Richard H. Hunt

Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer

BACKGROUND & AIMS Reports in the literature regarding the relationship of Helicobacter pylori infection to gastric cancer are conflicting. The aim of this study was to identify the source of heterogeneity between studies. METHODS Meta-analysis of cohort or case-control studies with age- and/or sex-matched controls, providing raw data on H. pylori infection detected by serology, was used. RESULTS A fully recursive literature search identified 19 qualified studies with 2491 patients and 3959 controls. Test for homogeneity found a significant difference in odds ratio between patients with early and advanced gastric cancer (6.35 vs. 2.13; P = 0.01), patients with cardiac and noncardiac gastric cancer (1.23 vs. 3.08; P = 0.003), and population- and hospital-based controls (2.11 vs. 1.49; P < 0.001). The summary odds ratio for gastric cancer in H. pylori-infected patients is 1.92 (95% confidence interval [CI], 1.32-2.78), 2.24 (95% CI, 1.15-4.4), and 1.81 (95% CI, 1.16-2.84) for all studies, cohort, and case-control studies, respectively. H. pylori-infected younger patients have a higher relative risk for gastric cancer than older patients with odds ratios decreasing from 9.29 at age < or = 29 years to 1.05 at age > or = 70 years. H. pylori infection is equally associated with the intestinal or diffuse type of gastric cancer. CONCLUSIONS H. pylori infection is a risk factor for gastric cancer. The heterogeneity of reported results is caused by differences in the selection of controls, patient age, and the site and stage of gastric cancer.

What Role Does Helicobacter pylori Play in Dyspepsia and Nonulcer Dyspepsia? Arguments For and Against H. pylori Being Associated With Dyspeptic Symptoms

A major role for Helicobacter pylori gastritis in nonulcer dyspepsia (NUD) is controversial. Gastroduodenal dysfunction may be associated with H. pylori infection, but there is little evidence for a causal link with dyspepsia. Population-based studies with appropriate methodology have generally failed to confirm an association between H. pylori and NUD. Furthermore, no definite association between subgroups of NUD (ulcer-like, dysmotility-like, reflux-like, and nonspecific) and H. pylori has been identified however the subgroups have been defined, and no specific symptom pattern characterizes patients with H. pylori infection. Whether H. pylori-induced alterations of gastric physiology can explain NUD remains open to debate while we await the results of more specific experiments. Although acid secretion in response to gastrin-releasing peptide may be increased in a subset of NUD patients who are infected with H. pylori, uninfected patients with NUD have not been assessed and the results require confirmation. Most studies suggest no association between H. pylori and gastroduodenal motor or sensory dysfunction in NUD. Treatment trials have been unconvincing. The trials with bismuth therapy have not been adequately blinded. Furthermore, some studies suggest that H. pylori-negative patients with NUD may respond to bismuth treatment, although the results have not been uniform. Therapies aimed at curing H. pylori infection have produced mixed results, with small positive and negative trials. The trials that have used adequate outcome measures have more often than not been negative. Based on current evidence, H. pylori is not established to be of causal importance in NUD.

Eradication of Helicobacter pylori Infection

Helicobacter pylori is probably the most common bacterial infection worldwide and the accepted cause of chronic active gastritis. It has a critical role in duodenal ulcer, where the prevalence of infection is 90-95%. There is a dramatic reduction in the rate of ulcer recurrence after successful eradication of the organism to about 4% per annum compared with up to 80% when the infection persists. What is true for duodenal ulcers is also true for patients with gastric ulcer who are infected with H. pylori. The risk of recurrent ulcer complications with bleeding is virtually abolished following successful eradication of H. pylori; in contrast, the risk of rebleeding is about 33% in patients still harboring the organism. The treatment of H. pylori infection in patients with confirmed peptic ulcer on first presentation or recurrence has been advocated by a Consensus Conference of the National Institutes of Health. The most evaluated regimens include dual therapy with a proton pump inhibitor and either amoxicillin or clarithromycin, and bismuth-based triple therapy with metronidazole and tetracycline. The use of a proton pump inhibitor-containing regimen offers the advantage of rapid symptom relief and the highest rates of duodenal ulcer healing. Moreover, combinations of a proton pump inhibitor and clarithromycin show more predictable and higher eradication rates than amoxicillin combinations. Newer triple therapies with a proton pump inhibitor plus two antibacterial agents given for 7-1O days are being increasingly described and may become the treatment of choice if initial results are confirmed. However, the optimum dosage regimen needs to be established. A new combination of ranitidine bismuth citrate and clarithromycin has also recently been shown to be effective. At this time it is reasonable to consider all patients with confirmed duodenal or gastric ulcer for eradication of H. pylori, and no patient should be considered for elective surgery without first being offered eradication therapy.

Effect of acupuncture on gastric acid secretion in healthy male volunteers

Six randomized, placebo controlled studies were performed to investigate the effect of electroacupuncture on gastric acid output in 38 healthy males. Electroacupuncture decreased basal acid output when compared to placebo acupuncture [from 3.50±0.59 mmol/hr to 2.54±0.56 mmol/hr (P<0.05)] as well as sham feeding-stimulated acid output [from 18.52±2.25 mmol/hr to 5.38±2.11 mmol/hr (P<0.005)], but had no effect on the pentagastrin stimulated acid output. The inhibitory effect of acupuncture on sham feeding-stimulated acid output was not affected by local anesthesia of the acupoint, but was prevented by a prior intravenous naloxone injection. Acupuncture did not alter plasma gastrin levels (20.7±7.6 μg/liter, vs control 21.2±7.2 μg/liter) but naloxone increased it (26.1±14.5 μg/liter) (P<0.05). We conclude that the antisecretory effects of electroacupuncture do not result from decreased gastrin release or decreased parietal cell sensitivity to gastrin, but are mediated through naloxone-sensitive opioid neural pathways and vagal efferent pathways.

Review: Eradication of Helicobacter pylori. Problems and recommendations

The successful isolation of Helicobacter pylori from the stomachs of patients with gastritis and peptic ulcer has revolutionized our concepts of the pathogenesis of gastritis, peptic ulcer, gastric cancer and gastric B cell lymphoma. Eradication of H. pylori heals gastritis and H. pylori‐related peptic ulcer. After a successful cure of H. pylori infection, virtually no recurrence of duodenal ulcer is seen. However, treatment to cure the infection has proved difficult. Numerous clinical trials have been attempted, but as yet no ideal regimen has been identified. Monotherapies have many drawbacks and should be avoided. Dual therapies combining a proton pump inhibitor (PPI) and an antimicrobial agent provide higher eradication rates than those involving two antimicrobial agents. Bismuth‐based triple therapies are more effective than dual therapies in eradicating H. pylori infection. However, poor compliance and frequent adverse effects have made these combinations less favourable in clinical practice. Proton pump inhibitor‐based triple therapies have shown more consistent and higher eradication rates with a short duration of treatment, good patient compliance, fewer side effects, prompt symptom relief and fast ulcer healing. Results from PPI‐based quadruple therapies are promising; however, large multicentre clinical trials are needed to confirm the effect and the complex regimen again may compromise compliance outside of the clinical trial setting. Eradication of H. pylori infection is cost‐effective in the long‐term management of peptic ulcer disease compared with maintenance therapy with antisecretory drugs.

Myths and facts in the use of anti-inflammatory drugs

Background. Because of the prominence of pain-related conditions and the growing complexities of clinical management we aimed to explore and attempt to dispel the several myths that surround these serious therapeutic issues. Aims. We aimed to provide a careful analysis of the evidence and draw factually based guidance for physicians who manage the broad range of patients with pain. Methods. Current myths were identified based on the authors’ clinical, scientific, and academic experience. Each contributor addressed specific topics and made his own selection of primary references and systematic reviews by searching in MEDLINE, EMBASE, and CINAHL databases (1990–2008) as well as in the proceedings of the major digestive and rheumatology meetings. The writing and references provided by each contributor were collectively analyzed and discussed by all authors during several meetings until the final manuscript was prepared and approved. Results. Seven major ‘historical’ myths that may perpetuate habits and beliefs in clinical practice were identified. Each of them was thoroughly examined and dispelled, drawing conclusions that should help guide physicians to better manage patients with pain. Conclusions. Pain relief must be considered a human right, and patients with osteoarthritis pain should be treated appropriately with analgesic or/and anti-inflammatory drugs. The risk of gastrointestinal (GI) complications with traditional non-steroidal anti-inflammatory drugs (t-NSAIDs) is present from the first dose (with both short-term and long-term use), and strategies to prevent GI complications should be considered regardless of the duration of therapy. Compared with t-NSAIDs, coxib use is associated with a small but significant reduction of dyspepsia. While protecting the stomach, proton pump inhibitors do not prevent NSAID-induced intestinal damage. To this end, coxib therapy could be the preferred option, although further randomized studies are needed. A substantial number of patients who need NSAIDs are also taking low-dose aspirin for cardiovascular prophylaxis. From a GI perspective, the combination of aspirin plus a coxib provides a preferred option compared with aspirin plus a t-NSAID, for patients at high GI risk. As the incidence of renovascular adverse effects with t-NSAIDs and coxibs is similar, blood pressure should be monitored and managed appropriately in patients taking these drugs, although they should be avoided in those with severe congestive heart failure. Due to increased cardiovascular risk, which is dependent on the dose, duration of therapy, and base-line cardiovascular risk, both t-NSAIDs and coxibs should be used with caution in patients with underlying prothrombotic states and/or concomitant cardiovascular risk factors.

The gain in quality-adjusted life months by switching to esomeprazole in those with continued reflux symptoms in primary care: EncomPASS--a cluster-randomized trial.

OBJECTIVES:Proton pump inhibitors (PPIs) are effective in gastroesophageal reflux disease (GERD), but their cost effectiveness is unknown. This is usually determined by cost/quality-adjusted life year (QALY) gained, but whether PPI therapy improves QALYs has not been assessed in a randomized trial. The PPI acid suppression symptom (PASS) test is a five-item questionnaire that identifies patients with persistent acid-related symptoms. We evaluated whether a PASS test-based management strategy of changing GERD therapy to esomeprazole in those with continued symptoms on another PPI or H2 receptor antagonist therapy would be cost effective. We expressed the data in terms of cost per quality-adjusted life months (QALM), as this was a 4-week trial.METHODS:This is a multicenter, cluster-randomized, open-label study in primary care physician centers across Canada. Primary care physician centers were randomized to intervention or control arms. Patients on acid-suppressing medication were identified from primary care records and asked to complete the PASS test. PASS test failures at baseline assessment continued current therapy in control practices or switched to esomeprazole 20 or 40 mg daily (the dose was at the clinicians discretion) for 4 weeks in intervention practices. A planned secondary end point was QALM gain, measured using the validated Euroqol (EQ-5D) completed at baseline and 4 weeks. Medication use was also assessed by questionnaire. Canadian unit generic costs were applied to all GERD drugs, except to esomeprazole and lansoprazole, wherein proprietary costs were used (all costs in Canadian

Effects of smoking on cure of Helicobacter pylori infection and duodenal ulcer recurrence in patients treated with clarithromycin and omeprazole.

). Data were analyzed using bootstrap sampling.RESULTS:A total of 1,564 patients were recruited from 134 intervention sites and 92 control sites. Data were evaluable for 808 intervention and 445 control patients. The mean (±standard deviation) QALM at 4 weeks in the intervention group was 0.885±0.164 compared with 0.814±0.179 in the control group, resulting in a mean 0.071 (95% CI=0.091–0.051) QALM gain (P<0.0001). Esomeprazole was cost effective for PASS test failures, with a mean cost of

Helicobacter pylori: From art to a science

763 (95% CI=456–1,414) per QALM gain.CONCLUSIONS:Esomeprazole was associated with a statistically significant gain in QALMs and was cost effective in primary care patients with persistent acid-related symptoms identified by the PASS test.

Precise Role of Acid in Non-Erosive Reflux Disease

Smoking may affect adversely the cure rate for Helicobacter pylori infection in patients treated with amoxicillin and omeprazole. Therapy with clarithromycin and omeprazole was tested for its effectiveness in the treatment of H. pylori infection in smokers and nonsmokers.