Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A critical evaluation has been made of the available evidence in man of the effects of prolonged low acid states on the structure and function of the stomach. Various human models have been examined. 1. Ageing does not affect acid output from the normal male stomach, and there may be an increase in women. With progressive atrophy of the corpus mucosa, which is more frequent and rapid in patients with gastric ulcer, there is an associated loss of secretory function. Chronic gastritis and atrophy are the most important age-related changes, which in many cultures are hypothesized to develop via a prior Helicobacter pylori-related gastritis. However, H. pylori colonization of the mucosa decreases with increasing grades of gastric atrophy probably because intestinal metaplasia provides a hostile environment. Atrophy and intestinal metaplasia are associated with precancerous lesions and gastric cancer. Apparent hyperplasia of the gastric argyrophil endocrine cells is a common and spontaneous phenomenon in patients with atrophic gastritis, which in part may be related to the preferential loss of nonendocrine cells. 2. Pernicious anemia is associated with a complete lack of acid production, marked hypergastrinemia, and endocrine cell hyperplasia in the majority of patients. ECL-cell carcinoids and gastric cancer occur with a prevalence of 3-7%, and endoscopic surveillance in routine clinical practice is not warranted. 3. Gastric ECL-cell carcinoids are rare events that have been described in association with two diseases in man, pernicious anemia and Zollinger-Ellison syndrome as part of multiple endocrine neoplasia syndrome type I, and usually relate to marked hypergastrinemia and the presence of chronic atrophic gastritis with gastric antibodies or a genetic defect rather than the presence or absence of acid. Regression or disappearance of ECL-cell carcinoids, either spontaneously or after removal of the gastrin drive, has been recorded. Lymph node, and rarely hepatic, metastases are documented but death in these cases has been anecdotal. 4. Therapy with H2 antagonists may result in up to a twofold rise in serum gastrin levels but in man no endocrine cell hyperplasia has been recorded. However, the data for H2 antagonists on these aspects are very limited. There is no drug-related risk of gastric or esophageal cancer, although the incidence of the latter may be raised. Long-term treatment with omeprazole is associated with a two- to fourfold increase in gastrin levels over baseline values in one third of patients and apparent endocrine cell hyperplasia in 7% of cases overall.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathophysiological effects of long-term acid suppression in man. 785 87

The syndrome of multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant tumour disease of the neuroendocrine system with manifestations in the parathyroids, pancreas, duodenum and pituitary gland and rarely also in the stomach and thymus. Recently, the MEN 1 gene locus has been mapped to the long arm of chromosome 11. This gene most likely belongs to the tumour suppressor genes, the allelic loss of which causes tumour development. The pancreatic and duodenal tumours may metastasize, but usually have a low malignant potential. Clinically, most MEN 1 patients present between the age of 20 and 35 with hyperparathyroidism and/or Zollinger-Ellison syndrome.
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PMID:[Multiple endocrine neoplasia type 1 (MEN 1). Molecular genetics, morphology and prognosis]. 791 16

Studies have shown that the duodenum is a more common site (30-40%) of primary gastrinomas than previously reported. These tumors are often occult to conventional exploration, and their detection requires duodenotomy and meticulous evaluation of the mucosa by eversion and direct palpation. Furthermore, tumors as small as 1 to 2 mm may be associated with lymph node metastases. Seven patients with duodenal gastrinomas treated during a 2-year period are reported. Four had sporadic Zollinger-Ellison syndrome (ZES), and three had multiple endocrine neoplasia type I (MEN-I) syndrome. All seven patients had malignant duodenal gastrinomas as proved by metastatic lymph nodes and in one case a large liver metastasis as well. Local excision of the tumor, lymph node excisions, and in one case liver lobectomy resulted in eugastrinemia in the 4 with sporadic ZES. Two of the three with MEN-I were also eugastrinemic after similar procedures, with the addition of distal pancreatectomy. Duodenotomy is considered an essential procedure in sporadic ZES patients when no pancreatic tumor is found and in all MEN-I/ZES patients, regardless of the pancreatic findings. Regional lymph node excisions are essential when a duodenal tumor has been found.
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PMID:Duodenal gastrinomas, duodenotomy, and duodenal exploration in the surgical management of Zollinger-Ellison syndrome. 810 49

During the three decades since the recognition of the Zollinger-Ellison syndrome (ZES), major progress has been made in the diagnosis and treatment of this disease. However, the many failed operations in patients with ZES, the existence of primary lymph node gastrinomas, and the surgical approach of patients with ZES and multiple endocrine neoplasia type I (MEN-I) have remained controversial issues. In this review, our experience with the pathology of immunocytochemically identified gastrinomas in 44 patients with ZES is presented and related to the relevant literature. (1) Gastrinomas occur frequently in the duodenum (> 40%) and are commonly small (< 1 cm). They can therefore easily be missed at surgical exploration; lymph node metastases from such occult gastrinomas may be mistaken for primary tumors. (2) Most pancreatic gastrinomas reside in the head of the gland and have a diameter of 1 to 3 cm. (3) Gastrinomas associated with MEN-I are predominantly of duodenal origin and frequently multicentric; sporadic gastrinomas are single and more often pancreatic. Because MEN-I associated pancreatic tumors seldom contain gastrin, ZES in MEN-I patients is almost never cured by resection of the pancreatic tumors. (4) The metastatic potential of most small duodenal gastrinomas seems to be restricted to the regional lymph nodes.
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PMID:Pathologic aspects of gastrinomas in patients with Zollinger-Ellison syndrome with and without multiple endocrine neoplasia type I. 810 50

Among endocrine tumors occurring in the gastrointestinal tract, midgut argentaffin EC cell carcinoids, gastric argyrophil ECL cell carcinoids, duodenal gastrin cell tumors, and rectal trabecular L cell carcinoids (in order of decreasing frequency) are those occurring more frequently. Together, they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas, and differentiated neuroendocrine carcinomas are also well-defined tumor entities. The carcinoid syndrome, either classical, with intermittent flushing, hypotension, and diarrhea, or atypical, with persistent histamine-type red flushing, bronchospasm, and no diarrhea, and Zollinger-Ellison syndrome, with severe peptide ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome occurs in about 10% of gastrointestinal carcinoids, usually in their advanced, metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of intestinal gastrin cell tumors, including small intramural growths. Tumor prognosis depends on the mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases), and associated clinical syndrome or background disease. Hormones, trophic factors, inherited genetic traits, somatic mutations, and some chronic inflammatory processes are pathogenetically important in a large proportion of cases.
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PMID:The pathology of the gastrointestinal endocrine system. 812 73

Somatostatin receptor scintigraphy (SRS) was performed in 14 patients (five men, nine women; mean age 51.5 [20-71] years) with Zollinger-Ellison syndrome (ZES), a gastrinoma proven in 7 and suspected on clinical or biochemical grounds in 7. The results were compared with those obtained by other methods (ultrasound, computed tomography, angiography). All 12 known tumour manifestations were demonstrated by SRS in seven patients with histologically confirmed gastrinoma. In four patients previously non-localized tumour was revealed by SRS, while in seven other patients the procedure led to modification of the treatment (primary tumour resection: n = 3, resection of metastases: n = 2, percutaneous radiation or chemoembolization: one each). These results suggest the following indications for SRS: (1) staging or re-staging in histologically proven gastrinoma and (2) search for primary tumour in clinically and biochemically suspected ZES.
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PMID:[Somatostatin receptor scintigraphy in the primary diagnosis and follow-up care of gastrinoma]. 813 15

It has been said that with the description of the Zollinger-Ellison syndrome in 1955, the clinical era of gastrointestinal endocrinology was inaugurated. Since that time, a virtual explosion of investigations, both basic and clinical, has occurred in which as many as 19 gastroenteropancreatic neuroendocrine cells have been identified and as many as 40 of their humoral products have been discovered. The pharmacologic and physiologic functions of some of these amines and peptides have been clearly identified and account for the clinical presentations of the various clinical syndromes so far described. However, the physiologic functions of many others remain to be elucidated. The interest in gastroenteropancreatic neuroendocrine tumors arising from these cells has markedly increased in recent years as a result of the creation of precise biochemical techniques to confirm the diagnosis and the refinement of localization techniques that allow for the identification of previously occult tumors. Therefore, the recognition and treatment of gastroenteropancreatic neuroendocrine tumors has improved so that an ever-increasing number of patients are diagnosed early and surgically treated before metastases occur. There are still more identified gastroenteropancreatic neuroendocrine cells and humoral products than there are recognized neoplasms and syndromes; continued investigation is essential. Undoubtedly, newer treatment modalities will continue to be created for chemotherapy and receptor modulation, but early surgical excision remains the cornerstone of successful treatment today.
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PMID:Gastrointestinal neuroendocrine tumors. 817 36

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.
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PMID:Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma. 826 71

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80,000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2,700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1,994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity (r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.
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PMID:Chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. 832 58

The surgical management of pancreatic islet cell carcinomas poses a complicated set of questions resulting from their rare occurrence and the difficulty in establishing a diagnosis in early cases or, conversely, the problems inherent in dealing with metastatic disease. However, because their biologic behavior is rather indolent, a real opportunity exists not only for cure but also for meaningful palliation. These goals apply both to the tumor itself and the effects of the hormones they may secrete. The challenge facing the multidisciplinary management team in general, and the surgeon specifically, is to achieve the optimal combination of surgical resection and other treatment options. While the precept of aggressive excision applies to most islet cell carcinomas, it is not universally applicable. In contrast to other islet cell tumors, insulinomas are overwhelmingly benign, and are well treated by enucleation or limited pancreatic resection. Although based on relatively few cases, cytoreductive surgery seems beneficial for malignant insulinomas. Advances that have occurred over the past decade in Zollinger-Ellison syndrome have markedly altered surgical management. Medication which reliably prevents ulcer formation has permitted the surgical perspective to be redirected from end organ ablation to curative tumor excision. Multicentricity and metastases, however, limit the extent to which cure can actually be achieved. Patients with vasoactive intestinal peptide-producing tumors and glucagonomas are very rare, and when possible, should undergo tumor resection to correct the severe hormonally caused metabolic derangements. Increasingly recognized are islet cell carcinomas that do not produce clinical syndromes. They may be confused with ductal carcinomas, but when resected, lead to distinctly superior survival rates among patients.
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PMID:Surgical management of malignant islet cell tumors. 839 50


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