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In response to concerns about health due to radiation exposure, the Fukushima Prefecture launched the Thyroid Ultrasound Examination program for residents aged 0-18 years at the time of the earthquake. Herein, we considered the confounding factors involved in the regional differences in the development of thyroid cancer. In this study, the 242 065 individuals who participated in both first- and second-round surveys were classified into four groups by address according to their air radiation dose. The number of participants diagnosed as malignant or suspicious for malignancy by cytological examination were 17, 38, 10 and 4 with detection rates of 53.8, 27.8, 21.7 and 14.5 per 100 000 participants in Regions 1, 2, 3 and 4, respectively. Sex (P = 0.0400), age at the time of the primary examination (P < 0.0001) and interval between the first- and second-round surveys (P < 0.0001) were significantly different among the four regions, and these were suspected to be confounding factors affecting regional differences in malignant nodule detection rates. In addition, significant regional differences were observed in the participation rate in the confirmatory examination (P = 0.0037) and the fine needle aspiration cytology implementation rate (P = 0.0037), which could be potential biases. No significant regional differences in the detection of malignant nodules were found in the multivariate logistic regression analysis after adjusting for the survey interval alone or for sex, age and survey interval. The confounding factors and biases identified in this study that may have important impacts on thyroid cancer detection rate should be fully considered in future studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The Great East Japan Earthquake on March 11, 2011, and the subsequent tsunami caused an accident at the Fukushima Daiichi Nuclear Power Plant, in which extensive damage to the nuclear power reactors resulted in massive radioactive contamination. Fukushima Prefecture implemented the Thyroid Ultrasound Examination (TUE) program as part of the Fukushima Health Management Survey project in response to residents' anxieties about health risks due to radiation exposure for residents aged 0-18 years at the time of the nuclear accident. This program consisted of the primary examination and the confirmatory examination. In the primary examination, thyroid nodules and cysts were examined using portable ultrasound apparatuses. The confirmatory examination was performed to have clinical or cytological diagnosis. As of June 30, 2021, 116, 71, 31, 36, and 9 examinees in the first, second, third, and fourth round of surveys, and the survey at age 25 years, respectively, were determined to have nodules cytologically diagnosed as malignant or suspicious for malignancy. The confirmatory examination of the fourth-round survey and the primary and confirmatory examination of fifth-round survey are currently in progress. Together with the low thyroid absorbed radiation dose estimated in the United Nations Scientific Committee on the Effects of Atomic Radiation 2020 report, our results suggested that the increased incidence of childhood thyroid cancer in Fukushima Prefecture was not caused by radiation exposure, but rather by the highly sensitive detection method. As detailed in this review, there were ongoing challenges in our program, such as actions against the risk of overdiagnosis and psychological support for participants and their families.

Background: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined., Methods: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level., Results: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52-2.59), 0.55 (95% CI, 0.31-0.97), 1.05 (95% CI, 0.79-1.40), and 1.24 (95% CI, 0.89-1.74)., Conclusion: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016-2017) in Fukushima Prefecture.

Background: The thyroid ultrasound examination (TUE) program was initiated among the residents of Fukushima Prefecture aged ≤18 years at the time of the Fukushima Dai-ichi Nuclear Power Plant accident. In this program, fine needle aspiration cytology (FNAC) was performed only in cases that conformed to the Japanese guidelines for the management of thyroid nodules. To analyze the suitability of the protocol in the TUE, we analyzed the implementation rate of FNAC and the detection rate of thyroid malignancy. Methods: There were 299,939 and 269,659 voluntary participants in the Preliminarily Baseline Survey (PLBS), first-round survey, and the first Full-scale Survey (FSS), second-round survey, of the TUE, respectively. FNAC is recommended for nodules with diameters 5.1-10.0 mm showing sonographic characteristics that are strongly suspicious for thyroid carcinoma; diameters 10.1-20.0 mm with characteristics that are suspicious for carcinoma; and all nodules with diameters >20 mm. Results: In the PLBS and the first FSS, 1362 and 1382 cases with thyroid nodules sized ≥5.1 mm in diameter were found, respectively. The implementation rates of FNAC in the PLBS were 20.1%, 63.2%, and 87.7% of subjects with nodules sized 5.1-10.0, 10.1-20.0, and ≥20.1 mm in diameter, respectively. In the first FSS, the FNAC implementation rates were 7.3%, 26.0%, and 50.0% in the subjects with nodules with diameters 5.1-10.0, 10.1-20.0, and ≥20.1 mm, respectively. In the subjects who underwent FNAC, the detection rates of malignant and suspected malignant nodules were 21.4% and 34.1% in the PLBS and first FSS, respectively. In the first FSS, malignant or suspected malignant nodules were found in 0.63% and 0.40% of subjects who had nodules of diameters ≤5.0 mm and 5.1-10.0 mm in the PLBS, respectively. In contrast, in the subjects with nodules measuring ≥10.0 mm in diameter in the PLBS, no malignancies were detected. Conclusions: The use of a protocol that conformed to the Japanese guidelines led to a reduction in the FNAC implementation rate and an increase in the malignancy detection rate in smaller nodules. In addition, the use of this strategy enabled us to avoid detection failure of thyroid carcinomas >10.0 mm.

Background: A significant increase in the incidence of papillary thyroid carcinoma (PTC) in subjects exposed to radiation at a young age is a well-documented health consequence of the Chernobyl accident. The ongoing Thyroid Ultrasound Examination (TUE) program in children and adolescents of Fukushima Prefecture in Japan also indicated a high prevalence of PTC although its attribution to radiation exposure is a subject of debate. The objective of this study was to perform histopathological analysis of tumor architecture and invasive properties in (i) radiogenic post-Chernobyl and sporadic PTCs from Ukraine, and (ii) PTCs in patients from Fukushima and other Prefectures of Japan of comparable age groups. Methods: The Ukrainian radiogenic PTCs included 245 PTCs from patients who resided in three highly 131 I-contaminated regions and 165 sporadic PTCs diagnosed in residents of the same regions who were born after the accident and therefore not exposed to radioiodine. The Japanese series included 115 PTCs detected during the preliminary and the first full-scale surveys of the TUE in Fukushima and 223 PTCs from patients resident in other Prefectures. All of the subjects were included in the main statistical analysis. Three additional analyses were performed limiting the subjects to children, adolescents, and adults. Results: Ukrainian radiogenic PTC was characterized by the higher frequency of tumors with a dominant solid-trabecular growth pattern and higher invasiveness, more frequent extrathyroidal extension, lymphatic/vascular invasion, regional and distant metastases when compared with sporadic Ukrainian PTC. The integrative "invasiveness score," based on five cancer characteristics, was also higher in the radiogenic group. The differences were most pronounced in children. In contrast, no significant differences in tumor morphology or invasiveness were observed between the two Japanese groups or the three age subgroups. The only statistically significant findings were the higher proportion of male patients, smaller mean tumor size, and higher frequency of T1b tumors in the Fukushima group. Conclusions: The difference in morphological features that indicate biological behavior of PTC between the radiation-related and sporadic groups from Ukraine, together with the lack of such in the two groups from Japan, strongly suggest a nonradiogenic etiology of PTC from Fukushima and other Prefectures.

Background and Purpose The Thyroid Ultrasound Examination (TUE) program is conducted as part of the Fukushima Health Management Survey. Following the established criteria, examinees are called in for a secondary confirmation examination, which may induce high anxiety related to a thyroid cancer for both the examinees and their families. Therefore, Fukushima Medical University created the Thyroid Support Team to reduce anxiety. The purpose of this study is to analyze the psychosocial support for examinees and their families through two types of records, and to clarify the current issues and determine future directions of support.Materials and methods We analyzed 223 records of support for the first visit of examinees who attended the secondary confirmatory examination, conducted at Fukushima Medical University from September 2018 to March 2019.Results During the first visit, frequent topics and questions brought up by the examinees and their families were about the "Thyroid Ultrasound Examination (TUE) program" and "Examination findings". The Thyroid Support Team members assisted them by "Responding to questions", "Confirming the doctor's explanation" and "Providing information". The percentage of people with high anxiety decreased in both examinees and their family members after the examination. The level of anxiety was lower among those who had already taken the secondary confirmatory examination. Family members' anxiety was significantly higher than that of the examinees, and anxiety levels were highly correlated between examinees and their families.Conclusion The psychosocial support for examinees and their families was important in reducing their anxiety.　Currently there are changes in social conditions and various opinions concerning the TUE.　Thus, careful explanation and the need for decision-making supports for the examinees and their families increased. Also, we should take into account the aging of the examinees and expanding the available psychosocial support.

The Fukushima Daiichi Nuclear Power Plant accident occurred on March 11 2011, following the Great East Japan Earthquake and tsunami. Radioactive materials, including I-131, were released into the environment after the accident. Shortly after, the prefectural government initiated the Fukushima Health Management Survey for monitoring the long-term health conditions of the residents of Fukushima Prefecture. In the survey, thyroid ultrasonography was scheduled for all people aged 18 years or younger who were living in Fukushima Prefecture at the time of disaster. The total number of examinees was approximately 370,000 in the Preliminary Baseline Survey (PBLS), and 380,000 in the first Full-scale Survey (FSS). First, thyroid ultrasonography was performed as the Primary Examination. When a thyroid nodule that meets the fine needle aspiration cytology (FNAC) guideline is detected, thyroid FNAC is performed. By the end of June 2017, the cytological specimens of 187 examinees had been interpreted as Malignant or Suspicious for Malignancy (SFM). In this article, the cytological results of whole categories are presented using the criteria of The Bethesda System for Reporting Thyroid Cytopathology. The total numbers of examinees with SFM or Malignant in PBLS and at the first FSS were 106 (62.0%) and 71 (38.0%), respectively. The data of the cytological results of SFM and Malignant were already reported. However, this is the first report of cytological data from categories other than SFM and Malignant. The results of the current study will contribute to future research into the thyroid conditions of children and adolescents.

Background: Thyroid ultrasound screening for children aged 0 to 18 years was performed in Fukushima following the accident at the Fukushima Daiichi Nuclear Power Plant. As a result, many thyroid cancer cases were detected. To explore the carcinogenic mechanisms of these cancers, we analyzed their clinicopathological and genetic features., Methods: We analyzed 138 cases (52 males and 86 females) who had undergone surgery between 2013 and 2016 at Fukushima Medical University Hospital. Postoperative pathological diagnosis revealed 136 (98.6%) cases of papillary thyroid cancer (PTC)., Results: The BRAFV600E mutation was detected using direct DNA sequencing in 96 (69.6%) of the thyroid cancer cases. In addition, oncogenic rearrangements were detected in 23 cases (16.7%). Regarding chromosomal rearrangements, 8 (5.8%) RET/PTC1, 6 (4.3%) ETV6(ex4)/NTRK3, 2 (1.4%) STRN/ALK, and 1 each of RET/PTC3, AFAP1L2/RET, PPFIBP/RET, KIAA1217/RET, ΔRFP/RET, SQSTM1/NTRK3 and TPR/NTRK1 were detected. Tumor size was smaller in the BRAFV600E mutation cases (12.8 ± 6.8 mm) than in wild-type BRAF cases (20.9 ± 10.5 mm). In the BRAFV600E mutation cases, 83 (86.5%) showed lymph node metastasis, whereas 26 (61.9%) of the wild-type BRAF cases showed lymph node metastasis., Conclusions: The BRAFV600E mutation was mainly detected in residents of Fukushima, which was different from post-Chernobyl PTC cases with RET/PTC3 rearrangement. PTC with the BRAFV600E mutation was smaller but was shown in the high rate of central cervical lymph node metastasis than the wild-type BRAF PTC in the young population of Fukushima., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The identification of thyroid cancers among children after the Chernobyl nuclear power plant accident propelled concerns regarding long-term radiation effects on thyroid cancer in children affected by the Fukushima Daiichi nuclear power plant accident in Fukushima, Japan. Herein we consider the potential association between absorbed dose in the thyroid and the risk of developing thyroid cancer as detected by ultrasonography on 300 473 children and adolescents aged 0-18 years in Fukushima. The absorbed dose mentioned in the present study indicates the sum of that from external exposure and that from internally deposited radionuclides. We grouped participants according to estimated absorbed doses in each of 59 municipalities in Fukushima Prefecture, based on The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2013 report. The 59 municipalities were assigned to quartiles by dose. We limited our analyses to participants aged ≥6 years because only one case of thyroid cancer was observed in participants aged ≤5 years; 164 299 participants were included in the final analysis. Compared with the lowest dose quartile, the age- and sex-adjusted rate ratios (95% confidence intervals) for the low-middle, high-middle and highest quartiles were 2.00 (0.84-4.80), 1.34 (0.50-3.59) and 1.42 (0.55-3.67) for the 6-14-year-old groups and 1.99 (0.70-5.70), 0.54 (0.13-2.31) and 0.51 (0.12-2.15) for the >15-year-old group, respectively. No dose-dependent pattern emerged from the geographical distribution of absorbed doses by municipality, as estimated by UNSCEAR, and the detection of thyroid cancer among participants within 4-6 years after the accident. Ongoing surveillance might further clarify the effects of low-dose radiation exposure on thyroid cancer in Fukushima., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The Great East Japan Earthquake, which occurred on March 11, 2011, and its subsequent Fukushima Daiichi Nuclear Power Plant accident, prompted implementation of the Thyroid Ultrasound Examination (TUE) program as a part of the Fukushima Health Management Survey. The purpose of this program is to support residents of Fukushima Prefecture, and to analyze the health effects of the released radionuclides. Regardless of relatively high participation rates and a well-planned diagnostic flow, it is conceivable that not all thyroid cancer cases can be detected by the TUE program. The aims of the present study were to identify and characterize these "outside" cases, targeting patients at Fukushima Medical University (FMU) Hospital. As of June 30, 2017, we have successfully identified 11 outside cases. These corresponded to 5.7% of the 194 subjects who were identified as having thyroid cancer or suspected thyroid cancer in the TUE program. Although the outside subjects of other institutes were not investigated, the present study may have identified the majority of outside subjects in Japan, considering that FMU Hospital treats a large number of thyroid cancer subjects. Furthermore, the characteristics of the 11 subjects were not different from those of the subjects identified in the TUE program. These findings confirm that the TUE program was able to identify subjects of thyroid cancer adequately and sufficiently.

Thyroid ultrasound screening of young residents in Fukushima Prefecture, Japan, showed a high detection rate of papillary thyroid carcinoma (PTC). Detailed morphological analysis of these tumors was not presented to date. This study sets out to evaluate changes in histopathological and invasive characteristics of Fukushima PTC with time after the nuclear accident of March 2011 in all available cases and in different age subgroups. Histological specimens of 115 PTCs from patients aged 18 years or younger at the time of the Fukushima Dai-ichi Nuclear Power Plant accident, who underwent surgical resection at Fukushima Medical University during 2012-2016, were reviewed. Patients were divided into those treated during the first 4 years after the accident (n = 78, shorter-onset) or later (n = 37, longer-onset). The whole group and 3 age subgroups: children (aged less than 15 years), adolescents (aged from 15 to less than 19 years), and young adults (aged from 19 years) at surgery were analyzed. No statistically significant time-related changes in tumor structure or invasiveness were found in the whole group or in age-matched subgroups. Statistically significant age-related downtrend was observed for intrathyroid spread in the whole group of patients. The absence of temporal changes in tumor morphological characteristics and tumor invasiveness strongly suggests common etiology of the shorter- and longer-onset Fukushima PTCs, which are unlikely related to the effect of exposure to very low doses of radiation., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: C-reactive protein (CRP) has been reported to be associated with poorer prognosis in various malignancies. However, the relationship between CRP and differentiated thyroid carcinoma (DTC) remains to be elucidated., Methods: A total of 45 patients, including 32 patients with preoperative DTC and 13 DTC patients with metastatic disease, were included in the study. The relationships between CRP levels and clinicopathological features were retrospectively analyzed., Results: Analysis using a receiver operating characteristic curve revealed a preoperative CRP cutoff value of 0.155 mg/dL. Patients with preoperative CRP ≥ 0.155 mg/dL, those with T3 + T4, those with extrathyroidal invasion, or those with stage II, showed a statistically shorter recurrent-free survival than those with preoperative CRP < 0.155 mg/dL, those with T1 + T2, those without extrathyroidal invasion, or those with stage I (P = 0.001, P = 0.004, P = 0.024, and P = 0.025, respectively). Preoperative CRP ≥ 0.155 mg/dL was an independent prognostic factor for recurrent-free survival in the DTC patients (hazard ratio = 6.334, 95% confidence interval: 1.023-39.234, P = 0.037). The proportion of patients aged ≥55 y, and those with T3 + T4, was statistically higher in those with preoperative CRP ≥ 0.155 mg/dL than in those with preoperative CRP < 0.155 mg/dL (P = 0.037 and P = 0.038, respectively)., Conclusions: Higher preoperative CRP levels have a robust prognostic impact on recurrence-free survival in DTC patients. In addition, higher preoperative CRP levels were associated with age ≥ 55 y and T3 + T4., (Copyright © 2018 Elsevier Inc. All rights reserved.)