Alp Tuna Beksac

Change in Platelet Count as a Prognostic Indicator for Response to Primary Tyrosine Kinase Inhibitor Therapy in Metastatic Renal Cell Carcinoma

To evaluate change in platelet count as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC).

Statin utilization improves oncologic and survival outcomes in patients with dyslipidemia and surgically treated renal cell carcinoma

BACKGROUND We evaluated the role of statins in patients who underwent surgery for renal cell carcinoma (RCC) and who had dyslipidemia, as use of statins has been suggested to improve outcomes in RCC. METHODS Two-center retrospective study of patients with dyslipidemia who underwent surgery for RCC from 7/1995 to 6/2005. Patients were managed by statins or ezetimibe, fibrate agents, or cholestyramine. Analysis was conducted between patients who received statin therapy versus those that did not. Primary outcome was progression-free survival (PFS). Secondary outcomes were cancer-specific (CSS) and overall survival (OS). Multivariable analysis was performed to identify risk factors associated with disease progression. RESULTS In this study 283 patients were analyzed (180 statin, 103 non-statin, median follow-up 68 months). There were no significant demographic differences. Median duration of antidyslipidemia therapy was similar (statin 31 months vs. non-statin 28 months, P=0.413). Tumor size (statin 5.4 cm vs. non-statin 5.6 cm, P=0.569), stage distribution (P=0.591), histology (P=0.801), and grade (P=0.807) were similar. Kaplan-Meier analysis demonstrated higher 5-yr PFS (91% vs. 70%, P<0.001), CSS (88% vs. 69%, P<0.001), and OS (71% vs. 67%, P=0.025) in statin vs. non-statin patients. Multivariable analysis for factors associated with disease progression found absence of statin therapy (OR 2.41, P<0.001), higher stage (OR 2.01-3.86 P<0.001), and higher grade tumors (OR 2.07, P=0.006) to be predictive. CONCLUSIONS In RCC patients with dyslipidemia, statin use was associated with improved survival outcomes, and was an independent predictor of PFS. Further investigations are requisite to determine utility of statins in RCC patients.

Can multiphase CT scan distinguish between papillary renal cell carcinoma type 1 and type 2

OBJECTIVE To investigate the utility of multiphase computed tomography (CT) and percutaneous renal mass biopsy (PRMB) in differentiating between papillary renal cell carcinoma (pRCC)-Type 1 and -Type 2, as emerging data have suggested differential enhancement patterns in different renal tumor histologies. MATERIAL AND METHODS Retrospective analysis of 51 patients (23 pRCC-Type 1/28 pRCC-Type 2) who underwent multiphase CT followed by surgery from July 2011 to April 2016 was performed. Data were analyzed between subgroups based on histology. Multiphase CT was analyzed for tumor size, and attenuation [Hounsfield Units (HU)]. Change in HU (ΔHU) was calculated between noncontrast (NC), corticomedullary (CM), nephrographic (N), and delayed (D) phases. Subset analysis was carried out on patients who underwent PRMB prior to surgery. RESULTS There was no difference in median tumor size (pRCC-Type 1 2.8 vs. pRCC-Type 2 2.6 cm, p=0.832). In addition to tumor size being similar between groups, distribution of tumor stages between groups was also similar (p=0.651). Greater proportion of high-grade tumors (III/IV) was noted in pRCC-Type 2 (42.9% vs. 8.7%) (p=0.011). There was no difference in HU values for NC (p=0.961), CM (p=0.118), N (p=0.277), and D (p=0.256) phases, and in ΔHU between CM-NC (p=0.278), N-NC (p=0.316), and D-NC (p=0.103). Thirteen patients underwent percutaneous biopsy, 11 of whom had diagnostic samples. Examination of 10/11 (90.9%) samples accurately predicted correct histology, and of 6/11 (54.5%) samples correctly identified high-vs. low-grade histology. CONCLUSION Our findings suggest substantial overlap of CT findings, despite pRCC-Type 2 having greater proportion of high-grade tumors. Utility of CT is limited in the differentiation between pRCC subtypes. Patients with suggested pRCC on CT imaging being considered for a non-extirpative strategy should undergo PRMB for risk stratification.

PD59-09 MANAGEMENT OF SMALL RENAL MASSES IN RENAL TRANSPLANT RECIPIENT CANDIDATES: A MULTI-INSTITUTIONAL SURVEY ANALYSIS

validate a criterion for AS eligibility based on tumour clinical size and age on a cohort of patients treated with surgery. METHODS: 1922 patients diagnosed with a cT1cN0cM0 renal mass elected for surgical treatment and collected into a prospective database were assessed. Under the assumption that older patients with smaller tumours are optimal candidates for AS relative to younger patients with larger tumours, we relied on the ratio [R] between tumour clinical size and age in order to differentiate patients suitable for AS (R<5) from patients unsuitable for AS (R 5). X2 test was used to compare the rate of malignant histology, stage pT3-pT4 and grade G3G4 at final pathology in patients suitable vs. unsuitable for AS. Smoothed Poisson’s incidence plots were used to examine the rate of cancer specific [CSM] and other cause mortality [OCM] in patients suitable vs. unsuitable for AS. RESULTS: According to the proposed definition, the rate of patients suitable for AS was 34%. Patient suitable for AS had a lower rate of malignant histology (78 vs. 87%; p<0.001), pT3-pT4 (4 vs. 10% p1⁄40.001) and grade G3-G4 (7 vs. 17% p<0.001) relative to patients unsuitable for AS. In patients suitable for AS, the 10-year rates of CSM and OCM were 1.7 and 19%, respectively (Fig. 1A). In patients unsuitable for AS, the 10-year rates of CSM and OCM were 6.7 and 11% (Fig. 1B), respectively. CONCLUSIONS: When validated in a cohort of surgically treated patients, the ratio between tumour clinical size and age is a useful parameter to differentiate patients with adverse pathologic outcomes from patients with more favourable pathologic outcomes. These differences translate into critically different relative rates of CSM and OCM. These findings suggest that the proposed strategy criterion deserve further examination as a potential criterion for AS.

MP67-07 PATHOLOGICAL DETERMINANTS OF ONCOLOGIC OUTCOMES IN STAGE II RENAL CELL CARCINOMA: AN INTERNATIONAL MULTICENTER ANALYSIS

bilateral kidneys with single eAML on the left). Only one patient suffered from spontaneous haemorrhage. Two cases developed distant metastasis: one had nodules over bilateral lungs and left anterior mediastinum; the other had recurrence over liver and retroperitoneum one year after surgical intervention. Three cases had venous thrombus (two in renal vein and one in inferior vena cava) and received thrombectomy. All 21 cases received surgical intervention: 13 radical nephrectomy, 7 partial nephrectomy, one was found with retroperitoneal eAML arising from renal capsule thus undergone tumor excision without kidney involvement. The follow up period ranges from 1 to 143 months (average 51 months). Only 2 cases died from unrelated cause. CONCLUSIONS: In our study, the rate of aggressive behavior is 24% (2 distant metastasis and 3 venous invasion in the 21 cases). Some noticeable accompanying characteristics including haemorrhage, coexisting with AML, coexisting with renal cell carcinoma are also seen in this series. The incidence of renal vein and inferior vena cava thrombus formation in our series is high (3 out of 21), therefore, detailed preoperative image evaluation is necessary.

MP72-03 COMPARATIVE ANALYSIS OF RADICAL AND PARTIAL NEPHRECTOMY IN PATIENTS WITH PREOPERATIVE STAGE 2 CHRONIC KIDNEY DISEASE: A MULTICENTER STUDY

Zachary Hamilton*, San Diego, CA; Alessandro Larcher, Milan, Italy; Brian Lane, Grand Rapids, MI; Umberto Capitanio, Milan, Italy; Sumi Dey, Grand Rapids, MI; Aaron Bloch, Charles Field, San Diego, CA; Samer Kirmiz, Grand Rapids, MI; Daniel Han, San Diego, CA; Adam Bezinque, Grand Rapids, MI; Alp Tuna Beksac, San Diego, CA; Cristina Carenzi, Milan, Italy; Fang Wan, James Proudfoot, San Diego, CA; Francesco Montorsi, Milan, Italy; Ithaar Derweesh, San Diego, CA

PD73-04 A COMPARISON OF OVERALL SURVIVAL BETWEEN PARTIAL AND RADICAL NEPHRECTOMY FOR T1 RENAL MASSES: A REPORT FROM THE NATIONAL CANCER DATABASE

INTRODUCTION AND OBJECTIVES: Partial nephrectomy (PN) is the recommended treatment for cT1a renal masses. Compared to radical nephrectomy (RN), PN offers comparable cancer specific survival, with better functional outcome. However, there are conflicting results regarding the benefit of PN on overall survival (OS). We sought to compare the OS of patients with a T1 renal mass who underwent PN or RN. METHODS: The American College of Surgeons National Cancer Database of 351,112 patients with kidney cancer was utilized to identify patients 39,346 patients who underwent RN (n1⁄432,665, 83.1%) or PN (n1⁄46,681, 16.9%) for a pT1N0M0 clear cell, chromophobe or papillary renal cell carcinoma from 2003 to 2012. OS for PN vs. RN for at a median follow-up of 4.1 years (IQR 2.3-6.2 years) was compared overall and separately for T1a and T1b renal masses. OS was specifically compared in a multivariable cox proportion hazards regression model adjusting for age, CharlsonDeyo score, race, ethnicity, histology, stage, treatment facility type and other socioeconomic factors. RESULTS: Patients who underwent RN were more likely to have a T1b renal mass, (48.8% vs. 42.2%, p<.001), be of Hispanic ethnicity (p1⁄4.002) and have clear cell vs. chromophobe or papillary RCC (p<.001) There were no differences in age (p1⁄4.131), insurance status (p1⁄4.927), gender (p1⁄4.431), race (p1⁄4.076), income (p1⁄4.565), year of diagnosis (p1⁄4.525), margins (p1⁄4.216) between groups. The 5-year OS was 83.0% for RN 82.8% for PN (p1⁄4.850). In multivariable analysis, no difference in OS between PN and RN was found for T1 overall (HR1⁄41.01; 95% CI1⁄40.94, 1.08; p1⁄4.782), for T1a (HR1⁄41.05; 95% CI1⁄40.96, 1.19; p1⁄4.331) or for T1b (HR1⁄40.97; 95% CI1⁄40.87, 1.07; p1⁄4.520). Furthermore, OS for PN did not differ for patients ? 75 years old with a T1 renal mass (HR1⁄41.06; 95% CI1⁄40.96, 1.19; p1⁄4.251) or patients < 75 years old with a CharlsonDeyo score of 0 and a T1 renal mass (HR1⁄41.01; 95% CI1⁄40.89, 1.09; p1⁄4.806). CONCLUSIONS: There was no difference in overall survival between PN and RN with a median follow up of 4.1 years. Longer-term studies are required to determine any impact on OS between PN and RN.

PD52-01 DIFFERENTIAL GENE EXPRESSION IN PATIENTS WITH INDOLENT VERSUS AGGRESSIVE CHROMOPHOBE RENAL CELL CARCINOMA: AN ANALYSIS OF THE CANCER GENOME ATLAS DATABASE

INTRODUCTION AND OBJECTIVES: Chromophobe subtype of renal cell carcinoma (chRCC) makes up approximately 5% of all RCC. It has a better prognosis compared to clear cell and papillary subtypes and shares similar traits to oncocytoma. However, a minority of these tumors behave aggressively. We sought to evaluate genomic differences between patients with indolent and aggressive chRCC. METHODS: We analyzed The Cancer Genome Atlas (TCGA) database and found 63 chRCC patients. RNA expression analysis compared deceased (n1⁄49, 14.2%) and alive patients (n1⁄454, 85.8%). Supervised whole genome differential expression analysis of RNA-Seq data for 20,536 genes was conducted using the SAMSeq package in R. Functional annotation analysis to evaluate biological significance of differentially expressed genes (FDR<0.05; Fold Change >2) was conducted in DAVID 6.8. RESULTS: Compared to patients who were alive, we identified 200 significantly overexpressed genes in the deceased group (FDR<0.05). 139 (75.1%) genes were involved in protein phosphorylation, 116 (62.7%) in alternative splicing, 108 (54.8%) in protein binding, and 103 genes (55.7%) were identified as nucleus proteins. The majority (56%) of genes were related to cell replication & cell cycle, followed by DNA repair (9%), intracellular metabolism (7.5%), transcription\translation (4.5%), signaling mechanisms (4%), transport proteins (2.5%) and others (6.5%). Interestingly, 5 genes associated with breast cancer were overexpressed in the deceased group (FDR<0.05). These genes included KIF15, BRCA2, RAD51, BRIP1 and HMMR. HMMR and BRIP1 proteins interact with BRCA1 in breast carcinogenesis. BRCA1 was overexpressed, but not significant (FDR1⁄40.126). Furthermore, Cyclin A2, Cyclin B1, Cyclin B2, Cyclin E2 and Cdk1 (cyclin-dependent kinase) were overexpressed (FDR <0.05). Cyclin A1, B1 and B2 are known mitotic regulators. Cyclin A2 regulates mitosis by activating Cyclin B1/Cdk1 complex. CONCLUSIONS: We identified several known genes that are differentially overexpressed in patients who died from chRCC. These expression profiles will need validation, but may be used as biomarkers to identify aggressive variants of chRCC.

Comparison of laparoendoscopic single-site (LESS) and multiport laparoscopic radical nephrectomy for clinical T1b and T2a renal masses.

BACKGROUND The aim of this study was to compare outcomes of laparoendoscopic single-site surgery (LESS) and multiport laparoscopic (MPL) radical nephrectomy (RN) for clinical T1b/T2a renal masses, as concerns continue regarding suitability and benefit of LESS for larger renal masses. METHODS Retrospective single-surgeon comparison of LESS- and MPL-RN between 7/2005 and 11/2014. Sixty-three patients underwent LESS-RN (44 cT1b/19 cT2a); 133 underwent MPL (83 cT1b/50 cT2a). All patients were managed with a standardized care pathway. Primary outcome was length of hospital stay (LOS). Secondary outcomes included operative time, estimated blood loss (EBL), complications, discharge pain score (visual analog pain, VAP), narcotic requirement (morphine equivalents, MSO4eq). RESULTS 130/133 MPL and 62/63 LESS were successfully performed. For MPL and LESS groups: mean tumor diameter (cm) for cT1b was 5.3 vs. 5.4 (P=0.689); and for cT2a was 8.2 vs. 8.3 (P=0.728); mean OR time (min) was 126.3 vs. 132.7 (P=0.314); mean EBL (mL) was 139.5 vs.127.8 (P=0.49). No significant differences in complications were noted (P=0.781). LESS was associated with significant reductions in LOS (2.14 vs. 2.45 days, P=0.043), discharge VAP (1.3 vs. 2.2, P<0.001), and narcotic use (5.9 vs. 10.7 MSO4eq, P<0.001). CONCLUSIONS LESS is comparable to MPL-RN for cT1b and T2a renal tumors in terms of perioperative parameters and may confer benefit with respect to LOS and analgesic requirement.

Gastrointestinal tract access for urological natural orifice transluminal endoscopic surgery.

We conducted a literature review of natural orifice transluminal endoscopic surgery (NOTES), focusing on urologic procedures with gastrointestinal tract access, to update on the development of this novel surgical approach. As part of the methods, a comprehensive electronic literature search for NOTES was conducted using PubMed and Cochrane Library from March 2002 to February 2016 for papers reporting urologic procedures performed utilizing gastrointestinal tract access. A total of 11 peer-reviewed studies examining utility of gastrointestinal access for NOTES urologic procedures were noted, with the first report in 2007. The procedures reported in the studies were total/radical nephrectomy, partial nephrectomy, adrenalectomy, and prostatectomy. The transgastric approach was identified in five studies examining total/radical nephrectomy (n = 2), partial nephrectomy (n = 1), partial cystectomy (n = 1), and adrenalectomy (n = 1). Six studies evaluated transrectal approach for NOTES, describing total/radical nephrectomy (n = 3), partial nephrectomy (n = 1), robotic nephrectomy with adrenalectomy (n = 1) and prostatectomy (n = 1). Feasibility was reported in all studies. Most studies were preclinical and acute, and limited by concerns regarding restricted instrumentation and infection risk. We concluded that gastrointestinal access for urologic NOTES demonstrates promise as described by outlined feasibility studies in preclinical models. Nonetheless, clinical application awaits further advancements in surgical technology and concerns regarding infectious potential.