Q1: What kind of people are prone to lung cancer?
A1: Usually we refer to lung cancer as primary lung cancer, which refers to malignant lung tumors originating from the bronchial mucosa, glands or alveolar epithelium. The risk factors for developing lung cancer are male, age 45 years or older and smoking >400 cigarettes/year.
Q2: What is the etiology and pathogenesis of lung cancer?
A2: Despite years of research, the exact cause and pathogenesis of lung cancer have not been fully clarified so far. Currently, Dr. Jun Zhou mainly believes that it is related to the following factors.
(1) Smoking. The more you smoke, the longer you have been smoking, and the earlier you start smoking, the higher the mortality rate of lung cancer. China is a big tobacco country! Smoking interacts with other environmental carcinogenic and occupational factors to influence the incidence and mortality trends of lung cancer. There are more than 40 carcinogens in tobacco smoke. The risk of lung cancer decreases significantly only after 5 years of smoking cessation and approaches that of a lifelong nonsmoker only after 15 to 20 years of sustained smoking cessation.
(2) Environmental tobacco smoke. It is inhaled by non-smokers, that is, “passive smoking”. Environmental tobacco smoke contains a variety of mutagenic and carcinogenic chemicals, some of which (such as nitrite, 4-aminobiphenyl and benzo(a)pyrene) are even more than smoking.
(3) Air pollution. It includes outdoor air pollution (such as PM2.5, etc.) and indoor air pollution (such as Chinese cooking fumes, etc.). There are many kinds of air pollution, and it is generally believed that the culprits are polycyclic hydrocarbons and benzopyrene produced by the use of petroleum, coal and other fossil fuels.
(4) Indoor radon gas. Radon gas (Rn) and its products after alpha decay can cause the occurrence of lung cancer.
(5) Occupational factors. Lung cancer caused by chromium salt manufacturing and (workplace) asbestos, chloromethyl ether, arsenic and coke oven fugitive has been identified as occupational disease in China.
(6) Chronic diseases of the lungs. Some studies have shown that the number of cases of lung cancer among patients with chronic lung diseases such as tuberculosis, silicosis, chronic bronchitis and emphysema is higher than that of the general population. Several cohort studies have also shown that COPD is an independent predictor of lung cancer development.
(7) Diet and nutrition. A diet rich in fresh vegetables, fruits and carrots will reduce the occurrence of lung cancer in all pathological types. Poorly structured diets resulting in (some) excess or deficient nutrition are associated with lung cancer.
(8) Genetic susceptibility. A large body of evidence supports the existence of a genetic component in the development of lung cancer. Currently, the master gene for lung cancer has not been identified. Its candidate genes mainly include genes related to carcinogen metabolism (e.g. CYP1A1 and GSTM1 genes in nicotine metabolism), DNA repair and α1-antitrypsin, whose polymorphisms may influence individual susceptibility to lung carcinogenesis.
Q3: How many categories of lung cancer pathology can be classified?
A3: WHO’s 2015 Classification of Lung Cancer Pathology broadly classifies primary lung cancer malignant epithelial-derived tumors into the following ten categories.
Adenocarcinoma (adenocarcinoma).
squamous cell carcinoma (SCC), and
neuroendocrine tumors, and
large cell carcinoma, and
adenosquamous carcinoma, sarcomatoid carcinoma
sarcomatoid carcinoma, sarcomatoid carcinoma, carcinosarcoma
carcinosarcoma, carcinoma
pulmonary blastoma
salivary gland tumors and other and unclassified carcinomas.
where 0 represents benign tumors.
1 represents junctional or unknown biological nature.
2 represents carcinoma in situ and high-grade intraepithelial neoplasia (grade III).
3 represents malignant tumors.
The WHO’s 2015 pathological classification of lung cancer has been adjusted somewhat from the WHO’s 2004 classification, which originally had the following classification.
squamous cell carcinoma (SCC).
small cell carcinoma (SCC), small cell carcinoma (SCC), and
adenocarcinoma, and
large cell carcinoma, and
adenosquamous carcinoma, sarcomatoid carcinoma
sarcomatoid carcinoma, sarcomatoid carcinoma, sarcomatoid carcinoma
carcinoid tumor
and salivary gland tumors, etc.
Q4：What are the symptoms to be considered as possible lung cancer?
A4：Lung cancer may have no obvious symptoms in the early stage. Nowadays, with the rise of various medical examinations and lung cancer screening mechanisms in China, the detection of incidentaloma in the lung has increased significantly, while the detection of premalignant lesions and early stage lung cancer has also increased accordingly, and at this time, Dr. Jun Zhou needs further examinations to differentially diagnose the benignity and malignancy of the lesions.
The possibility of lung cancer should be considered when a patient has the following symptoms.
(1) Cough, caused by lung cancer is mostly irritating dry cough, paroxysmal choking cough and cough without sputum or small amount of white mucous sputum.
(2) Hemoptysis (note: ka xue), which is caused by lung cancer invading the bronchus or small blood vessels breaking down due to tumor necrosis, resulting in blood in sputum or hematochezia repeatedly, is very different from vomiting blood caused by upper gastrointestinal tract in terms of volume, which is large and often more dangerous.
(3) Chest pain, when lung cancer invades the wall pleura or chest wall, it can cause persistent pain in the corresponding area, which is difficult to distinguish from the nodules of peripheral type lung abscess that are not yet obviously necrotic (I remember a professor who had chest pain caused by inflammation of lung abscess involving the pleura, which was removed before anti-inflammation, which I think is more tragic to receive a knife for no reason).
(4) Fever, lung cancer can also cause fever, which is often seen in obstructive pneumonia distal to the lung cancer, because the causative factors are not cleared, thus the disease is repeatedly prolonged.
(5) Chest tightness and shortness of breath, which occurs on the basis of chronic obstructive pulmonary disease, is a relatively insidious symptom for patients. Generally, when lung cancer grows in the bronchus causing tracheal narrowing or compression of the main bronchus, chest tightness and shortness of breath will occur; and when the tumor metastasizes to the pleura, the cancer cells stimulate the pleura to produce a large amount of stubborn pleural fluid compressing the lung parenchyma can also cause chest tightness and shortness of breath.
Clinically, if a patient cannot be cured after two weeks of anti-inflammation of respiratory tract disease, and the patient has blood in sputum and irritating dry cough, or the symptoms are not improved but further aggravated, the possibility of lung cancer should be highly alert. For malignant tumors, “early diagnosis and early treatment” is the best, and lung cancer is no exception.
Q5：What symptoms indicate that lung cancer may have significantly invaded or metastasized?
A5：(1) Dr. Jun Zhou mentioned earlier that lung cancer invades the pleura and causes a large amount of bloody pleural effusion, resulting in chest tightness and shortness of breath.
(2) When there is continuous severe chest pain, it is considered that lung cancer has invaded the pleura and chest wall.
(3) When the symptoms of superior vena cava syndrome such as facial and neck edema appear, it is considered that lung cancer severely compresses or invades the superior vena cava.
(4) When the patient has hoarseness of voice, it is considered that the lung cancer has invaded the left laryngeal nerve in the mediastinum around the main pulmonary artery window.
(5) When the patient presents with severe chest pain, upper extremity venous anger, edema, arm pain and upper extremity movement disorder, or/and cervical sympathetic nerve syndrome such as ipsilateral upper eyelid ptosis, pupil narrowing, intraocular filling and facial anhidrosis, the patient is considered to have upper lobe apical lung cancer (pancoast tumor) invading the first rib, subclavian artery, brachial plexus nerve and cervical sympathetic nerve.
(6) When nodules or masses are palpated under the skin, subcutaneous metastasis is considered.
(7) Brain metastasis is considered when the patient develops neurological symptoms or signs such as headache, nausea, vertigo or blurred vision.
(8) Bone metastasis is considered when persistent bone pain, elevated alkaline phosphatase or blood calcium are present.
(9) Consider liver metastasis when there is right upper abdominal pain, hepatomegaly, alkaline phosphatase, abnormal liver function, and elevated LDH or bilirubin.
(10) If other organs show corresponding abnormal symptoms, the possibility of hematogenous metastasis should be considered.
(11) When systemic endocrine symptoms appear, endocrine paraneoplastic syndrome caused by lung cancer should be considered, which is described in more detail in Dr. Zhou Jun’s article “10 Questions about Small Cell Carcinoma (I) A3” about small cell carcinoma.
Q6： What imaging methods can be selected for patients considering lung cancer?
A6：Early detection of lung cancer: X-ray chest radiographs (5%-15%) used to be and still are important screening tools. However, with the continuous improvement of material conditions in China, CT, especially low-dose CT, has become the preferred lung cancer screening tool in areas with slightly better economic conditions.
Diagnosis of lung cancer: CT is currently the most important tool, which can not only examine the location and extent of lesion involvement, and roughly distinguish benign and malignant lesions, but also perform histocytological examination by CT-guided puncture biopsy.
Lymph node metastasis in the mediastinum: PET/CT has higher sensitivity and specificity (78% and 81%, respectively) than CT (sensitivity 40% to 65%, specificity 45% to 90%), but it is expensive and is not routinely recommended except in a few cities where it is generally not covered by medical insurance.
Abdominal, peritoneal cavity and retroperitoneal lymph node metastases, lymph node metastases in the supraclavicular fossa, lesions adjacent to the chest wall or metastatic lesions in the chest wall: ultrasound (most commonly ultrasound) and biopsy are available, and in addition ultrasound is often used to draw pleural fluid.
MRI is the best method to detect cranial metastases, and it is also valuable for clinical staging of lung cancer. bone imaging by SPECT/CT (commonly known as ECT) is also a routine examination for bone metastases of lung cancer.
Postoperative follow-up of lung cancer: X-ray chest X-ray is the preferred examination method.
Q7: How to choose preoperative endoscopic examination for lung cancer instead?
A7: Diagnosis of lung cancer: fiberoptic bronchoscopy technique is the most commonly used method, which can brush, biopsy and bronchial lavage; while thoracoscopy can be used for early lung cancer that cannot obtain pathological specimens by puncture biopsy, especially tiny nodules in the lung and resected in order to make a clear diagnosis, in addition, thoracoscopy can also provide powerful help for middle and advanced lung cancer.
Lymph node staging: mediastinoscopy is currently the gold standard for assessing the status of mediastinal lymph nodes in lung cancer. Although N-staging by CT, MRI and PET/CT is of great clinical help, it still cannot replace the diagnostic value of mediastinoscopy. Transfiber ultrasound bronchoscopy-guided transmural lymph node aspiration biopsy (EBUS-TBNA) can provide safe and reliable accurate pathological diagnosis of N1 and N2 of lung cancer, while transfiber bronchoscopy-guided transmural lymph node aspiration biopsy (TBNA) can accurately stage N2 of lung cancer before treatment with a sensitivity of 92.3% and specificity of 100%.
Q8: Are there any other clinical tests for lung cancer before surgery?
A8：Sputum cytology examination: one of the simplest non-invasive diagnostic methods, continuous smear can increase the positive rate up to about 60%.
Transthoracic wall intrapulmonary mass puncture needle aspiration biopsy (TTNA): biopsy under CT or ultrasound guidance, with higher sensitivity and specificity.
Thoracentesis: mainly used for the cytological diagnosis of pleural fluid.
Pleural biopsy: mainly used to improve the positive detection rate after negative thoracentesis results.
Superficial lymph node biopsy: pathological diagnosis to determine the stage and guide clinical treatment.
Q9：What are the common blood biochemical and tumor marker tests for lung cancer before surgery?
A9：Blood biochemical examination: it is mainly used to detect abnormal blood biochemical indexes of bone metastasis and liver metastasis of lung cancer in Q4.
Blood tumor marker examination: Currently, Dr. Jun Zhou introduces the following four commonly used indicators for reference.
(1) Carcinoembryonic antigen (CEA) is mainly used to judge the prognosis of lung cancer and monitor the treatment process. 30%-70% of lung cancer patients have abnormal CEA in blood, but it is mainly seen in patients with advanced lung cancer.
(2) Neurospecific enolase (NSE) is mainly used as the preferred marker for diagnosis of small cell lung cancer and monitoring of treatment response, with sensitivity of 40%-70% and specificity of 65%-80%.
(3) Cytokeratin fragment 19 (CYFRA21-1) is mainly used for the diagnosis of lung squamous carcinoma, with sensitivity up to 60% and specificity up to 90%.
(4) Squamous cell antigen (SCC) is mainly used for monitoring the efficacy and prognosis of lung squamous carcinoma, and the positive rate of SCC in the serum of lung squamous carcinoma patients is 39%-78%.
Of course, with the continuous progress of scientific research, there are many blood tumor markers for lung cancer, so I, Dr. Zhou Jun, will not list them all here, if you are interested, you can read the relevant monographs.
Q10：How to detect lung nodules in CT, but other clinical tests are negative?
A10: Clinically, sputum examination should be performed several times. If lung cancer is highly suspected, fibrinoscopic biopsy or needle aspiration biopsy of intrapleural lung masses is feasible.
The American Fleischner Society recommends the following follow-up protocol for patients with solid isolated pulmonary nodules (SPN): for SPN ≤ 4 mm in diameter, low-risk patients do not require follow-up, and high-risk patients are followed up at 12 months; for SPN 5-6 mm in diameter, low-risk patients are followed up at 12 months, and high-risk patients are followed up at 6-12 months and 18-24 months; for SPN 5-6 mm in diameter For SPN diameters of 5-6 mm, low-risk patients are followed up at 6-12 months and 18-24 months, and high-risk patients are followed up at 3-6 months, 9-12 months, and 24 months; for SPN diameters >8 mm, both low- and high-risk patients are followed up at 3, 9, and 24 months, and enhanced CT, PET-CT, and puncture biopsy are considered. For more details on the management of pulmonary nodules, see Dr. Jun Zhou’s “What to do when an isolated pulmonary nodule is found?
Reference.
Chen Gang. Pathological classification of lung cancer (WHO, 4th, 2015) Lecture PPT. Department of Pathology, Zhongshan Hospital, Fudan University.
Liu, L. M., ed. Oncologic diseases: clinical diagnosis and differential diagnosis. Scientific and Technical Literature Press, 2005 edition.
Miao, Jianjun Honorary Editor-in-Chief. Han Shujun, Chen Jili, eds. Cytopathology of lung cancer: an atlas of antacid staining. Scientific and Technical Literature Publishing House, 2014 edition.