Publications by authors named "Yasuaki Nagami"

116 Publications

Easier attachment technique of polyglycolic acid sheet using thin-endoscope for prevention of stricture after esophageal endoscopic submucosal dissection.

Dig Endosc 2021 Jun 8. Epub 2021 Jun 8.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1111/den.14008DOI Listing
June 2021

Eosinophilic esophagitis and asymptomatic esophageal eosinophilia display similar immunohistological profiles.

J Clin Biochem Nutr 2021 May 14;68(3):246-252. Epub 2020 Nov 14.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.

Patients with asymptomatic esophageal eosinophilia (aEE) do not exhibit clinical symptoms because of esophageal dysfunction, although they have endoscopic and histological findings similar to those of eosinophilic esophagitis (EoE). The cause of the symptoms and the differences between aEE and EoE are unclear. The aim of this study is to determine whether aEE and EoE are same disease entities by comparing immune-related tissue biomarkers using immunohistological staining. Esophageal biopsy specimens from 61 patients, including 18 with aEE and 43 with EoE, were analyzed. Immunofluorescence staining was performed to quantify the immune-related tissue biomarkers such as major basic protein, eosinophil-derived neurotoxin, eotaxin-3, and immunoglobulin G4. Data are presented as median (interquartile range). There were no significant differences in clinical, endoscopic, or histological features, between patients with aEE and EoE, with the exception of body mass index. There were no significant differences in all immune-related tissue biomarkers between both groups. In conclusions, EoE and aEE displayed similar immunohistological profiles. Hence, they may be similar disease entities with some common pathogenic mechanisms. Our findings suggest that patients with aEE also have histopathological esophageal inflammation.
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http://dx.doi.org/10.3164/jcbn.20-49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129976PMC
May 2021

A case of nivolumab-induced cervical lymphadenopathy in a patient with gastric cancer.

J Gastrointest Oncol 2021 Apr;12(2):880-884

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Nivolumab is a monoclonal antibody targeting programmed cell death-1 (PD-1) that has been recently shown to exhibit clinical efficacy in patients with gastric cancer. However, various degrees of immune-related adverse events (irAEs) have been reported. We report the case of a 71-year-old male patient diagnosed with gastric cancer with peritoneal metastases. He was treated with nivolumab as third-line chemotherapy. On the 10 day after completing seven cycles of nivolumab treatment, he urgently visited the hospital because of mild left cervical lymphadenopathy. We suspected it to be due to inflammation and initiated treatment with levofloxacin hydrate. However, 3 days later, he was admitted to the emergency room due to exacerbation of his lymphadenopathy. A diagnosis of nivolumab-induced lymphadenopathy was made as the antibiotics were ineffective, and the patient was administered prednisolone (PSL) 20 mg. One day after admission, the pain and swelling of the lymph node greatly lessened, and the following day, the pain gradually disappeared; thereafter, the PSL dose was tapered and nivolumab treatment was resumed. The patient again developed cervical lymphadenopathy approximately 4-5 days after nivolumab was reintroduced, which disappeared 1 week later. During each episode of lymphadenopathy, he received a dose of 20 mg of PSL for 4 days, which would be eventually tapered to 10 mg without antibiotics and NSAIDs. After 2 months, cervical lymphadenopathy completely disappeared while 10 mg of PSL was continued, which was also eventually tapered off. To our knowledge, this is the first case report of nivolumab-induced lymphadenopathy in a patient with gastric cancer. This case suggested that we should keep in mind that various irAEs may occur during treatment with immune checkpoint inhibitors. It is necessary to ensure the absence of infection and metastasis before treatment and to promptly administer systemic corticosteroids to address them.
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http://dx.doi.org/10.21037/jgo-20-315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107580PMC
April 2021

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 Jun 15;10(12):3848-3861. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
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http://dx.doi.org/10.1002/cam4.3927DOI Listing
June 2021

Endoscopic Biopsy Technique using an Alcohol Swab to Prevent Transmission through the Instrument Channel in the COVID-19 Era.

Clin Endosc 2021 May 11. Epub 2021 May 11.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.5946/ce.2021.027DOI Listing
May 2021

Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan.

J Gastroenterol Hepatol 2021 May 7. Epub 2021 May 7.

Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.

Background And Aim: This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).

Methods: We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated.

Results: Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1).

Conclusion: We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.
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http://dx.doi.org/10.1111/jgh.15536DOI Listing
May 2021

Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.

PLoS One 2021 4;16(5):e0250862. Epub 2021 May 4.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Resolvin D1, a specialized pro-resolving lipid mediator produced from docosahexaenoic acid by 15- and 5-lipoxygenase, exerts anti-inflammatory effects driving to the resolution of inflammation. The present study aimed to elucidate its role in small intestinal damage induced by nonsteroidal anti-inflammatory drug (NSAID). Indomethacin was administered orally to C57BL/6J male mice, which were sacrificed 24 h later to collect small intestine specimens. Before administration of indomethacin, mice were subjected to intraperitoneal treatment with resolvin D1 or oral administration of baicalein, a 15-lipoxygenase inhibitor. Small intestinal damage induced by indomethacin was attenuated by pretreatment with resolvin D1. Furthermore, resolvin D1 reduced the gene expression levels of interleukin-1β, tumor necrosis factor-α, and CXCL1/keratinocyte chemoattractant. Conversely, the inhibition of 15-lipoxygenase activity by baicalein increased the expression of genes coding for these inflammatory cytokines and chemokine, leading to exacerbated small intestinal damage, and reduced the concentration of resolvin D1 in the small intestinal tissue. Exogenous treatment with resolvin D1 negated the deleterious effect of baicalein. 15-lipoxygenase was mainly expressed in the epithelium and inflammatory cells of the small intestine, and its gene and protein expression was not affected by the administration of indomethacin. Inhibition of the resolvin D1 receptor, lipoxin A4 receptor /formyl peptide receptor 2, by its specific inhibitors Boc-1 and WRW4 aggravated indomethacin-induced small intestinal damage. Collectively, these results indicate that resolvin D1 produced by 15-lipoxygenase contributes to mucoprotection against NSAID-induced small intestinal damage through its anti-inflammatory effect.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250862PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096073PMC
May 2021

The impact of cytochrome P450 3A genetic polymorphisms on tacrolimus pharmacokinetics in ulcerative colitis patients.

PLoS One 2021 22;16(4):e0250597. Epub 2021 Apr 22.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Tacrolimus (Tac) is an effective remission inducer of refractory ulcerative colitis (UC). Gene polymorphisms result in interindividual variability in Tac pharmacokinetics. In this study, we aimed to examine the relationships between gene polymorphisms and the metabolism, pharmacokinetics, and therapeutic effects of Tac in patients with UC. Forty-five patients with moderate-to-severe refractory UC treated with Tac were retrospectively enrolled. Genotyping for cytochrome P450 (CYP) 3A4*1G, CYP3A5*3, CYP2C19*2, CYP2C19*3, nuclear receptor subfamily 1 group I member 2 (NR1I2)-25385C>T, ATP-binding cassette subfamily C member 2 (ABCC2)-24C>T, ABCC2 1249G>A, and ABCC2 3972C>T was performed. Concentration/dose (C/D) ratio, clinical therapeutic effects, and adverse events were evaluated. The C/D ratio of Tac in UC patients with the CYP3A4*1G allele was statistically lower than in those with the CYP3A4*1/*1 allele (P = 0.005) and significantly lower in patients with CYP3A5*3/*3 than in those with CYP3A5*1 (P < 0.001). Among patients with the CYP3A4*1G allele, the C/D ratio was significantly lower in patients with CYP3A5*1 than in those with CYP3A5*3/*3 (P = 0.001). Patients with the NR1I2-25385C/C genotype presented significantly more overall adverse events than those with the C/T or T/T genotype (P = 0.03). Although CYP3A4*1G and CYP3A5*3 polymorphisms were related to Tac pharmacokinetics, CYP3A5 presented a stronger effect than CYP3A4. The NR1I2-25385C/C genotype was related to the overall adverse events. The evaluation of these polymorphisms could be useful in the treatment of UC with Tac.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250597PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062093PMC
April 2021

Gastrointestinal endoscopic practice during COVID-19 pandemic: a multi-institutional survey.

Rom J Intern Med 2021 Jun 8;59(2):166-173. Epub 2021 May 8.

Department of Gastroenterology, Osaka City University Graduate School of Medicine.

An on-going coronavirus disease 2019 (COVID-19) has become a challenge all over the world. Since an endoscopy unit and its staff are at potentially high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we conducted a survey for the management of the gastrointestinal endoscopic practice, personal protective equipment (PPE), and risk assessment for COVID-19 during the pandemic at multiple facilities. The 11-item survey questionnaire was sent to representative respondent of Department of Gastroenterology, Osaka City University Hospital, and its 19 related facilities. A total of 18 facilities submitted valid responses and a total of 373 health care professionals (HCPs) participated. All facilities (18/18: 100%) were screening patients at risk for SARS-CoV-2 infection before endoscopy. During the pandemic, we found that the total volume of endoscopic procedures decreased by 44%. Eleven facilities (11/18: 61%) followed recommendations of the Japan Gastroenterological Endoscopy Society (JGES); consequently, about 35%-50% of esophagogastroduodenoscopy and colonoscopy were canceled. Mask (surgical mask or N95 mask), face shield/goggle, gloves (one or two sets), and gown (with long or short sleeves) were being used by endoscopists, nurses, endoscopy technicians, and endoscope cleaning staff in all the facilities (18/18: 100%). SARS-CoV-2 infection risk assessment of HCPs was conducted daily in all the facilities (18/18: 100%), resulting in no subsequent SARS-CoV-2 infection in HCPs. COVID-19 has had a dramatic impact on the gastrointestinal endoscopic practice. The recommendations of the JGES were appropriate as preventive measures for the SARSCoV-2 infection in the endoscopy unit and its staff.
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http://dx.doi.org/10.2478/rjim-2020-0038DOI Listing
June 2021

Comparison of the Diagnostic Efficiency of Radial- and Convex-Arrayed Echoendoscopes for Indirect Findings of Pancreatic Cancer: A Retrospective Comparative Study Using Propensity Score Method.

Cancers (Basel) 2021 Mar 11;13(6). Epub 2021 Mar 11.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.

Endoscopic ultrasonography (EUS) is useful for detecting early-stage pancreatic cancer. Because the detection of small lesions is difficult, it is important to detect indirect findings, namely caliber change, retention cysts, and dilatation of the branch duct, during the procedure. Although two types of EUS endoscopes are frequently used, there is no comparative study on their efficacy for detecting indirect findings. Therefore, we aimed to compare the diagnostic efficacy of these two types for indirect findings. We retrospectively analyzed 316 consecutive patients who had undergone EUS for pancreaticobiliary disease at a single center between January 2017 and December 2018. The main outcome was the detection rate of indirect findings and its comparison between the two echoendoscope types. This outcome was achieved using the inverse probability of treatment weighting (IPTW) analysis. The detection rate of indirect findings was higher for the radial-arrayed endoscope than for the convex-arrayed echoendoscope (9.2% vs. 2.3% ( = 0.02)). The univariate analysis also revealed that the radial-arrayed echoendoscope was significantly superior to the convex-arrayed echoendoscope in terms of the detection of indirect findings (odds ratio, 5.94; 95% confidence interval, 1.68-21.10; = 0.01) after IPTW. After adjustment for magnetic resonance imaging (MRI) and computed tomography (CT), radial-arrayed echoendoscope remained an independent factor for indirect finding detection (odds ratio, 6.04; 95% confidence interval, 1.74-21.00; = 0.01). Finally, five patients who had indirect EUS findings were diagnosed with pancreatic cancer. Our results indicate that the radial-arrayed echoendoscope is useful for the detection of indirect findings.
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http://dx.doi.org/10.3390/cancers13061217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001660PMC
March 2021

Classification of patients with esophageal eosinophilia by patterns of sensitization revealed by a diagnostic assay for multiple allergen-specific IgEs.

J Gastroenterol 2021 May 16;56(5):422-433. Epub 2021 Feb 16.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Background: Eosinophilic esophagitis (EoE) is considered to be an immunoglobulin E (IgE)-mediated allergic disorder. Our goal was to examine IgE-mediated allergic sensitization patterns in patients with esophageal eosinophilia (EE).

Methods: We enrolled subjects with EE who underwent evaluation with a diagnostic panel to document multiple allergen-specific IgEs. Statistically significant groups were identified by cluster analysis. We also defined allergens based on their characteristics including outdoor, indoor, plant, and animal allergens.

Results: We classified patients with EE into 3 distinct groups, including cluster 1 (n = 62) who were minimally sensitized to most allergens except pollen and house dust, cluster 2 (n = 30) who were hypersensitized to outdoor and plant allergens, and cluster 3 (n = 15) who were hypersensitized to most allergens, most notably to indoor and animal allergens. Dysphagia reported among those in clusters 1, 2, and 3 at 35.5%, 46.7%, and 73.3%, respectively, (p = 0.028) and EoE endoscopic reference scores (EREFS) at 3.0, 6.0, and 8.0, respectively, (p < 0.001) differed significantly between the 3 clusters. Those in cluster 3 had a significantly higher prevalence of dysphagia (35.5% vs. 73.3%, p = 0.030), and higher EREFS with respect to rings (0.3 vs. 0.9, p = 0.003) and strictures (0.0 vs. 0.13, p = 0.011) compared to those in cluster 1.

Conclusions: IgE-mediated allergic sensitization patterns are associated with clinical features of patients with EE. Use of a diagnostic panel that detects multiple allergen-specific IgEs can help to explain the heterogeneous phenotype of this patient cohort.
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http://dx.doi.org/10.1007/s00535-021-01766-3DOI Listing
May 2021

Prevalence and risk factors of functional constipation in the Rome IV criteria during a medical check-up in Japan.

J Gastroenterol Hepatol 2021 Feb 8. Epub 2021 Feb 8.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background And Aim: Functional constipation (FC) is one of the functional bowel disorders with symptoms of constipation in the Rome IV criteria. This study aimed to examine the epidemiology of FC in a large-scale survey of individuals undergoing a medical check-up in Japan.

Methods: A total of 13 729 subjects who underwent a medical check-up at MedCity21 between April 2018 and March 2019 were given a questionnaire that inquired about bowel habits. Among them, 10 658 subjects participated in this study, and FC was diagnosed based on the Rome IV criteria.

Results: The number of subjects who fulfilled diagnostic criteria of FC was 220, and the prevalence of FC was 2.1%. Compared with subjects with non-FC, those with FC were more complaining of abdominal bloating and distension, feeling stressed, getting annoyed, lack of motivation, fatigue upon waking, and feeling depressed. The risk of FC was significantly lower among subjects who drank alcohol more than 5 days a week, exercised for more than 30 min at least twice a week for more than 1 year, and were getting enough rest by sleeping, whereas it was significantly higher among women and subjects who were eating faster than other people.

Conclusions: The prevalence of FC in Japanese subjects during a medical check-up was relatively low compared with that in Western countries. Subjects with FC had troublesome symptoms, and it might be suggested that female sex, lack of regular exercise with moderate activity, insufficient rest by sleeping, and eating faster were a risk of FC.
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http://dx.doi.org/10.1111/jgh.15436DOI Listing
February 2021

Rebleeding in patients with delayed bleeding after endoscopic submucosal dissection for early gastric cancer.

Dig Endosc 2021 Feb 4. Epub 2021 Feb 4.

Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan.

Objectives: Delayed bleeding is a major adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Some patients may experience rebleeding after successful hemostasis for delayed bleeding, yet the details of rebleeding remain unclear. We aimed to clarify the frequency and risk factors of rebleeding.

Methods: Among 11,452 patients who underwent ESD for EGC at 33 institutions in Japan between 2013 and 2016, we analyzed 489 patients showing delayed bleeding. The rate of rebleeding was investigated. Subsequently, 15 candidate variables were evaluated for their influence on the risk of rebleeding via logistic regression analysis.

Results: Rebleeding occurred in 11.2% (55/489) of the enrolled patients. Multivariate analysis revealed that warfarin [odds ratio (OR), 2.71; 95% confidence interval (CI), 1.26-5.84] and a resection size >40 mm (OR, 1.99; 95% CI, 1.08-3.67) were independent risk factors for rebleeding. In the analysis of the management of warfarin after index bleeding, only warfarin discontinuation (OR, 3.66; 95% CI, 1.37-9.78) was significantly associated with rebleeding in comparison with no use of warfarin. However, many rebleeding events (75.0%) occurred following the resumption of warfarin. The rebleeding rate during discontinuation status and that in taking warfarin (continuation or resumption) were 6.1% and 20.0%, respectively.

Conclusions: Rebleeding was not a rare event in patients experiencing delayed bleeding after ESD for EGC. In addition to having a resection size >40 mm, warfarin usage placed patients at high risk for rebleeding, especially at the timing of its resumption following discontinuation as well as its continuation.
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http://dx.doi.org/10.1111/den.13943DOI Listing
February 2021

Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota.

PLoS One 2021 28;16(1):e0245995. Epub 2021 Jan 28.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Non-steroidal anti-inflammatory drugs (NSAIDs) induce small intestinal damage. It has been reported that rebamipide, a mucoprotective drug, exerts a protective effect against NSAID-induced small intestinal damage; however, the underlying mechanism remains unknown. In this study, we investigated the significance of the small intestinal microbiota in the protective effect of rebamipide against indomethacin-induced small intestinal damage in mice. A comprehensive analysis of the 16S rRNA gene sequencing revealed an alteration in the composition of the small intestinal microbiota at the species level, modulated by the administration of rebamipide and omeprazole. The transplantation of the small intestinal microbiota of the mice treated with rebamipide suppressed the indomethacin-induced small intestinal damage. Omeprazole, a proton pump inhibitor, exacerbated the indomethacin-induced small intestinal damage, which was accompanied by the alteration of the small intestinal microbiota. We found that the transplantation of the small intestinal microbiota of the rebamipide-treated mice ameliorated indomethacin-induced small intestinal damage and the omeprazole-induced exacerbation of the damage. These results suggest that rebamipide exerts a protective effect against NSAID-induced small intestinal damage via the modulation of the small intestinal microbiota, and that its ameliorating effect extends also to the exacerbation of NSAID-induced small intestinal damage by proton pump inhibitors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245995PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842908PMC
January 2021

Continuous warfarin administration versus heparin bridging therapy in post colorectal polypectomy haemorrhage: a study protocol for a multicentre randomised controlled trial (WHICH study).

Trials 2021 Jan 7;22(1):33. Epub 2021 Jan 7.

Department of Gastroenterology and Hepatology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan.

Background: Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding.

Methods: We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events.

Discussion: The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy.

Trial Registration: UMIN-CTR UMIN000023720 . Registered on 22 August 2016.
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http://dx.doi.org/10.1186/s13063-020-04975-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791998PMC
January 2021

A Rare Case of Clival Metastasis in a Patient with Gastric Cancer.

Intern Med 2020 15;59(24):3161-3164. Epub 2020 Dec 15.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.

We report a rare case of clival metastasis from gastric cancer. A 73-year-old man with advanced gastric cancer treated with nivolumab as a third-line chemotherapy experienced headache, tongue deviation, and difficulties in speaking clearly. We suspected stroke or brain metastasis, but brain contrast-enhanced magnetic resonance imaging demonstrated a clival mass, diagnosed as clival metastasis from gastric cancer. The tumor could not be identified by plain computed tomography and plain magnetic resonance imaging alone. He received palliative radiotherapy (30 Gy/10 fr); his symptoms improved gradually. Although metastasis from gastric cancer to other organs is common, bone metastases are rare.
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http://dx.doi.org/10.2169/internalmedicine.5457-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807117PMC
April 2021

Utility of Kyoto Classification of Gastritis in subjects with a high-negative titer of anti- antibody during a medical check-up.

J Clin Biochem Nutr 2020 Nov 8;67(3):317-322. Epub 2020 May 8.

Departments of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.

Subjects with a high-negative titer (3-9.9 U/ml) of serum anti- () antibody represent a heterogeneous group of currently -infected, -uninfected, and previously -infected cases. We investigated the characteristics of subjects with a high-negative titer during a medical check-up and the utility of infection score, the sum of scores of endoscopic findings based on the Kyoto Classification of Gastritis, for diagnosing infection. Subjects with C-urea breath test-positive or stool antigen test-positive were diagnosed as currently -infected. Although around half of subjects with a high-negative titer were after eradication therapy (48.6%), currently -infected were considerably confirmed (11.7%). infection score showed a high value of area under the receiver operating characteristic curve [0.92; 95% confidence interval (CI), 0.84-1.00] with the most suitable cut-off value of 1.0 (sensitivity: 0.92; specificity: 0.90). Multivariate logistic regression analysis revealed that infection score was an independent factor associated with increased prevalence of infection (odds ratio, 9.53; 95% CI, 2.64-34.40; <0.001). Currently -infected subjects were considerably included among the subjects with a high-negative titer, and the Kyoto Classification of Gastritis was useful to predict current infection.
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http://dx.doi.org/10.3164/jcbn.20-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705079PMC
November 2020

Endoscopic findings of gastric lesions in patients with eosinophilic gastrointestinal disorders.

Endosc Int Open 2020 Dec 17;8(12):E1817-E1825. Epub 2020 Nov 17.

Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.

 Eosinophilic gastrointestinal disorders are classified into eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic colitis according to the site of eosinophilic infiltration. Although well established in eosinophilic esophagitis, endoscopic findings in eosinophilic gastritis and eosinophilic gastroenteritis with regard to gastric lesions have not been clearly described. The aim of this study was to identify endoscopic findings of gastric lesions associated with eosinophilic gastrointestinal disorders.  Out of 278 patients with eosinophilic gastrointestinal disorders, 18 had eosinophilic gastritis or eosinophilic gastroenteritis confirmed by biopsy; their endoscopic images were analyzed retrospectively. The association between endoscopic findings and number of eosinophils in the gastric mucosa was investigated.  Erythema was most frequently observed (72 %), followed by ulcers (39 %), discoloration (33 %), erosions (28 %), nodularity (28 %), and polyps (28 %). There were several unique endoscopic findings such as submucosal tumor-like deep large ulcers in three patients, antral -like appearances (small nodules radially lined toward the pyloric ring) in three patients, "muskmelon-like appearances" (discolored mucosa-composed mesh pattern) in three patients, multiple white granular elevations in two patients, cracks (appearance of furrows similar to those in eosinophilic esophagitis) in five patients, and antral rings in one patient. No significant association was observed between endoscopic findings and number of gastric eosinophils.  Several unique endoscopic findings of gastric lesions were observed in patients with eosinophilic gastritis or eosinophilic gastroenteritis. Submucosal tumor-like ulcers, antral -like appearances, muskmelon-like appearances, and cracks might be associated with eosinophilic gastrointestinal disorders.
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http://dx.doi.org/10.1055/a-1268-7312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676993PMC
December 2020

Effects of Colchicine on NSAID-Induced Severe Small Intestinal Damage: A Pilot Study.

Digestion 2020 Nov 17:1-6. Epub 2020 Nov 17.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: We previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) induced small intestinal damage through nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-dependent interleukin-1β secretion in mice. Our further study demonstrated that colchicine, a therapeutic agent for gout, significantly suppressed NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation in mice. However, clinical efficacy of colchicine for NSAID-induced small intestinal damage has not been established.

Objectives: We examined the clinical efficacy of colchicine in patients with NSAID-induced severe small intestinal damage as an animal-to-human translational research.

Methods: This is a single-center, single-arm, prospective pilot study. From February 2017 to March 2019, we performed video capsule endoscopy (VCE) to screen 10 patients who took NSAIDs continuously for more than 3 months, and 7 of those with severe small intestinal damage were enrolled. Participants were treated with oral colchicine 0.5 mg twice daily for 8 weeks and thereafter followed up with blood tests and VCE.

Results: After 8 weeks of colchicine treatment, complete healing was achieved in 4 patients (57.1%), and the median number of small erosions decreased significantly from 7.0 (range, 5.0-10.5) to 0.0 (range, 0.0-2.3) (p = 0.031). One patient withdrew due to diarrhea, and 5 patients revealed slightly elevated liver enzymes during the study. No other adverse events including changes in blood tests and clinical symptoms were observed.

Conclusions: Colchicine treatment achieved a high rate of complete healing in patients with NSAID-induced severe small intestinal damage.
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http://dx.doi.org/10.1159/000511255DOI Listing
November 2020

Long-term persistence of gastric dysbiosis after eradication of Helicobacter pylori in patients who underwent endoscopic submucosal dissection for early gastric cancer.

Gastric Cancer 2021 May 17;24(3):710-720. Epub 2020 Nov 17.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi Abeno-ku, Osaka, Japan.

Background: Gastric microbiome, other than Helicobacter pylori, plays a role in the tumorigenesis of gastric cancer (GC). Patients who undergo endoscopic submucosal dissection for early GC have a high risk of developing metachronous GC even after successful eradication of H. pylori. Thus, we investigated the microbial profiles and associated changes in such patients after the eradication of H. pylori.

Methods: A total of 19 H. pylori-infected patients with early GC who were or to be treated by endoscopic resection, with paired biopsy samples at pre- and post-eradication therapy, were retrospectively enrolled. Ten H. pylori-negative patients were enrolled as controls. Biopsy samples were analyzed using 16S rRNA sequencing.

Results: H. pylori-positive patients exhibited low richness and evenness of bacteria with the deletion of several genera, including Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas. H. pylori eradication partially restored microbial diversity, as assessed during a median follow-up at 13 months after eradication therapy. However, post-eradication patients had less diversity than that in the controls and possessed a lower abundance of the five genera mentioned above. The eradication of H. pylori also altered the bacterial composition, but not to the same extent as that in controls. The microbial communities could be clustered into three separate groups: H. pylori-negative, pre-eradication, and post-eradication.

Conclusion: Changes in dysbiosis may persist long after the eradication of H. pylori in patients with a history of GC. Dysbiosis may be involved in the development of both primary and metachronous GC after the eradication of H. pylori in such patients.
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http://dx.doi.org/10.1007/s10120-020-01141-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065006PMC
May 2021

Novel prognostic biomarkers of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis: Neutrophil-to-lymphocyte ratio.

PLoS One 2020 26;15(10):e0241322. Epub 2020 Oct 26.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Objectives: Pouchitis is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). Although there have been many investigations of the neutrophil-to-lymphocyte ratio (NLR) in various diseases, its role in predicting the development of pouchitis remains unclear. We aimed to evaluate the clinical utility of the NLR for predicting the development of pouchitis after IPAA in UC patients.

Materials And Methods: UC patients who underwent IPAA at Osaka City University Hospital between May 2006 and March 2019 were included. The incidence of pouchitis was estimated using the Kaplan-Meier method. Potential preoperative, intraoperative, and postoperative predictors for pouchitis, including various demographic and clinical variables, were analyzed. The combined impact of the NLR and other known prognostic factors were investigated using Cox proportional hazard regression with inverse probability of treatment weighting (IPTW).

Results: Forty-nine patients with UC who underwent IPAA were included. The median follow-up period was 18.3 months (interquartile range: 10.7-47.2 months). Eighteen patients (36.7%) developed pouchitis. The incidence of pouchitis was 19.2%, 32.6%, and 45.9% at 1, 2, and 5 years, respectively. NLR was significantly associated with the development of pouchitis in the univariate Cox regression analysis (hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.01-1.28; P = 0.03). The NLR cutoff value of 2.15 was predictive of the development of pouchitis according to receiver operating characteristic analysis (specificity: 67.7%, sensitivity: 72.2%). The incidence of pouchitis was significantly lower in the low NLR group than that in the high NLR group (P = 0.01, log-rank test). Cox regression analyses using IPTW also identified NLR as a prognostic factor for the development of pouchitis by statistically adjusting for background factors (HR, 3.60; 95% CI, 1.31-9.89; P = 0.01).

Conclusions: NLR may be a novel and useful indicator for predicting the development of pouchitis after IPAA in UC and should be introduced in clinical practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241322PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588073PMC
December 2020

Exploration of the characteristics of chronotypes in upper gastrointestinal tract diseases: a multicenter study in Japan.

Chronobiol Int 2021 Apr 15;38(4):534-542. Epub 2020 Oct 15.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Characteristics of the chronotypes of patients with gastrointestinal disease are unknown. We evaluated chronotypes of patients with upper gastrointestinal diseases with the Munich ChronoType Questionnaire (MCTQ). A total of 2027 subjects from 29 institutions in Japan who had undergone esophagogastroduodenoscopy were asked to answer the MCTQ. The subjects' chronotypes were divided into three groups (early, intermediate, and late chronotype) using the sleep-corrected mid-point of sleep on free days (MSF) values. According to their endoscopic diagnosis and abdominal symptoms, the subjects were divided into the reflux esophagitis (RE) group, gastroduodenal ulcer (GDU) group, upper gastrointestinal carcinoma (CA) group, functional dyspepsia (FD) group, non-FD group, and control group. In total, 1128 subjects were eligible for the analysis. The MSF (average ± standard deviation, clock hours, h) of each disease group was as follows: control group: 02.51 ± 1.22, non-FD group: 02.69 ± 1.14, FD group: 02.91 ± 1.19, RE group: 02.58 ± 1.05, GDU group: 02.47 ± 1.31, and CA group: 02.11 ± 1.08 h. Compared to the control group, the rate of late chronotype of the FD group significantly increased to 33.3%, whereas that of early chronotype of the CA group significantly increased to 38.3% ( = .0177 and 0.0036, respectively). In both the FD and CA groups, chronotype was the independent factor related to the diseases. The adjusted odds ratio of late chronotype to early chronotype was 3.01 [95% CI, 1.23-7.35] in the FD group and 0.44 [95% CI, 0.23-0.85] in the CA group. In conclusion, late chronotype was common in patients with FD, and early chronotype was common in patients with upper gastrointestinal carcinoma.
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http://dx.doi.org/10.1080/07420528.2020.1830791DOI Listing
April 2021

Safety of Endoscopic Mucosal Resection Using a Bipolar Snare for Superficial Nonampullary Duodenal Epithelial Tumors and the Predictive Factors of Piecemeal Resection.

Digestion 2020 Oct 12:1-9. Epub 2020 Oct 12.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Introduction: Endoscopic mucosal resection for small superficial nonampullary duodenal epithelial tumors is a noninvasive treatment; however, perforations can occur. Bipolar snares can reduce the risk of perforation due to small tissue damage. Currently, only few studies have reported endoscopic mucosal resection for small superficial nonampullary duodenal epithelial tumors using a bipolar snare and the effect of preoperative findings.

Objective: To investigate (1) resectability and adverse events of endoscopic mucosal resection using a bipolar snare for small superficial nonampullary duodenal epithelial tumors and (2) the predictions of piecemeal resection.

Methods: Between 2007 and 2017, 89 patients with 107 lesions underwent endoscopic mucosal resection using a bipolar snare. Among them, 88 lesions of 77 patients were evaluated. The primary outcome was the incidence of en bloc resection and R0 resection and adverse events. Risk factors associated with piecemeal resection, including preoperative lesion findings, were also examined.

Results: The incidence rates of en bloc and R0 resections were 85.2 and 48.9%, respectively. Neither intraoperative or delayed perforations nor procedure-related mortality was noted. The nonlifting sign after submucosal injection was associated with an increase in piecemeal resection (odds ratio: 20.3, 95% confidence interval: 2.53-162; p = 0.005).

Conclusion: Endoscopic resection for small superficial nonampullary duodenal epithelial tumors can cause perforation; however, endoscopic mucosal resection using a bipolar snare can be a safe treatment option as it does not cause perforations. The nonlifting sign after submucosal injection is a predictive factor for piecemeal resection.
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http://dx.doi.org/10.1159/000510601DOI Listing
October 2020

Safe technique of steroid injection utilizing submersion in saline to prevent stricture after esophageal endoscopic submucosal dissection.

Dig Endosc 2020 Nov 9;32(7):e169-e170. Epub 2020 Oct 9.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1111/den.13834DOI Listing
November 2020

New method for fixing an endoscopic nasobiliary drainage tube in the treatment of postoperative bile leakage.

Dig Endosc 2020 Nov 29;32(7):e155-e156. Epub 2020 Sep 29.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

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http://dx.doi.org/10.1111/den.13820DOI Listing
November 2020

Vonoprazan shows efficacy similar to that of proton pump inhibitors with respect to symptomatic, endoscopic, and histological responses in patients with eosinophilic esophagitis.

Esophagus 2021 Apr 22;18(2):372-379. Epub 2020 Sep 22.

Department of Gastroenterology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Background: Eosinophilic esophagitis (EoE) is a chronic allergic disease with esophageal symptoms and intraepithelial eosinophil infiltration. Effects of potassium-competitive acid blockers (P-CABs) on EoE have not been elucidated. We aimed to examine and compare the effects of P-CABs and PPIs on symptomatic, endoscopic, and histological responses of patients with EoE.

Methods: We analyzed 118 EoE patients who received PPI or P-CAB therapy with rabeprazole 10 mg (RPZ10, N = 22), rabeprazole 20 mg (RPZ20, N = 34), esomeprazole 20 mg (EPZ20, N = 25), or vonoprazan 20 mg (VPZ20, N = 33). We evaluated symptomatic responses by classifying the patients into three groups: complete relief, partial relief, and no change. Endoscopic responses were evaluated using the endoscopic reference score (EREFS) following PPI or P-CAB therapy. Histological responses were evaluated by determining eosinophil counts in esophageal biopsy samples and classifying the patients into two groups: complete remission [0/1 eosinophil/high-power field (eos/HPF)] and remission (< 15 eos/HPF).

Results: There were no differences among the therapy groups in terms of clinical characteristics, endoscopic findings, and histological findings of the patients before treatment. The rate of complete relief in clinical symptoms was 54.5% in the RPZ10 group, 64.7% in the RPZ20 group, 72.0% in the EPZ20 group, and 75.7% in the VPZ20 group. There were no significant differences in the therapeutic effect among the therapy groups. Similarly, endoscopic and histological complete remission rates were not significantly different among the therapy groups.

Conclusions: Vonoprazan showed similar efficacy to PPIs in EoE.
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http://dx.doi.org/10.1007/s10388-020-00783-0DOI Listing
April 2021

Repeated Endoscopic Submucosal Dissection for Esophageal Neoplasia Located Close to a Previous Endoscopic Submucosal Dissection Scar.

Clin Transl Gastroenterol 2020 08;11(8):e00226

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Introduction: Endoscopic submucosal dissection (ESD) could become a standard treatment for early stage esophageal neoplasia. Recurrence sometimes develops close to a previous ESD scar. These lesions are predictably difficult to treat with ESD because of severe fibrosis. We evaluated the clinical outcomes of ESD for esophageal neoplasia located close to a previous ESD scar.

Methods: This was a retrospective observational study in a single institution. A total of 549 consecutive patients with 927 esophageal lesions were treated with ESD. The primary outcomes were resectability and adverse events of esophageal neoplasia located close to previous ESD scars (ESD scar group) than in primary esophageal ESD (primary group). Furthermore, predictive factors of perforation were examined.

Results: A total of 545 primary and 29 ESD scars in consecutive patients were evaluated. En bloc and complete (R0) resection rates in the ESD scar group were lower than those in the primary group (79.3% vs 98.3%, P < 0.01 and 75.9% vs 93.4%, P < 0.01). Perforations occurred more frequently in the ESD scar group (10.3% vs 2.0%, P = 0.03). The ESD scar group was a predictive factor for perforation (odds ratio = 10.37, 95% confidence interval: 2.15-49.94, P = 0.004). There were similar results for inverse probability of treatment weighting methods (odds ratio = 6.78, 95% confidence interval: 1.40-32.98, P = 0.018).

Discussion: ESD for esophageal neoplasia located close to a previous ESD scar was difficult to completely resect and increased the likelihood of perforation but could be a treatment option.
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http://dx.doi.org/10.14309/ctg.0000000000000226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423925PMC
August 2020

Role of nucleotide binding oligomerization domain-like receptor protein 3 inflammasome in stress-induced gastric injury.

J Gastroenterol Hepatol 2021 Mar 30;36(3):740-750. Epub 2020 Sep 30.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background And Aim: The inflammasomes promote pro-caspase-1 cleavage, leading to processing of pro-interleukin (IL)-1β into its mature form. We investigated the role of the IL-1β and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in gastric injury in mice receiving water-immersion restraint stress (WIRS), focusing on the cyclooxygenase (COX)-2/prostaglandin (PG) E axis.

Methods: To induce gastric injury, the mice were placed in a restraint cage and immersed in the water bath to the level of the xiphoid process. Protein levels of mature caspase-1 and IL-1β were assessed by western blotting.

Results: Water-immersion restraint stress induced gastric injury with increase in IL-1β expression by activation of NLRP3 inflammasome. Exogenous IL-1β attenuated the injury, whereas anti-IL-1β neutralizing antibody and IL-1β receptor antibody aggravated it. NLRP3 and caspase-1 mice enhanced the injury with reducing of mature IL-1β, and this aggravation was reduced by exogenous IL-1β supplementation. Toll-like receptor 4 mice were hyporesponsive to WIRS in terms of mature IL-1β production. Rabeprazole attenuated the injury with preventing inflammasome activation. WIRS injured the stomach with promotion of COX-2 mRNA and PGE production, and exogenous IL-1β enhanced these molecules, while IL-1β immunoneutralization exerted opposite effect. PGE supplementation abolished the hypersensitivity in NLRP3 and caspase-1 mice through negative regulation of inflammatory cytokines.

Conclusion: These results suggest that NLRP3 inflammasome-derived IL-1β plays a protective role in stress-induced gastric injury via activation of the COX-2/PGE axis. Toll-like receptor 4 signaling and gastric acid may be involved in NLRP3 inflammasome activation.
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http://dx.doi.org/10.1111/jgh.15257DOI Listing
March 2021

Early Colon Cancer That Changed Its Morphology Twice.

Intern Med 2020 Nov 14;59(22):2961-2962. Epub 2020 Jul 14.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Japan.

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http://dx.doi.org/10.2169/internalmedicine.5279-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725620PMC
November 2020