Kiranpreet Khurana

Prostate cancer: value of multiparametric MR imaging at 3 T for detection--histopathologic correlation.

PURPOSE To determine utility of multiparametric imaging performed at 3 T for detection of prostate cancer by using T2-weighted magnetic resonance (MR) imaging, MR spectroscopy, and dynamic contrast material-enhanced MR imaging, with whole-mount pathologic findings as reference standard. MATERIALS AND METHODS This prospectively designed, HIPAA-compliant, single-institution study was approved by the local institutional review board. Seventy consecutive patients (mean age, 60.4 years; mean prostate-specific antigen level, 5.47 ng/mL [5.47 microg/L]; range, 1-19.9 ng/mL [1-19.9 microg/L]) were included; informed consent was obtained from each patient. All patients had biopsy-proved prostate cancer, with a median Gleason score of 7 (range, 6-9). Images were obtained by using a combination of six-channel cardiac and endorectal coils. MR imaging and pathologic findings were evaluated independently and blinded and then correlated with histopathologic findings by using side-by-side comparison. Analyses were conducted with a raw stringent approach and an alternative neighboring method, which accounted for surgical deformation, shrinkage, and nonuniform slicing factors in pathologic specimens. Generalized estimating equations (GEEs) were used to estimate the predictive value of region-specific, pathologically determined cancer for all three modalities. This approach accounts for the correlation among multiple regions in the same individual. RESULTS For T2-weighted MR imaging, sensitivity and specificity values obtained with stringent approach were 0.42 (95% confidence interval [CI]: 0.36, 0.47) and 0.83 (95% CI: 0.81, 0.86), and for the alternative neighboring approach, sensitivity and specificity values were 0.73 (95% CI: 0.67, 0.78) and 0.89 (95% CI: 0.85, 0.93), respectively. The combined diagnostic accuracy of T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy for peripheral zone tumors was examined by calculating their predictive value with different combinations of techniques; T2-weighted MR imaging, dynamic contrast-enhanced MR imaging, and MR spectroscopy provided significant independent and additive predictive value when GEEs were used (P < .001, P = .02, P = .002, respectively). CONCLUSION Multiparametric MR imaging (T2-weighted MR imaging, MR spectroscopy, dynamic contrast-enhanced MR imaging) of the prostate at 3 T enables tumor detection, with reasonable sensitivity and specificity values.

Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12

Intravesical BCG has been used successfully to treat superficial bladder cancer for three decades. However, 20% to 30% of patients will fail initial BCG therapy and 30% to 50% of patients will develop recurrent tumors within 5 years. Alternative or complementary strategies for the management of superficial bladder cancer are needed. Interleukin-12 (IL-12) is a potent T(H)1 cytokine with robust antitumor activity and the ability to potentiate immunologic memory. Unfortunately, intravesical IL-12 did not show antitumor efficacy in a recent clinical study of patients with recurrent superficial bladder cancer. We hypothesized that coformulation of IL-12 with chitosan, a biocompatible, mucoadhesive polysaccharide, could improve intravesical IL-12 delivery and provide an effective and durable alternative for the treatment of superficial bladder cancer. In antitumor studies, 88% to 100% of mice bearing orthotopic bladder tumors were cured after four intravesical treatments with chitosan/IL-12. In contrast, only 38% to 60% of mice treated with IL-12 alone and 0% treated with BCG were cured. Antitumor responses following chitosan/IL-12 treatments were durable and provided complete protection from intravesical tumor rechallenge. Urinary cytokine analysis showed that chitosan/IL-12 induced multiple T(H)1 cytokines at levels significantly higher than either IL-12 alone or BCG. Immunohistochemistry revealed moderate to intense tumor infiltration by T cells and macrophages following chitosan/IL-12 treatments. Bladder submucosa from cured mice contained residual populations of immune cells that returned to baseline levels after several months. Intravesical chitosan/IL-12 is a well-tolerated, effective immunotherapy that deserves further consideration for testing in humans for the management of superficial bladder cancer.

Repeat Partial Nephrectomy on the Solitary Kidney: Surgical, Functional and Oncological Outcomes

PURPOSE We examined outcomes in patients with recurrent or de novo renal lesions treated with repeat partial nephrectomy on a solitary kidney. MATERIALS AND METHODS We reviewed the records of patients who underwent nephron sparing surgery at the National Cancer Institute from 1989 to 2008. Patients were included in analysis if they underwent repeat partial nephrectomy on a solitary kidney. Perioperative, functional and oncological outcomes were assessed. Functional outcomes were evaluated using the Modification of Diet in Renal Disease equation for the estimated glomerular filtration rate. Oncological efficacy was examined by the need for subsequent repeat renal surgery and the development of metastatic disease. RESULTS A total of 25 patients were included in the analysis. A median of 4 tumors were resected. Median estimated blood loss was 2,400 ml and median operative time was 8.5 hours. Perioperative complications occurred in 52% of patients, including 1 death and the loss of 3 renal units. There was a decrease in the estimated glomerular filtration rate at followup visit 1 within 3 months after surgery but at 1-year followup the difference was not significant (p <0.01 and 0.12, respectively). Surgical intervention was recommended in 8 patients (38%) for recurrent or de novo tumors at a median of 36 months. The average metastasis-free survival rate in the cohort was 95% at 57 months (median 50, range 3 to 196). CONCLUSIONS Repeat partial nephrectomy in patients with solitary kidney is a high risk alternative. The complication rate is high and there is a modest decrease in renal function but most patients remain free of dialysis with acceptable oncological outcomes at intermediate followup.

Serum Testosterone Levels and Mortality in Men With CKD Stages 3-4

BACKGROUND Hypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD). STUDY DESIGN Retrospective, cohort study. SETTING & PARTICIPANTS 2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH. PREDICTORS Total testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL). OUTCOMES Factors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. RESULTS Hypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16). LIMITATIONS Single-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias. CONCLUSIONS Low total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed.

Prevalence of Circulating Tumor Cells in Localized Prostate Cancer

Background: Circulating tumor cells (CTC) predict overall survival in patients with metastatic prostate cancer. The objective of this study is to measure CTC before radical prostatectomy in intermediate- and high-risk prostate cancer patients. Materials and Methods: The study accrued 12 patients and 10 provided adequate peripheral blood sample. Blood was drawn preoperatively and assayed for CTC using the CellSearch system. Patients were categorized as CTC positive (≥ 1 CTC) or CTC negative (no CTC). Results: Median age was 64.5 years (range 49-77 years), median prostate specific antigen was 7.4 ng/ml (range 5.7-25.7 ng/ml). Seven patients had intermediate-risk and 3 patients had high-risk prostate cancer. One patient was found to be CTC positive. Conclusions: Our pilot study shows that CTC are rare in patients with clinically localized disease despite intermediate- to high-risk features. CTC may not be the optimal marker to predict prognosis or detect residual disease after radical prostatectomy.

V9-06 ROBOT ASSISTED PENILE INVERSION VAGINOPLASTY: A NOVEL TECHNIQUE

INTRODUCTION AND OBJECTIVES: Gender confirmation surgery is an essential component in the management of gender identity disorder. However, short vaginal length, vaginal stenosis, or complications in the perineal dissection are significant limitations of current techniques in male to female surgery. Here we describe our technique for the robot assisted penile inversion vaginoplasty that addresses these needs. METHODS: The patient is prepped and draped in low lithotomy position. The penis is degloved through a circumcision incision. The neurovascular bundle, urethra and corpora cavernosa are dissected out. A six cm bulbar perineal incision is then made, and the dissection is carried to the bulbar urethra. The dissected urethra, neurovascular bundle, glans and corpora are delivered through this incision. The bilateral corpora are transected at their most proximal limit and overswen. The penile skin is inverted and gently retracted to allow a two cm incision above the neovagina for the neoclitoris. Immediately below this, an incision for the neomeatus is made. The urethra is brought through this incision and sutured to the skin. The remaining urethral tissue is used as an inlay onto the incised dorsal epithelial surface of the penile skin. The robotic portion of the surgery uses 4 port incisions: periumbiical Gelport with two pre-placed robotic trocars, right and left lateral ports, and an assistant port in the upper right abdomen. The dissection is from the posterior prostate, staying above Denonviller’s fascia to reach the endopelvic fascia. Under direct vision, the endopelvics are opened sharply from below and opened to a width of two fingerbreadths. The neovagina is passed into robotic field and pexed to the anterior reflection of the posterior peritoneum. The peritoneal reflection is then closed. The neoclitoris is fashioned from the glans penis and approximated. Labia majora and minora are fashioned with local skin flaps. A foley catheter is left indwelling as well as a vaginal stent. RESULTS: The index case required 7 hours of surgical time with an estimated blood loss of 100 mL. The vaginal length was greater than 15 cm. The patient was discharged home on post-operative day three, with no complications. The patient endorses sensation at the neoclitoris and anterior neovagina, and finds the vaginal depth satisfactory CONCLUSIONS: Our novel method for robot assisted penile inversion vaginoplasty is an important step in optimizing outcomes for our patients. This technique achieves maximal vaginal length in a safe and reproducible manner.

IMPACT OF ISCHEMIA AND TISSUE PROCUREMENT CONDITIONS ON GENE EXPRESSION IN RENAL CELL CARCINOMA

Methods: Solid renal tumors from patients with von Hippel Lindau who underwent partial nephrectomy at the National Cancer Institute were included if they were resected without clamping of the renal hilum and had greater than 80% homogeneity on immediate gross examination. The procurement of the tumor was performed in the operating room. Immediately upon surgical resection, a piece of tumor was snap frozen to represent the zero time point. Remaining tissue samples were then stored in PBS at 4C, 22C and 37C and frozen at 5, 30, 60, 120, and 240 mins after surgical resection. All tissue samples were stored in liquid nitrogen until RNA extraction. Histopathologic evaluation was performed by a single pathologist on Hematoxylin & Eosin stained frozen sections obtained from each time point. Only tissue samples with at least 80% tumor on H & E were selected and used for RNA extraction, analysis, and gene expression microarrays. RNA integrity was confirmed by the presence of prominent 18S and 28S ribosomal peaks. Gene expression microarrays were performed using the Affymetrix platform. Class comparison paired t-test was performed between the zero time point and tissue samples from all other conditions obtained from the same tumor.

PD59-03 GROWTH KINETICS IN VON HIPPEL-LINDAU-ASSOCIATED RENAL TUMORS: DEFINING THE INFLUENCE OF GERMLINE MUTATION TYPE

free survival. Progressionwasstrictly definedasgrowth rate>0.5 cm/year, greatest tumor diameter >4.0 cm, metastatic disease, or elective crossover. Outcomes were evaluated using Kaplan-Meier survival analysis and comparisons were performed using the log-rank test. RESULTS: Of the 615 enrolled patients, 298 (48.5%) chose primary intervention and 317 (51.5%) chose active surveillance. From the active surveillance cohort, 45 (14.2%) patients underwent delayed intervention.Median follow-up time for theentire registrywas2.9years,with203 (33.0%) patients followed for 5 years or more. At baseline, patients who chose active surveillance were older (P < 0.001) and had higher comorbidity status (P< 0.001) than thosewho chose primary intervention. There was no difference in cancer-specific survival at 7 years between primary interventionandactive surveillance (99.0%vs100%, respectively,P1⁄4 0.3) [Figure 1A]. However, overall survival was higher in patients with primary intervention when compared to active surveillance at 5 years (93.0% vs 80.2%, respectively) and 7 years (91.7% vs 65.9%, respectively, P 1⁄4 0.002) [Figure 1B]. The 5-year and 7-year progression-free survival rate in the active surveillance cohort was 83.9% and 71.4%, respectively. CONCLUSIONS: In the intermediate-term, active surveillance appears to be as safe as and not inferior to primary intervention for carefully selected patients with small renal masses. As the registry matures, further studies will elucidate the effectiveness of active surveillance in the long-term.

MP79-09 TITLE: ROBOT ASSISTED PENILE INVERSION VAGINOPLASTY A DESCRIPTION OF A NOVEL TECHNIQUE

drainage of lesions is ineffective in curing the root cause of the problem, and persistence or worsening is the rule over time. Complete surgical resection followed by local flap or skin graft closure is possible, curative and most often successful, at the cost of a unsurprisingly high number of self limited wound complications. Urologists should endeavor to fix instead of merely manage this difficult problem.

V10-01 RECONSTRUCTION OF TWO CONCURRENT IPSILATERAL URETERAL STRICTURES WITH APPENDICEAL ONLAY AND NON-TRANSECTING URETERAL REIMPLANT

(RC) for muscle-invasive urothelial carcinoma of the bladder (UCB) failed to meet its accrual target. We sought to examine the comparative effectiveness of TMT vs. RC for muscle-invasive UCB in an observational cohort study. METHODS: Within the National Cancer Data Base (20042011), we identified 12,843 individuals who received TMT or RC for definitive treatment of cN0M0 muscle-invasive UCB. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses with time-varying covariate were used to compare overall survival (OS) of patients who received TMT vs. RC. Exploratory analyses according to patient characteristics were also performed. RESULTS: Overall, 1,257 (9.8%) and 11,586 (90.2%) patients received TMT and RC, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was similar between TMT and RC groups (39.6 [95% CI, 33.7-45.5] vs. 43.0 [95% CI, 40.9-45.1] months; P1⁄40.290; Figure 1). In IPTW-adjusted Cox regression analysis with time-varying covariate, TMT was associated with a significant adverse effect on OS after 25 months of follow-up (HR1⁄41.37;95%CI1⁄4[1.16-1.59];p<0.001). In exploratory analyses (Figure 2), there was no significant difference between TMT and RC with regard to long-term OS in individuals aged >1⁄470 (HR1⁄41.21;95% CI1⁄4[0.83-1.60];P1⁄40.225), of female gender (HR1⁄41.28;95%CI1⁄4[0.831.74];P1⁄40.170), with Charlson comorbidity index >1⁄41 (HR1⁄41.10;95% CI1⁄4[0.83-1.38];P1⁄40.439) and/or >1⁄4cT3 disease (HR1⁄41.16; 95% CI1⁄4[0.80-1.52];P1⁄40.338. CONCLUSIONS: We generally observed that TMT was associated with worse long-term OS compared to RC for muscle-invasive UCB. However, selected subgroups of patients may choose TMT over RC to avoid surgical toxicities with minimal impact on OS.