When people reach middle age, the functions and immunity of all organs in the body are gradually declining, and some people are in a subhealthy state. Due to factors such as living habits, occupation, atmospheric pollution, smoking, oil smoke, genetic inheritance and recessive infection, the incidence of lung cancer remains high and becomes one of the main killers that endanger human health.
Due to the development of science and technology, the national emphasis on people’s health and the continuous improvement of the health care system, regular medical checkups have become routine, therefore, more small lung nodules are detected every year, which has won valuable time for early diagnosis and early treatment, and for the isolated small nodules found in the lungs, the detected people are very worried and the physicians are also difficult to make a conclusion for a while. According to the relevant literature statistics and my clinical experience, a rough expression of the diagnosis and treatment of small nodules in the lung is given for reference.
According to the analysis of the surgical results of 390 cases of isolated pulmonary nodules by Prof. Wang Jun of the Department of Thoracic Surgery, Peking University People’s Hospital, 37% of the cases were malignant if the diameter was less than 5 mm; 45% were malignant if the diameter was 5-10 mm; 65% were malignant if the diameter was 10-20 mm; and 80% were malignant if the diameter was 20-30 mm, indicating that most of the lesions less than 5 mm were benign lesions, and most of the lesions were malignant if the diameter was >20 mm.
Lesion size and name: <4mm in diameter, called corn-like nodules, 5-9mm called micronodules, 10-20mm called small pulmonary nodules.
For nodules found in the lungs during physical examination, we should perform the following tests for a clear diagnosis.
I. Chest CT
CT scan can show the enhancement of the nodule and its edge part of the tiny vascular structure, cut thin layer, do enhancement, measure data, etc. to assess the benignity and malignancy of small lung nodules, mainly from the shape of the nodule, density, edge and calcification foci with the nodule. The nature of the nodule is mainly based on its shape, density, margin and relationship between the calcified foci and the surrounding area.
The main CT manifestation of fine bronchoalveolar carcinoma is ground glass nodule (GGN), which is a blurred increase in lung density at the lesion site on CT, and ground glass shadow (GGO) with blood vessels and bronchial shadow in the lung parenchyma is still visible within the lesion. It is caused by various reasons, such as inflammation, atypical adenomatous hyperplasia, fine bronchoalveolar carcinoma (BAC), mixed small adenocarcinoma of the lung, etc. Some of the nodules with solid nodules are mixed ground glass shadow (GGN), and the cancerous nodule component is greater than 50%, which may be bronchoalveolar carcinoma (BAC), which is pathologically in situ and has a five-year survival rate of 100%.
Atypical adenomatous hyperplasia (AAH) is the precursor lesion of bronchoalveolar carcinoma (BAC) adenocarcinoma, the lesion is usually about 5 mm, rarely larger than 10 mm. become invasive adenocarcinoma. Therefore, if there are any of these changes during the follow-up, further investigation should be actively performed to clarify the diagnosis. If the lesion shrinks or becomes faint during follow-up, it is an inflammatory lesion and CT is usually repeated in 1-3 months.
In the high-resolution thin-section enhanced CT scan, the presentation of small pulmonary nodules with different pathological types is also different: highly differentiated adenocarcinoma shows ground glass-like density with blurred margins; moderately differentiated adenocarcinoma is a soft tissue nodule with uniform density and clear borders; low-differentiated adenocarcinoma, squamous carcinoma, and small cell tumor are nodules with uniform and dense density and deeply lobulated margins. If lymph nodes larger than 10 mm are found in both the lung and mediastinum, the possibility of lung cancer cannot be excluded.
PET-CT
For those suspected cases with lesions between 8 mm and 10 mm, PET-CT is recommended (). For small nodules in the lung, SUV 2.5 is generally used as the threshold value to differentiate benign from malignant, and those with SUV > 2.5 are more likely to be malignant. However, bronchoalveolar carcinoma, carcinoid tumors, mucus-containing highland tumors, highly differentiated tumors and small lesions can be falsely negative (i.e., SUV <2.5), but active inflammation and infection, such as tuberculosis, aspergillosis, inflammatory pseudotumors, and sarcoidosis can be falsely positive. Therefore, SUV as a reference indicator needs to be combined with comprehensive analysis such as chest CT, etc. For nodules with high suspicion of malignancy, CT-guided lung aspiration cytology is recommended for definite diagnosis. PET-CT should be performed on an empty stomach before examination, and PET-CT cannot replace brain MR examination and bone nuclide scan imaging examination.
CT-guided lung puncture
It is generally applicable to peripheral nodules of the lung. For the diagnosis of malignant tumors: the success rate of puncture is about 90% for lesions <20mm and 95% for lesions larger than 20mm. The tissue obtained from the lesion by puncture is examined by cell smear and paraffin pathology section, and if heterotypic cells or cancer cells are found in the lesion, the diagnosis of lung cancer can be confirmed. However, if the lesion is too small or the puncture is in necrotic tissue or normal lung tissue, false negative results may occur. The puncture may have complications such as pneumothorax and bleeding, and anticoagulant drugs such as aspirin should be stopped for about one week before the operation.
Fiberoptic bronchoscopy
Fibrobronchoscopy is an indispensable test for lung cancer diagnosis and preoperative examination. For small lung nodules, if malignancy is highly suspected, this test can also be performed, and fibre bronchoscopy can generally enter sub-segmental bronchi.
The manifestations of lung cancer under fibronectomy are divided into two major categories: direct manifestations: exophytic tumors, infiltrative tumors, and polyp-like changes. Indirect manifestations: including congestion, edema, and stenosis. If tumor is seen microscopically, pathological examination can be performed. If only indirect manifestations are found without any findings, lavage can be passed and heterogeneous cells in the exfoliated cells can be searched in the lavage fluid.
V. Endobronchial ultrasound with transbronchial fine needle aspiration (EBUS-TBNA) or lung biopsy (TBUS-TBLB).
EBUS is mainly used to explore mediastinal lymph nodes and guide needle aspiration, and biopsy lymph nodes immediately adjacent to the bronchial wall. It is usually considered that lymph nodes >10 mm in diameter, round, with clear borders, uniform central echogenicity and hypoechogenicity are malignant metastatic lymph nodes; while those less than 10 mm in diameter, with faint borders, uneven central echogenicity and hypoechogenicity are mostly benign changes.
Pulmonary nodules located in the parabronchial region can also be biopsied by EBUS-TBLB aspiration.
Commonly used tumor marker tests
Marker tests are used as reference for the diagnosis of small lung nodules and dynamic observation of the efficacy of lung cancer treatment.
1.Cancer embryonic antigen (CEA) in non-small cell carcinoma (NSCLC), lower in early stage, it is closely related to the size of the tumor, the larger the tumor, the higher the CEA, adenocarcinoma is higher than other pathological types. Normal value: 0-5ng/ml for smoking, 0-2.5ng/ml for non-smoking.
2. Neuron-specific enolase (NSE) is elevated in small cell carcinoma (SCLC), and the highest sensitivity of SCLC is NSE, which is positively correlated with tumor stage. Normal value 0-16ng/ml.
3.Squamous cell carcinoma antigen (SCC-Ag): some pathological types of NSCLC can increase its serum level, normal value: 0-1.5ng/ml.
4.Cytokeratin 19 fragment: CK19 is most commonly used in lung cancer with high specificity, normal value 0-3.3ng/ml. in renal insufficiency. It is also elevated in patients with liver cirrhosis and chronic obstructive pulmonary disease.
EGFR is a tyrosine transmembrane protein receptor with a mutation rate of about 20% in lung cancer, mainly exon 19 deletion and exon 21 mutation. Disease control rate.
6. K-ras gene: RAS gene is a common oncogene in human tumors. The K-ras protein is a key downstream regulator of the EGFR transmission pathway. Mutations in the K-ras gene are associated with resistance to the NSCLC targeted therapies gefitinib and nilotinib, so detection of mutations in the K-ras gene can be used as an important indicator of resistance to EGFR targeted therapies.
VII. Thoracoscopic pathological examination of small pulmonary nodules
Thoracoscopic pathological examination of pulmonary nodules can be performed if the diagnosis is still unclear after chest CT, sputum examination, PET-CT, fibrinoscopy, percutaneous lung puncture, etc. After general anesthesia with double-lumen tracheal intubation, 90° lying position with the affected side on top, minimally invasive thoracoscopic technique is used to determine the site of the lesion based on chest CT localization, intraoperative exploration, oval forceps or lobe forceps to clamp the lesion, and Endo-GIA linear cutting sutures, more than 50px from the edge of the mass, to remove the lesion and surrounding lung tissue. There are two points to note: 1) the excised lung tissue must contain the lesion; 2) the excised lung tissue has no tumor at the edge and is a certain distance from the tumor. The excised lesion is immediately sent for pathological examination. If the frozen section is reported as malignant or suspected malignant, further lobectomy and lymph node dissection will be performed. If the freeze report is benign, only the lesion is excised. In addition to biopsy of small nodules, the intrapulmonary and extrapulmonary lymph nodes should also be explored and sent for examination. If the freeze report does not match the paraffin report, there is often a 5% error. If the freeze report is benign and the paraffin report is malignant, a second operation, i.e. lobectomy and lymph node dissection, is required within about two weeks. If the first resection is large enough, the margins are negative, there is no lymph node enlargement or metastasis, and the patient cannot tolerate or does not accept the second surgery, the patient should be closely monitored and followed up with chest CT every 3-4 months, and if there is recurrence or metastasis, radiotherapy or targeted therapy, or radiofrequency ablation should be performed.
Treatment
For small lung nodules with confirmed lung cancer or highly suspected lung cancer, they should be treated actively. Early detection and early treatment should be carried out to achieve the goal of cure. The treatment of tumor is divided into local and systemic treatment. Local treatment includes surgery and radiotherapy. Systemic treatment includes chemotherapy, targeted therapy, etc.
I. Surgical treatment
Lobectomy plus systemic lymph node dissection is the standard surgical procedure for lung cancer. In order to preserve more healthy lung tissues, segmental lobectomy is also advocated, especially for the dorsal segment of the right lower lung and the lingual segment of the left upper lobe.
According to the clinical pathway of lung cancer surgical treatment, preoperative examination and preparation are done well. For those small nodular lung cancers located in peripheral type, our department adopts thoracoscopic minimally invasive technique to perform lobectomy plus lymph node dissection. Since the thoracoscope has the function of magnification six times, the surgical view is clearer than direct vision, and the minimally invasive technique makes the surgery less traumatic, less painful and faster recovery.
The extent of surgical resection follows two maximal principles, i.e., maximum tumor removal and maximum preservation of healthy lung tissue.
Lung cancer surgery is divided into four types: complete resection, incomplete resection, indeterminate resection and dissection and exploration according to the degree and nature of thoroughness. For small lung nodule surgery, we should try to achieve complete resection, requiring that all cut edges including bronchi, arteries, veins, peribronchial tissues and tissues near the tumor are free of tumor residue, and systematic clearance of lymph nodes, including 3 groups in the lung and 3 groups in the mediastinum, and the highest lymph nodes must be removed and microscopically negative. There are also small lesions with large metastases, including lymph node metastases and hematogenous metastases, where complete resection is not possible. The indications for surgery follow the principle of anaplasia: that is, to protect the incision, to avoid compression of the tumor, and to treat the pulmonary veins before the pulmonary arteries.
In conclusion, the surgeon should understand the medical history and examination data in detail before surgery, whether there are comorbidities, such as old chronic branch, emphysema, diabetes, coronary heart disease, etc., whether there are taking anticoagulants, such as aspirin, to develop a suitable surgical plan, strictly follow the surgical principles, and strengthen observation and active treatment after surgery, so that the patient can recover as soon as possible.
II. Chemotherapy
Except for completely resected stage IA lung cancer, 4-6 cycles of adjuvant chemotherapy are recommended for other stages of lung cancer after surgery, and different chemotherapy regimens are selected according to the pathological types.
There are various types of chemotherapeutic agents, which are divided into cell cycle-specific and non-cell cycle-specific agents. The former mainly have a killing effect on cells in the S and M phases of proliferating cells. The S-phase drugs include: pemetrexed, irinotecan, 5-Fu, gemcitabine, and Tsuptacan. Those acting in M phase include: paclitaxel, docetaxel, vincristine, etc. Non-cell cycle-dependent drugs: they have killing effects on all stages of cells, including non-proliferating G0 stage cells, such as isocyclophosphamide (IFO), alkylating agents, platinum compounds, epi-amycin, etc.
For non-small cell carcinoma, cisplatin (DDP), vincristine (NVB), gemcitabine, paclitaxel, docetaxel, etc. are generally used, among which patients with non-squamous cell carcinoma such as lung adenocarcinoma, pemetrexed has better efficacy.
For small cell carcinoma, pemetrexed (VP-16), teniposide (VM26), isocyclophosphamide (IFO), irinotecan (CPT-11), Tsugepotecan (Hormexin), cisplatin (DDP), etc. are used.
Chemotherapy must be carried out under the guidance of a physician. Chemotherapy has certain side effects, which will generally be relieved after discontinuation of the drug. Blood routine, liver and kidney function and tumor markers should be tested before chemotherapy.
C. Targeted therapy
Patients with postoperative pathology of adenocarcinoma should be tested for EGFR, and if there are mutations, targeted drug therapy is available. Targeted drugs mainly include: ERSA (Gefitinib), Troche (Nilotinib), and Kemena. They are epidermal growth factor receptor tyrosinase inhibitors in the intracellular region of the receptor, (EGFR-TKis) inhibit EGFR tyrosinase phosphorylation, thus blocking tumor cell signaling and inhibiting tumor cell growth, metastasis and vascular growth. Promotes apoptosis of tumor cells.
Usual dosage: Erythropoietin 250 mg/d, Troche 150 mg/d, orally.
The simultaneous application of targeted drugs with chemotherapeutic drugs is generally not advocated. Because erlotinib and others induce cell arrest in the G1 phase, while many chemotherapeutic drugs act in the M and S phases of the cell cycle, the simultaneous use of the two types of drugs can produce antagonistic effects. However, targeted drugs can be applied sequentially after chemotherapy. Targeted therapy can also be applied in first line to those adenocarcinoma patients who cannot tolerate chemotherapy and have EGFR mutations.
The diagnosis of small isolated nodules in the lungs is a difficult problem. Once small nodules are found in the lungs during physical examination, one should seek further examination and analysis by an experienced specialist, and if the possibility of malignancy is high, one should choose thoracoscopy and minimally invasive surgery to do the corresponding follow-up treatment and regular review according to pathological typing and staging.