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INTRODUCTION: Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting. METHODS: We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience. RESULTS: A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%. DISCUSSION: The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice.
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Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/diagnóstico , Pólipos do Colo/patologia , Estudos Prospectivos , Valor Preditivo dos Testes , Colonoscopia/métodos , Computadores , Neoplasias Colorretais/patologia , Imagem de Banda Estreita/métodosRESUMO
Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.
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Anti-Infecciosos , Gastroenterologia , Infecções por Helicobacter , Helicobacter pylori , Úlcera Péptica , Humanos , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/etiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Anti-Infecciosos/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.
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Esôfago de Barrett , Refluxo Gastroesofágico , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/etiologia , Consenso , Junção Esofagogástrica , Humanos , Inflamação , MetaplasiaRESUMO
OBJECTIVE: To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. METHODS: A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). RESULTS: There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III-IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III-IV developed within 2 years (range: 12.7-44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III-IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II-IV. CONCLUSIONS: We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III-IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
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Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Humanos , Metaplasia , Lesões Pré-Cancerosas/epidemiologia , Estudos Prospectivos , Fatores de Risco , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologiaAssuntos
Pegada de Carbono , Mudança Climática , Conservação dos Recursos Naturais , Gastroenterologia , Gastroenteropatias , Eliminação de Resíduos de Serviços de Saúde , Resíduos de Serviços de Saúde , Equipamentos Descartáveis , Reutilização de Equipamento , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia , Humanos , Resíduos de Serviços de Saúde/efeitos adversos , ReciclagemRESUMO
Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.
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Mudança Climática , Gastroenterologia , HumanosRESUMO
BACKGROUND AND AIM: Artificial intelligence has been extensively studied to assist clinicians in polyp detection, but such systems usually require expansive processing power, making them prohibitively expensive and hindering wide adaption. The current study used a fast object detection algorithm, known as the YOLOv3 algorithm, to achieve real-time polyp detection on a laptop. In addition, we evaluated and classified the causes of false detections to further improve accuracy. METHODS: The YOLOv3 algorithm was trained and validated with 6038 and 2571 polyp images, respectively. Videos from live colonoscopies in a tertiary center and those obtained from public databases were used for the training and validation sets. The algorithm was tested on 10 unseen videos from the CVC-Video ClinicDB dataset. Only bounding boxes with an intersection over union area of > 0.3 were considered positive predictions. RESULTS: Polyp detection rate in our study was 100%, with the algorithm able to detect every polyp in each video. Sensitivity, specificity, and F1 score were 74.1%, 85.1%, and 83.3, respectively. The algorithm achieved a speed of 61.2 frames per second (fps) on a desktop RTX2070 GPU and 27.2 fps on a laptop GTX2060 GPU. Nearly a quarter of false negatives happened when the polyps were at the corner of an image. Image blurriness accounted for approximately 3% and 9% of false positive and false negative detections, respectively. CONCLUSION: The YOLOv3 algorithm can achieve real-time poly detection with high accuracy and speed on a desktop GPU, making it low cost and accessible to most endoscopy centers worldwide.
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Inteligência Artificial , Pólipos do Colo , Colonoscopia , Algoritmos , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Humanos , Redes Neurais de ComputaçãoRESUMO
BACKGROUND AND AIM: Gastrointestinal (GI) lesions may have subtle morphological changes. Linked color imaging (LCI) combines narrow-band wavelength light and white light imaging (WLI) in appropriate balance to enhance lesion detection. We compared the detection rates of upper GI lesions using LCI and WLI. METHOD: Patients were randomized in a 1:1 ratio to receive tandem gastroscopy with WLI inspection followed by LCI, or vice versa. Endoscopic examination was performed using the EG-L590ZW gastroscope and the LASEREO endoscope system (Fujifilm Co., Tokyo, Japan). Histology was reported by a specialist GI pathologist blinded to the technique of lesion detection and was used as the gold standard for diagnosis. RESULTS: Ninety patients (mean age 66.8 years, 51.5% male patients) were randomized to either LCI examination first followed by WLI (LCI-WLI), or vice versa (WLI-LCI). An 18.9% of gastroscopies in the study were for surveillance of previously known gastric cancer precursors. Ten patients (11.1%) had a history of Helicobacter pylori infection. There was no significant difference in the time taken for examination under LCI (311 ± 96 s) and WLI (342 ± 86 s) (P = 0.700). LCI detection rates were higher than WLI detection rates for gastric cancer precursors such as atrophic gastritis (2.19% vs 0.55%) (P < 0.01) and intestinal metaplasia (19.73% vs 7.67%) (P < 0.01). Both sensitivity (82.74% vs 50.96%) and specificity (98.71% vs 96.10%) of LCI were higher than WLI for detection of upper GI lesions. CONCLUSIONS: Linked color imaging had better detection rates, sensitivity, and specificity for detection of upper GI lesions compared with WLI.
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Gastroscopia , Imagem Óptica , Neoplasias Gástricas , Idoso , Cor , Feminino , Gastroscopia/métodos , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Imagem Óptica/métodos , Projetos Piloto , Estudos Prospectivos , Sensibilidade e Especificidade , Estômago/diagnóstico por imagem , Estômago/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND AND AIMS: Availability of transient elastography (TE) limits the application of Baveno-VI criteria. In a derivation study, the ABP criteria (Albumin >40â¯g/l, Bilirubin <22⯵mol/l and Platelet >114,000/µl) had been shown to perform well in identifying compensated advanced chronic liver disease (cACLD) patients without high-risk varices (HRV). We aim to externally validate this novel ABP criteria for the exclusion of HRVs among cACLD patients. METHODS: Data was retrospectively collected from consecutive cACLD patients with paired TE and esophagogastroduodenoscopy (EGD) performed between 2011 and 2017 in Changi General Hospital, Singapore. We estimate the discriminative ability of ABP criteria in validation cohort using AUROC and calibration-in-the-large. We subsequently compare the performance between ABP and Baveno-VI criteria in the validation cohort. RESULTS: Among 314 patients included in our validation cohort, 32 (10.2%) had HRV on screening EGD. Application of ABP criteria within this validation cohort has increased discriminative ability than the derivation cohort. The AUROC of validation and derivation cohort were 0.68 (0.60-0.76) and 0.66 (0.60-0.76), respectively. The mean and standard error for calibration-in-the-large and calibration slope were -0.08 (0.22) and 0.93 (0.26) respectively. The ABP criteria had excellent performance in excluding HRV and will spare more screening EGDs than the Baveno-VI criteria (39.2% vs 27.4%, pâ¯<â¯0.001), without missing more HRVs. CONCLUSION: We validated the performance of ABP criteria for the exclusion of HRVs in cACLD patients. ABP criteria is superior to Baveno-VI criteria by sparing more screening EGD without the need of TE.
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Bilirrubina , Varizes Esofágicas e Gástricas , Hepatopatias , Contagem de Plaquetas , Albumina Sérica , Bilirrubina/sangue , Biomarcadores/sangue , Doença Crônica , Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas/sangue , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Humanos , Hepatopatias/sangue , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND/AIMS: Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore. METHODS: In this retrospective study, we reviewed all incarcerated HCV-infected patients treated in our hospital during the restricted DAA era (2013-2018) and unrestricted DAA access era (2019). Study outcomes included the rate of sustained virological response (SVR), treatment completion and treatment default. Subgroup analysis was performed based on the presence of liver cirrhosis, HCV genotype and HCV treatment types. RESULTS: A total of 1,001 HCV patients was followed-up for 1,489 person-year. They were predominantly male (93%) with genotype-3 HCV infection (71%), and 38% were cirrhotic. The overall SVR during the restricted DAA access era and unrestricted DAA access era were 92.1% and 99.1%, respectively. Unrestricted access to DAA exponentially improved the treatment access among HCV-infected patients by 460%, resulting in a higher SVR rate (99% vs. 92%, P=0.003), higher treatment completion rate (99% vs. 93%, P<0.001) and lower treatment default rate (1% vs. 9%, P<0.001). CONCLUSION: In this large cohort of incarcerated HCV-infected patients, we demonstrated that unrestricted access to DAA is an impactful strategy to allow rapid treatment up-scale in HCV micro-elimination.
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Hepatite C Crônica , Prisioneiros , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Dietary factors have been linked to cancers. This review focuses on several nutrients, which have strong evidence showing increase in cancer risks in the esophagus and stomach. RECENT FINDINGS: Obesity is an important risk factor in upper gastrointestinal cancers. High sugar content in food and sugary drinks are the main drivers of obesity. Proinflammatory diet is another dietary factor, which is increasingly recognized as being associated with esophageal and gastric cancer. SUMMARY: Cancer has been predicted to be the leading cause of death in this century. Cancers of the esophagus and stomach are the six and third most common cause of death worldwide. Although Helicobacter pylori infection is a known cause of gastric cancer, obesity is a leading contributor to esophageal adenocarcinoma. Epidemiological data have shown that dietary factors are associated with the two cancers. Observational, case control, animal and recent large cohort studies have identified associations between dietary factors and upper gastrointestinal cancer. Data are also emerging from studies, which look at dietary patterns, such as reduction in the Dietary Inflammatory Index, as well as adherence to a modified Mediterranean diet, and its association with the incidence of esophageal and gastric cancer.
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Neoplasias Esofágicas , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Dieta , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Humanos , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologiaRESUMO
BACKGROUND AND AIM: Real-world data on sofosbuvir/velpatasvir with and without ribavirin (SOF/VEL ± RBV), particularly among patients with genotype 3 (GT3) decompensated cirrhosis, prior treatment, coinfection, and hepatocellular carcinoma (HCC), are scarce. We aimed to assess the efficacy and safety of SOF/VEL ± RBV in a real-world setting that included both community and incarcerated GT3 hepatitis C virus (HCV) patients. METHODS: We included all GT3 HCV patients treated with SOF/VEL ± RBV in our institution. The primary outcome measure was the overall sustained virological response 12 weeks after treatment (SVR12), reported in both intention-to-treat (ITT) and per-protocol analyses. The secondary outcome measures were SVR12 stratified by the presence of decompensated cirrhosis, prior treatment, HCC, and HIV/hepatitis C virus coinfection and the occurrence rate of serious adverse events requiring treatment cessation or hospitalization. RESULTS: A total of 779 HCV patients were treated with 12 weeks of SOF/VEL ± RBV, of which 85% were treated during incarceration. Among the 530 GT3 HCV patients, 31% had liver cirrhosis, and 6% were treatment-experienced. The overall SVR12 for GT3 was 98.7% (95% confidence interval: 97.3%, 99.5%) and 99.2% (95% confidence interval: 98.1%, 99.8%) in ITT and per-protocol analyses, respectively. High SVR12 was also seen in ITT analysis among GT3 HCV patients with decompensated cirrhosis (88%), prior treatment (100%), HCC (100%), and HIV/hepatitis B virus coinfection (100%). Apart from one patient who developed myositis, no other serious adverse events were observed. CONCLUSION: The SOF/VEL ± RBV is a safe and efficacious treatment option for GT3 HCV patients in a real-world setting. SOF/VEL with RBV may be considered for decompensated GT3 HCV patients.
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Carbamatos/administração & dosagem , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Coinfecção , Quimioterapia Combinada , Feminino , Infecções por HIV , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ribavirina/administração & dosagem , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate the present situation of epidemiology and diagnostic tests of FGID in clinical practice in some East and Southeast Asian countries. METHODS: The questionnaire focusing on current situation of FGID diagnosis and gastrointestinal motility testing was distributed to members of the International Gastroenterology Consensus Symposium study group and collected to be analyzed. RESULTS: The prevalence rates of subtypes of both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are relatively similar in all Asian countries. In these countries, most patients underwent both upper endoscopy and Helicobacter pylori test to diagnose FD. Colonoscopy was also frequently performed to diagnose IBS and chronic constipation. The frequency of gastrointestinal motility testing to examine gastric emptying and colonic transit time varied among Asian countries. CONCLUSIONS: This survey revealed epidemiology of FGIDs and current status of gastrointestinal motility testing in some East and Southeast Asian countries.
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INTRODUCTION AND OBJECTIVES: The novel coronavirus disease 2019 (COVID-19) has affected more than 5 million people globally. Data on the prevalence and degree of COVID-19 associated liver injury among patients with COVID-19 remain limited. We conducted a systematic review and meta-analysis to assess the prevalence and degree of liver injury between patients with severe and non-severe COVID-19. METHODS: We performed a systematic search of three electronic databases (PubMed/MEDLINE, EMBASE and Cochrane Library), from inception to 24th April 2020. We included all adult human studies (>20 subjects) regardless of language, region or publication date or status. We assessed the pooled odds ratio (OR), mean difference (MD) and 95% confidence interval (95%CI) using the random-effects model. RESULTS: Among 1543 citations, there were 24 studies (5961 subjects) which fulfilled our inclusion criteria. The pooled odds ratio for elevated ALT (ORâ¯=â¯2.5, 95%CI: 1.6-3.7, I2â¯=â¯57%), AST (ORâ¯=â¯3.4, 95%CI: 2.3-5.0, I2â¯=â¯56%), hyperbilirubinemia (ORâ¯=â¯1.7, 95%CI: 1.2-2.5, I2â¯=â¯0%) and hypoalbuminemia (ORâ¯=â¯7.1, 95%CI: 2.1-24.1, I2â¯=â¯71%) were higher subjects in critical COVID-19. CONCLUSION: COVID-19 associated liver injury is more common in severe COVID-19 than non-severe COVID-19. Physicians should be aware of possible progression to severe disease in subjects with COVID-19-associated liver injury.
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Betacoronavirus , Infecções por Coronavirus/complicações , Hepatopatias/epidemiologia , Hepatopatias/virologia , Pneumonia Viral/complicações , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Humanos , Hepatopatias/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , SARS-CoV-2RESUMO
Background and study aims Using personal protective equipment (PPE) can reduce risk of disease transmission. During the COVID-19 pandemic, enhanced PPE (EPPE) is recommended when performing endoscopy. We aimed to evaluate the impact of EPPE on colonoscopy performance when compared to standard PPE (SPPE). Patients and methods A review of electronic medical records and endoscopy reports of consecutive patients who underwent colonoscopy during two similar one-month time periods (in 2019 and during the COVID-19 pandemic in 2020) was performed. SPPE was used in 2019 and EPPE was used in 2020. Patient clinical data and procedure-related information were captured and analyzed. The primary outcomes were time to cecum (TTC) and total procedure time. Secondary outcomes were adenoma detection rate (ADR), polyp detection rate (PDR) and cecal intubation rate (CIR). Statistical analysis was performed using STATA v16.1. Results Two hundred and forty-seven colonoscopy procedures were analyzed. Baseline demographics and indications for colonoscopy of patients in both groups were similar. There were no significant differences in median TTC (10.0 vs 10.0âmin, P â=â0.524) or total procedure time (22.5 vs 23.0âmin, P â=â0.946) between colonoscopy performed in SPPE and EPPE. The ADR, PDR and CIR were also similar. Conclusion Our findings suggest that use of EPPE does not affect colonoscopy performance.
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OBJECTIVE: Intestinal metaplasia (IM) is a premalignant stage that poses a greater risk for subsequent gastric cancer (GC). However, factors regulating IM to GC progression remain unclear. Previously, activated DNA damage response (DDR) signalling factors were shown to engage tumour-suppressive networks in premalignant lesions. Here, we interrogate the relationship of DDR signalling to mutational accumulation in IM lesions. DESIGN: IM biopsies were procured from the gastric cancer epidemiology programme, an endoscopic surveillance programme where biopsies have been subjected to (epi)genomic characterisation. IM samples were classified as genome-stable or genome-unstable based on their mutational burden/somatic copy-number alteration (CNA) profiles. Samples were probed for DDR signalling and cell proliferation, using the markers γH2AX and MCM2, respectively. The expression of the gastric stem cell marker, CD44v9, was also assessed. Tissue microarrays representing the GC progression spectrum were included. RESULTS: MCM2-positivity increased during GC progression, while γH2AX-positivity showed modest increase from normal to gastritis and IM stages, with further increase in GC. γH2AX levels correlated with the extent of chronic inflammation. Interestingly, genome-stable IM lesions had higher γH2AX levels underscoring a protective anti-cancer role for DDR signalling. In contrast, genome-unstable IM lesions with higher mutational burden/CNAs had lower γH2AX levels, elevated CD44v9 expression and modest promoter hypermethylation of DNA repair genes WRN, MLH1 and RAD52. CONCLUSIONS: Our data suggest that IM lesions with active DDR will likely experience a longer latency at the premalignant state until additional hits that override DDR signalling clonally expand and promote progression. These observations provide insights on the factors governing IM progression.
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Mucosa Gástrica/patologia , Histonas/genética , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Proteína 1 Homóloga a MutL/genética , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Neoplasias Gástricas , Helicase da Síndrome de Werner/genética , Biópsia/métodos , Dano ao DNA/genética , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/análise , Masculino , Metaplasia/genética , Metaplasia/patologia , Pessoa de Meia-Idade , Mutação , Fatores de Proteção , Transdução de Sinais , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
INTRODUCTION: The Asia-Pacific consensus on the management of gastroesophageal reflux disease (GERD) and the GERD treatment guidelines of 2015 drawn up by the Japanese Society of Gastroenterology were proposed, and GERD management in Asian regions was assumed to be performed based on these consensuses. In this environment, the current status of GERD management in clinical practice among Asian regions is less well-known. OBJECTIVE: This questionnaire-based consensus survey was performed to clarify the current status of management of GERD in clinical practice in Asian regions. METHODS: A questionnaire related to management of GERD was distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire responses and compared the results among groups. RESULTS: The frequencies of erosive GERD (ERD), non-ERD, uninvestigated GERD, and Barrett's esophagus varied significantly among Asian countries. The most important factor in diagnosing GERD was the presence of symptoms in all countries. A proton pump inhibitor was the most commonly prescribed drug to treat GERD in all countries. Endoscopic surveillance for GERD was performed regularly. CONCLUSION: This questionnaire survey revealed the current status of management of GERD in clinical practice in various Asian countries.
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Esôfago de Barrett/diagnóstico , Esôfago de Barrett/epidemiologia , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Ásia/epidemiologia , Esôfago de Barrett/etiologia , Esôfago de Barrett/terapia , Consenso , Esofagoscopia , Fundoplicatura , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/terapia , Fármacos Gastrointestinais/uso terapêutico , Gastroscopia , Pesquisas sobre Atenção à Saúde , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/terapia , Helicobacter pylori/isolamento & purificação , Humanos , Vigilância da População , Guias de Prática Clínica como Assunto , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
BACKGROUND AND AIM: Perturbance in the composition of human gut microbiota has been associated with metabolic disorders such as obesity, diabetes mellitus, and insulin resistance. The objectives of this study are to examine the effects of ethnicity, central obesity, and recorded dietary components on potentially influencing the human gut microbiome. We hypothesize that these factors have an influence on the composition of the gut microbiome. METHODS: Subjects of Chinese (n = 14), Malay (n = 10), and Indian (n = 11) ancestry, with a median age of 39 years (range: 22-70 years old), provided stool samples for gut microbiome profiling using 16S rRNA sequencing and completed a dietary questionnaire. The serum samples were assayed for a panel of biomarkers (interleukin-6, tumor necrosis factor alpha, adiponectin, cleaved cytokeratin 18, lipopolysaccharide-binding protein, and limulus amebocyte lysate). Central obesity was defined by waist circumference cut-off values for Asians. RESULTS: There were no significant differences in Shannon alpha diversity for ethnicity and central obesity and no associations between levels of inflammatory cytokines and obesity. The relative abundances of Anaerofilum (P = 0.02), Gemellaceae (P = 0.02), Streptococcaceae (P = 0.03), and Rikenellaceae (P = 0.04) were significantly lower in the obese group. From principle coordinate analysis, the effects of the intake of fiber and fat/saturated fat were in contrast with each other, with clustering of obese individuals leaning toward fiber. CONCLUSION: The study demonstrated that there were differences in the gut microbiome in obese individuals. Certain bacterial taxa were present in lower abundance in the group with central obesity. Fiber and fat/saturated fat diets were not the key determinants of central obesity.