Kyle A. Blum

Heterogeneity in renal cell carcinoma

INTRODUCTION In recent years, molecular characterization of renal cell carcinoma has facilitated the identification of driver genes, specific molecular pathways, and characterization of the tumor microenvironment, which has led to a better understanding of the disease. This comprehension has revolutionized the treatment for patients with metastatic disease, but despite these advancements many patients will develop resistance leading to treatment failure. A primary cause of this resistance and subsequent treatment failure is tumor heterogeneity. We reviewed the literature on the mechanisms of tumor heterogeneity and its clinical implications. METHODS A comprehensive literature search was performed using the MEDLINE/PubMed Index. RESULTS Intertumor and intratumor heterogeneity is possibly a reason for treatment failure and development of resistance. Specifically, the genetic profile of a renal tumor differs spatially within a tumor as well as among patients. Genomic mutations can change temporally with resistant subclones becoming dominant over time. CONCLUSIONS Accounting for intratumor and intertumor heterogeneity with better sampling of cancer tissue is needed. This will hopefully lead to improved identification of driver mutations and actionable targets. Only then, we can move past the one-size-fits-all approach toward personalized treatment based on each individual׳s molecular profile.

Main Renal Artery Clamping With or Without Renal Vein Clamping During Robotic Partial Nephrectomy for Clinical T1 Renal Masses: Perioperative and Long-term Functional Outcomes

OBJECTIVE To compare renal function outcome between a contemporary cohort of propensity score-matched patients undergoing main renal artery clamping (MAC) alone and those undergoing main renal artery clamping with renal vein clamping (MVAC) during robotic partial nephrectomy. MATERIALS AND METHODS Patients with a solitary T1 renal mass undergoing robotic partial nephrectomy were propensity score-matched on American Society of Anesthesiologists score, RENAL Nephrometry score, tumor size, tumor laterality, and operating surgeon to provide 66 patients undergoing MAC and 66 patients undergoing MVAC for analysis. Demographic and tumor-specific characteristics in addition to perioperative and renal function outcomes at discharge and 9 months were compared. RESULTS No differences in any baseline characteristics including age (P = .847), baseline estimated glomerular filtration rate (eGFR) (P = .358), RENAL Nephrometry score (P = .617), and tumor size (P = .551) were identified. Warm ischemia time was longer in patients undergoing MVAC than in patients undergoing MAC (21.0 minutes vs 15.0, P <.001), with no differences in estimated blood loss (P = .413), length of hospitalization (P = .112), and postoperative complications (overall [P = .251], by Clavien-Dindo classification [P = .119]). No differences in the percent change in eGFR (P = .866) or acute kidney injury (P = .493) at discharge and no differences in the percent change in eGFR (P = .401) or progression to chronic kidney disease (P = .594) at 9 months were identified. CONCLUSION Compared with MAC, clamping of the renal vein in addition to the main renal artery does not appear to adversely affect postoperative renal function. Future studies comparing MAC with MVAC partial nephrectomy in patients with baseline chronic kidney disease, a solitary kidney and complex tumors with prolonged warm ischemia time are necessary.

Demographic and socioeconomic predictors of treatment delays, pathologic stage, and survival among patients with penile cancer: A report from the National Cancer Database

OBJECTIVES To evaluate whether socioeconomic factors affect pathologic stage, treatment delays, pathologic upstaging, and overall survival (OS) in patients with penile cancer (PC). PATIENTS AND METHODS A total of 13,283 eligible patients diagnosed with PC from 1998 to 2012 were identified from the National Cancer Database. Socioeconomic, demographic and pathologic variables were used in multivariable regression models to identify predictors of pathologic T stage ≥2, pathologic lymph node positivity, cT to pT upstaging, treatment delays, and OS. RESULTS A 5-year OS was 61.5% with a median follow-up of 41.7 months. Pathologic T stage ≥2 was identified in 3,521 patients (27.2%), 1,173 (9.2%) had ≥pN1 and 388 (7.9%) experienced cT to pT upstaging. Variables associated with a higher likelihood of pathologic T stage ≥2 included no insurance (OR = 1.79, P<0.001), lower higher education based on zip code (OR = 1.13, P = 0.027), black race (OR = 1.17, P = 0.046) and Hispanic ethnicity (OR = 1.66, P<0.001). Patients with Hispanic ethnicity (OR = 1.46; P<0.001) or living in nonmetropolitan areas were more likely to have ≥pN1 (P = 0.001). Lack of insurance was associated with cT to pT upstaging (OR = 2.05, P = 0.001) as was living in an urban vs. metropolitan area (OR = 1.35, P = 0.031). In addition to TNM stage, black vs. white race (HR = 1.56, P<0.001), living in an urban vs. metropolitan area (hazard ratio [HR] = 1.18, P = 0.022), age (HR = 1.04, P<0.001) and Charlson score (HR = 1.49, P<0.001) were associated with lower OS. CONCLUSION Socioeconomic variables including no insurance, lower education, race, Hispanic ethnicity, and nonmetropolitan residence were found to be poor prognostic factors. Increased educational awareness of this rare disease may help reduce delays in diagnosis, improve prognosis and ultimately prevent deaths among socioeconomically disadvantaged men with PC.

MP72-19 PLASMA GLYCOSAMINOGLYCAN SCORES IN RENAL CELL CARCINOMA

either ccA (less aggressive) or ccB (more aggressive) molecular subtypes. Age-and sex-adjusted logistic regression models estimated associations between sarcopenia and molecular subtype separately for obese and non-obese patients. Statistical significance was regarded as a p-value of<0.05. RESULTS: The cohort was predominantly male (77%), white (97%), and had localized disease (62%). Median age was 58.7 years (IQR: 34-86.7). Overall, 53% of patients were obese, 39% were sarcopenic, and 58% of tumors were ccB subtype. Sarcopenic patients were more likely to have ccB tumors (66.7%) compared to patients without sarcopenia (26.1%) p1⁄40.00008. Among patients who were not obese, aggressive ccB subtype was more common in sarcopenic (69.6%) than non-sarcopenic patients (30.8%) (p1⁄40.03). A similar pattern was observed among patients who were obese; aggressive ccB subtype was more common in sarcopenic (57.1%) than non-sarcopenic patients (24.2%) (p1⁄40.04). CONCLUSIONS: While preliminary, our findings suggest that sarcopenia is associated with aggressive ccRCC regardless of obesity and lend biologic support to the observation that sarcopenia is associated with poor prognosis. It is not clear whether sarcopenia is a cause or consequence of tumor aggressiveness. RNA-Seq analysis of tumor tissue is being carried out to explore specific mechanisms underlying these observations.

Modern Outcomes with Modified PCNL

Percutaneous nephrolithotomy (PCNL) is the treatment of choice for patients with renal calculi ≥ 2 cm as well as larger lower pole calculi [1,2]. The armamentarium of specialized rigid and flexible nephroscopes and powerful lithotripters allow for greater stone-free rates in the treatment of patients with large stone burdens [3]. However, in comparison to shockwave lithotripsy and ureteroscopy, PCNL is associated with greater morbidity, particularly with respect to bleeding risk. This is attributed to the creation of a nephrostomy tract with subsequent tract dilation resulting in shearing of renal parenchyma and bleeding [4]. As such, percutaneous surgery using smaller tracts has been explored as a means to limit the morbidity of PCNL. An assortment of options ranging from micro-, to ultramini-, to miniPCNL have been described [5-7]. Recent series have demonstrated improvements in bleeding risk [8], postoperative pain scores [9] and hospital length of stay [10] compared with standard PCNL. However, despite these benefits, technical limitations apply. Smaller access tracts require miniaturized instruments, precluding the use of many efficient stone fragmentation and retrieval devices routinely used in standard PCNL. Therefore, while reported stone-free rates are generally high, these studies are often limited to patients with stone burdens between 10-20 mm [5,6,8].

PD35-06 CAN CT IMAGING PREDICT STONE IMPACTION?

INTRODUCTION AND OBJECTIVES: There are many techniques for laser lithotripsy of urinary stones. The “popcorn” method involves placing a laser fiber in the center of a collection of stones and firing continuously, allowing fragments to further dust into smaller particles. Our aim was to examine different locations and laser settings on the efficiency of this lithotripsy method. METHODS: Pre-fragmented BegoStone phantoms were created between 2-4mm in size to mimic typical popcorning conditions. A 0.5g collection of fragments was placed into two 3D-printed models (a 2 cm spherical calyx model and 4x2 cm ellipsoid pelvis model, Figure 1) and a 200mm laser fiber was positioned at the top of the stones. The laser was fired for 2 minutes with constant irrigation, with 5 trials performed at each setting: 0.2J/50Hz, 0.5J/20Hz, 0.5J/40Hz, 1J/20Hz. The fragmentation efficiency was determined by calculating the mass of stones reduced to sub-2mm particles after 48h of drying. Statistical analysis was performed with ANOVA and Student’s T-test. Additionally, high-speed photography was used to examine the mechanism of the popcorn effect. RESULTS: The trials within the calyx model were significantly more efficient compared to the pelvis model (0.18g vs 0.13g, p<0.05). When comparing laser settings, there was a difference between groups by one-way ANOVA (F[3,36] 1⁄4 7.92, p 1⁄4 0.0003). Post hoc tests showed that 20W settings were significantly more efficient than 0.2J/ 50Hz (p<0.05) although 0.5J/20Hz was not significantly less efficient than the 20W settings (Figure 2). High-speed imaging shows the majority of fragmentation is due to intermittent stone contact with the laser as opposed to stone-stone interaction. CONCLUSIONS: The popcorn effect is most efficient in a smaller space as in the calyx model and as such we recommend displacement of stones into a calyx for popcorning. The 0.5J/20Hz setting produces efficient popcorning at a lower power of 10W, reducing fiber burnback and potential for injury, and is our recommended setting. Source of Funding: None

PD16-11 PERCUTANEOUS MANAGEMENT OF CALYCEAL DIVERTICULA: ASSOCIATED FACTORS AND OUTCOMES

INTRODUCTION AND OBJECTIVES: The choice of treatment for symptomatic calyceal diverticula (CD) depends on size, location, and degree of stone burden. Percutaneous treatment is preferred for large CD, lower pole CD, and CD with a large stone burden, but its safety for anterior CD has not been evaluated. In addition, the necessity to treat the diverticular neck and the need for metabolic evaluation remains controversial. We sought to shed some light on these issues based on our significant experience. METHODS: We identified 51 patients in our IRB approved Endourology database with stone bearing CD that were treated percutaneously by a single experienced surgeon. We separated patients into those with stones only in their CD (CD only) and those who also had renal calculi outside of their diverticulum (CD plus). Demographic data, size and location of the CD, treatment of the diverticular neck, intra-operative and post-operative outcomes, stone analysis, and 24-hr urine parameters were recorded. Urine parameters were also compared to stone formers without CD (non-CD). RESULTS: CD only patients are younger (44 vs. 54 y, p1⁄40.024), have lower BMI (23.2 vs. 27, p1⁄40.032), and are more often female (71% vs. 44%, p 1⁄4 0.046) compared to non-CD patients. Anterior CD (66%) were more common than posterior, and 52% of the CD were found in the upper pole. Average CD size was 2.5cm with a stone burden of 1.47 cm. PCNL was performed safely and completely in 98% of the patients, with a complication rate of 4%. The diverticular neck was dilated in 44% of the cases. In follow-up there was 1 symptomatic recurrence managed by ureteroscopy. Calcium phosphate was contained in 82% of stones. All CD patients had at least one metabolic derangement, similar to regular stone formers, but with unusually high levels of urinary calcium and pH (Table 1). CONCLUSIONS: Percutaneous treatment of CD is safe and effective regardless of size or location (including anterior CD). Infundibular neck dilation does not appear to be necessary. A significant proportion of CD patients have metabolic abnormalities. Stone formation is likely a result of stasis and metabolic factors, and CD patients are at risk for future renal calculi.

PD35-01 A RANDOMIZED DOUBLE-BLIND CONTROLLED STUDY ASSESSING ELECTRO-ACUPUNCTURE FOR THE MANAGEMENT OF POST-OPERATIVE PAIN AFTER PERCUTANEOUS NEPHROLITHOTOMY

INTRODUCTION AND OBJECTIVES: Percutaneous nephrolithotomy (PCNL) is the gold standard procedure for large renal calculi, but post-operative pain remains a major concern. Modifications of the PCNL technique have been developed in part to decrease pain. More recently, acupuncture has been described as an adjunct to reduce pain following abdominal, spinal, and orthopedic surgeries. Among the benefits of acupuncture are its ease of performance, non-invasiveness, and lack of significant side effects. In comparison to traditional acupuncture, electro-acupuncture has shown enhanced efficacy, possibly due to central endorphin release. We sought to investigate the effects of electro-acupuncture on patients undergoing PCNL. METHODS: A double blind, randomized, sham controlled study design was used. Fifty patients undergoing PCNL by a single surgeon were randomized to one of three groups: true electro-acupuncture (EA, n1⁄4 17), sham electro-acupuncture (Sham, n 1⁄4 20), and no acupuncture (Control, n 1⁄4 13). Acupuncture was performed by a licensed acupuncturist 1 hr prior to surgery. All study personnel, except the acupuncturist were blinded to the intervention. PCNL was performed according to standard protocol and without intra-operative nerve block or local anesthetic. Pain scores (visual analog scale (VAS)), narcotic use (morphine equivalents (ME)), and side effects were recorded at set intervals post-operatively. RESULTS: Mean VAS scores for flank and abdomen in the EA group were lower at all time periods compared to sham and control groups. In fact, 2 patients in the EA group did not require any postoperative narcotics. Mean cumulative opioid usage was lower in the EA group immediately post-operatively compared to both sham and control groups (Table 1). No differences between groups were found for nausea and vomiting. No adverse effects of EA were noted. CONCLUSIONS: Electro-acupuncture significantly reduces acute post-operative pain and narcotic usage without any adverse effects. This promising adjunct for post-operative pain control warrants further validation.

MP69-04 IDENTIFICATION OF MODIFIABLE RISK FACTORS ASSOCIATED WITH PATIENT-REPORTED ERECTILE DYSFUNCTION TO ENHANCE PATIENT HEALTH COUNSELING AND SEXUAL QUALITY OF LIFE

INTRODUCTION AND OBJECTIVES: Clinical trials have suggested that pelvic floor rehab (PFR) can improve early urinary control following radical prostatectomy. However, the details surrounding its use in clinical practice and its contribution to cost and value are not well understood. In this context, we examined the use of PFR in a diverse statewide quality improvement collaborative, including patient characteristics, implementation patterns, and costs. METHODS: Using registry data from the Michigan Urological Surgery Improvement Collaborative and claims data from Michigan Value Collaborative, we identified all men who underwent a laparoscopic radical prostatectomy from 04/2014 through 11/2015 with insurance from Medicare or a large commercial payer. All men reported pre-operative urinary function using the STAR questionnaire with scores ranging from 0 (worst) to 21 (best). We compared patient demographics, cancer characteristics, pre-operative urinary function, and 90-day total episode costs of patients who did and did not receive PFR. RESULTS: 142 menmet our inclusion criteria, of whom 53 (37%) received pelvic floor rehab. There were no differences in patient or cancer characteristics among patients who did and did not receive PFR. Patients initiated PFR an average of 34 days after discharge (range 15-83 days). Mean baseline urinary function scores were worse for PFR patients (17.8 vs 19.3, p1⁄40.01). Ninety-day episode costs were similar in the two cohorts, with PFR contributing an average of

MP90-09 THE METABOLIC SYNDROME AND ITS IMPACT ON CALCIUM OXALATE STONE TYPE

422, or 3% of total episode costs. CONCLUSIONS: In a statewide collaborative, PFR is used in the minority of cases, but its use appears to be concentrated among patients with worse baseline urinary function. Incremental costs from PFR are modest, accounting for 3% of 90-day episode costs. In the era of value-based care, decisions about further expanding this therapy will depend on studying its comparative impact on post-operative patient reported outcomes in large groups of non-clinical trial patients.