Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-acting somatostatin analogs, such as octreotide, comprise the therapeutic modality of choice for the symptomatic relief of flush and diarrhea in patients with carcinoid syndrome. The sequelae of gastric acid hypersecretion in patients with gastrin-producing duodenal carcinoids (gastrinoma) are perfectly controlled by proton pump inhibitors. Antiproliferative medical strategies to control the growth of metastatic carcinoid tumors include long-acting somatostatin analogs, interferon alpha, and the combination of the two. However, the success rate is less than 50%, and it is questionable whether true tumor regression can be expected. Controlled prospective studies are mandatory to address the question whether interferon or somatostatin analogs or the combination of the two should be used as first-line medical strategies and if hepatic artery embolization in patients with liver metastases should be performed before beginning medical therapy. Chemotherapy, including etoposide and cisplatin, has been shown to be effective only for purely differentiated neuroendocrine carcinomas and not for slowly growing carcinoids.
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PMID:Medical treatment of metastasizing carcinoid tumors. 866 18

Gastric carcinoids are the sequel of enterochromaffin-like (ECL) cell hyperplasia, and are usually associated with a low-acid state and hypergastrinaemia. The somatostatin (SRIF) analogue octreotide has been noted to decrease both plasma gastrin levels and ECL cell hyperplasia/neoplasia in human and rodent experimental models. The African rodent, mastomys, exhibits a genetic propensity to gastric carcinoid formation which can be significantly accelerated by acid-inhibition-induced hypergastrinaemia. Thus a low-acid state induced by either irreversible H2 blockade or proton pump inhibition shortens the natural 2-year induction time to 4 months. In vivo studies of this model demonstrate that, similar to the human situation, octreotide decreases plasma gastrin levels and inhibits low-acid-induced gastric carcinoid formation. In vitro, using isolated ECL cells, SRIF inhibits both gastrin-stimulated ECL cell histamine secretion and DNA synthesis. This mechanism appears to function via the SRIF receptor (SSTR) subtype 2, which we have identified in both naive and transformed ECL cells. Thus the direct effect of SRIF regulation of ECL cell function is mediated by at least a SSTR2 subtype. It is possible that the alteration of the SSTR2 during ECL cell transformation may contribute to the genetic susceptibility of the mastomys to carcinoid tumour formation. The precise anti-proliferative mechanism of SRIF and its role in neuroendocrine cell transformation remain to be defined. Pharmacological manipulation of the SSTR2 may provide a viable therapeutic and diagnostic target in the management not only of ECL cell neoplasia but also other types of neuroendocrine cell tumour.
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PMID:Somatostatin receptor regulation of gastric carcinoid tumours. 881 59

Rabeprazole, a new benzimidazole proton pump inhibitor (PPI), is among a class of agents known to be very potent inhibitors of gastric acid secretion. PPIs inhibit hydrogen-potassium adenosine triphosphatase activity on the luminal surface of the parietal cell, effectively blocking the final common pathway for gastric acid secretion. Raising gastric pH stimulates the production of gastrin by G cells in the antrum of the stomach, which can lead to enterochromaffin-like (ECL)-cell hyperplasia. In the past, these changes have been viewed with concern, particularly in the light of studies in rats indicating that hypergastrinaemia and ECL-cell hyperplasia induce gastric carcinoid tumour formation. All available clinical data indicate that long-term PPI use does not lead to carcinoid tumour formation in humans. In fact, both serum gastrin elevation and ECL-cell hyperplasia are now generally viewed as normal physiological responses to gastric acid suppression. Serum gastrin concentrations, in particular, correlate well with gastric acid suppression, which has led to the use of gastrin response by some investigators as a surrogate marker of antisecretory effectiveness. Long-term tolerability data indicate that PPIs have a favourable side-effect profile. Data obtained from patients receiving acute or long-term maintenance rabeprazole therapy support this conclusion. Furthermore, neither animal nor human data obtained with rabeprazole suggest a significant risk for neoplastic changes secondary to hypergastrinaemia.
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PMID:Review article: current perspectives on hypergastrinaemia and enterochromaffin-like-cell hyperplasia. 1055 3

This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long-term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may lead to enterochromaffin-like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long-term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long-term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger-Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high-dose proton pump inhibitors for many years. Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow-up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression.
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PMID:Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. 1142 86

Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.
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PMID:Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. 1643 85

Type 1 diabetes is usually associated with other autoimmune diseases. Parietal cell antibodies (PCA) are found in 20% of type 1 diabetic patients which might be an early sign of autoimmune gastritis and pernicious anemia. PCA destroy the gastric H+/K+ ATP-ase. The chronic auto-destruction of the proton pump leads to hypo/achlorhydria and hypergastrinemia which leads to the hyper/dysplasia of enterochromaffin-like cells (ECL). ECL hyper/dysplasia is known to increase the likelihood of gastric carcinoid tumor development in affected patients. Gastric carcinoid tumors forming from the hyperplasia of ECL cells are found in 4-9% of patients having autoimmune gastritis or pernicious anemia. The 29-years-old type 1 diabetic patient, having primer hyperthyroidism was admitted to our clinic because of gastric pain. Results of endoscopy and biopsy showed multiple small polyps in the fundus with non-antral hypergastrinemic (type A) atrophic gastritis. The parietal cell antibody test was positive, the serum chromogranin A level was 289,7 ng/ml (normal value $ 98 ng/ml), TSH level was 9,93 mIU/L. The histological examination indicated carcinoid tumor. Sandostatin therapy was started then partial gastrectomy was done. After the operation the plasma chromogranin level normalized. Non-antral, multiple polyps could cover silent neuroendocrine tumors, which are slowly growing benign endocrine tumors, however, they also might be high malignity endocrine carcinomas. These tumors could be easily recognized in the clinical practice by measuring the serum or tissue chromogranin A level and other markers of tumor growth. Thus screening of gastric endocrine tumors in type 1 diabetic patients with co-morbid autoimmune diseases is recommended.
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PMID:[Development of silent gastric carcinoid in a type 1 diabetic patient with primer hypothyreosis]. 1772 Jun 74

Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H(2)-receptor (H(2)R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies.
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PMID:Gastric epithelial cell modality and proton pump inhibitor. 1854 40

Proton pump inhibitors (PPIs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders including gastroesophageal reflux disease and peptic ulcer disease. Alltough these medications are generally accepted as safe, the long-term clinical consequences of the inducing hypochlorhydria are not completely clear. Gastric acid production is mainly controlled by the hormone gastrin through a negative feedback in which hypochlorhydria induces an increase in serum gastrin. PPIs have been shown to increase serum gastrin levels. Gastric endocrine cell hyperplasia can occur in 10 to 30% of patients without carcinoid tumors. Recent studies indicate no association between PPI use and the risk of colorectal and gastric cancers. Proton pump inhibitor-associated gastric polyps are totally benign tumors that should not be followed. There is an association between PPIs-induced acid suppression and an increased risk of enteric infection. PPIs do not inhibit intestinal absorption of lipids, iron, phosphorus, magnesium or zinc from food but can affect vitamin B12 status in older patients. Despite the undoubted benefits of PPIs, the practitioner always needs to consider risks and benefits before initiating them.
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PMID:[Risk of long-term treatment with proton pump inhibitors]. 1892 30

Proton pump inhibitors profoundly affect the stomach and have been associated with carcinoid tumors in female rats. There is now sufficient experience with this class of drugs to allow reasonable estimation of their safety in terms of cancer development in humans. Long-term use of proton pump inhibitors is associated with an increase in gastric inflammation and development of atrophy among those with active Helicobacter pylori infections. The actual risk is unknown but is clearly low. However, it can be markedly reduced or eliminated by H. pylori eradication. It is thus recommended that patients being considered for long-term proton pump inhibitor therapy should be tested for H. pylori infection and, if present, this pathogen should be eradicated. Oxyntic cell hyperplasia, glandular dilatations, and fundic gland polyps may develop in patients not infected with H. pylori, but these changes are believed to be reversible and without significant cancer risk.
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PMID:Long-term proton pump inhibitor use and gastrointestinal cancer. 1900 8

Many diseases of the upper gastrointestinal tract developed in patients with Helicobacter pylori (H. pylori) infection, thus the conditions unrelated to H. pylori are rare. Here, we described the therapeutic trends of diseases in H. pylori negative individuals. Proton pump inhibitor (PPI) is superior to H2 receptor antagonist in both gastroesohageal reflux disease (GERD) including reflux esophagitis and non-erosive reflux disease (NERD) whereas therapeutic gains of PPI treatment for NERD patients are lower than those reported in GERD because of heterogeneity of NERD pathophysiology. Endoscopic therapy for PPI refractory GERD patients remains to be established because there are few studies concerning the effectiveness or safety of the procedures. Main cause of H. pylori-negative ulcer diseases is the use of non-steroidal anti-inflammatory drugs (NSAIDs). PPI therapy is effective for both the prevention and treatment of NSAIDs-induced peptic ulcer. Considerations that should be entertained as causes of intractable peptic ulcers include Zollinger-Ellison syndrome or Crohn's disease. Gastric cancer and carcinoid tumor should be treated with endoscopic or surgical resection regardless of H. pylori infection. As for the treatment for gastric H. pylori-negative MALT lymphoma, radiation therapy (RT) should be selected first, and next chemotherapy will be given to the patients who failed to RT.
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PMID:[Therapeutic trends of diseases of the upper gastrointestinal tract in patients with negative H. pylori status]. 1999 28


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