Identification of a novel recurrent EEF2 gene amplification in familial prostate tumors.

Recurrent tumor copy number variations (CNVs) in prostate cancer (PrCa) have predominantly been discovered in sporadic tumor cohorts. Here, we examined familial prostate tumors for novel CNVs as prior studies suggest these harbor distinct CNVs. Array comparative genomic hybridization of 12 tumors from an Australian PrCa family, PcTas9, highlighted multiple recurrent CNVs, including amplification of EEF2 (19p13.3) in 100% of tumors. The EEF2 CNV was examined in a further 26 familial and seven sporadic tumors from the Australian cohort and in 494 tumors unselected for family history from The Cancer Genome Atlas (TCGA). EEF2 overexpression was observed in seven PcTas9 tumors, in addition to seven other predominantly familial tumors (ntotal  = 34%). EEF2 amplification was only observed in 1.4% of TCGA tumors, however 7.5% harbored an EEF2 deletion. Analysis of genes co-expressed with EEF2 revealed significant upregulation of two genes, ZNF74 and ADSL, and downregulation of PLSCR1 in both EEF2 amplified familial tumors and EEF2 deleted TCGA tumors. Furthermore, in TCGA tumors, EEF2 amplification and deletion were significantly associated with a higher Gleason score. In summary, we identified a novel PrCa CNV that was predominantly amplified in familial tumors and deleted in unselected tumors. Our results provide further evidence that familial tumors harbor distinct CNVs, potentially due to an inherited predisposition, but also suggest that regardless of how EEF2 is dysregulated, a similar set of genes involved in key cancer pathways are impacted. Given the current lack of gene-based biomarkers and clinical targets in PrCa, further investigation of EEF2 is warranted.

Urban-rural prostate cancer disparities in a regional state of Australia.

Men living in regional and remote areas experience disparities in prostate cancer (PrCa) diagnosis, clinical characteristics and treatment modalities. We sought to determine whether such disparities exist in PrCa patients from Tasmania; a regional state of Australia with the second-highest rate of diagnosis and where over a third of residents live in outer regional and remote areas. Our study included clinicopathological data from 1526 patients enrolled in the Prostate Cancer Outcomes Registry-Tasmania. Regression analyses were undertaken to determine whether demographic, clinical and treatment variables differed between inner regional and outer regional/remote patients. Men from outer regional/remote areas were significantly more likely to reside in lower socio-economic areas, be diagnosed at a later age and with more clinically aggressive features. However, in contrast to previous studies, there were no overall differences in diagnostic or treatment method, although men from outer regional/remote areas took longer to commence active treatment and travelled further to do so. This study is the first to investigate PrCa disparities in a wholly regional Australian state and highlights the need to develop systematic interventions at the patient and healthcare level to improve outcomes in outer regional and remote populations in Australia and across the globe.

Analysis of a large prostate cancer family identifies novel and recurrent gene fusion events providing evidence for inherited predisposition.

There is strong interest in the characterisation of gene fusions and their use to enhance clinical practices in prostate cancer (PrCa). Significantly, ~50% of prostate tumours harbour a gene fusion. Inherited factors are thought to predispose to these events but, to date, only one study has investigated gene fusions in a familial context. Here, we examined the prevalence and diversity of gene fusions in 14 tumours from a single large PrCa family, PcTas9, using the TruSight® RNA Fusion Panel and Sanger sequencing validation. These fusions were then explored in The Cancer Genome Atlas (TCGA) PrCa data set (n = 494). Overall, 64.3% of PcTas9 tumours harboured a gene fusion, including known erythroblast transformation-specific (ETS) fusions involving ERG and ETV1, and two novel gene fusions, C19orf48:ETV4 and RYBP:FOXP1. Although 3' ETS genes were overexpressed in PcTas9 and TCGA tumour samples, 3' fusion of FOXP1 did not appear to alter its expression. In addition, PcTas9 fusion carriers were more likely to have lower-grade disease than noncarriers (p = 0.02). Likewise, TCGA tumours with high-grade disease were less likely to harbour fusions (p = 0.03). Our study further implicates an inherited predisposition to PrCa gene fusion events, which are associated with less aggressive tumours. This knowledge could lead to clinical strategies to predict men at risk for fusion-positive PrCa and, thus, identify patients who are more or less at risk of aggressive disease and/or responsive to particular therapies.

Insulin resistance in prostate cancer patients and predisposing them to acute ischemic heart disease.

Lack of insulin or insulin resistance (IR) plays a central role in diabetes mellitus and makes diabetics prone to acute ischemic heart disease (AIHD). It has likewise been found that many cancer patients, including prostate cancer patients die of AIHD. Previously it has been delineated from our laboratory that dermcidin could induce anomalous platelet aggregation in AIHD and also impaired nitric oxide and insulin activity and furthermore dermcidin was also found in a few types of cancer patients. To determine the role of this protein in prostatic malignancy, a retrospective case-control study was conducted and blood was collected from prostate cancer patients and healthy normal volunteers. So, we measured the level of dermcidin protein and analyzed the IR by Homeostasis Model Assessment (HOMA) score calculation. Nitric oxide was measured by methemoglobin method. HDL, glycated hemoglobin (HbA1c), BMI, hs-cTroponin-T were measured for the validation of the patients' status in the presence of Dermcidin isoform-2 (DCN-2). Multiple logistic regression model adjusted for age and BMI identified that the HOMA score was significantly elevated in prostate cancer patients (OR = 7.19, P<0.001). Prostate cancer patients are associated with lower level of NO and higher level of both proteins dermcidin (OR = 1.12, P<0.001) and hs-TroponinT (OR = 1.76, P<0.001). From the results, it can be interpreted that IR plays a key role in the pathophysiology of prostate cancer where dermcidin was the cause of IR through NO inhibition leading to AIHD was also explained by high-sensitive fifth generation cTroponin-T (hs-cTroponinT) and HbA1c level which are associated with endothelial dysfunction.

Ins and outs of urinary catheters

BACKGROUND: Inserting an indwelling catheter (IDC) is a common medical procedure that is often performed poorly and inappropriately, and can lead to significant morbidity. Although most catheterisations are performed by nursing staff, medical personnel need to be aware of the procedure, products and common IDC complications. OBJECTIVE: Current guidelines and literature were reviewed to outline catheterisation indications, catheter types and provide a general understanding of complications associated with IDCs for the general practitioner (GP). DISCUSSION: There is evidence that IDCs are often used when not indicated and improperly managed when inserted. IDCs can cause significant morbidity, prolong hospital stay and increase healthcare costs. Infection and traumatic insertion are common complications; advances in catheter design have helped to limit these complications. Most complications are avoidable, do not require specialist input and can be managed by community nurses or GPs. Reviewing indications, adopting proper technique for insertion and defining management strategies can limit complications.

Photoselective vaporization of the prostate using the 180W lithium triborate laser.

INTRODUCTION: Photoselective vaporization of the prostate (PVP) is widely used to treat benign prostatic obstruction (BPO), but there is little experience reported on the new more powerful 180W lithium triborate (LBO) laser. This study evaluates the safety and efficacy of using the 180W LBO laser to treat BPO by examining a multicentre Australian experience. METHODS: Retrospective review of prospectively collected data on all men treated by 180W LBO laser PVP by eight urologists across six Australian hospitals, from July 2011 to August 2011, was performed. Perioperative and functional outcomes were examined at baseline and 3 months. RESULTS: Of the 85 men (median age 70 years, prostate volume 51 cm(3)) identified, 27% (23/85) were in urinary retention and 44% (37/85) were taking antiplatelet/anticoagulant medication. Median operating time was 46 min, laser time 27 min, energy use 211 kJ, post-operative duration of catheterization 15 h and hospitalization 22 h. Functional outcomes from baseline to 3 months, respectively, were for IPSS 25-7; QoL 5-2; Qmax 7.7-18.4; and PVR 147-38. All improvements were statistically significant (P < 0.01). Thirty-eight percent (32/85) of patients experienced at least one adverse event. Most adverse events were low Clavien-Dindo grade I-II. There were five grade III, two grade IV and no grade V adverse events. Sixty per cent (51/85) of men were able to be discharged home voiding successfully without a catheter within 24-h post-PVP. CONCLUSIONS: Our early multicentre Australian experience indicates the 180W LBO laser PVP is an efficacious and safe treatment for BPO.