Thyroid nodules are an extremely common disease and have a high incidence in the general population. First, we compared the demographic characteristics of the experimental group and the control group. We saw that there was no significant statistical difference in age and gender between the experimental group 1 and the control group 1. However, there were statistical differences in age and gender between the experimental group 2 and the control group 2. We saw that compared with the experimental group 2, the average age in the control group 2 was younger(46.76vs.53.21 p=0.037) and there were more male patients(19/42vs.0/15 p=0.016). This is consistent with the fact that men with thyroid cancer are usually younger.
A systematic review including 14 studies at a moderate risk of bias found the odds ratio for thyroid cancer to be lower in patients with a multinodular goiter than in those with single nodules (20). Moreover, thyroid nodules are usually bilateral nodules. Because of the anatomical characteristics of the thyroid, we regarded the bilateral thyroid gland as two independent units to evaluate whether bilateral thyroid nodules interact with each other in terms of malignant risk. Our study showed that there was no significant difference in malignant risk between the experimental group 1 and the control group 1, and the experimental group 2 and the control group 2 (20%vs. 35%, p=0.724, 63.16% vs. 76.32%, p=0.297, respectively).
Because the types of thyroid carcinoma in the a-side of the experimental group and the control group were all papillary thyroid cancer, including micropapillary thyroid carcinoma, we saw no significant difference in the proportion of micropapillary carcinoma between the two subgroups (p=0.200,p=0.620, respectively). Moreover, we also noticed that it was extremely high, especially in the experimental group 2 and the control group 2, reaching 83.33% and 89.66%, respectively. We saw that in the b-side of the experimental group, except for 1 medullary thyroid carcinoma in the experimental group 1 and 1 Anaplastic thyroid carcinoma in the experimental group 2, all other cases were thyroid papillary carcinoma.
Although thyroid nodules are prevalent in the general population, more than 90% of thyroid nodules have no clinical significance, because most of them are benign or even malignant thyroid nodules, especially those smaller than 1 cm, which usually show indolent or non-invasive behavior. Therefore, not all thyroid nodules require surgery(18.21-26). For benign thyroid nodules only need regular ultrasound examination, Surgery may be considered for growing solid nodules that are benign on repeat cytology if they are large (>4 cm), causing compressive or structural symptoms, or based upon clinical concern (21.27). There are four pathological types of thyroid carcinoma, and their treatment and prognosis are different based on the pathological types of thyroid cancer. Papillary and follicular thyroid cancers have a favorable prognosis, with mortality rates of 1% to 2% at 20 years for Papillary thyroid cancer (PTC)(28) and 10% to 20% at 20 years for follicular thyroid cancer(29). However, patients with medullary thyroid carcinoma have a mortality rate of 25% to 50% at 10 years, and most patients with poorly differentiated and Anaplastic thyroid cancer die within one year after diagnosis (5-year mortality, 90%)(29.30). Papillary thyroid cancer is generally perceived as low-risk thyroid cancer(29) and is not associated with well-recognized predictors of mortality(31.32). With the popularity of high-resolution thyroid ultrasound, the incidence of thyroid nodules has gradually increased(18.29), which is attributed to the increase in papillary thyroid cancer or micropapillary thyroid cancer, and more than 50% of them are labeled as low-risk thyroid cancer, It may not have any symptoms or affect the life span of the patient (33-35). For micropapillary thyroid cancer, we can consider active surveillance regularly(1.36.37). Generally speaking, the scope of surgery for thyroid cancer was determined by the initial clinical characteristics of thyroid nodules, the experience and preference of the surgeon, and the preference of the patient. The American Thyroid Association (ATA) guidelines recommended thyroid lobectomy for low-risk thyroid nodules, and bilateral thyroidectomy (including total thyroidectomy and subtotal thyroidectomy) or thyroid lobectomy for intermediate-risk thyroid nodules(1). many studies have demonstrated that overall survival and disease-free survival are not negatively impacted by lobectomy compared with thyroidectomy (38-44).
The increase in the incidence of thyroid nodules can be seen worldwide(45). In the US, a retrospective population-based evaluation of patients with thyroid cancer found that the incidence increased from 3.6/100000 in 1973 to 8.7/100000 in 2002, a 2.4-fold increase(46); Similarly, we saw that in South Korea between 1993 and 2011, thyroid cancer increased 15 times (47.48). However, the mortality rate of thyroid cancer remained stable or even declined(46-51). At the same time, we have also noticed that the number of thyroid surgeries increased dramatically. Two studies have shown a 2-4 times increase in the number of thyroid surgeries(49.50). Another study showed that between 2006 and 2011, the number of thyroid surgeries in the United States increased from 99,613 to 130,216 per year, with an average annual growth rate of 12% (52). This evidence also indirectly indicated that more aggressive treatment strategies were adopted for thyroid nodules in clinical practice. Because all the b-side thyroid glands were thyroid cancers in the experimental group, unilateral lobectomy was performed in all the b-side thyroid glands in the experimental group. In the pathological types of b-side thyroid nodules in the experimental group 1 and 2, the proportion of papillary thyroid carcinoma was 98.46% and 94.74%, respectively. Moreover, micropapillary thyroid carcinoma reached 47.69% and 36.84% respectively. We have known that papillary thyroid cancer, especially Papillary thyroid microcarcinoma, is an indolent tumor, most of which may not have an impact on the lifespan of patients. In our study, we found that almost all the b-side thyroid nodules in the experimental group were thyroid papillary carcinoma, and the a-side thyroid nodules in the experimental group were benign, but there were 46.15% and 85.71% lobectomy in the a-side of the experimental group 1 and 2, respectively. The a-side thyroid nodules were malignant, we saw a higher proportion, up to 84.62% and 96.55% in the experimental group 1 and 2, respectively. There were not many cases in our study, however, it reflected the current status of more aggressive treatment strategies for thyroid nodules to some extent. This was reflected not only in the substantial increase in the number of thyroid nodule surgeries but also in more thorough surgical procedures, which tend to subtotal thyroidectomy or total thyroidectomy. Many studies have confirmed that more resources were used for the diagnosis, treatment, and follow-up of those thyroid cancers, which may not affect the life of the patient or even have no symptoms(33.34). A large observational study based on the SEER database found that after controlling tumor size, for those patients with low-risk tumors, aggressive surgical treatment has no benefit in survival(41). Several studies have indirectly demonstrated the current status of overtreatment of thyroid nodules(20.33.34.50.52.53).
When it comes to thyroid surgery, postoperative complications are an inevitable issue. Common complications after thyroid surgery include dyspnea, nerve damage (including superior laryngeal nerve injury, and recurrent laryngeal nerve injury), hypoparathyroidism(54.55). One study showed that the risk of total thyroidectomy included recurrent laryngeal nerve injury (2.5%, rarely on both sides), hypocalcemia (8.1%), and bleeding (56). Does more aggressive surgery for thyroid nodules increase the risk of postoperative complications? A study showed that different thyroid surgical procedures and the incidence of postoperative hypocalcemia were not statistically significant(57). However, Another study showed that there was a significant difference in postoperative complications between total thyroidectomy and partial thyroidectomy. The incidence of permanent nerve injury was 7.0% vs 1.3% (p < 0.005), temporary nerve injury 8.6% vs 2.2% (p < 0.005), and postoperative transient hypoparathyroidism 18.0%vs 2.1% (p < 0.005) (38). moreover, Thyroid lobectomy can provide histological diagnosis and tumor removal with a lower risk of complications(18). Therefore, the current more aggressive treatment strategy for thyroid nodules may not be a good choice for patients and society.
we can take a more conservative treatment for the low-to medium-risk thyroid gland, which can retain enough thyroid tissue to meet normal physiological needs without affecting the prognosis of the patient while reducing the possibility of postoperative complications. Moreover, at present, patients with low-to medium-risk thyroid nodules are the most common patients in clinical practice, accounting for the vast majority of all patients. Nowadays, the increasing burden of health care in various countries, especially in the face of coronavirus this year, makes their medical funds tighter. For thyroid nodules, we should do more research on the treatment and benefits (including patients and society) to reduce the waste of medical resources and the risk of complications after thyroid surgery.
Although preliminary conclusions are drawn based on our trial data, there are still many limitations to be improved. Our study is a retrospective cohort study and has its limitations. There may be selective errors in the experimental group and the control group cases. But this also reflected the current status of surgical treatment of thyroid nodules. The study is a single-center case study with insufficient evidence and needs to be conducted in a multi-center and larger population. Our study almost only studied the effect of papillary thyroid carcinoma on the malignant risk of contralateral thyroid nodules, and other types of thyroid pathology can also be considered in the future. Our study did not conduct prospective studies on postoperative complications of thyroid surgery. We hope that there will be more studies on the correlation between different thyroid surgical procedures and complications in the future. Although many studies have indirectly confirmed that the current more aggressive thyroid treatment strategy leads to a large waste of medical resources, direct evidence are still lacking. Therefore, the treatment strategy of thyroid nodules still needs further research, so that it can find a balance point in terms of treatment effect, risk of postoperative complications, and economy, so that clinically significant thyroid nodules can be treated timely and appropriately, and It will not increase the burden on patients, including physical, mental, and economic aspects, and cause waste of medical resources.
Finally, the issue of fine-needle aspiration biopsy(FNAB) of thyroid nodules is specifically explained. Many thyroid treatment guidelines recommend FNAB before surgery, but FNAB has a high proportion of insufficient biopsy specimens and indeterminate pathological results. For those patients with insufficient biopsy specimens or indeterminate pathological results, FNAB may need to be performed again. However, some patients may not have clear pathological results after repeated FNAB. In our study, surgeons advised all patients with thyroid nodules to perform FNAB, but fully informed them of the pros and cons, and almost all patients refused to perform FNAB. Because of the improvement of surgical techniques, anesthesia, and nursing care, the length of hospital stay has been shortened, which is another reason.