Sameer Chopra

Effect of a Risk-stratified Grade of Nerve-sparing Technique on Early Return of Continence After Robot-assisted Laparoscopic Radical Prostatectomy

BACKGROUND The impact of nerve sparing (NS) on urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RALP) has yet to be defined. OBJECTIVE To evaluate the effect of a risk-stratified grade of NS technique on early return of urinary continence. DESIGN, SETTING, AND PARTICIPANTS Data were collected from 1546 patients who underwent RALP by a single surgeon at a tertiary care center from December 2008 to October 2011. Patients were categorized preoperatively by a risk-stratified approach into risk grades 1-4, with risk grade 1 patients more likely to receive NS grade 1 or complete hammock preservation. This categorization was also conducted for risk grades 2-4, with grade 4 patients receiving a non-NS procedure. INTERVENTION Risk-stratified grading of NS RALP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariate and multivariate analysis identified predictors of early return of urinary continence, defined as no pad use at ≤ 12 wk postoperatively. RESULTS AND LIMITATIONS Early return of continence was achieved by 791 of 1417 men (55.8%); of those, 199 of 277 (71.8%) were in NS grade 1, 440 of 805 (54.7%) were in NS grade 2, 132 of 289 (45.7%) were in NS grade 3, and 20 of 46 (43.5%) were in NS grade 4 (p<0.001). On multivariate analysis, better NS grade was a significant independent predictor of early return of urinary continence when NS grade 1 was the reference variable compared with NS grade 2 (p<0.001; odds ratio [OR]: 0.46), NS grade 3 (p<0.001; OR: 0.35), and NS grade 4 (p=0.001; OR: 0.29). Lower preoperative International Prostate Symptom Score (p=0.001; OR: 0.97) and higher preoperative Sexual Health Inventory for Men score (p=0.002; OR: 1.03) were indicative of early return of urinary continence. Positive surgical margin rates were 7.2% (20 of 277) of grade 1 cases, 7.6% (61 of 805) of grade 2 cases, 7.6% (22 of 289) of grade 3 cases, and 17.4% (8 of 46) of grade 4 cases (p=0.111). Extraprostatic extension occurred in 6.1% (17 of 277) of NS grade 1 cases, 17.5% (141 of 805) of NS grade 2 cases, 42.5% (123 of 289) of NS grade 3 cases, and 63% (29 of 46) of NS grade 4 cases (p<0.001). Some limitations of the study are that the study was not randomized, grading of NS was subjective, and possible selection bias existed. CONCLUSIONS Our study reports a correlation between risk-stratified grade of NS technique and early return of urinary continence as patients with a lower grade (higher degree) of NS achieved an early return of urinary continence without compromising oncologic safety.

Improving time to continence after robot-assisted laparoscopic prostatectomy: augmentation of the total anatomic reconstruction technique by adding dynamic detrusor cuff trigonoplasty and suprapubic tube placement.

After robot-assisted laparoscopic prostatectomy, total anatomic reconstruction (TR) with the additions of a circumapical urethral dissection, a dynamic detrusor cuff trigonoplasty, and placement of a suprapubic catheter was performed in 49 patients from June to July 2012. Continence at 6 weeks after catheter removal was assessed for an initial group of 23 patients, and also at 2 weeks in an additional 26 patients who most recently had undergone surgery. Follow-up appointments and telephone interviews were used to assess pad use and continence. Of the initial 23 patients receiving the modified TR, 60.9% had 0 pad use at 6 weeks. By 2 weeks, 65.4% of the most recent 26 patients operated on achieved continence with 0-1 pad use. Preservation and reconstruction of the pelvic floor and supporting bladder structures leads to an earlier return of continence. These key steps need to be validated and confirmed in larger and randomized trials.

Robotic radical prostatectomy: The new gold standard

Abstract Objectives: Open radical prostatectomy (RP) has been the standard and primary treatment for focal prostate cancer. However, in recent years this view has changed, as robot-assisted laparoscopic RP has gained acceptance among urologists. In this review we evaluate the importance and place of robotics in laparoscopic urological surgery, discussing several techniques that are currently being used and potentially new techniques that might be used in the future. Methods: We systematically reviewed papers published between 1998 and 2011 using the keywords ‘robotic prostatectomy’ ‘gold standard’ and the Medline database. In addition, after selecting relevant reports we searched ‘related citations’ of the documents to find further supporting published papers. Results: In all, 50 original papers were identified using the search criteria; we also found 28 through ‘related citations’ browsing. Papers were selected according to their relevance to the current topic (i.e. RP, original articles) and incorporated into this review. These papers were used for their information on the advantages of using robotics, as well as innovative ideas being used in the field of robotic urological surgery. Conclusion: Almost a decade after the first robotic RP many reports show the benefits and advantages of incorporating robotics into urological surgery. Robotic surgery decreases the learning curve necessary for surgeons when compared with laparoscopic techniques. In addition, patients prefer robotics, as the procedure is less invasive, diminishes the duration of hospitalisation and speeds the return to function.

V12-03 ROBOTIC UTERETAL REIMPLANTATION FOR URETERO-ENTERIC ANASTOMOTIC STRICTURES

tumor identification and characterization. Given their respective strengths and complementary characteristics, we postulate that combining wide-field (PDD and NBI) with microscopic (CLE) imaging technologies will further enhance TURBT. Towards that goal, we report our preliminary experience with multimodal enhanced cystoscopy. METHODS: The study received IRB approval. PDD was performed using hexaminolevulinate (Photocure) in combination with blue light cystoscope (Storz). NBI (Olympus) was performed with an NBIenabled camera head attached to the standard resectoscope. Probebased CLE was performed with fluorescein as the contrast agent along with 2.6 or 0.85 mm endomicroscopes (Cellvizio, Mauna Kea Technologies). Following TURBT with PDD or NBI, the resection bed was imaged with CLE. Imaging features of the resection bed were characterized by 3 urologists and achieved consensus. RESULTS: To date, 10 subjects have undergone multimodal imaging. No adverse events were noted due to the combination of instruments or imaging agents used. Confocal imaging features of the resection bed including elastin fibers (network of thin, interwoven strands), muscle fibers (sheets of straight, connected columns) and perivesical fat (collection of dark, round globules) were observed. Muscularis propria was present in the resected tissue on pathology assessment, confirming adequate resection. Patients are currently undergoing follow-up for cancer recurrence. CONCLUSIONS: We report real-time microscopic inspection of the resection bed to assess for adequate depth of resection with CLE in combination with the macroscopic imaging technologies PDD and NBI. Further studies are needed to determine if multimodal enhanced cystoscopy results in improved TURBT with adequate depth and margins of resection and decreased recurrence rate, which may eventually translate to a decreased need for repeat TURBT.

V4-03 CT/MRI-US FUSION GUIDED RENAL MASS BIOPSY: INITIAL EXPERIENCE

are placed using a combination of US and a transperineal electromagnetic-tracked MR/US fusion device (Invivo, Gainesville, FL). 48 hours’ post-ablation, the patient is imaged, fig 1, followed by re-imaging and MR/US fusion guided biopsy (FBx) at 3 months. All patient demographics, clinical variables, and complications were recorded. RESULTS: Todate, 2 patients havebeenenrolled in the trial, both with localizedGleason7PCadiagnosedusingMR/USFBx.Meanagewas 67 + 4.3 years and mean prostate specific antigen was 6.1 + 0.06 ng/ml. The mean tumor volume was 0.40 + 0.05 cc with a solitary lesion in each patient. Themean PSA decrease was 3.6 + 0.6 ng/ml, a 40.9% decrease at 1 month. No short-term complications were observed. The first patient underwent a follow up FBx at 3 months with no detectable cancer. CONCLUSIONS: Increasing interest in image guidance technologies and focal therapies has sparked a new generation of PCa treatment modalities. We have demonstrated the first safe and effective use of ultra-focal therapy using MR/US fusion technology in concert with GNP directed therapy to treat prostate tumors.

MP08-13 MR RADIOMICS IN THE RISK STRATIFICATION OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: The current paradigm in prostate cancer risk stratification, including DRE, PSA values, and prostate biopsy, has resulted in overdiagnosis and overtreatment. A noninvasive marker is needed to more accurately differentiate between aggressive and indolent disease. This study evaluated multiparametric magnetic resonance imaging (mpMRI)-derived texture metrics as a biomarker for prostate cancer risk stratification. METHODS: In this IRB approved, retrospective study, we identified 66 prostate cancer lesions in patients who underwent 3T mpMRI prior to prostate biopsy. Biopsy proven Prostate cancer lesions were divided into high, intermediate, and low risk categories per National Comprehensive Cancer Network guidelines. Lesion regions of interest were manually segmented from apparent diffusion coefficient (ADC) and T2 weighted images (T2WI). Texture analysis was performed using gray-level co-occurrence matrices (GLCM), fast Fourier transfer-based spectral metrics, and ADC and T2 signal intensity. Kruskall Wallis test and analysis of variance were used to determine if there is an association between texture metrics and prostate cancer risk categories. Stepwise logistic regression was used to select the best predictors in discriminating high risk lesions from other lesions. RESULTS: Of the spectral metrics, Complexity Index on ADC and T2WI was significantly different (p<0.01) between the risk categories. ADC-derived GLCM metrics variance, contrast, homogeneity, dissimilarity, and difference of average were significantly different (p<0.01) between the risk categories. Of the texture metrics, GLCM Variance on ADC (ADC_Var) and Information Measures of Correlation 1 on T2WI (T2_ICM1) were the best metrics in discriminating high risk lesions from intermediate and low risk lesions and were selected in the final prediction model. Used alone, the areas under the receiver operator curve (AUC) for ADC_Var and T2_IMC1 were 0.77 (95%CI: 0.64-0.9) and 0.71 (95%CI: 0.59-0.82) respectively. The AUC when using both metrics together was 0.83 (95%CI: 0.72-0.94). CONCLUSIONS: mpMRI-based texture analysis can differentiate high risk prostate cancer lesions from intermediate and low risk lesions, demonstrating promise as a biomarker for prostate cancer risk stratification.

MP100-14 HIGH INTENSITY FOCUSED ULTRASOUND KIDNEY ABLATION: PRE-CLINICAL SAFETY AND EFFICACY EVALUATION IN A PORCINE MODEL USING A 15MM LAPAROSCOPIC PROBE

INTRODUCTION AND OBJECTIVES: Irreversible Electroporation (IRE) is an emerging ablative modality for patients with renal tumors that are not candidates for surgery or conventional thermal ablation. This study aims to evaluate technical success, safety, and outcomes for IRE treated complicated renal tumors. METHODS: A single institution retrospective review of all renal tumors treatedwithComputed Tomography (CT) guided IREbetweenMay 2013 and February 2016 was performed. A total of 17 patients underwent IRE with NanoKnife (AngioDynamics, Queensbury, New York) for primary or secondary renal malignancies. Technical success was defined as delivery of all planned pulses during ablation and verifying complete ablation by immediatepost-procedureCT imaging. Local recurrencewasdefinedas residual enhancement or increased tumor size following technical success. Follow-up imaging was scheduled at 1, 3, 6, 12, 18, and 24 months. Complications were defined using Clavien-Dino (CD) classification. RESULTS: IRE was performed on 18 complicated renal tumors with median RENAL score of 6.5 ( 1st quartile 6, 3rd quartile 9) and median tumor size of 2.2 cm (1st quartile 2.0, 3rd quartile 3.1). Most were clear cell renal cell carcinomas (n1⁄413). Technical success was achieved in 17/18 tumor treatments (94.4%). One (5.6%) case was aborted due to bleeding (CD grade IIIb) requiring embolization. Minor CD grade one or two complications were present in 7/18 cases (38.9%), including post-procedural urinary retention (4/18, 22.2%), hypoglycemia (1/18, 5.6%), hematuria (1/18, 5.6%), and back pain (1/18, 5.6%). Patients lost to follow up were excluded (n1⁄43) from follow-up analysis. Median follow-up was 392 days, 1st quartile 203, 3rd quartile 696). Two local recurrences (14.2%) occurred on days 320 and 230 post-procedure with RENAL Scores of 9 and 8, respectively. Both cases were successfully treated with cryoablation and follow up showed no residual tumor at 723 and 617 days post cryoablation, respectively. CONCLUSIONS: IRE appears to be a safe and efficacious option for the treatment of renal tumors in patients that are not candidates for surgery or thermal ablation techniques. Further research is warranted with larger sample sizes and continued follow up.

MP18-13 TEXTURE ANALYSIS OF ENHANCING, NON-LIPID CONTAINING SOLID RENAL MASSES: DIFFERENTIATION OF MALIGNANT FROM BENIGN RENAL TUMORS.

INTRODUCTION AND OBJECTIVES: Contrast Enhanced Computed Tomography (CECT) is the most common modality of imaging a renal mass. While metrics including pixel enhancement have been described for differentiation of various types of tumors, we describe an additional technique of texture analysis. METHODS: In this Institutional Review Board (IRB) approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study, we identified 136 patients with solid, non-lipid containing enhancing renal tumors based on post-surgical pathology examination (94 Malignant, 42 Benign). Here, we test the feasibility using textural biomarkers, to objectively quantify and differentiate the textural heterogeneity of malignant subtypes, here, clear cell renal carcinoma, papillary renal carcinoma, and chromophobe from, benign subtypes, here, oncocytoma and lipid poor angiomyolipoma, using standard-of-care contrast-enhanced computed tomography (CECT) images. RESULTS: Three sets of stepwise logistic regression were used to select the best predictor among all candidate predictors from 2D GLCM, 3D GLCM and spectral (Table 1). The discrimination power gain from spectral metrics in addition to 2D and 3D GLCM combined was assessed using a one-degree freedom chi square test when comparing the area under the curve between the full model and the model without spectral metrics. The full model with 2D, 3D GLCM and spectral predictors yielded an AUC of 0.92 (95% CI: 0.87-0.96), while the model with 2D and 3D only already reached almost the same AUC. The difference between the two model was less than 0.01 (p1⁄40.89) (Figure 1). CONCLUSIONS: CECT-based texture metrics can differentiate between malignantand benign-renal tumors, with 2D and 3D GLCM metrics providing the most information for segregating malignant from benign renal tumors. In combination with other metrics such as contrast enhancement, shape metrics etc., texture metrics, have the potential to improve patient management and help stratify renal tumors using prostate CECT. Source of Funding: This project has received funding from the Whittier Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Foundation.

PD27-10 ROBOTIC SIMPLE PROSTATECTOMY: THE USC EXPERIENCE

(IPSS) were collected. Patients with prostate glands 80ml and LUTS related to BPH were retrospectively included in the analysis. Patients were matched and three groups of 50 patients treated with PVP, GreenLEP or OP were compared. RESULTS: Mean prostate volume was comparable in the three groups (120 vs 120.5 vs 122.2 mL, p1⁄40.952, respectively). A longer operative time, a lower rate of postoperative bleeding complications (p1⁄40.018) and a shorter length of bladder irrigation (p<0.001), catheterization (p<0.001) and hospital stay (p<0.001) were observed in PVP and GreenLEP groups(Table 1 & 2). At 3 and 12 months, PVP was associated with a lower maximal urinary flow and a higher IPSS than OP and GreenLEP (p<0.001, p1⁄40.025 and p1⁄40.020, respectively) (Figure 1). Patients treated with PVP had a higher risk of re-treatment than those treated with GreenLEP or OP (log rank test: p1⁄40.059). CONCLUSIONS: PVP and GreenLEP are associated with longer operative time but better post-operative outcomes than OP. However, regarding functional outcomes, PVP might be less effective than OP and GreenLEP in prostate glands over 80mL.

Abstract B03: Identification of epigenetic regulated genes through simultaneous analysis of DNA methylation and chromatin structure in uncultured tumors

The contribution of promoter DNA methylation to the alteration of caner related gene expression has been well studied, however, these genes can also potentially be altered by chromatin accessibility without involvement of DNA methylation and can be epigenetically inherited. In this study, we used an assay developed in our laboratory (AcceSssIble) that can simultaneously interrogate DNA methylation and chromatin accessibility allowing us to investigate the epigenetic changes in uncultured clear cell renal cell carcinoma (ccRCC) tumors and normal tissue to uncover genes that contribute to ccRCC tumorigenesis. AcceSssIble is both cost-effective and easily analyzed using simple and straightforward computational analysis. Our study revealed significant changes to the epigenome of ccRCC, especially identifying epigenetically up- (160) or down-regulated genes (180), which are dependent on accessibility changes with (30%) or without (70%) DNA methylation involvement, and which were validated by a cross-correlation of the identified genes with RNA-seq and DNA methylation data from larger cohorts of ccRCC samples from The Cancer Genome Atlas (TCGA). In addition, our findings also revealed these sets of genes not found to be commonly mutated in ccRCC and undergo epigenetic changes at higher frequencies than common ccRCC mutations. In addition, pathway analysis suggests that genetic and epigenetic alterations are independent events, and one such example includes a set of changes in HIF1α signaling pathway genes that are independent of the Von Hippel-Lindau (VHL) status. This suggests a novel epigenetic basis for HIF1αs role during tumorigenesis that may be a common occurrence in ccRCC. Thus, the AcceSssIble analysis on ccRCC samples revealed novel candidates for epigenetic driver genes which were previously undetectable by widely used methylation studies. Overall, this study provides a novel approach that can help identify new epigenetic therapeutic targets and treatment strategies complementing current approaches based primarily on the genetic makeup of primary tumors. Citation Format: Elinne Becket, Sameer Chopra, Christopher Duymich, Lin J. Justin, Jueng Soo You, Kurinji Pandiyan, Peter W. Nichols, Kimberly D. Siegmund, Peter A. Jones, Gangning Liang. Identification of epigenetic regulated genes through simultaneous analysis of DNA methylation and chromatin structure in uncultured tumors. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B03.