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[The application of 5-HT and 5-HIAA in the diagnosis of apudomas].

5-HT apudomas are rare. In our country, so far there has been no detailed report about using whole blood 5-HT and urinary 5-HIAA in the diagnosis of apudomas. Measurement of whole blood 5-HT in 87 and urinary 5-HIAA in 44 apudoma patients has been carried out in our laboratory since 1980. The results showed that the values of whole blood 5-HT and urinary 5-HIAA were significantly higher in apudoma patients than those in non-apudoma, postoperative apudoma and normal groups. The value of whole blood 5-HT over 130 micrograms/ml and urinary 5-HIAA over 30 mg/24 h were preliminarily recommended as diagnostic for apudomas.

Adolescent

APUDomas: acute complications and their medical management.

APUDomas are rare tumours originating from a variety of endocrine cells localized in different organs. Acute complications from APUDomas usually result from the increased biosynthesis and release of bioactive amines or polypeptide hormones by the tumour. Less frequently, bleeding or compression by the tumour can occur requiring emergency surgery. Increased gastrin production by gastrinomas is the cause of ZES (peptic ulceration and diarrhoea) by gastrin effects on gastric acid secretion. Volume depletion, hypokalaemia, severe bleeding, duodenal perforation, oesophageal stricture and pyloric stenosis are the most dramatic complications. Treatment of these complications and their prevention has been facilitated by the availability of antagonists to H2 receptors and H(+)-K+ proton pump. These medications should control acid output in every patient with ZES. Frequent manifestations of carcinoid tumours, VIPomas and medullary thyroid carcinomas are flushing and diarrhoea. Octreotide, a long-acting somatostatin analogue, has markedly changed the management of these patients, their symptoms decreasing in severity or disappearing in most cases. Octreotide has also been used with success in the prevention and treatment of the carcinoid crisis, a dreaded complication of carcinoid tumours. A better understanding of the pathophysiology of APUDomas has enabled new treatment designs which have considerably ameliorated the quality of life of patients affected by these tumours; efforts must be continued to affect their life expectancy.

Acute Disease

Oat cell carcinoma (apudoma) of the esophagus: a case report.

An oat cell carcinoma occurring in the esophagus of a 62-year-old man is described. A strong argyrophilia of the oat cells together with the presence electron microscopically of neurosecretory type granules in their cytoplasm suggests a derivation of this tumor from the cells of the APUD series, and the tumor is diagnosed as apudoma. An aberrant columnar epithelium on the esophageal surface is presumed to be the source of its origin. A rapid postoperative course of the patient despite a rather circumscribed growth pattern of the primary tumor appears to characterize the clinical aspect of this case. An apparent accumulation of the cases with esophageal apudoma in Japan is discussed.

Apudoma

Pancreatic apudomas.

Pancreatic apudomas are not common but are frequently curable. Thus, it is important for every clinician to be fully aware of the varied clinical syndromes that suggest their presence. The availability of specific radioimmunoassays has made confirmation of the diagnosis relatively simple. Advances in the techniques for staining the different cell types have led to the recognition that many of these tumors are mixed, and that the general term "pancreatic apudoma" is appropriate. Pancreatic endocrine tumors, as examples to "nature's experiments," have yielded considerable insight into the possible physiologic effects of the various peptides they produce. It is to be hoped that further study of tumors such as the somatostatinoma and PPoma may yield further information about these enigmatic compounds.

Animals

APUD cells and the apudomas. A concept relevant to anaesthesia and endocrinology.

A variety of cells found in the pituitary and pineal glands, sympathetic nervous system and adrenal glands, the gut, pancreas, thyroid (C-cells), chemoreceptors (type I-Cells), lungs (P-cells), skin (melanocytes) and the urogenital tract have a common origin from the neural crest. These cells are programmed for neuro-endocrine function and, as a group, can be regarded as one of the physiological control systems. They secrete a variety of amine and peptide hormones and have common cytochemical characteristics from which the term APUD cell is derived. Tumours of these cells are referred to as 'apudomas' and may synthesise not only their own hormones but also those which are normally produced by other APUD cells. The relevant physiological properties of some of the peptides which have been described relatively recently are discussed and the principal clinical syndromes produced by the APUDomas are described.

APUD Cells

Combination chemotherapy of an APUDoma. With special reference to the therapeutic value of monitoring hormonal substances.

Investigations are presented on the occurrence of tumour products during combination chemotherapy of a 49-year-old female with an APUDoma metastatic to the liver. Calcitonin was demonstrated in high concentration in the tumour tissue. Serum calcitonin, serum histaminase and 5-HIAA in a 24-hour urine sample increased immediately after the administration of cytotoxic agents, falling subsequently below the pretreatment level. These findings indicate a therapeutic effect with lysis of tumour cells. Continuous determination of the three tumour substances showed an increase in these products before clinical suspicion of progression. Electron microscopic examination during the initial course disclosed the tumour to be an APUDoma. Autopsy failed to disclose a primary site outside the liver. Further autopsy findings were an adenoma of the thyroid and a chromofobe adenoma of the pituitary, thus assigning the patient to type 1 multiple endocrine neoplasia.

Amine Oxidase (Copper-Containing)

Clinically silent gross hypergastrinaemia from a multiple hormone-secreting pancreatic apudoma.

A patient is described who had a malignant pancreatic islet cell apudoma secreting corticotrophin (ACTH) and melanocyte-stimulating hormone (MSH), both of which were clinically active, and very large quantities of immunoreactive gastrins, which were biologically active but clinically silent (normal gastric acid secretion and no peptic ulceration). The presence of parietal cell antibodies, with no increase in the plasma concentrations of hormones which can inhibit gastric acid secretion (secretin, GIP and VIP), suggests that many of the of the parietal cells may have been blocked by the autoantibodies.

Adenoma, Islet Cell

Cyclical release of vasoactive intestinal polypeptide (VIP) from a pancreatic islet cell apudoma.

A patient is described who presented with the classical symptomatology and profound electrolyte disturbance of the Verner-Morrison syndrome due to a pancreatic apudoma secreting vasoactive intestinal polypeptide (VIP). Diagnosis was confirmed by plasma VIP as measured by a radio-immunoassay technique now available. It is suggested that the cyclical nature of the symptoms in this case was due to cyclical release of VIP from the tumour in response to an unknown stimulus. Perfusion studies confirmed the excess secretory state of water, sodium and chloride in the small intestine. Symptoms were completely abolished by surgery and the progress is being monitored by means of serial plasma VIP estimations to detect any early recurrence of metastatic disease.

Adenoma, Islet Cell

Apudoma and subcorneal pustular dermatosis (Sneddon-Wilkinson disease).

The subcorneal pustular dermatosis (SPD) is a rare dermatosis. IgA monoclonal gammapathy is the most frequently associated disease with the SPD. We report a case of SPD in a patient with metastatic apudoma, an association not previously described. The rare nature of both diseases suggests that this association is not fortuitous.

Apudoma

[A poorly differentiated apudoma of the gallbladder].

Apudoma was found in the gall bladder removed in a 76-year-old woman because of the chronic calculous cholecystitis exacerbation. Carcinoid syndrome was absent clinically. Histologically, the tumour was a poorly differentiated carcinoid with areas of small cell and polymorphic carcinoma. Argyrophilic Pasquale reaction in the tumour cells was negative, electron microscopically small neurosecretory granules were found. Numerous ACTH-reactive cells and single serotonin-reactive cells were revealed in the tumour parenchyma by means of immunohistochemical PAP-method using antibodies against ACTH, serotonin, calcitonin, somatostatin, insulin, glucagon, P-substance. Focal hyperplasia and intestinal metaplasia of epithelium with the increase of the number of argyrophilic, ACTH-reactive cells were observed outside the tumour.

ACTH Syndrome, Ectopic

[Immunocytochemistry of pancreatic and pancreatico-duodenal apudomas].

Immunocytochemical techniques, applied to material fixed with Bouin's fluid and using immune sera specific to various hormonal polypeptide(s), give a classification of pancreatic and pancreatico-duodenal apudomas based upon cellular functional activity. With a rane containing a minimum of five antibodies (gastrin, insulin, glucagon, somatostatin and pancreatic polypeptide), 15 tumours could be identified amongst the 22 tested. They were either "monohormonal" tumours (10 cases) or "bi- or polyhormonal" tumours (5 cases). In the remaining 7 cases, only rare cells were immunoreactive. A large number of immunoreactivities thus revealed in histological sections are clinically silent or are present in a "forme fruste".

Animals

Argyrophil cell carcinoma (apudoma) of the esophagus. A histopathologic entity.

In a series of 79 cases of primary esophageal carcinoma resected at The Center for Adult Diseases, Osaka, there were six tumors with specific histopathologic features valid for the diagnosis of argyrophil cell carcinoma. Of the 6 tumors, 3 were studied electron microscopically and assay for ACTH content was performed on 4 tumors. Clinically, the ages of the 6 patients ranged from 56 to 71 years; two were women and four men. Four of the 6 patients died with widespread tumor recurrences within 9 months of operation. Microscopically, the 6 tumors were composed largely or almost entirely of small, spindle-shaped cells resembling those of oat cell carcinoma of the lung, and were characterized by the arrangement of tumor cells in solid sheets or anastomosing cords, the presence of argyrophil tumor cells, and the deposits of amyloid. Electron microscopically, the three tumors contained neurosecretory-type granules. Using bioassay or radioimmunoassay ACTH activity in the tumor tissues was detected in 3 out of the 4 tumors determined. From the light and electron microscopic characteristics and the assay evidence, it seems reasonable to conclude that the 6 tumors are endocrine polypeptide producing tumors (apudomas) that arise from argyrophil cells normally found among the basal cells of the esophageal mucosa, and that they represent a distinct histopathologic entity clearly distinguishable from other types of esophageal carcinomas.

Adrenocorticotropic Hormone

Argyrophil cell carcinomas (apudomas) of the uterine cervix. Light and electron microscopic observations of 5 cases.

Of a series of 97 invasive carcinomas of the cervix, 5 were found to have argyrophil tumor cells, and 3 of these 5 tumors were studied by electron microscopy. The ages of the 5 patients ranged from 36 to 49 years, with a mean age of 42.4 years. The morphologic features of these five tumors were well consistent with those described on a variety of endocrine polypeptide neoplasms such as thyroid medullary carcinomas, carcinoids, pancreatic islet-cell tumors, and oat cell carcinomas of the lung. Microscopically, the 5 tumors were characterized by the formation of solid-sheets, ribbons, streams, and rosettes. They were characterized electron microscopically by the presence of neurosecretory-type granules, the abundance of intracytoplasmic microfilaments, the absence of tonofibrils, and the paucity of desmosomal attachments. On the basis of the microscopic, electron microscopic and cytochemical characteristics, it is suggested that the tumors are a specific type of cervical carcinoma derived from the argyrophil cells, normally found among the linings of the endocervical glands and the cervical squamous epithelium. We believe these 5 tumors should be regarded as an endocrine tumor, another member of apudomas.

Adult

ACTH-secreting 'apudoma' of gallbladder.

The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side.

Adenocarcinoma

[Apudomas].

Apudomas, i.e. tumours deriving from apud system cells, comprise already known forms located in widely different organs at considerable distances one from the other. They present great cytochemical, biochemical and ultrastructural similarities and possess a common derivation in the neuroectodermal cells of the neural crest. They thus form part of that tumour group known as neurolophomas. They are also responsible for typical clinical pictures connected with the production of hormone-type substances, and are classified among multiple endocrine adenomatoses and in the ectopic hormone syndromes.

Carcinoma

[Malignant apudoma (argyrophilie carcinoma) of the uterine cervix in a 24-year-old woman in pregnancy].

Report on a case of the malignant APUDOMAP (argyrophil cell carcinoma) of the uterine cervix in a 24-years old women. The tumor appeared during the third pregnancy and fatal generalization resulted cca three month after operative delivery and panhysterectomy. Histologically argyrophil cells were proved both in the primary localization and distant metastases (liver, lymph nodes, ovaries, brain, meninges, skeleton). In the electron microscope of the bioptic specimen specific granules and microfilaments were identified in some tumour cells supporting the diagnosis of a cancer of the APUD-series. Some general features of primary cervical APUDOMAS also outlined.

Adult

Malignant apudoma of the liver with symptomatic intractable hypoglycemia.

This report documents a case of a fatal primary malignant neoplasm of the liver with metastases to the lymph nodes of the porta hepatis and the pubic bone. Profound, intractable hypoglycemia was seen during the course of the disease. No immunoassayable insulin was found in the blood during episodes of severe, symptomatic hypoglycemia. The neoplasm was composed of uniform polygonal cells with distinct cytoplasmic borders growing in broad strands with a tendency toward nesting and was morphologically similar to neoplasms of neural crest derivation. The presence of osmophilic, membrane-bound granules in the neoplastic cells was documented by ultrastructural studies. The tentative conclusion that the hypoglycemia was produced by the secretion of a substance with insulin-like activity, probably a polypeptide, by the secretory granules in the neoplastic cells is supported by clinical and laboratory data.

Apudoma

Duodenal carcinoid (apudoma) with psammoma bodies: a light and electron microscopic study.

An extremely rare case of psammomatous calcification in a nonfunctioning duodenal carcinoid tumor was studied by light and electron microscopy. The psammoma bodies were found most frequently within the lumina of the neoplastic glands. The ultrastructural features of the psammoma bodies were the marginal needle-shaped crystals and a coarse granular matrix in which a few organelles were embedded. The psammoma bodies appeared to be occasionally intracytoplasmic in position, showing no distinct limiting cytoplasmic membrane. Electron probe x-ray microanalysis revealed that the needle-shaped crystals contained calcium. The mechanism by which the psammoma bodies are formed has not been clearly explained. The above findings support the view that the psammoma bodies may occur initially in the cytoplasm of the tumor cells, followed by their release probably in a way of active excretion.

Adult