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Microsatellite alterations have been documented in a subset of sporadic tumors, including those of the colon, lung, bladder, stomach, and esophagus. This study documented the frequency of microsatellite alterations at 139 loci, comprising predominantly dinucleotide and tetranucleotide repeat units, in 17 cases of primary esophageal adenocarcinoma arising against a background of Barrett's metaplasia. Each tumor demonstrated alterations in at least one locus studied. Widespread microsatellite alterations, occurring at 45.3% (58 of 128) of loci tested, were detected in a single case. The remaining 16 tumors exhibited low levels of microsatellite instability, ranging from 0.8% (1 of 128) to 8.1% (10 of 123) of loci tested. The single case with ubiquitous somatic alterations showed no significant difference in the incidence of novel alleles at di- and tetranucleotide repeat loci. The 16 cases showing a low level of microsatellite alterations demonstrated a 3.3-fold higher incidence of novel alleles at tetranucleotide repeat loci compared to dinucleotide repeat loci. These data suggest that ubiquitous somatic alterations at microsatellite loci, considered a phenotypic expression of defective mismatch repair, occur infrequently in Barrett's-associated adenocarcinoma. However, the majority of these tumors demonstrate a low level of microsatellite alterations, perhaps reflecting the inherent instability of these markers.

An apparently unique case of diffuse calcification of the myometrium occurring in the puerperum in a 24-year-old woman is reported. Vaginal delivery by forceps of a healthy baby was followed by septic shock and massive postpartum hemorrhage, necessitating hysterectomy 4 weeks later. Examination of the uterus revealed widespread calcification of myometrial fibres. It is speculated that this widespread phenomenon represents dystrophic calcification secondary to myometrial necrosis and is a hitherto undescribed cause or complication of massive postpartum hemorrhage.

Objective: To examine differences in epithelial cell nuclear texture along the length of normal, well-oriented colorectal glands., Study Design: Histologically normal mucosa was obtained from four patients who had a family history of cancer and no hyperproliferation as assessed by bromodeoxyuridine immunohistochemistry. Serial sections were stained using the Feulgen technique and viewed to identify glands that were sectioned along their entire length. Two glands were sampled from each patient. Each gland was divided into three compartments based on epithelial cell counts along the length of the gland. Within each compartment, 10 nuclei were randomly selected and their nuclear texture features measured using computerized image analysis., Results: Analysis of variance demonstrated that significant differences exist in the nuclear texture of cells in the different compartments of the gland. Discriminant analysis selected three variables that were important and independent in the quantitative discrimination of the gland compartments. These features were related to the elliptical shape, optical density distribution and cooccurrence structure of the chromatin texture within the epithelial nuclei., Conclusion: It is clear that these differences are associated with the spatial variation in proliferation and differentiation status found within colorectal mucosal glands. Nuclear measurements from colorectal epithelium with near-normal architecture should therefore be stratified in relation to position within the gland. Nuclear texture and size measurements within defined compartments may provide a sensitive means of detecting early malignant transformation.

This study examined the association between 17p allelic loss and p53 gene mutation in a series of 16 esophageal adenocarcinomas arising on a background of Barrett's esophagus. Two highly polymorphic dinucleotide repeat polymorphisms mapping to 17p13 were analyzed to assess the frequency of 17p allelic loss in these tumors. Mutations in the p53 gene were detected by direct DNA sequencing. Ninety-four % (15 of 16) of samples were informative at one or both polymorphic loci. Allelic loss at one or both loci was detected in 80% (12 of 15) of samples. Mutations were detected in 69% (11 of 16) esophageal adenocarcinomas, and there was a close association between 17p allelic loss and p53 gene mutation (P = 0.00879; Fisher's Exact Test). The tumors that were analyzed demonstrated a specific p53 mutation spectrum, with G:C to A:T base transitions at CpG dinucleotides accounting for 80% (8 of 10) of single-base substitutions. In three cases, the same p53 mutation was detected in both high-grade dysplasia and adjacent tumor. These results indicate that p53 gene alterations contribute to the development of esophageal adenocarcinoma and precede the development of invasive carcinoma in patients with Barrett's esophagus.

The histopathologic grading of colorectal adenomatous dysplasia is a subjective process. In this study, automated image analysis using knowledge-guided software was used to quantitatively assess colorectal glandular characteristics. Cases of histologically normal mucosa and of low, moderate and high grade dysplasia were examined using the technique. A total of 19 morphometric and densitometric features were measured on each gland. These included gland shape, epithelial area, nuclear stratification and nuclear optical density. Discriminant analysis of the data revealed those morphometric features which provided the best discrimination between the various histologic groups. The area of epithelium occupied by nuclei was the strongest discriminating variable, and this, in combination with a discriminant function derived from the remaining variables, was used to plot cases in bivariate sample space. The plots revealed that the data for normal glands were consistently well separated from dysplastic gland data. Data sets belonging to the various grades of dysplasia showed varying degrees of separation, depending which two histologic groups the discriminant function was based on. This study showed that automated image analysis of complex histologic scenes is possible using knowledge-guided segmentation and that it can provide useful data for the objective classification of colorectal dysplasia.

The tumorigenesis of neuroendocrine tumours remains poorly understood, although a minority, the familial multiple endocrine neoplasia (MEN 1 and MEN 2), are known to be of uncommon genetic origin. Mutation of the tumour suppressor gene, p53, is now known to be a common genetic alteration in about half of all types of non-endocrine cancers. In the present study, immunocytochemistry using the monoclonal anti-p53 antibody, DO-7, has been employed to investigate the accumulation of p53 immunoreactivity in a wide range of primary neuroendocrine tumours. Tumours (n = 109) were fixed and processed to paraffin wax according to a constant protocol. Sections were subjected to microwave antigen retrieval prior to immunostaining for p53. Positive nuclear immunostaining was observed in one medullary carcinoma of the thyroid (MCT), one lung carcinoid, and five small cell carcinomas of the lung (SCCL). All other tumour samples were consistently negative. As the neoplasia investigated in this study comprised a wide spectrum of neuroendocrine tumour types and ranged from minute, relatively benign lesions to malignant metastasizing disease and as there was no relationship between the presence of p53 overexpression and clinico-pathological features, the present study suggests that p53 gene mutation may be relatively unimportant in the genesis of neuroendocrine tumours.

We report a patient with chronic bronchiectasis who developed systemic vasculitis. The patient was initially treated with immunosuppression; however, the addition of antibiotic therapy improved control of her vasculitis and the need for immunosuppression was reduced. Chronic bronchial suppuration may have an aetiological role in the pathogenesis of this condition.

The finding of epithelioid cell granulomas within liver biopsies is a not uncommon occurrence. We undertook this study to investigate the underlying conditions responsible for a diagnosis of granulomatous hepatitis in Northern Ireland during the thirteen year period 1980-1992. One hundred and sixty-three patients with hepatic granulomas were identified, accounting for 4% of all liver biopsies undertaken during the period of the study. In 145 cases (89%) a definite clinical diagnosis was established. The most common clinical diagnoses were primary biliary cirrhosis which accounted for 90 cases (55%) and sarcoidosis which accounted for 30 cases (18%). Other less common conditions associated with hepatic granulomas included tuberculosis (3 cases), Crohn's disease (3 cases), chronic active hepatitis (2 cases), drug hypersensitivity (2 cases) and extra-hepatic biliary obstruction (2 cases). Six patients were identified with a clinical diagnosis of psoriasis. Other miscellaneous conditions accounting for single examples of granulomatous inflammation were schistosomiasis, gout, Hodgkin's disease, secondary adenocarcinoma, collapse and necrosis of tumour following radiotherapy and chemotherapy, granulomatous inflammation within the wall of an abscess cavity and idiopathic cirrhosis. Only eighteen cases (11%) remained idiopathic with no definite diagnosis established after detailed investigation. The findings confirm the wide range of clinical conditions which can result in hepatic epithelioid cell granulomas. This has been emphasised in several previous major studies which are reviewed in this paper.

Although a high prevalence of antibodies to Helicobacter pylori has been documented within families, culture and DNA typing of strains from infected children and their parents has not been evaluated. This study aimed to analyse H pylori infection within family groups. Endoscopy, gastric biopsy, and H pylori culture were performed on all eight parents of four children who presented with dyspepsia and who had a positive H pylori culture. All biopsy specimens were cultured on Columbia based blood agar under microaerophilic conditions for four days. The DNA from each strain was extracted and electrophoretic patterns were compared after digestion with restriction endonucleases Hae III or Hind III. Ribotyping using a biotinylated cDNA probe prepared from 16S and 23S rRNA of H pylori NCTC 11638 was also used. Seven of the parents were positive for H pylori on urease testing, histology, and on culture. DNA typing showed the same or a similar strain to be present in at least two family members in three of the four family groups. In family 1, the mother, father, and child all had an identical strain; in family 2, father and son had a similar related strain; father and mother had the same strain in family 3; and all strains were unique in family 4. These data provide evidence for either intrafamilial cross infection or a common source of infection within family groups.

We report a case of bilateral ovarian cysts lined exclusively by squamous epithelium showing multifocal intraepithelial neoplasia. The cervix showed synchronous high-grade intraepithelial neoplasia (CIN III). We interpreted the ovarian lesions as squamous carcinoma of borderline malignancy and believe that they are part of a "field change" that also involves the cervix.

Scene segmentation in images of sections of colorectal glands is guided by a knowledge-based system. The construction of the knowledge file, processing sequences and computation of a crowding index for adenomatous glands are described. The histologic sections were stained by hematoxylin and eosin, and the image segmentation was difficult. The knowledge-based system has to determine, on the basis of context and logic, which detected object groups belong to which histologic components. Image segmentation was followed by a reconstruction process. Acceptable segmentation was attained in approximately 85% of the glands processed.

Using an antiserum raised to the C-terminal region of neuropeptide Y (NPY) which does not cross-react with pancreatic polypeptide (PP), immunoreactivity has been detected in two different endocrine tumours of the human pancreas in concentrations permitting isolation and structural analysis. In a clinically-typical gastrinoma, resected from the head of pancreas, the concentration of NPY immunoreactivity was 3.4 nmol/g. Reverse phase HPLC analysis of extracts of this tumour resolved a single immunoreactive peptide coeluting with synthetic human NPY. The molecular mass of the isolated peptide, determined by mass spectroscopy, was 4270 Da, which was in close agreement with that derived from the deduced primary structure of human tumour NPY (4271.7 Da), obtained by gas-phase sequencing. A somatostatinoma, resected from the region of the ampulla of Vater, contained 3.8 nmol/g of NPY immunoreactivity and isolation of this immunoreactive peptide followed by structural analyses, indicated a molecular structure consistent with NPY 3-36. These data suggest that NPY immunoreactivity detected in human pancreatic endocrine tumours is molecularly heterogenous, a finding which may be of relevance in the symptomatology of such tumours as attenuation of the N-terminus of this peptide generates receptor selectivity.

Carcinoembryonic antigen (CEA) has been reported in benign and malignant epithelium of the gall bladder, although cross-reactivity with CEA-related antigens cannot be excluded. We have investigated the immunoreactivity of three monoclonal and two polyclonal antisera to CEA in benign and malignant epithelium of the gall bladder, extrahepatic bile ducts, and ampulla of Vater. The results varied with the antisera, due to cross-reactivity with CEA-related antigens and according to the epitope specificities. Little CEA was found in benign epithelium using monoclonal antisera or following absorption of a polyclonal antiserum from Dako with human liver powder. The latter was the most reliable at detecting malignant epithelium of the gall bladder and extrahepatic bile ducts. All antisera showed equal immunoreactivity in tumours of the ampulla of Vater. The differences seen in the immunoreactivities between tumours of the upper and lower extrahepatic biliary tract probably indicate a variation in the occurrence of CEA epitopes.

The hypothesis that non-secretors of ABO blood group antigens, a group shown to be more susceptible to certain bacterial infections, may be at greater risk of gastroduodenal disease because of increased susceptibility to Helicobacter pylori infection was investigated. Of 101 patients with symptoms of dyspepsia who were undergoing endoscopy, 32% were non-secretors (determined from Lewis blood group phenotype), 36% had endoscopically visible gastroduodenal disease (antral gastritis, gastric ulcer, erosive duodenitis, duodenal ulcer or some combination), and 58% had H pylori detected in antral biopsy specimens. Non-secretors and patients with H pylori infection were significantly more likely to have gastroduodenal disease (p = 0.02 and p = 0.002 respectively). There was, however, no significant association between secretor status and H pylori infection, logistic regression analysis confirming that these were independently associated with gastroduodenal disease. Overall, the relative risk of gastroduodenal disease for non-secretors compared with secretors was 1.9 (95% confidence intervals 1.2, 3.2). Non-secretion of ABO blood group antigens is not related to H pylori infection but is independently and significantly associated with endoscopic gastroduodenal disease. The mechanism of this remains to be explained.

The role of Helicobacter pylori infection in the symptom complex associated with non-ulcer dyspepsia is uncertain, despite the presence of the organism in a high proportion of these patients. In order to exclude physician bias in history taking, 18 patients (9 female) diagnosed as non-ulcer dyspepsia, after endoscopy and gallbladder ultrasonography, underwent computer interrogation using the Glasgow Diagnostic System for Dyspepsia (GLADYS). Five antral and 3 fundal endoscopic biopsies from these patients were also histologically examined for the presence of Helicobacter pylori and quantitatively analysed for polymorph and chronic inflammatory cell densities per mm2 of lamina propria using computer-linked image analysis. In the group of 9/18 patients who were positive for Helicobacter pylori, there were significantly higher antral and fundal inflammatory cell counts than in negative patients. However, analysis of the GLADYS interrogation data showed no significant positive relationships between Helicobacter pylori positivity and any gastrointestinal symptoms. These results confirm a significant association between Helicobacter pylori and superficial gastritis but suggest that non-ulcer dyspepsia in patients with Helicobacter pylori colonisation is probably not a clinically identifiable and distinct syndrome.

A cell-counting technique and a photographic-based scoring system for assessing inflammatory cell infiltration were compared for agreement in 275 endoscopic gastric antral biopsies from 55 dyspeptic patients. Each biopsy was independently scored 0-5 for polymorphs and mononuclear cells using both methods, and a mean score was derived for each patient. There was a highly significant correlation between the mean patient scores obtained using each method (P less than 0.001). Agreement statistics showed that the mean score difference (cell-counting minus photographic score) was negative for polymorphonuclear and mononuclear cells, indicating that the photographic method yielded higher mean patient scores. Scatterplots of difference versus mean by the two methods showed that only 3.6 per cent of scores fell outside +/- 2 SD of the mean difference. The use of standard photomicrographs to grade superficial antral gastritis therefore provides accurate results, comparable to those obtained by cell counting, yet is a faster and much cheaper technique.

The clinical features, diagnostic methods, management and survival in 16 cases of Zollinger-Ellison syndrome encountered in Northern Ireland between the years 1970 and 1988 are described. While the majority of patients in the first decade of the study period had surgical treatment, those presenting in the latter period have been managed with medical therapy in the form of H2-receptor antagonists or omeprazole. The increasing use of these agents seems to be altering the severe clinical features of this condition, reducing the indications for surgery and maintaining patients, with or without evidence of metastatic disease, in clinical remission.

Goblet cell carcinoids are uncommon but distinctive tumours of the appendix. We have reviewed 11 cases diagnosed within the period 1976-1990. The mean age at presentation was 58 years (range 24-76), with a female:male ratio of 8:3. At presentation, in seven patients tumour was confined to the appendix or mesoappendix (mean age 51) and in four there was extension beyond the appendix (mean age 69). Of the seven patients with localized tumour, six are alive and without clinical disease after a mean follow-up period of 32 months and one died with recurrent tumour after 10 years. Of the four with more extensive disease, two died during follow-up (at 23 months with probable liver metastases and at 16 months with intestinal obstruction) and two are alive, one with disease and one clinically disease-free. Immunohistochemistry showed that all of the tumours stained positively for either neuron-specific enolase, chromogranin A or protein gene product 9.5. No tumour stained with antiserum to substance P and none showed glucagon-like immunoreactivity, but four cases stained positively for pancreatic polypeptide, an unusual feature in midgut carcinoids.

Thirty patients with early gastric cancer have been reviewed. Endoscopy demonstrated gastric abnormality in 93% of patients examined and biopsy was accurate in 96% of cases. Twenty-nine patients were treated by partial gastrectomy, although three required further procedures. The commonest morphological type was type III (45%). Five patients with early gastric cancer had lymph node spread at the time of presentation. The relative 5-year survival rate was 68%. Four patients eventually died of gastric cancer. Three patients (10%) developed a second primary carcinoma. The significance of this diagnosis is emphasized and selective screening is considered.

Inflammatory cell counting in endoscopic biopsy sections was carried out on duodenal mucosal samples from defined sites in patients with duodenal ulcer, duodenitis but no ulcer, non-ulcer dyspepsia, and asymptomatic controls using computer linked image analysis. The variables measured included polymorphonuclear and mononuclear cells per mm of superficial epithelium and per mm2 lamina propria. Duodenal ulcer crater margin and mucosal biopsy specimens from endoscopically inflamed mucosa in the group with duodenitis but no ulcer showed significantly higher inflammatory cell counts than endoscopically normal non-ulcer dyspepsia and control mucosa. Biopsy specimens from non-ulcer dyspepsia patients showed significantly higher lamina propria polymorphs than control group mucosa. Endoscopically normal duodenal ulcer and duodenitis but no ulcer mucosa also showed significantly higher acute and chronic inflammatory cell counts than controls. The prevalence of Helicobacter pylori in duodenal biopsy specimens was low (0-22%) and unrelated to local inflammatory response. Despite histological appearances, duodenal biopsy specimens from non-ulcer dyspepsia patients showed significantly higher inflammatory cell infiltration than control specimens, suggesting that at least some represent part of a spectrum of subclinical peptic disease.

A case of multiple ileal duplications presenting with gastrointestinal bleeding is described. Technetium-99m Pertechnetate scintigraphy in conjunction with barium studies provided the initial clue and accurately localised the abnormality pre-operatively.

Gastric biopsy specimens were taken in 33 patients before and after procedures to divert bile (construction of Roux loop in 19, closure of gastrojejunostomy in 14). Each biopsy specimen was assessed for dysplasia, intestinal metaplasia, atrophy, and gastritis, each variable being given a score ranging from 0 to 6. Patients were given preoperative and postoperative scores for each of these variables based on the average score of all preoperative or postoperative specimens. Comparison between preoperative and postoperative histology showed that there was no difference for gastritis, atrophy, or intestinal metaplasia. Patients who underwent closure of a gastrojejunostomy showed improvement in dysplasia that was not statistically significant. There was, however, a significant improvement in dysplasia in patients in whom a Roux loop was fashioned (p = 0.006) and in all patients taken together (p = 0.002). It was concluded that procedures that divert bile improve dysplasia but not other histological abnormalities in the stomach postoperatively.

Oesophageal transmucosal potential difference (PD) was measured in 76 patients during endoscopy. Twelve patients with no symptoms of gastro-oesophageal reflux, and normal oesophageal appearance on endoscopy and mucosal biopsy had a PD of -18.3 +/- 3.8 mV (mean +/- SD). Thirty three patients had reflux symptoms but the oesophagus appeared normal at endoscopy. Eighteen of these patients had reflux change on oesophageal suction biopsies and the PD in the same region of the oesophagus in this group was -18.1 +/- 7.5 mV. In 15 of the patients, mucosal biopsies were normal and the PD in this group was -18.8 +/- 9.9 mV. Thirty one patients had erosive oesophagitis and PD values in this group were markedly reduced. Twenty seven of these patients had PD values less than -10 mV. We conclude that PD measured by our technique is abnormal in erosive oesophagitis but that it is of no value in the diagnosis of mild mucosal damage in patients with reflux symptoms when endoscopic findings are normal.

A 2-year-old boy with peritoneal miliary Crohn's disease is described. In addition to vague gastrointestinal symptoms, ascites was a prominent feature. The jejunal mucosa was markedly atrophic, compatible with a diagnosis of coexistent coeliac disease.

The clinical and histological findings in 15 cases of carcinoma arising from the extrahepatic biliary tract are reviewed. The clinical findings are in agreement with previously reported series and the dismal prognosis is confirmed. The prognosis does not appear to be related to tumour size, site, mitotic count or laboratory data on presentation. Only histological grading of the tumour is related to prognosis. Perineural tumour infiltration was a prominent feature and dysplasia within adjacent bile duct epithelium was present in five cases. The value of carcinoembryonic antigen (CEA) as a histological tumour marker was investigated. All tumours from the upper and middle biliary tree expressed this antigen. Although immunocytochemistry is seldom needed to assess malignancy in large surgical resection specimens anti-CEA helps delineate the extent of tumour infiltration and discriminates between normal and dysplastic or malignant epithelium; anti-CEA may also be helpful in identifying foci of malignancy in small sclerotic biopsy specimens.

A high incidence of possible premalignant conditions of the gastric mucosa has been reported in the postoperative stomach and it has been suggested that bile plays a role in their pathogenesis. Fifty eight patients who had had a vagotomy and gastrojejunostomy between 1957 and 1967 underwent endoscopy and biopsy. Subsequently, samples of fasting and postprandial gastric juice were taken from all patients for analysis of total bile acid. The patients were divided into three histological groups: group 1 (24 patients) had gastritis or mucosal atrophy but no more than mild dysplasia; group 2 (23 patients) had intestinal metaplasia in one or more biopsies; group 3 (11 patients) had moderate or severe dysplasia in one or more biopsies. Group 2 and group 3 patients had higher fasting intragastric bile acid concentrations than group 1 (p less than 0.01 in both cases). There was no difference between fasting bile acid concentrations in groups 2 and 3. In the postprandial phase groups 2 and 3 also had higher peak intragastric concentrations than group 1 (p less than 0.01 in both cases). Again, there was no significant difference between groups 2 and 3. It is concluded that there is a relation between mucosal abnormality in the postoperative stomach and intragastric bile acid concentration. The possible aetiological link between bile acid and these mucosal abnormalities is discussed.

Histological examination of oesophageal rings removed at transection for varices reveals dilated intraepithelial blood filled channels. These are present in all oesophageal rings removed at transection for varices. A comparison has been made between rings removed from variceal patients with oesophageal rings removed during resections for oesophageal and gastric tumours. Although a small number of non-varices patients had intraepithelial channels they were significantly larger and more numerous in the varices patients (p less than 0.01). Similarly, the area and number of dilated subepithelial channels (just beneath the epithelium) and the area of lamina propria channels were significantly greater in the varices patients (p less than 0.05). Depth of papillae and thickness of the squamous epithelium were also significantly greater in the varices group (p less than 0.05, p less than 0.01 respectively). Under electron microscopy the channels were lined with flattened cells which were not typical of endothelial cells but stained positively for Factor VIII related antigen using indirect immunofluorescence. These channels may correspond to the cherry-red spots seen on endoscopy and may have a role in the pathogenesis of variceal haemorrhage.

Jejunal mucosal crypts were examined in jejunal biopsies from eight children with acute lymphoblastic leukaemia who had recently received methotrexate treatment. By comparison with biopsies from children under investigation for suspected malabsorption crypt mitosis was significantly reduced and showed a negative correlation with the dose of methotrexate given prior to biopsy. The three major cell types were studied under light and transmission electron microscopy. Gut endocrine cells were unaffected by therapy and immature crypt enterocytes showed only patchy degenerative abnormalities. By contrast a number of Paneth cells showed striking structural alterations with vacuolar dilatation of the cytoplasm. The extent of this correlated with the time since methotrexate treatment rather than its dose and may have been a functional response rather than of a toxic nature.

The occurrence and pathophysiology of peptic ulcer was studied in 117 uraemic patients. Ulcer disease was unusually frequent, and the highest incidence was found in patients on regular dialysis (48%). Factors implicated were hyperacidity, hypergastrinaemia, and the effect of dialysis itself. We found that the occurrence of gastrointestinal bleeding was lower post-transplant (7%), than pre-transplant (15%), and that bleeding in renal transplant patients was due more commonly to erosive gastritis than peptic ulcer. Cimetidene was given to 9 regular dialysis patients with peptic ulcer. Symptomatic relief and significant reduction of acid secretion was demonstrated, and no major side effects occured. There is a logical basis for conservative treatment of uncomplicated peptic ulcer in the dialysis patient, and further evaluation of cimetidene is indicated.

The development of diabetes in a small percentage of female beagles receiving large doses of synthetic progestogen for one year is described. The abnormalities in blood sugar and plasma insulin responses to oral glucose arising during induction of diabetes are presented. After a two-year period of diabetes, two animals were examined histologically. Lesions in the kidney and retina, similar to early lesions associated with human diabetic nephropathy and retinopathy, were present. Histologic changes related to the diabetes were also seen in the pancreas and pituitary. The means of induction of the diabetes is discussed. The study supports the view that the dog is a useful species in which to study the long-term pathology of diabetes,

Gastric mucosa was studied histologically in 141 patients. Eighty two had undergone vagotomy and gastrojejunostomy between 15 and 25 years previously for duodenal ulcer, and 59 control patients had a long history (minimum 15 years) of duodenal ulcer treated medically. No carcinoma was found in either group. Two patients with severe dysplasia and 13 patients with moderate dysplasia were found in the study group, compared with none in the control group (p less than 0.01). Intestinal metaplasia was seen in 44 (53%) of the study group and 16 (27%) of the control group (p less than 0.01). Atrophy and gastritis were more severe (p less than 0.01 for atrophy; p = 0.05 for gastritis) in the study group. Gastric mucosal changes were more severe after surgical treatment for duodenal ulcer than after medical treatment, and possibly a high incidence of gastric carcinoma may occur 25 years after vagotomy and gastrojejunostomy.

The reported incidence of gastrointestinal endocrine tumours is variable. In Northern Ireland circumstances allowing such an assessment are favourable with a central diagnostic laboratory and register established to collect data on tumours from a well-defined population of 1.5 million people. From 1970 to 1985, 368 cases were recorded of which 85 per cent were carcinoid tumours. The annual incidence of carcinoid tumours was 1.3 per 100,000 of the population and the majority occurred in the appendix (61 per cent). No patients presented with the carcinoid syndrome. The annual incidence for other tumours was 0.12 per 100,000 for insulinomas; islet cell tumours of unknown type 0.07; Zollinger-Ellison syndrome 0.05; and multiple endocrine neoplasia (MEN) 0.05. There were two cases of VIPoma, one glucagonoma, one neurotensinoma and one tumour producing ACTH. It is possible that some tumours are more uncommon than others because of difficulty in diagnosis.

In the absence of other precipitating factors, such as Sengstaken intubation, there is little evidence for acute esophagitis being a major factor in precipitating hemorrhage from varices. Superficial blood filled channels are described lying within the epithelium. They appear to arise from papillae, extend close to the esophageal lumen and are lined by epithelial-like cells. It is proposed that rupture of these channels may initiate variceal bleeding and, being connected to the underlying larger vessels, give rise to substantial hemorrhage. It is also suggested that these superficial vascular channels may correspond to the cherry red spots seen on endoscopic examination.

Pancreatic polypeptide immunoreactivity has been identified in primary medullary carcinoma of thyroid using radioimmunoassay and immunocytochemistry and subsequently characterised by HPLC. Two region-specific PP antisera were used in the study; one C-terminal and one non-C-terminal. These antisera demonstrate variable cross-reactivity with the molecular species of PP identified in the tumours. The immunoreactive material in the tumours corresponded to human PP and not PYY or NPY on the basis of immunoreactivity and HPLC behaviour. It was identified in all patients with familial-type disease but not in the two sporadic cases examined. We propose that estimation of the PP content of medullary carcinoma of thyroid may be a useful means of differentiating familial and sporadic types.

Gastric antral endoscopic pinch biopsies from a group of dyspeptic patients were analysed for acute and chronic inflammatory cell numbers in the lamina propria and surface epithelial layer using computer-linked graphic tablet planimetry, and independently graded for Campylobacter pylori (CP) infection using a visual scoring system with grade 1 assessed as patchy epithelial infection and grade 2 as a continuous layer of organisms on the mucosal surface extending into gastric pits. The study group consisted of 36 patients (18 duodenitis; 18 non-ulcer dyspepsia). Within the 140 biopsies analysed, grade 1 and 2 biopsies had significantly higher acute and chronic inflammatory cell counts than CP-negative biopsies (grade 0) in lamina and surface epithelium (P less than 0.001). Acute inflammatory cell counts were significantly higher in the surface epithelium in grade 1 (P less than 0.05) and grade 2 biopsies (P less than 0.001) but chronic inflammatory cells were only higher in grade 1 (P less than 0.01). No significant differences were present between grade 1 and grade 2 biopsies for any parameter. This study confirms that highly significant quantitative differences in the inflammatory status are related to the presence of CP.

Sixteen patients (aged 3.5-14.3 years) with normal jejunal mucosa, originally diagnosed as having coeliac disease at least 18 months before, were started on gluten challenge. The 'end point' of challenge was significant deterioration in jejunal mucosa morphologically and morphometrically. Studies carried out both before and after challenge included intestinal absorption of D-xylose and glucose, and release of insulin and N-terminal glucagon-like immunoreactivity (N-GLI). After gluten challenge, there were significant increases in plasma N-GLI at both 45 (P less than 0.05) and 120 minutes (P less than 0.03) after oral glucose. Significant reduction occurred in glucose absorption at 45 minutes (P less than 0.04), in one-hour D-xylose absorption (P less than 0.01) and fasting serum cholesterol (P less than 0.01). Plasma N-GLI showed significant negative correlations with D-xylose absorption (P less than 0.003) and serum cholesterol (P less than 0.004).

The purpose of this study was the quantitative assessment of mucosal inflammation and its relationship to Campylobacter pylori in gastric antral and body biopsies from patients with dyspepsia and controls. The study groups comprised patients with duodenal ulcer (DU; n = 20), duodenitis (DUN; n = 20), non-ulcer dyspepsia (NUD; n = 20). Using a semi-automatic, computer-linked image analyser (Kontron: MOP Videoplan), mucosal acute and chronic inflammatory cell densities were measured in defined gastric sites for each patient group and expressed as number per mm2 of lamina propria and number per mm length of epithelium. Measurements were also made on a group of asymptomatic controls (n = 9) who fulfilled strict exclusion criteria. All biopsies were analysed for the presence of Camplyobacter pylori (CP) with a Giemsa stain. Data between groups were compared using the Mann-Whitney U-test. In the antrum and body, the mononuclear cell count was significantly higher in lamina propria in DU patients than in DUN, NUD and controls. In the body, DU laminia propria mononuclear cell counts were higher than those of DUN and controls. Prevalence rates for CP for DU, DUN, and NUD were 94, 89, and 50 per cent for antral and 88, 83, and 56 per cent for body biopsies. Significant differences were present between CP-positive and negative subjects in the NUD group. Antral and body inflammation within these clinical groups shows a wide variation. Higher inflammatory cell counts in the DU group may reflect the prevalence of CP colonization.

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes.

Multiple specimens taken at oesophageal suction biopsy were obtained from 56 patients, of whom 44 had symptoms of gastro-oesophageal reflux and 24 had endoscopic evidence of erosive oesophagitis. Biopsies were examined independently by two histopathologists for the following criteria for reflux: epithelial hyperplasia, vascular dilatation and congestion, neutrophil infiltration, and eosinophil infiltration. The incidence of these criteria in patients with and without endoscopic evidence of oesophagitis or symptoms of reflux was investigated. It was concluded that vascular dilatation and epithelial hyperplasia, defined as basal zone thickness greater than or equal to 15% and papillary elongation greater than or equal to 66%, can be detected most reliably, but their diagnostic accuracy is limited unless multiple biopsies are examined.

One hundred patients who had undergone operation for duodenal ulcer (68 vagotomy and gastroenterostomy; seven vagotomy and pyloroplasty; 22 gastrectomy and three gastroenterostomy) 10 or more years previously each underwent endoscopy. Biopsies were taken and gastric juice aspirated for measurement of pH and nitrite concentration. Patients were divided into five histological grades; chronic superficial gastritis (+/- minimal atrophic gastritis) (35), atrophic gastritis/intestinal metaplasia (30), mild dysplasia (21), moderate/severe dysplasia (13) and carcinoma (one). A wide spectrum of pH values was found with 35 patients having a fasting intragastric pH below 4.0 and 65 above 4.0. A strong relationship was found between histological grade and pH. Patients with chronic superficial gastritis had a fasting intragastric pH below 4.0 more frequently than those with moderate/severe dysplasia (p less than 0.001). Gastric juice nitrite concentrations were higher in the moderate/severe dysplasia group than in the chronic superficial gastritis group (p = 0.02). The strong correlation between pH and nitrite concentration, previously documented, was confirmed. The implications of these findings in the pathogenesis of carcinogenesis in the postoperative stomach are discussed.

Proliferation of adipose tissue adjacent to intrasplenic transplants of whole isogeneic neonatal rat pancreas has consistently been noted. In this study over a period of 18 months there was a progressive increase in the amount of fatty tissue in the vicinity of surviving transplants. Immunohistochemistry demonstrated the presence of insulin, glucagon, somatostatin and pancreatic polypeptide within islet cells in long term grafts. Electron microscopy demonstrated a close association between islets and lipid droplets. Ductal elements within the transplants survived and showed close association with endocrine cells, but exocrine pancreatic tissue degenerated rapidly. Radioimmunoassay of extracts from surviving transplants in isogeneic rats confirmed the presence of high levels of insulin and glucagon after transplantation. In contrast, allogeneic intrasplenic transplants of rat pancreas failed to survive and showed no evidence of adipose tissue proliferation. Furthermore, isogeneic intrasplenic transplants of both adult rat fat and adrenal gland also failed to demonstrate adipocyte proliferation. It would appear that the presence of both adipocytes and pancreatic endocrine cells, particularly B cells, are required for the proliferation of adipocytes at the graft site.