Organ sparing treatment for penile cancer using a 3D-printed high-dose-rate brachytherapy applicator.

PURPOSE: We present a case study of the treatment of localized squamous cell carcinoma on the glans penis with a custom-fabricated high-dose-rate (HDR) brachytherapy applicator. METHODS AND MATERIALS: A cylindrically shaped applicator was fabricated with eight embedded channels suitable for standard plastic brachytherapy catheters. An additional custom silicone bolus/sleeve was designed to be used with the 3D-printed applicator to provide an additional offset from the source to skin to reduce the surface dose and for patient comfort. RESULTS: The patient (recurrent cT1a penile cancer) underwent CT simulation, and the brachytherapy plan was created with a nominal prescription dose of 40 Gy in 10 fractions given bidaily to the surface, and 35 Gy at 5 mm depth. Dose coverage to the clinical target volume was 94% (D90). Most fractions were treated with only 5-10 min of setup time. Follow up visits up to 1 year showed no evidence of disease with no significant changes in urinary and sexual function and limited cosmetic detriment to the patient. CONCLUSIONS: Patient-specific organ-sparing HDR plesiotherapy using 3D printing technology can provide reliable and reproducible patient setup and may be effective in achieving disease control for superficial penile cancer, although preserving patient quality of life.

Optimal Prostate Cancer Diagnostic Pathways for Men With Prostatomegaly in the MRI Era.

OBJECTIVE: To evaluate utilities of multiparametric MRI and targeted biopsy to detect clinically significant prostate cancer in men with prostatomegaly. MATERIALS AND METHODS: We conducted a retrospective review of multiparametric MRI obtained for elevated PSA between 2017 and 2020. We selected patients with prostates ≥80 g who had undergone biopsy. Clinically significant prostate cancer was defined as grade group ≥2. Predictive and logistic regression analyses quantified impacts of diagnostic components. RESULTS: A total of 338 patients met inclusion criteria: 89 (26.3%) had clinically significant prostate cancer. On MRI, positive predictive value for clinically significant prostate cancer was 26.5% for PIRADS 4% and 73.5% for PIRADS 5; negative predictive value for MRI without suspicious lesions was 98.8%. Applying PSA density to MRI yielded a negative predictive value of 78.9% for PIRADS 4 lesions at PSA density <0.05 and a positive predictive value of 90.5% for PIRADS 5 lesions at PSA density ≥0.15. Targeted (versus standard) biopsy reduced likelihood of missing clinically significant prostate cancer by >50% (12.2% vs 28.3%). MRI in-bore biopsies trended towards better accuracy versus MRI-transrectal ultrasound fusion biopsies (75% versus 52%). On logistic regression analyses, MRI improved predictive accuracy (area under the curve 0.91), and PIRADS score demonstrated the strongest association with clinically significant prostate cancer (odds ratio 6.42, P < .001). CONCLUSION: For large prostates, MRI is less predictive of clinically significant prostate cancer but effectively rules out malignancy. PSA density better informs biopsy decisions for PIRADS 4 and 5 lesions. There may be a pronounced role for targeted biopsy, specifically in-bore, in prostatomegaly.

PSA density is associated with BPH cellular composition.

BACKGROUND: Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making. METHODS: The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression. RESULTS: The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml2 associated with a glandular composition of ≤30% with 76% sensitivity. CONCLUSIONS: PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.

MRI Features Associated with Histology of Benign Prostatic Hyperplasia Nodules: Generation of a Predictive Model.

Background: Histologic phenotypic variation of benign prostatic hyperplasia (BPH) has been hypothesized to underlie response to medical therapy. We evaluate preoperative MRI of robot-assisted simple prostatectomy (RASP) specimens and determine imaging features associated with histologic phenotype. Materials and Methods: All patients undergoing RASP from November 2015 to November 2019 with a multiparametric MRI ≤1 year before RASP were included. Patients without identifiable BPH nodules on histologic specimens were excluded. Histology slides were obtained from whole mount adenoma specimens and corresponding MRI were reviewed and graded independently by a blinded expert in BPH histopathology (D.W.S.) and an experienced radiologist specializing in prostate imaging (D.N.C.), respectively. Each nodule was assigned a phenotypic score on a 5-point Likert scale (1 = predominantly glandular; 5 = predominantly stromal) by each reviewer. Scores were compared using the sign test and univariate analysis. Signal intensity relative to background transition zone and nodule texture were noted on T2, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) imaging sequences. Univariate and multivariate stepwise linear regression analysis were conducted to identify MRI features associated with histology score. All analyses were performed using Statistical Analysis System (version 9.4). Results: A total of 99 prostate nodules in 29 patients were included. Median phenotypic scores by histology and MRI were comparable (2, interquartile range [IQR] 2-3 vs 2, IQR 2-4, respectively; p = 0.63). Histology scores were positively correlated with MRI scores (Pearson's correlation 0.84, p < 0.0001). Multivariate stepwise linear regression analysis showed that low apparent diffusion coefficient (ADC) signal intensity (p < 0.001) and DCE wash-in (p = 0.03) were positively associated with more stromal histology, whereas ADC standard deviation (p = 0.03), DCE wash-out (p = 0.001), and heterogeneous T2 texture (p = 0.003) were associated with more glandular histology. Conclusion: There is a strong correlation between MRI features and the histologic phenotype of BPH nodules. MRI may provide a noninvasive method to determine underlying BPH nodule histology.

5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.

Single-cell analysis of mouse and human prostate reveals novel fibroblasts with specialized distribution and microenvironment interactions.

Stromal-epithelial interactions are critical to the morphogenesis, differentiation, and homeostasis of the prostate, but the molecular identity and anatomy of discrete stromal cell types is poorly understood. Using single-cell RNA sequencing, we identified and validated the in situ localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri-epithelial fibroblasts (APOD+) wrap around epithelial structures, whereas interstitial fibroblasts (C7+) are interspersed in extracellular matrix. In contrast, the mouse displayed three fibroblast subtypes with distinct proximal-distal and lobe-specific distribution patterns. Statistical analysis of mouse and human fibroblasts showed transcriptional correlation between mouse prostate (C3+) and urethral (Lgr5+) fibroblasts and the human interstitial fibroblast subtype. Both urethral fibroblasts (Lgr5+) and ductal fibroblasts (Wnt2+) in the mouse contribute to a proximal Wnt/Tgfb signaling niche that is absent in human prostate. Instead, human peri-epithelial fibroblasts express secreted WNT inhibitors SFRPs and DKK1, which could serve as a buffer against stromal WNT ligands by creating a localized signaling niche around individual prostate glands. We also identified proximal-distal fibroblast density differences in human prostate that could amplify stromal signaling around proximal prostate ducts. In human benign prostatic hyperplasia, fibroblast subtypes upregulate critical immunoregulatory pathways and show distinct distributions in stromal and glandular phenotypes. A detailed taxonomy of leukocytes in benign prostatic hyperplasia reveals an influx of myeloid dendritic cells, T cells and B cells, resembling a mucosal inflammatory disorder. A receptor-ligand interaction analysis of all cell types revealed a central role for fibroblasts in growth factor, morphogen, and chemokine signaling to endothelia, epithelia, and leukocytes. These data are foundational to the development of new therapeutic targets in benign prostatic hyperplasia. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Serum Small RNA Sequencing and miR-375 Assay Do Not Identify the Presence of Pure Teratoma at Postchemotherapy Retroperitoneal Lymph Node Dissection.

Existing tumor markers for testicular germ cell tumor (TGCT) cannot detect the presence of pure teratoma. Serum miRNAs have strong performance detecting other subtypes of TGCT. Previous reports suggest high levels of miR-375 expression in teratoma tissue. The purpose of this study was to explore the role of serum miRNA, including miR-375, in detecting the presence of teratoma at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We prospectively collected presurgical serum from 40 TGCT patients undergoing PC-RPLND (21 with teratoma at RPLND and 19 with no evidence of disease). We examined the utility of serum miR-375-3p and miR-375-5p by quantitative polymerase chain reaction, and searched for other putative serum miRNAs with small RNA sequencing. The area under the receiver operating characteristic curve (AUC) and univariate analyses were utilized to evaluate test characteristics and predictors of teratoma. Both serum miR-375-3p and miR-375-5p exhibited poor performance (miR-375-3p: 86% sensitivity, 32% specificity, AUC: 0.506; miR-375-5p: 55% sensitivity, 67% specificity, AUC: 0.556). Teratoma at orchiectomy was the only predictor of PC-RPLND teratoma. Small RNA sequencing identified three potentially discriminatory miRNAs, but further validation demonstrated no utility. Our results confirm prior reports that serum miR-375 cannot predict teratoma, and suggest that there may not exist a predictive serum miRNA for teratoma.

Real-World Application of Pre-Orchiectomy miR-371a-3p Test in Testicular Germ Cell Tumor Management.

PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/ß-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.

Perioperative outcomes and cost of robotic vs open simple prostatectomy in the modern robotic era: results from the National Inpatient Sample.

OBJECTIVES: To perform a comparative analysis of perioperative outcomes and hospitalisation cost between open (OSP) and robot-assisted simple prostatectomy (RASP) for treatment of benign prostatic hyperplasia (BPH) using the National Inpatient Sample (NIS) in the contemporary robotic era. MATERIALS AND METHODS: The NIS was queried for cases of OSP and RASP for the treatment of BPH between 2013 and 2016. Perioperative complications, unadjusted hospital cost and length of stay (LOS) were compared between RASP and OSP. Smoothed linear regression curves comparing hospitalisation cost by increasing LOS was stratified by surgical approach to identify point of cost equivalency between RASP and OSP. Multivariable linear regression analysis was used to construct a hospitalisation cost model to examine the contribution of the robotic approach and LOS to hospitalisation cost. RESULTS: The total analytical cohort included 2551 OSP and 704 RASP procedures. Patients undergoing RASP were younger, at a median (interquartile range [IQR]) age of 68 (63-73) vs 71 (65-77) years, and with less comorbidity (76.8% vs 86.5%, P < 0.01). RASP was associated with fewer total complications (11.1% vs 29.2%, P < 0.01) and a greater likelihood of routine discharge to home rather than another facility (88.9% vs 76.7%, P < 0.01). While LOS was shorter with RASP (median [IQR], 2 [1-3] vs 4 [3-6] days, P < 0.01), total unadjusted hospitalisation cost (in United States dollars) was greater (median [IQR], $10 855 [$7965-$15 675] vs $13 467 [$10 572-$17 722], P < 0.01). Presence of any complication increased both LOS and hospitalisation cost (P < 0.01). Linear regression modelling determined the point of cost equivalence between RASP staying a median of 2 days was an OSP case staying between 5 and 6 days. On multivariable regression analysis, the robotic approach contributed an additional $6175 (P < 0.01) to the cost model, whereas each additional day of hospitalisation contributed $1687 (P < 0.01), suggesting LOS would need to be 3-4 days shorter with RASP to offset surgical costs of the robot. CONCLUSIONS: While RASP appears to have significantly better perioperative complication rates with shorter LOS and likely discharge to home, total hospitalisation cost remained greater, likely related to upfront operative costs. While this retrospective study is limited by selection bias for patients undergoing RASP, the benefits of improved convalescence, discharge to home, and lower rate of perioperative complications appear to justify performance of RASP in an experienced pelvic robotic centre despite relatively greater hospitalisation cost if referral to an experienced holmium laser enucleation of the prostate centre is not feasible.

Dynamic differences between DNA damage repair responses in primary tumors and cell lines.

The study of DNA damage repair response (DDR) in prostate cancer is restricted by the limited number of prostate cancer cell lines and lack of surrogates for heterogeneity in clinical samples. Here, we sought to leverage our experience with patient derived explants (PDEs) cultured ex vivo to study dynamics of DDR in primary tumors following application of clinically relevant doses of ionizing radiation (IR) to tumor cells in their native 3-dimensional microenvironment. We compared DDR dynamics between prostate cancer cell lines, PDEs and xenograft derived explants (XDEs) following treatment with IR (2Gy) either alone or in combination with pharmacological modulators of DDR. We have shown that following treatment with 2Gy, DDR can be consistently detected in PDEs from multiple solid tumors, including prostate, kidney, testes, lung and breast, as evidenced by γ-H2AX, 53BP1, phospho-ATM and phospho-DNA-PKcs foci. By examining kinetics of resolution of IR-induced foci, we have shown that DDR in prostate PDEs (complete resolution in 8 h) is much faster than in prostate cancer cell lines (<50% resolution in 8 h). The transcriptional profile of DDR genes following 2Gy IR appears to be distinct between PDEs and cell lines. Pre-treatment with drugs targeting DDR pathways differentially alter the kinetics of DDR in the PDEs and cell lines, as evidenced by altered kinetics of foci resolution. This study highlights the utility of PDEs as a robust model system for short-term evaluation of DDR in primary solid tumors in clinically relevant microenvironment.

Urethral luminal epithelia are castration-insensitive cells of the proximal prostate.

BACKGROUND: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. METHODS: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. RESULTS: Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. CONCLUSIONS: Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.

Implementation of a Urology E-Consult Service at a Safety Net County Hospital.

INTRODUCTION: We assess the implementation of an e-consult service at a urology clinic in a safety net county hospital. METHODS: An e-consult system was introduced in 2018 at our institution. All e-consults for January to December 2018 were collected and data analyzed. Patient demographics were recorded. Total consults, clinic referrals, cystoscopy referrals, need to reschedule and need for followup were compared. Time from referral to in-person clinic visit was collected. Reason for e-consult and final visit diagnosis were placed into urological categories and subcategories. RESULTS: In 2018 472 e-consults were received for 454 patients. The majority were men (62.3%) with a median age of 55 years (IQR 44-63). The majority (52%) were Hispanic. Most patients (69.1%) were scheduled for an in-person clinic visit with 23.9% of these patients scheduled for a cystoscopy. Median time from referral to in-person clinic visit was 39.5 days (IQR 33-50). A quarter of the patients did not require further followup after initial in-person consultation. The majority of e-consults were for hematuria (24%), renal pathologies (20%), and benign prostatic hyperplasia and lower urinary tract symptoms (17%). CONCLUSIONS: Implementation of a urology e-consult service is feasible and decreases need for in-person clinic visits.

Minimally Invasive Endoscopic Aspiration of a Spinal Epidural Dermoid Cyst Extending From T10 to the Sacrum: 2-Dimensional Operative Video.

Dermoid cysts are space-occupying tumors that can occur anywhere in the neuroaxis. Although categorized as benign lesions, they can compromise normal structures, causing neurological function loss, and have a tendency to recur often requiring repeated surgical resections. We illustrate the case of an extensive epidural dermoid cyst in a 22-yr-old woman who presented with progressive loss of neurological motor function in her lower extremities as well as bowel and bladder incontinence. The tumor extended from T10 to the sacrum, and a conventional operation would have entailed serial laminectomies that would cross the thoracolumbar and lumbosacral junctions, possibly requiring an instrumented fusion. Given the fact that operation would have carried significant morbidity, especially with the high likelihood of symptomatic tumoral recurrence, we consulted with our urology colleagues to find a minimally invasive way of reducing the tumor burden and decompressing the neural elements. The patient was taken to the operating room and a limited open lumbosacral durotomy was performed. A flexible cystoscope was then passed in the epidural space and used to suction the tumor. Postoperative imaging showed adequate resection, and the patient recovered neurological function completely. She had mini-mal recurrence at 3 yr and remained asymptomatic. This technical video note showcases the potential for use of endoscopy for spine tumors that have an amenable consistency, even in highly eloquent areas such as the conus medullaris. It also serves to highlight the benefits of interdisciplinary cooperation when treating complex disease. This case report was written in compliance with our institutional ethical review board. Institutional Review Board (IRB) approval and patient consent was waived in light of the retrospective and deidentified nature of the data presented in accordance with the University of Texas SouthWestern IRB. Patient consent was waived for writing this manuscript in light of the retrospective and deidentified nature of the data presented in accordance with our institutional IRB.

A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.

A comprehensive cellular anatomy of normal human prostate is essential for solving the cellular origins of benign prostatic hyperplasia and prostate cancer. The tools used to analyze the contribution of individual cell types are not robust. We provide a cellular atlas of the young adult human prostate and prostatic urethra using an iterative process of single-cell RNA sequencing (scRNA-seq) and flow cytometry on ∼98,000 cells taken from different anatomical regions. Immunohistochemistry with newly derived cell type-specific markers revealed the distribution of each epithelial and stromal cell type on whole mounts, revising our understanding of zonal anatomy. Based on discovered cell surface markers, flow cytometry antibody panels were designed to improve the purification of each cell type, with each gate confirmed by scRNA-seq. The molecular classification, anatomical distribution, and purification tools for each cell type in the human prostate create a powerful resource for experimental design in human prostate disease.

Molecular pathogenesis of human prostate basal cell hyperplasia.

BACKGROUND: Understanding the molecular pathogenesis of distinct phenotypes in human benign prostatic hyperplasia (BPH) is essential to improving therapeutic intervention. Current therapies target smooth muscle and luminal epithelia for relief of lower urinary tract symptoms (LUTS) due to BPH, but basal cell hyperplasia (BCH) remains untargeted. The incidence of has been reported at 8-10%, but a molecular and cellular characterization has not been performed on this phenotype. METHODS: Using freshly digested tissue from surgical specimens, we performed RNA-seq analysis of flow cytometry-purified basal epithelia from 3 patients with and 4 patients without a majority BCH phenotype. qPCR was performed on 28 genes identified as significant from 13 non-BCH and 7 BCH specimens to confirm transcriptomic analysis. IHC was performed on several non-BCH and BCH specimens for 3 proteins identified as significant by transcriptomic analysis. RESULTS: A total of 141 human BPH specimens were analyzed for the presence of BCH. Clinical characteristics of non-BCH and BCH cohorts revealed no significant differences in age, PSA, prostate volume, medical treatment, or comorbidities. Quantitation of cellular subsets by flow cytometry in 11 BCH patients vs. 11 non-BCH patients demonstrated a significant increase in the ratio of basal to luminal epithelia in patients with BCH (P <0.05), but no significant differences in the total number of leukocytes. RNA-seq data from flow cytometry isolated basal epithelia from patients with and without BCH were subjected to gene set enrichment analysis of differentially expressed genes, which revealed increased expression of members of the epidermal differentiation complex. Transcriptomic data were complemented by immunohistochemistry for members of the epidermal differentiation complex, revealing a morphological similarity to other stratified squamous epithelial layers. CONCLUSIONS: Increased expression of epidermal differentiation complex members and altered epithelial stratification resembles the progression of other metaplastic diseases. These data provide insight into the plasticity of the human prostate epithelium and suggest a classification of basal cell hyperplasia as a metaplasia.

Non-Cell-Autonomous Regulation of Prostate Epithelial Homeostasis by Androgen Receptor.

Prostate inflammation has been suggested as an etiology for benign prostatic hyperplasia (BPH). We show that decreased expression of the androgen receptor (AR) in luminal cells of human BPH specimens correlates with a higher degree of regional prostatic inflammation. However, the cause-and-effect relationship between the two events remains unclear. We investigated specifically whether attenuating AR activity in prostate luminal cells induces inflammation. Disrupting luminal cell AR signaling in mouse models promotes cytokine production cell-autonomously, impairs epithelial barrier function, and induces immune cell infiltration, which further augments local production of cytokines and chemokines including Il-1 and Ccl2. This inflammatory microenvironment promotes AR-independent prostatic epithelial proliferation, which can be abolished by ablating IL-1 signaling or depleting its major cellular source, the macrophages. This study demonstrates that disrupting luminal AR signaling promotes prostate inflammation, which may serve as a mechanism for resistance to androgen-targeted therapy for prostate-related diseases.

Penile prosthesis insertion for acute priapism.

Shunt surgery is not universally successful toward detumescence, may lead to erectile dysfunction, and can make eventual penile prosthesis insertion difficult. Penile prosthesis insertion during a priapistic episode alleviates ischemic pain, allows the patient to resume sexual function sooner, and prevents corporal scarring and shortening that makes subsequent prosthesis implantation difficult.

Central role of Boari bladder flap and downward nephropexy in upper ureteral reconstruction.

PURPOSE: We defined the role of the Boari bladder flap procedure with or without downward nephropexy for proximal vs distal ureteral strictures. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent open ureteral reconstruction for refractory ureteral strictures, as done by a single surgeon between 2007 and 2010. Patients were grouped by stricture site into group 1--proximal third of the ureter and group 2--distal two-thirds. Operative techniques and outcomes were reviewed. RESULTS: During the 30-month study period a total of 29 ureteral reconstruction procedures were performed on 27 patients. A Boari bladder flap was used in 10 of the 12 patients (83%) in group 1 and 10 of the 17 (59%) in group 2. Concomitant downward nephropexy was done more commonly in group 1 (58% vs 12%, p = 0.014). At a mean followup of 11.4 months there was no difference in the overall failure rate between groups 1 and 2 (17% vs 12%). Complications developed more frequently in group 1 (75% vs 35%, p = 0.060), hospital stay was longer (mean 8.0 vs 4.4 days, p = 0.017) and mean estimated blood loss was greater (447 vs 224 ml, p = 0.008). CONCLUSIONS: The Boari bladder flap procedure is a reliable technique to reconstruct ureteral strictures regardless of site. Renal mobilization with downward nephropexy is a useful adjunctive maneuver for proximal strictures.