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DOI： 10.1002/jcb.10295

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DOI： 10.1038/sj.bjp.0703141

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DOI： 10.1038/sj.bjp.0703737

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DOI： 10.1038/sj.bjp.0702821

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DOI： 10.1055/a-2371-0911

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DOI： 10.1055/a-2291-9050

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DOI： 10.1055/a-2351-3985

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Publisher：南江堂  

DOI： 10.15106/j_naika134_603

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The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and antidiarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogues, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.

DOI： 10.1159/000541121

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EP4 prostanoid receptor (EP4R) contributes to the intestinal epithelial Cl- secretion, and inhibition of prostaglandin E (PGE) production by non-steroidal anti-inflammatory drugs (NSAIDs) plays a central role in NSAID-induced enteropathy. Although M3 muscarinic acetylcholine receptor (M3R) also contributes to the intestinal epithelial Cl- secretion, it remains unclear whether M3R is involved in NSAID-induced enteropathy due to a lack of selective agents. The present study explored how M3R is involved in the regulation of the intestinal epithelial Cl- secretion and its pathophysiological role in NSAID-induced enteropathy. Using the novel highly-selective M3 positive allosteric modulator PAM-369 that we recently developed, we evaluated the role of M3R in the intestinal epithelial secretion ex vivo by measuring the short circuit current (Isc) of intestinal epithelium with a Ussing chamber system and examined whether or not M3R protects against small intestinal injury in indomethacin-treated mice. Both the PGE1 derivative misoprostol and carbachol similarly increased the Isc in a concentration-dependent manner. The Isc increases were abolished either by receptor antagonists (an EP4R antagonist and a M3R antagonist, respectively) or by removal of extracellular Cl-. PAM-369 enhanced the carbachol-induced Isc by potentiating M3R, which could contribute to enhanced intestinal epithelial secretion. Treatment with PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. Importantly, the M3R expression was significantly up-regulated, and PAM-369 potentiation of M3R was augmented in indomethacin-treated mice compared to untreated mice. These findings show that M3R plays a role in maintaining the intestinal epithelial secretion, which could contribute to protection against indomethacin-induced small intestinal injury. M3R is a promising target for treating or preventing NSAID-induced enteropathy. KEY MESSAGES: PAM-369, the M3 positive allosteric modulator, was used to potentiate M3R. PAM-369 enhanced carbachol-induced Isc in mouse ileum. PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. M3R is a promising target for treating or preventing NSAID-induced enteropathy.

DOI： 10.1007/s00109-024-02474-0

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In July 2023 the Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced frequency of bowel movement frequency type or defecation difficulty type. The first line of treatment includes improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicine, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide.

DOI： 10.1159/000540912

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BACKGROUND: The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population. METHODS: Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year. RESULTS: A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1-3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1 cm, 0.026 (0.011-0.054)%/year for 1-3 cm, and 0.58 (0.042-2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively. CONCLUSIONS: By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE.

DOI： 10.1007/s00535-024-02139-2

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Language：Japanese   Publisher：(株)文光堂  

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DOI： 10.1111/den.14744

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

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食道平滑筋収縮の変化および関連する炎症性反応について検討することによりアカラシアの病態を明らかにし、アカラシアの進展における食道細菌叢の意義を評価した。経口的内視鏡的筋層切開術を施行したII型アカラシア症例から得た食道粘膜および下部食道括約筋(LES)標本を解析した。患者由来の食道調整培養液をマウス食道に投与し、食道内環境がアカラシアと関連するか否かについて検討した。安静時および刺激時における対照群のLESでは、20-kDaミオシン軽鎖(LC20)の約30%がリン酸化されていた。アカラシア症例では状況に関わらずLC20のリン酸化は10%未満であった。アカラシアにおける低リン酸化は、ミオシンリン酸化阻害蛋白質CPI-17の発現低下と関連していた。IL-17A、IL-17F、IL-22、IL-23Aを含む関連サイトカインは、アカラシアでは発現が増加していた。食道細菌叢のα-Diversity指数、およびActinomycesおよびDialisterを含む数種類の細菌の割合がアカラシアで増加していた。ActinomycesレベルはIL-23Aレベルと正の相関が認められ、DialisterレベルはIL-17A、IL-17F、IL-22レベルと正の相関が認められた。マウスにおいて、食道IL-17F値は調整培地の経口投与後に増加した。

Publisher：南江堂  

DOI： 10.15106/j_naika133_846

CiNii Research

Language：Japanese   Publisher：(株)南江堂  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J00974&link_issn=&doc_id=20240416090103&doc_link_id=issn%3D0022-1961%26volume%3D133%26issue%3D4%26spage%3D846&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D133%26issue%3D4%26spage%3D846&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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BACKGROUND: In gastric solid-type poorly differentiated adenocarcinoma (PDA), the role of microsatellite instability and immune escape mechanism remains unclear. The current study aimed to elucidate the clinical significance of mismatch repair (MMR) status, genome profile, C-X-C motif chemokine receptor 2 (CXCR2) expression, and myeloid-derived suppressor cell (MDSC) infiltration in solid-type PDA. METHODS: In total, 102 primary solid-type PDA cases were retrieved, and classified into 46 deficient-MMR (dMMR) and 56 proficient-MMR (pMMR) cases based on immunohistochemistry (IHC) and polymerase chain reaction-based molecular testing results. The mRNA expression profiles (NanoString nCounter Assay) of stage-matched dMMR (n = 6) and pMMR (n = 6) cases were examined. The CXCR2 expression and MDSC infiltration (CD11b- and CD33-positive cells) were investigated via IHC in all solid-type PDA cases. RESULTS: mRNA analysis revealed several differentially expressed genes and differences in biological behavior between the dMMR (n = 46) and pMMR (n = 56) groups. In the multivariate analysis, the dMMR status was significantly associated with a longer disease-free survival (hazard ratio = 5.152, p = 0.002) and overall survival (OS) (hazard ratio = 5.050, p = 0.005). CXCR2-high expression was significantly correlated with a shorter OS in the dMMR group (p = 0.018). A high infiltration of CD11b- and CD33-positive cells was significantly correlated with a shorter OS in the pMMR group (p = 0.022, 0.016, respectively). CONCLUSIONS: dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.

DOI： 10.1007/s10120-024-01474-w

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BACKGROUND: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. METHODS: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. RESULTS: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. CONCLUSIONS: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia.

DOI： 10.1007/s00535-024-02088-w

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

胃食道逆流症(GERD)は病的な酸逆流によって惹起される病態であるが、難治性GERDでは食道知覚過敏や食道運動異常症(EMDs)を考慮した病態評価が必要である。今回、高齢者ボノプラザン(P-CAB)抵抗性GERDの特徴を明らかにするため、75歳以上の高齢者20例と非高齢者51例の食道生理機能検査の結果を比較検討した。高解像度食道内圧検査では非高齢者の41%は正常であったが、高齢者では正常例は認めなかった。食道内多チャンネルインピーダンス・pHモニタリング検査では、非高齢者ではNERD、逆流過敏性食道、機能性胸焼けの3疾患を認めたが、高齢者では逆流過敏性食道は認めなかった。高齢者P-CAB抵抗性GERDでは、EMDsが目立ち食道知覚過敏の影響は小さい可能性がある。(著者抄録)

Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

胃食道逆流症(GERD)は病的な酸逆流によって惹起される病態であるが、難治性GERDでは食道知覚過敏や食道運動異常症(EMDs)を考慮した病態評価が必要である。今回、高齢者ボノプラザン(P-CAB)抵抗性GERDの特徴を明らかにするため、75歳以上の高齢者20例と非高齢者51例の食道生理機能検査の結果を比較検討した。高解像度食道内圧検査では非高齢者の41%は正常であったが、高齢者では正常例は認めなかった。食道内多チャンネルインピーダンス・pHモニタリング検査では、非高齢者ではNERD、逆流過敏性食道、機能性胸焼けの3疾患を認めたが、高齢者では逆流過敏性食道は認めなかった。高齢者P-CAB抵抗性GERDでは、EMDsが目立ち食道知覚過敏の影響は小さい可能性がある。(著者抄録)

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Publisher：東京医学社  

DOI： 10.24479/endo.0000001233

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Language：Japanese   Publisher：(株)東京医学社  

＜文献概要＞はじめに 炎症性腸疾患(inflammatory bowel disease:IBD)は,Crohn病(Crohn's disease:CD)と潰瘍性大腸炎(ulcerative colitis:UC)の2疾患からなる原因不明の慢性炎症性腸疾患である。CDは口腔から肛門まで全消化管に非連続性の炎症や潰瘍をきたし,炎症が壁の全層性に及ぶため,しばしば狭窄や瘻孔,穿通などの消化管合併症を伴うことが特徴である。一方,UCは直腸から連続・びまん性に口側へ広がり原則的には大腸のみに炎症や潰瘍をきたすが上部消化管病変を併発することもある。ただ,炎症の首座は基本的に粘膜であるため,CDのように狭窄や瘻孔,穿通が少ないことが特徴である。本稿では,CDとUCの胃病変について,内視鏡所見や頻度,鑑別疾患,治療を中心に概説する。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J02312&link_issn=&doc_id=20240308110013&doc_link_id=10.24479%2Fendo.0000001233&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fendo.0000001233&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD. METHODS: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study. DISCUSSION: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures. TRIAL REGISTRATION: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

DOI： 10.1186/s13063-023-07852-6

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Language：Japanese   Publisher：(一社)日本消化管学会  

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DOI： 10.1055/a-2219-8130

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DOI： 10.1055/a-2072-5740

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OBJECTIVES: Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. METHODS: The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. RESULTS: Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P < 0.05). The esophageal Bil value and NNRE were significantly positively correlated (P = 0.031). The area under the receiver operating characteristic curve for the differential diagnosis of RH was 0.817. CONCLUSION: The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

DOI： 10.1111/den.14749

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DOI： 10.1055/a-2072-3383

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DOI： 10.1055/a-2155-7172

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DOI： 10.1055/a-2173-8010

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DOI： 10.1055/a-2199-3398

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Language：Japanese   Publisher：日本消化器病学会-九州支部  

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DOI： 10.24479/endo.0000001032

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Publisher：東京医学社  

DOI： 10.24479/endo.0000000999

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Publisher：東京医学社  

DOI： 10.24479/endo.0000001034

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Publisher：医歯薬出版(株)  

DOI： 10.32118/j01532.2024052923

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Publisher：日本メディカルセンター  

DOI： 10.19020/cg.0000002753

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BACKGROUND: We have determined that the impaired accommodation of the lower esophageal sphincter (LES) underlies the pathogenesis of esophagogastric junction outflow obstruction (EGJOO). We have also found that acotiamide may treat EGJOO by improving impaired LES accommodation. The effects of acotiamide in patients with EGJOO need to be further confirmed in a prospective study. METHODS: This trial is a multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of acotiamide (300 mg/day or 600 mg/day) with those of a placebo in the treatment of patients with EGJOO. The primary endpoint will be the proportion of patients who report an improvement in symptom of food sticking in the chest after 4 weeks of treatment period 1. The secondary endpoints will be the proportion of patients with normalized integrated relaxation pressure (IRP), the value of change from baseline in the distal contractile integral, basal LES pressure, EGJOO-quality of life score, Gastrointestinal Symptom Rating Scale, and the correlation between IRP and each symptom score. During the 2-year trial period, 42 patients from five institutions will be enrolled. DISCUSSION: This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia. TRIAL REGISTRATION: This study was approved by the Institutional Review Board (IRB) of Kyushu University Hospital as well as the local IRBs of the participating sites for clinical trials and registered in the Japan Registry of Clinical Trials (jRCT: 2071210072). The registration date is on October 11, 2021.

DOI： 10.1186/s13063-023-07468-w

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BACKGROUND AND AIM: Colonic self-expandable metallic stent (SEMS) placement enables preoperative total colonoscopy (TCS) in patients with obstructive colorectal cancer. Following SEMS placement, it is possible to assess the presence or absence of synchronous proximal colon cancers and perform preoperative endoscopic resection (ER) for neoplastic lesions proximal to the primary lesion. The objective of this study was to determine the usefulness and safety of preoperative TCS and ER after SEMS placement in patients with obstructive colorectal cancer. METHODS: From April 2016 to March 2022, we enrolled 100 patients with obstructive colorectal cancer who underwent SEMS placement, including 86 patients who underwent preoperative TCS after SEMS placement. Complications associated with preoperative TCS and ER after SEMS placement and the characteristics of the neoplastic lesions were assessed. RESULTS: The success rate of SEMS placement as bridge-to-surgery was 98.0%; six patients had associated complications. Preoperative TCS was performed 8 (range: 1-30) days after SEMS placement. Four patients had synchronous advanced cancers. Nine non-advanced synchronous cancers, 116 adenomas, and 18 sessile-serrated lesions were treated by preoperative TCS and ER after SEMS placement. No procedure-related complications, namely stent migration, bleeding, and perforation were observed. Forty-five patients underwent follow-up TCS 1 year after surgery. Only one patient with submucosal invasive cancer required a second surgery. CONCLUSIONS: Preoperative TCS and ER after SEMS placement was performed with no complications. This approach allows preoperative evaluation of the entire colon and the treatment of precancerous lesions. (240 words).

DOI： 10.1186/s12876-023-02888-z

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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＜文献概要＞胃食道逆流症(GERD)は「胃内容物の逆流により,不快な症状あるいは合併症を生じた状態」と定義される.日常診療で遭遇する,症状のみで食道粘膜傷害のない非びらん性逆流症(NERD)には,GERD以外の病態が紛れ込む.NERDと鑑別すべき重要な病態に食道運動機能障害(EMDs)があるが,EMDsの一つである無蠕動は高頻度にGERDを合併するため,疾患の理解を複雑化させている.最近,食道生理機能検査の発展に基づいてGERDの病態,鑑別疾患の理解が飛躍的に進歩した.本稿では,EMDsに起因するGERDと鑑別すべき関連諸疾患について概説する.治療抵抗性GERDに遭遇した際には食道生理機能検査を行い,機能性食道疾患,食道運動機能障害,行動障害などの鑑別を行うことが重要である.

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DOI： 10.24479/endo.0000000731

CiNii Research

Language：English  

We report a rare case of gastric cancer presenting with a gastrocolic fistula during ramucirumab and paclitaxel combination therapy that was successfully managed with colonic stenting. A 75-year-old man was admitted to our hospital with the chief complaint of melena. Esophagogastroduodenoscopy revealed a large ulcerated tumor in the lower stomach, judged by laparoscopy as unresectable (sT4bN1M0). After four cycles of first-line chemotherapy with S-1 plus oxaliplatin, the patient showed disease progression, and second-line therapy with ramucirumab and paclitaxel was started. At the end of the third cycle, the patient had gastric antral stenosis, which necessitated the placement of a gastroduodenal stent. When the patient complained of diarrhea 10 days later, esophagogastroduodenoscopy revealed a fistula between the greater curvature of the stomach and the transverse colon. The fistula was covered by double colonic stenting, with a covered metal stent placed within an uncovered metal stent, after which leakage from the stomach to the colon stopped.

DOI： 10.5946/ce.2022.117

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Language：Japanese   Publisher：(株)東京医学社  

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A 68-year-old man was referred to our hospital for endoscopic treatment of colon polyps detected at a local clinic. Colonoscopy revealed not only classical adenomatous polyps in the transverse and sigmoid colon but also an atypical pedunculated polyp in the terminal ileum with the head of the lesion moving back and forth through the ileocecal valve. Based on the endoscopic findings, the pedunculated polyp was diagnosed as a non-epithelial tumor of the ileum. However, traction-assisted endoscopic submucosal dissection was performed because of the high risk of intestinal intussusception or obstruction. Histopathological analysis of the resected specimen revealed that the pedunculated polyp was a non-inverted ileal pseudodiverticulum filled with feces. We report the first case of a feces-filled non-inverted pseudodiverticulum presenting as a pedunculated polyp successfully treated by traction-assisted endoscopic submucosal dissection.

DOI： 10.1002/deo2.139

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

症例は68歳男性で、近医で指摘された大腸ポリープの内視鏡的治療目的で紹介受診した。大腸内視鏡検査で、典型的な腺腫様ポリープを横行結腸およびS状結腸に認めたが、それに加えて、先端が回盲弁を行き来する終末回腸に非典型的な有茎性ポリープが認められた。内視鏡的所見から、この有茎性ポリープは回腸由来の非上皮性腫瘍と診断された。重積および閉塞のリスクがあると考えられたため、牽引補助下内視鏡的粘膜下層剥離術(ESD)を施行した。組織病理学的には、有茎性ポリープは非反転回腸偽憩室で、内部に便が充満していた。ポリープ先端に認められた陥凹部は憩室の開口部で、異所性胃粘膜、異所性膵組織は認められず、メッケル憩室も除外された。処置後の経過に特に問題はなく、処置後2日目に退院した。

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Gastroenterology  

DOI： 10.11405/nisshoshi.120.218

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND/AIMS: The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori (H. pylori) infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. METHODS: This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. RESULTS: For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p<0.001). Non-atrophic mucosa (C0 to C1) was observed in 96 of 177 (54.2%) patients with SNADETs and 112 of 531 (21.1%) control patients (p<0.001). Conditional logistic regression analysis revealed that non-atrophic gastric mucosa was an independent risk factor for SNADETs (odds ratio, 5.10; 95% confidence interval, 2.44-8.40; p<0.001). CONCLUSIONS: Non-atrophic gastric mucosa, regardless of H. pylori infection status, was a factor independently associated with SNADETs.

DOI： 10.5946/ce.2022.059

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/a-1982-3875

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DOI： 10.1016/j.cgh.2022.12.004

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We aimed to establish a novel murine model of autoimmune autonomic ganglionopathy (AAG), which represents autoimmune dysautonomia, associated with MHC class II to understand its pathomechanism and the pathogenicity of nicotinic acetylcholine receptor (nAChR) antibodies. The amino acid sequence of the mouse nAChRα3 protein was analyzed using an epitope prediction tool to predict the possible MHC class II binding mouse nAChRα3 peptides. We focused on two nAChRα3 peptides in the extracellular region, and experimental AAG (EAAG) was induced by immunization of C57BL/6 mice with these two different peptides. EAAG mice were examined both physiologically and histologically. Mice with EAAG generated nAChRα3 antibodies and exhibited autonomic dysfunction, including reduced heart rate, excessive fluctuations in systolic blood pressure, and intestinal transit slowing. Additionally, we observed skin lesions, such as alopecia and skin ulcers, in immunized mice. Neuronal cell density in the sympathetic cervical ganglia in immunized mice was significantly lower than that in control mice at the light microscopic level. We interpreted that active immunization of mice with nAChRα3 peptides causes autonomic dysfunction similar to human AAG induced by an antibody-mediated mechanism. We suggested a mechanism by which different HLA class II molecules might preferentially affect the nAChR-specific immune response, thus controlling diversification of the autoantibody response. Our novel murine model mimics AAG in humans and provides a useful tool to investigate its pathomechanism.

DOI： 10.3389/fnins.2022.1006923

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INTRODUCTION: Endoscopic ultrasound guided fine-needle aspiration/biopsy (EUS-FNA/B) is the gold standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs <20 mm is low. We developed a new diagnostic method to differentiate between gastrointestinal stromal tumor (GIST) and non-GIST by measuring high-frequency impedance (H-impedance) using an EUS-FNB needle. METHODS: The H-impedance of gastric epithelial neoplasms from 16 cases were measured using a conventional impedance probe to confirm whether H-impedance is clinically useful for assessing cell density (Study 1). The H-impedance values of exposed SELs from 25 cases using the conventional probe (Study 2) and non-exposed SELs from 20 cases using the EUS-FNB needle probe (Study 3) were measured to determine the diagnostic ability of H-impedance for differentiating GISTs from non-GISTs. RESULTS: H-impedance significantly positively correlated with cell density (P=0.030) (Study 1). The H-impedance of GIST (99.5) measured using conventional probe was significantly higher than those of the muscular layer (82.4) and leiomyoma (89.2) (P<0.01) (Study 2). The H-impedance of GIST measured using the EUS-FNB needle was also significantly higher than that of leiomyoma (GIST: 80.2 vs. leiomyoma: 71.8, P=0.015). The diagnostic yield of the impedance method for differentiating GISTs from non-GISTs had 94.4% accuracy, 88.9% sensitivity, 100% specificity, and 0.95 area under the curve. Diagnostic ability was not affected by lesion size (P=0.86) (Study 3). CONCLUSION: Auxiliary differential diagnosis between gastric GISTs and non-GISTs by the H-impedance measurement during EUS-FNB could be a good option especially when the lesion is smaller than 20 mm.

DOI： 10.1016/j.gie.2022.11.022

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BACKGROUND & AIMS: Hybrid endoscopic submucosal dissection (H-ESD), which incorporates ESD with endoscopic mucosal resection, has been developed to make ESD technically easier. This study aimed to determine if H-ESD is superior to conventional ESD (C-ESD) for small early gastric neoplasms (EGN). METHODS: We conducted a multi-center, prospective, open-label, randomized controlled trial to compare the treatment outcomes of H-ESD and C-ESD (Hybrid-G Trial). The patients with differentiated-type intramucosal EGN ≤ 20 mm in diameter and without ulceration were randomly assigned (1:1) to groups that underwent H-ESD or C-ESD. A single multi-functional snare, SOUTEN (ST1850-20, Kaneka, Medix, Tokyo, Japan), was used for H-ESD. The primary outcome was procedure time. Secondary outcomes included mucosal incision time, time and speed of submucosal dissection, curability, and endoscopic procedural adverse events. RESULTS: A total of 39 and 40 patients underwent H-ESD and C-ESD, respectively. The procedure time of H-ESD was significantly shorter than that of C-ESD (33.16 min vs. 62.46 min, H-ESD/C-ESD ratio: 0.53, 95% confidence interval 0.41-0.69, P<0.0001). There was no significant difference in mucosal incision time between the two groups; the time and speed of submucosal dissection of H-ESD were significantly shorter than those of C-ESD. No difference was observed between the two groups in other outcomes. CONCLUSIONS: H-ESD has significantly shorter procedure time than C-ESD, with high and comparable curability and safety for both H-ESD and C-ESD. H-ESD can be a good option for the endoscopic treatment of small EGNs.

DOI： 10.1016/j.cgh.2022.10.030

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

食道運動障害性疾患(EMD)を診断するための新たな2所見を用いたバリウム食道造影検査(BE)によるスクリーニングを評価した。2013年1月から2020年10月にEMDが疑われ高解像度マノメトリー検査(HRM)とBEの両方が施行された244例を対象とした。EMDの診断はシカゴ分類第3.0版を用いてHRM所見に基づいて行った。BEは硫酸バリウムを用いて食道連続撮影を行った。従来からのBE所見(ニボー、数珠状/コルク栓抜き様所見、蠕動の消失/減弱)に加え、新規2所見(蠕動波出現、胃食道接合部上膨隆所見)を診断に用いた。新規2所見と従来の3所見を診断に用いた場合のBEスクリーニングの感度は79.4%、特異度は88%であった(受信者動作特性曲線下領域(AUC)=0.837)。新規2所見を診断に用いない場合には、感度は63.9%、特異度は96%(AUC=0.800)であった。アカラシアはニボー形成と特に関連性が強かった(88.7%)。収縮の消失は蠕動の消失/減弱と強く関連していた(85.7%)。遠位食道痙攣と数珠状/コルク栓抜き様所見との間(60%)およびアカラシアと蠕動波出現(59.7%)との間には比較的高い関連性が認められた。個々のBE所見の観察者内再現性、観察者間一致率はそれぞれ84.4%、75%であった。蠕動波出現は積算弛緩圧(IRP)高値および遠位潜時短縮と関連していた。食道胃接合部上膨隆はIRP高値と関連していた。新規の2所見を追加したBEスクリーニングによるEMDの診断は一般診療において有用である可能性が示された。

Language：English   Publishing type：Research paper (scientific journal)  

Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.

DOI： 10.1038/s41598-022-20863-8

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BACKGROUND & AIMS: Peroral endoscopic myotomy (POEM) is conducted for patients with esophageal motility disorders based on high-resolution manometry (HRM) findings. However, the impact of POEM on HRM findings and the associations between post-POEM HRM and outcomes have not been clarified. METHODS: In a multicenter, observational cohort study, patients with achalasia treated by POEM received follow-up HRM. Associations between patient characteristics, POEM procedures, and post-POEM HRM findings, including integrated relaxation pressure (IRP) and distal contractile integral (DCI), were investigated. Furthermore, the outcomes of the POEM procedure were compared with the post-POEM HRM findings. RESULTS: Of 2,171 patients, 151 (7.0%) showed residual high post-POEM IRP (≥26 mmHg, Starlet). In a multivariate analysis, high pre-POEM IRPs (odds ratio [OR]=24.3) and gastric myotomy >2 cm (OR=0.22) were found to be positive and negative predictive factors of high post-POEM IRPs, respectively. Peristalsis recovery (DCI ≥500 mmHg-cm-sec, at least one swallow, Starlet) was visible in 121 (19.6%) of 618 patients, and they were type II-III achalasia. High pre-POEM IRP (OR=2.65) and DCI ≥500 (OR=2.98) predicted peristalsis recovery, while esophageal dilation (OR=0.42) predicted a risk of no recovery. Extended myotomy did not reveal a significant impact on peristalsis recovery. High or low post-POEM IRP and DCI did not increase the incidence of clinical failure, reflux esophagitis, or symptomatic gastroesophageal reflux disease. CONCLUSIONS: Extended gastric myotomy decreased IRP values, while peristalsis recovery depended on the characteristics of achalasia. A residual high post-POEM IRP does not necessarily mean clinical failure. Routine HRM follow-up is not recommended after POEM.

DOI： 10.1016/j.gie.2022.10.039

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Language：English   Publisher：Endoscopy  

DOI： 10.1055/a-1662-4965

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DOI： 10.1055/a-1934-9752

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Publisher：日本メディカルセンター  

DOI： 10.19020/cg.0000002301

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DOI： 10.1055/a-1889-4838

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BACKGROUND: High-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders (EMDs); however, it requires specialized equipment. The development of more accessible screening examinations is expected. We evaluated the utility of barium esophagography (BE) screening using two novel findings to diagnose EMDs. METHODS: Between January 2013 and October 2020, 244 patients with suspected EMDs who underwent both HRM and BE were analyzed. The EMD diagnosis was based on HRM findings using Chicago Classification version 3.0. BE was performed using sequential esophagography with barium sulfate. Three conventional BE findings (air-fluid level, rosary-bead/corkscrew appearance, and absent/weak peristalsis) and two novel BE findings (wave appearance and supra-junctional ballooning) were used for diagnosis. RESULTS: The sensitivity and specificity of BE screening using the two novel findings and conventional findings to diagnose EMDs were 79.4% and 88%, respectively [area under the receiver-operating characteristic curve (AUC) = 0.837]. Without these novel findings, they were 63.9% and 96%, respectively (AUC = 0.800), respectively. Achalasia was highly correlated with the air-fluid level (88.7%). Absent contractility was highly correlated with absent/weak peristalsis (85.7%). Relatively high correlations were observed between distal esophageal spasm and rosary-bead/corkscrew appearance (60%), and between achalasia and wave appearance (59.7%). The intra-observer reproducibility and inter-observer agreement for individual BE findings were 84.4% and 75%, respectively. Wave appearance was associated with higher integrated relaxation pressure (IRP) and shorter distal latency. Supra-junctional ballooning was associated with higher IRP. CONCLUSIONS: BE screening using two additional novel findings to diagnose EMDs could be useful in general practice.

DOI： 10.1007/s00535-022-01913-4

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BACKGROUND: The specific role of the M3 muscarinic acetylcholine receptor in gastrointestinal motility under physiological conditions is unclear, due to a lack of subtype-selective compounds. AIMS: The objective of this study was to determine the region-specific role of the M3 receptor in gastrointestinal motility. METHODS: We developed a novel positive allosteric modulator (PAM) for the M3 receptor, PAM-369. The effects of PAM-369 on the carbachol-induced contractile response of porcine esophageal smooth muscle and mouse colonic smooth muscle (ex vivo) and on the transit in mouse small intestine and rat colon (in vivo) were examined. RESULTS: PAM-369 selectively potentiated the M3 receptor under the stimulation of its orthosteric ligands without agonistic or antagonistic activity. Half-maximal effective concentrations of PAM activity for human, mouse, and rat M3 receptors were 0.253, 0.345, and 0.127 μM, respectively. PAM-369 enhanced carbachol-induced contraction in porcine esophageal smooth muscle and mouse colonic smooth muscle without causing any contractile responses by itself. The oral administration of 30 mg/kg PAM-369 increased the small intestinal transit in both normal motility and loperamide-induced intestinal dysmotility mice but had no effects on the colonic transit, although the M3 receptor mRNA expression is higher in the colon than in the small intestine. CONCLUSIONS: This study provided the first direct evidence that the M3 receptor has different region-specific roles in the motility function between the small intestine and colon in physiological and pathophysiological contexts. Selective PAMs designed for targeted subtypes of muscarinic receptors are useful for elucidating the subtype-specific function.

DOI： 10.1007/s10620-022-07637-y

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Language：Japanese   Publisher：(株)日本メディカルセンター  

＜文献概要＞はじめに 胃食道逆流症(gastroesophageal reflux disease;GERD)は「胃内容物の逆流により,不快な症状あるいは合併症を生じた状態」と定義される.GERDは,粘膜傷害を伴う逆流性食道炎と粘膜傷害を認めない非びらん性胃食道逆流症(non-erosive reflux disease;NERD)に分類される.GERD診療の難しさは,症状から診断されるNERD(広義のNERD)の約半数にGERD以外の病態が紛れ込んでしまうことにある.最近,食道機能を可視化する食道生理機能検査の発展と共にGERD診療が飛躍的に進歩した.本稿ではGERD診断およびその鑑別診断に重要な検査法とその診断基準について概説する.

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Publisher：東京医学社  

DOI： 10.24479/endo.0000000262

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Endoscopic submucosal dissection (ESD) is globally performed to treat early epithelial tumors of the gastrointestinal tract, but delayed perforation is a problematic procedure-related complication. To address this problem, closure of ESD-induced mucosal defects with a detachable snare has been reported. However, one problem is that this method usually requires some degree of skill and replacing a single-channel scope with a two-channel scope. We developed the clip stopper closure (CSC) method using a detachable snare in combination with the ZEOCLIP, which can be easily performed with a single-channel scope, for ESD-induced mucosal defects. Six consecutive cases were treated with this closure method for colonic ESD-induced mucosal defects. The median closure time was 12.5 (10-24) min, and the success rate of this procedure was 100%. Our CSC method was able to be performed in any part of the colon. In conclusion, the CSC method using a detachable snare in combination with the ZEOCLIP is a simple but promising closure technique for ESD-induced mucosal defects.

DOI： 10.1111/den.14417

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BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64% of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100%) and EUS-FNAB (97.1%) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

DOI： 10.1007/s00464-022-09419-z

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DOI： 10.1055/a-1841-5907

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Although a large-caliber endoscope (LCE) is indispensable for through-the-scope placement of a self-expandable metallic stent (SEMS) in patients with malignant colonic obstruction (MCO), inaccessibility of the target obstructing lesion (TOL) by the endoscope is a significant cause of unsuccessful procedures. We herein present a novel salvage procedure when the TOL is not directly accessible by an LCE in conditions such as coexisting peritoneal carcinomatosis involving the colon. The salvage procedure, termed over-the-catheter endoscope replacement (OCER), starts with an ultraslim endoscope suitable for deep insertion beyond a tortuous colon for traversing a guidewire through the TOL. The ultraslim endoscope is then withdrawn and replaced by an LCE through the following steps. An endoscopic retrograde cholangiopancreatography catheter is preloaded in the LCE, the catheter alone is passed over the guidewire already traversed through the TOL, and the LCE is navigated over the catheter as far as possible toward the TOL to deliver the SEMS delivery system in a standard through-the-scope manner or further in an over-the-wire manner even if LCE insertion is incomplete. Among the 165 patients with MCO who underwent stenting during our study period, OCER led to successful procedures in all 9 patients whose TOLs were initially inaccessible because of colon-involving peritoneal carcinomatosis. By utilizing the functions of distinctive endoscopes in a unique and complementary way, OCER can be a practical salvage option for challenging cases of MCO that are highly prone to unsuccessful palliation by conventional SEMS placement.

DOI： 10.1111/den.14385

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Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403202920

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BACKGROUND: Neuroendocrine neoplasms of the ampulla of Vater (ampullary NEN) have features of both gastrointestinal and pancreato-biliary (PB) NEN. However, the limited number of studies examining ampullary NEN makes it difficult to clarify their unique characteristics. This study aimed to elucidate the clinical characteristics of ampullary NEN. METHODS: We enrolled 162 patients with PB-NEN diagnosed at Kyushu University Hospital between 2011 and 2020. Clinical features, pathological diagnoses, treatments, and prognoses were retrospectively analyzed. We also compared ampullary NEN with pancreatic NEN (PanNEN). RESULTS: We analyzed 10 ampullary NEN cases and 149 PanNEN cases. The ampullary NEN cases consisted of four cases of NET G1 (neuroendocrine tumor Grade 1), one NET G2 (Grade 2), and five NECs (neuroendocrine carcinoma). The incidences of NEC and cholangitis were significantly higher in ampullary NEN than in PanNEN. All ampullary NETs had a submucosal tumor-like appearance, as identified by endoscopic ultrasound-guided fine needle aspiration. We treated small NET G1 (<10 mm) with endoscopic papillectomy and large NET G1 with pancreaticoduodenectomy. There were no cases of recurrence after resection. All ampullary NECs presented with the characteristic endoscopic finding of a ''crater sign" similar to deep-mining ulcers seen in gastric malignant lymphoma. Four cases underwent surgical resection, and one case was unresectable. Two patients who underwent multidisciplinary treatment were maintained without recurrence for over 2 years. CONCLUSIONS: Endoscopic findings showed identifiable distinctions between ampullary NETs and NECs.

DOI： 10.1159/000525013

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は70歳代,女性.近医で十二指腸病変を指摘されたため,当科に紹介され受診となった.十二指腸内視鏡検査で十二指腸球部後壁に径20mm大の二段隆起を呈する粘膜下腫瘍様隆起性病変を認め,上部に広く浅い潰瘍を形成していた.潰瘍からの生検で神経内分泌腫瘍(NET)の診断となり,十二指腸部分切除術・リンパ節郭清が施行された.切除標本病理学的所見はNET G2,pT3(SS),ly0,v1であり,リンパ節転移を認めた.本症例は上皮が欠損し,さらに表層に腫瘍自体が露出し,かつ二段隆起を呈した症例であった.

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Congenital duodenal diaphragm (CDD) is a rare disease that is usually diagnosed in the neonatal period; however, it is sometimes diagnosed later in the adult period. A 39-year-old woman was referred to our hospital due to tarry stool and anemia. Emergent esophagogastroduodenoscopy (EGD) revealed an obstructing membranous structure with a small orifice in the second portion of the duodenum, together with dilatation of the bulbar part. The membranous structure was accompanied by a Dieulafoy-like vessel on the backside, which was considered to have caused tarry stool and anemia. The Dieulafoy-like vessel was successfully treated by endoscopic hemostasis. Based on the computed tomographic gastrography and barium duodenography findings, it was diagnosed as CDD. Later, endoscopic resection of the diaphragm was conducted by an endoscopic submucosal dissection (ESD)-based procedure, with the use of an electrosurgical grasping-type scissor forceps (ClutchCutter [CC]). There were no procedure-related complications. The definite diagnosis of CDD was made based on the observation of typical structures in a pathological examination. This is the first case report of adult CDD that was successfully treated by endoscopic resection using ESD-based techniques with a CC.

DOI： 10.1002/deo2.93

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Endoscopic submucosal dissection (ESD) is effective for the treatment of colorectal neoplasms. We have developed a self-completion ESD (S-ESD) using Endosaber without requiring additional instruments or assistance. This prospective cohort study was conducted to investigate the feasibility of S-ESD for colorectal neoplasms. Patients with colorectal neoplasms measuring 20-40 mm in size were enrolled. A single operator, without assistance, performed ESD using only the Endosaber. The primary outcome was the success rate of S-ESD. Secondary outcomes included procedure time, the rates of en bloc, complete, and curative resection, and complication rates, including the incidence of perforation and delayed bleeding. In total, 15 patients with 15 lesions were enrolled. The median size of the resected lesions was 28 mm (interquartile range 25-29 mm). S-ESD success rate of 100% was achieved. The median procedure time was 44 min (29.5-53.5 min). We observed en bloc, complete, and curative resection rates of 100%, 93.3%, and 86.7%, respectively, and a complication rate of 6.7% (perforation: 0%, delayed bleeding: 6.7%). S-ESD for colorectal neoplasms was successfully performed with favorable treatment outcomes and low complication rates. S-ESD reduces the number of devices and extent of assistance, making S-ESD a simple and cost-effective procedure.

DOI： 10.1038/s41598-022-09792-8

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Objective: To compare treatment outcomes between injection endoscopic submucosal dissection using ProKnife (P-ESD) and conventional ESD (C-ESD) for gastric lesions. Methods: In this randomized controlled trial, we compared treatment outcomes of P-ESD and C-ESD for simulated gastric lesions ≥3 cm in resected porcine stomachs. Predictive factors associated with ESD difficulties were investigated using logistic regression analysis. Results: Seventy lesions were screened; however, two lesions were excluded. A total of 12 endoscopists performed 68 ESDs: 34 P-ESDs and 34 C-ESDs. The ESD procedure time of P-ESD (36.3 [28.4-46.8] min) was significantly shorter than that of C-ESD (46 [36.4-64.6] min; p = 0.0014). The technical success rates did not differ between the P-ESD and C-ESD groups (en bloc resection rate, 100% in both groups; complete resection rate, 94.1% and 85.3%, respectively; p = 0.23). The number of injections during P-ESD (7.5 [6-10] times) was significantly higher than during C-ESD (4 [3-5] times; p < 0.001), but the total volume of injected solution during P-ESD (20 [16-26.3] ml) was significantly smaller than during C-ESD (27.5 [20-31.5] ml; p = 0.0019). In multivariate analysis, less ESD experience (odds ratio [OR], 3.9) and selection of C-ESD as the ESD method (OR, 3.8) were independent predictive factors associated with ESD difficulties. Conclusions: Compared with C-ESD, P-ESD had a shorter procedure time but also allowed for notable technical success and safety.

DOI： 10.1002/deo2.91

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DOI： 10.1055/a-1809-4967

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

消化管運動改善薬であるアコチアミドの、食道胃接合部流出路閉塞(EGJOO)に対する有効性を検討した。2014年10月から2020年3月までの間に、EGJOO 25例に対してアコチアミド(100mg、1日3回)を4週間投与した。治療開始直前と治療後に高解像度マノメトリー検査(HRM)を施行した。主要評価項目である積算弛緩厚(IRP)は、治療前(19.4、17.1-27.4mmHg)と比較して治療後(14.6、12.1-22.0mmHg)で有意に低かった。下部食道括約筋(LES)調節指数も、治療後(32.7,21.0-40.0mmHg)が治療前(39.3,31.2-50.2mmHg)と比較して有意に低かった。アコチアミドは、EGJOO25症例中13例(52%)でIRPを正常化(<15mmHg)し、IRPは25例のEGJOO症例中20例(80%)でIRPを減少させた。副次評価項目であるFSSGスコアには、治療前と治療後で有意な変化は認められなかった。アコチアミドが奏効した13例を対象としたサブグループ解析では、アコチアミドにより嚥下障害が有意に改善していた。アコチアミドは、基礎LES圧およびLES調節反応の両方を低下させることによりIRP値を減少させることで、EGJOO患者において治療効果を示すことが明らかになった。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Ex vivoブタモデルの胃病変70ヵ所に対して、ProKnifeを用いた内視鏡的粘膜下層剥離術(P-ESD)または従来法の内視鏡的粘膜下層剥離術(C-ESD)を無作為に振り分け、12名の内視鏡医が施行した。各群1病変を粘膜肥厚のため除外したことにより、検討対象は各群34病変となった。処置時間はP-ESD群が36.3(28.4-46.8)分、C-ESD群が46(36.4-64.6)分で、有意にP-ESD群が短かった(P=0.0014)。技術的成功率には差は認められなかった(一括切除率は両群とも100%、完全切除率はP-ESD群94.1%、C-ESD群85.3%、P=0.23)。P-ESD処置中の注入回数は7.5(6-10)回で、C-ESD群の4(3-5)回よりも有意に多かった(P<0.001)が、注入薬液総量はP-ESD群が20(16-26.3)ml、C-ESD群が27.5(20-31.5)mlで、P-ESD群が有意に少なかった(P=0.0019)。多変量解析の結果、ESD未熟練(オッズ比(OR)3.9)、C-ESD法(OR3.8)がESD困難性の独立した予測因子であった。

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

症例は39歳女性で、タール便および貧血のため紹介受診した。緊急上部消化管内視鏡検査で十二指腸下行脚に小孔を伴う膜様狭窄を認め、十二指腸球部の拡張を伴っていた。膜様構造の裏面にデュラフォイ様血管が認められ、タール便および貧血の原因と考えられた。デュラフォイ様血管に対しては、内視鏡的止血を施行した。CT胃造影検査およびバリウム十二指腸造影検査より、先天性十二指腸膜様狭窄症と診断した。内視鏡的粘膜下層剥離術(ESD)に準じた手法で、通電式把持型剪刀鉗子(ClutchCutter)を用いて十二指腸隔膜を切除した。処置関連合併症は認められなかった。切除標本の病理学的検査により、先天性十二指腸膜様狭窄症と確定診断された。

Language：English   Publisher：(一社)日本内科学会  

症例は74歳女性で、関節リウマチ(RA)と診断され、標準治療で改善しなかったため、紹介来院した。同年の毎年行う大腸内視鏡検査では、潰瘍や憩室は認めなかった。翌年、トシリズマブ治療を開始したところ、症状が改善した。トシリズマブ治療を開始後6ヵ月時に血便と腹痛を訴えた。緊急大腸内視鏡検査を行い、盲腸から横行結腸に広がる不整な多発性潰瘍が判明した。憩室の徴候は認めなかった。生検の病理学的所見では、陰窩上皮細胞に複数のアポトーシスが認められた。トシリズマブ以外の服用薬は、プレドニゾロン、メトトレキサート、ロキソプロフェン、フォリアミン、ランソプラゾール、レバミピド、レボチロキシン、ロスバスタチン、エゼチミブ、フルコナゾールであった。腸管粘膜損傷は、トシリズマブの合併症として発現したことが疑われた。トシリズマブを中止したところ、血便と腹痛が改善した。トシリズマブ中止後1ヵ月時の追跡大腸内視鏡検査において、潰瘍はすべて完全に治癒していた。トシリズマブの代わりにトファシチニブ投与を行ったが、RA再発は認められなかった。

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Endoscopic submucosal dissection (ESD) is widely accepted as a local treatment for gastrointestinal tract tumors. As a simplified endoscopic procedure, hybrid ESD (H-ESD) has been performed for colorectal neoplasms in recent times. However, whether H-ESD is superior to conventional ESD (C-ESD) for patients with early gastric neoplasms (EGN) remains unclear. In this trial, we will compare the treatment outcomes of H-ESD and C-ESD. We hypothesize that the procedure time for H-ESD is shorter than that for C-ESD. METHODS: This is an investigator-initiated, multi-center, prospective, randomized, open-label, parallel-group trial to be conducted beginning in August 2020 at nine institutions in Japan. We will determine if H-ESD is superior to C-ESD in terms of procedure time in patients with EGN diagnosed as macroscopically intramucosal (T1a) differentiated carcinoma ≤ 20 mm in diameter without ulcerative findings according to current Japanese gastric cancer treatment guidelines. A total of 82 patients will be recruited and randomly assigned to either the C-ESD or the H-ESD group. The primary outcome is ESD procedure time. Secondary outcomes include mucosal incision, time and speed of submucosal dissection, en bloc resection, complete resection, curability, adverse events related to the ESD procedure, extent of dissection before snaring, volume of injection solution, number and time of hemostasis, thickness of the submucosal layer in the resected specimen, and handover to another operator. The stated sample size was determined based on the primary outcome. According to a previous report comparing the procedure times of C-ESD and H-ESD, we hypothesized that H-ESD would provide a 0.2 reduction in logarithmically concerted procedure time (-37%). We estimated that a total of 82 participants were needed to reach a power of 80% for a t-test with a significance level of 0.05 and considering a 10% dropout. DISCUSSION: This trial will provide high-quality data on the benefits and risks of H-ESD for EGN patients. The results of this study could lead to improved outcomes in patients with EGN undergoing ESD. The results will be presented at national and international meetings and published in peer-reviewed journals. TRIAL REGISTRATION: UMIN-CTR UMIN000041244 . Registered on July 29, 2020.

DOI： 10.1186/s13063-022-06099-x

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In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

DOI： 10.1007/s00535-022-01861-z

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Language：Japanese   Publisher：(公社)日本医学放射線学会  

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Solid-type poorly differentiated adenocarcinoma (PDA) of the stomach is frequently associated with microsatellite instability (MSI) and aberrations of the SWI/SNF chromatin remodeling complex. Previous studies showed that aberrant ARID1A and SMARCA4 expression induces mesenchymal transition. We analyzed 51 primary-site cases and 209 metastatic lymph nodes among solid-type PDA for the expression of SWI/SNF complex subunits (ARID1A, SMARCA4, SMARCB1, SMARCC2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, β-catenin, Snail). We also analyzed 40 cases of non-solid-type PDA as a stage-matched control group. Aberrant expression of ARID1A (39%) and SMARCA4 (49%) was more common in solid-type PDA than in non-solid-type PDA (ARID1A, P = 0.0049; SMARCA4, P < 0.0001). The group of solid-type PDA with aberrant ARID1A showed significantly longer overall and progression-free survival than the corresponding ARID1A-retained group (P = 0.0405 and P = 0.0296, respectively). Aberrant expression of EMT factors inducing mesenchymal transition in the groups with solid-type PDA at the primary site or metastatic lymph nodes with aberrant ARID1A was less common than in the corresponding groups with retained ARID1A (E-cadherin, primary site P = 0.0341, lymph node P < 0.0001; β-catenin, primary site P = 0.0293, lymph node P = 0.0010; Snail, primary site P = 0.0169, lymph node P = 0.0828). Furthermore, N3 of the TNM classification was more frequently observed in the group with solid-type PDA with retained ARID1A than in the corresponding ARID1A-aberrant group (P = 0.0288). Mesenchymal transition was not induced in the ARID1A-aberrant group, in which patients had favorable prognosis, and preserved epithelial characteristics in EMT may play an important role in low tumor aggressiveness of solid-type PDA.

DOI： 10.1007/s00428-021-03261-9

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Objectives: The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. Methods: Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. Results: Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly (p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly (p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). Conclusion: Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. Clinical trial registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748).

DOI： 10.1177/17562848211065331

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DOI： 10.1007/s10388-021-00887-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japanese Society of Internal Medicine  

<p>Intestinal mucosal injury that develops as a complication of tocilizumab (TCZ) is usually associated with diverticulosis. We herein report a rare case of TCZ-induced intestinal mucosal injury in the absence of diverticulosis. A 74-year-old woman suffering from rheumatoid arthritis started taking TCZ. Six months later, she complained of hematochezia and abdominal pain. Colonoscopy revealed multiple ulcers spreading from the cecum to the transverse colon but no diverticulosis. These lesions were cured at three months after the discontinuation of TCZ. We should consider TCZ as a risk factor for intestinal mucosal injury, even if patients have no history of intestinal disease associated with diverticulosis. </p>

DOI： 10.2169/internalmedicine.8031-21

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DOI： 10.4103/EUS-D-21-00043

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DOI： 10.1016/j.ejphar.2021.174491

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DOI： 10.1007/s10620-021-07235-4

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DOI： 10.1007/s00535-021-01819-7

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DOI： 10.1080/17474124.2021.1924056

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DOI： 10.1111/den.13978

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DOI： 10.5056/jnm20138

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DOI： 10.1038/s41598-021-92870-0

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DOI： 10.4240/wjgs.v13.i6.563

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DOI： 10.1111/den.13954

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DOI： 10.1007/s10753-020-01358-y

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DOI： 10.1038/s41598-021-87052-x

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DOI： 10.1055/a-1422-2902

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DOI： 10.1007/s10753-020-01358-y

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DOI： 10.4240/wjgs.v13.i2.116

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DOI： 10.1186/s12876-021-01656-1

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DOI： 10.1159/000502771

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DOI： 10.1155/2021/6691705

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DOI： 10.4251/wjgo.v12.i8.918

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DOI： 10.1080/25785826.2020.1797319

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BACKGROUND/AIM: Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1β could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1β could predict the response to GC in patients with UC. METHODS: A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1β, GC receptor α (GRα), GRβ, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation. RESULTS: The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1β levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRβ, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0&#37; and specificity of 77.8&#37; based on mucosally expressed IL-1β. CONCLUSIONS: Mucosally expressed IL-1β can be used as a predictor of GC response in patients with UC.

DOI： 10.1159/000507435

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DOI： 10.1093/dote/doz077

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DOI： 10.1159/000503994

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DOI： 10.5946/ce.2019.129

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DOI： 10.1111/cas.14301

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DOI： 10.1055/a-0992-8900

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症例は46歳女性で、42歳時に慢性心房細動を指摘され、ワルファリン2mg内服を継続していた。受診3日前から腹痛、食欲不振が出現し、症状が持続するため当科受診した。血液生化学検査で白血球増多、低蛋白血症、低ナトリウム血症、PT-INR延長を認めた。腹部造影CTで近位空腸に全周性連続性の腸管壁肥厚と周囲脂肪織混濁を認めた。経口的シングルバルーン小腸内視鏡検査(第1病日)では、トライツ靱帯付近より暗紫色の粘膜が出現し、粘膜下腫瘤様隆起と発赤調粘膜が連続し、肛門側では内腔狭小化を認めた。凝固能低下に伴う小腸壁内血腫と診断し、保存的加療を行う方針とした。凝固能改善のためビタミンK投与を行い、ワルファリンは休薬とした。第2病日にはPT-INR 1.37と低下、ワルファリン1mgより内服再開、PT-INRコントロールを継続した。保存的治療によって、徐々に腹痛は改善を認めた。第8病日の経口的シングルバルーン小腸内視鏡検査では、粘膜発赤は軽度残存していたが、粘膜下腫瘤様隆起は消失し、粘膜浮腫・色調の改善を認めた。内視鏡下小腸X線検査でも、腸管狭窄、浮腫は改善し、造影剤の通過は良好となった。腹痛症状の改善のみならず、内視鏡所見上も改善を認め、第9病日に退院となった。

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DOI： 10.5152/tjg.2020.19207

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DOI： 10.1186/s12876-020-1170-2

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78歳男性。腹痛を主訴に受診。上部消化管内視鏡検査で十二指腸下行部に多数のびらんを伴う浮腫状変化を認めた。入院3日目、四肢に紫斑が出現し、十二指腸生検病理所見で壊死性血管炎を認め、IgA血管炎と診断した。入院6日目腹部所見が増悪し、閉塞起点を伴わないイレウスを認め、機能的イレウスと診断後にイレウスチューブを挿入した。その後プレドニゾロン投与で症状及び消化管・皮膚所見は改善した。消化管の内視鏡像及び内視鏡組織生検所見が本症の診断に有用となり、腸重積または腸穿孔を伴わないイレウスを合併したIgA血管炎の1例を経験したので報告する。(著者抄録)

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DOI： 10.1111/den.13476

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DOI： 10.1007/s10620-019-5470-8

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DOI： 10.1016/j.vgie.2019.05.003

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DOI： 10.1111/den.13393

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DOI： 10.1016/j.ejphar.2019.172405

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DOI： 10.1111/den.13367

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DOI： 10.1016/j.humpath.2019.03.006

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DOI： 10.9738/INTSURG-D-17-00137.1

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00535-018-1477-8

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.4251/wjgo.v10.i12.487

Language：English  

DOI： 10.1055/a-0631-7760

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12328-018-0838-4

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12876-018-0855-2

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00428-018-2398-x

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000487708

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00464-018-6188-y

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jcmgh.2017.11.004

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DOI： 10.11280/gee.60.131

Language：Japanese  

症例は73歳、女性。5年前に胃癌に対して胃全摘術、Roux-en-Y再建術を受けており、心窩部痛を主訴に当院へ救急搬送された。腹部造影CT検査でY脚全体の腸管拡張を認め、Y脚吻合部は盲端に終わっていた。輸入脚症候群と診断し緊急上部消化管内視鏡検査を行い、粘膜のわずかな引きつれと黄白色液漏出を手掛かりにpin hole状のY脚吻合部を同定しえた。同部に対し内視鏡的バルーン拡張術を施行すると大量の腸液流出を認めた。術後経過は良好で第6病日に退院となった。輸入脚症候群に対しては内視鏡的拡張術が極めて有効であり、CT検査による全体像把握に加え詳細な内視鏡観察によりY脚吻合部を同定することが有用である。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12876-018-0763-5

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/PAS.0000000000000947

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.4251/wjgo.v9.i10.416

Language：English  

DOI： 10.4253/wjge.v9.i7.334

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00535-016-1221-1

Language：Japanese  

症例は60歳代男性。上部消化管内視鏡検査で胃穹窿部に13mm大の胃神経内分泌腫瘍を認め、血清ガストリン値は3376pg/mlと高値であった。内視鏡を含む検査所見、また抗Helicobacter pylori抗体陽性より、A型胃炎、ガストリノーマは考えにくく、B型胃炎にともなうものと考えられた。高ガストリン血症をともない発生する胃神経内分泌腫瘍でB型胃炎を背景とするものはまれであり、さらなる症例の集積が望まれる。(著者抄録)

Language：English  

DOI： 10.1159/000452354

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3748/wjg.v23.i3.496

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1055/s-0042-116023

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5009/gnl15486

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1159/000447010

Language：Japanese  

Language：Japanese  

近年、高解像度食道内圧検査(HRM)が開発され、専門的な測定技術や経験がなくても上部食道括約筋から下部食道括約筋まで連続的に食道運動機能を評価できるようになった。このHRMの登場と共にシカゴ分類が提唱され、食道運動異常症の診断が飛躍的に発展した。最初に食道運動の機序について述べ、次いでHRMによる食道運動異常症のシカゴ分類に基づいた診断法と現状の治療戦略について概説した。

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/jgh.13262

Language：English  

【背景】内視鏡的粘膜下層剥離術は早期胃癌治療のスタンダードとなっている。しかしながら、80歳以上の超高齢者に適した治療であるかはいまだ明らかではない。【方法】ガイドライン絶対適応内病変と適応拡大病変と診断した89名の患者106症例を65歳以下のNE群、80歳以上のVE群とし両群の比較検討を行った。ガイドラインを満たさない18症例は適応外病変と定義した。【結果】一括完全切除率はVEとNE両群で良好であり、統計学的有意差は認めなかった。NE群と比較してVE群に虚血性心疾患の併存症と抗血栓薬の使用が多かったが、内視鏡的粘膜下層剥離術における合併症に有意差は認めなかった。適応外病変の患者18症例のうち7症例が超高齢者であり、うち2名が追加外科切除をうけ、残る5名は経過観察とした。すべての群で局所再発、遠隔転移、胃癌関連死は認めなかった。【結論】早期胃癌に対する内視鏡的粘膜下層剥離術の短期及び長期成績は超高齢者において非高齢者と同様に良好であった。(著者抄録)

Language：Japanese  

癌の緩和医療の中でも、癌の進行・転移による消化管閉塞に対する治療の選択肢は、これまで限られていた。本邦において、悪性腫瘍による消化管閉塞に対して、従来はバイパス術や人工肛門造設術が行われてきた。しかし、QOL改善のために手術を行うことへの抵抗感は否めず、消化管の閉塞解除を少ない負担で行える方法は長らく望まれていた。近年、内視鏡技術の急速な進歩によって、消化管狭窄には自己拡張型金属ステント(self-expandable metallic stent:SEMS)留置術が開発され、全消化管に臨床導入可能となった。本稿では、食道、胃十二指腸、大腸に分けて、最近の消化管ステントの現状を概説する。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3109/00365521.2015.1107752

Language：English   Publishing type：Research paper (scientific journal)  

Language：Others   Publishing type：Research paper (scientific journal)  

Language：Japanese  

症例は53歳男性。下部消化管内視鏡検査にて、終末回腸に3mm程度の黄色調の粘膜下腫瘍を認め、生検にてNETと診断された。造影CT、FDG-PET及び小腸内視鏡検査では、同時多発病変や転移性病変は明らかではなく、回腸NET(cT1、N0、M0、cStage I)と診断し、回腸部分切除および3群リンパ節郭清を施行した。術後病理所見にて回腸NET G2と確定診断した。また、病変は3mm大であったが、脈管侵襲を認め、主リンパ節である回結腸根リンパ節(#203)にリンパ節転移を認めた。回腸NETの治療は、病変の大きさに関係なくリンパ節郭清を含めた腸管切除が望ましいと考えられた。(著者抄録)

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ejphar.2015.02.008

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3109/00365521.2014.940377

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jphs.2015.02.002

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DOI： 10.1111/nmo.12491

Language：Japanese  

腸管運動能異常におけるサイトカインの平滑筋運動に及ぼす影響と大建中湯の治療効果について実験的検討を行なった。方法は抗CD3抗体をBALB/cマウスの腹腔内に投与して下痢型の機能性腸疾患モデルを作成し、大建中湯(2700mg/kg)を1日1回連日経口投与した。胃腸管輸送能をgeometric centerにより評価した結果、1)抗CD3抗体投与により一過性の腸炎が認められたが、投与後7日目以降には腸炎は終息していた。2)IL-17Aノックアウトマウスでは急性期において輸送能の顕著な低下がみられたが、終息期の輸送能の亢進は認められず、IL-17Aの腹腔内投与により輸送能の亢進がもたらされた。3)大建中湯の投与は炎症時の細胞浸潤、小腸組織のIL-17A産生誘導、終息期における輸送能の亢進を有意に抑制していた。以上より、本モデルにおける炎症終息後の腸管運動過亢進にはIL-17Aが関与している可能性が考えられ、大建中湯の投与は本モデルにおける腸管運動能異常に有効である可能性が示唆された。

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ans.12643

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/MIB.0000000000000028

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0092960

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/den.12134

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3109/00365521.2013.878745

Language：Japanese  

Language：Japanese  

炎症性腸疾患(IBD)の発症に腸管での過度のT helper(Th)反応が関与している。Th反応はTh1、Th2、Th17からなり、正常の腸管では免疫反応を制御するregulatory T cellとの間でバランスが保たれている。IBD腸管ではその調節機構が破綻しており、クローン病ではTh1、Th17反応の亢進が、潰瘍性大腸炎ではTh17反応の亢進とIL-13発現上昇がみられる。IBD腸管のTh制御機構破綻のメカニズムを明確にすることは、治療のターゲットを明らかにし、新規治療法開発に重要である。IBDにおけるTh反応制御異常に関して最新の知見を含めて解説する。(著者抄録)

DOI： 10.11405/nisshoshi.110.1889

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/den.12014

Language：Japanese  

症例は50歳の男性。背部痛を主訴に近医を受診した。腹部CTにて膵頭部に40mm大の不整な嚢胞性病変を認め、慢性膵炎の急性増悪、膵仮性嚢胞と診断され、保存的に症状が軽快した。5ヵ月後に皮膚黄染を認め、CTにて病変は75mmまで増大を認め、胆管圧迫に伴う閉塞性黄疸の診断にて当院に入院となった。内視鏡ドレナージ後も黄疸が遷延したため、減圧と組織学的評価を行うために超音波内視鏡下穿刺術(EUS-FNA)が施行され、膵腺房細胞癌(ACC)と診断された。自験例はACCとしては稀な画像所見を呈し、EUS-FNAによる病理学的評価が診断、治療方針決定に有用であった。(著者抄録)

Language：English  

DOI： 10.4253/wjge.v5.i4.191

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Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/jgh.12086

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DOI： 10.1007/s12328-012-0351-0

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DOI： 10.5009/gnl.2012.6.4.423

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10620-012-2218-0

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DOI： 10.1007/s10620-012-2129-0

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5009/gnl.2012.6.3.334

Language：Japanese  

症例は67歳、男性。嚥下困難を主訴に来院した。食道下部に長径1cmの狭窄を認め、超音波内視鏡検査で全周性の粘膜肥厚を認めること、狭窄症状を幼少時より認めていることから先天性食道狭窄症と診断した。内視鏡的バルーン拡張術で治療を行ったところ著明な改善を認めた。先天性食道狭窄症は稀な疾患であり、多くは乳児期、幼児期に診断・治療されるが、成人となって診断される事もあり嚥下障害のある患者の鑑別疾患として認識する必要がある。(著者抄録)

Language：Japanese  

症例は50歳代男性。病歴は、2009年Cowden病を疑われ当科紹介受診。歯肉の結節状乳頭腫、手掌に角化性丘疹、食道に多発小隆起、直腸神経鞘腫、腺腫様甲状腺腫を認め、Cowden病の診断に至った。PTEN遺伝子exon5 codon130に変異(CGA→TGA)を認めた。Cowden病は悪性腫瘍を合併する頻度が高いため、慎重な経過観察が必要である。(著者抄録)

Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00535-011-0502-y

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DOI： 10.4253/wjge.v4.i4.123

Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： 10.11405/nisshoshi.109.593

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DOI： 10.1007/s12328-011-0282-1

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DOI： 10.1111/j.1365-2982.2011.01821.x

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DOI： 10.1007/s10620-011-1780-1

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Brunner腺由来の腺腫・癌はともにまれな疾患である.Brunner腺腫は,無茎～亜有茎性の粘膜下腫瘍様の病変として認められ,一部には中心陥凹を伴うことがある.超音波内視鏡検査(EUS)では,第3層に連続した均一な等～低エコーレベルの充実性腫瘍として描出される.病理組織学的所見では,Brunner腺由来と考えられるが,正常Brunner腺と明らかに異なる組織異型を示す.またBrunner腺由来の十二指腸癌は,他の十二指腸癌と比べ,陥凹を伴う粘膜下腫瘍様の形態をとり,EUSでは第3層に等～高エコーな病変として描出され,腫瘍内には<gaj code="56CA" kind="unicode">のう</gaj>胞と考えられる低エコーな部分を認めることが多い.(著者抄録)

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese  

症例は44歳、女性。腹部膨満感、腹痛、食思不振を主訴に近医を受診。腹部造影CT検査にて多発肝腫瘤、巨大卵巣腫瘤を指摘され当院を紹介受診し、精査の結果S状結腸癌多発肝転移・卵巣転移と診断した。FOLFOX療法を6サイクル施行後、bevacizumab(BV)を追加し、さらに5サイクル施行。SDが得られていたが、oxaliplatinによる末梢神経障害のため、BV/FOLFIRI療法に変更した。3サイクル後の評価にてPDと判定。その間に末梢神経障害が改善したため、再度BV/FOLFOX療法を3サイクル施行したがPDであった。K-RAS野生型であったため、panitumumabを導入(+FOLFOX療法)したところ、肝転移・卵巣転移とも著明に縮小し、QOL阻害の原因であった腹部膨満感も著明に改善した。(著者抄録)

Language：Japanese  

63歳女性。患者は便秘の精査目的で受診、大腸内視鏡検査にて直腸Rbに径10mm大の粘膜下腫瘍が認められたが、生検による病理組織学的診断には至らなかった。そこで、内視鏡的に粘膜切開して腫瘍を露出させた上で直視下生検を施行したところ、病理組織学的所見では紡錘形細胞が束状索状に密に増殖しており、免疫染色ではCD34(+)、kit(+)、S-100(-)、desmin(-)であった。以上より、本症例はGISTと診断され、核分裂像では低悪性度が予想されたため経肛門的直腸腫瘍切除術が施行された。その結果、術後経過は良好で約2週間で退院となり、目下、半年経過で再発は認められていない。

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DOI： 10.4291/wjgp.v2.i2.19

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10620-010-1286-2

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DOI： 10.4291/wjgp.v1.i3.97

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1053/j.gastro.2010.03.045

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DOI： 10.1152/ajpgi.00228.2009

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpgi.00112.2009

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DOI： 10.1124/mol.108.049858

Language：Japanese  

症例は38歳女性。下腹部痛にて受診し、CTで回盲部の肥厚、少量の腹水、腸間膜リンパ節の腫大を認めた。大腸内視鏡は回盲弁の著明な肥厚のため小腸側へ通過不能で、小腸透視では回腸終末に全周性の狭窄がみられ、腹腔鏡補助下回盲部切除術を施行した。術中、回盲部漿膜を中心に多数の赤色小結節がみられた。病理診断は回腸結核、腸間膜リンパ節炎の所見で、赤色小結節は出血をともなう巨細胞性肉芽腫であった。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpgi.00214.2007

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpcell.00434.2006

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DOI： 10.1139/Y06-103

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1999年2月～2004年1月に咽喉頭異常感を主訴とし逆流性食道炎と診断された257名に,プロトンポンプ阻害剤を投与した.投与中止後に再発を認めた14名を対象に,年齢,性別,再発までの期間を検討した.再発を繰り返した2名については,長期的にランソプラゾールを投与し効果を判定した.14例のうち,男性は10例で平均52歳,再発までの平均期間は6ヵ月,女性は4例で平均57歳,再発までの平均期間は6ヵ月であり,平均年齢と再発までの期間に男女差はなかった.難治性の逆流性食道炎に対してはプロトンポンプ阻害剤の長期療法が有効であり,著者等は以下に提示する新しい治療法を提唱する.初期治療ではランソプラゾール30mg/dayで8週間投与し経過をみる.再発を認めたらランソプラゾール15mg/dayで投与し症状が消失するまで投与する.投与中に症状の悪化を認めたらランソプラゾールを30mg/dayに増量する,初期治療から1年後に上部消化管の内視鏡を行い効果を判定する.逆流性食道炎を認めたらランソプラゾール15mg/dayを投与し症状が消失するまで続ける

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.febslet.2004.08.014

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1067/S0016-5107(03)01876-5

Language：Japanese  

47歳男.17歳時に皮膚血管腫を認め,37歳頃から頻回な鼻出血及び口腔内出血が出現し,40歳時には胃の毛細血管拡張病変を指摘されていた.慢性副鼻腔炎に対する治療目的で入院し,術前検査で貧血を認めたため,上部消化管内視鏡検査を施行した結果,胃及び十二指腸に多発する毛細血管拡張病変が認められた.父親にも皮膚血管腫及び頻回な鼻出血歴があることから,遺伝性出血性毛細血管拡張症(Osler病)と診断した.胃病変を貧血の原因と考え,アルゴンプラズマ凝固法(APC法)を施行し,2日間で約100ヶ所の病変を焼灼した.術後,病変は消失,潰瘍瘢痕化し,現在まで消化管出血を認めず,経過は良好である

Language：English   Publishing type：Research paper (scientific journal)  

We previously reported synergistic induction of apoptosis by IFN-γ plus either cyclosporin A (CsA) or tacrolimus (FK506) in gastric carcinoma cells. In this study, we aimed to elucidate the mechanism for this synergistic induction of apoptosis. IFN-γ plus CsA synergistically induced caspase-3 mediated apoptosis in gastric carcinoma cells. Although IFN-γ induced activation of signal transducer and activator of transcription1 (STAT1) and expression of interferon regulatory factor-1 (IRF-1) mRNA, IFN-γ alone was not able to induce caspase-3 activation and apoptosis. When gastric carcinoma cells were treated with cyclohexamide, a protein synthesis inhibitor, following IFN-γ pretreatment, caspase-3 was activated, and apoptosis was markedly induced. These findings suggest the existence of IFN-γ-induced anti-apoptotic pathway and we evaluated the effect of IFN-γ and CsA on calcium-sensitive nuclear factor-κB (NF-κB) activation. IFN-γ increased intracellular calcium ion concentration ([Ca2+]i) consisting of a spike and a sustained phase, and the latter was completely abrogated by CsA. Activation of NF-κB occurred in response to IFN-γ, and which was markedly inhibited by either CsA or FK506. NF-κB decoy also enhanced the cytotoxic effect of IFN-γ. These results suggest that IFN-γ may simultaneously induce the STAT1-mediated apoptotic pathway and the anti-apoptotic pathway through calcium-activated NF-κB and that inhibition of the latter by CsA may result in dominance of the apoptosis-inducing pathway. © 2003 Elsevier Science (USA). All rights reserved.

DOI： 10.1016/S0006-291X(03)00853-2

Language：Japanese  

72歳女.diclofenac坐剤により終末回腸に出血性小潰瘍を発症し,絶食とNSAIDの減量,変更にて一度は軽快したが,再度の同座剤の投与により消化管穿孔を起こし緊急手術となった.症例2は94歳女.loxoprofen及びインドメタシン坐剤の投与により直腸から回腸への瘻孔を認め,便培養は陰性で生検で特異的な所見を認めず,NSAID起因性腸症を疑いNSAIDを中止し,1週間絶食したところ,NSAID中止後2ヵ月の大腸内視鏡検査では,依然として瘻孔は認めたものの,潰瘍は瘢痕化していた

Language：Japanese  

64歳女.嘔吐,食事摂取不能を主訴とした.鉄欠乏性貧血を指摘されてから1年3ヵ月経過した後,主訴が出現して外来受診中,ショック状態を呈して緊急入院した.諸検査により十二指腸上行脚部の腸閉塞を成因とした嘔吐,水分摂取不良により著明な脱水症状をきたし,急性前性腎不全,著明な低Cl性代謝性アルカローシスとショックを呈したと診断した.多量輸液,胃管挿入による減圧を開始したところ,腎機能は回復してアルカローシスも改善した.腹部単純X線検査で小腸上部の閉塞機転が疑われた為,小腸X線検査,腹部CT,上部消化管内視鏡検査を行った結果,原発性空腸癌と診断された.開腹手術を施行して経過良好で,現在外来経過観察中である

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1469-7793.2001.t01-1-00701.x

Language：Japanese  

48歳女.精神分裂病のため通院中であったが,自殺目的で住居用洗剤2種類を服用し,意識障害が認められて搬送された.上部消化管内視鏡検査で,前庭部に巨大な地図状潰瘍を認め,潰瘍は黄白色調の厚く汚い白苔に被われていた.胃体部に縦走する潰瘍を数条認め,粘膜は浮腫状に腫脹していた.生理用食塩水10lで胃洗浄を行い,絶食・輸液・H2受容体拮抗剤投与により保存的治療を行ったところ,全身状態・意識状態は徐々に改善した.第30病日,前庭部・胃角部に偽憩室形成を伴う著明な変形・狭窄を認め,それらはその後も残存した.経過観察を継続したが,胃体部の進展は良好で,通過障害等の消化器症状は認めていない.住居用洗剤による腐食性胃炎の報告は少ないが,アルカリ性物質,界面活性剤の粘膜刺激作用により,前庭部に変形・狭窄をきたすことがある為,早期の内視鏡検査,適切な治療および経過観察が必要である

Language：English  

Language：Japanese  

Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1572-0241.1998.354_q.x

Language：Japanese  

Language：Japanese  

Language：Japanese  

34歳女.長期間の多飲歴のある為に,初回の水制限試験では中枢性部分型尿崩症と考えられた心因性多飲症症例を報告した.両者の鑑別は時間をかけて慎重に行う必要がある

Language：Japanese   Book type：Scholarly book

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Event date： 2018.6

Language：English  

Country：United States  

Event date： 2018.6

Language：English  

Country：United States  

Event date： 2018.6

Language：English  

Country：United States  

Event date： 2018.6

Language：English  

Country：United States  

Event date： 2018.6

Language：English  

Country：United States  

Event date： 2017.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2017.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2017.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2016.8

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：仙台   Country：Japan  

Event date： 2016.8

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：仙台   Country：Japan  

Event date： 2016.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2016.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2016.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2016.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2016.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2016.2 - 2016.6

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2015.10

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2015.5

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：名古屋   Country：Japan  

Event date： 2015.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2015.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2015.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2015.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2015.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2015.4

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：仙台   Country：Japan  

Event date： 2015.2 - 2015.3

Language：English   Presentation type：Oral presentation (general)  

Venue：Banff, AB   Country：Canada  

Event date： 2014.10

Language：English   Presentation type：Oral presentation (general)  

Country：Austria  

Event date： 2014.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Event date： 2014.5

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2013.5

Language：English   Presentation type：Oral presentation (general)  

Country：Japan  

Trypsin induced biphasic contraction and relaxation in the porcine lower esophageal sphincter.

Event date： 2012.5

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Background and study aim: Endoscopic submucosal dissection (ESD)-associated techniques have been used in Japan for tissue sampling of suspected gastrointestinal stromal tumors (GISTs) instead of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of the present report was to evaluate the diagnostic yield and sensitivity of this procedure, which we named mucosal incision assisted biopsy (MIAB), for the histological diagnosis of gastric submucosal tumor (SMT).
Patients and methods: We performed a retrospective review of the 15 patients with suspected gastric GIST who underwent MIAB in our hospitals between January 2010 and March 2011. This technique involved making a mucosal incision in the same way as the circumferential mucosal incision is made for ESD, followed by careful submucosal dissection until a portion of the lesion was exposed, and taking biopsy specimens under direct vision.
Results: Tissue samples obtained by MIAB were sufficient for us to make a histological diagnosis of the gastric SMTs in 13 of the 15 patients. There were no significant differences in age, sex, SMT location or SMT size between diagnostic and non-diagnostic MIAB groups of patients, but there was a significant difference in SMT growth patterns between the groups (p < 0.05).
Conclusions: Although it is generally accepted that EUS-FNA is the gold standard for obtaining tissue specimens for histological and cytological analysis of suspected gastric GISTs, MIAB can be used as an alternative method for obtaining biopsy specimens of lesions with an intraluminal growth pattern.

Event date： 2012.5

Language：English   Presentation type：Oral presentation (general)  

Venue：San Diego, CA   Country：United States  

Event date： 2011.7 - 2011.8

Presentation type：Oral presentation (general)  

Country：Japan  

ERK and p38MAPK regulate myosin light chain phosphatase and contribute to carbachol-induced contraction in rat intestinal smooth muscle.

Event date： 2009.5 - 2009.6

Presentation type：Oral presentation (general)  

Country：United States  

Hypoxia Inducible Factor (HIF-1alpha) Plays a Critical Innate Protective Role in Clostridium Difficile (Cdif) Toxin-Induced Intestinal Injury and Inflammation.

Event date： 2009.2 - 2009.3

Presentation type：Oral presentation (general)  

Country：Canada  

Pharmacological stabilization of HIF-1a is protective in a mouse model of clostridium difficile-associated intestinal inflammation.

Event date： 2009.2 - 2009.3

Presentation type：Oral presentation (general)  

Country：Canada  

Protein kinase signaling pathways contribute to hypercontractility in murine experimental colitis.

Event date： 2008.5

Presentation type：Oral presentation (general)  

Country：United States  

Up-regulation of HIF-1alpha is associated with augmented Rho-kinase-mediated contraction of ileal smooth muscle following exposure to Clostridium difficile toxins in a mouse ileal loop model.

Event date： 2008.2

Presentation type：Oral presentation (general)  

Country：Canada  

Ca2+-sensitization of colonic smooth muscle is altered in a murine experimental colitis model.

Event date： 2008.2

Presentation type：Oral presentation (general)  

Country：Canada  

Alterations in the contractile properties of ileal smooth muscle exposed to Clostridium difficile toxins: the involvemen

Event date： 2007.10

Presentation type：Oral presentation (general)  

Country：France  

Colonic smooth muscle contractile dysfunction in experimental colitis and its underlying mechanisms.

Event date： 2007.2

Presentation type：Oral presentation (general)  

Country：Canada  

Protein kinases responsible for Ca2+-independent contraction of intestinal smooth muscle.

Event date： 2006.7 - 2006.8

Presentation type：Oral presentation (general)  

Country：United States  

Exploration of protein kinases responsible for Ca2+-independent, microcystin-induced contraction in intestinal smooth muscle.

Event date： 2002.10

Presentation type：Oral presentation (general)  

Country：Switzerland  

The Useful Approach to Obstructing or Stenotic Lesions in the Distal Ileum by Retrograde Ileography.

Event date： 1999.5

Presentation type：Oral presentation (general)  

Country：Japan  

Endothelium-dependent triphasic regulation of vascular tone induced by bradykinin in the porcine renal artery.

Language：English   Presentation type：Oral presentation (general)  

Country：United States  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：鹿児島   Country：Japan  

Language：Japanese   Presentation type：Symposium, workshop panel (public)  

Venue：東京   Country：Japan  

Event date： 2024.2

Language：English  

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Event date： 2021.12

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Event date： 2021.10

Language：Japanese  

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