Search

Superficial duodenal epithelial tumors are emerging targets for endoscopic submucosal dissection (ESD). However, it is unknown how competence is achieved in duodenal ESD. This study aimed to elucidate the learning curve for duodenal ESD.This retrospective observational study included 100 consecutive patients who underwent duodenal ESD by a single endoscopist between March 2014 and September 2021. The primary outcome was to define the learning curve for duodenal ESD by an endoscopist with sufficient non-duodenal ESD experience. Cumulative sum (CUSUM) curve analysis was used to assess the learning curve in terms of procedural speed. Comparative analyses of phases identified using the CUSUM method were performed.In total, 98 patients were included in the analysis. Evaluation of the cumulative sum curve revealed four distinct phases in the graph: phase I, cases 1-25 (learning phase); phase II, cases 26-47 (proficiency phase); phase III, cases 48-72 (mastery phase); and phase IV, cases 73-98 (after introduction of general anesthesia). The median procedural speed was significantly faster in phase II than in phase I (11.1 mmDuodenal ESD requires 25 cases to gain proficiency and 50 to achieve mastery even for an endoscopist with extensive non-duodenal ESD experience.

Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC.We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes.We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p 0.99).ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Methods and Figures

Centrosome amplification frequently occurs in human cancers and is a major cause of chromosome instability (CIN). In mouse cells, centrosome amplification can be readily induced by loss or mutational inactivation of p53. In human cells, however, silencing of endogenous p53 alone does not induce centrosome amplification or CIN, although high degrees of correlation between p53 mutation and CIN/centrosome amplification in human cancer can be detected, suggesting the presence of additional regulatory mechanism(s) in human cells that ensures the numeral integrity of centrosomes and genomic integrity. Cyclin E, a regulatory subunit for CDK2 that plays a key role in centrosome duplication, frequently is overexpressed in human cancers. We found that cyclin E overexpression, together with loss of p53, efficiently induces centrosome amplification and CIN in human bladder cancer cells but not by either cyclin E overexpression or loss of p53 alone. We extended these findings to bladder cancer specimens and found that centrosome amplification is strongly correlated with concomitant occurrence of cyclin E overexpression and p53 inactivation but not with either cyclin E overexpression or p53 inactivation alone. Because cyclin E expression is strictly controlled in human cells compared with mouse cells, our findings suggest that this stringent regulation of cyclin E expression plays an additional role underlying numeral homeostasis of centrosomes in human cells and that deregulation of cyclin E expression, together with inactivation of p53, results in centrosome amplification.

Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD.An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia.The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

Methods to label intercellular contact have attracted attention because of their potential in cell biological and medical applications for the analysis of intercellular communications. In this study, a simple and versatile method for chemoenzymatic labeling of intercellularly contacting cells is demonstrated using a cell-surface anchoring reagent of a poly(ethylene glycol)(PEG)-lipid conjugate. The surface of each cell in the cell pairs of interest were decorated with sortase A (SrtA) and triglycine peptide that were lipidated with PEG-lipid. In the mixture of the two-cell populations, the triglycine-modified cells were enzymatically labeled with a fluorescent labeling reagent when in contact with SrtA-modified cells on a substrate. The selective labeling of the contacting cells was confirmed by confocal microscopy. The method is a promising tool for selective visualization of intercellularly contacting cells in cell mixtures for cell-cell communication analysis.

Whole genome analysis has identified rare copy number variations (CNV) that are strongly involved in the pathogenesis of psychiatric disorders, and 3q29 deletion has been found to have the largest effect size. The 3q29 deletion mice model (3q29-del mice) has been established as a good pathological model for schizophrenia based on phenotypic analysis; however, circadian rhythm and sleep, which are also closely related to neuropsychiatric disorders, have not been investigated. In this study, our aims were to reevaluate the pathogenesis of 3q29-del by recreating model mice and analyzing their behavior and to identify novel new insights into the temporal activity and temperature fluctuations of the mouse model using a recently developed small implantable accelerometer chip, Nano-tag. We generated 3q29-del mice using genome editing technology and reevaluated common behavioral phenotypes. We next implanted Nano-tag in the abdominal cavity of mice for continuous measurements of long-time activity and body temperature. Our model mice exhibited weight loss similar to that of other mice reported previously. A general behavioral battery test in the model mice revealed phenotypes similar to those observed in mouse models of schizophrenia, including increased rearing frequency. Intraperitoneal implantation of Nano-tag, a miniature acceleration sensor, resulted in hypersensitive and rapid increases in the activity and body temperature of 3q29-del mice upon switching to lights-off condition. Similar to the 3q29-del mice reported previously, these mice are a promising model animal for schizophrenia. Successive quantitative analysis may provide results that could help in treating sleep disorders closely associated with neuropsychiatric disorders.

High-power (1 MW), long-pulse operations up to 300 s were demonstrated by multi-frequency oscillations at 170 GHz, 137 GHz, and 104 GHz. A multi-frequency gyrotron based on the design of the ITER gyrotron has been developed and studied. By redesigning the built-in mode convertor and internal mirrors of the ITER gyrotron, the internal scattered power of the gyrotron was reduced while maintaining the same output beam size and beam direction for the three frequencies. In addition, the mirrors of a matching optics unit were designed to efficiently couple the RF beam at 170 GHz, 137 GHz, and 104 GHz oscillations to a waveguide 50 mm in diameter, the same size that will be used in ITER. An HE 11 mode content of ∼94% was achieved for the three frequencies. Output powers of 1 MW at 170 GHz and 137 GHz, and 0.9 MW at 104 GHz were demonstrated up to 300 s. These oscillation frequencies can facilitate in a wide range of toroidal magnetic field operations at ITER, including plasma start-up and electron heating and current drive.

Methods to label intercellular contact attract particular attention due to their potential in cell biological and medical applications through analysis of intercellular communications. In this study, a simple and versatile method for chemoenzymatically labeling the intercellularly contacting cell was developed by using a cell-surface anchoring reagent of poly(ethylene glycol)(PEG)-lipid conjugate. The surfaces of each cell in cell pairs of interest were efficiently decorated with sortase A (SrtA) and triglycine peptide that were lipidated with PEG-lipid, respectively. In the mixture of the two cell populations, the triglycine-modified cells were enzymatically labeled with a fluorescent labeling reagent by contacting with the SrtA-modified cells both on the substrate and in cell suspensions. Such selective labeling of the contacting cells was confirmed by confocal microscopy and flow cytometry. The results show a proof of principle that the present method is a promising tool for selective visualization and quantification of the intercellularly contacting cells among cell mixtures in cell-cell communication analysis.

Superficial nonampullary duodenal epithelial tumors (SNADETs) have become frequently detected and referred for endoscopic resection (ER). However, optimal treatment methods and long-term outcomes after ER of SNADETs have not been fully elucidated. We aimed to clarify them by analyzing our large cohort of patients with SNADETs.We enrolled 190 consecutive tumors from 189 patients undergoing ER between January 2004 and September 2019. Cases were stratified into endoscopic submucosal dissection (ESD), conventional endoscopic mucosal resection, (CEMR) and underwater endoscopic mucosal resection (UEMR). Baseline characteristics and short-term outcomes were compared between the groups. Long-term outcomes were also investigated with a median follow-up of 36 months.ESD significantly exceeded CEMR (96.4% vs. 52.9%;While tumors ≤10 mm seem to be good indications for endoscopic mucosal resection, ESD should be considered for larger tumors to better achieve complete resection. Patients with submucosal invasive carcinomas have a great risk of cancer death. Therefore, a close follow-up and an additional treatment are desirable.

BACKGROUND Postoperative delayed bleeding (PDB) after gastric endoscopic submucosal dissection (ESD) is the most common adverse event in patients receiving antithrombotics even with second-look endoscopy. Moreover, with the increasing prevalence of cardiovascular and cerebrovascular diseases in an aging population with associated lifestyle-related diseases, an increasing number of patients receive antithrombotics. Several attempts have been made to prevent PDB in aging population; however, a consensus has yet to be reached. AIM To examine the efficacy of third-look endoscopy (TLE) for PDB prevention. METHODS One hundred patients with early gastric neoplasms receiving antithrombotics were prospectively enrolled and subjected to ESD with TLE between February 2017 and July 2019. The primary endpoint was PDB rate, which was compared with our preset threshold. Furthermore, we divided the bleeding period into early-and late-onset PDB (E-PDB and L-PDB, respectively) and analyzed its rate. As a secondary analysis, we compared PDB rates with those of a historical control group, using propensity score matching, and calculated the PDB rates per antithrombotic agent use in each group. RESULTS In total, 96 patients and 114 specimens were finally evaluated. The overall PDB rate was 7.9% (9/114) [90%CI: 4.7-13.1, P = 0.005], while the late-and early-onset PDB rates (L-PDB and E-PDB) were 5.3% [90%CI: 2.7-9.9, P < 0.0001] and 2.6% [90%CI: 1.1-6.4, P = 0.51], respectively. Propensity score matching generated 58 matched pairs for TLE and control groups. No differences were found in overall PDB incidence (10.3% vs 20.7%, P = 0.12), whereas L-PDB occurrence significantly differed (5.2% vs 17.2%, P = 0.04) between groups. Considering antithrombotics’ use, the overall PDB rate was higher for direct oral anticoagulants and multiple antithrombotics in the control group, while L-PDB incidence was lower in the TLE group for these agents (8.7% vs 23.1% and 5.0% vs 29.4%, respectively). CONCLUSION TLE for gastric ESD reduces overall PDB, and especially L-PDB incidence, among patients receiving antithrombotics.

OBJECTIVES Clinicopathologic characteristics and treatment outcomes of mixed-histological-type (MT) early gastric cancers (EGCs) treated with endoscopic submucosal dissection (ESD) have not been sufficiently elucidated. We aimed to clarify them in comparison with pure-histological-type EGCs. METHODS We used 3022 consecutive EGCs in 2281 patients treated with ESD from our prospectively maintained database. Cases were stratified into four groups according to the final diagnosis of the resected specimen are as follows: 2780 pure differentiated-type (DT), 127 DT-predominant MT (D-MT), 87 pure undifferentiated-type (UDT), and 28 UDT-predominant MT (U-MT). Clinicopathologic characteristics and treatment outcome were compared between pure DT and D-MT, and between pure UDT and U-MT separately. Risk factors for deep submucosal invasion, lymphovascular invasion, and a final diagnosis of MT were identified using multivariate analysis. RESULTS Both D-MT (41.7 vs. 92.0%; P

Objective This study compared the clinicopathological features and treatment outcomes of patients with primary early gastric cancers (EGCs) who had undergone Helicobacter pylori eradication and endoscopic submucosal dissection (ESD) with those of patients who were H. pylori-positive and had undergone ESD. Additionally, we investigated the incidence of metachronous cancer in these patients. Methods We retrospectively analyzed 1849 EGCs in 1407 patients who underwent ESD whom 201 primary EGCs were detected after H. pylori eradication (eradication group) and 1648 primary EGCs were detected in patients infected with H. pylori (infection group). We evaluated the clinicopathological features and treatment outcomes of the first ESD. We next divided 938 patients whose follow-up periods were >1 year into three groups, an eradication group (n = 61), an infection group (n = 562), and an eradication after ESD group (n = 315). The groups' cumulative metachronous occurrence rates were determined. Results The eradication group's median tumor size was significantly smaller, and the tumors were significantly more likely to be flat/depressed than those in the infection group. The groups did not differ regarding the treatment outcomes. The cumulative incidence of metachronous cancer was significantly higher in the eradication group than in the eradication after ESD group (P = 0.0454) and in the infection group than in the eradication after ESD group (P = 0.0233). Conclusion The treatment outcomes for EGC in the eradication group were favorable. The higher incidence of metachronous cancer in the eradication group suggests that careful endoscopic follow-up examinations are required.

Clinicopathological features of early gastric cancers arising in Helicobacter pylori uninfected patients

Aim A Japanese individual with schizophrenia harboring a novel exonic deletion in RELN was recently identified by genome-wide copy-number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether Reln deficiency is associated with the pathogenesis of schizophrenia. Methods A mouse line with a novel RELN exonic deletion (Reln-del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed. Results The phenotype of homozygous Reln-del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln-del mice was approximately half of that in wild-type mice. Conversely, behavioral analyses in heterozygous Reln-del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three-chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln-del mice. Conclusion The present results in novel Reln-del mice modeled after our patient with a novel exonic deletion in RELN are expected to contribute to the development of reelin-based therapies for schizophrenia.

Background In chronic lateral ankle instability (CLAI), the instability of the ankle joint results in repeated microtrauma to the articular cartilage. How the lesion condition or stage is affected by the presence of lateral instability in medial osteochondral lesions of the talus (OLT) is unclear. We aimed to examine whether CLAI is associated with the size and staging of medial OLT on radiographs, magnetic resonance (MR) images, and arthroscopy. Methods Forty-five patients with medial OLTs in 45 ankles were reviewed. Radiographs were assessed for damage and lesion classification. The tibio-talar tilting angle (TTA) was measured. The patients were divided into two groups: the CLAI group and the stable group. The lesion classification on radiographs, MR images, and arthroscopy, and size on MR images were statistically compared. Results The CLAI group had a mean TTA of 8.15 ± 3.41°, whereas the stable group had a mean TTA of 2.24 ± 1.64°. The CLAI group had a lower clinical score than the stable group at the initial visit to our clinic. The CLAI group presented with lesions of significantly shorter longitudinal and transverse diameters. Stages of medial OLT on radiographs, MR images, and arthroscopic evaluation were earlier in the CLAI group than those in the stable group. Conclusions Patients with CLAI presented in the early stages of OLT and had significantly smaller lesions than those without CLAI. The patients without CLAI may be selected for surgery at an early phase.

Developments of a two directional beam steering electron cyclotron heating/current drive launcher for JT-60SA have been progressed based on a linear motion antenna concept. A full-scale (˜7 m) mock-up of the mirror steering structure with two kinds of bellows structures and an in-vessel support structure has been fabricated and tested in vacuum successfully. The support structure consists of a pair of angular ball bearings made of Si3N4 for rotational motion and a linear guide assembled by a rail and a housing made of non-magnetic stainless steel and Si3N4 balls. Solid lubricant has been used for the linear guide and it results in the improvement of the life time by a factor greater than 10 with respect to the case without lubricant. Considering that the mock-up test results satisfied the requirements for the bellows and support structures (reliable 40 cm linear movement, 105 cycles and angular rotation 30°, 104 cycles), the final design of the launcher is underway targeting the start of its fabrication.

Introduction Calcaneal pitch angle and Meary’s angle are commonly used to assess longitudinal foot arches on lateral-view radiographs. However, the methods used to obtain the talar, first metatarsal, calcaneal, and plantar axes differ across multiple reports, and no study has evaluated the reproducibility of these approaches. The aim of this study was to determine the most reproducible methods for radiographically evaluating longitudinal axes. Methods Standing radiographic images of 40 feet from 21 consecutive outpatients were obtained to measure longitudinal axes of the talus, first metatarsal, calcaneus and plantar surface, which were defined using six, five, four and three different methods, respectively, selected from previous reports. Intraobserver and interobserver correlation coefficients were calculated. Results The best intraobserver and interobserver correlation coefficients for the talar, first metatarsal, and calcaneal axes were obtained using methods involving a line bisecting the angle formed by the lines tangential to the superior and inferior margins of the talus, a line connecting the centre of the first metatarsal head and the midpoint of the visualized base of the first metatarsal, and a line drawn tangential to the inferior surface of the calcaneus, respectively. For the plantar axis, a method that used the horizontal plane (as a reference axis) was regarded as the best approach, although intraobserver and interobserver correlation coefficients could not be calculated because all values were zero. Conclusions The aforementioned methods were considered to be optimal for the radiographic assessment of longitudinal foot arches. This study could contribute to more accurate assessments of foot deformities.

Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.

BACKGROUND AND AIM Endoscopic resection is feasible for superficial tumors in patients with ulcerative colitis; however, endoscopic resection options have not been evaluated comprehensively. We evaluated the efficacy and safety of endoscopic submucosal dissection and endoscopic mucosal resection, and decision making regarding endoscopic resection options for patients with ulcerative colitis. METHODS Endoscopically treated tumors from patients with ulcerative colitis were analyzed retrospectively. We evaluated en bloc and R0 resection, adverse events, local tumor recurrence, and metachronous lesion occurrence rates. RESULTS We examined 102 tumors (mean size, 12 mm; non-polypoid, 55 tumors) from 74 patients with ulcerative colitis, of whom, 39 and 63 underwent endoscopic submucosal dissection and endoscopic mucosal resection, respectively. The R0 resection rate was significantly higher for endoscopic submucosal dissection (97%) than for endoscopic mucosal resection (80%) (P = 0.0015). For 11-20-mm tumors, the R0 resection rate was significantly higher for endoscopic submucosal dissection (94%) than for endoscopic mucosal resection (55%) (P = 0.0027); the endoscopic submucosal dissection and endoscopic mucosal resection R0 rates did not differ for ≤ 10-mm tumors. The non-polypoid tumor R0 resection rates were significantly higher for endoscopic submucosal dissection (100%) than for endoscopic mucosal resection (65%) (P

BACKGROUND The undifferentiated-type (UDT) component profoundly affects the clinical course of early gastric cancers (EGCs). However, an accurate preoperative diagnosis of the histological types is unsatisfactory. To date, few studies have investigated whether the UDT component within mixed-histological-type (MT) EGCs can be recognized preoperatively. AIM To clarify the histopathological characteristics of the endoscopically-resected MT EGCs for investigating whether the UDT component could be recognized preoperatively. METHODS This was a single-center retrospective study. First, we attempted to clarify the histopathological characteristics of the endoscopically-resected MT EGCs with emphasis on the UDT component. Histopathological examination investigated each lesion’s UDT component: (1) Whole mucosal layer occupation of the UDT component; (2) UDT component exposure to the surface of the mucosa; and (3) existence of a clear border between the differentiated-type and UDT components. Then, preoperative endoscopic images with magnifying endoscopy with narrow-band imaging (ME-NBI) were examined to identify whether the endoscopic UDT component finding was recognizable within the area where it was present in the histopathological examination. The preoperative biopsy results and comparative relationships between endoscopic and histopathological findings were also examined. RESULTS In the histopathological examination, the whole mucosal layer occupation of the UDT component and exposure of the UDT component to the mucosal surface were observed in 67.3% (33/49) and 79.6% (39/49) of samples, respectively. A clear distinction of the border between the differentiated-type and UDT components could not be drawn in 65.3% (32/49) of MT lesions. In the endoscopic examination, the preoperative endoscopic images showed that only 24.5% (12/49) of MT EGCs revealed the UDT component within the area where it was present histopathologically. Histopathological UDT predominance was the single significant factor associated with the presence of the endoscopic UDT component finding (61.5% vs 11.1%, P = 0.0009). Only 26.5% (13/49) of the lesions were diagnosed from the pretreatment biopsy as having a UDT component. Combined results of the pretreatment biopsy and ME-NBI showed the preoperative presence of the UDT component in 40.8% (20/49) of MT EGCs. CONCLUSION Recognition of a UDT component within MT EGCs is difficult even when pretreatment biopsy and ME-NBI are combined. Endoscopic resection plays a significant role in both treatment and diagnosis.

A TE31,11 mode gyrotron has being developed to improve the output power for the ITER electron cyclotron (EC) system. Strong mode competition having counter-rotating modes in both the high and/or low field sides is, in general, the typical issue for high order mode oscillations. Active anode voltage control and beam radius control were introduced to overcome this issue and obtain stable 1 MW oscillation. The TE31,11 mode was oscillated in a hard-self excitation region and the efficiency was improved up to 50%. Long pulse operation of output power of 1 MW with total efficiency of 46% for 230 s was also performed. Oscillations of over–1 MW power of 1.1 MW and 1.2 MW for 2 s pulse were achieved.

A new fast directional switch for high power millimeter waves without frequency modulation was proposed. The principle is a triangle ring resonator of circular corrugated waveguides with a vibrating reflector. The switching frequency was obtained up to 300 Hz by a single vibration reflector. The deformed waveforms of the output powers were observed at large amplitude vibrations of a reflector.

For successful tokamak operation with adequate mode selection of the electron cyclotron wave, launching wave polarization should be accurately controlled. In this study, a new method is proposed to efficiently identify the response of polarizers using a geometric approach in the Stokes space, focusing on the fact that polarization can be represented as a vector in Stokes space and the response of a polarizer can be described as a rotation. The proposed methods are intended (i) to determine the response parameters of a polarizer or (ii) to determine the response parameters of two polarizers simultaneously. A simple measurement system was prepared to observe the polarizers’ output polarization in the 110/138 GHz transmission line. The determined response parameters of two polarizers can reproduce measured polarizations with sufficient accuracy above 99%. The direction of an output polarization circularity, the only feature of a polarization that could not be directly known from the prepared measurement, could also be determined with sufficient accuracy.

Based on the latest optical design of ITER ECH&CD equatorial launcher, the power absorption at the plasma breakdown is evaluated with considering reflections by the 3-dimensional first wall structure. The beam diffusion is simulated by a bunch of spreading rays and the reflections on the first wall are analyzed for each ray. The power absorption is evaluated by the optical thickness when the rays pass across the resonant surface. The frequency of EC wave is 170 GHz and the density of concern is from 2.5 × 10 15 m − 3 . As a result, at least 2 MW is absorbed out of 6.7 MW injection from the Top row in the case of fundamental O-mode injection even at the breakdown. In the case of 2nd harmonic X-mode injection, the total absorbing power is 200 kW at the electron density of 10 18 m − 3 and the electron temperature of 5 eV, which is proportional to the electron density and the electron temperature. It is found that a certain injection angle should be excluded in order to prevent intense stray RF injection up to 4 MW propagating toward specific ports within a few reflections.

Background and Aims Colorectal neoplasms with submucosal fibrosis are the most challenging targets of endoscopic resection. Water pressure endoscopic submucosal dissection (WP-ESD) is a recently introduced procedure that has several advantages over conventional endoscopic submucosal dissection (C-ESD). This study aimed to assess the efficacy and safety of WP-ESD for fibrotic colorectal neoplasms. Methods This retrospective observational study investigated 133 colorectal neoplasms expected to have submucosal fibrosis that were resected by WP-ESD or C-ESD between April 2012 and April 2020. Eighty-seven lesions after endoscopic or surgical treatment, 18 with biopsy scar with fold convergence and 28 in patients with ulcerative colitis, were included. The differences in treatment outcomes, including procedure time and adverse event proportions, between the WP-ESD and C-ESD groups were analyzed. The clinical course after perforation using WP-ESD was also evaluated, including postprocedural multidetector CT findings obtained immediately after WP-ESD. Results Severe submucosal fibrosis was observed in 96 lesions (72.2%). The median procedure time was significantly shorter in the WP-ESD group than in the C-ESD group (43.5 minutes [interquartile range {IQR}, 32.8-73] vs 72 minutes [IQR, 45-105]; P = .0041). The multivariate analysis revealed WP-ESD as an independent factor for a short procedure time (odds ratio, 2.90; 95% confidence interval, 1.28-6.55). The proportions of post-ESD electrocoagulation syndrome (11.6% vs 13.1%) and perforation (20.4% vs 22.8%) were similar between the groups. Four of 11 patients with perforation who underwent WP-ESD showed fluid collection on postprocedural multidetector CT images. Conclusions WP-ESD can shorten procedure time for treating fibrotic colorectal neoplasms.

A diplexer to be used as a fast switching device of high power millimeter wave for an electron cyclotron current drive system has been developed. The operation frequency of the device is tunable by controlling the thermal expansion of the cavity using a precision chiller. The tunable range of the diplexer is about 225 MHz at the frequency band of 170 GHz. The temperature dependence of the resonant frequency shift in the ring resonator diplexer is −3.4 to −3.9 MHz/K, which agrees with the theoretical prediction. The switching operation is confirmed up to rf power of 260 kW, a pulse duration of 100 ms, and a frequency of 170 GHz.

The ITER EC system includes both an equatorial port launcher and upper port launchers as RF power injection devices, The waveguide switch in the transmission line (TL) is used to select the operating launcher. Its operation is required even during plasma operation, primarily for the mid-pulse switch operation. Changing the waveguide switch requires that the gyrotron stop RF power during the switch operation since the direction is changed by mechanical movement of the mirror position which takes a few seconds. Since the ITER EC system is based on a multi-subsystem concept, each subsystem has its own subsystem control unit (SCU). The EC main controller supervises all subsystem controllers. Hence, cooperative operation requires the sharing of the information of both RF power status and switch status between the gyrotron SCU and TL SCU via the main controller. Since the design of the inter-subsystem control scheme is a key issue for ITER EC system control, its evaluation is required. At QST, the gyrotron and ITER-relevant TL test stand were utilized for demonstration of mid-pulse switch operation. For this purpose, SCUs for each subsystem and the main controller were developed using the ITER-relevant control system. The operation of the mechanical switch during gyrotron pulse was demonstrated. During the 150 s operation of the high power gyrotron at 400 kW level, the waveguide switch in the TL was operated to change the direction of RF power. The time duration for the switch operation with inter-subsystem control scheme took 1.5 s in total. The synchronizing of RF power suspend and resume with switch motion has therefore been realized, and RF power direction control during the gyrotron operation was successfully demonstrated.

Although magnifying endoscopy with narrow-band imaging (ME-NBI) can help identify the horizontal margin (HM) of early gastric cancer (EGC), little is known about the factors that can clarify the HM by using ME-NBI. We aimed to characterize the pathological features of lesions in which the HM was identified using ME-NBI. The HMs of 639 differentiated-type EGCs treated with endoscopic submucosal dissection or surgery were analyzed using conventional endoscopy and ME-NBI. The number and width of the intervening parts (IP) and the number, width, and depth of the subepithelial capillaries (SEC) in cancerous and noncancerous areas were measured. In 13 lesions (2.0%), more than 90% of the HM was not recognized with conventional endoscopy, but 11 of these lesions were detectable with ME-NBI (NBI group). The HMs of the other 626 lesions were mostly recognized using conventional endoscopy (WLI/CE group). In the NBI group, the IP width, standard deviation (SD), and number of IPs did not significantly differ between the cancerous and noncancerous areas. However, the SEC number was significantly larger and the depth was shallower in cancerous areas. In the WLI/CE group, the IP width and SD were significantly larger, but the IP number was significantly smaller in cancerous areas. The SEC depth was significantly shallower in cancerous areas. Differences of IP width, SD, and IP number may be factors for identifying HMs with conventional endoscopy. Because NBI can better visualize vessel structures, the increased SEC number and shallow SECs may clarify the HM.

The development of high-power gyrotrons needs matched loads with good performance capable of absorbing and measuring powers as high as 1 MW in the International Thermonuclear Experimental Reactor (ITER) and higher (up to two times) in the future devices, such as the DEMOnstrating fusion power reactor. At Istituto di Fisica del Plasma - Consiglio Nazionale delle Ricerche IFP-CNR (Milan), several spherical loads were developed, all with identical absorbing geometry but different heat removal systems for operations with pulselengths (PLs) from a few milliseconds to continuous wave (CW). A dummy load designed for 2-MW CW 170-GHz operations has been constructed in the frame of the development program of the European gyrotron for ITER. The first prototype hemisphere of this load, joined with an uncoated one, has been successfully tested with long pulses and under vacuum using the gyrotron for ITER of the National Institutes for Quantum and Radiological Science and Technology in Naka. The symmetry of the system is such that the equivalent power (EP) load of the absorbing (coated) hemisphere is doubled when the second one is reflective (uncoated), with an almost unchanged distribution with respect to a fully coated load. The tests demonstrate the capability of the IFP-CNR load to withstand and measure radiation at an EP in an excess of 1.5MW. Experiments involving gyrotron pulses with increasing power and PL have been performed in the load and are reported. The maximum EP load reached in the tests was $\approx 1.8$ MW for 15 s while the longest pulse was 300 s, at $\approx 1$ MW. During the experiments, the temperatures of either the load or the preload were monitored using thermocouples and multiple infrared cameras, while a pressure sensor and a hydrophone have been used for the monitoring of cavitation phenomena and water boiling in the cooling circuits. The results achieved in the tests are described in this paper.

BACKGROUND Persistent Helicobacter pylori (H. pylori) infection causes chronic inflammation, atrophy of the gastric mucosa, and a high risk of developing gastric cancer. In recent years, awareness of eradication therapy has increased in Japan. As H. pylori infections decrease, the proportion of gastric cancers arising from H. pylori uninfected gastric mucosa will increase. The emergence of gastric cancer arising in H. pylori uninfected patients though rarely reported, is a concern to be addressed and needs elucidation of its clinicopathological features. AIM To evaluate the clinicopathological features of early gastric cancer in H. pylori-uninfected patients. METHODS A total of 2462 patients with 3375 instances of early gastric cancers that were treated by endoscopic submucosal dissection were enrolled in our study between May 2000 and September 2019. Of these, 30 lesions in 30 patients were diagnosed as H. pylori-uninfected gastric cancer (HpUIGC). We defined a patient as H. pylori-uninfected using the following three criteria: (1) The patient did not receive treatment for H. pylori, which was determined by investigating medical records and conducting patient interviews; (2) Lack of endoscopic atrophy; and (3) The patient was negative for H. pylori after being tested at least twice using various diagnostic methods, including serum anti-H. pylori-IgG antibody, urease breath test, rapid urease test, and microscopic examination. RESULTS The frequency of HpUIGC was 1.2% (30/2462) for the patients in our study. The study included 19 males and 11 females with a mean age of 59 years. The location of the stomach lesions was divided into three sections; upper third (U), middle third (M), lower third (L). Of the 30 lesions, 15 were U, 1 was M, and 14 were L. Morphologically, 17 lesions were protruded and flat elevated type (0-I, 0-IIa, 0-IIa + IIc), and 13 lesions were flat and depressed type (0-IIb, 0-IIc). The median tumor diameter was 8 mm (range 2-98 mm). Histological analysis revealed that 22 lesions (73.3%) were differentiated type.The HpUIGC lesions were classified into fundic gland type adenocarcinoma (7 cases), foveolar type well-differentiated adenocarcinoma (8 cases), intestinal phenotype adenocarcinoma (7 cases), and pure signet-ring cell carcinoma (8 cases). Among 30 HpUIGCs, 24 lesions (80%) were limited to the mucosa; wherein, the remaining 6 lesions showed submucosal invasion. One of the submucosal invasive lesions showed more than 500 μm invasion. The mucin phenotype analysis identified 7 HpUIGC with intestinal phenotype and 23 with gastric phenotype. CONCLUSION We elucidated the clinicopathological characteristics of HpUIGC, revealing recognition not only undifferentiated-type but also differentiated-type. In addition, intestinal phenotype tumors were also observed and could be an important tip.

Background Endoscopic resection is recommended for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in diameter and confined to the submucosal layer, without lymph node or distant metastasis. However, the efficacy and safety of endoscopic submucosal dissection (ESD) for NAD-NET remains unclear. The aim of this study was to assess the short-term efficacy and safety and the long-term outcomes of ESD for NAD-NET. Methods Eight patients with 8 NAD-NETs who underwent ESD between 2015 and 2018 were included. The indications for ESD were: i) tumor ≤10 mm in diameter; ii) NET G1; iii) confined to the submucosal layer; and iv) without lymph node or distant metastasis. We retrospectively assessed the short- and long-term outcomes and safety. Results The median patient age was 69 (48-76) years. All tumors were located in the duodenal bulb and showed 0-Is morphology. The median size was 6.4 (3-9.3) mm. The rates of en bloc resection, histologically free horizontal and vertical margins, and curative resection were 100%, 88%, and 88%, respectively. Intraoperative and postoperative perforation each occurred in 13% of patients, all of whom were treated conservatively and avoided emergent surgery. Delayed bleeding was not observed. No local, lymph node or distant recurrence was observed during a median follow-up period of 34 (18.5-62.5) months. Conclusions The rates of en bloc and curative resection, and histologically free margins were sufficiently high. Although intraoperative and postoperative perforations occurred, emergency surgery was not needed. The results show that ESD is an efficacious and safe treatment for NAD-NET.

Although colorectal endoscopic submucosal dissection (ESD) has become a standardized procedure worldwide, the difficulty of the procedure is well known. However, there have been no studies assessing the causes of treatment interruption. The present study aimed to evaluate the factors involved in the interruption of colorectal ESD. We retrospectively analyzed 1116 consecutive superficial colorectal neoplasms of 1012 patients who were treated with ESD between August 2008 and September 2018. The clinicopathological characteristics and treatment outcomes were analyzed. Interrupted ESD was reported in 14 lesions (1.3%) of the total study population. Univariate analysis of clinical characteristics indicated that age, 0–I macroscopic-type tumor, and tumor location on the left side colon were risk factors for interruption. Multivariate analysis revealed that 0–I macroscopic-type tumor was the sole preoperative independent risk factor for interruption. Univariate analysis revealed that the presence of muscle-retracting sign (MRS), deep submucosal tumor invasion, and intermediate invasive growth pattern represented the etiology of interruption. Multivariate analysis indicated that MRS can be a sole key sign for the interruption. Additionally, the resectability and curability of 0–I type tumors were significantly inferior to those of predominantly lateral spreading tumors. Observations of 0–I macroscopic-type tumors, MRS, and submucosal deep invasion were significantly more frequent in interrupted cases. Conventional endoscopic images without magnification endoscopy were more associated with interruption than irregular surfaces or Vi pit patterns in cases with 0–I type tumors. ESD of 0–I type tumors is highly disruptive, and undiagnosable submucosal infiltration can reduce the curability.

The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBα and REV-ERBβ are involved in the cell-autonomous circadian transcriptional/translational feedback loops as transcriptional repressors. A number of studies have also demonstrated a pivotal role of REV-ERBs in regulation of metabolic, neuronal, and inflammatory functions including bile acid metabolism, lipid metabolism, and production of inflammatory cytokines. Given the multifunctional role of REV-ERBs, it is important to elucidate the mechanism through which REV-ERBs exert their functions. To this end, we established a Rev-erbα/Rev-erbβ double-knockout mouse embryonic stem (ES) cell model and analyzed the circadian clock and clock-controlled output gene expressions. A comprehensive mRNA-seq analysis revealed that the double knockout of both Rev-erbα and Rev-erbβ does not abrogate expression rhythms of E-box-regulated core clock genes but drastically changes a diverse set of other rhythmically-expressed output genes. Of note, REV-ERBα/β deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study highlight the relevance of REV-ERBs as pivotal output mediators of the mammalian circadian clock.

Stomach cancer rarely develops in patients with familial adenomatous polyposis (FAP), and Helicobacter pylori infection may increase the risk of FAP-related gastric cancer. We describe the case of a 64-year-old woman who developed multiple synchronous early gastric cancers without H. pylori infection. Nine cancer lesions were successfully treated by endoscopic submucosal dissection. An immunohistochemical analysis revealed that the tumors were positive for mucin (MUC)2, MUC6, and CDX2, but negative for MUC5AC, suggesting that the tumors were gastrointestinal mixed type. Periodical endoscopic surveillance is important for the detection of cancers at an early stage.