Several reports have suggested that skin tags may be a marker for the presence of colonic polyps in symptomatic patients referred for colonoscopy. In a prospective study of 100 asymptomatic patients, we found no association between skin tags and colonic polyps. A review of the literature and results of a metaanalysis show a significant association between skin tags and colonic polyps in 777 symptomatic patients, but no association in 268 asymptomatic patients. To explain this discrepancy, several possible biases are analyzed. As skin tags constitute a marker for colonic polyps only in symptomatic patients for whom a colonoscopy is already indicated, their detection is of no diagnostic value in asymptomatic patients.

The effect of total-body ionizing radiation on the digestive tract is dose-dependent and time-dependent. At low doses (1.5 Gy), one observes only a short prodromal syndrome consisting of nausea, vomiting, and gastric suppression. At doses greater than 6 Gy, the prodromal syndrome is more marked, and it is followed after a 2-5-day remission period by a subacute syndrome, characterized by diarrhea and hematochezia. This gastrointestinal syndrome is superimposed onto a radiation-induced bone marrow suppression. The combination of intestinal and hemopoietic syndromes results in dehydration, anemia, and infection, leading eventually to irreversible shock and death. The treatment of prodromal symptoms is based on the administration of antiemetics and gastrokinetics, although an effective treatment devoid of side effects is not yet available for human therapy. The treatment of the gastrointestinal subacute syndrome remains difficult and unsuccessful after exposure to total body doses greater than 8-10 Gy. Supportive therapy to prevent infection and dehydration may be effective if restoration or repopulation of the intestinal and bone marrow stem cells does occur. In addition, bone marrow transplantation may improve the prospect of treating the hemopoietic syndrome, although the experience gained in Chernobyl suggests that this treatment is difficult to apply in the case of nuclear accidents. Administration of radioprotectants before irradiation decreases damage to healthy cells, while not protecting cancerous tissues. In the future, stimulation of gastrointestinal and hemopoietic progenitor cells may be possible using cell growth regulators, but much remains to be done to improve the treatment of radiation damage to the gastrointestinal tract.

The use of sigmoidoscopy as a screening method for colorectal cancer is controversial. Evidence regarding its efficacy is reviewed critically, with special attention given to potential biases in screening studies. The vast majority of studies are uncontrolled and without follow-up information and thus shed little light on the actual benefits of sigmoidoscopy. Two uncontrolled studies with follow-up and one randomized trial suggest a colorectal cancer mortality reduction because of the use of sigmoidoscopy, but all three studies have major shortcomings. The authors conclude that the currently available data are insufficient to establish a national recommendation for screening with sigmoidoscopy. To establish such a recommendation, a properly conducted randomized trial with colorectal cancer mortality as an outcome is needed.

The irritable bowel syndrome (IBS) is a common and poorly understood chronic condition that is treated with a great variety of drugs and other therapies without notable enduring success. As there are no objective markers of improvement, and because there may be a very large placebo response, potential treatments for IBS are difficult to assess. Probably the only method that can reliably evaluate IBS therapies is the randomized, double-blind, placebo-controlled treatment trial. The purpose of this review is to critically examine issues central to establishing the efficacy of treatments for IBS in such trials. These include the definition of IBS, measures of efficacy, the placebo response, trial length, maintaining blindedness, the crossover design, ability to generalize, and statistical considerations. With this background, all published IBS treatment trials are examined. It is concluded that not a single study offers convincing evidence that any therapy is effective in treating the IBS symptom complex. Well-designed and executed IBS treatment trials are urgently needed; suggestions are given for essential features of such trials.

The efficacy of D-xylose testing in clinical situations has been reviewed in the light of recent kinetic studies. The standard 25-g D-xylose test in adults, based on analysis of 5-h urine collection and a 1-h serum sample, discriminates between normal subjects and patients with proximal small intestinal malabsorption with greater than 95% specificity and sensitivity. The 1-h serum level measured after administering this dose is also useful in evaluating malabsorption in patients with intermediate degrees of renal insufficiency and in the elderly. The 1-h serum test after administration of 5 g of D-xylose should be used in pediatrics and is greater than 91% sensitive and close to 100% specific. The [14C]D-xylose breath test with 1 g of D-xylose has been useful in identifying malabsorption caused by bacterial overgrowth in the small intestine.

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.

Antacids have served us well for over a century. The attitude in the late 1950s to 1970s that antacids should be taken only on demand was unjustified and was based on what can be seen nowadays as misinterpretation of scientific data. Twelve recent endoscopic controlled studies have confirmed the efficacy of antacids in the healing of duodenal ulcer, achieving about 75% healing in 4 weeks. Like H2-receptor antagonists, the efficacy of antacids in the healing of gastric ulcers is controversial, most probably related to the even greater pathogenetic heterogeneity of this condition. Antacids should be given at least four times a day and at least 1 hour after meals, since their therapeutic success most likely depends on neutralization of postprandial acid secretion. In vivo, the newer tablet forms are indistinguishable from the liquid forms in terms of neutralizing efficiency and healing efficacy. The ideal dose is one that neutralizes 400 mmol of acid. Combination with an anticholinergic drug is effective and a recent report suggests that this may lead to longer remission than with H2-receptor antagonists. As a long-term therapy, antacids appear to work but need to be taken in multiple daily doses, a regimen which is unlikely to meet with long-term patient compliance. The success of antacids in duodenal ulcer healing should alert us to the importance of controlling the meal-stimulated acid secretion in ulcer therapy, and to the hard fact that acid is a non-permissive factor in ulcer healing.

A great deal of information about the spiral bacteria of the stomach has accumulated in the past 5 years. These bacteria, currently named Campylobacter pylori but likely to be renamed as a new genus, have adapted to living beneath the mucus layer and above the gastric surface mucous cells. When metaplastic gastric mucous cells are also present in the duodenal bulb, C. pylori may also get a foothold in this latter location. Observations of the high prevalence of C. pylori in patients with gastritis and with duodenal ulcers, and the slightly lower prevalence in patients with gastric ulcer, have led to the hypothesis that the bacteria play an aetiological role in these three conditions. There is now fairly convincing evidence that the organisms can cause active chronic gastritis. The most persuasive of this comes from reports of the rapid development of gastritis and symptoms in two volunteers who swallowed the organism, plus two other series of accidental challenges. Other evidence is provided by the waning and waxing of gastritis, which has been correlated in several studies with clearance followed by recrudescence of the organisms. The role of the bacterium in peptic ulcer is less certain. The present data do not provide strong evidence for a causal role in gastric ulcer, although we cannot rule out that it may be important in some. The very high prevalence in patients with duodenal ulcer, including one series in children (who rarely harbour the organism), raises the distinct possibility that the bacteria play an aetiological role in this form of ulcer. Reports of ulcer healing with antibiotics and of lower recurrence rates in those cleared of the organism, increase the possibility, However, methodological flaws in some studies, plus the usual need for confirmation of key studies, indicate that we should await more definitive evidence before accepting that duodenal ulcer can be an infectious disease.

It seems that duodenal and gastric ulcers are caused by environmental ulcerogens, which are probably infectious or chemical. The reasons for individual susceptibility to these ulcerogens have not been defined and, indeed, it is not yet certain that the effects are not essentially random. Abnormalities of function of the mucosae of the upper alimentary tract do not appear to be necessary or sufficient for the production of ulcers. The two principal clinical aspects of ulcer disease--the tendency to form chronic mucosal wounds and the tendency of the wounds to recur during many years--point to, but cannot yet be explained in terms of, failure of the processes involved in wound repair. More specifically, it is not known whether there is interference with the processes involved in normal mucosal repair or whether there is failure of the repair processes. When these problems are closer to solution, it will perhaps be possible to assess how environmental factors influence ulcerogenesis.

The parietal cells possess the unique capacity to produce large quantities of acid at a high concentration, and this is reflected in unique properties at the cellular level. The cells are comparatively large, and they are equipped with secretory canaliculi, a multitude of mitochondria, and cytoplasmic tubulovesicles. During secretion many of the tubulovesicles merge with the secretory canaliculi, which then expand. In the process H+, K+-ATPase is transferred from the tubulovesicular membrane to the secretory membrane. This enzyme catalyses the final step in the production of HCl. Parietal cell activity is regulated through receptors on the basolateral cell surfaces. In the isolated gland and in the isolated parietal-cell fractions, stimulation of receptors for histamine evokes higher secretion than receptor stimulation with cholinergic compounds or with gastrin. In these experimental models, specific inhibitors are required to block acid secretion; for example histamine H2-receptor antagonists will block histamine-induced secretion but will be inactive when secretion is evoked by gastrin or by cholinergic stimulation. These stimuli cause a more or less marked increase in the intracellular levels of Ca2+, which acts as a second messenger, leading to the activation of phosphokinases and, ultimately, to morphological transformation of the parietal cells and acid secretion. Another such intracellular messenger is cAMP, which is formed in response to histamine stimulation only; prostaglandins may prevent this process and block acid secretion. The final step in the production of acid requires K+ and Cl- channels in the secretory membrane and the H+, K+-ATPase-catalysed exchange of K+ for H+ across this membrane. This reaction consumes large amounts of energy and depends on the aerobic production of ATP by the parietal cells. Substituted benzimidazoles, such as omeprazole, accumulate in the acid compartments of the parietal cells and inhibit the H+, K+-ATPase, thereby blocking acid production.