Disease relevance of Gastrinoma

• Selective intra-arterial methylene blue injection can enhance intraoperative detection of small gastrinomas and may improve the rate of curative resection in the Zollinger-Ellison syndrome [1].
• It is postulated that the abnormal stimulation of antral gastrin release may on occasions give rise to antral G-cell hyperplasia, and that the abnormal secretion of gastrin into gastric juice may on occasions give rise to gastrinomas [2].
• The dramatic clinical improvement after subsiding of the intercurrent illness was obviously linked to pronounced failure of the parietal cell mass for acid secretion and not to infarction of the gastrinoma because gastrin secretion by the tumor was unchanged [3].
• One copy of the MEN1 gene was found to be deleted in 25 of 27 (93%) sporadic gastrinomas and in 6 of 12 (50%) sporadic insulinomas [4].
• Analysis of CD44 splice variants showed that in all five gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic tumors and carcinoid tumors [5].

High impact information on Gastrinoma

• Brief report: a duodenal gastrinoma in a patient with diarrhea and normal serum gastrin concentrations [6].
• It is likely that these lesions precede the development of MEN1-associated duodenal gastrinomas [7].
• RESULTS: We confirmed the molecular nature of the secretin receptor in the gastrinomas with a positive provocative test result and identified a novel mechanism for a false-negative result [8].
• The exact identification of this gastrinoma in an extra-abdominal site was facilitated by the use of [111In-DTPA-DPhe1]octreotide scanning for somatostatin receptors, which these tumors characteristically possess in high numbers [9].
• If a primary gastrinoma cannot be identified by SRS or STIR-MRI, endoscopic ultrasonography should be undertaken because duodenal gastrinomas are often minute and multicentric [10].

Chemical compound and disease context of Gastrinoma

• The sensitivities of conventional techniques, Octreoscan scintigraphy, and their association were 58%, 58%, and 90%, respectively, for all resected gastrinomas [11].
• Thus, in this gastrinoma patient, secretin and somatostatin appeared to act directly on gastrinoma cells to stimulate and inhibit gastrin secretion, respectively, by modulating adenylate cyclase activation, probably via guanine nucleotide-binding proteins [12].
• Selective intra-arterial methylene blue injection: a novel method of localizing gastrinoma [1].
• Immunoaffinity chromatography studies of antral mucosal and gastrinoma extracts identified a molecular form of glycine-extended processing intermediates that was characterized by an amino terminus identical to that of gastrin heptadecapeptide [13].
• In the presence of 3-isobutyl-1-methylxanthine, secretin significantly stimulated gastrin release from dispersed gastrinoma cells, which was inhibited by somatostatin [12].

Biological context of Gastrinoma

• Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas [4].
• In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients [14].
• A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes [15].
• Furthermore, because it is independent of disease stage it is probably an early event in the pathogenesis and because it is independent of the primary gastrinoma location, which is now thought to have different origins, methylation of the p16INK4a gene is probably a central process in the molecular pathogenesis of these tumors [16].
• DNA was extracted from frozen gastrinomas from 51 patients and screened by dideoxyfinger-printing (ddF) for abnormalities in the 9 coding exons and adjacent splice junctions of the MEN1 gene [17].

Anatomical context of Gastrinoma

• Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D'etude Du Syndrome De Zollinger-Ellison [11].
• The abnormal amount of G17 in gastric juice may be responsible for releasing abnormal amounts of G34 into the circulation from the duodenum and from gastrinomas [2].
• A specific MEN1 mutation was detected in one gastrinoma and in the corresponding germ-line DNA of a patient who had no family history of MEN1 [4].
• A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management [18].
• Secretin was injected into a feeding or nonfeeding artery of a gastrinoma and blood samples were taken from the hepatic vein (HV) or a peripheral artery (PA) to measure the changes of serum immunoreactive gastrin concentration (IRG) [19].

Gene context of Gastrinoma

• CONCLUSIONS: Besides somatostatin receptors, most of gastrinomas and VIPomas also express receptors for bombesin, secretin, and vasoactive intestinal peptide [20].
• Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene [15].
• RESULTS: In each of the gastrinomas studied, detectable levels of EGFR and HGFR mRNA were present [21].
• In the human gastrinoma culture, RC-160 inhibited gastrin release significantly more than octreotide at 10(-12)- and 10(-14)-M concentrations (P < 0.01) [22].
• The patient was previously known to have a pancreatic gastrinoma and had first-degree relatives with MEN1 [23].

Analytical, diagnostic and therapeutic context of Gastrinoma

• These successes, the availability of techniques that permit early identification and localization of gastrinomas, and the advent of H2-receptor antagonists that can control gastric hypersecretion without gastrectomy must be considered in managing patients with gastrinomas [24].
• At laparotomy, methylene blue is injected through this catheter to selectively stain the gastrinoma, facilitating its identification [1].
• CONCLUSIONS: Both the secretin provocative test and fasting serum gastrin determination are necessary for the early diagnosis of cases of recurrent disease after gastrinoma resection [25].
• In a one-year period (1979-1980) nine (of 14 suspected) new gastrinoma patients were identified using a sensitive and specific gastrin radioimmunoassay in combination with provocative tests including IV secretin, calcium, and food [26].
• Chemotherapy consisting of Tubercidin, Streptozotocin and 5-Fluorouracil was given to 5 patients with extensive gastrinoma [27].

References