Predicting Survival in Patients with Advanced Non-squamous Non-small Cell Lung Cancer: Validating the Extent of Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: A number of factors related to overall survival (OS) have been addressed in advanced non-small cell lung cancer (NSCLC). This study was conducted to determine the impact of whole-body metastatic regions on survival outcome in advanced non-squamous NSCLC. MATERIALS AND METHODS: Between March 2005 and February 2011, 112 eligible patients with newly confirmed stage IV non-squamous NSCLC, available for epidermal growth factor receptor (EGFR) mutation status 18-21 analysis, and accessible for the determination of pretreatment whole-body metastatic regions were enrolled in this retrospective study. The total number of synchronous metastatic regions was scored according to the following disease sites: abdomen/pelvis, lung to lung/pulmonary lymphangitic spread, bone, pleura/pleural effusion/pericardial effusion, neck/axillary lymph nodes, other soft tissue, brain. RESULTS: The median age of the cohort was 65 years (range, 31 to 88 years). The median whole-body metastatic score was 2 (range, 1 to 6), and bone and lung to lung were the most common metastatic sites. EGFR mutations were observed in 40 (35.7%) patients with a deletion in exon 19 and Leu858Arg mutation in exon 21 being detected in 16 (40.0%) and 19 (47.5%) patients, respectively. Multivariate analysis for OS revealed that treatment factors (p=0.005), performance status (p=0.006), whole-body metastatic score (p<0.001), and EGFR mutation status (p=0.095) were significantly or marginally associated with OS. CONCLUSION: The results of the present study demonstrated that whole-body metastatic extent strongly affects survival outcome, even after adjustment for other significant variables in advanced non-squamous NSCLC. The clinical validity of more curative multimodal approaches in cohorts with limited metastases remains to be explored.

The Local Anesthetic Effect of Meperidine on the Direct Myocardial Depression in Isolated Ventricular Myocardium / 대한마취과학회지

BACKGROUND: The effects of various concentration (20, 50, 100 micrometer) of meperidine were studied in isolated guinea pig and rat ventricular papillary muscles. METHODS: Isometric force of guinea pig ventricular papillary muscle was examined in normal and 26 mM K+ Tyrode's solution. Experiments using rat and guinea pig papillary muscle under normal and low Na+ (40 mM), respectively, were performed to evaluate the effect on Ca2+ release from the sarcoplasmic reticulum (SR). Normal and slow action potentials (APs) were evaluated by using conventional microelectrode technique. Rapid cooling contractures were performed. RESULTS: Meperidine caused dose-dependent depression of peak force from rested-state (RS) to 3 Hz stimulation rates in guinea pig papillary muscles. Conduction block was frequently noted at high stimulation rates (2 and 3 Hz) at 150 micrometer meperidine. ~40% depression of peak force was shown at RS contraction under low Na+ Tyrode's solution, although contractile depression was not shown at RS and low stimulation rates in rat papillary muscles. 100 micrometer naloxone did not reverse the contractile depression caused by 100 micrometer meperidine. Either depression of dV/dt-max from 0.1 to 3 Hz stimulation rates or rate-dependent depression among 1, 2 and 3 Hz could be observed at 150 micrometer meperidine. In 26 mM K+ Tyrode's solution, 50 and 100 micrometer meperidine caused dose-dependent depression of early and late force development. In slow APs, changes of dV/dt-max were not shown at 100 micrometer meperidine. ~40% depression of contracture induced by rapid cooling following 2 Hz stimulation rates was shown at 100 micrometer meperidine. CONCLUSION: The direct myocardial depressant effect of meperidine seems likely to be caused by local anesthetic properties of meperidine, not by the opioid action. Inhibition of SR Ca2+ release, and decreased intracellular Ca2+ secondary to Na+ channel blocking action of meperidine may at least in part be related to direct myocardial depression.