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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.

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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.

量子科学技術研究開発機構では，国際熱核融合実験炉 ITER 用ジャイロトロンの研究開発を進めてきた．ITER で期待される 1 MW 出力での繰り返し連続運転に対して，空胴共振器の熱負荷を低減させた高次数 TE31,11モードのジャイロトロン試作機を開発した．この開発研究では，TE31,11モードの発振を阻害する不要な周波数の異なるモードの存在が明らかとなり，その発振抑制を実現する運転手法を開発し，安定した 1 MW 出力の定常運転を実証した．この成果をもとに，ITER ジャイロトロン実機の製作を開始し，２機のジャイロトロンの性能確認試験を完了させた．双方ともに出力 1 MW かつ効率５０％ の３００秒定常運転，0.8 MW 以上の６０秒間 5 kHz 出力変調運転，出力 1 MW／３００秒 の２０ショット高繰り返し運転にて運転信頼度９０％以上を達成し，ITER の要求条件を満足した．

量研では、全8機のITERジャイロトロン実機の製作を完了し、5機の性能試験を実施し、出力1MW/効率50％/300秒発振の高繰り返し運転を90%以上の運転信頼度で成功させている。また、ITERの幅広い運転領域に対応するために複数周波数ジャイロトロンの開発研究も進めている。開発試験では、狙い通りに170GHzと137GHz発振では1MW/300秒、104GHz発振では0.9MW/300秒という単一ジャイロトロンによる3周波数での高出力連続運転を成功させた。, 核融合エネルギー連合講演会

ITERをはじめとする大型トカマク装置で運用される1MW級電子サイクロトロン加熱電流駆動システムでは、あらゆる磁場配位に対して入射モード(O/X)を制御する目的で低損失のマイターベンド型偏波器が用いられる。本研究では、偏波器の応答関数を抽出し、偏波器を擁する伝送路から真空容器への出力偏波の計算手法を確立した。実際の伝送系を用いて検証を実施した結果、計算と実測偏波の差は十分小さく、モード純度98.5%以上を達成できることが分かった。本手法はITER水平ランチャー内部の可動ミラーの反射角を考慮した偏波計算にも適用できる。, 第14回核融合エネルギー連合講演会

JT-60SAの初期研究フェーズで用いられるECH/CD装置（138GHz/110GHz/82GHz）について伝送路のレイアウト設計と評価を行った。新たに設計したレイアウトでの伝送効率を評価するために、これまで考慮されてこなかった、伝送路を構成する導波管の接合部におけるミスアライメントによる傾きや、伝搬するミリ波の偏波角も考慮した、従来よりも現実に即した伝送損失の計算を行ってきた。今回、本計算の妥当性を評価するため、既存の伝送路を使用して、伝送効率を測定し、計算値と比較した。その結果、計算結果が実験結果とよく一致し、計算が現実の伝送効率をよく表すことが明らかとなった。新レイアウトの伝送効率は本計算によると、入射ポートまでの距離の長い系統で84%、より短距離の系統では87%（いずれも110GHz）であり、目標値である伝送効率80%以上を見込めるレイアウトとなっていることが分かった。また、本伝送路では2台の偏波器を用いた偏波制御を行うが、伝送路上に配置する偏波器の位置に依存して3周波数の一部に生成できない偏波が存在する。そこで、新レイアウト上での偏波器の位置に対する出力可能な偏波状態を総当たりで計算し、プラズマ実験で必要となる偏波状態と比較、その差が最小となる偏波器の最適な位置を求めた。これにより、新レイアウトにおいて3周波数いずれもプラズマ入射時のモード純度99%以上が達成可能な偏波器の配置に成功した。, 第14回核融合エネルギー連合講演会

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.

A research activity in the Institute for Plasma Science and Technology of National Research Council (ISTP-CNR, Italy, former IFP-CNR) and in L.T. Calcoli (LTC, Italy) is aimed at the design and construction of calorimetric loads for absorption and measurement of high power millimeter-waves in the electron cyclotron frequency range. Recently, two CW 170 GHz loads, one for the European ITER gyrotron test facility and the other for the FALCON test- bed, have been installed at the Swiss Plasma Center (SPC, Switzerland). One short pulse (2 s) load for 1 MW, designed and optimised to operate at two different frequencies (84 GHz and 126 GHz), was provided for testing and conditioning two new dual-frequency gyrotrons for the Tokamak à Configuration Variable (TCV, Switzerland). Two additional CW loads, designed for absorbing powers higher than 1 MW, have been delivered to the National Institutes for Quantum and Radiological Science and Technology (QST, Japan) and exploited for the acceptance tests and the conditioning of the prototype of the Japanese ITER gyrotron. The present status and the most recent experimental results achieved in the framework of this development activity are reported in the paper.

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.

On JT-60SA an integrated commissioning has been conducting. During the integrated commissioning phase, measurements of the transmission efficiency and the conditioning of the ECRF TLs have been carried out. In order to evaluate the transmission efficiency, the RF power was calorimetrically measured at the dummy loads (DLs) installed at two different positions close to the gyrotron and the end of each TL. As a result, the transmission efficiency was evaluated to be 70% for Unit 1, and 81-85% for three frequencies of Unit 2. The commissioning and conditioning of the ECRF systems has also been conducted. The progress of the commissioning is also reported., Korea-Japan Workshop on Physics and Technology of Heating and Current Drive

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.

JT-60SAの統合コミッショニング期において使用される二系統のECRF装置について、ジャイロトロンを用いた高パワーでの伝送効率の評価を行った。また、通常のコンディショニングに使用しているジャイロトロン近傍のダミーロード位置、および伝送効率測定に使用しているランチャー直近の二カ所に加え、MOU出口と伝送路上二カ所の計五カ所においても仮設の短パルスダミーロードを用いてパワー測定を行った。本会議ではパワー測定および伝送路中の各要素における損失評価の結果について報告する。, 第38回 プラズマ・核融合学会年会