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Wednesday, March 26, 2008

Brain Tumor

A Brain Tumor is any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself (neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells), lymphatic tissue, blood vessels), in the cranial nerves (myelin-producing Schwann cells), in the brain envelopes (meninges), skull, pituitary and pineal gland, or spread from cancers primarily located in other organs (metastatic tumors). Primary (true) brain tumors are commonly located in the posterior cranial fossa in children and in the anterior two-thirds of the cerebral hemispheres in adults, although they can affect any part of the brain. In the United States in the year 2005, it was estimated that there were 43,800 new cases of brain tumors (Central Brain Tumor Registry of the United States, Primary Brain Tumors in the United States, Statistical Report, 2005 - 2006), which accounted for 1.4 percent of all cancers, 2.4 percent of all cancer deaths, and 20–25 percent of pediatric cancers. Ultimately, it is estimated that there are 13,000 deaths/year as a result of brain tumors.

Classification:
Most primary brain tumors originate from glia (gliomas) such as astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), or ependymal cells (ependymoma). There are also mixed forms, with both an astrocytic and an oligodendroglial cell component. These are called mixed gliomas or oligoastrocytomas. Plus, mixed glio-neuronal tumors (tumors displaying a neuronal, as well as a glial component, e.g. gangliogliomas, disembryoplastic neuroepithelial tumors) and tumors originating from neuronal cells (e.g. gangliocytoma, central gangliocytoma) can also be encountered.

Other varieties of primary brain tumors include: primitive neuroectodermal tumors (PNET, e.g. medulloblastoma, medulloepithelioma, neuroblastoma, retinoblastoma, ependymoblastoma), tumors of the pineal parenchyma (e.g. pineocytoma, pineoblastoma), ependymal cell tumors, choroid plexus tumors, neuroepithelial tumors of uncertain origin (e.g. gliomatosis cerebri, astroblastoma), etc.

Secondary or metastatic brain tumors originate from malignant tumors (cancers) located primarily in other organs. Their incidence is higher than that of primary brain tumors. The most frequent types of metastatic brain tumors originate in the lung, skin (malignant melanoma), kidney (hypernephroma), breast (breast carcinoma), and colon (colon carcinoma). These tumor cells reach the brain via the blood-stream.

Some non-tumoral masses and lesions can mimic tumors of the central nervous system. These include tuberculosis of the brain, cerebral abscess (commonly in toxoplasmosis), and hamartomas (for example, in tuberous sclerosis and von Recklinghausen neurofibromatosis).

Diagnosis:
Although there is no specific clinical symptom or sign for brain tumours, slowly progressive focal neurologic signs and signs of elevated intracranial pressure, as well as epilepsy in a patient with a negative history for epilepsy should raise red flags. However, a sudden onset of symptoms, such as an epileptic seizure in a patient with no prior history of epilepsy, sudden intracranial hypertension (this may be due to bleeding within the tumour, brain swelling or obstruction of cerebrospinal fluid's passage) is also possible.

Imaging plays a central role in the diagnosis of brain tumours. Early imaging methods—invasive and sometimes dangerous—such as pneumoencephalography and cerebral angiography, have been abandoned in recent times in favour of non-invasive, high-resolution modalities, such as computed tomography (CT) and especially magnetic resonance imaging (MRI). Benign brain tumours often show up as hypodense (darker than brain tissue) mass lesions on cranial CT-scans. On MRI, they appear either hypo- (darker than brain tissue) or isointense (same intensity as brain tissue) on T1-weighted scans, or hyperintense (brighter than brain tissue) on T2-weighted MRI. Perifocal edema also appears hyperintense on T2-weighted MRI. Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI-scans in most malignant primary and metastatic brain tumours. This is due to the fact that these tumours disrupt the normal functioning of the blood-brain barrier and lead to an increase in its permeability.

Electrophysiological exams, such as electroencephalography (EEG) play a marginal role in the diagnosis of brain tumours.

The definitive diagnosis of brain tumour can only be confirmed by histological examination of tumour tissue samples obtained either by means of brain biopsy or open surgery. The histologic examination is essential for determining the appropriate treatment and the correct prognosis.

Treatment and Prognosis:
Meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically, but the chances are less than 50%. In more difficult cases, Stereotactic radiosurgery, such as Gamma Knife radiosurgery, remains a viable option.

Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans-nasal, trans-sphenoidal approach). Large pituitary adenomas require a craniotomy (opening of the skull) for their removal. Radiotherapy, including stereotactic approaches, is reserved for the inoperable cases.

Although there is no generally accepted therapeutic management for primary brain tumors, a surgical attempt at tumor removal or at least cytoreduction (that is, removal of as much tumor as possible, in order to reduce the number of tumor cells available for proliferation) is considered in most cases. However, due to the infiltrative nature of these lesions, tumor recurrence, even following an apparently complete surgical removal, is not uncommon. Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors. Radiotherapy may also be administered in cases of "low-grade" gliomas, when a significant tumor burden reduction could not be achieved surgically.

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal, to mention just a few factors.

Patients with benign gliomas may survive for many years while survival in most cases of glioblastoma multiforme is limited to a few months after diagnosis.

The main treatment option for single metastatic tumors is surgical removal, followed by radiotherapy and/or chemotherapy. Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy. Stereotactic radiosurgery, such as Gamma Knife radiosurgery, remains a viable option. However, the prognosis in such cases is determined by the primary tumor, and it is generally poor.

A shunt operation is used not as a cure but to relieve the symptoms. The hydrocephalus caused by the blocking drainage of the cerebrospinal fluid can be removed with this operation.

Research to treatment with the VSV-virus:
In 2008, Researchers of the Yale University, lead by Dr. Anthony van den Pol, have discovered that the Vesicular stomatitis virus, or VSV-virus, can infect and kill brain tumors, without affecting the other brain cells. The oncolytic properties of the virus, which normally applies to cancer cells, have shown to apply to brain tumors as well.

In the research, a human brain tumor was implanted into mice brains. The VSV-virus was injected via its tail and within 3 days all tumor cells were either killed or dying. On the 10,000 infected tumor cells, only one healthy brain cell was affected 'on accident'.

Research to virus-treatment like this has been some years old, but no other virusses has shown to be as efficient or specific as the VSV-virus. Future research will focus on the risks of this treatment, before it can be applied to humans.

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