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M. M. Haber - One of the best experts on this subject based on the ideXlab platform.
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Chromogranin A in patients with acid hypersecretion and/or hypergastrinaemia.
Alimentary pharmacology & therapeutics, 2007Co-Authors: Basil I. Hirschowitz, Julie Worthington, Jean Mohnen, M. M. HaberAbstract:Summary Background Chromogranin has been proposed as a marker for gastrin-dependent Enterochromaffin-Like Cell proliferation. Aim To examine this question in three populations: acid hypersecretors with gastrinoma (Zollinger–Ellison), or without gastrinoma (non-Zollinger–Ellison), and also in pernicious anaemia with achlorhydria-caused hypergastrinaemia. Methods We measured serum chromogranin, gastrin, gastric secretion and counted and quantified hyperplasia of Enterochromaffin-Like Cells in gastric biopsies from 38 Zollinger–Ellison and 13 non-Zollinger–Ellison patients being treated with lansoprazole, for 5 years (median) and again 2.5 years later. We also studied 12 patients with pernicious anaemia, half with gastric Enterochromaffin-Like Cell carcinoids. Results Serum chromogranin was elevated in patients with gastrinoma, even without any Enterochromaffin-Like Cell proliferation, but not in non-Zollinger–Ellison acid hypersecretors with normal gastrin (P
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Helicobacter pylori effects on gastritis, gastrin and Enterochromaffin‐Like Cells in Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome acid hypersecretors treated long‐term with lansoprazole
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: Basil I. Hirschowitz, M. M. HaberAbstract:Background: Helicobacter pylori is said to cause atrophy of the gastric corpus and Enterochromaffin-Like Cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. Aims: To determine the effect of H. pylori infection on gastritis, Enterochromaffin-Like Cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non-Zollinger–Ellison syndrome) before and during long-term treatment with lansoprazole. Methods: Lansoprazole was individually titrated to reduce basal acid output to
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helicobacter pylori effects on gastritis gastrin and Enterochromaffin Like Cells in zollinger ellison syndrome and non zollinger ellison syndrome acid hypersecretors treated long term with lansoprazole
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: Basil I. Hirschowitz, M. M. HaberAbstract:Background: Helicobacter pylori is said to cause atrophy of the gastric corpus and Enterochromaffin-Like Cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. Aims: To determine the effect of H. pylori infection on gastritis, Enterochromaffin-Like Cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non-Zollinger–Ellison syndrome) before and during long-term treatment with lansoprazole. Methods: Lansoprazole was individually titrated to reduce basal acid output to < 5 mmol/h (< 1 mmol/h in post-surgical Zollinger–Ellison syndrome). Gastric corpus biopsies were obtained every 6 months before treatment and up to 8 years later. Results: H. pylori was present in corpus biopsies in ≈ 50%, causing active gastritis which resolved rapidly in 15 subjects after elimination of H. pylori. Patchy mild/moderate corpus atrophy was present at entry in two and at the end in four out of 60 patients, one being H. pylori-positive. Intestinal metaplasia (< 10%) was seen in six isolated biopsies (1% of total). H. pylori did not affect serum gastrin, Enterochromaffin-Like Cell density or hyperplasia. Enterochromaffin-Like Cell density was twice as high in Zollinger–Ellison syndrome as in non-Zollinger–Ellison syndrome patients (241 vs. 126 Cells/mm2, P < 0.001). Enterochromaffin-Like Cells remained normal in the non-Zollinger–Ellison syndrome hypersecretors regardless of H. pylori status. Conclusion: Corpus Enterochromaffin-Like Cell increases were related to serum gastrin elevation, but neither H. pylori nor long-term treatment with lansoprazole alone or together had any effect on Enterochromaffin-Like Cell density or hyperplasia. Corpus acute gastritis resulted from H. pylori infection, but did not result in mucosal atrophy despite long-term proton pump inhibitor treatment and promptly resolved with loss of H. pylori.
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Helicobacter pylori effects on gastritis, gastrin and Enterochromaffin-Like Cells in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome acid hypersecretors treated long-term with lansoprazole.
Alimentary pharmacology & therapeutics, 2001Co-Authors: Basil I. Hirschowitz, M. M. HaberAbstract:Background: Helicobacter pylori is said to cause atrophy of the gastric corpus and Enterochromaffin-Like Cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. Aims: To determine the effect of H. pylori infection on gastritis, Enterochromaffin-Like Cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non-Zollinger–Ellison syndrome) before and during long-term treatment with lansoprazole. Methods: Lansoprazole was individually titrated to reduce basal acid output to
Basil I. Hirschowitz - One of the best experts on this subject based on the ideXlab platform.
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Chromogranin A in patients with acid hypersecretion and/or hypergastrinaemia.
Alimentary pharmacology & therapeutics, 2007Co-Authors: Basil I. Hirschowitz, Julie Worthington, Jean Mohnen, M. M. HaberAbstract:Summary Background Chromogranin has been proposed as a marker for gastrin-dependent Enterochromaffin-Like Cell proliferation. Aim To examine this question in three populations: acid hypersecretors with gastrinoma (Zollinger–Ellison), or without gastrinoma (non-Zollinger–Ellison), and also in pernicious anaemia with achlorhydria-caused hypergastrinaemia. Methods We measured serum chromogranin, gastrin, gastric secretion and counted and quantified hyperplasia of Enterochromaffin-Like Cells in gastric biopsies from 38 Zollinger–Ellison and 13 non-Zollinger–Ellison patients being treated with lansoprazole, for 5 years (median) and again 2.5 years later. We also studied 12 patients with pernicious anaemia, half with gastric Enterochromaffin-Like Cell carcinoids. Results Serum chromogranin was elevated in patients with gastrinoma, even without any Enterochromaffin-Like Cell proliferation, but not in non-Zollinger–Ellison acid hypersecretors with normal gastrin (P
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Helicobacter pylori effects on gastritis, gastrin and Enterochromaffin‐Like Cells in Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome acid hypersecretors treated long‐term with lansoprazole
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: Basil I. Hirschowitz, M. M. HaberAbstract:Background: Helicobacter pylori is said to cause atrophy of the gastric corpus and Enterochromaffin-Like Cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. Aims: To determine the effect of H. pylori infection on gastritis, Enterochromaffin-Like Cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non-Zollinger–Ellison syndrome) before and during long-term treatment with lansoprazole. Methods: Lansoprazole was individually titrated to reduce basal acid output to
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helicobacter pylori effects on gastritis gastrin and Enterochromaffin Like Cells in zollinger ellison syndrome and non zollinger ellison syndrome acid hypersecretors treated long term with lansoprazole
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: Basil I. Hirschowitz, M. M. HaberAbstract:Background: Helicobacter pylori is said to cause atrophy of the gastric corpus and Enterochromaffin-Like Cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. Aims: To determine the effect of H. pylori infection on gastritis, Enterochromaffin-Like Cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non-Zollinger–Ellison syndrome) before and during long-term treatment with lansoprazole. Methods: Lansoprazole was individually titrated to reduce basal acid output to < 5 mmol/h (< 1 mmol/h in post-surgical Zollinger–Ellison syndrome). Gastric corpus biopsies were obtained every 6 months before treatment and up to 8 years later. Results: H. pylori was present in corpus biopsies in ≈ 50%, causing active gastritis which resolved rapidly in 15 subjects after elimination of H. pylori. Patchy mild/moderate corpus atrophy was present at entry in two and at the end in four out of 60 patients, one being H. pylori-positive. Intestinal metaplasia (< 10%) was seen in six isolated biopsies (1% of total). H. pylori did not affect serum gastrin, Enterochromaffin-Like Cell density or hyperplasia. Enterochromaffin-Like Cell density was twice as high in Zollinger–Ellison syndrome as in non-Zollinger–Ellison syndrome patients (241 vs. 126 Cells/mm2, P < 0.001). Enterochromaffin-Like Cells remained normal in the non-Zollinger–Ellison syndrome hypersecretors regardless of H. pylori status. Conclusion: Corpus Enterochromaffin-Like Cell increases were related to serum gastrin elevation, but neither H. pylori nor long-term treatment with lansoprazole alone or together had any effect on Enterochromaffin-Like Cell density or hyperplasia. Corpus acute gastritis resulted from H. pylori infection, but did not result in mucosal atrophy despite long-term proton pump inhibitor treatment and promptly resolved with loss of H. pylori.
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Helicobacter pylori effects on gastritis, gastrin and Enterochromaffin-Like Cells in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome acid hypersecretors treated long-term with lansoprazole.
Alimentary pharmacology & therapeutics, 2001Co-Authors: Basil I. Hirschowitz, M. M. HaberAbstract:Background: Helicobacter pylori is said to cause atrophy of the gastric corpus and Enterochromaffin-Like Cell proliferation in gastro-oesophageal reflux disease (GERD) patients treated long-term with a proton pump inhibitor. Aims: To determine the effect of H. pylori infection on gastritis, Enterochromaffin-Like Cell density and hyperplasia, mucosal atrophy and serum gastrin in patients with gastric hypersecretion (basal acid output gt; 15 mmol/h) with either hypergastrinemia (Zollinger–Ellison syndrome) or normal gastrin (non-Zollinger–Ellison syndrome) before and during long-term treatment with lansoprazole. Methods: Lansoprazole was individually titrated to reduce basal acid output to
Helge L. Waldum - One of the best experts on this subject based on the ideXlab platform.
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The gastrin receptor antagonist netazepide (YF476) in patients with type 1 gastric Enterochromaffin-Like Cell neuroendocrine tumours: review of long-term treatment.
European journal of gastroenterology & hepatology, 2016Co-Authors: Liv Sagatun, Helge L. Waldum, Patricia Mjønes, Constantin S. Jianu, Malcolm Boyce, Reidar FossmarkAbstract:ObjectiveNetazepide (YF476) is a recently developed, orally active gastrin receptor antagonist that, in short trials in patients with type 1 gastric Enterochromaffin-Like Cell neuroendocrine tumours, has been shown to induce a significant reduction in the number and size of tumours as well as serum
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Ultrastructure and chromogranin A immunogold labelling of ECL Cell carcinoids.
APMIS : acta pathologica microbiologica et immunologica Scandinavica, 2005Co-Authors: Reidar Fossmark, Tom C. Martinsen, Gunnar Qvigstad, Marianne Ø. Bendheim, Gunnar Kopstad, Kenji Kashima, Helge L. WaldumAbstract:Poorly differentiated neuroendocrine Cells can be difficult to recognise. Sensitive methods are needed to label Cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, Enterochromaffin-Like Cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such Cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine Cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human Enterochromaffin-Like Cell carcinoids. Electron-dense granules of poorly differentiated Cells were less intensely labelled than granules in well-differentiated Cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 degrees C compared to a microwave at 100 degrees C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of Cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.
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spontaneous Enterochromaffin Like Cell carcinomas in cotton rats sigmodon hispidus are prevented by a somatostatin analogue
Endocrine-related Cancer, 2004Co-Authors: Reidar Fossmark, Shiro Kawase, Sverre H. Torp, Arne K. Sandvik, T. C. Martinsen, Helge L. WaldumAbstract:Among inbred female cotton rats (Sigmodon hispidus) 25–50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from Enterochromaffin-Like (ECL) Cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an exCellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer ðP < 0:05Þ; whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive Cells and Cells positive for Sevier–Munger staining. The malignant tissue also contained groups of Cells with Sevier–Munger staining. In conclusion, octreotide prevented ECL Cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.
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Hypergastrinaemia induced by partial corpectomy results in development of Enterochromaffin‐Like Cell carcinoma in male Japanese cotton rats
Scandinavian Journal of Gastroenterology, 2004Co-Authors: Reidar Fossmark, Shiro Kawase, Sverre H. Torp, T. C. Martinsen, Karin E. Bakkelund, Helge L. WaldumAbstract:Background: Among inbred female cotton rats (Sigmodon hispidus) 25%–50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are Enterochromaffin‐Like (ECL)‐Cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. Methods: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%–90% of the corpus. A control group was sham‐operated. Results: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized ani...
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Long-term safety of proton pump inhibitors: risks of gastric neoplasia and infections.
Expert Opinion on Drug Safety, 2002Co-Authors: Helge L. Waldum, Eiliv Brenna, Arne K. SandvikAbstract:After Helicobacter pylori eradication was introduced and largely eliminated the need for maintenance therapy for peptic ulcer disease, gastroesophageal reflux disease (GERD) became the main indication for prolonged gastric acid inhibition. The drug effect on GERD depends on the degree of acid inhibition, thus the efficacious proton pump inhibitors are preferred. The proton pump inhibitors have few immediate side effects, the main concern being the profound hypoacidity and hypergastrinaemia they induce. In short-term, hypergastrinaemia causes rebound hyperacidity, possibly worsening GERD and reducing the efficacy of histamine H2 blockers. In the long-term, hypergastrinaemia causes Enterochromaffin-Like Cell hyperplasia and carcinoids. Since Enterochromaffin-Like Cells may be important in gastric carcinogenesis, iatrogenic hypergastrinaemia may predispose to carcinoma. Gastric hypoacidity also increases gut bacterial infections, and the barrier function of acid against viral and prion infections requires fu...
H L Waldum - One of the best experts on this subject based on the ideXlab platform.
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five year follow up of patients treated for 1 year with octreotide long acting release for Enterochromaffin Like Cell carcinoids
Scandinavian Journal of Gastroenterology, 2011Co-Authors: Constantin S. Jianu, Reidar Fossmark, Unni Syversen, Vidar Fykse, Oyvind Hauso, H L WaldumAbstract:Abstract Background. Gastric carcinoids type 1 (GC1) are neuroendocrine tumors (NETs) arising from the Enterochromaffin-Like (ECL) Cells in patients with chronic atrophic gastritis (CAG). The treatment of GC1 has been endoscopic polypectomy or surgical tumor excision and antrectomy. One year treatment with somatostatin analogs (SSAs) diminished tumor load and ECL Cell density. The effect persisted 1 year after treatment was discontinued. However, the optimal SSA dose and treatment duration are unknown. Objectives. The aim of the present work was to study macroscopic and histopathological changes in the stomach and serum markers gastrin and chromogranin A (CgA) in GC1 patients 5 years after 1 year of octreotide long-acting release (LAR) treatment. Material and methods. Five patients with GC1 were included 5 years after the initial year of octreotide LAR treatment. All patients underwent upper gastrointestinal endoscopy including tumor and mucosal biopsies from oxyntic mucosa, chest and abdominal computer t...
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physiological and clinical significance of Enterochromaffin Like Cell activation in the regulation of gastric acid secretion
World Journal of Gastroenterology, 2007Co-Authors: Guanglin Cui, H L WaldumAbstract:Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal Cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G Cell is the principal physiological stimulus of gastric acid secretion. Activation of the Enterochromaffin-Like (ECL) Cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL Cell. However, long-term hypergastrinemia will induce ECL Cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels, leading to enlargement of oxyntic mucosa with ECL Cell hyperplasia. Accordingly, the induction of ECL Cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL Cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL Cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion.
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one year follow up study of patients with Enterochromaffin Like Cell carcinoids after treatment with octreotide long acting release
Scandinavian Journal of Gastroenterology, 2005Co-Authors: Vidar Fykse, Arne K. Sandvik, H L WaldumAbstract:Objective. In a one-year study of 5 patients with chronic atrophic gastritis (CAG), pernicious anaemia (PA), hypergastrinaemia and Enterochromaffin-Like (ECL) Cell tumours, the somatostatin analogue octreotide LAR (long-acting release) in a dose of 20 mg given intramuscularly at monthly intervals had an antiproliferative effect on the ECL Cells. The aim of the present study was to follow neuroendocrine (NE) markers in the blood and macroscopic and histopathological changes in the stomach during a 12-month follow-up after discontinuation of octreotide LAR treatment. Material and methods. Five patients underwent upper gastrointestinal endoscopy at 6 and 12 months’ follow-up after octreotide LAR treatment. Biopsies from flat, oxyntic mucosa and from tumours were obtained. Sections were stained with haematoxylin-erythrosin and immunostained for the NE Cell marker chromogranin A (CgA). Serum gastrin and CgA were measured every 3 months. Results. The number of visible tumours was unchanged (7) at 12 months’ fol...
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hypergastrinaemia induced by partial corpectomy results in development of Enterochromaffin Like Cell carcinoma in male japanese cotton rats
Scandinavian Journal of Gastroenterology, 2004Co-Authors: Reidar Fossmark, Shiro Kawase, Sverre H. Torp, T. C. Martinsen, Karin E. Bakkelund, H L WaldumAbstract:Background: Among inbred female cotton rats (Sigmodon hispidus) 25%–50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are Enterochromaffin‐Like (ECL)‐Cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. Methods: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%–90% of the corpus. A control group was sham‐operated. Results: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized ani...
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octreotide inhibits the Enterochromaffin Like Cell but not peroxisome proliferator induced hypergastrinemia
Journal of Molecular Endocrinology, 2000Co-Authors: Ingunn Bakke, Arne K. Sandvik, H L WaldumAbstract:The peroxisome proliferator ciprofibrate induces hypergastrinemia and as a consequence, Enterochromaffin-Like (ECL) Cell hyperplasia. The mechanism for the gastrin Cell stimulation is unknown. The somatostatin analog octreotide LAR (long-acting release) was used to see if the stimulating effects of ciprofibrate could be attenuated. Female Fischer rats were dosed with ciprofibrate (50 mg/kg body weight per day) alone or combined with octreotide LAR (10 mg/30 days) for 60 days. Plasma gastrin and histamine, gastric endocrine Cell densities and mRNA abundances were measured. Ciprofibrate increased gastrin mRNA abundance (P<0.05), gastrin Cell number (P<0. 001) and Cell area (P<0.01), and induced hypergastrinemia (P<0.001). These rats had profound ECL Cell hyperplasia, confirmed by an increase in chromogranin A (CgA) and histidine decarboxylase (HDC) mRNA, density of neuroendocrine and ECL Cells and plasma histamine levels (all P<0.001). Octreotide LAR did not affect ciprofibrate stimulation of gastrin Cells, but all parameters of ECL Cell hyperplasia were reduced (P<0.001). Octreotide LAR also significantly inhibited basal ECL Cell function and growth. Ciprofibrate stimulates gastrin Cell activity by a mechanism unaffected by octreotide, but octreotide does inhibit basal and gastrin-stimulated ECL Cell function and growth.
Reidar Fossmark - One of the best experts on this subject based on the ideXlab platform.
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The gastrin receptor antagonist netazepide (YF476) in patients with type 1 gastric Enterochromaffin-Like Cell neuroendocrine tumours: review of long-term treatment.
European journal of gastroenterology & hepatology, 2016Co-Authors: Liv Sagatun, Helge L. Waldum, Patricia Mjønes, Constantin S. Jianu, Malcolm Boyce, Reidar FossmarkAbstract:ObjectiveNetazepide (YF476) is a recently developed, orally active gastrin receptor antagonist that, in short trials in patients with type 1 gastric Enterochromaffin-Like Cell neuroendocrine tumours, has been shown to induce a significant reduction in the number and size of tumours as well as serum
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five year follow up of patients treated for 1 year with octreotide long acting release for Enterochromaffin Like Cell carcinoids
Scandinavian Journal of Gastroenterology, 2011Co-Authors: Constantin S. Jianu, Reidar Fossmark, Unni Syversen, Vidar Fykse, Oyvind Hauso, H L WaldumAbstract:Abstract Background. Gastric carcinoids type 1 (GC1) are neuroendocrine tumors (NETs) arising from the Enterochromaffin-Like (ECL) Cells in patients with chronic atrophic gastritis (CAG). The treatment of GC1 has been endoscopic polypectomy or surgical tumor excision and antrectomy. One year treatment with somatostatin analogs (SSAs) diminished tumor load and ECL Cell density. The effect persisted 1 year after treatment was discontinued. However, the optimal SSA dose and treatment duration are unknown. Objectives. The aim of the present work was to study macroscopic and histopathological changes in the stomach and serum markers gastrin and chromogranin A (CgA) in GC1 patients 5 years after 1 year of octreotide long-acting release (LAR) treatment. Material and methods. Five patients with GC1 were included 5 years after the initial year of octreotide LAR treatment. All patients underwent upper gastrointestinal endoscopy including tumor and mucosal biopsies from oxyntic mucosa, chest and abdominal computer t...
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Ultrastructure and chromogranin A immunogold labelling of ECL Cell carcinoids.
APMIS : acta pathologica microbiologica et immunologica Scandinavica, 2005Co-Authors: Reidar Fossmark, Tom C. Martinsen, Gunnar Qvigstad, Marianne Ø. Bendheim, Gunnar Kopstad, Kenji Kashima, Helge L. WaldumAbstract:Poorly differentiated neuroendocrine Cells can be difficult to recognise. Sensitive methods are needed to label Cells that have lost their ultrastructural features and have reduced concentrations of neuroendocrine markers. In gastric neoplasms, Enterochromaffin-Like Cells might dedifferentiate and lose their characteristic granules and secretory vesicles, making detection of such Cells increasingly difficult. However, chromogranin A (CgA) immunogold labelling could provide sensitive and specific detection of gastric neuroendocrine Cells. We present ultrastructural findings, CgA immunogold labelling as well as conventional immunohistochemical findings of two human Enterochromaffin-Like Cell carcinoids. Electron-dense granules of poorly differentiated Cells were less intensely labelled than granules in well-differentiated Cells. Granules with atypical shape as well as punctuate granules previously found in neuroendocrine neoplasms were also CgA labelled. The CgA labelling efficacy after antigen retrieval in an alkaline solution was higher after heating in an autoclave at 135 degrees C compared to a microwave at 100 degrees C for both granules and secretory vesicles without significant deterioration of the ultrastructure. In conclusion, the use of CgA immunogold labelling could ensure a specific classification of Cells with neuroendocrine granules and be a supplement to immunohistochemical examination of poorly differentiated tumours.
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spontaneous Enterochromaffin Like Cell carcinomas in cotton rats sigmodon hispidus are prevented by a somatostatin analogue
Endocrine-related Cancer, 2004Co-Authors: Reidar Fossmark, Shiro Kawase, Sverre H. Torp, Arne K. Sandvik, T. C. Martinsen, Helge L. WaldumAbstract:Among inbred female cotton rats (Sigmodon hispidus) 25–50% of the animals develop spontaneous gastric carcinomas; the corresponding figure for male cotton rats is approximately 1%. Animals with carcinomas have hypergastrinaemia and gastric hypo-anacidity and the tumours are derived from Enterochromaffin-Like (ECL) Cells. The mechanism behind the hypo-anacidity is unknown. Carcinomas are found in all female cotton rats with hypergastrinaemia lasting more than 4 months and this represents an exCellent animal model for studying gastric carcinogenesis. In this study, the somatostatin analogue octreotide was given to female cotton rats to prevent carcinoma development caused by hypergastrinaemia. Twelve female cotton rats were given monthly injections of long-acting octreotide (5 mg i.m.) for 6 months. A control group of 20 animals was not given injections. Of the 20 control animals, 13 developed hypergastrinaemia and histologically invasive carcinomas or dysplasia. Of the 12 animals in the octreotide group, five developed hypergastrinaemia. None of these five animals developed histological cancer ðP < 0:05Þ; whereas three had dysplasia. However, octreotide did not affect plasma gastrin concentration or antral gastrin mRNA abundance significantly. Dysplasia of the oxyntic mucosa in hypergastrinaemic animals was accompanied by a marked increase in chromogranin A-immunoreactive Cells and Cells positive for Sevier–Munger staining. The malignant tissue also contained groups of Cells with Sevier–Munger staining. In conclusion, octreotide prevented ECL Cell carcinomas in hypergastrinaemic cotton rats without lowering the gastrin concentration.
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Hypergastrinaemia induced by partial corpectomy results in development of Enterochromaffin‐Like Cell carcinoma in male Japanese cotton rats
Scandinavian Journal of Gastroenterology, 2004Co-Authors: Reidar Fossmark, Shiro Kawase, Sverre H. Torp, T. C. Martinsen, Karin E. Bakkelund, Helge L. WaldumAbstract:Background: Among inbred female cotton rats (Sigmodon hispidus) 25%–50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are Enterochromaffin‐Like (ECL)‐Cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. Methods: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%–90% of the corpus. A control group was sham‐operated. Results: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized ani...