Fukushima Thyroid Examination Fact Sheet:
September 2017
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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 link. Citation 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.
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 the 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
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.
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.
[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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