Carlo A Fallone

The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

OBJECTIVES:From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting.METHODS:Analysis of randomly selected patients endoscoped for nonvariceal upper gastrointestinal bleeding at 18 community and tertiary care institutions between 1999 and 2002. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression models identified predictors of outcomes.RESULTS:One thousand eight-hundred and sixty-nine patients were included (66 ± 17 yr, 38% female, 2.5 ± 1.6 comorbid conditions, hemoglobin, 96 ± 27 g/L, 54% received a mean of 2.9 ± 1.7 units of blood). Endoscopy was performed within 24 h in 76%, with ulcers (55%) most commonly noted. High-risk endoscopic stigmata and endoscopic therapy were reported in 37%. Rebleeding, surgery, and mortality rates were 14.1%, 6.5%, and 5.4%, respectively. Decreased rebleeding was significantly and independently associated with PPI use (85% of patients, mean daily dose 56 ± 53 mg) in all patients regardless of endoscopic stigmata, (odds ratio (OR):0.53, 95% confidence interval, 95% CI:0.37–0.77) and endoscopic hemostasis in patients with high-risk stigmata (OR:0.39, 95% CI:0.25–0.61). PPI use (OR:0.18, 95% CI:0.04–0.80) and endoscopic therapy (OR:0.31, 95% CI:0.11–0.91) were also each independently associated with decreased mortality in patients with high-risk stigmata.CONCLUSIONS:These results appear to confirm the protective role of endoscopic therapy in patients with high-risk stigmata, and suggest that acute use of PPIs may be associated with a reduction of rebleeding in all patients, and lower mortality in patients with high-risk stigmata. Independent prospective validation of these observational findings is now required.

Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - Update 2004

BACKGROUND Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barretts epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barretts epithelium may be considered in adults with GERD symptoms for more than 10 years; Barretts epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barretts epithelium and esophageal adenocarcinoma.

Canadian Helicobacter Study Group Consensus Conference: Update on the Approach to Helicobacter Pylori Infection in Children and Adolescents – an Evidence-Based Evaluation

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H. pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H. pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H. pylori infection; recurrent abdominal pain of childhood is not an indication to test for H. pylori infection; H. pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H. pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H. pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H. pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H. pylori infection; serological antibody tests are not recommended as diagnostic tools for H. pylori infection in children; first-line therapy for H. pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H. pylori infection in children is 14 days; and H. pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.

Is Helicobacter pylori eradication associated with gastroesophageal reflux disease

OBJECTIVES:A recent report has suggested an association between Helicobacter pylori eradication and the development of gastroesophageal reflux disease (GERD). We therefore assessed the incidence of GERD among comparable patients having undergone successful versus failed H. pylori eradication in a controlled trial. We also compared the H. pylori strains in the subjects that developed GERD to those that did not.METHODS:Patients with a history of proven duodenal ulcer and H. pylori infection were randomised into a H. pylori eradication study. Patients subsequently underwent gastroscopy with gastric biopsies every 3 months for 1 yr. At each visit, the presence of GERD symptoms and endoscopic esophagitis were noted, and the incidence of these variables among patients in whom H. pylori eradication was successful was compared to those in whom it was not. In a subgroup, the presence of the cagA, cagE, and vacA genotypes and of cagA antibodies were determined.RESULTS:Of 98 patients randomized into this study, 11 dropped out before determination of H. pylori eradication, leaving 87 patients with analyzable results. H. pylori eradication was successful in 63 (72%). By the end of the follow-up period, patients with GERD symptoms or endoscopic esophagitis were more prevalent in the successful than in the failed eradication group (37% [95% CI: 25–50%] vs 13% [95% CI: 3–32%], p = 0.04, 95% CI for the difference: 6–42%), as were patients with GERD symptoms alone (29% [95% CI: 18–41%] vs 8% [95% CI: 1–27%], p = 0.04, 95% CI for the difference: 4–36%) or esophagitis alone (21% [95% CI: 12–33%] vs 4% [95% CI: 0–21%], p = 0.10, 95% CI for the difference: 4–29%, respectively). Multivariate analysis revealed no significant association between the incidence of symptoms or esophagitis and age, gender, Quetelet index, caffeine or alcohol intake, smoking, weight change, or the presence of a hiatus hernia. There were also no differences in the prevalence of H. pylori genotypes from patients who developed GERD as compared to those who did not.CONCLUSIONS:In this patient population, the incidence of new GERD-type symptoms or endoscopic esophagitis was greater in patients in whom successful eradication was achieved. This difference does not appear to be attributable to weight gain, habits, or specific H. pylori strains.

Canadian Helicobacter Study Group Consensus Conference on the Approach to Helicobacter Pylori Infection in Children and Adolescents

Gastric infection with Helicobacter pylori is common in both children and adults, but children are considerably less susceptible to peptic ulcers and other pathological sequelae. As a result, the risk to benefit ratio of diagnostic studies and therapeutic regimens for H pylori in adults are likely different from those in pediatric populations. These guidelines for the management of pediatric H pylori infection, developed by the Canadian Helicobacter Study Group, are designed to identify when the diagnosis and treatment of H pylori may improve patient care. Given the low prevalence of this infection in Canada, it is important to recognize that indiscriminate testing and treatment programs in children are not recommended, and indeed may threaten the optimal care of children. Diagnostic tests should be employed judiciously and be reserved for children who are most likely to derive measurable benefit, such as those likely to have peptic ulcer disease. At this time a test and treat strategy in children cannot be considered prudent, evidence based or cost effective. It is appropriate to limit diagnosis and treatment to children and adolescents in whom H pylori has been identified during endoscopic investigation.

High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis

Background : The efficacy of high‐dose intravenous proton pump inhibition has recently been shown, yet its cost‐effectiveness remains poorly studied.

Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases

OBJECTIVE:Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls.METHODS:A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays.RESULTS:Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94–97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48–86%, p = 0.02) and GERD (69%, CI: 39–91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81–98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10–56%) versus 80% (CI: 59–93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies.CONCLUSIONS:The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.

cagE is a virulence factor associated with Helicobacter pylori-induced duodenal ulceration in children

This study was undertaken to determine whether infection with Helicobacter pylori strains that contain the cagE gene was associated with duodenal ulceration in children. The presence of flaA, cagA, and cagE genes was determined by polymerase chain reaction in H. pylori previously cultured from 29 children. Twelve (92%) of 13 children with duodenal ulcers were infected with cagE-positive isolates, compared with only 5 (31%) of 16 with gastritis alone (P<.01). Infection of gastric cells in tissue culture by cagE-positive H. pylori resulted in greater increments in interleukin-8 levels compared with cagE-negative strains (2.3+/-0.1 vs. 1.3+/-0.2 ng/mL in AGS cells [P<.005]; 1.5+/-0.3 vs. 0.5+/-0.2 ng/mL in KATO-III cells [P<.05]). H. pylori-containing cagE was associated with the presence of duodenal ulceration in children. Enhanced chemokine production after infection with cagE-positive H. pylori could affect disease outcome.

Host determinants of Helicobacter pylori infection and its clinical outcome.

Greater than one‐half of the worlds population harbors Helicobacter pylori. The majority of infected individuals, however, remain asymptomatic, with only 10% to 20% developing diseases, including peptic ulcer disease, gastric cancer, and gastric mucosa–associated lymphoid tissue lymphoma. This article reviews host factors that may predispose an individual to both the acquisition of H. pylori infection and subsequent clinical outcome. Individuals with specific blood group antigens and human leukocyte antigen genotypes may be more susceptible to H. pylori infection. Additional factors, such as the age of acquisition, the host immune response, the site of infection, acid secretion, and interactions with nonhost factors (including bacterial virulence factors and environmental influences) may play a role in determining clinical outcome. Further investigation is required to clarify the mechanisms by which these interactions occur and, more critically, to determine their relative importance. This knowledge will enable the identification of individuals at risk of developing clinical disease with H. pylori infection.

The cost-effectiveness of high-dose oral proton pump inhibition after endoscopy in the acute treatment of peptic ulcer bleeding

Background : Recent data suggest a role for high‐dose oral proton pump inhibition in ulcer bleeding.