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We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.

ObjectivesMany cross-sectional surveys have reported the prevalence of uninvestigated dyspepsia, but there has been no recent systematic review of data from all studies to determine its global prevalence and risk factors.DesignMEDLINE, EMBASE and EMBASE Classic were searched (until January 2014) to identify population-based studies that reported the prevalence of uninvestigated dyspepsia in adults (≥15 years old); dyspepsia was defined using symptom-based criteria or questionnaires. The prevalence of dyspepsia was extracted for all studies and according to the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, ORs and 95% CIs were calculated.ResultsOf the 306 citations evaluated, 103 reported the prevalence of uninvestigated dyspepsia in 100 separate study populations, containing 312 415 subjects. Overall pooled prevalence in all studies was 20.8% (95% CI 17.8% to 23.9%). The prevalence varied according to country (from 1.8% to 57.0%) and criteria used to define dyspepsia. The greatest prevalence values were found when a broad definition of dyspepsia (29.5%; 95% CI 25.3% to 33.8%) or upper abdominal or epigastric pain or discomfort (20.4%; 95% CI 16.3% to 24.8%) were used. The prevalence was higher in women (OR 1.24; 95% CI 1.13 to 1.36), smokers (OR 1.25; 95% CI 1.12 to 1.40), non-steroidal anti-inflammatory drug (NSAID) users (OR 1.59; 95% CI 1.27 to 1.99) and Helicobacter pylori-positive individuals (OR 1.18; 95% CI 1.04 to 1.33).ConclusionsThe overall pooled prevalence of uninvestigated dyspepsia was 21%, but varied among countries and according to the criteria used to define its presence. Prevalence is significantly higher in women, smokers, NSAID users and H. pylori-positive individuals, although these associations were modest.

Helicobacter pylori infection is one likely cause of functional dyspepsia. Here, the authors discuss the clinical evidence in relation to H. pylori eradication in patients with functional dyspepsia if they test positive for this bacterium. Functional dyspepsia is the most common reason for patients to experience chronic epigastric pain or discomfort. The causes of functional dyspepsia are multifactorial but Helicobacter pylori infection is one likely candidate. Infection with this bacterial pathogen clearly results in chronic mucosal inflammation in the stomach and duodenum, which, in turn, might lead to abnormalities in gastroduodenal motility and sensitivity. Chronic gastritis might also affect a variety of endocrine functions of the stomach including the production of the gastrointestinal hormones and neurotransmitters somatostatin, gastrin and ghrelin. Although these abnormalities might generate symptoms in some patients with functional dyspepsia, the clinical evidence needs to be critically evaluated before this hypothesis can be confirmed. A Cochrane review reported that eradication of H. pylori in these patients had a small but statistically significant long-term effect on symptom relief when compared with placebo, lasting at least 12 months after 1 week of eradication therapy. The efficacy of eradication therapy was seen in all symptom subtypes of functional dyspepsia, but was more marked in Asian than Western patients. This evidence has led to alterations in most of the major guidelines throughout the world, which now recommend H. pylori eradication in patients with functional dyspepsia if they test positive for this bacterium. Key Points Helicobacter pylori infection is a major cause of gastritis and is associated with a variety of motility, endocrine and acid-secretory abnormalities that could drive the symptoms of functional dyspepsia In a meta-analysis of randomized controlled trials, H. pylori eradication had a small but statistically significant effect in controlling the symptoms of functional dyspepsia H. pylori eradication improves symptoms in patients with epigastric-pain-predominant and postprandial-distress-predominant functional dyspepsia The majority of guidelines recommend H. pylori eradication in at least a subset of patients with functional dyspepsia

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain-gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective. We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or \"usual management\" were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or \"usual management\", and one compared both psychological therapy and antidepressants with placebo. Four of the trials of psychological therapies, and one of the RCTs of antidepressants, were identified since our previous meta-analysis. The RR of IBS symptoms not improving with antidepressants versus placebo was 0.66 (95% CI 0.57-0.76), with similar treatment effects for both tricyclic antidepressants and SSRIs, although with heterogeneity between RCTs of the latter (I = 49%, P = 0.07). The RR of symptoms not improving with psychological therapies was 0.69 (95% CI 0.62-0.76). Cognitive behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, and dynamic psychotherapy were all beneficial when data from two or more RCTs were pooled. There was significant heterogeneity between studies (I = 69%, P < 0.001) and significant funnel plot asymmetry. There were also issues regarding trial design, including lack of blinding. Antidepressants are efficacious in reducing symptoms in IBS patients. Psychological therapies also appear to be effective treatments for IBS, although there are limitations in the quality of the evidence, and treatment effects may be overestimated as a result.

ObjectivesNational 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.DesignWe 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.ResultsWe 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.ConclusionsSeveral 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 numberThe study protocol was published on the PROSPERO international prospective register of systematic reviews (registration number CRD 42020163246).

ObjectiveFunctional dyspepsia (FD) is a chronic gastroduodenal disorder. Individuals with FD demonstrate visceral hypersensitivity, abnormal central pain processing, and low mood, but it is unclear whether psychotropic drugs are an effective treatment for the condition. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs).DesignMEDLINE, EMBASE, EMBASE Classic, PsychINFO and the Cochrane Controlled Trials Register were searched (up to June 2015) for RCTs recruiting adults with FD comparing psychotropic drugs with placebo. We contacted authors directly to maximise trial eligibility and minimise risk of bias for studies. Dichotomous symptom data were pooled to obtain relative risk (RR) of remaining symptomatic after therapy, with 95% CIs.ResultsThe search identified 2795 citations; 13 RCTs (1241 patients) were eligible. Ten trials were at low risk of bias. The RR of FD symptoms not improving with psychotropic drugs versus placebo was 0.78 (95% CI 0.68 to 0.91) (number needed to treat=6; 95% CI 4 to 16). However, benefit was limited to antipsychotics and tricyclic antidepressants. When only studies that excluded individuals with coexistent mood disorder were considered, there was no benefit. Total numbers of adverse events and adverse events leading to withdrawal were significantly more common, with a number needed to harm of 21 for both.ConclusionsPsychotropic drugs may be an effective treatment for FD, but the effect appears to be limited to antipsychotics and tricyclic antidepressants with fewer trials for other agents, meaning that firm conclusions for efficacy cannot be made. More data from high quality RCTs are required to support their use in the treatment of FD.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI. The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70-0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02-1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67-0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn. Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain.

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI). The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80-0.94 and RR=0.88; 95% CI 0.83-0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65-0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57-0.91). Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD.

BackgroundAdditional 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.MethodsWe 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.ResultsWe 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.ConclusionsSeveral 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).