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The Authors Respond

Takahashi, Hideto; Ohira, Tetsuya; Ohtsuru, Akira; Shimura, Hiroki; Tsuboi, Kumiko; Yasumura, Seiji; Tanigawa, Koichi; Midorikawa, Sanae; Suzuki, Satoru

doi: 10.1097/EDE.0000000000000568

Radiation Medical Science Center for the Fukushima Health Management Survey Fukushima Medical University Fukushima, Japan

The authors report no conflicts of interest.

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To the Editor:

Regarding our letter1 pointing out methodologic problems in Professor Tsuda et al.’s paper,2 Professor Hamaoka3 recently claimed the reasonability of the latent period of 4 years based on his speculation that the nodules’ growth rate was fast. His grounds were (1) the fastest growth rate would be 17.3 mm/7 months (29.1 mm/year) because he detected four malignancies with a maximum tumor size of 17.3 mm in the minimum possible interval (7 months) between the first- and second-round examinations; (2) the misclassification of diagnosis would be small; and (3) the decrease in mean tumor size might indicate an effect of radiation, because the radiation-exposure level of the sequence of the survey sites was high to low although the mean tumor size increased with age.

However, regarding Professor Hamaoka’s first comment, there are two essential problems in his reasoning. First, essentially, the detection ability depends on the ultrasound characteristics, as well as the size of tumor. The detection of thyroid malignancy is based on the image of, microcalcifications, central vascularity, irregular margins, incomplete halo, the shape (height > width), and the documented enlargement of a nodule. In other words, a malignancy could not be detected if the margins show an incomplete halo, isoechoic, and hypovascular image even if the size of the tumor is >5 mm, for example. It is incorrect to assume that the size of an undetected tumor is 0 mm.

Second, it is not feasible to estimate the growth rate using insufficient information (i.e., with only one-point data, and/or a rough estimation of the time interval). Professor Hamaoka found the largest and fastest possible values in our report for the supervising committee, for which individual data were not included and the date of the first screening was not described. He estimated the fastest growth rate in a situation in which neither the date nor the size of the nodules of individuals in the first-round survey was known.

Regarding Professor Hamaoka’s second comment, our results were checked by multiple experts on thyroid diseases to confirm that the results were as certain as possible. However, on the other hand, the results were also dependent on the performance of the equipment.

For Professor Hamaoka’s third comment, he concluded the existence of a radiation effect because he apparently thought that the decrease of the mean tumor size (despite the increase in the mean age with time) was caused by the sequence of survey areas, with the exposure level from high to low in an ecologic study scheme. As is well known among epidemiology researchers, the results of ecologic studies should be considered carefully to exclude artifacts.

In addition, Professor Hamaoka did not consider the variation of the mean tumor size in light of the small sample size of the malignant cases in his speculation. Generally, representativeness does not always equate to “mean” in a small sample, because it is easily affected if extreme elements are entered in the sample. The case sizes 4 and 8 in the 17th and 18th reports were only single-digit sizes, unlike the case sizes 15, 25, 39, and 51 in the 19th report and further reports. If we question the representativeness of the mean in the single-digit cases (17th and 18th reports) and limit the consideration of the representativeness of the 19th and later reports, both the tumor sizes and the ages in the table increase, which directly contradicts Professor Hamaoka’s logic. A more careful consideration of the data is necessary.

Hideto Takahashi

Tetsuya Ohira

Akira Ohtsuru

Hiroki Shimura

Kumiko Tsuboi

Seiji Yasumura

Koichi Tanigawa

Sanae Midorikawa

Satoru Suzuki

Radiation Medical Science Center for the Fukushima Health Management Survey

Fukushima Medical University

Fukushima, Japan

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1. Takahashi H, Ohira T, Yasumura S, et al. Re: Thyroid cancer among young people in Fukushima. Epidemiology. 2016;27:e21.
2. Tsuda T, Tokinobu A, Yamamoto E, Suzuki E. Thyroid cancer detection by ultrasound among residents ages 18 years and younger in Fukushima, Japan: 2011 to 2014. Epidemiology. 2016;27:316–322.
3. Hamaoka Y. Re: Re: Thyroid cancer among young people in Fukushima. Epidemiology 2016;28:e4–e5.
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