In recent years, with the deterioration of living environment, the widespread use of high-frequency ultrasound in clinical practice and the increasing awareness of people’s health, the global detection rate of thyroid nodules has been increasing year by year. In the general population, the detection rate of thyroid nodules by palpation is 3%-7%, while the detection rate by high-resolution ultrasound is as high as 20%-76%, but only 5%-15% of them are malignant tumors [1]. Therefore, except for a few benign nodules and most malignant nodules that require surgery, most thyroid nodules require only non-surgical treatment [2]. Although guidelines for the diagnosis and treatment of thyroid nodules and thyroid cancer have been established in China, Europe and the United States, the management of thyroid nodules in China is currently very confusing, both in terms of surgical indications and surgical modalities, with the irregularities in the management of benign thyroid nodules being particularly prominent. The main reasons for this are, first, the serious lack of thyroid surgeons in China, with most general surgeons performing thyroid surgery, which is common in secondary and lower hospitals; second, the serious lack of training for thyroid specialists and the absence of an admission system; and third, academic differences in the understanding of the disease. In this paper, we discuss the indications for surgical treatment of thyroid nodules and the choice of surgical modality in the light of the literature and our own experience as follows.
1 Surgical indications
a. Indications for surgery of benign thyroid nodules
The indications for surgery of benign thyroid nodules are clearly described in our textbooks, monographs and guidelines, and are summarized as follows. Absolute indications: (1) the presence of local pressure symptoms clearly associated with the nodule; (2) follicular adenoma [confirmed by fine needle aspiration cytology (FNA)]; (3) toxic nodular goiter or Graves’ disease combined with nodule; (4) functionally autonomous adenoma; (5) retrosternal goiter; (6) malignant nodule or high clinical suspicion of malignancy; (7) progressive nodule growth with (7) progressive nodule growth with high risk factors for thyroid cancer and a strong desire for surgery. Relative indications: (1) maximum nodule diameter >4 cm; (2) psychological disorder due to appearance or severe anxiety, which affects normal life, and the patient strongly requests surgery [3]; (3) strategic surgery.
b. Indications for surgery of malignant thyroid nodules
In principle, surgery is appropriate for all malignant thyroid nodules. Differentiated thyroid cancer (DTC) with distant metastasis is not a contraindication to surgery. For medullary thyroid cancer (MTC) with distant metastases, surgery should be performed if the metastases can be surgically removed. It should be noted that surgery is not recommended for undifferentiated carcinoma (anaplastic thyroid cancer (ATC)) that breaks through the thyroid peritoneum and cannot be completely removed locally or has distant metastases.
Papillary thyroid microcarcinoma (PTMC) is one of the major concerns in the field, and many people think that the current surgery for PTMC is overtreatment [4]. Although the incidence of PTMC found at autopsy differs greatly from that of clinical PTC, there are no definite indicators to determine which PTMC will progress. Although the incidence of PTMC found at autopsy is very different from that of clinical PTC, there are no definite indicators to determine which PTMC will progress and which will be “dormant”; autopsy is only a “cross-section” and does not reflect the dynamic changes of PTMC; is the biological behavior of PTMC more than 10 years ago the same as that of PTMC today? PTC has the property of dedifferentiation, especially the possibility of dedifferentiation increases with the prolongation of tumor duration and the increase of patient’s age. The incidence of lymph node metastasis in cN0 stage PTMC is 20%-66%, and even higher in some cases, according to domestic and international reports [5-7]. Even for cN0 stage PTMC <5 mm, the incidence of cervical lymph node metastasis is as high as 19%-66% [5, 8-9]. Therefore, it is prudent to say that surgery for PTMC is overtreatment in our severe medical care environment.
If lymph node metastasis or infiltration of the thyroid peritoneum and surrounding tissues occurs, it is far from the imagined PTMC, and once it is dedifferentiated into hypodifferentiated or undifferentiated thyroid cancer, it will quickly endanger the patient’s life. Once dedifferentiated into hypofractionated or undifferentiated thyroid cancer, it will quickly endanger the patient’s life. Therefore, we should look at PTMC rationally and objectively, and we should divide PTMC into high-risk and low-risk groups for separate treatment. High risk group: (1) poor prognosis subtypes (hypercellular, columnar cell, diffuse sclerosis and solid/islet type); (2) cancer foci >5 mm in diameter; (3) progressive growth of cancer foci; (4) cancer foci breaking through or near the thyroid peritoneum, especially in the posterior superior thyroid division; (5) with or highly suspicious of cervical lymph node metastasis; (6) >45 years old; (7) BRAT or TETER positive; (8) with thyroid cancer ; (8) high risk factors for thyroid cancer. Low-risk group: (1) classic PTMC; (2) cancer foci <5 mm in diameter; (3) cancer foci located in the middle of the thyroid gland (not close to the thyroid peritoneum); (4) no growth of cancer foci under long-term observation; (5) no lymph node metastasis; (6) <45 years old; (7) negative BRAT or TETER; (8) no high-risk factors for thyroid cancer. For PTMC in the high-risk group, surgery should be performed at the same time as PTC. In the low-risk group, surgery is not definitive, but should be based on the patient's wishes, the availability of medical resources and dynamic observation. If the patient requests for aesthetic reasons, surgical complications and fluke (rather than doctor's recommendation), dynamic observation is perfectly acceptable; if medical resources are tight, surgery for intermediate to advanced thyroid cancer should be prioritized while PTMC is under observation; if progressive growth of cancer foci or lymph node metastasis is found during observation or the patient insists on surgery, surgery should be performed.
Surgical methods and indications
Thyroid surgery includes thyroidectomy and cervical lymph node dissection. Currently, authoritative international textbooks and guidelines point out that there are only three standardized thyroidectomy procedures, namely thyroid lobectomy (+isthmus) (lobectomy, LT) and total thyroidectomy/near total throidecomy (TT/NTT) [3, 10- 11]. 11], while in China, both thyroidectomy and cervical lymph node dissection are currently chaotic. In addition to the above-mentioned procedures, thyroidectomy is not standardized, such as en bloc, subtotal (subtotal) thyroidectomy, lobectomy + contralateral subtotal thyroidectomy, lobectomy + contralateral en bloc, bilateral subtotal thyroidectomy, and bilateral en bloc. Some scholars in China consider lobectomy for benign thyroid nodules to be overtreatment, especially TT/NTT, which is absolutely intolerable, but the author believes that the minimum surgical procedure for the thyroid should be lobectomy, which is in no way a pander to foreigners. This is because: (1) if the indication for surgery is met for a single nodule (>4 cm), there is not much “normal” thyroid tissue on the affected side; (2) due to changes in the spectrum of thyroid disease, most thyroid nodules are or are combined with nodular goiter, and because of the legal requirement and the implementation of universal salt iodization for 20 years, non-iodine-deficient goiter has become mainstream. It is characterized by ineffective iodine supplementation and TSH suppression therapy and high recurrence rate after total non-thyroidectomy; (3) thyroid function can be almost replaced by drugs; (4) the incidence of surgical complications after recurrent nodules is much higher than that of the initial surgery [12-14]; (5) with the improvement of surgical techniques and continuous improvement of surgical equipment, the safety of the initial surgery (including TT/NTT) is high. Therefore, if LT is the minimum procedure, a case of benign thyroid disease that meets the surgical indications should be completely resolved in one (TT/NTT) or at most two (LT) surgeries, which is beneficial both in terms of health economics and in terms of reducing patient suffering and effectively reducing medical disputes or saving medical resources. I do not agree with the principle of surgery for benign thyroid nodules in our guidelines, i.e., “complete removal of thyroid nodules while preserving as much normal thyroid tissue as possible”, which is difficult to consider and unnecessary. In the case of a nodular goiter, the lesion is diffuse and involves the entire thyroid organ, so where is the normal tissue? The so-called “normal tissue” is only that no bilateral or multiple nodules have formed yet. For the preoperative diagnosis of “benign follicular adenoma” on one side, in fact, the postoperative diagnosis is mostly a nodular goiter, and if only a major or subtotal thyroid excision or mass excision is performed, there is a greater possibility of recurrence of nodules after surgery, increasing the risk of reoperation. If only a major (subtotal) thyroidectomy or mass resection is performed, the postoperative pathological diagnosis of follicular adenocarcinoma will require reoperation. Therefore, treating a “benign thyroid nodule” with a surgical approach less than LT is not only ineffective but also harmful for most patients, which is truly overtreatment.
2.1 Surgical approach to benign thyroid nodules
Surgical treatment of benign thyroid nodules consists only of thyroidectomy. LT is indicated for nodules located in one lobe (either adenoma or nodular goiter). thyroiditis (HT), where the patient requires simultaneous cure of HT and full understanding of the surgical complications.
2.2 Surgical approach to malignant thyroid nodules
Surgical treatment of malignant thyroid nodules includes thyroidectomy and cervical lymph node dissection.
2.2.1 Thyroidectomy
(1) The absolute indications for LT are: (1) single PTMC; (2) non-invasive subtype; (3) no infiltration of the thyroid peritoneum and surrounding tissues; (4) no local or distant metastasis; (5) no nodule in the contralateral thyroid; (6) no risk factors for thyroid cancer. The relative indications are: (1) cancer foci <4 cm in diameter but all other conditions of the absolute indications must be met; (2) microinvasive follicular thyroid cancer; (3) malignant lymphoma with good prognosis involving one side. (2) The absolute indications for TT/NTT are: (i) all DTC (including ectopic PTC with lymph node metastasis) except for LT mentioned above; (ii) almost all MTC (including ectopic); (iii) malignant lymphoma involving both lobes of the thyroid; (iv) combined with positive TERT gene mutation [15]; and (v) cancer foci located in the isthmus [16]. The relative indications are: (1) PTMC compatible with LT, but with or without HT and BRAF positivity, where the patient strongly requests more thorough surgery; (2) ectopic PTC without significant local infiltration and lymph node metastasis, where the patient strongly requests more thorough surgery; (3) FTC without extensive infiltration; and (4) malignant lymphoma of the thyroid involving one lobe. 2.2.2 Cervical lymph node dissection The lymph node dissection is divided into central lymph node dissection (CLND) and lateral lymph node dissection (LLND). Since FTC rarely metastasizes through cervical lymph nodes, there is a consensus in China and abroad that cervical lymph node dissection is not routinely performed for FTC and therapeutic cervical lymph node dissection is performed for thyroid cancer. However, there is a big difference in the management of lymph nodes in the central region of PTC in China and abroad. Domestic guidelines are more aggressive than those in Europe and the United States in terms of lymph node dissection in the central region, advocating routine lymph node dissection in the central region of the affected side, based on the fact that there are many reports in China that stage cN0 PTC has a higher incidence of lymph node metastasis and increases the risk of reoperation [7, 17], and I agree with this view. In my opinion, the absolute indications for bilateral CLND are: (1) T3 and T4 stage PTC; (2) highly invasive subtype; (3) bilateral cancer foci; (4) anterior laryngeal lymph node metastases; (5) >3 anterior tracheal lymph node metastases; (6) mediastinal lymph node metastases; (7) ipsilateral and/or contralateral lymph node metastases in the lateral cervical region; (8) bilateral central lymph node metastases diagnosed preoperatively or intraoperatively; (9) MTC; (10) TER (9) MTC; (10) positive TERT gene mutation [15]. The relative indications are (1) pre-tracheal lymph node metastasis, (2) cancer foci >1 cm in diameter, (3) BRAF positivity, (4) with distant metastases, and (5) strong patient demand for more thorough surgery. The absolute indication for lymph node dissection in the lateral neck area is the presence of lymph node metastasis in the lateral area. The relative indications are: (1) CLN metastasis or metastases >3 [18-19]; (2) cancer foci located in the upper pole and infiltrating the peritoneum [20].
3 Precautions
3.1 Selection of surgical approach
Adequate consideration should be given to standardization, safety and thoroughness. It is important to properly assess whether the operator’s own skills are competent for the standardized surgical approach and the risks and benefits of the surgery to the patient.
3.2 Strategic surgery
Strategic surgery should meet all of the following criteria: (1) relatively advanced age of the patient (>70 years); (2) comorbid chronic disease or relatively poor health; (3) multiple bilateral thyroid nodules, nodules >2 cm in maximum diameter or more than 2 degrees of bilateral thyroid; (4) no absolute contraindication to surgery; and (5) a strong desire for surgery based on a full understanding of the risks of surgery. The purpose of strategic surgery is to treat the lesion while it is still physically tolerable, in anticipation or fear of future changes in the nodule (local compression, development of the nodule into the mediastinum, or malignant transformation) when surgery is necessary due to medical reasons. Therefore, strategic surgery must be elective rather than limited surgery, and the patient must be carefully selected for surgery at a time when he or she is in relatively good physical condition, so that the risk of surgery is kept to a minimum. Therefore, for nodular goiter, if one side of the nodule is large and the other side is small (<10 mm), and the patient is concerned about the risk of surgery and strongly requests surgery, only lobectomy + isthmus on the side of the large nodule can be considered. This is because it is difficult to compress the trachea and esophagus on one side of the nodule.
3.3 Change in surgical approach or treatment modality
Changes in the surgical approach (lumpectomy or open surgery) or treatment modality (surgery, ablation, etc.) cannot change the indication for surgery or the surgical modality of the disease itself. In the early stages of new technologies, it is easy to make the mistake of replacing the indications for the disease itself and the standardized surgical approach with their so-called indications at the time. This was the case when lumpectomy thyroid surgery was first performed, but as it has evolved it is now being standardized (although not yet enough). Radiofrequency ablation for thyroid disease (nodules) is currently being performed, and because of its “non-invasive”, “truly minimally invasive”, and “fast recovery” “advantages”, it has gained many uninformed patients. The advantages” have won the favor of many uninformed patients, so it is developing rapidly in China and is being carried out “in full swing”. In fact, it treats many microscopic nodules of nodular goiter that do not require surgical treatment and PTMC that should be treated surgically or under observation, as these small nodules can recur after ablation. For PTMC, as mentioned above, the incidence of lymph node metastasis is high, and radiofrequency ablation only “treats” the primary foci, but ignores the metastatic cervical lymph nodes, which is not in accordance with the principles of oncologic treatment and increases the risk of subsequent surgical treatment [21]. In the author’s opinion, the best indications should be patients who have indications for surgery but cannot tolerate surgical treatment; after standardized cervical lymph node dissection, those with localized single or few lymph node metastases in the lateral cervical region [22].
In conclusion, for the diagnosis and treatment of thyroid nodules, clinicians must grasp the essence of the disease, apply the method of evidence-based medicine, stand in the patient’s perspective to correctly select the treatment method, strictly grasp the indications for surgery, standardize the surgical approach, and effectively use medical resources so that patients can truly benefit.