To the best of my knowledge and understanding, I offer it to you for free, just so that you can face lung nodules correctly without being fooled!
Preface: The discovery of lung nodules is increasing, mainly due to the popularity of high-resolution CT, but also may be related to air pollution, the pace of life, poor lifestyle, mental stress, genetic predisposition and many other factors. However, because the current lung cancer treatment guidelines lag behind clinical practice, and because of the over-expansion of large hospitals and the irrational design of performance appraisal systems, excessive testing and over-treatment have proliferated, and there is obvious chaos in the diagnosis and treatment of lung nodules. From the clinical point of view, lung cancers with the manifestation of ground glass have distinctly different biological behaviors from traditional lung cancers, and their management may be biased and unfavorable to patients with lung nodules if they are treated with reference to the traditional view of lung cancer. In this paper, from the perspective of personal clinical experience and years of observation and summarization of the diagnosis and treatment of lung nodules, we try to make a relatively comprehensive summary for the reference of patients with lung nodules, and also for the exchange of fellow patients, who are currently trying to make their modest contribution to the diagnosis and treatment of lung nodules. This article only describes pure ground-glass nodules.
(1) Concept
Mulled-glass nodules in the lungs refer to clear or unclear intra-lung densities on CT, and their density is not enough to cover the traveling blood vessels and bronchial shadows. Its nature may be malignant tumor, benign tumor, inflammation, interstitial lung disease or intrapulmonary lymph nodes. Its pathologic basis is thickening of the alveolar septa or filling of part of the alveolar cavity with fluid, cells, or tissue debris. If the lesion contains a solid component, it is a mixed ground-glass nodule. Mixed ground-glass nodules that do not improve with anti-inflammatory therapy have a greater likelihood of being neoplastic in nature and should be treated more aggressively than pure ground-glass nodules.
(2) etiology
The official statement: the high incidence of lung nodules or tumors is the result of the combined effect of a variety of factors, the prevention of lung cancer, starting from smoking cessation. Currently more popular saying is three haze five gas, including haze, smoke haze, psychological haze; atmospheric pollution, smoke pollution, kitchen fume gas pollution, gas pollution released by the decoration materials and love to sulk and so on. In terms of publicity, these can be noted, such as smoking cessation, such as attention to environmental remediation, improve air pollution, but also green water and green hills; such as improving the kitchen fume extraction equipment; such as delayed occupancy after the renovation and after the detection of professional organizations; such as all of us to perform good deeds to see the openness, less angry, etc., these are positive and beneficial, so we say, lung cancer can be prevented and controlled. But is it true that lung nodules and lung cancer are caused by these factors? Can lung cancer be prevented by paying attention to these aspects? Personally, I was always skeptical, but I couldn't figure out why. Later on, I read an article entitled The Origin of Lung Grinding Glass Nodules (Prof. Sun Xiwen), which also analyzed the causes of lung cancer in terms of smoking, oil fumes, environmental pollution, lifestyle and heredity, and I was skeptical about it. Such a big-name professor also thinks that these reasons are not necessarily the real reason, so I will say my own opinion here: in fact, it is difficult to explain the occurrence of lung glass nodules or lung cancer by a single factor, my guess is: the extensive use of pesticides, the widespread use of genetically modified foods and their products, the pollution of decorative materials, the lack of rest due to work pressure, the exhaust of automobiles and the atmospheric pollution, the increase of psychological problems, the increase in the number of people with lung cancer, and the increase in the number of people with lung cancer, the increase in the number of people with lung cancer. I think it is the result of a combination of factors, such as the widespread use of pesticides, pesticide use, the increasing number of psychological problems, and genetic susceptibility. The widespread use of pesticides, genetically modified foods and their products may be important factors. Their toxic effects on the organism are certainly experienced for decades or affect a certain generation. Now when you go to the field and look at a small piece of land with whole bags of fertilizers waiting to be applied to the ground, won't they have an effect on the organism? Though the process may be long. When I was a child, the wow sound in the field is now gone, before your generation hoeing is an important element, and now there is no need, the medicine is sprayed, not to grow grass, the medicine to the soil, year after year in the use of, they will always be in their own way back to us!
(C) Pathology
First, let's look at a diagram, this is the general classification, firstly, pre-invasive lesions (including atypical adenomatous hyperplasia and adenocarcinoma in situ), followed by micro-invasive adenocarcinomas (adnexal growths predominantly), and then again invasive adenocarcinomas (with adnexal growths, follicular growths, and papillary or micro-papillary growths):<
Atypical adenomatous hyperplasia (AAH)
Pathological features: Usually 0.5 cm (not absolute), can be a single or multiple isolated foci of tumor cells along the alveolar wall in an appressed growth, with a continuity with the surrounding normal lung tissues, with mildly - moderately atypical cells, arranged in a relatively small number. The cells are mildly to moderately atypical, loosely arranged, with inter-cellular fissures; growth is very slow;
Note: AAH and AIS are a continuum, and it is sometimes difficult to differentiate them on the basis of cytology alone
It can be interpreted as: the cells are not in a normal form, but not yet in a typical form. : the cells are no longer in normal form, but typical cancer cells have not been seen yet, it is a precancerous lesion; it can be observed without surgery, and if surgery is performed due to the inability to exclude invasive lesions, only local excision will be sufficient, and there will be no recurrence or metastasis after excision.
Adenocarcinoma in situ (AIS)
Pathological features: Tumor cells grow strictly along the pre-existing alveolar structures (adherent growth), and there is a lack of mesenchymal, vascular and pleural invasion. It differs from AAH in increased cell density, lack of interstitial space between cells, and a very clear boundary with the surrounding normal lung tissue.AIS is classified as non-mucinous or mucinous, with the latter being extremely rare, and may be pure or mixed ground-glass nodules (with high relative density) up to 2 cm in size and slow-growing; foci increase in size or density, and may progress up to 10 mm towards invasive adenocarcinoma; mucinous AIS usually presents as solid or mostly solid tumors. solid or mostly solid lesions
Can be interpreted as: it is already lung cancer, the cancer cells are seen, but limited and have not broken through the alveolar wall; it can be observed without surgery, and if surgery is performed because invasive lesions cannot be excluded, local excision is sufficient, and there will not be recurrence or metastasis after excision.
Microinvasive adenocarcinoma (MIA)
Pathological features: it is a small, isolated adenocarcinoma (3 cm) with predominantly adherent growth, with a maximal diameter of infiltration of 0.5 cm in any one lesion; it usually presents as a partially solid nodule, i.e., with a gross glass component. with a 5-mm solid zone in the center.
It can be interpreted as: it is already lung cancer and there is infiltration (it will invade outward), but the distance is still short and it will not metastasize far away. Surgical resection is needed; sublobar resection (wedge resection or segmental resection) is possible; there is almost no recurrence or metastasis after resection.
Infiltrate adenocarcinoma (IAC)
Pathological features: tumor infiltrating foci with a maximal diameter of 0.5 cm. It is divided into: 1. predominantly invasive adenocarcinoma with adherent wall-like growth (LPA): it has a better prognosis than other histological subtypes of predominantly invasive adenocarcinomas.stage I. The prognosis of LPA is better than other subtypes. The 5-year recurrence-free survival rate of LPA reaches 90%; 2. vesicular predominantly invasive adenocarcinoma: round or ovoid adenoid configuration, and the glandular lumen or tumor cells may contain mucus; 3. papillary predominantly invasive adenocarcinoma; 4. micropapillary predominantly invasive adenocarcinoma: this type has strong invasive behavior and is prone to early metastasis. As with solid-predominant adenocarcinoma, the prognosis is poor; 5. solid-predominant invasive adenocarcinoma; 6. invasive adenocarcinoma variant: rare, omitted here.
Can be interpreted as: our usual or previous lung cancer, with relatively high malignancy and risk of recurrence or metastasis; requires active surgical treatment.
It is important to note that pure ground-glass nodules can be any of the above AAH, AIS, MIA, and invasive adenocarcinomas (wall-growth type). Of course the vast majority are adenomatous atypical hyperplasia or adenocarcinoma in situ, both of which are pre-invasive lesions that are not risky and may not even require surgery or intervention if they can be identified preoperatively. In the case of minimally invasive adenocarcinoma, local excision may also be sufficient to achieve the goal of cure. If it is really invasive adenocarcinoma with wall growth, although it meets the pathological manifestation of invasive, but still no metastatic case has ever been found, that is to say, it is still basically curable after surgical resection treatment.
(4) Clinical manifestations
Lung ground-glass nodules are unintentionally detected during examination or physical examination without clinical symptoms. Some people have chest tightness or coughing discomfort and go to the examination to find ground-glass nodules, and the symptoms are not caused by the nodule. Of course, if the nodule is quite large, we can't rule out the possibility that it may be slightly symptomatic, such as a cough.
(E) Ancillary tests
For pulmonary ground-glass nodules, the most important test is CT scanning of the chest, and if the nodule is small and the details are not clear, then target scanning and reconstruction of the lobe in which the lesion is located can be added. It can show the shape of the lesion, its margins, and its relationship with the surrounding blood vessels and bronchi from all directions. It is important to note that non-thin-layer CT scans cannot accurately diagnose ground-glass nodules; for example, a 5-mm-layer-thick scan may scan only the peripheral area of a nodule, which may show a ground-glass shadow, but a thin-layer scan will show a solid nodule.
It is also important to note that enhanced CT and PET-CT have no diagnostic value for purely ground-glass nodules, as they are both based on the abundance of blood supply to the lesion, but purely ground-glass nodules are unlikely to have an abundance of blood supply that is significant enough to be visualized with contrast.
Plain bronchoscopy is also generally not able to reach where the ground-glass nodules are located, and is of similarly limited significance.
Blood tests for tumor markers are essentially unlikely to be abnormal. However, if the tumor markers are normal, there is no way to rule out that the lesion is an early stage lung cancer.
(6) Judgment of benign and malignant
Milled glass nodules cannot be equated with lung cancer, but from the clinical observation and summarization of thousands of cases of imaging data, the following points are more reliable:
In short, some of the milled glass nodules of the lungs are early-stage lung cancers, and some are not, and the two are not equivalent.
(7) Follow-up strategy
At present, the most inconsistent and chaotic is the pure grinding glass nodule as the manifestation of lung cancer, some let observation, some let surgery, some let wedge cut, some let segmental cut, and some let lobe cut, and even let the patient take genetic testing or targeted drugs or chemotherapy after surgery. Since the pure ground glass manifestations are all early lung cancer, and the clinic has never encountered any metastasis, the follow-up observation is certainly safe.
1, 1 cm or less of pure ground glass nodules should not be opened, half a year or a year of review (personal recommendation should be half a year). 1-2 cm of pure ground glass nodules depending on the location of the nodule, if you can wedge cut the part of the wedge is recommended; wedge cut the deep, but can be resected in the segmental part of the lung is recommended to segmental cut; if you can only lobectomy part of the lung is recommended to not cut (because the follow-up to the part of the lobectomy is not enough), then it is recommended to cut. Do not cut first (because the follow-up to the progress or out of the realistic component, anyway, is a lobectomy, late 2 years, 3 years, maybe some can be late 4-5 years to open, at least these years of better maintenance of lung function, and no surgery caused by the corresponding discomfort). The reason why the site that can be sublobar cut is again recommended is to preserve more lung tissue, early cut can be sublobar, and if you progress the cut you may get a lobe, so cut early. Moreover, the lesion can grow to 1-2 centimeters, the next time period when (a few years not necessarily) will certainly continue to progress, sooner or later is to cut. If the lesion is larger than 2 cm, although some experts believe that it is safe to continue to follow up, but my opinion can be opened, as mentioned earlier, the lesion always grows from small to large, since the discovery of the lesion is already more than 2 centimeters, and then follow up, sooner or later, it is necessary to progress, and the current refers to the South Asian lobectomy of the primary condition is less than 2 centimeters, so it is recommended to find that can be cut. However, I personally think that as long as it is pure ground glass nodules, still do not recommend lobectomy, can wedge cut and segmental cut can still choose sublobar (this is not in line with the guidelines, but clinical point of view, the effect is no difference, because the pure grinding has never been found metastasis). To summarize, this is the opinion of the following table:
2. Follow-up of progressed pure ground-glass nodules, the increase in density or the emergence of a realistic component that requires immediate intervention, while only the expansion of the scope, it is still safe to follow, specifically to how much should be operated on, refer to the content of the previous paragraph. Relatively speaking, those that have progressed over the course of follow-up can be a little more aggressive, because if they are already increasing in size, they will always continue to do so if they wait.
3. The intervention for multiple ground-glass nodules should be more conservative, because if you cut the current lesion, there will be new lesions that will grow or small ones that will get bigger, so for the multiple ones, they should be followed up until there is a realistic component, that is to say, there is a risk of not intervening, and then they have to be dealt with, and wedge resection or segmental resection is the preferred option. Really, if there are too many, then only deal with the primary lesions, and take care of the others that you can, and leave the secondary lesions that you can't take care of for observation and follow-up.
(8) Surgery
Let's first look at the recommendations of the lung cancer treatment guidelines for surgical procedures:
The article says, "Anatomical pneumonectomy is still the standard procedure, and anatomical lobectomy is still the standard procedure for early-stage lung cancer". This is a basic, so under this guideline, as long as the pathology is lung cancer, including adenocarcinoma in situ, microinfiltrative adenocarcinoma and infiltrative adenocarcinoma, the doctor can do lobectomy if it does not violate the principle, and it is OK, and it is even not wrong to perform lobectomy in part of the atypical hyperplasia if the location is not good or if it has already existed persistently through the follow up and it is not possible to exclude the tumor. This is exactly what leads to the current lung grinding glass nodules pathologically early lung cancer when the chaos is at the root. If (a) lung function can not tolerate lobectomy; (b) the diameter is less than 2 cm and has one of the "adenocarcinoma in situ or microinvasive adenocarcinoma, ground glass component is more than 50%, doubling time is more than 400 days", you can choose to sub-lobar resection, compared with wedge resection is more recommended segmental resection. But I've always wondered, is segmental resection necessary? Is it a procedure worth promoting? If segmental resection is as effective as wedge resection, is it really appropriate to make an unnecessary surgery into a fine product, in terms of trauma to the patient and the expenditure of health insurance funds, as well as in terms of possible accidents and complications? If the lesion is indeed only localized, there is no airspace dissemination in the lungs, and there are no hilar or mediastinal lymph node metastases or lymph node metastases in groups 12-14, then there is no difference in terms of therapeutic outcome among the three types of surgical resection, namely, wedge resection, segmental resection, or lobectomy. However, in our hospital group, when all single-port thoracoscopic surgery, the current wedge resection surgery is roughly 5-10 minutes, segmental resection is about 1.5-2.0 hours, and lobectomy is about 1-1.5 hours, which may increase if the visualization is not good or the lymph nodes are more difficult to be divided, and it may be shorter if the anatomical development is very good. The cost of the surgery is then about 20,000 for wedge resection, 45,000-50,000 for lung segmentation, and 40,000 for lobes (because more instruments are used for lung segmentation). Post-op hospitalization is 1-3 days after wedge resection, 5-7 days for lung segments, and almost 5-7 days for lobes. People do the math on which is preferable when the treatment is equally effective and there is little risk wedge resection is a big risk. If the preoperative diagnosis of early lung cancer is a pure mill glass nodule on imaging (whether it is AAH, AIS or MIA, or even invasive adenocarcinoma, as long as it is a pure mill on imaging, and the pure mill never encounters metastasis), then: if there is no metastasis in the pure mill, wedge resection is enough; if there is metastasis in the pure mill, lung segmentation is not enough anyway! Segmental resection is suitable for the following situations: if the wedge cut is extensive, basically close to the extent of the lung segment to be resected, it is better to do segmental resection to stretch the remaining lung; if the location is near the segmental gate of the lung segment, it is more difficult to reach the wedge cut, whereas segmental resection can be sure to cut in; if the lung function is poor in solid nodules, lung segmentation is also a compromise procedure. There is also the case that wedge dissection sometimes does not always allow the lesion to be in the center of the dissection specimen, but when combined with subsegmental resection it is very good, always allowing the lesion to be in the center of the dissection specimen, ensuring the margins of the dissection. (Practically speaking, I wonder what is the point of the dissection ratio, if negative, being more than 2 cm away, or larger than the diameter of the lesion if there is no intraluminal dissemination).
(IX) postoperative adjuvant treatment issues
When the post-surgical pathology report of pure ground-glass nodules is adenomatous atypical hyperplasia, adenocarcinoma in situ, or minimally invasive adenocarcinoma, because there is no risk of metastatic recurrence, there is no need for genetic testing with the corresponding targeted therapy, and there is no need for radiotherapy, chemotherapy or immunotherapy. The treatment of traditional Chinese medicine can be used in terms of physical conditioning, but there is currently no conclusive evidence of a significant effect in terms of follow-up of tumorigenesis. Although I have always felt that the ultimate way out of tumor treatment is in traditional Chinese medicine, because traditional Chinese medicine emphasizes the unity of heaven and man, and the interactions of all things, there is this disease, there must be a drug that can overcome it, and although there are cases in which traditional Chinese medicine has cured tumors, the current level of traditional Chinese medicine is still not able to massively reproduce the successful cases of treatment.
In the case of invasive adenocarcinoma, pure ground-glass nodules are basically only likely to be invasive adenocarcinoma with adherent growth. Conventional postoperative adjuvant therapy for lung cancer is mainly used in stage 2A and later cases and some stage 1B cases with high-risk factors, and postoperative adjuvant therapy is clearly not needed for stage 1A in early lung cancer.
Therefore, all the lung cancers with ground-glass nodules are at stage 1A, and even if they are invasive adenocarcinoma, they do not need postoperative adjuvant therapy. In the case of multiple primary ground-glass lung cancers, since they are all stage 1A when evaluated individually, they should likewise not require postoperative adjuvant therapy. Moreover, this type of lung cancer is mostly inert, and there are studies showing that chemotherapy is ineffective in ground-glass nodular lung cancer:
Adjuvant therapies currently in use in the clinic, including chemotherapy, targeted therapies, and immunotherapies, are all aimed at advanced lung cancers or those with a greater risk of recurrence and metastasis in the mid-term considered after surgery. It is obviously absurd to use them on patients with early stage lung cancer, or to treat multiple primary lung cancers with ground glass nodules that cannot be removed cleanly by surgery with the same methods used to deal with advanced stage lung cancer. How much time for treatment? How many cycles? How is it assessed? Can you say that the fact that a patient lives more than 5 years is due to the efficacy of these systemic therapeutic measures, when you can go a long time without progression without drugs just by observing pure grinding?
(10) Multi-primary cancers
In recent years, we have encountered cases, especially early stage lung cancers presenting as ground-glass nodules, with a very high proportion of multi-primary cancers, including both synchronous and heterochronous ones. Their biological behavior is obviously different from that of lung cancer in the traditional sense. They are called lazy cancers, which means that they develop very slowly, and the 5-year survival rate can reach more than 95% without intervention (I didn't check the literature, I just estimate it myself), and the prognosis is significantly better than that of traditional lung cancers if timely intervention is made.
The current guideline for multiple primary cancers is just a general outline, an expression of principle, and there are too many variables on how to treat specific cases. For example, how to determine the main lesion? Is it according to density, or according to size? What kind of primary lesions need treatment intervention? Is there a difference between 1, 2, and N secondary lesions? What should happen to the secondary lesions after the primary lesion is treated? Follow-up is recommended, but what if it progresses? Is reoperation for patients with good lung function, and chemotherapy, targeted therapy, or immunotherapy for poor lung function? After the primary lesion is identified as lung cancer, is it necessary to determine whether there is a target through genetic testing, and is it feasible to use targeted and immunotherapy for the secondary lesion? How effective are they? Can the secondary lesion be cured? If not, is it meaningful or valuable to treat it accordingly ......
Multiple solid or multiple mixed ground-glass lesions can be dealt with according to the traditional opinion. The multiple primary ground glass nodules we are going to discuss in this article are all purely ground, which is the most messy area. My considerations are:
1. The primary lesion is more than 1 cm:
2. All lesions are sub-centimeter in size:
At this point, if the individual is 8 or 9 millimeters, and others are 5-7 millimeters, and still others even smaller at less than 5 millimeters, then we cannot assume that the The largest is the main lesion and is not at a stage where it should be treated for intervention (for multiple primary cancers). In my opinion in this case it is not clinically worthwhile to perform surgical resection of the larger nodes, or even segmental or lobectomy (in order to remove other nodes in the same lobe as the so-called main lesion), because it is still a lot of slightly smaller pure ground-glass nodes, which still have to be followed up anyway, and which are still worrying, and which may still be progressing. And if you don't cut it, it also progresses very slowly or doesn't progress, and the surgery doesn't achieve the goal of controlling the disease and curing it, but you experience trauma and loss of lung function.
(XI) Follow-up after surgery for ground-glass lung cancer
As we know, the examination found that ground-glass nodules need to be reviewed regularly, and if there is progress to be operated. The follow-up interval depends on the size and density of the nodule. If it is a sub-centimeter nodule (multiple or single can be), every 6-12 months to review, the results found to have increased in size, up to 2 cm or more, to be resected lung segments, pathologically confirmed lung cancer. Then, according to the current lung cancer guideline (there is no specific guideline for lung cancer with ground-glass nodules), how to follow up:
See? Review every 3-6 months for the first 3 years, or every 3 months if your doctor chooses to do so, than the pre-surgery checkups! Do you think this guideline can be used for ground glass lung cancer? So my opinion is: those who no longer have lesions after surgery, annual recheck (in fact, it can be rechecked for 2 years, but the physical examination of the unit of the normal population is once a year, does a postoperative lung cancer patient still check once every 2 years, it always seems to be wrong); those who still have secondary lesions in the postoperative period, depending on the size of the lesions, check every half a year or a year, until forever! If it is not for physical examination, only for lung cancer has no metastasis, then there is no need to check the color ultrasound, CT, MRI or PET-CT of other organs, and the review of CT of lungs is also for observing whether there is any progression of the surviving pure abrasive nodules.
With so many cases in China, lung cancer with ground-glass nodules is a completely new field compared with traditional lung cancer, and we really need to do more work to provide our own insights and lead the diagnosis, treatment, and basic research of ground-glass nodules worldwide, because we have a large number of patients and a large volume! The development of national treatment guidelines specifically for pulmonary ground-glass nodules is a matter of urgency!
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