Evaluation of extratumoral lymphatic permeation in non-small cell lung cancer as a means of predicting outcome

BACKGROUND: Lymphatic permeation (ly) has been described as a potential prognostic factor for non-small cell lung cancer (NSCLC). METHODS: The purpose of this study was to analyze whether evaluation of the presence or absence of ly and its location (ly 0: absent, N=464; ly 1: intratumoral, N=42; ly 2: extratumoral, N=52) provides an appropriate means of predicting the outcome of NSCLC. We investigated the clinical implications of ly in 558 consecutive patients with surgically resected NSCLC. RESULTS: Evaluation according to ly status showed that the recurrence-free survival (RFS) time of the ly 2 patients was significantly shorter than that of the ly 0 patients (P<0.0001), the ly 1 patients (P=0.0028). A significant difference in RFS time was also observed between the ly 0 patients and the ly 1 patients (P=0.0025). RFS time of the ly 0 patients was significantly longer than that of the ly 1 plus ly 2 patients (P<0.0001). We also evaluated the patients with pathological stage I disease (N=378) separately. The RFS time of the ly 2 patients (N=9) was significantly shorter than that of the ly 0 plus ly 1 patients (P<0.0001). In the nine ly 2 patients, six developed a distant metastasis within 1 year. A multivariate analysis revealed that ly status (ly 0 plus ly 1 versus ly 2) was an independent prognostic factor (P=0.0116), demonstrating the significant prognostic value of extratumoral lymphatic permeation in NSCLC. CONCLUSIONS: These results indicate that ly status is a good prognostic marker of poorer outcome in patients with resected NSCLC.     

Lymph node staging in esophageal squamous cell carcinoma: A comparative study of endoscopic ultrasonography versus computed tomography

Background and Aim:  Endoscopic ultrasonography (EUS) is established as a standard approach for locoregional staging of esophageal cancer. However, only a few published studies have attempted to correlate the station of the abnormal lymph nodes detected by EUS with the definitive histology. We compared EUS and computed tomography (CT) in the initial staging of esophageal squamous cell carcinoma.
Methods:  Consecutive patients with esophageal cancer undergoing EUS were evaluated. EUS findings and patient data including histopatology were collected prospectively and analyzed retrospectively. Lymph node locations were divided into three groups; abdominal (A), paraesophageal (B), and thoracic paratracheal (C).
Results:  A total of 365 consecutive patients underwent EUS and 159 patients underwent esophagectomy without neoadjuvant chemotherapy. Thirty-eight patients were excluded (insufficient EUS, etc.), and 121 patients were enrolled. The overall accuracy of EUS was 64% (sensitivity 68%, specificity 58%, positive predictive value [PPV] 68%), CT was 51% (sensitivity 33%, specificity 75%, PPV 64%), and CT + EUS was 64% (sensitivity 74%, specificity 50%, PPV 66%). The accuracy of EUS was higher than CT in Groups A and C. Sensitivity of CT was lower than that of EUS alone and CT + EUS.
Conclusions:  This study has demonstrated that EUS is a more accurate technique than contrast-enhanced CT for detecting abnormal lymph nodes. Sensitivity of CT was lower than that of EUS alone and CT + EUS. But some metastatic lymph nodes in neck and abdominal fields are only detectable by CT. Therefore, both EUS and CT should be undertaken for routine examination prior to treatment of esophageal cancer.     

Do local anesthetics interact preferentially with membrane lipid rafts? Comparative interactivities with raft-like membranes

Membranous lipid bilayers have been reconsidered as the site of action of local anesthetics (LAs). Recent understanding of biomembranes indicates the existence of lipid raft microdomains enriched in cholesterol and sphingolipids as potential platforms for channels and receptors. Based on the hypothesis that LAs may interact preferentially with lipid rafts over non-raft membranes, we compared their effects on raft model membranes and cardiolipin-containing biomimetic membranes. Liposomes were prepared with phospholipids, sphingomyelin, cerebroside, and cholesterol to have compositions corresponding to lipid rafts and cardiomyocyte mitochondrial membranes. After reacting LAs (50–200 μM) with the membrane preparations, their interactivities were determined by measuring fluorescence polarization with 1,6-diphenyl-1,3,5-hexatriene. Although bupivacaine and lidocaine acted on different raft-like liquid-ordered membranes to reduce polarization values, their effects on biomimetic less ordered membranes were much greater. LAs interacted with biomimetic membranes with the potency being R(+)-bupivacaine > racemic bupivacaine > S(−)-bupivacaine > ropivacaine > lidocaine > prilocaine, which is consistent with the rank order of pharmacotoxicological potency. However, raft model membranes showed neither structure-dependence nor stereoselectivity. The relevance of membrane lipid rafts to LAs is questionable at least in their effects on raft-like liquid-ordered membranes.     

Morphological changes of the hair roots in alopecia areata: A scanning electron microscopic study

Alopecia areata is a chronic inflammatory condition causing non‐scarring patchy hair loss. Diagnosis of alopecia areata is made by clinical observations, hair pluck test and dermoscopic signs. However, because differentiation from other alopecia diseases is occasionally difficult, an invasive diagnostic method using a punch biopsy is performed. In this study, to develop a reliable, less invasive diagnostic method for alopecia areata, we performed scanning electron microscopy of the hair roots of alopecia areata patients. This study identified four patterns of hair morphology specific to alopecia areata: (I) long tapering structure with no accumulation of scales; (II) club‐shaped hair root with fine scales; (III) proximal accumulation of scales; and (IV) sharp tapering of the proximal end of hair. On the basis of these results, we can distinguish alopecia areata by scanning electron microscopic observation of the proximal end of the hair shafts.     

Possible mechanisms involved in gastric hypermotility caused by indomethacin in the rat

Pathogenesis of indomethacin-induced gastric lesions was investigated in the rat by measuring lesions, gastric motility, and terminal blood glucose levels and correlating them with each other. Subcutaneously administered indomethacin (3-25 mg/kg) dose-dependently produced lesions in the stomach with concomitant gastric hypermotility and reduction of blood glucose levels. When the lesion score and the motility were plotted against terminal glucose levels, a highly significant relationship was found among these three factors (P less than 0.01). Gastric lesions and hypermotility induced by indomethacin (25 mg/kg) were suppressed significantly by 16,16-dmPGE2 (10 micrograms/kg) with no effect on the glucose levels, while intravenous infusion of glucose (25% w/w, 1.4 ml/hr) prevented these responses and restored the reduced glucose levels above the basal values. In addition, both 16,16-dmPGE2 and glucose infusion afforded a significant protection against gastric lesions induced by indomethacin even in the acid-perfused stomach (150 mM HCl). These results confirmed gastric hypermotility as a key element in the pathogenesis of indomethacin-induced lesions and further suggested that indomethacin may sensitive gastric contractility through glycoprivic receptors by inducing hypoglycemia and PG deficiency.