Walter L. Peterson

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.

Routine Early Endoscopy in Upper-Gastrointestinal-Tract Bleeding: A Randomized, Controlled Trial

To determine whether routine early endoscopy is beneficial to patients with upper-gastrointestinal-tract bleeding that ceases during hospitalization, we randomly assigned 206 patients to routine endoscopy (100 patients) or no routine endoscopy (106). Patients in the latter group underwent endoscopy only if recurrent bleeding occurred during hospitalization or if x-ray films disclosed gastric ulcer or suggested neoplasia. All patients were initially treated with an empiric antacid regimen. When the two groups were compared (experimental versus control), there were no significant differences in overall hospital deaths (11 versus eight), recurrence of bleeding (33 versus 32), number of transfusions required to treat recurrent bleeding (mean +/- S.E.M., 7.4 +/- 1.2 versus 6.3 +/- 0.7 units), deaths after recurrent bleeding (eight versus five), or duration of hospital stay. During the 12 months after discharge, there were also no significant differences in frequency of readmission to the hospital, incidence of further gastrointestinal bleeding, number of hemorrhage-related deaths, or frequency of gastrointestinal surgery. We conclude that endoscopy should not be a routine procedure in patients with upper-gastrointestinal-tract bleeding that ceases during treatment.

Healing of benign gastric ulcer with low-dose antacid or cimetidine. A double-blind, randomized, placebo-controlled trial.

We conducted a 12-week, double-blind, randomized, placebo-controlled trial to determine whether cimetidine (300 mg with meals and at bedtime) or a convenient, liquid aluminum-magnesium antacid regimen (15 ml one hour after meals and at bedtime) would expedite healing or relief of symptoms in patients with benign gastric ulcer. Of the 101 patients who completed the trial according to protocol, 32 received the antacid, 36 cimetidine, and 33 placebo. At 4, 8, and 12 weeks after entry, ulcers had healed in a larger percentage of patients treated with cimetidine than of those treated with placebo: 53, 86, and 89 per cent of the cimetidine group versus 26, 58, and 70 per cent of the placebo group (P = 0.02, 0.01, 0.05), respectively. Healing at the three intervals had occurred in 38, 70, and 84 per cent, respectively, of the antacid-treated patients. Neither cimetidine nor antacid was more effective than placebo in relieving symptoms. The presence or absence of symptoms during the fourth and eighth treatment weeks was a poor predictor of the presence of absence of an ulcer crater. We conclude that cimetidine significantly hastens the healing of benign gastric ulcer.

Effect of low-dose propantheline on food-stimulated gastric acid secretion: comparison with an "optimal effective dose" and interaction with cimetidine.

We evaluated the widely held notion that anticholinergic drugs must be used in near toxic doses to inhibit gastric acid secretion effectively. Nine patients with duodenal ulcer were studied after a low dose (15 mg) and after a near toxic dose (averaging 48 mg) of the anticholinergic, propantheline. Mean (+/- S.E.) inhibition of food-stimulated acid secretion was identical with the two doses of propantheline: 29 +/- 10 and 29 +/- 11 per cent, respectively. In addition, when 15 mg of propantheline was combined with the histamine H2-receptor antagonist, cimetidine, acid secretion was suppressed to a greater degree than with either drug alone. A low dose of propantheline is as effective as a near toxic dose in suppressing food-stimulated acid secretion and augments the inhibitory effect of cimetidine.

An evidence-based approach to gastroenterology therapy

PHILIP SCHOENFELD,* DEBORAH COOK,‡ FRANK HAMILTON,§ LOREN LAINE,6 DAVID MORGAN,¶ and WALTER PETERSON# for the EVIDENCE–BASED GASTROENTEROLOGY STEERING GROUP *Division of Gastroenterology, National Naval Medical Center, Bethesda, Maryland; ‡Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario; §Digestive Diseases Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Division of Digestive Diseases and Nutrition, Bethesda, Maryland; 6Division of Gastrointestinal and Liver Diseases, University of Southern California Medical Center, Los Angeles, California; ¶Division of Gastroenterology, McMaster University Medical Center, Hamilton, Ontario; and #University of Texas Southwestern Medical School and Medical Service, Dallas Veterans Affairs Medical Center, Dallas, Texas

Relationship between Campylobacter pylori and gastritis in healthy humans after administration of placebo or indomethacin

Endoscopic and microscopic appearances of antral and fundic mucosa were correlated with the presence or absence of Campylobacter pylori--and with plasma immunoglobulin G antibodies to that organism--in 23 healthy volunteers, 12 of whom had received indomethacin and 11 of whom had received no medication. Antral C. pylori, found in 9 of 23 biopsy specimens (3 of 11 controls, 6 of 12 indomethacin-treated patients; not significantly different), correlated strongly with histologic evidence of active superficial antral gastritis (p less than 0.005), but not with the endoscopic appearance of the antrum. In contrast to the antrum, fundic C. pylori, found in 14 of 23 biopsy specimens (61%), were frequently associated with histologically and endoscopically normal fundic mucosa. Campylobacter pylori-associated active antral gastritis occurred only in subjects whose fundus harbored this organism. Plasma immunoglobulin G antibody titers to C. pylori were highest in subjects with Campylobacter-associated antral gastritis and lowest in subjects without gastric Campylobacter. These studies suggest that healthy humans may harbor C. pylori in their proximal stomach without apparent ill effects. In some of these individuals, the organism also involves the antrum and is associated with active gastritis.

Quantitating the Occult

Physicians are faced all too frequently with middle-aged patients who present with vague abdominal problems or rectal bleeding and who on evaluation are found to have colon cancer. A discouraging p...

A Randomized Trial of Lansoprazole, Amoxycillin, and Clarithromycin versus Lansoprazole, Bismuth, Metronidazole and Tetracycline in the Retreatment of Patients Failing Initial Helicobacter pylori Therapy

Background/Aim: 10–30% of the patients treated for Helicobacter pylori fail to clear the infection after initial therapy. Little is known as to the efficacy of retreatment regimens in these patients. Proton pump inhibitor (PPI) -based triple and quadruple therapies demonstrate efficacies of 80–90% as initial therapy for H. pylori infection, but whether these regimens are as effective when used for retreatment is unknown. The efficacy of a metronidazole-containing regimen in this situation is also unknown. Our aim was to compare the efficacy of a nonmetronidazole-containing PPI-based triple versus a PPI-based quadruple therapy containing metronidazole in patients failing previous H. pylori therapy. Methods: 48 patients were enrolled in this study at two sites after failure of previous H. pylori therapy as determined by a positive 14C-urea breath test. Patients were stratified by prior treatment with a metronidazole-containing regimen and were then randomized to either lansoprazole (L) 30 mg twice daily, amoxycillin (A) 1,000 mg twice daily, and clarithromycin (C) 500 mg twice daily for 14 days (LAC) or L 30 mg four times daily, bismuth subsalicylate (B) 2 tablets four times daily, metronidazole (M) 250 mg four times daily and tetracycline (T) 250 mg four times daily for 14 days (LBMT). Side effects and compliance (pill count) were assessed at the completion of therapy. A repeat 14C-urea breath test was performed 4 or more weeks after completion of therapy, and cure was defined as a negative test result. Results: 48 patients (16 males and 32 females) were enrolled in this study. 20 patients received LAC (18 prior M), and 28 received LBMT (23 prior M). Per protocol and intention-to-treat efficacies were 82% (95% CI 64–100%) and 75% (95% CI 56–94%) for LAC and 80% (96% CI 64–96%) and 71% (95% CI 54–88%) for LBMT (p = 0.85 per protocol and p = 0.78 intention to treat between LAC and LBMT), respectively. The compliance (≧80% of pills taken) was found to be 89% in both treatment groups. Side effects were noted in 84% for LAC and in 82% for LBMT, but were mild and did not cause discontinuation of therapy. Conclusions: PPI-based triple and quadruple therapy with both LAC and LBMT are effective in retreating patients failing initial metronidazole-based H. pylori therapies. LAC was not statistically superior to LBMT as a ‘retreatment’ regimen in this clinical situation, but the small sample size and wide confidence limits do not preclude the possibility of a smaller but significant difference in efficacy between the regimens. To determine whether LAC or LBMT is as effective for retreating patients failing non-metronidazole-containing regimens requires further study.

An Evidence-Based Approach to Gastroenterology Diagnosis

PHILIP SCHOENFELD,* GORDON GUYATT,‡ FRANK HAMILTON,§ LOREN LAINE,\ DEBORAH COOK,‡ DAVID BJORKMAN,¶ DAVID MORGAN,# and WALTER PETERSON** for the EVIDENCE BASED GASTEROENTEROLOGY STEERING GROUP *Division of Gastroenterology, National Naval Medical Center, Bethesda, Maryland; ‡Department of Clinical Epidemiology and Biostatistics, McMaster University School of Medicine, Hamilton, Ontario, Canada; §Digestive Diseases Program, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; \Division of Gastrointestinal and Liver Diseases, University of Southern California School of Medicine, Los Angeles, California; ¶Division of Gastroenterology, University of Utah Medical Center, Salt Lake City, Utah; #Division of Gastroenterology, McMaster University Medical Center, Hamilton, Ontario, Canada; and **University of Texas Southwestern Medical School and Medical Service, Dallas Veterans Administration Medical Center, Dallas, Texas

Gastric adenocarcinoma masquerading endoscopically as benign gastric ulcer - A five-year experience

The pathologic features and five-year survival of patients in whom gastric cancer masquerades at endoscopy as a benign gastric ulcer has been poorly characterized. We reviewed retrospectively all cases of gastric adenocarcinoma in three hospitals for a five-year period. Of 266 patients with gastric adenocarcinoma, 169 (63.5%) had endoscopy with biopsy prior to diagnosis of cancer. In 159 of these 169 patients (94.1%), the endoscopic findings suggested cancer, while in the remaining 10 patients (5.9%) the endoscopic appearance suggested benign ulcer. In six of these 10 patients, the initial endoscopic biopsies did not reveal cancer and correct diagnosis was delayed for as long as 14 months. Three of the 10 patients had “early gastric cancer” by pathologic criteria at gastrectomy, although one had lymph node metastasis. The other seven patients had pathologic criteria for advanced gastric cancer, and three had lymph node metastasis. In spite of advanced cancer and/or lymph node metastasis in eight of our 10 patients, five-year survival in these patients with benign-appearing ulcers was 70%, as compared to 17% in patients whose gastric lesions appeared malignant at endoscopy.