INDICATIVE SUMMARY: Surgical treatment of thyroid cancer should be standardized and individualized. This article reviews the conceptual localization, preoperative evaluation, lymph node metastasis status and treatment, clinical significance and outlook of cN0 stage papillary thyroid cancer.
Background: papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for approximately 80% of all thyroid cancers [1] characterized by its high degree of differentiation, slow tumor growth, and high rate of lymph node metastasis. There is no dispute that combined radical treatment is performed for confirmed positive cervical lymph node (cN+) cases, but there are controversies both at home and abroad on whether to perform selective neck debridement for clinical cervical lymph node negative (cN0) cases, as well as the scope and timing of debridement. In this paper, we summarize and analyze by reviewing relevant domestic and foreign literature to explore the reasonable surgical treatment for cNo stage papillary thyroid cancer. Zhang Mei, Department of Two Gland Surgery, Shandong Qianfo Mountain Hospital
1. Cervical lymph node partitioning and TNM staging of thyroid cancer
There are two types of cervical lymph node partitioning: anatomical partitioning and clinical partitioning (Table 1). According to anatomy, cervical lymph nodes can be divided into 11 groups; in 1991, the American Academy 0f Otolaryngology-Head and Neek Surgery Foundation, Inc. divided cervical lymph nodes into 6 subdivisions for the convenience of clinical application [2], namely: Zone I is the subchin and submaxillary lymph node group, zones II, III and IV are the deep upper, middle and lower cervical lymph node groups, respectively; zone V is the posterior cervical lymph node group Zone VI is the paratracheal and pre-tracheal lymph node group; Zone VII is the former upper mediastinal lymph node group; Zones I-V are the lateral cervical zone, and Zones VI and VII are the central zone. Later, when the American Joint Committee on Cancer (AJCC) published the TNM staging, it added a seventh division, namely the upper mediastinal lymph nodes (Table 1). This recommendation for clinical subdivision of cervical lymph nodes in the United States has been agreed upon by head and neck oncologists and has been widely used by the academic community for more than 10 years.
Anatomic subdivision
Clinical subdivisions
Occipital lymph nodes
Unsegmented
Retroauricular lymph nodes
Undifferentiated
Parotid lymph nodes
Undivided
Facial lymph nodes
Not subdivided
Submandibular lymph nodes
Zone I(A,B)
Inferior chin lymph node
Zone I(A,B)
Sublingual lymph nodes
Undivided
Posterior pharyngeal lymph node unzoned
Undivided
Lateral cervical lymph nodes
Internal jugular vein lymph node superior group
Zone II(A,B)
Middle group of internal jugular vein lymph nodes
Zone III
Internal jugular vein lymph node inferior group
Zone IV
Paraspinal nerve lymph nodes
Zone V(A,B)
Transverse cervical lymph nodes (supraclavicular lymph nodes)
Zone V (A,B)
Anterior cervical lymph nodes (i.e. laryngeal, peritracheal, and esophageal lymph nodes; or central cervical lymph nodes)
Zone VI
Upper mediastinal lymph nodes
Zone VII
2002 AJCC thyroid cancer staging scheme [3].
1. Papillary or follicular carcinoma (under 45 years old) Stage I: any T any NM0; Stage II: any T any NM1.
2. papillary or follicular carcinoma (45 years of age or older). Stage I: T1NOM0; Stage II: T2NOMO; Stage III: T3N0M0; T1N1aM0; T2N1aM0; T3N1aM0; Stage IVA: T4aNOM0; T4aN1aMO; T1N1bM0; T2N1bMO; T4aN1bMO; Stage IVB: T4b any NM0; Stage IVC: any T any NM1.
2. Assessment of cN0 status before and during surgery
It is important to correctly determine the cNo status. We refer to the clinical evaluation criteria of cervical lymph nodes proposed by Kowalski [4] et al. and combine the following conditions as the criteria for diagnosing cN0 papillary thyroid carcinoma: (1) no enlarged lymph nodes are palpable on clinical examination or the maximum diameter of enlarged lymph nodes is <2 cm, and the texture is soft; (2) no enlarged lymph nodes are seen on imaging examination or the maximum diameter of enlarged lymph nodes is <1 cm, or the maximum diameter is 1-2 cm. However, there is no central liquefaction necrosis, peripheral enhancement and disappearance of paranodal fatty spaces; (3) palpation prevails in the absence of imaging data. In addition to physical examination, ultrasound and CT (especially enhanced CT) are important to understand and assess the nature of the thyroid nodule and the surrounding lymph nodes before surgery and as follow-up information after surgery. In addition, after intraoperative clarification of papillary thyroid carcinoma, the deep sternocleidomastoid muscle and lymph nodes in the lateral II, III and IV regions of the carotid artery should be further palpated and carefully explored for enlargement to clarify the cNo status again. First, cN0 and pN0 are different concepts. Likewise, cN+ and pN+ are not different. No author would disagree that cN+ requires cervical clearance of the affected side. However, there are differences in diagnostic cN outcomes due to the varying experience of surgeons. Therefore, it is particularly important to properly assess cN status preoperatively.
3. Biological characteristics of papillary thyroid cancer:
Papillary thyroid carcinoma is a differentiated thyroid carcinoma (DTC), which originates from the follicular cells of the thyroid gland. Radioactive iodine therapy is effective in treating primary and metastatic foci. The effectiveness of radioiodine scanning or treatment depends on the amount of thyroid tissue remaining in situ. According to the German Association of Endocrine Surgeons:If one side of the thyroid gland is left intact, it makes most of the radioiodine treatment fail [5]. Studies have shown that the success rate of radioactive iodine treatment can be 94% with a residual thyroid tissue of <2g. On the contrary, the success rate is only 68% for most of the retained thyroid gland. Radioiodine therapy prolongs the survival of patients and reduces the recurrence rate [6,7]. The use of small doses of radioiodine after total and near-total thyroidectomy can achieve therapeutic goals and also helps to monitor thyroid cancer recurrence and metastasis using radioiodine scans and TG. Papillary thyroid carcinoma, whether unilobar or bilobar, is 40-50% multifocal, especially in the presence of microscopic lesions in the contralateral lobe of the affected lobe. Papillary thyroid carcinoma is also degenerative and differentiated. Some DTC may later degenerate into poorly differentiated thyroid cancer. Some of the thyroid gland remaining after surgery may also degenerate into undifferentiated carcinoma. Serum thyrotropin TSH concentration is positively correlated with the growth and postoperative recurrence of papillary and follicular thyroid carcinoma. For the very few early cases of undifferentiated carcinoma, surgery is the main treatment, while the combination of palliative surgery + radiation therapy + chemotherapy is appropriate for patients with advanced stages.
4. cN0 stage papillary thyroid cancer cervical lymph node metastasis and treatment
4.1 Lymph nodes in the neck
Stage cN0 papillary thyroid cancer is only a clinical concept, and there are still a considerable number of patients with lymph node metastasis confirmed by postoperative pathology. As to whether cN0 stage papillary thyroid cancer has lymph node metastasis in the neck, reports vary. Xu Zhenzang [8] reported that 8% of cN0 stage papillary thyroid cancer without pre-lymph node dissection eventually developed into lymph node metastasis; McGregor [9] reported 7.0%-15.0%; Ge Minghua [10] reported 15.3%. Lu Zeng-Hong [11] showed that 19 cases of 78 cNO stage papillary thyroid carcinoma eventually developed cervical lymph node metastasis, 24.4% (19/78), and Sun Xiang-Dong et al [12] showed that there is a certain regularity of cervical lymph node metastasis in papillary thyroid carcinoma: most of them metastasize to the sentinel lymph nodes first, and then to other sites, and he considered the peritracheal lymph nodes (i.e., lymph nodes in area VI) as one of the sentinel lymph nodes. Roy et al. suggested that papillary thyroid cancer would first metastasize to the paraglottic lymph nodes regardless of its primary lesion. Zhu Yongxue et al [13] showed that the metastatic pattern of papillary thyroid cancer is usually considered to be primary focus, lymph nodes in area VI, lymph nodes in the lateral cervical area, and distant metastasis. Ouyang Wen et al [14] studied 186 cases of cN0 stage papillary thyroid carcinoma and showed that the incidence of lymph node metastasis in the lateral cervical regions was significantly different between those with positive lymph nodes in the paraglottic nerve and those with negative lymph node metastasis in the paraglottic nerve.
The rate of cervical lymph node metastasis in papillary thyroid cancer is high and there is a clear tendency of regional metastasis, with 60.9% of patients reported to have cervical lymph node metastasis at the first treatment [15]. Currently, many scholars have introduced the concept of sentinel lymph node research into thyroid cancer research and studied the lymph node metastasis pathway of papillary thyroid cancer [16-17], and the results showed that the distribution of lymph node metastasis of papillary thyroid cancer is regular, most commonly in the peritracheal lymph nodes, and ipsilateral Ⅲ and Ⅳ regional lymph nodes, and then metastasized to other regional lymph nodes, so it is believed that Ⅲ, Ⅳ and VI regional lymph nodes can be used as Therefore, it is believed that the lymph nodes in areas III, IV and VI can be used as the anterior lymph nodes of papillary thyroid cancer.
4.2 Treatment
Through a case analysis of 94 cases of cN0 stage papillary thyroid cancer, Zhao Ming [18] et al. concluded that for cases with a clear preoperative diagnosis, radical treatment of the primary site + central zone dissection is a better surgical option for the treatment of cN0 stage papillary thyroid cancer. It is believed that the rationale and advantages of selective central zone lymph node dissection are: (1) although the lymph node metastasis rate of papillary thyroid cancer is high, it does not affect the survival rate of patients. Yin Yulin et al [19] reported that the 5 and 10-year survival rate of 166 cases of cN0 papillary thyroid cancer without cervical lymph node dissection was more than 90%, and the lymph node metastasis rate was only 13.9%; the 5 and 10-year survival rate of 96 cases operated in our group was 100% and 92%. It is consistent with Li Shuling’s selective neck clearance surgery. 94.7% 10-year survival rate. (2) VI area is the primary site of lymph node metastasis, and the simultaneous clearance with the primary foci may have blocked its metastasis to the lateral cervical area, so the postoperative neck metastasis rate is not high. (3) The primary foci are eradicated and the VI area is cleared at one time, which results in short operation time and low impact on appearance and function, and improves the survival quality of patients. (4) The anatomical level is clear during the first treatment, and serious complications rarely occur for skilled surgeons. In contrast, postoperative recurrence is difficult to be completely removed by surgery again, which is an important factor of death. (5) Even if lateral cervical lymph node metastasis occurs later, it is not necessary to remove the VI area, which will not affect the completeness of surgery.
In conclusion, the use of radical treatment of the primary site + selective central cervical clearance in the treatment of cN0 papillary thyroid cancer is a surgical option that can both avoid over-medication and prevent under-medication. cN0 stage papillary thyroid cancer has a high rate of lymph node metastasis in region VI, and the probability of cervical lymph node metastasis in those with positive lymph nodes in region VI also tends to increase during follow-up. We suggest that the primary site can be resected and the lymph node dissection in region VI can be done together at the first surgery. The surgery can be performed in the same field, which will not increase the trauma of the surgery for experienced surgeons and will help to reduce the occurrence of lateral cervical lymph node metastases, and even if metastases appear in the lateral cervical region later, there is no need to clear region VI, which is beneficial to reduce the occurrence of complications.
5.Cervical lymph node management of cN0 stage papillary thyroid cancer
At present, there are different opinions on the management of cervical lymph nodes in stage cN0 papillary thyroid carcinoma at home and abroad. (1) The decision is based on the degree of primary cancer invasion. Li Shuling [20] advocated selective cervical lymph node dissection when the primary cancer invades the tumor envelope. The reasons are: (1) high misdiagnosis rate in clinical examination; (2) once the neck recurrence progresses to advanced stage, it is difficult to cure, and the chance of cure is lost after distant metastasis occurs. ③The 10-year tumor-free survival rate of selective neck clearance is much higher than that of therapeutic neck clearance. ④Selective neck clearance is mostly a functional surgery with little damage and little impact on function and appearance. (2) The decision is based on intraoperative exploration. According to Chen Fujin et al [21], intraoperative lymph nodes in area VI should be routinely explored, and if suspicious lymph nodes are found, intraoperative freezing examination should be performed, and simultaneous cervical lymph node dissection should be performed after pathological confirmation of lymph node metastasis, and cervical lymph node dissection should not be performed if pathology is negative. Selective neck dissection is generally not advocated. Liu Wensheng et al [22] believed that even if metastases have been found in area VI, the lateral cervical area can still be closely followed if there are no suspicious metastatic lymph nodes on exploration. The reason is that according to their data and experience, the metastasis rate in region VI is similar to that in the lateral neck, and the recurrence rate is not high in patients who have not undergone elective neck clearance, and the clearance of region VI may affect the function of the parathyroid glands. While Zhu Yongxue et al [23] supported resection of the affected adenoid lobe plus zone VI clearance in patients with stage cN0, they did not support selective lateral cervical lymph node clearance in lateral cervical zones II, III, IV, and V. Many foreign scholars have analyzed the prognostic factors of papillary thyroid cancer through their different sources and established prognostic scoring systems, with more applications such as the MACIS scoring system proposed by Hay et al [24], which showed that the 20-year postoperative survival rates of the <6, 6-6.99, 7-7.99 and ≥8 subgroups were .99%, 89% , 56% and 24%, respectively. . Each patient was evaluated and selective neck clearance, i.e., individualized treatment, was advocated for patients in the high-risk group.
In the author’s opinion, many of the above arguments stem from the lack of accurate preoperative determination of cervical lymph node metastasis. In the past, we mainly relied on clinical palpation examination, which was influenced by many factors and had large errors. With the development of imaging technology, the preoperative localization of positive lymph nodes can be accurate to 2-3 mm, and the accuracy of neck ultrasound and CT examination for metastatic cancer in the neck has been reported to be over 90%. The author experiences that neck ultrasound has high sensitivity to thyroid tumor and lymph nodes in the neck, while the examination of peritracheal and upper mediastinum is somewhat limited, and neck CT can precisely compensate for this deficiency. We routinely perform ultrasound examination of the neck in all cases, and perform CT examination of the neck in high-risk cases, such as ultrasound examination suggesting malignancy, large tumor with hard and restricted movement, advanced age, and bilateral. In this way, a more accurate diagnosis can be made before surgery.
6.Impact of papillary thyroid cancer tumor foci on treatment
Papillary thyroid carcinoma accounts for 70-80% of thyroid cancer and is less malignant. It mainly metastasizes to the cervical lymph nodes, especially the central group of cervical lymph nodes. Generally, thyroid cancer with tumor diameter ≤1cm is called microscopic thyroid cancer. Most of these patients have a good prognosis, but a few patients have metastasis to the lateral cervical lymph nodes, and the metastasis rate is not related to the size of the primary tumor. For patients with lymph node enlargement in the sixth region of the neck, selective lymph node dissection of the central group is recommended. For patients without palpable lymph node enlargement, prophylactic dissection is not recommended and unilateral lobectomy or subtotal thyroidectomy is sufficient [25]. For papillary carcinoma with a tumor diameter of >1 cm, a lobectomy and isthmus of the affected thyroid gland with a contralateral subtotal thyroidectomy is recommended, along with preoperative examination of the cervical lymph nodes. If lymph node metastasis in the sixth region of the neck is found, the central group of lymph nodes should be dissected. If no lymph node metastasis was found in the sixth region of the neck, central group lymph node dissection was not necessary, and long-term close follow-up was performed [26]. In one study, the prognosis of patients with papillary carcinoma who underwent total thyroidectomy and postoperative radioiodine therapy was not significantly different from those who underwent local excision of enlarged lymph nodes in the neck and those who underwent more extensive cervical lymph node dissection. Therefore, it is believed that patients with papillary carcinoma with cervical lymph node metastasis do not necessarily need to undergo conventional total cervical lymph node dissection, but rather central group lymph node dissection or local excision of enlarged lymph nodes [27]. Bilateral thyroid cancer is rare in clinical practice, accounting for 6.0% to 8.8% of thyroid cancer [28]. Because of the dense lymphatic network and blood circulation between the right and left lobes of the thyroid gland and the isthmus, there is no obvious anatomical boundary, so it is impossible to identify whether both sides of bilateral thyroid cancer are the primary cancer or one side is the primary cancer and the other side is metastatic cancer. Bilateral papillary thyroid cancer has a high rate of cervical lymph node metastasis, especially in the central group of cervical lymph nodes. Some people advocate routine bilateral total thyroidectomy and bilateral cervical lymph node dissection, at least for the central group of cervical lymph nodes. However, it is generally believed that performing prophylactic bilateral cervical lymph node dissection after total thyroidectomy for bilateral thyroid cancer is more damaging to the patient and increases the chance of laryngeal nerve injury and the risk of causing hypoparathyroidism. Therefore, it is recommended that after total thyroidectomy, if there are suspicious lymph nodes, intraoperative rapid pathological examination should be performed, and bilateral central group cervical lymph node dissection should be performed if metastatic cancer is proved, while patients without suspicious lymph nodes can be closely observed after surgery and cervical lymph node dissection should be performed when lymph node metastasis appears, with the same reliable results [29].
7. Diagnosis of cN0 stage papillary thyroid cancer
In clinical practice, the specific scope and clinical effect of central group lymph node dissection for papillary thyroid cancer, although there are many controversies, are becoming more and more common with the development of surgical techniques, and the efficacy will become better. Clinicians should not simply judge the applicable criteria of central group lymph node dissection for papillary thyroid cancer, but should make a comprehensive consideration based on the pathological type of thyroid cancer, tumor stage, preoperative ultrasound, and patient’s specific situation, and formulate a reasonable individualized surgical plan in order to achieve better treatment results.
Thyroid cancer is one of the most common malignant tumors of the head and neck, and most of them (80%-90%) are of differentiated type with relatively low malignancy. Because differentiated thyroid cancer, especially those without cervical lymph node metastasis, has no specific manifestation in early stage and is difficult to diagnose by imaging, its clinical features are very similar to benign tumors, and there is no specific detection method, so some thyroid cancers are treated as benign tumors at the first surgery and need to be treated by surgery again.
The early stage papillary thyroid carcinoma is a low-grade malignant tumor with variable biological characteristics, insidious onset, slow growth, and atypical early clinical manifestations, and it is sometimes difficult to distinguish early thyroid carcinoma from nodular goiter and thyroid adenoma because: (1) it is difficult to distinguish early thyroid carcinoma from nodular goiter and thyroid adenoma; (2) thyroid cyst and papillary thyroid carcinoma are sometimes very similar in terms of physical signs; (3) ultrasound and CT are very similar to each other. (3) Ultrasound, CT, MRI and nuclear scan lack specificity in the diagnosis of thyroid cancer [30]; (4) A few benign thyroid tumors become malignant, and Koh KB reported that 4%-17% of surgically resected multinodular goiters were pathologically confirmed to be cancerous [31]; (5) Early follicular adenocarcinoma and a very small number of papillary carcinomas with envelope have no clinical manifestation other than a single nodule in the thyroid gland; (6) Pathology (6) It is sometimes difficult for pathologists to distinguish follicular carcinoma from follicular adenocarcinoma. Inadequate resection of thyroid cancer in the first surgery not only has the possibility of residual cancer tissue and lymph node metastasis, but also increases the chance of hematogenous dissemination and local implantation. Although intraoperative frozen section examination can identify benign or malignant thyroid nodules, there is a 5% false-negative misdiagnosis rate. In our group, 34 cases of misdiagnosis led to the wrong choice of surgical approach. Thyroid cancer has a high rate of residual cancer and recurrence due to improper first surgical treatment, and reoperation is necessary. Wang Jing-swan et al. reported that the residual cancer rate in thyroid and surrounding tissues in reoperation for thyroid cancer was as high as 75% (24/32). After reoperation, the majority of patients can still get good treatment results and survival rate is greatly improved, which indicates that reoperation for thyroid cancer is valuable.
Compared with the other three types of thyroid cancer, PTC has the best prognosis, and the literature reports that the 5- and 10-year survival rates of PTC are as high as 93-96% and 86-90% [32, 33].Theresia et al. conducted a multifactorial analysis of factors related to the prognosis of PTC and found that gender, age, primary tumor size, degree of invasion, and clinical stage have specific influential relationships on the prognosis of patients with PTC [ 34].
8. exploration of secondary surgery after local excision of papillary thyroid cancer.
Thyroid cancer accounts for 1% of systemic malignant tumors, of which more than 90% are differentiated thyroid cancer [35]. Surgery is the preferred treatment method, and the correct first treatment is especially important for prognosis. Improper choice of surgical method often requires another surgical treatment. At present, there is a lack of unified standard for the surgical approach taken for thyroid tumors in China, so there is a wide range of surgical approaches and the preoperative confirmation rate of thyroid tumors is very low. Especially in primary hospitals, there is no rapid frozen pathology condition, FNA is not widely carried out, and there is a lack of experienced pathology and cytology diagnosing physicians, so secondary surgery cases are common. It is necessary to discuss the ways and reasons of secondary thyroid surgery.
There are some controversies about the operation style of thyroid tumor and the scope of cervical lymph node dissection for thyroid cancer, and the lymph node drainage area of thyroid cancer is mainly in the II, III, IV, and VI regions of the neck [36]. clinical data from Andenson Cancer Center [37] showed that the lymph node metastasis of thyroid cancer was in VI (90%), IV (52%), and III (45%). There is disagreement on whether to choose modified neck debulking for thyroid cancer with cN+ in the neck. Zhang Lun [38] et al. reported 1173 cases of papillary thyroid carcinoma without preoperative palpable enlarged lymph nodes (cNo cases), and their metastasis rate was 65.8% after pathological examination by neck clearance. If the differentiated thyroid carcinoma with clinical cNo is follicular, there is no need for prophylactic neck clearance, and it does not affect the prognosis for these patients to undergo therapeutic neck clearance when cervical lymph node metastasis is clinically present. In contrast, some people believe that modified neck clearance is preferred for thyroid carcinoma 〉1 cm (cN0 cases) by clearing cervical lymph nodes in regions II, III, IV, and VI, preserving the sternocleidomastoid muscle, internal jugular vein, and paraneoplastic nerve [39].
Thyroid cancer, especially differentiated thyroid cancer, accounts for 80%-90% of cases and has a low malignant biological behavior with slow progression [39]. Due to the lack of typical symptoms and signs, it is difficult to differentiate it from some benign lesions, especially some solitary nodules and occult carcinomas and adenoma carcinoma. Preoperative ECT, ultrasound, CT and lymphangiography can suggest possible lesions, but are not very reliable. Preoperative misdiagnosis: Early thyroid cancer is clinically indistinguishable from thyroid adenoma and goiter, and there are no special signs other than thyroid mass. However, the use of this method in China is still limited due to the influence of operation technique and diagnostic physician’s level, as well as the false negativity of this method, and the diagnosis rate of follicular thyroid cancer is even lower, and the lack of specificity of ultrasound, CT, MRI, and nuclear medicine examination in the diagnosis of thyroid cancer has led to preoperative misdiagnosis of benign thyroid tumor, improper selection of surgical approach, small resection area, and residual cancer cells in some cases. Therefore, the extent of surgical resection for thyroid cancer has been controversial for many years. The diagnosis of malignancy after surgery often requires a second operation, and the improper scope of the first operation not only increases the patient’s pain and the difficulty and complications of the second operation, but also is one of the main factors affecting the patient’s prognosis.
We believe that for single thyroid nodules of unknown nature, preoperative fine needle aspiration cytology and intraoperative frozen section examination are very important to clarify the pathological nature. Even if the diagnosis is benign, thyroid lobectomy should be performed on the affected side. For differentiated thyroid adenocarcinoma without lymph node metastasis, resection of the affected lobe plus isthmus should be performed. For those who are suspected to have cancer residue due to insufficient resection in the first operation, the adherent band-like muscle should be removed, the residual lobe of thyroid and isthmus should be resected, and depending on the extent of the lesion, sub-total or total resection of the contralateral lobe should be performed. The surgery of thyroid tumor emphasizes the anatomy of the recurrent laryngeal nerve. If preoperative ultrasound, CT, or clinical examination indicates suspected or confirmed lymph node metastasis, functional or radical neck dissection should be performed according to the size, location, and shape of the lymph nodes, as well as the patient’s age, sex, and occupation, etc. In particular, the surgical oncology principle of “large block resection” should be followed to avoid treating lymph node removal as functional neck dissection [42]. The lymph node removal should not be considered as functional neck clearance [42].
Zone VI is a common area of lymphatic metastasis in thyroid cancer. For cN1 patients, lymphatic dissection including zone VI is routinely performed. However, there is still no clear guideline for cN0 patients to routinely clear zone VI. This study investigates the characteristics of lymphatic metastasis in zone VI of thyroid cancer. It also clarified the significance of lymphatic clearance of region VI in the surgical treatment of thyroid cancer. Song Ming et al. retrospectively analyzed the clinical data of 130 patients with thyroid cancer who were admitted between January 1988 and January 2000, all of whom underwent cervical lymphatic dissection including zone VI. Statistical treatment was also performed. The results showed that 97 (74.6%) of the 130 patients had positive postoperative lymph nodes in region VI; the complication rate was l0.8% (14/l30), including 4 cases of laryngeal recurrent nerve injury. Multifactorial survival analysis showed that lymphatic metastasis in thyroid cancer region VI was a factor affecting patient survival. He concluded that routine lymphatic dissection of region VI in patients with thyroid cancer could help improve their survival; the complication rate of surgery could be reduced by improving surgical technique [43].
9. Prospects for development and concluding remarks
At present, resection of the primary lesion of thyroid cancer with negative clinical cervical lymph nodes occurring in the unilateral lobe of the gland including this lobe and the isthmus, and if necessary, a contralateral part of the proximal isthmus, can achieve satisfactory results. Some scholars believe that when the primary lesion invades outside the envelope, the metastasis of cervical lymph nodes can reach 55-75% [44], so prophylactic cervical dissection must be performed; some scholars believe that for thyroid cancer with negative cervical lymph nodes, regardless of whether the primary lesion invades outside the envelope, cervical dissection can be withheld, and if lymph node metastasis appears during the follow-up period, cervical dissection can be performed again. If lymph node metastasis occurs during the follow-up period, cervical dissection will not affect the prognosis. However, the rate of lymph node metastasis after cNo stage papillary thyroid cancer without cervical dissection is 7-15%, and the re-operation of cervical dissection in these patients not only expands the scope of dissection but also decreases the quality of survival, and the rate of damage to the laryngeal nerve is greatly increased. The lymph node metastasis of thyroid cancer is more regular, and the most common metastatic areas are the laryngeal regurgitation area and the pre-tracheal area. With this in mind, we can add the central region for clearance at the time of the first surgery.
Thyroid cancer is quite common, with a male to female ratio of about 1:2-3. The least malignant is papillary carcinoma and the most malignant is undifferentiated carcinoma, but fortunately, the most common thyroid cancer is papillary carcinoma, whose incidence accounts for 70% to 80% of thyroid malignancies. Needle aspiration cytology is one of the important tools to detect thyroid cancer and its diagnostic value has been generally recognized by clinicians. Qin Jianwu [45] et al. considered that N0 stage papillary thyroid cancer with the following conditions: (i) advanced T3T4 cases, (ii) cases with poor prognosis judged by age, gender and differentiation, and (iii) cases with lymph node metastasis suspected by imaging are all indications for prophylactic lateral neck debulking surgery. Papillary thyroid cancer has a good prognosis, but the rate of local lymph node metastasis is high, and lymph node metastasis is also one of the factors affecting prognosis. Therefore, prophylactic neck dissection should be performed for stage N0 cases with high likelihood of lymph node metastasis.
However, the clinical practice of predicting lymph node metastasis to determine the surgical approach is somewhat subjective and does not conform to the tenet of evidence-based medicine. Therefore, there is an urgent need for more objective diagnostic tools. Zhang Wenchao [46] et al. used immunohistochemistry to detect the expression status of Ret gene in benign thyroid lesions and papillary thyroid carcinoma and its relationship with local invasion and cervical lymph node metastasis in papillary thyroid carcinoma. The aim was to combine clinical and pathological data to determine the nature and biological behavior of thyroid nodules, and to provide a basis for clinical selection of scientific treatment options. The results revealed that the positive expression of Ret gene was closely related to the occurrence, development and cervical lymph node metastasis of papillary thyroid carcinoma, and could potentially be used as an independent indicator for early diagnosis and detection of cervical lymph node metastasis. With the development of molecular biology, it is believed that more tumor-related indicators will be found to guide clinical surgery and become strong evidence for preventive neck clearance for cN0 stage papillary thyroid cancer.
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