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PubMed1988

[A case of malignant pancreatic apudoma producer of serotonin and pancreatic polypeptide].

Taking as their starting point the observation of a pancreatic malignant endocrine neoplasm with mixed production of serotonin and pancreatic polypeptide, the authors go on to review the literature on the diagnosis and treatment of pancreatic apudomas. The possibility of performing an extempore intraoperative histological examination makes it possible to obtain a correct diagnosis of endocrine neoplasm and thus to proceed with surgery which could not be contemplated in adenocarcinomatous forms at an equivalent stage. Chemotherapy may then provide additional therapeutic possibilities, using specific markers for malignancies of the APUD system in order to detect possible recurrences.

Adenoma, Islet Cell↗
PubMedDate not supplied

[Effect of the acetyl derivatives of 4,5,6,7-tetrahydroindole on the enterochromaffin cells and mediator metabolism of the rat brain].

It was reported previously that the analogues of dimecabin (1,2-dimethyl-3-carbethoxy-5-oxyindole),2-methyl-3-carbethoxy-5-oxyindole and the derivatives of 2-methyl-3-carbethoxy-4, 5, 6, 7-tetrahydroindole substituted in the 1st position reduce the content of argentaffinic substance in enterochromaffin cells (EC) for a long period of time. It has been shown that "recognizability" of the acetyl derivatives of 4, 5, 6, 7-tetrahydroindole by the EC receptor systems is preserved. Administration of the acetyl derivatives into the stomach (10 mg/kg for 5 days) induce a prolonged decrease in the argentaffin substance content in EC, and augment the noradrenaline level without exerting a pronounced effect on the dopamine content. These substances also inhibit monoamine oxidase and acetylcholinesterase activity in the rat brain. Detection in EC of the biologically active substances common to the APUD-system and the brain suggests a new trend in the study into the action mode of indole compounds.

Animals↗
PubMed1983

Neuron-specific enolase in neuroendocrine tumors of the thymus, bronchus, and skin.

In order to better define the use of neuron-specific enolase (NSE) as a marker for neuroendocrine neoplasms, we studied 11 thymic carcinoid tumors, three bronchial small-cell carcinomas (all with cutaneous metastases), and 10 trabecular carcinomas of the skin for its presence, using the peroxidase-antiperoxidase (PAP) technic with an antiserum directed at NSE. All 11 carcinoid tumors stained positively, as did two of the bronchial small-cell carcinomas and seven of the trabecular carcinomas. We conclude that PAP staining for NSE content may be a useful adjunct to morphologic analysis in diagnostically identifying the tumors we studied and that our results support the concept of a functionally unified APUD system, as reflected in the tumors originating from it. Nevertheless, because of the vagaries of the PAP method, exemplified by the results in our small series, it cannot be relied upon as a sole indicator that a tumor contains NSE and is therefore neuroendocrine. Also, since it is hypothesized that NSE is present in all tumors of this type, staining for its presence would seem to be of little benefit in distinguishing primary from secondary neuroendocrine tumors or in identifying the origin of metastatic lesions that have a neuroendocrine histologic appearance.

Bronchial Neoplasms↗
PubMed1979

Multiple-hormone producing lung carcinoma.

Endocrine and immunohistochemical studies were performed in a patient with lung cancer associated with gynecomastia. Elevated level of human chorionic gonadotropin (hCG) in plasma and mild hyperadrenocorticism were demonstrated by hormone assays. Postmortem examination proved the existence of anaplastic small cell carcinoma of the lung mixed with a feature of chorioepithelioma. The presence of significant amounts of adrenocorticotropic hormone (ACTH), beta-melanocyte stimulating hormone (beta-MSH), calcitonin, gastrin, hCG, hCG-alpha, hCG-beta and human chorionic somatomammotropin (hCS) in tumor tissues was demonstrated by radioimmunoassays, bioassay and immunohistochemical techniques. We present here a unique case of multiple hormones producing tumor elaborating both hormones of amine precursor uptake and decarboxylation (APUD) series (ACTH, beta-MSH, calcitonin and gastrin) and of placental origin (hCG, hCG-alpha, hCG-beta and hCS).

Adrenocorticotropic Hormone↗
PubMed1996

Somatostatin receptor scintigraphy and therapy of neuroendocrine (APUD) tumors of the head and neck.

Through the development of somatostatin scintigraphy with the labeled somatostatin analog Indium111-Octreotide, it has recently become possible to accurately diagnose primary tumors of the APUD system as well as their metastases, since these tumors usually have somatostatin receptors. Experience with this method is already available for endocrine and exocrine tumors of the gastrointestinal tract, neuroendocrine and breast tumors, small cell bronchial carcinomas and certain lymphomas. In the present study, this new diagnostic technique was used for the first time in various head and neck tumors (carcinoid of the larynx, Merkel cell tumor, glomus tumor of the carotid and glomus jugulare tumor). Concurrently, some of these tumors shown by this diagnostic method to be somatostatin receptor positive were treated using the somatostatin analog Octreotide, a therapeutic approach new for the ENT-specialty. Our initial results prove that the detection of the ENT tumors which we studied by means of receptor scintigraphy is reliable. The preliminary results of this Octreotide therapy show a growth inhibitory effect, especially for those tumors of the head and neck which are inoperable or are difficult to approach surgically.

Adult↗
PubMedDate not supplied

[Cutis verticis gyrata, hypertrophic gastritis, motrice diarhea, and horse's tall syndrome, a new association an apudoma (carcinoid or chemodectoma) (author's transl)].

The authors report the observation of a 70 years male with Cutis Verticis Gyrata (without hypertrophying osteopathy), Menetrier's hypertrophic gastritis, motrice diarrhea of the endocrine type, flush syndrom, liver angiomatosis and a large sacral water clear cells tumor with horse's tail syndrom. The initial tumor was on the posterior wall of rectum, but was necrosed : bone metastasing chemodectoma, or locally invading carcinoid ? This new complex paraneoplastic disease seems to be associated with APUD tumor.

Acromegaly↗
PubMed1974

[Morphology and histochemistry of medullary thyroid carcinomas (author's transl)].

The medullary thyroid carcinoma was characterized as clinicopathological entity by Hazard, Hawk and Crile as early as 1959. As reported in literature the incidence of these tumors ranges from 3.5 to 11.9% of the thyroid carcinomas. In the study presented the morphological, histochemical and electron microscopical investigations in 8 cases of medullary thyroid carcinoma are reported. Different methods are used to demonstrate polysaccharides, proteins, especially polypeptide hormones, and amyloid. Furthermore several silver impregnation techniques for differentiation of argentaffin and argyrophilic cells were performed. The age of the 8 patients ranged from 30 to 65 years, 5 patients were females, the sex ratio of females to males runs to 1.7:1. In 4 cases metastases in regional lymph nodes were found. The tumor tissue preponderately showed a solid-travecular pattern. The tumor cells were seen in cord-like and nest-like arrangement. In places also a typical endocrine structure was present revealing an orientation of cells around capillaries here and there. A differentiation of light and dark cells was possible. Electron microscopically these light microscopical observations could be confirmed: dark cells possessed more organeles than light cells. Infiltrations of blood vessels did not occur, but infiltrations of lymph vessels were the rule. The tumors contained variable amounts of amyloid which could be seen by fluorescence and polarization microscopical methods in fine fiber-like structures or in coarse deposits. At the ultrastructural level typical secretory granules varying in electron density and having a diameter of 220-560 nm were visible. Some light tumor cells exhibited 50-120 A thick fibrils which could not be distinguished from extracellular amyloid fibrils. The histochemical findings evidenced moderately abundant proteins in the cytoplasm of tumor cells. Histochemically the amyloid corresponds to the so-called apudamyloid. A great deal of the proteins is orderly arranged in amyloid whereas this is not the case in the tumor cell cytoplasm as proved by the coupled tetrazonium reaction which was evaluated polarization microscopically. In amyloid tryptophan was absent. The medullary thyroid carcinoma has a low-grade malignancy and, in accordance to other authors, it is to be stated that this tumor is histogenetically related to the parafollicular cells (C-cells). Its distinction from other thyroid tumors is warranted basing on morphological and pathophysiological features. Structural patterns common with those of other endocrine tumors are demonstrable. The findings point to a relationship of medullary thyroid carcinoma with the APUD series or Feyrter's Helle-Zellen-System. Considering the possible simultaneous occurrence of pheochromocytomas and adenomas of the parathyroid gland it must be assumed that the medullary thyroid carcinoma is one of the dysplasias of the neural ectoderm.

Adult↗
PubMed1983

[Prognosis in tumor diagnosis].

This essay on prognosis in tumor diagnosis pathology resp. tumor etiology, cancerogenesis and molecular oncology is the authors personal opinion. Generally tumor diagnosis improves with progress in histo- and cytological methods for example in tumors of the APUD-system and precancerous lesions especially of the breast. Fundamental principle of developed tumor diagnosis is the knowledge of malignant transformation. Its profits favours the etiology in cancerogenesis and e.g. non Hodgkin lymphomas (Burkitt lymphoma, adult T-cell lymphoma) and to result from new methods in molecular biology and viral genetics (DNS-hybridizing, -recombination and gene technology). With the beginning century a stepwise fitted diagnosis of malignant lymphomas is evident up to monoclonal dedifferentiated lymphoid cells and their multifarious phenotypical markers. This concept may be of general significance in tumor diagnosis already indicated in prelymphomas. Finally the present prognosis of tumor diagnosis is evaluated by contents, tasks and strategies of its corresponding research lines in clinical and experimental tumor pathology resp. its organization.

B-Lymphocytes↗
PubMed1995

Mitoxantrone in metastatic apudomas: a phase II study of the EORTC Gastro-Intestinal Cancer Cooperative Group.

We performed a phase II study with mitoxantrone in patients with carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid. Thirty-five eligible patients received mitoxantrone 12 mg m-2 i.v. every 3 weeks. Among 18 previously untreated patients, three responded (17%, 95% CI = 4-41%); no responses were achieved in 17 previously treated patients. Of the 21 patients who had carcinoid tumours, 11 were previously untreated and two achieved a response (18%, 95% CI = 2-52%). Overall response rate was 9% (95% CI = 2-23%). At a median follow-up of 43 months, median overall survival was 16 months. The median survival of 21 patients with a normal alkaline phosphatase was 29 months and 9 months for 14 patients with elevated serum levels (P = 0.005). A similar observation was noticed for gamma-glutamyltransferase (P = 0.007). We concluded that mitoxantrone is not active in APUD tumours. Elevated alkaline phosphatase and gamma-glutamyltransferase are associated with a poor prognosis.

Adenoma, Islet Cell↗
PubMed1989

[Neurocristopathy. The association of Hirschsprung's disease-ganglioneuroma with autonomic nervous system dysfunction in 2 children].

Two children with the coexistence of long segment Hirschsprung's disease, ganglioneuroblastoma with Ondine's curse in one case and autonomic nervous system impairment in the other are presented. All lesions may be related to aberrations of neural crest cell growth, their migration, or differentiation. A genetic etiology, and the link between Hirschsprung's disease and multiple endocrine adenomatosis is discussed. The combination of Hirschsprung's disease and a neurocristopathy strongly suggests that exploration of the autonomic nervous system and APUD system be carried out.

Autonomic Nervous System Diseases↗
PubMed1990

[Non-functioning tumors of the endocrine pancreas. Concept, diagnosis, treatment].

Five cases of nonfunctioning islet cell tumors of the pancreas are reported. There were 3 males and 2 females aged from 34 to 83 years (Average: 55.8 years). Two tumors were malignant since already metastatic, one tumor was probably malignant and two tumors were judged as benign. One patient died post-operatively. The four remaining patients are alive without recurrence after from 1.4 to 7.3 years. The concepts of nonfunctioning tumors of the pancreas and APUD system are discussed in view of these 5 cases and the relevant literature. The value of tumor markers as well as the radiographic appearances of these tumors are reported. Having a better prognosis than the adenocarcinoma of the exocrine pancreas, the nonfunctioning tumors of the endocrine pancreas are best managed by surgery. The indications and the results of surgery and chemotherapy are discussed.

Adenoma, Islet Cell↗
PubMed1988

[Ultrastructural analysis in differential diagnosis of tumors].

Ultrastructures of 25 tumors were analyzed by electron microscopy (EM). Of the 25 cases, there were 9 amine precursor uptake and decarboxylation tumors (APUD) (2 carotid body tumor, 2 medullary carcinoma of thyroid and 5 carcinoid) in which the dense core granules of different sizes were seen in the cytoplasm. 4 cases of malignant melanoma were identified by EM basing on the premelanosome and melanosome in the cells. In 4 carcinomas from different locations, 2 had mucous secretory granules in the cytoplasm and junction complex between the tumor cells. The diagnosis was finally confirmed as adenocarcinoma. The other 2 cases were identified as epidermoid carcinoma or anaplastic carcinoma as desmosome and tonofilaments were found. 4 cases of malignant lymphoma without any cell junction complex were identified. Moreover, there were several cases of mesenchymal cell tumors, such as leiomyoma, rhabdomyosarcoma, chordoma and Schwannoma confirmed by their special organelles. This study shows that the ultrastructural analysis is valuable in the differential diagnosis and classification of tumors.

Adolescent↗
PubMed2001

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas.

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification. METHODS: Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis. The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P<0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P<0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-function classification of GC is helpful in indicating the characteristics of invasion and metastasis of GC with different cell-function differentiation phenotypes. Further study is needed to disclose the correlation between the cell-functional differentiation phenotypes and the relevant genotypes and the biological behavior of gastric carcinoma.

Biomarkers, Tumor↗
PubMed2004

The neuroendocrine system: organization and homeostatic role.

The neuroendocrine system (NES) of Vertebrates can be defined as a set of cells organized in single organs and diffuse elements, sharing co-production of amine hormone/transmitters, peptide hormone/transmitters and specific markers of neural determination. In this perspective, the hypothalamic-pituitary-target organ axis (H-P axis), the autonomic nervous system (ANS) and the diffuse neuroendocrine or APUD system contribute to the NES. However, in Mammals and man virtually any compartment of the body harbors elements, often with different embryologic origin, having at least some of the NES features. Thus, all anatomical structures may be part of a wide functional circuitry, based on "internal secretions", that supersedes the current view of the NES. Historically, metaphysical antecedents of this concept can be found in the biomedical tradition dealing with the idea of the so called "vital energy". Currently, the "internal secretions" circuitry can be envisaged as an informational supersystem encompassing the H-P axis, ANS, APUD, immune and any other body system performing autocrine, paracrine and/or endocrine regulations, that superintends the homeostatic balance. Evolutionary evidence shows that diffuse autocrine/paracrine/endocrine, peptidergic secretions would be the oldest and hierachically simplest signals, with respect to the later and hierarchically more complex ANS and H-P axis outputs, to regulate body homeostasis. Therefore, the new acronym "Triune Information Network" (TIN) is proposed for the informational supersystem of internal secretions acting in Mammals and man via progressively higher levels of control (diffuse autocrine/paracrine/endocrine secretions, ANS and H-P axis) on a common energetic substrate: the internal body milieu.

History, Ancient↗
PubMed1995

Ectopic ACTH syndrome.

Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4-6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.

Adrenal Glands↗
PubMed1985

Doxorubicin plus cisplatin in the treatment of apudomas.

Twelve patients with advanced apudomas--six with carcinoid tumors, two with chemodectomas, two with pancreatic islet cell tumor, and one each of medullary carcinoma of the thyroid and paraganglioma of unknown primary--were treated with a combination of doxorubicin 50 mg/m2 and cisplatin 50 mg/m2 every 3 to 4 weeks. Biochemical markers were present in 8 of the 12 patients. Five of the 12 patients (3 with carcinoid and 2 with chemodectomas) responded with more than 50% regression of tumor size measured as hypothetical area. Three others (two with islet cell tumors and one with carcinoid) had clinical and/or biochemical improvements. A median duration of response was 6 months. Nausea, vomiting, and alopecia were universal. Mild or moderate leukopenia was the most frequent toxicity. No sustained nephrotoxicity was seen. The combination of doxorubicin and cisplatin provides a new palliative therapy for patients with APUD tumors.

Adolescent↗
PubMed1979

[Sipple's syndrome: type II endocrine polyneoplasia (author's transl)].

Sipple's syndrome is a generally familial polyneoplastic affection associating a medullary thyroid cancer and a pheochromocytoma. The overall picture of the syndrome has, in fact, become larger now that it is known that there is previous hyperplasia of thyroid C cells and chromaffin cells in relation to neoplasms. Increase in plasma thyrocalcitonin levels is the best indicator of medullary cancer, and the discovery of this hormone in pheochromocytomas has shown the secretory origin of the two tumors, the cells of which have a common embryological origin in the neural crest. Sipple's syndrome is often associated with hyperparathyroidism, hyperplasia without adenoma (endocrine polyneoplasia type II a), or phacomatosis and a dystrophic condition (type II b or III). The authors discuss the nosology of the syndrome and its relation to the diffuse endocrine and APUD systems.

Adrenal Gland Neoplasms↗