Background: Somatostatin and its long-acting analogues are effective in symptom control in patients with functionally active neuroendocrine GEP tumours. Several in vitro and in vivo reports suggest that they are also able to control tumour growth. Methods: Critical review of published data on the effect of long-acting somatostatin analogues on symptom and growth control in patients with metastatic neuroendocrine GEP tumours. Results: With the exception of insulinoma and gastrinoma, octreotide acetate and other long-acting somatostatin formulations are currently the therapeutic principle of first choice to control hormone-mediated symptoms. The consequences of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome are best controlled by proton pump inhibitors. Available data on growth control indicate that stabilization of tumour growth seems to be the most beneficial antiproliferative effect occurring in up to 50% of patients. This effect is limited. However, it is unknown which tumour entity responds best to long- acting somatostatin analogues. Conclusion: Additional studies in patients with known spontaneous tumour growth and avoiding a mix-up of different entities of neuroendocrine malignancies are necessary to identify subpopulations of neuroendocrine tumours which respond to long-acting somatostatin analogues in terms of longer lasting growth inhibition.

The α-glucosidase inhibitor voglibose (AO-128) was designed to prevent rapid postprandial blood glucose rises in non-insulin-dependent diabetics. We analyzed its effect on the entero-insular axis in 72 healthy volunteers in a double-blind study design before, after the 1st dose, and on the 7th day of a 7-day treatment protocol (3 daily loads). Six parallel groups of 12 volunteers received voglibose (0.5, 1.0, 2.0, or 5.0 mg) or placebo (two groups). Blood was drawn at regular intervals up to 180 min after a standardized breakfast to analyze the levels of glucose, insulin, C peptide, gastric inhibitory polypeptide, and glucagon-like peptide 1 (GLP-1). As expected, after ingestion of voglibose, slight to moderate gastro-intestinal discomfort but no severe side-effects were reported. In a dose-dependent manner, voglibose significantly reduced postprandial increases of blood glucose, insulin, and C peptide. At the lower loads (0.5 and 1 mg voglibose three times daily), these effects were more pronounced after 7 days. The postprandial increase of gastric inhibitory polypeptide was already reduced after the first load of 2 and 5 mg voglibose. In comparison to the placebo group, this inhibition became also significant for the lower loads after 7 days. Interestingly, GLP-1, originating from the lower intestines, was increasingly released under voglibose treatment. The first administration of 1 mg voglibose enhanced GLP-1 secretion > 80% above controls. Treatment with 1 mg voglibose three times daily over 7 days revealed a maximal mobilizing effect on endogenous GLP-1 ( > 90% above controls) which was not further increased by 2- or 5-mg loads. We conclude that voglibose treatment effectively inhibits intestinal disaccharidases and thereby mobilizes the endogenous pool of insulinotropic GLP-1.

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\s=b\Certain epithelia of the human inner ear and human endolymphatic sac display somatostatin and/or somatostatinlike immunoreactivity. Histologic sections from 13 human temporal bones and from 15 endolymphatic sacs were studied using the unlabeled antibody peroxidaseantiperoxidase technique. The somatostatin and/or somatostatinlike immunoreactive cells were located exclusively in the covering epithelium of the spiral prominence and in the epithelium of the intermediate and rugosal part of the endolymphatic sac. In the epithelium of the spiral prominence and endolymphatic sac, secretory granules of the same size and appearance as those of intestinal or pancreatic somatostatin-producing cells were demonstrated ultrastructurally. The findings are consistent with a local exocrine, paracrine, and/or endocrine system of the inner ear. (Arch Otolaryngol Head Neck Surg 1986;112:934-937) The function of the spiral promi¬ nence is unknown. Its epithelium might exert a secretory1"4 and/or resorptive activity.511 In animals, the endolymphatic sac resorbs tracer substances, dyes, or cell debris from the cochlear endolymph1013 and actively transports potassium across the epi¬ thelium.1415 By immunohistochemical methods, the presence of IgA and the secretory component was demon¬ strated in distinct areas of the human endolymphatic sac epithelium.1617 Re¬ cent ultrastructural studies of the human endolymphatic sac in Me¬ niere's disease18 and of the normal human spiral prominence19 revealed secretory granules within epithelial cells that strongly resemble gastroin¬ testinal tract cells producing endo¬ crine, neurocrine, or paracrine sub¬ stances.20 The aim of this investiga¬ tion was to identify the character of these cells. MATERIALS AND METHODSThirteen human temporal bones and 15 human endolymphatic sacs from children and adults (age range, four months to 81 years) without known disease of the mid¬ dle or inner ear were removed at autopsy; fixed for three hours in a solution contain¬ ing 40% formaldehyde (10 mL), mercuric-(Il)-chloride (6 g), glacial acetic acid (5 mL), and distilled water to a total volume of 100 mL; and then rinsed for 21 hours in ethyl alcohol (70%). The temporal bones were decalcified in edetic acid and pro¬ cessed for conventional histology. Deparaffinized sections were stained for somato¬ statin, employing Sternberger's21 unla¬ beled antibody peroxidase-antiperoxidase technique. The somatostatin antiserum (antihuman somatostatin from goat, Dakopatts, Copenhagen) was used in a dilution of 1:3000.22 Tissue samples of human pancreas, small intestine, and colon were used as controls. The unlabeled anti¬ body peroxidase-antiperoxidase method was carried out with and without specific antisera; a positive somatostatin and/or somatostatinlike immunoreactive (SSLI) reaction was exclusively seen when using specific antisera. Sections were stained according to Grimelius to identify argyrophilic cells containing neurosecretory granules. Inner ear tissue from seven other healthy human temporal bones was pre¬ pa...

Aim: Many studies describe the sensitivities and specificities of computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) in patients with gastrointestinal neuroendocrine tumors (GNT). We performed a study to evaluate the influence of these techniques on the therapeutic management of patients with advanced stages of GNT. Patients and Methods: The results of either CT/MRI scans or SRS were reviewed by two independent observers who decided on the therapy of a patient. They then had to determine whether the results of the complementary imaging modality would change the decision. The study design was a matched cross-over study with two groups matching in respect to tumor type, imaging modality known first to the observer, and number of patients. For further analysis, patients were divided into three subgroups dependent on tumor stage (group 1, without metastases, group 2, liver metastases, group 3, recurrent disease/extrahepatic metastases). Results: 188 patients were included into the study. If SRS was known to the observers first, CT/MRI changed the therapeutic management in 16.2, 13.9 and 11.4% of the patients (subgroups 1–3). SRS changed the therapeutic management in 13.5, 12.5 and 10.3%. Overall, CT/MRI would have changed the management in 13.3% and SRS in 11.7% of the patients. Conclusion: Though the patients studied mainly suffered from already advanced stages of the disease, all imaging techniques change the therapeutic management to a comparable extent. Our results support the importance of combined imaging in the management of patients with GNT.