BACKGROUND Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895.)

Simvastatin attenuates leukocyte-endothelial cell interactions and ameliorates ischemic injury in hypercholesterolemic mice independently of lipid-lowering actions.

Abstract-We have previously demonstrated that simvastatin attenuates myocardial cell necrosis after acute myocardial ischemia and reperfusion via induction of endothelial cell NO synthase. However, it remains unknown whether the cardioprotective effects of statins can persist after extended periods of reperfusion. Furthermore, it is unknown whether simvastatin therapy can attenuate postischemic cardiac dysfunction. Pretreatment with simvastatin attenuated myocardial injury after 30 minutes of myocardial ischemia and 24 hours of reperfusion. However, the protective effects are not recognized unless simvastatin is given at least 3 hours before myocardial ischemia. Subsequently, we pretreated mice with vehicle or simvastatin and subjected the mice to 30 minutes of myocardial ischemia and 6 months of reperfusion. Myocardial infarct size (percentage of left ventricle) was significantly reduced by 51% in the simvastatin-treated group compared with the vehicle-treated group. Left ventricular diastolic and systolic dilatation was significantly (PϽ0.05) reduced in simvastatin-treated mice compared with vehicle-treated mice. Additionally, the decrement in fractional shortening after 6 months of reperfusion was minimized in simvastatin-treated mice (PϭNS versus baseline) compared with vehicle-treated mice (PϽ0.05 versus baseline). Left ventricular end-diastolic pressure was significantly (PϽ0.01) elevated in vehicle-treated mice (21Ϯ4 mm Hg) but not simvastatin-treated mice (5Ϯ2 mm Hg) compared with baseline values. These data demonstrate that simvastatin treatment before myocardial ischemia attenuates infarct size and preserves myocardial function after chronic reperfusion in mice.

Conventional examination of lymph nodes for CRC is inadequate for the detection of MM and ITC as described in the new TNM classification. Thus, LM and focused SN analysis should be considered to fully stage CRC.