iTRAQ identification of candidate serum biomarkers associated with metastatic progression of human prostate cancer.

A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer 'BPH', (ii) localised cancer with no evidence of progression, 'non-progressing' (iii) localised cancer with evidence of biochemical progression, 'progressing', and (iv) bone metastasis at presentation 'metastatic'. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (p<0.001). Comparisons of metastatic versus progressing groups identified the significant differential expression of 23 proteins. Mapping the differentially expressed proteins onto the prostate cancer progression pathway revealed the dysregulated expression of individual proteins, pairs of proteins and 'panels' of proteins to be associated with particular stages of disease development and progression. The median immunostaining intensity of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation.

Durability and cost-effectiveness of transurethral needle ablation of the prostate as an alternative to transurethral resection of the prostate when alpha-adrenergic antagonist therapy fails.

PURPOSE: We analyzed the adverse event profile, long-term efficacy and cost-effectiveness of transurethral needle ablation of the prostate for lower urinary tract symptoms associated with benign prostatic hyperplasia as an alternative to transurethral resection of the prostate in men with symptoms uncontrolled by medical therapy. MATERIALS AND METHODS: A total of 71 men on a waiting list for transurethral resection of the prostate after failed medical therapy underwent transurethral needle ablation of the prostate. Symptom scores, uroflowmetry and residual urine were measured before and up to 10 years following treatment. Transrectal ultrasound and pressure flow studies were performed before, and 3 and 12 months following treatment, respectively. Treatment failure was defined as lower urinary tract symptoms progression requiring further therapy or associated with deteriorating quality of life assessment. RESULTS: Apart from transient postoperative urinary retention, no significant treatment emergent adverse events due to transurethral needle ablation of the prostate were observed. Treatment failure occurred in 58 men (83%) at a median of 20 months. A total of 36 men (51%) underwent invasive treatment (transurethral resection of the prostate 33, bladder neck incision 2, microwave thermal ablation 1), 2 men (3%) were deemed unfit for anesthesia and now practice clean intermittent self-catheterization, 14 men (20%) reported improvement following resumption of treatment with an alpha-adrenergic antagonist after transurethral needle ablation of the prostate and 6 men (9%) have experienced deterioration in lower urinary tract symptoms with reduction in quality of life assessment (International Prostate Symptom Score 3 or greater) but have declined further intervention. There were 12 men (17%) who remained symptom-free up to 10 years after transurethral needle ablation of the prostate. The estimated additional cost of treatment for lower urinary tract symptoms per man treated with transurethral needle ablation of the prostate during the 10-year followup was $1,377. CONCLUSIONS: Despite documented safety and lack of morbidity, the high re-treatment rate associated with transurethral needle ablation of the prostate renders it relatively expensive when viewed as a long-term alternative to transurethral resection of the prostate for the management of lower urinary tract symptoms associated with benign prostatic hyperplasia in men in whom medical therapy failed. Of men failing alpha-blockade therapy 20% will benefit from a combination of transurethral needle ablation of the prostate and alpha-blockade.

DNA methylation and immunohistochemical analysis of the S100A4 calcium binding protein in human prostate cancer.

BACKGROUND: The role of DNA methylation in the transcriptional regulation of S100A4 is unknown in human prostate cancer. METHODS: Critical CpG sites within intron 1 of S100A4 were sequenced in DNA obtained from prostatic adenocarcinoma, non-malignant epithelium, and prostate cancer cell lines. S100A4 protein expression was assessed by immunohistochemistry and Western blotting. RESULTS: Methylation was seen in all cases of cancer, non-malignant epithelium, and in prostate cancer cell lines, but was absent in all cases of blood DNA. S100A4 immunoexpression was absent in all cases of malignant and non-malignant epithelium, while strong-moderate expression was seen in the stroma and lymphocytes. Western blotting showed absent S100A4 expression in LNCaP and Du145 cells and low levels in PC-3 cells. CONCLUSIONS: S100A4 protein is not expressed in benign or malignant prostatic epithelium nor in LNCaP and Du145 cells. The mechanism underlying absent S100A4 expression in prostatic epithelium and cell lines may involve methylation.

Anaerobic meningitis secondary to a rectothecal fistula arising from an anterior sacral meningocele: report of a case and review of the literature.

An anterior sacral meningocele is a diverticulum of the thecal sac protruding anteriorly from the sacral spinal canal into the extraperitoneal presacral space. It is a rare congenital anomaly comprising of a thin wall of fibrous connective tissue, and containing cerebrospinal fluid and, occasionally, adjacent nerve fibers. We report an unusual case of a 48-year-old male who presented with meningitis secondary to a rectothecal fistula arising from an anterior sacral meningocele.