Matthew D. Katz

Prospective Study of [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Staging of Muscle-Invasive Bladder Carcinoma

PURPOSE Novel imaging modalities are needed to detect occult metastatic disease in bladder carcinoma. Patients with regional lymphatic spread could be targeted for neoadjuvant chemotherapy, and patients with distant metastatic disease could be spared the unnecessary morbidity of radical cystectomy. Herein, we report a prospective study of positron emission tomography/computed tomography (PET/CT) with [(18)F]fluorodeoxyglucose (FDG) in patients undergoing radical cystectomy for cT2-3N0M0 urothelial carcinoma of the bladder. METHODS Forty-three chemotherapy-naïve patients underwent FDG-PET/CT before planned cystectomy. All had negative conventional CT and bone scintigraphy before enrollment. Positive FDG-PET/CT was confirmed by percutaneous biopsy or open surgical exploration, whereas negative FDG-PET/CT was confirmed by complete lymphadenectomy. Recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were described using the Kaplan-Meier method and compared using log-rank test. RESULTS Median follow-up was 14.9 months (range, 0.4 to 46.1 months). One patient who did not undergo lymphadenectomy was excluded from the pathology data analysis (n = 42), whereas another patient who failed to return for follow-up was excluded from survival analysis (n = 42). FDG-PET/CT demonstrated a positive predictive value of 78% (seven of nine), a negative predictive value of 91% (30 of 33), sensitivity of 70% (seven of 10), and specificity of 94% (30 of 32). RFS, DSS, and OS were all significantly poorer in the patients with positive FDG-PET/CT than in those with negative FDG-PET/CT. CONCLUSION FDG-PET/CT detected occult metastatic disease in seven of 42 patients with negative conventional preoperative evaluations. PET findings were strongly correlated with survival. As such, FDG-PET/CT may help in making treatment decisions before radical cystectomy.

Selective versus nonselective arterial clamping during laparoscopic partial nephrectomy: impact upon renal function in the setting of a solitary kidney in a porcine model.

INTRODUCTION Laparoscopic partial nephrectomy has emerged as a standard of care for small renal masses. Nevertheless, there remains concern over the potential for irreversible insult to the kidney as a result of exposure to warm ischemia. We aim to investigate the utility of selective segmental arterial clamping as a means to reduce the potential for ischemic damage to a solitary kidney during laparoscopic partial nephrectomy utilizing a porcine model. MATERIALS AND METHODS A total of 20 domestic swine were randomized into four equal groups. Each subject underwent laparoscopic radical nephrectomy to create the condition of a solitary kidney. On the contralateral side, a laparoscopic lower pole partial nephrectomy was performed, employing either selective or nonselective vascular clamping for either 60 or 90 minutes. Postoperatively, clinical status and serial serum studies were closely monitored for 1 week. RESULTS There were no intraoperative complications. The 90-minute nonselective clamping produced devastating effects, resulting in rapid deterioration into florid renal failure within 72 hours. The 60-minute nonselective clamping group experienced modest but significant rises in both blood urea nitrogen and creatinine. Both 60- and 90-minute selective clamping groups performed well, with no significant rises in creatinine over a 7-day period, and no instances of renal failure. CONCLUSIONS Selective arterial clamping is a safe and feasible means of vascular control during laparoscopic partial nephrectomy. In the porcine model, selective clamping appears to improve functional outcomes during prolonged periods of warm ischemic insult. Prospective evaluation of the technique in humans is necessary to determine if selective arterial control confers long-term functional benefits in patients with limited renal reserve.

The role of lymphovascular space invasion in renal cell carcinoma as a prognostic marker of survival after curative resection.

OBJECTIVES Lymphovascular invasion (LVI) correlates with adverse outcomes in numerous malignancies. However, its role in predicting outcomes in RCC is unclear. Herein, we evaluated what effect LVI had on metastasis free survival (MFS), disease-specific survival (DSS), and overall survival (OS) in patients with RCC treated with surgical excision. METHODS Eight hundred forty-one consecutive patients who underwent partial or radical nephrectomy from 1989 to 2004 were identified. Pathologic and gross features examined were LVI, subtype, Fuhrman grade, stage, and size. Age and gender were also analyzed. Slides were re-reviewed by a single pathologist (MS). Variables with P < 0.1 on univariate analysis were incorporated in a Cox proportional hazards multivariate model. MFS, DSS, and OS were described for patients with and without LVI using the Kaplan-Meier method, and compared with the log-rank test. RESULTS LVI was seen on H and E stained slides in 91 patients (11%); 120 (14%) developed metastatic disease, 91 (11%) died of RCC, and 306 (36%) died during a median follow-up of 61 months. While on univariate analysis, LVI was strongly associated with decreased MFS, DSS, and OS (P < 0.0001), on multivariate analysis, LVI was no longer statistically significant for MFS, DSS, and OS with a HR of 0.976 (95% CI: 0.583-1.63; P = 0.93), 0.96 (95% CI: 0.542-1.69; P = 0.88), and 1.24 (95% CI: 0.869-1.77; P = 0.24). CONCLUSIONS We found LVI to be associated with worse MFS, DSS, and OS on univariate analysis, but not on multivariate analysis for patients with nonmetastatic RCC. In contrast to previously reported studies, LVI may not be an independent prognostic variable in patients with localized RCC.

Percent Microscopic Tumor Necrosis and Survival After Curative Surgery for Renal Cell Carcinoma

PURPOSE Tumor necrosis is a potential marker of recurrence and survival after surgery for renal cell carcinoma. We determined whether a correlation exists between the amount (not just the presence/absence) of tumor necrosis, and metastasis-free, disease specific and overall survival after surgery for renal cell carcinoma. MATERIALS AND METHODS We identified 841 consecutive patients who underwent partial or radical nephrectomy from 1989 to 2004 for renal cell cancer. Specimens were re-reviewed by a single pathologist (MFS). The tumor necrosis percent was none in 586 cases, less than 50% in 198 and 50% or greater in 55. Grade, stage, subtype, size, gender and age were also analyzed. Variables at p <0.05 on univariate analysis were incorporated into a Cox proportional hazards multivariate model. Metastasis-free, disease specific and overall survival was described using the Kaplan-Meier method and compared with the log rank test. RESULTS Tumor necrosis was found in 253 specimens (30%). Univariate analysis revealed that the percent and presence of tumor necrosis correlated with metastasis-free, disease specific and overall survival. On multivariate analysis tumor necrosis presence/absence did not remain an independent predictor of disease specific (p = 0.7), metastasis-free (p = 0.7) or overall (p = 0.2) survival. Greater than 50% tumor necrosis was no longer a statistically significant predictor of metastasis-free survival (p = 0.45) but remained significant for disease specific (p = 0.02) and overall (p = 0.01) survival. CONCLUSIONS The presence of 50% or greater tumor necrosis correlates with worse disease specific and overall survival but not metastasis-free survival in patients with renal cell carcinoma. Results support the inclusion of percent tumor necrosis over the presence/absence of tumor necrosis in the risk assessment of patients who undergo surgical treatment for renal cell carcinoma.

Intravesical Bacille Calmette-Guérin Therapy for Non-Muscle-Invasive Bladder Cancer: Effects of Concurrent Statin Therapy

BACKGROUND Recent studies provide conflicting evidence about the association of statin use and decreased efficacy of intravesical bacille Calmette-Guérin (BCG) therapy for bladder cancer. Because statin drugs have immunomodulatory properties that could reduce the effectiveness of BCG, we investigated whether concurrent use of statin drugs was associated with worsened clinical outcomes in patients undergoing BCG treatment for non-muscle-invasive bladder cancer. STUDY DESIGN We retrospectively analyzed records of 120 patients undergoing BCG treatment during 1997 through 2007 at a single Department of Veterans Affairs Medical Center. Tumor-progression events, total recurrences, disease-specific and overall mortality were the outcomes relative to statin use. Fishers exact, Students t-tests, and logistic regression were used to compare the groups. RESULTS Among the 90 evaluable patients, there were no significant differences between groups with regard to tumor grade and stage distribution or smoking status. Statins were used during BCG therapy by 47.8% of patients. Comparing patients with no use versus use of statins, 8.5% versus 11.6% had local tumor progression (p = 0.44); 10.6% versus 9.3% underwent cystectomy, chemotherapy, or radiation therapy (p = 0.56); and metastatic disease developed in 6.7% versus 11.6% (p = 0.33). Of the 27 patients who died of any cause, 12.5% (2 of 16) versus 27.3% (3 of 11) in the nonstatin versus statin groups, respectively, died of disease (p = 0.32). CONCLUSIONS Concurrent statin use was not associated with adverse outcomes for patients undergoing BCG treatment for bladder cancer. While statins have a plausible biologic mechanism to reduce BCG efficacy, no differences were seen in this small pilot study.

Effect of Reclassification on the Incidence of Benign and Malignant Renal Tumors

PURPOSE The incidence of benign renal tumors has increased in recent years. This trend is commonly attributed to the increased use of cross-sectional imaging and minimally invasive surgical approaches. An alternative hypothesis is that recent changes in histological classification are responsible for the increasing incidence. To further investigate the impact of histological reclassification we reexamined all excised renal masses using the 2004 WHO criteria and compared this histological classification to the prior criteria. MATERIALS AND METHODS We identified 1,101 consecutive partial and radical nephrectomy cases managed at our institution from 1989 to 2003. All histopathological sections were rereviewed by a single pathologist and reclassified according to 2004 WHO criteria. The percentages of benign lesions per year according to the prior histological and current WHO 2004 histological criteria were compared. RESULTS Of the 1,101 renal masses 132 (12.0%) and 165 (15.0%) were classified as benign using prior and current WHO criteria, respectively. On average the WHO criteria diagnosed more benign tumors per year than the prior criteria (p = 0.004). Linear regression demonstrated a similar, persistent increase in benign diagnoses per year of 0.69% (WHO) and 1.22% (prior) during the 14-year period (p = 0.33). All masses reclassified as benign were oncocytoma (33). CONCLUSIONS Implementation of the 2004 WHO criteria is contributing to the increase in diagnosis of benign renal lesions, specifically oncocytoma. Changes in histological classification do not account for the entire increase. Other factors, which remain to be delineated, are also contributing to the increase in the diagnosis of benign renal lesions.

Open Versus Laparoscopic Retroperitoneal Lymph Node Dissection : Assessing Adequacy of Dissection in a Porcine Model

BACKGROUND AND PURPOSE Laparoscopic retroperitoneal lymph node dissection (L-RPLND) is emerging as a viable alternative to traditional open retroperitoneal lymph node dissection (O-RPLND). Despite numerous reports confirming clinical oncologic equivalency between the two approaches, however, concerns still remain over the adequacy of laparoscopic dissection. We therefore sought to compare the completeness of dissection between O-RPLND and L-RPLND in a porcine model. MATERIALS AND METHODS Fourteen domestic swine were divided into two equivalent groups. Both groups underwent bilateral retroperitoneal lymph node dissection, approximating templates used in human dissection. In one group, the procedure was performed through an open midline incision, while the other group underwent completely laparoscopic dissection. Tissue was independently analyzed by a pathologist, who recorded lymph node yield based on microscopic evaluation. RESULTS All animals in the L-RPLND group underwent successful procedures, without the need for conversion. Two open procedures were aborted because of hemorrhage. Mean lymph node yield from O-RPLND was 32, while the mean yield for L-RPLND was 29. This difference was not statistically significant (P=0.65). CONCLUSIONS In the porcine model, L-RPLND is capable of providing a quality of dissection equivalent to that of O-RPLND, in terms of absolute lymph node yield on microscopic examination. The applicability of this data to human patients, however, may be limited by significant anatomic differences between the human and the pig. Further prospective comparison in human patients is critically needed.

MP18-19 IMPACT OF MALNUTRITION ON RADICAL NEPHROURETERECTOMY MORBIDITY AND MORTALITY: OPPORTUNITY FOR PRE-OPERATIVE OPTIMIZATION

Introduction/background: Nutritional status is increasingly recognized as an important predictor of prognosis and surgical outcomes in cancer patients. We evaluated the impact of preoperative malnutrition on the development of surgical complications and mortality following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Materials and Methods: Using data from The American College of Surgeons National Surgical Quality Improvement Program, we evaluated the association of poor nutritional status with 30 day postoperative complications and overall mortality following RNU over years 2005-2015. Preoperative variables suggestive of poor nutritional status included hypoalbuminemia (<3.5 g/dL), weight loss 6 months before surgery (>10%), and low body mass index (BMI). Results: A total of 1,200 patients were identified who underwent RNU for UTUC. The overall complication rate was 20.5% (n=246) and mortality rate was 1.75% (n=21). On univariate analysis, patients who had a postoperative complication were more likely to have hypoalbuminemia (25.0% vs. 11.4% p<0.001) and weight loss (3.7% vs. 1.0% p=0.003). After controlling for baseline characteristics and comorbidities, hypoalbuminemia was found to be a significant independent predictor of postoperative complications (OR 2.09 95% CI 1.29-3.38 p=0.003). Hypoalbuminemia was also found to be significant independent predictor of mortality (OR 4.31 95% CI 1.45-12.79 p=0.008) on multivariable regression analysis. Conclusions: Hypoalbuminemia is a significant predictor of surgical complications and mortality following RNU for UTUC. This finding supports the importance of preoperative nutritional status in this population and suggests that effective nutritional interventions in the preoperative setting could improve patient outcomes. M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT 5

A PROSPECTIVE STUDY OF FDG-PET/CT FOR DETECTING OCCULT METASTATIC BLADDER CARCINOMA

INTRODUCTION AND OBJECTIVES: PET with 18F-FDG has been considered of limited value because of the urinary excretion of the tracer. The purpose of this study was to investigate the role of PET associated with Computed Tomography (CT) in the staging of new diagnosed bladder cancer (BC) or in restaging of BC during follow-up after cystectomy or chemotherapy using furosemide and oral hydration to remove the excreted 18-F-FDG from the bladder. METHODS: Thirty two patients (23 male, 9 female), with histologically proven muscle invasive BC by transurethral resection of the bladder (TUR/B), were included in this prospective study. Mean age was 69 years and mean follow up was of 4,7 months (0,3-10,3). All underwent a 18F-FDG from head to the upper thighs with additional pelvic images after 1 h I.V. furosemide and oral hydration at least 3 months after TUR/B. In 25 cases a CT of thorax and abdomen with contrast medium had also been preformed within the 2 weeks prior to PET/CT. For CT scan, nodes greater than 1 cm or defined as suspicious by the radiologist were considered positive. The 18F-FDG-PET/CT lesions with metabolic activity greater than 2.5 SUV on a confirmed anatomical structure were considered positive. Imaging findings were confirmed by histology or if not possible, by imaging follow-up. RESULTS: Of the 32 patients, 26 patients were studied with 18F-FDG-PET/CT before radical cystectomy or in 2 cases only pelvic lymphadenectomy. In the same group, 19 CT were also performed. 18F-FDG-PET/CT detected 21 of the 23 bladder lesions (91,3%) and 8/15 (53,3%) pelvic node metastasis, mostly N2. False negative were a pTis and a pT4. CT detected 12 of 17 bladder lesion (70.6%) and 4 out of 9 positive nodes (44.4%). 18F-FDG-PET/CT showed prostate metabolic activity in 4 cases. In 2 cases BC invasion was histologically proven. Metabolic activity was seen in 2 para-aortic lymph-nodes (LN), 3 mediastinal LN, 2 cervical LN and 4 pulmonary nodules. All these lesions showed progression on imaging follow up. CT was negative in all prostate lesions, 1 para-aortic LN and 2 pulmonary nodules. CONCLUSIONS: This prospective series shows that 18F-FDGPET/CT with furosemide wash out of the bladder was better than conventional CT for the detection of residual tumor in the bladder, pelvic LN metastasis and prostate infiltration. Moreover PET/CT detected earlier than conventional CT distant metastasis to retroperitoneal and cervical LN and pulmonary metastasis.

DOES PERCENT HIGH GRADE CORRELATE WITH SURVIVAL FOLLOWING SURGERY FOR RENAL CELL CARCINOMA

1201 DOES PERCENT HIGH GRADE CORRELATE WITH SURVIVAL FOLLOWING SURGERY FOR RENAL CELL CARCINOMA? Matthew D Katz*, Maria F Serrano, Yan Yan, Peter A Humphrey, Adam S Kibel. Saint Louis, MO. INTRODUCTION AND OBJECTIVE: It has been demonstrated that percent of high grade cancer correlates with survival for a wide variety of tumors. Recent work has demonstrated that the percentage of high grade cancer in prostatectomy specimens correlates with survival, raising the possibility that this pathologic parameter may provide prognostic information in other malignancies. Herein, we examine renal cell carcinoma (RCC) specimens to determine if a correlation exists between percentage of high grade tumor and metastasis-free survival