Family characteristics of gastric carcinoma.
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Biomedical subjects
Publications and source records attributed to P Sipponen.
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The occurrence of intestinal metaplasia with colonic-type sulphomucins: (abbreviated: s-IM or s-positive IM) in the gastric mucosa was studied in 125 patients with gastric carcinoma (GCA), 62 patients with pernicious anemia (PA), 301 and 183 first-degree relatives of GCA and PA patients, 406 outpatients and in 358 controls matched from a large population sample. The sulphomucins (s-mucins) were demonstrated histochemically in endoscopic biopsy specimens by using high iron diamine and Alcian blue (pH 1) methods. The prevalence of s-IM, especially the strongly s-positive IM, was significantly higher in GCA patients than in other series or controls of the same age group. Further, s-IM was significantly more common in PA patients and its prevalence higher in GCA relatives and outpatients than in other series or controls. The occurrence of s-IM was also age-dependent and dependent on the extent of IM. It was suggested that the occurrence of s-IM can be used as a sign of lesions that are more closely associated with GCA than IM is in general.
Morphological changes in the remnant mucosa 2-20 years after operation for duodenal ulcer (DU) were analyzed in 124 male subjects by means of stochastic mathematics. Fifty non-operated male DU patients and 168 age-matched males from a population sample served as controls. Substantially no progression of gastritis was found in the DU patients. In contrast, the operative intervention caused a rapid initial progression of gastritis, continuing after 2 years approximately at the same speed as in the population at large.
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The histochemical orcein reaction (orc) for mucosubstances in tissue samples from the human gastrointestinal tract was compared with PAS, high iron diamine (HID) and Alcian blue reactions at pH 1.0 or 2.5 (AB 1 and AB 2.5). Orc, HID and AB 1 reactions were performed also with prior oxidation of the tissue sections with potassium permanganate or performic acid (ox-orc, ox-HID and ox-AB reactions, respectively). Orc reaction stained mucosubstances similarly to HID and AB 1; only the brush border and goblet cells in the colon were stained. The reactions of the mucosubstances obtained with ox-orc differed from those with PAS, HID, AB 1 or AB 2.5 but were similar to those with ox-HID or ox-AB; the mucosubstances in the brush border and the goblet cells in the colon and small bowel and in the foveolar epithelium of the stomach were strongly stained. Pyloric and cardiac glands were stained faintly with ox-orc but not with ox-HID or ox-AB. Brunner's glands were negative with ox-orc, ox-HID and ox-AB reactions. It was assumed that the orc reaction stains, like HID or AB 1, sulphate groups in epithelial mucosubstances, and that sulphonic acid residues, resulting from oxidation of disulphide groups in the protein core of mucus glycoproteins, are responsible for the ox-orc as well as for the ox-HID and ox-AB reactions.
High iron diamine reactions after the prior methylation and oxidation of tissue sections with performic acid or potassium permanganate (metox-HID or ox-met-HID) in epithelial mucosubstances and in mucosal mast cells were studied in tissue samples from the human gastrointestinal tract and were compared with reactions with high iron diamine without any pretreatment (HID) and high iron diamine with the prior methylation (met-HID). High iron diamine reactions after the prior oxidation (met-ox-HID, ox-met-Hid and ox-Hid) demonstrated mucosubstances in a way which seemed to operate by the staining of acidic groups evoked by the oxidation of the tissue sections. These acidic groups were not blocked by the methylation. It was supposed that they are sulphonic acids resulting from sulphur groups (sulphydryls or disulphides) in some mucus glycoproteins. Met-ox-HID and ox-met-HID reactions seemed to stain mucosubstances and mast cells in a similar way but differed from the ox-HID reactions with the manner which could be interpretated to be due to the blocking of free sulphate ester groups in reactions of the former. Met-ox-HID (and ox-met-HID) positive and in goblet cells of small and large bowel.
Electron probe microanalysis for iodine, sulphur and phosphorus was performed in histological frozen sections from thyroid tissue of 5 patients undergone thyroid surgery for benign disease. Iodine seemed to be localized in the colloid of the thyroid follicles. Phosphorus localized in areas which corresponded with the epithelium of the follicles. Sulphur showed a strong association with iodine both in localization and in relative amounts. It was suggested that iodine and sulphur reflect the presence of thyroglobulin in the colloid of thyroid follicles.
The measurement of carcinoembryonic antigen (CEA) in serum and endoscopic brush specimens was evaluated for the differential diagnosis of malignant and nonmalignant gastric disease. Brush specimens were studied from 33 patients with gastric cancer and 36 patients with benign gastric lesions or apparently normal gastric mucosa. Demonstrable CEA immunoreactivity was found by radioimmunoassay in brush specimens from 24/33 cancer patients (73%) and from 23/36 patients with benign lesions (64%). Patients with CEA+ tissue in the immunoperoxidase test had somewhat higher CEA concentrations in the brush specimens than cases with CEA- biopsy tissue, although overlap was considerable. Thirty-five per cent of cancer patients had both a positive tissue CEA reaction and a CEA/DNA ratio greater than 10 ng/micrograms, whilst patients with benign lesions had only 15% of positives by these criteria (0.01 greater than P greater than 0.001). The serum CEA concentration was above the upper normal level of 5 ng/ml in 2/39 patients, both of whom had gastric cancer. The CEA immunoreactive material from benign and malignant lesions eluted in gel filtration on Sephadex G-200 in the same volume as CEA purified from liver metastases of cancer of the colon, showing that a glycoprotein sharing immunological and physicochemical properties with CEA is present both in malignant and nonmalignant lesions of the gastric mucosa, and that there is considerable overlapping in the amount of CEA. The estimation of CEA in gastric-brush specimens is therefore of limited value in the differential diagnosis of benign and malignant gastric lesions.
Rats chronically fed ethanol developed liver injury only if they also received low doses of the alcohol dehydrogenase inhibitor, 4-methylpyrazole, suggesting that the consistency of the influence of ethanol and its metabolism, rather than the level of acetaldehyde or the degree of the metabolic effects, contributes to the pathogenesis of alcoholic liver damage.
Carcinoembryonic antigen (CEA) was studied by the three-layer bridge immunoperoxidase technique in gastric biopsy specimens taken from 49 patients, 13--20 years after partial gastrectomy. Routine histological examination revealed various degrees of chronic atrophic gastritis in all patients. A positive CEA reaction was found in 6 out of 9 with malignant or premalignant mucosal changes and in 4 out of 40 without these changes. In two cases of carcinoma the biopsies revealed a positive CEA reaction. In 4 patients with carcinoma diagnosed 1--2 years after the first examination the initial nonmalignant biopsies were CEA-positive in one case. All biopsies from mucosa with severe dysplasia and adenomatous polyps were CEA-positive. Four patients without malignant or premalignant changes in the gastric mucosa had CEA-positive biopsies. No carcinoma has been found in these patients at re-examinations after 1 year. The results indicate that the occurrence of immunohistochemically detectable CEA may be associated with malignant transformation of the gastric mucosa. The value of this method in screening patients at increased risk of gastric carcinoma will be further explored.
Relative chief and parietal cell volume densities were estimated morphometrically in the remnant mucosa of 98 male patients ("series"), operated on for duodenal ulcer by the Billroth II, and in the body mucosa of 55 subjects, age and sex matched, from a random series of a Finnish population ("controls"). The relative volumes of chief and parietal cells were significantly lower in the series than in the controls. The mean chief cell: parietal cell ratio was significantly higher in the series than in the controls. In the controls the ratio decreased with increasing loss of normal tubules. However, no such decrease was discernable in the series, owing to wide scatter of the individual ratios. High ratios (greater than or equal 2.0) were found in 17 cases of the series and in one of the controls. These 17 patients with high ratios had a significantly higher mean length of the foveoles and a significantly lower mean score of the round cell infiltration than the operated patients with lower ratios.
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Two sisters who died at the age of 2.5 years and 5 weeks are described. Both showed signs of panhypopituitarism. At necropsy, no hypophysis could be found in the first child and a rudimentary and partly ectopic hypophysis was found in the other. Both children had a flat, poorly developed sella turcica, and the sellar anomaly could be seen in skull x-rays. These patients represent a hereditary syndrome characterised by neonatal panhypopituitarism, hypoplasia of the pituitary gland, and flat sella turcica.
Nine cases of cystic polyps were found among 15,000 routine gastroscopies. All but one of the subjects were women. The polyps were found only in the body of the stomach. They were less than 5 mm in size and in most cases multiple. Endoscopically they were verruca-like lesions and appeared to be loosely attached to the mucosal membrane. They consisted of mucosal cysts lined with normal but irregularly arranged epithelial cells of the body mucosa. No inflammatory reaction or metaplasia was seen in the polyps or outside them. These characteristics suggested the hamartomatous nature of these polyps.
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Familial nephronophthisis was diagnosed in a son and two daughters of a mother who herself died in uraemia at the age of 29 years. The son died at 33 years, two daughters are alive at 30 and 33 years. Our cases suggest a dominant autosomal type of inheritance because the mother married twice; the affected son was from the first marriage and the affected daughters from the second marriage. There was no known consanguinity between the parents. The pathogenesis of the disease can be explained by a slowly progressive process that leads to complete or partial obstruction of the tubules in the corticomedullary area, and also, therefore, to cystic dilatations. Histological evidence for this is provided by the proliferation of fibroblasts around the collecting ducts and other tubules, prominent thickening of the tubular basement membrane, and fibroblasts and collagen fibrils in or inside the thickened basement membranes. An ultrastructural description of affected kidneys is given.