Bladder neck contracture-incidence and management following contemporary robot assisted radical prostatectomy technique

PurposeBladder neck contracture (BNC) is a well-recognized complication following robot-assisted radical prostatectomy (RARP) for treatment of localized prostate cancer with a reported incidence of up to 1.4%. In this series, we report our institutional experience and management results.MethodsA prospectively collected database of patients who underwent RARP by a single surgeon from 2006 to 2012 was reviewed. Watertight bladder neck to urethral anastomosis was performed over 18-French foley catheter. BNC was diagnosed by flexible cystoscopy in patients who developed symptoms of bladder outlet obstruction. Subsequently, these patients underwent cold knife bladder neck incisions. Patients then followed a strict self regimen of clean intermittent catheterization (CIC). We identify the patient demographics, incidence of BNC, associated risk factors and success of subsequent management.ResultsTotal of 930 patients who underwent RARP for localized prostate cancer was identified. BNC was identified in 15 patients, 1.6% incidence. Mean patient age and preoperative prostate-specific antigen was 58.8 years old and 7.83 ng/mL (range, 2.5-14.55 ng/mL) respectively. Mean estimated blood loss was 361±193 mL (range, 50-650 mL). Follow-up was mean of 23.4 months. Average time to BNC diagnosis was 5.5 months. In three patients, a foreign body was identified at bladder neck. On multivariate analysis, estimated blood loss was significantly associated with development of BNC. All patients underwent cystoscopy and bladder neck incision with a 3-month CIC regimen. Out of 15 index patients, none had a BNC recurrence over the follow-up period.ConclusionsBNC was identified in 1.6% of patients in our series following RARP. Intraoperative blood loss was a significant risk factor for BNC. In 20% of BNC patients a migrated foreign body was noted at vesicourethral anastomosis. Primary management of patients with BNC following RARP should be bladder neck incision and self CIC regimen

Identification of C16orf74 as a Marker of Progression in Primary Non-Muscle Invasive Bladder Cancer

PURPOSE: Methylation-induced silencing of PRSS3 has been shown to be significantly associated with invasive bladder cancer, and expression of the C16orf74 gene locus has been shown to correlate positively with PRSS3. The aim of the current study was to evaluate the relationship between C16orf74 expression level and progression in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: C16orf74 mRNA levels were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis of 193 tumor specimens from patients with primary NMIBC. Expression data were analyzed in terms of clinical and experimental parameters. Kaplan-Meier curves and multivariate Cox regression models, respectively, were used to determine progression-free survival and to identify independent predictive parameters of progression. RESULTS: Analysis using Kaplan-Meier curves revealed prolonged progression-free survival of high-C16orf74-expressors as compared to low-expressors (p<0.001). Multivariate Cox regression analysis revealed that low C16orf74 mRNA expression levels are a significant risk factor for disease progression in patients with primary NMIBC (HR: 10.042, CI:2.699-37.360, p = 0.001). CONCLUSIONS: Decreased expression of C16orf74 correlates significantly with progression in primary NMIBC. C16orf74 expression level represents a potentially useful marker for predicting progression in primary NMIBC patients

Multi-institution analysis of racial disparity among African- American men eligible for prostate cancer active surveillance

There is a significant controversy on whether race should be a factor in considering active surveillance for low-risk prostate cancer. To address this question, we analyzed a multi-institution database to assess racial disparity between African-American and White-American men with low risk prostate cancer who were eligible for active surveillance but underwent radical prostatectomy. A retrospective analysis of prospectively collected clinical, pathologic and oncologic outcomes of men with low-risk prostate cancer from seven tertiary care institutions that underwent radical prostatectomy from 2003–2014 were used to assess potential racial disparity. Of the 333 (14.8%) African-American and 1923 (85.2%) White-American men meeting active surveillance criteria, African-American men were found to be slightly younger (57.5 vs 58.5 years old; p = 0.01) and have higher BMI (29.3 v 27.9; p \u3c 0.01), pre-op PSA (5.2 v 4.7; p \u3c 0.01), and maximum percentage cancer on biopsy (15.1% v 13.6%; p \u3c 0.01) compared to White-American men. Univariate and multivariate analysis demonstrated similar rates of upgrading, upstaging, positive surgical margin, and biochemical recurrence between races. These results suggest that single institution studies recommending more stringent AS enrollment criteria for AA men with a low-risk prostate cancer may not capture the complete oncologic landscape due to institutional variability in cancer outcomes. Since all seven institutions demonstrated no significant racial disparity, current active surveillance eligibility should not be modified based upon race until a prospective study has been completed. © Dinizo et al

JMASM 47: ANOVA_HOV: A SAS Macro for Testing Homogeneity of Variance in One-Factor ANOVA Models (SAS)

Variance homogeneity (HOV) is a critical assumption for ANOVA whose violation may lead to perturbations in Type I error rates. Minimal consensus exists on selecting an appropriate test. This SAS macro implements 14 different HOV approaches in one-way ANOVA. Examples are given and practical issues discussed

Decreased DBC1 Expression Is Associated With Poor Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer

Purpose The deleted in bladder cancer 1 (DBC1) gene is located within chromosome 9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but its prognostic value remains unclear. The aim of the present study was to investigate the value of DBC1 as a prognostic marker in BC. Materials and Methods The expression of DBC1 was determined by real-time polymerase chain reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and 124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The results were compared with clinicopathologic parameters, and the prognostic value of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression model. Results: DBC1 expression was significantly decreased in patients with MIBC compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05). By multivariate Cox regression analysis, low DBC1 expression was a predictor of progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates revealed a significant difference in tumor recurrence, progression to MIBC, and cancer-specific survival depending on the level of DBC1 expression in NMIBC (log-rank test, each, p<0.05). Conclusions: The expression of DBC1 was associated with tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results suggest that DBC1 expression can be a useful prognostic marker for patients with NMIBC

GSTM1 Tissue Genotype as a Recurrence Predictor in Non-muscle Invasive Bladder Cancer

Tissue genotyping is more useful approach than using blood genomic DNA, which can reflect the effects of the somatic mutations in cancer. Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC) development, few reports provide information about the prognosis of BC. We investigated glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) genotypes using genomic DNA from primary 165 BC tissue samples to assess the association with disease prognosis. DNA samples from tumor were analyzed by multiplex polymerase chain reaction (PCR). The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. Kaplan-Meier estimates revealed significant differences in time to tumor recurrence according to the GSTM1 tissue genotype (P = 0.038) in non-muscle invasive bladder cancer (NMIBC). Multivariate Cox regression analysis also revealed that the tissue GSTM1 genotype (hazards ratio [HR]: 0.377, P = 0.031) was an independent predictor of bladder tumor recurrence in NMIBC. This identification of GSTM1 tissue genotype as a prognosticator for determining recurrence in NMIBC should prove highly useful in a clinical setting

Oncologic outcomes in men with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institution international study

BackgroundThe presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population.MethodsData were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR).ResultsOf the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6%) were up-staged based on the pathologic analysis of PAFP and eight (9.1%) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8-10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7%) nodes were located in the middle portion of the PAFP.ConclusionsThere was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy

Bone Morphogenetic Protein Signaling: Implications in Urology

The bone morphogenetic proteins (BMPs), as members of the transforming growth factor-β (TGF-β) superfamily, not only control bone formation, but also regulate multiple key steps during embryonic development and differentiation. Furthermore, BMPs play critical roles in maintaining the homeostasis of the cardiovascular, pulmonary, reproductive, urogenital, and nervous systems in adult life. Like all members of the TGF-β superfamily, BMP signaling is mediated through a heteromeric complex of type I and type II transmembrane serine/threonine kinase receptors. The subsequent signal transduction cascade includes either the canonical Smad-dependent or non-canonical Smad-independent pathways. Reflecting the critical function of BMPs, BMP signaling is tightly regulated at multiple steps by various mechanisms including extracellular endogenous antagonists, neutralizing antibodies/extracellular soluble receptor domains, small molecule inhibitors, cytoplasmic inhibitory Smads, and transcriptional co-repressors. Recently, dorsomorphin, the first small molecule inhibitor of BMP signaling, was identified and suggested as a useful tool for dissecting the mechanisms of signaling pathways and for developing novel therapeutics for diverse human diseases that are related to the BMP signaling pathways. In this article, we discuss various mechanisms involved in regulating BMP signaling pathways and their implications for urology

Increased Expression of Herpes Virus-Encoded hsv1-miR-H18 and hsv2-miR-H9-5p in Cancer-Containing Prostate Tissue Compared to That in Benign Prostate Hyperplasia Tissue

Purpose: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. Methods: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. Results: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). Conclusions: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections