Pediatric Wilms' tumor

　　One: Etiology

　　1. Wilms' tumor may be caused by abnormal hyperplasia of posterior renal primordia due to undifferentiated formation of tubules and glomeruli. The nephroblastomatosis complex may also be a precursor lesion of Wilms' tumor. In recent years, it has been confirmed that the deletion of tumor suppressor genes WT1 and WT2 is related to the occurrence of some Wilms' tumors.

　　2. The etiology of Wilms' tumor is not yet clear, with a certain familial tendency to occur, with an incidence rate of 1% to 2%. Some people believe that it has a genetic component, with several children in a family developing the tumor sequentially; Schweisguth reported that in 600 cases, 5 pairs were siblings. Xinhua Hospital also encountered two pairs of brothers who developed the tumor sequentially, and met a young father who had undergone unilateral Wilms' tumor surgery in his childhood, and his son also developed Wilms' tumor at the age of 3. Some people have reported the occurrence of the disease in 3 pairs of twins. Brown and others have encountered extremely rare cases of three generations of the disease occurring sequentially.

　　Two: Pathogenesis

　　1. Renal cell carcinoma originates from renal tubular epithelial cells. Studies have shown that 88.5% of clear cell carcinomas express proximal tubule antigen, while 87.5% of granular cell carcinomas express distal tubule antigen. Therefore, it is speculated that clear cell carcinomas may originate from the proximal tubule, and granular cell carcinomas may originate from the distal tubule. Tumors of different pathological types have different appearances. Generally speaking, clear cell carcinomas are yellowish and have clear boundaries with normal tissue, resembling a capsule, grow slowly, and have a good prognosis. Granular cell carcinomas have cuboidal or polygonal cancer cells, with abundant organelles, especially mitochondria, in the cytoplasm of the cancer cells, resulting in a pink granular cytoplasm. The glandular tubular structure is clear, and the stroma is composed of capillaries. The nuclei of granular cell carcinomas show significant anaplasia, and the cell arrangement is relatively disordered, with a high degree of malignancy and poor prognosis. Undifferentiated carcinoma cells are fusiform or irregular in shape, resembling a sarcoma.

　　2. Staging Renal cell carcinoma can occur at any part of the renal parenchyma, with equal incidence of left and right renal cell carcinoma, and the vast majority are unilateral solitary lesions, with bilateral lesions accounting for only 1% to 2%.

　　(1) Gross examination: The tumor appears as an irregular circular or elliptical mass, with a pseudo-fibrous capsule formed by compressed renal parenchyma and fibrous tissue.

　　(2) It has a dense grayish-white texture, no obvious capsule, and poor prognosis. The dark red and red areas are usually hemorrhagic areas, sometimes accompanied by cystic change, necrosis, and irregular calcification.

　　(3) Microscopic examination: Undifferentiated cancer cells are fusiform, with larger or unevenly sized nuclei, more mitotic figures, and higher malignancy.

　　3. Metastasis and spread: The renal blastoma has a complete capsule in the early stage. When the tumor grows larger, it can cause rupture, leading to tumor cells directly侵入 the perirenal fat layer or adjacent tissues, such as the adrenal gland, mesentery of the colon, and the liver part in contact with it. Lymph node metastasis of renal blastoma is not common, and most of them are limited to local lymph nodes, but hematogenous spread is very common, primarily through the renal vein, where there are often tumor emboli, which can spread to the inferior vena cava, even to the right atrium. Hematogenous spread accounts for 80% to the lungs, sometimes to the liver, and occasionally to the bones.

　　4. The main pathological types of renal cell carcinoma under microscopic examination include: clear cell carcinoma, granular cell carcinoma, and undifferentiated cell carcinoma, etc. Clear cell carcinoma is the most common, with large clear cells, clear margins, polygonal shape, small and uniform nuclei with deep staining, and most cells are translucent. Cells often arrange in sheets, papillary, and tubular shapes. Granular cells are round, polygonal, or irregular in shape, dark in color, with a glassy cytoplasm, filled with small granules in the cytoplasm, less cell mass, and slightly deeper nuclear staining. Both types of cancer cells can exist alone or mixed within the same tumor. If the tumor is mostly clear cells, it is called renal clear cell carcinoma, otherwise, renal granular cell carcinoma. This tumor is 60% to 70% mixed renal carcinoma composed of two types of cancer cells. Undifferentiated cancer cells are fusiform, with larger or unevenly sized nuclei, more mitotic figures, and higher malignancy.

　　The experience of the International Society of Pediatric Oncology (SIOP) and the American Wilms Tumor Study (NWTS) proves that the histological type of the tumor plays an important role in estimating the prognosis. This tumor is divided into 2 types:

　　(1) Favorable histology (FH): Multilocular, fibroadenomatous.

　　(2) Unfavorable histology (UH): Anaplastic, clear cell sarcoma, spindle cell sarcoma. Currently, SIOP and NWTS formulate treatment plans based on the above histological types combined with staging.

　　小儿肾母细胞瘤可以并发哪些疾病：

　　12％～15％的肾母细胞瘤可伴发其他先天性畸形，有半身肥大、尿道下裂、睾丸未降、双性输尿管、双性肾脏、马蹄肾、无虹膜(aniridia)等症时，应考虑到本病存在的可能。常见者为：

　　1、虹膜缺如本瘤伴有非家族性双侧虹膜发育不良或完全缺如者并非少见，约70例中有1例。有时同时有先天性白内障，还可有中枢神经异常，如小头畸形、头面异形、耳郭异常、泌尿系统畸形和智能迟缓等，近年对虹膜缺如合并肾母细胞瘤患儿的细胞遗传学研究表明，其均有11号染色体短臂移位或部分缺如的现象。

　　2、偏身肥大一般为左侧或右侧身体肥大，或仅有下肢肥大。婴儿期多未被发现，甚至在诊断肿瘤时始被注意到。偏身肥大的发生率在人群中为1∶14300，而在肾母细胞瘤患儿32例中就有1例，以女孩居多。

　　3、泌尿生殖系畸形发生率为4.5％，如肾重复畸形、马蹄肾、多囊肾、异位肾等。合并尿道下裂和隐睾者也非罕见。此外，近年来还发现肾母细胞瘤伴外生殖器雌雄难辨的两性畸形患儿，RaIFer报道10例，其中7例发生在单侧肾母细胞瘤，3例双侧肾母细胞瘤。

　　4、Beckwith-Wiedemann综合征本综合征主要有内脏肥大(肾、胰、肾上腺、性腺、肝等)、脐膨出、巨舌和发育巨大或偏身肥大等。患此综合征者的肾、肾上腺皮质和肝等脏器容易发生恶性肿瘤，Reddy等报道34例Beckwith-Wiedemann综合征中，3例生长肾母细胞瘤，3例肾上腺皮质癌，肝母细胞瘤和性腺母细胞瘤各1例。

　　1、腹部肿块：80％～90％病例以腹部肿块就诊，大多是在无意中发现，可无症状，一般系母亲替小儿洗澡或穿衣时，或医务人员因其他原因做全身检查而发现腹部有包块存在。肿块位于腹部一侧季肋部，呈椭圆形，表面光滑平整，质地坚实，无压痛，边缘内侧和下界清楚，上界被肋缘所遮蔽多不能触及，双手腹腰触诊可感到腰部被肿瘤所填。肿瘤比较固定，不能移动。肿块大小不一，较大的可占全腹的1/3～1/2，较晚期病例肿块往往超过腹中线，将腹腔内脏推向对侧。应该指出，反复扪诊压挤肿瘤，可促使瘤细胞进入血流而发生远处转移，因而要特别注意。

　　2. Pain and gastrointestinal symptoms:Some reports indicate that 25% of the first symptoms of nephroblastoma are low back and leg pain. In fact, due to the fact that the pain is usually not severe and children are not good at describing it, most cases go unnoticed. Children may have acute abdominal symptoms when they fall, fall, or have abdominal trauma. Occasionally, children may have sudden paroxysmal pain, which is due to sudden bleeding within the tumor, excessive expansion of the renal capsule, or temporary obstruction of the ureter by blood clots. Children often have indistinct gastrointestinal symptoms, such as nausea, vomiting, and decreased appetite, etc.

　　3. Hematuria:Hematuria occurs in 20% of cases, and about 10% of cases are noted as the first symptom leading to the diagnosis of tumor. It is usually painless and intermittent gross hematuria, with little amount, and sometimes accompanied by blood clots. When pediatricians see this symptom, even if there is no palpable mass in the abdomen, they should perform B-ultrasound, intravenous pyelography, or CT, etc., which may detect small tumors in the central part of the kidney. However, in most cases, hematuria is a late symptom, and the tumor is quite large, infiltrating the renal pelvis. Urine microscopic examination shows that about 1/3 of cases contain multiple red blood cells.

　　4. Fever:Children with nephroblastoma may have varying degrees of fever, mostly intermittent, with rare cases of high fever (39℃). Some people have noticed that children with vomiting due to dehydration, metastasis, or necrosis in the tumor almost always have an increase in body temperature.

　　5. Hypertension:A considerable number of children may have mild or severe hypertension, but often due to the neglect of measuring the blood pressure of infants and young children, there are not many reports. However, there are also many cases of severe hypertension in the literature. After the tumor is removed, hypertension decreases, suggesting two possibilities: either the tumor compresses the renal artery to cause hypertension, or the tumor itself produces some kind of pressor substance. When the local tumor or metastatic lesions recur, blood pressure rises again. After radiotherapy and chemotherapy, the lesions disappear and blood pressure also decreases, which further explains that it may be due to the tumor secreting some kind of pressor substance. The plasma renin or hypertension proteinase content in children with nephroblastoma is higher than that in normal children, and it returns to normal after tumor resection. In recent years, some people have also conducted quantitative analysis of renin from the filtrate of nephroblastoma, which is much higher than that contained in normal renal cortex.

　　6. Overall condition:Generally, they are affected to some extent, with decreased appetite, slight weight loss, a lack of vitality and less playful than before, pale complexion, and discomfort all over the body, etc. When there is metastasis in the lungs, the overall condition of the body becomes more deteriorated, but there are few symptoms such as coughing or hemoptysis.

　　7. Symptoms of tumor rupture and metastasis:Occasionally, tumors may rupture spontaneously or after injury, usually preceded by severe pain, leading to acute anemia in children, and are often diagnosed as liver or spleen rupture. Tumors may rupture within the abdominal cavity, in the lumbar pouch of the retroperitoneal space, or there may be tumors with only a crack, with a hematoma under the capsule. Tumors mainly spread through blood flow, so lung metastasis is the most common, with few symptoms such as coughing or hemoptysis after metastasis, making X-ray examination of the lungs extremely important. Liver metastasis is less common.

　　One: Avoid the invasion of harmful substances

　　Prevent some related factors of tumor occurrence before the onset of the disease. Many cancers can be prevented before they form. A report by the United States in 1988 compared the international situation of malignant tumors in detail and proposed that the external factors of many known malignant tumors are principle preventable, that is, about 80% of malignant tumors can be prevented by simple lifestyle changes. Continuing to trace back, Dr. Higginson's research summary 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, our habits of activity, and social relationships, etc.

　　Two: Improve the body's

　　1. The focus of our current tumor prevention and treatment work should first be on improving those factors closely related to our lives, such as quitting smoking, eating a balanced diet, regular exercise, and weight loss. Anyone who adheres to these simple and reasonable lifestyle常识 can reduce the chance of getting cancer.

　　2. The most important thing to improve immune function is diet, exercise, and controlling stress. Choosing a healthy lifestyle can help us stay away from cancer. Maintaining a good emotional state and appropriate physical exercise can keep the body's immune system in the best condition, which is also beneficial for preventing tumors and other diseases. Additionally, studies have shown that moderate exercise not only strengthens the human immune system but also reduces the incidence of colon cancer by increasing the peristalsis of the human intestinal system. Here, we mainly recognize some issues related to diet in preventing the occurrence of tumors.

　　3. Epidemiological studies in humans and animal experiments show that vitamin A plays a crucial role in reducing the risk of cancer. Vitamin A supports normal mucous membranes and vision, and it directly or indirectly participates in the function of most tissues in the body. Vitamin A exists in animal tissues such as liver, whole eggs, and whole milk, and in plants it exists 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 beta-carotene and carotenoids do not have this effect. An increase in low vitamin A levels in the blood increases the risk of malignant tumors. Studies have shown that people with low levels of vitamin A intake in the blood are more likely to develop lung cancer, and for smokers, the risk of lung cancer is doubled due to low levels of vitamin A intake in the blood. Vitamin A and its mixtures can help clear free radicals in the body (free radicals can cause damage to genetic material), and secondly, they can stimulate the immune system and help differentiate cells in the body to form orderly tissues (while tumors are characterized by disorganization). Some theories suggest that vitamin A can help revert cells that have been early attacked by carcinogens and mutated back to normal growing cells.

　　4. In addition, some studies suggest that simply supplementing beta-carotene drugs cannot reduce the risk of cancer, on the contrary, it may slightly increase the incidence of lung cancer. However, when beta-carotene is combined with vitamin C, E, and other antitoxin substances, its protective effect becomes apparent. The reason is that when it is consumed, it can also increase the free radicals in the body, and there are interactions between different vitamins. Studies in humans and mice have shown that the use of beta-carotene can reduce the level of vitamin E in the body by 40%. A safer strategy is to eat a variety of foods to maintain a balance of vitamins to resist the invasion of cancer, because some protective factors have not been discovered yet.

　　5. Vitamin C and E are another type of antitumor substance. They can prevent the harm of carcinogens such as nitrosamines in food. Vitamin C can protect sperm from genetic damage and reduce the risk of leukemia, kidney cancer, and brain tumor in offspring. Vitamin E can reduce the risk of skin cancer. Vitamin E has antitumor effects like vitamin C and is a scavenger of toxins and free radicals. The combined use of vitamin A, C, and E has a better protective effect on the body against toxins than when used alone.

　　One, Blood picture examination

　　Routine blood tests may be normal, with mild anemia, but a few may have an increase in red blood cells, which may be related to the increase in erythropoietin. It can be used as an indicator to track whether there is bone marrow hematopoietic suppression during treatment.

　　Two, Blood examination

　　Renal function is normal. Erythrocyte sedimentation rate generally increases, ranging from 15 to 90 mm/h, and the sedimentation rate of large advanced tumors increases significantly, which is considered an indicator of poor prognosis. Blood urea nitrogen, creatinine, and other tests reflect the condition of kidney damage. When kidney damage is severe, the level of erythropoietin (erythropoietin) decreases. Liver function tests can be used to observe the toxic effects of treatment.

　　Three, Urine examination

　　Urinalysis often shows hematuria and proteinuria, but cancer cells are often not found in the urine. Urinalysis and culture can detect hematuria and urinary tract infections.

　　Four, Bone marrow examination

　　It is very rare for this disease to metastasize to the bone marrow, while neuroblastoma often has bone marrow metastasis, so bone marrow examination is quite helpful for the differential diagnosis of these two diseases.

　　Five, Puncture biopsy

　　In recent years, there have been reports on the use of fine needle rapid puncture aspiration cytology for diagnosis, which can be confirmed before surgery. The method is simple and the accuracy rate reaches 90%. Puncture biopsy has certain significance for large tumors that are estimated to be inoperable, as it can clearly determine the histological type before surgery, estimate the prognosis of the child, and facilitate the formulation of preoperative and postoperative chemotherapy and radiotherapy plans.

　　Six, X-ray examination

　　1. Abdominal X-ray: It can show the location and range of the tumor, and it is common for the intestine to be pushed to the opposite side. In most cases, the affected side of the rib abdomen is distended, and the gaseous intestine surrounds the soft tissue density shadow of the tumor and is pushed towards the middle of the abdomen. Calcified spots are extremely rare, and if they appear, they are mostly seen as curved lines at the edges. The lateral film shows a shadow of soft tissue mass in front of the spine, pushing the gaseous gastrointestinal tract forward.

　　2. Chest X-ray: Take posterior-anterior, lateral, and oblique photographs of the chest to search for metastatic foci in the lungs. Lung metastasis accounts for about 10%.

　　Seven, Intra-venous Pyelography

　　1. It is the main diagnostic method. Angiography should be performed for all cases suspected of having Wilms' tumor. About 2/3 of the children show deformation, displacement, or defects of the renal pelvis and calyces, and when the tumor compresses the renal pelvis, it is significantly elongated or hydrops. All these morphological changes should be carefully observed in anteroposterior and lateral photographs. The tumor at the upper pole of the kidney may rarely change the shape of the renal pelvis, or only have inversion and descent; the tumor at the lower pole of the kidney often pushes the ureter towards the midline, forming an outwardly concave arc. In 1/3 of the children, the affected kidney is not visible on the routine film because it is mostly compressed, and it should be delayed to 6 hours, even 24 hours, to take a film. Generally, there is a certain degree of excretion of contrast agent, and if the kidney still does not show, it suggests that the kidney has been severely damaged. Some reports in China reached 36%, while abroad it was only about 10%. It is necessary to pay attention to whether the morphology and function of the contralateral kidney are normal, and the author has encountered cases of malformation of the contralateral kidney (such as duplicated kidney).

　　2. Retrograde pyelography is generally not indicated. Cavity inferior vena cava angiography can determine whether the tumor has grown into the inferior vena cava. Selective renal artery angiography is a traumatic examination, which is only applied to bilateral Wilms' tumors to determine the extent of surgical resection based on the distribution of blood vessels, but it is generally not necessary for the diagnosis of this tumor. It is occasionally used to understand the metastasis of the liver and other abdominal organs. CT and MRI examinations are very valuable for diagnosis.

　　Eight, B-ultrasound examination

　　1. It can distinguish the mass as a solid type or cystic type. The renal blastoma ultrasound echo image shows a mixed image in front of the lumbar wall, which is mainly composed of solid matter with a small liquid level (necrosis, hemorrhage, renal pelvis hydrops). This method is non-invasive and painless, so it should be listed as the first choice for examination.

　　2. Ultrasound examination is very helpful for the differential diagnosis of this disease. If cystic signs are found, attention should be paid to the possibility of renal pelvis hydrops, polycystic kidney, or bile duct dilatation. If the tumor shows high-intensity irregular echoes on ultrasound, it indicates a malignant tumor.

　　Nine, Angiography

　　It can be used for retrograde aortography and inferior vena cava angiography. The blood flow in the renal artery distribution area of the affected side is rich, and abnormal vascular formation can be seen throughout the tumor range. It can be seen that the tumor blood vessels increase with the increase of the tumor, and the arrangement of blood vessels is often very chaotic. Angiography can also assist in the discovery of smaller tumors. Inferior vena cava angiography can determine the pressure of the tumor on the inferior vena cava.

　　1. Foods that are good for children with Wilms' tumor

　　1. Eat more fresh fruits and vegetables.

　　2. Fish, shrimp, old turtles, sea cucumbers, and other foods can be eaten. Strengthen nutrition

　　2. Foods that children with Wilms' tumor should not eat as much

　　Eat less salty and sweet foods. The greater the daily intake of fruits and vegetables, the lower the risk of disease. For example, people who eat 6 to 8 bananas a day have nearly half the risk of developing Wilms' tumor compared to those who do not eat at all. Similarly, regular intake of carrots or beets and other root plants can reduce the risk of disease by 50% to 65%.

　　1. Treatment

　　1. Surgical treatment

　　After the mass is found, it should be actively complete all necessary clinical and laboratory tests within 24-48 hours, and make a clear diagnosis. Wilms' tumor should be operated on within 2-3 days after admission. If there are other diseases, the operation time can be postponed accordingly, such as in children with Wilms' tumor accompanied by hypertension, or those with occasional concurrent congestive heart failure or pneumonia. For those with extensive lung metastases that affect lung function, radiotherapy or chemotherapy should be performed before surgery.

　　(1) For large tumors, preoperative chemotherapy and radiotherapy are required to shrink the tumor and reduce the spread of tumor cells caused by compression during surgery. The choice of surgery time should be based on the sensitivity of the tumor to radiotherapy and chemotherapy.

　　(2) The surgical method is to perform a transabdominal upper abdominal transmedian incision under tracheal intubation anesthesia, in order to avoid the rupture of the tumor capsule and the spread of cancer cells caused by the traction or rotation of the tumor. For large tumors, a diagonal incision can also be made, and it can be extended to a thoraco-diaphragmatic-abdominal incision if necessary, which is convenient for exposing the upper pole of the tumor and first ligating the renal arteries and veins. Once the abdomen is widely exposed, it is necessary to explore whether the liver and retroperitoneal lymph nodes are invaded or have suspicious metastatic foci, and check whether there is a tumor in the contralateral kidney. Then, the ascending (descending) colon is pushed inward, and the retroperitoneal peritoneum is incised laterally. In principle, it should be strived to ligate the renal pedicle vessels first, but it is not mandatory.

　　(3) An important principle in the surgical treatment of Wilms' tumor is to resect the tumor along with adjacent 'adhesions' and suspicious tissues, as well as the regional lymph nodes in large blocks. For this purpose, surgeons must pay close attention to the lymph nodes between the diaphragm and the inferior mesenteric artery during surgery. When dealing with the renal pedicle, it is necessary to carefully check whether the venous wall is infiltrated by the tumor, whether there are tumor masses in the venous lumen, and whether tumor thrombi have grown into the inferior vena cava. If so, the following methods can be used: after ligating the renal artery, the renal vein and inferior vena cava involved by the tumor are freed up, and the inferior vena cava above and below the renal vein is temporarily occluded as far as possible. Temporarily occlude the contralateral renal vein, incise the inferior vena cava and remove the tumor thrombus, which is usually not adherent and easy to remove, and then suture the inferior vena cava. The renal vein at the entrance to the inferior vena cava is cut off. It is also necessary to pay attention to whether the tumor thrombus has spread far into the hepatic segment of the inferior vena cava, even reaching the right atrium. Recently, there have been reports of cases where tumor thrombus was removed from the right atrium after thoracotomy and extracorporeal circulation.

　　(4) If the tumor invades the inferior vena cava (below the renal vein) and is adherent to it and cannot be separated, this segment of the inferior vena cava can be removed together without causing lower limb congestion and edema. The removed tumor thrombus and vascular wall should be subjected to detailed pathological examination. In addition to the upper pole tumor of the kidney, if the adrenal gland is normal in appearance, it may not need to be removed. The ureter must be completely resected, as the tumor can recur in the remaining ureter.

　　(5) For preoperative bilateral nephroblastoma, careful consideration should be given to the surgical plan. Generally, the contralateral kidney is resected for the larger tumor, and the smaller one is resected for a heminephrectomy or only for tumor resection. Some people advocate for tumor resection on both sides to retain as much healthy renal tissue as possible.

　　2. Radiotherapy

　　Nephroblastoma is quite sensitive to radiotherapy, but each tumor is different, which may be related to the histological type of the cells. There are advocates for both preoperative and postoperative radiotherapy. Preoperative radiotherapy can reduce the size of the tumor, making surgery more convenient and safe, and can reduce the risk of tumor rupture and cell implantation during surgery. In addition, some cases can be exempted from postoperative radiotherapy. However, preoperative radiotherapy can lead to the irradiation of benign tumors due to diagnostic errors. Postoperative radiotherapy mainly targets the tumor bed and suspicious areas, and can start on the day of surgery.

　　If the tumor has ruptured, the entire abdomen should be given radiotherapy. Children with right-side tumors are prone to radiation-induced hepatitis, and the dose should be reduced and chemotherapy should be added during radiotherapy. The addition of actinomycin D (dactinomycin) for chemotherapy in addition to surgical treatment and radiotherapy can achieve a survival rate of 89%; the survival rate for children with metastasis is only 15%. Vincristine can be used in combination with actinomycin D. After surgery, attention should be paid to the healing of the wound. Sufficient nutrition should be provided to promote wound healing and physical recovery. After treatment, a chest X-ray, blood count, and kidney and liver function tests should be performed to monitor efficacy and observe for any toxic reactions. The duration of treatment depends on the age of the child and the extent of the tumor.

　　3. Chemotherapy

　　Currently, the best drugs for the efficacy of nephroblastoma are actinomycin D, vincristine, and doxorubicin (adriamycin), which can significantly control local recurrence and metastasis. In early cases, if the results of the histopathological examination are good, less treatment volume and duration can be used, and radiotherapy can be omitted and only chemotherapy with vincristine and actinomycin D for several months can be given. For severe cases and those with metastasis, radiotherapy must be added, and the duration of chemotherapy should be prolonged, and daunorubicin (red daunomycin) should be added. Cyclophosphamide also has some efficacy for nephroblastoma. Attention should be paid to the side effects of chemotherapy drugs during the treatment process. Vincristine can cause constipation, neuritis, abdominal pain, hair loss, and so on; extravasation can cause subcutaneous tissue necrosis. Actinomycin D extravasation can also cause subcutaneous tissue necrosis, and its toxic and side effects include vomiting, hair loss, and bone marrow hematopoiesis inhibition, etc.

　　(1) Actinomycin D (AMD): Starting from the day after surgery, 15mg/kg is injected intravenously daily for 5 consecutive days, with a total dose of 75mg/kg as one course. Each dose should not exceed 500mg. If the child has poor tolerance, the dose should be less than 15mg/kg. If 10mg/kg is given daily, it needs to be administered for 7 consecutive days as one course, with a total dose of 70g/kg.

　　(2) Vincristine (VCR): Starting from the day after surgery, 1.5mg/m2 is injected intravenously once a week. The dose per dose should not exceed 2mg/m2.

　　(3) Doxorubicin (Adriamycin): Starting from the 6th week after surgery, 20mg/m2 is injected intravenously daily for 3 consecutive days as one course. Subsequently, the injection is repeated at the 4th, 5th, 7.5th, 10.5th, and 13.5th months. If whole abdominal, whole thoracic, or thoracoabdominal radiotherapy is required, the above dose should be halved. If only local lumbar radiotherapy is performed, the full dose can be used.

　　(4) For infants and young children under 12 months of age or weighing less than 10kg, the dose of the above drugs should be halved, otherwise the toxicity is too high and is not beneficial to the child.

　　(5) The above three drugs all have certain toxicity, and strict attention must be paid when used. Actinomycin D can cause nausea, vomiting, stomatitis, diarrhea, alopecia, and bone marrow suppression. Vincristine has toxicity to the nervous system, which can cause peripheral neuritis, gastrointestinal reactions caused by the nervous system, such as abdominal pain and constipation, and can also cause alopecia and bone marrow suppression. Doxorubicin has inhibitory effect on bone marrow, cardiotoxicity, gastrointestinal reactions, and other adverse reactions such as alopecia, liver function damage, and hemorrhagic erythema.

　　(6) For those with significant reactions during radiotherapy and chemotherapy, symptomatic therapy should be taken at any time: such as antipyretic, laxative, sedative, nasogastric feeding or intravenous hyperalimentation, etc. Blood routine examination, including platelet count, should be performed on the 1st, 7th, 11th, and 14th day of each process, and fresh blood should be transfused as necessary.

　　4. Treatment of metastatic tumors

　　At least 20% of the cases have metastasis when they seek medical attention, of which 80% are lung metastasis. Due to the application of chemotherapy, the cases of recurrence are greatly reduced.

　　(1) Lung metastasis: The lung metastasis of nephroblastoma is mostly multiple lesions in both lungs, which is very sensitive to radiotherapy, and the dose of radiotherapy generally does not exceed 20Gy. The irradiation field should include the entire double lungs, 4 to 5 times a week, completed in about 20 days, and performed simultaneously with chemotherapy, with significant efficacy. Single lung metastasis lesions on one side or both sides are relatively rare. In this case, surgical operation can be performed, local wedge resection of the lung, followed by radiotherapy and chemotherapy.

　　(2) Liver metastasis: Much less common than lung metastasis, unless there are significant large masses, small early lesions are often not discovered. If the metastasis is a single lesion limited to one lobe of the liver, liver lobectomy can be considered. If it is a disseminated multiple lesions metastasis, only radiotherapy can be done, with a dose of 30Gy, supplemented by chemotherapy. In recent years, there have been more and more reports of cured cases of liver metastasis in the literature.

　　(3) Bone metastasis: generally multiple foci, even with high-dose chemotherapy and radiotherapy, there are very few cured. But there are also reports of cured single bone metastasis after chemotherapy and radiotherapy.

　　(4) Brain metastasis: very rare, single brain tumor resection and adjuvant radiotherapy is worth trying, with reports of cure.

　　Second, Prognosis

　　The cure rate of complete resection of renal embryonal tumor is about 47%, and postoperative radiotherapy can increase the survival rate to 60%, which varies with the age of the child and the stage of the tumor.

　　1. According to extensive experience, children under 2 years of age, especially infants under 1 year of age who do not relapse after treatment, are much more than children of larger ages.

　　2. Of course, the size of the tumor is also one of the factors affecting the prognosis, the larger the worse the prognosis.

　　3. The histological type of the tumor has a great relationship with the prognosis.

　　4. The local invasion and distant spread of the tumor have the greatest impact on the prognosis, that is, the clinical-pathological staging of the tumor. The following is introduced:

　　(1) Stage Ⅰ: The tumor is confined to the kidney and can be completely removed. There is no infiltration on the renal capsule surface, and there is no rupture of the renal tumor before or during surgery. There is no obvious residual tumor after resection.

　　(2) Stage Ⅱ: The tumor has spread to the perirenal tissue, but can be completely removed. There is no obvious residual tumor outside the resection range, and there is no infiltration of extrarenal blood vessels or tumor thrombus in the renal vein. Tumor puncture and biopsy have been performed, and there is no obvious residual tumor.

　　(3) Stage Ⅲ: Abdominal residual non-blood-derived tumor, and one or more of the following conditions:

　　①Infiltration of the renal hilum and para-aortic lymph nodes.

　　②Diffuse peritoneal dissemination, tumor spillage before or during surgery.

　　③Microscopic or macroscopic examination of the resection surface shows residual tumor.

　　④Tumor implantation in the peritoneum.

　　⑤Due to local infiltration and adhesion, the tumor cannot be completely removed.

　　(4) Stage Ⅳ: Blood-borne metastasis to the lung, liver, bone, and brain.

　　(5) Stage Ⅴ: Both sides have tumors at diagnosis, and staging is performed separately according to the condition of each side.