vasoactive-intestinal-peptide and Carcinoid-Tumor

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended.

Topics: Adolescent; Adrenal Cortex Neoplasms; Adult; Aged; Aged, 80 and over; Angiofibroma; Carcinoid Tumor; Child; Facial Neoplasms; Female; Gastrinoma; Genetic Testing; Humans; Insulinoma; Lipoma; Male; Meningioma; Middle Aged; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Parathyroid Neoplasms; Pituitary Neoplasms; Prolactinoma; Proto-Oncogene Proteins; Thyroid Neoplasms; Vasoactive Intestinal Peptide; Young Adult

Topics: Antibodies, Monoclonal; Biomarkers; Biomarkers, Tumor; Carcinoid Tumor; Female; Graves Disease; Humans; Male; Neuroendocrine Tumors; Octreotide; Radionuclide Imaging; Receptors, Somatostatin; Sensitivity and Specificity; Vasoactive Intestinal Peptide

Over 80 peptides and amines secreted by more than 20 different types of neuroendocrine cells scattered throughout the gut have been identified. The physiologic function and clinical relevance of many of these hormones await elucidation. Nevertheless, the clinical use of these agents in either diagnostic or therapeutic modalities has greatly expanded the appreciation of the relevance of many of these peptides to malignant and nonmalignant pathobiology.

Topics: Carcinoid Tumor; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Humans; Insulin; Vasoactive Intestinal Peptide

A case of mixed (composite) glandular-endocrine cell carcinoma of the stomach is presented. Whereas the admixture of rare endocrine cells in ordinary adenocarcinoma of the stomach is a rather frequent occurrence, gastric tumors with an approximately equal proportion of glandular and endocrine cells are rare, and only 20 well-documented cases have been reported. Our case is unique in its range of histopathologic patterns, including well-differentiated and poorly differentiated adenoendocrine carcinoma as well as amphicrine differentiation. Immunohistochemical and electron microscopic findings are documented and the clinical characteristics of all reported cases tabulated. From the limited experience of these 21 cases, glandular-endocrine carcinoma of the stomach is found to have the following clinicopathologic features: It affects adults aged 32 to 74 years, (mean, 52.5 years) and has a male:female ratio of 1.3:1. It is located with almost equal frequency in the gastric body and antrum and has a poor prognosis, similar to that of advanced ordinary gastric carcinoma.

Topics: Adult; Aged; Carcinoid Tumor; Carcinoma; Chorionic Gonadotropin; Chromogranins; Female; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Stomach Neoplasms; Vasoactive Intestinal Peptide

Topics: Carcinoid Tumor; Colon; Endocrine Glands; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Glucagon-Like Peptides; Humans; Nervous System; Neuropeptides; Neurosecretory Systems; Peptide PHI; Peptide YY; Peptides; Rectum; Vasoactive Intestinal Peptide

Histopathological and experimental observations indicate that tumors composed wholly or in part of neuroendocrine elements may arise in tissues derived from ectoderm (including neuroectoderm), mesoderm, and endoderm. These tumors frequently exhibit multidirectional differentiation as manifested by multihormonality and by the presence of morphological features indicative of divergent differentiation both in vivo and in vitro. The existence of stem cells, plasticity of differentiated cells, microenvironmental influences, and random events are factors which might all interact to determine the characteristics of any particular tumor. The production of characteristic regulatory peptide products in association with tumors of specific histological subtypes and with other neuroendocrine markers suggests mechanisms for nonrandom activation of multiple genes common to neuroendocrine-programmed cells. Future studies applying new molecular biological techniques to intact tissues and to in vitro models may help to clarify the mechanisms that regulate the expression of the neuroendocrine phenotype in normal and neoplastic states.

Topics: Adrenal Gland Neoplasms; Animals; Apudoma; Calcitonin; Carcinoid Tumor; Cricetinae; Female; Gastrins; Hormones, Ectopic; Humans; Neurotensin; Ovarian Neoplasms; Pancreatic Neoplasms; Pheochromocytoma; Rats; Somatostatin; Thyroid Neoplasms; Uterine Neoplasms; Vasoactive Intestinal Peptide

As sensitive radioimmunoassays for the detection of polypeptide hormones are developed, the exciting discovery of a diffusely distributed system of interrelated endocrine cells has begun a new era of endocrinology. This system, although anatomically disassociated, is bound together by a number of common features such as its biosynthetic mechanism, histochemical and ultrastructural features, and embryologic origin (Table I). The most prominent feature, however, is their biosynthetic pathways for hormone production, from which the acronym APUD has been derived. These are the capacity for Amine Precursor Uptake such as DOPA and then subsequent Decarboxylation, resulting in the synthesis of bioactive amines or polypeptide hormones. Hyperplasias or neoplasms of these cells are defined as apudomas. In the last ten years a great deal of research has rapidly altered the original concepts of this system, especially in terms of its embryologic origin, physiologic interrelationships, classification, as well as the addition of many new APUD cell members. These will be reviewed, and the origin, diagnosis, and treatment of each recognized apudoma will be synthesized in light of its membership within the APUD system.

Topics: Adenoma, Islet Cell; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Endocrine Glands; Humans; Neural Crest; Neuroblastoma; Paraganglioma; Pheochromocytoma; Pituitary Neoplasms; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

The identification and description of a widely dispersed group of cells of common origin and biochemical characteristics, APUD cells, has allowed a better understanding and classification of endocrine tumors of the pancreas. Similarly, it has enabled the relationships between the endocrine tumors of the multiple endocrine neoplasia type I syndrome and the endocrine tumors of the pancreas to be better appreciated. This has facilitated both diagnosis and management of these conditions. The pluripotentiality of the cells of the APUD system combined with the certain existence of many unidentified peptides suggests the likelihood of other undescribed pancreatic endocrine tumors. Many of these are probably part of the heterogenous group of neoplasms currently designated as carcinoids, since their secretory products and exact cell types are not known. The recognition of the physiologic characteristics and cells of origin of these peptides, amines or other bioactive agents will allow delineation of the symptom complex and the identification of further functional tumors of the pancreas. The development of plasma radioimmunoassays for the various hormones and the appreciation of the specific clinical syndromes related to each tumor have enabled earlier diagnosis. The understanding of the hormonal physiopathologic functions has led to the evolution of specific therapeutic maneuvers. Provocative tests have allowed increased precision of the differential diagnosis, while selective arteriography and pancreatic venous sampling have greatly enhanced the accuracy of topical localization. The role of operation in tumor removal is still prominent, but malignant and recurrent tumors may now also be controlled with specific pharmacotherapy or appropriate endocrine cytotoxic agents. The use of peptides with antagonistic actions or the administration of specific antibodies to the active tumor products are areas of therapy that require further exploration.

Topics: Adult; Apudoma; Carcinoid Tumor; Child; Diagnosis, Differential; Gastrins; Glucagon; Humans; Infant; Insulin; Insulin Secretion; Islets of Langerhans; Neoplasms, Multiple Primary; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Adolescent; Adult; Aged; Carcinoid Tumor; Child; Dehydration; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Humans; Hyperplasia; Hypokalemia; Insulin; Insulin Secretion; Male; Middle Aged; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Precancerous Conditions; Serotonin; Somatostatin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Appendiceal Neoplasms; Carcinoid Tumor; Carcinoma, Small Cell; Cholecystokinin; Digestive System; Duodenum; Endocrine Glands; Fetus; Gastric Mucosa; Gastrins; Humans; Ileum; Peptides; Rectal Neoplasms; Respiratory System; Secretin; Substance P; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Diarrhea; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hormones, Ectopic; Humans; Insulin; Insulin Secretion; Neurosecretory Systems; Pancreatic Hormones; Paraneoplastic Endocrine Syndromes; Prostaglandins; Serotonin; Syndrome; Vasoactive Intestinal Peptide; Werner Syndrome; Zollinger-Ellison Syndrome

To report our experience with both (123)I-vasoactive intestinal peptide (VIP) and (111)In-DTPA-D-Phe(1)-octreotide for imaging to identify primary and metastatic tumor sites in carcinoid patients.. One hundred ninety-four patients with a verified or clinically suspected diagnosis of a carcinoid tumor were injected with (111)In-DTPA-D-Phe(1)-OCT for imaging purposes, while 133 patients underwent scanning with both (123)I-VIP and (111)In-DTPA-D-Phe(1)-OCT in random order. Imaging results were compared with computed tomography scans, results of conventional ultrasound, endosonography, and endoscopy, and results of surgical exploration in case of inconclusive conventional imaging.. Primary or recurrent carcinoid tumors could be visualized with (111)In-DTPA-D-Phe(1)-OCT in 95 (91%) of 104 patients; metastatic sites were identified in 110 (95%) of 116 patients. In 11 (51%) of 21 patients with suggestive symptoms but without identified lesions by conventional imaging, focal tracer uptake located the carcinoid tumor. In addition, metastatic disease was demonstrated in three patients after resection. In a direct comparison in the 133 patients who underwent both imaging modalities, (111)In-DTPA-D-Phe(1)-OCT was found to be superior to (123)I-VIP, with 35 (93%) of 38 versus 32 (82%) of 38 scans being positive in primary or recurrent tumors, 58 (90%) of 65 versus 53 (82%) of 65 being positive in patients with metastatic sites, and seven (44%) of 16 versus four (25%) of 16 being positive in patients with symptoms but otherwise negative work-ups. Overall, additional lesions not seen on conventional imaging were imaged in 43 (41%) of 158 versus 25 (25%) of 103 scans with (111)In-DTPA-D-Phe(1)-OCT and (123)I-VIP, respectively.. Both peptide tracers have a high sensitivity for localizing tumor sites in patients with ascertained or suspected carcinoid tumors, with (111)In-DTPA-D-Phe(1)-OCT scintigraphy being more sensitive than (123)I-VIP receptor scanning. Both, however, had a higher diagnostic yield than conventional imaging, as verified by surgical intervention or long-term follow-up. The combination of both peptide receptor scans does not seem to further enhance diagnostic information.

Topics: Adult; Aged; Carcinoid Tumor; Humans; Indium Radioisotopes; Iodine Radioisotopes; Middle Aged; Octreotide; Pentetic Acid; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Vasoactive Intestinal Peptide

Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors.. Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma.. Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors.. Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.

Topics: Adenocarcinoma; Carcinoid Tumor; Colorectal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Insulinoma; Iodine Radioisotopes; Male; Octreotide; Pancreatic Neoplasms; Radionuclide Imaging; Receptors, Somatostatin; Receptors, Vasoactive Intestinal Peptide; Stomach Neoplasms; Vasoactive Intestinal Peptide

Patterns of elevated serum peptides may reveal additional markers and permit better classification of tumors based on (secondary) peptide secretion.. Fasting peptide profiles were obtained from 31 carcinoid patients. vasoactive intestinal peptide (VIP), pancreatic polypeptide (PP), neurotensin, substance P, gastrin-releasing polypeptide (GRP), calcitonin, gastrin, and pancreastatin were measured. Peptide elevation patterns were correlated with disease sites, syndrome, and survival.. Elevations in patients were as follows: VIP 0%, PP 13%, neurotensin 10%, substance P 20%, GRP 3%, calcitonin 10%, and gastrin 3%. There were no consistent patterns of elevated peptides with regard to site or syndrome. Pancreastatin was elevated in 81% of profiles and was the only abnormal peptide in 57% of patients.. Peptide profile results do not permit improved classification, predict syndrome development, or correlate with survival. In contrast, pancreastatin is elevated in most cases and may be utilized to monitor disease progression and evaluate response to therapy.

Topics: Biomarkers, Tumor; Calcitonin; Carcinoid Tumor; Chromogranin A; Disease Progression; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Male; Neurotensin; Pancreatic Hormones; Pancreatic Polypeptide; Peptides; Predictive Value of Tests; Substance P; Vasoactive Intestinal Peptide

The case of a 33-year-old-woman with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome and acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion by a thymic carcinoid tumour is reported. Immunohistochemistry revealed positive immunoreactivity for GHRH, vasoactive intestinal polypeptide, somatostatin and alpha-subunit in the tumour cells. A previously undescribed new germ line mutation of the MEN1 protein gene was revealed.

Topics: Acromegaly; Adult; Antineoplastic Agents; Carcinoid Tumor; Fatal Outcome; Female; Germ-Line Mutation; Growth Hormone-Releasing Hormone; Humans; Immunohistochemistry; Multiple Endocrine Neoplasia Type 1; Neoplasm Proteins; Peptides, Cyclic; Somatostatin; Thymus Neoplasms; Vasoactive Intestinal Peptide

To study the relationship between clinical pathology and antigen expression and DNA content of gastrointestinal carcinoid tumors.. Fifty-two cases of paraffin-embedded gastrointestinal carcinoid specimens were collected. According to Gould's criteria, there were 20 cases of typical carcinoid, 20 cases of atypical carcinoid and 12 cases of undifferentiated carcinoid. Ten different kinds of antigen were examined by immunohistochemical staining and DNA contents by flow cytometry.. Calcitonin (CT), carcinoembryonic antigen (CEA) and vasoactive intestinal peptide (VIP) expression was significantly reduced in typical carcionoid compared to that in other two types of carcionoid. Their expression was more marked in progression than in early stage of the disease. VIP expression was significantly higher in patients with than without lymph node metastases. Cellular DNA analysis showed significant difference between the typical and the other two types of carcinoid. Tumors with expression of VIP and CEA were mostly aneuploid.. To study expression of relevant antigens in gastrointestinal carcinoid in relation to histological type and cellular DNA content helps determine its biologic behavior and prognosis.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Carcinoembryonic Antigen; Carcinoid Tumor; DNA, Neoplasm; Female; Gastrointestinal Neoplasms; Humans; Immunohistochemistry; Male; Middle Aged; Vasoactive Intestinal Peptide

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Bombesin; Calcitonin; Carcinoid Tumor; Carcinoma, Small Cell; Chromatography, Gel; Corticotropin-Releasing Hormone; Gastrin-Releasing Peptide; Gastrins; Humans; Hypothalamus; Lung Neoplasms; Neoplasms; Neuroblastoma; Pancreatic Neoplasms; Peptides; Pheochromocytoma; Somatostatin; Thyroid Neoplasms; Vasoactive Intestinal Peptide

The Mastomys (Praomys natalensis) species are a unique natural model in which the bioactivity of gastric carcinoids may be studied. Several investigators have previously demonstrated that these tumors contain large amounts of histamine. In this study we investigated the presence of peptides associated with the neoplasm. The levels and location of gastrin, gastric inhibitory peptide (GIP), neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), glucagon, bombesin, vasoactive intestinal peptide (VIP) and somatostatin (SRIF) were investigated by radioimmunoassay and immunocytochemistry. In addition the distribution of these peptides were evaluated in the gastrointestinal tract of young and old animals to investigate possible age-related changes. PYY and enteroglucagon (EG) were significantly (P less than 0.001) elevated in both tumor tissue (676 +/- 152, 551 +/- 164 pmol/g) and plasma (620 +/- 160, 500 +/- 147 pmol/l) of tumor-bearing animals. Immunocytochemistry revealed PYY- and EG-like immunoreactivity in 20-30% of tumor cells. A significant decrease (P less than 0.05) in bombesin was noted in older animals, but no changes in gastric tissue content of PYY or EG could be detected between young and old animals. Gastrin was not detected in tumors and there were no significant changes in tissue or plasma levels with age. Small bowel concentrations of VIP and PYY were higher in the older mastomys (P less than 0.05). In contrast, colonic levels of bombesin, VIP, somatostatin and PYY were significantly lower (P less than 0.05) in older mastomys compared with young. The age-related changes in several peptides may reflect an adaptive response to acid hypersecretion. The multi-hormonal character of these neoplasms suggests that these tumors develop from a pluripotential stem cell.

Topics: Age Factors; Animals; Bombesin; Carcinoid Tumor; Gastric Inhibitory Polypeptide; Gastrins; Immunohistochemistry; Muridae; Neoplasm Proteins; Neurotensin; Pancreatic Polypeptide; Peptide YY; Peptides; Radioimmunoassay; Stomach Neoplasms; Vasoactive Intestinal Peptide

The association of neurofibromatosis and pheochromocytoma is well recognized; more recently, attention has been drawn to links between neurofibromatosis, pheochromocytoma, and ampullary somatostatin-rich carcinoid. Because of this association, the duodenum was explored during a recent laparotomy for resection of bilateral pheochromocytoma in a patient with von Recklinghausen's disease. A clinically unsuspected ampullary tumor was discovered; this proved to be in part a ganglioneuroma and in part a somatostatin-rich carcinoid. This paper presents full details of this carefully investigated and documented case and reviews the recent advances in this field. These studies lead us to conclude that: the clinical association of neurofibromatosis, pheochromocytoma, and D cell carcinoids ("somatostatinomas") of the ampullary region is confirmed; this association may be more common than has been previously thought, and the duodenum should be carefully examined in any patient with neurofibromatosis who undergoes laparotomy for pheochromocytoma.

Topics: Adrenal Gland Neoplasms; Carcinoid Tumor; Catecholamines; Duodenal Neoplasms; Female; Histocytochemistry; Humans; Middle Aged; Neoplasms, Multiple Primary; Neurofibromatosis 1; Pheochromocytoma; Somatostatin; Vasoactive Intestinal Peptide

Mucinous carcinoid tumor of the vermiform appendix, an uncommon variant of appendiceal carcinoid, may present clinically with ovarian metastases. We studied a tumor by immunohistochemistry and electron microscopy and reviewed eight similar cases from the literature. The primary and metastatic tumors in our case were composed of mucin-producing cells and small argyrophilic cells arranged in cords and acini. Tumor cells in both primary and metastatic sites exhibited identical patterns of immunoreactivity for epithelial antigens (epithelial membrane antigen, carcinoembryonic antigen) and neuroendocrine antigens (serotonin, vasoactive intestinal polypeptide, adrenocorticotropic hormone). Ultrastructurally, the cells contained either mucin vacuoles or dense-core neurosecretory granules; rare individual cells contained both types of inclusions. When bilateral solid mucinous ovarian tumors are discovered at laparotomy, diagnostic appendectomy is indicated if no obvious extraovarian primary tumor can be found.

Topics: Adrenocorticotropic Hormone; Appendiceal Neoplasms; Carcinoembryonic Antigen; Carcinoid Tumor; Female; Humans; Membrane Proteins; Middle Aged; Mucin-1; Ovarian Neoplasms; Serotonin; Vasoactive Intestinal Peptide

We have attempted to characterize a group of bronchopulmonary neoplasms that share certain structural features with true carcinoids but appear distinctly more pleomorphic and behave far more aggressively. In reviewing our files from 1973 to 1982, 11 such neoplasms were identified; the original diagnoses were "atypical bronchial carcinoid" (3 cases), "malignant carcinoid" (1 case), "bronchial carcinoid" (3 cases), "peripheral carcinoid" (2 cases), and "peripheral oat cell carcinoma" (2 cases). Of the 11 neoplasms, 5 were central and 6 were peripherally located. At presentation, 7 patients had lymph node metastases and 1 had a distant metastasis. No patient had a conventionally defined hormonal syndrome; however, 2 patients had a history of episodic flushing, one of which was associated with diarrhea. All cases were studied by light microscopy and light microscopic immunohistochemistry for NSE (neuron-specific enolase), serotonin, and broad-spectrum neuropeptides. Five cases were studied by electron microscopy. By light microscopy, the tumors were composed of solid clusters of polygonal to fusiform cells in an evident organoid arrangement. Foci of glandular and/or squamous differentiation were seen in 7 cases. Pleomorphism was moderate and mitoses were readily found. Focal necrosis was seen. By immunohistochemistry, 10 cases expressed NSE immunoreactivity. All cases demonstrated hormonal immunoreactivity; in 9 cases, immunoreactivity for more than one hormone was observed. The hormones most frequently expressed were serotonin, bombesin, gastrin, leu-enkephalin, and ACTH. By electron microscopy, all cases studied contained heterogeneous populations of neurosecretory granules; the latter, however, were not abundant and tended to aggregate either in the basal pole of the cells or, more frequently, interlacing "dendritelike" cytoplasmic processes. Aggregates of intermediate filaments were frequently seen. Basal lamina deposition was seen but gaps and larger areas of discontinuity were frequent. We believe that these neoplasms constitute a distinct pathologic entity for which the term "well-differentiated neuroendocrine carcinoma" has been proposed. Clinically, these tumors merit special attention since they are demonstrably more aggressive than true carcinoids but are distinctly less malignant than the intermediate or small cell variants of neuroendocrine carcinoma.

Topics: Adult; Aged; Bombesin; Bronchial Neoplasms; Carcinoid Tumor; Carcinoma, Adenoid Cystic; Chorionic Gonadotropin; Cytoplasmic Granules; Enkephalin, Leucine; Female; Humans; Immunoenzyme Techniques; Lung Neoplasms; Male; Microscopy, Electron; Middle Aged; Serotonin; Somatostatin; Staining and Labeling; Vasoactive Intestinal Peptide

A total of 87 surgical cases of gastric carcinoma including 3 carcinoid tumors were investigated with the methods of silver reaction and immunoperoxidase stain for 8 different brain-gut hormones. Argyrophil (AP) cells were demonstrated in 38 cases (44%), argentaffin (AF) cells in 18 (21%) and endocrine cells in 13 (14%). The occurrence of endocrine cells had no relation with histological types. Glicentin cells were demonstrated in 10 cases, somatostatin in 7, motilin in 3, beta-endorphin in 2 and gastrin in one. Endocrine cells appeared generally in small numbers except one carcinoid tumor which had numerous somatostatin cells. No single cell positive for more than two kinds of hormones could be demonstrated. Two undifferentiated carcinomas looking like carcinoid tumors had argyrophil cells and endocrine cells of either somatostatin or beta-endorphin. These results suggest that carcinoid-like carcinoma or endocrine cell carcinoma may lie on the intermediate state between carcinoma and carcinoid tumor.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Carcinoid Tumor; Endorphins; Female; Gastrins; Gastrointestinal Hormones; Glucagon; Histocytochemistry; Humans; Male; Microscopy, Electron; Middle Aged; Motilin; Proglucagon; Protein Precursors; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide; Vasopressins

Topics: Adrenal Glands; Adult; C-Peptide; Carcinoid Tumor; Epidermolysis Bullosa; Female; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagonoma; Humans; Male; Middle Aged; Multiple Endocrine Neoplasia; Somatostatinoma; Thyroid Gland; Vasoactive Intestinal Peptide; Vipoma; Zollinger-Ellison Syndrome

A primary pure testicular carcinoid from a 48-year-old man was examined with antisera raised against various neurohormonal polypeptides. Histochemically, both argyrophil and argentaffin reactions were positive. The immunohistochemical finding of immunoreactive cells for 5-hydroxytryptamine (5-HT) (serotonin), substance P, and vasoactive intestinal polypeptide (VIP) demonstrated the multihormonal nature of this tumor.

Topics: Carcinoid Tumor; Gastrointestinal Hormones; Humans; Male; Middle Aged; Serotonin; Substance P; Testicular Neoplasms; Vasoactive Intestinal Peptide

Previous studies from our laboratory indicate that the lymph flow response of the cat ileum to net volume secretion is dependent upon the mechanism involved in the secretory process, i.e, active secretion (cholera toxin) decreases lymph flow while passive fluid secretion (increased portal pressure, plasma dilution) is associated with a rise in lymph flow. In the present study, we examined the effects of ricinoleic acid, vasoactive intestinal polypeptide, theophylline, histamine, and human carcinoid serum on lymph flow in autoperfused segments of cat ileum. Local intraarterial infusion of theophylline, vasoactive intestinal polypeptide, or human carcinoid serum caused lymph flow to decrease. However, intraluminal placement of ricinoleic acid or intraarterial infusion of histamine produced significant increases in lymph flow. The results indicate that the fluid secretion associated with vasoactive intestinal polypeptide, theophylline, and carcinoid serum are consistent with an active process while ricinoleic acid and histamine secretions are associated with a passive component.

Topics: Animals; Blood Proteins; Carcinoid Tumor; Cats; Histamine; Ileum; Intestinal Secretions; Lymph; Ricinoleic Acids; Secretory Rate; Theophylline; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Digestive System Neoplasms; Gastrointestinal Hormones; Hormones, Ectopic; Humans; Pancreatic Neoplasms; Somatostatin; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Achlorhydria; APUD Cells; Apudoma; Carcinoid Tumor; Carcinoma; Cholecystokinin; Diarrhea; Endocrine System Diseases; Humans; Hypokalemia; Malignant Carcinoid Syndrome; Neoplasms; Pancreatic Diseases; Paraganglioma; Paraneoplastic Endocrine Syndromes; Peptides; Prostaglandins E; Somatostatin; Syndrome; Thyroid Neoplasms; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Gastrointestinal Neoplasms; Glucagon; Growth Hormone-Releasing Hormone; Humans; Pancreatic Polypeptide; Peptide Biosynthesis; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Pancreas and gut hormones are involved in many endocrine and gastrointestinal diseases. Radioimmunoassays for these hormones have proved particularly valuable in diagnosis, localisation and control of treatment of endocrine tumours, of which many are mixed. An estimate based on ten years experience in a homogenous population of 5 million inhabitants (Denmark) suggests, that endocrine gut tumour-syndromes on an average appear with an incidence of 1 patient per year/syndrome/million. At present six different syndromes are known: 1) The insulinoma syndrome, 2) The Zollinger-Ellison syndrome.3) The Verner-Morrison syndrome. 4) The glucagonoma syndrome. 5) The somatostatinoma syndrome, and 6) the carcinoid syndrome. Accordingly diagnostically valuable RIAs for pancreas and gut hormones include those for insulin, gastrin, VIP, HPP, glucagon, somatostatin, and presumably also substance P. It is probably safe to predict that the need for gut and pancreas hormone RIAs within the next decade will increase greatly in order to assure proper management of tumours producing gastroentero-pancreatic hormones.

Topics: Adenoma, Islet Cell; Carcinoid Tumor; Cholecystokinin; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Intestinal Neoplasms; Motilin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Radioimmunoassay; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Apudoma; Carcinoid Tumor; Female; Gastrins; Gastrointestinal Neoplasms; Glucagon; Humans; Insulin; Insulin Secretion; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatin; Vasoactive Intestinal Peptide

Topics: Animals; Carcinoid Tumor; Cholecystokinin; Dogs; Enterochromaffin Cells; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Intestinal Neoplasms; Pancreatic Polypeptide; Rats; Secretin; Somatostatin; Stomach Neoplasms; Vasoactive Intestinal Peptide