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Details of Fukushima Thyroid Cancer Surgical Cases

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): 
  1. November 11, 2014 Thyroid Examination Evaluation Subcommittee meeting
  2. November 14, 2014 Japan Thyroid Association meeting
  3. 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.

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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 Suzuki, Toshihiko Fukushima, Michiko Matsuse, Yudai Hirata, Hirokazu Okayama 1, Chiyo Okouchi 1, Toshiyuki Monma 2, Hiroshi Mizunuma 1, Satoshi Suzuki, Norisato Mitsutake 3, Shunichi Yamashita 3
Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, Department of Organ Regulatory Surgery, Fukushima Medical University, Department 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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