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1.
Aliment Pharmacol Ther ; 53(1): 8-21, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936964

RESUMO

BACKGROUND: Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown. AIM: To perform a systematic review with network meta-analysis to resolve this uncertainty. METHODS: We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities. RESULTS: We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo. CONCLUSIONS: TCAs, histamine-2 receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.

2.
Gastrointest Endosc Clin N Am ; 31(1): 117-130, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33213791

RESUMO

Candidates for chemoprevention in Barrett's esophagus have long been suggested and there has been observational data to support many drugs, including statins, hormone replacement therapy, metformin, proton pump inhibitor therapy, and aspirin. Proton pump inhibitor therapy and aspirin are the most promising agents. Data suggest that aspirin and proton pump inhibitor therapy can decrease the risk of neoplastic progression in Barrett's esophagus. Further, the combination of aspirin and proton pump inhibitor therapy decrease all-cause mortality by approximately 33%. Future guideline groups need to evaluate the evidence rigorously, but the combination of proton pump inhibitor therapy and aspirin is promising.

4.
Aliment Pharmacol Ther ; 53(2): 253-264, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33280149

RESUMO

BACKGROUND: Conventionally, patients with functional dyspepsia are subgrouped based on upper gastrointestinal symptoms, according to the Rome criteria. However, psychological co-morbidity and extraintestinal symptoms are also relevant to functional gastrointestinal disorders. AIM: To investigate whether it is possible to subgroup people with functional dyspepsia using factors beyond upper gastrointestinal symptoms. METHODS: We collected demographic, symptom and psychological health data from adult subjects meeting the Rome III criteria for functional dyspepsia in two secondary care cross-sectional surveys in Canada and the UK. We performed latent class analysis, a method of model-based clustering, to identify specific subgroups (clusters). For each cluster, we drew a radar plot, and compared these by visual inspection, describing cluster characteristics. RESULTS: In total, 400 individuals met Rome III criteria for functional dyspepsia in the Canadian cohort, and 262 the UK cohort. A four-cluster model was the optimum solution and the characteristics of the clusters were almost identical between the two cohorts. The clusters were defined by a pattern of gastrointestinal symptoms and were further differentiated by the extent of extraintestinal and psychological co-morbidity. Cluster 1 (mean age 46.7 years, 66.7% female) consisted of epigastric pain and nausea with high psychological burden, cluster 2 (mean age 41.5 years, 77.7% female) high overall gastrointestinal symptom severity with high psychological burden, cluster 3 (45.8 years, 67.2% female) oesophageal symptoms and early satiety with low psychological burden, and cluster 4 (mean age 40.4 years, 71.5% female) postprandial fullness with low psychological burden. We validated the model derived using the Canadian study population externally by applying it to the UK dataset. We demonstrated reproducibility; it would perform similarly when applied to a different dataset. CONCLUSIONS: Latent class analysis identified four distinct functional dyspepsia subgroups characterised by varying degrees of gastrointestinal symptoms, extraintestinal symptoms and psychological co-morbidity. Further research is needed to assess whether they might be used to direct treatment.

5.
Carcinogenesis ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300568

RESUMO

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling, and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal components analysis (PCA) was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 SNPs in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases, and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17,159 controls). Global variation in the IGF pathway was associated with risk of BE (P=0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; p=0.00046, FDR q=0.0056) and IGF1R (IGF1 receptor; p=0.0090, q=0.0542). These gene-level signals remained significant at q<0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

6.
Curr Treat Options Gastroenterol ; : 1-17, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33199955

RESUMO

Purpose of review: Peptic ulcer disease (PUD) is a recognized complication of non-steroidal anti-inflammatory drugs (NSAIDs). Stress ulcers are a concern for intensive care unit (ICU) patients; PUD is also an issue for patients taking anticoagulation. Helicobacter pylori test and treat is an option for patients starting NSAID therapy, and proton pump inhibitors (PPIs) may reduce PUD in NSAID patients and other high-risk groups. Recent findings: There are a large number of trials that demonstrate that Helicobacter pylori eradication reduces PUD in NSAID patients. PPI is also effective at reducing PUD in this group and is also effective in ICU patients and those on anticoagulants. The effect is too modest for PPI to be recommended in everyone, and more research is needed as to which groups would benefit the most. Increasing age, past history of PUD, and comorbidity are the most important risk factors. Summary: H. pylori test and treat should be offered to older patients starting NSAIDS, while PPIs should be prescribed to patients that are at high risk of developing PUD and at risk of dying from PUD complications.

7.
BMJ Open ; 10(10): e041733, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087380

RESUMO

INTRODUCTION: Gut microbiome and diet may be important in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD) and comorbid psychiatric conditions, but the mechanisms are unclear. We will create a large cohort of patients with IBS, IBD and healthy controls, and follow them over time, collecting dietary and mental health information and biological samples, to assess their gastrointestinal (GI) and psychological symptoms in association with their diet, gut microbiome and metabolome. METHODS AND ANALYSIS: This 5-year observational prospective cohort study is recruiting 8000 participants from 15 Canadian centres. Persons with IBS who are 13 years of age and older or IBD ≥5 years will be recruited. Healthy controls will be recruited from the general public and from friends or relatives of those with IBD or IBS who do not have GI symptoms. Participants answer surveys and provide blood, urine and stool samples annually. Surveys assess disease activity, quality of life, physical pain, lifestyle factors, psychological status and diet. The main outcomes evaluated will be the association between the diet, inflammatory, genetic, microbiome and metabolomic profiles in those with IBD and IBS compared with healthy controls using multivariate logistic regression. We will also compare these profiles in those with active versus quiescent disease and those with and without psychological comorbidity. ETHICS AND DISSEMINATION: Approval has been obtained from the institutional review boards of all centres taking part in the study. We will develop evidence-based knowledge translation initiatives for patients, clinicians and policymakers to disseminate results to relevant stakeholders.Trial registration number: NCT03131414.

8.
BMC Med Genet ; 21(1): 204, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059653

RESUMO

BACKGROUND: Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset. METHODS: Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals. RESULTS: Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae. CONCLUSIONS: This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.


Assuntos
Doença de Crohn/genética , Fezes/microbiologia , Firmicutes/fisiologia , Predisposição Genética para Doença/genética , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Alelos , Criança , Estudos de Coortes , Doença de Crohn/diagnóstico , Doença de Crohn/microbiologia , Família , Feminino , Firmicutes/classificação , Firmicutes/genética , Frequência do Gene , Genótipo , Humanos , Masculino , Microbiota/genética , Microbiota/fisiologia , Adulto Jovem
9.
Gastroenterology ; 159(6): 2092-2100.e5, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32791132

RESUMO

BACKGROUND & AIMS: Increased intestinal permeability has been associated with Crohn's disease (CD), but it is not clear whether it is a cause or result of the disease. We performed a prospective study to determine whether increased intestinal permeability is associated with future development of CD. METHODS: We assessed the intestinal permeability, measured by the urinary fractional excretion of lactulose-to-mannitol ratio (LMR) at recruitment in 1420 asymptomatic first-degree relatives (6-35 years old) of patients with CD (collected from 2008 through 2015). Participants were then followed up for a diagnosis of CD from 2008 to 2017, with a median follow-up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017. We used the Cox proportional hazards model to evaluate time-related risk of CD based on the baseline LMR. RESULTS: An abnormal LMR (>0.03) was associated with a diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64-5.63; P = 3.97 × 10-4). This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62; 95% CI, 1.051-2.50; P = .029). CONCLUSIONS: Increased intestinal permeability is associated with later development of CD; these findings support a model in which altered intestinal barrier function contributes to pathogenesis. Abnormal gut barrier function might serve as a biomarker for risk of CD onset.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32827724

RESUMO

BACKGROUND & AIMS: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. METHODS: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. RESULTS: There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P = .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P = .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. CONCLUSIONS: Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.

11.
Am J Gastroenterol ; 115(10): 1584-1595, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32740074

RESUMO

INTRODUCTION: Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms and quality of life (QOL) in patients with CD. METHODS: We searched EMBASE, MEDLINE, CINAHL, Web of Science, CENTRAL, and DARE databases up to February 2019 for randomized controlled trials (RCTs) evaluating probiotics compared with placebo for treating CD. We collected data on GI symptoms, QOL, adverse events, serum tumor necrosis factor-α, intestinal permeability, and microbiota composition. RESULTS: We screened 2,831 records and found that 7 articles describing 6 RCTs (n = 5,279 participants) were eligible for quantitative analysis. Probiotics improved GI symptoms when assessed by the GI Symptoms Rating Scale (mean difference symptom reduction: 228.7%; 95% confidence interval [CI] 243.96-213.52; P = 0.0002). There was no difference in GI symptoms after probiotics when different questionnaires were pooled. The levels of Bifidobacteria increased after probiotics (mean difference: 0.85 log colony-forming units (CFU) per gram; 95% CI 0.38-1.32 log CFU per gram; P = 0.0003). There were insufficient data on tumor necrosis factor-a levels or QOL for probiotics compared with placebo. No difference in adverse events was observed between probiotics and placebo. The overall certainty of the evidence ranged from very low to low. DISCUSSION: Probiotics may improve GI symptoms in patients with CD. High-quality clinical trials are needed to improve the certainty in the evidence (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B595).


Assuntos
Doença Celíaca/terapia , Dieta Livre de Glúten , Microbioma Gastrointestinal , Probióticos/uso terapêutico , Qualidade de Vida , Doença Celíaca/sangue , Doença Celíaca/microbiologia , Doença Celíaca/fisiopatologia , Humanos , Mucosa Intestinal/metabolismo , Permeabilidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangue
12.
Cochrane Database Syst Rev ; 7: CD005583, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32628791

RESUMO

BACKGROUND: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. SEARCH METHODS: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.


Assuntos
Antibacterianos/uso terapêutico , Infecções Assintomáticas/terapia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Neoplasias Gástricas/prevenção & controle , Antiulcerosos/uso terapêutico , Carcinoma de Células Escamosas/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Neoplasias Esofágicas/epidemiologia , Humanos , Incidência , Lesões Pré-Cancerosas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade
13.
Curr Opin Gastroenterol ; 36(4): 317-322, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32487851

RESUMO

PURPOSE OF REVIEW: Proton pump inhibitors (PPIs) are widely prescribed and have excellent short-term tolerability. Administrative database studies have highlighted that many diseases are associated with PPI therapy including pneumonia, fracture, cardiovascular disease, and all-cause mortality. This review therefore reviews the evidence of the risks and benefits of these drugs. RECENT FINDINGS: There is high-to-moderate quality evidence that PPIs are effective at treating many acid-related disorders. Recent randomized trials have suggested that the associations between PPIs and various diseases are likely to be related to bias and residual confounding and these drugs appear to be safe apart from a possible increased risk of enteric infections. SUMMARY: PPIs should be used at the lowest dose and for the shortest duration possible. They are still relatively well-tolerated drugs but should only be prescribed for proven indications.

14.
Gastroenterology ; 159(3): 884-903.e31, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32416141

RESUMO

BACKGROUND & AIMS: There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD. METHODS: We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type. We used the Newcastle-Ottawa Scale to evaluate the risk of bias and GRADE to assess the certainty of the evidence. RESULTS: We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of CeD in patients with IBD vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23-7.02) and increased risk of IBD in patients with CeD vs controls (RR 9.88; 95% CI 4.03-24.21). There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with CeD vs controls (RR 6.22; 95% CI 2.44-15.84). There was low-certainty evidence for no difference in risk of HLA-DQ2 or DQ8 in patients with IBD vs controls (RR 1.04; 95% CI 0.42-2.56), and very low-certainty evidence for an increased risk of anti-tissue transglutaminase in patients with IBD vs controls (RR 1.52; 95% CI 0.52-4.40). Patients with IBD had a slight decrease in risk of anti-endomysial antibodies vs controls (RR 0.70; 95% CI 0.18-2.74), but these results are uncertain. CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of IBD in patients with CeD and increased risk of CeD in patients with IBD, compared with other patient populations. High-quality prospective cohort studies are needed to assess the risk of CeD-specific and IBD-specific biomarkers in patients with IBD and CeD.

16.
J Gastroenterol ; 55(8): 742-753, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32277297

RESUMO

BACKGROUND: Additional surgery for all patients with noncurative resection after endoscopic resection (ER) for early gastric cancer (EGC) may be excessive due to the relatively low rate of lymph node metastasis (LNM) in such patients. However, the prevalence and risk factors for LNM after noncurative ER have not been consistent across studies. METHODS: We performed a systematic review of electronic databases through August 10, 2018 to identify cohort studies with patients who underwent additional surgery after noncurative ER for EGC. The prevalence of LNM in such patients was extracted for all studies. Odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of LNM, when possible. RESULTS: We identified 24 studies comprising 3877 patients with 311 having LNM (pooled prevalence, 8.1%). The risk of LNM was significantly increased in lymphatic invasion (OR [95% confidence interval] = 4.22 [2.88-6.19]), lymphovascular invasion (LVI) (4.17 [2.90-5.99]), vascular invasion (2.38 [1.65-3.44]), positive vertical margin (2.16 [1.59-2.93]), submucosal invasion depth of ≥ 500 µm (2.14 [1.48-3.09]), and tumor size > 30 mm (1.77 [1.31-2.40]). In contrast, there was no significant association between undifferentiated-type or ulceration (scar) and LNM. When studies were restricted to those that evaluated the adjusted OR, the risk of vascular invasion for LNM did not reach statistical significance. CONCLUSIONS: Several pathological factors, most notably lymphatic invasion and LVI, were associated with LNM in patients with noncurative resection after ER for EGC. Lymphatic and vascular invasion should be assessed separately instead of LVI (PROSPERO CRD42018109996).

17.
Gut ; 69(8): 1441-1451, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32276950

RESUMO

OBJECTIVES: National guidelines for the management of irritable bowel syndrome (IBS) recommend that psychological therapies should be considered, but their relative efficacy is unknown, because there have been few head-to-head trials. We performed a systematic review and network meta-analysis to try to resolve this uncertainty. DESIGN: We searched the medical literature through January 2020 for randomised controlled trials (RCTs) assessing efficacy of psychological therapies for adults with IBS, compared with each other, or a control intervention. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic, with a 95% CI to summarise efficacy of each comparison tested, and ranked by therapy according to P score. RESULTS: We identified 41 eligible RCTs, containing 4072 participants. After completion of therapy, the psychological interventions with the largest numbers of trials, and patients recruited, demonstrating efficacy included self-administered or minimal contact cognitive behavioural therapy (CBT) (RR 0.61; 95% CI 0.45 to 0.83, P score 0.66), face-to-face CBT (RR 0.62; 95% CI 0.48 to 0.80, P score 0.65) and gut-directed hypnotherapy (RR 0.67; 95% CI 0.49 to 0.91, P score 0.57). After completion of therapy, among trials recruiting only patients with refractory symptoms, group CBT and gut-directed hypnotherapy were more efficacious than either education and/or support or routine care, and CBT via the telephone, contingency management, CBT via the internet and dynamic psychotherapy were all superior to routine care. Risk of bias of trials was high, with evidence of funnel plot asymmetry; the efficacy of psychological therapies is therefore likely to have been overestimated. CONCLUSIONS: Several psychological therapies are efficacious for IBS, although none were superior to another. CBT-based interventions and gut-directed hypnotherapy had the largest evidence base and were the most efficacious long term. TRIAL REGISTRATION NUMBER: The study protocol was published on the PROSPERO international prospective register of systematic reviews (registration number CRD 42020163246).

19.
Gut ; 69(12): 2113-2121, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32205420

RESUMO

OBJECTIVES: Gastric cancer is strongly associated with Helicobacter pylori (H. pylori). We conducted a previous systematic review and meta-analysis that suggested eradication therapy reduced future incidence of gastric cancer, but effect size was uncertain, and there was no reduction in gastric cancer-related mortality. We updated this meta-analysis, as more data has accumulated. We also evaluated impact of eradication therapy on future risk of gastric cancer in patients having endoscopic mucosal resection for gastric neoplasia. DESIGN: We searched the medical literature through February 2020 to identify randomised controlled trials (RCTs) examining effect of eradication therapy on subsequent occurrence of gastric cancer in healthy H. pylori-positive adults, and in H. pylori-positive patients with gastric neoplasia undergoing endoscopic mucosal resection. The control arm received placebo or no treatment. Follow-up was for ≥2 years. We estimated the relative risk (RR) number needed to treat (NNT), and evaluated the disability-adjusted life-years (DALYs) gained from screening from the meta-analysis. RESULTS: We identified 10 RCTs, seven recruited 8323 healthy individuals, and three randomised 1841 patients with gastric neoplasia. In healthy individuals, eradication therapy reduced incidence of gastric cancer (RR=0.54; 95% CI 0.40 to 0.72, NNT=72), and reduced mortality from gastric cancer (RR=0.61; 95% CI 0.40 to 0.92, NNT=135), but did not affect all-cause mortality. These data suggest that 8 743 815 DALYs (95% CI 5 646 173 to 11 847 456) would be gained if population screening and treatment was implemented globally. In patients with gastric neoplasia, eradication therapy also reduced incidence of future gastric cancer (RR=0.49; 95% CI 0.34 to 0.70, NNT=21). Adverse events were incompletely reported. CONCLUSION: There is moderate evidence to suggest that H. pylori eradication therapy reduces the incidence of gastric cancer in healthy individuals and patients with gastric neoplasia in East Asian countries. There also appears to be a reduction in gastric cancer-related mortality.

20.
Nat Rev Gastroenterol Hepatol ; 17(7): 406-413, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32123377

RESUMO

Exclusion diets are becoming increasingly popular in the management of irritable bowel syndrome (IBS). Several mechanisms exist by which food items might cause gastrointestinal symptoms, such as direct osmotic effects of food in the gut lumen, changes to the gut microbiota and immune activation. These effects have been demonstrated in animal models and in human studies, particularly in the case of gluten-free diets and diets low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs). Indeed, randomized controlled trials (RCTs) suggest that gluten-free diets and low-FODMAP diets improve IBS symptoms, and guidelines recommend the latter approach for treating symptoms in some patients with IBS. Designing such RCTs is challenging as participants need to eat so an 'inert' placebo is not an option. Blinding is also an issue with these studies; in the future, new exclusion diets should not advertise what the diet consists of until it is proved to reduce symptoms. In this Review, we outline the advantages and disadvantages of each choice of control group and emphasize the importance of collecting mechanistic data (regarding direct effects of food on the gut lumen, changes in gut microbiota and intestinal inflammation) as well as symptom data in RCTs of exclusion diets in IBS.


Assuntos
Dieta , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/terapia , Humanos , Síndrome do Intestino Irritável/fisiopatologia
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