Background Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. Objective We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. Design, setting, and participants We retrospectively queried Fox Chase Cancer Center’s prospectively maintained database for consecutive renal masses where a Nephrometry score was available. Intervention All patients in the cohort underwent either partial or radical nephrectomy. Measurements The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Results and limitations Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. Conclusions The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass.

Background The association between tumor complexity and postoperative complications after partial nephrectomy (PN) has not been well characterized. Objective We evaluated whether increasing renal tumor complexity, quantitated by nephrometry score (NS), is associated with increased complication rates following PN using the Clavien-Dindo classification system (CCS). Design, setting, and participants We queried our prospectively maintained kidney cancer database for patients undergoing PN from 2007 to 2010 for whom NS was available. Interventions All patients underwent PN. Measurements Tumors were categorized into low- (NS: 4–6), moderate- (NS: 7–9), and high-complexity (NS: 10–12) lesions. Complication rates within 30 d were graded (CCS: I–5), stratified as minor (CCS: I or 2) or major (CCS: 3–5), and compared between groups. Results and limitations A total of 390 patients (mean age: 58.0 ± 11.9 yr; 66.9% male) undergoing PN (44.6% open, 55.4% robotic) for low- (28%), moderate- (55.6%), and high-complexity (16.4%) tumors (mean tumor size: 3.74 ± 2.4 cm; median: 3.2 cm) from 2007 to 2010 were identified. Tumor size, estimated blood loss, and ischemia time all significantly differed (p < 0.0001) between groups; patient age, body mass index (BMI), and operative time were comparable. When stratified by CCS, minor and major complication rates for all patients were 26.7% and 11.5%, respectively. Minor complication rates were comparable (26.6 vs 24.9 vs 32.8%; p = 0.45), whereas major complication rates differed (6.4 vs 11.1 vs 21.9%; p = 0.009) among tumor complexity groups. Controlling for age, gender, BMI, type of surgical approach, operative duration, and tumor complexity, prolonged operative time (odds ratio [OR]: 1.01; confidence interval [CI], 1.0–1.02) and high tumor complexity (OR: 5.4; CI, 1.2–24.2) were associated with the postoperative development of a major complication. Lack of external validation is a limitation of this study. Conclusions Increasing tumor complexity is associated with the development of major complications after PN. This association should be validated externally and integrated into the decision-making process when counseling patients with complex renal tumors.

In our large institutional series of patients with moderate and highly complex solid renal tumors classified by the nephrometry score robotic partial nephrectomy offered comparable perioperative and functional outcomes with the added benefit of decreased hospital length of stay.

Objectives The treatment of localized renal cell carcinoma remains overly subjective. The R.E.N.A.L.- Nephrometry Score (NS) quantifies the salient characteristics of renal mass anatomy in an objective and reproducible manner. We evaluated treatment patterns of solid renal masses based on quantifiable anatomic features using Nephrometry. Methods Nephrometry scores were available in 615 patients in our prospective kidney tumor database (2000-2010). The NS sum and its individual component scores were analyzed to determine their relationship to treatment approach. Results Median age, age-adjusted Charlson Co-Morbidity Index (CCI), and estimated GFR were 60 years (25-89), 2 (0-10), and 80.5 ml/min (5.1-120.0), respectively. Increasing tumor complexity as measured by a higher overall Nephrometry Score was associated with both radical nephrectomy (RN) and open partial nephrectomy (PN) (p<0.0001). Compared to patients who underwent PN, patients treated with RN had significantly higher size (R), central proximity (N), and location (L) component scores (p<0.001). Furthermore, tumors treated with a RN were more often hilar (p<0.001). Similarly, compared to minimally-invasive PN (laparoscopic or robotic), open PN was associated with an increasing individual component score for size, endophycity and central proximity to the collecting system (p<0.001) and non-polar location (p=0.016). Conclusions The R.E.N.A.L. – Nephrometry score standardizes reporting of solid renal masses and appears to effectively stratify by treatment type. Although only one part of the treatment decision-making process, Nephrometry aids in objectifying previously subjective measures.

The findings of the present study show that PN can safely be performed in tumours ≥ 7 cm in size with acceptable technical, oncological and functional outcomes. Further studies are warranted.

Background Docetaxel is the mainline treatment approved by the FDA for castration-resistant prostate cancer (CRPC) yet its administration only increases median survival by two to four months. Docetaxel is metabolized in the liver by hepatic CYP3A4 activity. Piperine, a major plant alkaloid/amide, has been shown to inhibit the CYP3A4 enzymatic activity in a cell-free system. Thus, we investigated whether the co-administration of piperine and docetaxel could increase docetaxel’s pharmacokinetic activity in vitro and in vivo. Methods Liver CYP3A4 enzymatic activity was measured by fluorescence. In vivo docetaxel pharmacokinetic activity was analyzed by liquid chromatography. An in vivo xenograft model of human CRPC was utilized to assess the anti-tumor effect of docetaxel when co-administered with piperine. Results Inhibition of hepatic CYP3A4 activity resulted in an increased area under the curve (AUC), half-life and maximum plasma concentration of docetaxel when compared to docetaxel alone administration. The synergistic administration of piperine and docetaxel significantly improved the anti-tumor efficacy of docetaxel in a xenograft model of human CRPC. Conclusions Docetaxel is one of the most widely used cytotoxic chemotherapeutic agents and is currently the mainstay treatment for metastatic CRPC. Dietary constituents are important agents modifying drug metabolism and transport. In our studies, dietary consumption of piperine increases the therapeutic efficacy of docetaxel in a xenograft model without inducing more adverse effects on the treated mice.

Tyrosine kinase inhibitors (TKIs) exhibit impressive activity against advanced renal cell carcinoma. However, recent clinical studies have demonstrated an equivocal response to sunitinib in patients with castration-resistant prostate cancer. The tumor suppressor phosphatase and tensin homolog (PTEN) acts as a gatekeeper of the PI3K/Akt/mTOR cell-survival pathway. Our experiments demonstrate that PTEN expression inversely correlates with sunitinib resistance in renal and prostate cancer cells. Restoration of PTEN expression markedly increases sensitivity of tumor cells to sunitinib both in vitro and in vivo. In addition, pharmacologic manipulation of PI3K/Akt/mTOR signaling with PI3K/mTOR inhibitor, GDC-0980, mTOR inhibitor, temsirolimus, or pan-Akt inhibitor, GSK690693, was able to overcome sunitinib resistance in cancer cells. Our findings underscore the importance of PTEN expression in relation to sunitinib resistance and imply a direct cytotoxic effect by sunitinib on tumor cells in addition to its anti-angiogenic actions.

profile, and liver function tests (LFTs). Testosterone and PSA levels were assessed every 6-12 months. Patients with a biopsyconfirmed or recent history of prostatitis before treatment were excluded. TRT was discontinued in men who developed prostate cancer. RESULTSBefore and 36 months after treatment the total testosterone levels were 241.1 and 379.8 ng/dL ( P < 0.05), respectively. Four men (4.9%) developed prostate cancer at a mean (range) of 32.5 (22-41) months after starting TRT. In men without prostate cancer (95.1%), PSA levels did not increase significantly at 1-year intervals for 5 years. There was no statistical difference in PSA level change from baseline to 36 months when patients without prostate cancer were stratified into groups according to age ( ≤ 50, 55-65 and ≥ 70 years). In men with prostate cancer there was an increase in mean PSA level from baseline to 18 months of 1.8 ng/ mL, and to 36 months of 3.2 ng/mL ( P < 0.05). Total cholesterol improved from 203.8 to 166.6 mg/dL ( P < 0.05) after 36 months of TRT; the BMI, haematocrit and LFTs did not change significantly. CONCLUSIONSLOH is an increasingly prevalent disease characterized by a symptomatically low testosterone level, and TRT is effective in normalizing serum testosterone levels, providing a beneficial cardiovascular effect, and improving sexual function and overall quality of life. PSA levels remain stable after normalization of testosterone for ≥ 5 years, prostate cancer can be effectively diagnosed and treated in men taking TRT, and the incidence of prostate cancer among men with LOH on TRT is no greater than that in the general population. KEYWORDShypogonadism, prostate-specific antigen, testosterone replacement therapy, prostate cancer Study Type -Prognostic (case series) Level of Evidence 4 OBJECTIVESTo retrospectively review hypogonadal men receiving testosterone replacement therapy (TRT), and evaluate the changes in prostatespecific antigen (PSA) levels over an extended period, and thus evaluate the occurrence of prostate cancer, as a primary concern in treating late-onset hypogonadism (LOH) is the potential increased risk of prostate cancer; we also recorded the cardiovascular effects of TRT. PATIENTS AND METHODSIn all, 81 hypogonadal men (mean age 56.8 years) were followed for a mean (range) of 33.8 (6-144) months after starting TRT. All men had a normal baseline PSA level before TRT and had routine laboratory investigations, including measurements of body mass index (BMI), haematocrit, lipid