Kurt Borch

Gastric endocrine cell hyperplasia and carcinoid tumors in pernicious anemia

Endoscopic screening in 123 patients with pernicious anemia (PA) yielded 4 patients with solitary and 1 patient with multiple gastric carcinoid tumors. Quantitative histologic studies of multiple standardized biopsy specimens showed a significantly increased number of fundic mucosal argyrophil endocrine cells in 40 patients with PA when compared with 15 patients with simple fundic atrophic gastritis (p = 0.002) or 8 normal controls (p = 0.0001). Patients with simple atrophic gastritis had increased numbers of fundic mucosal argyrophil cells as compared with normal controls (p = 0.02). A significant difference was also noticed in the number of antral mucosal argyrophil cells between patients with PA and normal controls (p = 0.01), but not between patients with PA and patients with simple atrophic gastritis. It is concluded that, in addition to having hyperplasia of gastric mucosal argyrophil endocrine cells, patients with PA run an increased risk of developing gastric argyrophil cell carcinoid tumors, which should be regarded as potentially malignant.

Development of symptoms and complications in individuals with asymptomatic gallstones

Gallbladder stones are common in the developed world. Complications of gallstones contribute substantially to healthcare costs and may be life threatening. The identification of individuals likely to develop complications would be of benefit in clinical practice as elective cholecystectomy could then be performed.

Relations between Circulating Gastrin and Endocrine Cell Proliferation in the Atrophic Gastric Fundic Mucosa

It has been suggested that gastrin may be a causative factor in the proliferation of gastric fundic mucosal endocrine cells, as seen in the Zollinger-Ellison syndrome and in atrophic gastritis with hypergastrinemia of antral origin. In the present study, morphometrically determined densities of endocrine cells in fundic mucosal biopsy specimens were related to basal levels of serum gastrin in 10 normal controls and 60 patients with achlorhydric fundic atrophic gastritis, of which 45 had pernicious anemia (5 with fundic mucosal carcinoid) and 15 had atrophic gastritis without pernicious anemia. The densities of fundic mucosal endocrine cells were positively related to the levels of serum gastrin (atrophic gastritis, rs = 0.65; atrophic gastritis and normal controls, rs = 0.72). The highest levels of serum gastrin were found in patients with carcinoid tumors (mean, 1659.3 pmol/l), followed by those in patients with focal hyperplasias (cluster formation) of endocrine cells (mean, 503.2 pmol/l) and those in patients without focal hyperplasias (mean, 304.4 pmol/l) (p = 0.03 and p = 0.04, respectively).

Duodenal intraepithelial lymphocyte‐count revisited

Background: The number of intraepithelial lymphocytes in the duodenum was determined 30 years ago, the suggested normal upper limit being 40 lymphocytes per 100 epithelial cells. Methods: Duodenal mucosa was analysed from 18 healthy individuals and 56 consecutive patients biopsied because of epigastralgia (17 cases), diarrhoea (10 cases), oesophagitis (10 cases), iron‐deficiency (9 cases) and B12‐deficiency (10 cases) showing normal histology, along with 10 cases of active coeliac disease. The biopsies were fixed in 4% formalin overnight and embedded in paraffin. Three micrometre thick sections were stained with haematoxylin and eosin and CD3. At least 300 epithelial cells were counted, the number of intraepithelial lymphocytes was given as the mean/100 epithelial cells. Extensive statistical analyses were performed. Results: In the healthy individuals the mean number (s) of intraepithelial lymphocytes/100 epithelial cells was 10.8 (2.6) and 13.2 (3.8) in H&E and CD3 stained sections, respectively. The upper limit of the confidence interval for CD3 staining was 29. There was no significant difference between normal individuals and the clinical groups, with the exception of coeliac disease. Conclusion: Two‐step analysis of intraepithelial lymphocyte‐determination is suggested: (a) semiquantitative estimate on H&E‐stained sections (normal ratio of 1:5 between lymphocytes and enterocytes; upper normal limit 20 lymphocytes) and (b) CD3‐staining and counting if intraepithelial lymphocytosis is suspected. The upper normal range of intraepithelial lymphocytes is set at 25 CD3+ lymphocytes/100 epithelial cells. Values between 25 and 29 are regarded as ‘borderline’ and 30 or more represent pathologic intraepithelial lymphocytosis in the duodenum.

Value of routine intraoperative cholangiography in detecting aberrant bile ducts and bile duct injuries during laparoscopic cholecystectomy

A prospective study was performed to determine the frequency and type of bile duct abnormalities, and to determine whether routine use of intraoperative cholangiography during laparoscopic cholecystectomy might aid in the prevention of bile duct injuries. Overall, anatomical aberrations of the bile ducts were found in 98 (19 per cent) of 513 cholangiograms. The most common anomalies were at the hepatic confluence and constituted different types of right hepatic subsegmental ducts draining separately into the biliary tree (n=43, 8.4 per cent), either close to the cystic duct or directly into the cystic duct. Three bile duct injuries (0.5 per cent) occurred during the study period. These results show that routine intraoperative cholangiography is feasible and provides valuable information about the anatomy of the biliary tract, thereby improving the safety of laparoscopic cholecystectomy. If an injury to the biliary tract occurs early during operation, the cholangiogram allows the surgeon to detect the injury, to make a prompt repair and thereby reduce the morbidity associated with a delayed diagnosis. Routine use of intraoperative cholangiography is strongly recommended.

Profiling of bacterial flora in gastric biopsies from patients with Helicobacter pylori-associated gastritis and histologically normal control individuals by temperature gradient gel electrophoresis and 16S rDNA sequence analysis

The aim of this study was to establish bacterial profiles in gastric biopsy specimens from patients with Helicobacter pylori-associated gastritis by means of temporal temperature gradient gel electrophoresis (TTGE) of PCR-amplified 16S rDNA fragments. Specimens from eight patients with asymptomatic gastritis and five histologically normal controls revealed a Helicobacter-specific band in the TTGE profile with increased amounts of Helicobacter-specific DNA in the biopsies from most of the gastritis patients. DNA from other genera including Enterococcus, Pseudomonas, Streptococcus, Staphylococcus and Stomatococcus was also found in the stomach. In the absence of gastric inflammation, Helicobacter spp. appeared to be part of a complex, presumably indigenous microbial flora found in the biopsy specimens from the stomach.

Progastrin processing during antral G-cell hypersecretion in humans

Using radioimmunoassays specific for essential processing sites of human progastrin in combination with chromatography before and after cleavage with trypsin and carboxypeptidase B, we have examined antral biopsy specimens and serum from 10 hypergastrinemic patients with fundic atrophic gastritis and 7 normal control subjects. Four types of processing were studied: N-terminal proteolysis (at the N-terminus of component I, gastrin 34, and gastrin 17); C-terminal proteolysis (at the C-terminus of the amide donor, glycine93 in preprogastrin); alpha-carboxyamidation (of phenylalanine92); and O-sulfation (of tyrosine87). The results show that progastrin during permanent G-cell hypersecretion is less completely processed with respect to C-terminal proteolysis, alpha-amidation, and tyrosine-sulfation. In contrast, the degree of N-terminal proteolysis is normal. Thus, the processing of progastrin adjacent to the active site of gastrin is more restrictively controlled than N-terminal processing during G-cell hypersecretion associated with pernicious anemia.

Prevalence of gastroduodenitis and Helicobacter pylori infection in a general population sample relations to symptomatology and life-style.

Some benign and malignant diseases develop on the background of chronic gastritis or duodenitis. The present study was performed in order to determine the magnitude of these background changes with relations to symptomatology and life style in the general population. Examinations were performed in 501 volunteers (age 35–85 years). Fifty percent had gastritis; this was associated with H. pylori in 87%. H. pylori-negative gastritis was associated with regular use of NSAIDs [odds ratio 3.8 (1.6–9.9)]. Duodenitis, observed in 32%, was associated with H. pylori infection [odds ratio 2.3 (1.3–4.6)], previous cholecystectomy [odds ratio 3.6 (1.1–16.1)], and regular use of NSAIDs [odds ratio 3.0 (1.4–7.1)]. Neither gastritis nor duodenitis was associated with smoking or alcohol consumption. The rate of digestive symptoms did not differ between subjects with and without uncomplicated gastritis or duodenitis. In conclusion, half of this adult population had gastritis strongly associated with H. pylori infection. Gastritis without H. pylori infection was frequently associated with regular NSAID intake. One third had duodenitis, which was associated with H. pylori infection as well as with regular use of NSAIDs and previous cholecystectomy. Digestive symptoms were not overrepresented in uncomplicated gastritis or duodenitis.

Gastric carcinoid associated with the syndrome of hypergastrinemic atrophic gastritis. A prospective analysis of 11 cases

The prevalence of gastric carcinoid in fundic atrophic gastritis is probably greater than previously recognized. To help elucidate the clinicopathology of this syndrome, we report a series of 11 patients with solitary or multicentric carcinoid tumors. In these patients, basal gastrin levels and density of fundic mucosal endocrine cells were greater than that for patients with uncomplicated fundic atrophic gastritis (p=0.02 and p=0.002, respectively). The polypoid tumors, of which the largest measured 30 mm, frequently showed characteristic endoscopic features. They were all situated in the fundic mucosa, which showed micronodular endocrine cell hyperplasia. Small, endoscopically evident tumorlets, or “early carcinoids,” limited to the lamina propria were observed in some patients. These lesions may represent intermediate stages between micronodules and invasive carcinoids, all of which infiltrated at least into the muscularis mucosae of the gastric wall. Although some consistent characteristics features were noted, there were structural variations. The cells were argyrophil but nonargentaffin and did not stain with conventional mucus stains. They did not stain significantly for carcinoembryonic antigen (CEA). The secretory product of these tumors remains to be identified. Ultrastructurally, some tumors were mainly composed of enterochromaffinlike (ECL) cells, but in other tumors most of the cells could not be classified.

Diagnosis of gastritis by means of a combination of serological analyses

BACKGROUND Gastroscopy and examination of biopsy is normally required for diagnosis of gastritis. This is costly and inconvenient for the patient, and there is a need for a simple pregastroscopic screening method to reduce the endoscopy workload. Our aim was to develop a serological screening test for gastritis. METHODS Sera from subjects examined with gastroscopy and biopsy were analyzed for H,K-ATPase antibodies, Helicobacter pylori antibodies and pepsinogen I. The diagnoses were normal gastric mucosa (n=50), duodenal ulcer (n=53) and atrophic corpus gastritis, with (n=50) or without pernicious anemia (n=46). RESULTS An evaluation scheme was constructed to optimize the diagnostic agreement between serology and gastric mucosal morphology. The sensitivity to detect gastritis was 98% (146/149) (95% CI 94-100%) and the specificity 84% (42/50) (95% CI 71-93%). Additional sera from 483 subjects from the general population were analyzed. There was a good agreement between serology and gastric mucosal morphology. CONCLUSIONS Assays of multiple serum analytes are useful for the initial screening of gastritis. They are complementary to upper gastroscopy by identification of subjects with a normal gastric mucosa, those who qualify for eradication of H. pylori, and those who have developed atrophy and are at risk of developing malignancy and, therefore, require gastroscopic examination.