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A raised intraepithelial lymphocyte (IEL) count with normal villous architecture is a recognised finding in latent coeliac disease. Little information is available in cases without gluten sensitive enteropathy in adults.To assess the frequency of such a finding in routine practice and to determine whether it is clinically relevant.Patients with subjectively increased IELs as the only abnormality were identified prospectively from a routine duodenal biopsy series over a 12 month period. The biopsy specimens in these index cases were re-examined together with two controls with normal histology for each case, and three counts of IEL/100 epithelial cells were made in all samples. The index cases were then contacted and interviewed to obtain clinical information, approximately 12 months from the initial biopsy. Further data were obtained from their clinical records.Fourteen of 626 (2.2%) patients who had duodenal biopsies over the 12 month period had a subjective increase in IELs with normal villous architecture. Fifteen patients with newly diagnosed gluten sensitive enteropathy were also identified during the study period. Formal counting of the index cases and controls revealed a significant difference in IELs/100 epithelial cell counts between the two (mean, 38 (SD, 6.2) v 12.4 (4.6); p0.0001). Three of the 14 index cases tested had a positive coeliac antibody test compared with 12 of 15 newly diagnosed patients with coeliac disease and 10 of 93 patients with normal histology. The major clinical diagnostic categories in raised IEL cases were those with positive coeliac serology (n = 3), unexplained anaemia (n = 3), and chronic liver disease (n = 3). Six of 10 patients who were interviewed had ongoing gastrointestinal symptoms one year later. Three patients had had follow up duodenal biopsies, at the discretion of their responsible clinicians, with no change in IEL counts despite the commencement of a gluten free diet in two patients.A raised IEL count with normal villous architecture is not uncommon. Six of the 14 patients may have had latent coeliac disease. The cause in at least half of cases is not obvious at present. The finding of a raised IEL count with normal villous architecture is of sufficient clinical importance to be highlighted in routine duodenal biopsy reports.

Background: Proton pump inhibitor-based triple therapy is recommended as treatment for Helicobacter pylori eradication. The proton pump inhibitor may be given once or twice daily. However, little information is available on how these two treatment strategies compare. Methods: H. pylori-positive patients (two positive test results) with endoscopy-proven healed duodenal ulcer or non-ulcer dyspesia were randomly allocated to 1 week of double-blind treatment with pantoprazole 40 mg once or twice daily, plus clarithromycin 250 mg and metronidazole 400 mg twice daily. Eradication was defined as a negative 13C-urea breath test (13C-UBT) and histology, 4–5 weeks post-treatment. The follow-up phase comprised 12 months off therapy, with 13C-UBT at 6 and 12 months. Results: Two hundred and four patients received treatment: pantoprazole once daily (×1), n=104; twice daily (×2), n=100. Eradication rates were 84% in both the pantoprazole ×1 and pantoprazole ×2 groups by modified intention-to-treat analysis and 89% and 87%, respectively, by per protocol analysis. Metronidazole resistance was found in 44% of pre-treatment cultures of H. pylori. Eradication rates were similar in susceptible (72%) and resistant (75%) strains. During follow-up, recrudescence of infection occurred in 3/118 patients. Conclusion: When using pantoprazole plus clarithromycin and metronidazole, the proton pump inhibitor can be used once daily without loss of efficacy.

Since the isolation of Helicobacter pylori by Marshall in 1982, much evidence has accumulated to show the important role it plays in the pathogenesis of chronic gastritis and peptic ulceration. Revision of long established concepts on the aetiology of peptic ulceration as an acid diathesis has become essential. Dyspepsia is very common; 1% of the United Kingdom population present to their general practitioner with food related abdominal pain. On investigation, one third will have peptic ulceration, one third will have no obvious abnormalities (non-ulcer dyspepsia), and the remainder will have various other disorders such as gallstones, irritable bowel, and so on. It is now accepted that histologically confirmed chronic gastritis and duodenal ulceration is caused by H pylori infection in over 90% of cases and that H pylori is responsible for at least 50% of gastric ulcers. Complications such as bleeding, perforation, and stenosis occur in 3% of ulcer patients a year, and unless maintenance treatment is given 82% of ulcers treated with H2 receptor antagonists relapse within one year. Recurrence of peptic ulceration within two years after initial eradication of H pylori is reduced to 0–15%, 5 so the advantages of H pylori eradication in these patients are enormous. Determination of helicobacter status of patients with current or previous peptic ulcer disease, and treatment of the infection in those found positive, is now the recommended management for peptic ulcer disease. The role that H pylori plays in non-ulcer dyspepsia is more controversial, as studies with short follow up have shown no benefit. However, at one year the benefits of treatment become more evident. Patients with non-ulcer dyspepsia with H pylori have 20 times the risk of developing duodenal ulcer than those who are not infected and a lifetime risk of developing gastric cancer which is up to six times that of an uninfected individual. 8 Although the benefit of treating infected patients without peptic ulceration has not been established by clinical trials, individuals who test positive are increasingly being oVered treatment in view of the estimated 15% risk of subsequent complications and increasing public awareness of the infection. The diagnosis of H pylori infection is therefore very important but as yet there are no internationally agreed guidelines on the management of helicobacter associated dyspepsia—although there have been several national meetings and reports, the most recent being the Maastricht consensus report produced in Autumn 1996. The presence of H pylori should always be verified before initiation of anti-H pylori treatment, as the type of dyspeptic symptoms predicts only poorly the cause of dyspepsia or the presence of H pylori.

We wanted to assess the diagnostic value of pre-endoscopy screening by Helicobacter pylori serology, serum recognition of the CagA and VacA proteins, and serum pepsinogen I levels (sPGI) in patients up to 55 years of age with uncomplicated simple dyspepsia.Consecutive dyspeptic patients referred for open-access endoscopy, excluding patients with alarm symptoms, recent intake of acid suppressants, or ingestion of non-steroidal anti-inflammatory drugs. H. pylori status was determined by histology and urease testing. H. pylori serologic status was determined with the enzyme-linked immunosorbent assay (ELISA) and Western blotting, serum recognition of CagA and VacA with Western blot, and sPGI levels by radioimmunoassay.One hundred and fifteen patients were studied (mean age, 40 years: range, 20-55 years), of whom 58 were H. pylori-positive in biopsy-based tests. Twenty-one patients (18%) had significant gastroduodenal lesions (erosions, ulcers, or cancer). The sensitivity (specificity) of the ELISA (optimized) and Western blot in determining H. pylori status was 94.8% (89.5%) and 100% (96.4%), respectively. Screening strategies based on the ELISA or Western blot for determining H. pylori serologic status would have detected 95% or 100% of significant lesions, respectively, and each 'saved' 47% of endoscopies for simple dyspepsia. Serum recognition of the CagA protein would have detected 95% of significant lesions and 'saved' 55% of endoscopies, whereas recognition of the VacA protein would have detected only 81% of the lesions. Screening by H. pylori serology plus a 'low' (55 ng/ml) or 'high' sPGI (125 ng/ml) would detect only 57% of significant lesions, although the only case of cancer was included in the hypopepsinogenaemic subgroup of just 11 patients.In patients with uncomplicated, simple dyspepsia up to 55 years of age, screening by H. pylori serology identified 95%-100% of patients with significant gastroduodenal lesions while potentially saving 46.9% of endoscopies. Serum recognition of the CagA protein identified 95% of lesions and would have saved an additional number of endoscopies (7.9%) compared with basic serology. Measurement of sPGI was of limited diagnostic value.

AIMS: To isolate RNA and DNA simultaneously from formalin fixed paraffin wax embedded tissue to assess the clonality of enteropathy associated T cell lymphomas and to analyse it in detail by a non-radioactive method of T cell receptor complementarity determining region 3 (CDR3) spectratyping. METHODS: DNA and RNA were isolated simultaneously from formalin fixed paraffin wax embedded tissue blocks and subjected to the polymerase chain reaction (PCR) and semi-nested reverse transcription PCR (RT-PCR), respectively. The RT-PCR T cell receptor V beta products were analysed by CDR3 spectratyping using a denaturing polyacrylamide gel and silver staining. RESULTS: Usable DNA and RNA were isolated simultaneously from formalin fixed paraffin wax embedded tissue. The specific clonality of the tissue was successfully analysed by a non-radioactive method of T cell receptor CDR3 spectratyping of the RT-PCR products. CDR3 spectratying of the RT-PCR products demonstrated the precise clonal nature of the tumour and non-tumour tissue showing that the non-tumour tissue comprised an oligoclonal population of a number of different T cell receptor V beta families. The tumour tissue comprised two T cell subtypes of the one family, T cell receptor V beta 9. CONCLUSIONS: RNA and DNA were isolated from formalin fixed paraffin wax embedded enteropathy associated T cell lymphoma tissue. Detailed analysis of clonality can be carried out by a non-radioactive method of CDR3 spectratyping.

BACKGROUND: Interleukin-10 (IL-10) is an 18 kDa peptide with a range of anti-inflammatory and immunosuppressive properties. AIM: To determine whether this cytokine is involved in gastric mucosal inflammation in Helicobacter pylori infection. METHODS: The production of IL-10 by antral mucosal biopsy specimens during short term in vitro culture was determined by measuring IL-10 content of supernatants by enzyme linked immunosorbent assay (ELISA). H pylori status was determined by serology and histology, with gastritis scored using the Sydney system. Tumour necrosis factor-alpha (TNF-alpha) content of supernatants was also determined in a subgroup of patients. RESULTS: IL-10 secretion was significantly greater in patients with H pylori associated chronic gastritis than in patients who were H pylori negative with normal mucosa/reactive changes, and those with H pylori negative chronic gastritis (p < 0.01 and < 0.05 respectively). There was a significant correlation overall between IL-10 secretion and chronic inflammation score (r = 0.40). Secretion of TNF-alpha, which was significantly higher in H pylori infected patients than uninfected patients with a normal mucosa (p < 0.04), correlated with scores for chronic inflammation and activity (r = 0.39 and 0.38 respectively), but was only weakly correlated with IL-10 secretion (r = 0.22, NS). CONCLUSIONS: Gastric mucosal production of IL-10 and TNF-alpha are increased in chronic gastritis associated with H pylori infection, and mucosal cytokine secretion varies with important histopathological aspects of gastric inflammation. Whereas the secretion of IL-10 in H pylori infection may be protective, limiting tissue damage caused by inflammation, it may also contribute towards failure of the immune response to eliminate the organism.

Resection of liver metastases is accepted as an appropriate treatment for colorectal metastases in suitable patients. Liver transplant is not often used for malignant disease as there is a high incidence of undetectable micrometastases elsewhere and recurrence is likely. The effects of immunosuppression may also enhance the growth of malignant cells at other sites. We report a case where a young patient with undiagnosed breast cancer with axillary and liver metastases underwent liver transplantation and is effectively leading a normal life 33 months after transplant.

Gastritis associated with Helicobacter pylori was present in gastric biopsies from 24/95 (25%) children and adolescents undergoing endoscopy for recurrent abdominal pain and upper gastrointestinal symptoms. H pylori associated gastritis occurred mainly in older children (8-16 years) and was significantly associated with low socioeconomic class and a family history of peptic ulcer disease. Antral nodularity was a common endoscopic finding in H pylori positive children. Eighteen children, all over 5 years of age, were treated with tripotassium dicitratobismuthate (De-Nol) for two months and ampicillin for two weeks. In 12 children follow up gastric biopsies were obtained six weeks after completion of treatment. In 9/12 (75%) children H pylori was eradicated, and gastritis improved.

Aim: To investigate the volume and provision of local liver histopathology in the 11 hospitals of the Yorkshire region outside Leeds, as a potential model for a hepatopathology network. Methods: Postal questionnaire to all histopathologists in 11 hospital trusts in Yorkshire. Results: Liver biopsies represent about 0.5% histopathology requests in Yorkshire, with more medical than tumour biopsies. Pathologists often discuss these biopsies with each other and clinicians; a third had done liver continuing professional development (CPD) in the last 3 years, and 70% would like to do more. Overall, around 5% liver biopsies are reviewed in the hepatology centre, and most responders thought this about right. Conclusions: For primary reporting of liver biopsies, local pathologists need good communication with the responsible clinician, access to relevant CPD in liver pathology and a biopsy referral pathway for cases which are clinically or pathologically challenging.

Aim: there is conflicting evidence about the importance of synchronous metastases upon tumor outcome. The aim of this study is to identify the effect of finding synchronous colorectal liver metastases on the performance of the surgeon whilst operating on primary colorectal cancer. Methods: patients with completed colorectal cancer data who underwent liver resection for colorectal metastases between 1993 and 2001 were included. Two hundred seventy patients were categorised according to the site of the primary tumour (colon or rectum) and knowledge of the presence of liver metastases by the colorectal surgeon (SA = surgeon aware, n = 112, SNA = surgeon not aware, n = 158). The number of retrieved lymph nodes and colorectal resection margin involvement were used as surgical performance indicators. Survival and local recurrence rate were monitored. Results: the SA group had a higher rate of colorectal circumferential resection margin involvement, the local and intra-abdominal recurrence rate was also significantly higher in this group (p Conclusions: awareness of the presence of liver metastases by the operating surgeon is an independent predictor of intra abdominal extra hepatic recurrence of colorectal cancer following potentially curative hepatic resection. This is related to an increased rate of primary colorectal resection margin involvement

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 Sister Mary Joseph nodule is a peri-umbilical metastasis most commonly found with adenocarcinomas of the gastrointestinal tract and ovary. It was first described 140 years ago but has not previously been reported in association with primary gastric lymphoma.

Cytomegalovirus is a common infection worldwide and in the immunocompromised individual it can be a major cause of morbidity and mortality. In patients with inflammatory bowel disease cytomegalovirus infection has been described in both immunocompetent and immunocompromised individuals. A 34 year old man with an exacerbation of his colitis was diagnosed as having both cytomegalovirus colitis and hepatitis. The diagnosis was made on the classical appearance of “owl’s eye” inclusion bodies on colonic and hepatic biopsies and, in addition, viral serology and polymerase chain reaction (PCR) analysis of the cytomegalovirus DNA copy number. Fourteen days of treatment with ganciclovir led to a prompt improvement in the symptoms of colitis, resolution of the pyrexia, normalisation of the liver function tests, and clearance of the virus, as measured by a negative cytomegalovirus DNA PCR. Cytomegalovirus infection is a potentially fatal complication of treatment induced immunosuppression in patients with inflammatory bowel disease. As in this case, infection may be systemic and not confined to the intestine. Prompt diagnosis using histology, serology, and PCR analysis allows prompt introduction of therapy and an improved prognosis.

Hereditary haemorrhagic telangiectasia is a rare inherited disease in which telangiectases affect skin, mucous membranes and the gastrointestinal tract. Hepatic involvement is common but usually asymptomatic. We report a case of acute hepatic disintegration in hereditary haemorrhagic telangiectasia, document the histopathological findings and present a hypothesis to explain them.The patient presented at the age of 34 years with abdominal pain, leading to the surgical removal of a severely inflamed gallbladder. Signs of liver damage became increasingly apparent over the next few weeks, with disruption of the intrahepatic biliary tree and marked vascular shunting, necessitating liver transplantation. Six months after the transplant a diagnosis of hepatic hereditary haemorrhagic telangiectasia was made. The principal features of hepatic hereditary haemorrhagic telangiectasia are periportal telangiectases and sinusoidal congestion and dilatation. Acute hepatic disintegration is characterized by disruption of liver structure, hepatocyte necrosis, haemorrhage and extravasation of bile.Periportal telangiectases in a liver biopsy are highly suggestive of hereditary haemorrhagic telangiectasia. Acute hepatic disintegration is likely to be a consequence of rupture of telangiectases and ischaemic necrosis of intrahepatic bile ducts. Patients with hereditary haemorrhagic telangiectasia are at risk of acute hepatic disintegration following intra-abdominal sepsis.

A 42 year old man presented with gluten-responsive coeliac disease and secondary pancreatic insufficiency. Subsequently his symptoms relapsed and repeat small intestinal biopsy showed villous atrophy and infiltration by leukaemic cells, despite continuation of a gluten-free diet. Serious causes of relapse and non-responsiveness in coeliac disease include enteropathy-associated T-cell lymphoma, ulcerative jejunitis and an end-stage hypoplastic mucosa. This is the first report of non-responsiveness due to infiltration by leukaemia. Keywords: coeliac disease; villous atrophy; gluten sensitivity; leukaemia

Proton pump inhibitor-based triple therapy is recommended as treatment for Helicobacter pylori eradication. The proton pump inhibitor may be given once or twice daily. However, little information is available on how these two treatment strategies compare.H. pylori-positive patients (two positive test results) with endoscopy-proven healed duodenal ulcer or non-ulcer dyspesia were randomly allocated to 1 week of double-blind treatment with pantoprazole 40 mg once or twice daily, plus clarithromycin 250 mg and metronidazole 400 mg twice daily. Eradication was defined as a negative 13C-urea breath test (13C-UBT) and histology, 4-5 weeks post-treatment. The follow-up phase comprised 12 months off therapy, with 13C-UBT at 6 and 12 months.Two hundred and four patients received treatment: pantoprazole once daily (x1), n=104; twice daily (x2), n=100. Eradication rates were 84% in both the pantoprazole x1 and pantoprazole x2 groups by modified intention-to-treat analysis and 89% and 87%, respectively, by per protocol analysis. Metronidazole resistance was found in 44% of pre-treatment cultures of H. pylori. Eradication rates were similar in susceptible (72%) and resistant (75%) strains. During follow-up, recrudescence of infection occurred in 3/118 patients.When using pantoprazole plus clarithromycin and metronidazole, the proton pump inhibitor can be used once daily without loss of efficacy.

A 79 year old man presented with occult gastrointestinal bleeds and anaemia for two years. He had received 40 units of blood over a period of one year, following which he had a subtotal colectomy as no definite cause of the bleeding was apparent. Macroscopically the colon appeared unremarkable. Light microscopy showed prominent lymphocytic venulitis in the proximal portion, gradually merging into lymphocytic and collagenous colitis distally.

The frequency of oesophageal ulceration in 55 patients undergoing endoscopy for dyspeptic symptoms and who had recently used NSAIDs was studied, and compared with 86 patients seen in the same clinic who had not recently used these drugs. Oesophageal ulceration was significantly more common in those who had used NSAIDs (P = 0.012), and also showed a highly significant association with the presence of a hiatus hernia (P less than 0.001). No association was found between the presence of gastric Helicobacter pylori and either oesophageal ulceration or histological oesophagitis. Patients receiving NSAIDs, especially those with a hiatus hernia, are at risk of oesophageal ulceration and presumably subsequent stricture formation. This should be borne in mind when prescribing these agents.

To describe a patient with early gastric cancer, Menetrier's disease, lymphocytic gastritis and Helicobacter pylori infection.A single patient case report.A 73-year-old man presenting with lower limb deep venous thrombosis was found to have a gastric adenocarcinoma on upper gastrointestinal endoscopy. He subsequently had a total gastrectomy.Histological examination of the resected stomach showed an early gastric cancer and changes typical of Menetrier's disease, lymphocytic gastritis and Helicobacter-associated chronic gastritis.This case suggests a link between gastric adenocarcinoma, Menetrier's disease and lymphocytic gastritis. The presence of H. pylori is postulated as a possible aetiology.

Introduction Gastric and oesophageal cancers have a high mortality rate, particularly if diagnosed at a late stage. We aimed to determine whether Upper Gastrointestinal (UGI) cancers are being missed either endoscopically or histologically in Leeds, and the reasons for any delays identified. Methods As part of our rolling annual audit programme, histopathology records were gathered for all UGI cancers detected between September 2009 and August 2010 at Leeds Teaching Hospitals Trust. The endoscopy database was searched for endoscopies in the previous 3 years and the Trust Patient Pathway Manager reviewed for possible delays to diagnosis. Patients were classified into 1 m (possible significant delay). Previous biopsies were reviewed by a consultant histopathologist. Results 211 cases of UGI cancers were detected (range 25–94 years, mean 70 years, 1.89:1 M:F) representing malignancy in 6.1% of 3460 endoscopies with gastric/oesophageal biopsy. Excluded from further study were: no endoscopy report (13); follow-up of previous diagnosis (38); not primary adenocarcinoma (12). 16/148 (10.8%) cases had had endoscopy within the last 3 years, 6/16 (37.5%) had repeat endoscopy within 1m (mean delay 16.2 days). Reasons included: (2) suspicious endoscopy without histological confirmation of malignancy, (1) previous failed intubation, (1) follow-up of oesophageal ulcer. Of the 10 cases with previous endoscopy >1 m earlier, preventable delays were identified in six cases: Bleeding GU not biopsied at index endoscopy (42 days); failure to biopsy GOJ nodule due to triple anti-platelet therapy (91 days); a patient with known High Grade Dysplasia awaiting cardiology opinion before repeat under general anaesthetic (192 days); delayed surveillance interval for Barrett9s Oesophagus (1035 days from previous endoscopy). Only in two cases was the cancer likely to have been missed on the first endoscopy: delayed follow-up after EMR, synchronous gastric carcinoma in separate site (180 days) and repeat endoscopy for symptomatic dysphagia (SCC in high oesophagus) (526 days). The other 4 cases had endoscopies unrelated to the subsequent diagnosis more than 2 years earlier and the delay was considered unavoidable. Review of previous biopsies, including further stains, showed that no malignant diagnosis had been missed. Conclusion 6/148 (4.1%) patients had significant potentially avoidable delays to diagnosis of upper GI cancer. This is commensurate with audits in other centres. Most delays are systematic problems with bookings and appointments rather than endoscopic misses. We believe this simple rolling audit should be adopted as a mandatory Quality Assessment tool for MDTs and/or endoscopy units in order to improve delays in the diagnosis of UGI cancer in all hospitals. Competing interests None declared.

The bombesin-like peptides gastrin releasing peptide (GRP) and neuromedin B are found in the submucosal and myenteric plexuses of the human gastrointestinal tract. These peptides are potent mitogens to Swiss 3T3 fibroblasts and are important autocrine growth factors in human small cell lung cancer cells. We have recently described the presence of receptors for the bombesin-like peptide, GRP, on the human gastric cancer cell line St42. In this study, we examined fresh resected gastric cancer and uninvolved mucosa from 23 patients for the presence of binding sites to the bombesin-like peptides. Thirteen of 23 gastric cancers expressed high affinity binding sites for bombesin (mean Kd = 3.42 nM; mean Bmax = 40.5 pmol/mg protein), of which 12 were subsequently characterized and found to be of the GRP-preferring subtype. One of 23 mucosal samples specifically bound bombesin and was the only sample from a patient with Ménétrier's disease, a disorder of mucosal growth known to be premalignant. The early gastric cancer from this patient also possessed high affinity binding sites for GRP. This is the first description of binding sites to bombesin-like peptides on human gastric cancer and Ménétrier's mucosa. The role of bombesin/GRP antagonists in the treatment of gastric cancer warrants investigation.

The emergence of Helicobacter pylori as an important aetiological agent in gastroduodenal disease has led to the introduction of many methods for the detection of this organism. Current methods for H. pylori detection can be divided into two main categories, endoscopic and non-endoscopic. Endoscopy provides biopsy specimens for subsequent culture [3], histology [5], in situ hybridisation [20] or rapid urease testing [10]. The non-endoscopic techniques include serological tests [12] and the 14C or 13C breath tests [4, 23]. All of these techniques are unsatisfactory because they are insensitive to low bacterial densities and cannot identify “non-culturable” coccoid forms of H. pylori. Research has been hampered through the lack of a sensitive assay and the invasive nature of the best methods, and thus many key questions remain unresolved. The development of an extremely sensitive technique which can be applied to a wide variety of materials (including saliva or faeces), may allow the sources and routes of transmission of H. pylori to be elucidated.

Only a minority of patients treated with monotherapy using colloidal bismuth subcitrate (CBS) will be eradicated of Helicobacter pylori. However, temporary clearance of the bacteria is achieved in a higher proportion of patients and may be related to ulcer healing by CBS. It is not known what factors contribute to this variation in response rate, although previous work by McNulty et al. [1] suggested that elimination of H. pylori might be more successful in patients with initially more severe gastritis.

Dysphagia in a 79 year old lady was caused by a giant polypoid tumour in mid-oesophagus. Surgery was not appropriate. Shrinkage of the tumour and its eventual detachment were achieved by stopping its blood supply by YAG laser photocoagulation of the tumour stalk. Good, temporary palliation of the dysphagia was achieved.

We designed a polymerase chain reaction (PCR) for amplifying the Helicobacter pylori gene encoding 16S rRNA. Primers for the specific detection of H. pylori were designed for areas of the 16S rRNA gene in which there is the least sequence homology between H. pylori and its closest relatives. The specificity of detection was confirmed by ensuring that the primers did not amplify DNA extracts from the campylobacters H. cinaedi, H. mustelae, and Wolinella succinogenes, which are the closest relatives of H. pylori, as determined by 16S rRNA sequencing. Serial dilution experiments revealed the detection of as little as 0.1 pg of DNA by PCR and 0.01 pg by nested PCR. H. pylori DNA was detected successfully in clinical paraffin-embedded and fresh gastric biopsy specimens from patients positive for the bacterium and also in fecal suspensions seeded with the organism. The DNA from the nonculturable coccoid form of H. pylori was also identified by the primers. Universal primers designed for highly conserved areas on the 16S rRNA gene enabled large amplification products to be produced for direct sequencing analysis. Gastric bacteria resembling H. pylori have been isolated from animals. DNA of these animal gastric bacteria amplified with H. pylori-specific primers yielded PCR products identical to those from human isolates of H. pylori, as confirmed by the use of a 20-base radiolabelled probe complementary to an internal sequence flanked by the H. pylori-specific primers. The results of PCR amplification and partial 16S rRNA gene sequence analysis strongly support the contention that the gastric organisms previously recovered from a pig, a baboon, and rhesus monkeys are H. pylori.

The presence of abnormally located gastric-type epithelium in the duodenum was first described in experimental animals during healing of surgically induced mucosal defects [1] and subsequently in response to acid injury [2]. In 1962 James [3] reported the important observation of extensive gastric metaplasia in a patient with hyperacidity, subsequently confirmed in another report from Parrish and Rawlins [4]. Like instances of metaplastic change in general, this gastric metaplasia was attributed to chronic damage to the mucosa of the duodenum, and appeared to have little significance beyond that as a histological marker of mucosal injury.

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].

The immunoglobulin G antibody response to Helicobacter pylori was assessed in 78 patients with non-ulcer dyspepsia using five different antigen preparations. All patients were endoscoped and biopsied. The H pylori state was determined histologically on at least two endoscopic biopsy specimens using a modified Giemsa stain. The ultracentrifuged cell sonicate, acid glycine extract, and 120 kilodalton protein antigens were specific in diagnosing infection (95-98%), but had only moderate sensitivity (70-84%). By mixing either of the two complex antigens with the 120 kilodalton protein, the sensitivity of the test was increased to 97% without affecting the high specificity. The combination of ultracentrifuged sonicate or acid glycine extract with the 120 kilodalton protein therefore seems to be superior to the individual antigen preparations and is particularly suitable for the serodiagnosis of H pylori infection.

It is widely believed (Brandtzaeg, 1985; Delacroix & Vaerman, 1983; Tomana, Kulhavy & Mestecky, 1988; Brown & Kloppel, 1989) that the polymeric IgA receptor (pIgAR) cannot be detected in or on human hepatocytes. In rats and several other species it is accepted that hepatocytes synthesize the pIgAR and use it to transfer polymeric IgA (pIgA) across the cell from blood to bile. At the biliary face of the hepatocyte, the pIgAR is proteolytically cleaved, releasing either secretory IgA (sIgA) when pIgA has been bound or free secretory component (FSC).

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.

Gastric metaplasia (GM) is a response of intestinal mucosa to injury, and occurs at various sites along the gastrointestinal tract in response to mucosal ulceration. Examples of this have already been discussed (see p. 279, 292).

We report a young patient with a solitary intrahepatic cyst without demonstrable connection with the biliary tree. The operative appearances suggested hydatid disease but histological examination of the resected cyst showed that it was the result of Caroli's disease already complicated by severe dysplasia. This case provides further evidence for the premalignant nature of Caroli's disease.

The histological features of non-autoimmune chronic gastritis are consistent with those of a local immune response by the gastric mucosa. If Campylobacter pylori is causative in this condition, then the immune response will be in part specific for this organism. Antibodies to C. pylori are present in the gastric juice of infected patients. Coating of mucosal C. pylori by antibody in vivo can be demonstrated by immunohistochemistry, and a neutrophil infiltrate (active gastritis) is associated with coating by opsonising antibodies. Gastric mucosa from patients with C. pylori produces specific immunoglobulin in vitro, and this antibody production correlates with the plasma cell infiltrate seen in these patients. Lymphoid follicles in gastric mucosa, implying local antigenic stimulation, are a specific feature of campylobacter-associated gastritis. The inflammation gradually abates following eradication of the bacteria. We conclude that the morphological features of campylobacter-associated gastritis represen...

The organism that we now know as Campylobacter pylori was first isolated in 1982 by Marshall et al. [1] in Australia. The organism had, however, been intermittently noted on gastric epithelium by a variety of investigators in several countries since the turn of the century.

The stomach and upper gut are normally sterile with only transient flora appearing following ingestion of food. The gastric defences including acid, mucus, lysozyme and immunoglobulins protect the upper gut from bacterial colonization. With decreasing gastric acidity, which occurs normally with ageing and with conditions such as pernicious anaemia and following gastric surgery, the stomach may become colonized with faecal as well as oral bacteria1. Patients with hypochlorhydria are also more susceptible to enteric infections such as cholera and salmonellosis2.

The exact pathogenic mechanisms involved in Campylobacter pylori associated gastro-duodenal inflammation are unclear. C. pylori adheres to gastric type epithelium and colonisation is associated with a number of ultrastructural abnormalities. Other factors thought important include the marked bacterial urease activity, enzymatic degradation of the mucous layer and possible toxins. The induced inflammatory reaction will also contribute to tissue damage and a breakdown of normal defense mechanisms.

SUMMARYGastric campylobacter-like organisms (CLO) were isolated from gastric tissues removed at sacrifice from 17 mature ferrets; all animals were colonized, but no macroscopic mucosal lesions or histological features of chronic gastritis were seen. The isolates resembledCampylobacter pyloriin many cultural and biochemical characteristics, and produced substantial urease activity, but there were sufficient differences fromC. pylorito suggest that ferret gastric CLO represents a separate species. Comparison of humanC. pyloriand ferret gastric CLO may help to clucidate the pathogenicity of the former in patients with gastritis, and the ferret may serve as a useful animal model for the study ofC. pyloriinfection.

A monoclonal antibody raised against human colostrum secretory component produced even staining of hepatocyte plasma membranes, as well as bile duct lining cells, in all sections examined from eight normal and three abnormal human livers. Human bile samples incubated with free secretory component degraded it to varying extents, probably proteolytically; true levels of free secretory component will therefore often be higher than those reported. It seems likely that human liver resembles that of other mammals in transferring polymeric IgA through hepatocytes to the bile by means of the polymeric IgA receptor.

To determine whether the "congestive" gastropathy associated with portal hypertension showed distinctive histological features independent of inflammatory gastritis, endoscopic biopsy specimens of gastric mucosa from 23 patients with portal hypertension and 25 patients with non-ulcer dyspepsia were examined. Active chronic gastritis associated with Campylobacter pylori was found in three patients with portal hypertension compared with 13 patients with non-ulcer dyspepsia. The changes of reflux gastritis were seen in nine patients with portal hypertension compared with three patients with non-ulcer dyspepsia. Mucosal capillary dilatation, assessed on sections stained for factor VIII related antigen, a specific marker for endothelial cells, was significantly greater in biopsy specimens from patients with portal hypertension but this difference was not apparent on sections stained conventionally. The degree of capillary dilatation was unrelated to the presence of histological gastritis. These observations support the view that portal hypertension is associated with a distinctive gastropathy characterised by prominence and dilatation of mucosal capillaries.

Chronic gastritis is a histological diagnosis which cannot be accurately predicted on the basis of gastroscopic appearances. The diagnosis rests on the presence of a mononuclear inflammatory cell infiltrate in the lamina propria of the stomach. Chronic gastritis defined in this way is so common and so inconsistently related to symptoms that its pathological significance is debated. Its prevalence increased with age to approximately 50% in elderly persons, and it has thus been considered by some to be a ’normal’ aging phenomenon rather than a pathological abnormality.