This is a compilation of the most current information
on Fukushima thyroid cancer surgical cases from 3 different sources (screenshots of the abstracts for 2 & 3 can be seen in this post):
- November 11, 2014 Thyroid Examination Evaluation Subcommittee meeting
- November 14, 2014 Japan Thyroid Association meeting
- August 28, 2014 Japan Society of Clinical Oncology meeting
Due to
the span of the time amongst these 3 sources, they have different numbers for
the cases of thyroid cancer. For clarification, the most updated summary of the
thyroid cancer cases is presented first.
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Summary of
Fukushima thyroid cancer cases as of November 2014
Number of cases
suspected or confirmed of thyroid cancer = 104
Cases that had
surgery = 58
Cases confirmed of
thyroid cancer = 57 (1 of 58 turned out to be benign nodules)
55 of 58 cases
were operated on at Fukushima Medical University (FMU)
- 1 case turned out to be benign nodules
- 52 cases of papillary thyroid cancer
- 2 cases of poorly differentiated thyroid cancer
Pre-operative diagnosis:
42 cases (78%) had
pre-surgical tumor diameter > 10 mm
12 cases (22%) had
pre-surgical tumor diameter ≤ 10 mm:
- 3 cases were suspected to have lymph node or distant metastasis.
- 7 cases with proximity to trachea or recurrent laryngeal nerve, or extrathyroidal extension
- 2 cases of voluntary surgery despite recommendation of non-surgical follow-up
Overall, 17 cases
(31%) had lymph node metastasis and 2 cases (4%) had distant metastasis to the
lungs
Operative methods:
5 cases (8%) had
total thyroidectomy
49 cases (91%) had
hemithyroidectomy
All 54 cases had
lymph node dissection
Post-operative
pathological diagnosis:
15 cases (28%) had tumor diameter ≤ 10 mm,
and 3 (6%) of them had no lymph node metastasis or distant metastasis (pT1a pN0
M0)
37% (?20 cases?) had extrathyroidal extension
74% (?40 cases?) were positive for lymph node metastasis
No post-operative complications (post-surgical hemorrhage, permanent
paralysis of recurrent laryngeal nerve, hypoparathyroidism, or hypothyroidism
after hemithyoidectomy) observed.
Note: 2
cases of lung metastasis were papillary thyroid cancer cases.
*****
Thyroid Examination Evaluation Subcommittee
Information that was released by Shinichi Suzuki at
the Thyroid Examination Evaluation Subcommittee meeting held on November 11,
2014
Regarding
Surgically Indicated Cases
Three years have passed since the disaster struck. Of
1,848 subjects that underwent the secondary examination up to June 30, 2014, 485 had
cytological examinations. Suspicious or malignant cases totaled 104, and 58 of
them were already operated on.
Surgeries on 55 of 58 cases were conducted at the
Division of Thyroid and Endocrine Surgery, Fukushima Medical University. 3
cases were operated on at other facilities. As 1 of 55 cases turned out to be
benign nodule post-operatively, only the 54 thyroid cancer cases were
considered there.
According to the pathological evaluation, 52 cases
were papillary cancer, and 2 were poorly differentiated thyroid cancer.
In pre-operative diagnosis, 42 cases (78%) had tumor
diameter > 10 mm. and 12 (22%) were ≤ 10 mm in diameter. Also, of the 12
cases with tumor diameter of ≤10 mm, 3 (5%) were suspected to have lymph node
metastasis and/or distant metastasis. 9 (17%) cases were not suspected to have
lymph node or distant metastasis (cT1acN0cM0).
Of these 9 cases, 7 were suspected to be close to the
trachea or the recurrent laryngeal nerve, or have extrathyroidal extension. The
remaining 2 cases were operated on based on patients’ wishes, despite the
recommendation of non-surgical follow-up.
Furthermore, 17 cases (31%) were positive for lymph
node metastasis, and 2 cases (4%) were suspected of multiple lung metastasis.
Surgical methods included total thyroidectomy in 5
cases (9%), and hemithyroidectomy in 49 cases (91%). Lymph node dissection was
conducted in all cases, with 67% limited to the central compartment and 33%
including lateral compartment. As much as possible, small-size incisions of 3
cm were used.
Post-surgical
pathological diagnosis revealed 15 cases (28%) with tumor diameter ≤ 10 mm, and
3 (6%) of them had no lymph node or distant metastasis (pT1a pN0 M0).
Extrathyroidal extension, pEX1, was seen in 37%, and 74% was positive for lymph
node metastasis. No post-operative
complications (post-surgical hemorrhage, permanent paralysis of recurrent
laryngeal nerve, hypoparathyroidism, or hypothyroidism after hemithyoidectomy)
were observed.
The 57th Annual Meeting
of the Japan Thyroid Association
November 14, 2014
Identification of gene clusters related to initiation of thyroid
cancer and elucidation of pathogenesis in children and young adults
Shinichi
Suzuki１,
Toshihiko Fukushima１, Michiko Matsuse３, Yudai Hirata１, Hirokazu Okayama 1,
Chiyo Okouchi 1, Toshiyuki Monma 2, Hiroshi Mizunuma
1, Satoshi Suzuki１, Norisato Mitsutake 3, Shunichi Yamashita
3
１Department
of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University,
２Department
of Organ Regulatory Surgery, Fukushima Medical University, ３Department of Radiation
Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University
There has been an increase
in the number of pediatric and young adult patients diagnosed with thyroid
cancer due to the advance in diagnostic ultrasound technology and
implementation of pediatric thyroid ultrasound screening. However, pathogenesis
relating to initiation and development of these cancers is yet to be fully
understood. As it is anticipated the
number of cases will increase in the future, we will identify gene clusters
related to cancer initiation and elucidate the mechanism of pathogenesis in
order to reveal biological features of these cancers. In this study, we
investigated the gene clusters known to be related to thyroid cancer
initiation.
Study subjects: 24 surgical
cases (male:female = 1:2, average age 17.9 years (9-22 years)) in children and
young adults. 23 cases were papillary thyroid cancer and 1 was follicular
cancer. (Note: The actual presentation
referred to 23 cases of papillary thyroid cancer and 1 case of poorly
differentiated thyroid cancer).
Method: DNA and RNA were
extracted from excised tumor tissues and analyzed with direct sequencing and
PT-PCR. Mutation in BRAF, K-, N-, and H-RAS and rearrangement in RET/PTC1 and
RET/PTC3 were investigated.
Results: 67% was positive
for BRAF mutation. Also, 12.5 % had rearrangement of RET/PTC1, but no mutation
was found in RET/PTC3, K-, N-, and H-RAS.
Information
from the transcript of the presentation by Shinichi Suzuki
23 cases were papillary
thyroid cancer (19 cases of classical type, 1 case of follicular variant, and 3
cases of cribriform-morular variant or CMVPTC), and 1 case was poorly-differentiated
thyroid cancer.
23 patients were from the Fukushima
Health Management Survey Thyroid Examination, and 1 case of a 22-year-old
female was unrelated to the survey.
Genetic analysis results:
RET/PTC1: positive in 3
cases or 12.5%（average age 17.8 years)
ETV6/NTRK3: positive in 1
case or 4.2％ (16-year-old female）
BRAF (known to be common in
adults): positive in 18 cases or 67%（average age 18 years）
No RET/PTC3, K-, N-, H-RAS,
or TRK detected.
5 cases (all females,
average age 16.7 years) were negative for RET/PTC1, BRAF, or ETV6/NTRK3.
The patient unrelated to Fukushima
Health Management Survey, a 21-year-old female, was RET/PTC1 positive.
BRAF, RET/PTC1 and
ETV6/NTRK3 cases were all classical type papillary thyroid cancer.
Five all-negative cases
included 1 case of follicular variant papillary thyroid cancer, 1 case of
poorly-differentiated cancer, and 3 cases of cribriform-morular variant
papillary thyroid cancer (CMVPTC). CMVPTC cases are under investigation for APC
genetic mutations which are known to be causative. All 3 CMVPTC cases have
family history.
Five all-negative cases had
slightly larger tumor diameter than others. These 5 cases were the only cases
undergoing total thyroidectomy.
BRAF positive cases are said
to be aggressive. RET/PTC1 tends to be seen in older children and associated
with cases unrelated to radiation exposure. RET/PTC3 is seen in younger
children, and seen frequently in Chernobyl, although it is not considered to be
the definitive oncogene for radiation-induced PTC. It is commonly thought gene
rearrangements are more frequently seen in children, whereas point mutations
are seen more in adults.
As a conclusion, BRAF, the
genetic mutation detected most frequently, is what is usually seen in typical
adult PTC. It is highly possible that cases which may not have been detected if
it weren’t for the thyroid ultrasound screening are being discovered in
children and young adults as a result of the screening.
Note 1: Three cases of cribriform-morular variant
papillary thyroid cancer are not consistent with the information from the
August 2014 meeting of Japan Society of Clinical Oncology below, showing 3
cases of diffuse sclerosing variant papillary thyroid cancer. It is likely the
pathological diagnosis was updated after an outside review.
Note 2: Suzuki’s presentation of these details
outside the Thyroid Examination Evaluation Subcommittee, especially before the
information was shared with the Subcommittee and the public, created
controversy as to the handling of data. Suzuki claims the study was accepted by
the ethics committee at Fukushima Medical University, but the thyroid
examination itself is conducted with the money provided by the central
government to Fukushima Prefecture, and the data belongs to the prefecture and
the residents. Suzuki has a track record of not revealing the data to the
Thyroid Examination Evaluation Subcommittee or the Prefectural Oversight
Committee for Fukushima Health Management Survey before presenting it at an
academic meeting in August 2014, as described below.
Note 3: This meeting was
closed to media due to the decision of the conference chair, based on the
wishes of some of the presenters.
Note 4: Shigenobu Nagataki, a mentor to Shinichi Yamashita, revealed the following information during the questions and answers session:
Shigenobu Nagataki was invited to do a presentation
called “Fukushima Daiichi Accident and Thyroid Cancer” at “Meet-the-Professor
Workshop” on October 30, 2014 at the 84th Annual Meeting of the American Thyroid Association.
He
was asked by thyroid specialists attending the meeting if nodule sizes were the
only thing determined in this unprecedented, large-scale screening.
Participants wanted to know how many had Graves’ disease, autoimmune
thyroiditis, goiter, etc. [Note: Fukushima Health Management Survey has not released
hardly any data regarding non-cancer thyroid diseases]. Nagataki referred to
patient privacy in disclosing such information, but he was told patient privacy
meant such things as patients’ names and had nothing to do with how many
patients had Graves’ disease. [Note: Fukushima Medical University cites patient privacy when refusing to disclose details of their findings]. They asked him there must be a rough estimate of non-cancer thyroid diseases made by thyroid specialists conducting
ultrasound screening. Nagataki told them he would get back to them in
writing as he didn’t know what to say.
*****
The 52nd
Annual Meeting of Japan Society of Clinical Oncology
August
28-30, 2014
Organ
Specific Symposium 03, August 28, 2014
10:00-12:00
OS3-5 “Treatment of Pediatric Thyroid Cancer in Fukushima”
Shinichi Suzuki
Division of Thyroid and
Endocrinology, School of Medicine, Fukushima Medical University
Pediatric thyroid cancer has
been considered rare, consisting approximately 1-2% of all thyroid cancer. They
might appear to be advanced at first sight, with lung metastasis or widespread
lymph node metastasis discovered at the time of diagnosis, but long-term
survive is known to be extremely good.
After the Fukushima Daiichi
nuclear power plant accident following the Great East Japan earthquake and
tsunami on March 11, 2011, Fukushima Prefecture was burdened with the prospect
of faces long-term radiation health effects. Fukushima Health Management Survey
was launched in Fukushima Prefecture, with one of the surveys being thyroid
ultrasound examination of residents who were children at the time of the
accident. Initial Screening has already completed, and thyroid cancer cases
have been discovered. We report our experience in treating these asymptomatic
pediatric thyroid cancers detected through ultrasound screening, unlike the
usual symptomatic thyroid cancer.
Study subjects are 269,354
children (participation rate 80.8%) who underwent primary examination from
October 2011 to December 31, 2013. Of these, 1796 required secondary
examination, and 75 of them were diagnosed with malignant or suspicious tumor
as a result of fine-needle aspirational biopsy. 34 already had surgery, and 33
were confirmed to have thyroid cancer. We are reporting here on the 31 cases
operated on in our department.
Average age at the time of
surgery is 16.4 (9-20) years, the male
to female ratio is 14:17, and 9 cases were from Fiscal Year 2011 (from 13
municipalities designated by the government to be evacuation zone), and 22
cases were from Fiscal Year 2012.
Average tumor diameter at
the time of surgery was 14.9 mm (6-13 mm). Pre-operative diagnosis revealed 22
cases of T1 (7 T1a and 15 T1b), 7 cases of T2, and 2 cases of T3. 19 cases
were N0, 12 cases were N1 (4 N1a and 8 N1b), 29 cases of M0 and 2 cases of M1
(lungs). Surgical method was 28 cases of hemithyroidectomy and 3 cases of total
thyroidectomy, and lymph node dissection included 19 cases of central
compartment dissection, and12 cases of lateral compartment dissection.
Post-operative diagnosis revealed 24 cases of papillary thyroid cancer (usual
type), 3 cases of follicular-type papillary thyroid cancer, 3 cases of diffuse
sclerosing papillary thyroid cancer, and 1 case was suspicious of poorly
differentiated thyroid cancer. 21 cases
of pT1 (9 cases of pT1a, 12 cases of pT1b), 3 cases of pT2, 7 cases of pT3
(EX1), 7 cases of pN0, and 24 cases of pN1 (12 pN1a and 12 pN1b). Two cases with
pre-operative suspicion of M1 (lungs),
which had the Tg level in the blood dropping below detection range after total
thyroidectomy, will be scheduled for either CT scan of lungs or I131
scintigraphy.
In all cases, intraoperative
monitoring of the recurrent laryngeal nerve was conducted using NIM. Surgical
incision for neck dissection was limited to small skin incisions of 3 cm in the
central compartment dissection and 3-5 cm in the lateral compartment
dissection. No paralysis of the recurrent laryngeal nerve or hypoparathyroidism
was observed.
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