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1.
Z Gastroenterol ; 58(5): 456-460, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32392607

RESUMO

Clostridium (C.) ventriculi (known as Sarcina ventriculi) is a ubiquitous gram-positive, anaerobic, acidophilic coccus found in patients with gastric motility disorders. The microorganisms can be identified histologically by their characteristic presentation in tetrads or packets of 8 in hematoxylin and eosin stains. Severe cases of emphysematous gastritis or gastric perforation have been described. Nevertheless, the significance of C. ventriculi in an upper gastrointestinal tract and its pathogenic character remain unclear. We present a 67-year-old woman who underwent hiatoplasty with gastropexy. After 3 months, she underwent a gastroscopy showing gastroesophageal reflux. Biopsies showed ulcerative reflux esophagitis with presence of C.ventriculi, subsequently confirmed by 16S ribosomal RNA gene amplicon sequencing. The barium swallow study revealed an atonic stomach with delayed gastric emptying. The patient was treated with PPI and domperidone. On follow up, 15 months post-operatively, a control gastroscopy showed a stomach with food residues and reflux-associated small erosions. The Clostridium organisms were detected only in oxyntic mucosa biopsies without erosions or ulcerations. We speculate that the recognition of the organisms in the biopsy material is important and suggests dysmotility disorder. However, in our opinion, the presence of C. ventriculi, even in combination with mucosal damage, does not necessarily prompt antibiotic treatment since no complications occurred and inflammation as well as gastric function improved under PPI and prokinetic therapy in our patient. Larger study groups with long-term follow-up are needed to understand whether these organisms could behave as pathogens or are only bystanders in the setting of delayed gastric emptying.


Assuntos
Clostridium/isolamento & purificação , Domperidona/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/microbiologia , Refluxo Gastroesofágico/complicações , Complicações Pós-Operatórias/microbiologia , Idoso , Antibacterianos/uso terapêutico , Antieméticos/uso terapêutico , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Esofagite Péptica/diagnóstico , Feminino , Refluxo Gastroesofágico/diagnóstico por imagem , Gastropexia , Gastroscopia , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Estômago/cirurgia
2.
Gut ; 69(2): 224-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31409606

RESUMO

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.


Assuntos
Esofagite Péptica/tratamento farmacológico , Lansoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Cicatrização
3.
Eur J Pharmacol ; 864: 172720, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31586635

RESUMO

Gastro-esophageal reflux disease is one of the most common disorders in gastroenterology. The aim of this work was to investigate the protection of isorhamnetin against esophageal mucosal injury in rats with chronic reflux esophagitis (RE). Chronic RE model was established through fundus ligation and partial obstruction of the pylorus in rats. Then, the rats were treated with isorhamnetin (5 mg/kg) daily for a period of 14 days. Through histological and gross assessment, it was found that administration of isorhamnetin alleviated esophageal mucosal injury in RE rats. Treatment of RE rats with isorhamnetin improved esophageal barrier function, through upregulating proteins expression of occludin and zonula occludens-1 (ZO-1) and downregulating proteins expression of matrix matalloproteinases-3 (MMP3) and -9. Administration of isorhamnetin decreased CD68-positive cells and mRNA levels of IL-6, TNF-α, and IL-1ß in the esophagus of RE rats. Administration of isorhamnetin downregulated inducible nitric oxide synthase (iNOS) protein expression and decreased production of nitric oxide (NO) and 3-nitrotyrosin in the esophagus of RE rats. Administration of isorhamnetin enhanced heme oxygenase-1 (HO-1) activities and reduced malondialdehyde (MDA) levels in esophagus of RE rats. Additionally, treatment with isorhamnetin inhibited p38 MAPK and NFκB activation in RE esophagus. In conclusion, isorhamnetin attenuated esophageal mucosal injury in rats with chronic RE, possibly by suppressing formation of cytokines and infiltration of inflammatory cells, inhibiting p38 and NFκB pathways, and enhancing HO-1 activity.


Assuntos
Mucosa Esofágica/efeitos dos fármacos , Mucosa Esofágica/patologia , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/patologia , Quercetina/análogos & derivados , Animais , Doença Crônica , Modelos Animais de Doenças , Esofagite Péptica/metabolismo , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
J Gastroenterol Hepatol ; 34(8): 1316-1328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30883868

RESUMO

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD. METHODS: We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption. RESULTS: Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs. CONCLUSIONS: This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.


Assuntos
Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Cicatrização/efeitos dos fármacos , Teorema de Bayes , Esofagite Péptica/diagnóstico , Esofagite Péptica/fisiopatologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Humanos , Metanálise em Rede , Seleção de Pacientes , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
6.
Gan To Kagaku Ryoho ; 46(3): 595-597, 2019 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-30914625

RESUMO

In a 65-year-old woman, anemia was observed during outpatient follow-up after right lung cancer surgery, and upper gastrointestinal endoscopy was performed for examination.Gastrointestinal endoscopy revealed a Type 2 tumor on the small curvature in the middle part of the stomach, and she was diagnosed with gastric cancer.Distal gastrectomy with D2 lymph node dissection and BillrothⅠ reconstruction was performed for the gastric cancer.There were no postoperative complications, and she was discharged on the ninth day after surgery.The pathological diagnosis was gastric cancer, ML, Less, Type 2, 67×55×15 mm, muc>sig>por, pT4a(SE)N2M0, fStage ⅢB.S -1 adjuvant chemotherapy was administered, but then discontinued in the second course due to the development of adverse events.Reflux symptoms appeared after the surgery, and her dietary intake was poor.Her body weight and serum albumin level at 3 and 5 months after surgery were 51 kg and 52.5 kg, respectively, and 3.2 g/dL and 2.7 g/dL, respectively.Because there was no improvement in the reflux symptom, oral administration of acotiamide hydrochloride was initiated 7 months after the surgery.After initiating oral intake of acotiamide hydrochloride, her dietary intake improved, and her body weight and serum albumin level at 11 and 15 months after surgery were 54 kg and 57 kg, respectively, and 3.0 g/dL and 2.7 g/dL, respectively.Peritoneal recurrence was observed 23 months after surgery, and her oral intake decreased, but the recurrence of reflux symptoms was not observed.Acotiamide hydrochloride could be an option for the treatment of reflux symptoms after gastrectomy.


Assuntos
Benzamidas , Esofagite Péptica , Gastroenterostomia , Neoplasias Gástricas , Tiazóis , Idoso , Benzamidas/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Feminino , Gastrectomia , Gastroenterostomia/efeitos adversos , Humanos , Recidiva Local de Neoplasia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgia , Tiazóis/uso terapêutico
7.
Am J Gastroenterol ; 114(3): 414-421, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30323266

RESUMO

The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of "typical" symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and the identification of new therapies. Direct assessment of mucosal barrier function by measuring impedance is a promising candidate for improved diagnosis. Ultimately though the concept of GERD as a composite, symptom-based entity needs re-evaluation, so that new understandings of upper GI symptoms can direct more precise management.


Assuntos
Mucosa Esofágica/fisiopatologia , Refluxo Gastroesofágico/fisiopatologia , Azia/fisiopatologia , Sensibilização do Sistema Nervoso Central/fisiologia , Impedância Elétrica , Monitoramento do pH Esofágico , Esofagite Péptica/diagnóstico , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/fisiopatologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Inibidores da Bomba de Prótons/uso terapêutico
8.
Expert Opin Pharmacother ; 20(2): 231-239, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30496693

RESUMO

INTRODUCTION: Gastroesophageal reflux (GER), and its complicated form gastroesophageal reflux disease (GERD) is a common condition in infants and children. As GERD is often considered to cause extra-oesophageal symptoms in children and in the absence of standardized diagnostic and treatment algorithm, many children are inappropriately exposed to empirical anti-reflux treatments, with Acid-Suppressive Medications (ASM); mostly proton pump inhibitors (PPIs). AREAS COVERED: The authors summarize the pharmacological management of pediatric GERD and discuss the efficacy of PPIs as randomized controlled trials have failed to demonstrate their clinical efficacy in the pediatric population. They consider the controversies surrounding the use of PPIs in the pediatric population as increasing evidence suggests of, although controversially, an increased risk of adverse events such as infection of the respiratory or gastrointestinal tract. Esophagitis is a complication that has a significant impact on weight gain and growth, as well as on the quality of life, and in such case, the benefit of treatment largely outweighs the risk. EXPERT OPINION: Clinicians should reserve ASM use for infants and children with proven esophagitis and avoid their routine use in patients with merely symptoms of GER. Treatment need and options must be frequently re-evaluated to reduce the risks associated with ongoing therapy.


Assuntos
Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Qualidade de Vida , Criança , Humanos , Lactente , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Dig Dis Sci ; 64(2): 493-502, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30390234

RESUMO

BACKGROUND: In gastroesophageal reflux disease (GERD), the frequency of heartburn symptoms and erosive esophagitis (EE) increases with age in children and adolescents. Proton pump inhibitor, dexlansoprazole, is approved for healing EE of all grades, maintenance of healed EE, relief of heartburn, and treatment of symptomatic non-erosive GERD in patients ≥ 12 years. AIM: To assess safety and efficacy of dexlansoprazole dual delayed-release capsule in healing of EE and maintenance of healed EE in adolescents. METHODS: A multicenter, phase 2, 36-week study was conducted in 62 adolescents (12-17 years) with endoscopically confirmed EE. Patients received dexlansoprazole 60 mg once daily (QD) during open-label healing phase. Those with confirmed healing at week 8 were randomized to dexlansoprazole 30 mg QD or placebo during 16-week, double-blind maintenance phase, with subsequent treatment-free follow-up of ≥ 12 weeks. Primary endpoints were treatment-emergent adverse events (TEAEs) in ≥ 5% of patients during treatment. Secondary endpoints included percentages of patients with healing of EE and with maintenance of healed EE. RESULTS: 88% of patients achieved EE healing, and 61.3% reported a TEAE [headache (12.9%), oropharyngeal pain (8.1%), diarrhea (6.5%), and nasopharyngitis (6.5%)]. During maintenance phase, healing was maintained in 82% and 58% of dexlansoprazole and placebo groups, respectively. 72.0% of dexlansoprazole-treated patients reported TEAEs, which included headache (24.0%), abdominal pain (12.0%), nasopharyngitis (12.0%), pharyngitis (12.0%), sinusitis (12.0%), bronchitis (8.0%), upper respiratory tract infection (8.0%), and insomnia (8.0%); 61.5% experienced a TEAE with placebo. CONCLUSIONS: Dexlansoprazole is safe and efficacious for healing EE and maintenance of healed EE in adolescents.


Assuntos
Dexlansoprazol/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Dor Abdominal/induzido quimicamente , Adolescente , Criança , Preparações de Ação Retardada , Diarreia/induzido quimicamente , Método Duplo-Cego , Feminino , Cefaleia/induzido quimicamente , Humanos , Quimioterapia de Manutenção , Masculino , Nasofaringite/induzido quimicamente , Orofaringe , Dor/induzido quimicamente , Faringite/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Resultado do Tratamento
10.
Dig Dis Sci ; 64(3): 823-831, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30465175

RESUMO

BACKGROUND: Approximately 30% of patients who are treated with proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD) experience persistent symptoms. No prokinetic agent regiments are useful for symptom relief. AIMS: This study was conducted to examine the effect of adding acotiamide to PPI or vonoprazan refractory GERD. METHODS: This was a randomized, prospective, double-blind, placebo-controlled trial. Seventy-one patients were enrolled. Patients underwent upper endoscopy before initial therapy [15 reflux esophagitis and 55 non-erosive reflux disease (NERD)]. Patients with persistent reflux symptoms were administered 300 mg/day acotiamide or placebo for 2 weeks. The primary endpoint was overall treatment effect (OTE), and gastrointestinal symptoms were evaluated. High-resolution manometry (HRM) and 24-h multiple intraluminal impedance-pH (MII-pH) monitoring were conducted before and after treatment when possible. RESULTS: Seventy patients were randomized (35 acotiamide and 35 placebo). Sixteen and 10 patients in the acotiamide and placebo groups, respectively, completed MII-pH and HRM. The OTE improvement rates were 28.6% and 14.3% in patients administered acotiamide and placebo, respectively (p = 0.145). In patients with NERD, however, the OTE improvement rate and responder rate for regurgitation in the acotiamide group was significantly higher than those in the placebo group (29.6 vs. 7.1%; p = 0.030, 37.0 vs. 10.7%; p = 0.021, respectively). Acotiamide significantly reduced the total reflux episodes (p = 0.001), acid (p = 0.020), proximal reflux (p = 0.007), and liquid reflux (p = 0.013) episodes. CONCLUSION: Adding acotiamide to gastric acid inhibitors can improve symptoms in patients with refractory NERD.


Assuntos
Benzamidas/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Tiazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Quimioterapia Combinada , Monitoramento do pH Esofágico , Esofagite Péptica/complicações , Esofagite Péptica/diagnóstico , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Humanos , Japão , Masculino , Manometria , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
12.
Pathol Int ; 68(12): 706-711, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30511782

RESUMO

A fundic gland polyp (FGP) is a common gastric polyp. Intraepithelial neoplasia in FGPs, referred to as FGP with dysplasia, is often seen in patients with familial adenomatous polyposis (FAP). In sporadic FGPs, low-grade dysplasia (LGD) is rare, and high-grade dysplasia (HGD) or carcinoma arising from sporadic FGPs is extremely rare. Because of this rarity, the prognosis and appropriate management of these lesions have not been clarified. In the present case, a sporadic FGP with LGD did not develop into invasive carcinoma, but contained foci of HGD 14 years after diagnosis. The biopsy specimen of the polyp taken at the first esophagogastroduodenoscopy 15 years earlier was diagnosed as FGP without dysplasia. At the second histological examination, LGD was found. Because the polyp increased in size during proton pump inhibitor therapy for 14 years, endoscopic mucosal resection was performed. The pathological diagnosis of the resected specimen was FGP with HGD mixed in LGD, with no invasive carcinoma. Dysplasia in FGPs might have less malignant potential regardless of dysplasia or size.


Assuntos
Pólipos/patologia , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Gástricas/patologia , Esofagite Péptica/tratamento farmacológico , Feminino , Humanos , Hiperplasia/patologia , Pessoa de Meia-Idade
13.
Int J Mol Sci ; 19(11)2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30453554

RESUMO

Reflux esophagitis (RE) is a gastrointestinal disease caused by the reflux of gastric acid and stomach contents, and it leads to esophageal damage. Therefore, it is necessary to study the improvement of esophageal damage on a RE-induced model. The present study was accomplished to demonstrate the protective effects of a dichloromethane fraction of Geranium koreanum (DGK) plant on esophageal damage in an acute RE rat model. First, we examined the potential of anti-inflammatory effects of various fractions measured by cell cytotoxicity, morphological changes and nitric oxide (NO) production on lipopolysaccharide (LPS)-induced Raw 264.7 macrophage cells. Then, to evaluate the protective effects on RE, rats were partitioned into the following groups: normal control, RE-induced control and RE rats pre-treated with DGK 100 and 200 mg/kg body weight. The esophageal mucosal ulcer ratio was measured by the Image J program and histological changes were examined using a hematoxylin and eosin staining of the esophageal mucosa. The expression of pro-inflammatory proteins, cytokines and tight junction proteins involved in the esophageal mucosal damage were investigated using Western blotting and an enzyme-linked immunosorbent assay (ELISA) kit with esophagus tissue. DGK chemical profile and phenolic contents were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). The results showed that DGK exhibited anti-inflammatory effects against LPS-stimulated cells by significantly inhibiting NO production. Additionally, the results in vivo showed that improvement effects of DGK on esophageal mucosal damage. The expression of inflammatory proteins involved in nuclear factor κB (NF-κB) signaling pathways and tight junction protein (claudin-4 and -5) were significantly decreased in esophageal mucosa. We found the potential of DGK as source of replacement therapy products for inflammatory and RE disease.


Assuntos
Anti-Inflamatórios/uso terapêutico , Esofagite Péptica/tratamento farmacológico , Esôfago/patologia , Geranium/química , Cloreto de Metileno/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Claudinas/metabolismo , Esofagite Péptica/patologia , Esôfago/efeitos dos fármacos , Inflamação/complicações , Inflamação/patologia , Lipopolissacarídeos , Camundongos , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/patologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/análise , Células RAW 264.7 , Ratos , Espectrometria de Massas em Tandem , Junções Íntimas/metabolismo
14.
Aliment Pharmacol Ther ; 48(10): 1074-1081, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30294924

RESUMO

BACKGROUND: The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing. AIMS: To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated. METHODS: Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring. RESULTS: Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group. CONCLUSIONS: True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group.


Assuntos
Resistência a Medicamentos/efeitos dos fármacos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/epidemiologia , Resistência a Medicamentos/fisiologia , Eructação/diagnóstico , Eructação/tratamento farmacológico , Eructação/epidemiologia , Esomeprazol/farmacologia , Esomeprazol/uso terapêutico , Esofagite Péptica/diagnóstico , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/epidemiologia , Feminino , Refluxo Gastroesofágico/epidemiologia , Azia/diagnóstico , Azia/tratamento farmacológico , Azia/epidemiologia , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/epidemiologia , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Inibidores da Bomba de Prótons/farmacologia
16.
Aliment Pharmacol Ther ; 48(2): 219-225, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29863285

RESUMO

BACKGROUND: Although current American guidelines distinguish proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) from eosinophilic oesophagitis (EoE), these entities are broadly similar. While two microarray studies showed that they have similar transcriptomes, more extensive RNA sequencing studies have not been done previously. AIM: To determine whether RNA sequencing identifies genetic markers distinguishing PPI-REE from EoE. METHODS: We retrospectively examined 13 PPI-REE and 14 EoE biopsies, matched for tissue eosinophil content, and 14 normal controls. Patients and controls were not PPI-treated at the time of biopsy. We did RNA sequencing on formalin-fixed, paraffin-embedded tissue, with differential expression confirmation by quantitative polymerase chain reaction (PCR). We validated the use of formalin-fixed, paraffin-embedded vs RNAlater-preserved tissue, and compared our formalin-fixed, paraffin-embedded EoE results to a prior EoE study. RESULTS: By RNA sequencing, no genes were differentially expressed between the EoE and PPI-REE groups at the false discovery rate (FDR) ≤0.01 level. Compared to normal controls, 1996 genes were differentially expressed in the PPI-REE group and 1306 genes in the EoE group. By less stringent criteria, only MAPK8IP2 was differentially expressed between PPI-REE and EoE (FDR = 0.029, 2.2-fold less in EoE than in PPI-REE), with similar results by PCR. KCNJ2, which was differentially expressed in a prior study, was similar in the EoE and PPI-REE groups by both RNA sequencing and real-time PCR. CONCLUSION: Eosinophilic oesophagitis and PPI-REE have comparable transcriptomes, confirming that they are part of the same disease continuum.


Assuntos
Eosinofilia/tratamento farmacológico , Eosinofilia/genética , Esofagite Eosinofílica/genética , Esofagite Péptica/tratamento farmacológico , Esofagite Péptica/genética , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Eosinofilia/complicações , Eosinofilia/patologia , Esofagite Eosinofílica/patologia , Esofagite Péptica/complicações , Esofagite Péptica/patologia , Feminino , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/genética , Refluxo Gastroesofágico/patologia , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sequência de RNA , Transcriptoma , Resultado do Tratamento , Adulto Jovem
17.
World J Gastroenterol ; 24(14): 1550-1561, 2018 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-29662293

RESUMO

AIM: To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis (EE). METHODS: A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg (n = 201), vonoprazan 10 mg (n = 202), or vonoprazan 20 mg (n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa histopathology results. RESULTS: Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg (P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan (P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively. CONCLUSION: Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.


Assuntos
Esofagite Péptica/tratamento farmacológico , Lansoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Biópsia , Método Duplo-Cego , Esofagite Péptica/complicações , Esofagite Péptica/diagnóstico por imagem , Esofagite Péptica/patologia , Esofagoscopia , Esôfago/diagnóstico por imagem , Esôfago/patologia , Feminino , Mucosa Gástrica/patologia , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Azia/tratamento farmacológico , Azia/epidemiologia , Azia/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
19.
Digestion ; 97(4): 309-315, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29514137

RESUMO

BACKGROUND: The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). METHODS: On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. RESULTS: One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. CONCLUSION: On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE.


Assuntos
Esofagite Péptica/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Esofagite Péptica/sangue , Jejum , Feminino , Gastrinas/sangue , Humanos , Japão , Quimioterapia de Manutenção/normas , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
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