Etiology and pathogenesis
Although the detailed pathogenesis of hepatoblastoma is not fully understood, it is generally considered as an embryonic tumor. It may be that the proliferation and differentiation of hepatocytes are abnormal during embryonic development, and there are still immature embryonic tissues in the liver during fetal period or after birth. These tissues continue to proliferate abnormally and form immature tissue blocks, which may turn into malignant blastoma. The pathological process of this malignant tumor may occur in the late fetus, or it may not occur until adulthood, and the most common clinical phenomenon is infancy.
Relationship between biological characteristics and prognosis
The prognosis of hepatoblastoma is related to tissue type. According to the tissue type, the prognosis can be estimated. Fetal type is the best, embryonic type is the second, anaplastic type is the worst, and the mixed type depends on the differentiation degree of epithelial and interstitial components. It is reported abroad that the 6-year survival rate of fetal type can reach 7 1% ~ 100%, while that of embryonic type is only 20% ~ 3 1%. Schmidt et al. made DNA analysis of 29 cases of hepatoblastoma, and found that fetal type is often diploid, embryonic type and anaplastic type are more common in aneuploidy, and diploid prognosis is better than aneuploidy. However, some scholars believe that there is no obvious relationship between tissue type and chromosome ploidy and prognosis.
Some scholars have made clinicopathological analysis and histological classification on 24 cases of children's liver cancer, among which 18 cases have made immunohistochemical study on 7 markers, and the surgical cases have been followed up. Results: There were 22 cases of epithelial hepatoblastoma, including 3 cases of fetal type/kloc-0, 7 cases of embryonic type and 3 cases of anaplastic type. Mixed epithelial interstitial cells: 2 cases report. The expressions of cytokeratin, alpha-fetoprotein, S- 100 protein and vimentin in tumor cytoplasm were 14, 10, 9 and 4 respectively, and the expressions of carcinoembryonic antigen, p53 and p 16 protein in tumor nucleus were1/respectively. Among the cases with complete tumor resection 12, 8 cases survived 12, and 8 cases survived for more than 5 years. All the surviving cases are fetuses. It is considered that hepatoblastoma can be divided into several tissue types, and different types have different immune expressions, which are related to prognosis. Fetal hepatoblastoma can be completely cured as long as it is diagnosed early and completely removed.
clinical picture
In the early stage of the disease, it is atypical. Quite a few parents accidentally found a lump in the right upper abdomen when changing clothes or taking a bath for their children. In the future, there will be swelling of the upper abdomen or the whole abdomen, nausea and vomiting, loss of appetite, weight loss, diarrhea, abdominal varicose veins, fever, jaundice and other manifestations. Abdominal distension and pain occur due to the rapid growth of tumor, which increases the tension of capsule. Some children's tumors grow in the direction of chest cavity, which makes the abdominal mass inconspicuous. The main manifestation of the tumor is dyspnea because the diaphragm is elevated.
The liver can be touched during physical examination, showing diffuse or nodular enlargement, uneven height and hard mass. Sometimes accompanied by splenomegaly, abdominal vein exposure or varicose veins. The author encountered two cases of abdominal pain caused by tumor rupture, abdominal muscle tension and excessive coagulation during abdominal puncture and emergency laparotomy. In the late stage, the disease progresses rapidly, and cachexia soon appears. Another clinical feature is that it is often accompanied by fever, and the body temperature can reach 39 ~ 40℃. Another author reported an extremely rare case, because the tumor of hepatoblastoma contains tissue components that produce sex hormones, and about 3% of the cases showed abnormal development of sex organs and pubic hair. Typical naked eye jaundice is not common, but there are many children with elevated bilirubin.
Another rare manifestation is obvious osteoporosis caused by tumor, and its mechanism may be protein synthesis disorder or excessive cholesterol, which directly affects the structure of bones. Therefore, pathological fracture may occur under the action of slight external force. Very few cases are accompanied by clubbing fingers or hemiplegia.
Clinical stage
Clinical staging is of great significance for judging the condition, determining the treatment plan and estimating the prognosis. At present, there is no standard for staging diagnosis in the world. Generally, the staging system of children's liver malignant tumor of American Children's Tumor Research Group is adopted, mainly according to the scope of the tumor and whether it can be completely removed.
Table 16-3 Clinical Stages of Liver Malignant Tumors in Children
Criteria for judging cycle
Complete resection of stage I tumor can be performed by wedge resection of lung lobe or extended resection.
In stage ⅱa, the tumor can be completely removed by primary radiotherapy or chemotherapy.
The lesion was confined to one lobe.
Stage Ⅲ A lesions involved two hepatic lobes.
B has regional lymph node invasion
In stage Ⅳ, there is distant metastasis regardless of the degree of liver involvement.
treat cordially
In recent years, with the in-depth understanding of tumor biological characteristics and the progress of chemotherapy and vascular interventional therapy, the long-term survival rate of hepatoblastoma in children has been significantly improved. At present, the two-year survival rate of the disease has reached more than 80% after surgical resection and regular chemotherapy.
At present, surgical resection of tumor is still the most important and effective treatment. The principle of modern treatment should be radical resection of tumor, ensure the effective compensation of liver function, and achieve the purpose of curing or prolonging the survival period and improving the survival rate. Many cases that were previously considered unresectable can now be treated surgically through preoperative chemotherapy and interventional therapy, which can shrink the tumor and enlarge the normal liver.
Treatment of hepatoblastoma
Cases that can be removed by one-stage operation
Liver tumor resection-postoperative chemotherapy for 6 ~ 8 months.
A case of huge tumor that cannot be removed by one-stage operation
After 5 ~ 6 courses of preoperative chemotherapy (about 4 ~ 6 months), tumor reduction-delayed surgery was performed to remove the tumor.
Or combined with selective hepatic artery embolization, or even selective portal vein embolization for about 4 ~ 6 months, the tumor shrinks and the normal liver tissue compensatory increases-delaying surgical resection of the tumor.
Cases of huge tumor spreading to the whole liver or serious invasion that cannot be surgically removed.
Actively prepare for orthotopic liver transplantation.
First, the treatment of cases that can be removed by one-stage surgery.
Local anatomy of the liver and liver function compensation after liver tumor resection are key issues in liver tumor surgery. Through various preoperative imaging examinations, we can understand the location, scope and neighborhood of the tumor, especially the invasion of liver blood vessels. Experienced pediatric hepatobiliary surgeons can generally estimate whether the tumor can be safely removed in one stage and whether the residual liver can maintain the basic needs of the body. As a valuable imaging examination method, hepatic angiography is of great significance to judge the feasibility of operation. If hepatic angiography cannot be performed, the author thinks that enhanced CT examination is necessary and very effective. Enhanced CT can clearly see the boundary of tumor, especially judge the relationship between tumor and portal vein and hepatic vein according to the difference of arterial phase and venous phase, so as to accurately estimate the possibility of successful resection before operation. In recent years, the author has successfully resected more than 10 cases of giant liver tumors in children, the heaviest of which is 4.8 kg. Another 5-month-old child has the largest proportion of tumors, and the tumor weight accounts for 1/5 of the body weight.
1. Children with early preoperative preparation are generally in good condition, and can be operated with simple routine preoperative preparation. However, for children with this disease, the general situation is often poor, such as malnutrition and hypoproteinemia. Intravenous nutritional support and vitamin K should be given as soon as possible.
2. The surgical resection of hepatoblastoma in children is often large, and the resection ratio is often much larger than that in adults. However, the child's liver has a strong regenerative ability. It has been reported that as long as more than 20% of normal liver tissue is preserved, life can be maintained, and the regenerated liver can be restored to its original volume within 2 months. Therefore, we should actively strive for complete tumor resection.
Surgical methods can be selected according to the size and location of the tumor during the operation, and tumor resection, hepatectomy, hemihepatectomy or extended hepatectomy can be carried out as appropriate. For many cases of huge liver tumors, the author carefully dissected the first, third and second hepatic portal, and treated the related portal vein branches, second and third hepatic arteries, short hepatic veins, hepatic veins and bile ducts in advance, and then blocked the first hepatic portal to start tumor resection. In recent years, more than 10 patients have passed the perioperative period, and no one died. This surgical method has brought new hope to some patients with huge inoperable liver tumors.
In the previous surgery, the tumor was completely removed, and no tumor cells could be found under the edge microscope after the tumor was removed. Recently, it is advocated to completely remove the tumor if it can be safely removed. Otherwise, only palliative resection will be performed on most tumors, leaving only a little tumor tissue, and postoperative chemotherapy may survive for a long time.
3. Postoperative treatment after surgery, especially within 2 weeks after surgery, must provide children with adequate nutrition, including the absolutely necessary supply of protein, vitamins and energy.
Postoperative chemotherapy combined with comprehensive treatment is particularly important for children with liver malignant tumor. Chemotherapeutic drugs such as vincristine, cyclophosphamide and 5- fluorouracil have certain anti-liver cancer effects. Adriamycin has a good effect on hepatocellular carcinoma and hepatoblastoma, but it has great side effects. It has been reported abroad that 35% of patients who were completely removed with naked eyes and still had tumor tissue under microscope survived after chemotherapy. At present, many people advocate the implementation of multi-scheme combination and alternate medication. Some people also cooperate with hematopoietic stem cell transplantation or bone marrow transplantation.
The second is the treatment of huge tumors that cannot be removed by one-stage surgery.
Some advanced children often have poor general condition, obviously poor liver function and huge liver tumor, which cannot be removed by one-stage operation. For this kind of children, it is suggested that laparotomy and biopsy should be carried out first to make a clear diagnosis. Or for patients with extremely high serum alpha-fetoprotein, preoperative chemotherapy or interventional therapy combined with chemotherapy can be performed. After such preoperative treatment, the tumor in the liver will be significantly reduced, while the normal liver will be relatively enlarged, so it can be completely removed.
Malignant solid tumors in children have the clinical characteristics of rapid development and early metastasis. More than half of the children have metastasized to adjacent tissues, regional lymph nodes and even distant blood vessels when they come to the hospital. In terms of treatment, surgical resection and adjuvant chemotherapy are still the main treatment methods for malignant solid tumors in children in China. With the application of preoperative chemotherapy and vascular occlusion to control bleeding, the complete resection rate of tumor reached nearly 70.0%, and the complete resection rate of liver malignant tumor reached 75.0%. Adjuvant chemotherapy has been widely used before and after operation, which has positive significance for controlling metastasis, killing tiny lesions, preserving limb organs, maintaining physiological functions and improving survival rate. However, some cases can not adhere to the whole course of chemotherapy, and the treatment is not standardized and can not be ignored.
Liver transplantation for unresectable hepatoblastoma
Among the primary malignant tumors of children's liver, hepatoblastoma and hepatocellular carcinoma are estimated to be over 98%. Many tumors can be well controlled by preoperative chemotherapy and delayed surgery, and localized tumors are treated by primary tumor resection. More than 85% of the liver can be safely resected, and the liver can be completely regenerated 3 ~ 6 months after operation. Liver transplantation can be performed for patients with unresectable multilobar liver tumors, liver tumors invading blood vessels, liver tumors surrounding hepatic portal and main duct, and cases with recurrent liver tumors. Primary and metastatic liver tumors, such as hepatoblastoma, epithelioid hepatic angioendothelioma, hepatocellular carcinoma and fibrosarcoma, are suitable for liver transplantation.
With the development of human tissue and organ transplantation technology, liver transplantation is gradually applied to the treatment of unresectable hepatoblastoma in children. One group reported that 5 patients with unresectable liver tumor received liver transplantation, including 3 males and 2 females. There was no extrahepatic metastasis in all cases. Two children with hepatoblastoma, aged 3 years and 6 years respectively. Serum AFP increased significantly. B-ultrasound and CT confirmed that 1 case was multiple liver tumors, and the other 1 case was right lobe tumor with portal vein embolism. Partial liver transplantation and total liver transplantation were performed respectively. Hepatic artery embolism, liver abscess, biliary obstruction and cholestasis occurred after operation 1 case. 37 months and 25 months after liver transplantation, both children were healthy and went to school. 1 A 2.9-year-old girl suffered from hepatic hemangioendothelioma, which invaded the left and right hepatic lobes and bile ducts. Preoperative high-dose hormone therapy did not improve, and the tumor grew rapidly, so total liver transplantation was performed. Spinal metastasis was found 29 months after operation, and laminectomy was performed again. He died of multiple metastases 4 1 month after liver transplantation and 12 months after metastasis resection. Two children with moderately differentiated hepatocellular carcinoma died of metastatic tumor recurrence 8 months and 5 months after transplantation, respectively.
Surgical complications
The liver is the largest substantive organ of the human body, rich in blood, criss-crossing bile ducts and blood vessels, and it is the main organ for detoxification, synthesis, decomposition and storage of nutrients. A slight negligence in surgical design and operation may endanger life. During and after the operation, it should be noted that the following emergencies may occur:
1, bleeding Regular hepatectomy, especially irregular hepatectomy, has a large amount of bleeding, especially when various blood vessels are accidentally injured. Massive bleeding is the main cause of death during and shortly after operation. Insufficient or excessive blood transfusion, too slow blood transfusion speed or too fast heart overload input speed will all cause fatal circulatory disorders. In recent ten years, isolated perfusion and temporary occlusion of hepatic artery and portal vein have been explored at home and abroad, which is expected to reduce surgical bleeding, but the experience is not yet mature. Transfusion of a large amount of stored blood without timely and appropriate calcium supplementation may lead to sodium citrate poisoning, convulsion, blood pressure drop and arrhythmia in children, leading to cardiac arrest.
2, cardiac arrest moves or pulls the liver, twisting the inferior vena cava and suddenly reducing the amount of blood returning to the heart, leading to a sharp drop in blood pressure and cardiac arrest. Moving the liver can also lead to reflex shortness of breath, decreased blood pressure, slow heart rate and dull heart sounds, which will eventually lead to cardiac arrest. In liver surgery, it is emphasized that the operator should operate gently and steadily, and the anesthesiologist should observe carefully. Once the above phenomenon occurs, the operation should be suspended immediately, the liver should be put back in its original position, and symptomatic treatment should be actively carried out, and the operation should be continued after the danger has passed.
3. Air embolism is more common. The rupture of hepatic vein, especially inferior vena cava, is easy to inhale air and form air embolism, which can cause cardiac arrest. Accurate operation is the most effective measure to prevent air embolism. Using positive pressure breathing can reduce the amount and speed of air entering the vein rupture.
4. Postoperative hepatic coma is due to too little normal liver tissue retained, or the hardened liver is mistaken for normal liver tissue and retained. Only a few patients with mild coma are expected to survive after symptomatic treatment and liver tissue regeneration. Most of them died shortly after the operation.
5. Postoperative jaundice has been reported. Jaundice often occurs after right trilobal hepatectomy. As long as the remaining 10-30% left lateral lobe liver tissue proliferates rapidly, postoperative jaundice will disappear soon. If the hepatic duct displaced and deformed by tumor is stabbed or broken by mistake, jaundice will be aggravated progressively. The author has successfully operated on 1 45-day-old child with 4000 grams of liver tumor, and surgically removed 450 grams of right trilobal tumor liver, accounting for 80-85% of the total liver volume. Jaundice appeared after operation, but it subsided naturally after two weeks. Now 1 year after operation, compared with children of the same age, the growth and development are completely normal.
6. Hypothermia is related to low ambient temperature and large amount of blood input. Recently, semiconductor thermometers have been used to observe body temperature at any time and pay attention to heat preservation. Postoperative hypothermia in older children is rare, but it is more common in small infants and newborns, which should be paid great attention to.