at subsequent postoperative clinic visits. The gram weight of urine loss was recorded and subdivided into four groups defined according to the grams of urine loss: minimal (<1 g), mild (>1, <10 g), moderate (10–50 g) and severe (>50 g). Patients were evaluated: at 2 weeks (catheter removal), 6 weeks, 18 weeks, 30 weeks, 42 weeks and 54 weeks. The data set was analyzed for average urine loss as well as grams of urine loss at each time point, the percentage of patients and the distribution of patients in each category. RESULTS: Mean follow up was 118 weeks. The majority of patients experienced incontinence immediately after catheter removal at 2 weeks that gradually improved with time. While continued improvement was noted to 1 year, most patients who achieved continence did so by 18 weeks post-op. CONCLUSION: While the majority of patients experience mild to severe UI immediately following catheter removal, there is a rapid decrease in leaked weight during the first 18 weeks following RRP. Patients continue to improve out to 1 year with greater than 90% having minimal leakage by International Continence Society criteria

Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that the <it>ADIPOR1</it>, <it>ADORA1</it>, <it>BTG2 </it>and <it>CD46 </it>genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome.</p> <p>Methods</p> <p>Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers.</p> <p>Results</p> <p>BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (<it>P </it>= 0.026) and cell membrane specific expression (<it>P </it>= 0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling.</p> <p>Conclusions</p> <p>We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.</p

Molecular Signatures of Prostate Stem Cells Reveal Novel Signaling Pathways and Provide Insights into Prostate Cancer

BACKGROUND:The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS:A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis. There is also a significant lipid metabolism signature, marked by overexpression of lipid metabolizing enzymes and the presence of the binding motif for Srebp1. The fetal stem cell population, characterized by more rapid proliferation and self-renewal, expresses regulators of the cell cycle, such as E2f, Nfy, Tead2 and Ap2, at elevated levels, while adult stem cells show a signature in which TGF-beta has a prominent role. Finally, comparison of the signatures of primitive prostate cells with previously described profiles of human prostate tumors identified stem cell molecules and pathways with deregulated expression in prostate tumors including chromatin modifiers and the oncogene, Erg. CONCLUSIONS/SIGNIFICANCE:Our data indicate that adult prostate stem or progenitor cells may acquire characteristics of self-renewing primitive fetal prostate cells during oncogenesis and suggest that aberrant activation of components of prostate stem cell pathways may contribute to the development of prostate tumors

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases