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During a 3-year period, 258 infants and children underwent rectal biopsy to exclude Hirschsprung's disease (HD) and related disorders; 32 (12%) were found to have HD. Major morbidity occurred in 3 (2%) of 148 patients undergoing rectal suction biopsy (RSB) and 22 (13%) of 168 suction biopsies were inadequate for diagnosis. In 102 children over 6 months of age, Storz rectal cup biopsy forceps were used with no significant morbidity and adequate biopsies were obtained in 96% of cases. Open rectal biopsy was performed in 8 patients. The RSB tube is safe and reliable, but attention to technique is important. For children over 6 months of age undergoing rectal biopsy for HD, the Storz rectal cup biopsy forceps yields superior results.

BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems.

The progress and outcome of proctosigmoiditis (PS) varies from a benign self limited illness to severe or continuous disease which may require major surgery. This study identifies certain clinical features in the presenting attack which appear to influence the subsequent course of the disease. Ninety-nine patients with PS were referred to a colitis clinic between 1975 and 1985. Sixty have been followed for at least five years or have required surgery. They have been classified as follows. Group A-asymptomatic after presenting attack (n = 14), group B-symptoms after presenting attack for less than 10% of follow-up (n = 25), group C symptoms for greater than 10% of follow-up (n = 11), group D - patients requiring surgical intervention (n = 10). Data obtained during the initial attack, including sex, age, length of history, disease extent, length of first attack and therapy, were analysed. There was no significant difference in the length of history or extent of disease between groups. The mean ages in groups A-D were 40, 45, 30 and 24 years respectively. The ages of groups A and B were not significantly different, but differed from group C (p less than 0.05) and from group D (p less than 0.005). The length of the first attack was significantly shorter (p less than 0.01) in groups A and B (median 1.0 and 3.0 months respectively) than in groups C and D (median 5.0 and 6.0 months respectively).

II est admis depuis longtemps que le reflux de bile et d’un contenu intestinal alcalin dans l’estomac, peut provoquer des symptomes et une gastrite hyperhemique. Toutefois, l’identification d’une image histologique distincte est recente. Celle-ci comporte une hyperplasie foveolaire, de 1’œdeme et une congestion de la lamina propria de la muqueuse associes a un faible infiltrat cellulaire inflammatoire. Cersest le manque de reponse cellulaire inflammatoire a cette agression essentiellement chimique, qui a empeche l’identification de la « gastrite par reflux ». Comme il faut s’y attendre, l’image histologique est, apres intervention chirurgicale, plus frequente apres suppression du pylore ou anastomose gastro-intestinale qu’apres intervention conservatrice pour ulcere, telle la vagotomie supra-selective. L’apparition du reflux entero-gastrique transforme la gastrite chronique pre-chirurgicale aHelicobacter pylori en une gastrite par reflux, mais cette transformation s’etale sur plusieurs annees. L’hyperplasie foveolaire sur gastrite par reflux au niveau d’un estomac opere ne doit pas etre surestimee et considered comme une dysplasie de faible degre. Un nombre croissant d’alterations histologiques semblables au reflux ont ete diagnostiquees chez des patients dyspeptiques non operes. Lorsque ces malades presentent un reflux duodenogastrique « spontane », il faut suspecter la prise de AINS. Le diagnostic histologique s’en trouve elargi et le terme « gastrite chimique » a ete suggere en vue de qualifier la reponse de la muqueuse gastrique a diverses sortes d’agents agresseurs, tels la bile, les AINS et eventuellement l’alcool.

BACKGROUND AND STUDY AIMS: Surveillance in Barrett's esophagus relies on the detection of dysplasia by histopathology. However, the natural history of this condition, particularly that of low-grade dysplasia (LGD) is poorly understood. This paper describes our experience of LGD over a period of 21 years. PATIENTS AND METHODS: Between 1984 and January 1995, 357 patients with Barrett's esophagus without dysplasia were recruited for annual surveillance: 34 of these patients developed LGD during this period. This was a retrospective cohort study of this group in terms of survival and cancer outcomes ≥ 8 years after the original diagnosis of LGD, comparing them with the patients who did not develop LGD over the same period, with a histopathological review of the original diagnoses of LGD. The outcomes of 356/357 (99.7 %) of the patients were established in December 2004. RESULTS: After 8 years, high-grade dysplasia (HGD) or cancer had developed in 9/34 patients with LGD (27 %) and in 16/322 controls (5 %). Cox’s proportional hazards model revealed that the time from the first diagnosis of Barrett's esophagus to the first “event” of either HGD, esophageal cancer, or death did not show a statistically significant difference between the two groups. A further analysis treating death as “loss to follow-up” showed a significantly increased risk for the LGD group to progress to HGD or cancer (hazard ratio 5.9 [95 % confidence interval 2.6 - 13.4], P< 0.001). The histopathology review demonstrated a fair level of agreement between pathologists, with a kappa value of 0.48. CONCLUSIONS: Patients diagnosed with LGD during surveillance of Barrett's esophagus are at a considerably increased risk of progressing to develop esophageal cancer over an 8-year period but most deaths are not cancer-related.

AIM: To explore how often a diagnosis of gastric neoplasia is made on routine, non-targeted biopsies taken for determination of Helicobacter pylori status, compared with directed biopsies from endoscopically abnormal mucosa. METHODS: Records of all patients with a biopsy diagnosis of gastric cancer or dysplasia during a two year period were reviewed to determine whether the biopsy had been targeted at an area of mucosal abnormality, and whether there was any evidence of dysplasia or malignancy before endoscopy. RESULTS: Of the 8907 endoscopic examinations that included biopsy, histology showed malignancy in 115 cases and dysplasia in 20. Of these, in 128 cases the biopsies were targeted from focal abnormal areas of mucosa, and six were from areas of diffuse mucosal thickening. In one case, adenocarcinoma was diagnosed in a patient with a "normal" endoscopic appearance; this patient was undergoing repeat endoscopy for previous dysplasia. CONCLUSIONS: Gastric malignancy or dysplasia was detected histologically in 1.5% of endoscopies that included biopsy. The performance of routine biopsies not targeted at a visible lesion from patients without previous diagnosis of neoplasia did not increase the detection of gastric malignancy. Such biopsies are indicated, however, if histological aspects of a patient's gastritis (such as atrophy or intestinal metaplasia) influence the clinical management, as in the treatment of helicobacter gastritis.

The aim of the Expert Approach section is to contribute to the dissemination and standardization of new endoscopic procedures. Authors from three distinct geographic areas combine forces, sharing their experience to form a consensus of opinion. Readers' comments are welcome and will be published in the Mailbox which appears at the end of each Expert Approach article.

Primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma may develop from chronic infection with Helicobacter sp. in the mouse model. The mechanisms of pathogenesis remain unclear. Regulation of B-cell proliferation and death are important features to investigate. Proteins encoded by bcl-2 family genes, e.g., Bcl-X(L), regulate apoptosis; and alterations in the expression of these genes can contribute to the development of cancer. Our aim was to determine the role of Bcl-X(L) in B lymphocytes in the development of gastric MALT lymphoma associated with Helicobacter infection using the BALB/c mouse model. We analyzed 37 animals with Helicobacter-associated MALT (n = 25), low-grade MALT lymphoma (n = 10) and high-grade lymphoma (n = 2), investigating the in vivo distribution of Bcl-X(L) in B cells/B-lymphoma cells using immunohistochemical analysis. In vitro cultivation of B cells/B-lymphoma cells was employed to perform RT-PCR analysis of Bcl-X(L) mRNA expression after cell stimulation with Helicobacter antigen. We found significant Bcl-X(L) protein expression in B lymphocytes within MALT and low-grade MALT lymphoma, whereas there was no and minimal expression, respectively, of Bcl-X(L) in the 2 high-grade MALT lymphoma cases. Expression of bcl-X(L) mRNA in B lymphocytes was up-regulated in vitro upon Helicobacter-antigen stimulation and associated with prolonged cell survival. These findings support the hypothesis that Bcl-X(L) plays a role in the pathogenesis of B-cell MALT lymphoma by providing cell-survival signals and by triggering the acquisition of MALT.

As part of a multinational effort to reach a consensus in the definition and evaluation of atrophic gastritis, we applied morphometric techniques to 22 antral biopsy specimens examined visually by 12 experienced gastrointestinal pathologists.Atrophy was defined as loss of glands. Each pathologist graded atrophy with both non-standardized and standardized approaches. Discriminant function analyses of morphometric measurements were conducted to validate and grade atrophy. Kappa statistics were used to compare the performance of each pathologist against the group mode and against the discriminant functions' grading of atrophy. Three morphometric indexes showed significant differences among categories of atrophy utilizing non-standardized as well as standardized visual atrophy grades: (i) the ratio of glandular length to total mucosal thickness; (ii) the proportion of the secretory compartment area occupied by glands; and (iii) the number of glandular cross sections per 40x microscopic field. The discriminant function analyses verified all cases classified visually as either non-atrophic, or moderately/severely atrophic; it verified as mildly atrophic 40% of the cases classified visually as mildly atrophic; and classified the remaining 60% as moderately or severely atrophic. The kappa statistics were good or excellent for the majority of pathologists.The evaluation of antral atrophy, simply defined as loss of glands, can be reliable and reproducible. The visual grading of atrophy as absent, moderate and severe is entirely consistent with objective morphometric observations.

The aim of the study was to evaluate the current spectrum of gastroduodenal ulcers in children referred to a regional paediatric unit in the United Kingdom. During a 5-y period (1994-98), all children with a visibly discrete gastric and/or duodenal ulcer diagnosed at endoscopy were prospectively identified. Patients with ulcers associated with Helicobacter pylori gastritis underwent repeat endoscopy 2-3 mo after medical treatment. Thirty-seven children, 21 boys and 16 girls of median age 11 y (range 7 mo to 16 y), had gastric and/or duodenal ulceration. Specific aetiological factors were identified in 21 of 22 with H. pylori negative ulcers, including Crohn's disease (n = 6), coeliac disease (n = 4) and treatment with ulcerogenic drugs (n = 4). Fifteen children (41%) had ulcers associated with H. pylori gastritis, including all 10 children with a chronic ulcer. Endoscopically confirmed ulcer healing was achieved in 14 of these using a 1 wk triple therapy regimen (omeprazole and a combination of two antibiotics). In conclusion, the recognized spectrum and the management of gastroduodenal ulceration have changed during the last decade. Although H. pylori gastritis is an important aetiological factor, a wide range of other conditions needs to be considered. Surgical intervention is only rarely necessary.

Large differences have been found between Western and Japanese pathologists' diagnosis of adenoma/dysplasia versus early carcinoma for gastric, esophageal. and colorectal epithelial neoplastic lesions. In this study we examined whether differences in experience in gastrointestinal pathology can to some extent explain these differences in diagnostic practice. Three Japanese, one British, and two German pathologists with much experience and one North American pathologist with less experience in routine diagnostic work reviewed 52 microscopic slides: 16 gastric, 24 esophageal, and 12 colorectal biopsy and resection specimens obtained from patients with lesions ranging from early carcinoma to adenoma, dysplasia, and regenerative epithelium. The extent of agreement between the diagnoses of the four individual Western pathologists and the most common Japanese diagnoses was assessed by kappa statistics. For the 16 gastric lesions, a diagnosis of suspected or definite carcinoma was made by the Japanese pathologists in 69%-75% of the slides, by three experienced Western pathologists in 56%-63% (high kappa values: 0.61, 0.64, 0.65), and by the less experienced Western pathologist in only 31% of the slides (low kappa value: 0.10). For the 24 specimens of esophageal squamous lesions, carcinoma in situ and suspected or definite carcinoma were diagnosed by the Japanese in 96%-100% and by the Western pathologists in 63%-88% of the slides (low kappa values: 0.17, 0.25, 0.25, 0.27). For the 12 colorectal lesions, the Japanese diagnosed suspected or definite carcinoma in 58%-83%, whereas all Western pathologists followed the World Health Organization definition of colorectal carcinoma and diagnosed suspected or definite carcinoma in only 0-42% of the slides (kappa values: 0.04, 0.10,0.12, 0.49). In conclusion, there were few differences in diagnoses between experienced Western and Japanese pathologists for gastric lesions but considerable differences for esophageal and colorectal lesions. The differences in the diagnosis of adenoma/dysplasia versus early carcinoma between Western and Japanese pathologists found in previous studies may in large part be attributable to differences in experience with regard to gastric neoplasia and to differences in interpretation and nomenclature with regard to esophageal and colorectal neoplasia.

We have investigated the genetic basis of gastric carcinomas occurring in patients aged under 40 years from a Portuguese population with a relatively high incidence of gastric cancer. We analysed a panel of 12 microsatellite loci in DNA extracted from gastric carcinomas arising in 16 patients aged 24-39 years from Braga, Portugal. Overall, microsatellite instability (MI) in at least 1 locus was detected in 44% (7 of 16) of carcinomas. A single patient demonstrated a mutator phenotype suggestive of the hereditary nonpolyposis colorectal cancer syndrome with instability in 82% of loci. This carcinoma showed loss of expression of the hMLH1 mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset gastric carcinomas from an English population, which has a relatively low incidence of gastric cancer. Comparing the 2 series, we found that there was a significant difference (p = 0.04) in the prevalence of MI (at least 1 marker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastritis (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 of 8) in Portuguese carcinomas compared with English cases. Genetic mechanisms underlying the hereditary non-polyposis colorectal cancer syndrome may play a role in a small number of early onset gastric carcinomas. The difference in prevalence of low-level MI between these relatively high and low incidence European populations requires further investigation.

The usual form of inflammation seen in gastric biopsies is that of an active chronic gastritis associated with Helicobacter pylori infection. This can be diffuse (a pangastritis) or be more dominant in the antrum or corpus of the stomach. Occasionally, a mild diffuse inactive chronic gastritis without detectable helicobacters is encountered. This form could follow H. pylori infection which has been eradicated, either therapeutically or’ spontaneously’, or have a totally different aetiology. A focal pattern of chronic inflammation can be a microscopic feature of Crohn’s disease1. Unusual forms of H. pylori infection are also recognized. For instance, in children, infection frequently produces antral lymphoid hyperplasia giving rise to endoscopic nodularity. Likewise ‘giant fold’ gastritis is another gross pattern of response to H. pylori infection that can mimic Menetrier’s disease2.

AIMS: To investigate interleukin (IL)-12 (p40) and IL-10 mRNA expression levels in the gastric mucosa in relation to H pylori cag status, peptic ulceration, and histopathology. METHODS: In 81 dyspeptic patients, antral and corpus biopsies were taken for reverse transcriptase polymerase chain reaction (RT-PCR) and histology. G3PDH (control) and IL-10 and IL-12 were coamplified in a duplex PCR and the ratios of cytokines to G3PDH were determined. Bacterial ureA and cagA status was determined by RT-PCR. RESULTS: IL-10 mRNA expression in both the antral and corpus mucosa was greater (p < 0.01) in cagA positive infection than in H pylori negative patients with histologically normal mucosa. No increase in IL-10 mRNA expression was observed in cagA negative infection. Both in the antral and corpus mucosa, IL-12 mRNA expression was greater (p < 0.05) in cagA positive than in cagA negative infection and uninfected patients with normal gastric mucosa. In cagA positive infection, there was a correlation between IL-10 and IL-12 mRNA expression in both the antral mucosa (r = 0.515, p < 0.01) and the corpus mucosa (r = 0.6, p < 0.005). IL-12 mRNA expression in the antral mucosa was significantly more frequent in H pylori positive patients with duodenal ulcer than in those with gastric ulcer or nonulcer dyspepsia. No difference was observed in IL-10 mRNA expression in relation to endoscopic diagnosis. CONCLUSIONS: CagA positive H pylori infection is associated with increased IL-10 and IL-12 mRNA expression. The increased expression of IL-12 mRNA in the majority of patients with duodenal ulcer suggests that Th1 responses may predominate and play a role in the pathogenesis of duodenal ulceration.

Assessment of lesser or doubtful degrees of gastric atrophy can be difficult, especially in the antrum, since well established criteria are lacking. At the Houston Working Party on Gastritis in 1994 a visual analogue scale was designed for the grading of histopathological parameters. This was done to promote uniformity in grading by acting as a reference. The purpose of the present study was to measure interobserver variation between pathologists familiar with the Houston visual analogue scale in a specifically selected set of biopsies from patients with lesser or doubtful degrees of atrophy.Thirty cases with biopsies of the antrum and corpus from a long-term follow-up study on Helicobacter pylori gastritis comprised the current study material. The cases were selected from that study because there had been uncertainty or disagreement on the presence of gastric atrophy. The study set of haematoxylin and eosin (HE) slides was circulated amongst gastrointestinal pathologists familiar with the visual analogue scale who were unaware of the source of the study set nor had any other clinical information. Interobserver variability was analysed using kappa statistics. The overall agreement for the grade of atrophy in antral biopsies was 0.461; the kappa value was 0.18 (95% confidence limits 0.12-0.24), which is considered poor agreement. The kappa value was nevertheless statistically significant (P0. 01). The overall agreement on the grade of atrophy in the corpus biopsies was apparently good (0.833), but the kappa which adjusts for chance agreement was only moderate (0.48; 95% confidence limits 0.42-0.55; P0.001).The studied series comprised a self-selected sample in which there was doubt about the grade of atrophy and such a sample will produce lower kappa values than a random sample of gastric biopsies. The results nevertheless confirm that better guidelines and firm criteria are needed to properly diagnose and grade gastric atrophy. It is suggested that the use of two grades, low- and high-grade atrophy, akin to that in use for grading inflammatory bowel disorder (IBD)- associated dysplasia, could improve agreement. Furthermore optimal biopsy quality with full thickness mucosa and proper orientation appears important for grading gastric atrophy.

A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens.To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease.Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a 13C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment.Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n = 262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P = 0.85, chi-squared test) with regard to the healing of duodenal ulcer disease.The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis.To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori.Men or women with H pylori positive duodenal ulceration or gastritis, or both.A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment.H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported.All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.

Histopathology is the study of diseased tissue. Traditionally such studies have employed light microscopy and electron microscopy to investigate abnormalities in morphology, and histopathologists use a detailed knowledge of alterations in morphology to identify disease processes. It is worthy of repetition that Helicobacter pylori was (re)discovered by a clinical histopathologist using standard microscopy and simple techniques1. In recent years the assessment of tissue morphology has been supplemented by other techniques which yield information of value in differential diagnosis, or in furthering clinicopathological research. The use of specific antibodies in immunohistology allows the histopathologist to accurately identify infective agents, to determine the phenotype of gastric carcinomas and lymphomas including the presence of monoclonality, and to detect abnormal gene products in pre-neoplasia and tumours which are of diagnostic and prognostic value. More recently the search for additional diagnostic information has taken the pathologist into the realms of molecular technology, and the use of human tissues in such studies has given rise to a distinct branch of histopathology — ‘molecular pathology’. The search for genetic lesions in neoplasia and hereditary diseases, and the identification of viral or bacterial genomic material in tissues facilitated by the polymerase chain reaction (PCR), means that the old boundaries of histopathology are constantly shifting.

Since the seminal articles by Correa in the 1970s1,2 it has been widely accepted that the majority of gastric cancers arise through a multi-step process starting with chronic gastritis and progressing through atrophy, metaplasia and dysplasia to invasive carcinoma. Thus atrophy and metaplasia are generally held to be premalignant conditions, although the strength of the association is disputed. Dysplasia, certainly in its high-grade form, is universally considered to herald an imminent change to intramucosal carcinoma and is usually identified by pathologists as a premalignant lesion. Indeed a recent comparison of Western and Japanese pathologists3 revealed considerable overlap between diagnoses of high-grade dysplasia and carcinoma, thereby challenging the artificial histological boundaries that separate them.

Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome.DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer.There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci.The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

The Sydney System for the classification of gastritis emphasized the importance of combining topographical, morphological, and etiological information into a schema that would help to generate reproducible and clinically useful diagnoses. To reappraise the Sydney System 4 years after its introduction, a group of gastrointestinal pathologists from various parts of the world met in Houston, Texas, in September 1994. The aims of the workshop were (a) to establish an agreed terminology of gastritis; (b) to identify, define, and attempt to resolve some of the problems associated with the Sydney System. This article introduces the Sydney System as it was revised at the Houston Gastritis Workshop and represents the consensus of the participants. Overall, the principles and grading of the Sydney System were only slightly modified, the grading being aided by the provision of a visual analogue scale. The terminology of the final classification has been improved to emphasize the distinction between the atrophic and nonatrophic stomach; the names used for each entity were selected because they are generally acceptable to both pathologists and gastroenterologists. In addition to the main categories and atrophic and nonatrophic gastritis, the special or distinctive forms are described and their respective diagnostic criteria are provided. The article includes practical guidelines for optimal biopsy sampling of the stomach, for the use of the visual analogue scales for grading the histopathologic features, and for the formulation of a comprehensive standardized diagnosis. A glossary of gastritis-related terms as used in this article is provided.

The significance of the demonstration of a clonal B-cell population in gastric lymphoid infiltrates was investigated by analysis of immunoglobulin heavy chain (IgH) gene rearrangements using sensitive polymerase chain reactions, employing fluorescently labelled primers to target the FR3 and FR1 regions. Tissue blocks were studied showing different histological features (high-grade lymphoma, low-grade lymphoma, and chronic gastritis) from 12 gastrectomies for primary gastric lymphoma, together with blocks showing chronic gastritis from 13 cases of gastric adenocarcinoma and biopsies from 33 patients with active Helicobacter-associated chronic gastritis. Clonal IgH gene rearrangements were detected in lymphoma samples from eight of the gastrectomies for lymphoma (67 per cent). In four of these eight specimens, clonal rearrangements were also detectable in the samples showing only chronic gastritis. Three of 28 (11 per cent) informative biopsies showing active Helicobacter-associated chronic gastritis had detectable clonal populations. Clonal rearrangements were also demonstrated in two of eight (25 per cent) informative blocks showing chronic gastritis from eight gastrectomies for adenocarcinoma. It is concluded that the detection of a clonal population in a suspicious lymphoid infiltrate does not confirm the diagnosis of lymphoma, nor does the absence of such a population imply benignity.

Gastric lymphomas account for only a small proportion of gastric malignancies, between 1% and 7% depending on the geographical area1, but their incidence is increasing2. Almost all are B-cell lymphomas, a proportion of which recapitulate the appearances of mucosa-associated lymphoid tissue (MALT) and are similar to low-grade B-cell lymphomas arising in the lung, thyroid and salivary gland3. As with these latter two sites, the stomach has no intrinsic lymphoid tissue. It is now clear that the appearance of a lymphoid infiltrate in the gastric mucosa is largely a consequence of H. pylori infection. Thus it can be anticipated that H. pylori gastritis is a major precursor of gastric lymphoma, and evidence to this effect has accumulated over recent years.

It is interesting that the principal histological features of acute H. pylori gastritis, surface epithelial degeneration and neutrophil polymorph infiltration, remain as the most sensitive indicators of the 'activity' of infection in the chronic phase. It is not surprising therefore that these are the first features to resolve after successful H. pylori eradication therapy. In one of the earliest studies of histological response to eradication, McNulty et al (1986) endoscoped patients immediately after a three-week treatment regime and found a highly significant decline in polymorph scores. The response was even more striking four weeks after the end of treatment, as at that time biopsies from responders were virtually devoid of polymorphs (Valle et al, 1991). Indeed the disappearance of polymorphs from a post-treatment biopsy is a useful indicator of successful eradication. Less attention has been paid to the recovery of the surface epithelium yet this is an impressive feature when comparing pre- and post-treatment biopsies. Using subjective grading of surface epithelial lesions, Solcia et al (1994) found a dramatic and highly significant improvement in mean grade immediately after anti-H. pylori treatment. Recently a morphometric approach was used to demonstrate a significant increase in surface epithelial cell height corresponding to the recovery that accompanies successful H. pylori eradication (Hassan et al, 1993). Chronic inflammatory cell infiltrate resolution is much slower. There is only a gradual reduction in cell density so that even 6 months after eradication treatment the mean score had only fallen by 50% of pre-treatment values (Solcia et al, 1994). In the author's experience, a minor increase in such cells persists for many months and may never completely resolve, in that more lymphocytes and plasma cells are seen than in a truly normal (pre-infection) stomach. Valle et al (1991) found resolution of chronic inflammation in only 15% of subjects at 6 months and in 51% at one year after eradication. The long delay in disappearance of lymphocytes and plasma cells poses a question over continuing antigenic stimulation in the absence of infection. Possible answers could involve persistence of antigenic moieties in dendritic cells of the lamina propria, or sensitization to host antigens brought about by infection so that an element of autoimmunity persists after eradication. Unravelling these mechanisms will add important new elements to our understanding of the long-term consequences of this fascinating infection.

We aimed to produce a unifying hypothesis to explain the different locations of peptic ulcer and gastritis observed in different populations. The pre-Helicobacter pylori literature on patterns of gastroduodenal disease was reviewed and compared with recent human and animal findings on H. pylori infection. Early observations revealed that duodenal and non-pre-pyloric ulcers tend to be mutually exclusive. In duodenal ulcer patients, gastritis is usually restricted to the antrum, while gastric ulcer patients experience more severe pangastritis. The manipulation of acid output by surgery or acid suppressive therapy alters the distribution of gastritis. Recent experimental evidence in humans and animals has shown that these changes parallel changes in the distribution and cellular responses to H. pylori infection. We propose that the most important factor in the ecology of the H. pylori-infected stomach is local acid production. Local acid production determines the location and severity of inflammation and the clinical outcome of this bacterial infection. Priority research areas should be the investigation of the in vivo behaviour of H. pylori in the acid and the non-acid producing areas of the stomach and the measurement of acid output in populations known to have different patterns of gastroduodenal disease.

To examine the relationship between Helicobacter pylori and recurrent ulceration after highly selective vagotomy (HSV).Academic Department of Surgery at a teaching hospital.Thirty-eight patients (26 men and 12 women) were studied 2-21 years after HSV. Seven patients had recurrent ulceration. Each patient underwent tests of acid secretion before and 1 week after HSV together with later endoscopic examination of the stomach and duodenum. Four biopsies were taken from the duodenum and gastric antrum.There was no statistical difference in acid output between patients with and those without recurrent ulceration (peak acid output 46.9 versus 55.8 mmol/h, respectively; not significant) before operation. After operation, insulin stimulated acid secretion was significantly higher in patients who later developed recurrent ulceration (0.26 versus 4.1 mmol/h, respectively; P0.02). The endoscopic biopsies were tested for H. pylori infection (90 versus 86% for patients without and those with recurrent ulceration, respectively; not significant), gastric metaplasia within the duodenum (23 versus 14% for patients without and those with recurrent ulceration, respectively; not significant), antral gastritis (86 versus 71% for patients without and those with recurrent ulceration, respectively; not significant) and antral intestinal metaplasia (52 versus 43% for those without and those with recurrent ulceration, respectively; not significant).H. pylori infection is not influenced by HSV and ulcer recurrence is determined by the completeness of vagotomy rather than by H. pylori status.

We report a case of gastric colonization of large spiral-shaped bacteria in a patient with acute gastritis. Endoscopy showed an acute erosive and hemorrhagic gastroduodenitis. Histopathological examination of antral biopsies revealed intense neutrophil infiltrates with microabscesses. Numerous large spiral-shaped bacteria were seen in the Gram-stained smear of the gastric biopsy. The patient was treated with colloidal bismuth subcitrate and cimetidine. Biopsy taken after treatment showed resolution of infection and histological gastritis. The results provide further evidence that large spiral-shaped bacteria are another infective cause of acute neutrophilic gastritis in humans.

We have studied modulation of mucosal interleukin-6 (IL-6) secretion by T-cell activation and by anti-inflammatory agents in inflammatory bowel disease.In vitro secretion of IL-6 by biopsy specimens from patients with active ulcerative colitis was investigated in the presence of cyclosporin-A (CsA) and drugs that have other anti-inflammatory actions. Biopsy specimens from patients with quiescent ulcerative colitis or controls were stimulated with anti-CD3 antibody to activate mucosal T cells.Stimulation of control specimens increased IL-6 secretion (median increase, 147%; p0.003), which was prevented by CsA. In quiescent ulcerative colitis there was enhanced spontaneous secretion of IL-6 but a smaller, non-significant increase after T-cell activation (125%). Dexamethasone inhibited secretion in active ulcerative colitis (p0.006). 5-Aminosalicylic acid, 6-mercaptopurine, methotrexate, and indomethacin had no effect. There also tended to be a small reduction with CsA, but this just failed to reach statistical significance.In quiescent ulcerative colitis the enhanced spontaneous secretion of IL-6 may be a consequence of mucosal T-cell or macrophage activation: the smaller increase after T-cell stimulation suggests that one or both of these two cell types are already pre-activated.

The acute phase of Helicobacter infection is uncommon in gastric biopsies because the initial illness is trivial in its symptomatology or goes unnoticed by the patient. Usually the presence of an acute phase is inferred from serological findings. The published accounts are largely confined to human ingestion studies1,2, or from ‘naturally’ acquired infection in endoscopy personnel3.

Helicobacter pylori is now accepted as the major cause of chronic gastritis. The initial response to infection is acute neutrophilic gastritis, which progresses to active chronic gastritis in most people. To confirm the pathogenic role of H. pylori, both the individual histological features of chronic gastritis and its topographical patterns must be shown to be caused by the infection. Surface epithelial degeneration is a probable result of direct tissue injury by bacterial products. Candidates are ammonia or ammonium products, cytotoxins, phospholipases and pro-inflammatory products such as lipopolysaccharide and platelet-activating factor. Neutrophil polymorph and chronic inflammatory cell infiltration are consequences of the mucosal immune response to bacterial antigens. Complement products and interleukin (IL)-8 are polymorph chemotaxins, and monocyte processing of antigens, followed by T helper cell and B lymphocyte responses, explain the presence of these cells in the mucosa. Atrophy may be a consequence of autodestructive products of neutrophil and monocyte activation, such as reactive oxygen metabolites and proteases. Intestinal metaplasia is most probably an adaptive response, possibly to H. pylori infection, exacerbated by other injurious agents such as bile reflux and dietary irritants. Pangastritis is the usual outcome after H. pylori infection. This is followed by multifocal atrophy and intestinal metaplasia. The latter changes weaken mucosal defences further and peptic ulceration may ensue. Patients with an increased parietal cell mass who become infected with H. pylori will exhibit antral restriction of the gastritis because the high acid output protects the corpus mucosa from bacterial adhesion and the inflammatory consequences. Such patients also have acid-induced gastric metaplasia in the proximal duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

The gastrointestinal mucosa has a dense network of nerve fibres arising from intrinsic and extrinsic neuronal cell bodies1. In the pyloric antrum, mucosal nerves are involved in the regulation of gastrin (G) and somatostatin (D) cell function1. Cholinergic nerves inhibit D cell production of somatostatin, and gastrin release is stimulated by gastrin-releasing peptide2. Luminal factors (e.g. pH) and distension also regulate G and D cell function. Thus, the release of gastrin is modulated by luminal, paracrine and neurocrine mechanisms. Helicobacter pylori infection results in disruption of the G and D cell regulatory pathways, and can lead to increased basal and meal-stimulated serum gastrin levels3,4. Since gastrin acts in an endocrine fashion on the corpus mucosa5, increasing acid release, the increased level of this hormone is thought to be an important factor in the pathogenesis of peptic ulcers.

A family with the autosomal dominant form of familial visceral myopathy is described involving four generations. The members illustrate several different clinical presentations including severe constipation, diarrhea, alternating constipation and diarrhea, volvulus, urinary tract infection, and retention of urine. One patient's history suggested that the uterus may have been involved. Diagnosis of this rare disease requires an awareness of the variable presentation and a careful histological examination of full-thickness sections of bowel. The potential pitfalls in both histological and clinical diagnosis of this condition are demonstrated in this family's history. The extensive involvement of small and large bowel in at least two family members is unusual in the autosomal dominant form of the disease, but their course has so far been favorable, lending further evidence to the impression that prognosis is good. This is of importance for genetic counseling of families who have this very rare disease.

Gastrointestinal haemangiomas make up 0.05% of all intestinal neoplasms. They are sometimes multiple and usually present with pain, bleeding, and obstruction. An associated haemangiomatous change in regional lymph nodes has not been reported previously. A woman of 21 years presented with abdominal pain and vomiting. Abdominal ultrasound and computed tomography scan showed a lower abdominal mass. Laparotomy revealed a small bowel tumour causing an intussusception together with enlarged mesenteric lymph nodes. Pathological examination revealed a small bowel haemangioma with mesenteric node involvement. The pathogenesis of haemangiomatous involvement of lymph nodes is discussed. Hamartomatous change is the likely cause in this patient.

The presence of inflammation in the gastric mucosa is recognized morphologically by changes in cellularity, vascularity, and epithelial integrity. Acute purulent gastritis, which is rarely encountered by the histopathologist, is characterized by a neutrophil infiltrate and surface purulent exudate; such an effect has been attributed to the acute stage of Helicobacter pylori infection [1].

Demand for endoscopy services is growing inexorably and diverse strategies have been proposed to use them more effectively [1,8]. One suggestion has been centred around the close association between Helicobacter pylori and peptic ulcers and the development of accurate serological tests for the presence of this organism. This could allow endoscopy to be targetted to patients serologically positive for H. pylori, among whom nearly all peptic ulcers should occur. We have examined the likely results of implementing three different strategies for easing endoscopic workload, using retrospective data from dyspepsia clinics.

Although for many years a simple classification of ‘non-specific’ gastritis into acute, chronic superficial and chronic atrophic categories has sufficed in routine histopathological practice, the clinical significance of the latter diagnoses is uncertain. While acute gastritis has well established and consistent clinical associations (a recent history of drug ingestion or alcohol excess leading to haemorrhagic erosions), the clinical features of chronic gastritis are much more nebulous. The finding of chronic gastritis in ‘healthy volunteers’ (Kreuning et al. 1978) and in random population surveys (Villako et al. 1976) has led some to conclude that the condition is a normal aging process of no clinical consequence. While this is a minority view, even those who believe it to be a pathological process have difficulty in recognising at what point the density of the inflammatory cell infiltration becomes ‘abnormal’, and the relationship between this inflammatory process, symptomatology and associated pathology.