966 COMPARISON OF HILAR CLAMPING AND NON-HILAR CLAMPING PARTIAL NEPHRECTOMY FOR TUMORS INVOLVING A SOLITARY KIDNEY

Vol. 185, No. 4S, Supplement, Monday, May 16, 2011

THE JOURNAL OF UROLOGY姞

Table 1. Demographics, operative details, pathology and peri-operative outcomes Mean age (years) 60 ⫹/⫺ 12 White

196 (92%)

Black

5 (2%)

Asian

2 (1%)

Other/unknown race

30.8 ⫹/⫺ 6.3

Mean Charlson Comorbidity Index

1.1 ⫹/⫺ 1.7

Mean American Society of Anesthesiologists Class

2.3 ⫹/⫺ 0.5

Mean Preoperative eGFR (mL/min/1.73m2)

75 ⫹/⫺ 20

Solitary kidney

13 (6.1%)

Symptomatic presentation

48 (22.6%)

Bilateral masses

18 (8.5%)

Open

167 (79%)

Robotic or pure laparoscopic

45 (21%)

Vascular clamping

56 (26%) 26 ⫹/⫺ 9

Mean EBL (mL)

567 ⫹/⫺ 550

Mean procedure duration (minutes)

217 ⫹/⫺ 75

RCC

174 (82%)

pT1a

118 (67.8)

pT1b

43 (24.7%)

pT2

2 (1.1%)

pT3a

8 (4.6%)

pT3b

3 (1.7%)

Mean Fuhrman grade

2.1 ⫹/⫺ 0.6

Mean Pathologic Tumor size (cm)

3.2 ⫹/⫺ 1.6

Mean length of stay (days)

4.9 ⫹/⫺ 2.5

Mean post-operative eGFR (mL/min/1.73m2) Mean % Decrease in eGFR Mean num. days after surgery GFR checked

CONCLUSIONS: This methodology allows for quantitative estimation of PFVC using standard radiologic imaging software, and without the need for specialized radiologic software or expertise. Tumor features that determine PFVP include increased tumor size and depth. Source of Funding: None

9 (4%)

Mean Body Mass Index (kg/m2)

Mean clamp time (minutes)

e389

72 ⫹/⫺ 24 4.8 ⫹/⫺ 18.7 22 ⫹/⫺ 19

Source of Funding: None

964 A NOVEL METHOD TO ESTIMATE PERCENT FUNCTIONAL VOLUME PRESERVATION AFTER PARTIAL NEPHRECTOMY USING STANDARD CT IMAGING Matthew Simmons*, Amr Fergany, Steven Campbell, Cleveland, OH INTRODUCTION AND OBJECTIVES: Percent functional volume preservation (PFVP) is a major determinant of renal function after partial nephrectomy (PN). PFVP is difficult to predict preoperatively, and postoperative measurement can be complex. Here we describe a new method for estimating PFVP after PN using standard CT imaging software, and we assess pathologic features that predict PFVP. METHODS: PFVP measurements were conducted in pre- and postoperative CT studies in 39 patients with normal serum creatinine who underwent either open or laparoscopic PN for a single unilateral kidney tumors between January 2007 to December 2009. Cylindrical volumes that approximated the size of kidneys on pre- and postoperative CT scans were measured. The preoperative volume was adjusted to account for volume of nonfunctional tumor lying within the parenchymal boundary. PFVP was estimated based on the ratio of pre-and postoperative cylindrical volumes. Statistical analyses were conducted to identify tumor characteristics associated with PFVP. RESULTS: Tumors in this cohort had a median diameter of 3.5cm (range: 1.3-10 cm), a median volume of 20 cm3 (range: 1.3– 125.9 cm3) and median endophytic component percentage of 50% (range: 20%–100%). Median PFVP was 88% (range: 49 –102%) for a single kidney, and 94% when adjusted for both (range: 85–105%). Univariate regression analyses revealed significant associations of PFVP with endophytic component percentage ((p⫽0.01), tumor diameter (p⬍0.001), volume (p⫽0.03), surface area (p⫽0.002), and centrality index (p⬍0.001).

965 IMPACT OF INCREASED EXPRESSION OF GLUCOSEREGULATED PROTEIN 78 ON CLINICOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN RENAL CELL CARCINOMA Kenji Kuroda*, Akio Horiguchi, Takako Asano, Shinsuke Tasaki, Junichi Asakuma, Hidehiko Yoshii, Akinori Sato, Keiichi Ito, Kenji Seguchi, Makoto Sumitomo, Tomohiko Asano, Tokorozawa, Saitama, Japan INTRODUCTION AND OBJECTIVES: Glucose-regulated protein 78 (GRP78) acts as a chaperone for newly formed proteins during folding and glycosylation. The regulation and expression of GRP78 are associated with resistance to apoptosis in some forms of cancer, but the impact of GRP78 expression on the progression of renal cell carcinoma (RCC) is unclear. To better understand the effects of GRP78 on tumor progression and prognosis in RCC, we assessed its expression by using primary and metastatic tumor sections from patients with RCC and then correlated our findings with clinicopathological parameters, including the patients’ survival. METHODS: Immunohistochemistry was performed using formalin-fixed and paraffin-embedded specimens, all from the same 128 patients: 128 primary RCC specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. The determination of positive or negative staining was based on the intensity of staining and the percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters, including the patients’ survival, was evaluated. RESULTS: GRP78 positivity was found in 71 of 128 (55.5%) of the primary tumors and in 8 of 9 (88.9%) specimens taken from the 9 patients with metastasis. GRP78 positivity was also found in most (7 of 8, 87.5%) of the specimens of non-conventional RCC subtypes. Statistically significant associations were found between GRP78 positivity and higher tumor grade (G3; P ⬍ 0.0001), advanced T stage (ⱖ pT3; P ⫽ 0.0002), pathological vascular invasion (pV1; P ⬍ 0.0001), regional nodal involvement (ⱖ N1; P ⫽ 0.0086), and distant metastasis at presentation (M1; P ⫽ 0.001). Positivity for GRP78 was significantly associated with shortened disease-specific survival not only in the patients with conventional RCC (P ⫽ 0.0043) but also in all the patients (P ⫽ 0.0036). Progression-free survival was also shorter in the patients with positive GRP78 than in those with negative GRP78 (P ⫽ 0.0302 for the 106 N0M0 patients with tumors of any cancer cell type, and P ⫽ 0.0165 for the 101 N0M0 patients with conventional RCC). CONCLUSIONS: Our study showed that a high level of GRP78 expression might be a useful parameter for identifying poor diseasespecific and progression-free survival in RCC patients. GRP78 positivity might also contribute to metastatic progression of RCC and could also be used as a marker of aggressiveness for non-conventional RCC subtypes. The findings from the present study could be helpful in the diagnostic and prognostic assessment of RCC. Source of Funding: None

966 COMPARISON OF HILAR CLAMPING AND NON-HILAR CLAMPING PARTIAL NEPHRECTOMY FOR TUMORS INVOLVING A SOLITARY KIDNEY Matthew Wszolek*, Patrick Kenney, Burlington, MA; Yoojin Lee, Boston, MA; John Libertino, Burlington, MA INTRODUCTION AND OBJECTIVES: To compare outcomes of patients undergoing hilar clamping and non-hilar clamping partial nephrectomy for tumors involving a solitary functional kidney.

e390

THE JOURNAL OF UROLOGY姞

METHODS: Between 1990 and 2009, 104 partial nephrectomies, excluding bench and auto-transplant procedures, were performed on solitary functional kidneys. An institutional review boardapproved retrospective review was performed analyzing patient demographics, operative data, complications, oncologic outcomes and estimated glomerular filtration rate (GFR). GFR was calculated using the abbreviated Modification of Diet in Renal Disease equation. Preoperative GFR was compared to Nadir GFR (lowest measured GFR within 100 days postoperatively) and to Late GFR (GFR 101–365 days postoperatively). Chi-square test, Wilcox-two sample test, Fisher’s exact test and Kaplan-Meier estimator were utilized to compare the clamping and non-clamping groups. RESULTS: 29 partial nephrectomies with hilar clamping and 75 partial nephrectomies without hilar clamping were performed. Mean follow-up equaled 4.7 years. There was no difference in tumor size, location, and number of tumors resected between the two groups. Mean ischemia time for the clamping group was 25 minutes. Surgical time was shorter in the non-clamping group (median: 245 vs. 270 minutes, mean: 259 vs. 314 minutes, p⫽0.02). There was no difference in intra-operative estimated blood loss, transfusion requirement or length of hospital stay. The complication rate and spectrum of complications were similar between the two groups. Regarding oncologic outcomes, surgical margin positivity rate was higher in the clamping group (21% vs. 5%, p⫽0.01), however the local recurrence rate between the two groups was similar. The clamping and non-clamping groups had similar overall and cancer specific survival. The two groups had similar preoperative GFR and Nadir GFR. The non-clamping group had a significantly smaller decrement in Late GFR (median: 0 vs. 10 mL/min, mean: 6.6 vs. 15.4 mL/min, p⫽0.01) and a significantly smaller percent decrease in Late GFR (median: 0 vs. 22%, mean: 12% vs. 28%, p⫽0.01) than the clamping group. CONCLUSIONS: In our analysis, partial nephrectomy without hilar clamping in solitary kidneys provides similar complications and cancer control when compared to partial nephrectomy with hilar clamping. Partial nephrectomy without clamping was associated with superior preservation of renal function in the period of 101–365 days after surgery. Source of Funding: None

967 C-INDEX ASSOCIATES WITH FUNCTIONAL OUTCOMES AFTER LAPAROSCOPIC PARTIAL NEPHRECTOMY Mary Samplaski*, Adrian Hernandez, Cleveland, OH; Inderber Gill, Los Angeles, CA; Matthew Simmons, Cleveland, OH INTRODUCTION AND OBJECTIVES: C-index (CI) is a morphometric descriptor of renal masses that incorporates both tumor size and location. We aimed to examine associations of CI with kidney function after laparoscopic partial nephrectomy (LPN). METHODS: A retrospective review was conducted of 131 patients undergoing LPN for a single kidney tumor. CI was calculated from preoperative contrast-enhanced CT images. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD2 equation. Nadir eGFR was calculated using the peak SCr within 7 days of surgery. RESULTS: Median CI was 2.7 (0.7–9.6). Mean preoperative and nadir eGFR values were 79.4 and 57.3 ml/min/1.73m2 (S.D. ¡A`22.2 & 22ml/min/1.73m2, respectively; p⬍0.001). Mean total percent decrease in GFR was 28% (S.D. ¡A`16%). On univariate analysis a positive correlation was found between logCI and nadir eGFR (r⫽0.29; p⫽0.002), and a negative correlation was observed between logCI and percent decrease in eGFR (r⫽-0.4; p⬍0.001). On Multivariate analysis the percent decrease in eGFR was significantly associated with logCI (p⫽0.005) and WIT (p⬍0.001) but not with tumor diameter or preoperative eGFR. 70% of patients with a CI ¡u¨2.5 developed a ¡Y30% decrease in eGFR compared to 32% of patients with a CI ⬎2.5 (RR ⫽ 2.2; p⬍0.001).

Vol. 185, No. 4S, Supplement, Monday, May 16, 2011

CONCLUSIONS: CI is associated with both postoperative nadir eGFR and percent decrease in eGFR after LPN. A CI value of ⬍2.5 was found to correlate with a 2.2-fold increased risk for developing a ¡Y´30% decrease in eGFR after LPN. Source of Funding: None

968 CDK1 AND CDK2 ACTIVITY IS A STRONG PREDICTOR OF RENAL CELL CANCER RECURRENCE Fumiya Hongo*, Natsuki Takaha, Yasunori Kimura, Terukazu Nakamura, Kazuya Mikami, Kyoto, Japan; Satoshi Nakayama, Tomoko Matsushima, Hideaki Ishihara, Kobe, Japan; Toshiyuki Sakai, Tsuneharu Miki, Kyoto, Japan INTRODUCTION AND OBJECTIVES: We established original methods enabling simultaneous analysis of protein expressions and kinase activities of the CDK (cyclin-dependent kinase) molecules in lysate of tumor tissue in a clinical setting (C2P technology, Ishihara et al: Biochim Biophys Acta. 1741; 226 –233, 2005). The clinical utility of the technology was first evaluated in breast cancer, and combination analysis of CDK1 and CDK2 activity was shown to be a significant prognostic indicator for relapse (Kim et al: Ann Oncol. 19; 68 –72, 2009). The objective of our study is to evaluate the efficacy of CDK1 and CDK2 activity as a prognostic marker in human renal cell carcinoma (RCC). METHODS: Surgical specimens were obtained from 125 patients with RCC without metastasis. These patients were selected randomly for this study. Protein expression and kinase activity of CDKs and cyclins were analyzed using a newly developed assay system. The system to measure the CDK specific activity (SA) is named C2Ps (Sysmex, Kobe, Japan). We then examined the specific activities of CDK1 and CDK2 and calculated CDK2/CDK1 ratio in RCC. Also, risk score (RS) was examined as described in previous study (JGH van Nes et al: Br J Cancer. 100; 494 –500, 2009). Cut off value was calculated by ROC analysis. RESULTS: 125 cases were tested, though 34 cases were excluded of low sample quality (25 cases) and of assay failure (9 cases). 91 cases were analyzed. They included 68 male and 23 female patients, ranging in age from 19 to 83 years. At a median follow up of 36 months (1–109 M), tumor with low CDK2/CDK1 ratio showed significantly better 5-year progression free survival (PFS) than those with high CDK2/CDK1 ratio (88.7% vs 54.7%, P⫽0.00141). Also, RS enabled the classification of RCCs into high-risk and low-risk groups, patients with tumors classified as low RS showed better PFS than patients with tumors with high RS (88.7% vs 54.7%, P⫽0.0141). CONCLUSIONS: CDK1 specific activity of tumors and the CDK2 specific activity are both associated with recurrence and prognosis. Analysis of cyclin-dependent kinase activity in the clinical setting could be a powerful approach for predicting cancer recurrence and prognosis in RCC after surgery and has potential for use as a routine laboratory test. Source of Funding: None