Prognostic value of prostate volume in non-muscle invasive bladder cancer.

There is evidence that a history of benign prostatic hyperplasia increases the incidence of bladder cancer, and treatment with 5-alpha reductase inhibitor or androgen deprivation therapy reduces recurrence of non-muscle invasive bladder cancer. We aimed to evaluate whether prostate volume affects its prognosis. We reviewed medical records of men who underwent transurethral resection of bladder tumor due to non-muscle invasive bladder cancer from January 2012 to December 2017. Patients were divided into two groups based on prostate volume measured by computed tomography (group 1: 264 patients with ≤ 30 mL, group 2: 124 patients with > 30 mL). Propensity score matching analysis was used for adjust selection bias, and then assessed recurrence-free survival and progression-free survival. With a median follow up duration of 52 months, group 1 showed higher 5-year recurrence-free and progression-free survival (69.3% vs 47.0%, p = 0.001; 96.7% vs 87.7%, p = 0.002). Further, cox-regression analysis showed that tumor size (HR = 1.292 p < 0.001), multifocal tumor (HR = 1.993, p < 0.001), adjuvant intravesical therapy (chemotherapy: HR = 0.580, p = 0.037 and bacillus Calmette-Guérin: HR = 0.542, p = 0.004) and prostate volume (HR = 2.326, p < 0.001) were significant predictors of recurrence-free survival. Prostate volume (HR = 2.886, p = 0.014) was also associated with PFS with age (HR = 1.043, p = 0.044) and tumor grade (HR = 3.822, p = 0.013). We conclude higher prostate volume is associated with worse recurrence and progression-free survival in non-muscle invasive bladder cancer.

5α-reductase inhibitors impact prognosis of urothelial carcinoma.

BACKGROUND: 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. METHODS: The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. RESULTS: Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71-0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82-1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6-1.1). CONCLUSIONS: Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don't. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.

Impact of 5α-reductase inhibitor and α-blocker therapy for benign prostatic hyperplasia on prostate cancer incidence and mortality.

OBJECTIVE: To investigate the use of 5α-reductase inhibitors (5ARIs) and α-blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PCa) incidence, severity and mortality. PATIENTS AND METHODS: A retrospective 20-year cohort study in men residing in Saskatchewan, aged 40-89 years, with a BPH-coded medical claim between 1995 and 2014, was conducted. Cox proportional hazards regression was used to compare incidence of PCa diagnosis, metastatic PCa, Gleason score 8-10 PCa, and PCa mortality among 5ARI users (n = 4 571), α-blocker users (n = 7 764) and non-users (n = 11 677). RESULTS: In comparison with both non-users and α-blocker users, 5ARI users had a ~40% lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and α-blocker users had an 11% lower risk of a PCa diagnosis compared with non-users. Overall, the incidence of metastatic PCa and PCa mortality was not significantly different among 5ARI or α-blocker users compared with non-users (adjusted hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI and a-blocker users had ~30% higher risk of Gleason score 8-10 cancer, adjusted HR 1.37, 95% confidence interval [CI] 1.03-1.82, P = 0.03, and adjusted HR 1.28, 95% CI 1.03-1.59, P = 0.02, respectively compared with non-users. CONCLUSION: The use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of comparison group. Risk of high grade PCa was higher among both 5ARI users and α-blocker users compared with non-users; however, this did not translate into higher risk of PCa mortality.

Expressional profiling and clinical relevance of RNase κ in prostate cancer: a novel indicator of favorable progression-free survival.

PURPOSE: Considering the unmet need for novel molecular tumor markers capable of improving prostate cancer (CaP) patients' management along with the fruitful results regarding the future use of ribonucleases (RNases) as molecular diagnostic and prognostic markers in CaP, we aimed to study the expressional profile of RNase κ in CaP and BPH and to investigate its clinical significance in CaP. METHODS: Total RNA was extracted from 212 prostatic tissue samples (101 BPH and 111 CaP) and, following cDNA synthesis, quantitative real-time PCR (qPCR) was performed for the expressional quantification of RNase κ. Extensive statistical analysis, including bootstrap resampling, was performed to investigate the differential expression of RNase κ in patients with BPH and CaP and its associations with patients' clinicopathological and survival data. RESULTS: RNase κ was significantly downregulated (P = 0.002) in CaP patients compared to BPH ones. RNase κ overexpression was associated with decreased risk of CaP development and can discriminate between CaP and BPH independently of serum PSA levels (crude odds ratio = 0.93, P = 0.001). RNase κ upregulation was also associated with less advanced (P = 0.018) and less aggressive (P = 0.001) tumors as well as with longer progression-free survival (PFS) (P = 0.003). Finally univariate bootstrap Cox regression confirmed that RNase κ was associated with favorable prognosis (HR = 0.85, P = 0.002). CONCLUSIONS: RNase κ is a biomarker of favorable prognosis in CaP, which is significantly associated with less advanced and aggressive disease, as well as with enhanced PFS.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality.

OBJECTIVE: To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. METHODS: We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. RESULTS: In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). CONCLUSION: Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

Reoperation Rates and Mortality After Transurethral and Open Prostatectomy in a Long-term Nationwide Analysis: Have We Improved Over a Decade?

OBJECTIVE: To assess long-term reoperation rates and mortality after transurethral resection of the prostate (TURP) and open prostatectomy (PE) as therapy for lower urinary tract symptoms due to benign prostatic enlargement. METHODS: The present study analyzes a nationwide database of all patients who underwent TURP/open PE during 2002-2006 and who were followed up for 8 years. Actuarial cumulative incidences of reoperation (TURP, urethrotomy, bladder neck incision) and death were calculated. Data were provided by the Austrian Public Health Institute. This series was compared with a previously published almost equally sized nationwide cohort that underwent surgery during 1992-1996 in Austria. RESULTS: Between 2002 and 2006, a total of 21,674 patients underwent TURP (n = 20,388) or open PE (n = 1,286). At 8 years, the re-TURP rate after primary TURP was 8.3% vs 4.3% after open PE. The re-TURP rate was higher in the 80+ cohort. The overall endourological reintervention rate at 8 years was 12.7% for TURP and 8.8% for open PE. Reintervention rates did not improve compared with the 1992-1996 series. The 30-day in-hospital mortality rate was 0.1% for TURP and 0.2% for open PE. Mortality rates improved by approximately 20% compared with the 1992-1996 series. CONCLUSION: In Austria, TURP rates remained stable between 1992 and 2006, paralleled by a 50% decline of open PE. Within a decade, mortality rates declined by 20%, yet reintervention rates remained unchanged.

YRNA expression in prostate cancer patients: diagnostic and prognostic implications.

OBJECTIVE: To study the expression of YRNAs (Ro-associated Y), a novel class of non-coding RNAs, in prostate cancer (PCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival PCA (prostate adenocarcinoma, n = 56), normal (n = 36) and benign prostatic hyperplasia (BPH; n = 28) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for biochemical recurrence-free survival were analysed. RESULTS: All YRNAs were significantly downregulated in PCA tissue compared to normal tissue (all YRNAs) and to BPH tissue (RNY4 and RNY5; RNY1 and RNY3 as trend). Among tumor ISUP grade groups, the most prominent differences in the expression were evident between groups 1 and 2 (RNY1, RNY3 und RNY4; all p < 0.05). Discrimination ability for normal/BPH tissue versus tumor tissue in ROC analysis (area under curve) was ranging from 0.658 (RNY1) to 0.739 (RNY4). Higher RNY5 expression was associated with poor prognosis (biochemical recurrence-free survival). CONCLUSION: The expression of YRNAs is altered in PCA and associated with poor prognosis (RNY5). Possible diagnostic role of YRNAs in prostate cancer should be investigated in further studies.

[Morbi-mortality of transurethral resection of the prostate in patients aged 75 and over]. / Morbi-mortalité de la résection trans-urétrale de la prostate par courant monopolaire chez les patients âgés de 75 ans et plus.

INTRODUCTION: Monopolar transurethral resection of the prostate is one of standard surgical treatment of benign prostatic hyperplasia. The objective of this study was to evaluate early postoperative complications in patients aged 75 years old and more using a standardized classification. MATERIAL AND METHODS: We included all patients aged at least 75 on the day of surgery between 1 January 2008 and 31 December 2013. The reporting of complications was carried from the Clavien-Dindo classification. RESULTS: One hundred and seventy-six patients were included in this study. A total of 47.2% of patients experienced at least one complication. The majority of patients (79.5%) had complications grade 1 or 2 according to Clavien-Dindo classification. One patient died postoperatively at day 27. Most complications were urological (55%). A high Charlson score and low plasma hemoglobin levels have been identified as a risk factor for complications. CONCLUSION: Monopolar transurethral resection of the prostate is followed by significant morbidity in older patients, higher than in the general population. LEVEL OF EVIDENCE: 4.

Mortality is associated with inflammation, anemia, specific diseases and treatments, and molecular markers.

Lifespan is a complex trait, and longitudinal data for humans are naturally scarce. We report the results of Cox regression and Pearson correlation analyses using data of the Study of Health in Pomerania (SHIP), with mortality data of 1518 participants (113 of which died), over a time span of more than 10 years. We found that in the Cox regression model based on the Bayesian information criterion, apart from chronological age of the participant, six baseline variables were considerably associated with higher mortality rates: smoking, mean attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration, albumin/creatinine ratio, treated gastritis, and medication during the last 7 days. Except for smoking, the causative contribution of these variables to mortality was deemed inconclusive. In turn, four variables were found to be associated with decreased mortality rates: treatment of benign prostatic hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being female was an undisputed causative variable, the causal role of IFG-1 was deemed inconclusive, and the treatment effects were deemed protective to the degree that treated subjects feature better survival than respective controls. Using Cox modeling based on the Akaike information criterion, diabetes, mean corpuscular hemoglobin concentration, red blood cell count and serum calcium were also associated with mortality. The latter two, together with albumin and fibrinogen, aligned with an"integrated albunemia" model of aging proposed recently.

[Expressions of JNK and p-JNK in advanced prostate cancer and their clinical implications].

OBJECTIVE: To investigate the expressions of JNK and p-JNK in advanced prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their implications. METHODS: Using immunohistochemistry, we detected the expressions of JNK and p-JNK proteins in 40 cases of paraffin wax-embedded PCa and 21 cases of BPH tissues and analyzed their relationships with advanced PCa and BPH as well as with the pathologic features of advanced PCa. RESULTS: Statistically significant differences were not found in the positive expression rate of the JNK protein between BPH and PCa (42.86% vs 52.50%, P>0.05), non-metastatic and metastatic PCa (53.85% vs 51.85%, P >0.05), Gleason ≤7 and Gleason >7 (58.82% vs 47.82%, P >0.05), PSA ≤20 µg/L and PSA >20 µg/L (57.14% vs 51.52%, P >0.05), or survival >5 yr and survival ≤5 yr (60.00% vs 45.00%, P >0.05), nor in the expression level of p-JNK between BPH and PCa (33.33% vs 35.00%, P >0.05), non-metastatic and metastatic PCa (30.77% vs 37.03%, P >0.05), Gleason ≤7 and Gleason >7 (35.29% vs 34.78%, P >0.05), or PSA ≤20 µg/L and PSA >20 µg/L (43.75% vs 10.93%, P >0.05). However, the expression of p-JNK was significantly higher in the survival >5 yr than in the survival ≤5 yr group of the PCa patients (50.00% vs 20.00%, P <0.05). CONCLUSIONS: PCa patients with highly expressed p-JNK have a longer survival time and the high positive rate of p-JNK is associated with the prognosis of PCa.

[Quality assurance with administrative data (QSR): follow-up in quality measurement - an analysis of patient records]. / Qualitätssicherung mit Routinedaten (QSR): Follow-up in der Qualitätsmessung - Eine Analyse fallübergreifender Behandlungsverläufe.

The present study analyses the information gain obtained by evaluating adverse events during follow-up compared to the sole analysis of events during the initial hospital stay for quality measurement purposes. The analysis is based on AOK administrative data from the years 2010 to 2012. The analyses were carried out for 10 quality indicators from the 4 QSR sectors knee replacement for osteoarthritis, appendectomy, prostate surgery for benign prostatic syndrome (BPS) and therapeutic cardiac catheterization (PCI) in patients with myocardial infarction. A total of 409,774 AOK cases were included. For almost all indicators considered, a relevant share of complications can be found to have occurred only after discharge from the initial hospitalization (7.7 %-92.6 %). Furthermore, there is only a weak connection between the findings from the first hospitalization and those from the follow-up period (0.0449 < r < 0.1935). 26-66 % of the hospitals will be classified differently based on Standardized Mortality/Morbidity Ratio (SMR) quartiles if follow-up events are included in the quality assessment (with the exception of "Other Complications after PCI" of 14 %). In summary, quality assessment is improved considerably by evaluating the follow-up period for almost all indicators considered. A quality measurement based solely on events in the initial hospital stay obscures relevant adverse events that have an impact on a comparative hospital quality assessment for these indicators.

Electrosurgical transurethral resection of the prostate and transurethral incision of the prostate (monopolar techniques).

INTRODUCTION: We summarize the current guidelines, techniques, efficacy and complications associated with monopolar transurethral resection of the prostate (TURP) and transurethral incision of the prostate (TUIP) for benign prostatic hyperplasia (BPH). Patients who elect to have endoscopic surgical bladder outlet reduction are faced with an abundance of evolving treatment options. As new technology comes and goes, TURP and TUIP remain the gold standard for which new treatments are compared. MATERIALS AND METHODS: A review of past and contemporary data including American and European guidelines was performed. Techniques, efficacy, durability, short term and long term complications of TURP and TUIP are summarized. RESULTS: Small prostate sizes < 30 mL without a median lobe can be effectively treated with TUIP with decreased perioperative complications and sexual side effects compared to TURP. Monopolar TURP demonstrates significant improvements in IPSS, peak flow rate (Qmax), and quality of life (QoL) with durable (8 year-22 year) outcomes. Secondary intervention increases by 1%-2% annually. Thirty-day mortality rate is low (0.1%) as well as incidence of TUR syndrome (< 1.1%). Short term and long term complications include bleeding requiring transfusion, clot retention, acute urinary retention (AUR), and urinary tract infections as well as incontinence, bladder neck contracture, urethral stricture, and sexual dysfunction. CONCLUSIONS: Monopolar TURP and TUIP are effective endoscopic treatments for BPH with durable long term results. While the short term and long term complication rates are acceptable, new technologies aim to increase tolerability of bladder outlet reduction by decreasing treatment related morbidity.

Prostatectomy for benign prostate disease: open, laparoscopic and robotic techniques.

INTRODUCTION: Prostatectomy for benign disease, also known as a 'simple prostatectomy', is neither simple in indication nor approach. In the post-Medical Therapy of Prostatic Symptoms (MTOPS), NCT00021814 trial era, the medical management of benign prostatic hyperplasia (BPH) and consequent bladder outlet obstruction (BOO) has shifted surgical intervention to those patients who are medical-non responders, present with advanced signs of BOO and obstructive uropathy, and those with prostate gland volumes beyond the size normally approachable with standard transurethral resection of the prostate (TURP). Simple prostatectomy through an open surgical approach is associated with improvements in BOO and lower urinary tract symptoms (LUTS) but at the expense of considerable surgical and perioperative morbidity. Advances in technology have made it possible for patients to be offered standard open surgical approaches as well as transurethral approaches with photon-based energy sources (i.e. laser prostatectomy) and laparoscopic simple prostatectomy. A review of the historical challenges of BPH and the standard-of-care of open prostatectomy will put into perspective the potential advantages and disadvantages of laparoscopic and robotic prostatectomy for the treatment of benign BOO due to BPH. MATERIALS AND METHODS: A careful review of the literature was performed utilizing PubMed and ClinicalKey searches to identify relevant articles. Search terms 'simple prostatectomy', 'robotic simple prostatectomy' and 'laparoscopic simple prostatectomy'. RESULTS: Over 14 series of open simple prostatectomies and over 20 minimally invasive series were identified and used as a reference. Additionally, several review articles were identified and incorporated. CONCLUSIONS: Simple prostatectomy may be performed safely in appropriately selected patients utilizing either open or minimally invasive approaches. Clinical criteria should be used to determine the appropriateness of either retropubic versus transvesical approach.

Prostatic urethral lift: a novel approach for managing symptomatic BPH in the aging man.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is an obligate disorder of the aging male prostate with close associations to other metabolic conditions of aging including obesity. Clinical manifestations of this chronic disorder increase as men age suggesting that a growing number of older men will require intervention for progressive voiding symptoms or bladder dysfunction. MATERIALS AND METHODS: The Prostatic Urethral Lift (PUL) procedure represents a new endoscopic approach in which small permanent intraprostatic implants are positioned to correct bladder outlet obstruction without tissue destruction. An overview of the treatment modality, review of recent literature, and analysis of data in the context of cost considerations is presented. RESULTS: The mean symptom score improvement of the prospective, sham controlled, pivotal trial was 11 points, 88% greater than sham controls. Multiple studies have confirmed symptom score improvement of at least 52%. Durability has been established out to 3 years. A randomized comparison between PUL and transurethral resection of the prostate (TURP) established PUL as superior to TURP in terms of a composite BPH6 endpoint which incorporated symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation, and safety. The National Institute for Health and Care Excellence of the United Kingdom conducted an analysis that found PUL is less costly than TURP. Earlier management with PUL may even reduce overall cost for those patients managed with medication. CONCLUSION: Current reports have demonstrated rapid voiding symptom improvement with a low risk of adverse events suggesting that this procedure represents a safe and cost effective new paradigm for the early therapy for BPH/ LUTS.

Increase of Framingham cardiovascular disease risk score is associated with severity of lower urinary tract symptoms.

OBJECTIVE: To determine the relationship between lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and 10-year risk of cardiovascular disease (CVD) assessed by the Framingham CVD risk score in a cohort of patients without previous episodes of stroke and/or acute myocardial infarction. PATIENTS AND METHODS: From September 2010 to September 2014, 336 consecutive patients with BPH-related LUTS were prospectively enrolled. The general 10-year Framingham CVD risk score, expressed as percentage and assessing the risk of atherosclerotic CVD events, was calculated for each patient. Individuals with low risk had ≤10% CVD risk at 10 years, with intermediate risk 10-20% and with high risk ≥20%. Logistic regression analyses were used to identify variables for predicting a Framingham CVD risk score of ≥10% and moderate-severe LUTS (International Prostate Symptom Score [IPSS] ≥8), adjusted for confounding factors. RESULTS: As category of Framingham CVD risk score increased, we observed higher IPSS (18.0 vs 18.50 vs 19.0; P < 0.05), high IPSS-voiding (6.0 vs 9.0 vs 9.5; P < 0.05) and worse sexual function. Prostate volume significantly increased in those with intermediate- vs low-risk scores (54.5 vs 44.1 mL; P < 0.05). Multivariate logistic regression analysis showed that intermediate- [odds ratio (OR) 8.65; P < 0.01) and high-risk scores (OR 1.79; P < 0.05) were independently associated with moderate-severe LUTS. At age-adjusted logistic regression analysis, moderate-severe LUTS was independently associated with Framingham CVD risk score of ≥10% (OR 5.91; P < 0.05). CONCLUSION: Our cross-sectional study in a cohort of patients with LUTS-BPH showed an increase of more than five-fold of having a Framingham CVD risk score of ≥10% in men with moderate-severe LUTS.

PPM1D as a novel biomarker for prostate cancer after radical prostatectomy.

Protein phosphatase magnesium-dependent 1 delta (PPM1D) is involved in several types of cancer. The current study examined the role of PPM1D expression in prostate cancer (PCa) tissues and in PCa cell lines. Expression of PPM1D was evaluated using immunohistochemistry in 234 PCa tissues after radical prostatectomy and 80 benign prostatic hyperplasia (BPH) tissues. The associations of PPM1D expression with clinicopathological parameters and survival were analyzed. In vitro, tumor cells were transfected with small interfering RNA targeting PPM1D (siPPM1D) or si-Scramble, and the cell proliferation, migration and invasion were determined. We found that PPM1D expression was significantly higher in PCa tissues than that in BPH tissues. PPM1D expression was positively correlated with Gleason score (p=0.022), T stage (p=0.015) and lymph node status (p=0.016). Kaplan-Meier curve analysis showed that patients with positive PPM1D expression had shorter biochemical recurrence-free survival and overall survival. Furthermore, multivariate analyses showed that PPM1D expression was an independent predictor of both biochemical recurrence-free (hazard ratio=3.437, 95% confidence interval=1.154-6.209, p=0.016) and overall survival (hazard ratio=5.026, 95% confidence interval=2.545-8.109, p=0.007). Knockdown of PPM1D inhibited the proliferation, migration and invasion capabilities of PC-3 and LNCaP cells. PPM1D expression may predict for both overall and biochemical recurrence-free survival in patients after radical prostatectomy for PCa. Elevated PPM1D expression plays a key role in progression of PCa.

Prognostic value of tissue and circulating levels of IMP3 in prostate cancer.

Tissue levels of the oncofetal protein insulin-like growth factor 2 (IGF2) messenger RNA-binding protein 3 (IMP3) have been associated with poor prognosis in multiple human malignancies. However, its circulating levels have not yet been analyzed. Therefore, the aim of this study was to assess the prognostic value of both serum and tissue levels of IMP3 in prostate cancer (PC). IMP3 protein expression was analyzed in 124 PC and 13 benign prostate hyperplasia (BPH) patients using immunohistochemistry. Gene expression levels of IMP3 and its molecular target IGF2 were analyzed in 29 frozen and 26 paraffin-embedded PC tissues using real-time polymerase chain reaction and immunohistochemistry. Serum IMP3 levels were assessed in 94 PC and 20 BPH patients as well as in 20 controls using enzyme-linked immunosorbent assay. IMP3 immunostaining was present in 0% (0/13) of BPHs, 15% (15/101) of clinically localized PCs and 65% (15/23) of palliatively treated metastatic PCs (p < 0.001). Accordingly, serum IMP3 concentrations were significantly higher in PC compared to BPH patients which were higher than those in controls (p < 0.001 each). The highest concentrations were detected in metastatic PC patients (p = 0.036). In patients who underwent radical prostatectomy high IMP3 serum levels were independently associated with poor cancer-specific survival. IMP3 gene and protein expressions were not correlated with those of IGF2. In conclusion, we found enhanced IMP3 levels in tissue and serum samples of PC patients compared to non-PC men. Moreover, IMP3 was associated with metastasis and PC-specific survival. The tumor promoting effect of IMP3 appears to be independent from its regulatory role on IGF2 in PC.

Morbidity and mortality after benign prostatic hyperplasia surgery: data from the American College of Surgeons national surgical quality improvement program.

BACKGROUND AND PURPOSE: With the aging population, it is becoming increasingly important to identify patients at risk for postsurgical complications who might be more suited for conservative treatment. We sought to identify predictors of morbidity after surgical treatment of benign prostatic hyperplasia (BPH) using a large national contemporary population-based cohort. METHODS: Relying on the American College of Surgeons National Surgical-Quality Improvement Program (ACS-NSQIP; 2006-2011) database, we evaluated outcomes after transurethral resection of the prostate (TURP), laser vaporization of the prostate (LVP), and laser enucleation of the prostate (LEP). Outcomes included blood-transfusion rates, length of stay, complications, reintervention rates, and perioperative mortality. Multivariable logistic-regression analysis evaluated the predictors of perioperative morbidity and mortality. RESULTS: Overall, 4794 (65.2%), 2439 (33.1%), and 126 (1.7%) patients underwent TURP, LVP, and LEP, respectively. No significant difference in overall complications (P=0.3) or perioperative mortality (P=0.5) between the three surgical groups was found. LVP was found to be associated with decreased blood transfusions (odds ratio [OR]=0.21; P=0.001), length of stay (OR=0.12; P<0.001) and reintervention rates (OR=0.63; P=0.02). LEP was found to be associated with decreased prolonged length of stay (OR=0.35; P=0.01). Men with advanced age at surgery and non-Caucasians were at increased risk of morbidity and mortality. In contrast, normal preoperative albumin and higher preoperative hematocrit (>30%) levels were the only predictors of lower overall complications and perioperative mortality. CONCLUSIONS: All three surgical modalities for BPH management were found to be safe. Advanced age and non-Caucasian race were independent predictors of adverse outcomes after BPH surgery. In patients with these attributes, conservative treatment might be a reasonable alternative. Also, preoperative hematocrit and albumin levels represent reliable predictors of adverse outcomes, suggesting that these markers should be evaluated before BPH surgery.

A role of family doctors in taking care of men's health.

The aim of this study was to investigate, based on routinely collected data, the scope of family doctors work in the field of men's health. Based on the Croatian Health Service Yearbook in the period from 1995 to 2012, we collected the morbidity data related to male urogenital disorders. The total number of urogenital disorders almost doubled, but the number of diagnoses related to the men increased fourfold, mostly among the oldest patients. The number of prostate hyperplasia increased fivefold, again among the oldest people. The morbidity from other male-specific diseases increased threefold, mostly in the age group 7-19 years. In spite of the increase in the number of newly diagnosed cases of prostate cancer, the percentage of the deaths stabilized after 2001. Men's health problems are frequent sees and with an upward trend. We are not sure if this means deterioration of men's health, or just indicates the problem of "overdiagnosis".

Increased expression of EphA1 protein in prostate cancers correlates with high Gleason score.

The erythropoietin-producing hepatocellular (Eph) family of receptor tyrosine kinases regulates a multitude of physiological and pathological processes. EphA1 is the first member of Eph superfamily and is involved in carcinogenesis. The aim of this study was to investigate the expression of EphA1 in prostate cancers cell lines and the tissues, then explore the correlation with the clinicopathologic parameters. The EphA1 transcript expression in prostate cancer cell lines was detected by Quantitative real-time PCR. The expression of EphA1 protein in 138 prostate cancer tissue samples and 21 benign prostate hyperplasia samples were checked by using immunohistochemical staining. EphA1 mRNA was high expressed in LNCap, moderately expressed in 22RV1 and Du145, and lost in PC3. Loss of expression of EphA1 transcript was related to hypermethylation of CpG island around the translation start site. EphA1 protein was differentially expressed in prostate cancers and hyperplasia. Increased expression of EphA1 protein was more frequently detected in prostate cancers than in hyperplasia (P = 0.02), and more often detected in prostate cancer with high Gleason score (P < 0.001). Our data indicate that EphA1 receptor may have roles in carcinogenesis and progression of prostate cancer, and can be a potentially useful target for prognostic and therapeutic application.