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Background and Study Aims: Deep learning (DL) for video capsule endoscopy (VCE) is an emerging research field. It has shown high accuracy for the detection of Crohn's disease (CD) ulcers. Non-steroidal anti-inflammatory drugs (NSAIDS) are commonly used medications. In the small bowel, NSAIDs may cause a variety of gastrointestinal adverse events including NSAID-induced ulcers. These ulcers are the most important differential diagnosis for small bowel ulcers in patients evaluated for suspected CD. We evaluated a DL network that was trained using CD VCE ulcer images and evaluated its performance for NSAID ulcers.Patients and Methods: The network was trained using CD ulcers and normal mucosa from a large image bank created from VCE of diagnosed CD patients. NSAIDs-induced enteropathy images were extracted from the prospective Bifidobacterium breve (BIf95) trial dataset. All images were acquired from studies performed using PillCam SBIII. The area under the receiver operating curve (AUC) was used as a metric. We compared the network's AUC for detecting NSAID ulcers to that of detecting CD ulcers.Results: Overall, the CD training dataset included 17,640 CE images. The NSAIDs testing dataset included 1,605 CE images. The DL network exhibited an AUC of 0.97 (95% CI 0.97–0.98) for identifying images with NSAID mucosal ulcers. The diagnostic accuracy was similar to that obtained for CD related ulcers (AUC 0.94–0.99).Conclusions: A network trained on VCE CD ulcers similarly identified NSAID findings. As deep learning is transforming gastrointestinal endoscopy, this result should be taken into consideration in the future design and analysis of VCE deep learning applications.

Introduction This study evaluated corticosteroid and antibiotic prescribing during the first 12 months of first-line biologic therapy in patients with ulcerative colitis (UC) initiated on vedolizumab (VDZ) compared with patients initiated on anti-tumour necrosis factor-α (anti-TNF) agents. Methods A multicentre, retrospective observational study was conducted in six United Kingdom secondary care centres. Eligible consenting patients were aged ≥18 years at initiation, without primary fistulising disease or acute severe disease. Patients were matched for age, gender, Montreal classification of disease extent and steroid use at initiation. Results The study included 56 patients initiated on VDZ and 56 patients initiated on anti-TNF (table 1). During the overall 12 month post-initiation observation period, patients initiated on VDZ and anti-TNF were prescribed a median of 1.0 (interquartile range [IQR] 0.0–4.8) and 2.0 (IQR 0.0–7.8; Mann-Whitney U test P=0.16) courses of corticosteroids, respectively. During the post-initiation maintenance period (week 14 to month 12), 37% (95% confidence interval [CI] 24%–49%; n=52) of patients initiated on VDZ and 57% (95%CI 44%–70%; n=53; χ2P=0.039) of patients initiated on anti-TNF received at least one course of corticosteroids. During the overall 12 month post-initiation observation period, patients initiated on VDZ and anti-TNF were prescribed a median of 0 (range 0–4) and 0 (range 0–2; Mann-Whitney U test P=0.42) courses of antibiotics, respectively. During the post-initiation maintenance period, 11% (95%CI 3%–19%; n=56) of patients initiated on VDZ and 16% (95%CI 6%–26%; n=56; χ2 P=0.41) of patients initiated on anti-TNF received at least one course of antibiotics. Conclusions During the post-initiation maintenance period of first-line biologic therapy in patients with UC, patients initiated on VDZ were significantly less likely to be prescribed corticosteroids than matched patients initiated on anti-TNF agents. Numerically less patients on VDZ received antibiotics, however this did not reach significance.

Background & Aims Enteropathy and small-intestinal ulcers are common adverse effects of nonsteroidal anti-inflammatory drugs such as acetylsalicylic acid (ASA). Safe, cytoprotective strategies are needed to reduce this risk. Specific bifidobacteria might have cytoprotective activities, but little is known about these effects in humans. We used serial video capsule endoscopy (VCE) to assess the efficacy of a specific Bifidobacterium strain in healthy volunteers exposed to ASA. Methods We performed a single-site, double-blind, parallel-group, proof-of-concept analysis of 75 heathy volunteers given ASA (300 mg) daily for 6 weeks, from July 31 through October 24, 2017. The participants were randomly assigned (1:1) to groups given oral capsules of Bifidobacterium breve (Bif195) (≥5 × 1010 colony-forming units) or placebo daily for 8 weeks. Small-intestinal damage was analyzed by serial VCE at 6 visits. The area under the curve (AUC) for intestinal damage (Lewis score) and the AUC value for ulcers were the primary and first-ranked secondary end points of the trial, respectively. Results Efficacy data were obtained from 35 participants given Bif195 and 31 given placebo. The AUC for Lewis score was significantly lower in the Bif195 group (3040 ± 1340 arbitrary units) than the placebo group (4351 ± 3195) (P = .0376). The AUC for ulcer number was significantly lower in the Bif195 group (50.4 ± 53.1 arbitrary units) than in the placebo group (75.2 ± 85.3 arbitrary units) (P = .0258). Twelve adverse events were reported from the Bif195 group and 20 from the placebo group. None of the events was determined to be related to Bif195 intake. Conclusions In a randomized, double-blind trial of healthy volunteers, we found oral Bif195 to safely reduce the risk of small-intestinal enteropathy caused by ASA. ClinicalTrials.gov no: NCT03228589.

Background Helicobacter pylori is the major cause of chronic gastritis, and considered as a risk factor for peptic ulcer and gastric cancer. The H. pylori standard antibiotic therapy fails in about 25–30% of cases, particularly because of the increasing occurrence of resistance to antibiotics. The aim of the current study was to investigate whether the strain Lactobacillus reuteri DSM17648 which has been previously shown to reduce Helicobacter pylori load additionally improves gastrointestinal symptoms in H. pylori positive subjects when used in a 28 days supplementation. Methods In a single-blinded, placebo controlled study 24 H. pylori-positive adults (13 females, 11 males; median age: 43.5) with mild dyspepsia (mean GSRS score: 11.82) received placebo for 28 days followed by Pylopass™ containing the L. reuteri DSM 17648 (2 × 1010 cells per day) for the following 28 days. After 28 days of Pylopass™ supplementation the change in H. pylori load was measured by 13C urea breath test (13C-UBT) and the change in symptoms were determined by the Gastrointestinal Symptom Rating Scale (GSRS). In addition, blood assessments were conducted to measure the physiological changes relevant in terms of safety. Results After a 28-day supplementation phase with Pylopass™ there was a trend for reduction of H. pylori load in 62.5% of the subjects and for the overall GSRS scores in 66.7% of subjects. The overall GSRS scores from baseline to day 56 following all 24 subjects undergoing the placebo phase followed by the Pylopass™ phase was significantly decreased (p = 0.005). The mean 13C-UBT δ value decreased by 22.5% during the Pylopass™ supplementation phase (− 3.14), while the mean 13C-UBT δ increased by 37.3% (+ 3.79) in the placebo phase. No side effects were reported in either study phase. Conclusion The results demonstrated that L. reuteri DSM17648 has the potential to suppress H. pylori infection, and may lead to an improvement of H. pylori-associated gastro intestinal symptoms. Further studies with adequate power should be performed. Trial registration Clinicaltrials.gov: NCT02051348 (January 30, 2014).

Irish eradication rates for Helicobacter pylori are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies.To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations.Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The 'Grading of Recommendations Assessment, Development and Evaluation' approach was then used to rate the quality of available evidence and grade the resulting recommendations.Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days' duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low).These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS). To compare the prevalence of SIBO and its relationships to LPS receptor levels and systemic cytokines in NASH patients and healthy control subjects. Eighteen NASH patients (eight males) and 16 age-matched and gender-matched healthy volunteers were studied. SIBO was assessed by the lactulose breath hydrogen test (LHBT), plasma lipopolysaccharide binding protein (LBP) levels by ELISA, and expression (as a percentage) of TLR-2 and 4 on CD14-positive cells by flow cytometry. Pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) were measured in plasma. SIBO was more common in NASH patients than control subjects (77.78% vs. 31.25%; P

6-Thioguanine has been used as an alternative immunomodulator in the treatment of inflammatory bowel disease but data on its efficacy and safety are limited. The aim of this study was to analyse our experience of the efficacy and safety of 6-thioguanine in inflammatory bowel disease.Patients attending the inflammatory bowel disease clinic who were started on 6-thioguanine therapy were included in this prospective observational study. Indications for initiating 6-thioguanine therapy and other related clinical, pharmacological and laboratory parameters prior to and during therapy were recorded to determine the efficacy and safety of 6-thioguanine.A total of 40 patients were treated with 6-thioguanine, 28 with Crohn's disease, 10 with ulcerative colitis and 2 with indeterminate colitis, at a fixed daily dose of 40 mg and continued for a median duration of 34 weeks (range 2-90 weeks). The indications for 6-thioguanine therapy included previous clinical resistance to thiopurine analogues (n=21), intolerance to thiopurine analogues (n=8) and de novo 6-thioguanine use in steroid refractory disease (n=11). Disease remission was reached in 44%, 73% and 89% of these patient groups at 3, 6 and 12 months, respectively. Inflammatory markers and steroid use were significantly lower during 6-thioguanine therapy compared with in the period before therapy. Therapy was discontinued in 13 patients (33%), mainly because of thrombocytopenia and associated hepatotoxicity.6-Thioguanine is a useful addition to treatment in inflammatory bowel disease but the frequent occurrence of hepatotoxicity limits its routine use.

The genomic contents of Helicobacter pylori strain C1 from a patient with gastric cancer and strain 98587 from a patient with duodenal ulcer disease were compared using a rapid subtractive hybridisation approach. A total of 11 tester-specific sequences representing gene specificity, DNA rearrangement and sequence variation were identified. This included two novel sequences, clone P32 and clone F5, which have no significant homologue in the database. H. pylori strains positive for clone P32 were less prevalent in patients with gastric intestinal metaplasia (12.5%) than in duodenal ulcer (39.1%) (p = 0.036), or chronic gastritis (38.1%) (p = 0.036). The results suggest that H. pylori clone P32 is potentially a useful marker for distinguishing intestinal metaplasia associated strains from others. 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

This represents an overview of the main data published over the last year on the therapy of Helicobacter pylori. The problem of increasing failure of H. pylori eradication has been the main focus, with increasing resistance and poor patient compliance being the main culprits. Simple regimens are necessary to improve patient compliance. New antibiotics and novel agents are appraised with mixed results.

Hepatitis C (HCV) is a common cause of morbidity among patients who attend general practitioners (GPs) in Ireland for methadone maintenance treatment. To describe the development and content of guidelines for the management of HCV among current or former opiate users in the Eastern Regional Health Authority area attending GPs for methadone treatment. The guidelines were produced in five stages: identification of key stakeholders; development of evidence-based draft guidelines; discussion of content; determination of ‘Delphi’-facilitated consensus and review by a sample of GPs for whom the guidelines would be intended. The guidelines contain advice for GPs on all aspects of care of patients at risk of HCV, including general and preventative care, care of other bloodborne and hepatotoxic viruses, and the factors to be considered and appropriate evaluation prior to referring a patient for assessment at a hepatology unit. GPs have an important role to play in the care of patients at risk of, or Infected with, HCV.

Gastric antral vascular ectasia, or 'watermelon stomach', is a rare but important cause of gastrointestinal blood loss and anaemia, which has characteristic endoscopic and histological features. The pathogenesis of this condition remains unclear; however, many associated disorders have been documented. Various medical, surgical and endoscopic therapeutic modalities have been attempted with variable success. Leading contenders for the therapeutic modality of choice include hormonal therapy, endoscopic Nd:YAG laser and argon plasma coagulation. Randomized controlled trials to identify the ideal treatment method are lacking at present.

A 'test and treat' strategy is advocated for patients with dyspepsia under the age of 45 years, with endoscopy reserved for those with alarm symptoms or aged over 45 years. One of the consequences of this strategy will be a reduction in population infection rates of Helicobacter pylori. It is now clear that H. pylori is one of the prime initiators of gastric cancer with up to 70% of gastric cancers attributable to H. pylori. What remains unclear is if H. pylori reduction will lead to a reduction in gastric cancer.

Ultimately, we now know of course that gastric urease is bacterial in origin, and our raison d’etre in the treatment of peptic ulcer is not, as Fitzgerald thought, to enharice urease activity but to completely suppress it. In the 1980s, Oliver Fitzgerald maintained a keen interest in the rapidly evolving H. pylori saga, and his wry sense of deja vu was obvious in personal contacts and correspondence the authors had with him on the subject. With the benefit of hindsight, cynics might dismiss the work of the Fitzgerald group, but their ideas on peptic ulcer are as relevant today as they were 50 years ago. We are still striving to readjust the ill-adjusted interplay between secretion, neutralisation and mucosal resistance in the dyspeptic patient. The discovery of H. pylori has simply made our task a lot easier.

Recent epidemiological studies have reported a threefold increase in the incidence of adenocarcinoma of the lower oesophagus and gastro-oesophageal junction (cardia). There are conflicting reports available implicating both gastro-oesophageal reflux disease and Helicobacter pylori infection in the aetiology of carditis and cardia intestinal metaplasia, despite strong evidence to show that these two conditions are, if anything, inversely related. We aimed to determine the prevalence of carditis and cardia intestinal metaplasia in dyspeptic subjects and also their association with H. pylori infection and gastro-oesophageal reflux disease.Histological samples from the gastric cardia were obtained from dyspeptic subjects. H. pylori status was assessed based on histological, microbiological and rapid urease testing. Gastro-oesophageal disease was diagnosed on the basis of histological evidence and/or erosive oesophagitis. Patient demographics were recorded. Cardia intestinal metaplasia (CIM), when present, was subgrouped as complete or incomplete.Overall, 276 subjects were enrolled; 163 (59%) had carditis and 36 (13%) CIM. H. pylori infection and gastro-oesophageal reflux disease occurred in 64 (23%) and 150 (54%), respectively. H. pylori infection was strongly associated with carditis and CIM (P0.001 and P0.01). Older age and male gender were also associated with inflammation and intestinal metaplasia of the cardia. Gastro-oesophageal reflux was not associated with either entity.Carditis and CIM occur frequently. Both conditions are strongly associated with H. pylori infection, older age and male gender. There was no association with gastro-oesophageal reflux disease.

Dyspepsia is a common condition, reported to affect 40% of the adult population in the developed world annually, with an estimated incidence of 8%. Dyspepsia accounts for 2% to 3% of all general practice consultations. It has been estimated that only 10% of sufferers seek medical advice, and 22% of these are referered to a specialist. Older patients are more likely to present, probably because of concern about the possibility of significant underlying pathology. Nonulcer dyspepsia (NUD) is the underlying diagnosis in a considerable proportion of individuals with dyspepsia. The prevalence is highest in young patients (younger than 25 years old), but in patients older than age 60 with dyspepsia, 20% have a normal endoscopy. NUD comprises a symptom complex referable to the upper gastrointestinal tract that persists for longer than 4 weeks, for which neither a biochemical nor structural abnormality can be identified. Diagnostic criteria were established by the Rome Consensus Committee in 1991 59 and were updated in 1998 in Vienna. The cause of NUD appears to be multifactorial, and different mechanisms may result in different subtypes of disease, which have been subgrouped on the basis of the predominant symptom type—ulcerlike, refluxlike, and dysmotilitylike. The management of NUD is varied depending on the cause and individual response to treatment. The role of Helicobacter pylori infection in the pathogenesis and treatment of NUD is an area of ongoing avid research and remains controversial. Patients with NUD are more likely to be infected than asymptomatic individuals, and there is evidence to show benefit, in at least a subset of sufferers, after eradication of H. pylori . Dyspepsia causes considerable morbidity and has substantial socioeconomic implications, as a result of workdays lost and the expense of medical investigations and treatment. The estimated total cost of dyspepsia to the United States in 1993 was greater than $14 million.

Summary Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are well-recognized causes of gastroduodenal mucosal damage. This damage is mediated through the effects of both agents on acid secretion, neutrophil activity and function, and prosta- glandin metabolism. Clinical trials on the interrelation- ship between H. pylori, NSAIDs and gastroduodenal mucosal injury have yielded conflicting results. No consensus has been reached on what recommenda- tions should be implemented with regard to H. pylori eradication in patients on long-term NSAID therapy. At present, the presence of H. pylori is identified at endoscopy and eradication is carried out in symptomatic patients. Asymptomatic patients remain a dilemma that requires further investigation. Clinical practice will continue to be tailored to a patient's individual requirements. Therefore, in patients at risk of gastrointestinal haemorrhage, and on NSAID therapy, acid suppression therapy should be prescribed.

Background: Studies in young dyspeptic patients have suggested that screening strategies based on non-invasive H. pylori testing can reduce endoscopy workload by 25–40%. Such strategies usually propose that only H. pylori-positive individuals should undergo endoscopy. This approach may fail to diagnose idiopathic ulcers, ulcers in patients whose screening test is falsely negative and reflux disease. Aim: To investigate a hypothetical screening strategy in which endoscopy is initially performed only in H. pylori-negative dyspeptics. Methods: Seventy-two consecutive patients under 45 years of age undergoing investigation for ‘ulcer-like’ dyspepsia had invasive and non-invasive determination of H. pylori status. Individuals found to be H. pylori-positive at endoscopy received 1 week of proton pump inhibitor-based triple therapy. H. pylori-negative individuals received therapy tailored to their diagnosis. Endoscopy was repeated in the positive group to confirm successful eradication. Results were analysed according to our strategy, i.e. serologically-positive patients would have received eradication therapy without endoscopy, but patients found to be negative would have been referred for endoscopy. Results: According to the serology test there were 39 positive and 33 negative results. Symptoms failed to resolve during follow-up in nine of the serological positives despite successful eradication. There were also five false positives who were deemed likely treatment failures. Thus according to our strategy, these 14 serologically-positive patients would ultimately have required an endoscopy and the other 25 serologically-positive patients would have avoided an endoscopy, resulting in a 35% reduction in endoscopy usage in this population. In the serologically-negative group there were three cases of peptic ulcer disease where the test was falsely negative, but they were detected by the strategy. No cases of gastric malignancy were detected at endoscopy. Thus our strategy would have reduced initial endoscopy referrals by 35% in this selected population. Conclusion: A strategy of empirical H. pylori eradication therapy can safely reduce the requirement for endoscopy in young dyspeptic patients without sinister symptoms.

The purposes of this study were to analyse the prevalence and histologic impact of hepatitis G virus (HGV), a newly discovered virus, in alcoholic patients, a population known to be at risk for viral hepatitis.One hundred and thirty-nine consecutive alcoholics admitted to our liver unit (106 men and 33 women; mean age, 47.1 +/- 10.9 years) were included in the study. All patients had consumed more than 60 g of ethanol per day for at least 1 year. One hundred healthy blood donors constituted a control group. Antibodies to HGV E2 protein and HGV-RNA testing by reverse transcription-polymerase chain reaction (RT-PCR) with primers derived from the NS5 coding region were performed in all serum samples.A significantly higher seroprevalence of anti-E2 antibodies was observed in alcoholic patients than in healthy blood donors (41 (29.5%) versus 8 (8%); P0.0001). Moreover, the prevalence of HGV-RNA was significantly higher in alcoholic patients (13 (9.3%) versus 1 (1%); P = 0.01). HGV-RNA and anti-HGV antibodies were never detected simultaneously. HGV viraemia was not associated with an increased risk of cirrhosis or hepatocarcinoma in alcoholic subjects.Our study reports a high prevalence of HGV in alcoholic patients. HGV infection does not modify or aggravate the course of alcoholic liver disease.

There has been a significant increase in the prevalence of H. pylori resistance to metronidazole in recent years, while clarithromycin resistance is still relatively rare. In this study we assessed: (1) the effect of primary H. pylori resistance to metronidazole and clarithromycin on the clinical efficacy of a one-week regimen consisting of omeprazole, metronidazole, and clarithromycin; and (2) the rate of acquisition of secondary antimicrobial resistance after treatment failure. Eighty-seven patients with duodenal ulceration or nonulcer dyspepsia were included in the study. The primary metronidazole and clarithromycin resistance rates were 35.6% and 3.4%, respectively (all three pretreatment clarithromycin resistant strains had concurrent metronidazole resistance). H. pylori was eradicated in 81.6% of patients. The eradication rate for fully sensitive isolates was 98.2% (55/56) but was significantly reduced to 57.1% (16/28) for isolates that were resistant to metronidazole alone and 0% (0/3) in cases of dual resistance (P < 0.001). Secondary resistance to clarithromycin was acquired in 58.3% of cases of treatment failure. In areas of high prevalence of primary metronidazole resistance, this is a significant cause of treatment failure with this triple therapy regimen. This leads to the selection of strains with dual resistance that are difficult to eradicate and may contribute to an increase in the prevalence of clarithromycin resistance. In such areas an alternative first-line treatment should be prescribed.

We report an original observation of chronic pancreatitis associated with primary biliary cirrhosis and systemic sclerosis. The diagnosis of each of these conditions was unequivocally confirmed. Pancreatic involvement in this case was asymptomatic. The association of chronic pancreatitis with primary biliary cirrhosis has been previously reported and pancreatitis has been associated with other autoimmune disorders. We hypothesize about the underlying pathogenic mechanisms of chronic pancreatitis in our case.

Non-ulcer dyspepsia (NUD) is a common condition that often goes unrecognized. Although approximately 50% of patients with NUD are infected with Helicobacter pylori, attempts to establish a link between this organism and the pathogenesis of NUD have yielded conflicting results. Recent studies have shown that eradication of H. pylori leads to improvements in symptoms in patients with NUD, and have highlighted the importance of long-term follow-up in this condition. It is possible that patients with NUD and H. pylori infection have a discrete condition that forms part of a spectrum of peptic ulcer disease. Hence, it may soon be possible to recommend H. pylori eradication treatment for patients with NUD.

Mast cells might be involved in pathogenesis of functional dyspepsia because they can release a wide range of potent mediators, capable of altering gastric nerve and muscle function. This study aimed to determine whether mast cell numbers were increased in the gastric mucosa of patients with functional dyspepsia compared to control subjects.Biopsy samples were taken from the antrum and corpus of 111 patients: 20 asymptomatic control subjects, 62 patients with Rome criteria functional dyspepsia (33 Helicobacter pylori positive, 29 H. pylori negative), and 29 inflammatory control subjects (H. pylori positive). Mast cells were detected immunohistochemically by using a mouse monoclonal antibody specific for tryptase. Quantification was performed with light microscopy, and results were expressed as mast cells/mm(2) +/- standard error of mean.Mast cells were significantly increased in H. pylori negative functional dyspepsia samples compared to normal control samples in the antrum (230.1 +/- 11.3 vs. 94.8 +/- 8.4, P0.001) and corpus (264.1 +/- 27.1 vs. 123.9 +/- 11.5, P = 0.001). Mast cells were also significantly increased in the antrum of patients with H. pylori positive functional dyspepsia compared to asymptomatic control subjects (166.5 +/- 17.0 vs. 94.8 +/- 8.4, P0.03). However, there was no significant difference between mast cell numbers in patients with H. pylori positive functional dyspepsia compared to inflammatory control subjects.Mast cells are increased in functional dyspepsia, independently of inflammation. This might contribute to the pathogenesis of functional dyspepsia by altering signaling in the brain-gut axis.

"Best practice" in inflammatory bowel disease: an international survey and audit.Van Der Eijk I, Verheggen FW, Russel MG, Buckley M, Katsanos K, Munkholm P, Engdahl I, Politi P, Odes S, Fossen J, Stockbrugger RW; European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD) .Department of Gastroenterology and Hepatology, University Hospital of Maastricht, P.O. Box 5800, 6202 AZ Maastricht, Netherlands.Background: An observational study was conducted at eight university and four district hospitals in eight countries collaborating in clinical and epidemiological research in inflammatory bowel disease (IBD) to compare European health care facilities and to define current "best practice" with regard to IBD. Methods: The approach used in this multi-national survey was unique. Existing quality norms, developed for total hospital care by a specialized organization, were restricted to IBD-specific care and adapted to the frame of reference of the study group. In each center, these norms were surveyed by means of questionnaires and professional audits in all participating centers. The collected data were reported to the center, compared to data from other hospitals, and used to benchmark. Group consensus was reached with regard to defining current "best practice". Results: The observations in each center involved patient-oriented processes, technical and patient safety, and quality of the medical standard. Several findings could be directly implemented to improve IBD care in another hospital (benchmarks). These included a confidential relationship between health care worker(s) and patients, and availability of patient data. Conclusions: The observed benchmarks, in combination with other subjectively chosen "positive" procedures, have been defined as current "best practice in IBD", representing practical guidelines towards better quality of care in IBD.

The role of Helicobacter pylori infection in nonulcer dyspepsia remains controversial. To date studies exploring the effect of H. pylori eradication on symptoms have reported conflicting results. Randomised control trials employing validated outcome measures have also been difficult to interpret because of several important issues such as the large placebo response seen in patients with nonulcer dyspepsia and both the natural variability in symptoms and symptom severity with time. The association of symptom improvement with resolution of gastritis has meant that the length of follow up employed in most studies has been insufficient. We report the findings of a randomised placebo controlled trial (n = 100), using a validated symptom questionnaire and 5 year follow up to determine the effect of H. pylori eradication on symptoms in nonulcer dyspepsia. In all 64 that were reviewed at 5 years there was a significant difference between patients who were H. pylori negative and those who remained positive with regard to complete symptom resolution, consumption of relevant medications and peptic ulcer disease development, in favour of active treatment. There was a trend for gradual symptom improvement over time irrespective of H. pylori status, which may reflect the natural history of this condition. For those who remained symptomatic at 5 years, there was no difference in symptom severity based on H. pylori status. The findings of this study support the use of H. pylori eradication in symptomatic patients with nonulcer dyspepsia both to induce symptom resolution and to prevent disease progression.

Background: The prevalence of pancreatic disease in patients with alcohol-related liver cirrhosis is uncertain. We assessed the prevalence of pancreatic abnormalities in patients with alcoholic cirrhosis, and we compared endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) for the detection of chronic pancreatitis and other pancreatic lesions. In addition, we assessed the long-term significance of isolated pancreatic parenchymal abnormalities detected at EUS. Methods: EUS and ERCP were performed in each patient. Subjects with minimal parenchymal changes at initial EUS underwent clinical follow-up and subsequent EUS and/or ERCP to document the occurrence, absence, or progression of these changes. Results: Seventy-two patients with alcoholic cirrhosis were recruited. Chronic pancreatitis was diagnosed in 14 patients (19%) by both methods independently. Isolated parenchymal lesions were observed in 18 patients by EUS alone. After a mean follow-up of 22 months the EUS appearance was unchanged. Ten of the 18 patients underwent follow-up ERCP and this was normal in all cases. Conclusions: This study demonstrated that (1) 19% of patients with alcoholic cirrhosis have chronic pancreatitis, (2) an additional 25% have isolated pancreatic parenchymal changes at EUS, and (3) these parenchymal abnormalities do not progress during follow-up. (Gastrointest Endosc 1999;49:705-9.)

Objectives To document the epidemiology of Helicobacter pylori infection in a normal population, to assess asymptomatic H. pylori positive individuals for the presence of gastroduodenal disease, and to compare the macroscopic and microscopic findings at endoscopy in this group with those of patients presenting with dyspepsia. Design/Methods Serum was collected from blood donors and assessed for the presence of anti-H. pylori IgG antibodies. A randomly selected group of asymptomatic blood donors and dyspeptic patients underwent endoscopy. Results The seroprevalence of H. pylori in 1000 subjects was 43.0%. The prevalence of infection increased from 29% in 18-30 year olds to 62% in 46-60 year olds (P < 0.01). The infection was more prevalent in individuals from social classes IV and V (50.0%) than social classes I and II (36.9%) (P < 0.01). There was no difference between the H. pylori positive asymptomatic individuals (n = 37) and matched dyspeptic patients (n = 29) at endoscopy with regard to duodenal ulcer (13.5% vs. 17.2%) or gastroduodenal erosions (24.3% vs. 20.7%) while 5.4% of the former had gastro-oesophageal reflux compared to 27.6% of the latter. Overall, 56.8% of the H. pylori positive asymptomatic group had a normal macroscopic endoscopy compared with 31% of the dyspeptic group. Histology of the gastric mucosa did not reveal any significant differences between the two groups. In H. pylori negative asymptomatic individuals (n = 13) 92.3% had a normal endoscopy (7.7% had grade I gastro-oesophageal reflux) compared with 61.5% of a matched dyspeptic group (n = 13). Conclusion H. pylori infection, symptomatic and asymptomatic, is associated with significant pathology, and screening for the infection may be indicated for the prevention of gastroduodenal diseases.

The presence of gastric spirochaetal organisms was first documented over a century ago. Though repeatedly reported in the medical literature, it was felt that these spiral bacteria were merely contaminants and the reports were generally ignored by the medical community. On 22 October 1982, at a meeting of the Royal Australian College of Physicians, successful culture of these 'Campylobacterlike organisms' from gastric biopsy specimens was reported for the first time. Moreover, it was shown that their presence was associated with gastritis and, possibly, with peptic ulceration. The subsequent discovery of the pivotal role of Helicobacter pylori in a wide range of conditions has revolutionised our understanding of gastroduodenal diseases. Improvements in diagnostic and therapeutic options, combined with the gradual acceptance of the aetiological role of an infective agent in peptic disease, have led to a remarkable change in the management of gastroduodenal conditions in the past decade.

A woman who developed acute pancreatitis following ingestion of low dose codeine, with positive rechallenge, is described. As this is the first case report of pancreatitis being induced solely by codeine, this side effect must be rare in view of the widespread consumption of this drug.

The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is controversial.In a prospective, long-term, double-blind study we randomized 100 patients with non-ulcer dyspepsia and H. pylori infection to receive either of two treatment regimens: 1) bismuth-based triple therapy (n = 50) or 2) bismuth + placebo (n = 50).Triple therapy: subjects who became H. pylori-negative (n = 42) showed a significant symptomatic response when interviewed at 8 weeks, 6 months, and 1 year (P0.01). This improvement was evident in the 'ulcer-like' dyspepsia group at all times (P0.01) but in the 'reflux-like' and 'motility-like' groups at 6 months only (P0.01). Those who remained H. pylori-positive showed no decrease in symptoms at 8 weeks, 6 months, and 1 year. Bismuth-placebo therapy: subjects who became H. pylori-negative (n = 7) showed an improvement in symptoms at 8 weeks, 6 months, and 1 year. Those who continued to harbour the infection after treatment (n = 42) showed an insignificant improvement in the motility and non-specific groups only.This study shows that eradication of H. pylori results in a significant long-term reduction in symptoms of non-ulcer dyspepsia.

Background: Experimental and clinical studies suggest an association between SIBO and NASH. Liver injury and fibrosis could be related to exposure to a bacterial burden, notably endotoxins, of intestinal origin. Moreover, the gut microbiota and endotoxemia have been described to play a contributory role in metabolic dysfunction, particularly insulin resistance, which is a key factor in NASH development. The extracellular receptor molecules for LPS are Lipopolysaccharide Binding Protein (LBP), CD14, toll-like receptor-4 (TLR-4) and myeloid differentiation-2 (MD-2). Endotoxaemia also induces proinflammatory cytokine release from immune cells. Aim: To investigate the prevalence of small intestinal bacterial overgrowth (SIBO) and relationships to LPS receptors and systemic cytokines in NASH. Methods: 18 NASH patients (8 males and 10 females) and 16 ageand gender-matched healthy volunteers were studied. SIBO was assessed by the lactulose breath hydrogen test (LHBT), plasma LBP levels were measured by ELISA and expression (as a %) of TLR-2 and 4 on CD14 positive cells determined by flow cytometry. Proinflammatory mediators (IL-1β, IL-6, IL-8 and TNFα) were measured in plasma by MSD (Meso Scale Discovery). Results: SIBO was more common in NASH patients (71%) than in control subjects (35.7%). This was mainly due to H2 production which was significantly greater in NASH than control at time points 45, 60, 75 and 90minutes during the LHBT (p=0.0241, 0.0476, 0.0470 and 0.0139 respectively). On the other hand, CH4 production was similar in NASH and control groups. No significant differences were detected between NASH and controls for LBP levels, p=0.5448. TLR-4/ MD-2 expression on CD14 positive was significantly higher among NASH patients than in control subjects: % expression, mean ± SEM, NASH vs control: 20.95± 2.91% vs 12.73 ± 2.29%, p=0.048 while TLR-2 expression was not significantly different. Among the cytokines studied, IL-8 levels were significantly higher in patients than control (p=0.0413) and correlated positively with TLR-4 (r=0.5123, p=0.0355) expression but not with TLR-2 expression. Conclusion: Small intestinal bacterial overgrowth is common in NASH, largely related to excess production of H2 and is associated with increased circulating levels of IL-8 and upregulation of TLR-4/MD2.

We read with interest the study by Whiting and colleagues ( Gut 2002: 50 :378–81). The study has further highlighted the importance of early detection of gastric cancer and also given further emphasis on ways to prevent the multistep progression in gastric carcinogenesis. However, we would like to make the following comments. Firstly, one in five patients in this group had lesions which, according to Whiting et al , should be followed up by yearly …