Lung cancer is one of the most common malignant tumors with poor prognosis, and the 5-year survival rate is only about 8% in China and 4%-15% in Europe and the United States. The preoperative staging of lung cancer, especially the pathological staging of mediastinal lymph nodes (TNM staging), is very important for formulating reasonable treatment plans and judging the prognosis [1]. The prognosis of lung cancer is related to the type of cancer cells, the degree of differentiation and the accurate clinical surgical plan. The ideal TNM staging diagnosis should not only reflect the patient’s clinical reality and no obvious discomfort and complications in the patient’s diagnosis, but also the method should have a high sensitivity and specificity.
1.Application of spiral CT in clinical staging diagnosis of lung cancer
Spiral CT of the chest is the most commonly used means for TNM staging in clinical practice, and has been upgraded and improved in resolution over the past 20 years, but its sensitivity and specificity for diagnosis of hilar and mediastinal lymph nodes have not improved significantly. The sensitivity and specificity are about 50% and 70%, respectively, and there is a high rate of false positives (50%) and false negatives.
2.The application of positron emission computed tomography in the clinical staging of lung cancer
Positron emission tomography (PET)/PET CCT has better sensitivity, specificity and accuracy than CT in lung cancer staging [3].PET-CT is a new medical imaging technique that has been used since the 1990s and has higher accuracy in lung cancer N staging, but still has The sensitivity of PET for mediastinal lymph nodes ranged from 0.76 to 1.00 and the specificity from 0.81 to 1.00. In a total of 1,045 lung cancer patients evaluated in 18 multicenter studies, the sensitivity of PET was known to be 0.84 (95% CI 0.84) based on postoperative pathology. 0.84 (95% CI 0.78 to 0.89) and specificity of 0.89 (95% CI 0.83 to 0.93) [ 4 ]. However, in smaller N2 metastases, PET diagnosis is false negative and active lymph nodes are generally false positive, while in China mediastinal lymphatic tuberculosis and lymphadenitis are more common.Rebecca [5] analyzed PET scan data of 518 patients in several studies.
The sensitivity and specificity of PET for metastatic lymph nodes were 88% and 91%, respectively, compared with 63% and 76%, respectively, for CT. Edward et al [6] studied intrathoracic lymph node metastases in 42 patients with lung cancer and obtained 62 lymph node specimens (40 hilar and lobar lymph nodes (N1), 22 mediastinal lymph nodes (N2/N3); 11 lobar/portal lymph nodes and 12 mediastinal lymph nodes were pathologically confirmed as tumor metastases, while the remaining 39 lymph nodes were reactive; suggesting that not all enlarged intrathoracic lymph nodes in lung cancer patients are metastases from lung cancer. the sensitivity and specificity of PET for intrathoracic lymph node metastases in this group were 83% and 82%, respectively, compared with 43% and 85%, respectively, for CT. didier et al [7] obtained lymph nodes from The results showed that 88% of patients still required mediastinoscopy to define the pathology of mediastinal lymph nodes after PET examination. Since the clinical staging of PET CCT in the diagnosis of lung cancer is overestimated and underestimated, too high a staging may cause some patients to lose the time for surgery, and too low a staging may cause some patients to undergo unnecessary open-heart surgery.
3. Application of invasive diagnostic tools in clinical staging of lung cancer [8]
The TNM staging diagnosis of invasive lung cancer patients includes fiberoptic bronchoscopy, percutaneous fine-needle aspiration biopsy (TTNA), transbronchoscopic fine-needle aspiration biopsy (TBNA), transendoscopic fine-needle aspiration biopsy with ultrasound (EUS-FNA)
The following are some of the most important features of mediastinoscopy Because of the anatomical specificity and complexity of the mediastinum, although B ultrasound or CT-guided percutaneous lung aspiration or transtracheoscopic aspiration biopsy cytological diagnosis provides a more reliable basis for definite diagnosis to a certain extent, it is only applicable to biopsy of some anterior mediastinal masses, and the amount of specimens obtained is too small and the false-negative rate is high, especially for the diagnosis and staging of mediastinal lymphoma, which is very difficult due to the small amount of tissue obtained by this method and the disadvantages of cytological examination itself. Although CT-guided needle aspiration biopsy can obtain cytologic diagnosis, mediastinoscopic surgery can reduce patients’ medical expenses and the proportion of open-chest exploration due to the limitation of its operation technique. Mediastinoscopic surgery has the advantages of low trauma, safety, and reliable sampling, and is an effective method for determining preoperative N
It is an effective method to determine the preoperative N-stage of lung cancer. For those who have suspected lung cancer and have enlarged mediastinal lymph nodes on chest CT, it is necessary to perform TV mediastinoscopy.
4.The use of video mediastinoscopy in the diagnosis of lung cancer clinical staging
Video mediastinoscopy (VM) has unique advantages in the diagnosis and treatment of mediastinal diseases, as it can clearly display the field of view of the operative area, obtain biopsies of peritracheal, inferior bulbar, left and right hilum and anterior mediastinum masses, and obtain sufficient biopsies for reliable pathological examination results [ 9 ].
4.1 Advantages of TV mediastinoscopy
TV mediastinoscopy has been widely used as a diagnostic technique in clinical practice and is becoming one of the important tools for preoperative pathological staging of lung cancer and diagnosis of difficult mediastinal diseases [10]. The value of TV mediastinoscopy in clarifying the mediastinal lymph node staging of lung cancer and achieving standardized treatment of lung cancer is receiving increasing attention. Compared with TV mediastinoscopy, PET is relatively expensive and has false positives and false negatives. Mediastinoscopy, as a minimally invasive, safe and reliable means of examination and treatment, has high sensitivity, specificity and accuracy. In recent years, the emergence of TV mediastinoscopy effectively compensates for many shortcomings of traditional mediastinoscopy in operation, such as narrow field of view, one-handed operation and one-handed holding of the mirror by the operator only, only the operator himself can observe the intraoperative situation, and it is difficult to effectively cooperate with the assistant, the ability to distinguish the fine anatomical structures and bleeding is poor, and the operation is only based on experience, and it is not convenient for teaching and data preservation. The use of TV mediastinoscope effectively solves the above problems by combining the light source and optical lens together and connecting them with the microscopic camera system in real time. (3) TV mediastinoscopic surgery has obvious advantages in intraoperative teaching and postoperative experience exchange.
4.2 Significance of TV mediastinoscopy and comparison with conventional examination
Huang Guojun et al [11] analyzed the overall compliance rate between clinical TNM staging ( c-TNM) and pathological TNM staging (p-TNM) of 2,007 patients with surgically treated non-small cell lung cancer (NSCLC) was 39.0%, overstaging 15.8%, and understaging 45.2%. Among them, the clinical staging of T was easier, with an overall accuracy rate of 72.9%; the clinical staging of N was more difficult, with an overall accuracy rate of 53.5%. In the clinical work of lung cancer, accurate N staging is more meaningful, and patients with N0 or N1 should be actively treated by surgery; patients with N2 stage should generally be treated by adjuvant chemotherapy first, and then decide whether to be treated by surgery according to the specific situation; patients with N3 stage should give up surgery and be routinely given radiotherapy or chemotherapy, which can effectively reduce the rate of surgical exploration and incomplete resection. Preoperative clarification of p-TNM staging of lung cancer patients is important for determining the treatment plan and prognosis. For patients with non-small cell lung cancer (NSCLC) with surgical possibilities, preoperative clarification of the presence or absence of mediastinal lymph node (N2) metastasis is crucial. Neoadjuvant therapy for lung cancer has now been agreed by most scholars and is gradually becoming the standardized treatment for stage N2 lung cancer. PET has certain false positives and false negatives in lung cancer staging, and is too expensive to be widely used at present. The sensitivity and specificity of CT for the diagnosis of mediastinal lymph nodes are low, and the preoperative staging of NSCLC is overestimated and underestimated [1-3], Toloza
et al [12] reported that CT has a sensitivity of 57%, a specificity of 82%, a positive predictive value of 56% and a negative predictive value of 83% for the diagnosis of mediastinal lymph nodes. One study showed that the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of spiral CT and TV mediastinoscopy were 63%, 57%, 59%, 41%, 77% and 89%, 100%, 97%, 100% and 96%, respectively. It is now generally accepted that patients with mediastinal lymph nodes ≥1.0 cm on CT should undergo further mediastinoscopy to clarify their N-stage; and for patients with negative CT
PET is expensive, has a high false-positive and false-negative rate, and the number of patients with positive mediastinal lymph nodes on PET is high.
PET is expensive, the false-positive and false-negative rates are high, and patients with positive mediastinal lymph nodes on PET still require further confirmation by TV mediastinoscopy. One study comparing PET and TV mediastinoscopy concluded that patients with negative mediastinal lymph nodes on PET may not need to undergo TV mediastinoscopy. TV mediastinoscopy has high sensitivity and specificity for staging mediastinal lymph nodes in lung cancer, and mediastinoscopy is the most accurate method to date for determining whether the mediastinal lymph nodes of lung cancer have metastasized because it can obtain a clear pathological diagnosis[13] . The scope of mediastinoscopy can make up for the shortcomings of current diagnostic methods and help to formulate scientific treatment plans for lung cancer.
4.3 Classification of TV mediastinoscopy
The best indication for TV mediastinoscopy is mediastinal lymph node enlargement due to various causes, as the gold standard for determining the presence or absence of mediastinal lymph node metastases (e.g. N3 or multiple N2 lesions, extra-lymph node invasion and stage T4 tumors invading mediastinal organs). Television mediastinoscopy is generally divided into two types.
4.3.1 Cervical Mediastinoscopy (CMS) [14]
The patient is placed in the supine position with a small pillow under the shoulder about 10 cm high and the neck tilted back by a single endotracheal tube under general anesthesia. A skin incision of approximately 3 cm was made at the upper edge of the sternotomy, and the broad cervical muscle was incised and sharply separated along the cervical white line, and the anterior cervical muscles on both sides were retracted with small hooks to the anterior tracheal fascia, and the trachea was cut open to expose the anterior tracheal space. The large blood vessels, lymph nodes and masses were explored and their relationship with each other. After sufficient space was available, mediastinoscopy was placed, and the suspected enlarged lymph nodes on both sides of the trachea, under the bulge, and next to the left and right main bronchi were observed sequentially. Before biopsy, the swelling is routinely aspirated with a puncture needle, and after confirming the exclusion of blood vessels, the tissue is bitten with biopsy forceps and sent for pathological examination. Intraoperative attention should be paid to multiple sampling to ensure sufficient specimen volume to meet the needs of frozen and paraffin pathological sections. For lung cancer staging, the material should be taken at multiple points according to the U ICC mediastinal lymph node zoning map, and when a single lymph node is negative for frozen pathology, the material should be taken again for pathological examination to make a clear diagnosis. After the clamp is completed, the trauma is carefully hemostatic, and for those with bleeding several minutes of pressure hemostasis is often effective, if necessary gelatin sponge or hemostatic gauze or hemostatic powder can be placed.
4.3.2 Transthoracic parasternal mediastinoscopy (Parasternal
Mediastinoscopy (PMS)
PMS is also called Anterior Mediastinoscopy [15], and the anesthesia is the same as standard cervical mediastinoscopy. The mediastinoscope with the camera and TV monitor connected is slowly inserted, and the blunt freeing is continued with the stripper or the special mediastinoscope suction head. The operator and the assistant probe the mediastinum by observing the TV combined with direct mediastinoscopy, and use biopsy forceps to bite 3-4 small pieces of lymph nodes or tumor tissues seen and routinely send them for rapid freezing. If the anterior mediastinal mass is near the incision, biopsy can be taken directly. After the examination and biopsy are completed with proper hemostasis, the mediastinoscope can be withdrawn. The incision is sutured and no drainage is required. In case of intraoperative pleural rupture, a chest drain will be placed.
4.4 Indications for television mediastinoscopy
The indications of TV mediastinoscopy mainly include: (1) to understand whether there is metastasis in mediastinal lymph nodes, to diagnose lung cancer and to make accurate staging of lung cancer, so as to better guide the treatment. The application of TV mediastinoscopy is particularly reliable for the N-stage of TNM stage of lung cancer. About 1/3 of lung cancer patients have mediastinal lymph node metastasis at the time of diagnosis, especially small cell type lung cancer metastasis can be more than 2/3. (2) Lymph node biopsy should be performed for lymph node enlargement in the hilum or mediastinum with unknown diagnosis (lymphatic tuberculosis, nodular disease), or qualitative diagnosis should be made for those with unknown diagnosis of mediastinal masses to facilitate treatment selection. Due to the special location of the mediastinum, the diagnosis of mediastinal diseases is often difficult. Nodular disease and mediastinal lymph node tuberculosis are the most commonly misdiagnosed mediastinal diseases, but the positive rate of nodular disease diagnosed by TV mediastinoscopy is as high as 95% to 100%. (3) Smaller mediastinal cysts and thymic hyperplasia are removed by TV mediastinoscopy. (4) Others, including more accurate estimation of upper middle esophageal cancer for which radical resection is difficult to be determined, determination of pulmonary artery pressure, placement of cardiac pacing electrodes, etc. (5) Mediastinoscopy can also be performed for difficult procedures such as combined superior vena cava obstruction syndrome [ 16 ]. Parasternal mediastinoscopy is mainly used for biopsy of enlarged group 5 and 6 lymph nodes.
4.5 Limitations and considerations of TV mediastinoscopy
It should be noted that mediastinoscopy cannot change the long-term survival rate of lung cancer patients, and the prognosis of lung cancer patients is determined by the biological characteristics of the tumor. TV mediastinoscopy is easy to operate, safe and reliable, with high sensitivity and specificity, however, TV mediastinoscopy is an invasive operation with certain complications as well as certain blind spots, especially for left upper lung cancer it is difficult to examine group 5 and 6 lymph nodes, which is easy to produce false negatives, therefore it should be combined with PET or TV thoracoscopic surgery to better improve the accuracy of clinical staging. The greatest difficulty of mediastinoscopy is the judgment of the biopsy site, such as mistakenly biopsying blood vessels such as the odd vein, superior vena cava, and unnamed vein as masses and causing hemorrhage[15] . Therefore, biopsy must be confirmed by puncture before taking tissue to confirm that it is not vascular. Adequate tissue or intact lymph nodes must be removed as much as possible during the operation. Common complications of TV mediastinoscopy include pneumothorax, hemorrhage, paralysis of the recurrent laryngeal nerve, and infection[17] . ③Gentle operation, adequate anesthesia, minimize stimulation of the trachea, and reduce the increase of venous pressure caused by coughing; ④Accumulate certain skills and experience in microscopic operation to improve the accuracy of biopsy and avoid damage to the laryngeal recurrent nerve; ⑤Be sure to follow the principle of trial puncture before biopsy to avoid hemorrhage; ⑥Adequate amount of biopsy specimens should be taken from multiple locations when necessary to meet the needs of pathological sections and ensure accuracy.
5.The use of TV thoracoscopic surgery in diagnosing clinical stage of lung cancer
In recent years, TV thoracoscopic surgery can biopsy intrathoracic lymph nodes and diagnose peripheral lung nodules as well as pleural and mediastinal masses because of its clear vision and low invasiveness. However, as far as the diagnosis and differential diagnosis of difficult mediastinal diseases are concerned, thoracoscopic surgery still has many shortcomings compared with mediastinoscopic surgery [19]: (1) the operation is relatively complex, requiring general anesthesia with double-lumen tracheal intubation and single-lung ventilation; (2) the scope of examination is limited to the unilateral pleural cavity and mediastinum; and (3) complications are relatively high. One study [20] compared the results of mediastinoscopic surgery with thoracoscopic surgery for mediastinal lesion biopsy and concluded that there was no significant difference in diagnostic rate between the two, but postoperative complications and hospital days were significantly higher in the thoracoscopic group than in the mediastinoscopic group. Thus, it seems that thoracoscopic surgery is more suitable for mediastinal lesions that are difficult to reach by mediastinoscopy or require multiple biopsies in the pleural cavity at the same time.
In conclusion, spiral CT is beneficial in evaluating pre-tracheal lymph node enlargement, PET is beneficial in ruling out distant metastasis of lung cancer, and TV mediastinoscopy remains the gold standard for mediastinal lymph node staging [21]. Therefore, in the clinical work of lung cancer, chest CT should be routinely performed first, followed by PET if positive mediastinal lymph nodes are suspected, and then surgery should be routinely performed if negative mediastinal lymph nodes are suggested, with TV mediastinoscopy routinely performed before surgery except for N3, and if the pathological result is positive, surgery is not suitable and chemotherapy or radiotherapy should be performed. These measures increase the hospitalization cost of patients from the surface, but from the viewpoint of health economics, they save the government medical expenses and reduce the rate of open chest exploration. According to the results of TV mediastinoscopy, patients with N0 lung cancer are treated with aggressive surgery; those with N2 are treated with neoadjuvant chemotherapy first and then decided to be treated with surgery according to their specific conditions; those with N3 are treated with direct chemotherapy and radiotherapy, effectively reducing the rate of surgical exploration and incomplete resection. Although mediastinoscopy is an invasive examination method, it also has high safety as long as the operation skill is properly mastered.