【Overview】 Glioma is the most common intracranial tumor originating from glial cells in the brain, accounting for about 45% of all intracranial tumors. It ranks second among malignant tumors in children. In the past 30 years, the incidence of primary malignant brain tumors has been increasing year by year, with an annual growth rate of about 1.2%, which is especially obvious in the middle-aged and elderly population. According to the literature, the annual incidence rate of gliomas in China is 3-6 people/100,000 people, and the number of annual deaths reaches 30,000 people. Glioma is an infiltrative growth, it has no obvious boundary with normal brain tissue, it is difficult to be completely removed, it is not very sensitive to radiotherapy and chemotherapy, it is very easy to recur, and it is difficult to be removed by surgery or cannot be operated at all when it grows in the brain and other important parts of benign and malignant tumors. Chemical drugs and general anti-tumor traditional Chinese medicine, due to the influence of blood-brain barrier and other factors, the efficacy is not ideal, so glioma is still one of the tumors with the worst prognosis in the whole body. Epidemiology] Glioma is the most common intracranial tumor. Among gliomas, astrocytoma is the most common, followed by glioblastoma multiforme, and ventricular meningioma is the third most common. Gender is more common in males, especially in glioblastoma multiforme and medulloblastoma, which are significantly more common in males than females. Most of the gliomas are found between 20 and 50 years of age, with 30 to 40 years of age as the highest peak, and another small peak is seen in children around 10 years of age. Each type of glioma has its own age of prevalence, such as astrocytomas occurring in the prime of life, glioblastoma multiforme occurring in middle age, ventricular meningiomas occurring in children and young adults, and medulloblastomas occurring mostly in children. The occurrence site of each type of glioma is also different, such as astrocytoma occurs in the adult cerebral hemisphere, and occurs in the cerebellum in children; glioblastoma multiforme occurs in the cerebral hemisphere almost all the time; ventricular meningioma occurs in the fourth ventricle; oligodendroglioma occurs in the cerebral hemisphere most of the time, and medulloblastoma occurs in the cerebellum in the cerebellar earth part almost all of the time. Clinical manifestations] The course of gliomas varies according to the type of pathology and location, and the time from the onset of symptoms to diagnosis is usually a few weeks to a few months, with a few cases lasting several years. The history of highly malignant and posterior cranial fossa tumors tends to be shorter, and the history of more benign tumors or tumors located in the so-called quiet zone tends to be longer. The progression of symptoms can be accelerated in tumors with hemorrhage or cyst formation, and in some cases may even resemble the progression of cerebrovascular disease. Symptoms are manifested in two main ways. One is increased intracranial pressure and other general symptoms, such as headache, vomiting, vision loss, diplopia, seizures and psychiatric symptoms. The other is local symptoms resulting from compression, infiltration, and destruction of brain tissue by the tumor, causing neurological deficits. Headache is mostly due to increased intracranial pressure. Tumor growth gradually increases intracranial pressure, which compresses and involves intracranial pain-sensitive structures such as blood vessels, dura mater and certain cranial nerves to produce headache. Most of the headaches are throbbing and swelling pains, mostly in the frontotemporal or occipital area, and the headache may be mainly on the affected side in the superficial tumor of one cerebral hemisphere, which is intermittent and occurs in the early morning, and then worsens with the development of the tumor. Vomiting is due to the stimulation of the medullary vomiting center or vagus nerve, which may not be preceded by nausea and is projectile. In children, the headache is not significant due to the separation of the cranial sutures, and the vomiting is more prominent due to the prevalence of tumors in the posterior cranial fossa. Increased intracranial pressure may produce optic papillary edema, and for a long time lead to secondary atrophy of the optic nerve and vision loss. Tumor compression of the optic nerve produces primary optic nerve atrophy, which also leads to vision loss. The abducens nerve is easily compressed and pulled, often leading to paralysis and diplopia. A proportion of patients with tumors have epilepsy, which can be an early symptom. Epilepsy begins in adulthood and is usually symptomatic, mostly due to brain tumors. The presence of a brain tumor should be considered in patients who cannot be easily controlled by medications or who have a change in the nature of the seizures. Epilepsy is common in tumors adjacent to the cortex and rare in those deep within. Limited epilepsy has localizing significance. Some tumors, especially those located in the frontal lobe, may gradually develop psychiatric symptoms, such as personality changes, apathy, decreased speech and activity, poor concentration, memory loss, lack of concern for things, and lack of neatness. The local symptoms are according to the location of the tumor, and the symptoms will be aggravated progressively. Especially malignant glioma grows faster, infiltrates and destroys the brain tissue, and the surrounding brain edema is also significant, so the local symptoms are more obvious and develop faster. In the early stage of intraventricular tumors or tumors located in the quiet zone, there may be no local symptoms. Tumors in the brainstem and other important functional parts of the brain appear local symptoms in the early stage, and symptoms of increased intracranial pressure appear only after a long time. In some tumors with slow development, symptoms of increased intracranial pressure often appear only in the late stage due to compensatory effect. Auxiliary examination] CT and MRI scanning combined with enhancement can mostly lead to clinical diagnosis. Treatment: The growth of glioblastoma is characterized by infiltrative growth, with no obvious boundary with normal brain tissue, most of which are not limited to one lobe, but are finger-shaped to the outside of the brain tissue to destroy the brain tissue in depth, and the growth of benign tumors is slow, with a longer course of the disease, and an average of two years from the emergence of symptoms to the consultation, while malignant tumors grow fast, with a shorter course of the disease, and most of the tumors grow in three months from the emergence of symptoms to the consultation, and 70-80% of them develop within six months. Most of the tumors grow rapidly and have a short course. At present, the treatments for glioma at home and abroad are generally surgery, radiotherapy, chemotherapy, X-knife, γ-knife and so on. Based on the growth characteristics of glioma, theoretically it is impossible to completely remove the tumor by surgery, and some tumors growing in the brain stem and other important parts of the brain cannot be operated at all. Therefore, the therapeutic purpose of surgery can only be limited to the following five aspects: (1) to make clear pathological diagnosis; (2) to reduce the volume of tumor and lower the number of tumor cells; (3) to improve the symptoms and alleviate the symptoms of high cranial pressure; (4) to prolong the life and create the time for the subsequent other comprehensive treatment; (5) to obtain the tumor cytokinetics; and (6) to obtain the tumor cytokinetics. prolonging life and creating time for other subsequent comprehensive treatments; ⑤ obtaining tumor cytokinetic data to provide a basis for finding effective treatments. Individualized surgical treatment for glioma patients Surgical plan is one of the main factors determining the prognosis in individualized treatment. Individualized treatment is based on individualized diagnosis, which mainly refers to the assessment of the tumor size, nature, anatomical location, adjacency to the surrounding important neurocortex, nuclei, nerve fibers, secondary diseases secondary to glioma, and the overall functional status of the patient. On the basis of a clear diagnosis of the above conditions, individualized surgical treatment is performed. Guided by a variety of localization and monitoring techniques, glioma surgery in functional areas has been transformed from a purely anatomical model to an individualized anatomical-functional model. 1.1 Preoperative individualized diagnosis and evaluation 1. Individualized diagnosis of the adjacency between important functional cortex and glioma It is very necessary to utilize appropriate techniques and equipment to anatomically as well as functionally locate the important functional areas and fiber alignments of the patient’s cortex prior to surgery.MRI imaging techniques for preoperative planning can help with cortical localization in the intraoperative period. With the significant development of computer-assisted neuronavigation systems, it has made brain tumor surgery safer, more effective, and more cost-effective. Neuronavigation allows for more precise localization of intracranial tumors and allows the neurosurgeon to choose a safer surgical approach to remove the tumor. Individualized Diagnosis of Important Nerve Conduction Bundles in Relation to Glioma Adjacency In addition to the preservation of important functional cortex in the operative field, it is also important to identify subcortical white matter fibers and protect them intraoperatively, which requires a clear understanding of subcortical fibers for speech, motor, somatosensory, and visual pathways. Magnetic resonance can be used as a noninvasive means of studying the alignment of human nerve fibers. It can be used to show the downstream conduction tracts of motor neurons originating from the functional cortex. Combining intraoperative cortical mapping with DTI fiber conduction tract imaging to show subcortical motor conduction pathways can reduce mortality and permanent loss of neurological function due to tumor resection. 1.2 Intraoperative anesthesia and individualized diagnosis and treatment of glioma Depending on the location of the tumor and the patient’s general condition, surgery can be divided into surgery under conventional anesthesia and awake anesthesia. For the former, after the dura is opened, the motor area cortex is first identified, which can reduce postoperative epilepsy. Intraoperatively, the tumor boundaries and the extent of surgical resection are determined in conjunction with preoperative and intraoperative navigation information. Currently, more and more hospitals are engaging in awake craniotomy attempts. In general, tumors located in the dominant hemisphere and close to the language area are those for which awake craniotomy is of greater significance. This can reduce postoperative aphasia. 1.3, Intraoperative pathology Intraoperatively, rapid cryopathology is performed on suspicious tissues around the tumor to decide the surgical boundaries in order to reduce possible residual tumors and avoid excessive resection of functional cortex or fibers. In patients with a history of seizures in combination with a space-occupying lesion in the brain, especially in those for whom medication is ineffective, abnormal epileptogenic foci can be identified using cortical electrophysiologic monitoring techniques. Since those epileptogenic foci are non-functional, the epileptogenic foci can be removed at the same time as the tumor. Radiotherapy is a therapy that uses high-energy rays (e.g., X-rays, gamma rays, or charged ions) to kill tumor cells by damaging DNA. However, radiotherapy kills tumor cells and also destroys normal cells; therefore, radiotherapy needs to be carefully planned to minimize its side effects. The radiation used to treat tumors can come from outside the body (external radiation therapy) or from radioactive material implanted inside the body near the tumor tissue or injected into the body through blood vessels (internal radiation therapy). Depending on the type of tumor, radiotherapy can be given before, during, or after surgery. Radiotherapy can be given alone or in combination with chemotherapy. Current imaging-based radiotherapy ignores differences in tumor growth kinetics from patient to patient, which can vary significantly between patients with the same pathologic diagnosis. There is growing evidence that normal tissue response to radiotherapy-induced damage varies dramatically from patient to patient, even if they receive the same treatment. This may be due to differences in cell-intrinsic sensitivity to radiotherapy. Therefore, it is also necessary to study and implement individualized radiotherapy for gliomas. Intraoperatively, with navigation assistance, a number of points in the peripheral region of the tumor are selected for pathological examination, and according to the pathological findings, it is suggested that there are or may be tumor remnants in what location, which will be used as the focus of radiotherapy in the later stage, so as to realize the individualization of radiotherapy for glioma. Chemotherapy 3.1. The theoretical basis of individualized chemotherapy For each glioma patient, although the WHO classification is similar and the histological typing is the same, there still exists the change and difference of tumor biology related genes among individuals, which is the reason why different patients have different effects on the same treatment plan, and it is also the basis for individualized diagnosis and treatment of glioma. Individualized chemotherapy plan based on drug sensitivity test can avoid ineffective chemotherapy and effectively inhibit tumor recurrence, thus achieving good therapeutic effect. Since tumor drug resistance is one of the important reasons for chemotherapy failure, individualized chemotherapy can be guided according to the expression of tumor drug-resistant genes, which can avoid blind ineffective chemotherapy. 3.2 How to carry out individualized treatment Before carrying out individualized chemotherapy for glioma, it is necessary to carry out individualized molecular pathology diagnosis of glioma. In addition to conventional pathological typing and WHO classification, individualized molecular pathological diagnosis is more important to carry out molecular diagnosis for patients through chromosome and gene level testing; through molecular level testing, prognosis can be evaluated, and the types of chemotherapeutic drugs and their usage can be determined. Tumor drug sensitivity test is of great significance to the selection of chemotherapy drugs and the formulation of chemotherapy strategy, which provides the basis for the individualization of chemotherapy drugs. In addition to individualized diagnosis and chemotherapy at the gene level, individualized chemotherapy for glioma can also be carried out in different ways for different anatomical parts of the species, including oral drug chemotherapy, intravenous systemic chemotherapy, and placing the fluid storage capsule through the tumor cavity, so as to change the traditional systemic chemotherapy into local chemotherapy. At the same time, the use of the reservoir capsule facilitates the detection of chemical substance signals in the tumor cavity, and regular visits are made to determine tumor efficacy, recurrence and prognosis. During the dynamic monitoring process, new mutations in the tumor cells are found in time and the chemotherapy regimen is adjusted. At the same time, it helps to assess the prognosis of patients and determine the recurrence. In addition, under interventional assistance, the blood-supplying artery of the tumor is selected, and then the radiotherapy drug is released, realizing the change of systemic chemotherapy to local chemotherapy under the condition of non-craniotomy surgery. 3.3, Combining chemotherapy with the research results of glioma stem cells Glioma stem cells are cells of origin that directly generate brain tumors, or are called seed cells. Compared with ordinary tumor cells, they are more resistant to radiation and drugs, and they are the key factors determining tumor growth, invasion, and recurrence. We can compare a glioma mass to a nest of hornets, in which ordinary tumor cells are the ordinary hornets and glioma stem cells are the queen bees among them. Therefore, only killing the glioma stem cells can truly cure the brain tumor. This is an old Chinese saying, “Catch the thief first, catch the king”. The queen bee has functional characteristics that ordinary wasps do not have, and this glioma stem cell is the same. Normal chemotherapeutic drugs can kill normal glioma cells, but have no effect on glioma stem cells. It was found that glioma stem cells have proteins on their surface that can selectively pump foreign molecules (e.g., chemotherapeutic drugs) out of their cells, and that inhibiting these proteins would allow chemotherapeutic drugs to enter the glioma stem cells and thus have a killing effect. Illustration: Clinical observations of chemotherapy regimens developed based on the chemotherapy-resistant characteristics of glioma stem cells. From left to right, before and after the first chemotherapy, before the second chemotherapy (postoperative) MRI enhancement and after the second chemotherapy CT, the tumor enlarged and new foci appeared after the first chemotherapy, and the remaining small foci disappeared after the second chemotherapy.