Cases reported "Radiation Injuries"

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1/9. Widespread morphoea following radiotherapy for carcinoma of the breast.

    We report a case of a 60-year-old lady who was treated with radiotherapy for breast cancer of both breasts 8 years apart. Thirteen years after the first dose of radiotherapy she developed localized morphoea in all the irradiated skin of the chest wall and also the gaiter regions of both lower legs. radiation-induced localized morphoea has been previously reported; however, there is no previous publication of an occurrence at a distant site as in this case. This case demonstrates that morphoea can occur distant to the original breast carcinoma and site of radiotherapy. We postulate that radiotherapy can induce neoantigen formation, which initiates a T cell response and subsequent tissue growth factor alpha release. Tissue growth factor alpha induces fibroblast activation and collagen production may persist due to a positive feedback mechanism within the fibroblast. The reason why the disease did not generalize remains unclear.
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2/9. Pseudosclerodermatous panniculitis after irradiation and bronchiolitis obliterans organizing pneumonia: simultaneous onset suggesting a common origin.

    Due to the technical evolution of radiation therapy of breast carcinoma, new manifestations occur as side effects. Newly described unexpected cutaneous events are morphea of the breast and pseudosclerodermatous panniculitis after irradiation (PPAI). They appear as specific consequences of megavoltage radiation. radiotherapy-induced bronchiolitis obliterans organizing pneumonia (R-BOOP) is one of the pulmonary manifestations due to recent advances in radiotherapy of breast carcinoma. We report a case of PPAI and R-BOOP of simultaneous onset in a 60-year-old woman 6 months after megavoltage radiation therapy for breast carcinoma. We also noted an improvement of both unexpected reactions with systemic corticosteroid therapy and a common relapse when tapering the treatment. Only eight cases of PPAI have previously been reported. We believe that this entity is often underdiagnosed. The symmetrical onset and parallel evolution suggest a common origin for PPAI and BOOP in our case: the megavoltage radiation therapy. The pathogeny of R-BOOP is not direct toxicity of irradiation because untreated areas can also be affected. Pathogenesis of PPAI remains unknown, but a simultaneous onset with R-BOOP suggests a similar mechanism. While a cumulative dose of irradiation does not seem to be determinant an immune reaction to neoantigens induced by radiation could be an hypothesis.
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3/9. Monitoring of serum KL-6 antigen in a patient with radiation pneumonia.

    serum marker KL-6 antigen has been reported to be a valuable indicator of the disease activity of interstitial pneumonia. It is not clear how sensitive the serum KL-6 antigen level is in reflecting histologic changes in lung tissues. We report here the results of serial measurements of serum KL-6 antigen in a 76-year-old male patient with radiation pneumonia. serum KL-6 antigen levels were more sensitive than lactate dehydrogenase and procollagen type III N-terminal peptide. The level of serum KL-6 antigen appears to reflect the histologic changes of the lung more sensitively than does c-reactive protein.
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4/9. Graves' disease with ophthalmopathy following radiotherapy for Hodgkin's disease.

    The number of patients achieving long-term survival following neck irradiation for Hodgkin's disease and other malignancies is increasing. Paralleling this increase in survivors is the development of late complications of the therapy itself. Eleven patients have previously been reported who developed Graves' ophthalmopathy 18 months to seven years after receiving neck radiotherapy for nonthyroidal malignancies. The seven patients who had HLA typing were all HLA-B8 negative, despite the reported association of the hla-b8 antigen with Graves' disease. A patient who is HLA-B8 positive who developed Graves' ophthalmopathy and hyperthyroidism nine years after receiving mantle radiotherapy for Hodgkin's disease is reported. It is recommended that Graves' disease be included among the thyroid diseases that receive consideration during follow-up of patients who have received mantle radiotherapy.
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5/9. diethylstilbestrol-exposed monozygotic twins discordant for cervicovaginal clear cell adenocarcinoma.

    Monozygotic, 17-year-old, female twins exposed to diethylstilbestrol (DES) in utero and discordant for cervicovaginal clear cell adenocarcinoma are reported. Benign teratologic changes were present in both. The twin with cancer was treated by extensive operation and postoperative irradiation. No tumor has appeared in either twin in the 4 years subsequent to therapy. Discordance for cervicovaginal clear cell adenocarcinoma in this situation suggests that factors other than embryonic exposure to DES, extrauterine in location and nongenetic in character, were operative in tumorigenesis. The twins were compared in regard to lifetime radiation exposure and evidence of previous viral disease. The only substantial difference was an elevated titer of antibody in the twin with cancer to the capsid antigen of the Epstein-Barr virus, a herpesvirus with oncogenic capability.
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6/9. Cytogenetic and immunologic identification of clonal expansion of stem cells into T and B lymphocytes in one Atomic-bomb survivor.

    Chromosome aberration frequency in peripheral blood lymphocytes is elevated in radiation-exposed people, and identical karyotypic changes are not infrequently encountered in one blood sample as well as in separate samples from the same donor. Such clonal propagation originates either from a single immature stem cell able to expand and differentiate into several cell types or from a single mature lymphocyte able to expand after antigen stimulation in vivo. In the present study, a total 71 T-lymphocyte and 58 B-lymphocyte colonies were established from one atomic-bomb survivor, who showed a persistent clonal aberration t(4;6), t(5;13) in phytohemagglutinin culture of peripheral lymphocytes. Nearly 10% of the colonies (6 T-lymphocyte and 7 B-lymphocyte colonies) showed the same chromosome abnormality. Southern blot analyses of the T-cell-receptor or Ig heavy-chain gene showed all different rearrangement patterns among T- or B-lymphocyte colonies, respectively. Thus, the chromosome aberration occurred in a precursor cell before differentiation into T and B lineages and was not derived from monoclonal proliferation of mature T or B lymphocytes in the periphery. To confirm the issue, cells from erythroid burst-forming unit (BFU-E) colonies were examined by the chromosome-painting method. Two translocations, one between chromosomes 5 and 13 and the other between chromosomes 4 and one of group C, perfectly consistent with the t(4;6), t(5;13), were found in about 10% of the cells. The results imply that a single stem cell of an adult is capable of generating long-lived myeloid and lymphoid progeny amounting to several percent of the total population of circulating lymphocytes and hematopoietic progenitors.
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7/9. Paraneoplastic pemphigus triggered by radiotherapy.

    Paraneoplastic pemphigus is a recently described autoimmune disease characterized by painful mucosal ulceration and polymorphous skin lesions in association with an underlying neoplasm. Distinct autoantibodies bind desmoplakin I, desmoplakin II, bullous pemphigoid antigen and an uncharacterized 190 kDa antigen. A case is presented of paraneoplastic pemphigus that developed after radiotherapy for non-Hodgkin's lymphoma in a 53 year old man. Multiple skin biopsies showed a lichenoid reaction without acantholysis. Immunofluorescence and mucosal biopsies were required to establish the correct diagnosis. Corneal opacities resembling lichenoid graft-versus-host disease and retinal haemorrhages, which developed in the patient, have not been previously documented. Despite high doses of immunosuppressive agents and plasmaphoresis, the patient eventually died from respiratory failure.
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8/9. Sweet's syndrome in a patient with oral cancer associated with radiotherapy.

    Approximately 10-20% of the reported patients with acute febrile neutrophilic dermatosis (Sweet's syndrome) have an associated neoplasm. Oral findings of Sweet's syndrome are rarely reported, and no cases in patients with oral cancer have been reported to date. This report describes the clinico- and histopathological findings of Sweet's syndrome in a patient with oral cancer, treated with radiotherapy. After 10 fractions of external beam radiotherapy, treatment was interrupted because of severe oral mucositis which extended beyond the radiation fields. Two days later the patient developed multiple tender skin lesions and the diagnosis Sweet's syndrome was made. skin and oral lesions resolved without additional treatment and did not recur upon resuming radiotherapy. As suggested in previous case reports, tumour antigens might play a role in the development of Sweet's syndrome. In this case, irradiation therapy may also have been a trigger for this syndrome.
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9/9. Thyroid radiation doses during radioimmunotherapy of CEA-expressing tumours with 131I-labelled monoclonal antibodies.

    A number of radioimmunotherapy (RAIT) trials with iodinated antibodies have shown a high variability in the radiation doses to the thyroid. Therefore, the aim of this study was to evaluate which factors influence these thyroid doses during RAIT with 131iodinated monoclonal anti-carcinoembryonic antigen (CEA) antibodies. Data from 36 patients with CEA-expressing tumours were analysed. The patients underwent RAIT with the 131I-labelled IgG1 anti-CEA antibody, MN-14 (Ka = 10(9) l mol-1) or its F(ab')2 fragment (activity range 45.8-220.0 mCi). The thyroid was blocked with 120 mg iodine (lugol's orSSKI solution) and 400 mg perchlorate per day, starting 1 day prior to the first study. blood clearance and molecular composition of labelled plasma compounds were determined by blood sampling and size-exclusion high-performance liquid chromatography analysis. The cumulated activities of tissues were determined from daily imaging and blood clearance data. Doses were derived from the MIRD scheme. Thyroid radiation doses showed a high variability, between 1.2 and 37.7 cGy mCi-1 (mean /- S.D.: 11.1 /- 8.3 cGy mCi-1), corresponding to absolute doses between 2.5 and 43.6 Gy. However, the maximal iodine uptake in the thyroid was 2.4 /- 1.9 microCi mCi-1 (range 0.2-10.0 microCi mCi-1), which was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases. No correlation was found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I- in the mAb preparation, rapid metabolic breakdown of the labelled antibody due to human anti-mouse antibodies (HAMA), or immune complex formation with circulating antigen. However, a relationship between the thyroid doses and the patients' compliance in taking their Lugol's and perchlorate blocking medications, as well as to a relatively high variability in the biological half-life of the iodine in the thyroid (range from 31.1 h to virtual infinity), is indicated. No rising TSH titres or other signs of (latent) hypothyroidism were seen in these patients during a 2 year follow-up period. Longer follow-up was not possible because of the terminal condition of most of the patients. These data show that thyroid doses in an appropriately blocked individual given a standard, non-myeloablative dose of RAIT, are generally lower than those assumed to be required to cause late hypothyroidism. Even if higher activities are used, potential hypothyroidism may be overcome easily by hormone replacement. Thyroid doses are independent of parameters leading to an enhanced exposure of the thyroid to free radioiodine, suggesting that patient compliance in taking their blocking medication may be the most crucial factor for reducing thyroid doses in RAIT with 131I-labelled antibodies.
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