脳転移

WordNet

kill by smashing someones skull
mental ability; "hes got plenty of brains but no common sense" (同)brainpower, learning_ability, mental capacity, mentality, wit
that part of the central nervous system that includes all the higher nervous centers; enclosed within the skull; continuous with the spinal cord (同)encephalon
the brain of certain animals used as meat
hit on the head
the spreading of a disease (especially cancer) to another part of the body

PrepTutorEJDIC

『脳』,脳髄 / 《しばしば複数形で》『頭脳』,『知力』 / 《話》秀才,知的指導者 / …‘の'頭を打ち砕く
(癌(がん)などの)転移
=brassiere,　brassiere

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/26 21:34:24」(JST)

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Micrograph showing a colorectal carcinoma metastasis to the cerebellum. HPS stain.

Brain metastasis in the right cerebral hemisphere from lung cancer shown on T1-weighted magnetic resonance imaging with intravenous contrast.

A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body.^[1] As primary cancer treatments such as surgery, radiation therapy and chemotherapy have become more effective in the past few decades, people with cancer are living longer after initial treatment than ever before. However, brain metastases still occur in many patients months or even years after their original cancer treatment. Brain metastases have a poor prognosis for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.^[2]

Symptoms

Often, patients have no obvious symptoms to alert them that their cancer has spread to the brain. Follow-up doctor visits and brain scans may be needed to determine the presence of brain metastases.^[3]

Brain metastases can cause a wide variety of symptoms, many of which are also present in minor, more common conditions. They include:

Vertigo
New onset headaches
Cognitive, personality, and behavioral changes.
Nausea and vomiting
Memory loss
Increased intracranial pressure
Paraesthesias
Vision disorder
Bells palsy
Ataxia
Seizures

Causes

The most common sources of brain metastases in a case series of 2,700 patients undergoing treatment at the Memorial Sloan–Kettering Cancer Center were:

Lung cancer, 48%
Breast cancer, 15%
Genitourinary tract cancers, 11%
Osteosarcoma, 10%
Melanoma, 9%
Head and neck cancer, 6%
Neuroblastoma, 5%
Gastrointestinal cancers, especially colorectal and pancreatic carcinoma, 3%
Lymphoma, 1%

Treatment

Treatment for brain metastases is primarily palliative, with the goals of therapy being reduction of symptoms and prolongation of life. However, in some patients, particularly younger, healthier patients, aggressive therapy consisting of open craniotomy with maximal excision, aggressive chemotherapy, and radiosurgical intervention (gamma knife radiosurgery) may be attempted.

Symptomatic care

Symptomatic care should be given to all patients with brain metastases, as they often cause severe, debilitating symptoms. Treatment consists mainly of:

Corticosteroids - Corticosteroid therapy is essential for all patients with brain metastases, as it prevents development of cerebral edema (swelling of the brain tissue), as well as treating other neurological symptoms such as headaches, cognitive dysfunction, and emesis. Dexamethasone is the corticosteroid of choice.
Anticonvulsants - Anticonvulsants should be used in all of the 30-40% of patients with brain metastases who experience seizures, as there is a risk of status epilepticus and death, as is the case with other patients with possibly severe seizure types (particularly generalized tonic- clonic, or grand mal, seizures, where the entire brain, not just one local focus or lobe, is pathologically affected). Phenytoin is the most commonly used drug in this setting, but valproic acid and other anticonvulsants can also be used; newer anticonvulsants generally have the advantage of fewer toxic side effects.

Radiotherapy

Radiotherapy plays a critical role in the treatment of brain metastases, and includes whole-brain irradiation, fractionated radiotherapy, and radiosurgery. For decades, whole brain irradiation has been advocated for patients with multiple lesions, a life expectancy of less than three months, or a low Karnofsky performance score, and it does appear at least somewhat effective. However, it often causes severe side effects, including radiation necrosis, dementia, toxic leukoencephalopathy, partial to complete hair loss, nausea, headaches, and otitis media. In children this treatment may cause mental retardation, psychiatric disturbances, and other neuropsychiatric effects.^[4]

Surgery

Brain metastases are often managed surgically, with maximum surgical resection followed by stereotactic radiosurgery or whole-brain irradiation delivering superior survival compared to whole brain irradiation alone. Therefore, in patients with one metastatic brain lesion, limited, absent, or controlled systemic disease, a life expectancy of at least 3 months and good performance status might be expected.^[5]

Sterotactic Radiosurgery

Stereotactic radiosurgery is being increasingly utilized for the treatment of a limited number of brain metastases. Stereotactic radiosurgery alone or with whole brain radiation therapy has been shown to achieve excellent local tumor control. Addition of stereotactic radiosurgery to whole brain radiation can increase the control rate and functional status of patients.^[6]

Chemotherapy

Chemotherapy is rarely used for the treatment of brain metastases, as chemotherapeutic agents penetrate the blood brain barrier poorly.^[1] However, some cancers such as lymphomas,small cell lung carcinomas and breast cancer are highly chemosensitive and chemotherapy may be used to treat extracranial sites of metastatic disease in these cancers.^[1] An experimental treatment for brain metastases is intrathecal chemotherapy, a technique in which a chemotherapeutic drug is delivered via intralumbar injection into the cerebrospinal fluid. However, it is not approved by the U.S. Food and Drug Administration (FDA) for the treatment of brain metastases.^{[citation needed]}

Prognosis

The prognosis for brain metastases is variable. It depends on the type of primary cancer, the age of the patient, the absence or presence of extracranial metastases, and the number of metastatic sites in the brain. For all patients combined, median survival is only 2.3 months. However, in some patients, such as those with no extracranial metastases, those who are younger than 65, and those with a single site of metastasis in the brain only, prognosis is much better, with median survival rates of up to 13.5 months.^[1]

References

^ ^a ^b ^c ^d Tse, Victor (10 November 2009). "Brain Metastasis". Medscape. Retrieved 13 January 2010.
^ http://www.rtanswers.com/treatmentinformation/cancertypes/brainmets/index.aspx
^ http://www.rtanswers.com/treatmentinformation/cancertypes/brainmets/signs.aspx
^ http://www.astro.org/PressRoom/PressKit/AnnualMeeting/documents/Movsas.pdf
^ http://emedicine.net
^ Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases. Patil CG, Pricola K, Garg SK, Bryant A, Black KL. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD006121. Review. PMID 20556764

UpToDate Contents

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1. Overview of the treatment of brain metastases
2. Epidemiology, clinical manifestations, and diagnosis of brain metastases
3. 原発性および転移性脳腫瘍患者における血管原性浮腫のマネージメント management of vasogenic edema in patients with primary and metastatic brain tumors
4. 乳癌における脳転移のマネージメント management of brain metastases in breast cancer
5. 黒色腫（メラノーマ）の脳転移のマネージメント management of brain metastases in melanoma

English Journal

The proinflammatory peptide substance P promotes blood-brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions.

Rodriguez PL, Jiang S, Fu Y, Avraham S, Avraham HK.Author information The Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.AbstractNeuropeptide substance P (SP) has been implicated in inflammation, pain, depression and breast cancer cell (BCC) growth. Here, we examined the role of SP in trafficking of BCCs (human MDA-MB-231 and MDA-MB-231BrM2 cells) across the blood-brain barrier (BBB) and brain microvascular endothelial cells (BMECs) using in vitro and in vivo models. SP was secreted from BCCs and mediated adhesion and transmigration of BCCs across human BMECs (HBMECs) in vitro. SP induced activation of HBMECs, leading to secretion of Tumor Necrosis Factor alpha (TNF-α) and angiopoietin-2 (Ang-2) from HBMECs, resulting in changes in localization and distribution of tight junction (TJ) ZO-1 (tight junction protein zonula occludins-1) and claudin-5 structures as well as increased permeability of HBMECs. Using spontaneous breast cancer metastasis mouse model (syngeneic) of GFP-4T1-BrM5 mammary tumor cells administered into mammary fat pads of Balb/c mice, SP inhibitor spantide III inhibited in vivo changes in permeability of the BBB and BMEC-TJs ZO-1 and claudin-5 structures as well as decreased tumor cell colonization in brain. Thus, SP secreted from BCCs induces transmigration of BCCs across the BBB, leading to activation of BMECs and secretion of TNF-α and Ang-2, resulting in BBB impairment and colonization of tumor cells in brain. Therefore, therapies based on SP inhibition in combination with other therapies may prevent breaching of the BBB by BCCs and their colonization in brain.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 Mar 1;134(5):1034-44. doi: 10.1002/ijc.28433. Epub 2013 Sep 3.
Neuropeptide substance P (SP) has been implicated in inflammation, pain, depression and breast cancer cell (BCC) growth. Here, we examined the role of SP in trafficking of BCCs (human MDA-MB-231 and MDA-MB-231BrM2 cells) across the blood-brain barrier (BBB) and brain microvascular endothelial cells
PMID 23934616

Structural and functional effects of metastases in rat brain determined by multimodal MRI.

Serres S, Martin CJ, Sarmiento Soto M, Bristow C, O'Brien ER, Connell JJ, Khrapitchev AA, Sibson NR.Author information CR-UK/MRC Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, United Kingdom.AbstractMetastasis to the brain results in significant impairment of brain function and poor patient survival. Currently, magnetic resonance imaging (MRI) is under-utilised in monitoring brain metastases and their effects on brain function. Here, we sought to establish a model of focal brain metastasis in the rat that enables serial multimodal structural and functional MRI studies, and to assess the sensitivity of these approaches to metastatic growth. Female Berlin-Druckrey-IX rats were injected intracerebrally with metastatic ENU1564 cells in the ventroposterior medial nucleus (VPM) of the thalamus, a relay node of the whisker-to-barrel cortex pathway. Animals underwent multimodal structural and vascular MRI, as well as functional MRI of the cortical blood oxygenation level dependent (BOLD) responses to whisker pad stimulation. T2 , diffusion, magnetisation transfer and perfusion weighted MRI enabled differentiation between a central area of more advanced metastatic growth and penumbral regions of co-optive perivascular micrometastatic growth, with magnetisation transfer MRI being the most sensitive to micrometastatic growth. Areas of cortical BOLD activation in response to whisker pad stimulation were significantly reduced in the hemisphere containing metastases in the VPM. The reduction in BOLD response correlated with metastatic burden in the thalamus, and was sensitive to the presence of smaller metastases than currently detectable clinically. Our findings suggest that multimodal MRI provides greater sensitivity to tumour heterogeneity and micrometastatic growth than single modality contrast-enhanced MRI. Understanding the relationships between these MRI parameters and the underlying pathology may greatly enhance the utility of MRI in diagnosis, staging and monitoring of brain metastasis.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 Feb;134(4):885-96. doi: 10.1002/ijc.28406. Epub 2013 Aug 29.
Metastasis to the brain results in significant impairment of brain function and poor patient survival. Currently, magnetic resonance imaging (MRI) is under-utilised in monitoring brain metastases and their effects on brain function. Here, we sought to establish a model of focal brain metastasis in t
PMID 23913394

Vemurafenib in the French temporary authorization for use metastatic melanoma cohort: a single-centre trial.

Fennira F, Pagès C, Schneider P, Sidina I, Viguier M, Basset-Seguin N, Madjlessi-Ezra N, Madelaine I, Bagot M, Battistella M, Porcher R, Mourah S, Lebbé C.Author information Departments of aDermatology bPharmacy cPathology dPharmacology Laboratory, Saint Louis Hospital eDepartment of Biostatistics, Hotel Dieu Hospital fINSERM U976 gParis 7 Diderot University, Paris, France.AbstractVemurafenib, a selective BRAF inhibitor, has recently shown an improved overall survival (OS) in metastatic melanoma with V600E mutation in phase 2 and 3 trials. Patients with BRAF V600E metastatic melanoma received vemurafenib orally, in the French temporary authorization for use program from April 2011 to April 2012. We analysed the clinical benefit and safety of vemurafenib. Secondary analyses included the impact of brain metastases on median OS and progression-free survival (PFS). Fifty patients were enrolled, of whom 20% had stage IIIC and 80% stage IV disease. The majority were men (58%), with a median age of 58 years (51-69). Forty-three patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 (86%). Twenty patients had brain metastases (40%). Overall response rate was 53%. Complete response was achieved in five patients (10%), partial response in 21 patients (43%) and stable disease in seven patients (14%). Median OS was 7.5 months (95% confidence interval 5.6-12.7) and PFS was 3.6 months (95% confidence interval 2.9-5.9). Patients with brain metastasis had a response rate of 50% (nine partial response, one complete response), and median OS and PFS were, respectively, 4.3 and 3.1 months. Common adverse events were fatigue, arthralgia and cutaneous side effects. Sixteen per cent developed squamous cell carcinoma. Grade 3/4 was observed in 11 patients (22%). Six per cent required temporary discontinuation and/or dose reduction because of toxic effects. This study confirms the considerable clinical benefit of vemurafenib for patients with brain metastasis, with manageable toxicity.
Melanoma research.Melanoma Res.2014 Feb;24(1):75-82. doi: 10.1097/CMR.0000000000000034.
Vemurafenib, a selective BRAF inhibitor, has recently shown an improved overall survival (OS) in metastatic melanoma with V600E mutation in phase 2 and 3 trials. Patients with BRAF V600E metastatic melanoma received vemurafenib orally, in the French temporary authorization for use program from April
PMID 24241686