1.Overview
Thyroid nodules are masses of one or more abnormal tissue structures in the thyroid gland caused by various reasons, including tumors, masses composed of normal tissue from cysts, and thyroid masses 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. The prevalence of thyroid nodules obtained by palpation is 3%-7%, the prevalence of thyroid nodules obtained by high-resolution ultrasound examination is 20%-76%, and the prevalence of thyroid cancer is 5%-15%, with papillary thyroid cancer 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 nodules pressing on surrounding tissues. The thyroid gland is an important gland that secretes hormones that control metabolism. The diagnosis and treatment of thyroid nodules involves several clinical disciplines such as endocrinology, head and neck surgery, general surgery, and nuclear medicine, and 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 that most of them can be left untreated and the follow-up interval of 6-12 months can be maintained. There is a lack of consensus and standardization in the treatment of thyroid cancer, radioactive iodine therapy, TSH suppression therapy and monitoring of thyroid cancer recurrence, etc. At present, there is a great controversy in the treatment plan for papillary thyroid cancer less than 1 cm in diameter at home and abroad.
2.Etiology
The etiology of thyroid nodules is complex, and its occurrence is closely related to genetic and certain environmental factors. Studies have shown that the occurrence of benign thyroid nodules and various types of thyroid cancers may be related to mutations, radical brackets, inhibition, and deletion of certain oncogenes and oncogenes. Currently, several candidate genes are known to be involved in the development of thyroid nodules and especially thyroid tumors. For example, thyrotropin (TSH) receptor, gsp, ras, ret, etc. Secondly, high iodine and iodine deficiency both contribute to the increased incidence of thyroid nodules; in addition, patients with a history of head and neck radiation exposure or radiation therapy in childhood are also risk factors for the development of thyroid nodules.
3. Diagnosis
1) Most clinical thyroid nodules are detected by ultrasonography and have no clinical symptoms. Only a small percentage of thyroid nodules are detected by palpation of a neck lump or when clinical symptoms develop. When the nodule bleeds, it causes local pain and swelling. When the nodule compresses the surrounding tissues, corresponding clinical manifestations such as hoarseness, breath-holding, foreign body sensation in swallowing or difficulty in swallowing may occur. In combination with hyperthyroidism or hypothyroidism, the corresponding clinical manifestations of hyperthyroidism or hypothyroidism may appear, such as palpitations, excessive sweating, hand trembling, constipation, fear of cold, and unresponsiveness, etc.
2) Most of the thyroid function tests are normal, unless there is a combination of hyper- or hypothyroidism. Ultrasound is the best way to examine thyroid nodules, and can detect nodules as small as 2 mm with high reproducibility. Ultrasound of the thyroid and cervical lymph nodes should be performed for known or suspected thyroid nodules, nodular goiter, and other incidental findings on imaging (e.g., CT, MR, and PET/CT). The 2015 American Thyroid Association (ATA) Guidelines for the Diagnosis and Management of Adult Thyroid Nodules and Differentiated Thyroid Cancer (the 2015 edition of the Guidelines), begins with a clear statement about the importance of ultrasonography in the evaluation of thyroid nodules
3) The key to the diagnosis of thyroid nodules is to identify the benign and malignant nature of the nodules. The 2015 edition of the Guidelines introduced the concept of ultrasound malignancy risk stratification based on the results of a series of studies on ultrasound features. All patients with thyroid nodules should undergo thyroid ultrasound for malignancy risk assessment, and depending on the results of the assessment, diagnostic fine-needle aspiration biopsy (fineneedleaspiration, FNA) may be chosen for cytologic diagnosis. Molecular markers (e.g., BRAF, RAS, RET/PTC, Pax8PPARY, or galectin-3) may be considered to guide management for inconclusive FNA cytologic findings.
Ultrasound malignancy risk stratification includes highly suspicious malignancy, moderately suspicious malignancy, low suspicion of malignancy, very low suspicion of malignancy and benign nodules.
High suspicion of malignancy (70%-90% risk of malignancy): solid hypoechoic or cystic nodules with a solid component of hypoechoic with one or more of the following ultrasound features: ① irregular margins (infiltrative, small lobes or burrs); ② microcalcifications; ③ aspect ratio greater than 1; ④ interrupted marginal calcification with hypoechoic protrusion outside the calcification; ⑤ invasion of the thyroid peritoneum.
Moderate suspicion of malignancy (10%-20% risk of malignancy): ① solid hypoechoic nodules; ② smooth and regular margins; ③ no microcalcifications; ④ no longitudinal ratio greater than 1; ⑤ no extraperitoneal invasion.
Low suspicion of malignancy (malignancy risk 5%~10%): ① isoechoic or hyperechoic solid nodules; ② eccentric solid part of cystic nodules, no microcalcifications, regular margins, aspect ratio less than or equal to 1 and no extraglandular invasion.
Very low risk of suspected malignant malignancy less than 3%): ① sponge-like nodules; ② cystic nodules with non-eccentric solid portion, no microcalcifications, regular margins, aspect ratio less than or equal to 1 and no extraglandular invasion.
Benign nodules (risk of malignancy less than 1%): Benign nodules are mainly cystic nodules.
After the assessment of malignancy stratification by ultrasonography, the criteria for performing FNA are: (1) nodules with high suspicion of malignancy. When the nodule is larger than 1 cm, FNA should be performed, and when the nodule is smaller than 1 cm, close follow-up should be performed. (2) Moderately suspicious nodules. Diagnostic FNA should be performed for nodules larger than 1 cm to exclude or confirm malignancy. (3) Low suspicion malignant nodules larger than 1.5 cm are feasible for FNA.(4) Very low suspicion malignant nodules larger than 2.0 cm are feasible for FNA.(5) Benign nodules are mainly cystic nodules and do not require FNA.
4.Interventional treatment
In recent years, with the improvement of people’s health and quality of life, the detection rate of thyroid nodules is increasing year by year, and patients have higher and higher requirements for treatment of thyroid nodules. Traditional treatment includes thyroxine suppression therapy, surgical resection and radioiodine therapy. The role of thyroxine suppression therapy in reducing the size of thyroid nodules and preventing new nodules is controversial. Surgical excision is not only invasive and costly, but also affects the aesthetics of the surgical incision scar, especially for recurrent lesions, and repeated surgeries not only cause great pain to patients, but also make re-operation more risky and difficult due to unclear local anatomical level of adhesions in the neck. Radiation iodine treatment is likely to cause hypothyroidism, and the incidence of reduced thyroid function in patients with toxic goiter within 5 years after treatment is 14%. Thermal ablation technology, as an emerging treatment method, mainly includes radiofrequency ablation, microwave ablation, laser ablation, etc. It can inactivate the cells of nodules, coagulate the tissues, and then the necrotic tissues are immune phagocytosed by the body, and the lesions gradually shrink to disappear. It has the advantages of easy operation, safety, effectiveness, minimally invasive, short treatment time, precise efficacy, small side effects, few complications and light, etc. It has played a certain role in the treatment of thyroid nodules and gradually become a hot spot for research and clinical application.
Indications and contraindications】After several years of clinical research and follow-up, thermal ablation of benign thyroid nodules has been proven to have good effectiveness and is used in clinical practice. There are some controversies at home and abroad regarding the specification of thermal ablation treatment for thyroid nodules: the guidelines of “Guidelines for Thermal Ablation of Thyroid Nodules” formulated by the Committee of Minimally Invasive Treatment of Tumors of the Chinese Anti-Cancer Association in November 2013 include benign thyroid nodules (BTN) >2 cm in diameter as an indication, but the 2015 edition of the American Thyroid Association Guidelines for the Management of Adult Thyroid Nodules and Differentiated Thyroid Carcinoma contains the following criteria for benign nodules The Italian version of the indications for radiofrequency ablation of thyroid nodules published by Garberoglio et al [48] in June 2015 distinguished between absolute and relative indications, with thyroid nodules (>20m in volume) as an indication for thermal ablation. The indications and contraindications for thermal ablation of benign thyroid nodules and malignant nodules are summarized as follows:
Benign thyroid nodules
Indications: If 1-2 items are met at the same time and the third item is met: ① Ultrasound indicates benign and FNA confirms benign nodules. ②The patient’s condition is assessed to be intolerant of surgical treatment or the patient refuses surgical treatment of his own volition. The patient must also meet one of the following conditions: A. Autonomous functional nodules causing hyperthyroidism; B. Patients with excessive concerns affecting normal life and refusing clinical observation (patients requesting minimally invasive interventional treatment); C. Patients with obvious symptoms related to nodules (e.g. foreign body sensation, neck discomfort or pain, etc.) or affecting aesthetics and requesting treatment.
Contraindications: Any one of the following is excluded: ① Giant retrosternal goiter or a majority of thyroid nodules located behind the sternum (relatively contraindicated, but may be considered for fractionated ablation). (ii) The presence of coarse calcified foci within the thyroid nodule. (iii) Abnormal vocal cord function contralateral to the lesion. ④Severe coagulation disorders. ⑤Severe cardiopulmonary disease.
Microscopic thyroid cancer
Indications: The following three criteria must be met: ①Ultrasound indicates a solitary nodule with a diameter of ≤10mm, not close to the envelope (distance >2mm), FNA confirms a papillary carcinoma, and no suspicious lymph node metastasis in the neck. ②After assessment, the patient’s own condition cannot tolerate surgical treatment or the patient subjectively refuses surgical treatment. ③Patients with excessive ideological concerns affecting normal life and refusing clinical observation (patients requesting minimally invasive interventional treatment).
Contraindications: Any one of the following is excluded: ①Suspected metastatic lymph nodes in the neck are found and confirmed by puncture. (ii) The presence of large calcified foci within the microscopic thyroid cancer. ③Vocal cord function is abnormal on the opposite side of the lesion. ④Severe coagulation disorder. ⑤Severe cardiopulmonary disease;
Preparation before ablation
For thermal ablation of thyroid nodules, in principle, patients are required to exclude contraindications to treatment and to make adequate preoperative preparations for elective thermal ablation treatment.
Auxiliary examinations: blood, urine and stool routine, four infectious diseases, liver function, kidney function, blood glucose, electrolytes and coagulation set. Orthostatic chest X-ray and electrocardiogram. These examinations will help to understand the physiological status of important organs and determine the presence of other pathologies in the body. Fiberoptic broncholaryngoscopy to understand bilateral vocal fold movement.
Antibiotics: antibiotics are not recommended before and after treatment.
Thermal ablation operation]
Anatomy: The thyroid gland is the largest endocrine gland in the human body, with a thin layer, located under the thyroid cartilage immediately in front of the third and fourth cartilage ring of the trachea, consisting of both 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. The blood supply to the thyroid gland is rich because there are four main arteries, namely the upper and lower thyroid arteries, and the gland is innervated by the sympathetic and vagus nerves of the cervical sympathetic ganglion.
Equipment preparation: ① thermal ablation equipment 1; ② ultrasound inspection instrument 1; ③ sterile probe protection cover 1. ④conventional radiofrequency ablation surgical instruments.
Operation procedure: individualized treatment plan, strict aseptic operation of cystic nodules: after the cystic fluid is extracted by puncture needle under ultrasonic real-time monitoring, anhydrous alcohol sclerotherapy is performed. If the aspirate is jelly-like material, it can be extracted by repeated pressure flushing with saline until the jelly is completely extracted, and then anhydrous alcohol sclerotherapy is applied. If the extracted fluid is old bleeding, after the fluid is extracted, it is flushed with saline until it is clear, and then anhydrous alcohol sclerotherapy is applied. In the case of anhydrous alcohol sclerotherapy, the injected amount should not exceed 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 flushing with anhydrous alcohol until the effused fluid is clear. The anhydrous alcohol can be reserved according to the size of the cyst, and the reserved amount should not exceed 1/4 of the original cyst fluid in principle.
Determination of efficacy
(1)Increase the ultrasonography as the main evaluation index of the efficacy immediately after ablation and the follow-up after ablation. Ultrasonography should be performed immediately after thermal ablation to observe the extent of thermal destruction of ablated lesions and to detect residual lesions for timely supplemental ablation.
(2) The exactness of the efficacy can be judged by puncture pathology examination after the operation in medical units with conditions.
5.Post-intervention treatment and follow-up
(1) To prevent bleeding, after ablation treatment, local pressure should be applied for 15-30 minutes to prevent bleeding at the neck puncture site, and the neck should be braked appropriately for about 8 hours. If you cough during the monitoring process, ask the patient to press the affected area before coughing to avoid bleeding due to coughing. If sudden swelling of the neck is detected during the monitoring process, consider delayed bleeding and ask the patient to first apply pressure to the affected area and then notify the doctor urgently for treatment.
2) To prevent neck swelling, for patients with large nodules or intraoperative bleeding resulting in neck swelling, postoperative pressure with an ice pack for 6-8 hours can reduce neck swelling and relieve pain. To avoid frostbite, the ice bag was 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 indicators and corresponding tumor markers, including FT3, FT4, TSH, TG and PTH during follow-up.
4) Imaging examination, ultrasonography will be repeated 3 days after 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 lesions and calculate the volume and nodule shrinkage rate. The shrinkage rate of treated lesions: [(volume before treatment – volume at follow-up)/volume before treatment]*100%
6.Complication prevention and control
Complications after thyroid nodule ablation treatment mainly include pain, bleeding vagal reflex, bronchospasm and laryngeal nerve injury.
1) Pain: Pain is the most common complication of treatment, including neck pain, gum pain and ear pain, which are generally mild and do not require treatment. For a few patients who cannot tolerate pain, an appropriate amount of 1% lidocaine solution can be added to the ablation site between the ventral tegmental area of the thyroid and the anterior cervical muscle group to relieve pain.
2) Bleeding: Bleeding after thyroid treatment occurs mostly within 24 hours after surgery and is often an acute, progressive clinical process, with patients suddenly experiencing neck pain, swelling, irritability, lip cyanosis, and in severe cases, respiration or even ventricular respiration. If the patient’s breathing does not improve, tracheotomy should be performed immediately to save lives.
Most of the bleeding is due to injury to blood vessels, and treatment should be performed without injury to blood vessels during puncture. If subcutaneous bleeding occurs during surgery, continuous pressure can be applied to stop the bleeding, usually for 3-5 minutes, and the pressure should be applied without causing tracheal compression.
3) Vagus nerve reflex: The vagus nerve reflex is characterized by a drop in blood pressure, progressive slowing of heart rate, dizziness, pallor, sweating, nausea, vomiting, agitation, etc., and in severe cases, confusion. The process of stimulating the variant vagus nerve mental tension and pain stimulation are important triggers. Before treatment, actively communicate with patients to eliminate their anxiety and eliminate other triggers that cause 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 immediately placed in a flat or low-footed position with the head tilted to the side, oxygenated and intravenous access established to expand blood volume and maintain effective circulating blood volume; when blood pressure drops significantly, dobutamine 10-20mg should be injected rapidly by static push, followed by 250m saline + dobutamine 80-100mg by continuous intravenous drip until blood pressure stabilizes; when the heart rate account slows down significantly If there is no change in heart rate for 1-2 min, additional 0.5-1mg of atropine can be given; vomiting can be treated symptomatically by giving 10mg of intramuscular injection of gastric renformation.
4) Bronchospasm: Patients with preoperative chronic catarrh of the respiratory tract or a history of asthma have increased vagal tone and bronchial smooth muscle is in a state of stress, and bronchospasm can occur after a little provocation, such patients are called patients with high airway reaction. Preoperatively, antibiotics, hormones and bronchodilators should be used routinely to control respiratory inflammation and improve the ventilation function, and pulmonary function tests should be performed routinely. Minimize respiratory tract irritation during surgery. When bronchospasm occurs, the oxygen saturation decreases, and the croup or breath sounds disappear on auscultation, which can generally be relieved by itself after removing the trigger.