Tanner Miest

Targeted Entry of Enveloped Viruses: Measles and Herpes Simplex Virus I

We compare the receptor-based mechanisms that a small RNA virus and a larger DNA virus have evolved to drive the fusion of viral and cellular membranes. Both systems rely on tight control over triggering the concerted refolding of a trimeric fusion protein. While measles virus entry depends on a receptor-binding protein and a fusion protein only, the herpes simplex virus (HSV) is more complex and requires four viral proteins. Nevertheless, in both viruses a receptor-binding protein is required for triggering the membrane fusion process. Moreover, specificity domains can be appended to these receptor-binding proteins to target virus entry to cells expressing a designated receptor. We discuss how principles established with measles and HSV can be applied to targeting other enveloped viruses, and alternatively how retargeted envelopes can be fitted on foreign capsids.

PD66-12 OUTCOMES ON ILEAL MUCOSAL CUFF MANAGEMENT DURING RADICAL NEPHROURETERECTOMY

characteristics associated with patients’ risk of cancer-specific mortality (CSM). Kaplan-Meier analysis was used to evaluate recurrence free survival (RFS). RESULTS: Median patient age at RNU was 73.7 years (IQR 65.4, 79.5); 67% (n1⁄4249) were male and 64% (n1⁄4238) underwent extravesical excision. Median follow-up was 47 months (IQR 16.4, 101.4), during which time 52.4% (n1⁄4195) experienced a bladder or systemic recurrence and 17.5% (n1⁄465) died due to metastatic urothelial carcinoma. There was no statistically significant difference for 5-year RFS between the two groups (p1⁄40.29). On multivariable analysis features independently associated with increased risk of CSM included smoking history (HR 2.31; p1⁄40.03), high grade (HR 4.23; p<0.001), pT2 or higher (HR 2.51; p1⁄40.01), lymph node positive disease(HR 4.29; p<0.01) and tumor size > 3 cm (HR 2.10; p1⁄40.02). Importantly, approach to the bladder cuff excision was not associated with an increased risk of disease recurrence (HR1⁄41.11; p1⁄40.60) or CSM (HR 1.26; p1⁄40.52). CONCLUSIONS: Excision of the entire ureter, including the intramural component, is an important part of RNU. However, intraor extravesical approach to the distal ureter, does not affect RFS or CSM. Therefore, our data validates the oncologic safety of both approaches to the bladder cuff for patients undergoing RNU for UTUC.

MP84-04 PREDICTION OF FUTURE ERECTILE DYSFUNCTION USING COMORBID DISEASE AND MEDICATION PROFILES

by three observers at different time points, each being blinded to the goniometer assessment. The primary outcome was to compare the inter-observer and intra-observer reliability of GoSoft. We also aimed to compare the concordance between GoSoft and goniometry. We compare correlation for curvature 45 degrees and for > 45 degrees. We accepted a variability of 5 degrees and considered an under and over-estimation if the difference was >5 degrees. RESULTS: 53 subjects were included. The intra-observer reliability was excellent, representing a high correlation ( r1⁄40.96 to 0.98, p<0.001) with a variance between means of 1.3 0.6 degrees. The inter-observer reliability was also high (r1⁄40.89 to 0.95, p<0.001) (Figure 1) with a variance between means of 2.2 1 degrees. The Pearson correlation coefficients (r) between the goniometer and GoSoft for each rater were: Rater 1: r1⁄40.75, p<0.001; Rater 2: r1⁄40.73, p<0.001; and Rater 3: r1⁄40.80, p<0.001. This indicates strong agreement, but also suggests variability between the types of measurement. For the three raters, when comparing GoSoft to the goniometer, GoSoft accurately measured (within 5 degrees) 45% of the curvatures, underestimated it by >5 degrees in 25% of the curvatures, and overestimated it by >5 degrees in 30% of the curvatures. The correlation appears to be higher for greater curvatures. For curvature 45 degrees, the correlations between goniometer and GoSoft ranged from: r1⁄40.41-0.47, p1⁄40.03; while, for curvatures > 45 degrees, the correlations ranged from: r1⁄40.59-0.65, p<0.01. CONCLUSIONS: GoSoft assessment is consistent with goniometry. The excellent reliability and reproducibility might provide a more standardized instrument for CA in men with PD.

MP78-19 SURGICAL MANAGEMENT OF UROTHELIAL CARCINOMA IN PATIENTS WITH UPPER TRACT AND LOWER TRACT UROTHELIAL CARCINOMA: IMPACT OF SURGICAL SEQUENCE

RESULTS: The 26 (5.3%) patients who developed UUT-SPTs requiring surgical treatment after RC had predominantly invasive cancers (Ta 1⁄4 23.1%, Tis 1⁄4 11.5%, T1 1⁄4 26.9%, T2 1⁄4 19.2%, T31⁄4 15.4%, T4 1⁄4 3.9%) which were also predominantly high grade (G31⁄4 88.5%, G2 1⁄4 7.7 %, G1 1⁄4 3.8). The mean time from RC to the development of SPT was 33.8 months. In a linear regression analysis that controlled for age, bladder pathologic tumor stage was significantly associated with decreased time to SPT (p1⁄4 0.030). Neoadjuvant CBT was given to 11.5 % of bladder UC patients prior to RC and 19.2% received adjuvant CBT after RC . Mean eGFR decreased from 69.3 prior to RC to 55.7 prior to UUT-SPT surgical treatment. UUT-SPTs were managed with nephroureterectomy (92.3%) or ureterectomy (7.7%), and ipsilateral lymphadenectomy (77%). Neoadjuvant CBT prior to UUT surgery was administered to 15.4% of patients. Mean eGFR further decreased after UUT-SPT surgery to 39.5, and 23.1% of patients received adjuvant CBT following UUT surgery. Patient were followed for a mean of 76.1 months and 38.5% of patients died of disease, 29.9% died of unknown/other causes, and 34.6% are alive with no evidence of disease. CONCLUSIONS: UUT-SPTs manifest as more advanced disease after RC. Decreased renal function occurs frequently post RC and may impair the use of peri-operative CBT for patients with high grade SPTs of the UUT. This warrants further studies to develop novel nonnephrotoxic targeted therapies in the peri-operative setting of surgery for SPTs.

PD66-11 ONCOLOGICAL OUTCOMES COMPARING INTRAVESICAL AND EXTRAVESICAL BLADDER CUFF EXCISION FOLLOWING RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA

INTRODUCTION AND OBJECTIVES: Partial nephrectomy is widely utilized for surgical management of small renal masses. Robotic partial nephrectomy (RPN) has demonstrated improved postoperative morbidity and comparable oncologic outcomes compared to open partial nephrectomy (OPN). However, there is limited data regarding the utilization of RPN across different socio-economic strata and racial groups in the United States. We investigated trends and disparities in utilization of RPN for management of cT1 and cT2 renal masses. METHODS: Patients who underwent RPN and OPN for clinical stage T1 and T2, N0, M0 renal masses from 2010 to 2013 were identified in the National Cancer Data Base (NCDB). Univariate and multivariable logistic regression analyses were performed to evaluate differences in receiving RPN across various patient groups. RESULTS: A total of 23,681 patients fulfilled inclusion criteria. Utilization of RPN for management of cT1/cT2 renal masses significantly increased from 2010 to 2013 compared to OPN (Figure.1). Black (aOR1⁄40.91, 95%CI: 0.84-0.99) and Hispanic (aOR1⁄40.85, 95% CI: 0.76-0.94) patients were less likely to undergo RPN in favor of OPN. RPN was less likely to be performed in rural counties (aOR1⁄4 0.81, 95% CI: 0.66-0.98) and in patients with no insurance (aOR1⁄40.52, 95% CI: 0.45-0.61) or patients covered by Medicaid (aOR1⁄40.81, CI: 0.73-0.89). No significant difference was seen with respect to utilization of RPN between academic and non-academic facilities. Patients with higher clinical stage and co-morbidities were also less likely to undergo RPN (aOR1⁄40.23, 95% CI: 0.150.36 and 0.79, 95% CI: 0.71-0.87 respectively). CONCLUSIONS: Utilization of RPN continues to increase over time; however, there is significant disparity in utilization of RPN based on socio-economic status and race. Black or Hispanic patients and patients in rural communities and with limited insurance were more likely to be treated with OPN instead of RPN.

MP84-13 RISK FACTORS FOR ERECTILE DYSFUNCTION IN A POPULATION BASED COHORT

CONCLUSIONS: Only CFT and T:E ratio were predictive of positive libido response on IIEF11 & 12 questionnaire in our cohort. Estradiol, even at a cutoff of 5 ng/dL, was not independently associated with improved libido. Surprisingly total testosterone did not associate with IIEF11 (desire frequency). The effect of testosterone and estradiol administration on libido requires further prospective study.

MP88-16 A PROSPECTIVE EVALUATION OF COMPLICATIONS AFTER ARTIFICIAL URINARY SPHINCTER PLACEMENT AND THEIR IMPACT ON DEVICE SURVIVAL

within the space of Retzius (SOR) may be challenging and subject to troublesome complications. We report our longitudinal experience utilizing a novel high submuscular (HSM) PRB placement technique and compare functional outcomes to traditional SOR placement of the PRB. METHODS: We reviewed a prospectively maintained database of AUS patients between July 2007 and January 2014. Only 61-70 cm H2O PRBs were placed through a trans-scrotal approach via an HSM tunnel (2011-2014) or within the SOR (2007-2010). Our HSM technique consisted of uniform placement of the PRB beneath the rectus abdominis muscle while SOR placement involved perforation of the transversalis fascia at the pubic tubercle, beneath the external inguinal ring. Demographics, patient data, cuff durability, and functional outcomes were compared between groups. RESULTS: 232 consecutive patients underwent AUS placement with amean follow up of 38months. SOR placement was performed in 139 (60%) patients while HSM placement was performed in 93 (40%). Functional outcomes including continence (defined as0-1 pads/day) rates (88% vs. 81%, p1⁄40.15), erosion rates (9% vs. 5%, p1⁄40.32), and explantation rates (12% vs. 10%, p1⁄40.83) were similar between groups. Fewer AUS revisions for persistent incontinence were required in patients undergoing HSM PRB placement (6.5% vs. 18%, p1⁄40.01). Although mean follow-up was longer for patients undergoing SOR placement (51 vs. 20 months, p<0.001), Kaplan-Meier analysis revealed no difference between groups with regards to rates of explantation (p1⁄40.71) or revision (p1⁄40.36). CONCLUSIONS: High submuscular placement of the PRB at the time of AUS surgery offers a safe and effective alternative with equivalent functional outcomes to traditional SOR.