The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts.

Cirrhosis due to hepatitis C virus (HCV) is now the most common indication of liver transplantation in Western Europe and the United States. In the absence of effective prophylaxis, recurrent HCV infection is almost inevitable. Though the natural history and intermediate term outcome of recurrent HCV are now better documented, those factors which may influence the recurrence of hepatitis and consequent progression of graft disease remain unclear. Interferon (IFN) as a sole agent for the treatment of recurrent infection has proved unsatisfactory. Early intervention with a combination of IFN and ribavirin seems promising, and this approach may prevent or delay progression of HCV related graft disease after liver transplantation.

Current evidence suggests that impaired intestinal motility may facilitate gallstone formation by influencing biliary deoxycholate levels or by modulating interdigestive gall bladder motility (fig 2), although a primary intestinal defect in gallstone pathogenesis has not yet been demonstrated. In the cold war period, most interesting events, from a political point of view, occurred at the border between capitalist and communist systems, near the iron curtain. Similarly, the gall bladder and biliary tract can be viewed as the border between liver and intestinal tract, where many interesting things occur with profound impact on both systems. Combined efforts by researchers in the field of hepatology and gastrointestinal motility should brake down the Berlin wall of ignorance of one of the most common diseases in the Western world.

NF-kappaB is a pleiotropic transcription factor with key functions in the intestinal immune system. NF-kappaB family members control transcriptional activity of various promoters of proinflammatory cytokines, cell surface receptors, transcription factors, and adhesion molecules that are involved in intestinal inflammation. The perpetuated activation of NF-kappaB in patients with active inflammatory bowel disease suggests that regulation of NF-kappaB activity is a very attractive target for therapeutic intervention. Such strategies include antioxidants, proteasome inhibitors, inhibition of NF-kappaB by adenoviral I kappaB alpha expression vectors, and antisense DNA targeting of NF-kappaB. These approaches will hopefully permit the design of new treatment strategies for chronic intestinal inflammation.

Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread long term use.

The course of inflammatory bowel disease after liver transplantation has been reported as variable with usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity.

Acquired resistance of Helicobacter pylori to metronidazole and clarithromycin has been reported, with metronidazole resistance being very common. This has an important clinical impact on dual therapies, as well as on the standard triple therapies. However, when antisecretory drug based triple therapies with amoxycillin or clarithromycin and metronidazole are used, the resistance can be overcome in up to 75% of the cases in most of the studies. Clarithromycin seems to be a better choice than amoxycillin to achieve this goal. Nevertheless, resistance to metronidazole remains a risk factor for treatment failure. The most precise information comes from studies in which minimum inhibitory concentrations (MICs) are reported as well as whether the strain is susceptible or resistant. Few data are available from clinical trials to measure the impact of clarithromycin resistance. However, such resistance seems to have a negative impact on the clinical outcome of treatment. It is of greater importance that H pylori resistance is closely monitored in the future.

The ability of Helicobacter pylori to survive in the varying acidity of the stomach is considered to be linked to its ability to maintain a tolerable pH in its periplasmic space by acid dependent activation of internal urease activity. Whereas survival of H pylori can occur between a periplasmic pH of 4.0 to 8.0, growth can only occur between a periplasmic pH of 6.0 to 8.0. When urease activity is only able to elevate periplasmic pH to between 4.0 and 6.0, the organisms will survive but not divide. In the absence of division, antibiotics such as clarithromycin and amoxycillin are ineffective. Proton pump inhibitors, by elevating gastric pH, would increase the population of dividing organisms and hence synergise with these antibiotics.

The 13/14C-Urea breath test (UBT) is based on the simple principle that a solution of isotopically labelled urea will be rapidly hydrolysed by the abundantly expressed urease of H pylori. The released 13/14CO2 is absorbed across the mucus layer to the gastric mucosa and hence, via the systemic circulation, excreted in the expired breath. Distribution of urea throughout the stomach prevents sampling error and allows semiquantitative assessments of the extent of H pylori infection. Originally the 13C-UBT was complex, cumbersome and costly but, by simplifying the protocol and reducing the number of samples to be analysed, is now a much easier, quicker and cheaper test for detecting H pylori. Although mass spectrometry is needed for analysis of exhaled 13CO2, the use of the stable isotope, which is completely safe, provides advantages over the 14C-UBT using radioactive 14C-urea, such that it can be used in women and children and a user's licence is not required. The widespread availability of scintigraphy for 14CO2 analysis may make the 14C-UBT seem an attractive alternative to the 13C-UBT. However, there are no standard protocols for the 14C-UBT and although the methods are similar, several different cut off values are used which makes formal validation studies still necessary. Both tests are easy to perform with minimum opportunity for observer variation or methodological error; they are very sensitive and specific tests and provide a clinical "gold standard" against which the accuracy of other tests can be validated. The 13/14C-UBT detects only current infection and can be used to screen for H pylori infection and as the sole method for assessing eradication. In addition, because the 13C-UBT can be performed repeatedly in the same subject, it can be used to monitor the effects of novel anti-H pylori therapies and for epidemiological studies in children.

There are three main types of blood test available for the management of Helicobacter pylori infection: those that detect an antibody response; tests of the pathophysiological state of the stomach; and those that indicate an active infection. Enzyme linked immunosorbent assay (ELISA) based kits are the most numerous of the commercially available tests. Originally the kits used crude antigen preparations but many of the newer kits use a more purified antigen preparation giving increased specificity but a lower sensitivity. The sensitivity, specificity, and predictive values of the tests can also be affected by the population under test and coexistent disease in the patients. Near patient test kits are based on either latex agglutination or immunochromatography. Generally, they have low sensitivities compared with laboratory tests. Commercial western blotting kits have also been developed and are used to detect the presence of specific virulence markers. The exact role of serology in the management of Helicobacter infection has still to be defined, although there is evidence that, used as a screening procedure, it can reduce endoscopy cost and workload. Gastrin and pepsinogen blood concentrations may provide valuable information on the pathophysiological state of the stomach--for example, the presence of inflammation or gastric atrophy. A combination of serology and serum concentrations of gastrin and pepsinogen may be used effectively to detect serious gastroduodenal disease in patients.

Prolonged pharmacological acid suppression is associated with various histological changes in the gastric mucosa, particularly in Helicobacter pylori infected patients. In a number of subjects these changes include a shift in the gastric inflammation from the antrum to the corpus. This finding has been interpreted as gastric atrophy, and the possibility that acid suppression accelerates the progress of lesions that may lead to gastric cancer has been considered. Two recent studies on the relation between treatment with proton pump inhibitors and atrophic gastritis have yielded apparently contradictory results. These studies are reviewed in detail here and some of the possible reasons for the discrepant conclusions are explored. In particular, the way the terms "gastric atrophy" and "atrophic gastritis" are used is examined critically.

The role of Helicobacter pylori in gastric carcinogenesis is supported almost exclusively by epidemiological data and prospective histopathological studies. From biological and molecular points of view, there is no evidence that H pylori or its cytotoxic products have any mutagenic effects. Nevertheless, this infection is associated with profound changes in the pattern of epithelial cell turnover in gastric glands, though the importance of these changes in gastric carcinogenesis is still controversial. H pylori infection increases cell proliferation and alters the distribution of cycling cells within these glands, but these changes can be reversed by successful eradication of the infection. Apoptosis seems to be increased in gastric epithelial cells during H pylori infection, as shown by in vitro studies. There is some, though no conclusive, evidence that this finding also occurs in H pylori positive subjects. It seems that cagA status influences the effect of H pylori on epithelial apoptosis in infected patients. An association of in vitro H pylori induced apoptosis with changes in the expression of pro- and anti-apoptotic genes is reported in the literature, but further study is necessary to clarify the effect of H pylori infection on the molecular events of the apoptotic pathway.

Available evidence would suggest that Helicobacter pylori infection does not contribute to the pathogenesis of gastro-oesophageal reflux disease. The prevalence of H pylori infection in patients with reflux disease is no greater than that in control populations. There are some data suggesting that the organism has a protective role: patients with duodenal ulcers develop reflux disease after H pylori eradication, whereas in patients with oesophageal reflux those with H pylori infection have less severe reflux changes. There is also evidence indicating that the presence of H pylori augments the anti-secretory properties of both the H2 receptor antagonists and proton pump inhibitors (PPIs), suggesting that eradication therapy may not be beneficial. However, the considerable recent interest in the association between H pylori and reflux disease has largely been generated by studies outlining the interactions between H pylori infection and acid suppression in the long term. In H pylori positive patients, therapy with PPIs is associated with a proximal extension of the infection and its associated gastritis. In addition long term PPI therapy is reported to be associated with an accelerated development of atrophic gastritis, suggesting that H pylori should be diagnosed and treated. Although these latter findings in particular need confirmation, H pylori eradication therapy should be considered in this patient group, at least until there is evidence to the contrary.

When trying to decide which children with Helicobacter pylori infection should be treated and at what stage they should be tested, we should take into account the fact that eradication of the infection may be useful both to induce symptom remission and to prevent later complications in adulthood. However, well designed studies to identify those infected children who are at risk of developing complications or have symptoms due to the infection are still lacking. Current literature only gives information on how to treat children with H pylori infection. Treatment regimens that include two drugs are usually more effective than in adults, and produce an eradication rate of 70-80%, but they should be given for at least two weeks, shorter treatments being less effective. Antibiotic resistance can impair eradication rate and the frequency of resistant strains in children should be studied. Combinations of antibiotics with antisecretory drugs are highly effective in adults, but triple therapy with two antibiotics and an antisecretory drug has been seldom tried in children; compliance is often poor so that the eradication rate is often similar to that produced by dual therapy. Compliance strongly influences eradication, and short simple treatment regimens that produce rapid symptom remission with few side effects are needed to optimise patient compliance. After treatment, eradication must be proved. Serological tests can help, provided that pretreatment serum is available and three to six months have passed since the treatment. A 13C-ureabreath test (13C-UBT) should be performed at least six weeks after treatment, but false negative results can occur and cut-off must be adjusted.