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.

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment. METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions. RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment. CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).

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.

KEYNOTE-676: Phase III study of BCG and pembrolizumab for persistent/recurrent high-risk NMIBC.

Background: Nonmuscle-invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with high rates of disease recurrence and progression. Current treatment for high-risk NMIBC involves Bacillus Calmette-Guérin (BCG) therapy, but treatment options are limited for patients with recurrent or BCG-unresponsive disease. Aberrant programmed death 1 signaling has been implicated in BCG resistance and bladder cancer recurrence and progression, and pembrolizumab has shown efficacy in patients with BCG-unresponsive high-risk NMIBC. Aim: To describe the rationale and design for the randomized, comparator-controlled Phase III KEYNOTE-676 study, which will evaluate the efficacy and safety of pembrolizumab in combination with BCG in patients with persistent/recurrent high-risk NMIBC after BCG induction therapy. Trial registration number: NCT03711032.

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 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.

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.

Effect of Lesion Location on Prostate Cancer Detection Rate with Magnetic Resonance Imaging Targeted Biopsy in African Americans.

PURPOSE: The updated PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 defines different grading parameters for lesions located in the peripheral zone vs the transition zone. It has contributed to the implementation of magnetic resonance imaging targeted biopsy. In this study we evaluated the efficacy of magnetic resonance imaging targeted biopsy among African American patients with additional consideration for lesion location on magnetic resonance imaging. MATERIALS AND METHODS: We performed a retrospective review of magnetic resonance imaging targeted biopsy at a single institution where a racially diverse population is treated. A single radiology group read the prostate multiparametric magnetic resonance imaging scans and followed PI-RADS version 2 algorithms to categorize lesions. RESULTS: A total of 214 lesions from 125 men were included in the analysis, of which 162 (75.7%) were in the peripheral zone and 52 (24.3%) were in the transition zone. There were 64 lesions from African American patients and 150 from Caucasian patients with tumor location distributed proportionately. The 48 anterior lesions (22.4%) had a higher PI-RADS version 2 score and trended toward a larger size. The overall cancer detection rate was 50%, which did not differ significantly between prostate zones (p = 0.5468) or racial groups (p = 0.2294). The cancer upgrade rate was 41% and it also did not differ significantly between prostate zones (p = 0.5134) or racial groups (p = 0.2365). Anterior lesions had a higher cancer detection rate (p = 0.0117) and trended toward a higher cancer upgrade rate (p = 0.0781). CONCLUSIONS: This study provides evidence that magnetic resonance imaging targeted biopsy is equally effective in African American and Caucasian men, and does not preferentially identify prostate cancer in the peripheral zone or the transition zone.

Prostate cancer with comedonecrosis is frequently, but not exclusively, intraductal carcinoma: a need for reappraisal of grading criteria.

AIMS: Comedonecrosis in prostate cancer has always been Gleason pattern 5. However, we aimed to evaluate how intraductal carcinoma (not graded) with comedonecrosis should be considered. METHODS AND RESULTS: From 52 radical prostatectomy patients, 40 were informative and evaluated with immunohistochemistry for basal cells. Clinical outcome was assessed for biochemical recurrence, metastatic disease and the need for adjuvant therapy. Comedonecrosis was predominantly located in intraductal carcinoma (24, 60%). However, nine (23%) had comedonecrosis within invasive cancer and seven (18%) within both invasive and intraductal carcinoma. Extraprostatic extension rarely showed comedonecrosis (5, 13%), but rather perineural invasion within cribriform glands. Tumours were largely high-stage (15, 38% pT3a and 19, 48% pT3b), with 15 (37%) having positive lymph nodes and four distant metastases. Most cases (25, 63%) had other patterns of Gleason pattern 5 (single cells, solid), although 10 were reclassified as containing no invasive pattern 5. Of these, most were pT3 (eight of 10), but none had positive lymph nodes. Lymph node metastases were more common in patients with invasive cancer containing comedonecrosis (P = 0.02), and the need for androgen deprivation was near significance (P = 0.07), but biochemical recurrence was not significantly different (P = 0.58). CONCLUSIONS: Prostate cancer with comedonecrosis is often intraductal; however, these tumours are largely high-stage, showing a higher rate of positive lymph nodes with invasive comedonecrosis. Immunohistochemistry may be considered when comedonecrosis may significantly change the tumour grade. However, it is not clear at present that excluding intraductal carcinoma from the grade is superior to including it in grading when it is associated with high-grade invasive cancer.

Update of the International Consultation on Urological Diseases on bladder cancer 2018: non-urothelial cancers of the urinary bladder.

PURPOSE: To provide a comprehensive update of the joint consultation of the International Consultation on Urological Diseases (ICUD) for the diagnosis and management of non-urothelial cancer of the urinary bladder. METHODS: A detailed analysis of the literature was conducted reporting on the epidemiology, etiology, diagnosis, treatment and outcomes of non-urothelial cancer of the urinary bladder. An international, multidisciplinary expert committee evaluated and graded the evidence according to the Oxford System of Evidence-based Medicine modified by the ICUD. RESULTS: The major non-urothelial cancers of the urinary bladder are squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. Several other non-urothelial tumors are rare but important to identify because of their aggressive behavior when compared to urothelial bladder tumors. Radical cystectomy and urinary diversion, preceded by neoadjuvant radiation or chemotherapy in some of these tumors, is the main method or treatment for resectable disease. Adjuvant therapy is not usually successful and no novel targeted or immunotherapeutic agents have been identified to provide benefit. Patients with small cell neuroendocrine tumors of the bladder should be offered chemotherapy before surgery. Because non-urothelial cancers are usually locally advanced and/or metastatic at the time of diagnosis, 5-year survival is generally poor. CONCLUSIONS: Non-urothelial cancers of the urinary bladder are rare and mostly lack established protocols for treatment. The prognosis of most of these tumors is poor because they are usually advanced at the time of diagnosis. A multimodal treatment approach should be considered to improve outcomes.

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.

Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract are genetically different from nodular fasciitis and lack USP6, ROS1 and ETV6 gene rearrangements.

AIMS: Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract have a debatable relationship with inflammatory myofibroblastic tumour (generally lacking ALK rearrangement); however, they share several overlapping features with nodular fasciitis of soft tissue. As rearrangement of the USP6 gene has been recently recognised as a recurrent alteration in soft tissue nodular fasciitis, and several other alternative gene fusions have been recently recognised in inflammatory myofibroblastic tumour, the aim of this study was to investigate whether USP6, ROS1 or ETV6 rearrangements were present in these lesions (12 cases). METHODS AND RESULTS: Fluorescence in-situ hybridisation analysis was performed by the use of bacterial artificial chromosome-derived break-apart probes against USP6, ROS1, and ETV6. Two cases with adequate genetic material from recent paraffin tissue blocks were also tested by use of a solid tumour gene fusion detection assay via next-generation sequencing, targeting >50 known genes involved in recurrent fusions. None of the genitourinary pseudosarcomatous myofibroblastic proliferations was found to harbour USP6 (0/12), ROS1 (0/8) or ETV6 (0/7) rearrangements, and no gene fusions were detected in two cases studied by sequencing. CONCLUSIONS: Despite overlap in histological and immunohistochemical features between pseudosarcomatous myofibroblastic proliferation and nodular fasciitis, these tumours lack the recently recognised USP6 rearrangements that occur in nodular fasciitis, as well as alternative fusions found in ALK-negative inflammatory myofibroblastic tumours. At present, this diagnosis remains based primarily on clinical, histological and immunohistochemical features.

Endocrine, Sexual Function, and Infertility Side Effects of Immune Checkpoint Inhibitor Therapy for Genitourinary Cancers.

PURPOSE OF REVIEW: Immune checkpoint therapy has grown in prominence in the last few decades and is being increasingly utilized in treatment of advanced cancers. Although information on toxicities of these drugs is forthcoming, not much is known regarding the toxicity profile of these drugs from a sexual function standpoint. We undertook the current review to appraise the literature for endocrine/sexual side effects of anti-PD-1/PD-L1 and anti-CTLA-4 therapy. RECENT FINDINGS: Our review included 32 articles and focused primarily on the programmed death (PD) pathway. We found that endocrine side effects after anti-PD-1/PD-L1 therapy are relatively rare, with hypothyroidism (range < 1 to 40%) and hypophysitis (range < 1 to 10%) being the two most common. None of the studies specifically commented on the infertility or sexual side effects of these drugs. However, two studies evaluating biochemical profiles of patients undergoing therapy with ipilimumab (a CTLA-4 inhibitor) or combination therapy (CTLA-4 + PD-1/PD-L1 inhibitors) noted that about < 1 to ~ 60% of the patients developed hypogonadotropic hypogonadism. None of the studies provided information regarding clinically meaningful sexual health endpoints such as libido, erectile function assessments, or sexual function-related quality of life. Endocrine side effects, although uncommon, are important and unique side effects of immune checkpoint therapy because they are often complex and can be life threatening. While side effects on sexual health may not be life threatening, they are lifestyle limiting. Thus, long-term follow-up, post-marketing surveillance, and future studies will need to elucidate the true rates of endocrine/sexual side effects and the mechanisms underlying them. This will aid in better counseling of the patients, as more of them undergo these novel immune checkpoint inhibitor therapies.

Single nucleotide variant in Nucleoporin 107 may be predictive of sensitivity to chemotherapy in patients with ovarian cancer.

BACKGROUND: Alterations in nuclear pore complex (NPC) genes have been previously associated with response to chemotherapy. Using agnostic exome sequencing, we envisioned that new alleles in NPC genes, predictive of sensitivity to platinum treatment, could be discovered. METHODS: Twenty-two platinum-sensitive and six platinum-resistant ovarian cancer patients were tested. Platinum sensitivity was defined as disease-free survival greater than 6 months. Next-generation sequencing of exomes was used to compare platinum-sensitive and platinum-resistant patients. Single nucleotide variants (SNVs) associated with platinum sensitivity in NPC genes (n=30 genes) were identified. RESULTS: SNVs in three NPC genes were associated with response to platinum on univariate analysis. SNV rs79419059 (10T>C) in Nucleoporin 107 (Nup107) was associated with platinum resistance (P=0.0061), whereas rs2302811 (3662-4A>G) in Nucleoporin 188 (Nup188) and rs77246077 (3420-67T>A) in Nucleoporin 214 (Nup214) were associated with platinum sensitivity (P=0.0483 and 0.0091, respectively). Controlling for other confounders, multivariate age-adjusted Cox proportional hazard analysis showed rs79419059 to be significantly associated with platinum resistance (odds ratio: 4.519, 95% confidence interval: 1.317-15.501, P=0.0457). CONCLUSION: We identified a variant in the 3'-UTR region Nup107 unique to sensitivity to platinum in ovarian cancer. With validation of this variant, it is possible that a new marker predictive of patient response may be identified.

Evaluating the association of multiple single nucleotide polymorphisms with response to gemcitabine and platinum combination chemotherapy in urothelial carcinoma of the bladder
.

OBJECTIVE: To examine germline single nucleotide polymorphisms (SNPs) as markers of response to gemcitabine platinum (GP) combination chemotherapy in urothelial carcinoma (UC). METHODS: Saliva or blood was prospectively collected from 216 patients treated with GP for UC of the bladder between 1991 and 2011. Based on reported associations with gemcitabine and cisplatin response or putative mechanisms of gemcitabine or cisplatin/carboplatin activity, we selected SNPs of interest and were able to genotype 59 SNPs (using the SequenomMass ARRAYiPLEX platform) in 261 patients randomly split 2/3 into a training set (n = 174) and 1/3 into a test set (n = 87). Logistic regression was used to test the association between response to GP and SNPs. RESULTS: The median age at diagnosis was 64 years (range: 28 - 85) for the discovery set and 67 years (range: 30 - 84) for the validation set. Males composed 76% and 69%, and white non-Hispanics composed 88% and 91% of the training and test validation sets, respectively. Three SNPs on GALNTL4 (rs7937567, rs12278731, and rs9988868) and one intergenic SNP (rs1321391) were significantly associated with response to GP in the training set and were used to build a SNP score. However, when assessed in the test set, the SNP score was not significantly associated with response. CONCLUSION: Multiple SNPs selected from previous studies failed to predict response to GP in this cohort. Larger studies capable of accounting for population-based allele frequency heterogeneity may be required for replication of genetic alterations important to pharmacogenomics.
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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.

A1 Adenosine Receptor-Mediated Inhibition of Parasympathetic Neuromuscular Transmission in Human and Murine Urinary Bladder.

The potential role of A1 adenosine receptors in modulating neuromuscular transmission in the detrusor muscle of the urinary bladder has been tested in human and murine preparations with the intent to determine the viability of using adenosine receptor agonists as adjuncts to treat overactive bladder. In human detrusor muscle preparations, contractile responses to electrical field stimulation were inhibited by the selective A1 adenosine receptor agonists 2-chloro-N(6)-cyclopentyladenosine, N(6)-cyclopentyladenosine (CPA), and adenosine (rank order of potency: 2-chloro-N(6)-cyclopentyladenosine > CPA > adenosine). Pretreatment with 8-cyclopentyl-3-[3-[[4(fluorosulphonyl)benzoyl]oxy]propyl]-1-propylxanthine, an irreversible A1 antagonist, blocked the effects of CPA, thus confirming the role of A1 receptors in human detrusor preparations. In murine detrusor muscle preparations, contractions evoked by electrical field stimulation were reduced by CPA or adenosine. Amplitudes of the P2X purinoceptor-mediated excitatory junctional potentials (EJPs) recorded with intracellular microelectrodes were reduced in amplitude by CPA and adenosine with no effect on the spontaneous EJP amplitudes, confirming the prejunctional action of these agents. 8-Cyclopentyltheophylline, a selective A1 receptor antagonist, reversed the effects of CPA on EJP amplitudes with no effect of spontaneous EJPs, confirming the role of A1 receptors in mediating these effects.

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.

The Use of Urodynamics Assessment Before the Surgical Treatment of BPH.

Lower urinary tract symptoms (LUTS) are a common problem in men especially with aging. The International Continence Society (ICS) revealed an overall prevalence of LUTS of about two-thirds of men age 40 years and above. The treatment approach depends on accurate determination of the underlying etiology. LUTS is not unique to benign prostate enlargement (BPE) and can be secondary to other causes. In the era where quality of care is important, accurate diagnosis and counseling to meet patients' expectations is of extreme paramount. Thus, proper assessment of patients who present with BPE and LUTS should be an important part of the work up process. Accurate diagnosis and identification of the cause will help to improve quality of treatment, optimize counseling, and improve treatment outcomes. Pressure flow urodynamic studies (PFUDs) are not only important tools that help to identify the underlying causes of LUTS; it is considered the "gold standard" for diagnosis of bladder outlet obstruction (BOO) in patients with enlarged prostate [1, 2]. However, there is a continuous debate on the value of using PFUDs and its association with improved outcomes.