Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the immunocompromised patient, even mild forms of any combination of headache, meningismus, altered mental status, or focal neurologic signs should initiate an evaluation for possible CNS infection. The limited signs and symptoms of acute CNS infection are not due to specific organisms but to pathologic changes at the neuroanatomic site of infection. The initial clinical history, examination, laboratory, and neuroradiographic data will narrow the problem to one of several groups of agents, although it may not be possible to specify a single causative agent. It should be remembered that several concurrent infections (i.e., CMV and toxoplasmosis, aspergillosis, and bacterial sepsis) may be present. Thus, the clinician should rely on broad antibiotic coverage appropriate to the suspected causative agent or agents at the site of infection. It may be necessary to offer broad-spectrum antibiotic coverage for a CSF presentation that is subsequently found to result from a viral illness or from a noninfectious cause. However, one should avoid undertreating those infections for which specific therapy can be offered, and broad-spectrum treatment usually will not be regretted. Uncertainty in diagnosis following noninvasive procedures should lead to a brain biopsy. Although many of the infections discussed in this article have a poor prognosis, some of the most common pathogens, such as Cryptococcus, Listeria, and Toxoplasma, have effective specific therapies to which the patient should have access as rapidly as possible. The clinician who has successfully treated a patient with CNS infection should remain vigilant for late sequelae or recurrence of infection. Chronic treatment of some infections, such as toxoplasmosis or aspergillosis, may be necessary. The reintroduction of steroids for the treatment of an underlying cancer may reactivate previously treated disease, such as cryptococcosis, and periodic CSF surveillance is appropriate under these circumstances. Recurrence of the symptoms should raise the suspicion of recurrent or new infection, and the patient also should be evaluated with CT or MRI for the development of hydrocephalus or for new metastatic disease. In patients who have had varicella-zoster infection, postherpetic neuralgia and delayed arteritis may develop. Seizures, hearing loss, and neuropsychologic sequelae may follow any meningoencephalitis. The patient should always be reevaluated for the possibility of infection with a different opportunistic organism. CNS infections remain a major cause of morbidity and mortality in immunosuppressed patients with malignancies. In one series, 60% of such patients died as a result of their CNS infection, many at a time when the underlying disease had an otherwise good prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Central nervous system infections in cancer patients. 175 29

A mouse monoclonal antibody (MAb17-1A) (IgG2A) against colorectal carcinoma cells was used to treat patients with metastatic disease. Major direct effector functions of MAb seem to be ADCC (antibody dependent cellular cytotoxicity), CDC (complement dependent cytolysis) and apoptosis ('programmed cell death'). Thus, a high tumor cell saturation of the MAb should be achieved. Increasing doses of MAb to the patients increased the total area under the concentration curve and thus the exposure of tumor cells to MAb. However, the response rate (with complete + partial + minor response + stable disease defined as response) was not augmented. In total, 10/52 (19%) patients responded and in fact lower doses (less than 2 g) might induce a higher response frequency (9/52) than higher doses (greater than 2 g) (1/52). During treatment, the numbers of cytotoxic cells (lymphocytes and monocytes) increases in the tumor lesion and complement components were deposited. As ADCC may be important, effector mechanism attempts were made to augment the cytolytic capability of the effector cells by simultaneously giving the patients GM-CSF. The combination of MAb17-1A + GM-CSF augmented the ADCC activity of blood mononuclear cells and a heavy infiltration of monocytes could be noted in the tumor. Out of 15 available patients 6 (40%) showed a response.
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PMID:Therapy of colorectal carcinoma with monoclonal antibodies (MAb17-1A) alone and in combination with granulocyte monocyte-colony stimulating factor (GM-CSF). 177 44

The results of several studies of chemotherapy in treatment of soft tissue sarcomas of adults (except embryonic rhabdomyosarcoma) are presented. Most of these studies have been performed and published by the EORTC Bone and Soft tissue sarcoma group. In advanced disease, a randomized trial including 551 evaluable patients and comparing doxorubicin alone (75 mg/m2 q. 3 weeks), and two combination regimens: DI (Doxorubicin (50 mg/m2) + Ifosfamide (5 g/m2 + mesnum q. 3 weeks), and Cyvadic (Doxorubicin 50 mg/m2 d1, DTIC 750 mg/m2 d1, VCR 1.5 mg/m2 d1 (maximum 2 mg/m2), Cyclophosphamide 500 mg/m2 d1 q. 3 weeks), failed to prove any significant difference between these 3 treatments for response rate (25%, 31%, 28%), quality of the response and survival. There is a dose/effect relationship doxorubicin, it is possible that if combination is not superior to a single agent, the reason could be that the dose of doxorubicin is too low when used in combination as compared with the dose when used alone. So, in a phase II trial including 48 evaluable patients, optimal dose of doxorubicin (75 mg/m2 and Ifosfamide (5 g/m2) was given in association with rhGM-CSF. The response rate observed with this combination was 50%. For localized disease, in a randomized trial of the EORTC including 374 evaluable patients with resectable tumors with a mean follow-up of 44 months, the interest of 8 Cyvadic as adjuvant chemotherapy after adequate locoregional treatment (surgery with or without radiotherapy) was demonstrated only for locoregional relapse free survival but no for metastatic disease free survival or overall survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Chemotherapy of soft tissue sarcoma in adults]. 180 96

Using 14 transplantable murine tumors, we investigated a possible correlation between their ability to produce the cytokine GM-CSF and the spontaneous metastatic potential when mice were subcutaneously inoculated. The following results were obtained: (1) seven tumors, which produced severe pulmonary metastases and metastatic swelling of lymph nodes, exhibited the ability to produce GM-CSF activity in culture. The cell population analysis revealed that the cells producing GM-CSF were tumor cells themselves, but that contaminating macrophages/granulocytes and T lymphocytes did not produce GM-CSF. The mRNA for GM-CSF was also found in all of these highly metastatic tumors tested. In mice inoculated with a highly metastatic tumor, the GM-CSF mRNA was also found in lungs; (2) in 3 other tumors, which produced histological but not macroscopical pulmonary metastases, no GM-CSF activity could be detected in the culture fluids. GM-CSF mRNA was, however, detected in the tumor cells in the presence of an mRNA-stabilizing agent, cycloheximide, suggesting the possibility that the tumor cells of this type were transcribing GM-CSF gene, and secreting it in undetectable levels; (3) in culture of the 4 remaining poorly or non-metastatic tumors, neither CSF activity nor GM-CSF mRNA could be detected even in the presence of cycloheximide. GM-CSF mRNA was also not found in lungs of tumor-bearing mice. Our results indicate that there may be a correlation between GM-CSF gene expression in tumor cells and spontaneous metastases.
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PMID:A correlation between GM-CSF gene expression and metastases in murine tumors. 199 49

We reviewed 63 cases of cytologically confirmed leptomeningeal metastases (LM). 31 (49%) had solid tumors 17 (27%) had leukemia and 15 (24%) had lymphoma. The most common presenting symptom was pain (76%) with radicular discomfort (58%), headache (32%), neck or back pain (17%). The predominant neurological signs were mental status abnormalities (49%), weakness (47%), seizures (14%). The mode of presentation varied with tumor type. Patients with leukemia (18%) and lymphoma (13%) tended to present frequently with LM without systemic involvement, or during periods of apparent remission (leukemia 35%, lymphoma 27%), while patients with solid tumors had established systemic metastases (90%) at time of presentation. Laboratory studies did not vary among the groups. 71% had positive cytology on the first lumbar puncture (LP) and only 8% required more than 2 LPs. The cell count was a poor predictor of positive cytology as 29% of LP's with positive cytology and 36% of all LP's had less than 4 cells/mm. We conclude that 1) LM presents with pain and seizures more frequently than has been previously recognized; 2) LM is frequently the mode of presentation in patients with leukemia and lymphoma and; 3) cytology is positive frequently in CSF specimens with normal cell counts and chemistries.
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PMID:Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. 208 37

Studies of twenty-five patients with loculated leptomeningeal tumor metastases diagnosed by CT and/or MR were analyzed retrospectively. Medulloblastoma was the most frequent primary tumor (8/25, 32%). Four subgroups of loculated patterns were identified. Type A included mass(es) limited to the subarachnoid space without obvious direct parenchymal infiltration; this pattern occurred in 12 patients, of whom five had associated diffuse pattern. Type B was characterized by mass(es) still predominantly in the subarachnoid space but with minor transpinal parenchymal infiltration; this pattern was found in five patients. Type C comprised subarachnoid mass(es) with marked transpinal extension mimicking parenchymal lesion; this pattern was observed in three patients. Type D consisted of subarachnoid mass(es) growing along the perineural CSF space; this pattern was noted in two patients. Additionally, two patients presented with combined A and C patterns, and one patient had a combined B and C pattern. More than half the patients (14/25, 56%) presented with a single lesion. The most frequent locations were the suprasellar cistern, ventricular walls, and lateral recesses of the fourth ventricle, Gd-DTPA-enhanced T1-weighted MR images appeared best for demonstrating the site and extent of disease. Recognition of the loculated patterns of leptomeningeal metastases, which are less common than the diffuse pattern, is important to radiologists and clinicians for correct diagnosis and proper management of patients with this disease.
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PMID:Loculated intracranial leptomeningeal metastases: CT and MR characteristics. 210 30

Forty patients with positive CSF cytology for subarachnoid dissemination of neoplasms were examined by magnetic resonance (MR) imaging for the detection of intracranial or intraspinal CSF metastases. The MR evidence of cerebral leptomeningeal metastases was noted in 12 of 54 unenhanced (22.2%) and 7 of 20 (35%) gadolinium-enhanced studies. However, in only 2 of the 20 (10%) gadolinium-enhanced scans did the enhanced brain images alone demonstrate the presence of CSF seeding. Four of 29 (13.8%) unenhanced studies of the spine and 6 of 16 (37.5%) gadolinium-enhanced spine studies were positive for neoplastic deposits on the spinal nerves or cord. Magnetic resonance without and with gadolinium enhancement was most likely to be positive in studies of patients with a non-CNS primary malignancy (16/51 = 31.4%) and least accurate with lymphoma or leukemia (1/18 = 5.6%). Although gadolinium administration increases the ability of MR to detect leptomeningeal metastases (particularly in the spine), the overall sensitivity of unenhanced and enhanced MR examinations is low (19.3 and 36.1%, respectively) in patients with proven cytological evidence of neoplastic seeding.
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PMID:Leptomeningeal metastases: MR evaluation. 231 55

Studies of twenty-five patients with loculated leptomeningeal tumor metastases diagnosed by CT and/or MR were analyzed retrospectively. Medulloblastoma was the most frequent primary tumor (8/25, 32%). Four subgroups of loculated patterns were identified. Type A included mass(es) limited to the subarachnoid space without obvious direct parenchymal infiltration; this pattern occurred in 12 patients, of whom five had associated diffuse pattern. Type B was characterized by mass(es) still predominantly in the subarachnoid space but with minor transpinal parenchymal infiltration; this pattern was found in five patients. Type C comprised subarachnoid mass(es) with marked transpinal extension mimicking parenchymal lesion; this pattern was observed in three patients. Type D consisted of subarachnoid mass(es) growing along the perineural CSF space; this pattern was noted in two patients. Additionally, two patients presented with combined A and C patterns, and one patient had a combined B and C pattern. More than half the patients (14/25, 56%) presented with a single lesion. The most frequent locations were the suprasellar cistern, ventricular walls, and lateral recesses of the fourth ventricle, Gd-DTPA-enhanced T1-weighted MR images appeared best for demonstrating the site and extent of disease. Recognition of the loculated patterns of leptomeningeal metastases, which are less common than the diffuse pattern, is important to radiologists and clinicians for correct diagnosis and proper management of patients with this disease.
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PMID:Loculated intracranial leptomeningeal metastases: CT and MR characteristics. 251 78

We evaluated 44 patients with suspected spinal tumors or previous laminectomies with gadolinium-DTPA MR imaging in order to characterize the enhancement in normal, postoperative, and neoplastic intraspinal tissue. Using the signal intensity of CSF as an internal control, we calculated the percentage increase in signal intensity from pre- to postgadolinium studies. Tumors (astrocytoma, ependymoma, schwannoma) enhanced 70-350%; epidural scar, normal epidural venous plexus, and dorsal root ganglion enhanced up to 200%. Contrast enhancement does not per se distinguish neoplastic from normal tissue. Enhancement with gadolinium-DTPA appeared to increase the conspicuousness of intramedullary tumors but not intraosseous metastases. We believe that gadolinium-enhanced MR imaging is a valuable adjunct to routine MR imaging in the evaluation of intraspinal neoplastic processes and may be useful in delineating normal and postoperative structures in the spinal canal.
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PMID:Contrast enhancement in spinal MR imaging. 275 Jun 25

In 121 proven cases of intracranial metastases, lung cancer was as high as 48 per cent. Multiple lesions were noted (67.8%) in almost every type of organ source. Brain parenchyma (80.3%), predominantly supratentorium was the major site of metastases. The minority was observed in leptomeninge, cranial bone and subgaleal tissue. Subarachnoid seeding tumors along CSF pathways spread mainly from pineal neoplasms; a few cases from lung and choriocarcinoma. Extensive brain edema occurred in metastases from almost every type of primary organ source. Calcification exhibited 5.8 per cent and their origins were lung and breast. Bleeding tumors were noted in 10.7 per cent mainly from choriocarcinoma, a few from lung and GI. Hyperdense tumors occurred in 86.8 per cent on noncontrast scans. Almost all tumors (95.2%) showed contrast enhancement, predominantly ring-shaped lesions. Their organ sources were GI, lung and breast. A few patterns of enhancement were homogeneous and heterogeneous. Non-enhanced lesion were noted in 4.8 per cent mainly due to the high density of calcium and blood inside the tumors. Apart from seeding, calcified and bleeding tumors, the CT findings were not specific for various types of metastases.
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PMID:CT findings of brain metastases. 279 20


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