Introduction:
Neuroblastoma(neuroblastoma, NB) evolved from primitive neural crest cells, the most common primary site of the sympathetic chain and adrenal medulla. Different ages, tumor sites and different degrees of tissue differentiation make their biological characteristics and clinical manifestations very different, some of which can naturally subside or transform into benign tumors, but other patients are very refractory and have a poor prognosis. In the past 30 years, the prognosis of infants or early NB has improved significantly, but the prognosis of patients with advanced age is still very poor. There are many factors in NB that can affect prognosis, and age and stage are still the most important factors.
Cause:
(1) Causes of the disease
It is an embryonic tumor, mostly located in the cerebral hemisphere.
(two) pathogenesis
NB is derived from primitive pluripotent sympathetic nerve cells originating from neural crest, in the form of blue small round cells. Different degrees of differentiation, type and transition site of cells after neural crest migration form different normal tissues of sympathetic nervous system, including spinal sympathetic ganglia and adrenal chromaffin cells. The NB histological subtype is consistent with the normal differentiation model of the sympathetic nervous system. Classical pathological classification classifies NB into type 3, namely neuroblastoma, ganglion cell tumor, and ganglion cell tumor. These three types reflect the differentiation and maturation process of NB. A typical NB consists of consistent small cells, about 15% to 50% of cases, with eosinophilic neural fibers around the mother cells. Another fully differentiated, benign NB is a ganglioneuroma, composed of mature ganglion cells, neural fiber networks, and Schwann cells. Ganglioblastoma is between the first two and contains neuroblasts and ganglion cell components.
The Shimada classification combined with age divided the pathology into 4 subtypes and clinically divided into 2 groups. The four subtypes include NB (Schwannin less matrix type); GNB mixed type (matrix-rich); GN mature type and (3NB nodular type (including less matrix type and matrix rich type). The first 3 types represent NB The maturity process, while the last type is polyclonal. For NB, cell differentiation is divided into 3 levels, including undifferentiated, poorly differentiated, and differentiated; the mitotic index (MKI) of cells is also divided into low, medium, and high. Level 3. Shimada classifies the differentiation of tumor cells, mitotic index and age, and classifies NB into a good clinical prognosis group (FH) and a poor prognosis group (UFH):
1.FH includes the following types
(1) NB, MKI is low to moderate, age <1.5 years old.
(2) Differentiated NB, MKI is low, aged 1.5 to 5 years old.
(3) GNB hybrid type.
(4) GN.
2. UFH includes
(1) NB, MKI advanced.
(2) NB, MKI is intermediate, aged 1.5 to 5 years old.
(3) Undifferentiated or poorly differentiated NB, aged 1.5 to 5 years old.
(4) All NBs >5 years old.
(5) GNB nodule type.
In pathologically, in addition to HE staining, immunohistochemical examination can be performed to distinguish it from other small round cell tumors. The nerve specific esterase (NSE) is positive at NB, and a typical dense nucleus can be seen under electron microscope. The neurosecretory granules have microfilaments and microtubules arranged in parallel in the nerve fiber network.
symptom:
Clinical manifestations were associated with primary site, age, and stage. Sixty-five percent of the children had primary tumors in the abdomen. In older children, the primary adrenal gland accounted for 40%, while in infants, only 25%. Other common sites are the chest and neck. About 10% of cases have unclear primary sites. About 70% of NB develops before the age of 5, and very few develop after 10 years of age.
1. The most common symptoms of different parts of the mass are the masses in different parts.
(1) Primary in the abdomen: The sympathetic chain of the adrenal gland and the spine are common in the primary, and the symptoms usually appear when the mass is large. There may be abdominal pain, abdominal circumference, fullness of the back, sputum and mass, stomach. Intestinal symptoms.
(2) primary in the chest: there are symptoms associated with mediastinal compression and respiratory symptoms, such as shortness of breath, cough and so on.
2. Patients with advanced manifestations often have limb pain, anemia, fever, weight loss, and eyelid metastasis. The orbital metastasis forms a characteristic panda eye, which is characterized by prominent eyeballs and periorbital cyanosis. Others may have symptoms of hypertension and lumps associated with compression, such as dyskinesia and incontinence during spinal canal infiltration.
3. Metastatic route NB The main metastatic pathway is lymphatic and blood. About 35% of patients with localized lesions have local lymph node infiltration. Hematogenous metastasis mainly occurs in bone marrow, bone, liver and skin. Brain and lung metastasis may occur in terminal or recurrence, but it is rare. Localized lesions, localized lymph node metastasis, and disseminated lesions were 39%, 18%, and 25%, respectively, in infant cases, but 19%, 13%, and 68% in older children, respectively. That is, most of the children of the older age are at the advanced stage of the disease.
diagnosis:
1. Diagnostic methods Histopathological examination is the most important means of NB diagnosis, sometimes combined with immunohistochemistry, electron microscopy to confirm the diagnosis. Imaging studies revealed a mass consistent with NB characteristics, and NB tumor cells were found in the bone marrow, and a significantly elevated catecholamine metabolite (HVA or VMA) could also be diagnosed. If pathological diagnosis is difficult, chromosome examination revealed a 1p deletion or N-myc amplification to support NB diagnosis.
2. The diagnostic staging should also include the diagnostic staging. The US Childhood Tumor Collaborative Component System (CCSG) is as follows:
(1) Stage I: The tumor is confined to the primary organ.
(2) Stage II: The tumor is beyond the primary organ, but does not exceed the midline, and the ipsilateral lymph node may be involved.
(3) Stage III: The tumor exceeds the midline, and bilateral lymph nodes may be involved.
(4) Stage IV: distant transfer.
(5) VIs: <1 year old, the primary tumor is stage I and II, but there are metastases limited to liver, skin and bone marrow.
Identification
Different from other tumors, mainly diagnosed according to pathological examination.
complication:
Anemia, weight loss, high blood pressure, and movement disorders can occur. Transfer can occur.
treatment:
Western medicine treatment
(a) treatment
Because of the large difference in NB prognosis, some patients, such as small age, early NB prognosis is significantly better than the older age group, so should be based on the patient's prognostic factors, such as age, stage, N-myc amplification, 1p loss, etc. using graded treatment. Early patients without N-myc amplification and 1p deletion, only surgery, follow-up after surgery. Larger age, advanced stage, accompanied by N-myc amplification, 1p loss, need to receive strong chemotherapy and surgery until bone marrow transplantation.
Surgery, chemotherapy and radiotherapy are still the three main methods of NB treatment, and different intensity treatment plans are adopted according to their clinical prognostic factors. Generally, localized tumors are advocated for surgical resection and chemotherapy. The strategy of first chemotherapy, reoperation, re-chemotherapy or radiotherapy is recommended for patients who cannot be surgically resected. NB-sensitive drugs are availableCyclophosphamide,Vincristine,Etoposide(VP-16), carboplatin, cisplatin, antitumor antibiotics (doxorubicin), and isocyclic amide, etc. Each cooperating group used different drug combinations to treat chemotherapy in advanced patients, but the prognosis was still unsatisfactory.
The US CCSG Collaboration Group reported that the survival rate of advanced NB in the 4 years after receiving autologous bone marrow transplantation was 38%, and the results of various treatment programs did not show any difference. For those with other prognostic factors in stage IV (such as N-myc amplification, age > 2 years, induction therapy was not relieved), the prognosis of the autologous bone marrow transplantation group was better than conventional treatment. There was no difference between the results of allogeneic transplantation and autologous transplantation. The recovery of hematopoietic function during autologous peripheral blood stem cell transplantation is faster than that of bone marrow stem cell transplantation, and the chance of tumor cell contamination is relatively reduced.
NB is sensitive to radiotherapy, but the application of whole body radiotherapy in stem cell transplantation pretreatment is still controversial. The primary site of NB has a higher chance of recurrence. Therefore, patients with stage III and IV still advocate chemotherapy and local radiotherapy, but its effectiveness is not clear. Whole body illumination does not improve the prognosis. For patients with advanced pain, illumination can relieve pain.
The American Children's Oncology Coordination Group randomized a 13-cis-A acid treatment study in patients with advanced stage after stem cell transplantation. A group of patients received 160 mg/(m2·d) for 2 weeks per month for 3 to 6 months. Another group of patients did not take the drug after stopping chemotherapy. The results showed that the 3-year EFS was 47% in the retinoic acid group and 25% in the unaccepted group, P=0.013. In patients with stage IV and high-risk stage III, the effect of retinoic acid was more pronounced, 40% vs. 22%, and 77% vs. 49%, respectively. Commonly used reference chemotherapy regimen is shown in Table 1, generally 21 to 28 days for a course of treatment.
(two) prognosis
Related to the following factors:
1. Stage and age are the most important prognostic factors. Stages I and II have a significantly better prognosis than stage III and IV. <1 year old is significantly better than >2 years old. The long-term disease-free survival rate of children with advanced age is only 5% to 30%.
2. Biological characteristics N-myc amplification is common in NB, N-myc has a positive regulatory effect on cell division, and retinoic acid (RA) negatively regulates N-myc expression, so that NB cells stop proliferating and Differentiation, N-myc amplification >10 times is a poor prognostic factor. 1p36.3 deletion is a prone to recurrence, 1p may have a tumor suppressor, even without N-myc amplification, 1p36.3 deletion is still meaningful. The prognosis is poor when 17q is obtained. The expression of tyrosine kinase (Trk) family receptor kinase in NB is progressing rapidly, and the prognosis is good for TrkA and C; while the poor prognosis and N-myc are expressed for TrkB. CD44 is an adhesion molecule. The relationship between CD44 expression and NB progression in NB is opposite to that of other tumors. CD44-positive disease-free survival rate is significantly higher than CD44-negative group, and CD44 expression and N-myc multiplication are negative. Related.
3. The prognosis of UFH in pathological type Shimada classification is poor.
prevention:
According to the general tumor prevention methods, understanding the risk factors of tumors, and formulating corresponding prevention strategies can reduce the risk of tumors. There are two basic clues to prevent tumors. Even if tumors have begun to form in the body, they can help the body to increase resistance. These strategies are as follows:
1. Avoid harmful substances (promoting factors) that can help us avoid or minimize exposure to harmful substances.
Some related factors of tumorigenesis are prevented before onset. Many cancers are preventable before they are formed. A US report in 1988 compared the international malignant tumors in detail, suggesting that many of the known malignancies are preventable in principle, that is, about 80% of malignant tumors can be changed through simple lifestyles. prevention. Continuing with the retrospective, a study by Dr. Higginson in 1969 concluded that 90% of malignant tumors are caused by environmental factors. “Environmental factors” and “lifestyle” refer to the air we breathe, the water we drink, the food we choose to make, the habits of activities, and social relationships.
2. Improve the body's immunity against tumors can help improve and strengthen the body's immune system and cancer.
The focus of our current cancer prevention efforts should first focus on and improve those factors that are closely related to our lives, such as smoking cessation, proper diet, regular exercise, and weight loss. Anyone who follows these simple and reasonable lifestyles can reduce their chances of developing cancer.
The most important thing to improve the function of the immune system is: diet, exercise and control troubles, healthy lifestyle choices can help us stay away from cancer. Maintaining a good emotional state and proper physical exercise can keep your body's immune system at its best, and it is also good for preventing tumors and preventing other diseases. In addition, studies have shown that appropriate activities not only enhance the body's immune system, but also reduce the incidence of colon cancer by increasing the peristalsis of the human intestinal system. Here we mainly understand some of the problems of diet in preventing tumorigenesis.
Human epidemiology and animal studies have shown that vitamin A plays an important role in reducing the risk of cancer. Vitamin A supports normal mucosa and vision, and it directly or indirectly participates in most of the body's tissue functions. Vitamin A is found in animal tissues such as liver, whole egg and whole milk. Plants are in the form of beta-carotene and carotenoids, which can be converted into vitamin A in the human body. Excessive intake of vitamin A can cause adverse reactions in the body, while β-carotene and carotenoids do not. The low vitamin A content in the blood increases the risk of malignant tumors. Studies have shown that those with low levels of vitamin A in the blood People who enter are more likely to develop lung cancer, and those who have low levels of vitamin A in their bloodstream may have an increased risk of lung cancer. Vitamin A and its mixture can help remove free radicals in the body (free radicals can cause damage to genetic material), and secondly stimulate the immune system and help differentiate cells in the body to develop into ordered tissues (and tumors are characterized by disorder) . Some theories suggest that vitamin A can help cells that have been previously mutated by carcinogens to reverse and become normal growing cells.
In addition, some studies suggest that supplementation with β-carotene alone does not reduce the risk of cancer, but rather increases the incidence of lung cancer. However, when β-carotene binds to vitamins C, E and other antitoxins, its protective effect. It shows up. The reason is that when it consumes itself, it can also increase free radicals in the body. In addition, there are interactions between different vitamins. Both human and mouse studies have shown that the use of β-carotene can reduce 40% of vitamin E levels in the body, which is safer. The strategy is to eat different foods to maintain the balance of vitamins to fight cancer, because some protective factors have not been discovered so far.
Vitamins C and E are another anti-tumor substance that can prevent the harm of carcinogens such as nitrosamines in food. Vitamin C protects sperm from genetic damage and reduces the risk of leukemia, kidney cancer and brain tumors in their offspring. . Vitamin E can reduce the risk of skin cancer. Vitamin E has the same anti-tumor effect as vitamin C. It is an anti-toxin and a scavenger that scavenges free radicals. The combination of vitamins A, C, and E produces a protective effect against the toxin that is better than a single application.
At present, research on phytochemistry has attracted widespread attention. Phytochemistry is a chemical found in plants, including vitamins and other substances found in plants. The chemical constituents of thousands of plants have been found, many of which have anticancer effects. The protective mechanism of these chemicals not only reduces the activity of carcinogens but also enhances the body's immunity against carcinogens. Most plants provide antioxidant activity that exceeds the protective effects of vitamins A, C, and E. For example, a cup of cabbage contains only 50 mg of vitamin C and 13 U of vitamin E, but its antioxidant activity is equivalent to 800 mg of vitamin C and The antioxidant activity of 1100 U of vitamin E can be inferred that the antioxidant effects in fruits and vegetables are far more effective than the vitamins we know. Undoubtedly natural plant products will help future cancer prevention work.
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