MYC Overexpression Induces Prostatic Intraepithelial Neoplasia and Loss of Nkx3.1 in Mouse Luminal Epithelial Cells

Lo-MYC and Hi-MYC mice develop prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma as a result of MYC overexpression in the mouse prostate[1]. However, prior studies have not determined precisely when, and in which cell types, MYC is induced. Using immunohistochemistry (IHC) to localize MYC expression in Lo-MYC transgenic mice, we show that morphological and molecular alterations characteristic of high grade PIN arise in luminal epithelial cells as soon as MYC overexpression is detected. These changes include increased nuclear and nucleolar size and large scale chromatin remodeling. Mouse PIN cells retained a columnar architecture and abundant cytoplasm and appeared as either a single layer of neoplastic cells or as pseudo-stratified/multilayered structures with open glandular lumina—features highly analogous to human high grade PIN. Also using IHC, we show that the onset of MYC overexpression and PIN development coincided precisely with decreased expression of the homeodomain transcription factor and tumor suppressor, Nkx3.1. Virtually all normal appearing prostate luminal cells expressed high levels of Nkx3.1, but all cells expressing MYC in PIN lesions showed marked reductions in Nkx3.1, implicating MYC as a key factor that represses Nkx3.1 in PIN lesions. To determine the effects of less pronounced overexpression of MYC we generated a new line of mice expressing MYC in the prostate under the transcriptional control of the mouse Nkx3.1 control region. These “Super-Lo-MYC” mice also developed PIN, albeit a less aggressive form. We also identified a histologically defined intermediate step in the progression of mouse PIN into invasive adenocarcinoma. These lesions are characterized by a loss of cell polarity, multi-layering, and cribriform formation, and by a “paradoxical” increase in Nkx3.1 protein. Similar histopathological changes occurred in Hi-MYC mice, albeit with accelerated kinetics. Our results using IHC provide novel insights that support the contention that MYC overexpression is sufficient to transform prostate luminal epithelial cells into PIN cells in vivo. We also identified a novel histopathologically identifiable intermediate step prior to invasion that should facilitate studies of molecular pathway alterations occurring during early progression of prostatic adenocarcinomas

Suprapubic Cystostomy for the Management of Urethral Injuries During Penile Prosthesis Implantation

Introduction: Urethral injury is an uncommon surgical complication of penile prosthesis (PP) surgery. Conventional dogma requires abortion of the procedure if the adjacent corporal body is involved or delayed implantation to avert device infection associated with urinary extravasation. Besides the setback of the aborted surgery, this management approach also presents the possible difficulty of encountering corporal fibrosis at the time of reoperation. Aim: We report an approach using primary urethral repair and temporary suprapubic cystostomy for the management of incidental urethral injuries in a cohort of patients allowing for successful completion of unaborted PP implantation. Materials and Methods: We performed a retrospective analysis of all patients receiving PPs from 1990 to 2014 in which incidental urethral injuries were repaired and PP implantation was completed with suprapubic cystostomy (suprapubic tube [SPT] insertion). After allowing for urethral healing and urinary diversion via SPT for 4–8 weeks, the PP was activated. Main Outcome Measures: Successful management was determined by the absence of perioperative complications within 6 months of implantation. Results: We identified four cases, all receiving inflatable PPs, managed with temporary suprapubic cystostomy. These patients sustained urethral injuries during corporal dissection (one patient), corporal dilation (one patient), and penile straightening (two patients). All patients were managed safely and successfully. Conclusion: Primary urethral repair followed by temporary suprapubic cystostomy offers a surgical approach to complete PP implantation successfully in patients who sustain urethral injury complications, particularly for complex PP surgeries. Anele UA, Le BV, and Burnett AL. Suprapubic cystostomy for the management of urethral injuries during penile prosthesis implantation. Sex Med 2014;2:178–181

Report of Three Cases of AKI Following Weight-Based Gentamicin Prophylaxis for IPP Implantation: Potential Concerns for Patients with Preexisting Conditions

Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association published guidelines recommending single high-dose weight-based gentamicin prophylaxis of 5 mg/kg for procedures involving urologic prostheses. These guidelines are based on the theoretical renal safety and improved antimicrobial activity of a single large dose of gentamicin. However, the risk of nephrotoxicity after weight-based gentamicin prophylaxis specifically in penile prosthetic surgery has never been established with evidence-based studies. This is of special concern in light of the known high rates of preexisting conditions in this specific population. Therefore, in order to expose potential safety issues, we present three cases of postoperative acute kidney injury following weight-based gentamicin prophylaxis after implantation of inflatable penile prostheses

Optimization of renal function preservation during robotic partial nephrectomy

Over the past few years, the role of robotic-assisted partial nephrectomy (RPN) has exponentially grown. Multiple recognized factors contribute to postoperative renal function in patients undergoing RPN. The aim of this review is to identify these potential factors, and to evaluate strategies that may help optimize the goal of renal function preservation. A nonsystematic literature review was performed to retrieve the most recent evidence on factors contributing to renal function post-RPN. Analyzed elements include baseline factors (tumor complexity and patient characteristics), intraoperative (surgical) factors (control of the renal hilum and type of ischemia, resection technique, renorrhaphy technique), and pharmacotherapeutics. In conclusion, the advantages of robotic surgery in the setting of partial nephrectomy (PN) are becoming well established. Maximal preservation of renal function remains a priority goal of the procedure, and it is influenced by a plethora of factors. Adequate patient selection using radiomics, control of comorbidities, utilization of evidence-based intraoperative techniques/strategies, and postoperative care are key components of postoperative preservation of renal function. Further investigations regarding these factors and their effects on long-term renal function are necessary and will continue to aid in guiding appropriate patient care

Impact of Perioperative Blood Transfusions on the Outcomes of Patients Undergoing Kidney Cancer Surgery: A Systematic Review and Pooled Analysis

The aim of the present study is to systematically review current evidence regarding the association between perioperative blood transfusions (PBT) and oncological outcomes of patients with renal cell carcinoma undergoing nephrectomy procedures. A computerized bibliographic search was conducted to identify pertinent studies. The Population, Intervention, Comparator, Outcome (PICO) study design approach was used to define study eligibility according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Only 7 studies were deemed fully eligible for analysis. Most series included both open and laparoscopic cases. The rate of PBT varied between 9.6% and 76.6%, and the median number of transfused units was 2 for most of the studies. At pooled analysis, a statistically significant association was found between PBT and disease recurrence (HR, 1.79; 95% CI, 1.32-2.41; P <.001), cancer-specific mortality (HR, 1.62; 95% CI, 1.29-2.05; P ≤.001), and all-cause mortality (HR, 1.45; 95% CI, 1.25-1.69; P <.001). Current evidence suggests that indeed the use of PBT may be associated with worse oncologic outcomes in patients with renal cell carcinoma undergoing nephrectomy procedures. Although presents findings should be interpreted within the intrinsic limitations of this type of pooled analysis, they emphasize the need for evidence-based strategies to minimize the use of PBT during kidney cancer surgery