Is routine histological evaluation an accurate test for Helicobacter pylori infection?

AIM: To compare the diagnostic accuracy of routine histology for Helicobacter pylori infection, with histology by an expert pathologist, and to compare histology with the rapid urease test (RUT), 13C-urea breath test, IgG serology and culture of antrum and corpus specimens, in a consecutive series of untreated patients presenting for upper oesophago-gastro-duodenoscopy. MATERIALS AND METHODS: One-hundred and fifteen consecutive patients underwent multiple tests for H. pylori infection: rapid urease test, 13C-urea breath test, IgG serology and histology and culture on antrum and corpus biopsy specimens. Histology was first evaluated by the pathologists in a routine examination, and then blindly reviewed by an expert pathologist with a special interest in gastrointestinal pathology. The patients were considered to be H. pylori-positive if two or more tests were positive. RESULTS: Eighty-one patients (70.4%) were found to be H. pylori positive. 13C-urea breath test and IgG serology showed the best sensitivity and specificity (100%). Both the antral and body cultures, and the rapid urease test had the highest specificity (100%). Histological diagnosis after re-evaluation by an expert pathologist showed a high sensitivity (98. 8%) and specificity (100%), and was better than routine histology (sensitivity 92.6%; specificity 90.3%). The accuracy of the rapid urease test was greater than that of routine histology, and the combination of these two tests improved the sensitivity of H. pylori detection to up to 100%. CONCLUSION: All diagnostic tests usually utilised in clinical practice have a sensitivity higher than 90%. In patients who were not pre-treated with antisecretory agents or antibiotics, the sensitivity of histological diagnosis, however, seems to be influenced by the accuracy of the histological examination. The sensitivity of routine histology, but not of revised histological diagnosis, is improved by an additional rapid urease test.     

Is Helicobacter pylori eradication a cost-effective treatment of duodenal ulcer disease?

Treatment strategies aimed at eradicating Helicobacter pylori have shown positive results in the management of duodenal ulcer disease. Several cost-effectiveness studies comparing these regimens with traditional therapy have recently been conducted, and results are discussed in this review. Cost comparisons of different treatment strategies cannot be performed without first identifying whether the cost of ulcer diagnosis is included in the study. Assuming that only 20% of patients with dyspepsia actually have ulcer disease, costs may vary, depending on the study population. Importantly, treatment costs should not be compared between a patient population with confirmed ulcer disease and one without confirmed disease. In patients with confirmed ulcer disease, studies consistently show that H. pylori eradication strategies are associated with greater efficacy and lower costs than traditional treatment, and are therefore a more cost-effective alternative to standard therapy. Although all models used in the cost-effectiveness analyses assume that patients discontinue treatment following successful eradication of the microorganism, in clinical practice some patients continue antisecretory treatment beyond this period. Thus, savings as a result of H. pylori eradication may be less substantial than indicated in cost-effectiveness studies.     

Is a one‐week course of triple anti‐Helicobacter pylori therapy sufficient to control active duodenal ulcer?

BACKGROUND: Triple therapy currently forms the cornerstone of the treatment of patients with Helicobacter pylori-positive duodenal ulcer. AIM: To establish whether prolonged antisecretory therapy is necessary in patients with active duodenal ulcer. METHODS: A total of 77 patients with H. pylori-positive duodenal ulcer were included in a prospective, controlled, double-blind study. All patients received a 7-day treatment with omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxicillin 1000 mg b.d. Patients in the omeprazole group underwent an additional 14-day therapy with omeprazole 20 mg; patients in placebo group received placebo. Endoscopy was performed upon inclusion in the study and after 3 and 8 weeks. RESULTS: Seventy-four patients were eligible for a per protocol analysis after 3 weeks, and 65 after 8 weeks. After 3 weeks, the healing rate was 89% in the omeprazole group and 81% in the placebo group (P=0.51). After 8 weeks, the ulcer healed in 97% of the patients in the total group (95% CI: 92.7-100%). H. pylori was eradicated in 88% of patients in the omeprazole group and in 91% in the placebo group (P=1.0). No statistically significant differences between the groups were found in ulcer-related symptoms or in ulcer healing. CONCLUSION: In patients with H. pylori-positive duodenal ulcer, a 7-day triple therapy alone is sufficient to control the disease.     

Appropriate strategies for testing and treating Helicobacter pylori in children: When and how?

Helicobacter pylori infection is acquired primarily during childhood and carries a significant lifetime risk for morbidity. In developing countries, approximately 70% of children are infected with the bacterium by their 15th birthday. In the United States, the rate of H pylori infection among children varies widely—approximately 10% of all 10-year-olds are infected; however, this figure is substantially higher among populations of immigrant children and children born of recent immigrants to the United States. H pylori transmission is primarily “person-to-person” via fecal-oral, gastric-oral, or oral-oral routes, with evidence suggesting contaminated water as a potential source of infection. Risk factors for infection in childhood include an infected family member, having ≥2 siblings, crowded living conditions, lower socioeconomic means, and attendance at a daycare facility. The natural history of H pylori infection includes an increased lifetime risk for peptic ulcer and gastric adenocarcinoma or lymphoma. In children and adults who develop H pylori–related peptic ulcer, cure of the infection is associated with a <5% rate of ulcer recurrence. The ideal mode of H pylori detection among children is unclear—currently available serology and whole blood tests are unreliable, while the urea breath test and stool antigen tests have not been studied adequately. Children with confirmed H pylori–related peptic ulcer disease, iron-deficiency (sideropenic) anemia, or a first-degree relative with gastric cancer should be treated for the infection using 1 of 3 available 10- to 14-day triple therapy regimens recommended by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.     

Should we eradicate Helicobacter pylori in non‐steroidal anti‐inflammatory drug users?

The interaction between Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) in ulcerogenesis has been visited by many studies. Apparently these studies yielded conflicting results. This is a result of a wide diversity of methodology, selection of patient groups and definitions of outcome used by different investigators. This review attempts to analyse separately studies dealing with new or chronic NSAID users, primary or secondary prophylaxis, complicated or uncomplicated ulcers in NSAID or aspirin users. Evidence suggests that eradication of Helicobacter pylori infection may reduce the risk of ulcer and ulcer complications in patients requiring NSAIDs and aspirin. Whether or not one should test-and-treat H. pylori before prescribing NSAIDs is a complicated issue. Factors such as the ulcer risk of patients, previous history of NSAID usage and the use of aspirin or NSAIDs would guide the strategy.     

Helicobacter pylori‐associated ulcer bleeding: should we test for eradication after treatment?

BACKGROUND: Eradication of Helicobacter pylori after peptic ulcer haemorrhage reduces the risk of recurrence. Because H. pylori treatment is very effective, it is unclear whether testing to confirm eradication is worthwhile. AIMS: To examine whether patients with H. pylori-associated peptic ulcer haemorrhage should be tested for successful eradication after completion of antibiotic therapy. METHODS: A Markov cost-effectiveness model was developed to compare testing vs. non-testing of H. pylori eradication in peptic ulcer haemorrhage. Probability estimates and average costs were derived from published information. RESULTS: Testing for H. pylori eradication resulted in a benefit of 0.07 quality-adjusted life-years and cost 836 US dollars less than the strategy of not confirming eradication. Testing remained the superior strategy when varying the model regarding age, the initial success of eradication, various test and retreatment strategies, and the rate and costs of recurrent bleeding. Assuming a high eradication rate (95%), the test strategy becomes more expensive only if the cost of H. pylori testing reaches 265 US dollars; however, even under these conditions it remains cost-effective. CONCLUSIONS: Patients with H. pylori-associated peptic ulcer bleeding should be tested to confirm eradiation of H. pylori after completion of antibiotic treatment.     

Is Helicobacter pylori relevant in the management of reflux disease?

Data on the interaction of reflux disease and Helicobacter pylori infection are limited in scope and rigour, controversial and difficult to interpret. Despite this, a framework of understanding is emerging, which is consistent with known effects on gastric acid secretion. In patients with moderate to severe H. pylori-induced corpus gastritis, eradication can increase substantially impaired gastric acid secretion sufficiently to precipitate reflux disease in people with pre-existing sub-clinical defective gastro-oesophageal competence. By contrast, reflux disease in duodenal ulcer patients probably benefits from eradication of H. pylori. There appears to be no significant impact on reflux disease from eradication in healthy subjects or individuals whose primary problem is reflux disease. Helicobacter pylori-infected reflux disease patients respond slightly better to proton pump inhibitors. These agents cause a topographic alteration of gastritis from antrum to corpus, the clinical significance of which is controversial. Many practitioners misjudge the risks and benefits of the effects of H. pylori eradication on reflux disease. Regardless of patient diagnosis, the balance is in favour of H. pylori eradication. For those in whom reflux oesophagitis development is a defined possibility, oesophagitis is mild, easily treated and most unlikely to be associated with any major risk for development of oesophageal adenocarcinoma.     

Is Helicobacter pylori status relevant in the management of GORD?

There is growing interest in the relationship between H. pylori infection and gastro-oesophageal reflux disease (GORD). However, this relationship is complex, as yet not fully elucidated, and probably based on a multiplicity of factors. The prevalence of H. pylori infection in patients with GORD is similar, more often lower than in matched controls. There is a negative correlation between H. pylori infection and the severity of GORD. There are many hypothetical mechanisms by which H. pylori infection may protect from the development of GORD. Conversely, there are many possible mechanisms by which H. pylori infection could theoretically foster the GORD. Patients after H. pylori eradication may develop GORD, and this seems to suggest a protective role of H. pylori infection, but other possible explanations include weight gain after H. pylori eradication, changes in dietary habits and smoking, and pre-existing GORD. H. pylori infected patients treated by various acid-inhibiting therapies such as proton pump inhibitors (PPIs), H2-receptors antagonists (H2-RA) or vagotomy, have an increase of their corpus gastritis severity, both in the activity of inflammation and in the density of organisms. Long-term therapy of GORD in H. pylori infected may lead to rapid progression of atrophic gastritis intestinal metaplasia and dysplasia, and increase the risk of developing gastric cancer. More recently it has been shown that H. pylori infection may interfere with the acid suppressive therapies used for treating GORD. In our opinion the progression of gastritis depends on the threshold of acid output at which H. pylori can 'flourish'. Recently interest is growing on gastric transitional zones and Helicobacter ecology. Any decrease of acid secretion changes the behaviour of H. pylori: the activity of gastritis improves in the antrum, but it deteriorates in the body. During proton pump inhibitor treatment, H. pylori redistribution occurs within the stomach, from an antral to a corpus or fundus prevalent pattern; corpus-fundus gastritis, exacerbated by PPI therapy, may result both in a diminished acid secretion and gastro-oesophageal reflux. The interest in Barrett's oesophagus is growing due to the associated risk of adenocarcinoma. The literature seems to demonstrate that the prevalence of H. pylori infection of the stomach in Barrett's oesophagus patients is not different from that exhibited by controls, roughly one-third of the subjects. Intestinal metaplasia of the gastric cardia seems to be equally frequent in patients with and without GORD. Finally, it appears unlikely that a causal relationship exists between H. pylori infection and Barrett's-associated adenocarcinoma.     

Will eradication of Helicobacter pylori infection influence the risk of gastric cancer?

Gastric adenocarcinoma is a disease of high mortality and poor prognosis that is second only to lung cancer as a leading cause of cancer-related deaths worldwide. Although gastric cancer has a multifactorial etiology, infection with Helicobacter pylori is highly associated with its development. New information on bacterial and host genetics and results of epidemiologic studies suggest that better identification of individuals at high risk for gastric malignancy may be possible. Studies suggest that cure of H pylori infection may be associated with retardation of glandular atrophy and intestinal metaplasia but not reversal of dysplasia. Theoretically, it is attractive to believe that eradication of H pylori infection might prevent gastric cancer; however, studies supporting this hypothesis are not yet available. Public policy strategies for the identification of patients at risk for H pylori–related gastric malignancy are likely to be complex, but testing and treating for the infection earlier rather than later in life is anticipated to be the more beneficial approach.     

Would eradication of Helicobacter pylori infection reduce the risk of gastric cancer?

This article reviews the data on the epidemiology of gastric cancer, to determine if treatment of an asymptomatic individual can be justified. It reviews retrospective and prospective case-control studies of gastric cancer in Italy and other countries. Mucosa-associated lymphoid tissue lymphoma is associated with Helicobacter pylori infection. The risk of noncardia gastric cancer is higher (4-fold or greater) in those with H. pylori infection. Although no studies have shown prevention following treatment, eradication of asymptomatic H. pylori infection in an individual in the age group 40 or lower may be expected to reduce the risk of gastric cancer.     

Test and treat or test and scope for Helicobacter pylori infection. Any change in gastric cancer prevention?

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.     

Is a long‐term ranitidine‐based triple therapy against Helicobacter pylori only a heritage of the past? A prospective,randomized clinicopharmacological study

BACKGROUND: Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. Aims: To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. RESULTS: On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.