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Background Endoscopic submucosal dissection (ESD) has been used to treat patients with early gastric cancers (EGCs), including large and ulcerative lesions. Few published data exist on the long-term outcomes of this treatment with median follow-up periods of over 5 years; we therefore aimed to assess the long-term outcomes of EGC patients undergoing ESD. Methods A total of 1,956 consecutive patients with 2,210 EGC lesions at initial onset underwent ESD with curative intent at our hospital from 1999 to 2006. We performed a retrospective analysis of the 5-year survival of EGC patients undergoing curative ESD for absolute indications or for expanded indications. Results For the pathological curability, curative ESD for absolute indications, curative ESD for expanded indications of differentiated-type EGC, and curative ESD for undifferentiated-type EGC were achieved in 781, 713, and 43 patients, respectively. The median follow-up period was 83.3 months. Among the 1,537 patients, there were only two patients with recurrence, including one who developed a regional lymph node (LN) metastasis and one who developed a distant LN metastasis with local recurrence resulting in gastric cancer-related death. Seven died from metachronous gastric cancers. The 5-year rates of overall survival, disease-specific survival, and relative survival were 92.6, 99.9, and 105.0 %, respectively. Conclusions Based on the high rate of 5-year survival among EGC patients undergoing curative ESD for absolute indications or for expanded indications in the largest patient series with a median follow-up period of over 5 years, ESD could be employed as a standard treatment for EGC lesions.

Background A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. Methods A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. Results Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan–Meier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. Conclusion Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

Menthyl ester of valine (MV) has been developed as a plant defense potentiator to induce pest resistance in crops. In this study, we attempted to establish MV hydrochloride (MV-HCl) in lettuce and tomato crops. When MV-HCl solutions were used to treat soil or leaves of potted tomato and lettuce plants, 1 µM MV-HCl solution applied to potted plant soil was most effective in increasing the transcript level of defense genes such as pathogenesis-related 1 (PR1). As a result, leaf damage caused by Spodoptera litura and oviposition by Tetranychus urticae were significantly reduced. In addition, MV-HCl-treated plants showed an increased ability to attract Phytoseiulus persimilis, a predatory mite of T. urticae, when they were attacked by T. urticae. Overall, our findings showed that MV-HCl is likely to be effective in promoting not only direct defense by activating defense genes, but also indirect defense mediated by herbivore-induced plant volatiles. Moreover, based on the results of the sustainability of PR1 expression in tomato plants treated with MV-HCl every 3 days, field trials were conducted and showed a 70% reduction in natural leaf damage. Our results suggest a practical approach to promoting organic tomato and lettuce production using this new plant defense potentiator.

Background: Colorectal endoscopic submucosal dissection (ESD) is a relatively new therapy that has been accepted as the most effective treatment procedure for superficial colorectal neoplasms. Given the increasing acceptance and use of this procedure worldwide, the outcomes of colorectal ESD performed by trainees should be understood from a practical perspective and for developing strategies to introduce ESD to trainees. This study aimed to evaluate the clinical outcomes of ESD when conducted by less-experienced endoscopists. Summary: We retrospectively reviewed the clinical outcomes of 164 patients with 164 colorectal neoplasms who underwent ESD carried out by 20 trainees performing their first colorectal ESDs between April 2005 and March 2012. For each operator, clinical data were collected between the first and 30th cases. For evaluating the technical aspects of the ESD procedure, the endoscopic characteristics of the lesions, procedure time, en bloc resection rate, R0 resection rate, invasion depth and complications were evaluated. The median procedure time was 95 min; about 75% of the lesions were resected within 120 min. Apparent perforation or electric damage in the muscularis propria was seen in 4% of lesions. In terms of factors with the potential to effect procedure time, lesion size and pathological invasion depth were significantly different between shorter and longer treatment times for granular-type laterally spreading tumors (LST). Key Messages: A granular-type LST of <40 mm is a good lesion for introducing colorectal ESD to trainees. Trainees should have a strong ability to make a depth diagnosis before starting ESD.

We report the first three-dimensional structure of fungus-derived glucose dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor. This is currently the most advanced and popular enzyme used in glucose sensor strips manufactured for glycemic control by diabetic patients. We prepared recombinant nonglycosylated FAD-dependent glucose dehydrogenase (FADGDH) derived from Aspergillus flavus (AfGDH) and obtained the X-ray structures of the binary complex of enzyme and reduced FAD at a resolution of 1.78 Å and the ternary complex with reduced FAD and D-glucono-1,5-lactone (LGC) at a resolution of 1.57 Å. The overall structure is similar to that of fungal glucose oxidases (GOxs) reported till date. The ternary complex with reduced FAD and LGC revealed the residues recognizing the substrate. His505 and His548 were subjected for site-directed mutagenesis studies and these two residues were revealed to form the catalytic pair, as those conserved in GOxs. The absence of residues that recognize the sixth hydroxyl group of the glucose of AfGDH and the presence of significant cavity around the active site may account for this enzyme activity toward xylose. The structural information will contribute to the further engineering of FADGDH for use in more reliable and economical biosensing technology for diabetes management.

Members of the transforming growth factor-β superfamily play essential roles in various aspects of embryonic development and physiological organ function. Among them, bone morphogenetic protein (BMP) 9 and BMP10 regulate embryonic vascular development by activating their endothelial receptor ALK1 (activin receptor-like kinase 1, also called Acvrl1). ALK1-mediated intracellular signaling is implicated in the etiologies of human diseases, but their downstream functional proteins are largely unknown. In this study, we identified Tmem100 , a gene encoding a previously uncharacterized intracellular transmembrane protein, to be an embryonic endothelium-enriched gene activated by BMP9 and BMP10 through the ALK1 receptor. Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of the vascular abnormalities observed with the Acvrl1/Alk1 deficiency. The activity of Notch- and Akt-mediated signaling, which is essential for vascular development, was down-regulated in Tmem100 null mice. Cre -mediated deletion of Tmem100 in endothelial cells was sufficient to recapitulate the null phenotypes. These data indicated that TMEM100 may play indispensable roles downstream of BMP9/BMP10-ALK1 signaling during endothelial differentiation and vascular morphogenesis.

•The ATLAS-OCT (ST-elevation Acute myocardial infarcTion and cLinicAl outcomeS treated by Optical Coherence Tomography-guided percutaneous coronary intervention) trial aims to investigate the feasibility of optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).•This study will include 600 consecutive patients with STEMI undergoing primary PCI.•The primary endpoint is the rate of successful OCT imaging during primary PCI.•The study will clarify the feasibility of OCT-guided primary PCI for patients with STEMI.•The study may identify a suitable patient group for OCT-guided primary PCI. Even after successful revascularization with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), subsequent adverse events still occur. Previous studies have suggested potential benefits of intravascular imaging, including optical coherence tomography (OCT). However, the feasibility of OCT-guided primary PCI has not been systematically examined in these patients. The ATLAS-OCT (ST-elevation Acute myocardial infarcTion and cLinicAl outcomeS treated by Optical Coherence Tomography-guided percutaneous coronary intervention) trial was designed to investigate the feasibility of OCT guidance during primary PCI for STEMI in experienced centers with expertise on OCT-guided PCI as a prospective, multicenter registry of consecutive patients with STEMI who underwent a primary PCI. The sites’ inclusion criteria are as follows: (1) acute care hospitals providing 24/7 emergency care for STEMI, and (2) institutions where OCT-guided PCI is the first choice for primary PCI in STEMI. All patients with STEMI who underwent primary PCI at participating sites will be consecutively enrolled, irrespective of OCT use during PCI. The primary end point will be the rate of successful OCT imaging during the primary PCI. As an ancillary imaging modality to angiography, OCT provides morphologic information during PCI for the assessment of plaque phenotypes, vessel sizing, and PCI optimization. Major adverse cardiac events, defined as a composite of all-cause death, myocardial infarction, and target vessel revascularization at 1 year, will also be recorded. The ATLAS-OCT study will clarify the feasibility of OCT-guided primary PCI for patients with STEMI and further identify a suitable patient group for OCT-guided primary PCI.

Purpose This study evaluated the venous variations of the right colon using preoperative three-dimensional computed tomography (3D-CT), and to investigate its usefulness in laparoscopic complete mesocolic excision (CME) for right colon cancer. Methods 3D-CT was performed prior to surgery in 81 consecutive patients with right colon cancer. Results Laparoscopic right hemicolectomy was performed without conversion to open surgery in all cases (100 %). All 81 patients had a single ileocolic vein (ICV). The ICV flowed into the superior mesenteric vein (SMV) in 98 % of patients and the gastrocolic trunk (GCT) in 2 % of patients. The right colic vein (RCV) was absent in 6 % of patients. One RCV was present in 88 % of patients and two were present in 6 % of patients. The main RCV flowed into the GCT in 84 % of patients and the SMV in 10 % of patients. The superior RCV was present in 21 % of patients, and all cases flowed into the GCT. One middle colic vein (MCV) was present in 49 % of patients, two in 46 %, and three in 5 % of patients. The main MCV flowed into the SMV in 68 % of patients, GCT in 20 %, jejunal vein in 6 %, inferior mesenteric vein in 5 %, and the splenic vein in 1 % of patients. The GCT was present in 88 % of patients. Conclusions Although the venous tributaries of the right colon are variable, preoperative 3D-CT is informative and helpful for surgeons performing laparoscopic CME for right colon cancer.

OBJECTIVE: To improve the stability of E. coli-produced non-glycosylated fungal FAD-glucose dehydrogenase induced a disulfide bond by site-directed mutagenesis based on structural comparisons with glucose oxidases. RESULTS: The FAD-glucose dehydrogenase (GDH) mutant Val149Cys/Gly190Cys, which was constructed based on a comparison with the three dimensional structure of glucose oxidase, showed a 110 min half-life of thermal inactivation at 45 °C, which is 13-fold greater than that of the wild-type enzyme. The considerable increase in thermal stability was further supported by Eyring plot analysis. The kinetic parameters of Val149Cys/Gly190Cys (kcₐₜ = 760 s⁻¹, Kₘ = 35 mM, and catalytic efficiency (kcₐₜ/Kₘ) = 22 s⁻¹ mM⁻¹) were almost identical to those of the wild-type enzyme (kcₐₜ = 780 s⁻¹, Kₘ = 35 mM, kcₐₜ/Kₘ = 22 s⁻¹ mM⁻¹). The substrate specificity of Val149Cys/Gly190Cys is indistinguishable from that of the wild type. CONCLUSION: The constructed mutant, Val149Cys/Gly190Cys, had significantly increased structural stability without changing the catalytic activity and kinetic parameters of FAD-GDH, including its characteristic substrate specificity.