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.

Water vapor thermal therapy to alleviate catheter-dependent urinary retention secondary to benign prostatic hyperplasia.

BACKGROUND: Water vapor thermal therapy utilizes convectively delivered thermal energy to target ablation of obstructive prostatic tissue. We report results of this thermal therapy for relief of nonneurogenic complete urinary retention associated with BPH. PATIENTS AND METHODS: We conducted a retrospective analysis of 38 catheter-dependent men with complete urinary retention consecutively enrolled in a registry in two centers: median age 75.5 years and multiple comorbidities, median prostate volume 58.5 cc (23-153), median 2 failed trials without catheter (TWOCs), and median catheter dependency 3 months (0.3-35). The Rezum™ System thermal therapy procedure was performed in an ambulatory surgery center with conscious sedation or an office procedure room with a modified periprostatic block. Water vapor injections were customized to the configuration of the hyperplastic gland, including median lobe and/or enlarged central zone. RESULTS: Of the 38 treated patients, one was lost to follow-up and 26 of 37 (70.3%) voided spontaneously (mean of 1.6 ± 0.8 TWOCs) and were catheter free a median of 26 days (range 4-65) after the procedure; 18 of these 26 (69%) patients discontinued BPH medications. No significant differences in age, prostate volume, number of water vapor injections, or presence of the median lobe were associated with predicting a successful treatment outcome. Duration of follow-up for 20 catheter-free patients was a median of 475 days or 15.8 months (140-804 days); six patients were followed a median of 31.5 days (0-60). Adverse events were infrequent, mild, and resolved quickly including dysuria in five patients (13%), gross hematuria in four (10.5%), and UTIs in two (2.6%) with indwelling catheters. CONCLUSIONS: Water vapor thermal therapy may provide an effective and safe alternative to surgical treatment in this group of catheter-dependent patients in complete urinary retention.

Resident Impact on Patient & Surgeon Satisfaction and Outcomes: Evidence for Health System Support for Urology Education.

OBJECTIVE: To assess the effect of resident involvement on patient and physician satisfaction, we evaluated the outcomes from a private urology group both prior to and after initiation of resident coverage. METHODS: Urologic procedures completed by attending surgeons without residents from October 2010 to December 2011 were compared to the same surgeons working with residents from January 2012 to March 2013. Surgical case times, postoperative complications, readmission rate, length of stay, Press-Ganey consumer assessments, resident and physician self-report of training quality and quality of life were collected. RESULTS: 3316 operative and nonoperative cases were measured.Total 1565 were in preresident periods and 1751 were in postresident periods. With resident coverage, there was an increase in OR times. There was no difference in complications for surgical and nonsurgical cases (P = .2269 and P = 1.000, respectively). There was a statistically significant improvement of readmission rate in nonsurgical patients with resident coverage (P = .0344). Patients' satisfaction scores were higher in every category and they more often reported that they "always" received quality care (78.6 % vs 82.5%) with resident coverage. Resident and faculty perceptions of training, patient care, and satisfaction increased with resident coverage. CONCLUSION: Resident coverage of a private practice urology group resulted in no difference in surgical complications and improvement in readmission rates in nonsurgical patients. It resulted in longer OR times but greater satisfaction of faculty, residents and most important, patients. Our data demonstrate the beneficial effect of resident participation in patient care and provides further justification of residency financial support.

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.

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.

A Review of the FAERS Data on 5-Alpha Reductase Inhibitors: Implications for Postfinasteride Syndrome.

OBJECTIVE: To quantify reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS), create a demographic of patient reports, and examine the cluster of symptoms to correlate consistency of postfinasteride syndrome (PFS) complaints. PFS is a provisional diagnosis encompassing a cluster of sexual, physical, and psychological and/or neurologic symptoms associated with 5-alpha reductase inhibitor use that emerge or continue after discontinuation of medication. MATERIALS AND METHODS: FAERS dataset of 5-alpha reductase inhibitors from April 2011 to October 2014 was obtained. Each FAERS report had 16 categories for completion, but not every report was fully completed. Statistical analysis compared variables of interest between the 2 doses of finasteride (1 mg vs 5 mg). RESULTS: From FAERS, 2048 monotherapy cases were identified: 1581 of finasteride 1 mg, 240 of finasteride 5 mg, and 226 of unreported doses. Possibly related to labeling changes, from 2011 to 2014, there was a significant increase in adverse events (AEs) reported involving 1 mg dosing. Finasteride use was reported with many sexual AEs including diminished libido, erectile dysfunction, and ejaculatory complaints. Other common AEs included dermatologic, metabolic, and psychological and/or neurologic complaints. There were more AE reports with the 1 mg dose than the 5 mg dose. One case of dutasteride reported back pain, not generally attributed to PFS. CONCLUSION: FAERS data suggests that finasteride exposure is reported with a diverse collection of symptoms, particularly in younger men on 1 mg dosage compared to older men on 5 mg. Many of these complaints fall well out of the realm of previously established AEs from long-term controlled studies.

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.

Convective Radiofrequency Water Vapor Thermal Therapy with Rezum System.

PURPOSE: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are amongst the most commonly treated conditions by urologists. Minimally invasive therapies for the treatment of BPH/LUTS have garnered increased interest as new technology has emerged, improving durability, efficacy, and safety. This paper reviews the most recent literature regarding water vapor therapy, a convective thermal therapy that ablates prostatic tissue. RECENT FINDINGS: The current literature includes a pilot study of 65 men and a randomized controlled trial (RCT) of 197 men investigating the efficacy and safety profile of water vapor therapy up to 2 years. Subjects treated with water vapor therapy demonstrated a 51% reduction in IPSS from baseline, sustained at 24 months (p < 0.0001). Durable improvements in max flow rate (Qmax) and quality of life (QoL) were also achieved, while no changes in sexual function were observed. Reporting of adverse events (AEs) reveals predominantly Clavien grade I complications that were self-limited. The clinical efficacy and safety of water vapor therapy are durable to 24 months making it an attractive alternative for patients seeking a minimally invasive treatment for LUTS due to BPH.

The Effect of Targeted Therapy for Genitourinary Malignancies on Sexual Function and Fertility.

PURPOSE OF REVIEW: Targeted therapy for genitourinary cancer is being used at an increasing rate. These medications show great survival benefit but are relatively lacking in long-term adverse effect data. With increasing survivability, measures to improve quality of life must be considered for GU cancer and a large proponent of this is sexual function. RECENT FINDINGS: mTOR inhibitors have shown an effect on testosterone levels and may have a link to abnormal semen parameters. Tyrosine kinase inhibitors (TKIs) have shown no adverse sexual outcomes in the literature. There are laboratory links to tyrosine kinases having a beneficial effect on erectile and sexual function. Possible sexual side effects must be discussed with patients receiving a diagnosis of cancer. Further research is required to determine the exact mechanisms and outcomes of sexual function with new and emerging targeted therapy.

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.

Contemporary Experience with Partial Nephrectomy for Stage T2 or Greater Renal Tumors.

The purpose of this paper is to review current studies on the topic of partial nephrectomy (PN) for renal masses stage T2 and greater. We conducted a PubMed literature review of English language articles published from 2000 onward. Eight studies were selected for this review including 359 PN patients. Median tumor size was 7.5 to 8.7, and tumor histology was mainly clear cell. Technique was mainly open, the reported median ischemia time was 29-45 min, and median operative time 170-221 min. Positive margin rates were 0-31%. On a median follow-up range of 13.1 to 70 months, 5-year progression-free survival was 71-92.5%, and 5-year overall survival was 66-94.5% in the study populations. There is limited retrospective evidence in favor of preserved oncologic efficacy in patients with renal tumors larger than 7 cm in size treated with nephron-sparing surgery. This review emphasizes the need for more studies and long-term follow-up data to determine the proper role of partial nephrectomy in large kidney tumors.

Minimizing Penile Implant Infection: A Literature Review of Patient and Surgical Factors.

Inflatable penile prosthesis (IPP) is an effective treatment for erectile dysfunction in patients' refractory to oral or injectable treatment. While the rate of infection has decreased over the past decade, it is still the most feared complication of IPP placement. Here, we assemble possible patient and surgical factors attributing to the risk of infection. Studies have been gathered addressing each of these factors, and an Oxford Level of Evidence is assigned to each recommendation based on strength of the study. The goal of this review is to inform surgeons of possible risks in order to further reduce the risk of infection and thus increase success of IPP placement.

Prevalence and Prognostic Value of Lymph Node Dissection in Treating Adrenocortical Carcinoma: A National Experience.

AIM: We examined a national database to investigate the role of lymph node dissection (LND) in adrenocortical carcinoma (ACC) treated surgically. PATIENTS AND METHODS: Patient data diagnosed with ACC between 1991 and 2011 were extracted from a national database. Predictors of LND, positive lymph nodes on LND, and the association between positive LND and cancer-specific death were examined. RESULTS: Only 5.39% of patients underwent LND, and 31.03% had positive lymph nodes. Disease stage was the only significant predictor of LND (odds ratio=3.061; 95% confidence interval=1.158-8.091), and finding more than one positive lymph nodes on LND was the only significant predictor of cancer-specific death (hazard ratio=3.13; 95% confidence interval=1.233-7.95) in tumors larger than 3 cm in size. CONCLUSION: LND is not a common practice in treating ACC in the United States. The finding of more than one positive lymph nodes on LND for ACC is associated with poor prognosis.

Contemporary Incidence and Mortality Rates of Neuroendocrine Prostate Cancer.

AIM: The purpose of the study was to provide an update ever the incidence and mortality for neuroendocrine prostate cancer (NEPC) in the United States. PATIENTS AND METHODS: Using a large national database, we examined changes in age-adjusted incidence (AAIR), mortality rates (MR) and 5-year cancer-specific survival (CSS) for 378 patients diagnosed with NEPC between 1992 and 2011. Analysis was performed for all NEPC and for its two major sub-groups [small cell carcinoma (SCC) and neuroendocrine carcinoma (NEC)]. RESULTS: AAIR of NEPC continues to rise in recent years (2004-2011:+6.8%/year, p>0.05). AAIR of SCC has been increasing significantly by 6.94%/year since 2001 (from 0.470 to 0.582/1,000,000 person years, p<0.05). Overall incidence-based mortality rates for NEPC did not change significantly since 1992 and similar trends were observed for SCC and NEC. CONCLUSION: The AAIR of SCC is increasing with no change in the MR of NEPC over the past 20 years.

Partial nephrectomy for T2 renal masses: contemporary trends and oncologic efficacy.

PURPOSE: Increasing popularity and improved technical feasibility of partial nephrectomy (PN) has encouraged urologists to treat larger renal masses with nephron-sparing surgery. We used a national database to characterize practice patterns for the surgical management of patients with T2 renal tumors and examined the effect of PN on cancer-specific survival in such patients. METHODS: Between 2001 and 2011, 10,259 patients with primary tumor size >7 cm confined to the kidney (T2) were treated surgically for kidney cancer. PN trends were examined using annual percentage change (APC). Multivariate survival models were developed to identify independent determinants of PN use and cancer-specific survival (CSS) following surgical treatment of kidney cancer. RESULTS: Overall, 543 patients (5.29 %) were treated with PN versus 9716 (94.71 %) who underwent radical nephrectomy (RN). The use of PN increased progressively between 2001 and 2011 (APC +11.1 %, p < 0.05). Male gender, geographic location, year of diagnosis, and disease stage were independent determinants of increased PN use (all p values <0.05). Cancer-specific mortality was not inferior for patients treated with PN versus RN (HR 0.68, 95 % CI 0.50-0.94). Male gender, younger age, white race, tumor size >10 cm, localized disease, and papillary histology were all associated with improved CSS with PN (all p values <0.05). CONCLUSIONS: PN is increasingly utilized to treat T2 renal masses. Our analysis demonstrates that PN for T2 renal masses has no contraindicated effect on CSS.

Primary tumor size predicts pathologic findings in the retroperitoneal lymph nodes in patients with paratesticular rhabdomyosarcoma.

To determine patient and tumor characteristics that could predict pathologic findings after retroperitoneal lymph node dissection (RPLND) in paratesticular rhabdomyosarcoma (PTRMS), a total of 266 cases of PTRMS diagnosed between 1973 and 2010 were identified from a national database. RPLND dissection was performed in 67 patients, with a mean age of 14.9 years and median survival of 80 months. PTRMS occurred more often on the right side, had embryonal histology, and had an average size of 6.7 cm. Retroperitoneal lymph node (RPLN) metastasis occurred in 40 % (n = 27) of patients. Tumor size and age were strong predictors of finding rhabdomyosarcoma in the retroperitoneal lymph nodes when examined by pathologists. Primary tumors larger than 7 cm in size developing in males 12 years or older had four times more odds of being associated with positive findings on pathologic examinations of the retroperitoneal lymph nodes. Patient race, histology, and tumor laterality were not significant predictors of PTRMS metastasis to the RPLN basin. Patients 12 years or older with PTRMS larger than 7 cm have a significant risk of retroperitoneal lymph nodes involvement with PTRMS. Detailed pathologic examination of the lymph nodes in these patients is recommended.