Helicobacter pylori-related disease: guidelines for testing and treatment.

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. Non-endoscopic 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.

Review article: Helicobacter pylori and gastric adenocarcinoma.

Gastric adenocarcinoma is still the second most common cause of death from cancer, even though it is on the decline in developed countries. Although H. pylori gastritis appears to be a necessary antecedent to the development of gastric adenocarcinoma, it is not a sufficient factor in and of itself. Other required factors for the progression of this disease are poorly understood. Patients with antral predominant gastritis seem protected from the disease, while patients with pangastritis are predisposed to both diffuse- and intestinal-type adenocarcinoma. Development of a vaccine against H. pylori might yield promising results in decreasing the incidence of gastric adenocarcinoma.

The role of acid in upper gastrointestinal haemorrhage due to ulcer and stress-related mucosal damage.

A peptic ulcer is a lesion in which acid and pepsin are essential components of pathogenesis. Regardless of the type of patient or the setting in which the ulcer presents, the basic pathogenetic scheme is the same. The primary event is disruption of mucosal integrity. In the presence of acid and pepsin, such disruption of integrity leads to an ulcer. While rarely sufficient by itself to cause ulceration, the presence of acid is a necessary cofactor. The causes of disruption of mucosal integrity include nonsteroidal anti-inflammatory drugs (NSAIDs), Helicobacter pylori and critical illness. With the latter, tissue ischaemia may be the primary event, leading to back-diffusion of H+ ions through increased membrane permeability. Impaired mucosal buffering then leads to intramural acidosis and cell death. Risk factors for bleeding peptic ulcer in the intensive care unit (ICU) include severe trauma, sepsis, respiratory failure, and coagulopathy. Potential roles for decreasing gastric acidity in the treatment of bleeding peptic ulcer include cessation of active bleeding, prevention of rebleeding in hospital and primary prevention of bleeding. Most published studies dealing with the first two situations suggest no benefit with antisecretory therapy. However, the optimal pH for clot and platelet function may be > or = 7.0. Can such pH levels be maintained with antisecretory agents such as the proton pump inhibitors? Are the published trials adequate to demonstrate any benefit from antisecretory agents? Primary prevention of bleeding ulcer in the outpatient setting includes avoidance of NSAIDs, use of antisecretory agents and eradication of H. pylori.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of antisecretory drugs in the treatment of Helicobacter pylori infection.

The efficacy of antibiotics against Helicobacter pylori is enhanced by the co-administration of antisecretory drugs. While proton pump inhibitors appear to have some direct effect on H. pylori and extreme hypochlorhydria has a deleterious effect on the organism, the most likely mechanism by which antisecretory drugs as a class provide this effect is by improving the efficacy of the antibiotics themselves. Although proton pump inhibitors are the most widely used antisecretory agents, H2 receptor antagonists also enhance antibiotic effects.

Gastrin and acid in relation to Helicobacter pylori.

H. pylori infection, both in normal healthy subjects and patients with duodenal ulcer, results in modest elevations of serum gastrin concentrations in the fasting state and quite substantial elevations after a meal or gastrin releasing peptide (GRP) stimulation. Cure of the infection leads to normalization of gastrin homeostasis. Acid secretion in response to a submaximal infusion of GRP is three-fold higher in H. pylori-infected normal subjects and six-fold higher in DU patients than in non-infected controls. These changes also normalize after cure of the infection. H. pylori infection appears to lead to increased basal acid output in some patients with duodenal ulcer while effects on peak acid output to pentagastrin remain under debate. With the possible exception of peak acid output, the abnormalities of gastrin and acid secretion reported for patients with duodenal ulcer are largely a result of infection with H. pylori.

Review article: the management of Giardiasis.

Giardiasis is the intestinal infection resulting from infestation with the human parasite Giardia intestinalis, also called Giardia lamblia. The infection may be asymptomatic or present with a variety of symptoms such as diarrhoea, weight loss, abdominal cramps, and failure to thrive. Giardiasis is most often diagnosed after recent travel or in day care centres. The organism has two stages in its life cycle. It is usually ingested as a cyst with as few as 10-25 cysts being sufficient to cause infection. After excystation, the organism is a replicative trophozoite which may attach to the small bowel wall. Giardia intestinalis does not invade the bowel wall. Trophozoites may encyst and be shed in faeces for future ingestion by another host. Diagnosis of infection is by stool examination which may also eliminate other possible infectious agents. Small bowel biopsy may be necessary in difficult individual cases or to rule out non-infectious illnesses, and stool ELISA may serve for large population screening examinations. The mainstay of treatment is metronidazole 250-400 mg three times per day by mouth for 5 days.

Eradication of Helicobacter pylori infection after ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days.

BACKGROUND: We assessed the efficacy, tolerance, and compliance of twice-daily triple therapy for Helicobacter pylori with ranitidine bismuth citrate, metronidazole and tetracycline for 7 or 10 days. METHODS: 105 subjects with H. pylori infection documented by the 13C-urea breath test were randomly assigned to a 7 or 10-day course of ranitidine bismuth citrate 400 mg b.d., metronidazole 500 mg b.d. and tetracycline 500 mg b.d. Subjects returned at the end of therapy for assessment of side-effects and pill count. A repeat 13C-urea breath test was obtained 4 or more weeks after completion of therapy and cure of infection was defined as a negative test result. RESULTS: Poor compliance (< 80% of medications) was seen in 2% of subjects randomized to 7 days of therapy and in 10% randomized to 10 days of therapy (P = N.S.). Intention-to-treat eradication rates were 56% for 7-day and 60% for 10-day therapy (P = N.S.). Per protocol eradication rates were 58% for 7-day and 61% for 10-day therapy (P = N.S.). The 10-day intention-to-treat eradication rate for males was 78% and 32% for females (P < 0.01) and per protocol eradication rates were 79% and 31%, respectively (P < 0.01). CONCLUSIONS: Despite excellent compliance and tolerance, neither 7 nor 10 days of therapy with twice-daily ranitidine bismuth citrate, metronidazole and tetracycline are adequate as a treatment of H. pylori infection.

Ranitidine bismuth citrate plus clarithromycin is effective for healing duodenal ulcers, eradicating H. pylori and reducing ulcer recurrence. RBC H. pylori Study Group.

AIM: To compare the efficacy of the coadministration of ranitidine bismuth citrate plus the antibiotic clarithromycin, with ranitidine bismuth citrate alone or clarithromycin alone for the healing of duodenal ulcers, eradication of H. pylori and the reduction of ulcer recurrence. METHODS: This two-phase, randomized, double-blind, placebo-controlled, multicentre study consisted of a 4-week treatment phase followed by a 24-week post-treatment observation phase. Patients with an active duodenal ulcer were treated with either ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; ranitidine bismuth citrate 400 mg b.d. for 4 weeks plus placebo t.d.s. for first 2 weeks; placebo b.d. for 4 weeks plus clarithromycin 500 mg t.d.s. for the first 2 weeks; or placebo b.d. for 4 weeks plus placebo t.d.s. for the first 2 weeks. RESULTS: Ulcer healing rates after 4 weeks of treatment were highest with ranitidine bismuth citrate plus clarithromycin (82%) followed by ranitidine bismuth citrate alone (74%; P = 0.373), clarithromycin alone (73%; P = 0.33) and placebo (52%; P = 0.007). Ranitidine bismuth citrate plus clarithromycin provided significantly better ulcer symptom relief compared with clarithromycin alone or placebo (P < 0.05). The coadministration of ranitidine bismuth citrate plus clarithromycin resulted in significantly higher H. pylori eradication rates 4 weeks post-treatment (82%) than did treatment with either ranitidine bismuth citrate alone (0%; P < 0.001), clarithromycin alone (36%; P = 0.008) or placebo (0%; P < 0.001). Ulcer recurrence rates 24 weeks post-treatment were lower following treatment with ranitidine bismuth citrate plus clarithromycin (21%) compared with ranitidine bismuth citrate alone (86%; P < 0.001), clarithromycin alone (40%; P = 0.062) or placebo (88%; P = 0.006). All treatments were well tolerated. CONCLUSIONS: The coadministration of ranitidine bismuth citrate plus clarithromycin is a simple, well-tolerated and effective treatment for active H. pylori-associated duodenal ulcer disease. This treatment regimen effectively heals duodenal ulcers, provides effective symptom relief, eradicates H. pylori infection and reduces the rate of ulcer recurrence. The eradication of H. pylori infection in patients with recently healed duodenal ulcers is associated with a significant reduction in the rate of ulcer recurrence.

Daily omeprazole surpasses intermittent dosing in preventing relapse of oesophagitis: a US multi-centre double-blind study.

INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing. AIM: To assess the potential of different therapeutic regimens of omeprazole to prevent relapse of erosive reflux oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS: Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I) were eligible to join a multi-centre, 6-month double-blind, placebo-controlled maintenance study (phase II), which included endoscopy, symptom assessments, serum gastrin measurements, and gastric fundic biopsies. During phase I, endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472 patients (91%) were healed, and there were significant reductions in heartburn, dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined phase II and were randomized to one of three groups: 20 mg omeprazole daily (n = 138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at symptomatic relapse. RESULTS: The percentages of patients still in endoscopic remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and 70% for omeprazole daily. Both omeprazole regimens were superior to placebo in preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline, omeprazole therapy resulted in no significant differences among treatment groups in the distribution of gastric endocrine cells. CONCLUSIONS: These results show that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of patients with a maintenance regimen of 20 mg daily, but that intermittent dosing comprising 3 consecutive days each week significantly compromises efficacy.

Oral cholecystography in the early phase of acute alcoholic pancreatitis. A prospective, randomized comparison of Telepaque and Bilopaque.

Biliary tract disease is a major cause of acute pancreatitis. However, with traditionally employed Telepaque, radiographic visualization of the gallbladder during acute pancreatitis remains unreliable, even in patients with apparently normal gallbladders. Therefore, oral cholecystography has customarily been deferred for such patients for several weeks. Recently, successful oral cholecystography has been described during the acute episode of pancreatitis, using Bilopaque, a more water-soluble cholecystopaque. The relative intestinal absorption of Telepaque and Bilopaque and the ability of these agents to produce diagnostic oral cholecystograms of fasting patients with acute alcoholic pancreatitis were compared. Forty-five hospitalized patients were studied within 96 hours of admission. Mean peak plasma contrast concentrations for Bilopaque exceeded those for Telepaque. Thirty-one percent of the Bilopaque group achieved diagnostic single-dose oral cholecystograms, compared with to 11% of the Telepaque group (P less than 0.05).

Obscure gastrointestinal bleeding.

Modern diagnostic techniques have led to increased accuracy in the diagnosis of gastrointestinal bleeding. Occasionally, however, the source of bleeding remains obscure. A careful, step-wise approach, is required to provide a diagnosis in these cases.

Perspectives on training in gastroenterology.

Training in endoscopy has changed dramatically during the past 20 years and will probably change even more over the next 10 years. To confront these changes more effectively, the leaders of the four major digestive disease societies, collectively known as the Gastroenterology Leadership Council (GLC), encouraged the formation of a training director's committee. This article discusses several of the issues that the GLC Training Directors Committee has dealt with.

Evaluation and initial management of patients with upper gastrointestinal bleeding.

Evaluation and initial management of a patient with gastrointestinal (GI) bleeding progresses in stepwise fashion, beginning with assessment of the severity of bleeding. For this, the hematocrit must be considered in conjunction with factors reflecting vascular volume such as blood pressure and heart rate. Resuscitation to maintain tissue oxygenation should than be instituted with intravenous fluids and blood products in amounts appropriate to the severity of hemorrhage. Vital signs are monitored carefully. During resuscitation, attention is directed to determining whether bleeding comes from the upper or lower GI tract. If upper GI bleeding has been proven, gastric lavage is performed through a large-bore orogastric tube using copious quantities of fluid. Empiric therapy for upper GI bleeding, usually aimed at reducing gastric acidity, may be instituted as decisions regarding diagnostic techniques are considered. Endoscopy is a more accurate diagnostic tool than barium x-rays and can be performed in all but massively bleeding patients. There is overwhelming evidence, however, that, at least in patients who cease bleeding during resuscitation, endoscopy does not alter outcome. Since endoscopy is expensive, it should be reserved for selected patients in whom a specific diagnosis will dictate an important change in therapy.

The influence of food, beverages and NSAIDs on gastric acid secretion and mucosal integrity.

Gastric acid secretion is stimulated by all foods, especially proteins, and many beverages, the most potent beverages are milk and fermented substances such as beer and wine. The effects of food on mucosal integrity have been little studied, whereas non-steroidal anti-inflammatory drugs are well known to induce tissue injury.

Pathogenesis and therapy of peptic ulcer disease.

The epithelial cells of the stomach and duodenum are normally protected from the damaging effects of acid and pepsin by a balancing mechanism of mucosal resistance. If an imbalance occurs, peptic ulcer may result. Traditional teaching has emphasized the importance of acid (and pepsin) as the cause of this imbalance; however, it is clear that acid and pepsin are not the only important factors in the pathogenesis of peptic ulcer. More recent investigative efforts have been directed at what constitutes mucosal resistance and how it can be disrupted to produce, in the presence of gastric acid, a peptic ulcer. Depletion of endogenous prostaglandins and Helicobacter pylori gastritis have emerged as prominent theories. As evidence exists both to support and refute these theories in humans, any definitive conclusions cannot be made at this time. The acute management of peptic ulcer disease is directed at relieving pain, accelerating ulcer healing, and preventing complications. Peptic ulcers can be healed with antisecretory agents (i.e., H2-receptor antagonists, omeprazole), antacids, prostaglandins, and sucralfate. Because they are effective, safe, and convenient, the H2-receptor antagonists are the most widely used agents for the management of peptic ulcer disease. Because the H2-receptor antagonist agents are equally effective in their indicated uses and are equally safe based on scientifically valid data, selection should be based primarily on cost. Omeprazole is the newest antisecretory agent: a single morning dose of 20 mg suppresses acid secretion for 24 h. The agent offers little advantage over H2-receptor antagonists for the majority of patients with peptic ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleeding peptic ulcer. Epidemiology and nonsurgical management.

Bleeding peptic ulcer remains an important problem, particularly for the elderly. Recognition of the rule of nonsteroidal anti-inflammatories in bleeding ulcer and employment of endoscopic therapeutic modalities offer promise that morbidity and mortality from bleeding ulcer may be reduced.

Peptic ulcer--an infectious disease?

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143.

Helicobacter pylori and peptic ulcer disease.

Medical therapy for duodenal or gastric ulcer disease has traditionally involved gastric acid antisecretory therapy for 4 to 8 weeks to promote initial healing and indefinitely to prevent recurrences of ulcer. The discovery of Helicobacter pylori in most patients with peptic ulcer disease has led to a change in this approach. Therapy designed to eradicate H pylori may facilitate ulcer healing with acid antisecretory agents and, more important, may greatly reduce the incidence of ulcer recurrence, obviating the need for maintenance antisecretory therapy. Regimens designed to eradicate H pylori are difficult to comply with, however, and are associated with adverse effects in some patients. In this article we review the diagnosis and treatment of H pylori infection in patients with peptic ulcer disease and make recommendations regarding the use of conventional ulcer therapies and therapies designed to eradicate H pylori.

Injection sclerotherapy as a cause of Klebsiella pneumoniae peritonitis.

We report a case of Klebsiella pneumoniae peritonitis after endoscopic sclerotherapy and discuss its pathogenesis and risk factors. We also review previous cases in the literature and make recommendations for prophylactic therapy. Endoscopists should be aware of peritonitis as a possible complication of endoscopic sclerotherapy.