gastrins and Bile-Duct-Neoplasms

Topics: Adult; Bile Duct Neoplasms; Disease-Free Survival; Female; Gastrinoma; Gastrins; Hepatectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Omeprazole; Prognosis; Prospective Studies; Proton Pump Inhibitors; Secretin; Survival Rate; Zollinger-Ellison Syndrome

The authors report seven patients with carcinoid tumors of the extrahepatic bile ducts (EHBDs). All patients were women, with an average age at diagnosis of 49.8 years (range, 37-67 yrs). The most common presenting symptom was painless jaundice with or without pruritus. Although one patient had peptic ulcer disease before the onset of obstructive jaundice, none had systemic endocrine manifestations. These neoplasms were most often located in the common bile duct. Grossly, the carcinoid tumors were usually nodular and poorly demarcated, and ranged from 1.1 to 2.7 cm in size. Only one of the neoplasms was polypoid. Microscopically, the tumors had a trabecular or nesting pattern with occasional tubule formation, and were composed of relatively small cells with granular chromatin. All of the neoplasms expressed chromogranin and two expressed synaptophysin. Three expressed serotonin and two of the three were also immunoreactive for pancreatic polypeptide or somatostatin. Two tumors were focally positive for gastrin and one of these two tumors was also positive for serotonin and pancreatic polypeptide. All seven carcinoid tumors showed no immunoreactivity for p53, and assays for p53 loss of heterozygosity analysis were negative in two, suggesting that p53 mutations do not play a role in the pathogenesis of EHBD carcinoids. A mutation in codon 12 of K-ras was found in one carcinoid tumor whereas two of two showed immunoreactivity for Dpc4 protein. In view of the small number of carcinoids studied, the importance of these findings in the pathogenesis of these tumors is unclear. Ultrastructural examination of three of the tumors revealed numerous membrane-bound, round neurosecretory granules. Clinically, these lesions had an indolent course. Even in the presence of lymph node metastases (noted in two patients), all of the patients remained disease free 2 to 11 years (average follow up, 6.6 yrs) after segmental resection or pancreaticoduodenectomy (Whipple's procedure). Because carcinoid tumors of the EHBD are of low malignant potential, they should be separated from the more common adenocarcinomas in this location.

Topics: Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoid Tumor; Chromogranins; Cytoplasmic Granules; DNA-Binding Proteins; DNA, Neoplasm; Female; Follow-Up Studies; Gastrins; Humans; Immunoenzyme Techniques; Loss of Heterozygosity; Lymph Nodes; Lymphatic Metastasis; Microsatellite Repeats; Middle Aged; Neurosecretory Systems; Pancreatic Polypeptide; Pancreaticoduodenectomy; Serotonin; Smad4 Protein; Somatostatin; Synaptophysin; Trans-Activators; Treatment Outcome

Gastrin is a trophic factor within the normal gastrointestinal tract and is also a mitogen for a number of gastrointestinal and non-gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG) and glycine-extended gastrin (G-gly) as well as the fully processed amidated gastrin (G-NH2) are expressed by tumours. There has been little study of the role of gastrin in either normal liver or liver tumours. The aim of this study was to identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2 in normal liver and liver tumours.. Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-BR and gastrin isoforms.. Most liver tumours express CCK-BR and are able to process gastrin as far as proG and G-gly, although not as far as the amidated form. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver.. Liver tumours express the CCK-BR and precursor forms of gastrin. This expression may be associated with tumour proliferation.

Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cholangiocarcinoma; Gastrins; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Protein Processing, Post-Translational

A total of 44 extrahepatic bile duct carcinomas comprising 13 well-differentiated adenocarcinomas, 25 moderately differentiated adenocarcinomas, and 6 poorly differentiated adenocarcinomas were examined histologically and immunohistochemically for somatostatin, gastrin, and glicentin. Argyrophil cells, argentaffin cells, and somatostatin- and gastrin-immunoreactive cells within the tumor were detected in 46.2%, 15.4%, 23.1%, and 15.4% of well-differentiated adenocarcinomas, and in 16.0%, 8.0%, 12.0%, and 4.0% of moderately differentiated adenocarcinomas, respectively. No tumor tissues of poorly differentiated adenocarcinomas contained endocrine cells. A statistically significant difference in the frequency of argyrophil cells was observed between well and poorly differentiated adenocarcinoma. The incidence of argyrophil cells and somatostatin-immunoreactive cells in nonneoplastic mucosa adjacent to well-differentiated adenocarcinoma was higher than in that adjacent to poorly differentiated adenocarcinoma. Glicentin-immunoreactive cells could not be demonstrated either in tumor tissue or in nonneoplastic mucosa of the extrahepatic bile duct. With reference to the histogenesis of extrahepatic bile duct carcinoma, it was assumed from these results that the development of well-differentiated adenocarcinoma might be closely related to the occurrence of endocrine cells and that poorly differentiated adenocarcinoma might develop from ordinary mucosa.

Topics: Adenocarcinoma; Bile Duct Neoplasms; Endocrine Glands; Enterochromaffin Cells; Female; Gastrins; Glucagon; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Middle Aged; Mucous Membrane; Neoplasm Staging; Proglucagon; Protein Precursors; Somatostatin

Thirty specimens of stomach, duodenum, and jejunum, removed at operation, were examined by optical microscopical, cytochemical, and electron microscopical techniques. The overall distribution of four types of endocrine polypeptide cell in the stomach, and three in the intestine, was determined. The seven cell types are described by names and letters belonging to a scheme for nomenclature agreed upon at the 1969 Wiesbaden conference on gastrointestinal hormones. The gastrin-secreting G cell was the only cell for which firm identification with a known hormone was possible. Although there was wide variation in the distribution of the various cells, from one case to another, striking differences were nevertheless observable, with respect to the G cell, between antra from carcinoma and from ulcer cases.

Topics: Bile Duct Neoplasms; Carcinoma; Duodenal Ulcer; Duodenum; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Jejunum; Microscopy; Microscopy, Electron; Peptides; Placenta; Stomach; Stomach Neoplasms