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1.
Surg Case Rep ; 7(1): 207, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34529178

RESUMO

BACKGROUND: Gomez gastroplasty, which was developed in the 1970s as one of the gastric restrictive surgeries for severe obesity, partitions the stomach using a stapler from the lesser towards the greater curvature at the upper gastric body, leaving a small channel. This procedure is no longer performed due to poor outcomes, but surgeons can encounter late-onset complications even decades after the surgery. Here, we report a case of very late-onset stomal obstruction following Gomez gastroplasty which was successfully treated by revision surgery. CASE PRESENTATION: A 58-year-old man was referred to our institution with sudden-onset nausea and vomiting. He underwent weight loss surgery in the USA in 1979, but the details of the surgery were unclear. Esophagogastroduodenoscopy demonstrated a stoma at the greater curvature of the upper gastric body, and fluoroscopy showed retention of contrast medium in the fundus and poor outflow through the stoma. Abdominal computed tomography revealed a staple line partitioning the stomach. Considering these preoperative investigation findings and the period during which the surgery was performed, the patient was diagnosed with very late-onset stomal obstruction following Gomez gastroplasty. Supporting the preoperative diagnosis, the surgical findings revealed a staple line extending from the lesser towards the greater curvature of the upper gastric body and a channel reinforced by a running seromuscular suture on the greater curvature. Moreover, gastric torsion caused by the enlarged proximal gastric pouch was found. Re-gastroplasty involving wedge resection of the original channel was performed followed by construction of a new channel. Postoperative course was uneventful, and the patient no longer had symptoms of stomal obstruction after revision surgery. CONCLUSIONS: Re-gastroplasty was safe and feasible for very late-onset stomal obstruction following Gomez gastroplasty. Accurate preoperative diagnosis based on the patient's interview and the investigation findings was important for surgical planning. A careful follow-up is required to prevent excessive weight regain after revision surgery.

2.
J Clin Med ; 10(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34362152

RESUMO

PURPOSE: The surgical strategy for esophagogastric junction (EGJ) cancer depends on the tumor location as measured relative to the EGJ line. The purpose of this study was to clarify the accuracy of diagnostic endoscopy in different clinicopathological backgrounds. METHODS: Subjects were 74 consecutive patients with abdominal esophagus to upper gastric cancer who underwent surgical resection. Image-enhanced endoscopy with narrow-band imaging (NBI) was used to determine the EGJ line, prioritizing the presence of palisade vessels, followed by the upper end of gastric folds, as a landmark. The relative positional relationship between the tumor epicenter and the EGJ line was classified into six categories, and the agreement between endoscopic and pathologic diagnoses was examined to evaluate prediction accuracy. RESULTS: The concordance rate of 69 eligible cases was 87% with a kappa coefficient (K) of 0.81. The palisade vessels were observed in 62/69 patients (89.9%). Of the 37 pathological EGJ cancers centered within 2 cm above and below the EGJ line, Barrett's esophagus was found to be a significant risk factor for discordance (risk ratio, 4.40; p = 0.042); the concordance rate of 60% (K = 0.50) in the Barrett's esophagus group was lower than the rate of 91% (K = 0.84) in the non-Barrett's esophagus group. In five of six discordant cases, the EGJ line was estimated to be proximal to the actual line. CONCLUSION: Diagnostic endoscopy is beneficial for estimating the location of EGJ cancer, with a risk of underestimating esophageal invasion length in patients with Barrett's esophagus.

3.
Am J Gastroenterol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404084

RESUMO

INTRODUCTION: Placebo response rates are relatively higher in clinical trials of disorders of brain-gut interaction. However, placebo response in functional dyspepsia (FD) has not been well described. Minimizing placebo response is important in drug development. We therefore conducted a meta-analysis to determine placebo response in trials for FD and to identify factors affecting placebo response rates. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify double-blinded randomized controlled trials (RCTs) comparing medication with placebo in patients with FD. Both symptom improvement and complete relief were considered as separate primary endpoints in the analysis. Proportions of placebo patients experiencing any symptom improvement or complete relief were calculated. Dropouts after randomization for any reason were assumed to represent treatment failure for data extraction and analysis. Placebo response was pooled by a random-effects model, and effects of trial characteristics on the magnitude of placebo response were evaluated. RESULTS: In 58 eligible placebo-controlled RCTs of FD from 52 selected citations, 6,732 of 17,890 participants in all trials received placebo. Pooled placebo response rates for symptom improvement and complete relief were 44.3% and 15.6%, respectively. The placebo response rate was lower when improvements were assessed for ≥8 weeks. Trials assessing complete symptom relief showed lower placebo response rates even in trials for <8 weeks. DISCUSSION: Our systematic review and meta-analysis showed that pooled placebo response rates in double-blinded RCTs of FD depended on efficacy criteria. Trials assessing complete symptom relief showed stable low placebo response rates in short-term trials.

4.
In Vivo ; 35(4): 2247-2251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182503

RESUMO

BACKGROUND: Multimodality treatment including immune check point inhibitors is required for stage IV oesophagogastric junction cancer (OGJC). CASE REPORT: A 69-year-old man, was diagnosed with advanced OGJC and para-aortic lymph node metastasis (T3N+M1, stage IV), which upon biopsy, was shown to be an adenocarcinoma. After eight courses of nivolumab as third-line chemotherapy, the primary tumour and enlarged regional and para-aortic lymph nodes shrunk markedly, while tumour markers decreased within normal ranges. We performed a minimally invasive Ivor-Lewis oesophagectomy with completion of an abdominal D2 and transhiatal lower mediastinal lymph node dissection. Pathological findings revealed a complete response for the primary tumour and a regional lymph node metastasis. A biopsy of the previous sample revealed microsatellite instability-negativity, Epstein-Barr virus-negativity, and programmed cell death-1-ligand combined positive score of 2. He was followed up for 3 months without recurrence. CONCLUSION: Nivolumab may induce pathological complete response for stage IV OGJC even in cases negative for microsatellite instability and Epstein-Barr virus, besides the programmed cell death-1-ligand combined positive score of <5.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Esofagectomia , Junção Esofagogástrica/cirurgia , Herpesvirus Humano 4 , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
6.
7.
Biology (Basel) ; 10(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803334

RESUMO

Gastrointestinal (GI) disorders such as celiac disease and inflammatory bowel disease are attributed to intestinal barrier disruption. Imbalance of cytokines has been reported in the intestinal epithelium of patients with GI disorders. Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber in the intestine, have been reported to benefit the intestinal barrier. Accordingly, we evaluated the effect of specific SCFAs on intestinal barrier function under cytokine-stimulated conditions. Caco-2 cells were cultured on insert membranes to generate monolayers, which then were used to investigate the effects of SCFAs. Tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), or interleukin-13 (IL-13) was added to the basolateral side of the membrane while SCFAs were added to the apical side. After a 24 h stimulation, transepithelial electrical resistance (TEER) was measured, and the protein levels of claudin-1, claudin-2, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1) were evaluated by Western blot. Butyrate, but not acetate, propionate, or succinate, ameliorated the TNF-α/IFN-γ-induced decrease in TEER. TNF-α/IFN-γ stimulation significantly increased the protein level of claudin-2 and decreased the level of claudin-3. Butyrate significantly attenuated the upregulation of claudin-2 induced by TNF-α/IFN-γ. Butyrate blocked the decrease in TEER and the upregulation of claudin-2 induced by IL-13 without changing the level of other tight junction proteins. Our results suggested that butyrate is the main component of SCFAs to alleviate barrier dysfunction and that claudin-2 is the major target of this SCFA.

8.
J Clin Med ; 10(5)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804300

RESUMO

BACKGROUND: The frequency of delayed bleeding after colorectal polypectomy has been reported as 0.6-2.8%. With the increasing performance of polypectomy under continuous use of antithrombotic agents, care is required regarding delayed post-polypectomy bleeding (DPPB). Better instruction to educate endoscopists is therefore needed. We aimed to evaluate the effect of instruction and factors associated with delayed bleeding after endoscopic colorectal polyp resection. METHODS: This single-center, retrospective study was performed to assess instruction in checking complete hemostasis and risk factors for onset of DPPB. The incidence of delayed bleeding, comorbidities, and medications were evaluated from medical records. Characteristics of historical control patients and patients after instruction were compared. RESULTS: A total of 3318 polyps in 1002 patients were evaluated. The control group comprised 1479 polyps in 458 patients and the after-instruction group comprised 1839 polyps in 544 patients. DPPB occurred in 1.1% of polyps in control, and 0.4% in after-instruction. Instruction significantly decreased delayed bleeding, particularly in cases with antithrombotic agents. Hot polypectomy, clip placement, and use of antithrombotic agents were significant independent risk factors for DPPB even after instruction. CONCLUSION: The rate of delayed bleeding significantly decreased after instruction to check for complete hemostasis. Even after instruction, delayed bleeding can still occur in cases with antithrombotic agents or hot polypectomy.

10.
J Gastroenterol Hepatol ; 36(4): 951-958, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32839988

RESUMO

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, and bile acids are thought to be associated with the pathogenesis of IBS. Bile acid receptors are expressed on intestinal epithelial cells. However, no study has assessed bile acid receptor proteins in IBS. Therefore, we examined the intestinal mucosal expression of bile acid receptors in patients with IBS. METHODS: Intestinal biopsies were performed in patients with IBS and controls. Mast cells, vitamin D receptor (VDR), and somatostatin were stained with specific antibodies. Levels of VDR, farnesoid X receptor (FXR), takeda-G-protein-receptor-5 (TGR5), claudins, and transient-receptor-potential-cation-channel-subfamily-V-member 6 (TRPV6) were assessed by western blotting. RESULTS: 3Mast cell counts in the second part of the duodenum were significantly higher in patients with IBS than in controls. VDR protein levels were significantly elevated in the duodenum and terminal ileum of patients with IBS compared with controls, although this difference was not seen in the cecum or rectum. FXR and TGR5 protein levels did not differ in any part of the intestine. VDR-positive cryptal epithelia in IBS were distributed not only at basal crypt but also along the upper part of the basal crypt epithelial cells. In contrast, the pattern of gut somatostatin-positive cells, claudins, and TRPV6 levels did not differ. CONCLUSIONS: The number of mast cells in the duodenum was significantly increased, and the protein expression levels of VDR, but not those of FXR or TGR5, were elevated in the duodenal epithelial crypt in patients with IBS.

12.
Am J Gastroenterol ; 116(1): 152-161, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32969946

RESUMO

INTRODUCTION: This is the first prospective, double-blinded, randomized, placebo-controlled trial to evaluate the safety and efficacy of a stimulant laxative compared with an osmotic agent for the treatment of chronic idiopathic constipation. METHODS: Patients were randomly administered stimulant laxative (senna, 1.0 g), osmotic agent (magnesium oxide [MgO], 1.5 g), or placebo for 28 consecutive days. The primary endpoint was overall symptom improvement. Secondary endpoints were spontaneous bowel movement (SBM), complete SBM, and patient assessment of constipation quality of life (QOL). RESULTS: Ninety patients (mean age, 42 years; 93% women; mean duration of symptoms, 9.9 years) were enrolled; all completed the study. The response rate for overall improvement was 11.7% in the placebo group, 69.2% in the senna group, and 68.3% in the MgO group (P < 0.0001). Change in SBM was significantly greater in the senna and MgO groups than that in the placebo group (P < 0.001). Similarly, change in complete SBM was significantly greater in the senna and MgO groups than that in the placebo group (P < 0.01). On the patient assessment of constipation QOL, significant improvements were seen in the senna and MgO groups compared with those in the placebo group (senna, P < 0.05; MgO, P < 0.001). The frequency of severe treatment-related adverse events was 0%. DISCUSSION: Senna and MgO significantly improved the frequency of bowel movements and QOL score and seem to be effective in the treatment of constipation.


Assuntos
Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Óxido de Magnésio/uso terapêutico , Qualidade de Vida , Senosídeos/uso terapêutico , Adulto , Idoso , Doença Crônica , Constipação Intestinal/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
13.
Digestion ; 102(2): 170-179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31533100

RESUMO

INTRODUCTION: Impaired intestinal epithelial barrier function is a hallmark of a variety of pathological conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). IBD patients with IBS-like symptoms show higher interleukin-13 (IL-13) serum levels and poor psychological well-being. Supplementary glutamine reduced the daily bowel movement frequency, improved the stool form, and normalized intestinal hyperpermeability. This study was aimed at assessing the effects of IL-13 and supplementary glutamine on human intestinal epithelial function in vitro. METHODS: Caco-2 cells were grown on TranswellTM inserts. -IL-13 was added to the basolateral compartment, and transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability measured. Effects of glutamine or the phosphatidylinositol-3-kinase inhibitor LY294002 were assessed. Involvement of tight junction proteins was assessed using Western blotting and immunofluorescence staining. RESULTS: IL-13 significantly decreased TEER and increased FITC labeled-dextran epithelial permeability. IL-13 stimulation decreased the claudin-1 expression and increased the claudin-2 expression. Glutamine alleviated IL-13-induced decrease of TEER and increase of FITC labeled-dextran permeability. Further, the phosphatidylinositol-3-kinase inhibitor showed this alleviating effect while the signal transducer and activator of transcription 6 inhibitor did not. CONCLUSIONS: IL-13 induced barrier integrity impairment by decreasing claudin-1 and increasing claudin-2. Glutamine alleviated IL-13-induced barrier dysfunction by increasing claudin-1 expression, via disruption of the phosphatidylinositol-3-kinase/Akt signaling pathway.

14.
Am J Physiol Gastrointest Liver Physiol ; 320(2): G206-G216, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33174456

RESUMO

Gastric hypersensitivity is a major pathophysiological feature of functional dyspepsia (FD). Recent clinical studies have shown that a large number of patients with FD present with gastroduodenal microinflammation, which may be involved in the pathophysiology of FD. However, no animal model reflecting this clinical characteristic has been established. The underlying mechanism between microinflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal microinflammation and reveal the interaction between gastroduodenal microinflammation and gastric hypersensitivity. The MS model was established by separating newborn Sprague-Dawley rats for 2 h a day from postnatal day 1 to day 10. At 7-8 wk of age, electromyography was used to determine the visceromotor response to gastric distention (GD) and immunohistochemistry was performed to detect distension-associated neuronal activation as well as immunohistological changes. Our results demonstrated that MS-induced FD rats underwent gastric hypersensitivity with GD at 60 and 80 mmHg, which are related to increased p-ERK1/2 expression in the dorsal horn of T9-T10 spinal cords. Eosinophils, but not mast cells, were significantly increased in the gastroduodenal tract, and the coexpression rate of CD11b and major basic protein significantly increased in MS rats. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. These findings indicated that neonatal MS stress induces eosinophil-associated gastroduodenal microinflammation and gastric hypersensitivity in adulthood in rats. Microinflammation contributes to gastric hypersensitivity; therefore, anti-inflammatory therapy may be effective in treating patients with FD with gastroduodenal microinflammation.NEW & NOTEWORTHY We showed for the first time that neonatal MS stress-induced FD rats undergo gastroduodenal eosinophil-associated microinflammation in adulthood. Suppression of microinflammation attenuated gastric hypersensitivity in MS rats. These findings established a functional link between microinflammation and gastric hypersensitivity, which may provide a potential clue for the clinical treatment of FD.


Assuntos
Duodeno/patologia , Eosinófilos , Inflamação/patologia , Estômago/patologia , Animais , Animais Recém-Nascidos , Mucosa Gástrica/inervação , Mucosa Gástrica/patologia , Gastrite , Hipersensibilidade , Privação Materna , Pressão , Ratos , Ratos Sprague-Dawley , Estresse Fisiológico
15.
J Gastroenterol Hepatol ; 36(6): 1529-1537, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33047825

RESUMO

BACKGROUND AND AIM: The impact of chronic constipation on health-related quality of life (HRQoL), work productivity, and healthcare resource use in Japan is not well understood. This study aimed to evaluate and compare the humanistic burden of respondents with chronic constipation to respondents without chronic constipation and to respondents with type 2 diabetes mellitus (T2DM), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD), respectively. METHODS: This cross-sectional study collected demographic and general health data and HRQoL data as measured by the Short Form 12-Item (Version 2) Health Survey and EuroQol 5-dimension health surveys. Health impacts on employment-related activities and indirect costs were measured using the Work Productivity and Activity Impairment questionnaire. Propensity score matching was used to identify a control group without chronic constipation. Multivariate generalized linear models were used to identify potential factors that may impact the outcomes of respondents. RESULTS: A total of 30 001 individuals responded to the Japan National Health and Wellness Survey 2017, whereof 3373 (11.2%) reported having chronic constipation; 963 were physician diagnosed. Compared with matched controls, patients with physician-diagnosed chronic constipation had lower mean HRQoL scores and higher mean absenteeism, presenteeism, total Work Productivity and Activity Impairment, and indirect costs. Physician-diagnosed chronic constipation was associated with a higher health burden than T2DM, IBS, and GERD. CONCLUSIONS: Chronic constipation is associated with a considerable health burden, which is higher compared with T2DM, IBS, and GERD. These results suggest an urgent need for effective treatment of Japanese patients with chronic constipation to improve their quality of life.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33197076

RESUMO

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are a group of stress-sensitive gut-brain disorders. The COVID-19 outbreak has caused immense stress and anxiety among the general public. Strict measures to counter COVID-19 emergency, including physical distancing have also taken a toll on physical and mental health. We investigated the impact of the COVID-19 pandemic on the gastrointestinal and psychological symptoms of functional dyspepsia (FD) and irritable bowel syndrome (IBS). METHODS: An online survey was conducted in Japan for a group of randomly assigned panelists from May 26 to 27, 2020. Each respondent answered a questionnaire on stress, physical distancing, and worries about COVID-19. Gastrointestinal symptoms were assessed to diagnose FD and IBS (Rome III), and psychological symptoms were assessed using the Hospital Anxiety and Depression Scale. RESULTS: A total of 5157 subjects were finally enrolled, with FD in 8.5%, IBS in 16.6%, and FD-IBS overlap in 4.0%. For both gastrointestinal and psychological symptoms, respondents with FD-IBS overlap showed the worst scores, followed by IBS-alone, then FD-alone respondents. During the COVID-19 pandemic, 11.9% of respondents reported deterioration and 2.8% reported improvement of gastrointestinal symptoms. FD-IBS overlap, psychological disease comorbidity, and stress at work/school were significantly associated with symptom deterioration. Younger age, commuting by public transport, and work/study from home were associated with symptom improvement. CONCLUSIONS: The COVID-19 pandemic negatively affected FD/IBS subjects, with respondents showing FD-IBS overlap syndrome as the most important independent factor associated with deterioration in gastrointestinal symptoms. Physicians need to take extra care of FD/IBS patients in the post-COVID period.

17.
Mod Rheumatol Case Rep ; 4(2): 296-301, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33087010

RESUMO

A 39-year-old Japanese man presented with chest oppression in February 2017. Electrocardiogram showed ST-elevation myocardial infarction (MI), and cardiac catheterisation revealed thrombotic occlusion of the right coronary artery (RCA), which was treated with thrombectomy, and he received warfarin. Three days after discharge, he complained of chest oppression again, and re-cardiac catheterisation showed thrombi occlusion of the circumflex artery (LCX) and 90% stenosis with thrombosis in the proximal site of the anterior descending artery (LAD) and RCA. Drug eluting stent was implanted in the LAD and RCA; aspirin and prasugrel hydrochloride were added to warfarin. Before discharge, coronary computed tomography angiography (CTA) found new thrombi in the RCA, LAD, and LCX, and he was referred to our hospital on suspicion of Behçet's disease (BD). Past medical history was notable for recurrent aphthous stomatitis, a pudendal ulcer, and Crohn's disease, for which he had been taking infliximab (5 mg/kg) every 8 weeks until December 2016. Notably, his C-reactive protein (CRP) level increased before and after each MI, suggesting that the thrombi were caused by inflammation. Consequently, we concluded that his abnormalities were manifestations of vasculo-BD. After 3 days of hospitalisation, treatment with prednisolone and colchicine was started. His CRP and D-dimer levels decreased, and coronary CTA after 8 days showed disappearance of the thrombi. We tapered the prednisolone dose, and cardiovascular events have not been observed for 7 months after the treatment initiation. In summary, we report a rare case of MI associated with vasculo-BD and review the relevant literature.

18.
Int J Mol Sci ; 21(17)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854266

RESUMO

Although dysbiosis is likely to disturb the mucosal barrier system, the mechanism involved has remained unclear. Here, we investigated alterations of colonic mucosal permeability and tight junction (TJ) molecules in mice with antibiotic-induced dysbiosis. Mice were orally administered vancomycin or polymyxin B for 7 days, and then fecal samples were subjected to microbial 16S rRNA analysis. The colonic mucosal permeability was evaluated by chamber assay. The colonic expression of TJ molecules and cytokines was examined by real-time RT-PCR, Western blotting, and immunohistochemistry. Caco2 cells were stimulated with cytokines and their transepithelial electric resistance (TEER) was measured. Vancomycin-treated mice showed significantly lower gut microbiota diversity than controls, and the same tendency was evident in polymyxin B-treated mice. The colonic mucosal permeability was significantly elevated in both vancomycin- and polymyxin B-treated mice. The expression of claudin 4 in the colonic mucosa was decreased in both vancomycin- and polymyxin B-treated mice. Colonic expression of TNF-α and/or IFN-γ was significantly increased in mice that had been administered antibiotics. TNF-α and IFN-γ stimulation dose-dependently decreased TEER in Caco2 cells. Antibiotic-induced dysbiosis is correlated with the enhancement in colonic tissue permeability, accompanied by a reduction in claudin 4 expression and enhancement in TNF-α and/or IFN-γ expression in mice.


Assuntos
Antibacterianos/efeitos adversos , Bactérias/classificação , Disbiose/metabolismo , Mucosa Intestinal/metabolismo , Proteínas de Junções Íntimas/metabolismo , Administração Oral , Animais , Antibacterianos/administração & dosagem , Bactérias/genética , Bactérias/isolamento & purificação , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Disbiose/genética , Fezes/microbiologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Camundongos , Permeabilidade/efeitos dos fármacos , Filogenia , Polimixina B/administração & dosagem , Polimixina B/efeitos adversos , RNA Ribossômico 16S/genética , Análise de Sequência de RNA , Proteínas de Junções Íntimas/genética , Vancomicina/administração & dosagem , Vancomicina/efeitos adversos
19.
Oncol Lett ; 19(5): 3542-3550, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32269628

RESUMO

Gastric cancers (GCs) may develop in the gastric mucosa after elimination of Helicobacter pylori (H. pylori) using eradication therapy. Cytokine signaling is a key mechanism underlying GC development and progression, and STAT3 signaling may serve a central role in gastritis-associated tumorigenesis. In the present study, suppressor of cytokine signaling 3 (SOCS3) methylation was examined, as an activator of phosphorylated (p-)STAT3 expression in the non-neoplastic gastric mucosa (non-NGM) of patients with early GC. The methylation status of the SOCS3 gene promoter was analyzed using methylation-specific PCR in the non-NGM of patients with or without early GC. Expression levels of p-STAT3 and Ki67 were investigated immunohistochemically in non-NGM with early GC before and after H. pylori eradication. In non-NGM, SOCS3 promoter methylation was detected in 17/51 patients (33.3%) with early GC. In those patients, the non-NGM labeling indices of both Ki67 and p-STAT3 were significantly higher compared with that in patients with early GC without SOCS3 methylation. A significant correlation between Ki67 and p-STAT3 expression levels was demonstrated in the non-NGM of patients with early GC. In patients with early GC without SOCS3 methylation, the labeling indices of both Ki67 and p-STAT3 in non-NGM were significantly reduced after H. pylori eradication, whereas no such change was observed in patients with early GC with SOCS3 methylation. SOCS3 methylation is associated with continuous p-STAT3 overexpression and enhanced epithelial cell proliferation in non-NGM of patients with early GC.

20.
Gut Liver ; 14(3): 281-290, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31547640

RESUMO

Whether Helicobacter pylori eradication actually reduces the risk of metachronous gastric cancer (MGC) development remains a controversial question. In this review, we addressed this topic by reviewing the results of clinical investigations and molecular pathological analyses of the roles of H. pylori eradication and aspirin administration in the prevention of MGC. In regard to the clinical studies, the results of meta-analyses and randomized control trials differ from those of retrospective studies: the former trials show that H. pylori eradication has a preventive effect on MGC, while the latter studies do not. This discrepancy may be at least partly attributable to differences in the follow-up periods: H. pylori eradication is more likely to prevent MGC over a long-term follow-up period (≥5 years) than over a short-term follow-up period. In addition, many studies have shown that aspirin may have an additive effect on MGC-risk reduction after H. pylori eradication has been achieved. Both H. pylori eradication and aspirin use induce molecular alterations in the atrophic gastritis mucosa but not in the intestinal metaplasia. Unfortunately, the molecular pathological analyses of these interventions have been limited by short follow-up periods. Therefore, a long-term prospective cohort is needed to clarify the changes in molecular events caused by these interventions.


Assuntos
Aspirina/uso terapêutico , Infecções por Helicobacter/terapia , Helicobacter pylori , Neoplasias Epiteliais e Glandulares/cirurgia , Segunda Neoplasia Primária/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Neoplasias Gástricas/prevenção & controle , Ressecção Endoscópica de Mucosa , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastrite Atrófica/complicações , Gastrite Atrófica/microbiologia , Gastrite Atrófica/cirurgia , Infecções por Helicobacter/complicações , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/microbiologia , Segunda Neoplasia Primária/microbiologia , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/cirurgia
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