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

BACKGROUND AND AIM: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group. METHODS: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining. RESULTS: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone. CONCLUSIONS: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations.

DOI： 10.1111/jgh.16250

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BACKGROUND: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. METHODS: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. CONCLUSIONS: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP.

DOI： 10.1111/jgh.16065

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BACKGROUND AND AIM: Gastric atrophy is a precancerous lesion. We aimed to clarify whether gastric atrophy determined by artificial intelligence (AI) correlates with the diagnosis made by expert endoscopists using several endoscopic classifications, the Operative Link on Gastritis Assessment (OLGA) classification based on histological findings, and genotypes associated with gastric atrophy and cancer. METHODS: Two hundred seventy Helicobacter pylori-positive outpatients were enrolled. All patients' endoscopy data were retrospectively evaluated based on the Kimura-Takemoto, modified Kyoto, and OLGA classifications. The AI-trained neural network generated a continuous number between 0 and 1 for gastric atrophy. Nucleotide variance of some candidate genes was confirmed or selectively assessed for a variety of genotypes, including the COX-21195, IL-1β 511, and mPGES-1 genotypes. RESULTS: There were significant correlations between determinations of gastric atrophy by AI and by expert endoscopists using not only the Kimura-Takemoto classification (P < 0.001), but also the modified Kyoto classification (P = 0.046 and P < 0.001 for the two criteria). Moreover, there was a significant correlation with the OLGA classification (P = 0.009). Nucleotide variance of the COX-2, IL-1β, and mPGES-1genes was not significantly associated with gastric atrophy determined by AI. The area under the curve values of the combinations of AI and the modified Kyoto classification (0.746) and AI and the OLGA classification (0.675) were higher than in AI alone (0.665). CONCLUSION: Combinations of AI and the modified Kyoto classification or of AI and the OLGA classification could be useful tools for evaluating gastric atrophy in patients with H. pylori infection as the risk of gastric cancer.

DOI： 10.1002/jgh3.12810

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BACKGROUND AND AIM: To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan. METHODS: One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively. RESULTS: There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan. CONCLUSIONS: Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

DOI： 10.1111/jgh.15874

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

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BACKGROUND: Early chronic pancreatitis (ECP) has been reported to advance into chronic pancreatitis, it may be critical to differentiate the pathophysiology of ECP and functional dyspepsia (FD) in patients with pancreatic enzyme abnormalities (FD-P). This study aimed to clarify differences in the pathophysiology of ECP and FD-P and to determine whether duodenal inflammatory responses in the two diseases were associated with protease-activated receptor (PAR) 2, as the trypsin receptor. METHODS: Eighty patients who presented with FD-P and ECP were enrolled. In duodenal specimens, PAR2 mRNA levels were determined using real-time PCR. Using immunostaining, CD68-, GLP-1-, PRG2-, and CCR2-positive cells, tight junction proteins, and PAR 2 were evaluated. RESULTS: There were no significant differences in clinical symptoms and gastric motility between ECP and FD-P patients. The CD68-positive cells infiltrations and occludin expression levels in the duodenal mucosa of patients with FD-P were significantly (p<0.001 and p = 0.048, respectively) lower than those in patients with ECP. Although serum trypsin levels in ECP and FD-P patents were significantly (p<0.05 and p<0.001, respectively) associated with duodenal eosinophils counts, elevated trypsin levels were not significantly associated with degranulated eosinophils, occludin, claudin-1 and ZO-1 expression levels in the duodenum of either group. PAR2 mRNA levels were increased in the duodenum of patients with ECP and FD-P. PAR2 was localized in the epithelial cells of the duodenal mucosa and the surface of degranulated eosinophils in ECP and FD-P patients. CONCLUSIONS: Elevated trypsin levels might be partly associated with duodenal inflammatory responses through PAR2-related degranulated eosinophils and the reduction of occludin in patients with ECP and FD-P.

DOI： 10.1371/journal.pone.0275341

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Society for Free Radical Research Japan  

Since there were no available data about colonic diverticular bleeding in extremely elderly patients (>80 years old) treated with direct oral anticoagulants (DOACs), we tried to determine clinical characteristics in those with colonic diverticular bleeding taking DOACs and to compare clinical outcomes of those in DOAC-treated to those in warfarin-treated . We enrolled DOAC-treated (n = 20) and warfarin-treated (n = 23) extremely elderly patients with diverticular bleeding diagnosed by colonoscopy. We performed a retrospective review of patients' medical charts and endoscopic findings. We classified colonic diverticular bleeding based on endoscopic features due to modified previous study following three groups, type A (active bleeding), type B (non-active bleeding) and type C (bleeding suspected). Clinical outcomes such as number of recurrent bleeding, thrombotic events and mortality were estimated. There were no differences in endoscopical features and clinical characteristics between patients treated with DOAC and warfarin therapy. However, the number of recurrent bleeding, frequency of required blood transfusions and units of blood transfusion in warfarin-treated patients were significantly higher (p<0.05) compared to those in DOAC-treated groups. In addition, mortality and thrombotic events did not differ between DOAC- and warfarin-treated patients. Clinical outcomes suggest that DOACs can be recommended for extremely elderly patients with colonic diverticular disease.

DOI： 10.3164/jcbn.20-140

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We have reported that refractory functional dyspepsia patients with pancreatic enzyme abnormalities (FD-P). We tried to analyze the prevalence of exocrine pancreatic insufficiency (EPI) in FD-P patients to clarify whether the pathophysiology of FD patients including clinical symptoms and quality of life were associated with EPI. We enrolled forty-nine patients presenting with typical symptoms of FD-P patients (n = 20) and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 29). Five pancreatic enzymes (p-amylase, lipase, elastase-1, trypsin, and PLA2) were measured and STAI-state/-trait and SF-8 were evaluated. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). There were no significant differences in patient background between FD-P and AP-P patients. BT-PABA test scores for FD-P patients (61.67 ± 5.55) were significantly (p = 0.01) lower than in AP-P patients (95.38 ± 2.36). Physical component scale (PCS) in FD-P patients was significantly (p = 0.002) lower than that in AP-P patients. STAI-state was relatively (p = 0.054) associated with BT-PABA test in FD-P and AP-P patients by multiple logistic regression analysis. The prevalence of EPI in FD-P patients was significantly higher than that in AP-P patients and was relatively associated with state of anxiety. Further studies will be needed to clarify how EPI or pancreatic enzyme abnormalities are associated with the pathophysiology of FD-P patients.

DOI： 10.3164/jcbn.21-67

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Society for Free Radical Research Japan  

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.

DOI： 10.3164/jcbn.19-130

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

BACKGROUND: To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS-stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model. METHODS: Rats were divided into four groups. LPS-stimulated group (n = 4); LPS- and urocortin 2-treated group (n = 4); LPS- and acotiamide-treated group (n = 4); and LPS-, urocortin 2-, and acotiamide-treated group (n = 4). CD68-, CCR2-, and corticotropin-releasing hormone receptor type 2 (CRHR2)-positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF-α, IL-6, and IL-4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue. KEY RESULTS: Central administration of Ucn 2 significantly aggravated infiltrations of CD68- and CCR2-positive cells in the intestinal mucosa of LPS-stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68- and CCR2-positive cells in the jejunum of central Ucn 2-treated LPS-stimulated rat models. Acotiamide significantly reduced the expression levels of IkB-α phosphorylation in LPS- and MCP-1-stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF-α and IL-6 productions in LPS-stimulated NR8383 cells and astressin B reversed the inhibition of TNF-α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF-α and IL-6 productions in LPS- and MCP-1-stimulated NR8383 cells. CONCLUSIONS AND INFERENCES: Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.

DOI： 10.1111/nmo.13813

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/nmo.13813

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

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Functional dyspepsia (FD) is a common disease that can markedly impair quality of life. In the 2016 Rome IV criteria, a diagnosis of FD requires the presence of bothersome FD symptoms. In 2009, a new diagnosis, early chronic pancreatitis (ECP), was proposed as a means to facilitate early treatment of chronic pancreatitis and prevent progression to chronic pancreatitis. Although chronic pancreatitis was reported to be a cause of dyspepsia, data on the relation between ECP and FD patients are limited. We therefore investigated differences between ECP patients and FD patients in the percentages of those with severe epigastric pain, early satiety, and postprandial abdominal fullness. Several studies reported an association between the cause of chronic pancreatitis and endosonographic features. In addition, endosonography was useful for distinguishing ECP patients from FD patients with pancreatic enzyme abnormalities. Thus, we compared endosonographic characteristics in these patient groups. Future studies should attempt to determine why selected FD patients with pancreatic enzyme abnormalities develop ECP.

DOI： 10.1272/jnms.JNMS.2020_87-101

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Language：Japanese   Publisher：(一社)日本臨床薬理学会  

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BACKGROUND AND AIMS: To determine whether serum acylated ghrelin levels were associated with anxiety, clinical symptoms, depressive status, quality of life, gastric motility and endoscopic findings based on Kyoto classification in functional dyspepsia (FD) patients. METHODS: We enrolled three groups, FD patients (n = 15) with high levels of acylated ghrelin, FD patients (n = 33) with normal levels of acylated ghrelin and FD patients (n = 35) with low levels of acylated ghrelin. There was no significant differences in the positivity of Helicobacter pylori infection among the three groups. Clinical symptoms were evaluated by Gastrointestinal Symptom Rating Scale (GSRS) and FD symptoms based on Rome III classification. Acylated ghrelin levels were measured by ELISA methods. Depressive status, anxiety, sleep disturbance were respectively asscessed by Self-rating questionnaire for depression (SRQ-D) score, STAI-state/-trait, Pittsburgh sleep quality index (PSQI) scores. Endoscopic findings were evaluated based on Kyoto classification. RESULTS: Body Mass Index (BMI) in FD patients with low levels of acylated ghrelin was significantly higher (p<0.001 and p = 0.008, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. SRQ-D scores in FD patients with low levels of acylated ghrelin was significantly lower (p = 0.008 and p<0.001, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. Scoring of gastric atrophy, intestinal metaplasia, xanthoma and mucus based on Kyoto classification in FD patients with low levels of acylated ghrelin were significantly higher (p<0.001, p = 0.0077, p = 0.036 and p = 0.0063, respectively) compared to those in FD patients with more than low levels of acylated ghrelin. CONCLUSION: Acylated ghrelin levels were associated with BMI, depressive status, and endoscopic findings based on Kyoto classification in FD patients.

DOI： 10.3164/jcbn.18-111

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Language：English   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2019.03.1085

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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

BACKGROUND/AIMS: The aims of the study are to clarify the pathophysiological differences among early chronic pancreatitis (ECP), functional dyspepsia with pancreatic (FD-P) enzyme abnormalities and FD patients and to determine whether camostat mesilate, pancrelipase, and rabeprazole triple therapy improve FD symptoms in the ECP patients and FD-P patients in cross-over way. METHODS: We enrolled 84 consecutive patients presenting with typical symptoms of FD patients (n = 42), ECP patients (n = 15), and FD-P patients (n = 27). Gastric emptying was assessed by the 13C-acetate breath test. ECP was diagnosed based on the criteria recommended by the Japan Pancreatic Association. RESULTS: The proportions of female in ECP patients and FD-P were significantly higher compared to that in FD patients. The early phase of gastric emptying in ECP and FD-P patients was significantly disturbed compared to that in FD patients. The primary outcome of this study is that 4 weeks of camostat mesilate, pancrelipase, and rabeprazole triple therapy significantly ameliorated epigastric pain in ECP patients compared to acotiamide and rabeprazole combination therapy. CONCLUSION: Although there were no significant differences in pathophysiology between ECP patients and FD-P patients, triple therapy can significantly ameliorate epigastric pain in ECP patients. Further studies will be needed to clarify why triple therapy can improve epigastric pain in ECP patients.

DOI： 10.1159/000492813

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BACKGROUND AND AIMS: Three-dimensional (3D) rigid endoscopy has been clinically introduced in surgical fields to enable safer and more accurate procedures. To explore the feasibility of 3D flexible endoscopy, we conducted a study comparing 2-dimensional (2D) and 3D visions for the performance of esophageal endoscopic submucosal dissection (ESD). METHODS: Six endoscopists (3 experts and 3 trainees) performed ESD of target lesions in isolated porcine esophagus using a prototype 3D flexible endoscope under 2D or 3D vision. Study endpoints were procedure time, speed of mucosal incision and submucosal dissection, number of technical adverse events (perforation, muscle layer damage, and sample damage), and degree of sense of security, fatigue, and eye strain. RESULTS: Procedure time and speed of mucosal incision/submucosal dissection were equivalent for 2D and 3D visions in both experts and trainees. The number of technical adverse events using 2D vision (mean [standard deviation], 3.5 [4.09]) tended to be higher than that using 3D vision in trainees (1.33 [2.80]; P = .06). In experts, 2D and 3D visions were equivalent. The degree of sense of security using 3D vision (3.67 [0.82]) was significantly higher than that using 2D vision (2.67 [0.52]) in trainees (P = .04), but was equivalent in experts. The degree of eye strain using 3D vision (3.00 [0.00]) was significantly higher than that using 2D vision (2.17 [0.41]) in trainees, but was equivalent in experts. CONCLUSIONS: 3D vision improves the sense of security during ESD and may reduce technical errors, especially in trainees, indicating the feasibility of a clinical trial of ESD under 3D vision.

DOI： 10.1155/2019/4051956

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BACKGROUND: There was no available data concerning the clinical differentiation between the updated definition of early chronic pancreatitis (ECP) and anti-acid therapy-resistant functional dyspepsia (RFD). AIMS: We aimed to determine whether clinical symptoms, gastric motility, psychogenic factors and fat intake can help distinguish early chronic pancreatitis (ECP) from anti-acid therapy-resistant functional dyspepsia patients with pancreatic enzyme abnormalities (RFD-P) and anti-acid therapy-resistant functional dyspepsia (RFD) patients using endosonography. METHODS: We enrolled 102 consecutive patients presenting with typical symptoms of RFD patients (n = 52), ECP patients (n = 25) and RFD-P patients (n = 25). ECP patients were diagnosed based on the criteria recommended by the Japan Pancreatic Association. Gastric motility was evaluated by 13C-acetate breath tests. Severity of duodenal inflammation was examined. RESULTS: 24.5% of RFD patients were determined as ECP using endosonography. Abdominal pain score in Gastrointestinal Symptom Rating Scale (GSRS) in the patients with ECP was significantly lower compared to that in the patients with RFD-P. There were no significant differences in State-Trait Inventory (STAI)-state/-trait scores, Self-Rating Questionnaire for Depression (SRQ-D) scores and clinical symptoms for fat intake among three groups. The early phase of gastric emptying (AUC5; AUC15) in ECP and RFD-P patients were significantly disturbed compared to those in RFD patients. CONCLUSIONS: Evaluation of severity of abdominal pain and measurement of the early phase of gastric emptying will be useful tools to distinguish ECP patients from RFD patients. Accurate diagnosis of ECP patients may contribute to the prevention from advancing of chronic pancreatitis.

DOI： 10.1371/journal.pone.0205165

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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DOI： 10.21037/tgh.2018.09.12

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

There was not available data about the overlap between functional dyspepsia (FD) and pancreatic diseases. We aimed to determine whether epigastric pain syndrome (EPS) accompanying with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by Japan Pancreas Society (JPS) using endosonography. We enrolled 99 consecutive patients presenting with typical symptoms of FD, including patients with postprandial distress syndrome (PDS) (n = 59), EPS with pancreatic enzyme abnormalities (n = 41) and EPS without pancreatic enzyme abnormalities (n = 42) based on Rome Ill criteria. Gastric motility was evaluated using the C-13-acetate breath test. Early chronic pancreatitis was detected by endosonography and graded from 0 to 7. The ratio of female patients among EPS patients (34/41) with pancreatic enzyme abnormalities was significantly (p = 0.0018) higher than the ratio of female EPS patients (20/42) without it. Postprandial abdominal distention and physical component summary (PCS) scores in EPS patients with pancreatic enzyme abnormalities were significantly disturbed compared to those in EPS patients without it. Interestingly, AUC(5) and AUC(15) values (24.85 +/- 1.31 and 56.11 +/- 2.51, respectively) in EPS patients with pancreatic enzyme abnormalities were also significantly (p = 0.002 and p = 0.001, respectively) increased compared to those (19.75 +/- 1.01 and 47.02 +/- 1.99, respectively) in EPS patients without it. Overall, 64% of EPS patients with pancreatic enzyme abnormalities were diagnosed by endosonography as having concomitant early chronic pancreatitis proposed by JPS. Further studies are warranted to clarify how EPS patients with pancreatic enzyme abnormalities were associated with early chronic pancreatitis proposed by JPS.

DOI： 10.3164/jcbn.17-41

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

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BACKGROUND: Recent updated guidelines of the Japanese Society of Gastroenterology recommend the use of a single dose of antiplatelet agents in patients undergoing endoscopic submucosal dissection (ESD). However, the postoperative bleeding risk after gastric ESD associated with the continuation or interruption of antithrombotic therapy remains controversial. We aimed to evaluate whether certain factors including interrupted antithrombotic therapy could affect early and delayed post-ESD bleeding risk. METHODS: Three hundred sixty-four patients with gastric neoplasms were treated with ESD at our hospital between October 2005 and December 2012. Seventy-four patients with interrupted antithrombotic therapy were undertaken with ESD. Early and delayed postoperative bleeding patterns were estimated. Various clinical characteristics such as gender, age, tumor location, tumor size, ESD procedure time, platelet count, and comorbidity were evaluated. RESULTS: There was a significant difference (p = 0.042) in the ESD procedure time between the patients with postoperative bleeding and those without it. There was no significant difference in postoperative bleeding between the patients on antithrombotic therapy and not on it. Moreover, interrupted antithrombotic therapy and platelet count were significantly (p = 0.0461 and p = 0.0059, respectively) associated with early postoperative bleeding in multivariate analysis. In addition, in univariate analysis, ESD procedure time was significantly (p = 0.041) associated with delayed postoperative bleeding. CONCLUSIONS: Antithrombotic therapy and prolonged ESD procedure time were significantly associated with early and delayed postoperative bleeding, respectively.

DOI： 10.1159/000475924

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BACKGROUND/AIMS: We aimed to clarify whether cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) genotypes were associated with certain histological findings and endoscopical appearances based on Kyoto classification. METHODS: We enrolled 285 Helicobacter pylori-infected gastritis patients. Genotypes of COX-2 1195, COX-2 1290, mPGES-1, interleukin-1β (IL-1β) 511 and tumour necrosis factor-α (TNF-α) 308 were analyzed. Genotyping was performed by polymerase chain reaction. Endoscopic appearances and histological assessment were determined by using Kyoto classification, operative link on gastritic intestinal metaplasia assessment and the updated Sydney system. RESULTS: There was a significant (p = 0.027) relationship between the IL-1β 511 C-carrier and histological gastric inflammation in H. pylori-infected gastritis patients. There was a significant (p = 0.009) correlation between the COX-2 1195 G-carrier genotype and histological intestinal metaplasia in the gastric antrum of H. pylori-infected gastritis patients and gastric xanthoma (p = 0.027). The COX-2 1195 G-carrier genotype was also significantly (p = 0.038) associated with the score of endoscopic intestinal metaplasia based on Kyoto classification. The mPGES-1 genotype was significantly (p = 0.002) associated with endoscopic swelling of area. CONCLUSION: Our results suggest that in Japan, there exists a significant correlation between the COX-2 1195 G-carrier genotype and intestinal metaplasia in histological and endoscopic findings based on Kyoto classification in H. pylori-infected gastric mucosa.

DOI： 10.1159/000479864

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An 81-year-old man was admitted with upper abdominal pain and weight loss. Esophagogastroduodenoscopy revealed a large tumor located from the gastric angle to the body. Histological analysis of a biopsy revealed a moderately differentiated adenocarcinoma. Computed tomography revealed metastases in the liver and lung and the patient was subsequently diagnosed with metastatic advanced gastric cancer. He was treated with chemotherapy using S-1 (80 mg/m2) and cisplatin (CDDP) (60 mg/m2). Twenty-two months after chemotherapy, the gastric tumor, and the nodules in the liver and lung, had disappeared. We subsequently diagnosed a clinical complete response. The patient was treated with further S-1 monotherapy for 7 months after complete response assessment. He has lived for more than 7 years since the initial diagnosis without recurrence. Chemotherapy using S-1 and CDDP may be a potent strategy for improving survival in elderly patients with advanced gastric cancer.

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

BACKGROUND: Impact of acid suppressants on lower gastrointestinal bleeding remains unclear in low-dose aspirin users; we aimed to investigate this relationship. METHODS: Retrospective cohort study of low-dose aspirin users who underwent coronary angiography for ischaemic heart disease in our institution between October 2005 and December 2006; patients were evaluated for upper or lower gastrointestinal bleedings within 3 years post-angiography. RESULTS: 538 patients were enrolled (males, 74.4%; mean age 67.4±10.6 years). Risk for upper gastrointestinal bleeding decreased with concomitant use of statins (HR, 0.37; 95% CI, 0.15-0.89), calcium channel blockers (HR, 0.29; 95% CI, 0.10-0.85), and histamine-2 receptor antagonists (HR, 0.26; 95% CI, 0.08-0.89). Concomitant use of proton pump inhibitors tended to decrease risk of upper gastrointestinal bleeding (HR, 0.27; 95% CI, 0.06-1.18). Risk for lower gastrointestinal bleeding increased with both concomitant use of warfarin (HR, 15.68; 95% CI, 4.43-55.53) and proton pump inhibitors (HR, 6.55; 95% CI, 2.01-21.32), but not with histamine-2 receptor antagonists. Hyperuricemia lowered risk for lower gastrointestinal bleeding (HR, 0.12; 95% CI, 0.02-0.88). CONCLUSIONS: In low-dose aspirin users, concomitant use of proton pump inhibitors increased lower gastrointestinal bleeding risk, independent from effects on upper gastrointestinal bleeding.

DOI： 10.1016/j.dld.2015.05.020

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BACKGROUND: In Japanese routine clinical practice, endoscopy is generally carried out without sedation. The present study aimed to identify the factors essential for appropriate selection of transnasal esophagogastroduodenoscopy (TN-EGD) as an alternative to unsedated transoral esophagogastroduodenoscopy (TO-EGD). PATIENTS AND METHODS: Subjects in this prospective cohort study comprised consecutive outpatients who underwent EGD at a single center. Factors predicting TO-EGD-induced distress were evaluated on a visual analog scale (VAS) and analyzed. Patients were classified into a two-layered system on the basis of these predictive factors, and the severity of distress between the TN-EGD and TO-EGD groups was compared using VAS and the change in the rate-pressure product as subjective and objective indices, respectively. RESULTS: In total, 728 outpatients (390 male, 338 female; mean age, 63.1 ± 0.5 years; TO-EGD group, 630; TN-EGD group, 98)met the inclusion criteria. Multivariate logistic regression analysis confirmed that age <65 years (P < 0.01; odds ratio [OR], 1.69; 95% confidence interval [CI], 1.14-2.52), gender (female; P < 0.01; OR,1.97; 95% CI, 1.34-2.91), marital status (single; P < 0.01; OR, 1.96; 95% CI, 1.18-3.27), and anxiety towards TO-EGD (P < 0.001; OR, 3.62; 95% CI, 2.44-5.37) were independently associated with intolerance. Both indices were significantly higher in the TO-EGD subgroup than in the TN-EGD subgroup in the high predictive class, but not in the low predictive class. CONCLUSION: Predictive factors for detecting intolerance to unsedated TO-EGD may be useful to appropriately select patients who transpose unsedated TO-EGD to TN-EGD.

DOI： 10.1111/den.12006

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BACKGROUND AND AIM: Little is known about the clinical significance of treatment for endoscopically determined peptic ulcers (EPU), incidentally detected as surrogate endpoints for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulcers complication, such as overt bleeding and perforation. Even uncomplicated-EPU without overt bleeding signs when antithrombotic agents (AT) were cotherapied may be of potential bleeding sites. The aim of the present study was to evaluate whether microcytic anemia, implying potential bleeding, is associated with NSAIDs-associated EPU or cotherapies with AT. METHODS: Two hundred and thirty-eight outpatients with rheumatoid arthritis under long-term NSAIDs therapies underwent upper endoscopy and were divided into the following four groups according to the pattern (presence: + or absence: -) of AT cotherapy/EPU, respectively: A, -/- (n = 165); B, -/+ (n = 44); C, +/- (n = 25); and D, +/+ (n = 4). RESULTS: EPU were found in 48 of the 238 studied patients (20.2%). After significant interactions among four groups hadstatistically been identified, hemoglobin (Hb) and mean corpuscular volume (MCV) as biomarkers for potential bleeding were compared between the groups.Hb and MCV were significantly lower in the D group than in the A,B, or C groups (Hb: P < 0.01, respectively; P < 0.05, MCV; P < 0.01 or P < 0.05, respectively). CONCLUSIONS: Patients with NSAIDs-associated EPU and AT cotherapy indicated significantly more severe microcytic anemia pattern than those without EPU or AT cotherapy, despite no evidence of overt bleeding. Even uncomplicated-EPU without overt bleeding when ATs were cotherapied may be of potential bleeding sites.

DOI： 10.1111/j.1443-1661.2012.01334.x

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We investigated over time whether contemporary Japanese patients with complicated peptic ulcers have any water-soluble vitamin deficiencies soon after the onset of the complicated peptic ulcers. In this prospective cohort study, fasting serum levels of water-soluble vitamins (vitamins B1, B2, B6, B12, C, and folic acid) and homocysteine were measured at 3 time points (at admission, hospital discharge, and 3 mo after hospital discharge). Among the 20 patients who were enrolled in the study, 10 consecutive patients who completed measurements at all 3 time points were analyzed. The proportion of patients in whom any of the serum water-soluble vitamins that we examined were deficient was as high as 80% at admission, and remained at 70% at discharge. The proportion of patients with vitamin B6 deficiency was significantly higher at admission and discharge (50% and 60%, respectively, p<0.05) than at 3 mo after discharge (10%). In conclusion, most patients with complicated peptic ulcers may have a deficiency of one or more water-soluble vitamins in the early phase of the disease after the onset of ulcer complications, even in a contemporary Japanese population.

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BACKGROUND: Endoscopic submucosal dissection (ESD) is more invasive than other common endoscopic procedures and may increase the risk for deep vein thrombosis (DVT)/pulmonary embolism. The incidence of DVT/pulmonary embolism after ESD has not been adequately studied. OBJECTIVE: To evaluate DVT incidence and disease-specific features of D-dimer levels in ESD patients. DESIGN: Prospective cohort study. SETTING: Single academic center. PATIENTS: This study involved 60 patients with superficial gastric neoplasms indicated for ESD. INTERVENTION: For all patients who underwent ESD, ultrasonography of the lower limbs was performed to detect DVT the day after ESD. D-dimer levels were measured 3 times: before ESD, immediately after ESD, and the day after ESD. MAIN OUTCOME MEASUREMENTS: DVT incidence after ESD. RESULTS: The DVT incidence was 10.0% (6/60). At all 3 time points, D-dimer measurements were higher in patients with DVT than in patients without DVT. According to receiver operating characteristic curve analysis, the resulting cut-off value of the D-dimer level the day after ESD was 1.9 μg/mL (sensitivity 83.3%; specificity 79.6%) for ESD patients, with superior association to pre-ESD or immediately after ESD. In univariate analyses, high D-dimer levels the day after ESD and the presence of comorbidities were significantly associated with DVT development. LIMITATIONS: Single center and small number of patients. CONCLUSION: ESD procedures have a moderate risk for venous thromboembolism. In patients undergoing ESD, D-dimer levels, especially on the day after ESD, may have specific features associated with DVT development.

DOI： 10.1016/j.gie.2011.06.015

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Language：English   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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

Low-dose aspirin, one of non-steroidal anti-inflammatory drugs(NSAIDs), has been increasingly used to prevent cardiovascular and cerebrovascular disease through its antiplatelet effect, mainly in the aged population, but aspirin treatment has been associated with gastrointestinal injures, especially peptic ulcer bleedings. However, as discontinuation of aspirin, unlike NSAIDs, may precipitate cardiovascular and cerebrovascular events, treatment of aspirin-associated ulcers should re-start aspirin as soon as possible, using proton pump inhibitor (PPI). Therefore, high risk patients for peptic ulcers should be prevented with antisecretory drugs, such as PPI or histamine H2-receptor antagonists, because ulcer bleedings in patients with treatment of low-dose aspirin can be serious.

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PURPOSE: The aim of this study was to pathologically investigate the developmental pattern of undifferentiated mucosal gastric cancer and to determine safe surgical margins for curative resection by endoscopic resection. RESULTS: Intramucosal cancer spread, or the width of the proliferative zone, was pathologically investigated in 47 cases of undifferentiated mucosal gastric cancer of size 20 mm or smaller without ulceration (scars). The 47 cases comprised 40 IIc and 7 IIb cases. The IIc cases consisted of 5 (12.5%) of intermediate-layer type (cancer localized at the intermediate layer of the mucosa), 31 (77.5%) of superficial type, and 4 of whole-layer type (10%). The IIb cases consisted of six of intermediate-layer type (85.7%) and one of superficial type (14.3%). The width of the proliferative zone in the 40 IIc cases ranged from 0 to 2,390 microm (average 605.5 microm). There was no significant correlation between width of proliferative zone and background mucosa. With regard to lesion size, average width was 243.6 microm in cases with longest diameter <or=5 mm, while it was significantly larger (617.1 microm) in cases with diameter >5 mm. CONCLUSIONS: In endoscopic treatment of undifferentiated mucosal gastric cancer of size 20 mm or smaller without ulceration (scars), the lateral safety margin should be 3 mm or more.

DOI： 10.1007/s10620-009-0883-4

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AIM: The aim of the present study was to examine therapeutic outcomes of endoscopic submucosal dissection (ESD) of undifferentiated-type intramucosal gastric cancer and the problems of diagnosis. METHODS: We reviewed 58 patients with preoperatively diagnosed undifferentiated-type intramucosal early gastric cancer (EGC) without ulceration with a diameter of 20 mm or smaller (expanded-indication lesion) who underwent ESD at the Cancer Institute Hospital between September 2003 and August 2008. RESULTS: The overall rates of one-piece resection and complete resection were 98% and 90% respectively, and the median operation time was 70 min. Bleeding was seen in 8.6% and perforation in 3.4%. The curative resection rate was low at 79%. Factors responsible for non-curative resection were most commonly submucosal invasions. If limited to pathologically diagnosed expanded-indication lesions, the curative resection rate was 98%. The difference in tumor size between a macroscopic diameter and a histological diameter was within +/-5 mm in 96% of expanded-indication lesions, with none of these cases having a histological diameter that exceeded the macroscopic diameter by more than 5 mm. CONCLUSION: ESD was technically feasible for expanded-indication lesions of undifferentiated-type EGC. We achieved a high rate of curative resection by the markings at sites 5 mm beyond the preoperatively determined lesion area. Factors responsible for non-curative resection were most commonly submucosal invasions. We should diagnose the depth of such lesions more carefully.

DOI： 10.1111/j.1443-1661.2010.00945.x

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Currently, transnasal esophagogastroduodenoscopy using an ultrathin endoscope is being widely carried out as a screening test for early gastric cancer. We compared the diagnostic utility of ultrathin esophagogastroduodenoscopy with that of conventional esophagogastroduodenoscopy in detecting 42 lesions of early gastric cancer that had a diameter of <or=20 mm. Only 27 lesions (64%) could be accurately diagnosed using ultrathin esophagogastroduodenoscopy. In nine lesions (22%), we failed to discern whether they were malignant. Six lesions (14%) could not even be detected. We found that the diagnostic utility of ultrathin esophagogastroduodenoscopy was inadequate, especially in the case of lesions that were located in the upper third region of the stomach and variegated lesions. In conclusion, the diagnostic utility of ultrathin esophagogastroduodenoscopy might be lower than that of conventional esophagogastroduodenoscopy in terms of screening for early gastric cancer. The disadvantages of ultrathin esophagogastroduodenoscopy should be taken carefully into consideration while examining lesions.

DOI： 10.1111/j.1443-1661.2009.00840.x

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BACKGROUND: The establishment of an optimal second-line regimen for Helicobacter pylori infection is required. Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole, the effects of a quadruple regimen in second-line therapy are unknown. This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection. MATERIALS AND METHODS: Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed. Before starting second-line therapy, patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests. Patients were randomized to receive rabeprazole (10 mg), amoxicillin (750 mg), and metronidazole (250 mg), either with clarithromycin (200 mg; RAMC group) or without (RAM group); all treatments were administered twice daily for 7 days. H. pylori eradication was confirmed by (13)C-urea breath tests performed 2 to 3 months post-therapy. RESULTS: As shown by intention-to-treat/per-protocol analyses, the cure rates for H. pylori infection were 88.5%/93.9% and 82.7%/84.3% for the RAMC and RAM groups. Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens, the eradication rates showed a clear trend in favor of the RAMC group. There were no severe side-effects in any group. CONCLUSIONS: In Japan, the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection.

DOI： 10.1111/j.1523-5378.2009.00664.x

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BACKGROUND AND AIMS: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases. METHODS: One hundred and fifty-one patients presenting with typical symptoms of FD (EPS, n = 36; PDS, n = 76) or NERD (n = 39), and 20 healthy volunteers were enrolled. Gastric motility was evaluated with the T(max) value as a marker of gastric emptying using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and SRQ-D scores to determine depression status. We measured both acylated and des-acylated ghrelin levels by ELISA methods. RESULTS: The Tmax value in PDS patients was significantly higher than in healthy volunteers. Acylated ghrelin levels were significantly lower in NERD and PDS patients than in healthy volunteers. Interestingly, there was significant correlation between the acylated ghrelin levels and Tmax value in PDS patients but not in EPS or NERD patients. CONCLUSION: Our results suggest that acylated ghrelin might play an important role in the pathophysiology of PDS patients through its effect on gastric emptying.

DOI： 10.1159/000205740

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BACKGROUND: Recent studies have shown that CD40, a key player in angiogenesis and tubular formation, is an extracellular receptor of the heat shock protein 70 (HSP70)-peptide complex in endothelial cells. The aim of the present study was to determine the effect of extracellular HSP70 treatment on CD40L-suppressed apoptosis and CD40L-induced tubular formation in human umbilical vein endothelial cells (HUVEC). METHODS: The apoptotic index of CD40L-stimulated HUVEC with or without recombinant human HSP70 was evaluated using terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay analysis. Binding of HSP70-peptide complex to CD40 on HUVEC was determined by double-labeling immunofluorescence methods. To evaluate the biological activity of CD40 engagement pretreated with rhHSP70 (0.5, 1 and 3 ng/mL), the extent of new capillary-like networking structure (tubular formation) formation in HUVEC was counted using an Olympus digital camera. Vascular invasion into MNK-28 cell clusters was assessed by counting the number of tubular structures extending from the HUVEC into growth factor-depleted Matrigel. Scores for CD34, HSP70 and CD40L expression levels in gastric cancer tissues were determined by immunostaining. RESULTS: CD40L stimulation inhibited vincristine-induced apoptosis of HUVEC in a dose-dependent manner. Extracellular HSP70 treatment significantly blocked the inhibition of apoptosis by CD40L in HUVEC exposed to vincristine. HSP70-peptide complex bound to CD40 on HUVEC. Extracellular HSP70 treatment also significantly reduced CD40L-induced tubular formation in a dose-dependent manner. HSP70 treatment also suppressed invasive tubular formation into MKN-28 cells clusters by CD40L-activated HUVEC. There was a significant relationship between CD40L expression levels and microvessel density; however, the relationship between HSP70 expression level and microvessel density in gastric cancer tissues was not significant. CONCLUSIONS: Extracellular HSP70 treatment blocks CD40L inhibition of apoptosis and CD40L induction of tubular formation in HUVEC.

DOI： 10.1111/j.1440-1746.2008.05442.x

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Recent studies have reported that expression of MCP-1 and its receptor, CCR2; and CD40-CD40 ligand (CD40L) interaction on mesenchymal cells play important roles in tumor development. Studies have also connected MCP-1, CCR2, and CD40L to COX-2 expression. The aim of this study was to examine the effect of MCP-1/CCR2 and CD40-CD40L interaction on COX-2 and VEGF expression in endothelial cells. We also investigated the localization of these proteins in gastric cancer tissue. COX-2 and CCR2 levels were evaluated in CD40L-stimulated HUVECs by Western blot and real-time PCR. VEGF secreted in the culture media was quantified by ELISA. Localizations of MCP-1, CD40L, CD34, CD40 and CCR2 in 34 gastric cancer tissue specimens were evaluated by immunohistochemistry. CD40-CD40L interaction-induced COX-2 production and subsequently, upregulated COX-2 production contributed to elevated VEGF and CCR2 levels in CD40L-stimulated HUVECs. CD40L-stimulated VEGF production was COX-2 but not COX-1 dependent. RS-102895, a CCR2-specific antagonist, significantly reduced VEGF production in CD40L- and MCP-1-stimulated HUVECs. MCP-1 had a synergistic effect on COX-2, CCR2 and VEGF levels in CD40L-stimulated HUVECs. In gastric cancer tissue, there was significant correlation between microvessel density and scores for CD40L, MCP-1 and CCR2 protein expression. Thus, MCP-1 had a synergistic effect on COX-2 and CCR2 protein expression in CD40L-stimulated HUVECs and thereby stimulated VEGF production in these cells.

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BACKGROUND: Recent studies have reported that expression of monocyte chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40 ligation on mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 (COX-2) has also been shown to contribute to tumor angiogenesis. We examined the interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric cancer to determine the effect of these factors on vascular endothelial growth factor (VEGF) production via upregulation of COX-2 expression. METHODS: COX-2, prostaglandin E2 (PGE2), and VEGF production were evaluated in CD40 ligand (CD40L)-stimulated macrophages. CD40L and MCP-1 mRNA levels in gastric cancer tissues were evaluated by real-time polymerase chain reaction (PCR). Localizations of MCP-1, CD40L, CD34, CD40, and CCR2 in 34 gastric cancer tissue specimens were evaluated by single-or double-label immunohistochemistry. RESULTS: COX-2 expression levels were significantly higher in CD40L-stimulated macrophages and correlated with increased PGE2 and VEGF production. Addition of MCP-1 to CD40L-stimulated macrophages had a synergistic effect on COX-2 expression and subsequent PGE2 and VEGF production. CD40L and MCP-1 mRNA levels were significantly higher in poorly differentiated gastric cancers than in H. pylori-infected gastritis patients. High microvessel density was significantly associated with MCP-1 and CCR2 scores and lymph node metastasis. CONCLUSIONS: MCP-1 and CD40L had a synergistic effect on COX-2 expression and subsequent VEGF production in gastric cancer.

DOI： 10.1007/s00535-007-2151-8

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BACKGROUND/AIM: The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylori-infected Mongolian gerbils. METHODS: Fifty-two Mongolian gerbils were divided into 3 groups and given 5 biweekly doses of N-methyl-N-nitrosourea (MNU; 30 ppm). At week 12, group 2 (n = 20) and group 3 (n = 22) gerbils were then given an injection of H. pylori, while group 1 controls (n = 10) received Brucella broth alone. In addition, 7 weeks after H. pylori inoculation, at week 19, group 3 gerbils also received a 36-week administration course of celecoxib (1,500 ppm) in their diet. The incidence of gastric adenocarcinoma was determined at week 54 by histological analysis. COX-2 and Cdx2 protein expression and COX activity were evaluated for each group. The extent of intestinal metaplasia, Cdx2 and MUC2 expression, and the apoptotic index were evaluated semi-quantitatively by immunohistochemistry. RESULTS: The incidence of gastric adenocarcinoma was: group 1, 0% (0/10); group 2, 65% (13/20), and group 3, 23% (5/22; p < 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and MUC2 protein immunoreactivity, and the extent of Alcian blue periodic acid-Schiff-positive intestinal metaplasia in H. pylori-infected gerbils. Celecoxib also induced apoptosis in these gerbils. Significant inhibition of Cdx2 expression in group 3 gerbils was also shown by Western blot analysis. CONCLUSIONS: Prior to the first appearance of intestinal metaplasia, timely administration of celecoxib prevents gastric cancer occurrence by disrupting the progression of intestinal metaplasia into gastric carcinoma through its inhibition of Cdx2 expression in MNU-pretreated H. pylori-infected Mongolian gerbils.

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Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pre-treatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM-1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.

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

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本膵臓学会  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

機能性ディスペプシア(Functional dyspepsia:FD)に対するガイドラインが2021年に上梓され,FDに対する理解が深まってきたと同時に難治性FD患者が臨床上問題となっている.難治性FD患者の中には,超音波内視鏡検査によって,早期慢性膵炎などの膵疾患が包含されていることが指摘されており,鑑別診断に準じた治療によって,臨床症状が改善することが報告されている.難治性FD患者においても十二指腸粘膜における炎症細胞浸潤が指摘されており,FDの動物実験モデルにおいても,十二指腸粘膜の炎症が指摘されている.FD患者においては,膵機能低下症例も少数ながら報告されており,膵酵素異常を伴うFD患者のうち,早期慢性膵炎へと進展する少数例があることを勘案すると一部の難治性FD患者においてはElastographyを用いた膵線維化の評価も今後必要と思われる.今後,難治性FD患者においては,超音波内視鏡やElastographyによる複合的な評価が重要であると思われる.現在われわれは,こうしたことに加え,特殊光を用いたFD患者の十二指腸粘膜の画像解析を進めている.(著者抄録)

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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Language：Japanese   Publisher：(一社)日本総合健診医学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J03750&link_issn=&doc_id=20230116240016&doc_link_id=10.7143%2Fjhep.50.97&url=https%3A%2F%2Fdoi.org%2F10.7143%2Fjhep.50.97&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：日本臨床生理学会  

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Authorship：Lead author   Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：日本臨床外科学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：日本消化器病学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)日本臨床社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01205&link_issn=&doc_id=20190925180008&doc_link_id=%2Fag6niria%2F2019%2F007710%2F008%2F1625-1631%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag6niria%2F2019%2F007710%2F008%2F1625-1631%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本潰瘍学会  

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

ラットにLPS 600μgを腹腔内投与し、8日目にUrocortin 2.016μgを脳槽内に投与し、9日目に消化管粘膜を摘出した。LPS単独投与群、LPS+Urocortin投与群の2群に分け、ラットの回腸・空腸粘膜におけるCD68、CCR2の免疫染色を行い、粘膜内・筋層内で比較検討した。LPS+Urocortin II投与群における回腸・空腸粘膜の粘膜内・筋層内のCD68陽性細胞・CCR2陽性細胞数はLPS単独投与群と比べ有意に増加していた。さらにLPS+MCP-1刺激したラット由来マクロファージcell-line(NR8383)の上清中のIL-6、TNF-αレベルはLPS単独刺激群と比較して増加していた。LPS刺激Urocortin脳槽内投与ラットモデルではUrocortin投与により粘膜内・筋層内炎症細胞浸潤を認めたが、その増加にはラット由来マクロファージのIL-6やTNF-αが関与している可能性があることが示唆された。

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

症例は60歳代女性で、40歳代に慢性腎不全で血液透析を導入、50歳代で大動脈弁と僧帽弁の弁置換術を受け、心房細動を発症した。60歳代で総胆管結石に対し内視鏡的逆行性胆管膵管造影を行い、ヘパリン化の際に腸腰筋血腫を発症し動脈塞栓術で止血されていた。今回、温泉旅行から帰宅途中に嘔気を感じ、自宅安静時に突然多量の血塊を嘔吐したため緊急入院となった。CTおよび上部消化管内視鏡所見から胃粘膜下血腫と診断した。内視鏡的には止血が困難であり、輸血とワルファリン内服中止で加療を開始した。第2病日に貧血が進行し、動脈塞栓術(TAE)を試みたが責任血管は指摘できなかった。さらに第4病日に貧血が進行し、再度血管造影を行ったところ、胃大網動脈の分枝に造影剤の貯留を認め、責任血管と判断しTAEを行った。その後もさらに貧血が進行し、第8病日に再度血管造影を行い、胃十二指腸動脈分枝をTAEし、その後貧血は改善した。第11病日の内視鏡検査では血腫は自壊し、前庭部に3型腫瘍類似の潰瘍を形成していた。第18病日の内視鏡検査では血腫は除去され、白苔を有する平坦な潰瘍底を認めた。その後の経過は良好であり、第27病日に退院した。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J04450&link_issn=&doc_id=20180627080017&doc_link_id=%2Fdw9poden%2F2018%2F009201%2F028%2F0096-0098%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2018%2F009201%2F028%2F0096-0098%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞接触型光学超拡大内視鏡であるECS(endocytoscopy system)はリアルタイムに生体粘膜細胞を観察でき,生検病理診断に匹敵しうる内視鏡診断を実現するoptical biopsyを可能とする.腺管構造異型と細胞異型に相当するECS所見を高度ECS異型と定義し,高度ECS異型陽性を癌診断基準とすると,早期胃癌診断感度は約90%,特異度は90～100%と高い診断能を有する.生検は患者・病変因子などで実施困難な場合があり,またsampling error・瘢痕形成によるESDへの悪影響・医療コスト増大などの課題もある.このため,ECSによるoptical biopsyのみで生検を省略するアプローチは有益な臨床応用となりえる.胃粘膜では生体染色が不良でECS観察が困難な症例が1割あるなどの課題はあるものの,ECSの発展普及が期待される.

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(株)南江堂  

高齢化に伴い,アテローム血栓症に対する抗血小板療法および静脈血栓症,心房細動,心弁膜症などに対する抗凝固療法の必要性は増している.抗血栓薬による抗血栓作用は,顕在性の潰瘍出血だけでなく,わずかな粘膜傷害でも長期的・潜在的消化管出血をきたしうる.服用者の多くが高齢者で基礎疾患を有するため,消化管出血および貧血が身体へ及ぼす影響は大きい.新規経口抗凝固薬(NOAC)による頭蓋内出血のリスクはwarfarinに比べ,きわめて低く,かつ脳卒中/全身性塞栓症の発症抑制効果における非劣性以上の結果が示されている.一方,消化管出血の年間発症率においてdabigatranとrivaroxabanは,warfarinに比べ有意に高率である.近年,より高い抗血栓効果を求めて,抗血栓薬を組み合わせる機会が増加している.消化管出血のリスクを高めるため,予防治療の必要性は増す.上部消化管障害の治療としては,まず適正な服薬指導と,粘膜刺激の少ない食事が望まれる.必要に応じて,プロトンポンプ阻害薬(PPI)による酸分泌抑制療法を行う.しかしながら,抗血栓薬を代表とする薬剤起因性消化管障害は,上部だけでなく下部消化管にも発症するため,より繊細な予防治療戦略が求められるが,今後の課題である.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2015&ichushi_jid=J00974&link_issn=&doc_id=20151210100068&doc_link_id=issn%3D0022-1961%26volume%3D116%26issue%3D6%26spage%3D1144&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D116%26issue%3D6%26spage%3D1144&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本内科学会-関東地方会  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

背景および目的:内視鏡的消化性潰瘍は、非ステロイド性抗炎症薬(NSAID)に関連する消化性潰瘍合併症(顕在性の出血および穿孔)の代用マーカーとして偶発的に発見され、潰瘍合併症の疫学的調査に使用されてきた。たとえ偶発的に発見される無症候性の内視鏡的消化性潰瘍でさえ、抗血栓薬の併用が潜在性出血の原因となっているかもしれない。そこで、今回われわれは、潜在性出血を示唆する小球性貧血が、NSAIDに関連する内視鏡的消化性潰瘍または抗血栓薬の併用とどのような関連があるか検討した。方法:238人の長期NSAIDを服用する関節リウマチ患者が上部内視鏡検査を行い、その結果から抗血栓薬の併用および内視鏡的消化性潰瘍の有無のパターンの組み合わせから4つのグループに分類(抗血栓薬の併用/内視鏡的消化性潰瘍があり:+またはなし:-)した:それぞれ:A、-/-(n=165);B、-/+(n=44);C、+/-(n=25);and D、+/+(n=4)。結果:内視鏡的消化性潰瘍は、48人(20.2%)に認められた。4群間に統計学的な有意な相互作用が見られることを同定した上で、ヘモグロビン(Hb)とmean corpuscular volume(MCV)を潜在性出血の指標として、各グループ間において比較した。HbとMCVはいずれも、A、BおよびC群よりD群において有意に低値であった(Hb:それぞれP<0.01;P<0.05、MCV;それぞれP<0.01またはP<0.05)。結論:抗血栓薬を併用しかつ内視鏡的消化性潰瘍を有する長期NSAID服用者は、顕性出血のエビデンスがなくても、他の長期NSAID服用者と比べ、有意に高度な小球性貧血が認められた。たとえ無症候性の内視鏡的消化性潰瘍であったとしても、抗血栓薬併用時には、潜在性に出血すると考えられた。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J00192&link_issn=&doc_id=20140703080012&doc_link_id=10.11280%2Fgee.56.2019&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.56.2019&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

低用量アスピリンによる消化管出血のリスクは、非ステロイド性抗炎症薬(NSAIDs)と同等またはそれ以上と考えられ、低用量アスピリン潰瘍の予防として酸分泌抑制薬を併用する機会が増えている。筆者らの検討では、プロトンポンプ阻害薬(PPI)の併用は、従来型のNSAIDsと同様、アスピリンに関連する下部消化管出血のリスクを高める。このPPIの影響は高齢者ではなく、非高齢者において顕著であった。したがって、PPIによる消化性潰瘍予防が一般化すればするほど、低用量アスピリンによる下部消化管傷害や出血が増加する可能性がある。今後、酸分泌抑制薬の併用が、どのようにアスピリン消化管傷害および出血に影響するか、さらなる検討が必要と思われた。(著者抄録)

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

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

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

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Language：Japanese   Publisher：日本臨床生理学会  

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

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本潰瘍学会  

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

高齢者では、非ステロイド系抗炎症薬(NSAIDs)だけでなく、抗血栓薬併用時における消化性潰瘍(PU)への対応策が求められている。3ヵ月以上NSAIDを服用するRA外来患者を対象とし、内視鏡的PUを調査した。PU発症率は、高齢者(61歳以上)群が非高齢者群と比べ有意に高率であった。高齢者群における、抗リウマチ薬、ビスフォスフォネートおよび抗血栓薬の併用は、PU発症率を高めた。プロトンポンプ阻害薬(PPI)またはプロスタグランジンE1製剤(PG)は、年齢に関係なくPU予防効果を認めたが、高齢者におけるヒスタミンH2-受容体拮抗薬(H2-RA)によるPU予防効果は非高齢者に比べ低かった。高齢者はNSAID潰瘍リスクが高く、併用薬がPU発症に影響を及ぼしやすい。長期NSAIDsを服用する高齢者では、PPIまたはPGによる潰瘍予防が望まれる。(著者抄録)

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Language：Japanese   Publisher：(株)ヴァンメディカル  

低用量アスピリンはアテローム硬化症がもたらす心血管系疾患の予防を目的とした抗血小板療法において中心的な役割を果たしている。一方で、低用量アスピリン療法に関連した粘膜傷害や潰瘍出血イベントが問題となっている。アスピリン潰瘍の有病率はおおむね10～15%であり、従来型非ステロイド性抗炎症薬(non-steroidal anti-inflammatory drugs:NSAIDs)と比べやや低率である。抗血小板薬としてのアスピリンは低用量のため、粘膜傷害作用は基本的に弱いことが、アスピリンとNSAIDsによる潰瘍発症リスクの違いに反映していると思われる。しかし、低用量アスピリンによる潰瘍出血リスクは、従来型のNSAIDsと同等と考えられる。(著者抄録)

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

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

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

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2011&ichushi_jid=J01539&link_issn=&doc_id=20110831440023&doc_link_id=10.11477%2Fmf.1407103720&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1407103720&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

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)医学書院  

患者は19歳,女性.主訴は心窩部痛,吐下血.前医で上部消化管内視鏡検査にて出血性胃潰瘍と診断されプロトンポンプ阻害剤(proton pump inhibitor ; PPI)を投与されていたが,胃潰瘍の再発を認め,当院に紹介となった.胃角から前庭部の前壁から小彎にかけてひだの集中像を伴った陥凹性病変を認めた.ひだは一部に融合を伴い,陥凹面は発赤した粘膜面を呈し,所々に白苔が付着した不整な潰瘍を認めた.生検でMALTリンパ腫と診断され,Helicobacter pyloriが陽性であった.CTやガリウムシンチにてLugano分類のI期と診断し,除菌療法を行った.二次除菌で除菌され,3ヵ月後には症状は消失し,上部消化管内視鏡検査,組織検査にて寛解した.その後に再発は認めていない.(著者抄録)

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

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

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Language：Japanese   Publisher：(有)科学評論社  

著者らは75歳以上の切除不能胃癌20例(高齢者群)を対象にS-1ベース化学療法を施行し、治療成績を75歳未満の非高齢者群20例と比較検討した。化学療法のレジメンはS-1単独療法、S-1+低用量CDDP療法、S-1+CDDP療法のいずれが施行された。その結果、BSCとなった症例は高齢者群で7例(35%)、非高齢者群で2例(10%)であった。推定50%生存期間中央値は非高齢者群18例で11.3ヵ月、高齢者群13例で14.5ヵ月と有意差はなかった。grade 3/4の有害事象は非高齢者群では白血球減少、貧血が3例(16.5%)、好中球減少が2例(11%)、食欲不振、吐気、口内炎、疲労、皮疹がそれぞれ1例(5.5%)で、高齢者群では好中球減少と血小板減少が2例(15%)、白血球減少、貧血、Cre上昇、食欲不振、下痢がそれぞれ1例(7.5%)と、両群間で有意差はなく、いずれの群も治療関連死はなかった。尚、在宅期間率は、非高齢者群で60.4%、高齢者群で78.8%と有意差はみられなかった。

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Language：Japanese   Publisher：(株)日本臨床社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J01205&link_issn=&doc_id=20101022100022&doc_link_id=1520291855268121600&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1520291855268121600&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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

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

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

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Language：English   Publisher：日本癌学会  

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Language：Japanese   Publisher：(NPO)日本食道学会  

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

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Language：Japanese   Publisher：(株)勁草書房コミュニケーション事業部  

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Language：Japanese   Publisher：(有)科学評論社  

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

低用量アスピリン(L-ASA)長期服用者における、消化管出血関連症状(吐下血、無症候性貧血)と内視鏡的消化性潰瘍(UL)との関連を検討した。対象は、心臓カテーテル検査(CAG)を行った長期L-ASAを服用した虚血性心疾患患者で、CAG後2年間に施行した上部内視鏡検査記録および診療録から情報を抽出した。患者538例のうち96例に上部内視鏡検査を行い、そのうち出血症状を認めた33例中14例でULを認めたが、症状がない63例では2例のみであった。抗潰瘍薬併用例のUL発症率は、非併用例と比べ有意に低かった。長期L-ASA服用患者では明らかな吐下血がないULでも、潜在性出血をきたす可能性があり、抗潰瘍薬を用いた予防・治療が望まれる。(著者抄録)

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

切除不能胃癌症例において、75歳以下のPS良好例に対してはS-1ベース化学療法が生存期間延長に有効であると報告されている。今回、我々は75歳以上の切除不能胃がん症例を対象にS-1ベース化学療法の有効性を検討した。75歳以上の患者12例と75歳未満の患者12例を対象としレトロスペクティブに解析した。S-1ベース化学療法の生存期間中央値は非高齢者(75歳未満)群で9.7ヵ月、高齢者(75歳以上)群で9.5ヵ月であった。各群の有害事象は容認できる範囲であった。75歳以上の切除不能胃癌症例であってもPS良好例ではS-1ベース化学療法は生存期間延長に有用である可能性が示唆された。(著者抄録)

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

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

75歳以上の切除不能胃癌症例を対象に、S-1ベース化学療法が有効か検討した。切除不能胃癌と診断した75歳以上の患者(高齢者群)8例と、75歳未満の患者(非高齢者群)10例を対象とした。S-1単独療法かS-1+低用量CDDP療法のいずれかを施行した。S-1ベース化学療法全体の生存期間中央値(MST)は、非高齢者群9.7ヵ月、高齢者群9.5ヵ月で有意差はなかった。非高齢者群でのS-1単独療法と、S-1+低用量CDDP療法のMSTはそれぞれ、15ヵ月、8.65ヵ月、高齢者群でそれぞれ10.5ヵ月、7.75ヵ月であった。grade3/4の有害事象は、非高齢者群では10例中、白血球減少、貧血、疲労、皮疹が各1例で、高齢者群では8例中、白血球減少が2例、貧血、クレアチニン上昇、食欲不振、下痢が各1例であった。いずれも治療関連死はなく、容認可能な範囲であった。

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Language：Japanese   Publisher：日本医科大学医学会  

胃液中の酸、ペプシンによる消化作用によって形成される胃・十二指腸潰瘍が消化性潰瘍と総称されてきた。現在ではHelicobacter pylori感染、非ステロイド性抗炎症薬(NSAID)およびストレスによる粘膜防護機構の破綻が、潰瘍発症の主因と考えられている。消化性潰瘍の現状について、潰瘍の2大要因である、H.pylori感染とNSAIDを中心に、消化性潰瘍の解明と治療の工夫について概説した。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2010&ichushi_jid=J04260&link_issn=&doc_id=20100219390003&doc_link_id=%2Fcw1nimed%2F2010%2F000601%2F003%2F0007-0012%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw1nimed%2F2010%2F000601%2F003%2F0007-0012%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

上部消化管内視鏡検査における低用量鎮静剤投与の効果について検討した。対象は2005年3月～2008年3月までのドック受診者のべ8389例(うち初回検査3371例、2回以上経験者5018例)で、鎮静剤ミダゾラムの体表面積あたりの投与量別にA群:1.5mg/m2未満(2196例)、B群:1.5～2.0mg/m2未満(3174例)、C群:2.0mg/m2以上(1017例)、D群:鎮静剤非投与(2002例)に分けて比較した。その結果、A、B、C、D群の偶発症の発生頻度は経皮的動脈血酸素飽和度(SpO2)の低下例がそれぞれ1.3%、1.4%、1.5%、0.2%、血圧低下例が2.8%、3.0%、3.2%、0.1%、血圧上昇例が0.3%、0.5%、1.0%、0.5%、脈拍数低下例が2.6%、1.9%、2.3%、1.4%、更に脈拍数増加例が1.7%、2.3%、3.8%、1.4%、心拍血圧積(RPP)比2.5以上例が0.1%、0.2%、0.4%、0.1%と、いずれも4群間に有意差は認められなかった。しかし、検査後の感想で「楽だった」との回答では鎮静剤使用群では80%以上、非投与群では28.3%と有意差が確認された。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J00192&link_issn=&doc_id=20091026100010&doc_link_id=10.11280%2Fgee.51.2739&url=https%3A%2F%2Fdoi.org%2F10.11280%2Fgee.51.2739&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

症例は60歳代、女性。胃体下部大彎の早期胃癌に対して、幽門側胃切除(Billroth-I法)を施行後に異時性多発病変として早期胃癌を認め、ESDを行った。術翌日に遅発性穿孔に気がつき、クリップによる縫縮術にて保存的に改善した。ESD後の遅発性穿孔は比較的稀とされており、発症機序の考察も含め、報告する。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J04450&link_issn=&doc_id=20090622120011&doc_link_id=%2Fdw9poden%2F2009%2F007402%2F017%2F0052-0054%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2009%2F007402%2F017%2F0052-0054%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

噴門側胃切除後の逆流性食道炎軽減目的で、空腸間置術が施行されている。最近では残胃早期癌に対し内視鏡的粘膜下層切開剥離術(ESD)が行われるようになってきた。定期的なサーベイランス内視鏡で早期に発見された噴門側胃切除・空腸間置術後の残胃早期癌に対し、ESDで完全一括切除が可能であった3症例を経験した。3例とも治療時の内視鏡操作性に問題なく切除可能であった。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2008&ichushi_jid=J04450&link_issn=&doc_id=20080710140010&doc_link_id=%2Fdw9poden%2F2008%2F007202%2F017%2F0052-0054%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2008%2F007202%2F017%2F0052-0054%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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Language：Japanese   Publisher：(株)ヴァンメディカル  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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

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Language：Japanese   Publisher：(一社)日本ヘリコバクター学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

症例は62歳、男性。2006年8月末より食欲不振、嘔気あり。9月11日近医受診し、上部消化管内視鏡検査施行した。胃角部から体部にかけて広範な病変認められ、胃癌が疑われたため、9月16日当院紹介となった。当院で行った上部消化管内視鏡検査所見および梅毒血清反応高値から臨床的に胃梅毒と診断した。ペニシリン内服を開始し、症状は速やかに改善。12月に行った内視鏡検査で所見の改善を認めた。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2007&ichushi_jid=J04450&link_issn=&doc_id=20071203060015&doc_link_id=%2Fdw9poden%2F2007%2F007102%2F024%2F0066-0068%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2007%2F007102%2F024%2F0066-0068%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)勁草書房コミュニケーション事業部  

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Language：Japanese   Publisher：(株)勁草書房コミュニケーション事業部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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

超高齢者の早期胃癌内視鏡治療施行例における併存合併症、施行手技、施行時間、鎮静剤使用量、偶発症について検討した。検討症例は46例であり、内訳はESD施行32例、EMRC施行13例、ポリペクトミー施行1例であった。いずれの症例も鎮静剤としてミダゾラム、鎮痛剤として塩酸ペチジンを使用した。他臓器癌治療後の症例が約30%にみられた。全身的な合併症としては、高血圧以外では、脳梗塞後の症例が5例にみられた。施行時間はEMRCで約30分、ESDで約59分、鎮静剤は、それぞれミダゾラム2.2mg,3.69mg、塩酸ペチジン29.8mg,33.3mgであった。これらの量の鎮静・鎮痛剤の組み合わせでは、当院では呼吸抑制、循環動態変動などの副作用はみられず、安全に治療を遂行することができた。超高齢者においては、併存する合併症や体重にもよるが、ミダゾラム2～3mg前後、塩酸ペチジン35mg以下の使用で十分安全に使用できると考えられた。(著者抄録)

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

62歳男。2年前より胃粘膜下腫瘍を指摘されていた。上部消化管内視鏡で胃体中部大彎に15mm大の中央が軽度陥凹する粘膜下腫瘍様の隆起性病変を認めた。生検、ボーリングバイオプシーでは軽度の炎症細胞浸潤で、穿刺吸引細胞診でもリンパ球を少数認めるのみであった。超音波内視鏡では第3層を主座に均一な低エコーの充実性腫瘍を認め、一部隔壁を伴っていた。粘膜から粘膜下層に病変が存在し、内視鏡的切除が可能と判断した。2チャンネル法による内視鏡的粘膜切除術を施行し、出血・穿孔などの偶発症はなく、切除病変の切除径は20mm、病変は15mm大であった。病理組織所見では粘膜下層を中心に結節状のリンパ組織がみられ、不整形の腫瘍性胚中心の増生を認めた。免疫染色ではCD3、CD5が陰性、CD10、CD20、BCL-2蛋白が陽性で、Follicular lymphoma(Grade 1)と診断した。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2006&ichushi_jid=J04450&link_issn=&doc_id=20061214090020&doc_link_id=%2Fdw9poden%2F2006%2F006902%2F028%2F0076-0078%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdw9poden%2F2006%2F006902%2F028%2F0076-0078%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)医薬情報研究所  

胃腺腫に対するNarrow Band Imaging(NBI)併用拡大内視鏡観察の有用性を検討した.EMR施行前の生検で腺腫と診断した106病変を対象とした.NBI併用拡大内視鏡観察所見と切除標本の病理組織像を対比検討した.術後病理診断では,106病変中36例が腺腫内癌であった.微細血管構造が観察される病変,特に網目パターンを観察する病変は癌合併の可能性,敷石状腺管構造のみを観察する病変は胃型形質が強く,病変内に癌合併の可能性が示唆された.管状腺管構造のみ観察する病変は腸型形質を有し,特に白色均一病変は腺腫の可能性が極めて高かった

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Language：Japanese   Publisher：(株)勁草書房コミュニケーション事業部  

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Language：Japanese   Publisher：(株)勁草書房コミュニケーション事業部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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Language：Japanese   Publisher：(株)ヴァンメディカル  

Barrett食道は逆流性食道炎の修復過程で出現してくる合併症で,食道腺癌の発生母地として重要視されている.わが国においても,逆流性食道炎と診断される患者が明らかに増加していることから,胃食道逆流症(GERD)やBarrett食道が注目されるようになっている.Barrett食道腺癌の早期発見を前提としたBarrett食道の診断の工夫がなされ,近年,拡大内視鏡観察が最も多く検討されている.特にNarrow Band Imaging(NBI)を併用した拡大内視鏡観察は,粘膜微細模様や血管パターンを鮮明に観察することが可能で,その有用性が期待されている(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器外科学会  

日本住血吸虫卵が介在した多発早期大腸癌症例を経験したので報告する.症例は85歳の女性で,高血圧,糖尿病で当院内科通院中,血便を自覚し精査施行した.S状結腸に1'型の隆起性病変および上行結腸に多発ポリープを指摘され,手術目的で当院入院となった.S状結腸切除および上行結腸粘膜切除術を施行した.病理結果はS状結腸が腺腫内癌,上行結腸が腺腫(2病変)と腺腫内癌(1病変)であった.また,摘出したS状結腸および上行結腸の粘膜下を中心に多数の日本住血虫卵を認めた.日本住血吸虫症と大腸癌発生との関連性については相反する報告があり一定の見解を得ていない.本症例は虫卵が非癌部の粘膜下層に多く認められ,虫卵と発癌との因果関係を強く示唆するものではなかったが,多発性病変を有することからpseudopolypからadenomaへ,さらには癌へ移行する発癌機序が完全に否定されるものではないと考えられた(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2005&ichushi_jid=J01117&link_issn=&doc_id=20051209010009&doc_link_id=10.5833%2Fjjgs.38.1839&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.38.1839&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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

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

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

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Language：Japanese   Publisher：日本臨床生理学会  

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Language：Japanese   Publisher：(株)勁草書房コミュニケーション事業部  

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

NSAIDsはH.pylori感染と並ぶ消化性潰瘍の二大要因である.今回われわれは当院リウマチ科との共同研究により,長期NSAIDs服用RA患者の粘膜病変の実態調査を行ったところ,前庭部小彎に平坦・陥凹型胃癌との鑑別を要する症例を経験した.典型例を3例提示し,うち1例のLADG手術標本組織所見から,早期胃癌様の形態を呈する原因について若干の考察を加えて報告する(著者抄録)

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

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

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

血管新生因子として代表的なvascular endothelial growth factor(VEGF)に着目し,H.pyloriに感染した胃上皮細胞からのVEGF産生,およびこのVEGF産生に与えるteprenoneの影響を検討した.H.pylori感染MKN28細胞から産生される上清中のIL-8とVEGF産生は,H.pylori感染後,3,6,12および24時間においていずれも経時的に増加した.VEGF産生に対するteprenoneの影響を,H.pylori感染後24時問の培養上清で検討した.H.pyloriを添加していないMKN28細胞では,VEGF産生はわずかしかみられず,VEGF産生に対するteprenoneによる影響も認められなかった.H.pyloriを添加したMKN28細胞では,VEGF産生が有意に亢進し,teprenoneはその亢進したVEGF産生を用量依存的に抑制した

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本創傷治癒学会  

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

50歳男.下血と心窩部痛を主訴に来院し,上部消化管内視鏡にて胃角部に血管断端を伴う活動性胃潰瘍および十二指腸球部に潰瘍瘢痕が認められ,内視鏡的止血後に入院となった.入院後H2ブロッカー点滴静注を開始し,Helicobacter pylori(H.pylori)陽性所見から第30病日から除菌療法を施行した.8週間のプロトンポンプインヒビター(PPI)投与により除菌2ヵ月後の内視鏡ではH1 stageに改善していた.その後,受診が中断されていたが,除菌8ヵ月後に再び心窩部痛が出現,内視鏡では潰瘍は瘢痕化していたが,以前からの十二指腸球部前壁の瘢痕に加えA1 stageの潰瘍を認めたためPPI内服を再開した.5週間後の内視鏡で瘢痕化を認めPPIの服用を中止し,6ヵ月経過後には胃潰瘍は瘢痕化したままであったが,上十二指腸角近傍には再び線状のA2 stageの潰瘍が再発した.本症例のように非H.pylori,非NSAIDsの潰瘍再発症例が増加傾向にあり,今後,症例集積と病態解明が必要と考えられた

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2004&ichushi_jid=J04450&link_issn=&doc_id=20040621170001&doc_link_id=10.11641%2Fpde.64.2_28&url=https%3A%2F%2Fdoi.org%2F10.11641%2Fpde.64.2_28&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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

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

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

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会-関東支部  

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Language：Japanese   Publisher：(一社)日本循環器学会  

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