Fukushima Thyroid Examination October 2017: 154 Surgically Confirmed as Thyroid Cancer Among 193 Cytology Suspected Cases



Highlights:

  • Only 3 suspected/confirmed cases—all in the third round—were newly diagnosed by cytology since the last report. Total number of suspected/confirmed thyroid cancer = 193 (excluding a single case of benign tumor; 115 in the first round, 71 in the second round, and 7 in the third round).
  • Two additional cases of surgery since the last report, one each in the second and the third round: total number of surgically confirmed cancer cases =154 (101 in the first round, 50 in the second round, and 3 in the third round)
  • The second round screening is nearly complete; the final report to be released at the next Oversight Committee or Thyroid Examination Assessment Committee. 
  • A new two-year term begins for newly appointed and returning members of the Oversight Committee as well as the Thyroid Examination Assessment Subcommittee. Surprisingly, Kazuo Shimizu—former Subcommittee Chair—was not even appointed to be on the Subcommittee
On October 23, 2017, the 28th Oversight Committee for Fukushima Health Management Survey convened in Fukushima City, Fukushima Prefecture. Among other information, the Oversight Committee released the latest results (as of June 30, 2017) of the second and third rounds of the Thyroid Ultrasound Examination (TUE).  Official English translation of the results are posted here. Minutes of the proceedings are only released in Japanese, and the transcript of the press conference held immediately after the committee meeting is not officially released. The narrative below includes pertinent information covered during the committee meeting and the press conference.

Overview
This Oversight Committee meeting was nearly 2 months overdue. In fact, it was held so late that it could have presented data as of September 30, 2017. But no, all that was presented was rather "old" data as of June 30, 2017, which changed very little in terms of the number of cancer cases compared to the previous data as of March 31, 2017. As schools in Japan go into summer recess in the last one-third of July through the end of August, more cancer cases might be included in the next set of data as of September 30.

Here's the summary of the latest results as of June 30, 2017

Notable new members
With the past term for committee members ending on July 9, 2017, this Oversight Committee opened with some new members. (See the Oversight Committee roster in Japanese here). The most controversial might be Toru Takano, an Osaka University physician researcher who advocates fetal cell carcinogenesis as opposed to multistep carcinogenesis. Takano's hypothesis claims thyroid cancer already exists in childhood which "nicely" explains away a large number of thyroid cancer detected in Fukushima. Takano has called for scaling down Fukushima's TUE in the January 14, 2017 blog post. Takano was recommended to be on the Oversight Committee and the Thyroid Examination Assessment Subcommittee by the Japan Thyroid Association.

As for the new roster of the Thyroid Examination Assessment Subcommittee, Kazuo Shimizu—former Subcommittee Chair—and Fumiko Kasuga—who one might say acted as "conscience" of the Subcommittee—were no longer on it. Takano is joined by Gen Suzuki (recommended by the the Japanese Radiation Research Society) and Tomotaka Sobue (recommended by the Japan Epidemiological Association), both of who have actively participated on various government committees related to health effects of radiation exposure. Kota Katanoda from Division of Cancer Statistics Integration, National Cancer Center appears to have replaced Shoichiro Tsugane. Katanoda and Tsugane have worked on a document submitted to the Subcommittee previously.

Interim report on dose reconstruction studies
Most of the meeting time was spent on presentation by Gen Suzuki on a 3-year interim report of "Comprehensive studies on the dose reconstruction for residents in Fukushima nuclear accidents." Suzuki's presentation slides (in Japanese) can be found here, and an English abstract can be found on pages 437-439 (pages 27-29 of PDF) of the interim report to the Ministry of the Environment. 

"Comprehensive studies" consist of 4 separate studies (English abstract page in parenthesis) on 1) updating source term and atmospheric transport dispersion simulations (page 508), 2) retrospective reconstruction of iodine 131 release through iodine 129 (page 516), 3) dose reconstruction of Fukushima residents in early stages (page 528), and 4) prediction of blood deposition and thyroid accumulation of radioiodine (page 542).

Among loads of complicated pieces of information, the take home message was that estimated doses (external and internal) for a 1-year-old are now (successfully?) reduced to 7% to 69% of estimated doses in the UNSCEAR 2013 report. 

Full-Scale Screening (FSS) (second and third rounds)
To be conducted every 2 years until age 20 and every 5 years after age 20, the FSS began with the second round screening (the first FSS) in April 2014, including those who were born in the first year after the accident. There are 381,256 eligible individuals born between April 2, 1992 and April 1, 2012. As of June 30, 2017, 270,516 (5 more than previously) have actually participated in the primary examination. 

A participation rate of 71.0% is lower than 81.7% from the first round screening. Results of the primary examination have been finalized in 270,515 participants, and 2,227 (1 more than previously) turned out to require the confirmatory examination. 

The confirmatory examination appears to be still ongoing for the second round. Of 2,227 requiring the confirmatory examination, 1,844 (12 more than previously) have participated at a participation rate of 82.8%—lower than 92.9% from the first round screening. So far 1,788 have received the final results including 205 (5 more than previously) that underwent fine needle aspiration cytology (FNAC) which revealed 71 cases suspicious for cancer with no new case diagnosed at this time. 

Confirmation of thyroid cancer requires pathological examination of the resected thyroid tissue obtained during surgery. There has been only 1 additional surgical case in the second round since the last reporting. As of June 30, 2019, 50 underwent surgery and 49 were confirmed to have papillary thyroid cancer. One remaining case was confirmed to have "other thyroid cancer" according to the classification in the seventh revision of Japan's unique thyroid cancer diagnostic guidelines. (A specific diagnosis was not revealed, but it has been reported as a differentiated thyroid cancer that is not known to be related to radiation exposure and it is allegedly neither poorly differentiated thyroid cancer nor medullary cancer). 

The third round screening or the second FSS has covered 138,422 or 41.1% of the survey population of 336,631, which excludes those born in FY1992 and FY1993 who are eligible for the age 25 milestone screening. The primary examination results have been finalized in 123,857 or 89.5% of the participants, revealing 754 (63 more than previously) to require the confirmatory examination. Results of the confirmatory examination have been finalized in 367 of 438 (83.8%) that have been examined. FNAC was conducted in 18 (7 more than previously) individuals, and 3 were newly diagnosed with suspected thyroid cancer (2 females and 1 male). There was 1 new surgical case in the third round.  

A confusing issue on composition of target populations
Conducted every 2 years up to age 20, the TUE transitions at age 25 to "milestone screenings" to be conducted every 5 years. Some residents are beginning to participate in the age 25 milestone screening, and if they have never participated in the TUE, their milestone screening results were added to the second round screening results. Thus the number of the second round screening participants kept increasing even though the screening period technically ended in March 2016. 

However, the third round screening survey population excludes the age 25 milestone screening participants: their results will be tallied up separately.

Also in some cases, confirmatory examinations from the second and third rounds might be simultaneously ongoing, or there could be significant delays in conducting confirmatory examinations due to logistical issues such as the lack of manpower. A two-year screening period originally designed for subsequent rounds of the Full-Scale Screening is essentially spread over a longer time period, overlapping with the next round of screening. A precise interpretation of the results from each round of screening might be nearly impossible.

Participants beyond age 23 dropped from released datasets
As mentioned in the previous section, participants eventually move onto the "milestone screening," every 5 years beginning at age 25. No more than 5 years are to pass between examinations up to age 25. 

The chart shown below is the FSS implementation plan from the third round onward (taken from the blue link in this document on the prefectural website on the TUE for residents). It represents ages of participants by their birth years (leftmost vertical column) at particular years of screening (top row). (Years here are "fiscal years" which run from April 2 of one year to April 1 of next year). Darker blue color denotes the milestone screening participants, yellow the participants in the FSS to bridge the gap before the milestone screening, and lighter blue the regular FSS participants. White color denotes no screening during a given fiscal year.


Based on this chart, the third round excludes those who were born in FY1992 and FY1993 as described earlier. This breaks down to 23- and 24-year-olds from the FY2016 targeted municipalities and 24- and 25-year-olds from the FY2017 municipalities. Thus technically, the third round screening includes only half of 23-year-old residents, with the other half of 23-year-olds and all of 24-year-olds not even screened until FY2018.

Although the milestone screening are being tallied up separately, there has been no talk about when and how—or if—the separate results are to be shared with the Oversight Committee.

From the above chart, it should be noted that as the TUE goes on, the age distribution graph will be skewed to younger ages, and the results will not represent all the residents who were 18 or younger at the time of the accident. The "age-at-exposure" distribution graph shows an X-axis up to age 18, but older age group won't even show up there with each successive round of screening: for the third round, that means all residents who were 17 or 18 and some who were 16 on March 11, 2011. 
Fig 3 Age distribution of suspected/confirmed cancer cases (age at exposure)
Second round on left, third round on right

When looking at the age-at-examination distribution graph as below, the "dropping" of older residents as they turn 23 (some) and 24 is something that should be kept in mind.
Fig 4 Age distribution of suspected/confirmed cancer cases (age at confirmatory exam) 
Second round on left, third round on right

Newly diagnosed cases
The second round: No new case diagnosed.

The third round: Three cases were newly diagnosed by FNAC with suspicion of cancer. One was from the evacuation area, and the other two are from Nakadori, the central part of Fukushima Prefecture. Two are males whose ages-at-exposure were 11 and 12, and one was a female who was age 10 at exposure.

Prior diagnostic status of the cases newly diagnosed with cancer
The second round: Of 71 total cases suspected or confirmed with cancer in the second round, 33 were A1, 32 were A2 (7 nodules, 25 other non-nodular lesions), and 5 were B (at least 2 having undergone the confirmatory examination) in the first round. One remaining case never underwent the first round screening (no information such as age, sex or place or residence, is available regarding this case).

The third round: Of 3 newly diagnosed cases, 1 was A1 and 2 were non-nodular A2.

This means at least 63 (34 "A1" and 29 "A2 other") of 78 cases (81%) had no nodules detected by ultrasound in the previous round which could have developed into cancer. Akira Ohtsuru, the head of the TUE essentially reiterated that they were "newly detected" rather than "newly formed." (See this post for details of Ohtsuru's previous claim). 

An issue of the female to male ratio
The female to male ratio of cancer cases warrants a special attention. For thyroid cancer, the female to male ratio is nearly 1:1 in the very young, but it is known to increase with age and decrease with radiation exposure. (See below Slide 2 in this post for more information). In the second round, the overall female to male ratio is 1.22:1, but the FY2015 municipalities have consistently shown a higher number of males than females with the most recent female to male ratio of 1:1.38. For the third round, the female to male ratio started out with 1:1, and now 1:1.33.

What Ohtsuru said about the the female to male ratio is essentially the same as his statement at the previous two meetings, justifying the low female to male ratios observed in this population without concrete scientific evidence. (Refer to this post or the fact sheet for details).

Reporting results by regions, not municipalities
From the third round onward, confirmatory examination results are no longer available by individual municipalities as before. Rather, the results are reported by four regions:
1) 13 municipalities in the evacuation zone (some municipalities only partially evacuated)
2) Nakadori (central region)
3) Hamadori (eastern, coastal region)
4) Aizu (western region)

Reasoning behind this, according to FMU, is to protect privacy and deter discrimination against those from smaller municipalities diagnosed with thyroid cancer. Ohtsuru backed up the new reporting format by explaining how medical data based on the national insurance claim are protected by not disclosing the number of cases in municipalities with population fewer than 2,000, as per the guidelines established by the Ministry of Health, Labour and Welfare. This regional reporting of cancer cases will essentially make comparisons between the second round and the third round data impossible.

New study to document unreported cases of thyroid cancer
It was announced that a new "research" project was to be launched to investigate how many cases of thyroid cancer were not included in the official count (see the document in Japanese here). Currently awaiting approval from the Ethics Board of FMU, this research project is to be conducted through September 30, 2019 by Susumu Yokoya, Director of Thyroid and Endocrine Center at Fukushima Global Medical Science Center, Fukushima Medical University.

The issue of unreported cancer cases came to light back in March 2017, when it was discovered that thyroid cancer diagnosed in a boy (age 4 at exposure) during follow-up medical visits was not included in the official count. The boy apparently had surgery at FMU, but his case wasn't in the official count because he was under regular medical care using national health insurance.

The new research project apparently will go through medical records at FMU to find cases that had positive fine-needle aspiration cytology results and/or surgery. For each case, an inquiry will be made with the Radiation Medical Science Center to see if it's been included in the official count, in order to tally up unreported cases of thyroid cancer.

Just why it would take UP TO SEPTEMBER 2019 to conduct this seemingly simple investigation was the question on everyone's mind. Also, this project would identify unreported cases diagnosed at FMU only.

International Expert Committee
Incidentally, this meeting coincided with the first day of the First Expert Meeting of Thyroid Monitoring after Nuclear Accidents (TM-NUC) by IARC, held on October 23-25, 2017 in Lyon, France. TM-NUC is the final product of a call for a new third-party committee" by Chairman Hoshi at the 26th Oversight Committee held on December 27, 2016. This call for a new "international, third-party, neutral, scientific, up-to-date and evidence-based" expert committee appears to have originated from the October 31, 2016 recommendations (PDF link here) by the 5th International Expert Symposium on Radiation and Health held on September 26-27, 2016. 


Details on circumstances regarding how TM-NUC came about are described in this post.


*****

Below is the summary of the basic information from each round of screening.

First Round Screening (October 2011 - April 2015)
(This is the updated final results as of March 31, 2017).
The number of confirmed and suspected cancer cases remains the same, but some information has been corrected for duplicates.

Total number targeted: 367,649
Number of participants in primary examination: 300,473
Number with confirmed results: 300,473
  • A1   154,605 (51.5%) (no nodules or cysts found)
  • A2   143,574 (47.8%) (nodules ≦ 5.0 mm or cysts ≦ 20.0 mm)
  • B        2,293   (0.8%) (nodules ≧ 5.1 mm or cysts ≧ 20.1 mm)
  • C               1   (0.0%) (requiring immediate secondary examination)
(Note: Cysts with solid components are treated as nodules).

Number eligible for confirmatory (secondary) examination: 2,293
Number of participants in confirmatory (secondary) examination: 2,130
Number with confirmed results : 2,090
Number of fine-needle aspiration cytology (FNAC): 547
Number of cases suspicious or confirmed of malignancy: 116 (including one case of benign nodules)
Number with confirmed tissue diagnosis after surgery: 102
  • 1 benign nodule
  • 100 papillary thyroid cancer
  • 1 poorly differentiated cancer
Second Round Screening (April 2014 - March 2016) (see report here)
Total number targeted: 381,256
Number of participants in primary examination: 270,516
Number with confirmed results: 270,515
  • A1   108,710 (40.2%) (no nodules or cysts found)
  • A2   159,578 (59.0%) (nodules ≦ 5.0 mm or cysts ≦ 20.0 mm)
  • B        2,227  (0.8%) (nodules ≧ 5.1 mm or cysts ≧ 20.1 mm)
  • C              0   (0.0%) (requiring immediate secondary examination)
(Note: Cysts with solid components are treated as nodules).

Number eligible for confirmatory (secondary) examination: 2,227
Number of participants in confirmatory (secondary) examination: 1,844
Number with confirmed results : 1,788
Number of fine-needle aspiration cytology (FNAC): 205
Number of cases suspicious or confirmed of malignancy: 71
Number with confirmed tissue diagnosis after surgery: 50
  • 49 papillary thyroid cancer
  • 1 "other" thyroid cancer
Third Round Screening (May 2016 - March 2018) (see report here)
Total number targeted: 336,631
Number of participants in primary examination: 138,422
Number with confirmed results: 123,857
  • A1   43,388 (35.0%) (no nodules or cysts found)
  • A2   79.715 (64.4%) (nodules ≦ 5.0 mm or cysts ≦ 20.0 mm)
  • B          754  (0.6%) (nodules ≧ 5.1 mm or cysts ≧ 20.1 mm)
  • C             0   (0.0%) (requiring immediate secondary examination)
(Note: Cysts with solid components are treated as nodules).

Number eligible for confirmatory (secondary) examination: 754
Number of participants in confirmatory (secondary) examination: 438
Number with confirmed results : 367
Number of fine-needle aspiration cytology (FNAC): 18
Number of cases suspicious or confirmed of malignancy: 7
Number with confirmed tissue diagnosis after surgery: 3
  • 3 papillary thyroid cancer

Table 6. Cytology results (as of June 30, 2017) 
(including information from Appendix 6: Number of surgeries among cases with malignancy or suspicion of malignancy)

Second Round Screening

Third Round Screening

Age distribution (age at the time of the March 2011 accident)



Circumstances Regarding the Japan-Sponsored IARC Expert Group on Thyroid Monitoring After Nuclear Accidents (TM-NUC)


On October 23-25, 2017, the Expert Group on Thyroid Monitoring after Nuclear Accidents (TM-NUC) met in Lyon, France for the first of two planned sessions (see this PDF for the agenda). The TM-NUC project was established by the International Agency for Research on Cancer (IARC) in order to "develop strategies and recommendations on how to plan and implement thyroid monitoring in populations possibly affected by radiation exposure due to nuclear accidents." 



The aims of the TM-NUC project are to: 
assess the latest scientific evidence on the epidemiology, natural history, and clinical management of thyroid cancer, to develop principles for thyroid ultrasound examinations after nuclear accidents. This includes reviewing the scientific literature and compiling knowledge and experience from relevant countries. 
identify unmet research needs and propose epidemiological study designs to address these gaps in knowledge.          
According to the TM-NUC website
The Expert Group consists of 16 international experts from a variety of fields, including cancer screening, radiation epidemiology, radiation dosimetry, pathology, oncology, endocrinology, and surgery, and is supported by a Scientific Secretariat (Chair and Scientific Coordinator) from the IARC Section of Environment and Radiation 
The primary goal of the Thyroid Monitoring after Nuclear Accidents (TM-NUC) project is to use current scientific evidence and past experience to develop principles for thyroid monitoring in populations possibly affected by radiation exposure due to nuclear accidents. Such principles will help guide policy-makers and health professionals in planning thyroid monitoring in case of nuclear accidents.
The TM-NUC project is funded by the Ministry of the Environment of Japan.     
Next meeting is scheduled for February 21-23, 2018, and the final recommendations are expected by the end of April 2018.

The first day of the first meeting coincided with the 28th Oversight Committee for the Fukushima Health Management Survey (FHMS) held in Fukushima City, Fukushima on October 23, 2017. That the Oversight Committee—nearly 2 months overdue and rumored to have been originally scheduled for October 16—convened on the first day of the TM-NUC Expert Group meeting may be purely coincidental. Nevertheless, circumstances leading to the birth of the TM-NUC are curious enough to warrant further consideration.

At the 26th Oversight Committee meeting held on December 27, 2016, Chairman Hokuto Hoshi stunned everyone by unexpectedly calling for a new "international, third-party, neutral, scientific, up-to-date and evidence-based" expert committee. This expert committee would discuss issues surrounding the Thyroid Ultrasound Examination (TUE) and present information in a manner that would "aid the understanding by Fukushima residents." This proposal apparently originated from the October 31, 2016 recommendations (PDF link here) by the 5th International Expert Symposium on Radiation and Health held on September 26-27, 2016. An excerpt from the item 4 of the recommendations reads as follows:
One possibility would be to convene expert working groups on issues related to the mitigation of health impacts of the Fukushima Daiichi NPP accident, and health monitoring. One of the expert working groups on “Nuclear Disasters and Health Monitoring”, especially focusing on thyroid problems, could provide professional recommendations to the current TUE in Fukushima in future. The international consensus should be shared with all stakeholders, such as national and local governments and public representatives of the affected communities, to improve the current TUE program.
Hoshi's proposal was received skeptically by some committee members as well as journalists but quickly embraced by Tamami Umeda, a committee member representing the Ministry of the Environment (MOE). According to the minutes of the proceedings (in Japanese), a committee member Fumiko Kasuga suggested an expanded role for the Thyroid Examination Assessment Subcommittee (referred as the "Subcommittee" herein) instead, with input from invited international experts, rather than establishing a brand new expert group. Kasuga's suggestion made sense if the new expert group was actually going to focus on Fukushima's TUE, especially when the Subcommittee hadn't met since March 24, 2015 and no official discussion hasn't been conducted beyond the first round results. During the press conference, some journalists questioned why a new committee was even necessary and if the need for a new committee implied that the Oversight Committee wasn't scientific enough.

Two months later, at the 26th Oversight Committee meeting held on February 20, 2017, a prefectural official stated that this "third-party" committee with a neutral standpoint was expected to organize the latest knowledge to be incorporated into discussions at the Oversight Committee and the Subcommittee. He stated that prefectural officials, assisted by the central government, were consulting with international organizations in establishing a third-party committee. Representing the MOE, Umeda stated that she envisioned a new expert group to be separate from yet supplemental to the Subcommittee. 

Three months later, on May 31, 2017, an establishment of a new international expert committee was announced in the Fukushima Minpo article (archived here). According to the article, the international expert committee, established by Fukushima Prefecture and Ministry of the Environment, would investigate causality between the nuclear accident and thyroid cancer. The article stated that selection of the committee members would be based upon recommendations from relevant academic societies within Japan as well as from international organizations specializing in radiation protection or medicine and health. Fukushima Prefecture was to explain about the plan at the June 5th Oversight Committee meeting. 

Five days later, the story took a sharp turn when a new development was revealed at the 27th Oversight Committee meeting held on June 5, 2017. This is described in more detail in this postunder the subheading "The status of the new third-party committee." In short, Umeda was searching for a World Health Organization (WHO) agency that might be a good candidate as an expert committee, when she came across an already planned international expert group by IARC that was tasked with investigation of thyroid monitoring after nuclear accidents. Umeda thought this expert group by IARC might be a good match even though it would not be actually analyzing Fukushima's TUE data(See the minutes of the proceedings in Japanese here). Her fluent explanation of finding a planned IARC expert group made it sound as if it were a happenstance, but the details that emerged 2 days later suggest otherwise: It is very likely that this was a done deal merely being reported to the Oversight Committee.

Two days later on June 7, 2017, Umeda posted on the MOE website an open competitive bidding notice for a commissioned project involving administrative support services for the IARC expert group. A draft contract for the commissioned project (PDF in Japanese available here) is quite revealing and suggests that this might have been planned by the MOE for some time. 

The draft contract explains that IARC has proposed an establishment of an international expert group aiming to offer scientific information and advice on radiation health effects to policy makers and medical professionals in "countries" (probably means "WHO member states"). It claims that the purpose of the commissioned project is to collect information necessary for discussions regarding the FHMS by supporting the IARC expert group. The project is necessary for translation of two reports to be compiled by the IARC expert group and for compilation of a summary report and a manual. The commissioned project is expected to last until the end of December 2018, encompassing two fiscal years—FY2017 to FY2018. 

Two reports to be created by the IARC expert group already have titles: 

  • Report 1: Review the latest scientific evidence and development of principles of TUE as long-term health monitoring instrument for populations possibly affected by radiation exposure due to the nuclear accidents. Research agenda how to address gaps in scientific knowledge. 
  • Report 2: Detailing study and features for activities from the research agenda. 

According to the job description, the commissioned project consists of three parts: 

  1. administrative work related to holding two expert group meetings and translating the final reports into Japanese
  2. administrative work related to a visit to Fukushima Prefecture by the expert group (including a site visit to FDNPP and the TUE facilities, and a panel discussion with domestic experts) and creating a summary report
  3. side-by-side English/Japanese translation of reports from the expert meetings and from the visit to Fukushima, with technical supervision from the standpoint of radiation health effects

The job description also lays out concrete details such as the amount of stipend to be paid to each expert member (17,700 yen or 155 USD daily), and the coverage of reimbursable travel costs (business class tickets on direct flights or flights with the fewest number of connections to Tokyo). Group members are to be about 15—4 from France, 1 from Finland, 3 from the U.S., 1 from Japan, 1 from South Korea, 1 from Germany, 1 from Ukraine, 1 from the U.K., 1 from Italy and 1 from Switzerland. 

Most administrative duties related to the expert group are to be outsourced to the IARC for 281,700 Euro. These duties include member selection and invitation, setting up and running the expert meeting, compiling meeting materials, and making payments to members for travel costs and stipends. Further, one of the FY2018 duties for the commissioned project includes making a payment of 80,700 Euro to IARC to cover the cost of the meeting. In total, the Japanese government is paying 362,400 Euro (over 422,000 USD) to cover the entire cost of the IARC expert group in the TC-NUC project. 

It is doubtful if the TM-NUC project, fully funded by the Japanese government, actually fulfills qualities originally proposed by Chairman Hoshi—international, third-party, neutral, scientific, up-to-date and evidence-based. It certainly is "international." A quick glance at the member list shows some "familiar names" such as Geraldine Thomas, casting doubt on its neutrality. A critical examination of the member composition reveals connections with entities with potential biases such as United Nations Scientific Committee on Atomic Radiation (UNSCEAR), Radiation Effects Research Foundation (RERF), and the 5th International Expert Symposium on Radiation and Health sponsored by the Nippon Foundation. 

The Expert Group may appear "third-party" to Fukushima Medical University (FMU) that conducts the TUE, with an exception of an FMU official, Hiroki Shimura. However, IARC itself has had a close relationship with FMU, visiting FMU as early as November 2012, signing Letter of Collaboration with FMU in January 2013, and conducting a joint workshop at FMU as well as a special seminar to the Fukushima Medical Association in October 2013. A report of the 2013 joint workshop has been published

There is also an inherent problem in the seemingly "closed" field of radiation protection with a premise to allow the use of radiation, medical or industrial. Radiation risk assessment relies on the atomic bomb survivor data as the "gold standard." However, this gold standard is actually far from perfect with missing data and disregard for internal exposure from the black rain and neutron-activated radioactive manganese 56. Any "evidence" built upon faulty assumptions is faulty by default, yet it is exceedingly difficult for "outsiders" to gain insight into such inconsistencies.

Some of the researchers may appear "neutral," yet their research interests might encompass "overdiagnosis" which is what Fukushima's cases are being attributed to by FMU officials despite lacking proper analysis of data with scientific integrity and transparency as described below. 

Included in the TM-NUC agenda is a presentation on Fukushima's TUE by Shimura. Most likely the Expert Group was given only officially released information, which is missing data on at least one unreported thyroid cancer case and potentially more. Existence of the missing data implies any studies published by FMU using the TUE data potentially lack scientific integrity. Consequently, any international organizations—UNSCEAR, WHO, IAEA, to name a few—relying on such studies would not be able to conduct proper analysis on health effects of radiation exposure. FMU officials so far have not documented the issue of missing data in English publications. Long before the missing data surfaced, members of the Oversight Committee and the Subcommittee have repeatedly asked for more detailed information on the TUE data to no avail. It is notable that even UNSCEAR has urged a release of more pertinent information, such as "more detailed breakdowns of the numbers of young people screened, and of confirmed/suspected thyroid cancers by tumour size, and by age at irradiation, and age at screening, and sex," in the 2017 White Paper (see paragraph 123).

The TM-NUC agenda also includes a presentation on EC-funded SHAMISEN project ("SHAMISEN" is a reverse acronym for "Nuclear Emergency Situations Improvement of Medical and Health Surveillance") which issued a recommendation against systematic thyroid cancer screening. (Click on "R25" here for details. See the whole recommendations here). This presentation was given by Evgenia Ostroumova and Ausrele Kesminiene from IARC's Section of Environment and Radiation. Timing of the presentation towards the end of the meeting by members affiliated with IARC—which constitutes the core of the Expert Group—easily leads to speculation that IARC might be facilitating political, rather than scientific, decision-making. 

Even at this point when the first meeting has already occurred, no official announcement has been made in Japan regarding the progress of the IARC Expert Group or its member composition. Moreover, existence of the SHAMISEN project itself has not been officially announced to the general public in Japan. 

The SHAMISEN recommendations are supposedly based on science but actually characterized by a political overtone prioritizing psychological, social, and economic effects. They appear to be directed towards political policy-making. Ironically, contrary to the notion put forth by Umeda that the Expert Group would not be actually analyzing Fukushima's TUE data, the SHAMISEN recommendations, part of the presentation, already incorporate Fukushima's incomplete and biased data. It appears that IARC's TM-NUC Expert Group may be a vehicle for the SHAMISEN recommendations to be distorted into scientifically neutral recommendations to form an international consensus, with a strong potential to influence situations in post-Fukushima Japan where the future of the TUE is in debate.

Chairman Hoshi's original proposal has morphed into something far from the international committee he envisioned. What the MOE and the Japanese government will likely gain from the TM-NUC Expert Group may be an international consensus built on faulty assumptions and biased data, but perhaps that is exactly what is sought by the reconstruction-hungry government and thus totally worth 362,400 Euro.





Fukushima Thyroid Examination Fact Sheet: September 2017 (Long Version)


Fukushima Thyroid Examination Fact Sheet:  September 2017

✴Copying or re-posting part or whole of this post is not permitted. Please link to this post instead.

Corrections on July 24, 2018: 
Paragraph 5 in "4. Geographic distribution" in section "Official stance on radiation effects." 
"...a clear regional difference of thyroid cancer occurrence (per million) in the second round results: 49.2, 25.7, 19.6 and 15.5 in the evacuation zone, Hamadori, Nakadori, and Aizu, respectively." was corrected (correction shown in red) to "...a clear regional difference of thyroid cancer occurrence (per 100,000) in the second round results: 49.2, 25.7, 19.6 and 15.5 in the evacuation zone, Nakadori, Hamadori, and Aizu, respectively."

Note: Corrections were made in the following paragraphs in pink color on October 17, 2017.
Second paragraph in section "Screening protocol"
First paragraph in section "Thyroid cancer cases"
First paragraph in section "Transparency and integrity of data"
Second paragraph in subsection "1. A limited time interval after the accident" in section "Official stance on radiation effects"
Fourth paragraph in subsection "2. Very low doses" in section "Official stance on radiation effects"

Note: A shorter version of this fact sheet has been e-published on the website of Kagaku by the Iwanami Publishers. It can be downloaded from this linkCitation in AMA style is as follows: Hiranuma Y. Fukushima thyroid examination fact sheet: September 2017. Kagaku. 2017;87(9):e0001-e0011.


This fact sheet reviews the current status of the Thyroid Ultrasound Examination (TUE) in Fukushima Prefecture. In its seventh year, all the data and information from the TUE have become quite large and complex. Drawing from official meetings, documents, data and publications—some available only in Japanese, some only in English, this fact sheet is intended to act as an English overview.

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

The TUE is conducted as part of the Fukushima Health Management Survey (FHMS),[1]  comprising the Basic Survey and the Detailed Surveys. The Basic Survey estimates external radiation exposure dose for the first four post-accident months from behavior questionnaires. The Detailed Surveys consist of the TUE, Comprehensive Health Check, Mental Health and Lifestyle Survey, and Pregnancy and Birth Survey. The study protocol for the FHMS was published in 2012.[2] The 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
The TUE, conducted every 2 years up to and every 5 years beyond age 20, consists of the primary and confirmatory examinations. The primary examination uses thyroid ultrasound screening to detect cysts and/or nodules. Cysts and nodules that meet certain diagnostic criteria (category B and above, as explained later) are recommended to undergo the confirmatory examination for more detailed ultrasound examination including Doppler ultrasound and elastography as well as urine and blood testing. Suspicious cases undergo fine-needle aspiration cytology (FNAC) to examine thyroid cells for signs of malignancy. FNAC positive cases are followed by surgery or observation. Definitive diagnosis of thyroid cancer requires pathological examination of surgically excised thyroid tissue. Thus the TUE results are reported as the number of suspected or confirmed of cancer cases. (Note: So far there has been only one case—early in the screening process—that turned out to be benign after surgery).

The first round was expected to produce a baseline[i] for this population due to a supposed latency of 4 years for radiation-induced thyroid cancer in children based on the Chernobyl data. There has been no thyroid cancer screening of similar magnitude and quality in unexposed children in Japan to compare to. Thus the first round screening was called “Initial Screening” at first and later renamed “Preliminary Baseline Screening (PBLS).” The second and third rounds are called “First Full-Scale Screening” and “Second Full-Scale Screening,” respectively.

The first round[5] of the TUE was scheduled to be conducted from October 9, 2011 through March 31, 2014, with each fiscal year—from April through the following March—covering residents from a set of municipalities grouped in a descending order of the air dose level of radiation. In order to boost the participation rate (by 1.5% to 81.7%), the first round was continued through April 30, 2015, concurrent with the first year of the second round. This meant that first time participants were still being registered for the first round while others were already going through the second round.[ii]

The second round
[6] began in April 2014, immediately after the first round supposedly completed and included residents who were born between April 2, 2012 and April 1, 2013.[iii] The primary examination of the second round, with a participation rate of 71.0% and progress rate of 100.0%, is essentially complete. But the confirmatory examination, with a participation rate of 82.3% and progress rate of 95.4%, is still ongoing.

The third round[7] began on May 1, 2016 and is scheduled to run through March 2018—the end of Fiscal Year 2017. As of March 31, 2017, 120,596 out of the survey population of 336,616 residents—about 45,000 fewer than previous rounds as the milestone screening participants are excluded[iv]—have participated in the ongoing primary examination at a participation rate of 35.8%. The confirmatory examination began on October 1, 2016 with a participation rate of 48.0% and progress rate of 67.8% so far. 

The unique diagnostic categories of A1, A2, B and C for the TUE were established by the "Sectional Meeting for Considering the Diagnostic Criteria of the Thyroid Ultrasound Examination” (referred as the Diagnostic Criteria Subcommittee[v] from here in). These diagnostic categories are: 
  • A1: no nodules or cysts found
  • A2: nodules 5.0 mm or cysts[vi] 20.0 mm
  • B: nodules 5.1 mm or cysts 20.1 mm
  • C: requiring immediate confirmatory examination

The A1 and A2 categories are followed in the subsequent round of screening two years later. The B and C categories require confirmatory examination. There has only been one case of the C category which requires confirmatory examination immediately.

Results of the Thyroid Ultrasound Examination
English translation of the results are found on the website of the Office of International Cooperation, Radiation Medical Science Center, Fukushima Medical University.[8] (Note: Shunichi Yamashita is listed as Founding Senior Director of Radiation Medical Science Center for Fukushima Health Management Survey).

The most current official summaries in English are found in Chapters 14 and 15 of “Thyroid Cancer and Nuclear Accidents,” a book featuring presentations from the “Fifth International Expert Symposium in Fukushima on Radiation and Health: Chernobyl+30, Fukushima+5: Lessons and Solutions for Fukushima’s Thyroid Question” held in Fukushima City on September 25-26, 2016.[9],[10] Though the most current official version in print, these reports are missing some information—some too new to be included (ex: additional cancer cases) and some that should have been reflected (ex: solid variant PTC).

The primary examination results show an increasing proportion of the A2 category from the first (47.8%) to the second round[6] (59.0%) as well as in the successive fiscal year cohort within each round (36.4% to 44.6% to 55.5% in the first round and 57.4% to 61.2% in the second round). The ongoing third round screening shows an A2 proportion of 64.5% so far.[7] The proportion of B is the same in the first and second rounds at 0.8%.

Thyroid cancer cases
The report of the first cancer case was documented in the minutes of the proceeding[11] at the Eighth Oversight Committee meeting held on September 11, 2012,[12] exactly eighteen months after the accident. After the first reporting of the FNAC results on June 5, 2013,[13] subsequent reports revealed an increasing number (14 to 16 more each time) of malignant or suspicious cases for about a year with the number of surgically confirmed cancer cases lagging behind. The first 4 cancer cases from the second round were reported on December 25, 2014.[14] At present, the second round results are yet to be finalized due to the still ongoing confirmatory examination, but the most recent data released on June 5, 2017,[6] show 71 suspected cancer cases including 49 cases surgically confirmed. The current third round screening, called “Second Full-Scale Thyroid Screening,” has so far detected 4 suspected cancer cases with 2 cases surgically confirmed.[7] 

The latest results
Table 1 shows the most recent results reported on June 5, 2017.[15]

Table 1: The latest results (data as of March 31, 2017)
  
*Includes a single case of benign nodules

Transparency and integrity of data
Once the confirmatory examination reveals the need for a closer clinical follow-up, FNAC and/or surgery, the case is no longer part of the TUE and enters regular medical care under the national health care system. On the premise that “disclosure of clinical information is prohibited in principle,” most data from such “follow-up” cases are not shared with the Oversight Committee or Fukushima residents. However, FMU researchers have allowed themselves to disclose such clinical information at academic meetings and in medical journals. 

Recently it became known that FMU has not publicized all cancer cases, let alone details, because only cancer cases diagnosed directly during the confirmatory examination are reported to the Oversight Committee. This came to light in March 2017 when an unreported cancer case was discovered in a boy who was 4 at the time of the accident.[16] FMU explains that cases followed up under regular medical insurance are deemed outside the boundaries and responsibilities of the TUE, with no obligation or actual system to collect such data for reporting.[17] The actual number of follow-up cases is uncertain due to potential duplicates in the subsequent rounds, but about 1,250 cases have been followed up from the first round. There is no way to know how many cancer cases might have been diagnosed in this group, if any.

This means the FMU studies[18],[19] using the official, incomplete data lack scientific integrity.

Surgical and pathological features 
Due to the reasons explained above, surgical and pathological details of the cases are not readily available. The most detailed and updated—albeit incomplete—surgical and pathological information on 125 cases operated at FMU, has been published in the aforementioned book, “Thyroid Cancer and Nuclear Accidents.” (The presentation slides can be downloaded from the Radiation Medical Science Center website[20] and information on the slides is explained in detail on the author’s blog post[21]).

Of 125 cases, 121 (96.8%) were ipsilateral and 4 (3.2%) were bilateral. Hemithyroidectomy was conducted in 114 cases (91.2%) while 11 cases (8.8%) underwent total thyroidectomy.[vii] All cases underwent the central lymph node dissection, and 24 cases also had dissection of the lateral neck lymph nodes (20 unilateral and 4 bilateral). The intraoperative nerve monitoring system (IONM) was used in all cases to prevent recurrent laryngeal nerve (RLN) injury.

There were no surgical complications such as hypoparathyroidism, permanent RLN palsy, or postoperative bleeding. One case had persistent RLN palsy despite the use of the IONM system.

Histopathological diagnosis showed 121 cases (96.8%) of papillary thyroid cancer (PTC), 3 cases of poorly differentiated thyroid cancer (PDTC), and 1 case of thyroid cancer categorized as “other” in Japan’s thyroid cancer management guideline. Subtypes of 121 PTC included 110 classical variants, 4 follicular variants, 3 diffuse sclerosing variants and 4 cribriform morula variants associated with familial adenomatous polyposis. A special mention was made that no case of solid variant of PTC was found. Absence of solid variant PTC has been allegedly one of the distinguishing points between Fukushima and Chernobyl cases.

However, the Supplemental Report of PBLS5 released on June 6, 2016 revealed the fact that 2 of 3 PDTC cases—one each from FY2011 and FY2012—were reclassified as PTC in accordance with the November 2015 revision of Japan's thyroid cancer diagnostic guidelines. Definition of PDTC in the previous guidelines included the solid variant of PTC, unlike the World Health Organization (WHO) classification of Tumors of Endocrine Organs. FMU has yet to specify PTC subtypes of the 2 reclassified cases, and Suzuki inexplicably neglected to mention the reclassification of 2 PDTC cases during the September 2016 symposium.

Existence of the solid variant PTC in Fukushima is confirmed in a recent study (in Japanese) by Suzuki et al., “Ultrasound findings of childhood thyroid cancer”[22] that covers childhood thyroid cancer cases treated at FMU including cases diagnosed during the TUE: “Cases previously classified as poorly differentiated thyroid cancer in the Sixth Edition of Thyroid Cancer Management Guidelines are reclassified as solid variant PTC in the Seventh Edition. Solid variant PTC is known to be not uncommon in pediatric thyroid cancer cases in Japan, but there have been extremely few cases operated in Fukushima at this time.”

Table 2: Pre-operative (clinical) and post-operative (pathological) TNM findings[viii]
(T=tumor size, N=lymph node metastasis, Ex=extrathyroidal extension, M=distant metastasis)

The post-operative TNM classification (Table 2) shows about 60% of tumors with a diameter of 20 mm or less (pT1a & pT1b), 78% with lymph node metastasis (pN1a & pN1b), and 39% with cancer cells spreading outside the thyroid (pEx1).[ix] Of 44 microcarcinoma cases (cT1a cN0 M0), 33 had surgical indications such as suspicion of extrathyroidal extension (20), lymph node metastasis (1), RNL invasion (10), tracheal invasion (7), Graves disease (1), and ground-glass opacity of lungs (1).[x] Of these, 3 cases turned out to be pT1apN0pEx0, justifying surgery in 30 cases. Of 11 cases which opted for surgery against the recommendation of non-surgical observational follow-up, 2 turned out to be pT1a pN0 pEx0. Details of 3 cases with lung metastasis (M1) are: 1) male age 16 at exposure, cT3 cN1a, pT3 pN1a; 2) male age 16 at exposure, cT3 cN1b, pT2 pN1b; and 3) female age 10 at exposure, cT1 cN1b, pT3 pN1b pEx1.

Other thyroid cancer data
A direct comparison between the prevalence obtained by screening of the asymptomatic population and the incidence based on clinical diagnosis is considered inappropriate. However, as a reference, the 2012 national incidence estimated in Japan for thyroid cancer in ages 0-19 was 4.6 per million for both sexes, 1.4 per million for male, and 7.9 per million for female.[23] 

Assuming all the suspicious FNAC cases are to be confirmed as cancer, excluding the single case surgically confirmed to be a benign nodule, the first round screening data yields thyroid cancer prevalence of 386 per million (116 cancer cases per 300,473 participants) for both sexes in those who were 0-18 years old at the time of the accident.

Table 3: 2012 Thyroid cancer incidence rate in Japan by age and sex (per million)

In t
he so-called “3-prefecture study,[xi]” thyroid ultrasound screening was conducted on 4,365 children aged 3-18 in Aomori, Yamanashi and Nagasaki Prefectures.[24] Findings of similar proportions of cysts and nodules[24] to the TUE and one cancer case[25] in 4,365 led the officials to hail the 3-prefecture study as a control study: the TUE results were declared “about the same as other unexposed areas in Japan.” However, the 3-Prefecture Study is an inappropriate control due to unmatched age range and sex distribution as well as the small size of the study cohort leading to a high margin of error.[26] A single case of thyroid cancer diagnosed in the 3-prefecture study makes a point estimate of 229 per 1 million with a 95% confidence interval of  6 to 1,276 per million,[27] but the wide bound of the confidence interval weakens the meaningfulness of the point estimate.

Tsuda et al. published in October 2015, the first epidemiological analysis of the publicly available thyroid cancer data (the first round screening data as of December 31, 2014) in Epidemiology, the official, peer-reviewed journal of the International Society for Environmental Epidemiology.[28] They 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 modern epidemiology, it generated seven criticisms[29],[30],[31],[32],[33],[34],[35] and an authors’ response.[36]  

The National Cancer Center research shows the observed/expected ratio of thyroid cancer prevalence to be as much as 30.8,[37] attributing this increase to overdiagnosis.

Official stance on the high prevalence of thyroid cancer
FMU officials claim that the high prevalence of thyroid cancer diagnosed in Fukushima Prefecture is not excess occurrence but excess detection due to screening of asymptomatic individuals by highly sensitive ultrasound equipment, i.e. screening effect. As early as February 2013 officials began to use the term, “screening effect” and suggested that Fukushima cases constituted diagnosis of indolent “latent” cancer that would not cause any symptoms until much later date, i.e. overdiagnosis.

The National Cancer Center researchers say the high number of thyroid cancer cases detected during the first round is “difficult to explain by screening effect alone” in a document[xii] submitted to the Thyroid Examination Evaluation Subcommittee in November 2014.[38]  Shoichiro Tsugane and Kota Katanoda estimated the 2010 (pre-accident) prevalence of thyroid cancer in ages 0-18 in Fukushima Prefecture from available data. The estimated prevalence was then compared with the first round results of 104 suspected and confirmed thyroid cancer cases at the time: The first round results were 61 times the estimated prevalence before the Fukushima accident. This increase was attributed to either excess occurrence due to some unknown reason or overdiagnosis, and not explainable by screening effect alone.

Researchers claiming screening effect and/or overdiagnosis do not appear to take clinical characteristics of these cancer cases into consideration. Perhaps defending validity of surgery, Suzuki refrains from claiming overdiagnosis, yet he does attribute the high number of thyroid cancer cases diagnosed to screening itself. Screening effect presupposes the cancer cases would not have been discovered until much later date, but aggressive features of even microcarcinoma (≤10 mm in diameter) make this a weak argument.

Prior diagnostic status of the newly diagnosed cancer cases
For 71 suspected cancer cases found during the second round screening, their first round results were: 33 A1, 32 A2 (7 nodules and 25 others such as cysts), 5 B, and one case that did not undergo the first round. The 58 cases (33 A1 and 25 non-nodular A2) which had no lesions with malignancy potential suggest a few possibilities: 1) missed diagnoses; or 2) rapid growth of cancerous lesions in 2-3 years since the first round screening, contradicting the known latency of 4 years for childhood thyroid cancer.

The official explanation is neither.

Akira Ohtsuru, the head of the TUE, states no missed diagnosis was confirmed when prior ultrasound images were reviewed. (This claim has not been independently verified). He rejects the notion of rapid growth, insisting that these are not “newly formed” but “newly detected.” His explanations—officially documented in the minutes of the proceedings[39]—are that even though some of the small nodules are very easy to detect by ultrasound, exceptions arise when 1) the border of the lesion is ambiguous, 2) the density of the lesion is so low that it blends into the normal tissue, or 3) the lesion resembles the normal tissue. Thus, the nodules were simply not detected even though they were there. Ohtsuru said that when such previously undetected nodules grow relatively large enough to become detectable by ultrasound, they might look as if they suddenly appeared. (This suggests a possibility that other “newly detected” cancer cases might exist at a similar proportion amongst individuals who received A1 or A2 assessments in the first round and elected not to participate in the subsequent rounds. Such cases would not be in the official count). Ohtsuru added that nodules that have already been detected by ultrasound do not to appear to grow very rapidly in general.

An issue of the sex ratio
For thyroid cancer, the female to male ratio is nearly 1:1 in the very young, but it is known to increase with age[40],[41] and decrease with radiation exposure.[42] The overall female to male ratio was 1.97:1 and 1.22:1 in the first and second round, respectively, both much lower than most recent clinically observed ratio of 7.9:1.[43] Curiously, the FY2015 municipalities have consistently shown a higher number of males than females with the overall female to male ratio of 1:1.38, but this has not been officially investigated.

In February 2017, after explaining that the cancer registry showed the female to male ratio close to 1:1 up to around puberty and the autopsy data showed the female to male ratio of 1:1 or smaller in adults, Ohtsuru concluded, “It is scientifically expected that thyroid cancer screening in general leads to a smaller female to male ratio even in adults.”[39]

His “scientific” explanation does not hold up. An analysis of the cancer registry data from 2000 to 2012 shows the female to male ratio up to puberty is closer to 2:1 than 1:1 (Table 4). Validity of extrapolation from autopsy data to screening is highly questionable, and there is no evidence to show thyroid cancer screening will yield a smaller female to male ratio as evident in the thyroid cancer incidence from South Korea[44] where active screening increased the incidence of thyroid cancer (Table 5).

Table 4: Thyroid cancer incidence calculated from the 2012 national incidence estimates in Japan[23]

Table 5: Incidence by sex and age group in South Korea compiled from supplementary tables 2&3 in Ahn et al.[44] (per 100,000)

Official stance on radiation effects 
FMU’s stance is summarized in the following excerpt[9]:

The relationship between a high prevalence of thyroid cancer and radiation exposure is thought to be very unlikely because of several standpoints; e.g., a limited time interval after the accident, very low doses, age and geographic distributions of thyroid cancer patients, driver mutation patterns, and pathological characteristics. This finding suggests overdiagnosis due to screening effects over the past 5 years.

This statement is inconsistent and contradictory. By “over the past 5 years” officials are clumping the first and second rounds together, contradicting their own assertion that the first round is the baseline.

Each of the official claims, 1) a limited time interval after the accident, 2) very low doses, 3) age distribution, 4) geographic distribution, 5) driver mutation patterns, and 6) pathological characteristics, is separately reviewed below.

1.    A limited time interval after the accident
This means the latency of 4-5 years would not have allowed radiation-induced thyroid cancer to appear during the first round.

The minimum latency for all childhood cancers other than lymphoproliferative and hematopoietic cancer has been determined as 1 year in “Minimum Latency & Types or Categories of Cancer,”[45] a policy document used by the Center for Disease Control in the World Trade Center Health Program (accessible from the website, https://www.cdc.gov/wtc/policies.html). The document also establishes 2.5 years as minimum latency for thyroid cancer in adults.

The common notion of radiation carcinogenesis focuses on radiation-induced DNA damage leading to mutations, and “radiation-induced” cancer refers to carcinogenesis “initiated” by radiation. However, radiation is considered a “complete carcinogen”, i.e. able to both initiate and promote cancer development.[46],[47] In reality it is difficult to completely separate initiation from promotion and progression since radiation-induced DNA damage can activate myriad pathways that result in genomic instability and may be involved in multiple stages of carcinogenesis.[46]

Even Otsura Niwa, the current chairman of the Radiation Effect Research Foundation, suggested in 1995 that “radiation induces cancer by enhancement of the spontaneous carcinogenesis process” and that “the first step of radiation carcinogenesis may not be the direct induction of mutation.”[48]

Ionizing radiation meets at least three of ten key characteristics of carcinogen as defined by the International Agency for Research on Cancer: 1) genotoxic, 2) altering DNA repair or causing genomic instability, and 3) inducing oxidative stress.[49] Oxidative stress produces ROS which are known to contribute to the bystander effect extracellularly and also intracellularly.[50] Thus carcinogenic characteristics of radiation by definition include both genetic and non-targeted effects. Induction of oxidative stress leads to cellular injury, affecting the microenvironment.

It has been proposed from the systems biology perspective that non-targeted radiation effects create the critical context that promotes cancer development by influencing the microenvironment.[51],[52]

It is then plausible to consider that some, if not all, of the thyroid cancer cases in Fukushima may be the result of radiation exposure via promotion of preexisting premalignant cells into malignancy, which constitutes a radiation effect in a broad sense. This in turn invalidates the notion of the first round as the baseline without the radiation effects.

2.    Very low doses
While the total radiation exposure doses in Fukushima may be lower than in Chernobyl, it is crucial to recognize that thyroid exposure doses in Fukushima are not known for the majority of residents due to insufficient direct measurements and estimated doses are underestimated on many levels. Officials use direct measurements in 1080 children (so-called the 1080 survey)[53] to show “how low the doses were,” but what is hardly ever discussed are the conditions for these measurements to lead to underestimation. The 1080 survey 1) used equipment with low sensitivity , 2) was conducted after the half-life of radioactive iodine 131 passed, 3) was conducted in the high background levels, and 4) subtracted the radiation level at the individual shoulder—rather than the air dose level—as the background level from the actual measurement, potentially leading to oversubtraction.[54] High readings were never confirmed with a more sensitive thyroid counter“ so as not to create worries for and discrimination against the individual, family, and communities.”[55],[xiii] Besides, the sample size of 1080—only 0.3% of about 360,000 Fukushima residents who were 18 or younger in March 2011—can hardly be considered to be representative of the whole cohort. Individual dose reconstruction is difficult at this point due to a short half-life of iodine 131. More detailed diet and behavior history from individuals diagnosed with thyroid cancer would be helpful, but it has not been done.

Also, the possibility that residents ingested highly contaminated food and water cannot be eliminated. Contrary to the official claim that milk and other foodstuffs were swiftly banned,[56] the central government did not establish the provisional regulatory limits for food until March 17, 2011, six days after the accident. Meanwhile, raw milk collected in Kawamata Town, Fukushima Prefecture showed radioactive iodine levels of 1190 Bq/kg on March 16 and 1510 Bq/kg on March 17, far exceeding the provisional regulatory limits for milk/milk products of 300 Bq/kg.[57] However, the test results of the Fukushima raw milk as well as the Ibaraki spinach were not publicized until March 19, 2011.[58]

Officials also claim the exposure doses were low in general due to swift evacuation and indoor sheltering orders by the government, but evacuation did not always go as swiftly as officially recognized, and actual exposure doses depended on the timing and direction of evacuation.[59],[60] The post-earthquake water outage led many families outside to seek out water rations rather than staying indoor without any forewarning against the approaching radioactive plume.

Shunichi Yamashita is one of the officials known to emphasize that “the excess risk of solid cancer is not statistically significant, especially below 100 mSv.”[61] However, a growing body of evidence supports the fact that there is no threshold dose below which radiation has no effect and health effects are seen at much lower doses than 100 mSv.[62],[63],[64],[65],[66],[67],[68] (Addendum: The contextual picture  of the so-called 100 mSv threshold discourse as it relates to the thyroid cancer issue is discussed in “Ethical Issues Related to the Promotion of a “100 mSv Threshold Assumption” in Japan after the Fukushima Nuclear Accident in 2011: Background and Consequences” by Tsuda et al).

It is also important to note that the majority of children in Fukushima did not receive iodine tablets to mitigate the effect of radioactive iodine isotopes, mainly iodine 131, on their thyroid glands. High iodine diet in Japan is considered to reduce uptake of radioactive iodine and thus thyroid cancer risk, but actual urinary iodine levels in children show 16.6% with mild to moderate iodine deficiency.[69] A higher risk for iodine deficiency was seen in ages <6 and 12-18, mostly reflecting age groups outside the school lunch program. Furthermore, the lack of iodine supplementation in the infant formula in Japan means a higher risk in the already vulnerable population.

Another factor that is frequently overlooked is the contribution from short-lived radionuclides that potentially affect the thyroid, such as iodine 132/tellurium 132 and iodine 133.[59]

3.    Age distribution
Ohtsuru et al. state, “In the early phase of the Chernobyl accident, the increased number of thyroid cancer cases was predominantly among younger children, especially those aged 0-4 years at the time of the accident; thus, the age distribution we observed was completely different (Williams, 2015; Takamura et al., 2016). Therefore, it can be concluded that the lesions identified during the two cycles of the examination over the past 5 years represent the natural incidence in a young population when ultrasound screening is used as a detection methodology.”

There are a few issues with this statement. It is true that the average age for Fukushima’s thyroid cancer cases from the first round is 14.9 years, and 62% were ages 15 or older at exposure. Takamura et al. state,[70] “starting from 1990, the incidence of thyroid cancer increased greatly in children who were aged 0–5 years at the time of the accident, which suggests that this age group is particularly vulnerable to the effects of radiation.” Official have stated multiple times that Fukushima’s thyroid cancer cases were not due to radiation exposure because those aged 0-5 at exposure were not diagnosed.[71]

When a 5-year-old (at exposure) boy was diagnosed with thyroid cancer during the second round, officials dismissed that a single case didn’t mean anything. Now the officials are shifting the number from ages 0-5 to 0-4 years, as evident in the excerpted statement by Ohtsuru et al. (Actually, an “unofficial” thyroid cancer case in a 4-year-old at exposure has surfaced,19 but the case is not included in the official count and remains unacknowledged by officials).

Next issue is an inappropriate data comparison. “In the early phase of the Chernobyl accident” actually should say “beginning four years after the Chernobyl accident” when thyroid cancer cases began to skyrocket in ages 0-5 at exposure. Fukushima’s TUE began 7 months after the accident, while in Chernobyl no organized screening activities were conducted during the first several years. Williams used a graph of the number of thyroid cancer cases by age in Chernobyl in an unspecified time span superimposed with that in Fukushima during the first 3 years after the accident.[72] Takamura et al. used 2 separate graphs, one showing thyroid cancer surgical cases in Belarus during different time periods after the Chernobyl accident and another showing the age distribution of the Fukushima cases during the first 3 post-accident years.[xiv]

Comparing data from different time periods in this manner is unscientific and misleading. Actually, It’s not surprising that the age distribution was “completely different” in both examples. When similar post-accident periods were compared in a correspondence to Thyroid, the age distribution of cancer cases in Fukushima was described as “strikingly similar” to that in Ukraine.[73]

To conclude that the absence of ages 0-5 in Fukushima thyroid cancer cases during the first 3-4 post-accident years when there was no increase in that age group in Chernobyl is at best illogical[74] and actually contradicts the official designation of the first 3-4 post-accident years as latency period.

4.    Geographic distribution
The FMU study[19] suggested no geographical differences after “no significant association between the individual external doses and thyroid cancer prevalence” was found. However, this study suffers from inadequate or inappropriate study designs, an inappropriate geographical classification[xv] and a misleading reliance on the external doses.[xvi]

It is the thyroid dose, not the external dose, that is of concern in evaluating the thyroid cancer risk, and relying on the external doses is simply misleading. Furthermore, their external dose classification, purportedly “generally consistent” with the WHO 2013[75] classification, amplifies the problem: The study includes municipalities wholly or partly in the 20 km zone in the middle dose area, while thyroid doses in the WHO 2013 excludes the 20 km zone. UNSCEAR 2013 shows some thyroid dose estimates in the 20 km zone to be higher than some municipalities designated as the “middle dose area.”[76],[77]

Further, inclusion of Iwaki City in the lowest dose group is inappropriate because the estimated thyroid dose in Iwaki City is as high as that in the highest dose group such as Iitate Village or Kawamata Town. In fact, the highest thyroid dose from the 1080 survey was found in a child from Iwaki City.[59] Located 40 km south of the FDNPP outside the evacuation or indoor sheltering zones, Iwaki City was hit with the radioactive plume in the early morning hours of March 15, 2011, with the highest radiation reading at 23.72 µSv/hr. However, very little rainfall resulted in low ground deposits of radionuclides,[78] leading to low external doses. Thus, Iwaki City’s thyroid doses are incongruous with external doses.The fact Iwaki City was chosen for thyroid survey to directly measure radioactive iodine contents of the thyroid should speak for itself, except only a fraction of children in Iwaki City (134 of 49,429 or 0.3%) actually went through the direct measurements with a survey meter.

For the first round results, FMU officials divided the entire prefecture into four geographical regions (the evacuation zone plus other 3 geographical regions of Hamadori, Nakadori and Aizu) and reported no regional differences in the proportion of suspected or confirmed cancer cases from the first round (Table 9 of the PBLS report[5]). However, this analysis is not very meaningful due to lack of age adjustment and a weak relationship between the regional division and exposure doses.

Meanwhile, an independent analysis of the second round data reveals a lower rate of thyroid cancer—age-adjusted and statistically significant—in the less exposed FY2015 cohort (excluding Iwaki City) compared to the more exposed FY2014 cohort.[79] For cancer cases with estimated external doses, a significant difference was found between < 1 mSv and ≥ 1 mSv: the rate of cancer in the ≥ 1 mSv group was more than twice as large as the < 1 mSv group. A further analysis according to the official regional division—even though the division has low statistical power[80]—shows a clear regional difference of thyroid cancer occurrence (per 100,000) in the second round results: 49.2, 25.7, 19.6 and 15.5 in the evacuation zone, Hamadori, Nakadori, and Aizu, respectively.[81],[xvii] This regional difference, i.e. dose-response, contradicts the official claim dismissing a relationship between the high prevalence of thyroid cancer and radiation exposure.

Also, it should be noted that the individual external dose estimates are based on a voluntary, questionnaire survey with a low response rate of 26.4%, hardly representative of the prefecture.

Officials also refer to the 3-prefecture study to claim no geographical difference. However, as discussed earlier under the section, Other thyroid cancer data, the 3-prefecture study is an inappropriate control due to unmatched age range and sex distribution as well as the small size of the study cohort leading to a high margin of error.[26]

5.    Driver mutation patterns
Different driver mutation patterns—dominance of BRAF point mutation in Fukushima vs. RET/PTC gene arrangement in Chernobyl—does not necessarily rule out radiation effects. Reasons are clearly stated by Gerry Thomas, a British molecular pathologist, in Chapter 12of the very book the official claims are laid out[82]: “RET rearrangement and BRAF mutation are not related to exposure to radiation, but show a strong association with age of the patient at operation.” That is, RET gene arrangements—often seen in Chernobyl and ascribed to radiation exposure—are actually not related to radiation but to the morphology of PTC which in turn is associated with the age of the patient. RET gene arrangements are not unique to radiation-induced thyroid cancer[83] and may be related to the dietary iodine status.[84] BRAF V600E point mutation is more commonly seen in adults and Asian populations[85] and also related to the dietary iodine status.[86] As a matter of fact, 40 percent of 62 thyroid cancer cases diagnosed in the Ukrainian-American study had no known mutation including RET/PTC and BRAF.[87]  

6.    Pathological characteristics
By the same token, the absence of the solid variant PTC in Fukushima (at least officially[xviii])—the only pathological characteristic that purportedly sets Fukushima apart from Chernobyl—most likely simply reflects different age distributions that are inappropriately compared.

As described in the section above, the morphology of PTC is associated with the age of the patient, and the solid variant, common in Chernobyl, is seen in younger children. In Fukushima, reclassification of poorly differentiated thyroid cancer in accordance with updated diagnostic guidelines supposedly added 2 cases of the solid variant PTC to the morphological profile. However, officials have not publicized this change, perhaps to keep the story straight in their favor.

Officials have maintained the age distributions are different in Chernobyl and Fukushima, albeit over different post-accident time periods. In Chernobyl many cases were diagnosed in children younger than 4 or 5 at exposure, but this wasn’t seen until 4-5 years after the accident.

In summary, there is an interrelationship among age distributions, tumor morphology, and oncogenic profiles. In regards to exposure doses, potential underestimation and lack of data create large uncertainties.   

Fukushima and Chernobyl are indeed different, but the differences so far are not definitive enough to claim no radiation effects. Rather, the differences merely underscore the very fact they are different datasets. This misleading emphasis on “differences” has boomeranged by revealing logical inconsistencies.

Conclusive remarks
Future of the TUE is a controversial topic. FMU officials who claim overdiagnosis seem to be interested in reducing its scale and facilitating the opt out process in order to lessen psychosocial impacts of cancer diagnosis.[88] Recently, U.S. Preventive Task Force Services (USPTFS) recommended against thyroid cancer screening in adults but an exception was made for those with a history of radiation exposure.[89] The SHAMISEN project by EU recently issued recommendations  on health surveillance after a nuclear accident including a recommendation against a systematic thyroid cancer screening.[90] FMU has posted these recommendation on the English website,[91] implying its endorsement. Meanwhile, Suzuki, an FMU thyroid surgeon, advocates a long-term continuance of the TUE. Changing the course of the TUE seems premature when the second round results have not even been properly analyzed. With FMU’s transparency as well as scientific and data integrity in question, it is critical for a truly independent analysis to be conducted by qualified experts, based on the latest evidence.




Notes
[i] Scientific validity of establishing a baseline in the exposed population is unclear.
[ii] Confirmatory examinations from the second and third rounds might be simultaneously ongoing, or there could be significant delays in conducting confirmatory examinations due to logistical issues such as the lack of manpower. Originally scheduled screening periods are essentially spread over a longer time period, overlapping with the next round of screening. A precise interpretation of results from each round of screening might be nearly impossible.
[iii] This cohort includes those who were exposed in utero.  The cohort coverage reflects a Japanese school year because the TUE is conducted in school settings for elementary and middle schools.
[iv] Conducted every 2 years up to age 20, the TUE transitions at age 25 to milestone screenings to be conducted every 5 years. Some residents are beginning to participate in the age 25 milestone screening, and if they have never participated in the TUE, their milestone screening results will be added to the second round screening results. Thus the number of the second round screening participants is expected to increase even though the screening period technically ended in March 2016.
[v] The Diagnostic Criteria Subcommittee consists of members from 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. The minutes of the proceeding (in Japanese) have revealed that the Diagnostic Criteria Subcommittee have met regularly behind closed doors where pre-released versions of the results were discussed amongst thyroid experts whose names are not publicized. (Accessible at https://www.i-repository.net/il/meta_pub/ssearch)
[vi] “Cysts” in the TUE are said to be colloid or simple cysts with no malignant potential: cysts with any solid components are classified as “nodules” by the size of the cysts themselves. In other words, a 20.0 mm cyst with a solid component would be classified as a 20.0 mm nodule and thus placed in the B category.
[vii] Japan’s clinical guidelines recommend hemithyroidectomy with prophylactic lymph node dissection unless total thyroidectomy is absolutely indicated.
[viii] Japan’s own clinical guidelines on cancers use essentially the same classification as the TNM classification, with the exception of the "Ex" notation which refers to the degree of extension outside the thyroid capsule: Ex1, equivalent to T3, means minimal extension (example: extension to sternothyroid muscle or perithyroid soft tissues); and Ex2, equivalent to T4, means further extension.
[ix] Review of Suzuki’s presentation video (https://www.youtube.com/watch?v=Gsq1_eF93V8) shows that 49 cases were pT3 due to minimal extrathyroidal extension, i.e. pEx1, rather than tumor > 4 cm limited to the thyroid .
[x] Numbers in parentheses denote the number of cases which do not add up to 33 because some cases apparently meet more than 2 surgical indications listed.
[xi] If the screening prevalence from the first round were indeed the true baseline for Japanese children and no different than the prevalence in the 3 prefecture study, it would suggest nationwide occurrence of pediatric thyroid cancer of similar prevalence as well as stages of cancer progression.
[xii] This document is available only in Japanese, but English translation is provided on the author’s blog post http://fukushimavoice-eng2.blogspot.com/2015/08/the-estimated-number-of-prevalent-cases.html
[xiii] A document dated April 1, 2011 refers to an opinion of Yoshiharu Yonekura, president of the Japan National Institute of Radiological Sciences and the 2015-2016 chair of the United Nations Scientific Committee on the Effects of Atomic Radiation, that the follow-up with a thyroid counter was not warranted (Supplementary document 23 on page 74 of reference 62).
[xiv] The final count from the first round, which is what is referred here, is 116 cases, while Williams mentions 110 and Takamura et al. 113 cases.
[xv] Municipalities wholly or partly in the 20 km zone are included in the middle dose area. UNSCEAR 2013 shows some thyroid dose estimates in the 20 km zone to be higher than some municipalities designated as the middle dose area. 
[xvi] External dose estimates are based on a voluntary, questionnaire survey with a low response rate of 26.4%—hardly representative of the residents. 
[xvii] These numbers can be verified by analyzing data presented in Table 10 of the latest report on the second round, http://fmu-global.jp/download/thyroid-ultrasound-examination-first-full-scale-thyroid-screening-program-5/?wpdmdl=2692. Municipalities can be divided into 4 groups according to the original analysis of the first round shown in Table 9 of this report, http://fmu-global.jp/download/thyroid-ultrasound-examination-initial-screening-3/?wpdmdl=1387. For reference, the numbers for the second round presented in the main text can be compared with those in the second row from the bottom in Table 9 from the first round report.
[xviii] In Fukushima, reclassification of poorly differentiated thyroid cancer in accordance with updated diagnostic guidelines supposedly added 2 cases of the solid variant PTC to the morphological profile.





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How the "Conclusion" Transpired on Thyroid Cancer in the Second Round in Fukushima

Note: In translation of the official documents, "detection rate(s)" is used instead of "incidence rate" or "prevale...