Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study.

Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleotide polymorphisms. Results Three hundred and eight patients (median age at inclusion 61 years, interquartile range (IQR: 17; male 48.4 %; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7 %) showed progression of IM and six patients (1.9 %) developed high-grade dysplasia or GC. The minor allele (C) on TLR4 (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95 %CI 0.4-1.0). Family history (HR 1.5; 95 %CI 0.9-2.4) and smoking (HR 1.6; 95 %CI 0.9-2.7) showed trends towards progression of GIM. Alcohol use, body mass index, history of H. pylori infection, and serological markers were not associated with progression. Conclusions Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. TLR4 (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.

How the concept of biochemical response influenced the management of primary biliary cholangitis over time.

BACKGROUND: Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. METHODS: 851 Dutch PBC patients diagnosed between 1988 and 2012 were reviewed to assess patient management in relation to liver test results during UDCA treatment. To do so, biochemical response at one year was analysed retrospectively according to Paris-1 criteria. RESULTS: Response was assessable for 687/851 (81%) patients; 157/687 non-responders. During a follow-up of 8.8 years (IQR 4.8-13.9), 141 died and 30 underwent liver transplantation. Transplant-free survival of non-responders (60%) was significantly worse compared with responders (87%) (p < 0.0001). Management was modified in 46/157 (29%) non-responders. The most frequent change observed, noted in 26/46 patients, was an increase in UDCA dosage. Subsequently, 9/26 (35%) non-responders became responders within the next two years. Steroid treatment was started in one patient; 19 patients were referred to a tertiary centre. No trend towards more frequent changes in management over time was observed (p = 0.10). CONCLUSION: Changes in medical management occurred in a minority of non-responders. This can largely be explained by the lack of accepted response criteria and of established second-line treatments for PBC. Nevertheless, the observation that response-guided management did not increase over time suggests that awareness of the concept of biochemical response requires further attention,particularly since new treatment options for PBC will soon become available.

Is there any association between referral indications for open-access upper gastrointestinal endoscopy and endoscopic findings?

BACKGROUND AND STUDY AIM: The total number of upper gastrointestinal endoscopies is increasing, and despite guidelines for endoscopy referral for general practitioners, the proportion of patients found to have no endoscopic abnormalities is still up to 60% (and increasing). The aim of this study was to assess the association between general practitioners' referral indications and endoscopic findings. PATIENTS AND METHODS: General practitioners of patients referred for an open-access endoscopy between January 2002 and December 2004 were asked to specify the reason for referral on a specially designed form. The relative frequency of patients actually having an endoscopic abnormality was assessed for each referral indication. RESULTS: A total of 1298 people were included in the study. A relevant endoscopic abnormality was found in 48% of patients. Patients with an endoscopic abnormality were not more often referred with "alarm" symptoms or failure of empirical treatment than patients without an abnormal endoscopic finding (31% with an endoscopic abnormality vs. 30% without an endoscopic abnormality had alarm symptoms; 57% of people in both groups experienced failure of empirical treatment). Referral with alarm symptoms had a positive predictive value of 4% for cancer (prevalence 2%; P < 0.01), and referral with reflux-like symptoms had a positive predictive value of 33% for finding reflux esophagitis (prevalence 22%; P < 0.01). CONCLUSIONS: General practitioners' referral indications for open-access endoscopy did not add any relevant predictive value for endoscopic findings in comparison with what might have been expected from overall prevalence. Only alarm symptoms slightly increased the probability of finding cancer and only reflux-like symptoms slightly increased the probability of finding reflux esophagitis.

Anxiety, depression and psychotropic medication use in patients with persistent upper and lower gastrointestinal symptoms.

BACKGROUND: Limited information is available about anxiety, depression and psychotropic medication use in patients referred for gastrointestinal endoscopy. AIM: To determine anxiety and depression and its association with endoscopic findings in a representative sample of patients with persistent gastrointestinal symptoms prior to endoscopy. METHODS: Patients referred to the hospital for endoscopy between February 2002 and February 2004 were asked to score anxiety and depression on the Hospital Anxiety and Depression Scale 2 weeks prior to endoscopy. Information about endoscopic diagnoses was obtained from medical files. RESULTS: A total of 1298 subjects was studied (600 upper gastrointestinal endoscopies and 698 lower gastrointestinal endoscopies). Patients referred for upper gastrointestinal endoscopy used most psychotropic agents (24%; odds ratio = 3.1; 95% confidence interval = 2.3-4.2), especially patients with an organic abnormality when compared with patients without an organic abnormality (42% versus 8%; odds ratio = 8.6; 95% confidence interval = 5.4-14.0). Patients with colonic polyps were more anxious (odds ratio = 1.7; 95% confidence interval = 1.0-2.9) and depressed (odds ratio = 1.8; 95% confidence interval = 1.1-3.1) than other patients referred for lower gastrointestinal endoscopy. CONCLUSIONS: There is no difference in anxiety nor depression between patients with and without organic abnormalities at endoscopy. Patients with colonic polyps are more anxious and depressed than other patients referred for lower gastrointestinal endoscopy. Psychotropic medication use is highest among patients with an organic abnormality in the proximal gastrointestinal tract.

Health-related quality of life of patients with gastrointestinal symptoms.

BACKGROUND: Little is known about the variation in health-related quality of life among patients with different presentations of gastrointestinal symptoms. AIM: To study the association between health-related quality of life and presentations of gastrointestinal symptoms. METHODS: Health-related quality of life and demographic information was obtained from 873 patients referred to the hospital for endoscopy, using a questionnaire. RESULTS: A total of 436 patients (50%) reported predominantly upper gastrointestinal symptoms, 344 (39%) predominantly lower symptoms, and 93 (11%) patients reported both upper and lower symptoms. Patients with mild, moderate and severe symptoms, reported mean scores on a 100-point visual analogue scale (95% CI) of 90 (79-100), 75 (64-86) and 64 (53-76), respectively (P < 0.001). Mean visual analogue scale scores (95% CI) almost linearly declined from 81 (77-85) to 49 (46-52) for those with one to those with more than eight symptoms. Patients who reported upper gastrointestinal symptoms and in particular epigastric pain, bloating and vomiting had significantly impaired health status in comparison to patients without these symptoms (P < 0.05). CONCLUSIONS: Severity of gastrointestinal symptoms is the most important factor in affecting health status, followed by the numbers and type of gastrointestinal symptoms.

Short-term follow-up by serology of patients given antibiotic treatment for Helicobacter pylori infection.

Helicobacter pylori serology and in particular enzyme-linked immunosorbent assays for the measurement of immunoglobulin G (IgG) antibody titers form an accurate means of diagnosing H. pylori infection in patients before treatment. H. pylori serology is of limited value in monitoring treatment because of the slow decline in antibody titers. In the present study we aimed to measure the most suitable moment after antibiotic treatment at which serology should be used to monitor treatment. Sixty-four patients who had nonulcer dyspepsia and H. pylori infection and who underwent upper gastrointestinal endoscopy because of persistent dyspeptic symptoms were included in the study. H. pylori cure was confirmed by histology and culture 5 weeks after the completion of the antibiotic treatment. Serological examination was performed before therapy and at 5 weeks, 10 weeks, and 1 year after the completion of antibiotic treatment. Diagnostic performance was assessed by receiver-operating characteristic analysis. The areas under the receiver-operating characteristic curves of the H. pylori antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment were 0.53 (95% confidence interval [CI], 0.36 to 0.69), 0.60 (95% CI, 0.43 to 0.76), and 0.78 (95% CI, 0.63 to 0.93), respectively. The areas under the receiver-operating characteristic curves of the changes in H. pylori IgG antibody titers at 5 weeks, 10 weeks, and 1 year after the completion of treatment in comparison with the pretreatment titers were 0.85 (95% CI, 0.72 to 0.97), 0.96 (95% CI, 0.89 to 1.0), and 1.0 (95% CI, not estimable), respectively. We conclude that serology forms a useful means of monitoring treatment in patients with nonulcer dyspepsia and H. pylori infection as early as 10 weeks and maybe even sooner after the completion of treatment for the infection.

Functional dyspepsia.

Functional dyspepsia is defined as persistent or recurrent upper abdominal pain or discomfort not explained by structural or biochemical abnormalities. In about half of the patients who present to their practitioner with chronic dyspepsia, no underlying disease is established after clinical investigation. Many clinical trials have been performed to demonstrate a certain relationship between functional dyspepsia and several pathogenic mechanisms like dysmotility, Helicobacter pylori infection, acid output and hypersensitivity to distension. Unfortunately, the conclusions of those studies are conflicting. Short-term follow-up, lack of consensus about diagnostic criteria for functional dyspepsia and unvalidated symptom measures make it difficult to interpret their results.

Improvement of gastric inflammation and resolution of epithelial damage one year after eradication of Helicobacter pylori.

AIMS: To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system. METHODS: Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylori related gastritis. RESULTS: The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores were higher in the antrum than in the corpus or fundus. Eradication of H pylori resulted in an improvement in the mean inflammatory score in antral biopsy specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to 0.13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0.60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pylori none of the biopsy specimens revealed evidence of epithelial damage. CONCLUSION: Eradication of H pylori is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.

Basal serum gastrin concentrations before and after eradication of Helicobacter pylori infection measured by sequence specific radioimmunoassays.

BACKGROUND: Helicobacter pylori infection of the antral mucosa is responsible for an increase in basal and stimulated serum gastrin. In the present study we have investigated whether gastritis induced by H. pylori is responsible for abnormalities in the processing of gastrin in dyspeptic patients. METHODS: Basal serum gastrin was measured by radioimmunoassay before, 5 weeks, and 1 year after anti-H. pylori therapy in 73 H. pylori positive functional dyspeptic patients. Three region-specific antisera were used, specific for the biologically active carboxy-terminal part, the biologically inactive amino-terminal part of gastrin 1-17, and for the non-sulphated tyrosyl residue in gastrin 1-17. RESULTS: Basal serum gastrin levels were markedly (P < 0.01) decreased 5 weeks and 1 year after successful eradication of H. pylori (n = 39) but not in the patients in whom treatment failed (n = 34). A decline of gastrin was observed for each of the three radioimmunoassays. CONCLUSION: The decrease of serum gastrin levels in all three radioimmunoassays after a successful eradication of H. pylori does not point to major changes in the processing of gastrin. These results suggest that G-cells in the antral mucosa are not functionally affected by the inflammation.

Short report: smoking habits and the acquisition of metronidazole resistance in patients with Helicobacter pylori-related gastritis.

Thirty-three dyspeptic patients with colonization of Helicobacter pylori in the gastric antrum were treated with tripotassium dicitrate bismuthate 120 mg q.d.s. for 28 days and metronidazole 250 mg q.d.s. for 10 days starting on day 19. Five weeks after cessation of this treatment regimen H. pylori was eradicated in 23 patients. In 8 of the remaining 10 patients, H. pylori had become resistant to metronidazole. In this study resistance was significantly associated with smoking habits, but not with age, bacterial load, gastritis score or alcohol consumption.