The Current State of Adjuvant Therapy Following Surgery for High-risk Renal Cell Carcinoma.

Cancer recurs in up to 40% of patients following surgery for high-risk, locoregional renal cell carcinoma (RCC). To date, little progress has been made in identifying systemic adjuvant treatment options to reduce the mortality risk after surgery for high-risk RCC. Several randomized trials exploring the efficacy of adjuvant targeted therapies in the postoperative setting have recently reported results. We examine these trials to assess the contemporary role of targeted therapy following surgery in high-risk RCC and briefly consider trials that are currently accruing with a focus on immunotherapy agents in the adjuvant setting. PATIENT SUMMARY: Kidney cancer often recurs despite initial surgery in patients with high-risk tumors. So far, adding systemic treatments such as targeted therapies after surgery has not resulted in improved survival outcomes. Future studies that include immunotherapy after surgery to reduce the risk of recurrence in patients with high-risk disease are eagerly anticipated.

Use of High-Dose Phenylephrine in the Treatment of Ischemic Priapism: Five-Year Experience at a Single Institution.

INTRODUCTION: Ischemic priapism is an uncommon urologic emergency characterized by a compartment syndrome-like ischemic insult to the corpora cavernosa of the penis. The goal of treatment in ischemic priapism is rapid detumescence to prevent long-term erectile dysfunction. Non-surgical treatment options include aspiration, irrigation, and intracavernous injections of sympathomimetic agents. At our institution, phenylephrine is used in the treatment of ischemic priapism at concentrations and doses that are higher than those recommended in established guidelines. AIM: To characterize our experience with high-concentration intracavernous phenylephrine in the treatment of ischemic priapism at an urban tertiary care center. METHODS: A retrospective chart review identified 58 unique patients presenting to the emergency department on 136 occasions and receiving the diagnosis of ischemic priapism by urologic physicians. Patients' charts were reviewed to record the dosing of phenylephrine and the outcomes and circumstances of the presentation. MAIN OUTCOME MEASURES: Success rates of different treatment strategies for different circumstances of presentation. RESULTS: Successful detumescence was achieved with non-surgical management in 86% of unique patients and the overall resolution rate when including repeat visits was 94%. All patients presenting within less than 36 hours of priapism were successfully treated with non-surgical management. There were no reported complications or associated symptoms related to the use of intracavernous phenylephrine during the 5-year period. CONCLUSION: The use of high concentration and dosing of intracavernous phenylephrine demonstrates a high success rate in the treatment of ischemic priapism. Future prospective studies are needed to further characterize appropriate phenylephrine dosing for its efficacy and safety.

Caprini venous thromboembolism risk assessment permits selection for postdischarge prophylactic anticoagulation in patients with resectable lung cancer.

OBJECTIVE: Postoperative venous thromboembolism (VTE) creates an 8-fold increase in mortality after lung resection. About one third of postoperative VTEs occur after discharge. The Caprini risk assessment model has been used by other specialties to calculate the risk of a VTE. Patients deemed high risk by the model are candidates for prophylactic anticoagulation after discharge, reducing the VTE risk by 60%. Our primary aims were to determine the frequency of VTE events and evaluate whether the Caprini model could risk-stratify patients. METHODS: Patients undergoing lung cancer resections during 2005 to 2013 were evaluated. Exclusion criteria were preoperative filter and therapeutic anticoagulation. A total of 232 patients were reviewed and Caprini scores calculated. Subjects were risk stratified into groups of low risk (0-4), moderate risk (5-8), and high risk (≥ 9). Occurrence of VTE events (deep vein thrombosis; pulmonary embolism) were identified by imaging. RESULTS: The 60-day VTE incidence was 5.2% (12 of 232); 33.3% occurred postdischarge (n = 4). Half (6 of 12) were pulmonary emboli, 1 of which caused a death, in an inpatient with a score of 16. The VTE incidence increased with Caprini score. Scores in the low, moderate, and high risk groups were associated with a VTE incidence of 0%, 1.7%, and 10.3%, respectively. With a high risk score cutoff of 9, the sensitivity, specificity, and accuracy are 83.3%, 60.5%, and 61.6%, respectively. CONCLUSIONS: One third of VTE events occurred after discharge. Postoperative VTE incidence was correlated with increasing Caprini scores. Patients in the high risk group had an incidence of 10.3%. Elevated scores may warrant extended chemoprophylaxis for patients after discharge.

Endothelial nitric oxide synthase mediates the first and inducible nitric oxide synthase mediates the second window of desflurane-induced preconditioning.

OBJECTIVES: Nitric oxide synthases (NOSs) mediate the first window of anesthetic-induced preconditioning (APC). The authors tested the hypothesis that endothelial NOS (eNOS) mediates the first window and inducible NOS (iNOS) mediates the second window of APC. DESIGN: Randomized, prospective, blinded laboratory investigation. SETTING: Experimental laboratory. PARTICIPANTS: Mice. INTERVENTIONS: Mice were subjected to a 45-minute coronary artery occlusion (CAO) and a 180-minute reperfusion. C57BL/6 mice received desflurane, 1.0 minimum alveolar concentration, for 30 minutes or 12, 24, 48, or 96 hours before CAO. In eNOS(-/-) and iNOS(-/-) mice, desflurane was given 30 minutes and 48 hours before CAO. In the control groups, no desflurane was administered. Myocardial infarct size (IS) was determined after staining with Evans blue and triphenyltetrazolium chloride. MEASUREMENTS AND MAIN RESULTS: The second window of APC was detectable at 48 hours but not at 12, 24, and 96 hours after preconditioning. In the control groups, IS was not different among the wild-type (50 ± 10%), eNOS(-/-) (52 ± 14%), and iNOS(-/-) (46 ± 10%) mice. The IS decreased significantly (p < 0.05) when desflurane was administered 30 minutes (10 ± 6%) or 48 hours (16 ± 7%) before CAO in wild-type mice, 48 hours (21 ± 13%) before CAO in eNOS(-/-) mice, and 30 minutes (13 ± 6%) before CAO in iNOS(-/-) mice. Desflurane given 30 minutes before CAO in eNOS(-/-) mice (60 ± 10%) and 48 hours before CAO in iNOS(-/-) mice (48 ± 21%) did not decrease the IS significantly compared with controls. CONCLUSIONS: Endothelial NOS and iNOS work independently to mediate the first and second windows of APC, respectively. Endothelial NOS is not necessary to trigger the second window of APC.