1.Overview Thyroid nodules are masses of abnormal tissue structure in the thyroid gland caused by various reasons, including tumors, cysts, normal tissue masses, and thyroid lumps caused by other diseases. Thyroid nodules are a frequent and common disease of the endocrine system. In recent years, the incidence of thyroid nodules in China has shown an increasing trend, with the prevalence of thyroid nodules obtained by palpation ranging from 3% to 7%, the prevalence of thyroid nodules obtained by high-resolution ultrasound ranging from 20% to 76%, and the prevalence of thyroid cancer ranging from 5% to 15%, with papillary thyroid carcinoma being the most common. Most patients with thyroid nodules have no clinical symptoms. When combined with abnormal thyroid function, corresponding clinical manifestations may appear. Some patients develop pressure symptoms such as hoarseness, difficulty in breathing or swallowing due to the pressure of nodules on the surrounding tissues. The thyroid is an important gland that secretes hormones that control metabolism. The diagnosis and treatment of thyroid nodules involves a number of clinical disciplines such as endocrinology, head and neck surgery, general surgery, nuclear medicine, etc. It is a typical interdisciplinary disease. Benign thyroid nodules include thyroid cysts, nodular goiter, thyroid adenoma, and some inflammatory nodules. For the treatment of benign thyroid nodules. Domestic and foreign experts have reached a consensus: most of them can be left untreated for the time being, keeping the follow-up interval of 6-12 months There is a lack of consensus and standardization in the treatment of thyroid cancer in terms of operative modality, radioactive iodine therapy, TSH inhibition therapy and monitoring of recurrence of thyroid cancer, etc. At present, there is a great controversy at home and abroad over the treatment plan for papillary carcinoma of thyroid with a diameter of less than 1cm. 2. Etiology The etiology of thyroid nodules is complex, and its occurrence is closely related to heredity and certain environmental factors. Studies have shown that the occurrence of benign thyroid nodules and various types of thyroid cancers may be related to the mutation, kinetic bracketing, suppression and deletion of certain oncogenes and oncogenes. Currently, a variety of candidate genes are known to be involved in the pathogenesis of thyroid nodules, especially thyroid tumors. For example, thyroid stimulating hormone (TSH) receptor, gsp, ras, ret, etc. Secondly, high iodine and iodine deficiency cause the increase of the incidence of thyroid nodules; in addition, patients who have a history of exposure to head and neck radiation in childhood or who have received radiation therapy are also risk factors for the development of thyroid nodules. Diagnosis 1) Clinically, most thyroid nodules are detected by ultrasonography and have no clinical symptoms. Only a small percentage of thyroid nodules are detected by palpation of a lump in the neck or when clinical symptoms appear. When the nodule bleeds, it may cause localized pain and swelling, and when the nodule presses on the surrounding tissues, corresponding clinical manifestations, such as hoarseness, breathlessness, foreign body sensation in swallowing, or dysphagia, may occur. When combined with hyperthyroidism or hypothyroidism, the corresponding clinical manifestations of hyperthyroidism or hypothyroidism may appear, such as palpitations, excessive sweating, hand tremor, constipation, fear of cold, unresponsiveness, etc. 2) Auxiliary examination: Most of the thyroid function tests are normal, unless combined with hyperthyroidism or hypothyroidism. Imaging is essential. Ultrasound is the best way to detect thyroid nodules, which can detect nodules as small as 2mm and is highly reproducible. Ultrasound of the thyroid and cervical lymph nodes should be performed for known or suspected thyroid nodules, nodular goiter, and incidentally detected thyroid nodules on other imaging studies (e.g., CT, MR, and PET/CT). 2015 American Thyroid Association (ATA) Guidelines for the Diagnosis and Management of Thyroid Nodules and Differentiated Thyroid Cancer in Adults. Guidelines for the Diagnosis and Management of Adult Thyroid Nodules and Differentiated Thyroid Cancer (hereinafter referred to as the 2015 edition of the Guidelines), opens with a clear statement about the importance of ultrasonography in the evaluation of thyroid nodules 3) Diagnosis The key to the diagnosis of thyroid nodules is to identify the benignity and malignancy of the nodules. The 2015 edition of the Guidelines introduces the concept of ultrasound malignancy risk stratification based on the results of a series of studies of ultrasound characterization. All patients with thyroid nodules should undergo thyroid ultrasound for malignancy risk assessment, based on which diagnostic fine-needle aspiration biopsy (fineneedleaspiration, FNA) may be used for cytologic diagnosis. Molecular markers (e.g., BRAF, RAS, RET/PTC, Pax8PPARY, or galectin-3) may be considered to guide management in cases where the cytologic results of FNA are inconclusive. Ultrasound malignancy risk stratification included highly suspicious malignancy, moderately suspicious malignancy, low suspicious malignancy, very low suspicious malignancy and benign nodules. (1) Highly suspected malignancy (malignancy risk of 70% to 90%): solid hypoechoic or cystic solid nodules in which the solid component is hypoechoic, with one or more of the following ultrasound features: (1) irregular margins (infiltrative, lobulated, or burr); (2) microcalcifications (3) aspect ratio greater than 1; (4) interruption of the marginal calcification, with hypoechoic protrusion outside the calcification; and (5) invasion of the peritrochlear membrane of the thyroid gland. (2) Moderately suspected malignancy (malignancy risk of 10% to 20%): ① solid hypoechoic nodule; ② smooth and regular margins; ③ no microcalcification; ④ no aspect ratio greater than 1; ⑤ no extraperitoneal invasion. (3) Low-grade suspected malignancy (malignancy risk 5%~10%): ① isoechoic or hypoechoic solid nodule; ② solid portion of cystic solid nodule is eccentric, no microcalcification, regular margins, aspect ratio less than or equal to 1 and no extraperitoneal invasion. (4) Very low suspicion of malignancy (less than 3% risk of malignancy): (i) spongy nodules; (ii) cystic solid nodules with solid portions that are not eccentric, no microcalcifications, regular margins, aspect ratio less than or equal to 1, and no extra-glandular invasion. (5) Benign nodules (less than 1% risk of malignancy): benign nodules are mainly cystic nodules. The criteria for FNA after ultrasonographic evaluation of malignancy stratification are: (1) Nodules that are highly suspicious of malignancy. FNA should be performed when the nodule is larger than 1 cm, and when the nodule is smaller than 1 cm, it should be closely followed up. (2) Moderately suspicious nodules. Diagnostic FNA should be performed when the nodule is larger than 1 cm to rule out or confirm malignancy. (3) low suspected malignant nodules greater than 1.5cm can be FNA. (4) very low suspected malignant greater than 2.0cm can be FNA. (5) benign nodules are mainly cystic nodules, do not need to carry out FNA. 4, interventional therapy In recent years, with the improvement of the people’s health and quality of life requirements, the detection rate of thyroid nodules year by year, the patient’s demand for the thyroid nodules to negotiate the treatment of the more and more high. Patients’ demand for thyroid nodule treatment is increasing. Traditional treatments mainly include thyroxine suppression therapy, surgical resection and radioiodine therapy. The effect of thyroxine suppression therapy on shrinking thyroid nodules and preventing new nodules is still controversial. Surgical resection is not only traumatic and costly, but also affects the aesthetics of the surgical incision scar, especially for recurrent lesions. Repeated surgeries not only bring great pain to the patients, but also increase the risk and difficulty of reoperation due to the unclear adhesion of local anatomical layers in the neck. Radiation iodine therapy is prone to cause hypothyroidism, and the incidence of hypothyroidism in patients with toxic goiter is 14% within 5 years after treatment. Thermal ablation technology, as an emerging treatment method, mainly includes radiofrequency ablation, microwave ablation, laser ablation, etc., which can inactivate the cells of nodules, coagulate the tissues, and then the necrotic tissues are phagocytosed by the body’s immune system, and the foci gradually atrophy to disappear, and not only can it be accurately localized, but it can also be used to determine the scope of the coagulative necrosis of tissues in a relatively precise manner, and has the features of simple operation, safety, effectiveness, minimally invasive, short treatment time, precise efficacy, little side effects, and complications. With the advantages of easy operation, safety, effectiveness, minimally invasive, short treatment time, precise efficacy, small side effects, and fewer and lighter complications, etc., it has played a certain role in the treatment of thyroid nodules, and has gradually become a hotspot for research and application in the clinic. Indications and contraindications】After years of clinical research and follow-up, thermal ablation of benign thyroid nodules has been proved to be effective and used in clinical practice. There are some controversies at home and abroad about the specifications of thermal ablation of thyroid nodules: the Guidelines for Thermal Ablation of Thyroid Nodules formulated by the Minimally Invasive Therapy Committee of the Chinese Anti-cancer Association in November 2013 include benign thyroid nodules (BTN) with a diameter of >2 cm as an indication, but in the 2015 Edition of the Guidelines for the Diagnosis and Treatment of Thyroid Nodules and Differentiated Thyroid Cancer in Adults of the American Thyroid Association, the criteria for surgery of BTN are nodules larger than 4cm, and the criteria for surgery are nodules larger than 4 cm, and the criteria for surgery of BTN are nodules larger than 4cm. However, in the 2015 American Thyroid Association Guidelines for the Diagnosis and Management of Adult Thyroid Nodules and Differentiated Thyroid Cancer, benign nodules were considered to be greater than 4 cm in the 2015 American Thyroid Association Guidelines for the Diagnosis and Management of Adult Thyroid Nodules and Differentiated Thyroid Cancer, and the criteria for surgery were nodules greater than 4 cm, and in the Italian version of the indications for radiofrequency ablation of thyroid nodules published by Garberoglio et al in June 2015,[48] we differentiated between absolute indications and relative indications. We summarize the domestic and international guidelines for thermal ablation of thyroid nodules, and the indications and contraindications for benign and malignant thyroid nodules are as follows: 1) Benign thyroid nodules (1) Indications: the patient must meet the 1-2 items and the 3rd item at the same time: ① Ultrasound suggests that it is benign, and FNA confirms that it is a benign nodule. (2) The patient’s own condition is assessed to be unable to tolerate surgical treatment or the patient’s subjective will to refuse surgical treatment. ③At the same time, one of the following conditions must be met: A autonomous functional nodule causing hyperthyroidism symptoms; B patients with excessive anxiety affecting normal life and refusing clinical observation (patients request minimally invasive interventional therapy); C patients with symptoms related to the nodule (such as: foreign body sensation, neck discomfort or pain, etc.), or affecting the aesthetics of the patient, requesting treatment. (2) Contraindications: meet any one of the following is excluded: ① huge retrosternal goiter or most of the thyroid nodules are located in the posterior sternum (relative contraindication, subablation can be considered). (2) The presence of large calcified foci within the thyroid nodule. Vocal cord function is abnormal on the opposite side of the lesion. Serious coagulation disorders. ⑤ Severe cardiopulmonary disease. 2) Microscopic thyroid cancer (1) Indications: the patient should meet the following three criteria: ① ultrasound indicates single nodule, diameter ≤10mm, not close to the peritoneum (distance >2mm), FNA confirms papillary carcinoma, and there is no suspicious lymph node metastasis in the neck. ② The patient’s own conditions cannot tolerate surgical treatment or the patient subjectively refuses surgical treatment. (iii) The patient is too worried about the impact on normal life and refuses clinical observation (the patient requests minimally invasive interventional therapy). (2) Contraindications: any one of the following is excluded: ① suspected metastatic lymph nodes found in the neck and confirmed by puncture. (2) The presence of large calcified foci within the microscopic thyroid cancer. (iii) Vocal cord function on the opposite side of the lesion is abnormal. Serious blood clotting mechanism disorder. ⑤ Serious cardiopulmonary disease; [Preparation before ablation] For thermal ablation of thyroid nodules, in principle, patients are required to exclude contraindications to treatment and undergo elective thermal ablation with adequate preoperative preparation. 1) Auxiliary examination: blood, urine, fecal routine, four infectious diseases, liver function, renal function, blood glucose, electrolytes and coagulation set. Orthopantomogram and electrocardiogram. The above examinations can help to understand the physiological status of important organs and determine whether there are other pathologies in the body. Fiberoptic broncholaryngoscopy to understand the bilateral vocal cord movement. 2) Antibiotics: antibiotics are not recommended before or after treatment. Thermal ablation operation] 1) Anatomy: The thyroid gland is the largest endocrine gland in the human body, presenting a thin layer, located under the thyroid cartilage immediately in front of the third and fourth cartilage rings of the trachea, consisting of the two lobes and the isthmus, with an average weight of about 20-25g, slightly heavier in women. Behind the thyroid gland are four parathyroid glands and the recurrent laryngeal nerve. There are four arteries, i.e., the upper and lower thyroid arteries, so the thyroid gland has a rich blood supply, and the gland is innervated by the sympathetic and vagus nerves of the cervical sympathetic ganglion. 2) Equipment preparation: ① thermal ablation equipment 1 unit; ② ultrasonic examination instrument 1 unit; ③ sterile probe protective sleeve 1. ④ Conventional radiofrequency ablation surgical instruments. Operation process: the development of individualized treatment plans, strict aseptic operation of cystic nodules: ultrasound real-time monitoring of the puncture needle to withdraw the cystic fluid, anhydrous alcohol sclerotherapy. If the extracted fluid is jelly-like, it can be extracted by repeated pressure rinsing with saline, until the jelly is completely extracted, and then anhydrous alcohol sclerotherapy is applied. If the extracted fluid is old hemorrhage, the fluid should be extracted and rinsed with saline until it is clear, and then anhydrous alcohol sclerotherapy should be applied. When anhydrous alcohol sclerotherapy is performed, the amount injected should not be more than 1/2 of the cystic fluid to prevent leakage of anhydrous alcohol due to excessive intracapsular pressure, and the treatment should be terminated after repeated rinsing with anhydrous alcohol until the evacuated fluid is clear. According to the size of the cyst, the anhydrous alcohol can be retained, and the amount of retained alcohol should not be more than 1/4 of the original cystic fluid in principle. 4) Determination of the efficacy of the treatment (1) Increase the ultrasonography as the main evaluation index of the efficacy of the ablation immediately after the ablation operation and the follow-up after the ablation operation. Immediately after thermal ablation, ultrasonography was performed to observe the extent of thermal destruction of the ablated lesion, and to find the residual lesion tissue for timely supplemental ablation. (2) Conditional medical units can determine the accuracy of the therapeutic effect by puncture pathology examination after the operation. 5. Post-intervention treatment and follow-up 1) Prevention of bleeding, in order to prevent bleeding at the puncture site of the neck after ablation treatment, local pressure should be applied for 15-30 minutes, and the neck should be properly braked for about 8 hours. If there is coughing during the monitoring process, patients should be advised to press the affected area before coughing, so as to avoid bleeding caused by coughing. If sudden swelling of the neck is detected during monitoring, consider delayed hemorrhage, and ask the patient to press the affected area first, and then notify the doctor urgently for treatment. 2) Prevent neck swelling, for patients with large nodules or intraoperative bleeding leading to neck swelling, applying pressure with ice packs for 6-8 hours after surgery can reduce neck swelling and relieve pain. In order to avoid frostbite, the ice bag should be covered with a towel. 3)Serological monitoring,patients with thyroid tumor and metastatic lymph node thermal ablation in the neck should be tested for thyroid function indexes and corresponding tumor markers, including FT3, FT4, TSH, TG and PTH, etc. during follow-up. 4) Imaging examination, repeat ultrasonography 3 days after the end of treatment to assess the blood supply and necrosis of the lesion. Ultrasonography was repeated at 1, 3, 6 and 12 months after treatment to observe the size of the lesion and calculate the volume and nodule shrinkage rate. Reduction rate of treated lesions: [(volume before treatment – volume at follow-up)/volume before treatment]*100% 6. Complications and prevention and treatment Complications after ablation treatment of thyroid nodules mainly include pain, hemorrhage, vagal reflex, bronchospasm, and laryngeal reentrant nerve injury. 1) Pain: Pain is the most common complication of the treatment, there can be neck pain, gingival pain, ear root pain, generally mild, no need to deal with. A small number of patients can not tolerate pain, can be in the ablation site of the thyroid ventral peritoneum and anterior cervical muscle group gap additional appropriate amount of 1% lidocaine solution, to relieve pain. 2) Bleeding: post-thyroid therapy bleeding occurs within 24 hours after surgery, often acute, progressive aggravation of the clinical process, patients often suddenly appear neck pain, swelling irritability, cyanosis of the lips, and in severe cases, respiratory or even ventricular respiration. If the above situation occurs, we should make a quick judgment, timely pressure and monitoring, at the same time oxygen, if the patient’s respiration does not improve, then immediately perform a tracheotomy to save lives. Bleeding is often caused by damage to blood vessels, treatment should be avoided during puncture damage to blood vessels. If subcutaneous hemorrhage occurs during surgery, continuous pressure can be applied to stop the bleeding, usually for 3-5 minutes, and the pressure should be strong enough not to cause tracheal compression. 3) Vagal reflex: Vagal reflex is manifested as drop in blood pressure, progressive slowing of heart rate, dizziness, pallor, sweating, nausea, vomiting, agitation, etc., and in severe cases, blurring of consciousness occurs. Stimulation of the mutated vagus nerve in the process of mental stress, pain stimulation is an important trigger. Before treatment, we should actively communicate with the patients to eliminate their anxiety and other triggers leading to vagal reflexes. The needle path should avoid the vagus nerve travel area as much as possible. Once the vagal reflex occurs, the patient should be placed flat or in the head-down position, with the head tilted to one side, and oxygen should be administered, intravenous access should be established to expand blood volume and maintain effective circulating blood volume; if the blood pressure drops significantly, dopamine should be injected 10-20mg static rapidly, and then 250m of saline + dopamine 80-100mg should be injected intravenously until the blood pressure is stabilized; if the heart rate accounts for a significant decrease, intravenous atropine should be injected immediately, and the heart rate should be reduced. If the heart rate slows down, immediately inject 0.5-1mg of atropine intravenously to block the vagus nerve; if there is no change in the heart rate in 1-2min, add 0.5-1mg of atropine; if the patient vomits, give 10mg of gastroretentive intramuscularly and other symptomatic treatments. 4) Bronchospasm: preoperative respiratory tract chronic catastrophic disease or patients with a history of asthma, the vagal nerve tone increases, bronchial smooth muscle is in a state of stress, a little provocation can be bronchospasm, such patients are known as the airway hyperresponsive patients. Preoperative antibiotics, hormones, bronchodilators should be routinely used to control respiratory inflammation, improve ventilation, and should be routinely checked for pulmonary function. Minimize respiratory tract irritation during surgery. When bronchospasm occurs, oxygen saturation decreases, the lungs sound rales or breath sounds disappear on auscultation, after removing the triggers, it can be relieved on its own, if the symptoms are mild, aminophylline and dexamethasone should be applied, followed by pressurized oxygen inhalation to prevent hypoxia, and if the symptoms are not relieved, tracheal intubation can be carried out if necessary.