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DerekvG/sandbox/old braintumor

A brain tumor is an abnormal growth of cells within the brain, which can be cancerous (malignant) or non-cancerous (benign). It is defined as any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself (neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells, myelin-producing Schwann cells), lymphatic tissue, blood vessels), in the cranial nerves, 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 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),[1] which accounted for 1.4 percent of all cancers, 2.4 percent of all cancer deaths,[2] and 20–25 percent of pediatric cancers.[2][3] Ultimately, it is estimated there are 13,000 deaths per year in the United States alone as a result of brain tumors.[1]

Signs and symptoms

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Symptoms of brain tumors may depend on two factors: tumor size (volume) and tumor location. The time point of symptom onset in the course of disease correlates in many cases with the nature of the tumor ("benign", i.e. slow-growing/late symptom onset, or malignant, fast growing/early symptom onset) is a frequent reason for seeking medical attention in brain tumor cases..

Large tumors or tumors with extensive perifocal swelling edema inevitably lead to elevated intracranial pressure (intracranial hypertension), which translates clinically into headaches, vomiting (sometimes without nausea), altered state of consciousness (somnolence, coma), dilatation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic disc at the funduscopic eye examination). However, even small tumors obstructing the passage of cerebrospinal fluid (CSF) may cause early signs of increased intracranial pressure. Increased intracranial pressure may result in herniation (i.e. displacement) of certain parts of the brain, such as the cerebellar tonsils or the temporal uncus, resulting in lethal brainstem compression. In young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.

Depending on the tumor location and the damage it may have caused to surrounding brain structures, either through compression or infiltration, any type of focal neurologic symptoms may occur, such as cognitive and behavioral impairment, personality changes, hemiparesis, hypoesthesia, aphasia, ataxia, visual field impairment, facial paralysis, double vision, tremor etc. These symptoms are not specific for brain tumors—they may be caused by a large variety of neurologic conditions (e.g. stroke, traumatic brain injury). What counts, however, is the location of the lesion and the functional systems (e.g. motor, sensory, visual, etc.) it affects.

A bilateral temporal visual field defect (bitemporal hemianopia—due to compression of the optic chiasm), often associated with endocrine disfunction—either hypopituitarism or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.


Causes

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Metastatic cancers are far more common than primary tumors of the brain and spinal cord.

Apart from exposure to vinyl chloride or ionizing radiation, there are no known environmental factors associated with brain tumors. Mutations and deletions of so-called tumor suppressor genes are thought to be the cause of some forms of brain tumors. Patients with various inherited diseases, such as Von Hippel-Lindau syndrome, multiple endocrine neoplasia, neurofibromatosis type 2 are at high risk of developing brain tumors. It is alleged that mobile phones/cell phones might be a cause of brain tumors, according to one report.[4] (see Mobile phone radiation and health) There is an association of brain tumor incidence and malaria, suggesting that the anopheles mosquito, the carrier of malaria, might transmit a virus or other agent that could cause a brain tumor.[5] Malignant brain tumor incidence and Alzheimer's disease prevalence are associated in 19 US states. The two diseases may share a common cause, possibly inflammation.[6]

Diagnosis

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Micrograph of an oligodendroglioma, a type of brain cancer. Brain biopsy. H&E stain.

Although there is no specific clinical symptom or sign for brain tumors, 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 tumor, brain swelling or obstruction of cerebrospinal fluid's passage) is also possible.

Glioblastoma multiforme and anaplastic astrocytoma have been associated in case reports on PubMed[who?] with the genetic acute hepatic porphyrias (PCT, AIP, HCP and VP), including positive testing associated with drug refractory seizures. Unexplained complications associated with drug treatments with these tumors should alert physicians to an undiagnosed neurological porphyria.

Imaging plays a central role in the diagnosis of brain tumors. Early imaging methods—invasive and sometimes dangerous—such as pneumoencephalography and cerebral angiography, have been abandoned in recent times in favor of non-invasive, high-resolution modalities, such as computed tomography (CT) and especially magnetic resonance imaging (MRI). Benign brain tumors 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, although the appearance is variable. 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 tumors. This is because these tumors disrupt the normal functioning of the blood-brain barrier and lead to an increase in its permeability. However it is not possible to diagnose high versus low grame gliomas based on enhancement pattern alone.

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

The definitive diagnosis of brain tumor can only be confirmed by histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological examination is essential for determining the appropriate treatment and the correct prognosis. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and followup examination of prepared tissues after immunohistochemical staining or genetic analysis.

Another possible diagnosis would be neurofibromatosis which can be in type one or type two.

Types

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Treatment

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Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically. In more difficult cases, stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery, remains a viable option.[8]

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.[9] However, due to the infiltrative nature of these lesions, tumor recurrence, even following an apparently complete surgical removal, is not uncommon. Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with a chemical (5-aminolevulinic acid) that causes them to fluoresce.[10] 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.[11]

UCLA Neuro-Oncology publishes real-time survival data for patients with this diagnosis. They are the only institution in the United States that shows how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high grade glioma tumors.

Patients with benign gliomas may survive for many years,[12][13] while survival in most cases of glioblastoma multiforme is limited to a few months after diagnosis if treatment is ignored.

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 (SRS), such as Gamma Knife, Cyberknife or Novalis Tx, radiosurgery, remains a viable option. However, the prognosis in such cases is determined by the primary tumor, and it is generally poor.

Radiotherapy is the most common treatment for secondary cancer brain tumors. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam whole brain radiotherapy treatment (WBRT) or 'whole brain irradiation' may be suggested if there is a risk that other secondary tumors will develop in the future.[14] Stereotactic radiotherapy is usually recommended in cases of under three small secondary brain tumors.

In 2008 a study published by the University of Texas M. D. Anderson Cancer Center indicated that cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone.[15][16]

A shunt operation is used not as a cure but to relieve the symptoms.[3] The hydrocephalus caused by the blocking drainage of the cerebrospinal fluid can be removed with this operation.

Prognosis

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The prognosis of brain cancer varies based on the type of cancer. Medulloblastoma has a good prognosis with chemotherpy, radiotherapy, surgical resection, and chemotherapy while glioblastoma multiforme has a median survival of only 12 months even with aggressive chemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. However, one type of brainstem glioma, a focal,[17] seems open to exceptional prognosis and long-term survival has frequently been reported.

Glioblastoma multiforme

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Main article: Glioblastoma multiforme

Glioblastoma multiforme is the deadliest and most common form of malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer. This is followed by chemotherapy. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to palliate symptoms. Experimental treatments include gamma-knife radiosurgery.[18]

Oligodendrogliomas

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Main article: Oligodendroglioma

Oligodendroglioma is an incurable but slowly progressive malignant brain tumor. They can be treated with chemotherapy, surgical resection, and radiotherapy, but initially most neuro-oncologists opt for a course of watchful waiting, with only symptomatic therapy. Median survival for these types of tumors is up to 11.6 years in cases of low grade oligodendroglioma.

In pediatrics

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A brain-stem glioma in four year old. MRI sagittal, without contrast

In the US, about 2000 children and adolescents younger than 20 years of age are diagnosed with malignant brain tumors each year. Higher incidence rates were reported in 1975–83 than in 1985–94. There is some debate as to the reasons; one theory is that the trend is the result of improved diagnosis and reporting, since the jump occurred at the same time that MRIs became available widely, and there was no coincident jump in mortality. The CNS cancer survival rate in children is approximately 60%. The rate varies with the type of cancer and the age of onset: younger patients have higher mortality.[19]

In children under 2, about 70% of brain tumors are medulloblastoma, ependymoma, and low-grade glioma. Less commonly, and seen usually in infants, are teratoma and atypical teratoid rhabdoid tumor.[20] Germ cell tumors, including teratoma, make up just 3% of pediatric primary brain tumors, but the worldwide incidence varies significantly.[21]

Research

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In 2000, researchers at the University of Ottawa, led by John Bell PhD., have discovered that the vesicular stomatitis virus, or VSV, can infect and kill cancer cells, without affecting healthy cells if coadministered with interferon.[22]

The initial discovery of the virus' oncolytic properties were limited to only a few types of cancer. Several independent studies have identified many more types susceptible to the virus, including glioblastoma multiforme cancer cells, which account for the majority of brain tumors.

In 2008, researchers artificially engineered strains of VSV that were less cytotoxic to normal cells. This advance allows administration of the virus without coadministration with interferon. Consequently administration of the virus can be given intravenously or through the olfactory nerve. In the research, a human brain tumor was implanted into mice brains. The VSV was injected via their tails and within 3 days all tumor cells were either dead or dying.[citation needed][dubious – discuss]

Research on virus treatment like this has been conducted for some years, but no other viruses have been shown to be as efficient or specific as the VSV mutant strains. Future research will focus on the risks of this treatment, before it can be applied to humans.[23]

See also

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References

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  1. ^ a b Greenlee RT, Murray T, Bolden S, Wingo PA (2000). "Cancer statistics, 2000". CA Cancer J Clin. 50 (1): 7–33. doi:10.3322/canjclin.50.1.7. PMID 10735013. S2CID 26315886.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ a b American Cancer Society. Accessed June 2000.
  3. ^ Chamberlain MC, Kormanik PA (Feb 1998). "Practical guidelines for the treatment of malignant gliomas". West J Med. 168 (2): 114–20. PMC 1304839. PMID 9499745.{{cite journal}}: CS1 maint: date and year (link)
  4. ^ Nancy McVicar Study Finds Cell Phones Could Cause Noncancerous Tumors
  5. ^ Lehrer S. Anopheles mosquito transmission of brain tumor. Med Hypotheses. 2010 Jan;74(1):167-8. Epub 2009 Aug 4. [1]
  6. ^ Lehrer S. Glioblastoma and dementia may share a common cause. Med Hypotheses. 2010 Feb 22. Epub ahead of print. [2]
  7. ^ http://www.braintumor.org/Tumor Types/
  8. ^ Radiosurgery treatment comparisons - Cyberknife, Gamma knife, Novalis Tx
  9. ^ Nakamura M, Konishi N, Tsunoda S (Feb 2000). "Analysis of prognostic and survival factors related to treatment of low-grade astrocytomas in adults". Oncology. 58 (2): 108–16. doi:10.1159/000012087. PMID 10705237. S2CID 25943854.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  10. ^ Clinical trials in brain tumors.. Accessed June 2000.
  11. ^ Nicolato A, Gerosa MA, Fina P, Iuzzolino P, Giorgiutti F, Bricolo A (Sep 1995). "Prognostic factors in low-grade supratentorial astrocytomas: a uni-multivariate statistical analysis in 76 surgically treated adult patients". Surg Neurol. 44 (3): 208–21, discussion 221–3. doi:10.1016/0090-3019(95)00184-0. PMID 8545771.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  12. ^ Janny P, Cure H, Mohr M (Apr 1994). "Low grade supratentorial astrocytomas. Management and prognostic factors". Cancer. 73 (7): 1937–45. doi:10.1002/1097-0142(19940401)73:7<1937::AID-CNCR2820730727>3.0.CO;2-G. PMID 8137221. S2CID 34884141.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  13. ^ Piepmeier J, Christopher S, Spencer D (May 1996). "Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas". Neurosurgery. 38 (5): 872–8, discussion 878–9. doi:10.1097/00006123-199605000-00002. PMID 8727811.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  14. ^ Treating secondary brain tumours with WBRT
  15. ^ Whole Brain Radiation increases risk of learning and memory problems in cancer patients with brain metastases
  16. ^ IRSA - International RadioSurgery Association - Metastatic brain tumors
  17. ^ http://www.childhoodbraintumor.org/index.php/articles/34-brain-tumor-types-and-imaging/57-brain-stem-gliomas-in-childhood.html
  18. ^ http://brain.mgh.harvard.edu/patientguide.htm
  19. ^ Gurney, James G. "CNS and Miscellaneous Intracranial and Instraspinal Neoplasms" (PDF). SEER Pediatric Monograph. National Cancer Institute. pp. 51–52 (incidence), pp. 56–57 (trends), p. 57 (survival). Retrieved 4 December 2008. [re incidence] In the US, approximately 2,200 children and adolescents younger than 20 years of age are diagnosed with malignant central nervous system tumors each year. More than 90 percent of primary CNS malignancies in children are located within the brain. {{cite web}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  20. ^ Infantile Brain Tumors by Brian Rood for The Childhood Brain Tumor Foundation (accessed July 2007)
  21. ^ Echevarría ME, Fangusaro J, Goldman S (June 2008). "Pediatric central nervous system germ cell tumors: a review". Oncologist. 13 (6): 690–9. doi:10.1634/theoncologist.2008-0037. PMID 18586924. S2CID 8114229.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  22. ^ Researchers Find Cancer-Killing Virus; July 24, 2000.
  23. ^ Yale Lab Engineers Virus That Can Kill Deadly Brain Tumors; February 21, 2008.
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Category:Brain Category:Oncology Category:Disorders causing seizures Category:Brain tumor

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