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Notes: The long-term safety and efficacy of lansoprazole were studied in 21 patients with Zollinger-Ellison syndrome. The initial maintenance dose was determined by acid inhibition studies. In all patients lansoprazole controlled gastric acid hypersecretion and peptic symptoms in both the short and long term. Patients were treated for a mean of 31 months (range 1–43 months) with all but 4 patients followed for 〉 18 months. The mean initial dose was 60 mg/day, with 2 patients requiring a twice daily dose and the others a single daily dose. During long-term treatment 6 patients required an increased dosage, 5 within the first year. Long-term maintenance doses were reduced in 5 of the 6 patients in whom this was attempted. No changes in serum gastrin concentration, haematological parameters, liver function studies or other biochemical parameters occurred due to lansoprazole. No patient developed a gastric carcinoid tumour while being treated with lansoprazole. These results demonstrate that long-term treatment with lansoprazole is both safe and effective in patients with Zollinger-Ellison syndrome, and suggest that this drug will be useful in such patients. Furthermore, maintenance doses of lansoprazole, determined by the currently recommended method of acute acid titration studies in patients with Zollinger-Ellison syndrome, are too high.

Notes: Background : Effective symptom control is a primary concern of most heartburn suffers.Aim : To compare the safety and efficacy of pantoprazole, placebo and the H2 antagonist nizatidine in relieving symptoms in patients with erosive oesophagitis.Methods : Data from two randomized, double-blind studies were pooled. Patients received pantoprazole 10, 20 or 40 mg, or placebo daily (study 1, n = 603), or pantoprazole 20 or 40 mg daily or 150-mg nizatidine b.d. (study 2, n = 243) for either 4 or 8 weeks. Endoscopy was performed at baseline, week 4 and week 8. Persistent absence of symptoms was defined as the first day that no symptoms were reported by the patient on that day or any subsequent study day.Results : A significantly higher percentage (P 〈 0.05) of pantoprazole patients reported elimination of all symptoms by week 8. Daytime heartburn, night-time heartburn and regurgitation were significantly better controlled with pantoprazole (with a dose–response at most time-points). Absence of symptoms was a powerful predictor of healing; presence of symptoms correlated poorly.Conclusion : Pantoprazole is more effective than placebo or nizatidine for controlling heartburn and acid regurgitation in patients with erosive oesophagitis. Relief of GERD symptoms is highly predictive of healing of erosive oesophagitis at 4 and 8 weeks.

Notes: Although biologically-derived porcine secretin is approved for the diagnosis of Zollinger–Ellison Syndrome, it is no longer available in the United States. Pure human and porcine secretins have now been synthesized and new drug applications have been filed with the Federal Drug Administration (FDA).〈section xml:id="abs1-2"〉〈title type="main"〉Methods:In the current study we compared secretin testing results in six confirmed Zollinger–Ellison Syndrome patients using the biologically-derived product and both synthetic products (human and porcine) in a three-way, randomized, single-blind Latin-squares crossover study.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Using the FDA-approved criterion for positive secretin testing (i.e. a serum gastrin concentration increase of 〉 110 pg/mL), there was complete agreement between all three agents for all patients. With the more stringent NIH criterion (i.e. a serum gastrin concentration increase of 〉 200 pg/mL), positive results persisted in five out of six, six out of six and four out of six patients using biologically-derived secretin, synthetic porcine secretin, and synthetic human secretin, respectively (six out of six, six out of six and four out of six if a positive test was defined as a 50% increase in serum gastrin concentration). The time to peak serum gastrin concentration after secretin injection occurred within 15 min in all studies (in 94% by 10 min and in 77% by 5 min). Three-way comparisons of serum gastrin concentrations showed a single statistically significant difference (the change from baseline at 15 min between synthetic human and synthetic porcine secretin, P=0.0274). Statistically significant changes from baseline occurred at 1, 2 and 5 min for biologically-derived porcine secretin and at 2 and 5 min for both synthetic porcine and synthetic human secretin, in keeping with the expected time curve for positive tests. All three agents were well-tolerated.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:These data suggest that either synthetic secretin product, when released onto the United States market, can be used to confirm Zollinger–Ellison Syndrome.

Notes: A long-term cure is now possible in more than 30% of selected patients with Zollinger–Ellison syndrome who undergo gastrinoma resection. The need, however, for continued gastric acid antisecretory therapy in these patients remains controversial. The current study was designed to determine whether post-operative antisecretory therapy is needed in patients who have undergone successful gastrinoma resection and, if so, to attempt to define criteria with which to identify patients who require therapy. Twenty-eight consecutive patients who had previously undergone curative gastrinoma resection were prospectively studied. When antisecretory therapy was discontinued, 43% (12/28) of these patients developed gastro-oesophageal reflux, diarrhoea, acid–peptic symptoms or endoscopic evidence of acid-peptic disease within 2 weeks and were deemed to have failed a trial of antisecretory drug withdrawal. The remaining 57% (16/28) of patients who successfully discontinued antisecretory therapy were followed for a mean time of 31 months after withdrawal of therapy. Analysis of acid output studies pre-operatively, as well as at the time of drug withdrawal, demonstrated that patients who were unable to discontinue antisecretory therapy exhibited higher pre-operative maximal acid output values and higher basal acid output values at the time of attempted drug withdrawal than patients who were able to discontinue therapy. Despite these findings, there was significant overlap in acid output values between groups so that it was not possible to define specific acid output criteria for successful drug withdrawal. Pre-operative clinical characteristics, such as the presence or absence of gastro-esophageal reflux or acid-peptic disease, or post-operative laboratory values, such as the fasting serum gastrin level, did not correlate with the ability to discontinue antisecretory therapy. We conclude that following successful curative gastrinoma resection, 40% of patients still require antisecretory therapy and that both symptom evaluation as well as upper endoscopy should be used to guide attempted drug withdrawal. Although patients who are not able to discontinue therapy have significantly higher acid output measurements than those who are able to discontinue therapy, neither acid output criteria nor any other laboratory or clinical characteristics are able to predict the need for continued antisecretory therapy in these patients.

Notes: Background : Measurement of oesophageal acid exposure parameters postprandially has been shown to distinguish gastro-oesophageal reflux disease patients from normal individuals.Aims : To calculate the accuracy of postprandial oesophageal integrated acidity in diagnosing gastro-oesophageal reflux disease.Methods : Ambulatory 24-h pH studies of 626 patients were analysed retrospectively. Gastro-oesophageal reflux disease, defined as pH 〈 4 for 〉4.2% of time, was identified in 305 subjects. Postprandial oesophageal integrated acidity was measured for 2 and 3 h after the largest meal peak as determined from gastric pH. Postprandial symptom-associated probability was calculated.Results : Gastro-oesophageal reflux disease subjects had a greater postprandial oesophageal integrated acidity than non-gastro-oesophageal reflux disease subjects [median (IQR): 0.57 (0.08–2.66) vs. 0.03 (0.01–0.15) mmol*h/L]. Median postprandial oesophageal integrated acidity did not differ with gender or age in gastro-oesophageal reflux disease and non-gastro-oesophageal reflux disease subjects (P 〉 0.05 for all). A 3-h postprandial oesophageal integrated acidity value of 0.121 mmol*h/L had a 71.1% sensitivity and 71.7% specificity in diagnosing gastro-oesophageal reflux disease. Gastro-oesophageal reflux disease subjects with symptoms had a higher postprandial oesophageal integrated acidity than those without (P = 0.043), whereas non-gastro-oesophageal reflux disease subjects with and without symptoms did not differ (P = 0.74). The correlation between symptom-associated probability and postprandial oesophageal integrated acidity was poor (gastro-oesophageal reflux disease: r = 0.15; non-gastro-oesophageal reflux disease: r = 0.25).Conclusion : Postprandial oesophageal integrated acidity provides a robust estimation of oesophageal acid exposure and may predict symptoms in gastro-oesophageal reflux disease patients.

Notes: Objectives : To compare the safety and efficacy of pantoprazole with ranitidine for the maintenance of endoscopically documented healed (grade 0 or 1) erosive oesophagitis.Methods : Patients (371) were randomly assigned to receive pantoprazole 10, 20 or 40 mg or ranitidine 150 mg. Endoscopies were performed after 1, 3, 6 and 12 months or when symptoms suggesting relapse (grade = 2) developed. Gastric biopsies were obtained at baseline and on at least one postbaseline visit. Symptom-free days and Gelusil use were assessed.Results : Pantoprazole was significantly (P 〈 0.001) more effective in maintaining erosive oesophagitis healing. After 12 months, 33%, 40%, 68% and 82% of patients remained healed for the ranitidine and pantoprazole 10, 20 and 40 mg groups, respectively. Daytime and night-time heartburn were eliminated in 〉 90% of days for the pantoprazole 40 mg group. Gelusil use was significantly lower with pantoprazole 20 and 40 mg than with ranitidine (P 〈 0.02) during the first 9 months.Conclusions : Twelve months of maintenance therapy with pantoprazole (10–40 mg once daily) was superior to ranitidine (150 mg twice daily) in maintaining erosive oesophagitis healing. Pantoprazole 40 mg provided the most consistent efficacy and was well tolerated.

Notes: H+, K+-ATPase inhibitors such as omeprazole are the antisecretory agents of choice for the management of gastric acid hypersecretory states, including the Zollinger-Ellison syndrome. However, long-term follow-up data on the overall efficacy and safety of these agents in large numbers of patients are lacking. In the current study we examined the long-term efficacy and safety of omeprazole in 116 patients with Zollinger-Ellison syndrome treated with oral omeprazole at a single centre for up to 114 months (mean ± S.E.M. = 38 ± 3 months). The initial omeprazole maintenance dose was established according to the acute upward dose titration method in 89/116 patients (77%). Gastric acid output was effectively controlled using 60 mg of omeprazole once daily in 41/89 patients (46%) and 22/89 patients (25 %) required twice daily omeprazole therapy. The mean ranitidine equivalent dose for patients who required 60 mg omeprazole once daily (2.5 ± 0.2 g/day) was significantly lower than the mean ranitidine equivalent dose for patients who required more than 60 mg omeprazole once daily (4.3 ± 0.3 g/day). Long-term omeprazole maintenance therapy was discontinued in 36/116 patients (31%) but in no cases was discontinuation due either to drug-induced side-effects or uncontrolled gastric acid output. Fasting serum gastrin levels were significantly elevated above pre-treatment levels at only one time point during follow-up and were likely due to tumour growth rather than a drug effect. The final long-term omeprazole maintenance doses were lower than the initial doses but correlated closely with the preomeprazole basal acid output (r= 0.41, P 〈 0.001) and ranitidine equivalent dose requirements (r= 0.49, P 〈 0.001). We conclude that omeprazole effectively and safely controls gastric acid hypersecretion in all patients with Zollinger-Ellison syndrome for up to nine years without evidence by tachyphylaxis.

Notes: Background : Intravenous esomeprazole may be beneficial for patients who cannot take oral medications.Aim : To compare intravenous esomeprazole with oral esomeprazole for effects on maximal acid output during pentagastrin stimulation in patients with gastro-oesophageal reflux disease symptoms.Methods : In four separate open-label, randomized, two-way crossover studies, adult patients were administered esomeprazole 20 or 40 mg once daily either orally or intravenously (by 15-min infusion or 3-min injection) for 10 days and switched to the other formulation with no washout period. Basal acid output and maximal acid output were measured on days 11, 13 and 21.Results : In the four studies (total of 183 patients), least-squares mean maximal acid output ranged from 3.0 to 4.1 mmol/h after intravenous esomeprazole 40 or 20 mg and from 2.2 to 3.3 mmol/h after oral esomeprazole 20 or 40 mg. Differences between formulations were small and not statistically significant but did not meet the prospectively defined criterion for non-inferiority of the intravenous formulation. Median basal acid output values ranged from 0.04 to 0.27 mmol/h after intravenous administration and from 0.05 to 0.25 mmol/h after oral esomeprazole.Conclusions : Intravenous esomeprazole is an acceptable alternative to the oral formulation for treatment of up to 10 days of duration.

Notes: Background : Some patients requiring acid suppression may be unable to take oral medications.Aim : To compare the gastric acid inhibition effects of lansoprazole 30 mg administered either intravenous or orally in erosive oesophagitis patients.Methods : The study included 87 Helicobacter pylori-negative patients with erosive oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated acid output were measured on days 8, 9 and 15.Results : Median pentagastrin-stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo (P 〈 0.001).Conclusions : Lansoprazole 30 mg administered intravenous was equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous proton pump inhibitor therapy represents an important treatment option for those with acid-related diseases who are unable to take oral medications.