Ye Jianming talks about pulmonary grinding: guidelines for the treatment of pulmonary grinding glass nodules (personal edition)

As far as I know, I provide it to you for free, just to let you face pulmonary nodules correctly and not be fooled!

The discovery of pulmonary nodules is increasing, which is mainly due to the popularity of high-resolution CT, and may also be related to air pollution, pace of life, unhealthy lifestyle, mental stress, genetic susceptibility and many other comprehensive factors. However, because the current guidelines for the treatment of lung cancer lag behind the clinic, and because of the over-expansion of large hospitals and unreasonable system design of performance appraisal, over-examination and over-treatment are rampant, there is obvious chaos in the field of diagnosis and treatment of pulmonary nodules. Clinically, the biological behavior of lung cancer expressed by ground glass is obviously different from that of traditional lung cancer. If we refer to the traditional view of lung cancer, it may bring deviation, which is not conducive to patients with pulmonary nodules. From the perspective of personal clinical experience and observation and summary of diagnosis and treatment of pulmonary nodules for many years, this paper tries to make a relatively comprehensive summary for the reference of patients with pulmonary nodules and for communication with others. At present, I want to do my bit for the diagnosis and treatment of pulmonary nodules. This paper only describes pure wool glass nodules.

(A) the concept

Ground-glass nodule of lung refers to the shadow of increased lung density with clear or unclear boundary on CT, and its lesion density is not enough to cover the shadow of blood vessels and bronchi running in it. Its nature may be malignant tumor, benign tumor, inflammation, interstitial lung disease or intrapulmonary lymph nodes. Its pathological basis is thickening of alveolar septa or partial alveolar cavities filled with liquid, cells or tissue fragments. If the lesion contains solid components, it is a mixed ground-glass nodule. If the anti-inflammatory treatment does not improve, it is likely to be tumor-like, and the treatment is more active than the simple ground glass nodule.

(II) Etiology

Officials believe that the high incidence of pulmonary nodules or tumors is the result of a combination of factors, and the prevention of lung cancer begins with quitting smoking. At present, the popular saying is three haze and five qi, including haze, haze and psychological haze; Air pollution, smoke pollution, kitchen fume pollution, gas pollution released by decoration materials, sulking. For mass propaganda, these can be noticed, such as quitting smoking, such as paying attention to environmental improvement, improving air pollution, and making everyone green and green; For example, improve the equipment for absorbing and exhausting oil smoke in the kitchen; For example, the delay in occupancy after renovation is detected by professional institutions; For example, everyone should do good deeds, be open-minded and be less angry. These are all positive and beneficial, so we say that lung cancer can be prevented and controlled. But are pulmonary nodules and lung cancer really caused by these factors? Can paying attention to these aspects prevent lung cancer? Personally, I am often skeptical, but I don't understand why. Later, I saw an article "The Origin of Ground Glass Nodules in the Lung" (Professor Sun Xiwen), which also analyzed smoking, lampblack, environmental pollution, lifestyle and heredity. In short, I am skeptical. Such a famous professor also thinks that these reasons are not necessarily the real reasons, so let's talk about his own views here: in fact, it is difficult to explain the causes of ground glass nodules or lung cancer with a single factor. My guess is that the widespread use of pesticides, the wide application of genetically modified foods and their products, the pollution of decoration materials, the lack of work pressure, the fuel and air pollution of automobile exhaust, psychological problems and the increase of genetic susceptibility are the results of a series of comprehensive factors. Among them, the widespread use of pesticides and genetically modified foods and their products may be an important factor. Their toxic effects on the body must have lasted for decades or affected a certain generation. Now go to the field and see, in a small field, bags of fertilizer are waiting to be applied to the field. Won't they affect the body? Although this process may be very long. When I was a child, the wow in the field is gone now. Weeding used to be an important part of your generation, but now it is not needed. When the medicine is sprayed, it will not grow grass. All the medicines are in the soil and are used every year. They always give back to us in their own way!

(3) Pathology

Let's look at a picture first, which is a general classification. First, pre-invasive lesions (including atypical adenomatous hyperplasia and adenocarcinoma in situ), followed by micro-invasive adenocarcinoma (mainly adherent growth), and then invasive adenocarcinoma (adherent growth, acinar growth and papillary or micropapillary growth):

Atypical adenomatous hyperplasia (AAH)

Pathological features: usually 0.5 cm (non-absolute), tumor cells with single or multiple isolated lesions can grow along the alveolar wall, continuous with the surrounding normal lung tissue, with mild to moderate atypical cells, loose arrangement and cracks between cells; Growth is very slow;

Note: AAH and AIS can be a continuous process, and sometimes it is difficult to distinguish them only by cytology.

It can be understood as follows: the cell morphology is abnormal, but typical cancer cells have not yet been seen, which is precancerous lesions; It can be observed that there is no operation. If surgery is performed because invasive lesions cannot be ruled out, only local resection is needed, and there will be no recurrence or metastasis after resection.

Adenocarcinoma in situ

Pathological features: tumor cells grow strictly along the pre-existing alveolar structure (adherent growth), lacking interstitial, vascular and pleural infiltration. The difference from AAH is that the cell density increases, there is no gap between cells, and the boundary with the surrounding normal lung tissue is clear. AIS can be divided into two types: non-mucinous and mucinous. The latter is extremely rare, which can be pure ground glass nodules or mixed ground glass nodules (relatively high density), with a size of 2cm and slow growth. The focus is enlarged or the density is increased, which can progress to invasive adenocarcinoma10 mm; ; Mucinous AIS usually presents as solid or mostly solid lesions.

It can be understood as: it is lung cancer, and cancer cells are seen, but they are limited and have not broken through the alveolar wall; It can be observed that there is no operation. If surgery is performed because invasive lesions cannot be ruled out, local resection is enough, and there will be no recurrence or metastasis after resection.

Microinvasive adenocarcinoma

Pathological features: small solitary adenocarcinoma (3cm) with adherent growth, and the largest diameter of any lesion infiltration is 0.5cm；; ; Usually it is a partial solid nodule, that is, there is a 5mm solid area in the center of the ground glass component.

It can be understood as: it is already lung cancer, with infiltration (it will invade outwards), but the distance is still very short and it will not metastasize in the distance. Need surgical resection; Lobectomy (wedge resection or segmental resection) can be performed; There was almost no recurrence or metastasis after resection.

Invasive adenocarcinoma

Pathological features: The largest diameter of tumor infiltration focus is 0.5cm, which is divided into: 1, and adhesive invasive adenocarcinoma (LPA): Compared with other histological subtypes, its prognosis is better. The 5-year recurrence-free survival rate of stage ⅰ LPA was 90%. 2. Invasive adenocarcinoma dominated by acinus: round or oval glandular structure with mucus or tumor cells in the glandular cavity; 3. Invasive adenocarcinoma with papillary structure; 4. Invasive adenocarcinoma dominated by micropapillary: This type is aggressive and easy to metastasize early. Like solid adenocarcinoma, the prognosis is very poor; 5. Solid invasive adenocarcinoma; 6. Abnormal development of invasive gonadal carcinogenesis: rare, omitted here.

It can be understood as follows: lung cancer, which we usually or are used to talking about, has a high degree of malignancy and is at risk of recurrence or metastasis; Active surgical treatment is needed.

It should be noted that pure ground-glass nodules can be any of the above AAH, AIS, MIA and invasive adenocarcinoma (adherent growth type). Of course, most of them are adenomatous atypical hyperplasia or adenocarcinoma in situ, both of which belong to pre-invasive lesions and there is no risk. If the diagnosis can be made before operation, there may be no need for surgery or intervention. If it is a micro-invasive adenocarcinoma, it can be cured by local resection. If it is the adherent growth type of invasive adenocarcinoma, although it conforms to the pathological manifestations of infiltration, no cases of metastasis have been found, indicating that surgical resection can basically be cured.

(4) Clinical manifestations

Ground-glass nodules in the lungs were found during unintentional examination or physical examination, and there were no clinical symptoms. Some people have chest tightness or cough discomfort and find ground glass nodules. The symptoms are not caused by nodules. Of course, if it is a large ground glass nodule, it does not rule out that there may be mild symptoms, such as cough.

(5) Auxiliary inspection

For ground-glass pulmonary nodules, the most important examination method is chest CT plain scan. If the nodule is small and the details are unclear, targeted scanning and reconstruction of the lung lobe where the lesion is located can be increased. It can show the shape, edge and relationship with peripheral blood vessels and bronchus of the lesion from all directions. It should be noted that non-thin scan CT can not accurately diagnose ground glass nodules. For example, a 5 mm thick scan may only scan the peripheral area of the nodule and may show ground glass shadow, but a thin-layer scan will show solid nodules.

In addition, it should be noted that enhanced CT and PET-CT have no diagnostic value for pure ground-glass nodules, because they are all based on whether the blood supply of the lesion is rich or not, while pure ground-glass nodules are basically not rich enough for contrast media to display.

Ordinary bronchoscopy can't reach the position of ground glass nodules generally, and its significance is limited.

There is basically no abnormality in the blood test tumor index. However, if the tumor index is normal, it cannot be used as a basis for excluding the lesion as early lung cancer.

(6) the judgment of benign and malignant.

Ground-glass nodules cannot be equated with lung cancer, but from the clinical observation and the summary of thousands of imaging data, the following points are more reliable:

In short, some of the ground glass nodules in the lungs are early lung cancer, and some are not. The two cannot be equated.

(vii) Follow-up strategy

At present, the most inconsistent and confusing is the lung cancer manifested by pure ground glass nodules, including observation, surgery, wedge cutting, segmental cutting, Yuzryha cutting, and even allowing patients to undergo genetic testing or take targeted drugs or chemotherapy after surgery. Because pure ground glass shows early lung cancer, it has never encountered metastasis in clinic, so follow-up observation is definitely safe. So:

Don't open the pure ground glass nodules below 1 and 1 cm, and review them in half a year or one year (half a year is personally recommended). 1-2 cm pure ground glass nodule depends on the nodule position. Wedge cutting is recommended if it can be cut. The wedge-shaped incision is deep, but it is recommended to cut the part that can be cut in sections. If only part of the lung can be removed, it is recommended not to remove it first (because the follow-up shows that there is progress or realistic components, it is still lobectomy anyway, with a delay of 2 or 3 years, and some may be delayed by 4-5 years. At least in recent years, lung function has been well maintained, and there is no corresponding discomfort caused by surgery. It is suggested to remove the resectable part of the lung in order to preserve more lung tissue. Cut the lung as soon as possible, if it is in progress, you may get the lung, so cut it early. Moreover, the lesion can grow to 1-2 cm, and it will definitely continue to progress in the next period of time (not necessarily a few years), and it will be cut sooner or later. If the lesion is larger than 2 cm, although some experts think that safe follow-up can be continued, my opinion can be opened. As mentioned earlier, the lesions always change from small to large. Since it was more than 2 cm when it was found, it will improve sooner or later if it is followed up. However, at present, the primary condition of lobectomy guidelines is less than 2 cm, so it is recommended to cut it when found. However, personally, as long as it is pure ground glass nodules, it is still not recommended to remove them all. If wedge-shaped segments can be cut, you can still choose lobulated ones (this does not conform to the guidelines, but the clinical effect is no different, because pure grinding has never found metastasis). To sum up, it is the opinion in the following table:

2. Follow up the progress of pure ground glass nodules. If the density increases or the actual composition needs immediate intervention, it can still be safely followed up only if the scope is expanded. See the previous paragraph for details. Relatively speaking, those who have made progress after follow-up can be positive, because if they have increased, they will continue to increase after waiting.

3. The intervention of multiple ground-glass nodules should be conservative, because if you remove the current lesions, new lesions will grow out or small lesions will grow out, so for multiple ones, follow-up should be made to have realistic components, that is to say, if re-intervention is dangerous, it must be handled, and wedge resection or pneumonectomy is the first choice. If it is really too much, then only deal with the main lesions and take care of others. For the secondary lesions that cannot be taken care of, keep observation and follow-up.

(8) Surgical treatment

Let's first look at the recommendations of the Guidelines for the Treatment of Lung Cancer on surgical methods:

The article said that "anatomical pneumonectomy is still the standard operation, and the standard operation for early lung cancer is still anatomical lobectomy". This is basic, so under the guidance of this guide, as long as the pathology is lung cancer, including carcinoma in situ, micro-invasive adenocarcinoma and invasive adenocarcinoma, it is ok for doctors to perform lobectomy. Even for some atypical hyperplasia, if the location is not good or the tumor cannot be ruled out after follow-up, there is nothing wrong with doing lobectomy. This is the fundamental reason for the pathological confusion of ground-glass nodules in early lung cancer. If (1) lung function cannot tolerate lobectomy; (2) If the diameter is less than 2 cm, there is one of "carcinoma in situ or slightly invasive adenocarcinoma, ground glass content is more than 50%, and doubling time is more than 400 days", lobectomy can be selected, and segmental resection is more recommended than wedge resection. But I've been thinking, is segmentation necessary? Is it a surgical method worth popularizing? If segmented cutting is as effective as wedge cutting, is it really appropriate to make an unnecessary operation into a boutique from the perspective of trauma to patients and medical insurance funds, as well as possible accidents and complications? If the lesion is indeed localized, there is no air cavity spread in the lung, no hilar and mediastinal lymph node metastasis, and there is no lymph node metastasis in the 12- 14 group, then there is no difference in the therapeutic effects of wedge resection, segmental resection or lobectomy. However, when performing single-hole thoracoscopic surgery in our hospital group, at present, wedge resection takes about 5- 10 minutes, segmental resection takes about 1.5-2.0 hours, and lobectomy takes about 1- 1.5 hours. If the exposure is poor or the lymph nodes are difficult to distinguish, they may be enlarged, and if the anatomy is well developed, they may be shorter. The operation cost is about 20,000 wedge resection, the lung segment is about 45,000-50,000, the lung lobe is about 40,000 (because there are many instruments used in the lung segment), and the postoperative hospitalization 1-3 days wedge resection, lung segment is 5-7 days, and lung lobe is almost 5-7 days. We calculate, in the case of the same treatment effect, which is the best, and the risk of wedge cutting is almost small. If the early lung cancer is diagnosed before operation, and the image is pure ground glass nodule (whether it is AAH, AIS or MIA, or even invasive adenocarcinoma, as long as the image is pure ground, pure ground never touches metastasis), then: if there is no pure ground, wedge-shaped cutting is enough; If there is pure grinding of transfer, the lung segment is not enough anyway! Segmental resection is suitable for the following situations: if wedge resection is relatively large, it is basically close to the scope of segmental resection, and it is better to stretch the lung after segmental resection; If the location is near the hilar lung segment, wedge-shaped cutting is difficult to reach, and the lung segment cutting can definitely be cut inside; If there are solid nodules with poor lung function, lung segment is also a compromise surgical method. On the other hand, sometimes the lesion may not be in the center of the specimen, but if the combined segmental resection is good, the lesion is always in the center of the specimen, so as to ensure the trimming (in fact, I also think that if there is no diffusion in the air cavity, if the tangential ratio is negative, the distance exceeds 2 cm or exceeds the diameter of the lesion, what's the point? )

(9) postoperative adjuvant therapy

When the postoperative pathological report shows that the pure ground glass nodule is adenomatous atypical hyperplasia, carcinoma in situ or micro-invasive adenocarcinoma, there is no risk of metastasis and recurrence, and there is no need for gene detection and corresponding targeted therapy, nor for radiotherapy, chemotherapy or immunotherapy. The treatment of traditional Chinese medicine can start with conditioning the body, but from the follow-up of tumor occurrence, there is no definite evidence that it has a significant effect. Although I have always felt that the ultimate way out for tumor treatment lies in Chinese medicine, because Chinese medicine pays attention to the unity of nature and man, and everything is born together. With this disease, there must be other drugs, and although there are cases of Chinese medicine curing tumors, the current level of Chinese medicine can not replicate successful cases on a large scale.

If it is an invasive adenocarcinoma, the pure ground glass nodule can only be an invasive adenocarcinoma that grows on the wall. Traditional postoperative adjuvant therapy for lung cancer is mainly used for cases after stage 2A and some high-risk cases in stage 1B, and it is clear that postoperative adjuvant therapy is not needed for early lung cancer1a.

Therefore, ground-glass nodular lung cancer is all in 1A stage, and even invasive adenocarcinoma does not need postoperative adjuvant treatment. If it is multiple primary ground-glass lung cancer, postoperative adjuvant therapy should not be needed because the single evaluation is also 1A stage. What's more, this kind of lung cancer is mostly inert, and studies have shown that chemotherapy is ineffective for ground-glass nodule lung cancer:

At present, the adjuvant therapies used in clinic, including chemotherapy, targeted therapy and immunotherapy, are all aimed at advanced lung cancer, or the risk of recurrence and metastasis in the middle after operation is high. It is obviously absurd to use them in patients with early lung cancer or to treat patients with advanced lung cancer with multiple primary lung cancer, which cannot be removed by surgery. How long will the treatment last? How many cycles? How to evaluate? It is impossible to make long-term progress by observing pure grinding without medication. Can you say that patients have lived more than five years because of these systematic treatment measures?

(x) Questions about multiple primary cancers.

The cases encountered in recent years, especially the early lung cancer with ground-glass nodules, have a very high proportion of multiple primary diseases, including simultaneity and metachronous. Their biological behavior is obviously different from traditional lung cancer. It is called lazy cancer in the industry, which means that it develops very slowly. Even without intervention, the 5-year survival rate can basically reach over 95% (I estimate it casually without consulting the literature). If timely intervention, the prognosis is obviously better than that of traditional lung cancer.

The description of multiple primary cancers in the current guidelines is only a rough outline, and it is a statement in principle. How to treat specific cases is too variable. For example: how to determine the main lesions? By density or by size? What major diseases need treatment and intervention? Is there a difference between the secondary focus 1, 2, n? After the primary lesion is treated, what about the secondary lesion? Suggest follow-up, but how is it going? Are patients with good lung function reoperated, and those with poor lung function are chemotherapy, targeted therapy or immunotherapy? After the primary lesion is identified as lung cancer, is it necessary to determine whether there is targeting through genetic testing, and is it feasible to target the secondary lesion? What's the effect? Can secondary lesions be cured? If not, is it meaningful or valuable to give corresponding treatment? ...

More solid or mixed ground glass can be treated according to the traditional view. Many of the primary ground glass nodules we are going to discuss in this paper are pure grinding, which is the most chaotic field. My consideration is:

1, the main lesion is greater than1cm;

2. All the damages are below cm in size:

At this time, if the individual is 8, 9 mm, others are 5-7 mm, and some smaller ones are smaller than 5 mm, then we can't think that the biggest one is the main lesion and it is not in the stage of interventional therapy (for multiple primary cancers). Personal opinion: In this case, surgical resection of larger nodules, or even resection of lung segments or lobes (in order to simultaneously remove other nodules in the same lobe as the so-called main lesions) has no clinical value, because there are many smaller pure ground glass nodules that still need follow-up, worry and progress. Regardless of it, progress is slow or not. Surgery did not achieve the goal of controlling and curing the disease, but experienced trauma and lost lung function.

(1 1) postoperative follow-up of ground glass lung cancer

We know that the inspection found ground glass nodules, which need regular review, and surgery is needed if there is progress. The follow-up interval depends on the size and density of nodules. If it is a sub-centimeter nodule (multiple or single), it will be reexamined every 6- 12 months, and the result shows that it is larger than 2 cm, then it will be removed and pathologically diagnosed as lung cancer. Then follow-up suggests how to follow up according to the current guidelines for lung cancer (there is no specific guideline for ground glass nodule lung cancer):

Did you get a look at him? Check every 3-6 months for the first 3 years. If doctors choose once every three months, they will be more diligent than before the operation! Do you think this guide can be used for ground glass lung cancer? So my opinion is: if there is no pathological change after operation, it can be rechecked once a year (in fact, it can be rechecked once every two years, but the physical examination of normal people is once a year). Is it wrong for patients with lung cancer to have an examination every two years after operation? ); If there are still lesions after surgery, check them once every six months or once a year, depending on the size of the lesions, until forever! If it is not a physical examination, but a metastasis of lung cancer, there is no need to check the color Doppler ultrasound, CT, MRI or PET-CT of other organs. The CT reexamination of lung is only to observe the progress of the remaining pure grinding nodules.

There are many cases of ground-glass nodular lung cancer in China, which is a brand-new field compared with traditional lung cancer. We really need to do more work, put forward our own opinions and lead the diagnosis, treatment and basic research of ground glass nodules all over the world, because we have a large number of patients! There is an urgent need to formulate domestic treatment guidelines specifically for pulmonary ground glass nodules!

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