Magnifying endoscopy combined with narrow-band imaging for differential diagnosis of superficial depressed gastric lesions.

BACKGROUND AND AIM: Magnifying endoscopy combined with narrow-band imaging (ME-NBI) has been used for differential diagnosis of various focal lesions. The aim of our study was to evaluate ME-NBI criteria for cancer diagnosis in superficial depressed gastric lesions in comparison to conventional white light endoscopy (WLE). PATIENTS AND METHODS: ME-NBI and WLE images of 100 superficial gastric depressions (55 depressed cancers, 45 benign depressions) were independently evaluated by 11 endoscopists blinded to the diagnosis in each case. The presence or absence of predefined ME-NBI findings relating to microvasculature and fine mucosal structure (FMS) was recorded. A general diagnosis of benign or malignant also had to be given on the basis of a general assessment of features of color and shape as shown in the ME-NBI and WLE images, respectively, without regard to any prespecified criteria. RESULTS: Multivariate and ROC analysis demonstrated that the triad of FMS disappearance, microvascular dilation, and heterogeneity appeared to be the best combination for diagnosis of gastric cancer. ME-NBI diagnosis with the triad attained a good specificity (85 %, theoretically calculated if all of the triad were positive), which was significantly ( P < 0.001) superior to WLE general diagnosis (65 %), and comparable with ME-NBI general diagnosis (80 %). The sensitivities of the three diagnoses (ME-NBI with the triad 69 %, WLE general diagnosis 71 %, ME-NBI general diagnosis 72 %) were comparably moderate. The kappa values (interobserver concordance) for ME-NBI diagnosis with the triad (0.47) and ME-NBI general diagnosis (0.48) were superior to the kappa value for WLE diagnosis (0.34). CONCLUSION: The triad of FMS disappearance, microvascular dilation, and heterogeneity has good specificity for the diagnosis of superficial depressed gastric carcinoma, but the sensitivity needs to be improved.

Autofluorescence endoscopy versus conventional white light endoscopy for the detection of superficial gastric neoplasia: a prospective comparative study.

BACKGROUND AND STUDY AIMS: Preliminary studies have suggested autofluorescence endoscopy (AFE) to be accurate in the diagnosis of gastric tumors. Our prospective blinded study systematically compared AFE with white light endoscopy (WLE) for the detection of superficial gastric neoplasia. PATIENTS AND METHODS: An enriched population included 33 patients with superficial gastric neoplasia referred for endoscopic submucosal dissection (ESD), and 18 control patients undergoing follow-up endoscopy after curative ESD. At the direction of a study coordinator, two endoscopists who were blinded to the patient's history and to each other's findings, performed WLE followed by AFE or performed AFE alone, in random order. Both endoscopists independently recorded the presence of lesions seen at AFE and WLE. All lesions identified in either test were biopsied and the pathological results were used as the gold standard. RESULTS: 39 gastric neoplasias were histologically confirmed and 52 non-neoplastic lesions were found to be either WLE- and/or AFE-positive. Sensitivities of WLE and AFE alone were 74 % vs. 64 % (n. s.) and specificities were 83 % vs. 40 % ( P = 0.0003), respectively. WLE followed by AFE had a sensitivity of 69 % (n. s.) and a specificity of 64 % ( P = 0.046 compared with WLE alone). Of all neoplasias finally diagnosed, 13 % (or in the case of elevated neoplasias, 23 %) were detected by AFE but not by WLE. CONCLUSIONS: Although one quarter of elevated gastric neoplasias were detected only by AFE, its specificity is poor; therefore its clinical value is limited.

A novel double-channel therapeutic endoscope ("R-scope") facilitates endoscopic submucosal dissection of superficial gastric neoplasms.

BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) is a new and radical treatment for superficial gastrointestinal neoplasms that provides high rates of en bloc resection compared with treatment by conventional mucosal resection. However, ESD is a complex procedure that is associated with long operating times and a higher complication rate. This feasibility study assessed the use of a novel double-channel therapeutic endoscope for performing en-bloc ESD in order to assess whether the procedure time could be shortened. PATIENTS AND METHODS: The therapeutic endoscope we used (the "R-scope") is equipped with a multibending system and has two movable instrument channels: one moves a grasping forceps vertically for lesion countertraction; the other swings a cutting knife horizontally for dissection. Twenty consecutive patients (18 men, 2 women; mean age 63 years, range 54 - 80 years) with superficial gastric neoplasms in the distal two-thirds of the stomach underwent resection of their tumor by ESD using the R-scope. Forty size- and location-matched gastric neoplasms resected by conventional ESD were reviewed retrospectively for the purposes of comparison. RESULTS: The rates of curative en-bloc resection, complications, and local recurrence using the two ESD methods were comparable. The mean +/- SD operating time was significantly shorter for ESD using the R-scope than for conventional ESD (57.9 +/- 29.7 minutes vs. 92.8 +/- 58.9 minutes, P = 0.016). CONCLUSION: The R-scope appears to shorten the operating time of ESD with comparable efficacy and complication rates.

Safety, tolerability, and pharmacokinetics of TAS-108 in normal healthy post-menopausal female subjects: a phase I study on single oral dose.

OBJECTIVES: The present study was conducted to evaluate the safety, tolerability, and pharmacokinetics of TAS-108 after ascending single oral doses and to analyse preliminarily the effect of food on the pharmacokinetics of TAS-108 in normal healthy post-menopausal female subjects. METHODS: Twelve healthy subjects participated in an open-label, ascending single-dose, alternating group, safety, tolerance, and pharmacokinetic study of TAS-108 administered orally to two groups of the subjects, one given alternating doses of 10, 40, 120 mg (group A) and the other of 20, 80, 160 mg (group B), in the fasting state. In addition, six subjects (group A) were administered an additional dose at 120 mg TAS-108 after food consumption. Plasma and urine samples for measurement of TAS-108 were analysed by validated analytical procedures using a liquid chromatographic method with tandem mass spectrometric detection (LC/MS/MS). RESULTS: There was no dose-dependent increase in any adverse events (AEs), and there were no serious AEs or deaths. TAS-108 was readily absorbed following oral administration of the 80-, 120- and 160-mg doses. Plasma TAS-108 levels steadily declined, generally in a mono-exponential manner, with overall mean t(1/2) values ranging from 3.04 to 4.43 h in the fasting groups. Administration of TAS-108 after a high-fat meal markedly increased the bioavailability of the drug. The mean C(max) and AUC(0--t) values increased after a high-fat breakfast by 182 and 191% compared with the fasting value respectively. CONCLUSIONS: In this escalating dose study of TAS-108, the drug was well tolerated by the participants. The maximum and systemic exposure to TAS-108 tended to increase with increasing dose and its bioavailability markedly increased after high-fat food intake.

Purification and characterization of a dimeric phenylalanine dehydrogenase from Rhodococcus maris K-18.

NAD+-dependent phenylalanine dehydrogenase (EC 1.4.1.) was purified to homogeneity from a crude extract of Rhodococcus maris K-18 isolated from soil. The enzyme had a molecular mass of about 70,000 daltons and consisted of two identical subunits. The enzyme catalyzed the oxidative deamination of L-phenylalanine and several other L-amino acids and the reductive amination of phenylpyruvate and p-hydroxyphenylpyruvate. The enzyme required NAD+ as a natural coenzyme. The NAD+ analog 3-acetylpyridine-NAD+ showed much greater coenzyme activity than did NAD+. D-Phenylalanine, D-tyrosine, and phenylethylamine inhibited the oxidative deamination of L-phenylalanine. The enzyme reaction was inhibited by p-chloromercuribenzoate and HgCl2. Initial-velocity and product inhibition studies showed that the reductive amination proceeded through a sequential ordered ternary-binary mechanism. NADH bound first to the enzyme, followed by phenylpyruvate and then ammonia, and the products were released in the order L-phenylalanine and NAD+. The Michaelis constants were as follows: L-phenylalanine, 3.8 mM; NAD+, 0.25 mM; NADH, 43 microM; phenylpyruvate, 0.50 mM; and ammonia, 70 mM.