Diana Mehedint

Learning curves for robot-assisted and laparoscopic partial nephrectomy.

OBJECTIVES To evaluate the learning curve of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) between two surgeons at a single institution. METHODS A prospectively maintained, Institutional Review Board (IRB)-approved kidney surgery database was reviewed retrospectively and the first 116 consecutive LPNs performed by one surgeon (Hyung Kim) and 116 consecutive RPNs performed by a second surgeon (Thomas Schwaab) were identified. The learning curve was evaluated by examining the operative times, warm ischemia times (WITs), estimated blood loss, the postoperative estimated glomerular filtration rate (eGFR), and intra- and postoperative complications in the quartiles of 29 patients. The LPNs performed by Hyung Kim were done following completion of a minimally invasive fellowship. Thomas Schwaab had minimal experience with LPN and no fellowship training before starting RAPN. RESULTS The RAPN and LPN groups had similar patient and tumor characteristics. The RAPN group had a higher preoperative eGFR (74.1±22.04 vs. 80.95±21.25 mL/minutes, p=0.015) and a worse Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 1+ in 12% vs. 2.6%, p<0.001) compared with the LPN group. Rates of intraoperative (p=0.203) and postoperative (p=0.193) complications were similar. In the RAPN group, operating room (OR) time (161±51 vs. 203±55 minutes, p<0.001) and WIT (17.7±14.8 vs. 21.8±9.1 minutes, p<0.001) were shorter. Postoperative stay was longer in the RAPN group (2.4±2.2 vs. 1.67±1.1 days, p<0.001). The percentage decrease in postoperative eGFR was lower in the RAPN group versus the LPN (9.6% vs. 10%). The learning curves differed for log tumor size, log WIT, and postoperative complications. CONCLUSIONS The variables of the learning curve for RAPN can be obtained earlier than the same variables for LPN. RAPN had a shorter OR time and WITs. The shorter WITs, earlier in the series, led to consistently lower fluctuations in GFR and preservation of the renal function. The learning curves for each procedure need to be re-evaluated at longer intervals to ensure their accuracy.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes

PURPOSE Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer

To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens.

The association between calcium channel blocker use and prostate cancer outcome

Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined.

External validation of preoperative and postoperative nomograms for prediction of cancer-specific survival, overall survival and recurrence after robot-assisted radical cystectomy for urothelial carcinoma of the bladder

To externally validate currently available bladder cancer nomograms for prediction of all‐cause survival (ACS), cancer‐specific survival (CSS), other‐cause mortality (OCM) and progression‐free survival (PFS).

Comparison of ACINUS, caspase-3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis.

The balance between apoptotic and proliferative processes determines the enlargement of a tumor. Accurate measurement of apoptotic and proliferative rates from diagnostic prostate biopsies would allow calculation of tumor growth rates in a population‐based prostate cancer (CaP) study. Automated image analysis may be used if proliferation and apoptotic biomarkers provide clearly resolved immunostained images.

Blinded review of archival radical prostatectomy specimens supports that contemporary Gleason score 6 prostate cancer lacks metastatic potential

Retrospective identification of Gleason pattern 4 in metastatic Gleason score 3 + 3 = 6 (GS6) radical prostatectomy (RP) specimens has suggested true GS6 prostate cancer (CaP) lacks metastatic potential. However, pathologist awareness of study design and metastasis outcomes at the time of RP review might have introduced upgrading bias. We used pathologist‐blinded methodology for unbiased characterization of metastasis rates for contemporarily defined pathologic GS6 (pGS6) CaP.

Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy

Background:Fatty-acid synthase (FASN), selectively overexpressed in prostate cancer (PCa) cells, has been described as linked to the aggressiveness of PCa. Constitutional genetic variation of the FASN gene and the expression levels of FASN protein in cancer cells could thus be expected to predict outcome after radical prostatectomy (RP). This study evaluates the associations of malignant tissue status, neoadjuvant androgen deprivation therapy (NADT) and single-nucleotide polymorphisms (SNPs) of FASN with FASN protein expression in prostate tissue. The study then examines the associations of FASN SNPs and gene expression with three measures of post-prostatectomy outcome.Methods:Seven tagging FASN SNPs were genotyped in 659 European American men who underwent RP at Roswell Park Cancer Institute between 1993 and 2005. FASN protein expression was assessed using immunohistochemistry. The patients were followed for an average of 6.9 years (range: 0.1–20.6 years). Outcome was assessed using three end points: biochemical failure, treatment failure and development of distant metastatic PCa. Cox proportional hazards analyses were used to evaluate the associations of the tagging SNPs and FASN expression with these end points. Bivariate associations with outcomes were considered; the associations also were controlled for known aggressiveness indicators.Results:Overall, no SNPs were associated with any known aggressiveness indicators. FASN staining intensity was stronger in malignant than in benign tissue, and NADT was associated with decreased FASN staining in both benign and malignant tissue. The relationships of FASN SNPs and staining intensity with outcome were less clear. One SNP, rs4246444, showed a weak association with outcome. FASN staining intensity also showed a weak and seemingly contradictory relationship with outcome.Conclusions:Additional study with longer follow-up and populations that include more metastatic patients is warranted.

Prediction of systemic spread independent of local extension or nodal disease by venous tumor thrombus in renal cell carcinoma.

435 Background: Renal cell carcinoma (RCC) venous extension is a challenging condition. Its prognostic significance is not well established. We investigated possible prognostic correlations between venous extension in RCC, with its various levels, and local extension, lymphatic spread and systemic metastasis; and its impact on progression free survival (PFS) and overall survival (OS). METHODS We analyzed an IRB-approved prospectively-maintained kidney cancer database at Roswell Park Cancer Institute. Patients with venous involvement were identified, classified according to the highest cephalic venous thrombus extension into 3 groups; group 1, renal vein; group 2, infrahepatic; group 3, subdiaphragmatic. Preoperative, postoperative, and pathologic factors were recorded. Patient characteristics were compared between groups using Kruskal-Wallis and Chi-Square tests for quantitative and categorical variables respectively. RESULTS 711 patients underwent nephrectomy for RCC between 2004 and 2011. Out of 63 patients with RCC and venous tumor thrombus, 55 patients were analyzed in this study who underwent radical nephrectomy and venous thrombectomy. Median age was 63 years and median follow-up was 18.7 months. 37 patients were group 1, 10 were group 2, and 8 were group 3. 1 and 3 year PFS were 66% and 38.5% respectively, and 1 and 3 year OS were 74.2% and 47.4% respectively. There were no statistically significant differences in OS or PFS between different groups. Among several factors examined, venous extension was associated with increased risk of distant metastasis, and that risk did not increase with higher cephalic venous extension (p = 0.011). When patients were categorized by local extension and nodal disease spread, there was no statistically significant association with venous tumor extension (p =0.24 and 0.35 respectively), though they were independently associated with distant spread (p = 0.002 and 0.013 respectively) and OS (p =0.005 and0.03 respectively). CONCLUSIONS Venous tumor extension alone can serve as an independent predictor of distant metastasis in patients with RCC. Our analysis suggests that cephalic venous thrombus extension does not impact patient survival.

Abstract 4853: Comparison of automated and a semi-automated methods for assessing Ki-67 staining.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Human evaluation of immuno-staining is limited by the subjectivity of the human evaluator, is time-consuming and is expensive. Semi-automated means of tissue evaluation have been proposed, but most of these have large subjective components. This study assesses semi-automated and newly-developed fully automated methods of evaluating Ki-67 staining of benign and malignant tissue from radical prostatectomy specimens. A research tissue microarray was constructed from 68 prostatectomy specimens and contained 3 core samples of benign and 3 of malignant tissue from each research subject. Tissue microarray sections were immune-stained for Ki-67. Two technicians (SG & CM) evaluated each TMA core and labeled the nuclei positive for Ki-67 with a green dot, and negative with a red dot. Images were collected and Image-Pro software was used to count the number of green and red dots. In a separate procedure, Image-Pro (IP) software was used to identify nuclei, and grade each nucleus as positive or negative, and the percentage of positive nuclei was calculated. The semi-automated results correlated with each other (0.58, P<0.001). The semi-automated and fully automated results also correlated (0.8, P<0.001, CM vs. IP and 0.59, P<0.001, SG vs. IP). When stratified by tissue type (benign vs. malignant), the semi-automated results and the fully-automated results also correlated (benign tissue: 0.68, P<0.001, CM vs. IP, and 0.80, P<0.001, SG vs. IP; tumor tissue: 0.89, P<0.001, CM vs. IP and 0.47, P<0.001, SG vs. IP). These results suggest that semi-automated and automated analysis of Ki-67 staining of prostate tissue produces comparable results, and automated analysis can be used for prostate cancer research. Citation Format: Rochelle P. Ondracek, James Marshall, Karin Kasza, Christopher Morrison, Simoya Ghajar, Carl Morrison, Diana Mehedint, James L. Mohler. Comparison of automated and a semi-automated methods for assessing Ki-67 staining. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4853. doi:10.1158/1538-7445.AM2013-4853