Objective L‐dopa is the most widely used and most effective therapy for Parkinson disease (PD), but chronic treatment is associated with motor complications in the majority of patients. It has been hypothesized that providing more continuous delivery of L‐dopa to the brain would reduce the risk of motor complications, and that this might be accomplished by combining L‐dopa with entacapone, an inhibitor of catechol‐O‐methyltransferase, to extend its elimination half‐life. Methods We performed a prospective 134‐week double‐blind trial comparing the risk of developing dyskinesia in 747 PD patients randomized to initiate L‐dopa therapy with L‐dopa/carbidopa (LC) or L‐dopa/carbidopa/entacapone (LCE), administered 4× daily at 3.5‐hour intervals. The primary endpoint was time to onset of dyskinesia. Results In comparison to LC, patients receiving LCE had a shorter time to onset of dyskinesia (hazard ratio, 1.29; p = 0.04) and increased frequency at week 134 (42% vs 32%; p = 0.02). These effects were more pronounced in patients receiving dopamine agonists at baseline. Time to wearing off and motor scores were not significantly different, but trended in favor of LCE treatment. Patients in the LCE group received greater L‐dopa dose equivalents than LC‐treated patients (p < 0.001). Interpretation Initiating L‐dopa therapy with LCE failed to delay the time of onset or reduce the frequency of dyskinesia compared to LC. In fact, LCE was associated with a shorter time to onset and increased frequency of dyskinesia compared to LC. These results may reflect that the treatment protocol employed did not provide continuous L‐dopa availability and the higher L‐dopa dose equivalents in the LCE group. ANN NEUROL 2010;68:18–27

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non–muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non–muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

Purpose Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether sB7-H1 levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome. Experimental Design We developed an ELISA for quantification of sB7-H1 in biologic fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein micro-sequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome. Results sB7-H1 was detected in the cell-supernatants of some B7-H1-positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver pro-apoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (p<0.001), tumors of advanced stage (p=0.017) and grade (p=0.044), and tumors with necrosis (p=0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (p=0.010). Conclusion Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome.