Low-grade dysplasia in Barrett's esophagus has a high risk of progression.

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.

Protection against Helicobacter pylori infection in the Mongolian gerbil after prophylactic vaccination.

Vaccines against Helicobacter pylori could circumvent the problem of increasing antibiotic resistance. They would be particularly useful in developing countries, where re-infection rates are high following standard eradication regimes. The Mongolian gerbil is a good model for H. pylori infection, as the gastric pathology induced by infection is similar to that in humans. The H. pylori-induced inflammatory response in gerbils is considerably greater than in murine models. The aim of this study was to determine if gerbils could be vaccinated against H. pylori. Mongolian gerbils were vaccinated orally with an H. pylori whole cell sonicate preparation and cholera toxin adjuvant. Vaccinated gerbils and controls were challenged with the autologous H. pylori strain 42GX. All infection, and cholera toxin, control gerbils were H. pylori positive 6 weeks post-challenge. By contrast, a significant degree of protection was demonstrated in vaccinated gerbils. Only two of 10 of gerbils were H. pylori positive (P<0.001). Protection was associated with increased serum H. pylori IgG antibodies. Protected gerbils had histologically normal gastric mucosa and, in contrast to mice, no post-immunisation gastritis was evident. In the control groups, the degree of inflammation was variable, with some of the animals having corpus gastritis and corpus mucous metaplasia. The levels of gastric IL-12p40 and IFNgamma transcripts were significantly decreased in vaccinated animals compared to infection and cholera toxin controls (P<0.01). Gastric IL-10 and TGFbeta transcripts were found only at relatively low levels. These results demonstrate that Mongolian gerbils can be successfully vaccinated against H. pylori and protected from H. pylori-induced pathology.

Prognostic significance of microsatellite instability in patients with gastric carcinoma.

A proportion of gastric adenocarcinomas exhibit replication errors manifested as microsatellite instability. The clinicopathological and prognostic significance of this abnormality remains uncertain. This study aimed to determine the importance of microsatellite instability by analysing a large series of gastric carcinomas from an English population. Using a novel fluorescent polymerase chain reaction technique, we amplified 11 microsatellite sequences from paired normal and carcinoma DNA from 101 patients who underwent a potentially curative resection for gastric carcinoma. Overall, 21% of cases demonstrated microsatellite instability in at least one locus. At least four loci were examined in each case. A replication error positive phenotype (minimum of 29% of loci affected) was detected in 9% of cases. There was no statistically significant association between the presence of microsatellite instability or replication error positive phenotype and the patient's age, sex, tumour site, stage, node status, histological subtype or grade. Carcinomas confined to the mucosa or submucosa (T1) showed a significantly higher frequency of instability and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05, respectively). A larger proportion of patients who were microsatellite instability or replication error positive were alive at 5 years compared with those who were negative but this did not reach statistical significance (P = 0.15 and P = 0.16, respectively). We identified a subset of gastric carcinomas from a relatively low-risk population which showed evidence of microsatellite instability. There were no statistically significant 5-year survival advantages in cases demonstrating microsatellite instability or replication error positive phenotypes. The detection of microsatellite instability is of limited prognostic value in gastric carcinoma.

A flow cytometric, clinical, and histological study of stromal neoplasms of the gastrointestinal tract.

Histological sections of 102 stromal neoplasms of the gastrointestinal tract occurring in 100 patients have been assessed for 23 clinical and histological parameters and the corresponding paraffin embedded (archival) material processed for flow cytometry. Where possible, information as to clinical presentation and survival was obtained. The only absolute criterion for malignancy was the presence of spread of tumour beyond the organ of origin at the time of diagnosis. Of the remaining tumours (i.e., tumours locally confined at diagnosis), those found incidentally at operation and those of a small size (less than 60 mm diameter) behaved in a generally benign fashion. Of the histological parameters, six correlated with malignant behaviour: high mitotic count, high cellularity, marked nuclear pleomorphism, rounded as opposed to spindle cell shape, bizarre mitoses, and vascular invasion. The presence of DNA aneuploidy as shown by flow cytometry correlated strongly with a poor prognosis (p less than 0.0005). Tumours with a high mitotic count [greater than 9 per 10 high-power fields (hpf) (1.59 mm2)] behaved in an almost uniformly malignant fashion. Those with a low mitotic count [less than 3/10hpf (1.59 mm2)], behaved in a benign fashion apart from one case where no mitoses were discernible yet the tumour metastasised and killed the patient. The intermediate group of tumours (3-9 mitoses per 10 hpf inclusive) were difficult to predict, although the majority behaved in a malignant fashion. Within this group the presence of DNA aneuploidy appeared most useful in predicting prognosis.

Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994.

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.

Gastric dysplasia: the Padova international classification.

A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.

Choline acetyltransferase (ChAT) immunoreactivity in paraffin sections of normal and diseased intestines.

There is increasing interest in localizing nerves in the intestine, especially specific populations of nerves. At present, the usual histochemical marker for cholinergic nerves in tissue sections is acetylcholinesterase activity. However, such techniques are applicable only to frozen sections and have uncertain specificity. Choline acetyltransferase (ChAT) is also present in cholinergic nerves, and we therefore aimed to establish a paraffin section immunocytochemical technique using an anti-ChAT antibody. Monoclonal anti-choline acetyltransferase (1.B3.9B3) and a biotin-streptavidin detection system were used to study the distribution of ChAT immunoreactivity (ChAT IR) in paraffin-embedded normal and diseased gastrointestinal tracts from both rats and humans. Optimal staining was seen after 6-24 hr of fixation in neutral buffered formalin and overnight incubation in 1 microgram/ml of 1.B3.9B3, with a similar distribution to that seen in frozen sections. In the rat diaphragm (used as a positive control), axons and motor endplates were ChAT IR. Proportions of ganglion cells and nerve fibers in the intramural plexi of both human and rat gastrointestinal tracts were also ChAT IR, as well as extrinsic nerve bundles in aganglionic segments of Hirschsprung's disease. Mucosal cholinergic nerves, however, were not visualized. In addition, non-neuronal cells such as endothelium, epithelium, and inflammatory cells were ChAT IR. We were able to localize ChAT to nerves in formalin-fixed, paraffin-embedded sections. The presence of ChAT IR in non-neuronal cells indicates that this method should be used in conjunction with other antibodies. Nevertheless, it proves to be a useful technique for studying cholinergic neuronal distinction in normal tissues and pathological disorders.

Gastric metaplasia: its role in duodenal ulceration.

There is good evidence to suggest that gastric metaplasia in the proximal duodenum and Helicobacter pylori gastritis are essential requirements for the development of duodenal ulceration in most cases. Gastric metaplasia is most likely to be a defence response or adaptation to excess acid reaching the duodenum. The appearance of gastric-type epithelium over the duodenal villi probably results from substitution by cells migrating from Brunner's gland ducts. These metaplastic foci provide sites for colonization by H. pylori passing through the duodenum; the organisms do not attach to native duodenal epithelial cells. Having colonized the metaplastic areas, H. pylori provokes an active chronic inflammatory response akin to that seen in the gastric mucosa. Active chronic duodenitis leads to a weakening of mucosal defence against acid-peptic attack, and erosion and ulceration may ensue. Healing of ulcers by conventional acid-reducing treatments does not influence the extent of gastric metaplasia, (although there may be some reduction with long-term proton pump inhibitors); nor do such regimens affect the background duodenitis. Only with eradication of H. pylori is there resolution of inflammation, but studies to date indicate that eradication alone has no substantial effect on the prevalence or extent of gastric metaplasia. Nevertheless the elimination of H. pylori appears to remove one of the essential co-factors for duodenal ulceration and the patient can be considered cured, despite the persistence of gastric metaplasia.

The efficacy of tobramycin in the treatment of ulcerative colitis.

This paper reports a double-blind placebo-controlled trial of oral tobramycin in acute ulcerative colitis. Eighty-four patients with an acute relapse of ulcerative colitis were randomized to receive oral tobramycin or placebo for 1 week as an adjunct to steroid therapy. At endpoint, 31 of 42 (74%) in the tobramycin group achieved complete symptomatic remission compared with 18 of 42 (43%) in the placebo group (P = 0.008). The tobramycin group achieved better histological scores (P less than 0.05) at endpoint. These findings show that treatment with oral tobramycin improves the short-term outcome of patients with ulcerative colitis in relapse.

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori. The Lansoprazole Helicobacter Study Group.

BACKGROUND: 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. AIM: To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease. METHODS: 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. RESULTS: 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. CONCLUSIONS: The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading.

BACKGROUND AND AIMS: Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers. METHODS: After redefining atrophy as the 'loss of appropriate glands' and examining histological samples from different gastric compartments, three categories were identified: (i) negative; (ii) indefinite; (iii) atrophy, with and without intestinalization. Atrophy was graded on a three-level scale. Interobserver reproducibility of the classification was tested by kappa statistics (general and weighted) in a series of 48 cases. RESULTS: The medians of the general agreement and weighted kappa values were 0.78 and 0.73, respectively. The weighted kappa coefficients, obtained by cross-tabulating the evaluation of each pathologist against all others, were, with only one exception, > 0.4 (moderate to excellent agreement). CONCLUSIONS: By using the definition of atrophy as the loss of appropriate glands and distinguishing the two main morphological entities of metaplastic and non-metaplastic types, a high level of agreement was achieved by a group of gastrointestinal pathologists trained in different cultural contexts.

Value of routine, non-targeted biopsies in the diagnosis of gastric neoplasia.

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.

Quantitative assessment of the mucosal architecture of jejunal biopsy specimens: a comparison between linear measurement, stereology, and computer aided microscopy.

Fifty jejunal biopsy specimens obtained from normal subjects and from untreated and treated patients with coeliac disease were assessed blindly by three independent observers, each of them using different morphometric techniques-namely, linear measurement, stereology, and computer aided microscopy. In two of 26 control biopsy specimens linear measurement was not possible because of distortion of villi. Highly significant (p less than 0.001) correlation coefficients were found between the different techniques. With all methods significant differences between controls and patients with coeliac disease and between treated and untreated coeliac patients were found. Only by stereology, however, was there no overlap between results for patients and those for controls. In view of the limitations of linear measurement and the high cost and complexity of computer aided microscopy, we propose that a simple stereological technique using an eyepiece graticule is the method of choice in the quantitative assessment of mucosal architecture in jejunal biopsy specimens.

Assessment of dysplasia in colorectal adenomas: an observer variation and morphometric study.

Observer variation in the grading of dysplasia in 100 colorectal adenomas has been analysed by kappa statistics. Intraobserver agreement was only 70% and 67% for the two principal observers, and, as would be expected, interobserver agreement was even lower at 59% and 66%. Although the kappa values were significantly different from chance at the 0.1% level, there were substantial disagreements. When the study was extended to four observers, agreement between observer pairings was considerably worse (as low as 34%), and in four pairings the kappa values did not differ significantly from those expected by chance alone even at the 5% level. In an endeavour to improve agreement we adopted a percentage estimation grading method; but this failed to achieve any improvement when comparing overall grades. The percentage estimates of the two observers, however, showed a highly significant correlation. To identify the cytological features given most weight by the principal observers in assessing dysplasia we undertook morphometry on 30 adenomas using an image analysis computer. The nuclear to cytoplasmic ratio, variation in nuclear area, and variation in nuclear height above the basement membrane showed significant differences between mild, moderate, and severely dysplastic epithelia. While evaluation of these parameters therefore appears to be most important in the subjective interpretation of dysplasia, this study has shown that such evaluation is poorly standardised between observers and poorly reproduced within observers. Our findings of poor agreement in the grading of dysplasia in colorectal adenomas has serious implications for the assessment of dysplasia in inflammatory bowel disease, where the added problem of reactive cellular atypia brings greater complexity to these subjective judgments.

Abnormal intestinal permeability and jejunal morphometry.

The cellobiose and mannitol differential sugar test is a non-invasive investigation of small bowel permeability, in which urinary recoveries of cellobiose and mannitol after a hyperosmolar oral load are expressed as a ratio to give a permeability index. Changes in the cellobiose:mannitol ratio often occur in coeliac disease, but some patients with abnormal permeability have normal jejunums by routine microscopy. Using computed morphometry the perimeter:lamina propria area index of jejunal biopsy samples was measured and compared with the cellobiose:mannitol ratio in three groups of patients: (i) those with coeliac disease with villous atrophy; (ii) those with normal jejunums and sugar test results: and (iii) those with normal jejunums but abnormal sugar test results. In addition to the expected difference in perimeter:lamina propria area index between patients with coeliac disease and those with normal findings (p less than 0.001), the index was also abnormal in patients with normal jejunums but abnormal sugar test results: (p less than 0.001 compared with group 1) and (0.01 greater than p greater than 0.001 compared with group 2). There was a significant overall correlation between the perimeter:lamina propria area index and cellobiose:mannitol ratio (p = 0.001). This study shows that computed jejunal morphometry can identify patients with subtle morphological changes that are related to abnormal intestinal permeability.

Histological identification of Helicobacter pylori: comparison of staining methods.

AIM: To determine whether two recently described staining methods (the modified McMullen's and the Helicobacter pylori silver stain HpSS methods) used for the histological identification of H pylori organisms are superior to two established techniques (the modified Giemsa and anti-H pylori antibody immunostain) in terms of availability, reproducibility, rapidity, sensitivity, and cost. METHODS: Histological sections from 63 paired gastric biopsies from adult patients previously investigated for dyspepsia were stained with the four methods and these were assessed blindly and independently by two observers. Of the 63 patients, 30 were originally negative in all tests for H pylori infection, 30 were positive, and the remaining three cases had discordant results using a combination of five tests (rapid biopsy urease test, urea breath test, culture, serology, and histology). RESULTS: Interobserver agreement was best with the antibody method (98%), followed by the McMullen's (90%), Giemsa (87%), and HpSS (85%). Of the 60 "gold standard" positive and negative cases, 30 were positive by the modified Giemsa stain, 29 by the McMullen's method, 29 by HpSS, and 30 by the antibody stain. However, there were two false positives with the HpSS method. The modified Giemsa is the cheapest and easiest to perform technically. CONCLUSIONS: When H pylori are present, careful examination will almost always reveal them, whichever of these stains is used. However, the modified Giemsa stain is the method of choice because it is sensitive, cheap, easy to perform, and reproducible.

Small bowel haemangioma with local lymph node involvement presenting as intussusception.

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.

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma.

Quantitation of intraepithelial lymphocytes in human duodenum: what is normal?

BACKGROUND: An increase in intraepithelial lymphocytes (IELs) is mandatory for the histological diagnosis of coeliac disease (CD). Currently, duodenal biopsies are used almost exclusively to establish the diagnosis, yet published work continues to cite an upper limit of 40 lymphocytes/100 epithelial cells, a figure derived from jejunal biopsies over 30 years ago. AIM: To establish the normal range for IEL counts in distal duodenal biopsies. MATERIALS/METHODS: Twenty subjects (seven men, 13 women; median age, 34 years; range, 20-65) with a normal sugar permeability test and concurrent distal duodenal biopsies were identified. The number of IELs and epithelial cell nuclei in an uninterrupted length of surface (villous) epithelium (> 500 cells) was counted. An image analysis system was used to assess villous architecture by calculating the villous height to crypt depth ratio. RESULTS: The range of IEL counts in 20 subjects was 1.8-26/100 villous epithelial cells, with a mean value of 11 and SD of 6.8. The mean villous to crypt ratio was 1.82 (SD, 0.38; range, 1.22-2.46). There was no correlation between IEL counts and villous to crypt ratio (Spearman rank correlation, -0.066; p = 0.80). CONCLUSIONS: These results suggest that 25 IELs/100 epithelial cells (mean +2 SD) should be taken as the upper limit of the normal range for duodenal mucosa.

Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis.

Biopsy specimens of gastric and duodenal mucosa from 290 patients were examined histologically for metaplasia and Campylobacter pyloridis. Estimates of pH on samples of fasting gastric juice from 55 of the patients were performed, and mucosal biopsy specimens from 33 patients were also cultured for C pyloridis. Active duodenitis was seen in 34 duodenal biopsy specimens. Thirty (88%) of the patients with active duodenitis had both greater than 5% gastric metaplasia in the duodenal specimen and C pyloridis associated gastritis. These two factors coexisted in only 0.43% of patients with no duodenal inflammation. When C pyloridis were seen histologically in duodenal biopsy specimens they were confined to areas of gastric metaplasia and never occurred in the absence of a polymorph infiltrate. Of the 55 patients with measurements of gastric juice pH, gastric metaplasia was present in the duodenum in 20 of 42 with a pH of less than 2.5, and in 0 of 13 with a pH of greater than 2.5. These results suggest that acid induced gastric metaplasia in the duodenum and C pyloridis associated gastritis may be synergistic in the pathogenesis of duodenitis; the metaplastic gastric epithelium allows C pyloridis to colonise the duodenal mucosa, where it produces an acute inflammatory response.