BMP4 and GREM1 are targets of SHH signaling and downstream regulators of collagen in the penis.

BACKGROUND: Cavernous nerve (CN) injury, caused by prostatectomy and diabetes, initiates a remodeling process (smooth muscle apoptosis and increased collagen) in the corpora cavernosa of the penis of patients and animal models that is an underlying cause of erectile dysfunction (ED), and the Sonic hedgehog (SHH) pathway plays an essential role in the response of the penis to denervation, as collagen increases with SHH inhibition and decreases with SHH treatment. AIM: We examined if part of the mechanism of how SHH prevents penile remodeling and increased collagen with CN injury involves bone morphogenetic protein 4 (BMP4) and gremlin1 (GREM1) and examined the relationship between SHH, BMP4, GREM1, and collagen in penis of ED patients and rat models of CN injury, SHH inhibition, and SHH, BMP4, and GREM1 treatment. METHODS: Corpora cavernosa of Peyronie's disease (control), prostatectomy, and diabetic ED patients were obtained (N = 30). Adult Sprague Dawley rats (n = 90) underwent (1) CN crush (1-7 days) or sham surgery; (2) CN injury and BMP4, GREM1, or mouse serum albumin (control) treatment via Affi-Gel beads or peptide amphiphile (PA) for 14 days; (3) 5E1 SHH inhibitor, IgG, or phosphate-buffered saline (control) treatment for 2 to 4 days; or (4) CN crush with mouse serum albumin or SHH for 9 days. OUTCOMES: Immunohistochemical and Western analysis for BMP4 and GREM1, and collagen analysis by hydroxyproline and trichrome stain were performed. RESULTS: BMP4 and GREM1 proteins were identified in corpora cavernosa smooth muscle of prostatectomy, diabetic, and Peyronie's patients, and in rat smooth muscle, sympathetic nerve fibers, perineurium, blood vessels, and urethra. Collagen decreased 25.4% in rats with CN injury and BMP4 treatment (P = .02) and increased 61.3% with CN injury and GREM1 treatment (P = .005). Trichrome stain showed increased collagen in rats treated with GREM1. Western analysis identified increased BMP4 and GREM1 in corpora cavernosa of prostatectomy and diabetic patients, and after CN injury (1-2 days) in our rat model. Localization of BMP4 and GREM1 changed with SHH inhibition. SHH treatment increased the monomer form of BMP4 and GREM1, altering their range of signaling. CLINICAL IMPLICATIONS: A better understanding of penile remodeling and how fibrosis occurs with loss of innervation is essential for development of novel ED therapies. STRENGTHS AND LIMITATIONS: The relationship between SHH, BMP4, GREM1, and collagen is complex in the penis. CONCLUSION: BMP4 and GREM1 are downstream targets of SHH that impact collagen and may be useful in collaboration with SHH to prevent penile remodeling and ED.

Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue From Prostatectomy, Diabetic, and Peyronie's Patients.

BACKGROUND: Cavernous nerve (CN) injury causes penile remodeling, including smooth muscle apoptosis and increased collagen, which results in erectile dysfunction (ED), and prevention of this remodeling is critical for novel ED therapy development. AIM: We developed 2 peptide amphiphile (PA) hydrogel delivery vehicles for Sonic hedgehog (SHH) protein to the penis and CN, which effectively suppress penile distrophic remodeling (apoptosis and fibrosis), in vivo in a rat CN injury model, and the aim of this study is to determine if SHH PA can be used to regenerate human corpora cavernosal smooth muscle deriving from multiple ED origins. METHODS: Corpora cavernosal tissue was obtained from prostatectomy, diabetic, hypertension, cardiovascular disease and Peyronie's (control) patients (n = 21). Primary cultures (n = 21) were established, and corpora cavernosal cells were treated with SHH protein, MSA (control), 5E1 SHH inhibitor, and PBS (control). Growth was quantified by counting the number of cells at 3-4 days. Statistics were performed by ANOVA with Scheffe's post hoc test. Concentration of SHH protein for maximal growth was optimized, and a more active SHH protein examined. OUTCOMES: Cultures were characterized by immunohistochemical analysis with ACTA2, CD31, nNOS and P4HB, and smooth muscle was quantified in comparison to DAPI. RESULTS: Cultures established were >97% smooth muscle. SHH protein increased growth of smooth muscle cells from prostatectomy, diabetic, and Peyronie's patients in a similar manner (49%-51%), and SHH inhibition decreased growth (20%-33%). There was no difference in growth using 25 ug and 10 ug SHH protein, suggesting a threshold concentration of SHH protein above which smooth muscle growth is enhanced. A more active lipid modified SHH peptide further enhanced growth (15%), indicating a more robust growth response. SHH increased growth in smooth muscle cells from hypertension (37%) and cardiovascular disease (32%) patients. SHH protein increased growth under normal and high glucose conditions, suggesting that high glucose conditions that may be present in under controlled diabetic patients would not detract from SHH regenerative capacity. CLINICAL IMPLICATIONS: SHH PA would be beneficial to enhance smooth muscle regeneration in patients with ED of multiple etiologies. STRENGTHS AND LIMITATIONS: Understanding how human corpora cavernosal tissue responds to SHH treatment is critical for clinical translation of SHH PA to ED patients. CONCLUSION: Corpora cavernosal smooth muscle from all ED patients responded to SHH treatment with increased growth. Stupp, SI. Sonic Hedgehog Signaling in Primary Culture of Human Corpora Cavernosal Tissue From Prostatectomy, Diabetic, and Peyronie's Patients. J Sex Med 2022;19:1228-1242.

Randomized Trial of Bupivacaine Versus Liposomal Bupivacaine in Minimally Invasive Lobectomy.

BACKGROUND: The objective of this single-blind randomized study is to compare local infiltration of bupivacaine or liposomal bupivacaine (LipoB) in narcotic naïve patients undergoing minimally invasive lobectomy for early stage lung cancer. METHODS: Adult patients without previous lung surgery undergoing minimally invasive lobectomy (robotic or thoracoscopic) for early stage lung cancer were randomly assigned to bupivacaine (with epinephrine 0.25%, 1:200 000) or LipoB 1.3%. Pain level was documented using the visual analog scale and morphine equivalents for narcotic pain medications. Inhospital treatment cost and pharmacy cost were compared. RESULTS: The study enrolled 50 patients (bupivacaine, 24; LipoB, 26). The mean age of patients was 66 years, 94% were non-Hispanic white, and 48% were male. There was no difference in baseline characteristics and comorbidities. Duration of surgery (105 vs 137 minutes, P = .152), chest tube duration (49 vs 55 hours, P = .126), and length of stay (2.45 vs 3.28 days, P = .326) were similar between treatments. Inhospital morphine equivalents were 42.7 mg vs 48 mg (P = .714), and the median pain score was 5.2 vs 4.75 (P = .602) for bupivacaine vs LipoB, respectively. There was no difference in narcotic use at 2 to 4 weeks (57.1% [12 of 21] vs 54.5% [12 of 22], P = 1.00), and at 6 months (5.9% [1 of 17] vs 9.5% [2 of 21], P = 1.00) after surgery. The overall cost ($20 252 vs $22 775, P = .225) was similar; however, pharmacy cost for LipoB was higher ($1052 vs $596, P = .0001). CONCLUSIONS: In narcotic naïve patients undergoing minimally invasive lobectomy, short-term narcotic use, postoperative pain scores, length of stay, and long-term narcotic use were similar between bupivacaine and LipoB.

Developing a Novel, At-Home Procedure Curriculum for Fourth-Year Medical Students in Response to the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic provided our institution a unique opportunity to develop a new procedural curriculum for our fourth-year, emergency medicine-bound medical students. A significant portion of our ED's fourth-year elective has traditionally been centered in our simulation center, using high-fidelity simulation models to practice important emergency medicine procedures. Due to the pandemic, the simulation center was unavailable for our use, and this new curriculum was created in an effort to fill this gap in procedural education.

Mirabegron improves sleep measures, nocturia, and lower urinary tract symptoms in those with urinary symptoms associated with disordered sleep.

INTRODUCTION: The role of organized sleep in overall health and quality-of-life (QoL) is critical. Nocturia necessarily disrupts the normal sleep cycle and negatively impacts one's health, work productivity, and QoL. We investigated, for the first time in an exploratory pilot, the effectiveness of mirabegron for improving sleep disturbance and nocturia. MATERIALS AND METHODS: This was a prospective, open-label 12-week trial evaluating the efficacy of mirabegron in 34 men and women with disordered sleep and lower urinary tract symptoms (LUTS). Subjects received mirabegron 25 mg daily for 4 weeks, then increased to 50 mg. Subjects completed the Patient-Reported Outcome Measurement Information System Sleep Disturbance Short Form (PROMIS-SDSF), Jenkins Sleep Scale (JSS), International Prostate Symptom Score (IPSS), voiding diaries, and QoL questionnaires. RESULTS: PROMIS-SDSF scores decreased from 26.5 points to 19.3, representing a categorical improvement from clinically 'mild' to 'none to slight' sleep disturbance (p < 0.001). JSS scores also decreased from 14.1 to 8.3 (p < 0.001). IPSS decreased from 21.0 to 12.4, denoting a categorical improvement from 'severe' to 'moderate' LUTS (p < 0.001). Voiding diaries revealed 1.9 fewer voids per day (p < 0.01) and 0.8 fewer nighttime voids (p < 0.05). QoL improved from 0% in subjects who selected 'mostly satisfied,' 'pleased,' or 'delighted' to 29.6% at follow up. CONCLUSIONS: Mirabegron use improves nocturia and produces rapid, durable, and clinically significant improvement in sleep disturbance and LUTS in males and females with urinary symptoms associated with disordered sleep.

The effect of the urinary and faecal microbiota on lower urinary tract symptoms measured by the International Prostate Symptom Score: analysis utilising next-generation sequencing.

OBJECTIVE: To examine the correlation between urinary and faecal microbial profiles and the different aspects of lower urinary tract symptoms (LUTS) in men, as there is accumulating evidence that variations in the human microbiota may promote different benign disease conditions. PATIENTS AND METHODS: We extracted total DNA from urine and faecal samples of a group of men, under an Institutional Review Board-approved protocol. At the same time, International Prostate Symptom Score (IPSS) data were collected. We then amplified the extracted DNA and sequenced it using bacterial 16S ribosomal RNA gene high-throughput next-generation sequencing platform, and analysed the microbial profiles for taxonomy to examine the correlation between the different operational taxonomy units (OTUs) and LUTS represented by the total IPSS, the different symptom levels of the IPSS (mild, moderate, and severe) and its subcomponents of storage, nocturia, voiding, and bother. RESULTS: We included 30 patients (60 samples; one urine and one faecal per patient). In all, 48 faecal OTUs showed a significant correlation with one or more of the IPSS components; 27 with nocturia, 19 with bother, 16 with storage symptoms, and nine with voiding symptoms. The most substantial negative (protective) correlation was between Lachnospiraceae Blautia, a bacteria that increases the availability of gut anxiolytic and antidepressant short-chain fatty acids, and bother (correlation coefficient 0.702; P = 0.001). The abundance of L. Blautia continued to have a protective correlation against LUTS when looking at the different levels of IPSS severity (moderate and severe vs mild, correlation coefficient 0.6132; P = 0.002). Ten unique urinary OTUs showed significant correlation with LUTS; eight with nocturia, one with bother, three with storage, and one with voiding, but no faecal OUT had more than a low correlation with the outcomes of interest in this study. CONCLUSIONS: Our prospective work finds a plausible correlation between L. Blautia and LUTS. Additional studies are needed to determine if the correlations found in the present research are applicable to the general population of patients affected by LUTS.

Age and sex have no impact on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy.

OBJECTIVES: Advanced age and female sex have been associated with worse outcomes in patients undergoing radical cystectomy for muscle-invasive bladder cancer. A reduced immune response has been implicated as a mechanism. The objective of our study was to analyze the expression patterns of various cellular proteins active in bladder cancer immune pathways, and assess the correlation between age, sex, and the expression of these immune markers. METHODS: We obtained surgical tissue samples from equally distributed male/female patients with/without lymph node metastasis who had undergone radical cystectomy for urothelial carcinoma (UC) of the bladder (n = 50). Immunohistochemistry (IHC) for CD3 (cluster of differentiation), CD4, CD8, CD56, LAG-3 (lymphocyte-activation gene), TIM-3 (T-cell immunoglobulin and mucin-domain), PD-1 (programmed death) and PD-L1 molecules was performed and scored by a single pathologist (high versus low). Spearman's correlation and Chi square tests investigated the association between age, sex, and IHC results. RESULTS: Mean age at surgery was 67 years (range 50-78 years); all patients were Caucasians. The following percent of patients scored high for a stain: 18% CD3, 10% CD4, 0% CD8, 0% CD56, 20% LAG-3, 4% TIM-3, 0% PD-1 and 0% PD-L1. There was no association between patients' age, sex, and the expression of any of the immune markers (p > 0.05 for all). CONCLUSIONS: The association between advanced age, female sex, and worse outcomes in bladder cancer may be independent of the immune pathways active in the disease that we examined in this study.

Scrotoplasty at Time of Penile Implant is at High Risk for Dehiscence in Diabetics.

INTRODUCTION: Scrotoplasty has become a common practice during insertion of penile prosthesis, improving patient perception of penile length. Previous reports on scrotoplasty outcomes have only focused on the perceived benefits. The risk of wound complications after scrotoplasty is unknown. AIM: Identify wound complications and associated risk factors of scrotoplasty with insertion of penile prosthesis. METHODS: A retrospective review of a single-surgeon series (T.S.K.) of patients who underwent scrotoplasty with initial insertion of inflatable penile prosthesis (IPP) was performed from 2009-2014. Surgical outcomes and wound complications after scrotoplasty were examined, along with patient information, including basic demographics, medical comorbidities, and perioperative data. MAIN OUTCOME MEASURES: Studied outcomes included rate of wound complications after scrotoplasty and IPP insertion and identification of risk factors for wound dehiscence. RESULTS: Of the 103 scrotoplasties performed during the study period, a total of 15 had mild, moderate, or major wound dehiscence. Of these 15 cases, 9 had mild dehiscence and 5 cases had moderate dehiscence and required stitches to be placed in clinic to reinforce the closure. 1 patient had a major dehiscence requiring a return to the operating room for a washout, with exchange of IPP to malleable prosthesis. Multiple risk factors for wound dehiscence were found, including diabetes (odds ratio 6.1, CI 1.5, 25.0, P = .0129) and scrotoplasty technique (odds ratio 4.9, CI 1.2, 8.6, P = .003). Other examined variables, including patient age, Peyronie's disease, hypertension, intraoperative penile modeling, smoking, and device manufacturer, were not associated with wound dehiscence. CLINICAL IMPLICATIONS: Patients with diabetes and scrotoplasties performed via V-Y plasty are more likely to experience wound dehiscence. STRENGTHS & LIMITATIONS: Strengths include a single surgeon, thus lending continuity of skill and technique, a consecutive series, and 100% short-term follow-up. Limitations include retrospective design, single institution series, and lack of long-term follow-up. CONCLUSION: Although scrotoplasty can improve patient satisfaction with IPP, scrotoplasty can lead to increased patient morbidity. Diabetic patients are at increased risk for wound complication after scrotoplasty. Gupta NK, Sulaver R, Welliver C, et al. Scrotoplasty at Time of Penile Implant is at High Risk for Dehiscence in Diabetics. J Sex Med 2019;16:602-608.

Prospective examination of the changes in the urinary microbiome induced by transrectal biopsy of the prostate using 16S rRNA gene analysis.

OBJECTIVES: To prospectively examine the changes in microbiota within the urinary tract after transrectal prostate biopsy. MATERIALS AND METHODS: Data, urine, and fecal samples prospectively collected from 30 patients before and after transrectal biopsy of the prostate. DNA was extracted from urine collected after a prostate massage before and after prostate biopsy, and from fecal samples collected before the biopsy. We sequenced DNA using the bacterial 16S rRNA high-throughput next-generation sequencing and analyzed changes in microbial profiles for taxonomy comparison between samples. RESULTS: Pre-biopsy urinary microbial profiles contained Lactobacillus and Staphylococcus bacteria. Post-biopsy urinary microbial profiles included lower levels of Lactobacillus and higher levels of Prevotella bacteria. Bacteroides bacteria were predominant in fecal samples. We identified two clustering patterns containing both pre- and post-biopsy urine samples. Cluster 1 had a urine cluster pattern that was distinct from fecal, whereas cluster 2 was similar to fecal. We observed two different modes of microbial changes, 11 patients had both of their urine (pre and post) samples associated with a particular cluster group, whereas others (n = 15) had movement between clusters 1 and 2 following the biopsy procedure. Four patient's post-biopsy urine microbial profiles clustered very tightly to the fecal microbial profile. CONCLUSIONS: We describe two models of change in the urinary tract microbiota after prostate biopsy using 16S RNA gene analysis. Further research to determine what controls changes in the urinary microbiota after prostate biopsy can help us understand why some patients are more susceptible to develop post-biopsy infections.

A prospective study to examine the association of the urinary and fecal microbiota with prostate cancer diagnosis after transrectal biopsy of the prostate using 16sRNA gene analysis.

INTRODUCTION: There is accumulating evidence that variations in the human microbiota may promote disease states including cancer. Our goal was to examine the association between urinary and fecal microbial profiles and the diagnosis of prostate cancer (PC) in patients undergoing transrectal biopsy of the prostate. MATERIALS AND METHODS: We extracted total DNA from urine and fecal samples collected before a prostate biopsy performed for elevated prostatic specific antigen in patients suspected of having PC. We then amplified the extracted DNA and sequenced it using bacterial 16S rRNA gene high-throughput next-generation sequencing platform, and analyzed microbial profiles for taxonomy comparing those patients diagnosed with PC with those who did not receive that diagnosis. RESULTS: We included 30 patients in our analysis (60 samples, one urine and one fecal per patient). The majority of patients with PC (10/14) had similar bacterial communities within their urinary sample profile and clustered separately than patients without cancer (n = 16). Differential analysis of the operational taxonomical units (OTUs) in urine samples revealed decreased abundance of several bacterial species in patients with prostate cancer. Analysis of the bacterial taxonomies of the fecal samples did not reveal any clustering in concordance with benign or malignant prostate biopsies. Patients who had a Gleason score (GS) of 6 (n = 11) were present in both urine bacterial community clusters, but patients with GS 7 or higher (n = 3) did not cluster tightly with non-cancer subjects. CONCLUSIONS: The urinary microbiota of patients with PC tends to cluster separately from those without this disease. Further research is needed to investigate the urinary microbiome potential of serving as a biomarker that could be used to improve the accuracy of pre-biopsy models predicting the presence of PC in post-biopsy tissue examination.

Death due to sepsis in patients diagnosed with prostate cancer.

BACKGROUND: To examine the prevalence and determinants of death due to sepsis in patients diagnosed with prostate cancer (Pca). PATIENTS AND METHODS: We performed a retrospective analysis of 910 986 patients diagnosed with Pca between 1992 and 2010 identified from the Surveillance, Epidemiology, and End Results (SEER) database. Prevalence of death due to sepsis after diagnosis was determined. Trends in incidence-based mortality rate (IBMR) due to sepsis were compared with those of patients diagnosed with other common cancers. Competing risk analysis was utilized to examine the determinants of the endpoint of sepsis-specific death (SSD) in Pca patients. RESULTS: Of the Pca patients examined, 2593 died because of sepsis. Sepsis-related IBMR in Pca patients increased by 19-folds from 0.62/1000 000 in 1992-12.26/1000 000 in 2010. Compared with other selected cancers, patients with Pca had the highest IBMR due to sepsis post-cancer diagnosis, and the highest annual percentage change in IBMR due to sepsis (average annual percentage change, 13.1%; 95%CI, 9.4-16.9%). Age, race, education, marital status, and definitive therapy were all significant predictors of death due to sepsis after Pca diagnosis (all P values < 0.05). CONCLUSION: Patients diagnosed with Pca are at increased risk of dying from sepsis, and the sepsis-related IBMR in these patients is increasing over time. There are significant disparities in the outcome of sepsis among Pca patients that require further research.

Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence.

AIMS: Rhabdosphincter (RS) muscle injury occurs during prostatectomy, and is a leading cause of stress urinary incontinence (SUI). Current SUI treatments engender significant side effects, which negatively impact patient quality of life. Thus an unmet need exists to develop novel RS regeneration methods. We have shown that Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and we have developed novel peptide amphiphile nanofiber hydrogel delivery of SHH protein to the penis to regenerate smooth muscle after prostatectomy induced injury. If similar SHH signaling mechanisms regulate RS muscle homeostasis, this innovative technology may be adapted for RS regeneration post-prostatectomy. We examine the SHH pathway in human RS muscle. METHODS: Human RS obtained during radical cystoprostatectomy (n = 13), underwent SHH pathway analysis. Primary cultures were established (n = 5), and RS cells were treated with SHH protein, SHH inhibitor, or PBS (control). Immunohistochemical analysis for SHH pathway, skeletal muscle actin, and trichrome stain were performed. RS growth was quantified at 3 and 6 days. RESULTS: SHH, it is receptors patched and smoothened, and transcriptional activators, GLI proteins, were identified in human RS muscle. At 3 and 6 days, RS cells increased 62% and 78% (P = 0.0001) with SHH treatment and decreased 40% (P = 0.0001) and 18% (P = 0.039) with SHH inhibition. CONCLUSIONS: The SHH pathway was identified in human RS. RS growth increased with SHH treatment, indicating intervention may be possible to enhance RS regeneration, and impact SUI. Peptide amphiphile delivery of SHH may be applicable for RS regeneration and SUI prevention.

Ileus and small bowel obstruction after radical cystectomy for bladder cancer: Analysis from the Nationwide Inpatient Sample.

PURPOSE: To investigate prevalence and predictors of postoperative small bowel obstruction (SBO) and ileus in a large cohort of bladder cancer (BCa) patients treated with radical cystectomy (RC). METHODS: All patients within the Nationwide Inpatient Sample who underwent RC for BCa between 2006 and 2012 were identified. First, prevalence of SBO and ileus was analyzed. Second, predictors of these bowel-related complications were identified using multivariable regression analyses. Third, the association between SBO, ileus, and length of stay was evaluated using logistic regression models adjusted for clustering. Prolonged length of stay was defined as hospital stay above mean stay of the population (>10 days). Fourth, the effect of SBO and ileus on mean inpatient cost of healthcare was examined. RESULTS: Of overall 41,498 patients, 1071 (2.6%) experienced SBO, and 11,155 (26.9%) experienced ileus. Predictors of ileus included age, male gender, black race, hospital characteristics, anemia, chronic pulmonary disease, drug abuse, hypothyroidism, fluid and electrolyte disorders, and neurological disorders (all p < 0.05) Predictors of SBO included male gender, Asian/Pacific islander race, hospital characteristics, congestive heart failure, fluid and electrolyte disorders, and psychosis (all p < 0.05). . Postoperative SBO (odds ratio (OR) 19.587; 95% confidence interval (CI):15.869-24.167) and ileus (OR 5.646; 95% CI:5.336-5.974) were associated with prolonged length of stay (all p < 0.001).Median cost of hospital stay was $56.315 for patients who developed SBO, $32,472 for patients who developed ileus, and $24,600 for patients after cystectomy without ileus or SBO. CONCLUSIONS: Significant prevalence of bowel-related complications in patients after RC was observed. These complications are strongly associated with prolonged length of stay and higher healthcare cost. Increasing awareness of SBO and ileus, identification of patients at risk prior to surgery, and implementation of protective strategies are strongly indicated in cystectomy patients..

Three-Year Treatment Outcomes of Water Vapor Thermal Therapy Compared to Doxazosin, Finasteride and Combination Drug Therapy in Men with Benign Prostatic Hyperplasia: Cohort Data from the MTOPS Trial.

PURPOSE: We evaluated the long-term outcomes of treatment of lower urinary tract symptoms due to benign prostatic hyperplasia to compare a 1-time water vapor thermal therapy procedure with daily medical therapy in cohorts from the MTOPS (Medical Therapy of Prostatic Symptoms) study. MATERIALS AND METHODS: Results in the treatment arm of a randomized, controlled trial of thermal therapy using the Rezum® System were compared to MTOPS subjects treated with doxazosin and/or finasteride. Evaluations were restricted to medical therapy subjects, representing 1,140 of the original 3,047 (37.4%), with a prostate volume of 30 to 80 cc and an International Prostate Symptom Score of 13 or greater to include men who met key criteria of the Rezum and MTOPS trials. Outcomes were compared during 3 years for symptom changes and clinical progression rates. RESULTS: Thermal therapy improved symptom scores by approximately 50% throughout 36 months (p <0.0001). Symptom improvement was greater than with either drug alone but similar to that of combination drugs (p ≤0.02 and 0.73, respectively). The peak flow rate improved 4 to 5 ml per second after thermal therapy and doxazosin while thermal therapy was superior to finasteride and combination drugs for 24 and 12 months (p <0.001 and <0.01, respectively). Observed rates of clinical progression during 3 years corroborate these outcomes with approximately 5 times greater progression for any medical therapy vs a single thermal therapy procedure. CONCLUSIONS: A single water vapor thermal therapy procedure provided effective and durable improvements in symptom scores with lower observed clinical progression rates compared to daily long-term use of pharmaceutical agents.

Impact of County Rurality and Urologist Density on the Practice of Inguinal Lymph Node Dissection and Mortality in Patients Diagnosed with Squamous Cell Carcinoma of the Penis.

BACKGROUND: Inguinal lymphadenectomy (LND) is influential in reducing the mortality of squamous cell carcinoma of the penis (SCCP). We investigated the impact of urologic workforce density (UD) and rural residence (RR) on the practice of LND and mortality of SCCP (SCCP-RM). MATERIALS AND METHODS: UD was determined from the 2014 to 2015 Area Health Resource File data, while RR was determined using the 2003 rural-urban continuum codes. All cases of SCCP within the surveillance, epidemiology, and end results 18 registry with known county codes were used for analysis (n = 2863). RESULTS: Overall, 48.69% of cases lived in a county with less than the mean UD, 8.38% lived in counties with no urologists, 14.60% lived in a rural county, and 19.2% (n = 550) had LND performed. UD and RR had no impact on the prevalence of LND, number of lymph nodes examined, or the mean number of lymph nodes positive for SCCP (all p > 0.05). Adjusted analysis indicated that older patients and patients with regional stage of cancer were at a greater risk for post-LND SCCP-RM (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.28-2.21, and HR 4.32, 95% CI 3.09-6.06, respectively). There was no difference in the HR of SCCP-RM dependent on race, marital status, education, RR, UD, or LND. CONCLUSION: While demand on the urologist workforce has increased in rural demographics, no impact of limited access to urologists on the practice of LND in SCCP could be identified in this study. In addition, there was no significant difference in the risk of SCCP-specific mortality related to lower UD or RR.

Immune Characterization of the Programmed Death Receptor Pathway in High Risk Prostate Cancer.

BACKGROUND: Programmed cell death-1 (PD-1), a T-cell inhibitory receptor, and its ligand, PD-L1, have been reported to be expressed in many tumor types, and this expression has led to the development of many drugs targeting the PD-1 pathway. The objective of this study was to determine the expression of PD-1 and PD-L1 in high-grade prostate cancer tissues, and correlate the expression with disease and patient characteristics. MATERIALS AND METHODS: Immunohistochemistry for PD-1 (CD279), PD-L1 (B7-H1), and CD3 was performed and scored from 0 to 5 on prostatectomy/biopsy tissue samples taken from 25 men with high-grade prostate cancer. Charts were then retrospectively reviewed for numerous patient and disease characteristics. Statistical analyses were done to investigate the association of these patient and disease characteristics with PD-1, PD-L1, and CD3 expression. RESULTS: A score of 3 to 5 on the semiquantitative 0 to 5 score was deemed "high" expression whereas a score of 0 to 2 was deemed "low" expression. Of the 25 samples, 2 (8%) scored high for PD-1 expression, 2 (8%) scored high for PD-L1 expression, and 18 (72%) scored high for CD3 expression. There was no statistically significant difference between high and low expression groups of PD-1, PD-L1, or CD3 for any of the variables we collected. CONCLUSION: An overall low expression of PD-1 and PD-L1, and a concurrent high expression of CD3+ T cells was found in high-risk prostate cancer tissue. No significant association was found between expression of PD-1, PD-L1, or CD3, and patient or disease characteristics. Because of this, one might be able to question the role of PD-L1 in local immune suppression in prostate cancer.

Impact of Urologist Density and County Rurality on the Practice of Retroperitoneal Lymph Node Dissection and Cancer-Specific Death in Patients with Nonseminomatous Germ Cell Tumors.

PURPOSE: To investigate the impact of rural status and urologist density on the practice of retroperitoneal lymph node dissection (RPLND) and cancer-specific death (CSD) in patients with nonseminomatous germ cell tumor (NSGCT). METHODS: Urologist density was determined from 2014 to 2015 Area Health Resource File data, and rural residence was determined using the 2003 Rural-Urban Continuum Codes. All cases of NSGCT within Surveillance, Epidemiology and End Results (SEER) 18 with known county code were used for analysis (n = 9473). Fisher's exact test, t-tests, and Cox proportional hazard analysis were used to examine the association between variables of interest and study endpoints. RESULTS: Overall, 26.7% of cases lived in a county with less than the mean urologist density, 6.23% lived in counties with no urologists, 9.0% lived in a rural county, and 23.1% (n = 2208) had RPLND performed. RPLND was performed more in cases who lived in a county with a urologist and more in cases with urban residence (p < 0.05). The mean number of lymph nodes examined was lower in patients who lived in rural counties and counties with fewer urologists (p < 0.05). There was no difference in the number of positive nodes dependent upon either urologist density categorization or rurality (p > 0.05). Rurality and low urologist density were not associated with a higher risk of CSD related to NSGCT. CONCLUSIONS: Patient's residence and access to urologists affect their surgical NSGCT treatment, and efforts aimed at improving access to high-quality RPLND may be indicated.

Long-acting liposomal bupivacaine decreases inpatient narcotic requirements in men undergoing penile prosthesis implantation.

OBJECTIVE: A new extended-release bupivacaine suspension bupivacaine (ERSB) delivers 3 days of local anesthetic and has been shown to reduce pain and narcotic usage in some patient groups but this issue is largely unstudied in urologic surgery. MATERIAL AND METHODS: We performed a single-surgeon retrospective chart review of the patients who underwent penile prosthesis implantation. Pain scores and standardized morphine equivalent (ME) dose data were collected during 23 hour- observation period. Subjects who received ERSB were compared with those who received standard bupivacaine or no local anesthesia. RESULTS: In a study population of 37 patients, those who received (n=13), and did not receive (n=24) ERSB were grouped, respectively. The groups were comparable demographically. ME was used 3.2 fold more frequently in the non-ERSB group (18.0, and 5.6 for non-ERSB, and ESRB groups, respectively (p=0.04). Mean overall pain scores were 3.8/10 for ERSB and 3.9/10 for non-ERSB group, respectively. Per patient medication cost for the control, and ERSB groups were $5.16 and $285.54, respectively. CONCLUSION: The use of a new ERSB in penile prosthesis implants did lead to reduced narcotic consumption with comparable postoperative pain control to the non-ERSB group. However, the cost of the ERSB ($285/dose) may be prohibitive for its use.

Disparities in long-term radiographic follow-up after cystectomy for bladder cancer: Analysis of the SEER-Medicare database.

INTRODUCTION: It is uncertain whether there are disparities related to receiving long-term radiographic follow-up after cystectomy performed for bladder cancer, and whether intensive follow-up influences survival. MATERIALS AND METHODS: We analyzed 2080 patients treated with cystectomy between 1992 and 2004 isolated from the SEER-Medicare database. The number of abdominal computerized tomography scans performed in patients surviving 2 years after surgery was used as an indicator of long-term radiographic follow-up to exclude patients with early failures. RESULTS: Patients were mainly males (83.18%), had a mean age at diagnosis of 73.4 ± 6.6 (standard deviation) years, and mean survival of 4.6 ± 3.2 years. Multivariate analysis showed age >70 (odds ratio [OR]: 0.796, 95% confidence interval [CI]: 0.651-0.974), African American race (OR: 0.180, 95% CI: 0.081-0.279), and Charlson comorbidity score >2 (OR: 0.694, 95% CI: 0.505-0.954) to be associated with lower odds of long-term radiographic follow-up. Higher disease stage (Stage T4N1) (OR: 1.873, 95% CI: 1.491-2.353), higher quartile for education (OR: 5.203, 95% CI: 1.072-9.350) and higher quartile for income (OR: 6.940, 95% CI: 1.444-12.436) were associated with increased odds of long-term radiographic follow-up. Interestingly, more follow-up with imaging after cystectomy did not improve cancer-specific or overall survival in these patients. CONCLUSION: There are significant age, race, and socioeconomic disparities in long-term radiographic follow-up after radical cystectomy. However, more radiographic follow-up may not be associated with better survival.