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Helicobacter pylori–Related Disease
Guidelines for Testing and Treatment
Walter L. Peterson, MD;
A. Mark Fendrick, MD;
David R. Cave, MD, PhD;
David A. Peura, MD;
Susan M. Garabedian-Ruffalo, PharmD;
Loren Laine, MD
Arch Intern Med. 2000;160:1285-1291.
ABSTRACT
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Objective To develop practical guidelines for the treatment of patients with suspected and documented Helicobacter pylori–related gastroduodenal diseases.
Methods A panel of physicians with expertise in H pylori reviewed, critically appraised, and synthesized the literature on assigned topics and presented their overviews to the panel. Consensus was obtained in controversial areas through discussion.
Results and Conclusions The panel recommended testing for H pylori in patients with active ulcers, a history of ulcers, or gastric mucosa-associated lymphoid tissue lymphomas. Young, otherwise healthy patients with ulcerlike dyspepsia and those with a family history or fear of gastric cancer may also undergo H pylori testing. Nonendoscopic methods are preferred for H pylori diagnosis. Dual medication regimens should not be used for therapy; twice-daily triple therapy with a proton pump inhibitor or ranitidine bismuth citrate, clarithromycin, and amoxicillin for 10 to 14 days is an appropriate therapy. Posttreatment assessment of H pylori status using urea breath testing should be considered in patients with a documented history of ulcer disease or with persistent symptoms.
INTRODUCTION
AN ESTIMATED 30% to 40% of the US population is infected with Helicobacter pylori.1 Infection with this spiral, urease-producing organism causes histological gastritis in all those infected, is the major cause of peptic ulcer disease, and is an important risk factor for the development of gastric adenocarcinoma and lymphoma.2-3
Helicobacter pylori gastritis is found in up to 95% of patients with duodenal ulcers and 80% of patients with gastric ulcers in some parts of the world.4 In the United States, the percentage is closer to 75%, perhaps reflecting a larger role for nonsteroidal anti-inflammatory drug–induced ulcer disease.5 In individuals with H pylori infection, the estimated lifetime risk for peptic ulcer disease is approximately 15%.4, 6
Infection with H pylori increases the risk for gastric adenocarcinoma up to 9-fold as determined by a meta-analysis of 3 nested case-control studies.7-9 Given these findings, the International Agency for Research on Cancer10 classified H pylori as a group 1 (a definite cause of cancer in humans) carcinogen.
Helicobacter pylori–related peptic ulcer disease significantly impacts patient quality of life and functional status. In a 1989 National Health Interview Survey11 of 41,457 individuals, up to 25% of those with a recent ulcer reported being in poor health, incapable of major activity, restricted in daily activity, unable to perform work, or confined to bed for more than 7 days during the previous 12 months.
The overall economic impact of H pylori infection is staggering. It is estimated that the direct costs of treating H pylori–related diseases and associated complications and lost productivity is $3.0 to $5.6 billion annually.11-13
Studies14-15 have documented that cure of H pylori infection in patients with peptic ulcers is associated with a reduction in ulcer recurrence and, in many patients, obviation of maintenance antisecretory therapy. In addition, cure of H pylori infection may produce regression or resolution of low-grade gastric mucosa-associated lymphoid tissue lymphomas.16 Given the potential benefits of eradication of H pylori, a group of gastroenterologists and primary care physicians met to critically appraise and synthesize the current literature on H pylori infection to develop practical guidelines for diagnosis and treatment of patients with H pylori–related diseases.
WHO SHOULD BE TESTED FOR H PYLORI?
Tests designed to detect H pylori should be performed only if the result will affect patient treatment. Specifically, H pylori diagnostic testing should be ordered only if a decision has been made to treat patients who have a positive result.
The clinical superiority and cost benefits of H pylori testing of patients with newly diagnosed (by endoscopy or radiography) gastric or duodenal ulcer has been well studied.12, 17-19 Given the strong association between H pylori infection and ulcer disease, patients with a history of ulcer disease who are currently receiving maintenance antisecretory therapy should also be tested for H pylori infection.20 In addition, decision and cost-benefit analyses support nonendoscopic diagnostic testing of young, otherwise healthy patients with symptoms of ulcerlike dyspepsia.21-23 Finally, patients with mucosa-associated lymphoid tissue lymphoma should be tested and treated.7, 10, 24-30 The role of testing for H pylori infection in individuals receiving nonsteroidal anti-inflammatory agents is controversial.
Decision analyses31-32 suggest that screening for H pylori to prevent gastric cancer may also be cost-effective. In a study by Parsonnet and colleagues,31 if H pylori eradication prevented only 30% of attributable cancers, screening the entire US population at age 50 years would cost $1 billion—an amount similar to the estimated costs of colorectal screening—and provide a cost-benefit ratio of $25,000 per year of life saved. If screening were performed in high-risk populations such as Japanese Americans, H pylori cure would only have to reduce the risk of gastric cancer by 5% to be cost-effective at the benchmark of $50,000 per year of life saved. Although these data are compelling, no controlled clinical trials have been performed and no study has documented that eradication of H pylori will decrease the risk of developing gastric cancer.31 Therefore, routine population-based screening for H pylori cannot be recommended at this time. On the other hand, it is rational clinical behavior to screen individuals who come to a physician with a fear or strong family history of gastric adenocarcinoma.
METHODS OF H PYLORI DETECTION
Methods used to detect H pylori are typically referred to as endoscopic and nonendoscopic, with each having its advantages and disadvantages based on a patient's clinical history and current presentation.
Endoscopic methods involve assessing several gastric biopsy samples for the presence of H pylori by histological examination, urease activity, or culture.33 Of these assessment methods, histological examination is considered the reference standard. Use of special stains such as Giemsa or "Genta" stain may make identification of the organism easier on histological examination.34 Assessment of the biopsy sample for urease activity (rapid urease test) is a highly sensitive (approximately 90%) and specific (approaching 100%) method of H pylori detection.35 A limitation to the use of urease testing is in patients receiving proton pump inhibitors (PPIs) or high-dose histamine2 receptor antagonists (H2RAs), which might decrease H pylori density and consequently urease activity, thereby producing a false-negative result.36-40 Culturing of H pylori is generally not used in establishing a primary diagnosis because of the potential for false-negative results due to errors in specimen acquisition, storage, or transportation and its time-consuming nature (ie, requires up to 2 weeks for growth to occur).41 The performance of culture is useful for the determination of antibiotic resistance, especially in patients who continue to be positive for H pylori after an initial treatment regimen.
Helicobacter pylori detection by nonendoscopic methods such as blood antibody detection tests, urea breath tests (UBTs), and the recently approved assay for the detection of H pylori antigen in stool specimens42 is indicated in clinical situations in which endoscopy is not indicated. Unlike blood antibody detection methods, UBT and fecal antigen detection denote active H pylori infection.
Antibody tests to detect IgG antibodies to H pylori are less expensive and more convenient to use than UBTs but are somewhat less accurate.43-45 Antibody tests can now be done in the office setting on fingerstick whole blood specimens, with results obtained within 10 minutes. Antibody testing is commonly used in the evaluation of dyspeptic patients before or in place of endoscopy. Because antibody titers often take many months to decrease after successful treatment and remain positive in many patients for years, blood antibody testing (eg, serologic testing) is less useful for the monitoring of posttreatment H pylori status.
The UBT is a measure of current H pylori infection, relying on H pylori urease to hydrolyze urea labeled with radioactive carbon (13C or 14C) and produce isotopically labeled carbon dioxide in the breath. As with biopsy-based rapid urease tests, there is the potential for false-negative UBT test results in individuals receiving antisecretory agents such as PPIs or high-dose H2RAs, antimicrobial agents, or bismuth-containing compounds, which reduce H pylori density.37-39,46-47 Therefore, UBT should be avoided in those who have received bismuth or antibiotic drugs within the previous 4 weeks or antisecretory agents within the previous 2 weeks.
Stool antigen testing has emerged as a rapid, nonendoscopic method of H pylori detection. A recently published study42 found that stool antigen testing is highly sensitive and specific in the detection of H pylori in patients with dyspepsia and in those who have completed an H pylori eradication regimen. In the diagnosis of H pylori infection, the stool antigen detection method was highly sensitive (80%-100%) and comparable to that of the UBT (84%-100%). Stool antigen detection performed 4 weeks after completion of an H pylori eradication regimen had a sensitivity of 90%, a specificity of 95%, and a negative predictive value of 98%, rates that were comparable to those obtained with 13C UBT.42 Although the high rates of sensitivity and specificity with the stool antigen test in patients enrolled in the study by Vaira et al42 are promising, several other investigators found a high rate of false-positive results in patients tested 4 weeks after completion of anti–H pylori treatment.48-50
CHOICE OF H PYLORI DETECTION METHOD BY CLINICAL SITUATION
New-Onset Peptic Ulcer
Patients with a newly established diagnosis of ulcer disease made by endoscopy or radiography should have as their initial diagnostic test a rapid urease test or a serum antibody test, respectively. If the results are positive, the patient should be treated with an effective H pylori eradication regimen (ie, antimicrobial agents plus an antisecretory agent). If the initial test results are negative, H pylori status should be confirmed by another test given the importance this knowledge will have on future therapy. In the case of an endoscopically documented ulcer, this confirmation could be by histological examination, blood antibody detection, UBT, or stool antigen test. In patients whose ulcer is found by radiographic means, a UBT or stool antigen test should be done to confirm the patient's H pylori status. In either scenario, if the confirmatory test result is also negative, the patient's ulcer should be treated in standard fashion (eg, with a PPI or H2RA) and other causes for ulcer disease should be considered. If the confirmatory test result is positive, suggesting that the initial test was falsely negative, the patient should be treated with an effective anti–H pylori regimen.
History of Peptic Ulcer Disease
All patients who are currently receiving antisecretory agents, who have a history of uncomplicated ulcer disease documented by endoscopy or radiography, or who have a self-reported history of ulcer disease should be tested for H pylori infection using nonendoscopic detection methods. If the results are negative, use of the maintenance antisecretory drug can be discontinued if the sole indication for its use was history of peptic ulcer disease. Negative H pylori status can be confirmed by a UBT at least 2 weeks after cessation of therapy or by stool antigen detection at least 4 weeks after therapy cessation in objectively diagnosed patients and on symptom recurrence in clinically diagnosed patients. The rationale for the difference in approach relates to a greater probability that patients with objectively diagnosed disease will be infected than will patients without such documentation.
Dyspepsia
Patients with new-onset dyspepsia who are 50 years and younger and who have no alarm symptoms suggestive of underlying malignancy (eg, bleeding, weight loss, anemia, or early satiety) should undergo H pylori antibody testing. Alternatively, these patients may be tested using the UBT or stool antigen detection. Patients undergoing H pylori testing by UBT should not have ingested PPIs or high-dose H2RAs within the previous 2 weeks or antimicrobial agents within the previous 4 weeks. If the test results are positive, these patients should be offered H pylori eradication therapy, the rationale being that some of these individuals will have active ulcer disease and benefit from therapy. A proportion of those who do not have an ulcer (ie, functional dyspepsia) may also benefit from eradication of H pylori and should also be at lower risk for development of gastric adenocarcinoma.
Patients with new-onset dyspepsia who are older than 50 years or those of any age who have alarm symptoms should undergo upper endoscopy. If objective disease is found (ie, malignancy or ulcer disease) during endoscopy, H pylori infection should be detected by rapid urease testing of biopsy specimens. Patients who are positive for H pylori should have their infection treated within the context of the clinical diagnosis. If the rapid urease test results are negative, H pylori status can be confirmed using antibody testing or histological examination. Alternatively, a UBT can be used to confirm H pylori status.
TREATMENT OF H PYLORI INFECTION
Numerous regimens designed to cure H pylori infection have been evaluated and reported in the literature. Most regimens combine 1, 2, or 3 antibiotic agents (including bismuth compounds) with an antisecretory agent. Use of antisecretory agents combined with antimicrobial drugs increases the H pylori eradication rate (probably because an increase in the pH of the stomach increases the efficacy of some antimicrobial agents).51-52 In addition, PPIs have been found40 to have intrinsic in vitro inhibitory activity against H pylori. The use of antisecretory therapy also seems to hasten relief of ulcer symptoms.53-54
No therapy is 100% effective for H pylori infection. However, several regimens have been devised that attain cure rates between 80% and 90%. These regimens consist of twice-daily triple therapy with a PPI or ranitidine bismuth citrate along with 2 antimicrobial agents such as clarithromycin and either amoxicillin or metronidazole.55-60 Classic bismuth-based triple therapy (bismuth subsalicylate, metronidazole, and tetracycline all given 4 times a day) achieves eradication rates of approximately 80% in the United States61; the eradication rate potentially can be increased by addition of a PPI.62-63 The major concern regarding bismuth-based triple therapy relates to patient compliance because of the complexity of the regimen. Currently available dual therapies are not recommended for treatment of H pylori infection.
Factors that significantly affect H pylori cure rate are patient compliance with the regimen, duration of therapy, and presence of antimicrobial resistance. Regardless of the regimen selected to treat H pylori infection, patients should be advised that full treatment compliance is necessary to maximize their potential for infection cure. Despite the results of numerous European studies62, 64-65 that suggest that 7 days of triple therapy is sufficient, clinical trials55-57 performed in the United States have found that the highest rates of cure are associated with treatment durations of 10 to 14 days. Therefore, we recommend that PPI or ranitidine bismuth citrate–based triple therapy be administered for 10 to 14 days.
Primary resistance to metronidazole therapy is common, 28% to 39% in the United States.66 The rate of clarithromycin-resistant strains of H pylori is approximately 11%, and amoxicillin- or tetracycline-resistant strains have been reported only rarely.66-69 However, after failed treatment with metronidazole or clarithromycin, resistance to these agents must be assumed if susceptibility testing is not available.
FOLLOW-UP OF H PYLORI THERAPY
Evaluation of patients after completion of H pylori therapy is helpful in determining the patient's future clinical course. Duodenal ulcers recurred in 6% of patients cured of infection compared with 67% of those who remained positive for H pylori.70 Similar findings70 were noted in patients with gastric ulcers: ulcer recurrence after treatment occurred in 4% of cured patients and 59% of those who continued to harbor H pylori.
Patient symptoms after H pylori therapy do not always correlate with eradication success or failure. Relief of dyspepsia does not always suggest H pylori cure, although 2 studies71-72 found that persistence of certain ulcer-related symptoms (ie, nausea, epigastric discomfort, and ulcer pain) were predictive of continued infection. In one study,72 symptoms or their absence were highly sensitive and specific for confirming eradication 6 months after treatment. However, the authors caution that symptom-based assessment should not be used to assess treatment outcome in high-risk patients. Conversely, continued symptoms do not always denote treatment failure. Therefore, follow-up and confirmatory testing might be useful in determining a patient's response to treatment and risk of ulcer recurrence.
Nonendoscopic methods (eg, UBT) are recommended for confirming H pylori eradication after completion of therapy if such confirmation is deemed necessary.58, 73-74 A UBT should be performed no sooner than 4 to 6 weeks after completion of H pylori therapy. Use of PPIs or high-dose H2RAs should be discontinued for at least 2 weeks before administration of the UBT.37 A recent study42 found stool antigen detection to be a reliable method of confirmatory testing when performed 4 weeks after treatment. However, some studies48-50 have found a high rate of false-positive results using stool antigen detection 4 weeks after treatment.
Antibody testing is less useful in the immediate evaluation of posttreatment response because high levels of antibodies to H pylori remain for variable and extended periods.75 However, for an individual more than a year after therapy, seroconversion is a reliable indicator of successful eradication.76 If endoscopy is clinically indicated (ie, to confirm ulcer healing) after treatment, the clinician should obtain multiple biopsy specimens from the gastric body and antrum for histological examination and urease testing to exclude persistent infection.
Findings of a recent study77 suggest that patients have a desire to know their H pylori status after completion of an H pylori eradication regimen. However, economic factors might limit the utility of performing confirmatory testing in all patients. Follow-up testing to confirm eradication should be performed routinely in all patients with a confirmed diagnosis of new ulcer disease or a documented history of complicated ulcer disease. Patients with a reported history of uncomplicated ulcer disease not documented by endoscopy or radiography and those with a history of dyspepsia should have follow-up testing if symptoms recur. Confirmatory testing may also be performed in patients in whom their unknown H pylori status is causing excess worrying or loss of sleep.
MANAGEMENT OF PERSISTENT H PYLORI INFECTION AFTER TREATMENT
Patients who remain positive for H pylori after completion of an effective anti–H pylori regimen should be assessed with regard to treatment compliance. However, many patients may continue to experience symptoms or remain positive for H pylori despite full treatment compliance.77
ALTERNATIVE REGIMENS IN PATIENTS FAILING INITIAL H PYLORI THERAPY
The choice of an alternative regimen should be based on the initial treatment regimen. For example, if triple therapy consisting of a PPI or ranitidine bismuth citrate, clarithromycin, and amoxicillin was used as first-line treatment, the second treatment course should consist of a PPI, metronidazole, bismuth subsalicylate, and tetracycline.78-80 Alternatively, patients who do not respond to the initial treatment course may be referred to a gastroenterologist for further workup.
It is recommended that patients who do not respond to an initial and a secondary course of anti–H pylori therapy be referred to a gastroenterologist. These patients often require endoscopy with biopsy and culture for the determination of antibiotic resistance. Further therapy would then be based on the resistance patterns detected.
SUMMARY AND RECOMMENDATIONS
Helicobacter pylori is a ubiquitous organism that is associated with histological gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and an increased risk of gastric adenocarcinoma. Studies have documented that cure of the infection is associated with ulcer healing, symptom resolution, and cure of the H pylori–related ulcer disease. Cure of H pylori infection reduces the morbidity associated with ulcer disease, conserves health care resources, and frequently eliminates the need for maintenance antisecretory drug therapy. Figure 1, Figure 2, and Figure 3 are proposed to aid physicians in caring for patients with a newly diagnosed ulcer, a previous history of peptic ulcer disease, and dyspepsia, respectively.
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Figure 1. Patients with a diagnosis of new ulcer. The diagnosis of Helicobacter pylori infection should be made using the rapid urease test in those undergoing endoscopy and blood antibody testing in those undergoing an upper gastrointestinal tract series. Negative H pylori test results should be confirmed using nonendoscopic methods. Patients with positive H pylori test results should be treated with 10 to 14 days of a twice-daily regimen that includes a proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC), clarithromycin, and amoxicillin or metronidazole. Patients with ulcer who are negative for H pylori should be treated with 4 to 6 weeks of a PPI or a histamine2 receptor antagonist (H2RA). *, Nonendoscopic methods for active infection include urea breath test (UBT) and stool antigen detection. The UBT should be performed only after use of antisecretory agents has been discontinued for at least 2 weeks and use of antimicrobial agents and bismuth has been discontinued for at least 4 weeks. Stool detection should be performed at least 4 weeks after H pylori eradiction therapy. Clinicians should keep in mind the potential for false-positive results with this test in patients who have completed a course of anti–H pylori treatment.  , Patients who do not respond to a first course of therapy with a PPI or RBC, clarithromycin, and amoxicillin should be retreated with a PPI, metronidazole, bismuth subsalicylate, and tetracycline. Those who continue to have positiveH pylori test results after 2 courses of anti–H pylori treatment should be referred to a gastroenterologist.  , Patients with complicated ulcer disease who are positive for H pylori (by blood antibody testing or rapid urease test) should be treated for their infection followed by 6 weeks of antisecretory drug therapy. Cure of the infection should be assessed using the UBT 2 weeks after completion of the antisecretory agent therapy or by stool antigen testing.
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Figure 2. Patients with previous uncomplicated ulcer disease currently receiving maintenance antisecretory agents. Determination of Helicobacter pylori status in these patients should be made using blood antibody testing. Patients who are positive for H pylori should be treated with 10 to 14 days of a twice-daily regimen that includes a proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC), clarithromycin, and amoxicillin or metronidazole. Patients who are negative for H pylori can stop taking maintenance antisecretory agents provided that a history of uncomplicated peptic ulcer disease was the sole reason for its use. Items listed with an asterisk and dagger are explained in the legend to Figure 1.
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Figure 3. Patients with dyspepsia. These patients should be treated according to their age and presenting symptoms. Those older than 50 years and those of any age with alarm symptoms should undergo endoscopy. Patients 50 years or younger and without alarm symptoms should be evaluated for Helicobacter pylori infection using blood antibody testing. Patients who are positive for H pylori should be treated with 10 to 14 days of a twice-daily regimen that includes a proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC), clarithromycin, and amoxicillin or metronidazole. Items listed with an asterisk and dagger are explained in the legend to Figure 1. GERD indicates gastroesophageal reflux disease.
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Patients with confirmed ulcer disease should be evaluated for H pylori infection. Nonendoscopic testing for H pylori infection is also recommended for individuals 50 years and younger with symptoms suggestive of ulcer disease and without alarm symptoms suggestive of malignancy. Other subgroups of individuals might also warrant H pylori evaluation. The method of H pylori detection depends on the patient's clinical presentation. Regardless of how or why they were diagnosed, patients who are positive for H pylori should be offered treatment with an effective anti–H pylori regimen. After treatment, patients with documented ulcer disease warrant follow-up evaluation of their posttreatment H pylori status.
AUTHOR INFORMATION
Accepted for publication September 15, 1999.
This work was supported by an unrestricted educational grant from TAP Pharmaceuticals Inc, Deerfield, Ill.
Corresponding author: Walter L. Peterson, MD, Veterans Affairs Medical Center (111 B-1), 4500 S Lancaster Rd, Dallas, TX 75216.
From the Medical Service, Dallas VA Medical Center, and the Department of Medicine, University of Texas Southwestern Medical School at Dallas (Dr Peterson); the Departments of Internal Medicine and Health Management and Policy, University of Michigan, Ann Arbor (Dr Fendrick); the Department of Medicine, Tufts University Medical School, Boston, Mass (Dr Cave); Department of Medicine, University of Virginia, Charlottesville (Dr Peura); and the Department of Clinical Pharmacy Practice (Dr Garabedian-Ruffalo) and the School of Medicine, Department of Medicine (Dr Laine), University of Southern California, Los Angeles.
REFERENCES
| |
1. Parsonnet J. Helicobacter pylori and gastric cancer. Gastroenterol Clin North Am. 1993;22:89-104.
ISI
| PUBMED
2. National Institutes of Health. Helicobacter pylori in peptic ulcer disease. NIH Consens Statement. 1994;12:1-23.
3. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311-1315.
FULL TEXT
|
ISI
| PUBMED
4. Kuipers EJ, Thijs JC, Festen HPM. The prevalence of Helicobacter pylori in peptic ulcer disease. Aliment Pharmacol Ther. 1995;9(suppl 2):59-69.
5. Laine I, Hopkins RJ, Girardi LS. Has the impact of Helicobacter pylori therapy on ulcer recurrence in the United States been overstated? a meta-analysis of rigorously designed trials. Am J Gastroenterol. 1998;93:1409-1415.
ISI
| PUBMED
6. Valle J, Kekki M, Sipponen P, Ihamaki T, Siurala M. Long-term course and consequences of Helicobacter pylori gastritis. Scand J Gastroenterol. 1996;31:546-550.
ISI
| PUBMED
7. Forman D, Webb P, Parsonnett J. Helicobacter pylori and gastric cancer. Lancet. 1994;343:243-244.
FULL TEXT
|
ISI
| PUBMED
8. Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325:1127-1131.
ABSTRACT
9. Nomura A, Stemmermann GN, Chyou P, et al. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991;325:1132-1136.
ABSTRACT
10. Infection with Helicobacter pylori. In: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Schistosomes, Liver Flukes and Helicobacter pylori: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol 61. Lyon, France: International Agency for Research on Cancer; 1994:177-240.
11. Sonnenberg A, Everhart JE. Health impact of peptic ulcer in the United States. Am J Gastroenterol. 1997;92:614-620.
ISI
| PUBMED
12. Imperiale TF, Speroff T, Cebul RD, McCullough AJ. A cost analysis of alternative treatments for duodenal ulcer. Ann Intern Med. 1995;123:665-672.
FREE FULL TEXT
13. Vakil N, Fennerty B. The economics of eradicating Helicobacter pylori infection in duodenal ulcer disease. Am J Med. 1996;100(suppl 5A):60-63.
14. Tytgat GNJ, Noach IA, Rauws EAJ. Helicobacter pylori infection and duodenal ulcer disease. Gastroenterol Clin North Am. 1993;22:127-140.
ISI
| PUBMED
15. Laine L. Helicobacter pylori and complicated ulcer disease. Am J Med. 1996;100(suppl):52S-59S.
16. Bayerdorffer E, Neubauer A, Rudolph B, et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet. 1995;345:1591-1594.
FULL TEXT
|
ISI
| PUBMED
17. Sonneberg A, Townsend WF. Costs of duodenal ulcer therapy with antibiotics. Arch Intern Med. 1995;155:922-928.
FREE FULL TEXT
18. O'Brien B, Goeree R, Mohamed H, Hunt R. Cost-effectiveness of Helicobacter pylori eradication for the long-term management of duodenal ulcer in Canada. Arch Intern Med. 1995;155:1958-1964.
FREE FULL TEXT
19. Unge P, Jonsson B, Stalhammar N-O. The cost-effectiveness of Helicobacter pylori eradication versus maintenance and episodic treatment in duodenal ulcer patients in Sweden. Pharmacoeconomics. 1995;8:410-427.
ISI
| PUBMED
20. Fendrick AM, McCort JT, Chernew ME, Hirth RA, Patel C, Bloom BS. Immediate eradication of Helicobacter pylori in patients with previously documented peptic ulcer disease: clinical and economic effects. Am J Gastroenterol. 1997;11:2017-2024.
21. Ofman JJ, Etchason J, Fullerton S, Kahn KL, Soll AH. Management strategies for Helicobacter pylori–seropositive patients with dyspepsia: clinical and economic consequences. Ann Intern Med. 1997;126:280-291.
FREE FULL TEXT
22. Silverstein MD, Petterson T, Talley N. Initial endoscopy or empirical therapy with or without testing for Helicobacter pylori for dyspepsia: a decision analysis. Gastroenterology. 1996;110:72-83.
FULL TEXT
|
ISI
| PUBMED
23. Fendrick AM, Chernew ME, Hirth RA, Bloom BS. Alternative management strategies for patients with suspected peptic ulcer disease. Ann Intern Med. 1995;123:260-268.
FREE FULL TEXT
24. Steinbach G, Ford R, Glober G, et al. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999;131:88-95.
FREE FULL TEXT
25. Wotherspoon AC, Doglioni C, Diss TC, et al. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993;342:575-577.
FULL TEXT
|
ISI
| PUBMED
26. Weber DM, Dimopoulos MA, Anandu DP, Pugh WC, Steinbach G. Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori. Gastroenterology. 1994;107:1835-1838.
ISI
| PUBMED
27. Roggero E, Zucca E, Pinotti G, et al. Eradication of Helicobacter pylori infection in primary low-grade gastric lymphoma of mucosa-associated lymphoid tissue. Ann Intern Med. 1995;122:767-769.
FREE FULL TEXT
28. Blecker U, McKeithan TW, Hart J, Kirschner BS. Resolution of Helicobacter pylori–associated gastric lymphoproliferative disease in a child. Gastroenterology. 1995;109:973-977.
FULL TEXT
|
ISI
| PUBMED
29. Montalban C, Manzanal A, Boixeda D, et al. Helicobacter pylori eradication for the treatment of low-grade gastric MALT lymphoma: follow-up together with sequential molecular studies. Ann Oncol. 1997;8(suppl 2):37-39.
30. Neubauer A, Thiede C, Morgner A, et al. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst. 1997;89:1350-1355.
FREE FULL TEXT
31. Parsonnet J, Harris RA, Hack HM, Owens DK. Modeling cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer: a mandate for clinical trials. Lancet. 1996;348:150-154.
FULL TEXT
|
ISI
| PUBMED
32. Fendrick AM, Chernew ME, Hirth RA, Bloom BS, Bandekar RR, Scheiman JM. Clinical and economic effects of H. pylori screening to prevent gastric cancer. Arch Intern Med. 1999;159:142-148.
FREE FULL TEXT
33. Genta RM, Graham DY. Comparison of biopsy sites for the histopathological diagnosis of Helicobacter pylori: a topographic study of H. pylori density and distribution. Gastrointest Endosc. 1994;40:342-345.
ISI
| PUBMED
34. Genta RM, Robason GO, Graham DY. Simultaneous visualization of Helicobacter pylori and gastric morphology: a new stain. Hum Pathol. 1994;25:221-226.
FULL TEXT
|
ISI
| PUBMED
35. Laine L, Lewin DN, Naritoku W, Estrada R, Cohen H. Prospective comparison of commercially available rapid urease tests for the diagnosis of Helicobacter pylori. Gastrointest Endosc. 1996;44:523-526.
FULL TEXT
|
ISI
| PUBMED
36. Graham DY, Genta R, Evans DG, et al. Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole. Am J Gastroenterol. 1996;91:2120-2124.
ISI
| PUBMED
37. Laine L, Estrada R, Trujillo M, Knigge K, Fennerty MB. Effect of proton-pump inhibitor therapy on diagnostic testing for Helicobacter pylori. Ann Intern Med. 1998;129:547-550.
FREE FULL TEXT
38. Chey WD, Woods M, Scheiman JM, Nostrant TT, DelValle J. Lansoprazole and ranitidine affect the accuracy of the 14C-urea breath test by a pH-dependent mechanism. Am J Gastroenterol. 1997;92:446-450.
ISI
| PUBMED
39. Chey WD, Spybrook M, Carpenter S, Nostrant TT, Elta GH, Scheiman JM. Prolonged effect of omeprazole on the 14C-urea breath test. Am J Gastroenterol. 1996;91:89-92.
ISI
| PUBMED
40. McGowan CC, Cover TL, Blaser MJ. The proton pump inhibitor omeprazole inhibits acid survival of Helicobacter pylori by a urease-independent mechanism. Gastroenterology. 1994;107:1573-1578.
PUBMED
41. Cohen H, Laine L. Endoscopic methods for the diagnosis of H. pylori. Aliment Pharmacol Ther. 1997;11(suppl 1):3-9.
42. Vaira D, Malfertheiner P, Megraud F, et al. Diagnosis of Helicobacter pylori infection with a new non-invasive antigen-based assay: multicentre study. Lancet. 1999;354:30-33.
FULL TEXT
|
ISI
| PUBMED
43. Ormand JE, Talley JF, Carpenter HA, et al. C-urea breath test for diagnosis of Helicobacter pylori. Dig Dis Sci. 1990;35:879-884.
FULL TEXT
|
ISI
| PUBMED
44. Cutler AF, Havstad S, Ma CK, Blaser MJ, Perez-Perez GI, Schubert TT. Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection. Gastroenterology. 1995;109:136-141.
FULL TEXT
|
ISI
| PUBMED
45. Marchildon PA, Ciota LM, Zamaniyan FZ, Peacock JS, Graham DY. Evaluation of three commercial enzyme immunoassays compared with the C urea breath test for detection of Helicobacter pylori infection. J Clin Microbiol. 1996;34:1147-1152.
ABSTRACT
46. Perri F, Maes B, Geypens B, et al. The influence of isolated doses of drugs, feeding and colonic bacterial ureolysis on urea breath test results. Aliment Pharmacol Ther. 1995;9:705-709.
ISI
| PUBMED
47. Savarino V, Bisso G, Pivari M, et al. Effect of omeprazole and ranitidine on the accuracy of 13C-urea breath test (UBT) [abstract]. Gut. 1998;43(suppl 2):A51.
48. Makristathis A, Pasching E, Schutze K, et al. Detection of Helicobacter pylori in stool specimens by PCR and antigen enzyme immunoassay. J Clin Microbiol. 1998;36:2772-2774.
FREE FULL TEXT
49. Trevisani L, Sartori S, Galvani F, et al. Evaluation of a new enzyme immunoassay for detecting Helicobacter pylori in feces: a prospective pilot study. Am J Gastroenterol. 1999;94:1830-1833.
FULL TEXT
|
ISI
| PUBMED
50. Calvet X, Feu F, Forne M, et al. The evaluation of a new immunoenzyme analysis for the detection of Helicobacter pylori infection in stool samples. Gastroenterol Hepatol. 1999;22:270-272.
PUBMED
51. Goddard AF, Spiller RC. The effect of omeprazole on gastric juice viscosity, pH, and bacterial counts. Aliment Pharmacol Ther. 1996;10:105-109.
ISI
| PUBMED
52. Unge P, Gad A, Gnarpe H, Olsson J. Does omeprazole improve antimicrobial therapy directed towards Campylobacter pylori in patients with antral gastritis? Scand J Gastroenterol. 1989;167:49-54.
53. Hosking SW, Ling TKW, Chung SCS, et al. Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomized controlled trial. Lancet. 1994;343:508-510.
FULL TEXT
|
ISI
| PUBMED
54. Lam SK, Ching CK, Lai KC, et al. Does treatment of Helicobacter pylori (Hp) with antibiotics alone heal duodenal ulcer (DU)? a randomized double-blind placebo controlled study. Gut. 1997;41:43-48.
FREE FULL TEXT
55. Laine L, Estrada R, Trujillo M, Fukanaga K, Neil G. Randomized comparison of differing periods of twice-a-day triple therapy for the eradication of Helicobacter pylori. Aliment Pharmacol Ther. 1996;10:1029-1033.
FULL TEXT
|
ISI
| PUBMED
56. Yousfi MM, El-Zimaity HMT, Al-Assi MT, Cole RA, Genta RM, Graham DY. Metronidazole, omeprazole, and clarithromycin: an effective combination therapy for Helicobacter pylori infection. Aliment Pharmacol Ther. 1995;9:209-212.
ISI
| PUBMED
57. Laine L, Estrada R, Trujillo M, Emami S. Randomized comparison of ranitidine bismuth citrate–based triple therapies for Helicobacter pylori. Am J Gastroenterol. 1997;92:2213-2215.
ISI
| PUBMED
58. Soll AH for the Practice Parameters Committee of the American College of Gastroenterology. Medical treatment of peptic ulcer disease: practice guidelines. JAMA. 1996;275:622-629.
FREE FULL TEXT
59. Van der Hulst RWM, Keller JJ, Rauws EAJ, Tytgat GNJ. Treatment of Helicobacter pylori infection: a review of the world literature. Helicobacter. 1996;1:6-19.
PUBMED
60. Peura DA. The report of the Digestive Health Initiative International Update Conference on Helicobacter pylori. Gastroenterology. 1997;113(suppl):S4-S8.
61. Helidac [package insert]. Norwich, NY: Procter & Gamble.
62. de Boer WA, Driessen WMM, Jansz AR, et al. Effect of acid suppression on efficacy of treatment for Helicobacter pylori infection. Lancet. 1995;345:817-820.
FULL TEXT
|
ISI
| PUBMED
63. Borody TJ, Andrews P, Fracchia G, et al. Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori. Gut. 1995;37:477-481.
FREE FULL TEXT
64. Lind T, Veldhuyzen van Zanten SJO, Unge P, et al. Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH-1 Study. Helicobacter. 1996;1:138-144.
PUBMED
65. Misiewicz JJ, Harris AW, Bardham KD, et al. One week triple therapy for Helicobacter pylori: a multicentre comparative study. Gut. 1997;41:735-739.
FREE FULL TEXT
66. Laine L, Malone T, Boechenek W, Wang W. Current US rates of H. pylori antibiotic resistance and factors predicting resistance: results from ongoing trials at 77 sites [abstract]. Gastroenterology. 1999;116:A228.
67. Riff DS, Kidd S, Rose P, Haber M, Weissfeld Siepman N. Triple therapy with lansoprazole, clarithromycin, and amoxicillin for the cure of Helicobacter pylori infection: a short report. Helicobacter. 1996;1:238-242.
PUBMED
68. Lamouliatte H, Cayla R, Zerbib F, Talbi P, Megraud F, de Mascarel A. Triple therapy with PPI-amoxicillin-clarithromycin for H. pylori eradication: the optimal regimen in 1996 [abstract]. Gastroenterology. 1996;110:A171.
69. Weissfeld AS, Simmons DE, Vance PH, Trevino E, Kidd S, Greski-Rose P. In vitro susceptibility of pre-treatment isolates of Helicobacter pylori from two multicenter United States clinical trials. Gastroenterology. 1996;110:A295.
70. Hopkins RJ, Girardi LS, Turney EA. Relationship between Helicobacter pylori eradication and reduced duodenal and gastric ulcer recurrence: a review. Gastroenterology. 1996;110:1244-1252.
FULL TEXT
|
ISI
| PUBMED
71. Vakil N, Hahn B, McSorley D. Recurrent symptoms and gastro-esophageal reflux disease in patients with duodenal ulcer treated for Helicobacter pylori infection. Aliment Pharmacol Ther. 2000;14:45-51.
FULL TEXT
|
ISI
| PUBMED
72. Phull PS, Halliday D, Price AB, Jacyna MR. Absence of dyspeptic symptoms as a test for Helicobacter pylori eradication. BMJ. 1996;312:349-350.
FREE FULL TEXT
73. Klein PD, Graham DY. Minimum analysis requirements for the detection of Helicobacter pylori infection by the 13C-urea breath test. Am J Gastroenterol. 1993;88:1865-1969.
ISI
| PUBMED
74. Van de Wouw BAM, de Boer WA, Hermsen HWEM, Valkenburg JGM, Geuskens LM, Tytgat GNJ. Usefulness of the 14C-urea breath test as a semi-quantitative monitoring instrument after therapy for Helicobacter pylori infection. Scand J Gastroenterol. 1997;32:112-117.
PUBMED
75. Kousunen TU, Seppala K, Sarna S, Sipponen P. Diagnostic value of decreasing IgG, IgA, and IgM antibody titres after eradication of Helicobacter pylori. Lancet. 1992;339:893-895.
FULL TEXT
|
ISI
| PUBMED
76. Feldman M, Cryer B, Lee E, Peterson WL. Role of seroconversion in confirming cure of Helicobacter pylori infection. JAMA. 1998;280:363-365.
FREE FULL TEXT
77. Fendrick AM, Chey WD, Magaret N, Palaniappan J, Fennerty MB. Symptom status and the desire for Helicobacter pylori confirmatory testing after eradication therapy in patients with peptic ulcer disease. Am J Med. 1999;107:133-136.
FULL TEXT
|
ISI
| PUBMED
78. The European Helicobacter pylori Study Group (EHPSG). Current European concepts in the management of Helicobacter pylori infection: the Maastricht Consensus Report. Gut. 1997;41:8-13.
FREE FULL TEXT
79. Chiba N, Hunt RH. Bismuth, metronidazole and tetracycline (BMT) acid suppression in H. pylori eradication: a meta-analysis [abstract]. Gut. 1996;39(suppl 2):A36.
80. de Boer WA. How to achieve a near 100% cure rate for H pylori infection in peptic ulcer patients: a personal viewpoint. J Clin Gastroenterol. 1996;22:313-316.
FULL TEXT
|
ISI
| PUBMED
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