According to the results of the SEER database of the National Cancer Center of the United States, the incidence of both PTC < 1.0 cm and thyroid cancers 1.0–4.0 cm increased from 1980 to 2010, especially among highly educated groups(Alwithenani R et al.2019). Statistical data from the United States and South Korea show an increase in the incidence of thyroid cancer(Jingqiang Z et al.2016). Further, the results of surveys in Denmark, Finland, Israel, Japan, Spain, and Switzerland also demonstrate increases in thyroid cancer incidence, which is mainly PTC, with significant sex differences in the relative extent of the rise. This phenomenon cannot be fully explained by improvements in the sensitivity of testing methods, nor increased awareness among doctors and patients of screening(McDow AD et al.2019). Scholars from other countries have actively researched the risk factors associated with thyroid cancer, and found that autoimmune disorders, ionizing radiation, iodine intake, estrogen, environmental endocrine disruptors, negative psychosocial factors, and heredity may contribute to increases in thyroid cancer incidence(Huang T.2016,Dettmer MS et al.2019).
From 1984 to 2010, the incidence of differentiated thyroid carcinoma in the United States increased, with tumors of diameter ≤ 0.5 rising by 5.09%, while those of 0.5–0.99 cm in diameter increased by 8.45%, average diameter tumors (1.0–1.99 cm) by 3.42%, and large tumors ≥ 2.0 cm by 2.96%. These data suggest that most PTMCs will develop into tumors with diameter > 1 cm, but over varying periods of time. In particular, the possibility of dedifferentiation increases with prolonged tumor-bearing time and patient age(Dong F et al.2016,Li N et al.2013). It is generally recognized that, over time, the degree of malignancy and dedifferentiation of PTC tumors increases; however, when the level of malignancy changes, what causes changes in the tumor genome has not been fully or satisfactorily explained(Ahn HS et al.2014).
As available therapies for thyroid cancer are effective, there is little drive for early diagnosis and surgical treatment, which is counterintuitive and violates the basic principles of pursuing early detection, with the aim of early diagnosis and treatment of malignant tumors. In addition, the psychological pressure on patients of the uncertainty of following up while waiting for the diagnosis of malignancies to change before taking action, is undoubtedly considerable. Cancer does not have specific Chinese characteristics. In 2014, the Memorial Sloan-Kettering Cancer Center in the United States launched a “wait-and-see” program for patients with thyroid cancer(Pellegriti G et al.2013). Patients diagnosed with microcarcinoma of the thyroid could choose not to have it removed for a while, but rather to have it checked regularly; however, the vast majority of patients with PTMC did not hesitate to choose surgical treatment. Further, some patients who chose the observation option eventually asked for surgery, and doctors feared being sued for missing the optimal treatment time. Early treatment is not only effective, it is also associated with reduced risk and fewer complications(Choi WR et al.2019). Once lymphatic metastases, or distant lung and bone metastases, occur, the cost of medical care often increases considerably, which can even endanger the life of the patient.
According to our clinical and pathological data, as the diameter of the mass increases, the proportion of lymph node metastasis increases, from 44.68–77.53%. The proportion of micropapillary carcinoma ≤ 1 was 47.10%, and the rate of lymph node metastasis was 46.92%, which did not mean that the risk of microcarcinoma was low. Lymph node metastasis is also an indicator of malignancy. With the passage of time, the tumor size, the proportion and the number of lymph node metastasis will further increase, leading to the disease progression, the difficulty and risk of surgery, and the risk of recurrence and metastasis gradually increased. When the mass rises above 2 cm, the lymph node metastasis ratio rises to 77.53%, indicating that thyroid papillary carcinoma is progressing, the malignant degree and the disdifferentiation increases, although there is no way to evaluate and predict it.
Compared with the National Comprehensive Cancer Network (NCCN) and the American Thyroid Association (ATA) guidelines for the diagnosis and treatment of differentiated thyroid cancer, Chinese guidelines for patients undergoing thyroid surgery to remove all indications do not include any specific age-based requirements. The NCCN guidelines recommend that patients with PTC aged < 15 or > 45 years should undergo total thyroidectomy. While the ATA guidelines recommend total thyroidectomy for all patients with PTC with tumor diameters > 1 cm, unlike Chinese guidelines. Further, total thyroidectomy is also recommended for all patients with thyroid nodules in the contralateral gland and for patients with PTC with tumor diameters 1.0–1.5 cm, aged > 45 years. In addition, Chinese guidelines indicate that all patients with differentiated thyroid cancer should receive central region lymph node dissection, as this provides effective protection from recurrent laryngeal nerve and parathyroid gland involvement. The NCCN and ATA guidelines recommend no dissection of the central lymph node without involvement, except for abnormal palpation or clear metastasis diagnosed by puncture biopsy. Total thyroidectomy can have advantages for patients, including: 1) single treatment of multiple lesions, particularly bilateral cancer lesions; 2) facilitates postoperative monitoring of tumor recurrence and metastasis; 3) beneficial for postoperative I131 treatment; 4) reduces the recurrence rate of tumors and the probability of reoperation, which avoids increasing the incidence of serious complications due to reoperation; 5) accurate assessment of postoperative staging and risk stratification of patients; 6) prevention of recurrence of thyroid cancer from development into poorly differentiated thyroid cancer.
The bilateral tumor metastasis rate is 65.27%, the recurrent cancer metastasis rate is 72.21%, the tumor breakthrough membrane metastasis rate is 67.08%, and the metastasis rate is higher than the average metastasis rate. The analysis is statistically significant. When combined with high risk factors, such as bilateral lesions, multiple lesions and tumor rupture membranes, the lymph node metastasis rate will increase significantly(Ruggiero R et al.2019). It is recommended that we conduct more comprehensive preoperative clinical assessments to facilitate us to obtain more comprehensive patient disease information. Thyroidectomy and central lymph node dissection may be more reasonable, thorough, and safe procedures for clinicians to consider.At present, some preoperative examinations used in clinical practice cannot reveal suspected cancer lesions in the contralateral glandular lobe. Total thyroidectomy completely removes any such lesions and glands with potential lesions, thereby avoiding the risk of undetected cancer lesions, reducing the recurrence rate, and improving patient prognosis(Zheng X et al.2019,Chen Y et al.2014). In patients with PTC, thyroid globulin levels can be assessed postoperatively to determine whether there is residual tumor or recurrence. For patients with all thyroid tissue removed, there should be no thyroid globulin present in the body; hence, if thyroid globulin is detected in the serum, it generally indicates that some lesion remains or has relapsed, which is also an important prognostic indicator.
Total thyroidectomy increases the incidence of recurrent laryngeal nerve and parathyroid gland injury, and any complications will have a serious impact on the mental health and quality of life of patients postoperatively. Therefore, surgeons must receive strict guidance and training to reduce or avoid surgical complications. Doctors undergoing training who may conduct lateral + isthmus + contralateral subtotal thyroidectomy should ensure that very small amounts of non-tumor thyroid tissue is left on the contralateral glandular lobe only to avoid recurrent disease of the laryngeal nerve and around the parathyroid gland. Simultaneously, in combination with the application of nano-carbon and nerve monitoring during surgery, to avoid bilateral recurrent laryngeal nerve or parathyroid gland damage, residual thyroid tissue can be dealt with using radioactive I131 therapy following surgery.
The cervical lymph node metastasis rate was also positively correlated with the tumor diameter. In all tumors, 49.32% of patients had cervical regional metastasis, of which 69.40% were T1c and above tumor patients. Of the patients with T1c, 76.97% had central lymph node metastasis, of which 65.50% had cervical lymph node metastasis at the same time. Although only 6.78% of patients had jump metastasis, T1c patients accounted for 30.67%, and T1c and above patients accounted for 78.55%. It is suggested that when we treat T1c patients, we should fully evaluate the preoperative evaluation. As far as possible, the original lesion and metastatic lesion should be cleaned together during the initial operation to avoid reoperation. The surgical method can consider cervical lymph node clearance.Thyroid cancer has a good prognosis and long survival. Therefore, we should try our best to protect the function of the tumor while improving the quality of life. It is recommended to keep the sternocleidomastoid, the internal jugular vein and the accessory nerve, and try to keep the cervical plexus neurocutaneous branch. At present, the modified radical neck dissection (MRND) is the most commonly used procedure for both thorough surgery and preservation of the body function. Lymph node metastasis of thyroid papillary carcinoma is common to the ipsilateral side, and it is transferred along the lymphatic drainage path. The lymphatic metastasis is usually first to the paratracheal lymph node, and then drained to the jugular vein lymph node (levelⅡ-Ⅳ) and the posterior cervical lymph nodes (levelⅤ), or down the trachea to the upper mediastinum. The most common site in the 6th district, followed by the neck Ⅲ,Ⅳ,Ⅱ,Ⅴlevel, and the lymph node metastasis of papillary thyroid carcinoma is mainly metastasis.
At present, surgical treatment of cervical lymph node metastasis of papillary thyroid carcinoma is recommended for the treatment of cervical lymph node dissection. Prophylactic dissection is not recommended. The occult metastasis of cervical lymph nodes does not reduce the survival rate of patients, so prophylactic cervical lymph node dissection is not recommended in patients with cN0.
For patients with cN1, lymph node metastasis is an independent risk factor for the survival of patients with > 45-year-old papillary thyroid carcinoma(Hodax JK et al.2019,Morris LG et al.2016). levelⅡ-Ⅳis the main area of thyroid lymphatic drainage, and levelⅢ,Ⅳis the most common lymph node metastasis. Domestic experts agree that levelⅡa,Ⅲ,Ⅳ,Ⅴb is the standard range of cervical lymph node dissection(Yan L et al.2019). It is recommended that patients with cervical lymph node metastasis confirmed by preoperative evaluation or intraoperative frozen pathological examination receive cervical lymph node dissection, but preventive cervical lymph node dissection is not recommended(Kaliszewski K et al.2019).Reoperation will increase the complications of surgery, and it will lead to recurrence of disease after thyroid cancer surgery, and even affect survival. At the same time, as the number of operations increases, the degree of tumor dedifferentiation will increase, and the difficulty and risk of surgery will increase. It is impossible to completely remove the surgery again, so that the patient who can be cured can lose the opportunity to cure(Eanaola NF et al.2002,Gimm O et al.2002).
Thyroidectomy can lead to complications, primarily parathyroid injury (3–5%) and recurrent laryngeal nerve injury (1–5%). It is accepted that patients who undergo total or partial thyroidectomy must use thyroxine replacement, or even suppression, therapy for the rest of their lives(Haugen BR et al.2016,Polistena A et al.2017). Data from our hospital related to hypocalcemia, hoarseness, and sensory dysfunction of the shoulder after thyroid surgery currently undergoing statistical analysis and will be presented in future reports. The pathological characteristics of PTC mean that analysis of the influence of surgical approach on survival and prognosis will be a long-term project, and we will continue to analyze follow-up data for these patients. Only a small number of patients were found to have BRAF gene mutations in our study, as there is no comprehensive promotion of genetic testing in our hospital, hence not all patients were evaluated.
According to the CTA, endocrine inhibition therapy is essential, regardless of surgical approach. Hence, long-term endocrine suppression therapy was required for all patients with PTC, including those who underwent lobectomy + central lymph node dissection. Radioactive I131 therapy is also an important part of comprehensive treatment of thyroid cancer(Yang T et al.2019,Conzo G et al.2014). All patients with lymph node metastasis, whether in the central or cervical region, were treated with I131 administered at doses of 80–130 mCi, according to risk stratification assessment, with additional rounds of treatment if needed, based on the results of follow-up observation.
The method of treatment of thyroid cancer is influenced not only by surgeons, but also by nuclear medicine, imaging, and other clinicians, and even by health insurance companies. Careful preoperative staging and risk stratification of thyroid carcinoma results in better outcomes for patients with thyroid carcinoma. This is because such an approach facilitates more accurate surgery, and individualized treatment, as well as allowing collection of data on national trends in this disease. The authors consider that surgeons should fully embrace the principles of tumor prevention and treatment, and be mindful that thyroid cancer is a malignant tumor; hence, the scope of treatment should not be reduced unnecessarily, to avoid the need for reoperation several years later. Therefore, it is necessary to assess patients, according to current scientific knowledge, to make a comprehensive judgment of the safety of surgery, the willingness of the patient, and medical resources available, together with the national considerations and regional factors in China, and the degree of acceptance of the operation and possible secondary surgery by the patient. Together, this information can inform implementation of rational diagnosis and treatment plans.