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Preoperative physical assessment of thyroid glands in previously irradiated patients.

The Evanston Hospital maintains an Irradiated Thyroid Evaluation Clinic that has evaluated 695 patients since 1975. One hundred fourteen patients were retrospectively analyzed, and an attempt was made to correlate the preoperative physical examination with the pathologic specimen after thyroidectomy. There was no statistically significant difference between the incidence of carcinoma in glands containing a single nodule (23 per cent) and in multinodular glands. Postirradiation thyroiditis complicated the physical description of glands preoperatively. The categorization of physical findings served only to identify persistent thyroid abnormalities, which must be explored surgically. The overall incidence of carcinoma in the 114 available cases was 34 per cent, with nodal metastases in 18 per cent of the patients with carcinoma.

Female↗

Anaplastic cardcinoma of the thyroid in a population irradiated for Hodgkin Disease, 1910--1960.

Post-irradiation carcinoma of the thyroid is usually histologically well-differentiated. In general, those subjects who developed carcinoma had been exposed to low-to-moderate doses of irradiation for benign conditions. We reviewed the charts of 520 patients with Hodgkin's disease seen at Roswell Park Memorial Institute, and found 2 cases of anaplastic carcinoma amongst other thyroidal abnormalities. The existing reports of post-irradiation carcinoma are reviewed and suggestions are made for the management of heavily irradiated, potentially cured patients with Hodgkin's disease.

Adult↗

Chromosome radiation-induced aberrations in patients with Hodgkin's disease. Possible correlation with second malignancy?

The karyotype of peripheral blood lymphocytes has been studied in a group of patients with Hodgkin's disease. Before any therapy, the karyotype was either normal or aneuploid. A few months after radiotherapy (total nodal irradiation) a conspicuous amount of structural chromosome aberrations was found. Three to six years after completion of radiotherapy, the lymphocyte karyotype was almost normal, even if stable ionizing radiation-induced aberrations were still detectable. This is consistent with the normal behaviour of these patients and with the long-lasting effect of radiations on nuclear D.N.A. Owing to the close relationship between ionizing raditions and chromosome aberrations on one hand, and abnormal karyotypes and tumors on the other, it cannot be overlooked that these aberrations may play an important role, together with other carcinogenic factors, in the development of second malignancies in these patients.

Adolescent↗

Serum albumin and antibodies in the diagnosis of thyroid cancer.

Anti-thyroglobulin antibodies, anti-thyroid microsomal antibodies, serum thyroglobulin, and carcinoembryonic antigen were assayed in sera of patients with a history of thyroid irradiation and in patients with thyroid cancer. In irradiated patients, the frequency of positive results for each test was increased above the frequency found in a control population, with a significant increase at P less than .05 for TGHA and TG levels. However, the tests (with the exception of serum thyroglobulin) did not clearly segregate irradiated patients with benign or malignant lesions from those with no clinically detectable abnormalities. Elevations of serum thyroglobulin above 300 ng/ml were found only in patients with thyroid cancer, but in these patients the diagnosis was usually clinically obvious.

Adult↗

Cytogenetics of juvenile type chronic granulocytic leukemia.

Cytogenetic examination of bone marrow cells from three patients with juvenile chronic granulocytic leukemia (CGL) showed 46,XX,3p-,11p+ ,t(11p:3p) in one case, 45XY,-E in another, and 45X(X),-C/47,XX,+G in the third. The case with the translocated chromosome originally presented like an acute lymphocytic leukemia (ALL). TAn overt clinical picture of juvenile CGL emerged two and a half years later. Serial study of this case revealed no cytogenetic abnormalities until two years after the diagnosis of ALL, when the translocated chromosome was first observed. Unlike the Ph1 chromosome in adult type CGL, chromosomal abnormalities in juvenile CGL lack specificity, resembling ALL in this respect.

Bone Marrow↗

Radiation-related thyroid carcinoma.

Of 1,825 subjects with a history of head or neck irradiation, 358 (19.6%) were found to have thyroid abnormalities. One hundred sixty-five (9%) had either single or multiple nodules 153 (8.4%) had diffuse thyromegaly, and 40 (2.2%) had had thyroid surgery. Surgery was performed on 113 subjects with nodules; carcinoma was found in 34 (30.1%). Clinical examination of the neck was the most valuable method of detecting abnormalities. Detection of nodules was not significantly enhanced by routine use of thyroid imaging studies. Measurements of levels of serum thyroid-stimulating hormone, thyroxine, triidothyronine resin uptake, and thyroid antibodies were not useful in screening for nodules or carcinoma.

Adult↗

Second malignancies complicating Hodgkin's disease in remission.

The incidence of second tumours occurring in the course of Hodgkin's disease has been investigated in a series of 452 patients treated with standard chemotherapy or radiotherapy, combination chemotherapy alone, intensive radiotherapy alone, or both intensive radiotherapy and combination chemotherapy administered in sequence. 16 tumours were noted. When analysed according to mode of treatment, 6 cases occurred in a group of 62 patients who received both modalities. When analysed for age, sex, and man-years of follow-up, this group appears to have 14-5 times the risk of developing a second tumour. However, that subgroup which had a complete remission after intensive radiotherapy followed by a relapse of disease, prior to receiving combination chemotherapy, had the highest risk with 18-5 times greater incidence of second tumour than expected. It is noteworthy that, of the 16 second tumours, 2 were acute myeloid leukaemia; in both cases a similar chromosomal abnormality (45 chromosomes, C-group deletion) was noted. The mechanism of oncogenesis may represent a combination of the immunosuppressive effects and cellular effects of those forms of treatment.

Adolescent↗

Acute monocytic leukemia in an irradiated Beagle.

A purebred female Beagle dog that had received 2,000 R of protracted wholebody gamma-irradiation from 60Co when 14 months old had hematologic changes consistent with a myeloproliferative disorder 3 years after the termination of radiation exposure. Peripheral blood and bone marrow findings during the 7-month period before death showed progressive anemia with increased numbers of platelets; immature granulocytes, monocytes and promonocytes. A period of partial remission occurred during which time the peripheral blood was aleukemic, although there was marked thrombocytosis and abnormal erythropoiesis which was evidenced by bizarre circulating nucleated red cells, anisocytosis, poikilocytosis and Howell-Jolly bodies. The dog had a terminal crisis with marked leukocytosis, most cells in the peripheral blood being bizarre monocytes and promonocytes. Tissues obtained at necropsy showed diffuse as well as focal infiltration of the spleen, liver, lymph nodes, heart, kidney and gastrointestinal wall with immature neoplastic cells resembling monocytes and monocytic precursors. The monocytic differentiation of the invasive cell population was confirmed by morphological, cytochemical, histological, ultrastructural and in vitro cell culture studies.

Animals↗

Parathyroid adenomas following irradiation.

Parathyroid adenomas have been demonstrated to occur following external head and neck irradiation. The median latency interval is 30 years. In a series of 74 consecutive patients with histologically diagnosed parathyroid adenomas, 25% gave a history of prior radiation exposure. When compared to a matched control incidence of 7.9%, statistical significance is reached at p less than 0.01. Thyroid abnormalities were present in 68% of the irradiated patients, and 30% of these were malignant. Tumor of skin, breast, and parotid gland also occurrred more frequently than expected. Forty-seven percent of the irradiated group had malignant neoplasms within the radiation field. The histopathology of the radiation-associated parathyroid adenomas is similar to that seen experimentally.

Acne Vulgaris↗

Acute non-lymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia: cytogenetic studies.

Seven cases of acute nonlymphocytic leukemia (ANLL) and one of malignant myeloproliferative syndrome were identified from a pool of 189 cases of non-Hodgkin's lymphoma (NHL) and CLL treated primarily with extensive radiotherapy at the Clinical Center, the National Institutes of Health. Four patients also received chemotherapy, two for only short periods. The median time interval from the diagnosis of the primary malignancy to the development of leukemia was 61 months (range 33 to 98 months) and the median survival after the diagnosis of leukemia was two months (0 to 9 months). All eight patients were cytogenetically abnormal and serial chromosome studies revealed that hypodiploidy was the most commonly observed chromosomal abnormality. Abnormalities of chromosome no. 7 were seen in all five patients analyzed by the chromosome banding technique; four of them had monosomy 7. The next most frequently involved chromosome was no. 5. The complexity, extensive nature, and long duration of the cytogenetic abnormalities prior to the diagnosis of leukemia in these patients may be characteristic of secondary leukemia in radiation-treated lymphoma and the presence of such anomalies may predict leukemic transformation.

Adult↗

Acute nonlymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia: clinical studies.

Seven cases of acute nonlymphocytic leukemia (ANLL) and one case of a malignant myeloproliferative syndrome have been seen after extensive radiation therapy for non-Hodgkin's lymphoma or chronic lymphocytic leukemia. A myeloproliferative syndrome with abnormalities in granulocytic, erythrocytic, and thrombocytic cell lines was present in all patients and in seven patients preceded ANLL by 2--18 months. The median time to the development of ANLL after primary disease therapy was 61 months (33--98 range). The leukemia was extremely refractory to therapy and median survival after diagnosis of ANLL was two months (range 0--9 months). Leukemia was seen only in those patients who received multiple courses and multiple techniques of radiation therapy.

Adult↗

[Correlation between radiological, scintigraphic and histological changes in bone in rabbits following irradiation with single and fractionated doses (author's transl)].

The left hind legs of eight rabbits were irradiated with 1.750 rad in a single dose or with 4,650 rad divided over a period of three weeks. These animals, as well as four who had not been irradiated, were examined periodically radiologically and with 99m Technetium pyrophosphate scintigrams during one year. No difference could be detected between the results of the single and fractionated doses. Scintigraphically there was a biphasic increase in uptake, the first peak co-inciding with the irradiation and of vascular origin, whereas the second peak occurred at four months and was due to a change in bone metabolism. At the end of a year uptake in the irradiated limb was slightly reduced. The earliest radiological changes were found after six months, at the end of the second scintigraphic peak; they consisted of coarsening and blurring of the trabeculae, nonhomogeneous spotty mineralisation and endosteal scalloping. Six animals developed a radiation-induced bone sarcoma, first demonstrated either by scintigraphy or radiology depending on its histology. The value of combining radiological and scintigraphic examinations for the early detection of post-radiation abnormalities is stressed.

Animals↗

Trisomy no. 15 in murine thymomas induced by chemical carcinogens, X-irradiation, and an endogenous murine leukemia virus.

Chromosome banding techniques were used to examine the karyotype of tumor cells from thymic lymphomas induced by three different carcinogens (X-irradiation, polycyclic aromatic hydrocarbons, and an endogenous leukemogenic virus) after injection into neonatal mice of 2 different inbred mouse strains (CFW/D and C57BL/Ka). A total of 89 tumors were studied, and of these 85.4% were characterized by a modal chromosome number of 41. The additional chromosome was the result of a specific abnormality identified as trisomy of chromosome no. 15. The results obtained were independent of the carcinogenic agents and the strain of mouse used. Of the 13 tumors found to have a normal chromosome complement, 4 were induced by X-irradiation and the remaining 9 by the chemical carcinogens. All 15 virus-induced tumors analyzed had a modal chromosome number of 41.

Animals↗

Effects of single dose supervoltage whole brain radiation in Macaca mulatta.

Three groups of four Macaca mulatta were exposed respectively to a single dose of 1000, 1500, and 2000 rads of 20 MeV whole brain radiation with one animal from each group and a control scheduled for sacrifice at 6, 12, 18, and 24 months. With 1000 rads there were no abnormalities. The characteristic lesions in the animals exposed to 1500 and 2000 rads were small foci of delayed radiation necrosis that in the acute phase were relatively large due to marked local accumulation of edema fluid and at later stages were decreased in volume and showed early mineralization. Correspondingly the monkeys frequently showed papilledema, evidently from brain swelling, as the initial clinical finding, and upon histological examination at later stages, brain atrophy and ventricular dilatation. After exposure to 1500 rads the necrotic process was primarily in the white matter of the cerebral hemisphere and progressed from a small number of lesions in this location at 6 months to confluent necrosis at 12 months. At 18 and 24 months, although there was no evidence of further necrosis, there was evidence of increasing gliosis and at 24 months the occurrence of three independent glioblastomas. With exposure to 2000 rads there was a profuse wide scatter of focal necrotic lesions with a predilection for the basis pontis and a clinical deficit inconsistent with survival past 6 months. Accumulation of minute mineral deposits and atherosclerotic plaques were also noted in these monkeys and appeared to be related to both dose and survival time.

Animals↗

[Hereditary melanotic tumors of Drosophila. Determination of the tumorous transformation of larva hemocytes].

Two different phenomena contribute to the histogenesis of melanotic formations in tumoral strains of drosophila : an abnormal multiplication of certain blood cells and their encapsulation by normal hemocytes. The statistical distribution of melanotic tumors in populations of individuals submitted during precise periods of their life to the action of agents such as supraoptimal temperature or ionizing radiations, permits to suggest for the tumoral transformation of larval hemocytes in drosophila, the following mechanism : this transformation is caused by an event occuring in the cytoplasm and determined by the activity of a nuclear gene.

Animals↗