NSAID--induced gastroduodenal ulcers: exploring the silent dilemma.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective medications and are very commonly prescribed. They are used by a large proportion of elderly persons who are most prone to adverse events. NSAID gastropathy is the commonest side effect. The relative risk of adverse events is high, but the absolute risk for any individual patient is low. Individualizing the risk/benefit ratio would lead to cost effective care.

Effects of chronic NSAIDs on gastric mucosal injury related to mucosal prostanoids, and plasma drug concentrations in human volunteers.

The relationship between endoscopically observed gastric mucosal damage, elicited following repeated oral intake for 7 d of four NSAIDs, to their effects on antral and fundic production of PGE2, 6-keto-PGF1 alpha and TxB2 (assayed by GC-MS), mucosal histology and plasma concentration profiles was studied in 40 normal males. Subjects received azapropazone (APZ) 600 mg b.i.d., indomethacin (IND) 50 mg t.i.d., naproxen (NAP) 500 mg b.i.d., piroxicam (PIR) 20 mg qq.d., or one placebo capsule t.i.d. (N = 8/group). Plasma NSAIDs (HPLC) levelled at 7 d. Mucosal damage occurred in the antrum region with IND and NAP. APZ and PIR exhibited no differences compared to placebo. NAP and IND reduced all three prostanoids in the antrum while APZ and PIR were ineffective. Fundic PGE2 was reduced by IND, NAP and PIR; APZ had no effects. Thus, mucosal damage relates to effects on prostanoid production in the antrum but not in the fundus.

Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis.

Endoscopic hemostatic therapy for upper gastrointestinal bleeding is gaining widespread acceptance despite often conflicting results of randomized controlled trials. To examine the effect of endoscopic therapy in acute nonvariceal upper gastrointestinal hemorrhage, a meta-analysis was performed using a computerized search of the English-language literature and a bibliographic review. The methodology, population, intervention, and outcomes of each relevant trial were evaluated by duplicate independent review. Thirty randomized controlled trials evaluating hemostatic endoscopic treatment were identified. Endoscopic therapy significantly reduced rates of further bleeding (odds ratio, 0.38; 95% confidence interval, 0.32-0.45), surgery (odds ratio, 0.36; 95% confidence interval, 0.28-0.45), and mortality (odds ratio, 0.55; 95% confidence interval, 0.40-0.76). When analyzed separately, thermal-contact devices (monopolar and bipolar electrocoagulation and heater probe), laser treatment, and injection therapy all significantly decreased further bleeding and surgery rates. The reductions in mortality were comparable for all three forms of therapy, but the decrease reached statistical significance only for laser therapy. Further examination of subgroups indicated that endoscopic treatment decreased rates of further bleeding, surgery, and mortality in patients with high-risk endoscopic features of active bleeding or nonbleeding visible vessels. Rebleeding was not reduced by endoscopic therapy in patients with ulcers containing flat pigmented spots or adherent clots. Endoscopic hemostatic therapy provides a clinically important reduction in morbidity and mortality in patients with acute nonvariceal upper gastrointestinal hemorrhage.

Do hourly averaged pH readings correlate with those from point readings of aspiration? Comparison of two different electrode positions with simultaneous aspiration.

Hourly averaged data from continuous intraluminal pH recording were compared with the point aspiration in five 24-hour studies performed on healthy volunteers. Two different electrode positions were compared simultaneously with aspiration. The correlation was performed using the median from the whole hour's recording of the electrode against the aspiration point. There was a significant correlation between both electrodes and aspiration (p less than 0.001), although both electrodes read consistently lower than aspiration: electrode A (gastric antrum), median pH = 1.4; electrode B (gastric body), pH = 1.9; aspiration, pH = 2.3. These findings show that data reported in clinical trials using different recording techniques are not directly comparable and must be interpreted appropriately. The position of the electrode may also be important.

Does misoprostol given as a single large dose improve its antisecretory effect?

H2-receptor antagonists have been shown to be effective in the suppression of nocturnal acidity. This double-blind, randomized, crossover Latin-square study of 24-h intragastric pH in 12 normal volunteers investigated the effect of large single-dose administration of misoprostol on intragastric acidity. Efficacy of 800 micrograms misoprostol h.s., 600 micrograms h.s., 400 micrograms h.s. and 800 micrograms after supper was compared to placebo and 200 micrograms misoprostol q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. Twenty-four hour mean pH +/- s.d. was placebo 2.1 +/- 0.3, misoprostol 200 micrograms q.d.s. 2.2 +/- 0.3, 800 micrograms p.m. 2.6 +/- 1.1, 400 micrograms h.s. 2.6 +/- 0.7, 600 micrograms h.s. 2.6 +/- 0.4, 800 micrograms h.s. 2.6 +/- 0.5. The effect of misoprostol on gastric acidity was short and limited to the nocturnal period. Only misoprostol 800 micrograms and 600 micrograms reduced 24-h acidity compared to placebo (P less than 0.04).

Adenomyoma of the common bile duct.

We report an unusual case of biliary obstruction secondary to adenomyoma of the common bile duct. Adenomyomas are benign tumors, found infrequently in the biliary tree. Clinical presentation, biochemical, radiographic, and endoscopic investigations do not distinguish adenomyomas from malignant or other lesions; diagnosis requires histological examination. The natural history and optimal treatment of these tumors have not been established.

The limitations of current therapy in peptic ulcer disease.

The current therapeutic approach to peptic ulcer disease includes agents that reduce gastric acidity and hence peptic activity, inactivate or adsorb pepsin, create a physical barrier against the effects of acid and pepsin, or enhance mucosal defence. Profound gastric acid reduction may predispose to infection, and it has been suggested that carcinogenesis is possible, although a cause-effect relationship has never been established. The side-effects of therapy are well-described, and may limit the therapeutic approach. Healing rates correlate closely with acid suppression in duodenal ulcer, but not entirely in gastric ulcer. Maintenance therapy lowers the relapse rate, but does not alter the ulcer diathesis. The optimal strategy for long-term management remains unclear, but in the future one should consider outcome measures which include a decrease in pain, improvement in the quality of life, reduction work loss, and a reduction of complications, in addition to ulcer healing. The ideal therapy should be efficacious, safe, and convenient--with no side-effects--and cost-effective. New agents should suppress acid and peptic activity, while enhancing the gastric mucosal defence mechanisms (such as mucosal blood flow, mucus, and bicarbonate secretion) and stimulating gastric cellular regeneration and restitution.