Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma.

OBJECTIVE: To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence. RESULTS: The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets. CONCLUSION: We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC.

Molecular profile of urothelial carcinoma of the upper urinary tract: are pelvicalyceal and ureteral tumors different?

PURPOSE: To assess the potential biologic impact of tumor location on oncological outcomes for patients with upper tract urothelial carcinoma (UTUC), we used prospectively collected molecular signatures of high-grade UTUC. METHODS: Immunohistochemical staining for p21, p27, p53, cyclin E, and Ki-67 was prospectively performed on 96 UTUC specimens of patients with non-metastatic high-grade UTUC treated with extirpative surgery. Patients were grouped according to primary tumor location (pelvicalyceal vs. ureteral) where primary tumor was defined as the highest tumor stage and diameter. Primary outcome was assessment of differences in marker expression between groups. Secondary outcome was difference in survival according to marker status. RESULTS: Pelvicalyceal and ureteral tumors were found in 52.1 and 47.9 %, respectively, and 42.7 % of patients had non-organ-confined disease. Over a median follow-up of 22.0 months, 31.2 and 20.8 % of patients experienced disease recurrence and died of UTUC, respectively. The total number of altered markers stained for was 0-2 in 67.7 and 3-5 in 32.3 % of patients. The number of altered markers and alteration status of markers were not significantly different between patients with primary pelvicalyceal versus ureteral tumors when stratified by tumor stage and nodal status. There were no significant differences in survival outcomes between both groups when stratified by number of altered markers (0-2 and 3-5). CONCLUSIONS: The prospective assessment of selected cell cycle and proliferative markers suggests no molecular difference between UTUC of the pelvicalyceal system and that of the ureter. Our study is limited by its size and definition of location.

Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.

BACKGROUND: The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. METHODS: We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998-2006 and 2006-2012, were assessed. RESULTS: The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24-83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p < .001) and OS (HR 2.6, CI 1.5-4.7 and p = .001) in all patients. CONCLUSIONS: Our data suggest that patients with RCC and VTT can be treated safely utilizing a multidisciplinary team approach leading to a decrease in complication rates.

Prospective evaluation of plasma levels of ANGPT2, TuM2PK, and VEGF in patients with renal cell carcinoma.

BACKGROUND: To assess pathological correlations and temporal trends of Angiopoietin-2 (ANGPT2), vascular endothelial growth factor (VEGF) and M2 Pyruvate kinase (TuM2PK), markers of tumor vascular development and metabolism, in patients with renal cell carcinoma (RCC). METHODS: We prospectively collected plasma samples from 89 patients who underwent surgical/ablative therapy for RCC and 38 patients with benign disease (nephrolithiasis, hematuria without apparent neoplastic origin, or renal cysts). In RCC patients, marker levels were compared between at least 1 preoperative and 1 postoperative time point generally 3 weeks after surgery. Marker temporal trends were assessed using the Wilcoxon sign-rank test. Plasma VEGF, ANGPT2, and TuM2PK levels were determined by ELISA and tested for association with pathological variables. RESULTS: Median age was comparable between groups. 83/89 (93%) of the cohort underwent surgical extirpation. 82% of the tumors were organ confined (T ≤ 2, N0). Only ANGPT2 exhibited significantly elevated preoperative levels in patients with RCC compared to benign disease (p = 0.046). Elevated preoperative levels of ANGPT2 and TuM2PK significantly correlated with increased tumor size and advanced grade (p < 0.05). Chromophobe RCC exhibited higher levels of ANGPT2 compared to other histologies (p < 0.05). A decline in marker level after surgery was not observed, likely due to the timing of the analyses. CONCLUSION: Our results suggest that ANGPT2 is a marker of RCC. Additionally, ANGPT2 and TuM2PK significantly correlated with several adverse pathological features. Further studies are needed to determine clinical applicability.

Dysregulation of ß-catenin is an independent predictor of oncologic outcomes in patients with clear cell renal cell carcinoma.

PURPOSE: Epithelial-to-mesenchymal transition is thought to have a crucial role in cancer progression and metastatic egress. We evaluated the association of ß-catenin, an important mediator of epithelial-to-mesenchymal transition, with pathological parameters and oncologic outcomes in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining was performed for ß-catenin on tissue microarrays of patients with nonmetastatic clear cell renal cell carcinoma. Membranous and cytoplasmic expression patterns were assessed separately. ß-Catenin was considered dysregulated if membranous as well as cytoplasmic expression was abnormal. Groups were compared based on normal vs dysregulated ß-catenin. Survival probabilities were assessed by the Kaplan-Meier method. Cox proportional hazard models were used to identify predictors of oncologic outcomes. RESULTS: Included in the study were 406 patients with a median followup of 58 months. Of the patients 52 (12.8%) and 25 (6.2%) experienced recurrence and died of clear cell renal cell carcinoma, respectively. ß-Catenin was dysregulated in 70 patients (17.2%). Dysregulation was uniformly associated with adverse pathological features, including advanced T stage, larger tumor diameter, nodal positivity, higher Fuhrman grade, tumor thrombus, sarcomatoid features, necrosis and lymphovascular invasion (each p<0.001). Patients with dysregulated ß-catenin had inferior recurrence-free and cancer specific survival (each p<0.001). On multivariate analysis adjusting for tumor stage, nodal status and grade dysregulation was an independent predictor of recurrence-free and cancer specific survival (HR 2.2, 95% CI 1.2-3.9, p=0.008 and HR 2.4, 95% CI 1.1-5.6, p=0.044, respectively). CONCLUSIONS: Dysregulation of ß-catenin may be an important phenomenon in clear cell renal cell carcinoma carcinogenesis. These findings support further study of ß-catenin, and systematic assessment of ß-catenin and epithelial-to-mesenchymal transition in clear cell renal cell carcinoma.

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?

PURPOSE: Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel. MATERIALS AND METHODS: Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status. RESULTS: During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score. CONCLUSIONS: Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma.

Prospective analysis of Ki-67 as an independent predictor of oncologic outcomes in patients with high grade upper tract urothelial carcinoma.

PURPOSE: We determined the association of the proliferation marker Ki-67 with pathological parameters and oncologic outcomes in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for Ki-67 was done prospectively in 101 consecutive patients undergoing radical nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma. Data were compared based on Ki-67 status (normal vs over expressed). Survival was assessed by the Kaplan-Meier method. Cox regression analysis was done to identify independent predictors of time dependent outcomes. RESULTS: Median patient age was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall, 30.2% of the population experienced recurrence and 24.8% died of upper tract urothelial carcinoma. Organ confined disease (T2 or less and lymph node negative), lymphovascular invasion and sessile architecture were present in 56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in 73.3% of patients and associated with adverse pathological features. Patients with over expressed Ki-67 had significantly worse recurrence-free survival (43.2 vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p = 0.031) than patients with normal Ki-67. Patients with nonmetastatic disease similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and cancer specific survival (41 months vs not attained, p = 0.008) for over expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan confined disease Ki-67 over expression was an independent predictor of recurrence-free survival in the total cohort (HR 4.3, p = 0.05) and in patients with nonmetastatic disease (HR 8.5, p = 0.038). CONCLUSIONS: Ki-67 over expression was associated with adverse pathological features in cases of upper tract urothelial carcinoma. It was also an independent predictor of recurrence-free survival in patients with high grade upper tract urothelial carcinoma.

Oncologic outcomes following surgical resection of renal cell carcinoma with inferior vena caval thrombus extending above the hepatic veins: a contemporary multicenter cohort.

PURPOSE: Suprahepatic inferior vena caval tumor thrombus in renal cell carcinoma cases has historically portended a poor prognosis. With advances in perioperative treatment of patients with high level thrombus contemporary outcomes are hypothesized to be improved. We evaluated long-term oncologic outcomes of contemporary surgical treatment of patients with renal cell carcinoma in whom level III-IV inferior vena caval thrombus was managed at high volume centers. MATERIALS AND METHODS: We examined clinical and pathological data on patients with renal cell carcinoma and level III-IV thrombus treated with surgery from January 2000 to June 2013 at 4 tertiary referral centers. Survival outcomes and associated prognostic variables were assessed by Kaplan-Meier and multivariate Cox regression analyses. RESULTS: We identified 166 patients, including 69 with level III and 97 with level IV thrombus. Median postoperative followup was 27.8 months. Patients with no evidence of nodal or distant metastasis (pN0/X, M0) had 5-year 49.0% cancer specific survival and 42.2% overall survival. There was no difference in survival based on tumor thrombus level or pathological tumor stage. Variables associated with an increased risk of death from kidney cancer on multivariate analysis were regional nodal metastases (HR 3.94, p <0.0001), systemic metastases (HR 2.39, p = 0.01), tumor grade 4 (HR 2.25, p = 0.02), histological tissue necrosis (HR 3.11, p = 0.004) and increased preoperative serum alkaline phosphatase (HR 2.30, p = 0.006). CONCLUSIONS: Contemporary surgical management achieves almost 50% 5-year survival in patients without metastasis who have renal cell carcinoma thrombus above the hepatic veins. Factors associated with increased mortality included nodal/distant metastases, advanced grade, histological necrosis and increased preoperative serum alkaline phosphatase. These findings support an aggressive surgical approach to the treatment of patients with renal cell carcinoma who have advanced tumor thrombus.

Ki67 is an independent predictor of oncological outcomes in patients with localized clear-cell renal cell carcinoma.

OBJECTIVE: To validate the impact of Ki67 expression on oncological outcomes of patients treated for clinically localized clear-cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: Immunohistochemistry for Ki67 was performed on tissue microarray constructs of patients treated with radical or partial nephrectomy for clinically localized (M0) ccRCC and Ki67 expression >10% was considered abnormal. Clinical and pathological data elements were entered into an institutional review board-approved database. The Kaplan-Meier method and Cox regression models were used to analyse disease-free survival (DFS) and cancer-specific survival (CSS) probabilities. RESULTS: Of 401 patients, 59.6% were males. The median (range) age was 58 (17-85) years, follow-up was 22 (0-150) months and time to death was 27 (0-150) months. A total of 20.2% of patients had advanced stage (pT3-T4) and 31% had advanced grade (3-4) disease. Abnormal expression of Ki67 was seen in 6.5% of our cohort and was associated with adverse pathological features (P < 0.05). Patients with high expression of Ki67 were found to have 5-year DFS and CSS rates of 67 and 84%, respectively, vs 87 and 95%, respectively, in those with normal expression (P < 0.001 and P < 0.05, respectively). In multivariable analyses, adjusting for stage and grade, abnormal Ki67 expression was an independent predictor of DFS (hazard ratio [HR] 3.77, P = 0.011, 95% confidence interval [CI] 1.35-10.52), but not of CSS (HR 3.51 P = 0.137, 95% CI 0.671-18.35). CONCLUSIONS: Our findings support the role of Ki67 as a powerful independent predictor of inferior oncological outcomes in patients with ccRCC. Further prospective studies are needed to determine the clinical applicability of these findings.

Emerging therapies in castration resistant prostate cancer.

INTRODUCTION: Prostate cancer continues to be the second leading cause of cancer related mortality in men within the United States. Despite a consistent decline in prostate cancer mortality over the past two decades, the prognosis for men with metastatic prostate cancer remains poor with no curative therapies. In this article, we review the recently approved and emerging therapeutics for patients with castrate resistant prostate cancer. MATERIALS AND METHODS: An advanced search was conducted on the clinicaltrials.gov database, using search terms "metastatic prostate cancer", and limiting results to phase II-IV clinical trials. Clinically relevant emerging therapeutics were selected and a Medline search for supporting documents was performed. An emphasis was placed on newly approved and promising new therapeutics. RESULTS: A total of four Food and Drug Administration approved medications and eight investigational agents were chosen for review. The background and role of these therapeutics in the treatment of prostate cancer treatment is discussed. CONCLUSIONS: The past few years have yielded a near exponential increase in treatments for metastatic prostate cancer, many of which have a unique mechanism of action. The estimated median survival for patients with metastatic prostate cancer remains dynamic as we begin to integrate these therapeutics into clinical practice and determine the optimal sequence and timing of treatment.

Cost-effectiveness of fluorescence in situ hybridization in patients with atypical cytology for the detection of urothelial carcinoma.

PURPOSE: Patients with atypical cytology and equivocal or negative cystoscopy pose a challenge due to uncertainty about the presence of cancer. We determined the cost-effectiveness of using fluorescence in situ hybridization assays to determine the need for biopsy in patients with atypical cytology and equivocal or negative cystoscopy. MATERIALS AND METHODS: Data from 2 large prospective studies evaluating the usefulness of fluorescence in situ hybridization in the setting of atypical cytology to detect urothelial carcinoma were combined. The data were used to calculate sensitivity and specificity for the UroVysion fluorescence in situ hybridization assay in various clinical scenarios. Cost data were obtained from our institution and Medicare reimbursement rates. Evaluations with or without bladder biopsy and with or without upper tract evaluation were considered. RESULTS: The study included 263 patients with atypical cytology and equivocal (62) or negative (201) cystoscopy. In patients with equivocal cystoscopy (assuming biopsy was performed in the operating room) biopsy based on fluorescence in situ hybridization results saved $1,740 per patient ($3,267 vs $1,527 per patient) and avoided 42 biopsies compared to biopsy in all patients. If office based biopsies were used then cost savings using fluorescence in situ hybridization results were $95 per patient. Among patients with negative cystoscopy biopsy based on fluorescence in situ hybridization resulted in costs savings of $2,241 per patient, avoiding 167 biopsies, compared to biopsy in all patients. Assuming office based biopsy, the cost savings were $216 per patient. CONCLUSIONS: The decision to perform biopsy based on fluorescence in situ hybridization assay in patients with atypical cytology and equivocal or negative cystoscopy was associated with a significant decrease in bladder cancer associated costs.

Prognostic role of cell cycle and proliferative biomarkers in patients with clear cell renal cell carcinoma.

PURPOSE: Cell cycle regulatory molecules are implicated in various stages of carcinogenesis. In this proof of principle study we systematically evaluate the association of aberrant expression of cell cycle regulators and proliferative markers and their effect on oncologic outcomes of patients with clear cell renal carcinoma. MATERIALS AND METHODS: Immunohistochemistry for Cyclin D, Cyclin E, p16, p21, p27, p53, p57 and Ki67 was performed on tissue microarray constructs of 452 patients treated with extirpative therapy for clear cell renal cell carcinoma between 1997 and 2010. Clinical and pathological data elements were collected. A prognostic marker score was defined as unfavorable if more than 4 biomarkers were altered. The relationship between marker score and pathological features and oncologic outcomes was evaluated. RESULTS: Median age was 57 years (range 17 to 85) and median followup was 24 months (range 6 to 150). An unfavorable marker score was found in 55 (12.2%) patients and was associated with adverse pathological features. A significant correlation between unfavorable marker score and disease-free survival (HR 26.62, 95% CI 43.38-100.04, p=0.000) and with cancer specific survival (HR 8.15, 95% CI 74.42-101.56, p=0.004) was demonstrated on Kaplan-Meier survival analysis. On multivariate analysis an unfavorable marker score was an independent predictor of disease-free survival (HR 2.63, 95% CI 1.08-6.38, p=0.033). CONCLUSIONS: The cumulative number of aberrantly expressed cell cycle and proliferative biomarkers correlates with aggressive pathological features and inferior oncologic outcomes in patients with clear cell renal cell carcinoma. Our findings indicate that interrogation of cell cycle and proliferative markers is feasible, and further prospective pathway based exploration of biomarkers is needed.

Emerging drugs for prostate cancer.

INTRODUCTION: Androgen deprivation therapy is the mainstay treatment for patients with prostate cancer who are not candidates for definitive treatment, are diagnosed with advanced disease on initial presentation or progress after primary treatment. Patients who stop responding to androgen deprivation therapy develop castration resistant prostate cancer (CRPC). Emerging drugs undergoing clinical evaluation and drugs that have recently received FDA approval for the treatment of CRPC are reviewed. AREAS COVERED: As the natural history and signaling pathways of prostate cancer are better understood, new treatments and targeted therapies will be developed. The FDA recently approved 5 medications that increase survival in patients with CRPC. Additional medications and drug classes are being explored that may eventually lead to new treatment options. Articles were identified using a PubMed database search. EXPERT OPINION: Recent FDA medication approvals and the development of emerging treatments are promising for the future of patients with prostate cancer. The addition of new medications challenges physicians to identify the optimal sequence and/or combination in which newer and older medications should be administered. Physicians treating patients with prostate cancer have a growing responsibility to keep pace with these new medications so that they may counsel and treat patients appropriately.

The role of systemic chemotherapy in management of upper tract urothelial cancer.

Upper tract urothelial cancer (UTUC) accounts for roughly 5 % of all urothelial cancers. At presentation, 30 % of patients demonstrate invasive and/or locally advanced disease, 30-40 % have regional lymph node involvement, and 20 % harbor metastatic disease. Systemic recurrence and progression rates after surgery for patients with advanced disease range between 45-60 %. Five-year cancer specific survival rates for pT2 and pT3 tumors are 73 % and 40 %, respectively. Median survival for patients with pT4 disease is approximately 6 months. Nonetheless, there is a lack of improvement in the rates of systemic recurrence and progression in patients with advanced UTUC. Extrapolating evidence obtained from experience with multi-modal therapy of patients with urothelial bladder cancer, additional improvements in oncological outcomes for patients with UTUC can be achieved through integration of effective systemic chemotherapy with local tumor control. We provide an overview of the rationale and utilization strategies of peri-operative systemic chemotherapy in patients with UTUC.

Factors that impact the outcome of minimally invasive pyeloplasty: results of the Multi-institutional Laparoscopic and Robotic Pyeloplasty Collaborative Group.

PURPOSE: We compared laparoscopic and robotic pyeloplasty to identify factors associated with procedural efficacy. MATERIALS AND METHODS: We conducted a retrospective multicenter trial incorporating 865 cases from 15 centers. We collected perioperative data including anatomical and procedural factors. Failure was defined subjectively as pain that was unchanged or worse per medical records after surgery. Radiographic failure was defined as unchanged or worsening drainage on renal scans or worsening hydronephrosis on computerized tomography. Bivariate analyses were performed on all outcomes and multivariate analysis was used to assess factors associated with decreased freedom from secondary procedures. RESULTS: Of the cases 759 (274 laparoscopic pyeloplasties with a mean followup of 15 months and 465 robotic pyeloplasties with a mean followup of 11 months, p <0.001) had sufficient data. Laparoscopic pyeloplasty, previous endopyelotomy and intraoperative crossing vessels were associated with decreased freedom from secondary procedures on bivariate analysis, with a 2-year freedom from secondary procedures of 87% for laparoscopic pyeloplasty vs 95% for robotic pyeloplasty, 81% vs 93% for patients with vs without previous endopyelotomy and 88% vs 95% for patients with vs without intraoperative crossing vessels, respectively. However, on multivariate analysis only previous endopyelotomy (HR 4.35) and intraoperative crossing vessels (HR 2.73) significantly impacted freedom from secondary procedures. CONCLUSIONS: Laparoscopic and robotic pyeloplasty are highly effective in treating ureteropelvic junction obstruction. There was no difference in their abilities to render the patient free from secondary procedures on multivariate analysis. Previous endopyelotomy and intraoperative crossing vessels reduced freedom from secondary procedures.

The current role of percutaneous biopsy of renal masses.

INTRODUCTION: There has been an increased incidence of small renal masses with a majority incidentally discovered in elderly patients or patients with several comorbidities. The historic role of renal biopsy has been limited due to initial concerns about accuracy and safety. This review analyses the current role of percutaneous renal biopsy. MATERIALS AND METHODS: A comprehensive literature review of PubMed and MEDLINE for reports of percutaneous needle core biopsy and fine needle aspiration of renal tumors that were published from 1977 to 2012. RESULTS: With the adoption of new biopsy techniques, there is a very low risk of tumor seeding. Symptomatic complications are relatively low; less than 2% require any form of intervention. The accuracy has dramatically improved over the past decade. While about 10%-15% of small renal mass biopsies are indeterminate, the rate of false negative renal biopsies is only 1% in contemporary series. Recent studies suggest that biopsy results can be improved by combining histological and molecular analysis. CONCLUSIONS: In contemporary series, renal mass biopsies (RMB) have a low complication rate and significantly improved accuracy. RMBs can better stratify patients into an active surveillance protocol and therefore potentially decrease the over treatment of small renal masses, especially in the elderly or patients with comorbidities.

Management of bilateral synchronous renal cell carcinoma in a single versus staged procedure.

OBJECTIVES: The presentation of synchronous bilateral renal lesions is rare. We report our experience with the surgical management of these lesions in both a single and staged procedure. METHODS: We retrospectively reviewed the records of all patients with bilateral synchronous renal lesions who underwent surgical management by one surgeon between 2000-2007. We compared characteristics including pre and postoperative renal function, complication rates, and oncological outcomes between the single and staged cohorts. Data were analyzed using descriptive statistics, Student's t-test, and Fisher's exact test. RESULTS: A total of 26 patients (73% male, mean age 65.5 +/- 12.2 years) with bilateral synchronous lesions were identified with a mean follow-up of 25.9 +/- 19.7 months. Of these, 18 (69%) were performed as a single procedure, 5 (19%) were done as a staged procedure, and 3 (12%) had only the first part of the staged procedure performed. The single and staged cohorts were comparable in regards to preoperative creatinine (Cr) (1.1 +/- 0.4 mg/dl versus 1.1 +/- 0.2 mg/dl, p = 0.70), postoperative Cr (1.5 +/- 1.0 mg/dl versus 1.4 +/- 0.5 mg/dl, p = 0.73), and median hospital length of stay (HLOS) (5 days versus 4 days). The complication rate was 22% and 20% for the single and staged cohorts, respectively. One patient had a local recurrence and one patient developed metastatic disease in the single cohort versus no local recurrence or metastatic disease in the staged cohort. CONCLUSION: In the appropriate setting, surgical management of synchronous bilateral renal lesions can be done safely in a single procedure with comparable outcomes to those done in a staged manner.

Small Renal Masses in Close Proximity to the Collecting System and Renal Sinus Are Enriched for Malignancy and High Fuhrman Grade and Should Be Considered for Early Intervention.

INTRODUCTION: Recent reports show a correlation between renal tumor radiographic characteristics and pathologic features. We hypothesize that a more central location within the relatively hypoxic renal medulla might confer a more aggressive tumor phenotype. To test this, radiographic tumor characteristics were compared with tumor grade and histology. MATERIALS AND METHODS: We retrospectively reviewed renal masses <4 cm in diameter that underwent resection between 2008 and 2013. Tumor location was recorded using standard R.E.N.A.L. Nephrometry Score. Multivariate logistic regression was performed to compare independent anatomic features with incidence of malignancy and high nuclear grade. RESULTS: A total of 334 renal tumors had information available for analysis. Univariate analysis showed that increasing endophycity and proximity to the collecting system (<4 mm) were predictors of malignancy and high-grade features. In multivariate analysis, proximity to the collecting system <4 mm remained the as the only anatomical variable predictive of malignancy (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.06-12.05; P = .04) and high nuclear grade (OR, 2.81; 95% CI, 1.44-5.51; P = .003). CONCLUSION: Malignancy and high tumor grade occur with much greater frequency when tumors are located deep in the kidney, in close proximity to the collecting system and renal sinus. Ninety-six percent of small renal masses in this region were cancers and nearly half were Fuhrman Grade 3 or 4, suggesting that these small centrally located tumors should be targeted for early intervention.

Current management of paratesticular rhabdomyosarcoma.

OBJECTIVES: Paratesticular rhabdomyosarcoma accounts for 7-10% of genitourinary rhabdomyosarcoma tumors and is the 3rd most common after RMS of the prostate and bladder. Though most (60%-80%) patients with paratesticular rhabdomysarcoma present with localized disease, assessment of systemic disease is vital. The treatment of paratesticular rhabdomyosarcoma has evolved over several decades; the current standard of care is multimodal treatment including surgery, chemotherapy, and radiation. We give insight into the evolution of treatment, present the oncologic outcomes of seminal studies, and summarize the current recommendations for the management of these patients. METHODS: A comprehensive search of the literature on the electronic databases PubMed was conducted for management of paratesticular rhabdomyosarcoma. Case reports were excluded, clinical trials from all the oncologic society were reviewed and relevant articles are included in the review. RESULTS: The treatment regimen is based on following principles: (1) local control of the primary site with radical orchiectomy and (2) assessment of local control and distant sites. Further treatment is directed according to disease stage, histology, and age of the patient. The goal of treatment is to achieve cure or maximum tumor control while minimizing toxicity. CONCLUSIONS: With the changing landscape in the management of paratesticular rhabomyosarcoma, significant improvement is evident in the oncologic outcomes. Further advance in genomic testing would lead us to tailor treatment based on individual risk factors and minimize long-term side effects.