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Wednesday, May 11, 2016

Response to the Chicago Tribune Editorial "The children of Fukushima: When medical tests mislead"

The following is the letter to the Editor for the Chicago Tribune editorial, "The children of Fukushima: When medical tests mislead." The letter was submitted through the online form on April 19, 2016, but there has been no response from Chicago Tribune. (Brevity of the content is due to the 400-word limit for letters).

*****

Dear Editor,

The March 25, 2016 Chicago Tribune editorial, “The children of Fukushima: When medical tests mislead” is misleading on its own regarding the childhood thyroid cancer situation in Fukushima Prefecture, Japan.

Differences in cancer rates by distance from the accident site and contamination levels may not be obvious, but an epidemiological analysis by Tsuda et al. (http://journals.lww.com/epidem/Fulltext/2016/05000/The_Authors_Respond.37.aspx) found a dose response tendency with proximity to the accident site after adjusting for the length of time between the accident and the time of screening. It is also important to remember only 1,080 children had their thyroid exposure doses directly measured and that is only 0.36% of 300,000 children who underwent thyroid ultrasound examination. Taken under high background levels, the doses are far from being accurate.

Children younger than age 5 showed an increased rate of thyroid cancer beginning at 4-5 years after the Chernobyl accident, so the first 3 years after the Fukushima accident, covered by the completed first round screening, would not expect to see that age group affected. The first cancer case was diagnosed about 17 months after the accident, not within a year, and some of these early cases might have been the result of radiation exposure promoting the growth of latent cancer that might not have become large enough to be detected until much later in life if unexposed to radiation.

Comparison with three other prefectures where one cancer case was diagnosed in 4,365 subjects is invalid as its small sample size lacks the necessary statistical power. The Korean screening is in adults and should not be compared with children.

It is true that unnecessary medical testing can lead to overdiagnosis and overtreatment, but the clinical information provided by Fukushima Medical University, such as metastasis and physical proximity of tumor to other vital structures, validates surgical interventions for the majority of the operated cases in Fukushima. Thyroid cancer is believed to grow slowly, but 80% of thyroid cancer cases discovered in the ongoing second round screening had no suspicious findings in the first round screening only 2-3 years earlier.

It is not just a cancer death but cancer diagnosis itself that is concerning for patients and their loved ones, and the causality should not be prematurely prejudged. A lesson of the Fukushima children may be the importance of conducting a timely and adequate collection of the exposure data and a comprehensive evaluation of data in a transparent and unbiased manner.

Yuri Hiranuma, D.O.
Member, Radiation and Health Committee
Physicians for Social Responsibility

Saturday, April 23, 2016

Thyroid Cancer in Fukushima Children: When the Language and Information Gaps Mislead

With the year 2016 marking the passage of five years since the Fukushima nuclear accident, many writings—articles, editorials, academic papers—have been released reflecting on the first five years after the accident. Some of the writings address a psychosocial aspect of the accident such as “problems” caused by the stress of evacuation and the “unwarranted” fear of radiation, dismissing the potential health effects of radiation exposure, even ignoring the science. Others focus on the alleged withholding of medical data by authorities, speculating on the health effects of the Fukushima accident reaching even the United States. 

Official data and information available in English are often limited and biased. Transparency and impartiality of such information, released by the government and international agencies, can be influenced by ulterior motives other than public health protection. However, without a fluency in Japanese and an ability to navigate through and comprehend the mass of official and unofficial information only available in Japanese, it may not become obvious that the transmission of accurate information is indeed hindered by the language barrier.

Furthermore, followers of numerous government committee meetings regarding the health effects of the Fukushima nuclear accidents—most of them live streamed on the Internet—have witnessed a systematic underestimation of health effects due to low-dose radiation exposure, with the claim of the outdated and unscientific 100 mSv threshold discourse. Despite concerns from local medical associations, potential health effects in prefectures adjacent to Fukushima Prefecture were dismissed, as if the radioactive plume was blocked by an invisible wall at prefectural borders. This is a far cry from the precautionary principle that should be in place for the protection of public health. 

Consider the Japanese government’s haste to return evacuees to their still contaminated hometowns. This must be done so things appear “back to normal” for the purpose of recovery (mostly economic), even though it is clearly impossible to decontaminate a whole community in a natural setting of mountains and forests. Radiation doses of returned residents are to be monitored to keep an additional exposure dose below the regulatory limit. (But how good is it to know what your exposure dose is after the fact?) 

In essence, the health effects by the Fukushima nuclear accident are being maximally minimized. 

One of the most controversial topics about the health effects of the Fukushima nuclear accident is the thyroid cancer cases detected in Fukushima children as a result of the thyroid ultrasound screening. Most of the English writings on this topic accept, at face value, certain claims made by Fukushima Medical University as well as Japanese government officials in order to dismiss any connection between the Fukushima thyroid cancer cases and radiation. 

Below, some items in the March 25, 2016 editorial in Chicago Tribune, “The children of Fukushima: When medical tests mislead,” are addressed to point out the misleading information that is widespread even amongst the academic circle. 


1. There is no regional difference of thyroid cancer occurrence.

The March 25, 2016 Chicago Tribune editorial states:

“Children living closer to the accident in areas of greatest contamination had no greater rate of early cancer than those living farther away.”

This essentially refers to the lack of dose response, but it might depend on how the prefecture is divided into regions. 

According to the official data by Fukushima Medical University (FMU) and Fukushima Prefecture in the final report of the first round screening [1], no regional difference was reported based on the comparison amongst 4 regions—one region including 13 municipalities with the highest dose and the evacuation zone, and three other geographically-divided regions. However, topography can vary even within the same geographical region, potentially affecting the flow of the radioactive plume. In other words, regional divisions like this might mask critical differences.

On the other hand, the biggest surprise in the official comparison was the Aizu region in western part of Fukushima Prefecture where the prevalence rate of 32.6 per 100,000 was very close to the prevalence rate in the highest dose area, 33.5 per 100,000. (See the second row from the bottom in Table 9). 



The Aizu region supposedly received very little contamination owing to the mountain range to its east, and the officials seem to attribute the higher-than-expected prevalence to the screening activity. According to this logic, other uncontaminated areas of Japan might have similar prevalence. In fact, thyroid ultrasound screening of 4,365 subjects in three other prefectures—Yamanashi, Aomori and Nagasaki—called the three-prefecture study [2] in short, revealed about the same frequency of ultrasound findings such as cysts and nodules as Fukushima, and one case of papillary thyroid cancer was diagnosed in the follow-up study [3].  Very little discussed are the limitations of this study, such as a small sample size leading to a bigger uncertainty, and different age and gender distributions (no age 0-2 and more female adolescents) than Fukushima.

If the three-prefecture study is indeed a proof of screening effects in Fukushima, then it can be deduced that similar prevalence might be found in the rest of Japan. Judging from the clinical information provided by Shinichi Suzuki, a thyroid surgeon at FMU, the vast majority of the operated cases in Fukushima had surgical indications, i.e. required surgery, such as the metastasis and proximity to vital structures, even in the absence of subjective symptoms at the time of diagnosis. Then, it logically follows that there may be other such cases outside Fukushima. However, no attempt is made to conduct a nationwide survey for fear of causing detriments to asymptomatic individuals through unnecessary medical tests and treatments.

In October 2015, the Okayama University team headed by an environmental epidemiologist and public health specialist, Toshihide Tsuda, published in Epidemiology the first epidemiological analysis of the publicly available Fukushima thyroid cancer data [4]. Tsuda et al. first divided the entire Fukushima Prefecture into 3 areas by the year of screening and subdivided them into 9 districts based on the population size, enabling a statistical analysis. 

For external comparison, they calculated for each area/district the incidence rate ratio from the prevalence rate assuming a latency period of 4 years. The calculated incident rate ratios showed thyroid cancer occurrence in some regions were 30 to 50 times the expected rate. Tsuda et al. concluded the excess occurrence was beyond what could be explained by screening effect. Internal comparison did not appear to show dose response amongst the 3 regions by the screening year, which supposedly represented the degree of contamination. 



However, when the data (updated to June 30, 2015) was adjusted for “latency” or the length of time elapsed between the accident and time of screening in their response to letters to the editor [5], a dose response tendency showed up with higher prevalent odds ratios in districts closer to the Fukushima Daiichi nuclear power plant.



Other points to keep in mind include the fact the dose estimation is far from perfect with insufficient direct measurements of the thyroid dose and that the soil contamination does not necessarily reflect the amount of radioactive plume that was in the air at the time of exposure, and that the cesium soil deposition does not necessarily correlate with the amount of radioactive iodine that might have been inhaled or ingested.

A small number of measurements conducted in some 1080+ children aged 0-15 from three municipalities—small considering there were over 360,000 children aged 18 or younger in Fukushima Prefecture at the time of the accident—were ladened with technical issues such as high background radiation levels. The March 30, 2011 internal document, a correspondence from the Emergency Response Center to the Nuclear Safety Commission [6], states how 11 highest readings, taken in Iwaki City, were adjusted to yield lower thyroid equivalent doses as shown in the table below. 
    

From left of the table, column 1 shows measurement dates of March 26 or March 27, 2011. Columns 2 and 3, blacked out for privacy protection on the original document, correspond to the identification number and age of the subject, respectively. Column 4 shows the actual reading ranging from 0.22 μSv/h to 0.27 μSv/h. Columns 5 and 6 correspond to the net measurement after subtraction of the average air dose in μSv/h as the background level in and the resultant thyroid equivalent dose in mSv, respectively. Columns 7 and 8 correspond to the net measurement in μSv/h after subtraction of the measurement at the clothed shoulder as the individual background level and the resultant  thyroid equivalent doses in mSv, respectively. 

For example, in the first subject with the actual measurement of 0.22 μSv/h, the net measurement went down from 0.05 μSv/h to 0.04 μSv/h and the thyroid equivalent dose went down from 19 mSv to 7.1 mSv. For subject 8 with the highest reading of 0.24 μSv/h who had the highest thyroid equivalent dose of 43 mSv before the adjustment, using the individual background level taken at the clothed shoulder reduced the thyroid dose to 25 mSv. 

The problem with using the measurement taken at the clothed shoulder is the potential contamination on clothing might lead to a smaller net measurement. For instance, if the skin and the clothing have the same amount of radioactive contamination, subtracting the measurement of clothing from the measurement of the thyroid will yield the net measurement of zero, but this may not reflect the actual thyroid measurement. 

Despite its limitations and the potential underestimation, the so-called 1080 survey data is considered to represent the exposure dose of Fukushima children, and it seems to be widely accepted by overseas researchers who rely on information published in peer-reviewed English language journals that the maximum thyroid dose in Fukushima children was 35 mSv. Yet there are many other children who might have been exposed to higher doses but never had thyroid doses measured. For instance, children from non-evacuation zone led regular daily activities without any protective measures in the absence of any warnings about the approaching radioactive plume. Many were outside unprotected, and there is no way to accurately estimate the exposure doses for them.

In addition, the Ministry of the Environment expert committee chaired by Shigenobu Nagataki heard presentations by experts who actually conducted the 1080 survey who acknowledged that they thought the survey was only preliminary and more detailed measurements would be conducted if necessary. In the end, officials never conducted a more detailed thyroid survey measurement in a boy from Iwaki City who registered the highest thyroid measurement, 35 mSv, for fear of “scaring the family and the community” upon a recommendation [7] of Yoshiharu Yonekura, the chair of the National Institute of Radiological Sciences as well as the current chair of UNSCEAR. (Incidentally, Iwaki City, not one of the evacuated municipalities, was hit by the radioactive plume when the wind turned south, but the lack of precipitation afterwards prevented a heavy ground deposition of radioactive substances as in Iitate Village).  

Maintaining a sense of security and preempting panic and mass chaos took precedence over accurate recording/reporting of exposure doses. 

2. Age distribution

The March 25, 2016 Chicago Tribune editorial states:

“Younger children and infants, whose thyroids are more likely to be affected than those of older children, did not show an expected higher rate of abnormal findings.”

It is well known that beginning about 4 years after the Chernobyl accident, an increased number of thyroid cancer cases were detected in children in Russia, Belarus and Ukraine who were infants at the time of the accident. In the first 3 years after the Fukushima accident, the youngest cancer case was 6 years old at the time of the accident according to the data published so far. This is depicted in the age distribution graph in a letter to the editor of Thyroid [8].



The top panel shows the number of thyroid cancer cases by age in Ukraine in two different time periods: 1986-1989 (black) and 1990-1993 (dark gray). The 1986-1989 age distribution resembles the graph in the bottom panel showing the first three years in Fukushima (light gray). 

Japanese authorities, notably Shunichi Yamashita, have referred to this resemblance to make certain points: 1) Fukushima’s age distribution in the first three years resembles the first three years in Chernobyl during the latency period when radiation-induced thyroid cancer was still growing, and thus the Fukushima cases are not related to radiation; 2) Fukushima’s thyroid cancer cases are not related to radiation exposure since they do not include younger children under age 4 or 5. 

It might be this second point that is addressed by author(s) of the Chicago Tribune editorial. However, this cannot be a valid claim since a large number of cancer cases in younger children under 4 or 5 were not seen until 4 to 5 years after the Chernobyl accident, and it should not be compared to the first 3 years in Fukushima. Yet this misguided direct comparison is done by none other than the authoritative researchers in radiation-induced thyroid cancer such as Williams [9] and Wakeford [10].



(From: Williams D, Thyroid Growth and Cancer. Eur Thyroid J 2015;4:164-173)


(Wakeford J. Radiol. Prot.  36  (2016) E1)


It remains to be seen whether a similar increase in thyroid cancer cases in younger children will be seen in Fukushima from the fourth year onward, when the complete results of the ongoing second round screening covering the fourth and fifth post-accident years become available, probably later in 2016.


3. Latency issues

The Chicago Tribune editorial states:

“Some cancers were observed less than a year after the meltdown. It generally takes years for thyroid cancer to develop after radiation exposure.”

For clarification, the first case suspicious for thyroid cancer in Fukushima children was reported in September 2012, or 18 months after the accident, not less than a year. 

A traditional view of carcinogenesis is a multi-stage process of mutations transforming normal cells into cancer cells through initiation, promotion, and malignant transformation , and it is considered to take a long time. Radiation-induced thyroid cancer in children is thought to take several years to develop after DNA damage is “initiated” by radiation,  which might explain the increase in thyroid cancer cases 4-5 years after the Chernobyl accident in children who were younger than age 5 at the time of the accident.

On the other hand, there were higher-than-expected number of thyroid cancer cases diagnosed in Belarus the first year after the 1986 Chernobyl accident [12,13].

As a complete carcinogen, radiation can affect all stages of carcinogenesis. Radiation can also affect the so-called “cancer niche,” or the tumor microenvironment necessary for clinical development of cancer [14]. In other words, radiation might facilitate the growth of pre-existing precancerous cells or latent cancers through promotion as well as creation and/or expansion of the cancer niche.

It might then be feasible to consider that some of these early cases manifested because exposure to radiation affected the growth of pre-malignant cells or pre-existing cancer. This might not be considered “radiation-induced” in the field of radiobiology, but it can be considered as the effect of radiation nonetheless.


4. Overdiagnosis?

Yet, the reason for detection of so many thyroid cancer cases in the first 3-4 years after the Fukushima accident is not completely clear. Is it because of the screening activity alone as claimed by the officials? Or is it due to radiation exposure? Or is it for some other causes?  

The Chicago Tribune editorial concludes that thyroid ultrasound screening in Fukushima is causing overdiagnosis and suggests overtreatment might be damaging the Fukushima children, but clearly author(s) did not review the clinical details of the operated cases. 

This is not surprising because clinical and pathological information of the operated cases has not been officially released in English and thus not readily available. Pieces of information have trickled out, mostly in Japanses, as abstracts for presentations at Japanese academic conferences and two reports submitted to the Thyroid Examination Evaluation Subcommittee of the Fukushima Health Management Survey Oversight Committee (see the November 29, 2014 post, the June 23, 2015 post, and the September 10, 2015 post for details).

It is important to understand that clinical and pathological information released by FMU is not comprehensive enough to allow for any meaningful analysis of the surgical cases. However, even with such limited information, it is clear that  surgeries were medically indicated for the vast majority of the cases for reasons such as lymph node and/or distant metastases and close proximity of the tumor to vital structures such as the vocal cord, trachea, or recurrent laryngeal nerve. Pathological analysis of the surgical specimen revealed 39% had mild extrathyroidal extension (cancer cells spreading beyond the covering of the thyroid gland), and 74% had lymph node metastasis. In order to preserve thyroid hormone secretion, only half of the thyroid gland was removed in 94% of the operated cases. (At the press conference of a newly launched “311 Thyroid Cancer Family Group [15],” a physician advisor to the group revealed there were a few cases of recurrence, but this information has been neither released nor confirmed by FMU). 

Furthermore, the interim result of the second round screening shows 40 (80%) of 51 cases suspected or confirmed of thyroid cancer had no ultrasound findings of precancerous tumor in the first round screening—in fact, 25 cases (50%) had no ultrasound findings at all. In other words, for the majority of the cancer cases diagnosed in the second round screening, cancer grew in two to two and a half years since the first round screening.  

Thus the clinical information suggests aggressiveness and fast progression of the thyroid cancer being diagnosed in Fukushima children. (Incidentally, the April 14, 2016 New York Times article [16] reports a type of thyroid cancer, encapsulated follicular variant of papillary thyroid cancer, is reclassified as a benign thyroid tumor [17]. It has been reported that 3 of 87 thyroid cancer cases operated by the end of 2014 were classified as the follicular variant of papillary thyroid cancer [18]. However, there is no sufficient information regarding whether these 3 cases were encapsulated or not).

Two groups of Japanese researchers did calculations to conclude the thyroid cancer occurrence is about 20-60 times the expected rate. Both groups seem to agree this is more than expected from the screening effect—detection of “quiet” and asymptomatic thyroid cancer due to the screening activity—alone.

Tsuda et al., aforementioned in section 1, claim that the excess cases might reflect some screening effect but the radiation effect should also be considered, pointing out the potentially higher exposure doses and the clinical features of the cancer cases.

The study by Tsuda et al. drew a number of criticisms domestically and internationally, mainly for comparing prevalence obtained from screening with incidence of clinically diagnosed cases. Local newspapers in Fukushima Prefecture never covered the release of the Tsuda et al. study. However, a second group of researchers conducted a similar comparison using different methods without such overt criticisms. 

In November 2014, Shoichiro Tsugane, a National Cancer Center epidemiologist and a member of the Fukushima Health Management Survey as well as the Thyroid Examination Evaluation Subcommittee, presented to the Subcommittee a document showing how many cases of thyroid cancer would have been diagnosed in Fukushima Prefecture in 2010, the year before the accident, calculated from the national annual incidence rate [19, 20]. He concluded the observed cancer cases were 61 times the expected and attributed the excess to overdiagnosis. The same estimate was also published in English [21]. In 2015, a related paper was published by Tsugane’s team with updated data, showing the observed rate was about 30 times the expected rate and attributing this increase to overdiagnosis due to screening [22]. Their estimate is included in the Interim Summary by the Fukushima Health Management Survey Oversight Committee [23] as the expression, “several tens of time larger than expected.” 

From published interviews of Tsugane, it is clear he is not considering clinical details of the surgical cases [24] in claiming overdiagnosis which means diagnosis of cancer that does not necessarily need medical intervention. 


Conclusion

When writings such as the March 25, 2016 Chicago Tribune editorial mislead readers on facts of the issue, it is damaging to Fukushima people whose plight is lessened and disregarded. But the core issue is the release of biased information by the authorities, especially in English. This gap in information only adds to the pre-existing language barrier, distorting information transmission.

It is essential for every one of us to be well informed and develop critical thinking in order to counter the one-sided flow of distorted information. The recently established family support group for thyroid cancer patients, “311 Thyroid Cancer Family Group,” will provide the platform for the patients and families to voice their concerns. What is urgently called for is a comprehensive evaluation of data in a transparent and unbiased manner by third-party expert groups, such as the International Society for Environmental Epidemiologists [25].

  1. http://fmu-global.jp/?wpdmdl=1222
  2. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083220
  3. http://www.nature.com/articles/srep09046
  4. http://journals.lww.com/epidem/Fulltext/2016/05000/Thyroid_Cancer_Detection_by_Ultrasound_Among.3.aspx
  5. http://journals.lww.com/epidem/Fulltext/2016/05000/The_Authors_Respond.37.aspx
  6. https://www.iwanami.co.jp/kagaku/20120913_2.pdf#69
  7. https://www.iwanami.co.jp/kagaku/20120913_2.pdf#74
  8. http://online.liebertpub.com/doi/abs/10.1089/thy.2014.0198
  9. http://www.karger.com/Article/FullText/437263
  10. http://iopscience.iop.org/article/10.1088/0952-4746/36/2/E1
  11. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1007563/?page=1
  12. http://www.rri.kyoto-u.ac.jp/NSRG/reports/kr79/kr79pdf/Malko2.pdf
  13. http://www.aec.go.jp/jicst/NC/tyoki/bunka5/siryo5/siryo42.htm
  14. http://www.nature.com/nrc/journal/v13/n7/full/nrc3536.html
  15. http://www.asahi.com/ajw/articles/AJ201603240025.html
  16. http://www.nytimes.com/2016/04/15/health/thyroid-tumor-cancer-reclassification.html?_r=1&referer=
  17. http://oncology.jamanetwork.com/article.aspx?articleid=2513250
  18. http://fukushimavoice-eng2.blogspot.com/2015/06/2015-update-details-of-fukushima.html
  19. https://www.pref.fukushima.lg.jp/uploaded/attachment/91000.pdf
  20. http://fukushimavoice-eng2.blogspot.com/2015/08/the-estimated-number-of-prevalent-cases.html
  21. http://www.bmj.com/content/346/bmj.f1271/rr
  22. https://jjco.oxfordjournals.org/content/early/2016/01/10/jjco.hyv191.full
  23. https://www.pref.fukushima.lg.jp/uploaded/attachment/158522.pdf
  24. http://fukushimavoice-eng2.blogspot.com/2015/09/surgical-and-pathological-details-of.html
  25. http://www.isee-europe.com/blog/open-discussion-on-isees-letter-to-the-authorities-in-japan-concerning-the-paper-by-tsuda-et-al-2015#comments




Friday, March 4, 2016

Fukushima Thyroid Examination Fact Sheet: March 2016

Fukushima Thyroid Examination Fact Sheet:  March 2016

This fact sheet was compiled mostly from the official documents and data, some available only in Japanese, for the purpose of reviewing the first four and a half years of the post-accident thyroid ultrasound screening in Fukushima Prefecture. It is intended as a common knowledge base of the history, basic principle and current status of the largest thyroid ultrasound screening undertaken with controversial results. (For the shorter version of the fact sheet, please refer to this).



Introduction

On October 9, 2011, Fukushima Prefecture began the Thyroid Ultrasound Examination (TUE) on about 360,000 residents who were age 18 or younger at the time of the triple disaster of the earthquake, tsunami, and nuclear accident on March 11, 2011. As the exposure to radioactive iodine dramatically increased the incidence of pediatric thyroid cancer cases after the 1986 Chernobyl nuclear accident, TUE was implemented to monitor the exposed children in Fukushima Prefecture. The majority of Fukushima residents did not receive stable iodine for protection of their thyroid glands.

TUE is part of the Fukushima Health Management Survey (FHMS) [1],  consisting of Basic Survey for external radiation exposure dose for the first four post-accident months estimated from behavior questionnaire and Detailed Surveys including TUE, Comprehensive Health Check, Mental Health and Lifestyle Survey, and Pregnancy and Birth Survey. Its study protocol was published in 2012 [2] . FHMS is funded by the central government [3] and commissioned by the prefectural government to the prefectural-run Fukushima Medical University (FMU) [4].

Screening protocol

TUE consists of the primary examination by thyroid ultrasound screening and the confirmatory examination, if necessary, including more detailed ultrasound examination and urine/blood testing and possible biopsy when needed. The first round of TUE was scheduled to be conducted from October 9, 2011 through March 31, 2014, with each fiscal year from April to the following March covering residents from a set of municipalities grouped according to the air dose level of radiation. 

The second round was scheduled to begin in April 2014, immediately after the first round completed, including residents who were born between April 2, 2012 and April 1, 2013. However, in reality, the primary examination from the first round continued another year through April 30, 2015, concurrent with the second round examination scheduled from April 1, 2014 through March 31, 2015. (FHMS allowed the first timers to participate in the first round even though the second round was going on, as long as they hadn’t received notification for the second round, in order to raise the participation rate of the first round TUE. This effort increased the participation rate by 1.5% to the final participation rate of 81.7%).

The unique diagnostic categories of A1, A2, B and C for TUE were established by the "Diagnostic Criteria Inquiry Subcommittee of Thyroid Examination Advisory Committee," consisting of the following seven organizations: Japan Thyroid Association; Japan Association of Endocrine Surgeons; Japan Association of Thyroid Surgery; The Japan Society of Ultrasonics in Medicine; The Japan Society of Sonographers; The Japanese Society for Pediatric Endocrinology; and Japan Association of Breast and Thyroid Sonology. These diagnostic categories are: 

  • A1: no nodules or cysts found
  • A2: nodules ≦ 5.0 mm or cysts ≦ 20.0 mm
  • B: nodules ≧ 5.1 mm or cysts ≧ 20.1 mm
  • C: requiring immediate secondary examination

(“Cysts” in the TUE are said to be colloid cysts with no malignant potential, as cysts with solid components are classified as “nodules” by the size of the cysts themselves. In other words, a 20.0mm cyst with a solid component would be classified as a 20.0mm nodule and thus placed in the B category).

There was one problem: the lack of baseline data for comparison. Such a large-scale thyroid cancer screening in unexposed children has never been conducted in the world. The FMU officials determined that the screening conducted in the first 3 years after the Fukushima Daiichi nuclear power plant accident be considered baseline [Note] on the premise that the data obtained during this 3-year period would not reflect the effect of radiation exposure since the radiation-induced thyroid cancer only began to appear about 4 years after the Chernobyl accident, establishing the latency of radiation-induced thyroid cancer in children to be about 4 years. Thus the first screening was named “Initial Screening” and later renamed “Preliminary Baseline Screening.” 

  • Note: However, calling the screening conducted after exposure “baseline” does not seem like an appropriate methodology. This presumes any thyroid cancer cases detected in Initial Screening to be due to not radiation effects but screening effect: detection of latent thyroid cancer already present before the accident that would not have been discovered without the screening activity. Can such presumption hold up? In general, radiation-induced cancer seems to refer to cancer whose growth is initiated due to exposure to ionizing radiation as a carcinogen. What if the growth of the pre-existing cancer gets promoted due to radiation exposure? Why would that not be considered radiation effect?

Thyroid ultrasound examination results

As this was the first time such a large-scale thyroid ultrasound screening examination was conducted, each set of the results, released by the Oversight Committee approximately every 3 months beginning on January 25, 2012, caused quite a stir: the public was initially concerned with any ultrasound findings reported, while the officials claimed some of the findings, such as nodules and cysts, were only detected due to high sensitivity of the modern ultrasound equipment and could be physiological and transient. 

The first report [5] officially translated into English, from the Eighth Oversight Committee [6] held on September 11, 2012, shows the rate of A2 at 35-43% and B at 0.5-0.6% for each screening fiscal year (FY). Subsequent reports show a generally increasing tendency for the proportion of A2 from FY 2011 to FY 2013, with the final report [7] of the first round, now called Preliminary Baseline Screening, showing the A2 proportion of 36.4% for FY 2011, 44.6% for FY 2012, and 55.5% for FY 2013, with an overall average of 47.8%. The vast majority (over 98%) of A2 are cysts. Incidentally, the most recent February 2016 second round screening results [8] show the average A2 proportion of 58.5%, slightly higher than the first round. The proportion of B increased from year to year, at 0.5% for FY 2011, 0.7% for FY 2012, and 0.9% for FY 2013, with an overall average of 0.8%. The second round so far shows the B proportion of 0.8 to 0.9%.

Thyroid cancer cases

The first cancer case was reported at the Eighth Oversight Committee meeting held on September 11, 2012. It’s not clearly indicated in the reported results [9] per se, but the minutes of the proceeding (unavailable in English) refer to “one cancer case confirmed after biopsy was conducted in 14 individuals.” Reporting of the biopsy results began, as the confirmatory examination progressed, at the Eleventh Oversight Committee meeting held on June 5, 2013: what was reported included the number of cases suspicious for cancer fine-needle aspiration cytology as well as the number of surgically confirmed cases. Each subsequent reporting of the results revealed an increasing number (14 to 16 more each time) of malignant or suspicious cases, but the number of surgically confirmed cancer cases increased at a slower rate, as surgeries were usually scheduled at the discretion of patients’ life priorities. (Final confirmation of thyroid cancer usually requires pathological examination of the tissue from the resected thyroid gland, and the biopsy results normally only lead to “suspicion” of cancer).

Officials maintained that these findings constituted “screening effect,” that is, widespread screening of asymptomatic individuals often leads to discovery of “latent” cancer that would not have been found if it weren’t for screening. 

As the first round screening wound down, with the primary examination nearly complete and the confirmatory examination progressing further, the second round screening, which began in April 2014, started to show cases suspected or confirmed of cancer. The first thyroid examination report from the second round screening [10] was released at the Seventeenth Oversight Committee meeting held on December 25, 2014 [11], showing 4 cases suspected of cancer. Less than 2 months later, on February 12, 2015, this increased to 8 cases suspected of cancer of which one was surgically confirmed as thyroid cancer [12]. Three months later on May 18, 2015, this nearly doubled to 15 cases suspected of cancer of which 5 were confirmed cancer cases, and yet three months later on August 30, 2015, 10 more were added so there were 25 cases suspected of cancer including 6 cases confirmed as thyroid cancer. November 30, 2015 report revealed 39 cases suspected of cancer, 15 of which have been surgically confirmed as cancer. The most recent data [13] released on February 15, 2016, show 51 suspected cancer cases including 16 surgically confirmed cancer cases.



At the 58th Annual Meeting of Japan Thyroid Association, held November 5-7, 2015, in Fukushima City, Fukushima Prefecture, Dr. Shunichi Yamashita is said to have pointed to screening effect to explain the current increase in thyroid cancer cases. 

However, an important fact needs considered: as seen in the bottom row of the table above, 40 of the 51 cases suspected or confirmed of cancer had either no ultrasound findings (25 cases) or only cysts with no malignant potential (15 cases) in the first round screening. This means, either some ultrasound findings were missed in the first round screening, or new lesions appeared since the first round screening and proved to be cancerous. Fukushima Medical University officials claim there were no missed findings, so these cancers must have grown since the first round screening. This means most of the cancer cases detected during the second round appeared in 2-3 years since the first round screening, contradicting the so-called “latency of four years” that the officials heavily rely on.

The latest tally

The table below shows the most recent results (data as of December 30, 2015) released at the Twenty-First Oversight Committee meeting [14,15],  held on February 15, 2016.



Comparison with annual incidence in Japan

Although it is not appropriate to directly compare between prevalence obtained by screening of general population and incidence based on clinical diagnosis, as a reference the 2010 national incidence [16] estimated in Japan for thyroid cancer in ages 0-19 was 3.3 per million for both sexes, 1.0 per million for male, and 5.6 per million for female [17]. 

Assuming all the suspicious FNAC cases are to be confirmed as cancer, excluding  the single case surgically confirmed to be benign lesions, the first round screening data yields a prevalence of 383 per million (115 cancer cases per 300,478 participants) for both sexes for thyroid cancer in those 0-18 years old at the time of the accident. (However, the estimated incidence significantly increases with age, as shown in the table below, from 1.2 per million for age 10-14 to 11.2 per million for age 15-19, or even 31.1 per million for age 20-24, and about half of the Fukushima cases are over age 18 at diagnosis).

2010 Number of thyroid cancer cases in Japan by age and sex



2010 All (including foreigners) population in Japan by age and sex: “All (including foreigners) population” is used for incidence rate calculation.



2010 Thyroid cancer incidence rate in Japan by age and sex (per million)




Comparison with Chernobyl and other parts of Japan

As the only other major nuclear power plant accident, the Chernobyl accident is often used as a point of reference for many aspects of the Fukushima accident. Official positions as to why Fukushima thyroid cancers, unlike the Chernobyl thyroid cancers, are not considered radiation-induced are roughly summarized in the following 5 points:

  1. Exposure dose is too low (less than 100 mSv above which an increase in cancer occurrence may be statistically shown) in Fukushima.
  2. Unlike Chernobyl where children kept consuming contaminated food, such as milk, internal exposure through consumption of contaminated milk was minimal in Japan due to regulation of food distribution.
  3. In Fukushima, no children under age 5 at exposure have so far been diagnosed with thyroid cancer and latency of the diagnosed cases is too short (therefore the cancer must have already been present at the time of the accident).
  4. Occurrence of ultrasound abnormalities and thyroid cancer in Fukushima Prefecture is comparable to other, “unexposed” areas of Japan.
  5. Genetic analyses of the Fukushima thyroid cancers show a pattern dissimilar to the Chernobyl radiation-induced cancer cases [18].

Point 1: Whereas the Chernobyl exposure doses, often directly measured and swiftly recorded shortly after the Chernobyl accident, might have been significantly higher than the Fukushima exposure doses, the fact is that only 1,083 direct thyroid measurements were conducted in children after the Fukushima accident. Unfortunately, it is an undeniable fact that the reliability of these measurements is questionable due to high background radiation levels. These simple thyroid measurements were intended to be a quick survey, with more detailed testing promised if needed. However, one child from Iwaki City who showed the highest exposure dose of 35 mSv [19] never received any further monitoring: the reason was so as not to “worry and scare” the family and the community. For most, the true exposure dose to radioactive iodine is not known. More detailed diet and behavior history, even at least for those diagnosed with thyroid cancer, might lead to a more accurate dose reconstruction, but  it has not been done.

Furthermore, there are a number of studies showing radiation effects at much lower doses than 100 mSv [20,21,23,24,25].

Regarding point 2, nearly a week had elapsed since the accident by the time the central government established the provisional regulation values for food on March 17, 2011. Meanwhile, raw milk collected in Kawamata Town, Fukushima Prefecture as early as March 16, 2011, showed radioactive iodine levels exceeding the provisional regulation value for milk/milk products of 300 Bq/kg [26]. However, the testing results of the Fukushima raw milk as well as the Ibaraki spinach were not publicized until March 19, 2011 [27]. In the post-earthquake chaos and disruption of food distribution, some might have consumed untested local water, milk, leafy vegetables and other produce which might have been contaminated with high levels of radioactive iodine. Moreover, even when contaminated food might have been avoided, exposure via inhalation might have been unavoidable especially when there was no warning against the approach of the radioactive plume.

As for point 3, in Chernobyl, official stance is that children younger than 5 at exposure began to be diagnosed with thyroid cancer beginning in 1990, the fourth year after the accident. So far in Fukushima, at 4 years after the accident, no cancer case has been seen in children age 5 or younger at exposure. However, TUE is still ongoing for the year 4, with the announcement of the results lagging about 2 months behind the date those results are actually confirmed. No cancer case has been found in children age 5 or younger at exposure in the evacuated municipalities in the 20-30 km zones, but a municipality such as Iwaki City, located in the southern part of Fukushima Prefecture, south of the Fukushima Daiichi NPP, is still undergoing the second round TUE. Iwaki City is a place where unsuspecting residents went about their post-earthquake days, taking care of necessities, lining up outside for water rations, and waiting outside stores for their turns to go inside to purchase needed goods, often with children in tow, totally unaware of the radioactive plume permeating through their city when the wind turned south. Those residents do not know how much radiation they were exposed to from breathing in the contaminated air when the plume came. Lack of post-accident precipitation in Iwaki City, unlike in Iitate Village, means the lack of surface deposition of radioactive substances: the radiation testing of the soil does not reflect the degree of the early exposure doses sustained by residents.

Point 4 refers to the so-called control study [28,29] in Yamanashi, Nagasaki and Aomori Prefectures (a.k.a. the 3-prefecture study)  in which the sample size is much smaller (4,365 vs. 360,000 in Fukushima), and the age distribution and gender proportion are different from the Fukushima study. Although widely (and almost too eagerly) referred to as a control study, it may not really be an appropriate comparison study due to the degree of uncertainty stemming from a large variance from the small sample size: a single case of thyroid cancer diagnosed in the 3-prefecture study makes a point estimate of 229 per 1 million (95% CI: 6 to 1,276 per million).

Genetic analyses mentioned in Point 5 do not constitute a definite proof of radiogenicity and can be influenced by other factors. As a matter of fact, no clear and convenient “fingerprint” exists that can discern radiation effects at this time, although more research is underway [30].

Surgical and pathological features 

Even though TUE is funded by the central government (and administered by the prefectural government), once the participant progresses into the confirmatory examination and needs a closer clinical follow-up, biopsy and/or surgery, the case becomes part of regular medical care under the national health care system. Because biopsy and cancer cases are no longer considered part of TUE, clinical details, such as presence/absence of symptoms, family history, and pathological and molecular genetic findings of thyroid cancer cases are not openly shared for protection of patient privacy. 

The only information reported at quarterly Oversight Committee meetings include age and sex distribution, tumor diameter range, and the types of thyroid cancer (Two types--  papillary thyroid cancer and poorly differentiated thyroid cancer—have been reported so far). During committee proceedings and post-committee press conferences, questions regarding symptoms are often asked by other committee members or journalists. The answer has been consistently, “No symptoms.”

In addition, there have been two reports on surgical and pathological features of thyroid cancer cases operated at FMU. The first was released in November 2014 [31] at the 4th Thyroid Examination Evaluation Subcommittee meeting. The second report was released in August 2015 [32] at the 20th Oversight Committee meeting. Both reports were prepared in response to doubts about over treatment and complaints about lack of clinical data release from the committee members.  

Furthermore, some data have been presented at domestic academic meetings without being released to the prefecture. Abstracts available online are usually in Japanese, but they have been unofficially translated, along with the two reports mentioned above [33,34,35]. 

Pieces of information from different sources are summarized:
As of March 31, 2015, pre-surgical diagnosis revealed that 33 of 96 surgically confirmed thyroid cancer cases had a diameter of 10 mm or smaller. (Surgical treatment of papillary thyroid cancer 10 mm or smaller, called papillary thyroid microcarcinoma or PTMC, is controversial in adults). 8 cases had nodal/distant metastasis or mild extrathyroidal extension. 22 of remaining 25 had proximity to vital organs such as trachea or recurrent laryngeal nerve or cancer cells extending beyond the capsular covering of thyroid gland. In other words, excluding 3 cases which underwent surgeries against recommendations of non-surgical observation, 30 PTMC cases had indications for surgery. Post-surgically, there were 42 PTMC including 14 with mild extrathyroidal extension and 8 with no nodal/distant metastasis or extrathyroidal extension. Overall, 39% had mild extrathyroidal extension and 74% had nodal metastasis.

Below are excerpts from translation of abstracts for presentation at the 27th Annual Congress of the Japan Association of Endocrine Surgeons [36].  The number of cases described differs among them since each study looked at dataset at various points of time:

“(…) there were 84 cases (96.6%) of papillary thyroid cancer amongst 87 surgical cases of pediatric and adolescent thyroid cancer at the end of 2014. They included 3 cases of follicular variants and 4 cases of cribriform-morular type. The solid variant, seen in high frequency after the Chernobyl accident, is classified as poorly differentiated thyroid cancer in the Sixth Edition of Thyroid Cancer Management Guideline.”

“(…) 65 surgical cases of pediatric and adolescent papillary thyroid cancer: 22 males and 43 females; average age 17.4 years; 59 cases of classic subtype, 2 cases of follicular variant, and 4 cases of cribriform-morular type. “

“Surgical methods included total thyroidectomy in 6 cases (8%) and hemithyroidectomy in 73 cases (92%). Lymph node dissection was conducted in all cases, with 82% limited to the central compartment and 18% including the central and lateral compartments. Post-operative pathological diagnosis revealed 17 cases (22%) with tumor diameter ≤ 10 mm, and 44% with extrathyroidal extension, pEx1*, and 75% with lymph node metastasis.”

Although some information can be sought out which provide bits and pieces of information, without having exact and comprehensive details of each cancer case, such as age, sex, municipality of residence at the time of the accident, size and location of tumor, a state of nodal/distant metastasis, and a degree of invasiveness, it is difficult to conduct a further analysis. Lack of sufficient exposure dose information is hailed as one of the main reasons for not being able to conduct a dose-response analysis. In that respect, even a general idea of where the patient was when the radioactive plume came might give a clue to the dose range. 

Release and Analysis of data

FMU and Fukushima Prefecture have not conducted their own epidemiological analysis of the thyroid cancer data. Nor have they released all the available data to make a complete third-party analysis possible. FMU has even prioritized presentations of previously withheld information at academic conferences. Some journalists have repeatedly requested, in vain, the release of information that might offer a clue to any relationship of specific cancer cases with the place of residence as a surrogate for exposure doses. Data released do include the gender and age distributions and the place of residence, without possibility to cross-reference: only the total number of cases is available on the municipality-basis, with no way of knowing the gender and/or age of specific cases. Clinical details of each case are said to be beyond the scope of the Oversight Committee, since the confirmatory examination transitions some cases (biopsy and beyond) from the government-paid screening by the TUE team to the regular medical care by specialists through the national health insurance incurring self-pay costs. At this level, the privacy wall is reinforced, and information from individual cases is not necessarily collected centrally by the prefecture.

In October 2015, the first epidemiological analysis [37] of the publicly available thyroid cancer data (the first round screening data as of December 31, 2014) was published by Tsuda et al. in the online, ahead-of-print edition of Epidemiology, the official, peer-reviewed journal of the International Society for Environmental Epidemiology. The study by Tsuda et al. found a regional variability of the prevalence within Fukushima Prefecture as well as increased incidence rate ratios in most of Fukushima Prefecture compared to the national incidence rate.  Despite the claim by the authors that the study used standard epidemiological methods based on the concept of the discipline of modern epidemiology, it created quite a controversy. There have been criticisms from within and outside Japan [38,39,40,41,42,43,44]. A counterargument by Tsuda et al. has also been published [45].

A group of researchers from the National Cancer Center recently published their analysis [46] and showed the observed/expected ratio of thyroid cancer prevalence to be as much as 30.8. However, they attribute this increase to overdiagnosis.

Jacob et al. (2014) [47] estimated the prevalence of the first round screening and then determined the screening factor for the subsequent screenings. However, a careful consideration of the studies cited by Jacob et al. reveals that data used in estimation was derived from the data obtained 12 to 14 years post-Chernobyl, unlike the first several years post-Fukushima, and involved other factors potentially leading to large uncertainties.

Potential issues

Publicly available TUE data is limited, and the official English translation that is eventually provided may not include the entire data. Additional information might be extracted during the Oversight Committee meeting or the subsequent press conference, but the official minutes, only available in Japanese, do not include the press conference material. Information presented at domestic academic meetings may be available online, but often only in Japanese. All these make it difficult for non-Japanese speakers to obtain thorough information.

Given the fact that the second round has not completed, some say it is too premature to draw any definite conclusion from the data. Ideally, unbiased, collaboratory effort amongst clinicians and researchers to integrate all the available information might lead to a more effective and congruent analytical process that could be useful towards policy making to benefit the public. Such information might include the exposure dose (with a more comprehensive effort to conduct dose reconstruction), the TUE results, and clinical data such as surgical and pathological details. Rather, in reality, various parties are presenting and defending their own claims with little interdisciplinary crossover, reflecting vertical divisions permeating the Japanese society.  

What to think of all this

Radiation epidemiologists and others think that it is premature to determine if the thyroid cancer cases detected in Fukushima children are due to the radiation exposure from the Fukushima Daiichi nuclear power plant accident, as the conventionally accepted latency for childhood thyroid cancer is about 5 years. 

One of UNSCEAR’s conclusions from the 2013 report [48], “No discernible increases in future cancer rates,” is upheld in the 2015 White Paper [49], as presented at the February 9-10, 2016 Public Dialogues held in Fukushima Prefecture [50]. Meanwhile the second round screening is identifying more cancer cases than can be explained by screening effect which should not play a large role due to harvest effect of most latent cancers having been “harvested” in the first round. At the aforementioned Public Dialogues, UNSCEAR officials cited screening effect as an explanation for the thyroid cancer cases. UNSCEAR’s 2015 White Paper only included update information from October 2012 to December 2014, and the second round screening results were not considered.

On January 22, 2016, the International Society for Environmental Epidemiology sent an open letter to the Japanese government [51] expressing their concern about a “12-fold higher risk of developing thyroid cancer among residents of Fukushima” compared to the Japan’s annual incidence, as demonstrated in the study by Tsuda et al. ISEE called for the need to develop scientific studies of health risks from the accident and offered to the government of Japan its expertise as an independent international professional organization of environmental epidemiologists. To date, the Japanese government is yet to acknowledge the ISEE letter [52].

With the report of thyroid cancer cases outside Fukushima Prefecture [53], it is critical for the public health sector to be ready for what might be coming. Assistance from independent bodies of experts would seem wise and desirable.


Yuri Hiranuma, D.O. 
Portland, Oregon, U.S.A.
yurihrnm@gmail.com


References



  1.   http://fmu-global.jp/fukushima-health-management-survey/
  2.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798631/
  3.   http://www.env.go.jp/chemi/rhm/support.html
  4.   http://clearinghouse.main.jp/wp/?p=738
  5.   http://fmu-global.jp/?wpdmdl=37
  6.   http://fmu-global.jp/survey/proceedings-of-the-8th-prefectural-oversight-committee-meeting-for-fukushima-health-management-survey/
  7.   http://fmu-global.jp/?wpdmdl=1222
  8.   http://fmu-global.jp/?wpdmdl=1563
  9.   http://fmu-global.jp/?wpdmdl=37
  10.   http://fmu-global.jp/?wpdmdl=158
  11.   http://fmu-global.jp/survey/proceedings-of-the-17th-prefectural-oversight-committee-meeting-for-fukushima-health-management-survey/
  12.   http://fmu-global.jp/?wpdmdl=170
  13.   http://fmu-global.jp/?wpdmdl=1563
  14.   Ibid.
  15.   http://fukushimavoice-eng2.blogspot.com/2016/02/fukushima-thyroid-examination-february.html
  16.   http://ganjoho.jp/en/professional/statistics/table_download.html
  17.   Ibid.
  18.   http://www.nature.com/articles/srep16976
  19.   http://www.bioone.org/doi/10.1667/RR13351.1
  20.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2009418/
  21.   http://www.bmj.com/content/331/7508/77
  22.   http://ehp.niehs.nih.gov/1408548/
  23.   http://www.bmj.com/content/346/bmj.f2360
  24.   http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026%2815%2900094-0/fulltext
  25.   http://www.bmj.com/content/351/bmj.h5359
  26.   http://www.maff.go.jp/j/kanbo/joho/saigai/seisan_kensa/pdf/2011_3g.pdf
  27.   http://www3.nhk.or.jp/news/genpatsu-fukushima/20110319/2010_s_shokuhin_taiou.html
  28.  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083220
  29.   http://www.nature.com/articles/srep09046
  30.   http://link.springer.com/article/10.1007/s00259-015-3303-3
  31.   https://www.pref.fukushima.lg.jp/uploaded/attachment/90997.pdf
  32.   https://www.pref.fukushima.lg.jp/uploaded/attachment/129308.pdf
  33.   http://fukushimavoice-eng2.blogspot.com/2014/11/details-of-fukushima-thyroid-cancer.html
  34.   http://fukushimavoice-eng2.blogspot.com/2015/06/2015-update-details-of-fukushima.html
  35.   http://fukushimavoice-eng2.blogspot.com/2015/09/surgical-and-pathological-details-of.html
  36.   http://fukushimavoice-eng2.blogspot.com/2015/08/3-thyroid-cancer-cases-diagnosed-in.html
  37.  http://journals.lww.com/epidem/Fulltext/2016/05000/Thyroid_Cancer_Detection_by_Ultrasound_Among.3.aspx
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  42.  http://journals.lww.com/epidem/Citation/publishahead/Re___Thyroid_Cancer_Among_Young_People_in.99065.aspx
  43.  http://journals.lww.com/epidem/Citation/publishahead/Re___Thyroid_Cancer_Among_Young_People_in.99066.aspx
  44.  http://journals.lww.com/epidem/Citation/publishahead/Re__Thyroid_Cancer_among_Young_People_in.99063.aspx
  45.  http://journals.lww.com/epidem/Citation/publishahead/Response_to_the_Commentary_by_Professor_Davis_and.99060.aspx
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  48.   http://www.unscear.org/unscear/en/publications/2013_1.html
  49.   http://www.unscear.org/unscear/en/publications/Fukushima_WP2015.html
  50.   http://www.unis.unvienna.org/unis/en/pressrels/2016/unisma129.html
  51.   http://www.iseepi.org/documents/Fukushimaletter.pdf
  52.   http://www.isee-europe.com/blog/open-discussion-on-isees-letter-to-the-authorities-in-japan-concerning-the-paper-by-tsuda-et-al-2015
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