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BACKGROUND AND AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) damage the small intestine via neutrophil infiltration driven by the mucosal invasion of enterobacteria. The antimicrobial function of neutrophils is partially dependent on neutrophil extracellular traps (NETs). Excessive NET formation has been associated with several inflammatory diseases. Here, we aimed to investigate the role of NETs in NSAID-induced small intestinal damage using human samples and an experimental mouse model. METHODS: Human small intestine specimens were obtained from NSAID users during double-balloon enteroscopy. Wild-type, protein arginine deiminase 4 (PAD4) knockout, and antibiotic-treated mice were administered indomethacin to induce small intestinal injury. The expression of NET-associated proteins, including PAD4, citrullinated histone H3 (CitH3), cell-free DNA, and myeloperoxidase (MPO), was evaluated. RESULTS: The double-positive stained area with CitH3 and MPO, which is specific for neutrophil-derived extracellular traps, was significantly high in the injured small intestinal mucosa of NSAID users. In a mouse model, small intestinal damage developed at 6 h after indomethacin administration, accompanied by increased mRNA levels of interleukin-1ß and keratinocyte chemoattractant and elevated NET-associated protein levels of PAD4, CitH3, and MPO in small intestine and serum levels of cell-free DNA. Both genetic deletion and pharmacological inhibition of PAD4 attenuated this damage by reducing the mRNA expression of inflammatory cytokines and NET-associated proteins. Furthermore, mice pretreated with antibiotics showed resistance to indomethacin-induced small intestinal damage, with less NET formation. CONCLUSION: These results suggest that NETs aggravate NSAID-induced small intestinal injury. Therefore, NET inhibition could be a potential treatment for NSAID-induced small intestinal injury.
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Anti-Inflamatórios não Esteroides , Modelos Animais de Doenças , Armadilhas Extracelulares , Indometacina , Intestino Delgado , Peroxidase , Proteína-Arginina Desiminase do Tipo 4 , Animais , Armadilhas Extracelulares/metabolismo , Anti-Inflamatórios não Esteroides/efeitos adversos , Intestino Delgado/patologia , Intestino Delgado/metabolismo , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Humanos , Indometacina/efeitos adversos , Peroxidase/metabolismo , Masculino , Neutrófilos/metabolismo , Histonas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Enteropatias/induzido quimicamente , Enteropatias/patologia , Interleucina-1beta/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Camundongos Knockout , Feminino , Ácidos Nucleicos Livres/sangue , CitrulinaçãoRESUMO
We used standardized detection ratio to evaluate the quality of nasal upper gastrointestinal endoscopy screening for the secondary prevention of gastric cancer, and examined the gastric cancer risk in the era of total Helicobacter pylori (H. pylori) eradication. We performed 21,931 upper gastrointestinal endoscopies, 77 subjects were diagnosed with gastric cancer. Of these, 28 had gastric cancer after H. pylori eradication, 47 had gastric cancer with H. pylori-positive or others, and 2 had H. pylori-negative gastric cancer. The Standardized detection ratios for men and women were 5.33 and 4.82, respectively. Multivariable logistic regression analyses performed exclusively on first endoscopy subjects, excluding H. pylori-negative gastric cancer, revealed that smoking was a risk factor for developing gastric cancer (adjusted odds ratio, 3.31; 95% confidence interval, 1.65-6.64; pâ =â 0.001). A statistically significant interaction was found between daily alcohol consumpption and H. pylori eradication on gastric cancer development (pâ =â 0.005). In conclusion, relatively high standardized detection ratio values suggest that an appropriate endoscopic diagnosis of gastric cancer should be performed during a medical check-up. Smoking is a risk factor for developing gastric cancer, and continued alcohol consumption suggests a possible risk for developing gastric cancer after H. pylori eradication.
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BACKGROUND: The Rome IV criteria have been established as an international standard for diagnosing disorders of gut-brain interaction. In this study, we aimed to examine the upper gastrointestinal (GI) endoscopic findings and symptoms of subjects with functional constipation (FC) and irritable bowel syndrome (IBS) of individuals undergoing a medical check-up. METHODS: A total of 13,729 subjects underwent a medical check-up at Osaka City University-affiliated clinic, MedCity21, between April 2018 and March 2019. Among the 5,840 subjects who underwent screening upper GI endoscopy and completed a questionnaire based on the Rome IV criteria, 5,402 subjects were consecutively enrolled after excluding subjects with a large amount of gastric residue (n = 6), those who had previously undergone partial or total gastrectomy (n = 40), or those with daily use of low-dose aspirin (n = 82), nonsteroidal anti-inflammatory drugs (n = 63), or acid secretion inhibitors (n = 308). RESULTS: Robust Poisson regression analyses adjusted for age, sex, Helicobacter pylori infection status, alcohol intake, and smoking habits showed a significant association between FC and corpus erosion (adjusted prevalence ratio [aPR], 2.93; 95% confidence interval [CI], 1.51-5.67; p < 0.01) and red streaks (aPR, 3.83; 95% CI, 2.53-5.79; p < 0.01), whereas IBS was significantly associated with erosive gastritis (aPR, 8.46; 95% CI, 4.89-14.67; p < 0.01) and duodenitis (aPR, 7.28; 95% CI, 3.64-14.59; p < 0.01). Red streaks tended to be associated with IBS (aPR, 1.96; 95% CI, 1.00-3.83; p = 0.05). Subjects with IBS were the most to complain of both upper and lower GI symptoms and psychological symptoms, followed by those with FC and controls. IBS subjects with erosive gastritis or duodenitis had significantly more complaints of stomachache and feeling stressed than those without erosive gastritis or duodenitis (54.5% vs. 18.8%; p = 0.03 and 66.7% vs. 25.0%; p = 0.01). CONCLUSIONS: Subjects with FC and IBS had a variety of upper GI and psychological symptoms. In the upper GI endoscopic findings, corpus erosion and red streaks were associated with FC, and erosive gastritis, duodenitis, and possibly red streaks were associated with IBS.
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Duodenite , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Estudos Transversais , Japão/epidemiologia , Duodenite/complicações , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Cidade de Roma , Constipação Intestinal/diagnóstico , Inquéritos e Questionários , Gastrite/complicações , Gastrite/diagnósticoRESUMO
BACKGROUND AND AIMS: Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30-40% of patients have been reported to lose clinical response within 2 years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short-term and long-term efficacy in Crohn's disease. METHODS: Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay. RESULTS: Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1 year and 58.9% at 2 years. Univariate Cox regression analysis revealed that Harvey-Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458-0.5774) and MCP-1 concentrations (HR: 1.038, 95% CI: 1.015-1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment. CONCLUSIONS: Our findings suggest that pretreatment serum MCP-1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease.
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Produtos Biológicos , Doença de Crohn , Humanos , Ustekinumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Quimiocina CCL2 , Indução de Remissão , Produtos Biológicos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Superficial pharyngeal cancer can be treated with curative intent while preserving function using minimally invasive peroral endoscopic resection techniques such as endoscopic submucosal dissection (ESD). However, severe adverse events occasionally occur, such as laryngeal edema requiring temporary tracheotomy and fistula formation. Therefore, we investigated the risk factors for adverse events associated with ESD for superficial pharyngeal cancer. METHODS: This retrospective observational study was conducted at a single institution, and 63 patients who underwent ESD were enrolled. The primary outcome was the risk factors for adverse events associated with ESD. The secondary outcomes were adverse events associated with ESD and their frequency. RESULTS: The overall adverse event rate was 15.9% (10/63). The incidence of laryngeal edema requiring prophylactic temporary tracheotomy was 11.1%, while laryngeal edema requiring emergency temporary tracheotomy, postoperative bleeding, aspiration pneumonia, fistula, abscess, and stricture formation occurred in 1.6% of patients, respectively. Logistic regression analyses showed that a history of radiotherapy for head and neck cancer was a risk factor for adverse events (odds ratio [OR], 16.67; 95% confidence interval [CI], 3.04-91.34; p = 0.001). After adjusting the model for differences in the baseline risk factors using the inverse probability of treatment weighting method, the adverse events were found to increase in association with a history of radiotherapy for head and neck cancer (OR, 39.66; 95% CI,5.85-268.72; p < 0.001). CONCLUSION: History of radiotherapy for head and neck cancer is an independent risk factor for adverse events associated with ESD for superficial pharyngeal cancer. Among adverse events, laryngeal edema requiring prophylactic temporary tracheotomy was particularly high.
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Ressecção Endoscópica de Mucosa , Neoplasias Faríngeas , Fatores de Risco , Estudos Retrospectivos , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Faríngeas/cirurgia , EndoscopiaRESUMO
BACKGROUND: Eosinophilic esophagitis (EoE) is a type 2 helper T-cell (Th2)-mediated allergic disease that involves mast cells. This study aimed to clarify the relationship between perception of symptoms and mast cell levels in patients with EoE. METHODS: We enrolled patients with asymptomatic esophageal eosinophilia (aEE) and those with symptomatic EoE. Immunofluorescence staining was performed on esophageal biopsy specimens to quantify mast cell-related molecules, such as tryptase, proteinase-activated receptor (PAR)-2, and vasoactive intestinal peptide receptor (VPAC)-1. RESULTS: We evaluated 28 and 58 patients with aEE and EoE, respectively. There were no significant differences in clinical and endoscopic features and peak eosinophil counts between both groups. Mast cell tryptase-positive areas were significantly higher in EoE than in aEE (4.9 [3.5-6.2] vs. 2.0 [1.2-3.4] %, p < 0.01). The number of PAR-2-positive cells was significantly higher in EoE than in aEE (14 [8.8-20.0] vs. 4 [2.8-8.0] cells/high-power field [HPF], p < 0.01). The number of VPAC-1-positive cells was significantly higher in the EoE group than in the aEE group (13 [8.8-16.0] vs. 6 [3.0-9.3] cells/HPF, p < 0.01). A positive correlation was observed between the numbers of PAR-2-positive cells and VPAC-1-positive cells (r = 0.851, p < 0.01). Moreover, mast cell tryptase-positive areas positively correlated with the number of PAR-2- and VPAC-1-positive cells (r = 0.352, p < 0.01; r = 0.355, p < 0.01, respectively). CONCLUSIONS: Esophageal mast cells and their receptors, PAR-2 and VPAC-1, may contribute to the perception of symptoms in patients with EoE.
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Esofagite Eosinofílica , Humanos , Mastócitos/patologia , Triptases , PercepçãoRESUMO
BACKGROUND AND AIMS: The incidence of rebleeding in obscure GI bleeding (OGIB) remains unclear. This study used capsule endoscopy (CE) to determine the long-term rebleeding rate and predictive factors for rebleeding in patients with OGIB. METHODS: This single-center, observational study enrolled consecutive patients with OGIB who underwent CE as the first small intestinal examination between March 2004 and December 2015 and were followed up through medical records or letters. RESULTS: Three hundred eighty-nine patients were included in the analysis. Survival curve analysis showed that the overall cumulative rebleeding rate in OGIB during the 5 years was 41.7%. Multivariate analysis using the Cox proportional hazards model revealed that overt OGIB (hazard ratio [HR], 2.017; 95% confidence interval [CI], 1.299-3.131; P = .002), anticoagulants (HR, 1.930; 95% CI, 1.093-3.410; P = .023), positive balloon-assisted enteroscopy findings after CE (HR, 2.927; 95% CI, 1.791-4.783; P < .001), and iron supplements without therapeutic intervention (HR, 2.202; 95% CI, 1.386-3.498; P = .001) were associated with rebleeding, whereas a higher minimum hemoglobin level (HR, .902; 95% CI, .834-.975; P = .009) and therapeutic intervention (HR, .288; 95% CI, .145-.570; P < .001) significantly reduced the risk of rebleeding. Among the Charlson Comorbidity Index components, liver cirrhosis was an independent predictor associated with rebleeding in patients with OGIB (HR, 4.362; 95% CI, 2.622-7.259; P < .001) and in patients with negative CE findings (HR, 8.961; 95% CI, 4.424-18.150; P < .001). CONCLUSIONS: Rebleeding is common during the long-term follow-up of patients with OGIB. Careful follow-up is required for patients with liver cirrhosis or previous massive bleeding.
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Endoscopia por Cápsula , Humanos , Endoscopia por Cápsula/efeitos adversos , Recidiva , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/diagnóstico , Intestino Delgado , Cirrose Hepática/complicações , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic precipitated lifestyle changes. We aimed to clarify whether COVID-19-induced lifestyle changes affected the development of metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: This retrospective longitudinal study included 973 participants who underwent health check-ups between 2018 and 2020. We used data from the MedCity21 health examination registry. Participants' clinical characteristics and lifestyle habits were investigated. Independent lifestyle predictors of MAFLD development before the pandemic (2018-2019) and during the pandemic (2019-2020) were identified using logistic regression analysis. RESULTS: In 2018, 261 (27%) patients were diagnosed with MAFLD. Before the pandemic, 22 patients developed new MAFLD. During this time, routine late-night meals were identified as an independent lifestyle predictor of MAFLD development (hazard ratio [HR] 2.54, 95% confidence interval [CI] 1.02-6.36, P = .046). In contrast, 44 patients developed new MAFLD during the pandemic. During this time, higher daily alcohol intake was identified as an independent lifestyle predictor of MAFLD development (HR 1.03, 95% CI 1.01-1.05, P = .008). In participants aged <60 years, daily alcohol intake and the proportion of participants who ate 2 times/day were significantly higher in patients who developed MAFLD during the pandemic than in those who did not. In participants aged ≥60 years, no lifestyle habits were associated with MAFLD development before or during the pandemic. CONCLUSIONS: New MAFLD diagnoses increased during the COVID-19 pandemic. Changes in lifestyle factors, particularly in those aged <60 years, must be monitored and addressed as the pandemic continues.
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COVID-19 , Hepatopatia Gordurosa não Alcoólica , Humanos , Estilo de Vida , Estudos Longitudinais , Hepatopatia Gordurosa não Alcoólica/complicações , Pandemias , Estudos RetrospectivosRESUMO
BACKGROUND AND AIM: Esophageal injury often results in a scar, leading to refractory strictures. The NLRP3 inflammasome activates caspase-1, causing the maturation of interleukin (IL)-1ß. Here, we aimed to investigate the preventive effect of pirfenidone (PFD), an antifibrotic drug, on esophageal stricture after ulcer healing and studied its mechanism by focusing on the activation of the NLRP3 inflammasome. METHODS: Esophageal ulcers were induced in rats via the local application of acetic acid in the serosa. PFD was intraperitoneally administered to the rats 3 days after ulcer induction. The effect of PFD on esophageal stricture after ulcer healing was assessed by esophagography on day 9. The protein levels of mature caspase-1 and IL-1ß were assessed by western blotting. RESULTS: The ulcers fully developed 3 days after induction and were almost scarred by day 9 with severe strictures. PFD promoted ulcer healing and attenuated fibrotic collagen in the submucosa by suppressing the increase in NLRP3, cleaved caspase-1, and mature IL-1ß expression, improving stricture rate (PFD vs vehicle = 55% vs 81%). Exogenous IL-1ß abolished the therapeutic effects of PFD on ulcer healing and stricture formation. Furthermore, NLRP3 and caspase-1 inhibitors mimicked the effects of PFD on ulcer healing and stricture formation, with suppression of the increase in cleaved caspase-1 and mature IL-1ß proteins and expression of fibrosis-related molecules including transforming growth factor (TGF)-ß1. CONCLUSION: The NLRP3 inflammasome promotes esophageal stricture formation following ulcer healing, and PFD exerts potential prophylactic activity against strictures, possibly via the inhibition of the NLRP3/IL-1ß/TGF-ß1 axis.
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Estenose Esofágica , Inflamassomos , Animais , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Constrição Patológica , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Fibrose , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nucleotídeos , Piridonas , Ratos , ÚlceraRESUMO
BACKGROUND: The pathogenesis of eosinophilic esophagitis involves immunoglobulin G4 (IgG4) deposition. However, the relationship between IgG4 and eosinophilic gastroenteritis (EGE) is unclear. AIMS: To investigate gastrointestinal deposition of IgG4 in EGE. METHODS: Biopsies of the esophagus, stomach, and small intestine were evaluated in patients with and without EGE. Immunohistochemical staining for IgG4 was performed, and the proportions of the stained areas were compared. Sera from patients with EGE were assayed for food-specific IgG4, including egg white, wheat, rice, soy, and cow milk. RESULTS: Seventeen patients were included in this study (EGE group, n = 10; control group, n = 7). Compared with the control group, the proportion of IgG4-stained area in the EGE group was approximately threefold higher (40.2% [32.3-49.5]) vs. 12.1% [4.0-21.9], p = 0.014) in the esophagus, fivefold higher in the stomach (17.3% [11.1-26.2] vs. 3.7% [1.5-5.2], p = 0.014), and sixfold higher in the small intestine (28.0% [15.0-33.2] vs. 4.5% [2.6-9.8], p = 0.019). There was no significant association between the proportion of IgG4-stained area and the number of infiltrating eosinophils. Serum egg white-specific IgG4 levels were correlated with the proportion of IgG4-stained areas in the small intestine (R = 0.7, p = 0.035). CONCLUSIONS: IgG4 accumulated within the gastrointestinal mucosa in EGE. The positive correlation between serum egg white-specific IgG4 levels and the proportion of IgG4-stained areas in the small intestine suggests a role for IgG4 in the disease pathophysiology.
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Enterite , Esofagite Eosinofílica , Gastrite , Alérgenos , Animais , Bovinos , Eosinofilia , Feminino , Imunoglobulina GRESUMO
BACKGROUND: Endoscopic submucosal dissection (ESD) is becoming widely popular as a less invasive treatment option for superficial esophageal squamous cell carcinoma. However, data on long-term survival after esophageal ESD in patients with severe comorbidities are limited. This study aimed to evaluate long-term survival after ESD in such patients. METHODS: Altogether, 584 consecutive patients underwent esophageal ESD at our institution from May 2004 to September 2016. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification system, patients were grouped according to severe (ASA-PS ≥ 3) or non-severe comorbidities (ASA-PS 1/2). The overall survival (OS), disease-specific survival (DSS), and risk factors for mortality were compared between the groups using a propensity score matching analysis. RESULTS: In a matched cohort of 69 pairs, the 5-year OS rate was poorer in ASA-PS 3 patients than in ASA-PS 1/2 patients (63.9% vs. 92.5%, P < 0.01), while the 5-year DSS rate was similar between the groups (100% vs. 100%). The mortality rate was significantly higher in ASA-PS 3 patients than in ASA-PS 1/2 patients (hazard ratio 3.47; 95% confidence interval 1.79-6.74; P < 0.01). Death due to exacerbation of comorbidities was significantly more frequent in ASA-PS 3 patients than in ASA-PS 1/2 patients (42.4% vs. 8.3%, P < 0.04). CONCLUSION: Because of the exacerbation of comorbidities, patients with severe comorbidities had poorer long-term outcomes after esophageal ESD than those with non-severe comorbidities. Further studies will be necessary to evaluate esophageal ESD in patients with severe comorbidities.
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Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ressecção Endoscópica de Mucosa/efeitos adversos , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase ß2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model.
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Hormônio Liberador da Corticotropina , Mastócitos , Animais , Hormônio Liberador da Corticotropina/metabolismo , Modelos Animais de Doenças , Enterite , Eosinofilia , Gastrite , Íleo/metabolismo , Inflamação/metabolismo , Interleucina-13/metabolismo , Interleucina-5 , Mastócitos/metabolismo , Camundongos , RNA Mensageiro/metabolismo , Receptores de Hormônio Liberador da Corticotropina/genética , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Estresse Psicológico/complicaçõesRESUMO
The study group of the Japanese Society of Gastroenterology released evidence-based clinical practice guidelines for chronic constipation (CC) in 2017, and irritable bowel syndrome (IBS) was treated as one of the causes of CC. We examined the differences in characteristics between IBS and non-IBS subjects with CC who underwent a medical check-up in Japan. A total of 10,658 subjects participated in this study, and we focused on 467 subjects who fulfilled the diagnostic criteria of CC using a questionnaire survey. The number of IBS subjects was 21, and they had sleep disorders, were more symptomatic (e.g., abdominal pain, abdominal bloating/distension, feeling stressed, annoyance, lack of motivation, fatigue upon waking, and feeling depressed), and had more episodes of sensation of incomplete evacuation and anorectal obstruction/blockage during defecation than non-IBS subjects. Furthermore, stool frequency of IBS subjects was significantly different from non-IBS subjects. Multivariate ordinal logistic regression analysis revealed that the factors associated with a higher stool frequency were IBS [odds ratio (OR), 2.46; 95% confidence interval (CI), 1.00-6.05; pâ =â 0.049], male sex (OR, 1.97; 95% CI, 1.20-3.23; pâ =â 0.007), and regular exercise (OR, 1.80; 95% CI, 1.05-3.07; pâ =â 0.033). These findings suggest that IBS has unique characteristics in subjects with CC.
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A total of 306 patients with eosinophilic esophagitis (EoE) were analyzed at our department. Proton pump inhibitors or potassium-competitive acid blockers were used as the first-line treatment in 286 (93.5%) patients. Fifty-five (18.0%) patients received topical steroid swallowing therapy. During 17.7-month mean follow-up, 46.4% of the patients were followed-up with no medications, 37.3% of the patients received maintenance or on-demand therapy using acid-suppressive drugs, and 9.8% of the patients received maintenance therapy with steroid swallowing. The majority of patients with EoE were treated using a therapeutic strategy similar to that used for gastroesophageal reflux disease. However, some patients were refractory to the treatment. Current real-world treatment strategies for Japanese patients with EoE are clarified.
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Esofagite Eosinofílica , Refluxo Gastroesofágico , Enterite , Eosinofilia , Esofagite Eosinofílica/tratamento farmacológico , Gastrite , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Japão , Potássio/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
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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Disbiose/patologia , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas/cirurgia , Idoso , Ressecção Endoscópica de Mucosa , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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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Constipação Intestinal , Adulto , Idoso , Constipação Intestinal/diagnóstico , Constipação Intestinal/epidemiologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Cidade de RomaRESUMO
BACKGROUND AND AIM: The inflammasomes promote pro-caspase-1 cleavage, leading to processing of pro-interleukin (IL)-1ß into its mature form. We investigated the role of the IL-1ß 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) E2 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-1ß were assessed by western blotting. RESULTS: Water-immersion restraint stress induced gastric injury with increase in IL-1ß expression by activation of NLRP3 inflammasome. Exogenous IL-1ß attenuated the injury, whereas anti-IL-1ß neutralizing antibody and IL-1ß receptor antibody aggravated it. NLRP3-/- and caspase-1-/- mice enhanced the injury with reducing of mature IL-1ß, and this aggravation was reduced by exogenous IL-1ß supplementation. Toll-like receptor 4-/- mice were hyporesponsive to WIRS in terms of mature IL-1ß production. Rabeprazole attenuated the injury with preventing inflammasome activation. WIRS injured the stomach with promotion of COX-2 mRNA and PGE2 production, and exogenous IL-1ß enhanced these molecules, while IL-1ß immunoneutralization exerted opposite effect. PGE2 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-1ß plays a protective role in stress-induced gastric injury via activation of the COX-2/PGE2 axis. Toll-like receptor 4 signaling and gastric acid may be involved in NLRP3 inflammasome activation.
Assuntos
Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Gastropatias/etiologia , Gastropatias/prevenção & controle , Estresse Psicológico/complicações , Animais , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Ácido Gástrico/metabolismo , Camundongos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Gastropatias/genética , Gastropatias/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
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-1ß 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.
Assuntos
Anti-Inflamatórios não Esteroides , Colchicina , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Humanos , Intestino Delgado , Camundongos , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND AND AIM: 5-Fluorouracil (5-FU) is an anticancer agent that induces intestinal mucositis, which causes diarrhea and dehydration. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is responsible for inflammatory response activation via caspase-1 cleavage and subsequent interleukin-1ß (IL-1ß) and IL-18 activation and secretion. The objective of this study was to determine the role of the NLRP3 inflammasome in 5-FU-induced small intestinal mucositis. METHODS: Small intestinal mucositis was induced in wild-type, NLRP3-/-, and caspase-1-/- mice by intraperitoneal injection of 5-FU. Some mice received intraperitoneal injection of a caspase-1 inhibitor, recombinant IL-1ß or IL-18, or neutralizing antibody against IL-1ß. RESULTS: Mice treated with 5-FU developed small intestinal mucositis with diarrhea and body weight loss, characterized by a decrease in villus height and the villus height-to-crypt depth ratio. These histological changes peaked on day 3 and were accompanied by an increase in mRNA expression of NLRP3 and IL-1ß and protein expression of cleaved caspase-1 and mature IL-1ß. Mature IL-18 protein expression was not affected by 5-FU administration. NLRP3-/- mice exhibited less severe 5-FU-induced mucositis, and this phenotype was mimicked by genetic depletion or pharmacological inhibition of caspase-1. Small intestinal mucositis was aggravated by exogenous IL-1ß and neutralized by IL-1ß antibody treatment. Administration of exogenous IL-18 or anti-IL-18 antibody did not affect any parameters associated with mucositis. NLRP3, cleaved caspase-1, and IL-1ß were expressed by inflammatory cells (mainly macrophages) in the lamina propria and damaged epithelial cells. CONCLUSIONS: NLRP3 inflammasome activation may exacerbate 5-FU-induced small intestinal mucositis via IL-1ß maturation.
Assuntos
Inflamassomos , Mucosite , Animais , Caspase 1/genética , Caspase 1/metabolismo , Fluoruracila/toxicidade , Interleucina-1beta , Camundongos , Camundongos Endogâmicos C57BL , Mucosite/induzido quimicamente , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR , Domínio PirinaRESUMO
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.