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R F Gagel

Publications and source records attributed to R F Gagel.

118 records · Page 7Linked to original sources
PubMed1979

C-cell hyperplasia and medullary thyroid carcinoma in the rat. An immunohistochemical and ultrastructural analysis.

Medullary thyroid carcinoma (MTC) is a distinctive neoplasm which is derived from the calcitonin-producing intrathyroidal C-cell system and which develops commonly in untreated rats of various strains. Thyroid glands of Long-Evans rats ranging in age from 3 months to 3 years showed a spectrum of C-cell proliferative abnormalities. As compared to 3-month-old control rats, thyroids from 9- to 12-month-old animals exhibited mild diffuse C-cell hyperplasia (CCH). Thyroids from animals ranging from 1 to 3 years of age exhibited progressively more severe C-cell abnormalities including severe diffuse CCH, nodular CCH, and/or MTC. In contrast to the normal basal serum calcitonin levels in controls and in animals with mild diffuse CCH, animals with severe diffuse CCH, nodular CCH, or MTC had elevated basal serum calcitonin values. Nodular CCH was characterized by the replacement and enlargement of individual follicles by C-cells. Larger foci of nodular CCH were characterized by similar changes in multiple adjacent follicles or by an irregular expansion of individual follicles. MTC was characterized by penetration of the follicular basal lamina by C-cells with extension into the adjacent thyroid stroma. In addition to the high incidence of thyroidal C-cell abnormalities, diffuse and/or nodular parathyroid hyperplasia was commonly found. There was no evidence of chronic renal failure in these animals, and the serum calcium levels were within normal limits. Although the stimulus for the initial C-cell proliferation remains unknown, the appearance of MTC is preceded by relatively prolonged phases of CCH. These findings are essentially identical with those noted in human familial MTC and indicate that the rat provides a useful model system for studying the regulation of C-cell proliferation during the processes of neoplastic development and progression.

Aging↗
PubMed1978

Natural history of familial medullary thyroid carcinoma: effect of a program for early diagnosis.

To detect familial medullary thyroid carcinoma in a premetastatic stage, we administered tests provocative of calcitonin secretion (infusion of calcium or pentagastrin or both) each year for seven years to members of a pedigree now numbering 107. Since 1970, 21 patients converted from normal to abnormal secretory responses (two separate tests in which calcitonin levels exceeded 0.58 ng per milliliter). Twenty of 21 glands removed showed C-cell hyperplasia, and eight of the 20 also showed foci of carcinoma. As compared to the 12 patients with tumors detected during the first year of screening, all of whom had bilateral carcinoma (seven of 12 with local metastases), later carcinomas were smaller (mean diameter of 0.2 vs. 0.8 cm), were unilateral (in all but two cases) and occurred in younger patients (mean age of 14.9 vs. 36.4 years), and none had detectable metastases.

Adolescent↗
PubMed1976

Gastrinoma of duodenal G-cell origin.

A 65-year-old man with hypergastrinemia associated with the Zollinger-Ellison syndrome was found to have a duodenal "carcinoid-islet cell tumor." Gastrin levels have remained normal for more than 1 year following total gastrectomy and removal of the duodenal tumor. Immunohistochemical studies for gastrin localization revealed positive staining of the tumor and of a population of nonneoplastic G-cells in the adjacent duodenal mucosa and Brunner's glands. These results support the hypothesis that gastrinomas may arise as primary tumors from duodenal G-cells rather than from ectopic pancreatic tissue. "Carcinoidislet cell tumors," like other tumors of APUD-cell origin, may express dual biochemical functions in the form of polypeptide hormone and/or amine secretion. Their content of specific hormonal products may be predicted on the basis of sensitive histochemical and immunohistochemical techniques.

Adenoma, Islet Cell↗
PubMed1976

Total thyroidectomy for occult familial medullary carcinoma of the thyroid in children.

Experience with 17 children in one kindred with familial medullary carcinoma of the thyroid and pheochromocytoma has demonstrated the utility and validity of periodic provocative testing by calcium infusion or pentagastrin injection in the identification of children with early medullary carcinoma of the thyroid or its premalignant precursor, C-cell hyperplasia. In these 17 patients with two consecutive elevations of calcitonin levels greater than 0.55 ng/ml after stimulation all but one have had MTC or CCH at operation. Total thyroidectomy has been well tolerated and can be performed with an acceptably low incidence of complications in this group of patients.

Adolescent↗
PubMed1976

Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma.

The syndrome of familial medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia is inherited as an autosomal dominant trait, and is characterized by development of bilateral and multicentric thyroidal and adrenal medullary tumors. One of the earliest manifestations of adrenal medullary hyperfunction in patients with this syndrome is an increased ratio of epinephrine to norepinephrine in urine. In order to define the morphologic correlates of these early catecholamine abnormalities in a large kindred with familial MTC, a morphometric analysis based on a point-counting system to asses adrenal medullary volume was undertaken. These studies clearly revealed adrenal medullary hyperplasia as reflected by a two- to three-fold increase in medullary volume and weight as compared to age- and sex-matched controls. The increase in total medullary mass resulted from diffuse and multifocal modular proliferations of adrenal medullary cells primarily within the head and body regions of the glands. These results support the hypothesis that the pheochromocytomas in patients with familial MTC may, in fact, represent extreme degrees of nodular hyperplasia of the medulla.

Adrenal Medulla↗
PubMed1976

Streptozocin-treated Verner-Morrison Syndrome: plasma vasoactive intestinal peptide and tumor responses.

A patient with watery diarrhea, hypokalemia, hypochlorhydria, and a non-beta islet cell carcinoma of the pancreas (Verner-Morrison syndrome) was found to have an elevated vasoactive intestinal peptide (VIP) concentration in the plasma as well as in the tumor. Treatment with streptozocin resulted in a dramatic subjective and objective tumor response in this patient. Plasma VIP concentration fell into the normal range after four courses of treatment, diarrhea ceased after the third course of therapy, and measurable tumor mass markedly decreased during that same period of time. The patient remains in clinical remission with no evidence of tumor regrowth 18 months after the beginning of treatment. In this patient, plasma VIP measurements were an excellent marker of tumor activity and correlated well with objective disease measurements and clinical response.

Adenoma, Islet Cell↗
PubMed1975

Natural history of the familial medullary thyroid carcinoma-pheochromocytoma syndrome and the identification of preneoplastic stages by screening studies: a five-year report.

1. In the fifth year of followup, 8 of 12 original patients thyroidectomized for MTC, diagnosed solely by abnormal calcitonin values, are disease free by all criteria. Elevated calcitonin levels are the only manifestation of active disease in three patients with presumed metastases. 2. Routine annual screening of susceptible individuals is a practical measure and has in 6 cases detected the premalignant condition of G-cell hyperplasia and in 1 patient a premetastatic state of MTC. It is premature to conclude that yearly screening is sufficient to detect all cases of premetastatic disease and for this reason we are recommending a yearly screen with pentagastrin and calcium tests and the more convenient pentagastrin test at 6 month intervals for those in the high-risk age group between 8 and 18. If screening at such intervals proves to be ineffective in preventing the disease in every case, consideration must be given to prophylactic thyroidectomy although we are not currently recommending this precedure. 3. Pentagastrin injection is often a more effective secretagogue for calcitonin than is calcium infusion, but this is not uniformly true. We therefore recommend use of both tests as the most appropriate screening procedure. 4. Epinephrine is a major secretory product of pheochromocytomas in the J-kindred and sequential E/N ratios may be of use in the early detection of pheochromocytoma in other kindreds. 5. Adrenal medullary hyperplasia has been found in 3 adrenal glands and is probably a preneoplastic condition analogous to C-cell hyperplasia.

Adolescent↗
PubMedDate not supplied

The surgical treatment of medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a unique disease in solid tumor oncology due to its ability to secrete calcitonin (iCT), a highly sensitive and specific serum marker of persistent or recurrent disease even at a microscopic level. The relatively long duration of survival experienced by most patients with MTC combined with the visible nature of surgical complications, when they occur, has caused most surgeons to take a conservative approach to the operative management and follow-up of patients with MTC. In contrast, the patient, family physician, and endocrinologist watch the iCT slowly rise, indicative of persistent and usually progressive invasive cancer. Amidst this clinical dilemma, we developed a standardized diagnostic and operative strategy to maximize local-regional tumor control and facilitate patient management.

Calcitonin↗
PubMedDate not supplied

Changing concepts in the pathogenesis and management of thyroid carcinoma.

A wealth of knowledge regarding the molecular causation of thyroid carcinoma has been accumulated over the past five years. This information has already had a significant impact on the management of some forms of thyroid carcinoma. The challenge during the next 10 years will be to incorporate newly acquired information into diagnostic and therapeutic approaches to thyroid carcinoma and to coordinate use of this information with time-tested approaches to further decrease morbidity and mortality from thyroid carcinoma.

Carcinoma↗