Bronchial carcinoids. Review of 124 cases.

A total of 124 patients with bronchial carcinoid were seen at Memorial Sloan-Kettering Cancer Center between 1949 and 1983. Of these, 68 were female and 56 were male. The age range was 12 to 82 years (median 55 years). Eleven of the tumors were incidental pathological findings at autopsy or operation and were excluded from survival data determinations. At the time of diagnosis, 82 patients had disease confined to the lung or bronchus, 19 had regional lymph node metastases, and 12 had distant metastases. Patients with distant metastases were more commonly male and smokers, and their tumors were mainly atypical carcinoids histologically, compared with those of patients with localized disease. Patients with distant disease were treated with external radiation and/or chemotherapy, and their median survival was 8 months. Of the 101 patients with disease localized to one hemithorax, endobronchial resection was performed in six and pulmonary resection in 95 (pneumonectomy 14, bilobectomy nine, lobectomy 52, sleeve resection five, segmentectomy 15). Recurrence following endobronchial resection was observed in four of six patients. Disease-free actuarial survival (calculated by the Kaplan-Meier method) following pulmonary resection was 92% at 5 years and 77% at 10 years. Factors predisposing to recurrence were tumor size greater than 3 cm (p less than 0.004), an atypical carcinoid on histologic study (p less than 0.001), and regional lymph node metastases (p = 0.01). Disease-free survival at 5 and 10 years in 19 patients who had regional lymphatic metastases was 74% and 53%, compared with 96% and 84% in those without lymphatic metastases. We conclude that (1) carcinoid tumors are malignant and 10% of patients present with metastases and (2) for patients with clinically localized tumors, the prognosis is determined by the size and histologic features of the tumor and the status of the regional lymph nodes, which must be assessed at thoracotomy.

The diffuse neuroendocrine (APUD) system.

The bulk of experimental evidence indicates that the APUD series of cells is a distinct system based upon common pathophysiological features. The diffuse nature of this system with elements in the central and peripheral nervous system suggests a more complex interaction of the body's homeostasis than has been established. It is probable that as radioimmunological and radioenzymatic assays become more widely available and standardized, other apudomas will be described. Finally, an understanding of the APUD concept, with its peculiar pluripotential for the production of biogenic amines and peptides, the multicentric nature of the disease and the possibility of multiple cell involvement, is of key importance in managing patients. Studies of the apudomas will also advance the understanding of the normal physiologic interrelationships of the APUD cells.

Clinical significance of the association of the Von Hippel-Lindau disease with pheochromocytoma and pancreatic apudoma.

Von Hippel-Lindau disease (VHLD) is a rare disorder known to occur with pheochromocytoma. We report a case with this association and also with pancreatic apudoma. We believe that this is the fifth reported case of this triad, which represents an overlap in the multiple endocrine neoplasia (MEN) classification. Many recent reports of overlap of MEN syndromes challenge the validity of this classification. New understanding of the embryologic origin of cells of endocrine organs has led to the elucidation of the APUD (amine precursor uptake and decarboxylation)-neuroendocrine system. Integration of the APUD system may be important to understanding the pathogenesis of the MEN-like syndromes as well as their relationship to the neurocutaneous syndromes. Any endocrine tumor or neurocutaneous syndrome should be evaluated to exclude a spectrum of possible associations.

[APUD system (problems of structural and functional organization, histogenesis and pathology)]. / APUD-sistema (voprosy strukturno-funktsional'noi organizatsii, gistogeneza, patologii).

The aspects of structure and function of the APUD-system under normal and pathological conditions are analysed. New terms and concepts (apudocyte, apudoblast, apudogenesis, apudopathies) applicable to the APUD-system are introduced. It is suggested that some apudocytes originate from polypotential stem cells. The dysfunctions of the APUD-system (apudopathies) are described, their classification is suggested, and the role of apudocytes in the endogenous mechanisms of oncogenesis is analysed.

Relationships between neural crest cells and serotonin in newborn mice.

The experimental newborn mice injected intraperitoneally with serotonin within 24 h after birth and survived up to 2-days showed multiple APUDomas, hyperplasia, heterotopic melanin pigmentation and the cell death of neural crest cells. Further, the degeneration occurred in the Auerbach, Meisner nerve plexus, autonomic ganglia. The flocculent densities were seen in the brain, and in the pulps and the periodontal membrane of teeth. It is thought that these phenomena may be associated with not only cyclic AMP but also calcium, and that neural crest cells may be autoreceptor.

[Neurocristopathies : embryology, physiology, and pathology of the neural crest derivatives (author's transl)]. / Les neurocristopathies. Embryologie, physiologie et pathologie des dérivés de la crête neurale.

The authors review various of the derivatives of the neural crest, consider their relationship with the APUD System, and deduce the physiopathological consequences applicable to these cells, whose only similarity lies in their common embryologic origin. They propose a system of classification of interrelated pathological conditions that these cells may show, an detail clinical information as well as the mode of genetic transmission of the principal neurocristopathic syndroms.

[Neuroendocrine tumors. Biochemical and physiopathological aspects]. / Tumeurs neuro-endocriniennes. Aspects biochimiques et physio-pathologiques.

Neuroendocrine tumors (secreting bioamines, peptides, hormones, prostaglandins...) represent rather homogeneous group since they correspond to a benign or malignant proliferation of cells belonging to the diffuse neuroendocrine system. This system might be considered as an extension of the concept (APUD System) proposed by Pearse to account for the common properties of these largely distributed cells. Among neuroendocrine tumors we focused since some years on apudomas and particularly carcinoïd tumors. The determination of their various secretion products in biological fluids allows the early and efficient detection of such tumors exhibiting a very slow growth. Finally the in vitro culture of carcinoïd cells appears to be of great interest in various research fields such as oncology, biochemistry and pharmacology.

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.

Apudomas. Parte II. Tumores APUD del pancreas. / Apudoma. Part II - Apud tumors of the pancreas

Most of the digestive tract "APUDomas" originated in cells of the pancreatic islets (islets of Langerhans). The islets of Langerhans consist of aproximately one million clusters of cells dispersed among the pancreatic acinar cells. The various islets cells are believed to arise from the neural crest and along with other secretory cells belong to a family of cells designated of the APUD (amine precursor uptake and decarboxylation) series. On the basis of histochemical, ultrastructural and immunofluorescent techniques as well as the hormonal secretory products the islet cells as recognized as consisting of five distinct types: Alpha, Beta, Delta, f and enterochromaffin. Hyperinsulinemia resorting in hypoglycemia is the major clinical manifestation of insulin-producing islets cell tumors (insulinomas). This tumors may be either begin or malignant, the later representing up to 15 percent of the total. They may occur in any part of the gland, but over 60 percent occur in the body and tail of the pancreas. The diagnosis is usually made by finding an abnormally low plasma glucose concentration and an elevated (inappropiate) plasma insulin in the fasting state; but it may be necessary to fast the pacient for 72 hours. In rare instances hypoglycemia may be associated with a normal plasma insulin concentration. In such circunstances the insulin/glucose ratio may be helpful; a ratio in excess of 0.30 is indicative of hyperinsulinism. Once the diagnosis of insulinoma has been made, the tumor should be excised surgically. Gastrinomas (Zollinger-Ellison syndrome are non-beta-cell islet cell tumors which secrete excessive amounts of gastrin. The hallmarks of the Zollinger-Ellison syndrome are recurrent and intractable duodena ulcers and diarrhea. In a patient in whom gastrinoma is suspected provocative testing may be necessary to establish the diagnosis