The currently accepted definition of a pulmonary nodule is a well-defined, opaque, single or multiple pulmonary nodule with a diameter of 75 px, completely surrounded by air-containing lung tissue, without pulmonary atelectasis, hilar enlargement, or pleural effusion. Pulmonary nodules can be classified as solid or subsolid nodules based on whether they completely obscure the lung parenchyma on CT, which can be subdivided into purely ground glass nodules and partially solid nodules. Pulmonary nodules ≤8 mm are defined as subcentimeter nodules based on the size of the nodule, which is defined as 8 mm. Lesions larger than 75 px in diameter are defined as lung masses rather than nodules, which are usually malignant according to previous studies. When CT reveals benign features such as benign calcified foci (in the form of diffuse, central, thin or popcorn-like calcifications), intra-nodular fatty hypodensities (e.g., misshapen tumors) or arteriovenous malformations, the nodule density can be followed up for observation or not to avoid unnecessary detection of hobbling hills! In recent years, with the development of imaging techniques and equipment, especially the popularity of multilayer spiral CT, the detection rate of pulmonary nodules has increased significantly. Therefore, the clinical management and decision making of pulmonary nodules has gradually become one of the problems that plague clinicians. In addition to determining the risk of benign and malignant based on imaging features at the initial diagnosis and selecting further investigations, follow-up is a common method. What tools to use for follow-up, how often to follow up, and how long to monitor the follow-up is a very important practical issue in clinical work. This article reviews advances in the clinical management of pulmonary nodules of uncertain nature based on the 3rd edition of the American College of Chest Physicians (ACCP) clinical management pathway guidelines for single or multiple pulmonary nodules published in 2013. I. Imaging evaluation In the chest X-ray examination, the highest peak is 0.09% to 0.20%, while CT can {40% to 60%, and the current CT examination is the main basis for determining the characteristics of pulmonary nodules (including nodule size, border features and density). When a patient’s chest CT examination determines the presence of a pulmonary nodule, the same area of the patient’s previous CT images needs to be reexamined. Information on the size and characteristics of the nodule has important implications for the determination of benignity and malignancy as well as for the development of subsequent treatment plans. The results of the study showed that subcentimeter nodules were less malignant, regardless of whether they were solid or subsolid nodules. Lung nodules with burrs or irregular borders were 5 times more likely to be malignant than those with smooth borders; pulmonary nodules with pleural depression sign were 1 times more likely to be malignant; and vascular sign and lobar shape increased the probability of malignancy by 70% and 10%, respectively. II. Clinical management strategies Currently, there are 3 basic management strategies for patients with pulmonary nodules based on the type of nodule, the classification of malignancy probability (very low: << span="">5%; low-moderate: 5%-65%; {degree: >65%), lung cancer risk factors and potential surgical risks (including preoperative cardiovascular and pulmonary function assessment, postoperative complications, etc.): (1) surgical treatment; (2) non-surgical biopsy; and (3) close follow-up observation with serial CT scans. There is no doubt that surgical treatment is the gold standard for definitive diagnosis. For pulmonary nodules with a high probability of malignancy (>65%), the recommended management strategy is surgery, unless the patient is a contraindication to surgery or cannot tolerate it. The main surgical treatments include televised thoracoscopic surgery (VATS), open chest, and mediastinoscopy. Thoracoscopic wedge resection is the method of choice for diagnosing highly malignant pulmonary nodules, and results of a large clinical study showed that the complication rate of lung segment or lobectomy under VATS (26%) was significantly lower than that of open-chest surgical treatment (35%). Non-surgical biopsy, as an invasive test, is often used to clarify the diagnosis of benign malignancy with potential risks and is indicated for a definitive diagnosis of a pulmonary nodule with a moderate probability of malignancy (10% to 60%) or when the patient requires definitive preoperative evidence of malignancy, especially in patients with a high expectation of surgical complications. Non-surgical biopsies include CT-guided percutaneous transluminal needle aspiration biopsy (TTNB), bronchoscopy combined with endobronchial ultrasound (EBUS), electromagnetic navigation bronchoscopy (ENB) (our hospital became the first hospital in Asia to officially perform electromagnetic navigation bronchoscopy technology, mainly for the diagnosis of small pulmonary nodules), and virtual bronchoscopic navigation (VBN). TTNB is indicated for pulmonary nodules close to the chest wall or deeper, requiring the absence of surrounding emphysema, while the bronchoscopic technique is indicated for pulmonary nodules located closer to the bronchi. A meta-analysis based on 39 studies showed that EBUS, ENB, and VBN all had a sensitivity of about 70% for the diagnosis of pulmonary nodules, with 82% for nodules larger than 50 px in diameter and 61% for nodules ≤50 px in diameter. All CT surveillance follow-up observations should be performed with thin-layer low-dose non-enhanced CT scans. The advantage of CT surveillance over surgical treatment and non-surgical biopsy is that it avoids unnecessary invasive sex checks for benign lesions. This suggests that CT screening is particularly important for people at risk for lung cancer. A clinical study of 162 isolated lung nodules in China showed that follow-up observation was an important factor in delaying diagnosis and treatment. However, the 2013 ACCP 3rd edition clinical management pathway guidelines for pulmonary nodules conclude that CT surveillance has no clear impact on survival in patients with pulmonary nodules, based on the majority of previous studies. (2) contraindication to surgical treatment or non-surgical biopsy; (3) intolerance to surgical treatment or non-surgical biopsy. Monitoring of lesion volume changes during follow-up is recommended, and lung nodules that remain stable in lesion volume for 2 years are suggestive of benign lesions, as evidence suggests that the volume doubling time (VDT) for malignant solid lung nodules is usually less than 400 d, but VDT for subsolid lung nodules requires a longer time. Clinical management pathway In 2013, the ACCP published the 3rd edition of its clinical management pathway guidelines for single or multiple pulmonary nodules, which are summarized below, depending on the size and nature of the nodule. 1. Solid pulmonary nodules ≥8 mm in diameter: For solid pulmonary nodules ≥8 mm in diameter, the clinician first needs to determine the patient’s surgical risk, the probability of malignancy of the nodule, and the PET scan assessment. If the probability of malignancy is low (<< span="">5%) or if the probability of malignancy is low to moderate (5% to 65%) but the patient is at high risk for surgery, strict periodic follow-up with CT scans at 3-6, 9-12, and 18-24 months after the initial examination is recommended. For low to moderate (5% to 65%) and highly malignant (>65%) probable pulmonary nodules that can tolerate surgery, surgical treatment, non-surgical biopsy and CT monitoring can be chosen after evaluation of metabolism and staging using PET scan; for highly malignant probable pulmonary nodules that cannot tolerate surgery, chemotherapy, radiotherapy, radiotherapy and radiofrequency ablation are feasible after PET evaluation. 2, Diameter << span="">8 mm solid pulmonary nodules: The 2013 ACCP 3rd edition guidelines are consistent with the 2005 American Fleischner Society guidelines for follow-up of small solid nodules, which determine the timing and interval of CT surveillance based on lung cancer risk factors such as size of the nodule, patient age, and smoking history. 3. Subsolid lung nodules: Detterbeck and Homer suggest that pure ground-glass lung nodules ≤10 mm in diameter are usually confirmed as atypical adenomatous hyperplasia (AAH) or adenocarcinoma in situ (AIS), whereas pure ground-glass lung nodules >10 mm in diameter are more likely to be invasive adenocarcinoma (IA). Malignancy is highly suspected if the solid portion of a partially solid nodule exceeds 50% of the total nodule volume, or if a pre-existing purely ground glass pulmonary nodule develops into a partially solid pulmonary nodule. The 2013 ACCP recommends the following management pathway for subsolid pulmonary nodules (1) For pure ground-glass nodules ≤5 mm in diameter, follow-up is usually not required. For pure ground glass nodules 5-10 mm in diameter, repeat CT once a year for 3 years. For pure ground-glass lung nodules >10 mm in diameter, repeat CT 3 months after the initial CT examination and recommend non-surgical biopsy or surgical treatment if the lesion persists, unless the patient is intolerant of surgery. (2) For partially solid pulmonary nodules ≤8 mm in diameter, CT scans should be performed at 3, 12, and 24 months after the first examination for strict periodic follow-up, and I CT scan should be repeated annually for 3 years thereafter. non-surgical biopsy or surgical treatment should be performed as soon as an enlargement of the solid portion is detected during the follow-up. For partially solid pulmonary nodules >8 mm in diameter, CT should be repeated 3 months after the first tear, and if the lesion persists, PET scan, non-surgical biopsy, and surgical treatment should be actively managed. For subsolid pulmonary nodules >15 mm in diameter, no review CT is required and active management should be done directly. 4. Multiple pulmonary nodules: For patients with confirmed or highly suspected lung cancer, CT scan usually reveals multiple pulmonary nodules. The 2013 ACCP recommends that for multiple pulmonary nodules, each individual nodule should be treated with caution and further evaluated with PET scanning, rather than arbitrarily assuming that the additional nodules are metastases or benign lesions. lesions. The management of multiple pulmonary nodules is challenging and requires a combination of systems and should be treated aggressively unless metastases are confirmed. Clinicians should provide an effective and cost-effective management pathway for patients with pulmonary nodules based on guidelines and adequate information about potential risks and benefits. For the estimation of malignancy probability of isolated pulmonary nodules, scholars in China have also conducted research on the logistic mathematical prediction model, which has a high prediction accuracy after preliminary clinical validation and has better clinical application value than foreign models for the Chinese population, but there is still a long way to go for the popular application and large-scale clinical validation of this model in Chinese clinical hospitals. In addition, as a common problem in clinical work, pulmonary nodules have been improved through decades of research and several editions of clinical management guidelines, but there are still many issues to be resolved, such as the safety of CT follow-up and the impact on patient prognosis, the search for noninvasive biomarkers (e.g., serum vascular endothelial growth factor) that can help determine the probability of benign and malignant pulmonary nodules and/or predict patient prognosis, etc. etc., all need to be validated and explored in larger and longer prospective clinical studies. (zz)