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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The therapeutic principles in the management of endocrine gastroenteropancreatic (GEP) tumours include surgical extirpation of the primary tumour in the absence of metastases and medical control of symptoms in the preoperative phase. In the presence of metastases only palliative procedures are available. Tumour growth might be controlled by surgical procedures as debulking of tumour masses, medically by chemotherapy and more recently by new developments as a long-acting somatostatin analogue (SMS 201-995) and alpha-interferon. Their efficacy is currently evaluated in prospective studies. In contrast to inhibition of growth symptoms derived from excessive hormone production by GEP tumours can be well controlled. SMS 201-995 effectively prevents or at least improves flush and diarrhoea in the carcinoid syndrome, disabling diarrhoea in the Verner-Morrison syndrome and migratory erythema in the glucagonoma syndrome. SMS acts by inhibition of hormone release from the tumour and by a direct mechanism at the site of the target cell via SMS receptors present on tumour and target cells. For control of acid hypersecretion in gastrinoma patients omeprazole is superior to all former and present alternatives and replaced total gastrectomy completely. A similarly effective drug to prevent hypoglycaemia due to uncontrolled insulin release from insulinomas is not available since neither SMS nor diazoxide are effective in every insulinoma patient.
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PMID:Therapeutic strategies in the management of endocrine GEP tumours. 170 88

A 57 year old male presented with episodic behavioural abnormalities and loss of consciousness for 2 years. His fasting blood glucose was 20 mg/dl and corresponding insulin level 119 uU/ml. His EEG showed intermittent rhythmic delta activity. Abdominal CT scan revealed an enhancing mass in the tail of the pancreas and secondaries in the liver. After distal pancreatectomy, resection of the left lobe of the liver and chemotherapy, the hypoglycaemic spells subsided. Histopathology revealed an islet cell tumour with metastases in the liver. Episodic neurobehavioural dysfunction should alert towards the possibility of hypoglycaemia.
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PMID:Malignant insulinoma presenting with recurrent episodic loss of consciousness. 181 6

In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypoglycaemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (less than or equal to 2.3 mmol l-1) within 2-44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR-insulin) concentrations. IR-proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady-state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4-5.0 mmol l-1 was significantly (P less than or equal to 0.001) higher in insulinoma patients (2.5 +/- 0.6 mg kg-1 min-1) than in pancreas resected patients (0.6 +/- 0.2 mg kg-1 min-1), or in control subjects (0.5 +/- 0.1 mg kg-1 min-1). Due to a considerable degree of overlap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR-insulin values (r = 0.024, P = 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR-insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of 'amended' insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR-C-peptide plasma concentrations) by 52-88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de-differentiated tumours. In contrast to this significant (P = 0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal beta-granules, and does not distinguish adenomas from carcinomas.
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PMID:Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients. 196 48

Insulinomas in dogs have been described frequently. The clinical signs of this tumor result from neuroglycopenia and increased concentrations of plasma catecholamines. Laboratory confirmation of hypoglycemia in association with an inappropriately high serum insulin concentration helps establish a tentative diagnosis of insulinoma. Surgical exploration of the pancreas and histologic evaluation is required for definitive diagnosis of insulinoma. Whenever possible, surgical excision of the primary lesion and associated metastases should be performed. The distinction between benign and malignant insulinomas is based on the presence or absence of metastases and clinical course of disease. Histologically, it is difficult to determine the malignant potential of these tumors. Careful medical management is essential to the dog with signs referable to an insulinoma, whether the patient is awaiting surgery, is not a surgical candidate, or has a relapse of signs after surgical resection. This chapter will review the clinical and diagnostic features of insulinoma in dogs and address the problem of refractory hypoglycemia and its management.
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PMID:Management of insuloma patients with refractory hypoglycemia. 198 99

The pituitary regulates the body's endocrine system, including the thyroid gland, adrenal cortex, ovaries and testes, through the release of numerous hormones. Pituitary function, in turn, is regulated through complex feedback loops involving the hypothalamus and the target endocrine glands. Hypopituitarism may result from multiple causes, including primary and metastatic cancer, ischemic and granulomatous disease, infection, developmental abnormalities and trauma, which may affect the gland itself (primary hypopituitarism) or the hypothalamus (secondary hypopituitarism). Depending on the anatomic lesion, patients with hypopituitarism may present with signs or symptoms of multiple endocrine abnormalities, such as hypothyroidism, adrenal insufficiency, diabetes insipidus, hypoglycemia, sexual dysfunction and growth retardation. A thorough clinical history, detailed examination, laboratory evaluation of endocrine function and radiographic views of the pituitary and sella turcica can suggest the diagnosis and etiology. Treatment, usually lifelong, may include hormone replacement and medical or surgical correction of the underlying disease.
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PMID:Hypopituitarism. 204 46

Based on observations of five of own patients the author analyzes the causes of spontaneous hypoglycaemia in malignant tumours and assumes three mechanisms of development: 1. Metastatic affection of the liver reduces the reserves of homeostatically usable glycogen and can reduce also the amount of utilized insulin and glucagon, and this weakens the effectivity of contraregulating hormones. 2. In case of large mesenchymal tumours it is assumed that the cause of hypoglycaemia is the neoplastic formation of IGF II. For these hypoglycaemic states a low concentration of C-peptide, IRI (immunoreactive insulin), absence of response of growth hormone to hypoglycaemia, high IGF II in the tumour and plasma and high mRNA for IGF II in the tumour is typical. 3. In hypoglycaemic states with massive metastases in the liver, high IRI and C-peptide it is assumed the cause of hypoglycaemia is a metastatizing insular tumour or a nes.dioblastoma. In those instances concurrent peptic ulcers (gastrin production) are frequent.
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PMID:[Neuroglycopenic syndromes in malignant tumors]. 225 61

Serum glucose levels up to 700 mg/dl were achieved and maintained for 3 h in patients with advanced metastatic cancer by infusion of concentrated glucose solutions. Even with infusions of large amounts of glucose, the maximum sustainable level of serum glucose did not exceed 700 mg/dl. The apparent ceiling of serum glucose level appeared to be due to a large and rapid loss of glucose from the kidneys. With adequate fluid volume replacement there was no rebound hypoglycaemia and there was no significant changes in haematocrit or electrolytes.
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PMID:Induction of transient hyperglycaemia in cancer patients. 239 24

Fifteen endocrine pancreatic tumours (8 insulinomas, 3 gastrinomas, 1 vipoma, 3 tumours without hormonal activity) and two cases with dysplasia of the endocrine pancreas are reported. Immunohistochemical and electronmicroscopical investigations produced evidence of multihormonality in adenomas that clinically appeared to be monohormonal. The S-phase fraction of such tumours is below 1% which indicates their low proliferative potential. The malignancy of endocrine pancreatic tumours cannot be seen from cytochemical or histological symptoms; it can be established with certainty only from the presence of metastases. Multiple endocrine adenomas should suggest the possibility of hereditary endocrine polyadenomatosis. Hyperplasia and distribution disorder of the endocrine tissue as well as pathologically increased nesidioblastic activity represent the morphologic substrate of dysplasia of the endocrine pancreas as a potential cause of hyperinsulinaemic hypoglycaemia in infancy.
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PMID:Pancreatic endocrine tumours: histological, immuncytochemical and electronmicroscopical investigations. 242 31

Endocrine pancreatic tumors are slowly growing neuroendocrine neoplasms with a malignant potential which may cause symptoms such as hypoglycemia, multiple ulcers, diarrhea, flush, hyperglycemia and skin rash. A prospective study was performed on 84 patients with endocrine pancreatic tumors. In 59 patients (70%) the tumors were malignant. Of the 84 patients, 23 had insulinomas, 25 gastrinomas, 20 nonfunctioning tumors, 14 the WDHA syndrome, 1 somatostatinoma and 1 glucagonoma. The median age at diagnosis was 53 years and the median delay from first symptom to diagnosis was 2 years. The most common site of the pancreatic primary tumor was the tail (41%), and metastases were most frequently located in the liver (60%) and lymph nodes (44%). Plasma chromogranin A + B was elevated in 94%, serum pancreatic polypeptide (PP) in 74%, plasma neurotensin in 67% and serum gastrin in 62%. Serum HCG-alpha and -beta subunits were elevated in 41 and 30% respectively, all except 3 having a verified malignant tumor. The median survival from first symptom and diagnosis was 14.2 and 8.7 years respectively. Patients with MEN-1 had a significantly better survival from diagnosis than sporadic cases (median 15.1 versus 5.8 years). Patients who received interferon after failing chemotherapy had a significantly better survival than those given chemotherapy alone (5-year survival 65 and 50% respectively).
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PMID:Neuroendocrine pancreatic tumors. Clinical findings in a prospective study of 84 patients. 247 25

Adult sarcoma-bearing mice were used to demonstrate whether hypoglycemia was the immediate cause of death in experimental animals with rapidly growing tumors without metastases. This kind of tumor model is representative of the majority of animal models used in experimental cancer research. Tumor-bearing animals died with severe hypoglycemia under all experimental conditions, while pair-killed controls were normoglycemic. Anorexia prevented tumor-bearing animals from attenuating the hypoglycemia by drinking glucose-containing water while completely starved control animals survived more than 14 days with glucose-containing water as the only energy source. Adrenalectomy shortened survival in tumor-bearing animals, but survival of adrenalectomized tumor-bearing animals could be normalized by daily injections of pharmacologic doses of hydrocortisone (25 mg/25 g body wt/day) but not by physiologic replacement (20 micrograms/25 g body wt/day). Injections of pharmacologic doses of hydrocortisone did not influence on survival or body composition in tumor-bearing animals with intact adrenals. Glucagon was without effect on either survival, tumor growth or body composition. Based on the results in this study and in our previous reports we conclude that hypoglycemia is the cause of death in the majority of murine tumor models. This hypoglycemic theory is important, since any treatment modality in animal experiments that influences glucose metabolism in the host may indirectly change tumor growth and may thus be misinterpreted as a direct tumor effect.
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PMID:The cause of death in non-metastasizing sarcoma-bearing mice. A study with relevance for tumor treatment experiments in mice. 280 52


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