Jonathan Yamzon

MP47-13 ROBOT-ASSISTED RADICAL CYSTECTOMY IN OCTOGENARIANS AND THE EFFECT OF AN ENHANCED RECOVERY PATHWAY ON PERI-OPERATIVE INDICES

METHODS: Patients undergoing open radical cystectomy (ORC) and robotic assisted radical cystectomy (RARC) and urinary diversion with ERAS for bladder urothelial carcinoma from May 2012 to December 2016 were studied. Surgical and clinical outcomes within 90 days after surgery were compared between ORC and RARC, including LOS, readmission and major complication rates (Clavien-Dindo grade 3). Multivariable logistic regression modeling was used to determine factors that predict extended LOS (>4 days), readmission and major complications. RESULTS: A total of 345 and 143 patients underwent ORC and RARC, respectively. The ORC group had a greater proportion of continent urinary diversion (71.9 vs 40.6%, p<0.001), shorter operative time (5.4 vs 7.3 h, p<0.001), higher estimated blood loss (500 vs 200 ml, p<0.001), and higher intraoperative and postoperative transfusion rates (20.9 vs 9.1%, p1⁄40.002 and 20 vs 11.9%, p1⁄40.04, respectively). Median LOS was 4 days for ORC (IQR 4-6 days) and 6 days for RARC (IQR 4-7 days) (p<0.001). There was no significant difference in readmission rates or major complication rates within 30 and 90 days after surgery. Patients with extended LOS had older age (73 vs 68, p<0.001), more comorbidities (p<0.001), longer operative time (6.3 vs 5.6 h, p<0.001), higher intraoperative and postoperative transfusion rate (24 vs 9.5%, p<0.001 and 22.5 vs 11.8%, p1⁄40.002, respectively). Patients who were readmitted within 90 days had older age (73 vs 70, p1⁄40.007), greater proportion of diabetes (32.7 vs 17.5%, p<0.001), and higher transfusion rate (42 vs 24.5%, p<0.001). Patients having major complications had older age (73 vs 70, p1⁄40.01), lower baseline of hemoglobin (11.5 vs 12.2 g/dL, p1⁄40.05) and hematocrit (36 vs 36.8, p1⁄40.04), and higher transfusion rates (41.2 vs 27.5%, p1⁄40.01). Multivariable logistic regression analysis showed that surgical approach was not an independent factor predictive of extended LOS, readmission or major complications. CONCLUSIONS: In the framework of an ERAS protocol, surgical approach was not a determinate factor of clinical outcomes of RC. The evidence-based ERAS protocol is the key factor for optimal patient recovery.

MP64-07 LYMPH NODE YIELD AND POSITIVITY RATE BY LOCATION IN 1000 ROBOTIC PROSTATECTOMY PATIENTS THAT UNDERWENT EXTENDED PELVIC LYMPH NODE DISSECTIONS AT A SINGLE INSTITUTION

INTRODUCTION AND OBJECTIVES: The current evidence for lymphadenectomy (LND) at the time of radical prostatectomy (RP) for Gleason 7 intermediate-risk prostate cancer (PCa) is not as robust as for high-risk prostate cancer. Current guidelines defer to various nomograms regarding the risk of lymph node involvement to dictate the need for LND. The objective of this study was to examine utilization trends and survival data for patients who underwent LND for Gleason 7 PCa. METHODS: The SEER database was queried for all patients with either Gleason 3+4 (G34) or 4+3 (G43) PCa from 2004-2013, limited to patients with no evidence of metastatic disease or prior radiotherapy. Distributions and trends of LND, cancer-specific survival (CSS) and overall-survival (OS) were calculated. Memorial-Sloan Kettering Cancer Center (MSKCC) nomogram was applied to stratify patients based on risk of nodal disease at time of RP (<5% risk or >5% risk). Finally, multivariate logistic regression analyses (MVA) were performed to determine covariates associated with the likelihood of receiving LND. RESULTS: A total of 78641 patients with either G34 or G43 PCa underwent RP (59194 and 19447, respectively) with mean followup of 57.9 months. Of these patients, 61.2% of G34 and 73.5% of G43 patients underwent LND. During this time, the proportion of G43 patients undergoing LND remained relatively stable. The proportion of G34 patients undergoing LND varied between 55.9% in 2008 and 67.9% in 2013 despite decreasing RP rates in that same time frame. On MVA, the primary contributor to the variability in LND completion was socioeconomic status (SES): patients with higher SES were less likely to receive LND when indicated (OR 0.82, p < 0.05) and more likely to receive LND when not indicated (OR 1.15, p < 0.05). Age, race and insurance status were not significant predictors of LND. The incidence of pN+ disease was 1.5% and 5.2% in the <5% and >5% risk groups, respectively. Completion of LND at time of RP did not significantly change CSS in patients with G34 PCa (99.50% with LND and 99.59% without LND, p 1⁄4 0.14.) In G43 patients, however, CSS was better in patients who did not undergo LND (98.81% with LND and 99.33% without LND, p 1⁄4 0.002), the difference primarily driven by pN1 patients. CONCLUSIONS: The role of LND for Gleason 7 prostate adenocarcinoma is not yet standardized, as indicated by the variability of LND dissection rates over an 11-year period in the United States. SES was the primary predictor of LND completion at time of RP. As CSS was not affected by completion of LND for G34 PCa, further evaluation of oncologic benefit in this patient population is warranted.

MP03-16 UTILITY OF MULTI-PARAMETRIC MRI/ULTRASOUND FUSION: COGNITIVE NOT INFERIOR TO TARGETED SOFTWARE-BASED PROSTATE BIOPSIES

INTRODUCTION AND OBJECTIVES: Prostate cancer (PCa) remains the only solid organ tumor that is diagnosed by a non-targeted sampling method. Recently, multi-parametric MRI (MP-MRI) in conjunction with an MRIultrasound (US) fusion guided biopsy (bx) has demonstrated improved PCa detection. Unfortunately, this technology has been limited to tertiary care centers. Therefore, we sought to compare cognitive versus targeted software to assess the ability of cognitive registration to disseminate more readily into the community. METHODS: Consecutive patients underwent an MRI-US fusion prostate bx for elevated PSA, abnormal DRE, active surveillance or prior negative bx with a persistently elevated PSA. All subjects underwent pre-bx MP-MRI and lesions visible on MRI were graded using the PI-RADS version 2 classification system. The UroNav bx tracking system was used to fuse the stored MR images with real-time US generating a 3D model, which was then used to sequentially perform cognitive, targeted, and standard 12 core systematic biopsies in an office setting under local anesthesia. Descriptive statistics included patient characteristics and univariate analysis was done using logistic regression analysis to detect the associations between presence of cancer, clinically significant cancer, demographic variables, and bx method. Signed rank test was used for paired comparisons amongst bx method. RESULTS: 44 patients (median age 66 yrs, median PSA 6.4) underwent an MRI-US fusion bx between July 2014 and October 2015 with an overall CDR of 59%. Cognitive CDR was 40.9% with 25% being clinical significant disease. The targeted CDR was 27.3% with 22.7% being clinically significant disease. Overall, the cognitive approach had a sensitivity of 69.2% (95% CI: 50%, 88%) whereas the targeted approach had sensitivity of 46.2% (95% CI: 26%, 67%). Furthermore, the targeted approach missed 8 cancers when compared to the cognitive approach, whereas, the cognitive approach missed 2 cancer when compared to the targeted approach. The difference in sensitivity is most pronounced when comparing standard and targeted methods (p1⁄40.02) and approaches significance when comparing cognitive and targeted methods (p1⁄40.11). CONCLUSIONS: MRI-US fusion targeted software when compared to the cognitive platform, was not found to have higher cancer detection rate nor sensitivity. We believe this highlights the importance of the MRI itself, rather than the platform used.

MP74-11 PRE-SURGICAL EXPRESSED PROSTATIC SECRETION BIOMARKER PERFORMANCE IN THE DETECTION OF GLEASON UPGRADING IN PROSTATE CANCER.

was followed by an inverse change of equal or greater magnitude. To determine clinically meaningful variation, we used an increase of 1ng/ mL that was followed by a decrease of equal magnitude across measurements. The association between each measure of variation and number of PSA measurements was assessed using linear regression. RESULTS: In 541 men studied, the cumulative incidence of discontinuing AS for definitive treatment within 5 years was 13%. Among 251(46%) patients who reached a PSA of 7ng/mL, 186(74%) decreased from this threshold at least once. 417 (77%) patients reached a PSA of 4ng/mL but their PSA measurements fluctuated around this threshold less often. In patients who reached a PSA of 4ng/ mL or 7ng/mL, the number of PSA measurements was significantly associated with the frequency of variation across each threshold (p<0.001). Examining PSA direction, 471 (87%) patients experienced at least one change in PSA direction and the frequency of these changes was significantly associated with the number of PSA measurements (p<0.001). 238 (44%) patients experienced a clinically meaningful change in PSA direction and the frequency of these changes was significantly associated with the number of PSA measurements (p<0.001), suggesting that these changes would be observed with continued follow up. CONCLUSIONS: Among men with PC managed with AS, considerable variability in PSA levels exists. The frequency of changes in PSA direction, including clinically meaningful changes, increases with more PSA measurements. Therefore, an isolated change in PSA level should not be used as an indication for reclassification biopsy.

FIBROBLAST GROWTH FACTOR 10-MEDIATED DELAY IN BLADDER WOUND HEALING IN INDUCIBLE TRANSGENIC MICE

and identified by N-terminal sequencing. MAL cDNAs were cloned and sequenced, antibodies to MAL were used to localize it in bladder urothelium by LM and EM techniques. Mice lacking the MAL gene, and those over-expressing the MAL gene, were generated by transgenic techniques. RESULTS: N-terminal sequencing of the bovine p18 identified it as the ‘myelin-and-lymphocyte-protein’ (MAL). This protein has four transmembrane domains interconnected by short hydrophilic domains. It is expressed in bladder urothelium in a differentiation-dependent manner. EM localization studies showed that it is associated with the uroplakin-delivering vesicles of all stages in urothelial umbrella cells, including the small discoidal vesicles, the mature fusiform vesicles, and the apical urothelial surface. In the latter two cases, the MAL is selectively associated with the ‘hinge areas’ that interconnect the urothelial plaques. Genetic ablation of the mouse MAL gene results in the accumulation of fusiform vesicles. Conversely, over-expression of MAL in transgenic mouse urothelium results in a reduction of the fusiform vesicles and, concurrently, the accumulation of multivesicular bodies that are involved in the endocytic degradation of uroplakins. CONCLUSIONS: Our results indicate that (i) MAL is highly expressed in bladder urothelium as a major urothelial differentiation marker, (ii) MAL knockout blocks the fusion of the fusiform vesicles with the urothelial apical surface, and (iii) MAL over-expression increases the delivery of uroplakins to apical surface and their endocytic degradation. Therefore, MAL is a key component in regulating the targeting and degradation of the uroplakin complexes, which serve as the receptor for the uropathogenic E. coli, and contribute to the bladder permeability barrier function.

FIBROBLAST GROWTH FACTOR 10-MEDIATED DIFFERENTIATION OF HUMAN AMNIOTIC FLUID STEM CELLS INTO UROTHELIAL CELLS BY CO-CULTIVATION WITH HUMAN BLADDER CANCER CELLS

RESULTS: Based on qPCR analysis, RA treatment (10μM) elicited significant downregulation of the pluripotency factor OCT-4, but marked upregulation of UP1A, UP1B, UP2, UP3A, and UP3B mRNA levels in comparison to naive ESCs and spontaneously differentiating controls in both 2-D and 3-D systems. Immunohistochemistry revealed robust expression of UPs 1A, 1B, 2, and 3A in RA-treated cultures, with FACS analysis showing ~60% of the population expressing UP3A. Transient induction of early endoderm markers, SOX17, FOXA1 and FOXA2, was also observed in RA-treated ESCs at 3 and 6 d, respectively, while GATA6 expression was sustained from 6 to 9 d corresponding to maximal UP expression. GATA6-/ESCs failed to undergo RA-induced UP 1A, 1B, 2, and 3A expression while GATA6+/ESCs showed partial recovery of UP1B and UP3A expression compared to WT cells. CONCLUSIONS: We show for the first time that UE differentiation of ESCs is mediated by RA signaling mechanisms and demonstrate that GATA6 is essential in this process. In addition, the development of ESC-derived UE cells from both 2-D and 3-D cell culture systems offers a prospective cell source and delivery system for bladder tissue engineering applications.