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2015 Update: Details of Fukushima Thyroid Cancer Surgical Cases

This post contains a translation of the first three abstracts presented at the Symposium 1 "Diagnosis and Treatment of Childhood and Adolescent Thyroid Cancer" during the 27th Annual Congress of the Japan Association of Endocrine Surgeons held on May 28-29, 2015, in Fukushima City.

Shinichi Suzuki, a thyroid surgeon at Fukushima Medical University and director of Thyroid Ultrasound Examination, was the program chair. (See his greeting here in Japanese).

Background on lack of information disclosure and Suzuki's stance

On May 18, 2015, only 10 days before the Annual Congress of the Japan Association of Endocrine Surgeons, the Nineteenth Oversight Committee for Fukushima Health Management Survey convened, where Suzuki's unexpected absence surprised journalists and audience on site as well as on the Internet. Suzuki's potential absence from the Oversight Committee was not mentioned at the previous Oversight Committee session on February 12, 2015. Masafumi Abe, vice president of Fukushima Medical University, explained during the press conference that Suzuki would be focusing on clinical aspects of Thyroid Ultrasound Examination--namely, surgery and training of medical personnel. Having been involved with the Thyroid Ultrasound Examination from the planning stage, for the past four years, Suzuki has been doing double duty running the program and conducting surgeries. It was decided that Suzuki would hand over the day-to-day operation of Thyroid Ultrasound Examination to Akira Ohtsuru, an internist who was dispatched from Nagasaki University to become a professor at the Department of Radiation Health Management at Fukushima Medical University. (By the way, although it is not clearly stated in Japanese sites, Shunichi Yamashita still presides over Thyroid Ultrasound Examination as Senior Director according to this site).

Even though Suzuki never willingly shared clinical details of the thyroid cancer cases at either the Oversight Committee or the Thyroid Examination Assessment Subcommittee, he was at least quite knowledgeable about the results being presented, eloquently reading aloud the printed results with almost a salesman's pitch. The reason clinical details have not been openly shared is because, during the confirmatory examination, from the point of the fine-needle aspiration cytology (FNAC) on, the medical care of the patients technically leaves the Fukushima Health Management Survey, shifting from "screening" covered by a special prefectural budget to "regular medical care" utilizing the national health insurance. This meant a stricter layer of protection for patient privacy. In addition, there was no comprehensive data collection system organized by any one entity, and no one had data compiled of all the surgical cases, given the small number of patients operated at facilities other than Fukushima Medical University.

To his credit, during the Sixteenth Oversight Committee meeting held on August 24, 2014, Suzuki asked the Committee to discuss and decide which information needed to be disclosed and how the information would be handled so that his team could decide which clinical information would be released. On one hand, he appeared genuinely concerned about the handling of medical information, but on the other hand, it seemed as if he were trying to release as little information as he could get away with. In the past, Fukushima Medical University refused repeated requests from committee members and journalists to release details of demographic data on the cancer cases, which might offer a glimpse into exposure doses of individual cases, 

Given the above circumstance, it was a shock when news articles reported that Suzuki released detailed information on surgical cases, only 4 days later, at the 52nd Annual Meeting of Japan Society of Clinical Oncology held during August 28-30, 2014. He reported an updated version of this detailed information on surgical cases at the November 11, 2014 Thyroid Examination Assessment Subcommittee meeting, only after Fukushima Prefecture requested it. An even more updated version of information on surgical cases is what was presented at an endocrine surgeons' meeting on May 28, 2015, as translated below. 

Incidentally, Suzuki caused quite a stir at the November 11, 2014, Thyroid Examination Assessment Subcommittee meeting when he stated his intention to present results of the genetic testing at the Japan Thyroid Association meeting to be held several days later. Subcommittee members were not pleased and asked Suzuki to present the abstract of the upcoming presentation, which is in the public domain, but Suzuki declined stating the abstract belonged to the Japan Thyroid Association and he could not release any information unless the Subcommittee could provide an official procedure or guideline for information release on the spot.  

The screening portion of Thyroid Ultrasound Examination is managed by the government of Fukushima Prefecture, which in turn commissions the work to Fukushima Medical University. However, when the cases enter the stream of regular medical care, how the data is utilized in research appears to be beyond the grasp of Fukushima Prefecture. Suzuki says the research is approved by the Ethics Committee of Fukushima Medical University and consent forms have been signed by the patients. 

What is clear is that Fukushima Medical University is prioritizing academic achievements over sharing of information with the very people the information belongs to--Fukushima residents. A prefectural official stated during the press conference after the Fourth Session of Thyroid Examination Assessment Subcommittee that the data itself belonged to Fukushima residents. He continued to state that although he understood the data might be processed and analyzed for publication or presentation at academic conferences and it might not be possible for it to be publicized beforehand, he would like at least the original "raw" data to be shared with Fukushima Prefecture residents at committee meetings.

Even as of now, it seems that no clear procedure has been set regarding sharing of data with Fukushima residents. The Oversight Committee should be where such procedures are developed, yet recent sessions have not attempted it.

Since he is no longer attending the Oversight Committee, and the Thyroid Examination Assessment Subcommittee essentially finished its course as of March 2015 with no future meetings scheduled, Suzuki will not have an opportunity to present detailed information on surgical cases to the public or be held accountable for prioritizing academic meetings when disclosing information. His successor, Ohtsuru, did a less than adequate job of verbally presenting printed results, barely able to answer questions from committee members and journalists. To the journalists who were hoping to push for disclosure of not just surgical details but demographic details of cancer cases, this seemed like backtracking.

The abstracts translated below do not by any means offer comprehensive analyses up to date with the most current results of Thyroid Ultrasound Examination. However, they do present findings and analyses of some of the cases detected during the Initial Screening. This presentation by Kenneth Nollet at the 62nd session of UNSCEAR held during June 1-2, 2015, in Vienna, Austria, includes an easy-to understand overview of Thyroid Ultrasound Screening program and its most recent results reported on May 18, 2015. (Some expressions in this presentation might be disputable, such as calling "A2" as "normal thyroids"). Nollet is Director of the Department of International Cooperation, Radiation Medical Science Center for the Fukushima Health Management Survey at Fukushima Medical University.

Recap of the most recent results of FNAC from Initial Screening as of March 31, 2015, reported on May 18, 2015



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SY1-1 “Cytological and Tissue Diagnosis in Pediatric and Adolescent Thyroid Cancer”

Atsuhiko Sakamoto
Department of Pathology and Laboratory Medicine
Omori Red Cross Hospital

Fine-needle aspiration cytology is highly regarded as a method to confirm diagnosis before starting treatment of thyroid lesions such as tumor. Tissue diagnosis plays a role of confirmatory diagnosis (final diagnosis) in the examination of surgical specimen.

While pediatric and adolescent thyroid cancer has been considered rare in general, it attracted attention due to its high incidence as radiation-induced cancer after the Chernobyl accident. It drew interest in Japan after the Fukushima Daiichi nuclear power plant accident due to the Great East Japan earthquake and tsunami, and thyroid examination was started in Fukushima residents 18 or younger at the time of the accident, as part of the Fukushima Health Management Survey. I am involved with the cytological assessment and tissue diagnosis as a member of the Diagnostic Criteria Inquiry Subcommittee of the Thyroid Examination Expert Committee at Fukushima Medical University. From that standpoint, I would like to show during this session general characteristics of pediatric and adolescent thyroid cancer in terms of cytological and tissue diagnosis, along with the results from evaluation of radiation exposure cases in the Fukushima Health Management Survey.
Papillary thyroid cancer is the most common subtype of primary thyroid cancer. Papillary thyroid cancer occurs in high frequency, more than 50%, in both adult and pediatric/adolescent cases. Papillary thyroid cancer has many variants other than the classical type. According to the Sixth Edition of Thyroid Cancer Management Guideline (2005), based on the WHO Classification of Tumours (2004), special subtypes of papillary thyroid cancer can be divided into: 1) follicular, 2) encapsulated, 3) macrofollicular, 4) oxyphilic cell type, 5) diffuse sclerosing, 6) tall cell, and 7) cribriform-morular variants.

According to the tally by the Fukushima Health Management Survey, there were 84 cases (96.6%) of papillary thyroid cancer amongst 87 surgical cases of pediatric and adolescent thyroid cancer at the end of 2014. They included 3 cases of follicular variants and 4 cases of cribriform-morular type. The solid variant, seen in high frequency after the Chernobyl accident, is classified as poorly differentiated thyroid cancer in the Sixth Edition of Thyroid Cancer Management Guideline.
The Fukushima data include many small-size cancers, offering big hints for the elucidation of the behavior of microcarcinoma and for clinical management consideration.

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SY1-2 “Genetic Mutations in Pediatric and Adolescent Thyroid Cancer”


1Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University; 2Department of Global Health, Medicine and Welfare, Atomic Bomb Disease Institute, Nagasaki University; 3Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University; 4Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University

Norisato Mitsutake1, Michiko Matsuse1, Tatiana Rogounovitch2, Vladimir Saenko3, Toshihiko Fukushima4, Shinichi Suzuki4, Shunichi Yamashita1

An increasing number of patients are diagnosed with asymptomatic pediatric/adolescent thyroid cancer due to a dramatic advancement of diagnostic ultrasound technology as well as an increase in thyroid ultrasound examinations in pediatric and adolescent populations. For the purpose of elucidating biological characteristics of these cancers, analysis and assessment were conducted on the relationship between the known oncogene mutations and the clinico-pathological findings reported in papillary thyroid cancer so far. Subjects were 65 surgical cases of pediatric and adolescent papillary thyroid cancer: 22 males and 43 females; average age 17.4 years; 59 cases of classic subtype, 2 cases of follicular variant, and 4 cases of cribriform-morular type. Oncogene mutations investigated and the number of cases in each type of mutation are as follows: BRAFV600E mutation — 42 cases (64.6%); RAS mutation (including NRAS, KRAS and HRAS) — 0 case; RET/PTC1 — 5 cases (7.7%); RET/PTC3 — 1 case (1.5%); ETV6/NTRK3 — 4 cases (6.2%); AKAP9/BRAF — 0 case; and TERT promoter mutation — 0 case. Cases with BRAFV600E mutation were characterized by significantly older age and smaller tumor diameter compared to other cases. The pattern of these oncogene mutations was nearly identical to the pattern seen in adults, except for the TERT promoter mutation, observed in approximately 10% of adults (usually only in cases aged 45 and older, and in highly correlation with age), which was not at all observed in these subjects. This is considered to be extremely important information in mechanistic considerations of the carcinogenesis and development of thyroid cancer in human.


(Note: Even though the cases presented here are not specified as being from Fukushima Thyroid Ultrasound Examination, similarities of data to the previous presentation on genetic testing results suggest most of them are indeed from the Fukushima data).

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SY1-3 “Facts about the Pediatric Thyroid Cancer Treatment in Fukushima Prefecture”

1Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, 2Department of Organ Regulatory Surgery, Fukushima Medical University, 3Department of Laboratory Medicine, Fukushima Medical University

Izumi Nakamura1, Shinichi Suzuki1, Yudai Hirata1, Takahiro Nakajima1, Nobuhiro Hoshi2, Yuko Murakami2, Hirokazu Okayama2, Chiyo Ohkouchi1, Satoshi Suzuki1, Keiichi Nakano1, Hiroshi Mizunuma1, Toshihiko Fukushima1, Satoshi Suzuki1, Hiroki Shimura3, Seiichi Takenoshita2

Introduction

Even now when four years have passed since the Fukushima disaster, the thyroid ultrasound examination quietly continues as part of the Fukushima Health Management Survey in Fukushima Prefecture. We report here some facts about the post-accident pediatric thyroid cancer treatment in Fukushima up to October 31, 2014.

Subjects

109 of the confirmatory examination participants in the thyroid ultrasound examination, conducted as part of the Fukushima Health Management Survey, were diagnosed with suspicious or confirmed malignancy, and 85 of them had surgeries. We discuss 79 of the 80 cases operated on at Fukushima Medical University, excluding the single case which was post-operatively diagnosed as benign nodules. Pathological diagnosis confirmed 76 cases as papillary thyroid cancer and 3 as poorly-differentiated thyroid cancer.

Results

Of 79 cases, pre-operative diagnosis showed 25 cases (32%) had tumor diameter ≤ 10 mm, including 13 (16%) cases classified as cT1acN0cM0 [i.e. no lymph node or distant metastasis]. Surgery was indicated in 10 of these 13 cases as they were suspected to be close to the trachea or the recurrent laryngeal nerve, or have extrathyroidal extension. The remaining 3 cases were operated on due to wishes of patients and/or families, despite discussion on the possibility of non-surgical follow-up. Pre-operatively, 25 cases (31%) were positive for lymph node metastasis, and 3 cases (4%) were suspected to have lung metastasis. Surgical methods included total thyroidectomy in 6 cases (8%) and hemithyroidectomy in 73 cases (92%). Lymph node dissection was conducted in all cases, with 82% limited to the central compartment and 18% including the central and lateral compartments. Post-operative pathological diagnosis revealed 17 cases (22%) with tumor diameter ≤ 10 mm, and 44% with extrathyroidal extension, pEx1*, and 75% with lymph node metastasis. No post-operative complications (post-operative hemorrhage, permanent paralysis of recurrent laryngeal nerve, hypothyroidism in cases other than total thyoidectomy cases, and hypoparathyroidism) were observed.

Conclusion

We reported the current situation of pediatric thyroid cancer treatment in Fukushima. Treatment of pediatric thyroid cancer calls for consensus-building, and we expect findings in Fukushima will become useful in revising guidelines in the future.


*Note: Ex1, a designation defined in Japan's unique guideline, "The Sixth Edition of Thyroid Cancer Management Guideline," is considered to be equivalent to T3 in the TNM classification. The following is translation of the information on thyroid cancer classification from the National Cancer Center.
  • T3: Tumor greater than 4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues)
  • Ex1: Minimal extrathyroid extension limited to sternothyroid muscle or adipose tissues. (Note: Cases with adhesion to organs other than sternothyroid muscle or adipose tissues which can be detached using a sharp instrument are considered Ex1). 
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Some comparisons with the previous report on surgical cases:

The third abstract above includes information based on Thyroid Ultrasound Examination results as of October 31, 2014, reported at the meeting of the Seventeenth Oversight Committee for Fukushima Health Management Survey held on December 25, 2014. It is an updated version of the report, "Regarding the Surgically Indicated Cases" submitted by Suzuki to the fourth session of Thyroid Examination Assessment Subcommittee on November 11, 2014 (see Section 1 of this post), adding detailed information for 25 more cases which underwent surgery during the four-month period between July 1, 2014 and October 31, 2014.

Of these 25 additional surgical cases, 24 were papillary thyroid cancer and 1 was poorly differentiated thyroid cancer. Compared with the June 30 data, the number of cases with a pre-operative tumor diameter ≤ 10 mm increased by 13 from 12 (22%) to 25 (32%), while the number of cases with a post-operative tumor diameter ≤ 10 mm only increased by 2 from 15 (28%) to 17 (22%). This means that 13 of the 25 additional cases had a pre-operative tumor diameter ≤ 10 mm, but 11 of those 13 cases were actually larger than 10.1 mm post-operatively. 10 of the 13 cases were operated on because they were close to the trachea or the recurrent laryngeal nerve or because the tumor extended outside the thyroid gland into the surrounding tissues or organs. (By the way, it has never been clarified whether any of the patients had any subjective symptoms at examination).
Proportions of pre-operatively diagnosed lymph node metastasis and lung metastasis remained the same at 31% and 4%, respectively. Of the 25 additional cases, only one underwent total thyroidectomy and the remaining 24 had hemithyroidectomy which leaves a half of the thyroid gland intact to produce thyroid hormones.

The proportion of those receiving lymph node dissection limited to the central compartment increased from 63% to 82%, while lymph node dissection extending to the lateral compartment was performed in 18%, down from 33%. (Without further information available, it is not clear why these proportions changed).

In the post-operative diagnosis, the proportion of cases with extrathyroidal extension, pEx1, slightly increased from 37% to 44%, while the lymph node metastasis was seen in 75%, about the same as 74% reported previously. 

Based on the above information, it appears that the operated cases meet the indications for surgery by the Japanese guidelines.




















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