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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplastic meningitis is an increasingly recognized complication of advanced metastatic cancer and, if left undiagnosed or untreated, is characterized by rapid neurologic deterioration and death. Thus, the diagnosis and treatment of neoplastic meningitis present challenges for the clinical oncologist. The diagnosis of neoplastic meningitis is based on clinical signs and symptoms, laboratory analysis of cerebrospinal fluid to determine cell count and cytology, and analysis of neuroimaging studies for evidence of leptomeningeal or cranial nerve enhancement. Once diagnosed, conventional treatment regimens may include radiotherapy combined with systemic or intrathecal chemotherapy, often with the antimetabolites cytarabine and/or methotrexate. However, the prognosis for neoplastic meningitis secondary to an underlying solid tumor or recurrent leukemia is poor with conventional treatment regimens. Therefore, novel agents for intrathecal administration, including DepoCyttrade mark, mafosfamide, and topotecan, or novel therapeutic approaches, including conjugated monoclonal antibodies and immunotoxins or gene therapy, are currently under investigation. Such new agents and therapeutic approaches will facilitate the development of effective treatment strategies and will ultimately improve the outcome for patients with this devastating disease. This article provides an overview of the approaches to the diagnosis, evaluation, and treatment of neoplastic meningitis.
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PMID:Neoplastic meningitis: diagnosis and treatment considerations. 1096 24

Neoplastic meningitis is a disease of the entire neuraxis and is pleomorphic in its clinical presentation. Diagnosis is achieved by recognition of the clinical manifestations of neoplastic meningitis followed by neuroradiography of the brain and spinal cord and examination of the cerebrospinal fluid. Treatment, if clinically warranted, includes irradiation of symptomatic or bulky disease and intracerebrospinal fluid chemotherapy following an assessment of the extent of metastatic disease treatment is based on the results of four randomized intracerebrospinal fluid chemotherapy trials.
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PMID:Neoplastic meningitis: a guide to diagnosis and treatment. 1114 63

Leptomeningeal metastases (LM) is often an elusive disease frequently diagnosed at an advanced clinical stage. Early diagnosis may allow for prompt initiation of treatment with minimal tumor burden and maximal chance of survival, especially in solid tumors such as breast cancer. Although the method of choice for imaging LM currently is by gadolinium enhanced magnetic resonance imaging (MRI), the technique has a high sensitivity but low specificity. We report the first case of Carbon 11-labelled methionine (Cmet) positron emission tomography (PET) imaging of leptomeningeal metastases in a patient with primary breast cancer. This patient presented with clinical features suggestive of LM, but had inconclusive cerebrospinal fluid (CSF) findings. Although, the contrast enhanced MRI revealed calvarial and meningeal lesions, it is known that meningeal enhancement on MRI does not always indicate metastases. In this clinical dilemma the strong methionine uptake on PET helped steer the diagnosis in favor of cancerous infiltration even before the CSF cytology became positive for malignancy.
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PMID:11C-methionine PET imaging of leptomeningeal metastases from primary breast cancer--a case report. 1180 81

Neoplastic meningitis is recognized clinically in 4% to 7% of patients with extraneural cancer, but it remains dramatically under-diagnosed. The frequency of neoplastic meningitis is increasing because of heightened clinical suspicion, improved neuroimaging techniques, and longer survival in patients with extraneural cancer Longer survival allows residual tumor cells within central nervous system sanctuary sites time to become symptomatic. Affected patients may present with cerebral, cranial nerve, or spinal signs and symptoms, depending on the specific sites of central nervous system (CNS) involvement. Magnetic Resonance Imaging (MRI) seems to be sensitive for detecting metastatic deposits along the neuraxis. However, metastases at a microscopic level are below the resolution of MRI scanning. As a result, the standard diagnostic test for neoplastic meningitis remains the cytologic identification of malignant cells in cerebrospinal fluid (CSF). Although CSF cytology is useful, malignant cells are not detected in as many as one third of patients who have compelling clinical or radiographic evidence of neoplastic meningitis. Novel assays are being tested that may enhance the early identification of malignant cells in CSF. Currently, the diagnosis occurs generally after the onset of neurologic manifestations and heralds a rapidly fatal course for most patients. By the time symptoms appear, most tumors have disseminated widely within the CNS, due to cortical irritation, compression of nervous system structures, or obstruction of CSF flow. At this stage surgery, cranial irradiation, and chemotherapy are rarely, if ever, curative. The goals of treatment are to improve or to stabilize the neurologic status of patients and to prolong survival. A major problem in treating neoplastic meningitis is that the entire neuraxis must be treated. If only symptomatic areas are treated, reseeding of the neuraxis with tumor cells will occur. Therefore, intrathecal chemotherapy remains a mainstay of therapy. Currently, four therapeutic agents are available for intrathecal treatment: methotrexate, ara-C, sustained-release ara-C (DepoCyt; Chiron Therapeutics, San Francisco, CA), and thiotepa. Unfortunately, intrathecal chemotherapy does not treat bulky disease in the subarachnoid space, and often is slow to stabilize progressive neurologic deficits. For these reasons, radiation therapy to sites of symptomatic disease and sites of bulky disease on imaging studies is recommended. High dose intravenous methotrexate may be as effective as intrathecal methotrexate. Alternative approaches (which offer less toxicity, enhanced therapeutic effect, and prolonged survival) are being investigated.
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PMID:Neoplastic meningitis. 1205 97

Metastasis to the leptomeninges occurs in many common cancers, including leukemia; lung, breast, and gastrointestinal cancers; and tumors of the brain. By way of the flow of cerebrospinal fluid, leptomeningeal metastasis spreads throughout the neuraxis. Consequently, therapy for leptomeningeal metastasis must be directed to the entire central nervous system (CNS). Treatment often consists of involved-field radiotherapy, systemic chemotherapy, and intrathecal chemotherapy. However, because meningeal spread occurs most often in advanced disease, treatment is mainly palliative, except in childhood leukemia, where durable remission has been reported. This article outlines the role of systemic and intrathecal chemotherapy in patients with leptomeningeal metastases. Strategies for symptom management in these patients are also described.
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PMID:Systemic chemotherapy, intrathecal chemotherapy, and symptom management in the treatment of leptomeningeal metastasis. 1249 48

Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus. Here, we examined the ability of human reovirus to kill MB cells lines and surgical specimens in vitro and inhibit tumor growth/metastases in vivo. Most human MB cell lines tested (five of seven = 71.4%), two MB cell lines derived from spontaneously arising tumors in Patched-1(+/-) mice (two of two = 100%) and three MB primary cultures derived from surgical specimens, were susceptible to reovirus infection. Reovirus was internalized and transcribed in both susceptible and resistant cell lines. However, viral protein synthesis was restricted to cell lines with higher levels of activated Ras, suggesting that Ras plays a critical role in reovirus oncolysis in MB. Using an in vivo Daoy orthotopic animal model, we found that a single i.t. injection of reovirus dramatically prolonged survival compared with controls (160 versus 70 days, respectively; P = 0.0003). Repeating this experiment with GFP-labeled Daoy cells and multiple i.t. administrations of reovirus, we again found prolonged survival and a dramatic reduction in spinal and leptomeningeal metastases (66.7% in control injections versus 0.0% in the live virus group). These data suggest that this oncolytic virus may be a potentially effective novel therapy against human MB. Its ability to reduce metastases to the spinal cord could allow a reduction in the dose/field of total neuroaxis cerebral-spinal radiotherapy currently used to treat/prevent cerebral spinal fluid dissemination.
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PMID:Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma. 1281 Jun 44

We report two patients with leptomeningeal metastases from squamous cell cancer of the skin. In one patient cauda equina metastases appeared 6 years after initial presentation; the tumor from radical neck dissection demonstrated perineural invasion suggesting a possible route for subarachnoid dissemination. The other patient presented 2 years after initial diagnosis with confusion and cranial nerve seven and twelve palsies. Both patients died from complications of leptomeningeal metastases.
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PMID:Leptomeningeal metastases from recurrent squamous cell cancer of the skin. 1289 36

To develop new treatment strategies for patients with leptomeningeal metastases (LM), potential therapeutic agents have to be tested in murine models first. In vivo magnetic resonance imaging has an additive value in non-invasive monitoring of the effects of therapeutic agents on LM. Previously, we described a reproducible mouse model for B16F-10 melanoma LM. In this paper, we visualize leptomeningeal melanoma metastases in mice on both T2 weighted MR images and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced T1 weighted MR images, using a 4.7T MR spectrometer. We conclude that both MR sequences can be used to detect and monitor LM of melanoma cells in mice. Our data further suggest that LM are more clearly visualized using T1 weighted Gd-DTPA enhanced subtraction imaging than T2 weighted imaging.
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PMID:MR imaging of mouse leptomeningeal metastases. 1521 48

A 14-year-old girl was found to have a large, non-tender breast mass with anemia and thrombocytopenia. The diagnosis of an undifferentiated carcinoma of unknown primary was made after open breast biopsy of the mass with negative immunohistochemical studies for breast malignancies. Further evaluation showed extensive metastatic disease affecting the bone marrow, ribs, liver, and brain with magnetic resonance imaging evidence of carcinomatous meningitis. Despite 2 months of chemotherapy and intensive supportive care, the patient died of severe lactic acidosis and disseminated intravascular coagulation after exaggerated menstrual bleeding. The association of severe lactic acidosis and undifferentiated carcinoma of unknown primary in an adolescent has not been previously described.
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PMID:Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary. 1554 20

We report 4 cases of spinal cord metastases of lung cancer detected by MRI. Histologically, 3 of the 4 cases were small cell carcinoma and the other was adenocarcinoma. All 3 cases of small cell carcinoma had neoplastic meningitis. MRI taken in these cases showed the multiple nodules in the cauda equina, which were seeded from brain metastases. One of them had intramedullary spinal cord metastases, which appeared as enlargement of the spinal cord or nodules in the spinal cord on MRI. Leg paralysis and incontinence progressed in all cases. The other case of adenocarcinoma had epidural spinal cord compression due to spinal metastasis. In this case irradiation and corticosteroids relieved her leg and back pain. Spinal cord metastases should be considered as a differential diagnosis in patients with numbness, pain or weakness in the extremities.
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PMID:[Spinal cord metastases in lung cancer: a clinical review of four cases]. 1596 11


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