Lung adenocarcinoma

　　The etiology of lung cancer is not yet completely clear. A large amount of medical literature indicates that the risk factors for lung cancer include smoking (including second-hand smoke), asbestos, radon, arsenic, ionizing radiation, halogenated alkenes, polycyclic aromatic compounds, nickel, and so on. Specifically, as follows:

　　1. Smoking:Long-term smoking can cause hyperplasia of bronchial mucosal epithelial cells, squamous epithelial hyperplasia, and induce squamous cell carcinoma or undifferentiated small cell carcinoma. Even those without a smoking habit can also develop lung cancer, but adenocarcinoma is more common, and carcinogenic substances are released when cigarettes are burned.

　　2. Air pollution.

　　3. Occupational factors:Long-term exposure to radioactive substances such as uranium and radium, their derivatives, carcinogenic hydrocarbons, arsenic, chromium, nickel, copper, tin, iron, coal tar, asphalt, petroleum, asbestos, mustard gas, and other substances can induce lung cancer, mainly squamous cell carcinoma and undifferentiated small cell carcinoma.

　　4. Chronic lung diseases:Lung diseases such as tuberculosis, silicosis, and pneumoconiosis can coexist with lung cancer. The incidence of cancer in these cases is higher than in normal people. In addition, chronic inflammation of the lung bronchial mucosa and fibrous scar lesions in the healing process may cause squamous epithelial metaplasia or hyperplasia. On this basis, some cases may develop into cancer.

　　5. Intrinsic factors of the human body:Such as family inheritance, decreased immune function, metabolic activity, and endocrine dysfunction.

　　1. Respiratory complications:Such as sputum retention, atelectasis, pneumonia, respiratory insufficiency, etc. The incidence is higher in the elderly and weak, those with chronic bronchitis, and emphysema.

　　2. Postoperative hemothorax, empyema, and bronchopleural fistula:The incidence is very low. Postoperative hemothorax is a serious complication that requires emergency treatment, and timely reoperation may be necessary to stop bleeding if necessary.

　　3. Cardiovascular system complications:Old age, weakness, traction and stimulation of the mediastinum and pulmonary hilum during surgery, hypokalemia, hypoxia, and massive hemorrhage often become the causes. Common cardiovascular complications include: postoperative hypotension, arrhythmia, pericardial tamponade, heart failure, etc.

　　First, the population with multiple occurrences

　　Adenocarcinoma accounts for about 40% of primary lung tumors. It is more likely to occur in women and non-smokers.

　　Second, disease symptoms

　　Lung cancer does not have any special symptoms in the early stage, only common symptoms of respiratory system diseases, such as cough, hemoptysis, low fever, chest pain, and shortness of breath, which are easy to overlook.

　　1. Early extrapulmonary manifestations include bone and joint symptoms:These symptoms are relatively common. Due to the ability of lung cancer cells to produce certain special endocrine hormones (ectopic hormones), antigens, and enzymes, these substances operate on the bone and joint sites, causing swelling and pain, often involving the tibia, fibula, ulna, radius, and joints, with the tips of the fingers and toes often swelling into a club-like shape, and radiographic examination can show periosteal hyperplasia. Shoulder and back pain: peripheral lung cancer often develops posteriorly and superiorly, eroding the pleura, involving the ribs and chest wall tissues, thus causing shoulder and back pain. These patients rarely have respiratory symptoms. Hoarseness: compression of the laryngeal nerve by the metastatic focus of lung cancer can cause the vocal cords to become monopolar and lead to hoarseness. Since the metastatic focus of lung cancer can appear in the early stage, and sometimes the metastatic focus can grow faster than the primary focus, the clinical manifestations of the metastatic focus can appear before those of the primary focus.

　　The symptoms of advanced lung cancer may vary depending on the physical condition of the patient. The condition is relatively serious at the advanced stage of lung cancer, and timely symptomatic treatment is required.Pain is a common symptom in advanced lung cancer patients, and most patients with lung cancer that has spread regionally within the chest have symptoms of chest pain. Hoarseness is one of the symptoms of advanced lung cancer. The recurrent laryngeal nerve, which controls the left side of the vocal function, descends from the neck to the chest, circles around the great vessels of the heart, and returns upwards to the larynx, thus controlling the left side of the vocal organs. Therefore, if the tumor invades the left side of the mediastinum, compressing the recurrent laryngeal nerve, hoarseness will occur, but there will be no symptoms of pharyngitis or other symptoms of upper respiratory tract infection. Swelling of the face and neck is also a relatively common symptom in advanced lung cancer. If the tumor invades the right side of the mediastinum and compresses the superior vena cava, it will initially cause the jugular vein to dilate due to poor blood return, and finally lead to swelling of the face and neck, which requires timely diagnosis and treatment. Shortness of breath and pleural effusion are also manifestations of advanced lung cancer.

　　1. Ban and control smoking:The mechanism of smoking causing lung cancer has now been studied relatively clear, and epidemiological data and a large number of animal experiments have fully proven that smoking is the main factor causing lung cancer. The following discusses the issue of banning smoking.

　　1. Smoking should be banned immediately.

　　2. The state should formulate strong laws and publicize that tobacco contains carcinogenic substances that cause lung cancer.

　　3. Reduce the harm of passive smoking.

　　2. Reducing the harm of industrial pollution:The following aspects should be started from.

　　1. Workers in dust-polluted environments should wear masks or other protective masks to reduce the inhalation of harmful substances.

　　2. Improve the ventilation environment of the workplace, reduce the concentration of harmful substances in the air.

　　3. Transform the production process, reduce the production of harmful substances.

　　3. Reducing environmental pollution:Air pollution is an important factor causing lung cancer. Among them, there are mainly 3,4-benzo(a)pyrene, sulfur dioxide, nitrogen oxides, and carbon monoxide, etc. The reduction of environmental pollution and measures include the following aspects:

　　1. Limit the development of urban motor vehicles, improve the combustion equipment of motor vehicles, and reduce the emission of toxic gases.

　　2. Research on harmless energy, gradually replace or eliminate harmful energy sources.

　　For the diagnosis and examination of lung cancer, the commonly used methods in clinical practice include the following several kinds:

　　1. X-ray examination:X-ray examination is the most commonly used and important means for the diagnosis of lung cancer. Through X-ray examination, the location and size of lung cancer can be understood. Although X-ray examination of early lung cancer cases has not yet been able to show a mass, it may show local emphysema, atelectasis, or infiltrative lesions or lung inflammation in the vicinity of the lesion due to bronchial obstruction.

　　2. Bronchoscopy:Bronchoscopy is an important measure for the diagnosis of lung cancer. Through bronchoscopy, the pathological changes of the bronchial mucosa and lumen can be directly observed. If cancer or cancerous infiltration is seen, tissue can be taken for pathological section examination, or bronchial secretions can be aspirated for cytological examination to clarify the diagnosis and determine the histological type.

　　3. Radioisotope examination:The radioactive drugs such as 67Ga-citrate have an affinity for lung cancer and its metastatic lesions, and can accumulate in the tumor after intravenous injection, which can be used for the localization of lung cancer, showing the range of the disease, with a positive rate of about 90%.

　　4. Cytological examination:Most primary lung cancer patients can find shed cancer cells in their sputum, and the histological type of the cancer cells can be determined. Therefore, sputum cytology examination is a simple and effective method for lung cancer screening and diagnosis. The positive rate of sputum cytology examination for central lung cancer can reach 70-90%, while the positive rate of sputum examination for peripheral lung cancer is only about 50%, so negative sputum cytology examination cannot exclude the possibility of lung cancer.

　　5. Thoracotomy exploration:Lung mass has not been determined in nature after examination by various methods and short-term exploratory treatment. The possibility of lung cancer cannot be ruled out. If the patient's overall condition permits, a thoracotomy exploration should be performed. During the operation, appropriate treatment is given based on the condition of the lesion and the results of pathological tissue examination. This can avoid delaying the disease and missing the opportunity for early treatment of lung cancer cases.

　　Due to the different biological characteristics of cancer cells, lung cancer is divided into small cell lung cancer and non-small cell lung cancer in medicine. The latter is further divided into squamous cell carcinoma, adenocarcinoma, large cell lung cancer, and so on.

　　Lung cancer, like other malignant tumors, can produce some hormone enzymes, antigens, and fetal proteins, but these tumor markers have no application value for the diagnosis of lung cancer. Clinical physicians should be highly alert to cases of persistent cough or hemoptysis in middle-aged and older patients, or chest X-ray findings of unexplained masses or inflammatory changes. Lung cancer patients should be detected early, diagnosed early, and treated early to reduce the possibility of late-stage metastasis and deterioration.

　　6. ECT examination:ECT bone imaging can detect lesions 3 to 6 months earlier than ordinary X-ray films, and can detect bone metastases earlier. If the lesions have reached the middle stage, the decalcification of the bone lesions reaches more than 30% to 50% of their content, both X-ray films and bone imaging show positive findings. If the osteogenic response at the lesion site is static and metabolism is inactive, bone imaging is negative and X-ray films are positive. The two complement each other, which can improve the diagnostic rate.

　　7. Mediastinoscopy:When there is enlargement of the mediastinal lymph nodes in front of the trachea, beside the trachea, and below the carina (groups 2, 4, 7) as seen on CT, mediastinoscopy should be performed under general anesthesia. A transverse incision is made in the depression above the sternum, and the soft tissues in front of the neck are bluntly separated to reach the pre-tracheal space. The pre-tracheal passage is bluntly freed, and an observation scope is slowly passed behind the innominate artery. The enlarged lymph nodes beside the trachea, at the tracheobronchial angle, and below the carina are observed. Specimens are obtained by using a special biopsy forceps. Clinical data show a total positive rate of 39%, with a mortality rate of about 0.04%, and complications such as pneumothorax, laryngeal recurrent nerve palsy, hemorrhage, and fever occur in 1.2% of cases.

　　1. Quit smoking, which is the most effective method to prevent lung cancer.

　　2. Drink less strong alcohol.

　　3. Do not eat moldy and deteriorated food; eat less preserved food.

　　4. Chew food slowly and do not eat overly hot food.

　　5. Do not consume too much fat; keep the intake below 30% of the total calories, which is 50g to 80g of animal and plant fats per day; eat more fresh vegetables and fruits, providing 10g of fiber and general levels of vitamins daily.

　　6. Eat less smoked food.

　　7. Avoid drug abuse, especially do not abuse sex hormone drugs and cytotoxic drugs, to prevent the risk of drug-induced cancer.

　　8. Consume fruits, vegetables, and coarse grains daily.

　　1. Treatment principles:Comprehensive treatment principles should be adopted, that is: according to the patient's physical condition, the cytological and pathological type of the tumor, the extent of invasion (clinical staging), and the development trend, a multidisciplinary comprehensive treatment (MDT) model should be adopted. Surgery, chemotherapy, radiotherapy, and biological targeted therapy should be applied in a planned and reasonable manner to achieve radical or maximum control of the tumor, improve the cure rate, improve the quality of life of patients, and extend the survival period of patients. Currently, the treatment of lung cancer still focuses on surgery, radiotherapy, and drug therapy.

　　Second, surgical treatment

　　1. Principles of surgical treatment

　　Surgical resection is the main treatment method for lung cancer and the only method currently available for clinical cure of lung cancer. Lung cancer surgery is divided into radical surgery and palliative surgery, and efforts should be made to achieve radical resection. The aim is to achieve the best and most thorough resection of the tumor, reduce tumor metastasis and recurrence, and perform the final pathological TNM staging to guide postoperative comprehensive treatment. For lung cancer that can be surgically resected, the following surgical principles should be followed:

　　(1) Comprehensive treatment plans and necessary imaging examinations (clinical staging examinations) should be completed before non-emergency surgical treatment. A full assessment should be made to determine the possibility of surgical resection and to formulate a surgical plan.

　　(2) Try to achieve complete resection of the tumor and regional lymph nodes while trying to preserve healthy lung tissue with functional capacity.

　　(3) Video-assisted thoracic surgery (VATS) is a minimally invasive surgical technique that has developed rapidly in recent years and is mainly applicable to stage I lung cancer patients.

　　(4) If the patient's condition permits, anatomical lung resection (lobectomy, sleeve lobectomy, or pneumonectomy) should be performed. If the condition does not allow, limited resection can be performed: segmental resection (the preferred option) or wedge resection, or VATS (Video-Assisted Thoracic Surgery) can also be chosen.

　　(5) In addition to the complete resection of the primary tumor, complete resection surgery (R0 surgery) should routinely involve the resection and marking of regional lymph nodes (N1 and N2 lymph nodes) at the hilum and mediastinum, and these should be sent for pathological examination. At least, sampling or lymph node dissection should be performed in 3 mediastinal drainage areas (N2 stations), and efforts should be made to ensure en bloc resection of the lymph nodes. The recommended extent of clearance on the right chest is: 2R, 3a, 3p, 4R, 7-9 groups of lymph nodes, and surrounding soft tissue; on the left chest, it is: 4L, 5-9 groups of lymph nodes, and surrounding soft tissue.

　　(6) The pulmonary veins, pulmonary arteries, and finally the bronchi should be processed in sequence during surgery.

　　(7) Sleeve lobectomy should be performed as much as possible to preserve more lung function (including bronchi or pulmonary vessels) while ensuring negative margins (including bronchial, pulmonary arterial, or venous truncal) during intraoperative rapid pathological examination, leading to better postoperative quality of life compared to pneumonectomy patients.

　　(8) For patients with recurrent lung cancer or solitary lung metastases after complete resection of lung cancer, and excluding distant metastases outside the lung, resection of the remaining lung on the side of recurrence or resection of the lung metastasis lesion can be performed.

　　(9) Patients in stages I and II with organ conditions such as cardiovascular and pulmonary function that cannot be accepted for surgery can undergo radical radiotherapy, radiofrequency ablation, and drug therapy, among other treatments.

　　2. Indications for surgery

　　(1) Stage I, II, and some stage IIIa (T3N1-2M0; T1-2N2M0; T4N0-1M0 can be completely resected) non-small cell lung cancer and some small cell lung cancer (T1-2N0-1M0).

　　(2) N2 stage non-small cell lung cancer that is effective after neoadjuvant therapy (chemotherapy or chemotherapy combined with radiotherapy).

　　(3) Some stage IIIb non-small cell lung cancer (T4N0-1M0) that can be locally completely resected, including invasion of superior vena cava, other adjacent large blood vessels, atrium, carina, etc.

　　(4) Some stage IV non-small cell lung cancer with single-sided lung metastasis, single brain or adrenal metastasis.

　　(5) Lung nodules highly suspected of lung cancer, which cannot be diagnosed definitively after various examinations, can consider surgical exploration.

　　3. Contraindications to surgery

　　(1) Patients with systemic conditions that cannot tolerate surgery, and those with cardiac, pulmonary, liver, kidney, and other important organ functions that cannot tolerate surgery.

　　(2) Most of the stage IV, most of the stage IIIb, and some stage IIIa non-small cell lung cancer, as well as small cell lung cancer with a stage later than T1-2N0-1M0, etc.

　　3. Radiotherapy:Lung cancer radiotherapy includes radical radiotherapy, palliative radiotherapy, adjuvant radiotherapy, and prophylactic radiotherapy, etc.

　　1. Principles of radiotherapy

　　(1) Radical radiotherapy is applicable to patients with a KPS score ≥70 (Karnofsky score see attachment 2), including early non-small cell lung cancer that cannot be surgically removed due to medical or personal factors, unresectable locally advanced non-small cell lung cancer, and limited stage small cell lung cancer.

　　(2) Palliative radiotherapy is applicable for symptomatic treatment of primary and metastatic lesions in advanced lung cancer. For patients with single brain metastasis from non-small cell lung cancer who have undergone surgical resection, whole brain radiotherapy can be performed.

　　(3) Adjuvant radiotherapy is indicated for patients who require preoperative radiotherapy or postoperative positive margins, and for patients with postoperative pN2 positivity, it is encouraged to participate in clinical studies.

　　(4) The design of postoperative radiotherapy should refer to the patient's surgical pathological report and surgical records.

　　(5) Prophylactic radiotherapy is applicable to patients with small cell lung cancer who have received effective systemic treatment and require whole brain radiotherapy.

　　(6) Radiotherapy is usually combined with chemotherapy to treat lung cancer. Depending on the stage, treatment goals, and general condition of the patient, combined regimens can include concurrent chemoradiotherapy and sequential chemoradiotherapy. The recommended concurrent chemoradiotherapy regimen is EP and regimens containing taxanes.

　　(7) For patients receiving chemoradiotherapy, potential adverse reactions may increase, and patients should be informed before treatment; attention should be paid to the protection of the lung, heart, esophagus, and spinal cord during radiotherapy design and implementation; efforts should be made to avoid unplanned interruptions in radiotherapy due to improper management of adverse reactions during treatment.

　　(8) It is recommended to adopt advanced radiotherapy techniques such as three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT).

　　(9) Patients receiving radiotherapy or chemoradiotherapy should receive sufficient monitoring and supportive treatment during the treatment rest period.

　　2. Indications for radiotherapy in non-small cell lung cancer (NSCLC)

　　Radiotherapy can be used for radical treatment in early-stage NSCLC patients who cannot undergo surgery due to physical conditions, preoperative and postoperative adjuvant treatment in operable patients, local treatment in patients with locally advanced lesions that cannot be resected, and important palliative treatment for patients with incurable advanced cancer.

　　For patients with stage I NSCLC who cannot undergo surgical treatment, radiotherapy is one of the effective means of local control of the lesion. For patients with NSCLC who undergo surgical treatment, if the postoperative pathological surgical margin is negative and the mediastinal lymph nodes are positive (pN2), in addition to routine postoperative adjuvant chemotherapy, it is also recommended to add postoperative radiotherapy. For pN2 tumors with positive margins, if the patient's physical condition permits, it is recommended to use postoperative concurrent radiochemotherapy. For patients with positive margins, radiotherapy should be started as early as possible.

　　For patients with stage II-III NSCLC who cannot undergo surgery due to physical conditions, appropriate radiotherapy combined with concurrent chemotherapy should be given if the physical conditions permit. For patients with curative hope, through more appropriate radiotherapy plans and more active supportive treatment, efforts should be made to minimize interruptions in treatment time or reductions in treatment dosage when receiving radiotherapy or concurrent radiochemotherapy.

　　For patients with widely metastatic stage IV NSCLC, some patients can receive radiotherapy for the primary and metastatic sites to achieve the purpose of palliative symptom relief.

　　4. Drug treatment for lung cancer:The drug treatment for lung cancer includes chemotherapy and molecular targeted drug treatment (EGFR-TKI treatment). Chemotherapy is divided into palliative chemotherapy, adjuvant chemotherapy, and neoadjuvant chemotherapy, and the clinical indications should be strictly controlled, and implemented under the guidance of oncologists. Chemotherapy should fully consider the patient's stage of disease, physical condition, adverse reactions, quality of life, and patient's wishes, to avoid over-treatment or under-treatment. The efficacy of chemotherapy should be evaluated in a timely manner, adverse reactions should be closely monitored and prevented, and drugs and/or dosages should be adjusted accordingly.

　　The indications for chemotherapy are: PS score ≤2, vital organ functions can tolerate chemotherapy, and for SCLC, the PS score for chemotherapy can be relaxed to 3. Encourage patients to participate in clinical trials.

　　1. Drug treatment for advanced NSCLC

　　(1) First-line drug treatment.

　　The platinum double-drug regimen is the standard first-line treatment; for patients with EGFR mutations, targeted therapy can be chosen; those with conditions can combine antitumor angiogenesis drugs on the basis of chemotherapy. Currently available chemotherapy drugs are listed in Attachment 7. For patients who achieve disease control (CR+PR+SD) in first-line treatment, those with conditions can choose maintenance treatment.

　　(2) Second-line drug treatment. Second-line treatment options include docetaxel, pemetrexed, and targeted drugs EGFR-TKI.

　　(3) Third-line drug treatment. EGFR-TKI or entry into a clinical trial can be chosen.

　　2. Drug treatment for NSCLC that cannot be surgically resected

　　Recommending combined radiotherapy and chemotherapy, the choice between concurrent or sequential radiochemotherapy can be made according to specific conditions. Concurrent treatment recommends chemotherapy drugs such as etoposide/platinum or carboplatin (EP/EC) combined with paclitaxel or docetaxel/platinum. Sequential treatment chemotherapy drugs can be found in first-line treatment.

　　3. Perioperative adjuvant treatment for NSCLC

　　For completely resected stage II-III NSCLC, adjuvant chemotherapy with a platinum double drug regimen is recommended for 3-4 cycles. Adjuvant chemotherapy should start when the patient's physical condition has basically recovered, usually starting 3-4 weeks after surgery.

　　Neoadjuvant chemotherapy: For resectable stage III NSCLC, platinum double drug, 2 cycles of preoperative neoadjuvant chemotherapy can be selected. The efficacy should be evaluated in a timely manner, and adverse reactions should be judged to avoid increasing surgical complications. Surgery is usually performed 2-4 weeks after chemotherapy. Postoperative adjuvant treatment should be based on the preoperative staging and the efficacy of neoadjuvant chemotherapy, and the original regimen should be continued or adjusted appropriately according to the patient's tolerance if effective, or a new regimen should be changed if ineffective.

　　4. Principles of Lung Cancer Chemotherapy

　　(1) Lung cancer patients with KPS2 are not suitable for chemotherapy.

　　(2) Lung cancer patients with white blood cells less than 3.0×10^9/L, neutrophils less than 1.5×10^9/L, platelets less than 6×10^10/L, red blood cells less than 2×10^12/L, and hemoglobin below 8.0g/dl are generally not suitable for chemotherapy.

　　(3) Lung cancer patients with abnormal liver and kidney function, laboratory indicators exceeding twice the normal values, or with severe complications and infections, fever, and bleeding tendency are not suitable for chemotherapy.

　　(4) If the following situations occur during chemotherapy, consider stopping the medication or changing the regimen:

　　If the lesion progresses after 2 cycles of treatment or reverts to a worse condition during the rest period of the chemotherapy cycle, the original regimen should be stopped, and other regimens should be selected appropriately; if the adverse reactions of chemotherapy reach grade 3-4 and pose a significant threat to the patient's life, the medication should be stopped, and other regimens should be used for the next treatment; if serious complications occur, the medication should be stopped, and other regimens should be used for the next treatment.

　　(5) It must be emphasized that the treatment plan should be standardized and individualized. The basic requirements of chemotherapy must be mastered. In addition to the routine use of antiemetic drugs, platinum drugs other than carboplatin require hydration and diuresis. Routine blood tests should be conducted twice a week after chemotherapy.

　　(6) The efficacy evaluation of chemotherapy should refer to the WHO Solid Tumor Response Evaluation Criteria or the RECIST Efficacy Evaluation Criteria.