Zollinger-Ellison syndrome: presentation, response to therapy, and outcome.

BACKGROUND: Recent series describing the clinical presentation, response to therapy, and long-term outcome of Zollinger-Ellison syndrome are limited. AIMS: To assess the clinical characteristics and long-term outcome of patients with Zollinger-Ellison syndrome. METHODS: Over a 20-year period, patients with Zollinger-Ellison syndrome were enrolled in a prospective trial evaluating the efficacy of lansoprazole. Following dose stabilization, patients were followed on a 6-monthly basis with interval history, physical examination, endoscopy with gastric biopsies, gastric acid analysis and laboratory studies. RESULTS: 72 patients (mean age 54±12 years, % male 58%, % Caucasian 69%) were prospectively enrolled. The clinical presentation was stereotypical for Zollinger-Ellison syndrome. Symptoms had been reported for a median of 9 years prior to diagnosis. Cross-sectional abdominal imaging was often negative for demonstrable tumour. All patients had gastric acid hypersecretion controlled with variable doses of lansoprazole (median dose 60 mg/day, range 15-480 mg/day). The median survival from the time of diagnosis was 6.6 years; only two of 19 deaths were due to metastatic gastrinoma. CONCLUSIONS: The clinical presentation of Zollinger-Ellison syndrome was similar to prior reports. Acid hypersecretion was controlled in all patients with variable doses of lansoprazole. Long-term survival was principally related to underlying co-morbidity.

Costs and risks in the management of patients with gastric acid hypersecretion.

GOALS: To define both risks and costs of optimal care of patients with gastric acid hypersecretion. BACKGROUND: The management of Zollinger-Ellison syndrome and other gastric acid hypersecretory disorders remains challenging. The optimal strategy for follow-up including gastric acid analysis, laboratory studies, and endoscopy is unknown but important given the potential complications from uncontrolled acid secretion. STUDY: Over the last 18 years, patients with gastric acid hypersecretory disorders have been followed prospectively with gastric acid analysis and endoscopy titrating oral lansoprazole and evaluating for complications. Protocol driven charges were calculated using the most recent information available. RESULTS: After 1 year of treatment optimization, 19 of 67 patients had 43 relapses, (once only in 10 patients). Risk markers for relapse included: (1) antrectomy, 67% relapsed versus 21% in unoperated patients; (2) basal acid output >5 mmol/h (risk=5.17); and (3) poor compliance. On treatment, 79% of 58 intact patients (excluding antrectomy) were lesion-free; 11% had only 1 relapse. Thus 90% were well managed with optimized lansoprazole alone. Protocol driven charges exceeded $25,000 the first year and $7000 annually thereafter. CONCLUSIONS: Relapse is infrequent and generally mild with acid secreting status closely monitored. The ideal strategy to balance costs and testing awaits further study.

Absence of gastrointestinal infections in a cohort of patients with Zollinger-Ellison syndrome and other acid hypersecretors receiving long-term acid suppression with lansoprazole.

BACKGROUND: The relationship between proton pump inhibitor therapy and other acid suppressing medications and the risk of gastrointestinal infections remains controversial. METHODS: Patients enrolled in a long-term trial of lansoprazole for Zollinger-Ellison syndrome and other acid hypersecretory states had interval histories taken every six months regarding hospitalizations or other intercurrent medical conditions. All medications taken were also reviewed at each visit. In addition, available patients were specifically queried during the study period 2006-2007 regarding the development of any gastrointestinal infections, hospitalizations, and prescriptions for antibiotics. RESULTS: Ninety patients were enrolled in our long-term study and 81 were available for review. The median basal gastric pH for the cohort after stabilization on therapy was 2.9 and ranged from 1.1 - 8.4 with a median pentagastrin stimulated gastric pH of 1.60 (range 1.0 - 8.2). No patient developed a clinically significant gastrointestinal infection during the study. The median patient years of follow-up were 6.25 years. CONCLUSION: In a cohort of patients with gastric acid hypersecretion in whom acid secretion status was monitored on lansoprazole, all were free of significant gastrointestinal infections on long-term follow-up. TRIAL REGISTRATION: NCT00204373.

Clinical outcome using lansoprazole in acid hypersecretors with and without Zollinger-Ellison syndrome: a 13-year prospective study.

BACKGROUND & AIMS: Unremitting gastric acid and pepsin hypersecretion causes serious persistent and relapsing lesions, but the natural history with medical treatment alone has not been well-defined. The aims of this study were to heal and prevent relapse of acid/peptic lesions during acid suppression and to analyze benefits and risks during long-term lansoprazole treatment. METHODS: Sixty-seven patients (49 with Zollinger-Ellison syndrome [ZES], 18 without), with basal acid output (BAO) >15 mmol/h or >5 mmol/h if post-antrectomy (n = 9, all ZES), were treated with individually optimized doses of lansoprazole (7.5-450 mg/day; median, 75 mg/day) to reduce BAO to <5 mmol/h or <1 mmol/h post-antrectomy and underwent endoscopy every 3-6 months for up to 13 years (median, 6.25 years). RESULTS: Before treatment, 94% had duodenal ulcer, 64% had esophagitis, 60% had 1 or more bleeding episodes, 13% had perforated ulcers, 90% had pain, 60% had heartburn, and 40%-48% had diarrhea, vomiting, and/or weight loss. Forty-seven patients (70%) remained symptom- and lesion-free, whereas 13 (20%) had mild, transient relapses, and 7 (10%) had more complicated relapses. Overall, symptoms were reduced 90+%; ulcer or esophagitis relapsed in 4.8% of patients/year, unrelated to Helicobacter pylori , whereas complications declined to <2%/y. Post-antrectomy ZES patients had 3.6-fold higher relapse rates than unoperated ZES patients (67% vs 18%, respectively). With BAO >5 mmol/h in intact patients, relative risk of relapse was 4.1, confidence interval 2.1-8.1, P < .001. Twenty patients died, 3 as a result of ZES (2 metastatic gastrinomas). CONCLUSIONS: With individually optimized medical suppression of acid secretion, 90% of patients had good to excellent long-term outcomes without surgery, with an annualized total relapse rate of <5%.

Risk factors for esophagitis in extreme acid hypersecretors with and without Zollinger-Ellison syndrome.

BACKGROUND & AIMS: Whereas severe duodenal ulcer is the hallmark of acid hypersecretion in Zollinger-Ellison syndrome (ZE) and similar states, the esophagus also is at high risk. We quantified the incidence of esophagitis and various risk factors that might contribute to it. METHODS: Sixty-eight acid hypersecretors (basal acid output >15 mmol/h), 50 patients with ZE, and 18 patients without ZE with normal gastrin levels were studied by gastric analysis, serum gastrin levels, and endoscopy. In 44 of 68 patients, esophageal manometry was performed after the esophagus had healed. RESULTS: Erosive esophagitis, grade 2 or worse, was found in 65%; an additional 15% had heartburn only, for a total reflux disease incidence of 80%. ZE accounted for 95% of severe esophagitis. Patients with and without esophagitis had the same high overnight fasting gastric residual volume and acidity, as well as basal and peak acid and pepsin outputs. However, patients with esophagitis had a lower median lower esophageal sphincter pressure (LESP) of 15.5 vs. 23 mm Hg in those without symptoms; the critical discriminator threshold was 16 mm Hg. Multivariate analysis further identified frequent vomiting and obesity as positive predictors of esophagitis, whereas Helicobacter pylori was a strong negative predictor (odds ratio, 0.16), possibly related to an elevated LESP in patients infected with H. pylori. CONCLUSIONS: Erosive esophagitis is very common in acid hypersecretors. Identified risk factors that could promote abnormal esophageal exposure to the high acid and pepsin levels in our population of hypersecretors were vomiting, LESP < 16 mm Hg, and obesity, whereas H. pylori appeared to protect the esophagus not by reduced acid, but through an elevated LESP.