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Fukushima Thyroid Examination December 2017: 159 Surgically Confirmed as Thyroid Cancer Among 193 Cytology Suspected Cases


Note: Corrections were made on March 8, 2018 regarding an additional surgical case (i.e. confirmed thyroid cancer case) for the second round that was presented during the December 25 Oversight Committee meeting but overlooked in the original version of this post.

Highlights:

  • No new data One new surgical case for the second round since the last report
  • The third round saw no newly diagnosed cases but an addition of 4 new surgical cases means all 7 cases diagnosed so far have been confirmed as thyroid cancer. 
  • Total number of suspected/confirmed thyroid cancer remains the same at 193 (excluding a single case of benign tumor; 115 in the first round, 71 in the second round, and 7 in the third round).
  • Total number of surgically confirmed cancer cases has increased to 158 159 (101 in the first round,  50 51 in the second round, and 7 in the third round)
  • The final report of the second round, released at the Eighth Thyroid Examination Assessment Committee held on November 30, 2017, is essentially identical to the last second round report which is available in English on this web page, other than Table 11 showing the regional comparison.
  • Gen Suzuki was selected as chair of the Thyroid Examination Evaluation Subcommittee which convened with new and returning members (information available only in Japanese on this web page).
On December 25, 2017, the 29th Oversight Committee for Fukushima Health Management Survey (FHMS) convened in Fukushima City, Fukushima Prefecture. Among other information, the Oversight Committee released the latest results (as of September 30, 2017) of the third round of the Thyroid Ultrasound Examination (TUE).  Official English translation of the results are to be posted here

Minutes of the proceedings are only released in Japanese, and no official transcript is released for the press conference held immediately after the committee meeting. Information released regarding the TUE at this Oversight Committee meeting was limited, and the narrative below includes pertinent information covered during the committee meeting and the November 30, 2017 Thyroid Examination Assessment Subcommittee as well as respective press conferences.

Overview
This Oversight Committee meeting was held only 2 months after the October 23, 2017 meeting. The final report of the second round released at the 8th Thyroid Examination Assessment Subcommittee on November 30, 2017 was reviewed, but and the latest results from the confirmatory examination of the second round as of September 30, 2017, was NOT presented. Because some participants of the confirmatory examination might postpone biopsy and/or surgery until the summer recess from the last one-third of July through the end of August, data as of September 30, 2017 is considered a critical addition for the second round. Previously, any addition to the final report of the first round results (released on August 31, 2015) such as the number of new cytology-suspected or surgically-confirmed thyroid cancer cases was at least shared orally at subsequent Oversight Committee meetings, with an eventual release of an updated version of the final report (FY2015FY2016) as of March 31—the end of each fiscal year.

The third round saw 4 additional surgical cases, as of September 30, 2017, meaning all cases from the third round have so far been operated on. 

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

Below is Table 11 that shows data by four administrative regions. This was the only addition to the final report of the second round that was presented at the 8th Thyroid Examination Assessment Subcommittee. This table is discussed further later.


Note 10: Excluding duplicates.
Note 11: Excluding unconfirmed results. 
Note 12: The number of FNAC, out of (c), including those who were reclassified as A1 or A2.
Note 13: Tamura City, Minamisoma City, Date City, Kawamata Town, Hirono Town, Naraha Town, Tomioka Town, Kawauchi Village, Okuma Town, Futaba Town, Namie Town, Katsurao Village and Iitate Village
Note 14: Fukushima City, Koriyama city, Shirakawa City, Sukagawa City, Nihonmatsu City, Motomiya City, Koori Town, Kunimi Town, Otamamura Village, Kagamiishi Town, Tenei Village, Nishigou Village, Izumizaki Village, Nakajima Village, Yabuki Town, Tanagura Town, Yamatsuri Town, Hanawa Town, Samegawa Village, Ishikawa Town, Tamakawa Village, Hirata Village, Asakawa Town, Furudono Town, Miharu Town, and Ono Town
Note 15: Iwaki City, Soma City, Shinchi Town
Note 16: Aizuwakamatsu City, Kitakata City, Shimogo Town, Hinoemata Village, Tadami Town, Minamiaizu Town, Kitashiobara Village, Nishiaizu Town, Bandai Town, Inawashiro Town, Aizubange Town, Yugawa Village, Yanaizu Town, Mishima Town, Showa Village, and Aizumisato Town


Notable information

Toru Takano voiced 3 concerns about the TUE. First was a tremendous amount of overdiagnosis expected from the TUE being planned up to 2036. During the press conference, a freelance journalist Mako Oshidori pointed out a post on Takano's web page stated that autopsy data showed there was no worry about overdiagnosis below age 15. Takano confirmed that students younger than high school ages would not be prone to overdiagnosis based on autopsy data showing no latent cancer below age 15. He stated thyroid cancer cases detected below age 15 are due to reasons other than overdiagnosis.

Takano then questioned if the informed consent form for the TUE is adequate to inform residents about pros and cons of thyroid cancer screening. Takano wondered if parents understand that early diagnosis is not necessarily beneficial or that the TUE is just a survey and not intended to improve their children's health. FMU's Sanae Midorikawa replied that the consent form gained an opt-out option beginning in the third round and the form mentions that screening might lead to some worries. Midorikawa explained that the consent form has no adequate explanation regarding a potential problem of overdiagnosis or lack of merits of early diagnosis. Even when more verbal explanations are offered to parents, it is Midorikawa's impression that those explanations are well understood. Takano suggested that the consent form be reformed.

Takano then questioned about the school-based screening again, after raising the same issue at the November 30, 2017 Thyroid Examination Assessment Subcommittee (see below). He said he understood the school-based screening was conducted between classes (he was previously told it was conducted during classes) which might make students feel that they are forced to take it. Midorikawa explained that screening is conduced during classes. The entire class goes to a room where the screening is conducted, but only those with signed consent forms are screened. The participation rate of the school-based screening exceeds 90% as very few express their intention not to participate ahead of time. Midorikawa states that the school-based screening appears to discourage advanced opt-out.

Kazuo Shimizu raised an interesting point when he revealed that he operated on a Fukushima resident from Koriyama City at his hospital and reported the case to FMU but the case does not seem to be reflected in the official count. The patient apparently participated in the first round screening, evacuated from Koriyama City, and never participated in subsequent screenings. The patient was diagnosed with thyroid cancer at another hospital, and Shimizu learned that the patient participated in the first round the night before he operated on the patient. An FMU official stated that a case would not be included in the official count unless the patient had participated in the second and third rounds.

Kanae Narui, a clinical psychologist, commented on one of the new efforts proposed for the fourth round screening regarding enrichment of psychological support. The proposal will initiate sharing information with facilities conducting the confirmatory examination and strengthen support offered to patients and families regarding worries about the TUE. Narui wanted to know just how the psychological support would be enriched. She went on to illustrate a case of a student she encountered as a school counselor. The student was apparently under clinical follow-up after the confirmatory examination. The student's condition was kept from the school or other students, and it was Narui's impression that the student was not well informed about her own condition. The student stated the only thing she was told by the doctor was that something serious would happen unless she took her medication. When Narui explained to the student that her condition was not as severe as she understood, she felt so relieved that she broke into a big smile and began shaking so badly that she could barely walk. Narui's point was that keeping patient information confidential needs to be balanced with protecting patients' mental/psychological/emotional health. Patients should not feel so isolated and helpless at school. Sufficient information should be shared with school so that patients can receive good support at school.  

Because the rest of data released at this Oversight Committee was essentially similar to what was presented at the last Oversight Committee, the remainder of this post will cover selective information from the 8th Thyroid Examination Assessment Subcommittee, which was held on November 30, 2017.  

(Note: Information presented at the previous Thyroid Examination Evaluation Subcommittees has never been officially translated into English. Some unofficial translation  can be found here and here).

**********

Thyroid Examination Assessment Subcommittee members
For the new two-year term, the previously 9-member subcommittee was scaled down to 8 members, retaining only one returning member, Ryohei Katoh. Most notably, Kazuo Shimizu, a thyroid surgeon and the former subcommittee chair, was not included on the roster.

Member roster
Hirofumi Ami: Chair, Department of Surgery, Ohara General Hospital, Fukushima City, Fukushima Prefecture (long involved in treating thyroid cancer patients in Fukushima Prefecture; recommended by the Fukushima Hospital Association)
Kota Katanoda: Chief, Division of Cancer Statistics Integration, Center for Cancer Control and Information, National Cancer Center (recommended by the National Cancer Center for his thorough knowledge of cancer registry and cancer statistics)
Ryohei Katoh, M.D., Ph.D.: Professor, Department of Human Pathology, University of Yamanashi (recommended by the Japanese Society of Pathology for his thorough knowledge of thyroid pathology)
Gen Suzuki: Managing Director, IUHW Clinic, International University of Health and Welfare, Tochigi Prefecture (recommended by the Japanese Radiation Research Society for his long involvement with research on radiation effects)
Tomotaka Sobue: Professor, Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Osaka University Graduate School of Medicine (taking part in cancer research from an epidemiological viewpoint; recommended by the Japan Epidemiological Association)
Toru Takano: Instructor, Department of Metabolic Medicine, and Associate Professor, Department of Laboratory MedicineOsaka University Graduate School of Medicine. (long involved in research and clinical management of thyroid diseases; recommended by the Japan Thyroid Association)
Kanshi Minamitani: Clinical Professor, Department of Pediatrics, Teikyo University Medical Center, Chiba Prefecture (long involved in research and clinical management of pediatric thyroid diseases; recommended by the Japanese Society for Pediatric Endocrinology)
Akira Yoshida: Chair, Department of Gynecological Examination, Kanagawa Health Service Association; the former president, the Japanese Society of Thyroid Surgery (An endocrinology and thyroid surgery specialist and the first chair of the planning committee for the Japanese clinical guidelines for treatment of thyroid tumor; recommended by the Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery)

*****
As written previously, the new roster was a surprise because Kazuo Shimizu—the former subcommittee chair—and Fumiko Kasuga—who one might say acted as "conscience" of the subcommittee—were no longer on it. The Oversight Committee Chair, Hokuto Hoshi, sort of explained their absences that care was taken to avoid dual memberships on the Thyroid Examination Assessment Subcommittee and the Oversight Committee. However, this does not explain the fact that Toru Takano was indeed given a dual membership. Takano advocates fetal cell carcinogenesis as opposed to multistep carcinogenesis, claiming thyroid cancer already exists in childhood which "nicely" explains away a large number of thyroid cancer detected in Fukushima. Takano has called for scaling down Fukushima's TUE in the January 14, 2017 blog post. Takano's presence on both the Oversight Committee and the Thyroid Examination Assessment Subcommittee was recommended by the Japan Thyroid Association, and it is difficult to dismiss it as coincidence.

Gen Suzuki and Tomotaka Sobue have actively participated on various government committees related to health effects of radiation exposure, usually representing the interests of the government. As covered in the previous post, Suzuki is in charge of the government-funded research project on dose reconstruction, effectively reducing exposure doses from the Fukushima nuclear accident: estimated doses (external and internal) for a 1-year-old are now reduced to 7% to 69% of estimated doses in the UNSCEAR 2013 report. Sobue has so far tried to apply pros and cons of adult cancer screening to a unique situation in Fukushima where children were exposed to radiation without the protection of stable iodine tablets. Kota Katanoda, apparently replaced Shoichiro Tsugane, with whom he worked on a document submitted to the Subcommittee in November 2014.

Selection of the subcommittee chair 

When Gen Suzuki was appointed the subcommittee chair by prefectural officials due to lack of nomination from the subcommittee members, a collective gasp was felt in the SNS timeline—across the computer screen—among those who consider him a "master under-estimator" of radiation effects. Added to the absence of Shimizu and Kasuga, installment of Suzuki as chair appeared to effectively set the tone of the subcommittee: a charade. Actual discussions that ensued were productive in some sense and the subcommittee members might be participating earnestly, but Suzuki tactfully and systematically—in his usual manner—dismissed key issues such as the sex ratio and the regional differences in detection rates suggestive of dose-response.

While effectively facilitating discussions amongst the subcommittee members and engaging appropriate officials from Fukushima Medical University (FMU), Suzuki took liberty to utilize his position as chair to infuse the discussions with his own opinions. His nonchalant manner is deceiving, and viewers are almost tricked into accepting Suzuki's opinion as a consensus of the subcommittee. His contemptuous manner sharply contrasts modesty of the former chair Shimizu who refrained from thrusting his own opinions as he presided over the subcommittee, despite his past experience of operating on thyroid cancer patients in Chernobyl.

Adjusted detection rates

Table 11 from the final report of the second round (below) shows cancer detection rates (per 100,000) from four administrative regions (evacuation region, Nakadori, Hamadori, and Aizu) as 49.2, 25.5, 19.6 and 15.5, respectively. 

This sharply differs from the similar table (shown below) from the first round (FY2016 revised version) that shows cancer detection rates (per 100, 000) from the same four regions as 33.5, 38.4, 43.0 and 35.6, respectively. These numbers formed the basis of FMU's claim that there was no regional difference, i.e., dose-response in the first round.



According to Handout 2-3 (in Japanese only) distributed at the 8th Thyroid Examination Assessment Subcommittee, detection rates by region are influenced by factors such as age, sex, interval between screenings, participation rates in the primary and confirmatory examinations by age group. Akira Ohtsuru, head of the Thyroid Ultrasound Examination (TUE), pointed out that the mean age at exposure decreases to the right of the table whereas the mean age at diagnosis increases, and that the proportion of female participants varies by region. It was claimed that further analyses be conducted by making adjustments by such confounding factors, and FMU appeared to be looking to the Thyroid Examination Assessment Subcommittee for guidance on which factors to adjust for. 

As an example, an adjustment was made for the interval between the first and the second round screenings. The table below is an unofficial English translation of the adjusted table: an increase in number is denoted in red, and a decrease in blue. Including only those who participated in both the first and the second round actually increased  detection rates per 100,000 in 3 regions other than Aizu, but the main point made by FMU appears to be the fact that adjusting the detection rates by the interval between the first and second round screenings decreased those numbers from 53.1 (per 100,000) to 21.4 (per 100,000 per year) for the evacuation region, 27.7 to 13.4 for Nakadori, 21.5 to 9.9 for Hamadori, and 14.4 to 7.7 for Aizu.


Essentially, this adjustment proved informative by converting prevalence (per 100,000) to incidence (per 100,000 per year) among those who participated in both the first and the second rounds. As seen on the bottom row of the adjusted table, there is a clear regional difference. There were multiple questions—from members of the subcommittee and the press—about what to make of the regional difference. FMU's answer was that further adjustments were needed to draw any conclusion, and Suzuki stated that the results are likely biased and an adjustment by tumor diameter was due because the average tumor diameter differed between FY2014 (9.4 ± 3.1 mm) and FY2015 (15.8 ± 8.0 mm) (see Table 6 here). 

Handout on sex ratio of thyroid cancer 

Handout 2-2 (in Japanese only) released by FMU contains existing information gathered by FMU regarding the sex ratio of thyroid cancer. This handout consists of 3 parts: 1) sex ratios from the national cancer registry data from 1975 to 2013; 2) past studies on radiation effects, namely the atomic bomb survivor study (Preston et al. 2007), the Belarus study (Zablotska et al. 2011), and the Ukraine study (Tronko et al. 2017); and 3) autopsy studies (JAMA 209, 1969Cancer 36, 1975; and Cancer 65, 1990).

This handout was apparently prepared to present scientific evidence to back up the repeated statement by Akira Ohtsuru—excerpted below from this post—in an attempt to justify the smaller-than-expected female to male ratio (F:M) consistently observed in the TUE (1.97:1 in the first round and 1.22:1 in the second round).

The female to male ratio in Japan's cancer registry data, including all ages, is around 3:1, but it used to be bigger at 4:1 or 6:1 in the 1980's and earlier. In Fukushima, the TUE was conducted in asymptomatic youth around puberty--a different condition than the cancer registry. Yet even in the cancer registry, the female to male ratio tends to be close to 1:1 up to the puberty. Autopsy data of occult thyroid cancer in individuals who died of causes other than thyroid cancer show the female to male ratio of 1:1 or smaller (more males) in adults. This fact indicates that thyroid cancer screening would yield the female to male ratio close to 1:1 even in adults. Thus, it is scientifically expected that thyroid cancer screening in general leads to a smaller female to male ratio.

The cancer registry data from 1975 to 2013 shows the female to male (F:M) ratios of 0.7:1 in ages 5-9, 1.8:1 in ages 10-14, and 4.3:1 in ages 15-19. Considering that 99 of 116 thyroid cancer cases in the first round and 56 of 71 cases in the second round were ages 15 or older at diagnosis, the cancer registry data as presented in the handout merely supports the fact that the female to male ratio observed is indeed smaller than expected.

The handout then refers to three radiation studies which reported "no statistically significant difference by sex in thyroid cancer risks due to radiation." These are the studies of childhood exposure with cancer mostly diagnosed as adults. But this is missing the point: what has been of concern is the actual sex ratio of Fukushima's thyroid cancer cases being diagnosed in youths. In the second round, the FY2015 cohort from supposedly less contaminated municipalities than the FY2014 cohort (see the map on page 3 here) even shows a "flipped" ratio with male dominance (F:M=1:1.38). This flipped ratio raised a question about whether these individuals were potentially exposed to higher radiation doses than estimated from, for instance, more athletic activities outdoors leading to higher inhalation doses.

Needless to say, the autopsy data on usually including older individuals does not offer good evidence for the sex ratio in children and adolescents. 

As asserted by a freelance journalist Mako Oshidori during the press conference, a study such as this shows smaller female to male ratios in radiation-induced thyroid cancer in children. When Oshidori questioned if the sex ratio issue would be pursued beyond the handout in the future, Suzuki kept stating that the sex ratio was "no good indicator" of radiation effects.

A long debated issue that has raised repeated questions and calls for investigation from Oshidori and the former chair Shimizu, the sex ratio issue appears to have been effectively dismissed by Suzuki's arbitrary claim. 

Outdated clinical information 

Also revealed at the 8th Thyroid Examination Assessment Subcommittee was a handout titled "Regarding surgically indicated cases." Disappointingly, this handout comprised outdated information in a collection of power point slides from the September 2016 international symposium that were partly revised and translated into Japanese. The original slides are discussed in detail in this post. The only useful piece of information was a verbal confirmation by Susumu Yokoya, Director of the Thyroid and Endocrine Center at Fukushima Global Medical Science Center, Fukushima Medical University, that 2 of 3 poorly-differentiated thyroid cancer cases from the first round were indeed reclassified as the solid variant of papillary thyroid cancer in accordance with the latest 7th edition of diagnostic guidelines.

Other issues

Other issues that were brought up during the subcommittee meeting include the status of the national and regional cancer registry and the school-based screening.

Sobue explained that the national cancer registry, implemented in 2016, might not be ready for use due to data collection taking time, but that the regional cancer registry by prefecture that was in place prior to 2016 should have data that can be used to gather information on thyroid cancer cases which have been diagnosed and clinically followed outside FMU as well as the FHMS-TUE system. Fukushima Prefecture began the regional cancer registry in 2008. Seiji Yasumura, head of the Public Health Department at FMU stated that FMU has been going over the regional cancer registry data, following trends of various cancers before and after the 2011 nuclear disaster. FMU apparently intends to conduct analyses on not just thyroid cancer but all cancers.

Regarding the school-based screening, a question was raised by Takano as to whether students are examined during school hours which might make the screening appear mandatory. According to Sanae Midorikawa from FMU, the school-based screening is conducted on weekdays year round. Children from elementary school through high school undergo the TUE usually during the first 2 class periods in the morning. (Just like school-based health examinations routinely conducted in Japan). 









Comments

  1. Thank you again for your painstaking work. Can you possibly update us on the number of metastases among the thyroid cancer cases? It is a critical issue, and I understand the government is not readily giving out such data.

    ReplyDelete
  2. Thank you for your comment, Nick.

    If you are referring to the number of regional and distant metastases, please refer to Slides 3 and 6 in this post, http://fukushimavoice-eng2.blogspot.com/2016/10/clinicopathological-findings-of.html.
    Keep in mind that this information only covers 125 surgical cases.

    Slide 3 shows there have been 3 cases of lung metastasis.
    Slide 6 shows 97 (77.6%) of 125 cases had regional lymph node metastasis.

    It's not so much the government but Fukushima Medical University that is not giving out or updating clinical data.

    ReplyDelete

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