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Purpose: A PENTEC (Pediatric Normal Tissue Effects in the Clinic) review was performed to estimate the dose-volume effects of radiation therapy on spine deformities and growth impairment for patients who underwent radiation therapy as children., Methods and Materials: A systematic literature search was performed to identify published data for spine deformities and growth stunting. Data were extracted from 12 reports of children irradiated to the spine (N = 603 patients). The extracted data were analyzed to find associations between complication risks and the radiation dose (conventional fractionation throughout) as impacted by exposed volumes and age using the mixed-effects logistic regression model. When appropriate, corrections were made for radiation modality, namely orthovoltage beams., Results: In the regression analysis, the association between vertebral dose and scoliosis rate was highly significant (P < .001). Additionally, young age at time of radiation was highly predictive of adverse outcomes. Clinically significant scoliosis can occur with doses ≥15 Gy to vertebrae during infancy (<2 years of age). For children irradiated at 2 to 6 years of age, overall scoliosis rates of any grade were >30% with doses >20 Gy; grade 2 or higher scoliosis was correlated with doses ≥30 Gy. Children >6 years of age remain at risk for scoliosis with doses >30 Gy; however, most cases will be mild. There are limited data regarding the effect of dose gradients across the spine on degree of scoliosis. The risk of clinically meaningful height loss was minimal when irradiating small volumes of the spine up to 20 Gy (eg, flank irradiation), except in infants who are more vulnerable to lower doses. Growth stunting was more frequent when larger segments of the spine (eg, the entire spine or craniospinal irradiation) were irradiated before puberty to doses >20 Gy. The effect was modest when patients were irradiated after puberty to doses >20 Gy., Conclusions: To reduce the risk of kyphoscoliosis and growth impairment, the dose to the spine should be kept to <20 Gy for children <6 years of age and to <10 to 15 Gy in infants. The number of vertebral bodies irradiated and dose gradients across the spine should also be limited when possible., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To provide a synthesis of the published evidence pertaining to the intergenerational health effects of parental preconceptional exposure to ionizing radiation in humans., Methods: The study populations are the descendants of those who were exposed to ionizing radiation prior to conception. A Boolean search identified publications for review in accordance with Office of Health Assessment and Translation guidelines. Initially, a risk of bias assessment was conducted for each published study and relevant data extracted. Information was organized into adverse health outcome groups and exposure situations. To make an assessment from the body of evidence within each group, an initial confidence rating was assigned, before factors including inconsistencies between studies, magnitude of effect, dose response and confounders were considered. From this, 'an effect', 'no effect' or whether the evidence remained 'inadequate' to determine either effect or no effect, was ascertained. This assessment was based primarily upon the author's conclusions within that evidence-base and, by binomial probability testing of the direction of effect reported., Results: 2441 publications were identified for review which after screening was reduced to 127. For the majority of the adverse health groups, we find there to be inadequate evidence from which to determine whether the health effect was, or was not, associated with parental preconceptional radiation exposure. This was largely due to heterogeneity between individual study's findings and conclusions within each group and, the limited number of studies within each group. We did observe one health grouping (congenital abnormalities) in occupationally exposed populations, where an increase in effect relative to their controls or large magnitude of effects, were reported, although it is noted that the authors of these studies interpreted their findings as most likely not to be associated with parental radiation exposure., Conclusions: We find there to be a lack of evidence to enable the formal assessment of radiation-related adverse effects in offspring of exposed humans. This is not the same as there being no clear evidence that effects may occur but does infer that if adverse health effects do arise in children of exposed parents, then these effects are small and difficult to reproducibly measure. Inconsistencies in designing studies are unavoidable, however we highlight the need for an element of standardization and, more sharing of primary datasets as part of open access initiatives, in order for future reviews to make reasonable conclusions. Overall, there is a need for future work to ensure comparable measures between studies where possible.

Purpose: It has been known for many decades that radiation exposure of the developing embryo or fetus may cause two fundamentally different types of severe health effects: on the one hand, radiation may interfere with the normal intrauterine development, on the other hand, radiation may induce leukemia and cancer which become manifest in childhood. A large amount of epidemiological and experimental data has recently been presented which might be used to improve our understanding of underlying mechanisms and setting radiation protection standards. Yet, ecological studies in the populations exposed to increased levels of radiation in regions contaminated by radioactivity released from reactor accidents (Chernobyl, Fukushima) do not provide solid evidence which would contribute to this aim. On the other hand, well designed experimental studies demonstrated the multifactorial mechanisms which lead to different health effects after radiation exposure in utero., Conclusion: There is no convincing evidence, neither from epidemiological nor experimental data of the existence of a dose threshold for developmental defects after radiation exposure in utero. This must be taken into account in the revision of rules and regulations of radiation protection in medicine.

Purpose: Computed tomographic (CT) scans in adolescents have increased dramatically in recent years. However, the effects of cumulative low-dose exposures on the development of radiation sensitive organs, such as the mammary gland, is unknown. The purpose of this work was to define the effects of dose rate on mammary organ formation during puberty, an especially sensitive window in mammary development. We used a fractionated low-dose x-ray exposure to mimic multiple higher dose CT scans, and we hypothesized that fractionated exposure would have less of an effect on the number of mammary gland defects compared with an acute exposure., Methods and Materials: Female mice were subjected to fractionated low-dose x-ray exposure (10 cGy/d for 5 days), acute x-ray exposure (1 × 50 cGy), or sham exposure. As the wide genetic diversity in humans can play a role in a person's response to irradiation, 2 genetically diverse mouse strains differing in radiation sensitivity (BALB/c-sensitive; C57BL/6-resistant) were used to investigate the role of genetic background on the magnitude of the effect., Results: Unexpectedly, our data reveal that multiple low-dose exposures produce greater immune and mammary defects for weeks after exposure compared with controls. The most pronounced defects being increased ductal branching in both strains and a greater percentage of terminal end buds in the BALB/c strain of mice exposed to fractionated radiation compared with sham. Radiation-induced defects near the terminal end bud were also increased in both strains., Conclusions: The findings suggest that fractionated low-dose exposures are potentially more damaging to organ development compared with an equivalent, single acute exposure and that genetic background is an important parameter modifying the severity of these effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: This study assessed the incidence of late rectal toxicities and evaluated potential predictive factors for late proctitis in patients treated with prostate-specific intensity-modulated radiotherapy in Hong Kong., Methods: This retrospective longitudinal observational study included patients with localised prostate cancer who were treated with intensity-modulated radiation therapy in an oncology unit in Hong Kong between January 2007 and December 2011, and who had >1 year of follow-up. Clinical, pharmacological, and radiation parameters were recorded. Toxicities were measured by Common Terminology Criteria for Adverse Events version 4., Results: In total, 232 patients were included in this analysis. The mean follow-up time was 7.3 ± 2.1 years and 46.5% of the patients had late rectal toxicities. Late proctitis occurred in 30.5% of patients; 25% of the patients with late proctitis exhibited grade ≥2 toxicity. Median onset times for late proctitis and rectal bleeding were 15 and 18.4 months, respectively. Multivariable regression showed increased odds for the occurrence of late proctitis in patients with older age (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.04-1.19, P=0.003), higher V70 (OR=1.08, 95% CI=1.01-1.15, P=0.027), and presence of acute rectal toxicities (OR=4.47, 95% CI=2.37-8.43, P<0.001). Antiplatelet use was not significantly associated with the occurrence of late proctitis (OR=1.98, 95% CI=0.95-4.14, P=0.07)., Conclusions: The incidence of late rectal toxicities was considerable among patients in this study. Clinicians should consider the possibility of late proctitis for patients with older age, acute rectal toxicities, and higher V70. High doses to rectal volumes should be limited because of the significant association with V70., Competing Interests: All authors have disclosed no conflict of interest.

Autologous fat grafting has been extensively and successfully adopted in a number of pathologic conditions in regenerative surgery especially on irradiated fields in order to improve pain symptoms and tissue trophism promoting scar release. In the present study, we report our experience with autologous fat grafting for the treatment of postirradiation fibrosis and pain on three consecutive patients undergoing orbital enucleation for locally advanced retinoblastoma (RB) and subsequent radiotherapy. We selected three consecutive patients who underwent orbital enucleation for locally advanced RB and subsequent local radiotherapy showing severe reduction in orbital volume and eyelid length and retraction due to fibrosis, spontaneous local pain exacerbated after digital pressure with no possibility to place an ocular implant. They underwent autologous fat grafting in the orbital cavity and results were evaluated by clinical examination at 5 and 14 days, and 1, 3, 6 months, and 1 year after surgery. A significant release of scar retraction, reduction of fibrosis and orbital rim contraction together with an important improvement of pain symptoms was observed in all patients. The local changes observed enabled an ease placement of an ocular prosthetic implant (implant). No local or systemic complication occurred. Fat grafting is a promising treatment for patients showing radiotherapy related complication in the orbital area and it should be adopted by all oculoplastic surgeon in order to improve pain syndrome creating the ideal local conditions for the placement of an ocular prosthetic implant.

Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity., Methods: Hippocampal cultures expressing enhanced green fluorescent protein were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy. Excitatory synapses, defined by co-localization of the pre- and postsynaptic markers vesicular glutamate transporter 1 and postsynaptic density protein 95, were also analyzed. Neurons were pretreated with vehicle, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine, or the glutamate scavenger glutamate pyruvate transaminase to assess glutamate signaling. For animal studies, Thy-1-YFP mice were treated with whole-brain radiotherapy or sham with or without memantine., Results: Unlike previously reported long-term losses of dendritic spines, we found that the acute response to radiation is an initial increase in spines and excitatory synapses followed by a decrease in spine/synapse density with altered spine dynamics. Memantine pre-administration prevented this radiation-induced synaptic remodeling., Conclusion: These results demonstrate that radiation causes rapid, dynamic changes in synaptic structural plasticity, implicate abnormal glutamate signaling in cognitive dysfunction following brain irradiation, and describe a protective mechanism of memantine.

Background: Thyroid hemiagenesis is a rare congenital variant characterized by the lack of development of one thyroid lobe with no clinical manifestations., Methods: This study was performed to determine the prevalence and characteristics of thyroid hemiagenesis in a normal Japanese population. This cross-sectional study was performed from October 9, 2011, to April 30, 2015. In total, 299,908 children and young adults in the Fukushima Health Management Survey were examined to determine the presence of thyroid agenesis or hemiagenesis. Thyroid width, thickness, and length were measured in 292,452 of these subjects., Results: Thyroid agenesis was diagnosed in 13 subjects, and hemiagenesis was detected in 67 subjects (0.02%; 22.3/100,000 individuals). Although there was no significant sex-related difference (p = 0.067), the female:male ratio was 1.67:1.00. Females were significantly dominant in right hemiagenesis, while there was no difference in left hemiagenesis between males and females. The thyroid volumes at the 2.5th and 97.5th percentiles for age and body surface area were determined for each sex. Multivariate regression analysis showed that a large hemithyroid volume was independently associated with the presence of contralateral hemiagenesis (p < 0.001)., Conclusion: The prevalence of thyroid hemiagenesis in the present study is in agreement with that reported in other countries. The prevalence of right hemiagenesis was higher in females, and the larger contralateral lobe in patients with rather than without hemiagenesis may have been caused by a compensatory feedback mechanism to prevent hypothyroidism. In addition, the prevalence of hemiagenesis, especially right hemiagenesis, may be affected by sex-related factors similar to those in patients with an ectopic thyroid gland.

The diagnostic of cancer during pregnancy is a rare and delicate situation. As the developments of the embryo and the human fetus are extremely sensitive to ionizing radiations, the treatment of these tumors should be discussed. The studies - preclinical and clinical - based mostly on exposure accidents show that subdiaphragmatic treatments are possible during pregnancy. When radiotherapy is used, phantom estimations of the dose to the fetus, confirmed by in vivo measurements are required. Irradiation and imaging techniques should be arranged to decrease as much as possible the dose delivered to the fetus and hold below the threshold of 0.1Gy., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: The potential adverse effect of mobile phone radiation is currently an area of great concern in the field of public health. In the present study, we aimed to investigate the effect of mobile phone radiation (900 MHz radiofrequency) during hatching on postnatal social behaviors in chicks, as well as the effect on brain size and structural maturity estimated using 3.0 T magnetic resonance imaging. At day 4 of incubation, 76 normally developing chick embryos were divided into the control group (n = 39) and the radiation group (n = 37). Eggs in the radiation group were exposed to mobile phone radiation for 10 h each day from day 4 to 19 of incubation. Behavioral tests were performed 4 days after hatching. T2-weighted MR imaging and diffusion tensor imaging (DTI) were subsequently performed. The size of different brain subdivisions (telencephalon, optic lobe, brain stem, and cerebellum) and corresponding DTI parameters were measured. The Chi-square test and the student's t test were used for statistical analysis. P < 0.05 was considered statistically significant., Results: Compared with controls, chicks in the radiation group showed significantly slower aggregation responses (14.87 ± 10.06 vs. 7.48 ± 4.31 s, respectively; P < 0.05), lower belongingness (23.71 ± 8.72 vs. 11.45 ± 6.53 s, respectively; P < 0.05), and weaker vocalization (53.23 ± 8.60 vs. 60.01 ± 10.45 dB/30 s, respectively; P < 0.05). No significant differences were found between the radiation and control group for brain size and structural maturity, except for cerebellum size, which was significantly smaller in the radiation group (28.40 ± 1.95 vs. 29.95 ± 1.41 cm(2), P < 0.05). The hatching and heteroplasia rates were also calculated and no significant difference was found between the two groups., Conclusions: Mobile phone radiation exposure during chick embryogenesis impaired social behaviors after hatching and possibly induced cerebellar retardation. This indicates potential adverse effects of mobile phone radiation on brain development.

Background: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects., Methods: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects., Results: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy., Conclusion: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies., (© 2015 Wiley Periodicals, Inc.)

This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors., (© 2014 The Authors. Congenital Anomalies published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Teratology Society.)

OBJECTIVE. The purpose of this article is to describe how to address patients' past-and future potential-radiation exposures when making an imaging decision in a given situation. CONCLUSION. The Biologic Effects of Ionizing Radiation committee has endorsed a linear no-threshold model to explain the relationship between radiation exposure and cancer risk. This model implies that past and future potential exposures should not impact current decisions. We present an analogy that deconstructs these counterintuitive conclusions and facilitates translation of key radiation risk principles to practice.

Background: Exposure to electromagnetic fields (EMFs) and its effects at different frequencies on living beings has been investigated for decades. However, there are fewer studies that have been conducted on humans, thus this study aims to determine the effect of extremely low frequency (ELF) -EMFs on pregnancy, fetal growth and development in humans., Material: In this epidemiologic analytical cohort study, cases included pregnant women and their newborns. There were 222 women exposed to ELF-EMFs from high voltage electricity towers and cables during pregnancy and 158 women who had no exposure during pregnancy. Data that included pregnancy duration, neonatal birth weight, length, head circumference, gender and congenital malformations were collected through direct questions, measurements and referral to the registered data of related hospital or health center documents. Collected data was analyzed by SPSS-16. P < 0.05 was considered significant., Results: No significant difference was found in pregnancy duration and preterm labor, neonatal birth weight, length, head circumference and congenital malformations in the two studied groups., Conclusion: Although the results of this study have shown no significant effects of ELF-EMFs on human pregnancy, fetal growth and development, taking precautionary measures to reduce exposure to EMFs by pregnant women seems logical. Conducting similar studies is strongly recommended.

Aims: This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD)., Main Methods: Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed., Key Findings: Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus., Significance: The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In experimental organisms such as fruit flies and mice, increased frequencies in germ cell mutations have been detected following exposure to ionizing radiation. In contrast, there has been no clear evidence for radiation-induced germ cell mutations in humans that lead to birth defects, chromosome aberrations, Mendelian disorders, etc. This situation exists partly because no sensitive and practical genetic marker is available for human studies and also because the number of people exposed to large doses of radiation and subsequently having offspring was small until childhood cancer survivors became an important study population. In addition, the genome of apparently normal individuals seems to contain large numbers of alterations, including dozens to hundreds of nonfunctional alleles. With the number of mutational events in protein-coding genes estimated as less than one per genome after 1 gray (Gy) exposure, it is unsurprising that genetic effects from radiation have not yet been detected conclusively in humans.

Objective: To analyze the frequency and structure of the urinary system malformations in children born to parents exposed to radiation., Material and Methods: The study included 1,139 children with various congenital malformations of the urinary system, which were examined and treated in the Department of Congenital and Hereditary Diseases from 2000 to 2011. The standard clinical, laboratory, instrumental and radiographic methods were applied to verify the diagnosis., Results and Conclusions: 1. The proportion of children with congenital malformations of the urinary system among all examined in the Department of Congenital and Hereditary Diseases in the 12 years was 68.24%. 2. The congenital malformations accounted for 31.16%, small anomalies for 68.31%, and their combinations for 4.57% among all malformations of the urinary system. 3. Such complications as a secondary pyelonephritis occurred in 4.39% of cases and developed mainly in children with obstructive uropathy., (Stepanova E. Y., Skvarskaja E. A., Usatenko Zh. V., Leonovych E. S., Abramova T. Ja., 2013.)

Background: Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice., Methods: Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/μm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction., Results: Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles., Conclusions: Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero., (© 2012 Wiley Periodicals, Inc.)

Results obtained from the end of the 1950s suggested that ionizing radiation could induce foetal malformations in some mouse strains when administered during early pre-implantation stages. Starting in 1989, data obtained in Germany also showed that radiation exposure during that period could lead to a genomic instability in the surviving foetuses. Furthermore, the same group reported that both malformations and genomic instability could be transmitted to the next generation foetuses after exposure of zygotes to relatively high doses of radiation. As such results were of concern for radiation protection, we investigated this in more detail during recent years, using mice with varying genetic backgrounds including mice heterozygous for mutations involved in important cellular processes like DNA repair, cell cycle regulation or apoptosis. The main parameters which were investigated included morphological development, genomic instability and gene expression in the irradiated embryos or their own progeny. The aim of this review is to critically reassess the results obtained in that field in the different laboratories and to try to draw general conclusions on the risks of developmental defects and genomic instability from an exposure of early embryos to moderate doses of ionizing radiation. Altogether and in the range of doses normally used in diagnostic radiology, the risk of induction of embryonic death and of congenital malformation following the irradiation of a newly fertilised egg is certainly very low when compared to the 'spontaneous' risks for such effects. Similarly, the risk of radiation induction of a genomic instability under such circumstances seems to be very small. However, this is not a reason to not apply some precaution principles when possible. One way of doing this is to restrict the use of higher dose examinations on all potentially pregnant women to the first ten days of their menstrual cycle when conception is very unlikely to have occurred (the so-called ten-day rule), as already recommended by the Health Protection Agency. Such a precautionary attitude would also be supported by the uncertainties associated with later changes in gene expression which might result from irradiation or early embryos with moderate doses.

Over the last decade, advances in oncology led to improved treatment results and increasing numbers of long-term cancer survivors. Fulfilling the desire to have children is important for many patients after cancer treatment. Consequently, oncologists, gynecologists and obstetricians are seeing more patients who wish to conceive after treatment. The necessary prerequisites that should be considered when supporting a planned pregnancy after cancer treatment are discussed in this article. The possible consequences of chemotherapy and radiotherapy on the course of pregnancy and the health of the offspring, as well as the interactions between cancer and pregnancy, are reviewed with the focus on childhood cancer, malignant lymphomas, and breast cancer. Despite chemo- or radiotherapy, neither the teratogenic risk nor the risk of adventitious cancers appears to be increased for the offspring of cancer survivors. However, there is a slightly higher risk of miscarriage after chemotherapy. In case of radiation to the uterus, there is a higher risk of premature birth, intrauterine growth retardation, and increased perinatal mortality. The effect is more pronounced after prepubertal radiation than for postpubertal radiation. The former cancer patient's desire to conceive can nevertheless be supported, given that pregnancy and birth are closely monitored., (Copyright © 2012 S. Karger AG, Basel.)

The most recent Recommendations (Publication 103) issued by the International Commission for Radiological Protection (ICRP) are based on the data that have been published since 1990 up to now. The basic task of the ICRP Committee 1 was to formulate the key implications of studies on radiobiological effects for the purposes of radiological protection. Presented in the paper are the new achievements in the field of biology, radiobiology and radiation epidemiology which were taken into account by the ICRP in the process of Publication 103 preparation. The Recommendations provide present-day values of weighting factors for radiation exposure and tissue weighting factors, as well as radiation detriment and radiogenic risk factors for cancer and genetic diseases. Also considered are tissue reactions to radiation exposure, consequences of in utero exposure and the risks of developing non-cancer diseases for exposed individuals. It should be noted that the key inferences and recommendations are to a considerable degree related to biological effects accounted for by acute and chronic exposure to ionizing radiation in the range of small doses (up to 100 mSv).

Fetal sensitivity to radiation-induced health effects is related to gestational age, and it is highly dependent on fetal dose. Typical fetal doses from diagnostic radiology are usually below any level of concern. Although rare, significant fetal radiation doses can result from interventional medical exposures (fluoroscopically guided techniques), radiation therapy, or radiological or nuclear incidents, including terrorism. The potential health effects from these large radiation doses (possibly large enough to result in acute radiation syndrome in the expectant mother) include growth retardation, malformations, impaired brain function, and neoplasia. If exposure occurs during blastogenesis (and the embryo survives), there is a low risk for congenital abnormalities. (In all stages of gestation, radiation-induced noncancer health effects have not been reported for fetal doses below about 0.05 Gy [5 rad].) The additional risk for childhood cancer from prenatal radiation exposure is about 12% per Gy (0.12%/rad) above the background incidence., (©2011 American Medical Association. All rights reserved.)

Concerns regarding radiation exposure and its effects during pregnancy are often quoted as an important barrier preventing many women from pursuing a career in Interventional Cardiology. Finding the true risk of radiation exposure from performing cardiac catheterization procedures can be challenging and guidelines for pregnancy exposure have been inadequate. The Women in Innovations group of Cardiologists with endorsement of the Society for Cardiovascular Angiography and Interventions aim to provide guidance in this publication by describing the risk of radiation exposure to pregnant physicians and cardiac catheterization personnel, to educate on appropriate radiation monitoring and to encourage mechanisms to reduce radiation exposure. Current data do not suggest a significant increased risk to the fetus of pregnant women in the cardiac catheterization laboratory and thus do not justify precluding pregnant physicians from performing procedures in the cardiac catheterization laboratory. However, radiation exposure among pregnant physicians should be properly monitored and adequate radiation safety measures are still warranted., (Copyright © 2011 Wiley-Liss, Inc.)

A total 156 children of the main group (children born to parents irradiated during the Chernobyl disaster), who according to echocardiography revealed a different number of isolated abnormal chords of the left ventricle, 20 healthy children, 24 children of nosological control group and 50 children of referent group have been observed. It was found that isolated AHLV in children born to irradiated parents, was associated with changes in standard ECG, reflecting the presence of arrhythmias or predictors of their development. No significant differences in subgroups of children with different number of isolated AHLV have been established. Children with isolated AHLV born to parents irradiated during the Chernobyl accident, as all patients with minor structural anomalies of the heart, should be refered to a risk group in connection with the possibility of the development, in the first place, ventricular extrasystoles, paroxysmal ventricular tachycardia. Early diagnosis of isolated AHLV will allow to assess the outlook for further course of the disease and develop a plan of treatment and preventive measures.

Objectives: The health effects of chronic low-dose radiation exposure remains a controversial question. Monitoring after the Chernobyl nuclear accident in Ukraine suggested that chronic low-dose radiation exposure was not linked to cancer mortality among the general population. However, elevated rates of birth defects in contaminated compared to uncontaminated regions suggest that exposure to radiation in utero might impact development and that chronic radiation exposure might represent an underestimated risk to human health., Methods: We sought to determine current radiation exposure routes in Rivne-Polissia, a region of Ukraine contaminated by the Chernobyl accident. This represents a first step toward comprehensive studies of the effects of chronic radiation exposure on human health. We designed and administered a dietary and activity survey to 344 women in Polissia. We assessed types and sources of food consumed, types of outdoor activities, and alcohol intake., Results: Alcohol intake was low and alone does not account for the observed high rates of birth defects. Wild foods, especially mushrooms and berries, and locally produced foods, especially milk related, were major radiation exposure routes. Additionally, women were exposed to radiation through inhalation while burning grasses and potato vines in fields, and wood for cooking and heating., Conclusions: Twenty four years after the Chernobyl accident, women continue to be chronically exposed to low-dose radiation at levels exceeding current recommendations. This might contribute (especially synergistically with alcohol consumption and micronutrient deficiencies) to higher prevalence of birth defects in areas of Ukraine with high levels of radiation contamination compared to uncontaminated areas., ((c) 2010 Wiley-Liss, Inc.)

Anticancer treatments-induced central nervous system neurotoxicity has become a major problem in recent years. Real advances in therapeutic results for cancer treatments have improved patients' survival. Nowadays, central nervous system radiation therapy is widely prescribed, both for palliative and curative treatments in the management of malignant or benign tumors. Recent data on tolerance of normal central nervous system to radiation therapy are reviewed here, early and delayed radiation-induced effects are described and dose recommendations are suggested for clinical practice., (Copyright (c) 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Radiation myelopathy is one of the most dreadful complications of radiation therapy. Despite multiple animal experiments and human autopsic series, its pathogenesis remains largely unknown. In most instances, the classical aspect of myelomalacy combines glial and vascular injuries in various sequences. Recent studies point out the role of oligodendrocytes and their precusors, as well as of intercellular mediators (cytokines and stress molecules). The clinical presentation comprises a spectrum of non specific neurological symptoms whose evolution is sometimes regressive but more commonly progressive and life-threatening. Usually, it occurs following a latent period of six months to two years after irradiation of the cervical, thoracic or upper lumbar spine to a dose in excess of 50 Gy, conventionally fractionated. Nonetheless, these typical features can be altered by extrinsic factors, such as hypofractionation/acceleration of the dose, multiple surgical procedures, chemotherapy especially megatherapy, or neurotoxic drugs. Conversely, hyperfractionated regimens that take into account protracted half-time repair of sublethal damages to the CNS, as well as sophisticated estimates of the dose to the cord and QA programs during the treatment course minimize such risks., (Copyright (c) 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Two Drosophila melanogaster strains (Canton-S and ri-lines) for 20 generations were in the controlled terms of chronic irradiation with 3-dose rate (1,2 x 10(-8); 0,3 x 10(-8); 0,12 x 10(-8) Gy/c). The dynamics of hybrid dysgenesis frequency was explored for each generation of F1 descendants from Canton-S and ri-lines crossing. The gradual change of dose response of hybrid dispense depending on duration of irradiation of ancestors and dose rate was shown. The complex dynamics of hybrid dysgenesis frequency depending on irradiation duration of ancestors and dose rate was detected. The cumulative effect of the prolonged irradiation shows up as adaptation at the lowest dose rate and as exhaustion at the highest dose rate. Question comes into discussion about the features of transitional process and including of protective and adaptive reactions hierarchy at the conditions of radiation factor chronic action.

156 children of the main group (were born to parents irradiated in the result of Chernobyl disaster), in which according to Doppler echocardiography isolated abnormal chords of the left ventricle (AHLV) identified, 44 children of control group and 50 children of referent group were involved in the study Analysis of indicators of operational regulation of heart rate in children of primary group indicate the existence of autonomic dysregulation, which has the maximum expression in children with a threshold number of isolated abnormal chords. Evidence of autonomic dysregulation in children born to parents irradiated in the result of the Chernobyl disaster with isolated AHLV requires primary and secondary prevention to reduce the frequency of unfavourable clinical course.

Congenital heart diseases--the most prevalent and fatal birth defects worldwide--result from a combination of genetic predisposition and environmental factors. Currently, there is a growing body of epidemiological literature on parental and occupational prenatal risk factors. We report a case of a 4-months-old infant whose mother was professionally exposed to the cardiovascular catheterization laboratory during the first 4 weeks of pregnancy. The total radiation dose recorded by dosimeters under apron was 4220 microSiviert equivalent to 210 chest X-rays, suggesting the hypothesis of maternal ionising radiation induced-teratogenic effect.

In early 2008, the very large Kinderkrebs in der Umgebung von Kernkraftwerken [Childhood Cancer near Nuclear Power Plants] (KiKK) study in Germany reported increases in leukaemias and solid cancers among children living near all German nuclear power plants (NPPs). This study, previously described in Medicine, Conflict and Survival, has triggered debates in many countries as to the cause or causes of these increased cancers. An accompanying article reports on the recent developments on the KiKK study including the responses by German radiation agencies, and the results of recent epidemiological studies near United Kingdom and French nuclear installations. This article outlines a possible explanation for the increased cancers. In essence, doses from environmental NPP emissions to embryos/foetuses in pregnant women near NPPs may be larger than suspected, and haematopoietic tissues may be considerably more radiosensitive in embryos/foetuses than in newborn babies. The article concludes with recommendations for further research.

As a continuation of our previous study, we performed a teratological evaluation of the importance of gestational age with regards to the exposure of 20 kHz intermediate frequency magnetic field (IF) on pregnant ICR mice. The pregnant mice were exposed to a 20 kHz IF magnetic field for 8 h/day in a carousel irradiator at 30 microT which is the limit standard for occupational population in Korea. The animals were sacrificed on the 18th day of gestation and the fetuses were examined for mortality, growth retardation, changes in head size and other morphological abnormalities. We concluded that exposure to 30 microT with 20 kHz IF did not cause any observable adverse effects on mouse fetuses., (Copyright 2009 Wiley-Liss, Inc.)

Many pregnant women are exposed to radiation either as a patient or as an employee. Ignorance of the issues surrounding the radiation exposure of pregnant females is encountered among medical and other professionals, often leading to undue concern. The exposure of pregnant patients has to be justified and the risk/benefit carefully assessed. Diagnostic radiological and nuclear medicine procedures do not usually pose an increased risk to the fetus but therapeutic procedures and radiotherapy may do so. Risks are greatest during organogenesis and the first trimester. Informed consent and counseling of the patient are important. Pregnant females working with radiation also need separate consideration and careful monitoring. The author has personal experience of this working as an interventional radiologist throughout pregnancy. Education of professionals working with radiation and in medicine is essential and international organizations in radiation protection should continue to provide and support this role.

Several lines of evidence have linked limb teratogenesis to radiation-induced apoptosis and to the p53 status in murine fetuses. In previous reports, we studied the occurrence of various malformations after intrauterine irradiation and showed that these malformations were modulated by p53-deficiency as well as by the developmental stage at which embryos were irradiated. In this new study, we focused onto one particular phenotype namely forelimb defects to further unravel the cellular and molecular mechanisms underlying this malformation. We measured various parameters expected to be directly or indirectly influenced by irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post conception) and examined for forelimb defects on gestational days 15, 16, 17 and 19 of development. The release of inflammatory cytokines was determined in the amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12, 13 and 19 p.c. Differential gene expression within the forelimb bud tissues was determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation. Apoptosis was investigated in the normal and malformed fetuses using the TUNEL assay and RTqPCR. First, we found that irradiated fetuses with forelimb defects displayed excessive apoptosis in the predigital regions. Besides, overexpression of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death. Secondly, our results showed overexpression of MKK3 and MKK7 (members of the stress-activated MAP kinase family) within the malformed fetuses. The latter could be involved in radiation-induced apoptosis through activation of the p38 and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb defects showed a marked telomere shortening. Interestingly, telomere shortening was observed as the malformations became apparent. Fourthly, we measured cytokine levels in the amniotic fluid and detected a considerable inflammatory reaction among the irradiated fetuses as evidenced by the increase in pro-inflammatory cytokine levels. Altogether, our data suggest that transcriptional modulations of apoptotic, inflammation, stress, and DNA damage players are early events in radiation-induced forelimb defects. These changes resulted in harsh developmental conditions as indicated by a marked increase in cytokine levels in the amniotic fluid and telomere shortening, two features concomitant with the onset of the forelimb defect phenotype in our study.

Background: Although there are some reports on neutron teratology, there is little information on the adaptive response of gamma radiation for protection against neutron-induced teratogenesis. This study examined whether or not a low dose of gamma radiation can induce an adaptive response in mouse fetuses exposed to a subsequent dose of neutrons in vivo., Methods: Pregnant ICR mice were exposed to a priming dose of 0.3 Gy (0.9 Gy/min) of gamma rays on day 10.5 of gestation and challenged with 0.8 Gy (0.94 Gy/minute) of neutrons 24 h later. The mice were sacrificed on day 18.5 of gestation. The fetuses were examined for mortality, growth retardation, and other morphologic abnormalities., Results: The tail length in the 0.3 Gy of gamma rays + 0.8 Gy of neutrons group was significantly shorter than in the 0.8 Gy of neutrons group. Although there was no significant difference compared with the 0.8 Gy of neutrons group, the number of live fetuses in the 0.3 Gy of gamma rays +0.8 Gy of neutrons group was lower. There was no evidence of primed exposure-related reductions in the malformed fetuses. Although there was no significant difference compared with the unprimed group, the number of malformed offspring in the primed group was higher. Furthermore, the incidence of kinked tail and adactyly was significantly higher in the primed mice than in the unprimed mice., Conclusions: Overall, this study shows that exposure to 0.3 Gy of gamma rays failed to induce an adaptive response of fetogenesis to a neutron challenge dose., ((c) 2008 Wiley-Liss, Inc.)

Objective: To assess the desire to have children, the actual number of children, and children's health in a survey of 752 adult survivors of paediatric or adolescent cancer in Berlin, Germany., Patients: The German Childhood Cancer Registry ( Deutsches Kinderkrebsregister, DKKR) listed 752 paediatric cancer patients who had been treated in 1 of the 2 paediatric oncology centres in Berlin since 1980 and were 18 years of age or older at the time of the survey., Methods: A 4-page questionnaire assessing pubertal development, fertility, the desire to have children, the actual number of children, and children's health was sent to 574 former patients located using data from the DKKR and German Residents' Registration Office., Results: In total, 45% (n=260) of patients (140 women, 120 men) returned the questionnaire. The mean age was 10.9 years at the time of diagnosis and 24.3 years at the time of the present survey. Various aspects of puberty were assessed to evaluate pubertal development. Of all study participants, 77% indicated a general desire to have children. Reasons given for not having children included 'Still too early to have children' (67%), 'Fear that my child will develop cancer' (9%), and 'Fear that cancer will recur' (6%). Transient amenorrhoea, lasting from 1 to 30 months, occurred in 25 of 74 patients after chemo- and radiotherapy. Five of 136 participants indicated that they had already reached menopause. Seventeen per cent of all participants or their partners had already been pregnant. The miscarriage rate was 13%. Thirty participants gave birth to or fathered a total of 41 children, of whom 40 were healthy and 1 was born with a foot deformity (Pes equinovarus). Among participants' children, mean weight at birth was 3 458 g, and mean head circumference was 35 cm., Discussion: The desire to have children was lower among our survey participants than in the general population of the same age (77% vs. 90%). Participants' fears that their children might develop cancer or that their own cancer might recur are often unfounded. Paediatric cancer survivors, relatives, and attending physicians should be well informed about this issue by paediatric oncologists. The proportion of miscarriages, mean weight at birth, and mean head circumference at birth in our study were comparable to the German general population., Outlook: We intend to conduct a nationwide survey entitled 'Fertility after Chemo- and Radiotherapy in Paediatric and Adolescent Patients' (FeCt). The aim is to gain valuable data with a larger number of participants and more statistical power to determine whether specific cytotoxic drugs or radiation increase the risk of infertility, and if so, at what doses. For the study, the DKKR has the addresses of more than 5 000 former patients in Germany who are now adults. The results will be used to plan future treatment optimisation studies, and to assess the need for prophylactic measures in cases where fertility-compromising therapies are unavoidable. This nationwide survey 'FeCt' will be supported by the Deutsche Kinderkrebsstiftung.

It has been widely reported that prenatal exposure to ionizing radiation can interfere with embryonic and fetal development, depending on dose and gestational age in which exposure occurs. According to several studies on animal models, different well-defined stages during prenatal life can be distinguished in relation to teratogenic effects. During the preimplantation stage, elevated doses of radiation can result in abortion, while lower doses may produce genomic damage that is usually repaired. On the other hand, during the organogenesis stage in mice (embryonic day 6.5 [E6.5] to E13.5), irradiation is associated with increased incidence of malformation and intrauterine growth restriction (IUGR). Later exposure is linked to brain damage. Doses used in animal studies are generally higher than those used for diagnostic procedures in humans. Usually, radiation exposure to diagnostic range (<0.05 Gy = 5 rads) is not associated with an increased risk of congenital anomalies. In human studies, elevated doses produce adverse outcomes, depending on stage of development, as in animal studies. Blastogenesis (up to two weeks) is associated with failure to implant or no significant health effects. An increased risk of malformation and growth retardation can be observed for two to seven weeks exposure (organogenesis stage), while exposure at later stages (fetogenesis) is mainly associated with brain damage. In this review we focus on the relevance of estimating the cumulative dose of radiation to the fetus and the gestational age in which exposure occurs, to provide appropriate counseling to pregnant women., ((c) 2007 Wiley-Liss, Inc.)

Objectives: To evaluate abortion and fetal congenital anomaly rates in women previously submitted to radioiodine therapy for differentiated thyroid carcinoma., Study Design: A case-control study of 108 pregnant women, 48 cases whose pregnancies were evaluated after they had undergone radioiodine therapy for differentiated thyroid carcinoma, and the control group consisted of 60 healthy pregnant women., Results: Of a total of 66 pregnancies, 14 conceived within the first year, 51 one or more years after the last administration of 131I, the medical record of one patient was not available. The interval between the last radioiodine therapy administration and conception ranged from 1 month to 10 years. There were a total of 4 miscarriages, 2 of them for unknown reasons. There was one case of congenital anomaly and two preterms birth. Nine women presented the following pregnancy events: placental insufficiency, hypertensive crisis, placental detachment, risk of miscarriage, preterm labour and four miscarriages. No statistical difference was observed between the studied and control groups., Conclusion: Radioiodine was followed by no significant increase in untoward effects in neither the pregnancy nor the offspring.

The purpose of the present research was the estimation of probable genetic consequences at the liquidators of the consequences of Chernobyl accident in 1986-1987. The research is made on two groups of the liquidators. The first group included the liquidators taking place on the account in the branch register and working now at the enterprises of a nuclear industry. The second group included 902 liquidators of consequences of Chernobyl accident in 1986 constantly living in the Ryazan area and which are taking place on permanent observation the account in regional hospital. For an estimation of probable genetic effects analyzed the data on frequency and outcomes pregnancy of the wives of the liquidators, on condition and on diseases of newborn, on switching intrauterine development defects (IDD). The analysis carried out depending on dozes of an irradiation: up to 5 cGy; 5-10 cGy and 10-25 cGy. Received materials testify, that at the liquidators, at a doze of an external irradiation 10-25 cGy, the determined effects--period long sterility, kept at a part them till 3 years come to light. The set of the received data, such as depending from the dose increase of frequency of spontaneous abortions and of inherent defects of development of newborn, the increase of frequency diseases of newborn and share newborn with low weight, allows to make a conclusion about an induction of genetic effects in sexual cells of the liquidators of consequences of Chernobyl accident at dozes of an external irradiation more than 10 cGy. Taking into account high biological efficiency of alpha-radiation (K = 20), and of beta-radiation (K = 2-4), the equivalent effective doze male gonads (testes) in 3-5 times is higher, than estimated only from external gamma-radiation.