Chinese research challenges international views!

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Professor Li Wangen: In recent years, due to the suspicion that it is related to the over-diagnosis of thyroid cancer, there has been controversy about whether or not thyroid ultrasound screening should be performed.
However, it needs to be pointed out that a balance should also be found between "over-diagnosis" and "missed diagnosis".

Compared with the negative attitude of foreign guidelines, according to our research, "not recommend or oppose" seems to be a more correct attitude towards ultrasound screening for thyroid nodules.

Expert introduction Professor Li Wangen, chief physician, doctoral supervisor, director of the Endocrinology Department of the Second Affiliated Hospital of Guangzhou Medical University, and deputy director of the Diabetes Branch of the Guangdong Medical Association.
Thyroid cancer-a balance between overdiagnosis and missed diagnosis is needed.
Thyroid nodules are usually The first sign of thyroid cancer, the primary goal of treatment is to distinguish between malignant and benign lesions.

 In clinical practice, thyroid ultrasonography is more and more used as the preferred inspection method because it is non-invasive and economical.

Studies have reported that: thyroid cancer screening has led to a significant increase in the global diagnosis rate of the disease, but the mortality rate has not changed.

The American Association of Clinical Endocrinologists (AACE) does not recommend ultrasound as a screening method for the general population or palpation of patients with normal thyroid and low clinical risk of thyroid disease.

Similarly, the US Preventive Services Task Force recommends against screening for thyroid cancer in asymptomatic adults.

Behind this is the concern about "over-diagnosis".

 "Ultrasound screening is not recommended" will lead to overcorrection-missed diagnosis? Considering that AACE’s recommendations for “ultrasound screening” content are only Level 4 evidence and Level C recommendation, this means that it is only based on expert experience and there is no evidence to prove its risks or benefits.

Some scholars believe that it is necessary to assess the risk of malignancy for nodules that can only be detected by ultrasound; and for patients whose nodules are not found on palpation, doctors should make their own judgments on whether ultrasound examinations should be performed for the purpose of preventing missed diagnosis.

However, so far, no research has directly compared whether there is a significant difference in the risk of malignant nodules between "discovered by ultrasound" and "discovered by palpation.
"
 How to find a balance between overdiagnosis and missed diagnosis? Obviously more evidence is needed.

 To this end, Professor Li Wangen’s research team from the Endocrinology Department of the Second Affiliated Hospital of Guangzhou Medical University conducted a retrospective study aimed at investigating the "incidence of malignant nodules detected by ultrasound" in a large cohort study.
The first author of the study is Chen Zhi, and the study was published in the journal BMC Endocrine Disorders.

 Study description Researchers performed a retrospective analysis of 2957 patients who underwent thyroid ultrasound assessment and fine needle aspiration (FNA) between January 2013 and December 2019.

Patients were divided into two groups according to different nodule detection methods: ➤ Ultrasound discovery group: included participants whose nodules were found by ultrasound examination; ➤ Palpation discovery group: included those discovered by the patient himself or by the doctor during the physical examination Participants of nodules.

The Bethesda system was used for cytological examination and analysis [The six diagnostic categories include: (I) poor or unsatisfactory materials; (II) benign; (III) atypical or unexplained follicular lesions; (IV) follicular Tumor; (V) suspiciously malignant; (VI) malignant].

For nodules that are suspected to be follicular tumors or other malignant tumors by cytology, it is recommended that patients undergo surgery and histopathological examinations.

Researchers conducted a detailed comparative analysis of the "pure cystic ratio", "size", "TI-RADS score", and "proportion of non-small cancers" of the two groups of nodules.

  What is the difference between the nodules found through different ways? (Ultrasound vs.
Palpation) The study found that the nodules found by ultrasound (n=1212) and the nodules found by palpation (n=1745) are significantly different in many aspects, such as the ratio of pure cysticity is significantly higher Low, significantly smaller, TI-RADS score significantly higher, other differences are shown in the table below.

 Table 1 Nodules found by ultrasound vs.
nodules found by palpation.
In addition, among the nodules that were confirmed to be malignant by histopathology, the proportion of microcarcinomas was significantly higher in the nodules found by ultrasound (35.
3% vs.
16.
2%, p=0.
004) (Figure 2).

 Figure 1 Proportion of microcarcinomas in the two groups Compared with palpation, nodules found by ultrasound have a higher risk of malignancy! This study shows that nodules found by ultrasound have a higher risk of malignancy than nodules found by palpation.

For this result, the researchers propose two explanations: First, only 10% of the nodules found on ultrasound are pure cystic (probably benign).

In contrast, pure cystic nodules found on palpation accounted for nearly 40%.

Secondly, although the size of the nodules found on ultrasound is small, the TI-RADS score is higher than the nodules found on palpation.

 Three challenges to mainstream views 1.
AACE does not recommend ultrasound screening of thyroid nodules.
Recommendations on the timing of FNA are based on the size of the nodules.
The American Thyroid Association (ATA) also gives similar recommendations.

However, in this study, the average diameter of the nodules found by ultrasound was 1.
75cm, which is already in the recommended range of "opportunity for FNA".

 2.
AACE opposes ultrasound screening on the grounds that the global prevalence of thyroid cancer has increased significantly, but the mortality rate has not increased.

However, a newly published study found that the incidence-based thyroid cancer mortality rate in the United States increased from 0.
40 per 100,000 person-years in 1994-1997 to 0.
46 per 100,000 person-years in 2010-2013.

In China, the mortality rate of thyroid cancer increased from 0.
30/100,000 in 2005 to 0.
35/100,000 in 2015.  3.
If according to current guidelines, only a small percentage of patients with microcancers can receive reasonable active monitoring, a considerable number of them may be missed.

In addition, in this study, the proportion of non-small cancers in the "nodules found by ultrasound" was as high as two-thirds, and for these nodules with a diameter> 1 cm, it is generally believed that the benefits of surgery outweigh the risks.

 Professor Li Wangen: Regarding ultrasound screening for thyroid nodules, “not recommended nor opposed” seems to be a more correct attitude.
As for the clinical significance of this study, Professor Li Wangen accepted an interview with Yimaitong: Professor Li Wangen does not know, one It was a shock.

Originally thought that the nodules found by ultrasound would be mostly benign, this study gave the opposite conclusion—mostly malignant.

Not only that, among the malignant nodules found by ultrasound, nearly 2/3 are non-micro cancers (> 1cm); at the same time, only non-micro cancers that need attention, the detection rate of nodules found by ultrasound (7.
2 %) is also more than twice the amount found by palpation (3.
3%).

Many guidelines do not recommend or even object to "screening of thyroid nodules in the general population", mainly based on the fact that although the detection rate of thyroid nodules has increased, the mortality rate has not changed.

In fact, the materials cited in these views are relatively old.

The latest data quoted in our article shows that the mortality rate of thyroid cancer has increased in recent years, regardless of the data from China or the United States.

Opposing ultrasound screening of thyroid nodules, it sounds reasonable at first that "there is an objection to over-diagnosis", but after a little reasoning, it is found to be inconsistent with existing accepted opinions.

Because the nodules found by ultrasound screening are nothing more than the nodules found by palpation, and it is recognized that the benign and malignant nodules have nothing to do with the size.

If the nodules found by palpation are worth paying attention to, why can the nodules found by ultrasound be ignored? The correct approach seems to be that ultrasound screening of thyroid nodules is neither recommended nor opposed, and the focus is on individualized and precise treatment after the nodules are found.

In this way, it is possible to achieve a balance between social benefits and medical procedures without excessive or missed diagnosis.

 Reference: Chen, Z.
, Mosha, SS, Zhang, T.
et al.
Incidence of microcarcinoma and non-microcarcinoma in ultrasound-found thyroid nodules.
BMC Endocr Disord 21,38 (2021).
https://doi.
org /10.
1186/s12902-021-00700-1.