Pharmacological Approach to Gastric Acid Suppression: Past, Present, and Future

Less than 2 centuries have elapsed since the identification of hydrochloric acid in the stomach. The clarification of the molecular mechanisms allowed the effective therapeutic suppression of gastric acid secretion. The spectacular advances in the treatment of acid-related disorders represent a synthesis of the contributions of several brilliant pharmacologists, basic scientists, and clinical physicians. Effective gastric acid suppressive therapy has dramatically improved the therapy and outcome of acid-related disorders. The introduction of proton pump inhibitors (PPIs) in clinical practice has significantly changed the medical management of upper gastrointestinal disorders. PPIs represent the “gold-standard” therapy in acid-related disorders. However, some challenges persist in the therapy of acid related diseases, including management of patients who respond inadequately to PPI therapy, more effective gastroprotection, or more powerful antisecretory treatment for the eradication of Helicobacter pylori infection. New antisecretory drugs are currently being developed and investigated to further provide a more effective and profound gastric acid secretion inhibition. The major advance has been the development of acid pump ­antagonists, the potassium channel acid blocking drugs (­P-CABs). Long-term studies comparing P-CABs with PPIs will help to define the exact place and safety profile of this class of drug in the management of acid-related disorders.

Placebo-Controlled Discontinuation of Long-Term Acid-Suppressant Therapy: A Randomised Trial in General Practice

Objective. To investigate whether patients on long-term antisecretory medication need to continue treatment to control symptoms. Methods. A double-blinded randomised placebo-controlled trial in general practices in Denmark. Patients aged 18–90 who were treated with antisecretory drugs on a long-term basis were randomized to esomeprazole 40 mg or identical placebo. Outcome measures were time to discontinuation with trial medication due to failed symptom control analysed as survival data. The proportion of patients stopping trial medication during the one-year follow-up was estimated. Results. A total of 171 patients were included with a median prior duration of antisecretory treatment of four years (range: 0.5 to 14.6 years). 86 patients received esomeprazole 40 mg and 85 patients received placebo. At 12 months, statistically significantly more patients in the placebo group had discontinued (73% (62/85)) compared with the esomeprazole group (21% (18/86); p < 0.001). Conclusions. Long-term users of antisecretory drugs showed a preference for the active drug compared to placebo. However, 27% of patients continued on placebo throughout the study and did not need to reinstitute usual treatment. One in five patients treated with esomeprazole discontinued trial medication due to unsatisfactory symptom control. Discontinuation of antisecretory treatment should be considered in long-term users of antisecretory drugs. This trial is registered with Trial registration ClinicalTrials.gov ID: NCT00120315.

Failure of radiotherapy in acromegaly

BACKGROUND: Recent data has raised skepticism regarding the long-term effectiveness of radiotherapy (RxT) in acromegaly and its role as an ancillary tool to neurosurgery (Tx). PATIENTS: We evaluated 72 acromegalic patients previously submitted to RxT. Data were discarded in 23 patients, who were lost to follow-up, operated on after RxT or irradiated with techniques different from external conventional fractionated RxT. Among the remaining 49 (five with mixed GH-prolactin adenoma), 34 were irradiated after surgical failure and 15 as primary treatment. A second cycle of RxT was administered in two. RESULTS: (i) GH/IGF-I. After a median follow-up of 14 years (range 3-41), normal age-matched IGF-I levels were reached in eight patients (16%) after 10 years, and GH levels <2.5 microg/l in six (12%) after 9 years. The rate of persistently pathological hormonal levels was still 90% at 25 years. All patients with GH/IGF-I normalization had undergone irradiation without any antisecretory drug. Neither basal GH nor tumor size affected the outcome of RxT. In three patients (6%) a relapse/worsening occurred. (ii) Tumor size. Tumor shrank after 8.5 years in 24 patients (49%), in nine of whom during GH-suppressive treatment. Tumor shrinkage was not predictive of hormonal normalization. (iii) Side-effects. Hypopituitarism was diagnosed in four patients (selective in three and global in one) and GH deficiency in one. Three patients had neurological side-effects and meningioma was shown in two patients. CONCLUSION: RxT is unable to cure acromegaly, because it seldom achieves hormonal normalization even after a very prolonged follow-up. Concomitant antisecretory treatment seems to counteract its effects. RxT can still play a role in those patients with large tumor remnants, because of its capacity to shrink tumor size.