Thyroid cancer: relationship to radiation exposure and to pregnancy

Exposure to radiation results in an increased occurrence of nodularity to the thyroid and, more important, the development of cancer in a significant proportion of patients. Near-total thyroidectomy is recommended in those patients with a history of irradiation who are found on physical examination of the thyroid to have one or more nodules. Although pregnancy appears to have no effect on the course of thyroid carcinoma and the tumor has no effect on pregnancy, because of the numerous stimuli to thyroid growth during pregnancy, we feel that pregnancy is best avoided by women with known residual disease.     

A case study comparing a meta-analysis and a pooled analysis of studies of sinonasal cancer among wood workers

Infectious tolerance can be induced in many ways, does not require a thymus or clonal deletion and can spread to third-party antigens linked on the same antigen-presenting cell-the process being variously described as linked-, bystanderor epitope-suppression. We here review the evidence concerning the mechanisms involved and attempt to make a consistent hypothesis, that during tolerance induction in the Th1-mediated autoimmune diseases and transplantation systems there would seem to be a phase of immune deviation towards Th2 cytokines, like IL-4 and IL-10; however, this may lead to an IL-10-induced form of anergy or nonresponsiveness and generation of the recently characterized Th3/T-regulatory-1 CD4+ T cell subset which is thought to downregulate the antigen-presenting cell, possibly via transforming growth factor beta.     

Thyroid cancer: a review

Thyroid cancer is a rare and complex disease. The thyroid contains various cell types from which distinct diseases arise. These malignancies range from indolent to extremely aggressive. Diagnosis includes attention to risk factors, family history, and subjective reports. The most valuable tool for diagnosis is the fine-needle aspiration. Primary treatment is surgery with postoperative hormone therapy. Radiation and chemotherapy serve palliative and adjuvant roles in advanced, recurrent, or metastatic disease. Nurses make a significant contribution to patient understanding and successful treatment outcome.     

Evaluation of external radiation exposure rate from radioiodine-treated hyperthyroid patients and radiation safety considerations

Hyperthyroid patients treated with radioiodine (131I) pose an external radiation risk to individuals who come into close contact with them. In order to determine changes in levels of external radiation with time in relation to the dose administered, 38 hyperthyroid patients being treated with 131I were evaluated Thyroid uptake, plasma T3, T4 and TSH levels were measured prior to treatment. Using a Geiger-Muller probe, levels of external radiation were measured at distances of 0.3, 0.6, 1.0 and 2.0 m from the patient -at the level at which the maximum activity was recorded -30 min, 1, 3, 7 and 10 days post-therapy. The patients were split into two groups. Group I comprised 22 patients treated with < or = 370 MBq 131I, 5 (23%) of whom registered > 0.46 mC kg-1 at a distance of 1.0 m 30 min post-therapy. Group II comprised 16 patients treated with > 370 MBq 131I, 13 (81%) of whom registered 0.46 mC kg-1 at a distance of 1.0 m one day post-therapy. At 3 days in Group I and 7 days in Group II, the estimated total radiation exposure rates were found to exceed the 1994 US Nuclear Regulatory Commission dose limits for children and pregnant women. Based on the results obtained, we present some guidelines intended to prevent the public from unnecessary radiation exposures.     

Measurement of DNA damage after exposure to 2450 MHz electromagnetic radiation

Recent reports suggest that exposure to 2450 MHz electromagnetic radiation causes DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) in cells of rat brain irradiated in vivo (Lai and Singh, Bioelectromagnetics 16, 207-210, 1995; Int. J. Radiat. Biol. 69, 513-521, 1996). Therefore, we endeavored to determine if exposure of cultured mammalian cells in vitro to 2450 MHz radiation causes DNA damage. The alkaline comet assay (single-cell gel electrophoresis), which is reportedly the most sensitive method to assay DNA damage in individual cells, was used to measure DNA damage after in vitro 2450 MHz irradiation. Exponentially growing U87MG and C3H 10T1/2 cells were exposed to 2450 MHz continuous-wave (CW) radiation in specially designed radial transmission lines (RTLs) that provided relatively uniform microwave exposure. Specific absorption rates (SARs) were calculated to be 0.7 and 1.9 W/kg. Temperatures in the RTLs were measured in real time and were maintained at 37 +/- 0.3 degrees C. Every experiment included sham exposure(s) in an RTL. Cells were irradiated for 2 h, 2 h followed by a 4-h incubation at 37 degrees C in an incubator, 4 h and 24 h. After these treatments samples were subjected to the alkaline comet assay as described by Olive et al. (Exp. Cell Res. 198, 259-267, 1992). Images of comets were digitized and analyzed using a PC-based image analysis system, and the "normalized comet moment" and "comet length" were determined. No significant differences were observed between the test group and the controls after exposure to 2450 MHz CW irradiation. Thus 2450 MHz irradiation does not appear to cause DNA damage in cultured mammalian cells under these exposure conditions as measured by this assay.     

Thyroid carcinoma after high-dose external radiotherapy for Hodgkin's disease: report of three cases

Three patients (two female and one male), who had received mantle irradiation for Hodgkin's disease eight, ten, and twelve years previously, developed papillary thyroid carcinoma. The radiation doses to the necks overlying the site of thyroid cancers were 3000, 4000, and 4100 rads, respectively. It has been stated that there is no risk of developing thyroid cancer with such high doses of external irradiation but apparently this complication will be encountered in a small number of patients.     

Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies

BACKGROUND AND PURPOSE: The available data on low-dose oral contraceptive pill (OCP) use and stroke risk in US women are limited by small numbers. We sought more precise estimates by conducting a pooled analysis of data from 2 US population-based case-control studies. METHODS: We analyzed interview data from 175 ischemic stroke cases, 198 hemorrhagic stroke cases, and 1191 control subjects 18 to 44 years of age. RESULTS: For ischemic stroke, the pooled odds ratio (pOR) adjusted for stroke risk factors for current use of low-dose OCPs compared with women who had never used OCP (never users) was 0.66 (95% confidence interval [CI], 0.29 to 1.47) and compared with women not currently using OCPs (nonusers) the pOR was 1.09 (95% CI, 0.54 to 2.21). For hemorrhagic stroke, the pOR for current use of low-dose OCPs compared with never users was 0.95 (95% CI, 0.46 to 1.93) and compared with nonusers the pOR was 1.11 (95% CI, 0.61 to 2.01). The pORs for current low-dose OCP use and either stroke type were not elevated among women who were >/=35 years, cigarette smokers, obese, or not receiving medical therapy for hypertension. pORs for current low-dose OCP use were 2.08 (95% CI, 1. 19 to 3.65) for ischemic stroke and 2.15 (95% CI, 0.85 to 5.45) for hemorrhagic stroke among women reporting a history of migraine but were not elevated among women without such a history. Past OCP use (irrespective of formulation) was inversely related to ischemic stroke but unrelated to hemorrhagic stroke. CONCLUSIONS: Women who use low-dose OCPs are, in the aggregate, not at increased risk of stroke. Studies are needed to clarify the risk of stroke among users who may be susceptible on the basis of age, smoking, obesity, hypertension, or migraine history.     

Prostate cancer volume adds significantly to prostate-specific antigen in the prediction of early biochemical failure after external beam radiation therapy

PURPOSE: A new clinical pretreatment quantity that closely approximates the true prostate cancer volume is defined. METHODS AND MATERIALS: The cancer-specific prostate-specific antigen (PSA), PSA density, prostate cancer volume (VCa), and the volume fraction of the gland involved with carcinoma (VCafx) were calculated for 227 prostate cancer patients managed definitively with external beam radiation therapy. 1. PSA density = PSA/ultrasound prostate gland volume. 2. Cancer-specific PSA = PSA - [PSA from benign epithelial tissue] 3. VCa = Cancer-specific PSA/[PSA in serum per cm3 of cancer] 4. VCafx = VCa/ultrasound prostate gland volume A Cox multiple regression analysis was used to test whether any of these clinical pretreatment parameters added significantly to PSA in predicting early postradiation PSA failure. RESULTS: The prostate cancer volume (p = 0.039) and the volume fraction of the gland involved by carcinoma (p = 0.035) significantly added to the PSA in predicting postradiation PSA failure. Conversely, the PSA density and the cancer-specific PSA did not add significantly (p > 0.05) to PSA in predicting postradiation PSA failure. The 20-month actuarial PSA failure-free rates for patients with calculated tumor volumes of < or = 0.5 cm3, 0.5-4.0 cm3, and > 4.0 cm3 were 92, 80, and 47%, respectively (p = 0.00004). CONCLUSION: The volume of prostate cancer (VCa) and the resulting volume fraction of cancer both added significantly to PSA in their ability to predict for early postradiation PSA failure. These new parameters may be used to select patients in prospective randomized trials that examine the efficacy of combining radiation and androgen ablative therapy in patients with clinically localized disease, who are at high risk for early postradiation PSA failure.     

Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: radiation port scleroderma

OBJECTIVES: Analysis of an experience in treating girls with dysfunctional voiding with an outpatient pelvic-floor therapy consisting of voiding and drinking schedule, pelvic-floor relaxation biofeedback, instructions on toilet behavior, and uroflowmetry. METHODS: The files of 50 girls (between 6 and 13 years of age) with urodynamically proven dysfunctional voiding who participated in the training program were analyzed retrospectively. Thirty-five girls received anticholinergics during the entire course of the training. The long-term absence of diurnal incontinence was used as the criterion for the success of the therapy. The duration of treatment before reaching this success was used as a parameter to measure the intensity of therapy. For a portion of the study group, a comparison is made with the duration of the preceding therapies to demonstrate indirectly the cumulative effect of the pelvic-floor therapy. RESULTS: Forty-six girls (92%) normalized their flow and bladder capacity after therapy and saw their daytime incontinence disappearing. All of these girls achieved this result in a maximum of 18 sessions within a 6-month period. At the follow-up examination after 6 months, five of the girls had relapsed (10%), which brings the ultimate success after 6 months of follow-up to 82%. CONCLUSIONS: Pelvic-floor therapy seems to be a reasonable and meaningful component in the treatment of bladder dysfunction in which detrusor-sphincter dyscoordination plays a role.     

Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

CONTEXT: Interstitial radiation (implant) therapy is used to treat clinically localized adenocarcinoma of the prostate, but how it compares with other treatments is not known. OBJECTIVE: To estimate control of prostate-specific antigen (PSA) after radical prostatectomy (RP), external beam radiation (RT), or implant with or without neoadjuvant androgen deprivation therapy in patients with clinically localized prostate cancer. DESIGN: Retrospective cohort study of outcome data compared using Cox regression multivariable analyses. SETTING AND PATIENTS: A total of 1872 men treated between January 1989 and October 1997 with an RP (n = 888) or implant with or without neoadjuvant androgen deprivation therapy (n = 218) at the Hospital of the University of Pennsylvania, Philadelphia, or RT (n = 766) at the Joint Center for Radiation Therapy, Boston, Mass, were enrolled. MAIN OUTCOME MEASURE: Actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk (RR) of PSA failure in low-risk patients (stage T1c, T2a and PSA level < or =10 ng/mL and Gleason score < or =6) treated using RT, implant plus androgen deprivation therapy, or implant therapy was 1.1 (95% confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI, 0.3-3.6), respectively, compared with those patients treated with RP. The RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason score of 7 or PSA level >10 and < or =20 ng/mL) and high-risk patients (stage T2c or PSA level >20 ng/mL or Gleason score > or =8) treated with implant compared with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively. The addition of androgen deprivation to implant therapy did not improve PSA outcome in high-risk patients but resulted in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients. These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10. CONCLUSIONS: Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant. Prospective randomized trials are needed to verify these findings.     

A comparative analysis of the existing standards for exposure to ultraviolet radiation

Medical imaging technology is rapidly expanding and the role of each modality is being redefined constantly. PET has been around since the early sixties and gained clinical acceptance in oncology only after an extreme number of scientific publications. Although PET has the unique ability to image biochemical processes in vivo, this ability is not fully used as a clinical imaging tool. In this overview, the role of PET in relation to other tumor imaging modalities will be discussed and the reported results in the literature will be reviewed. In predicting the future of PET, technical improvements of other imaging modalities need to be dealt with. The fundamental physical principles for image formation with computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), photon-emission tomography (PET), and single photon emission CT (SPECT) will not change. The potential variety of radiopharmaceuticals which may be developed is unlimited, however, and this provides nuclear imaging techniques with a significant advantage and adaptive features for future biologic imaging. The current applications of PET in oncology have been in characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. The articles discussed in this review were selected from a literature search covering the last 3 years, and in which comparisons of PET with conventional imaging were addressed specifically. PET studies with the glucose analogue fluorine-18-labeled deoxyglucose (FDG) have shown the ability of detecting tumor foci in a variety of histological neoplasms such as thyroid cancer, breast cancer, lymphoma, lung cancer, head and neck carcinoma, colorectal cancer, ovarian carcinoma, and musculoskeletal tumors. Also, the contribution of the whole body PET (WBPET) imaging technique in diagnosis will be discussed. In the current health care environment, a successful imaging technology must not only change medical management but also demonstrate that those changes improve patient outcome.     

Thyroid neoplasms in some regions of Russia after radiation accident in Chernobyl

There is an increase of thyroid carcinoma incidence in regions contaminated after the Chernobyl accident as well as in Russia on the whole. The most considerable increase occurred in younger age groups of population. No difference in thyroid tumors structure was found in polluted with radionuclides and non-polluted regions.     

Proton magnetic resonance spectroscopy: a metabolic approach of cerebral tumors and their follow-up after external radiation therapy

The same physical principles are the basis of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). Proton MRS is easily performed with clinical magnets (> or = 1.5 T) and may be added to routine MRI studies to provide metabolic information on pathological tissues. It represents an important tool to detect several metabolic compounds. The article will review the current status of proton MRS with a particular emphasis upon its clinical utility for the diagnosis of brain tumors and for the evaluation of the efficacy of radiotherapy.     

Aloe barbadensis extracts reduce the production of interleukin-10 after exposure to ultraviolet radiation

Cutaneous exposure to ultraviolet radiation suppresses the induction of T cell mediated responses such as contact and delayed type hypersensitivity (DTH) by altering the function of immune cells in the skin and causing the release of immunoregulatory cytokines. Extracts of crude Aloe barbadensis gel prevent this photosuppression. Because the regulation of contact hypersensitivity and DTH responses differ, we investigated whether protection was afforded by a single or multiple agents in Aloe and the mechanism by which this material prevents suppression of DTH immunity. The ability of Aloe gel to prevent suppression of contact hypersensitivity responses to hapten decayed rapidly after manufacture. In contrast, agents that protected against systemic suppression of DTH responses to Candida albicans were stable over time. Oligosaccharides prepared from purified Aloe polysaccharide prevented suppression of DTH responses in vivo and reduced the amount of IL-10 observed in ultraviolet irradiated murine epidermis. To assess the effect of Aloe extracts on keratinocytes, Pam 212 cells were exposed in vitro to ultraviolet radiation and treated for 1 h with Aloe oligosaccharides. Culture supernatants were collected 24 h later and injected into mice. Supernatants from ultraviolet irradiated keratinocytes suppressed the induction of DTH responses, whereas Aloe oligosaccharide treatment reduced IL-10 and blocked the suppressive activity of the supernatants. These results indicate that Aloe contains multiple immunoprotective factors and that Aloe oligosaccharides may prevent ultraviolet induced suppression of DTH by reducing keratinocyte derived immunosuppressive cytokines.     

Variations with time and age in the risks of solid cancer incidence after radiation exposure in childhood

The Japanese atomic bomb survivor incidence data set and data on five other groups exposed to ionizing radiation in childhood are analysed and evidence found for a reduction in the radiation-induced relative risk of cancers other than leukaemia with increasing time since exposure. Overall, reductions of 5.7-6.1 per cent per year of time since exposure are indicated, depending on the time at which the reduction is presumed to start, and all the reductions are statistically significant at the 5 per cent level. There is no significant heterogeneity in the speed of the reductions in relative risk with time by cohort, by cancer type, sex, or age at exposure group. There is a significant reduction of relative risk with increasing age at exposure, but adjustment for age at exposure does not markedly affect the time trends of relative risk. For all of the groups considered, there is a statistically significant increase in the excess absolute risk with increasing time since exposure. However, by contrast with the relative homogeneity of the time trends of relative risk, there is statistically significant heterogeneity by cancer type within the Japanese cohort (P = 0.05) and between the cohorts (P < 0.0001) in the speed of increase of the excess absolute risk with time since exposure.     

Early stage vocal cord cancer: results after external beam radiotherapy

Much has been written about suck confusion due to a baby's oral experience with objects other than the breast--but how much difference is there in the relative impacts on a baby's ineffective suck if a teat is used instead of other currently accepted techniques such as cup and finger feeding? Mothers who seek the help of a lactation consultant will commonly already be using bottles and teats as part of their management regime for a difficult situation. Especially if the problems are well developed and complex, many mothers will not be able to accept unfamiliar alternatives such as cup and finger feeding and prefer to wean rather than do so. Current teat designs have evolved with no reference to Woolridge's landmark research published over ten years ago which clearly demonstrated how normal breastfeeding works. Rather, manufacturers offer consumers an array of teats which have been shortened in length and distorted in conformation when compared with teats available thirty years ago which coincidentally were a closer physiological match with the positioning of the nipple and breast tissues in the mouth of a breastfeeding baby than teats designed and produced since then. Fortunately one UK manufacturer still markets this thirty year old style of teat in a flow rate suitable for very young babies. Over a three year period, we at first hesitantly, but with increasing confidence asked mothers to use this teat when suck retraining and supplementation were indicated. We are able to report that use of these teats has resulted in a success rate in excess of 90% converting babies with significant sucking problems into fully effective breastfeeders.     

Oncogenic rearrangements of the ret proto-oncogene in thyroid tumors induced after exposure to ionizing radiation

A high frequency (approximately 60%) of ret rearrangements in Chernobyl papillary thyroid carcinomas (PTC) has been reported recently. The data suggested that the radiation exposure may be a direct inducer of activating rearrangements in the ret gene. In our study, we have analyzed for the presence of RET/PTC oncogenes using the RT-PCR, XL-PCR, Southern blot and direct sequencing techniques, 39 human thyroid tumors from patients who had received external radiation for benign or malignant conditions. As controls, we studied 39 'spontaneous' tumors. Our results indicate that: 1) the overall frequency of ret rearrangements was 84% in papillary carcinomas (16/19) and 45% (9/20) in follicular adenomas; 2) in contrast with the results obtained in the Chernobyl tumors, the most frequently observed chimeric gene was RET/PTC1; and 3) all the tumors were negative for RET/PTC2. In the 'spontaneous' tumors, only the papillary carcinomas presented a ret rearrangement (15%: 3/20). Our data confirm the crucial role played by the ret proto-oncogene activating rearrangements in the development of radiation-associated thyroid tumors, and show, for the first time, the presence of RET/PTC genes in follicular adenomas appeared after external irradiation.     

Prenatal exposure to diethylstilbestrol in mice: toxicological studies

The effect of prenatal exposure to diethylstilbestrol (DES) on the postnatal development of male and female genital tract function was studied. The placental transfer or radiolabeled (3H or 14C) DES was studied in pregnant mice. DES-associated radioactivity in the fetal plasma approximated that in maternal plasma 1/2 hr after intravenous administration of [3H]DES; 3H activity corresponding to DES in the fetal genital tract was about threefold higher. The decrease in reproductive capacity of female offspring from mice treated with DES during gestation was dose-related; a low incidence (10% or less) of cancer of the vagina, cervix, and/or uterus was also observed in these mice. Male offspring exposed prenatally to the highest dose (100 microng/kg) of DES in this study also had lower reproductive capacities. Lesions in the genital tract of these mice included epididymal cysts, inflammation, cryptorchidism, and nodular masses in the seminal vesicles and/or prostate gland. Such lesions and sterility were not observed at the lower DES doses. Histological studies with neonatal mice raise the possibility that Müllerian duct tissue may represent a site for the transplacental toxicity of DES in both the male and female fetus.