The first cause of death among children under 15 years of age is death from accidental injury, and the second is tumors of all types and sites, which account for about 11% of the total mortality rate among children. Among all types and sites of tumors in children, the first incidence rate is leukemia, accounting for about 33%, i.e., 1 out of 3 pediatric tumor patients is leukemia; the second incidence rate is central nervous system tumors (mainly brain tumors), accounting for about 20%, i.e., 1 out of 5 pediatric tumor patients is brain tumor. With the improvement and popularization of neurological examination methods, especially the popularization of cranial CT and MRI in primary hospitals, the detection rate of brain tumors in children has increased significantly, and more and more brain tumors in children need to be treated. The annual incidence of new childhood brain tumors is 2~5 per 100,000 population, and according to the calculation of China’s 1.3 billion population, 26,000~65,000 new childhood brain tumors are detected in China every year. At present, the medical profession and the society at home and abroad are concerned about childhood leukemia, but little concern about childhood brain tumor. Whether in terms of social public attention or governmental investment in scientific research, pediatric brain tumors have not been given due attention.
According to the statistics of 1267 cases of pediatric neurosurgery, the top 5 most common brain tumors in children are: astrocytoma (30%), craniopharyngioma (20%), medulloblastoma (16%), germ cell tumor (8%) and ventricular meningioma (6%), which are all malignant tumors and account for 80% of the neurological tumors in children. Malignant tumors accounted for 91% of all neurological tumors in children, while benign tumors accounted for only 9%. The following is an analysis of the treatment progress of the top 4 astrocytomas, craniopharyngiomas, medulloblastomas and germ cell tumors.
1.Childhood astrocytoma
The treatment outcome of childhood astrocytomas is closely related to their different pathological subtypes and growth sites. In terms of treatment, the extent of tumor resection is the primary requirement, and postoperative radiotherapy and chemotherapy are extremely helpful in improving the survival rate of children with the disease. Hairy cell astrocytoma is very sensitive to radiation and has a good prognosis for children. The following is an analysis of the treatment strategies for astrocytomas at different sites.
For optic glioma, hypothalamic glioma and third ventricular glioma (intermediate mass glioma) growing in the suprasellar region, the pathology is mostly hairy cell astrocytoma, and surgical removal of most of the tumor is sufficient to avoid damage to the hypothalamus caused by excessive removal of the tumor. In contrast, astrocytomas growing in the cerebral hemispheres and thalamus are less likely to be of the hairy cell type, and even if total or near-total resection is achieved with postoperative radiotherapy and/or chemotherapy, the prognosis for the child is still poor. Astrocytomas growing in the cerebellar hemispheres are benign tumors, not malignant. Morphologically, there are three types of astrocytomas: solid, intracapsular, and intracapsular. If the solid tumor and intracapsular tumor can be fully resected, the child can achieve long-term survival (even lifelong survival) with the aid of conventional postoperative external radiotherapy. Brain stem glioma is divided into diffuse type, limited type and exophytic type. Diffuse type is inoperable, while limited type and exophytic astrocytoma can achieve long-term survival with adjuvant radiotherapy and chemotherapy after surgery. The fine surgical operation of the operator is the key to ensure the surgical effect of brainstem tumor.
2.Craniopharyngioma in children
Due to the close anatomical and functional relationship between craniopharyngioma and hypothalamus, the treatment of craniopharyngioma becomes a challenge for every neurosurgeon. The current treatment methods for craniopharyngioma include: surgical resection, external radiotherapy, isotope internal radiotherapy, intrathecal chemotherapy, intrathecal cystic fluid extraction, the above methods alone and in different combinations, and so on. The mainstream view of domestic and foreign scholars is that total surgical resection of the tumor and postoperative external radiotherapy are the most fundamental treatment methods for craniopharyngioma, while other treatment methods are only palliative and adjuvant methods. At present, the total resection rate of craniopharyngioma surgery is over 90%, and the surgical mortality rate is 1%~3%.
There are two pathological types of craniopharyngioma: the enamel type and the squamous papillary type. Traditionally, craniopharyngiomas are considered benign tumors, but pathologic studies, oncologic studies, and clinical studies have confirmed the aggressive nature of enamel-type craniopharyngiomas, which are supposed to be malignant. Almost all craniopharyngiomas in children are cystic craniopharyngiomas of the enamel type. The morphologic diversity of childhood craniopharyngiomas is related to the growth of the cystic wall. The growth of the soft cystic wall can be impeded by the more fixed anatomical structures surrounding the tumor: optic nerve, anterior communicating artery, internal carotid artery, pituitary stalk, saddle nodes, and saddle back. The cyst wall then grows toward less resistant spaces, such as the first interspace, second interspace, lateral fissure, interpeduncular pool, and third ventricle. Intrasellar craniopharyngioma originates from the anterior pituitary gland (adenopituitary gland), and the surface of the cyst wall is the saddle diaphragm, which gradually bulges upward as the tumor grows. The suprasellar craniopharyngioma originates from the pituitary stalk and can grow forward through the first hiatus, laterally through the second hiatus toward the lateral fissure, upward through the floor of the third ventricle into the third ventricle, and backward toward the interpeduncular pool and slope. This growth pattern is the main basis for choosing the surgical approach.
The principle of rational selection of surgical approach is that the tumor is fully exposed and the adhesions between the tumor and hypothalamus should be separated under direct vision. For the surgeon, the medial aspect of the hypothalamus (anterior inferior lateral wall of the third ventricle) is the area we should focus on to protect, where the tumor capsule wall has very serious adhesions with the anterior inferior lateral wall of the third ventricle. It should be emphasized that total or near-total resection of the tumor should be achieved as much as possible during the first surgery, and gross resection of the craniopharyngioma is not a therapeutic goal. The cystic wall of the craniopharyngioma is the true tumor tissue and the cystic fluid is secreted from the cystic wall. Therefore, surgical resection of cystic craniopharyngioma must include removal of the cystic wall, not just aspiration of the cystic fluid.
About 70%~80% of children with craniopharyngioma have endocrine function impairment before surgery, and about 80%~90% of children have water-electrolyte disorder after surgery, and 10% of epilepsy occurrence after surgery, the higher the rate of total tumor removal, the higher the rate of postoperative complications. Therefore, the focus of perioperative management is to prevent and control hypothalamic functional impairment. Preoperative hormone supplementation (e.g., prednisone and thyroxine) is required. Postoperative changes in blood sodium are an important factor in triggering epilepsy, and postoperative monitoring of blood sodium changes should be focused on, as both hypernatremia and hyponatremia have a detrimental effect on the recovery of the child, but the more detrimental factor is the drastic change in blood sodium level (e.g., rising too fast or falling too fast). Smooth adjustment of sodium levels is the key to treating electrolyte disorders. Once epilepsy occurs, all children have blood sodium abnormalities, and it is important to adjust blood sodium levels in a timely manner while controlling seizures with medication. In children with total craniopharyngioma resection, radiotherapy can be avoided, while children with near-total resection should be given routine postoperative radiotherapy. In contrast, children with largely resected tumors should not be treated with radiotherapy, but should seek a second surgery to remove the tumor, and postoperative radiotherapy can be given in cases where total or near-total resection is achieved. The main problem of long-term postoperative survival in children with craniopharyngioma is hypothalamic-pituitary hypofunction, e.g., poor development of secondary sex syndromes, short stature, obesity, and enuresis. How to give appropriate hormone replacement therapy during the growth and developmental stages of the sick child is one of the future research directions. Related to endocrine hypofunction and the impact of surgery is the problem of intellectual development of children, which is also a key research direction in the future.
3. Childhood medulloblastoma
Children with medulloblastoma are divided into high-risk and low-risk groups. The grading is mainly based on the presence or absence of subarachnoid metastasis, the age of the patient and the size of postoperative residuals.
The improvement in the outcome of childhood medulloblastoma is attributed to three main aspects: the increase in the rate of total surgical resection, postoperative whole brain and whole spinal cord radiotherapy and chemotherapy. We can now achieve a tumor microscopic total resection rate of more than 95% and a surgical mortality rate of about 1% (unpublished data). After tumor resection, the dura is sutured and the bone flap is reset as much as possible, which can reduce many complications caused by opening the dura and removing the bone flap, and improve the quality of survival of the sick child.
Postoperatively, radiotherapy followed by chemotherapy is usually the treatment plan. Medulloblastoma is very sensitive to radiotherapy, and whole brain and whole spinal cord radiotherapy is the first choice for children with medulloblastoma, with a 5-year survival rate of about 90%. Radiotherapy is followed by reasonable chemotherapy regimens, such as vincristine, CCNU, cisplatin and prednisone in different combinations. Chemotherapy should be preferred for some children with whole brain tumor dissemination. Both radiotherapy and chemotherapy can cause different degrees of damage to the neurological system of children. One of the future research directions is how to reduce the side effects of radiotherapy and chemotherapy while enhancing their effects, such as the application of hyper-segmentation radiotherapy measurement and new chemotherapy drugs.
For younger children under 3 years of age, post-surgical radiotherapy and chemotherapy are both relatively contraindicated. Regardless of whether chemotherapy is adopted first, followed by radiotherapy after 3 years of age, or single chemotherapy, the prognosis of children with the disease is poor. Therefore, postoperative adjuvant therapy for medulloblastoma under 3 years of age is one of the priorities of future research.
4. Childhood germ cell tumor
This tumor is highly sensitive to radiotherapy and chemotherapy, and if correctly diagnosed before surgery, it can become one of the curable intracranial malignancies without surgery. Intracranial germ cell tumors mainly occur in the pineal region, suprasellar region and basal ganglia region. The tumors have their own characteristics in terms of gender ratio, disease duration, clinical symptoms and imaging performance.
Germ cell tumors in the pineal region are more common in males, and the age of onset is around 15 years old. The main manifestations include precocious puberty, rough and dark skin, and more beard. The tumor is mostly spherical in shape, with uniform texture, smooth margins, obvious enhancement, and rare cystic degeneration, necrosis and hemorrhage. There may be metastases in the saddle area. Characteristic presentation of suprasellar germ cell tumor: Mostly girls around 10 years old with chronic polyhydramnios and polyuria. Imaging shows a solid tumor with homogeneous texture in the saddle area without calcification. Characteristic presentation of basal ganglia germ cell tumor: boys, early onset of limb weakness or hemiparesis, slow course of disease, imaging characteristics of diffuse growth, poorly defined margins, irregular morphology, uniform density, cystic degeneration, necrosis and hemorrhage are more common. If the tumor is large in size, but the occupying effect is not obvious and the paraneoplastic edema is mild, it is often accompanied by atrophy of the cerebral cortex in the ipsilateral lateral fissure. The enhancement scan shows irregular wreath-like enhancement or speckle-like enhancement.
The detection of tumor markers in cerebrospinal fluid and blood is an important basis for the diagnosis of germ cell tumors. The detection of alpha-fetoprotein (AFP), chorionic gonadotropin (-HCG), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) is important for the differential diagnosis of germ cell tumors and has certain value in the evaluation of efficacy, prognosis, and recurrence monitoring. It is valuable in the evaluation of efficacy, prognosis and monitoring of recurrence.
For children with high suspicion of germ cell tumor, diagnostic radiotherapy (or experimental radiotherapy) should be given first. 10Gy should be used as the initial dose of diagnostic radiotherapy, with a single dose of 1.8-2.0Gy, and MRI (first) should be repeated after 5 irradiations. For cases with progressive shrinkage of tumor volume, irradiation will be continued to 35-40Gy (35Gy for children <10 years old). For cases with no significant reduction in tumor volume on the first or second review MRI, observation can be done for 2-4 weeks, and if the tumor shrinks, the radiation dose will continue to be completed; if the tumor still does not shrink, the diagnosis of non-germ cell tumor can be considered and surgery should be chosen.
Surgery is not a routine option for germ cell tumors. For tumor cryopathology reported as germ cell tumor during surgery, resection of the tumor should be stopped, safe hemostasis should be achieved, and postoperative radiotherapy or chemotherapy should be administered. If intraoperative hemostasis is difficult, the tumor may be continued to be removed until successful hemostasis can be achieved. Removing as little tumor as possible during surgery and surrendering the opportunity to eliminate residual tumor to radiotherapy or chemotherapy reduces surgical complications and improves the quality of survival of the sick child.