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We report a multicenter international cohort representing what is to our knowledge the largest surgical experience with managing isolated retroperitoneal nodal recurrence of renal cell carcinoma, a unique subset of locoregional disease, yet to be described in detail.Patients with isolated nodal recurrence of pTanyN+M0 disease after nephrectomy were identified by retrospective chart review at 3 independent institutions. Progression-free survival was estimated by the Kaplan-Meier method and used to compare survival outcomes between primary T(1-2)N(any)M0 and T3N(any)M0 tumors as well as clear cell and nonclear cell histology renal cell carcinoma.A total of 22 patients met study inclusion criteria. Median time to local postoperative recurrence was 31.5 months (IQR 12.9-43.3). After resection of isolated nodal recurrence 10 patients (46%) had a secondary recurrence at a median of 11.2 months (IQR 8.1-18.4), of whom 2 (9%) died of the disease. Overall median progression-free survival was 12.7 months, including 24.8 months for T(1-2)N(any)M0 tumors, 9.9 months for T3N(any)M0 tumors, and 13.4 and 17.6 months for clear and nonclear cell renal cell carcinoma, respectively.Surgical resection represents the best curative option for patients who present with isolated retroperitoneal lymph node recurrence of renal cell carcinoma. Durable postoperative progression-free survival is attainable in many patients regardless of histology or clinical TNM stage. In addition, our cohort showed a lower renal cell carcinoma related mortality rate than in previous series of local metastasis. As such, all patients free of precluding comorbidities should be considered candidates for complete surgical resection performed by an experienced genitourinary surgeon.

Nephron-sparing surgery is the accepted standard of care for the small renal mass, and minimally invasive techniques have increasingly gained recognition. Robotic-assisted transperitoneal partial nephrectomy (RATPN) has been well described but there are few reports assessing the retroperitoneal approach. Therefore, we present our initial experience with robotic-assisted retroperitoneal partial nephrectomy (RARPN). We identified 14 patients from a single-surgeon IRB-approved database who underwent RARPN for suspected renal cell carcinoma. Our results showed a mean pathologic tumor size of 2.6 cm (SD = 0.9) and a median R.E.N.A.L. nephrometry score of 8. Mean estimated blood loss was 178 cc (SD = 182) and mean warm ischemia time was 28.9 min (SD = 8.9). There were no intra-operative or post-operative complications and mean length of stay was 2.9 days (SD = 1.6). At an average of 4-month follow-up, the mean decrease in renal function was 7.3 %. RARPN is an effective alternative to RATPN and can be safely and successfully applied to selected patients with tumors amenable to nephron preservation.

Penile cancer is an uncommon disease in the industrialized world that most frequently presents at low stage and is cured with treatment of local and regional surgery. In cases of advanced cancer, the use of more aggressive surgical techniques and the addition of adjuvant therapy may be warranted. So far, few agents have been found that improve survival with metastatic disease and thus aggressive primary treatment is required. This review discusses diagnosis, staging, and therapy for high risk penile cancer.

Multiple Endocrine Neoplasia type 2A (MEN-2a) is a rare disease associated with tumors of endocrine organs. Presentation most commonly is with medullary thyroid cancer and infrequently with other complaints. Pituitary adenoma has been seen coincidentally with this disease very rarely. Presented is a case of coincident MEN-2a with a symptomatic pituitary adenoma and an asymptomatic pheochromocytoma. A brief review is also provided.

BackgroundNephron-sparing treatments remain underutilized for the management of small renal masses despite a rise in incidentally detected renal cell carcinoma and a downward stage migration.MethodsHistorical publications representative of currently accepted paradigms were reviewed, and the results of a contemporary scientific literature search conducted in PubMed focusing on studies involving humans, published in English, and inclusive of clinical trials, meta-analyses, randomized controlled trials, and practice guidelines are included. Results from contemporary retrospective trials augment the data when level I or II evidence is absent.ResultsPhase III clinical trial results substantiate the long-held tenet that partial nephrectomy is equivalent to radical nephrectomy with respect to safety and oncologic efficacy. Further, minimally invasive techniques using laparoscopy and robotic assistance to achieve partial nephrectomy appear equally effective to traditional open techniques. Although no prospective randomized studies are available, large retrospective studies support the notion that active surveillance and thermal ablative techniques are viable options for carefully selected patients.ConclusionsThe management of small renal masses encompasses a host of therapeutic options, all of which must be considered and discussed with the individual patient.

In the era of widespread prostate-specific antigen screening, low-risk and very-low-risk prostate cancers are commonly identified, many of which will be of clinical insignificance. This has led to overtreatment and undue exposure to treatment-related morbidity in men harboring indolent tumors. Over the past 10 years, active surveillance (AS) has been evolving as a management strategy for these cancers. With continual reevaluation, the intent is to definitively treat tumors that are clearly progressive before the window of opportunity for cure has closed. To date, many of the surveillance parameters are without validation of utility, variably used, and without a standardized schedule. However, new instruments for characterizing prostate cancer offer the potential to better distinguish which men are best managed definitively at the outset from those who would be better served with observation. The findings of currently available AS cohorts suggest that initial expectant management of early prostate cancer is reasonable, showing that only approximately 30% of observed tumors are reclassified to ones of intermediate risk with short-term follow-up. Prostate cancer survival for men undergoing AS is close to 100% in all available studies, but long-term data remain scarce for those requiring delayed curative therapy.

INTRODUCTION AND OBJECTIVES: Recently, the R.E.N.A.L. nephrometry scoring system was introduced to objectively describe renal masses with respect to size, the degree to which they are exo/endophytic, the nearness to the collecting system, whether they are anterior or posterior and the location relative to polar lines. It is our aim to evaluate the R.E.N.A.L. nephrometry scoring system’s ability to predict functional renal loss attributed to nephron sparing surgery (NSS). METHODS: We evaluated 42 patients presenting with either an anatomic (32) or functionally solitary (10) kidney undergoing partial nephrectomy (PN). Each renal unit was assigned a R.E.N.A.L. nephrometry score utilizing pre-operative cross sectional imaging. The CKD EPI equation was applied to serum creatinine levels to generate corresponding estimated glomerular filtration rates (eGFR). The difference between the eGFR at baseline and at post operative time points served as a measurement of renal function loss attributed to PN. RESULTS: Forty two patients underwent PN with mean pre operative eGFR of 61.5 mL/min/1.73m2. The median total nephrometry score was 8, ranging from 4 10. Twenty eight (66.7%) of the renal lesions were iU 4 cm, 13 (31%) were between 4 and 7 cm, and 1 (2.4%) was 7 cm in diameter. The majority (54.8%) of the patients had tumors with more than 50% of tumor burden lying outside the expected renal border whereas 3 patients (7.1%) had tumors considered to be completely endophytic. Twenty seven (64.3%) were within 4 mm of the collecting system. Tumor locations defined as: completely polar, interpolar, and completely central were assigned to 11, 15, and 16 lesions respectively. By post operative month 6, the overall average eGFR of 53.9 mL/min/1.73m2 (a 12.3% reduction) was significantly less (p 0.0293) than the pre operative value. However, we were unable to correlate a change in eGFR with the pre-operatively assigned individual component scores nor the total R.E.N.A.L. score. CONCLUSIONS: Neither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score correlated with realized functional loss as assessed by percent change in eGFR in patients with a solitary kidney undergoing NSS.

We evaluated the ability of renal tumor complexity, as assessed by the R.E.N.A.L. (radius, exophytic, nearness to collecting system, anterior/posterior and location) nephrometry scoring system, to predict the functional efficacy of nephron sparing surgery.We evaluated 42 patients who presented with an anatomically (32) or a functionally (10) solitary kidney and underwent partial nephrectomy. Each renal unit was assigned a R.E.N.A.L. nephrometry score using preoperative imaging. The CKD-EPI equation was applied to calculate the estimated glomerular filtration rate. The difference between the estimated glomerular filtration rate at baseline and at postoperative time points served as a measurement of the renal functional loss attributable to partial nephrectomy.In the 42 patients who underwent partial nephrectomy the mean preoperative estimated glomerular filtration rate was 61.5 ml/minute/1.73 m(2). The median total nephrometry score was 8 (range 4 to 10). In the immediate postoperative period the cohort mean estimated glomerular filtration rate of 48.6 ml/minute/1.73 m(2) was significantly less than the preoperative value (p0.0001). At 6-month followup the mean estimated glomerular filtration rate had recovered at 54.1 ml/minute/1.73 m(2) but it remained significantly less than the preoperative value (p = 0.0002). We noted no relationship between the postoperative decrease in the estimated glomerular filtration rate and the assigned total nephrometry score or in any individual component of the R.E.N.A.L. scoring system related to the targeted lesion.Neither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score predicted the realized functional loss, as assessed by the estimated glomerular filtration rate in patients with a solitary kidney treated with nephron sparing surgery. However, nephron sparing surgery was quite efficacious for preserving renal function since only a durable 11.6% decrease was noted in the estimated glomerular filtration rate.

Primary large cell neuroendocrine carcinomas (NECs) of the bladder are rarely encountered, and only a few reports have been documented. Frequently, they are found to be admixed with other histologies. In this report, we describe such a tumor found in a 65-year-old man who underwent radical cystectomy, after initial transurethral resection discovered a small cell NEC pathology. We also reviewed the limited number of neuroendocrine tumors reported containing a large cell component. Given the paucity of these tumors and the resultant difficulty in developing generalized treatment protocols, we promote the use of gene expression models to tailor chemotherapeutic regimens for individual tumors.

378 Background: Post-chemotherapy retroperitoneal lymph node dissections (PC-RPLND) performed at high-volume centers are safe and comparable in risk to primary RPLNDs. The desmoplastic reaction encountered during PC-RPLND in patients with seminoma components increases the complexity of surgical dissection. We examined whether the presence of seminoma at diagnosis was associated with more adverse events in the perioperative setting. Methods: A single institution review board approved retrospective review identified 108 patients undergoing PC−RPLND from 1992 to 2012. All patients had received at least first-line cisplatin-based induction chemotherapy. Of these, 11 patients undergoing redo PC-RPLNDs were excluded from analysis. Patients were divided into two groups; those with any seminoma element in their orchiectomy or retroperitoneal specimens and those without seminoma elements. We performed independent t-tests and Chi-squared analysis of the data. Results: Of 97 patients undergoing PC-RPLND, 33 had seminoma components in their diagnostic specimens. Using the Clavien classification system to stratify post-operative complications, the percentage of seminomatous elements (less than 50% compared to more than 50%) within the primary tumor did not correlate with a higher incidence of complications; even when examining only major complications (p=0.673). There was a trend towards higher nephrectomy rate for tumors with seminoma elements compared to those without (27% vs. 8.5%, p = .058). The nephrectomy rate did show a dependence on the pathologic size of the residual mass regardless of histology (31% for more than 10 cm, 6.8% for 5 to 10 cm, 0% for 0 to 5 cm p = 0.021). There was also a trend towards blood loss greater than one liter for patients with seminoma elements compared to those without (63% vs. 43%, p = 0.078), while the transfusion rate was similar between the two groups (p=0.785). Post−operative length of stay was independent of a patient’s histology (p=0.94). Conclusions: PC-RPLND remains a safe and necessary therapeutic procedure. The presence of seminoma germ cell elements in our patient cohort did not result in a more complicated perioperative course surrounding PC-RPLND.

238 Background: Limited derived benefit from definitive treatment has been observed with respect to prostate cancer−specific mortality (PCSM) in those low−risk disease and only small absolute risk reductions in both overall PCSM and incidence of metastasis have been demonstrated. Thus, active surveillance (AS) strategies have been adopted to monitor for disease progression with intent for intervention at time of disease reclassification. Yet, the timing and frequency of surveillance remain without evidence-based standardization. We assessed the relationship between the frequency of surveillance prostate biopsies and the oncologic outcomes in those patients with low−risk prostate cancer (CaP) managed by AS. Methods: An IRB approved retrospective chart review identified 114 patients placed on AS for their CaP between November of 1997 and November of 2000. Of those, 96 patients meet study inclusion criteria mandating a Gleason sum of < 7, tumor presence in < 4 sextets, involvement of

170 Background: Prostate cancer (CaP) has exhibited a downward stage migration during the PSA era. Approximately 70% of those newly diagnosed with CaP, harbor tumors of low-risk. Such tumors often prove to be of low-volume and of clinical insignificance at time of radical prostatectomy (RP), suggesting over treatment and excessive exposure to the morbidity associated with definitive management. Over the last decade, active surveillance (AS) strategies have become a more accepted practice when addressing low-risk tumors. We present the long-term oncologic outcomes of patients placed on AS. Methods: An IRB approved retrospective chart review identified 114 patients placed on AS for their CaP between November of 1997 and November of 2000. Of those, 96 patients meet study inclusion criteria mandating a Gleason sum of < 7, tumor presence in < 4 sextets, and involvement of

430 Background: Over the past decade, there has been an increasing interest in combining surgical and systemic therapy to combat metastatic renal cell carcinoma (mRCC) with upfront cytoreductive nephrectomy (CN) favored in well selected patients. This study presents a novel risk stratification model to identify those who may benefit from upfront CN within the current targeted therapy era. Methods: Eighty-two patients with mRCC who underwent CN within our tertiary care referral center were identified. Potential pre-operative clinical and serologic predictors of overall survival (OS) were evaluated using both univariate and multivariable Cox-Regression analyses. A Recursive Partitioning and Regression Tree (RPART) model was subsequently developed allowing for stratification of patients into risk groups on the basis of OS. Results: The derived RPART tree, was able to stratify patients into 4 risk groups ranging from “low risk” to “very high risk” with respect to their expected OS utilizing the number of metastatic sites at diagnosis, serum hemoglobin (Hgb), and serum white blood cell count (WBC) count as partitioning parameters. Within the 4 groups, the median OS ranged from 4.3 months to 72 months. Conclusions: Our proposed simple quantitative risk-stratification model based on the pre-operative metastatic burden, Hgb, and WBC count is useful to predict OS when contemplating upfront CN prior to systemic therapy. Furthermore, a pre-operative serum WBC count ≥ 7.15 K/uL appears to be indicative of a poor prognosis.

399 Background: Recently, the R.E.N.A.L. nephrometry scoring system was introduced to objectively describe renal masses with respect to size, the degree to which they are exo/endophytic, the nearness to the collecting system, whether they are anterior or posterior and the location relative to polar lines. It is our aim to evaluate the R.E.N.A.L. nephrometry scoring system’s ability to predict functional renal loss attributed to nephron-sparing surgery (NSS). Methods: We evaluated 42 patients presenting with either an anatomic (32) or functionally solitary (10) kidneys undergoing partial nephrectomy (PN). Each renal unit was assigned a R.E.N.A.L. nephrometry score utilizing pre-operative cross-sectional imaging. The CKD−EPI equation was applied to serum creatinine levels to generate corresponding estimated glomerular filtration rates (eGFR). The difference between the eGFR at baseline and at post-operative time points served as a measurement of renal function loss attributed to PN. Results: Forty-two patients underwent PN with mean pre-operative eGFR of 61.5 mL/min/1.73m2. The median total nephrometry score was 8, ranging from 4–10. Twenty-eight (66.7%) of the renal lesions were ≤ 4 cm, 13 (31%) were between 4 and 7 cm, and 1 (2.4%) was >7 cm in diameter. The majority (54.8%) of the patients had tumors with more than 50% of tumor burden lying outside the expected renal border whereas 3 patients (7.1%) had tumors considered to be completely endophytic. Twenty-seven (64.3%) were within 4 mm of the collecting system. Tumor locations defined as: completely polar, interpolar, and completely central were assigned to 11, 15, and 16 lesions respectively. By post-operative month 6, the overall average eGFR of 53.9 mL/min/1.73m2 was significantly less (p = 0.0293) than the pre-operative value. However, we were unable to correlate change in post-operative eGFR with pre-operative total or individual R.E.N.A.L. scoring parameters. Conclusions: Neither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score correlated with realized functional loss as assessed by eGFR in patients with a solitary kidney undergoing NSS.

A statistically robust and biologically-based approach for analysis of microarray data is described that integrates independent biological knowledge and data with a global F-test for finding genes of interest that minimizes the need for replicates when used for hypothesis generation. First, each microarray is normalized to its noise level around zero. The microarray dataset is then globally adjusted by robust linear regression. Second, genes of interest that capture significant responses to experimental conditions are selected by finding those that express significantly higher variance than those expressing only technical variability. Clustering expression data and identifying expression-independent properties of genes of interest including upstream transcriptional regulatory elements (TREs), ontologies and networks or pathways organizes the data into a biologically meaningful system. We demonstrate that when the number of genes of interest is inconveniently large, identifying a subset of "beacon genes" representing the largest changes will identify pathways or networks altered by biological manipulation. The entire dataset is then used to complete the picture outlined by the "beacon genes." This allow construction of a structured model of a system that can generate biologically testable hypotheses. We illustrate this approach by comparing cells cultured on plastic or an extracellular matrix which organizes a dataset of over 2,000 genes of interest from a genome wide scan of transcription. The resulting model was confirmed by comparing the predicted pattern of TREs with experimental determination of active transcription factors.