Due to its high specificity, CgA determination may help to discriminate the endocrine character of a GEP tumour and to indicate a pancreatic tumour in MEN-1. However, its low NPV in nonsecreting tumours limits its interest for diagnosis and staging. By contrast, serial evaluation of CgA seems of particular interest for the follow-up of GEP-ET tumours.

Aims: To clarify the role of b-catenin in digestive endocrine carcinogenesis, a large and representative series of gastroenteropancreatic endocrine tumours was analysed in order to determine the incidence and pattern of b-catenin changes and to analyse the clinical and histological characteristics of the tumours presenting immunohistochemically detectable changes in b-catenin expression. Methods: 229 cases of gastroenteropancreatic endocrine tumours (stomach, 11; duodenum and ampulla, 29; jejunum and ileum, 51; appendix, 13; colon and rectum, 17; and pancreas, 108) were studied by immunohistochemistry to assess the pattern of distribution of b-catenin (membranous, cytoplasmic or nuclear). DNA was analysed to detect mutations in exon 3 of the CTNNB1 gene. Results: The distribution of immunoreactive b-catenin protein was membranous in 164 cases, cytoplasmic in 58 cases and nuclear in seven cases. No mutation was detected in exon 3 of the CTNNB1 gene in any case. The seven cases with nuclear accumulation of b-catenin were large tumours (mean size 44 (standard deviation (SD) 18.5) mm) with metastases, including liver metastases in five cases, high Ki-67 index (mean 34% (SD 16.5%)) and cyclin D1 overexpression; p53 accumulation was detected in six cases. Five patients died of disease; the mean (SD) survival was 13.6 (4.8) months. Conclusions: Immunohistochemically detectable nuclear accumulation of b-catenin is infrequent in gastroenteropancreatic endocrine tumours and is usually not associated with mutations in CNNTB1 exon 3. Changes in b-catenin expression are late events in digestive endocrine carcinogenesis, associated with tumour progression and dissemination.

Summary ― Changes in the concentrations of cholecystokinin, gastric inhibitory peptide, gastrin, motilin, pancreatic polypeptide, secretin, somatostatin, and vasoactive intestinal peptide in calf plasma and antral, duodenal and/or pancreatic tissues were assessed by radioimmunoassay during postnatal development and after weaning in 50 male Holstein-Friesian calves (randomly distributed into 10 groups of 5 animals each). The calves in the first group were killed at birth while those in 6 other groups were colostrum-fed for 2 days and then milk-fed until 7, 28, 56, 70

The effects of graded duodenal acidification on plasma concentration of immunoreactive secretin, and motilin in portal vein (PV) and carotid artery (CA) were investigated in 6 anaesthetised pigs in which the proximal duodenum was excluded and sequentially irrigated with isotonic saline (pH 7.0) and with hydrochloric acid (HC1) delivered at successive rates of 2, 8 and 40 mM H⁺/40 min(pH of 2.8, 1.9 and 1.0, respectively) under a constant flow of 10 ml/min. The release of secretin was first observed at pH 1.9 (from basal 4.2 ± 0.3 to a peak of 26.6 ± 9.8 pM in PV and from 3.4 ± 0.3 to 6.8 ± 0.9 pM in CA) and further increased at pH 1.0 (peaks of 60.9 ± 16.3 in PV and 16.8 ± 2.6 pM in CA). In contrast, only the highest HC1 concentration (pH of effluent: 1.0) induced significant increases of plasma motilin (PV: peak of 25.2 ± 4.9 for basal 13.3 ± 1.1 pM, CA: 14.3 ± 2.4 for basal 10.5 ± 0.6 pM). A sharp decrease of the plasma secretin and motilin concentration was observed when the venous drainage of the duodenal segment was occluded, followed by a rapid increase when the clamp was released. In the present experimental conditions, duodenal motilin-producing sites were less sensitive to graded luminal acidification than secretin cells. Thus, the release of duodenal motilin in response to variations of luminal pH may be expected to occur primarily from the most proximal part of the duodenum in physiological conditions.