title: Failure of histamine H2-receptor antagonist therapy in Zollinger-Ellison syndrome.
abstract: Review of a 5 year clinical experience with the histamine H2-receptor antagonists metiamide, cimetidine, and ranitidine in 20 patients with Zollinger-Ellison syndrome disclosed a treatment failure rate of 50 percent. The criterion for failure was hemorrhage in four patients, obstruction followed by hemorrhage in one patient, perforation in one, and intractable pain in four. Nine of the 10 patients in whom treatment failed required total gastrectomy for control of complications; the 10th patient refused operation. Retrospective analysis identified hepatic metastases, the multiple endocrine adenomatosis-type I syndrome, refractory diarrhea, and breaks in the medication schedule as being more common in the treatment failure group, but these trends were not statistically significant in our small series of patients. Nonhealing or recurrent ulcers were found in 90 percent of the patients in whom drug therapy failed and in only 10 percent of those patients in whom therapy was successful (p less than 0.01). There were no differences related to age, sex, duration of symptoms, previous gastric operation, ulcer location, presence of diarrhea, or amount of drug prescribed. Basal and peak acid outputs, basal serum gastrin levels, and response to secretin challenge were also nondiscriminatory. The degree of acid inhibition in response to cimetidine was highly variable from one patient to another and on repeat testing in individual patients, and there was no correlation between acid secretory inhibition and clinical course. When severe complications occurred, reinstituting H2-receptor antagonist therapy or increasing the dose did not avert the need for total gastrectomy. Patients refractory to drug treatment who have persistent or recurrent ulcers should be managed with prompt total gastrectomy to prevent life-threatening complications.
mesh_terms: D000328:Adult; D000368:Aged; D002927:Cimetidine / Q000627:therapeutic use; D005260:Female; D005663:Furans / Q000627:therapeutic use; D005745:Gastric Acidity Determination; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008785:Metiamide / Q000627:therapeutic use; D008875:Middle Aged; D011899:Ranitidine; D012008:Recurrence; D012189:Retrospective Studies; D012306:Risk; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy*
chemical_list: D005663:Furans; D006635:Histamine H2 Antagonists; D008785:Metiamide; D002927:Cimetidine; D011899:Ranitidine