Chad W.M. Ritenour

Formalin Disinfection of Biopsy Needle Minimizes the Risk of Sepsis Following Prostate Biopsy

PURPOSE We describe a simple and effective method to reduce the risk of infection after prostate biopsy. MATERIALS AND METHODS A total of 1,642 consecutive prostate biopsy procedures during a 4-year period (2008 to 2012) were included in the study. Inclusion criteria consisted of pre-biopsy negative urine culture, bisacodyl enema and fluoroquinolone antibiotics (3 days). Formalin (10%) was used to disinfect the needle tip after each biopsy core. All patients were monitored for post-biopsy infection. The rate of infection was compared to that of a historical series of 990 procedures. Two ex vivo experiments were conducted to test the disinfectant effectiveness of formalin against fluoroquinolone resistant Escherichia coli, and another experiment was performed to quantitate formalin exposure. RESULTS Post-biopsy clinical sepsis with positive urine and blood cultures (quinolone resistant E. coli) developed in 2 patients (0.122%). Both patients were hospitalized, treated with intravenous antibiotics and had a full recovery without long-term sequelae. Mild uncomplicated urinary infection developed in 3 additional patients (0.183%). All were treated with outpatient oral antibiotics and had a complete recovery. The overall rate of urinary infection and sepsis using formalin disinfection was approximately a third of that of a prior series (0.30% vs 0.80%, p=0.13). Ex vivo experiments showed a complete lack of growth of fluoroquinolone resistant E. coli on blood and MacConkey agars after exposure to formalin. The amount of formalin exposure was negligible and well within the safe parameters of the Environmental Protection Agency. CONCLUSIONS Formalin disinfection of the biopsy needle after each prostate biopsy core is associated with a low incidence of urinary infection and sepsis. This technique is simple, effective and cost neutral.

The prostate anesthetic block for outpatient prostate surgery.

Abstract With the emergence of minimally invasive techniques for the treatment of benign prostate hyperplasia and the need to reduce health care costs, a simple and effective prostate anesthetic block may allow more procedures to be done in an outpatient or office setting. As based on neuroanatomy studies of the prostate, the perineal approach appeared to be the best way to anesthetize the prostate. This technique was used in 43 patients who underwent interstitial laser coagulation an outpatient or office setting. The perineal prostatic block was effective for pain control whether lidocaine or lidocaine/bupivacaine was used as determined by visual analog scale, linear pain scale, or global pain questionnaire. The use of intravenous (i.v.) sedation did not influence the efficacy of the prostate anesthetic block. Thus, the perineal prostate anesthetic block may be employed in patients undergoing minimally invasive surgery for benign prostatic hyperplasia in the outpatient/office location.

PDGF Upregulates Mcl-1 Through Activation of β-Catenin and HIF-1α-Dependent Signaling in Human Prostate Cancer Cells

Background Aberrant platelet derived growth factor (PDGF) signaling has been associated with prostate cancer (PCa) progression. However, its role in the regulation of PCa cell growth and survival has not been well characterized. Methodology/Principal Findings Using experimental models that closely mimic clinical pathophysiology of PCa progression, we demonstrated that PDGF is a survival factor in PCa cells through upregulation of myeloid cell leukemia-1 (Mcl-1). PDGF treatment induced rapid nuclear translocation of β-catenin, presumably mediated by c-Abl and p68 signaling. Intriguingly, PDGF promoted formation of a nuclear transcriptional complex consisting of β-catenin and hypoxia-inducible factor (HIF)-1α, and its binding to Mcl-1 promoter. Deletion of a putative hypoxia response element (HRE) within the Mcl-1 promoter attenuated PDGF effects on Mcl-1 expression. Blockade of PDGF receptor (PDGFR) signaling with a pharmacological inhibitor AG-17 abrogated PDGF induction of Mcl-1, and induced apoptosis in metastatic PCa cells. Conclusions/Significance Our study elucidated a crucial survival mechanism in PCa cells, indicating that interruption of the PDGF-Mcl-1 survival signal may provide a novel strategy for treating PCa metastasis.

Epidermal Growth Factor Promotes Protein Degradation of Epithelial Protein Lost in Neoplasm (EPLIN), a Putative Metastasis Suppressor, during Epithelial-mesenchymal Transition

Background: The mechanism of EGF signaling in the regulation of prostate cancer (PCa) metastasis remains unclear. Results: EGF promotes epithelial-mesenchymal transition (EMT) and induces degradation of epithelial protein lost in neoplasm (EPLIN), a putative suppressor of PCa metastasis. Conclusion: EGF activates ERK1/2-dependent phosphorylation, ubiquitination, and protein turnover of EPLIN. Significance: This study suggested that blockade of EGF signaling could retard EMT and inhibit invasiveness of PCa cells. Aberrant expression of EGF receptors has been associated with hormone-refractory and metastatic prostate cancer (PCa). However, the molecular mechanism for EGF signaling in promoting PCa metastasis remains elusive. Using experimental models of PCa metastasis, we demonstrated that EGF could induce robust epithelial-mesenchymal transition (EMT) and increase invasiveness. Interestingly, EGF was found to be capable of promoting protein turnover of epithelial protein lost in neoplasm (EPLIN), a putative suppressor of EMT and tumor metastasis. Mechanistic study revealed that EGF could activate the phosphorylation, ubiquitination, and degradation of EPLIN through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent signaling cascade. Pharmacological inhibition of the ERK1/2 pathway effectively antagonized EGF-induced EPLIN degradation. Two serine residues, i.e. serine 362 and serine 604, were identified as putative ERK1/2 phosphorylation sites in human EPLIN, whose point mutation rendered resistance to EGF-induced protein turnover. This study elucidated a novel molecular mechanism for EGF regulation of EMT and invasiveness in PCa cells, indicating that blockade of EGF signaling could be beneficial in preventing and retarding PCa metastasis at early stages.

Exercise is Associated with Better Erectile Function in Men Under 40 as Evaluated by the International Index of Erectile Function

INTRODUCTION Studies have shown an association between erectile dysfunction and sedentary lifestyle in middle-aged men, with a direct correlation between increased physical activity and improved erectile function. Whether or not this relationship is present in young, healthy men has yet to be demonstrated. AIM The aim of this study was to assess the association between physical activity and erectile function in young, healthy men. MAIN OUTCOME MEASURES The primary end points for our study were: (i) differences in baseline scores of greater than one point per question for the International Index of Erectile Function (IIEF); (ii) differences in baseline scores of greater than one point per question for each domain of the IIEF; (iii) exercise energy expenditure; and (iv) predictors of dysfunction as seen on the IIEF. METHODS The participants were men between the ages of 18 and 40 years old at an academic urology practice. Patients self-administered the Paffenbarger Physical Activity Questionnaire and the IIEF. Patients were stratified by physical activity into two groups: a sedentary group (≤1,400 calories/week) and an active group (>1,400 calories/week). Men presenting for the primary reason of erectile dysfunction or Peyronies disease were excluded. RESULTS Seventy-eight patients had complete information in this study: 27 patients (34.6%) in the sedentary group (≤1,400 kcal/week) and 51 patients (65.4%) in the active group (>1,400 kcal/week). Sedentary lifestyle was associated with increased dysfunction in the following domains of the IIEF: erectile function (44.4% vs. 21.6%, P = 0.04), orgasm function (44.4% vs. 17.7%, P = 0.01), intercourse satisfaction (59.3% vs. 35.3%, P = 0.04), and overall satisfaction (63.0% vs. 35.3%, P = 0.02). There was a trend toward more dysfunction in the sedentary group for total score on the IIEF (44.4% vs. 23.5%, P = 0.057), while sexual desire domain scores were similar in both groups (51.9% vs. 41.2%, P = 0.37). CONCLUSIONS We have demonstrated that increased physical activity is associated with better sexual function measured by a validated questionnaire in a young, healthy population. Further studies are needed on the long-term effects of exercise, or lack thereof, on erectile function as these men age.

Comparison of 12-Core Versus 8-Core Prostate Biopsy: Multivariate Analysis of Large Series of US Veterans

OBJECTIVES To investigate the impact of additional biopsy cores on prostate cancer diagnosis among US veterans. The reported rate of positive biopsy results varies from 20% to 40%. METHODS We analyzed 1546 consecutive initial prostate biopsy procedures (8-core and 12-core biopsy protocols) at the Atlanta VA Medical Center. Both biopsy protocols targeted the peripheral zone. Cancer detection rates were compared between the 2 protocols in univariate and multivariate analyses with results expressed as odds ratios and corresponding 95% confidence intervals. Characteristics of cancer detected were also compared. Sensitivity analyses were performed for different population subgroups. RESULTS The overall positive biopsy rate was 49.9%, 51.2% in the 8-core group and 49.2% in the 12-core group. There was no difference between the 2 biopsy groups (adjusted odds ratio = 0.97, 95% confidence interval = 0.76-1.25). Advanced age and high body mass index were significantly associated with higher likelihood of prostate cancer, whereas larger prostate volumes were associated with lower risk. CONCLUSIONS In this large series of prostate biopsy procedures, in which the peripheral zone was well targeted, there was no evidence that 12-core biopsy improved the likelihood of prostate cancer diagnosis compared with 8-core biopsy. As such, the results of this cohort from a US veteran population suggest that targeting the peripheral zone is more important than the absolute number of biopsy cores. However, in certain subgroups of patients with specific clinical characteristics, such as those with very large prostates, more cores may be required. Further studies are needed to identify such characteristics.

Prospective Evaluation of Patient Satisfaction, and Surgeon and Patient Trainer Assessment of the Coloplast Titan One Touch Release Three-Piece Inflatable Penile Prosthesis

INTRODUCTION A single-armed, prospective, multicenter international study evaluated the redesigned Coloplast Titan One Touch Release (OTR) pump inflatable penile prosthesis. The OTR pump has a unique release valve that permits deflation of the implant with one squeeze of opposing touch pads. AIMS To assess the impact of a new penile prosthesis design, the Titan OTR, on patient ease of operation. Furthermore, to assess patient satisfaction, surgeon acceptance, and the ease with which patients were trained in device operation in the clinic setting. METHODS A total of 113 eligible patients from eight centers were recruited from men presenting with erectile dysfunction without prior prosthetic implantation. The subjects had a mean age of 61 years, and had a number of comorbidities, including diabetes (31.9%), hypertension (34.5%), and Peyronies disease (23.9%). All underwent implantation of the study device. MAIN OUTCOME MEASURES Questionnaires were used to capture patient satisfaction as well as physician feedback on ease of implantation and patient education. A paired analysis was completed for patient satisfaction at 6 (N = 96) and 12 (N = 90) months. RESULTS Overall satisfaction with the device was 90.6% and 90.0% at 6 and 12 months, respectively. The primary end point, ease of deflation, was seen in 70.8% and 73.3% at these two time points, with the 12-month value statistically better than historical controls. Physicians overwhelmingly reported straightforward/simple intraoperative product preparation (97.3%) and equivalent or easier training compared with their previous pump of choice (96.4%). Adverse events for all subjects (N = 113) included removal of the device in four cases (3.5%) for infection and one case for chronic pain (0.8%). CONCLUSIONS The Titan OTR represents an advance in penile prosthetic technology that is well accepted by patients and physicians. The study design allowed for realistic evaluation of the new technology aimed at enhancing clinical outcomes.

Numeracy Among Trainees: Are We Preparing Physicians for Evidence-Based Medicine?

INTRODUCTION In the era of evidence-based medicine, all physicians who communicate with patients need numerical literacy (numeracy). Single-institution studies suggest imperfect numeracy among medical students. Therefore, we sought to examine numeracy and understanding of risk analysis among medical students and surgical residents at several institutions. METHODS Following a validated 3-item numeracy questionnaire, 308 medical students and 50 surgical residents from 4 institutions were asked whether they would recommend adjuvant chemotherapy for a patient based on presented survival data. Main outcome measures included numeracy, understanding of risk with a question requiring simple calculation of risk reduction, and confidence in understanding risk reduction using a Likert score (0 = no confidence and 7 = complete confidence). Binary logistic regression analysis identified predictors of misunderstanding of risk and Pearson correlation coefficients measured differences in confidence by level of training and numeracy. RESULTS Students across institutions did not differ demographically and were grouped by educational level. Of all participants, 69.0% had perfect basic numeracy (score = 3), with no significant difference in numeracy across training levels (p = 0.433). Mean (standard deviation) confidence in recommending treatment increased from 4.5 (1.6) for first-year medical students to 4.8 (1.1) for fourth-year medical students, and 4.9 (1.5) for surgical residents (p = 0.580). Controlling for other demographics, poorly numerate students had a 7-fold increased likelihood (odds ratio: 7.330; 95% confidence interval: 1.384-38.809) of misunderstanding risk compared with more numerate students. CONCLUSIONS A significant number of students at various levels of medical training lack numeracy skills, which increases misunderstanding and miscommunication of risk that can be communicated to patients and families. This deficiency could potentially affect patient safety and care.

Serum Testosterone May Be Associated with Calcium Oxalate Urolithogenesis

BACKGROUND The incidence of urolithiasis is twofold to threefold higher in men than in women. Several animal studies have suggested an association between testosterone levels and the formation of kidney stones. Specifically, castration has been shown to decrease stone formation in rat models. The association between testosterone and stone formation in humans, however, has not been well investigated. PATIENTS AND METHODS Early morning total and free testosterone levels were recorded for 55 male patients. Participants completed a demographics questionnaire, and clinical records of enrolled subjects were reviewed. When available, stone composition was determined in the stone formers. Mann-Whitney tests and logistic regression models were used to examine the data. RESULTS Of the 55 patients, 25 had no history of urolithiasis and 30 had a history of urolithiasis. Although the differences between the two groups were not statistically significant, the stone formers compared with stone-free controls tended to be older (median age 48.4 vs 36.5 years, P = 0.072) and have higher serum levels of testosterone (median serum concentration 384 vs 346 ng/dL, P = 0.112). In the multivariate analyses, after adjusting for age and body mass index, the testosterone-related odds ratio was 1.004 with a corresponding P value 0.051. CONCLUSIONS Male stone formers were found to have higher serum total testosterone levels compared with a similar cohort without stones. This result is consistent with several animal models that have demonstrated that testosterone is a risk factor for stone formation. Our findings warrant confirmation in a larger, prospective study. There are potential therapeutic implications if testosterone is found to be a risk factor in urolithogenesis.

Genistein enhances the efficacy of cabazitaxel chemotherapy in metastatic castration-resistant prostate cancer cells

Cabazitaxel (Jevtana) has been approved for the treatment of metastatic castration‐resistant prostate cancer (mCRPC). However, most patients progress and become chemoresistant, which remains a major challenge in the management of advanced PCa. In this study, we investigated whether genistein, an isoflavone abundant in soy products, could sensitize mCRPC cells to cabazitaxel treatment in experimental models.