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)

A 59-year-old demented Japanese man who was proven to have high titer of serum alpha-fetoprotein (AFP) and carcino-embryonic antigen (CEA) was admitted to our hospital. Neurological examinations revealed moderate dementia with deterioration and loss of memory, and decreased deep tendon reflexes in all extremities. Sensory disturbances were not obvious. There were no significant changes in the usual laboratory findings including CSF, except for elevated serum AFP and CEA. Three months after admission, he died of gastric cancer and its metastases in liver and lymph nodes. Post-mortem examination in the central nervous system (CNS) revealed many senile plaques and neurofibrillary tangles throughout the cerebral cortex and hippocampus. There was marked loss of neurons in the hippocampus. All the neuropathological findings in the CNS were consistent with those in Alzheimer disease. In the peripheral nervous system, necrotizing arteritis was found throughout the length of sciatic nerve. Large myelinated fibers seemed to be preferentially degenerated with proximo-distal gradient. Teased fiber preparation revealed de/remyelination and axonal degeneration more frequently at the distal portion. Immunohistologically, the serum IgG of this patient specifically reacted to the endothelial cells of all vessels in control organs, which strongly suggested the autoimmune mechanism for the necrotizing arteritis in this patient. The pathogenetic role of this antibody for necrotizing arteritis, found selectively in the peripheral nervous system, still remained unclear. However, paraneoplastic neuropathy due to necrotizing arteritis is a distinct entity in addition to common form of paraneoplastic subacute sensory neuropathy.
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PMID:[A case of paraneoplastic neuropathy with necrotizing arteritis localized in the peripheral nervous system]. 165 26

The localization and size of a high-grade soft tissue sarcoma of an extremity are generally the limiting factor in limb-saving surgery. Since 1982 nine patients with a high-grade soft tissue sarcoma of an extremity, which usually requires amputation, have been treated by intraarterial chemotherapy, preoperative and postoperative radiotherapy, and surgery. The limb was saved in eight patients (89%). During a median follow-up of 24 months (mean follow-up 32 months, range 12 to 64 months) one local recurrence and four distant metastases were diagnosed. Three patients developed complications due to the intraarterial chemotherapy, a motor and sensory neuropathy of the sciatic nerve was diagnosed in one patient, and two patients developed a flexion contracture of the knee. The results obtained in this small series show that the combination of intraarterial doxorubicin, preoperative and postoperative radiotherapy, and surgery is feasible in limb-saving treatment of primarily "unresectable" high-grade soft tissue sarcomas of the extremities without increasing the risk of a local recurrence.
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PMID:A combination of intraarterial chemotherapy, preoperative and postoperative radiotherapy, and surgery as limb-saving treatment of primarily unresectable high-grade soft tissue sarcomas of the extremities. 291 Apr 24

Since June 1991 the IORT facility has operated a dedicated linear accelerator, which was installed within the central operating theater of the Department of Surgery. As of 9/92 a total of 28 patients suffering from peripheral (n = 20) or centrally (n = 8) located soft tissue sarcomas had been were treated. Thirteen patients revealed a primary and 15 patients a recurrent tumor. Tumor resection with negative margins was performed in 20 patients, positive margins remained in 5 patients, and gross macroscopic residual disease in 3 patients. Combined intraoperative and external beam radiotherapy was applied in 22 patients, using IORT doses of 10-20 Gy and an external beam dose of 26-50 Gy. Three patients were irradiated intraoperatively twice with a time interval of 24 h. After a median follow-up of 9.9 months, 20 patients are disease free. Two patients died 4 and 5 months after the end of therapy with rapidly progressive distant metastases. An infield failure within the external beam target volume was seen in 1 patient and local failure at the field margin of the external field in 3 patients. So far, there have been no IORT infield failures. Follow-up is performed with magnetic resonance imaging. In 3 patients a second operation was necessary because of a severe wound infection, including one patient suffering from osteomyelitis of a neighboring bone. Mild sensory neuropathy occurred in 1 patient 7 months after treatment. Overall only mild and reversible postoperative and posttherapeutic complications were seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Methodology, technical prerequisites and postoperative morbidity of intraoperative radiotherapy (IORT) of soft tissue sarcomas. Heidelberg Krankengut 6/91-9/92]. 823 80

Clinicopathological and immunohistochemical studies were performed in a patient with paraneoplastic limbic encephalitis, myelitis, sensory neuropathy and cerebellar degeneration secondary to small cell lung cancer. A 67-year-old male smoker developed orthostatic dizziness 6 months prior to admission. Over the following months, his wife noticed that he became forgetful and confused. Over the next three weeks, he became unable to sit or stand unaided and admitted to our service. On admission, he was lethargic and disoriented in time and place. Neurological examination revealed marked limb weakness with distal dominant muscle atrophy. A chest radiograph demonstrated a mass in the right middle lobe and a bronchial biopsy revealed a small cell carcinoma. CT scan and MRI of the brain revealed abnormalities in the bilateral medial temporal lobes and putamen. He was treated with anti-cancer chemotherapy, but died of respiratory failure after 13 months illness. Postmortem examination showed a mass in the right middle lobe of the lung. No tumor metastases were noted in the nervous tissue. Microscopical examinations of the nervous system revealed neuronal loss, astrogliosis and perivascular and parenchymatous lymphocytic infiltration in the hippocampus, subiculum, amygdala, putamen, medulla oblongata, spinal cord and dorsal root ganglia. Loss of Purkinje cells was also seen in the cerebellum without lymphocytic infiltration. Immunohistochemical analysis of the patient's serum and CSF by the use of adult rat brain revealed immunoreactivity at the hippocampal pyramidal neurons CA3 and CA4. At the higher dilution, neuronal nuclei were specifically stained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A clinicopathological study of a patient with paraneoplastic limbic encephalitis, myelitis, sensory neuropathy and cerebellar degeneration, associated with a unique antineuronal antibody]. 839 16

The aim of this phase II study was to characterise the efficacy and toxicity of semisynthetic paclitaxel in patients with metastatic breast cancer. Eligible patients had measurable disease and had been treated with one prior chemotherapy regimen either as adjuvant or for metastatic disease. Semisynthetic paclitaxel was given at a dose of 175 mg/m2 over 3 h every 21 days with dexamethasone, cimetidine and diphenhydramine premedications. 31 patients were entered. All were evaluable for toxicity. 30 patients were evaluable for response because 1 patient was lost to follow-up after receiving one cycle. One patient achieved a complete response and 10 patients achieved partial responses for an overall response rate (CR + PR) of 37% (95% confidence interval 20-56%). 17 patients (55%) experienced at least one episode of grade 3 or 4 neutropenia. There were two episodes of febrile neutropenia complicating 155 cycles of therapy. One of these resulted in a treatment-related death in a patient with pulmonary metastasis. 3 patients required dose reductions for grade 3 sensory neuropathy. Our study shows that the antitumour activity and toxic effects of semisynthetic paclitaxel appear to be identical to the naturally occurring product.
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PMID:Phase II study of semisynthetic paclitaxel in metastatic breast cancer. 947 Aug 6

Paraneoplastic syndromes are disorders associated with cancer but without a direct effect of the tumor mass or its metastases on the nervous system. Small cell carcinoma of lung associated with paraneoplastic sensory neuronopathy and/or paraneoplastic encephalomyelitis with the presence of anti-Hu antibodies has been termed "anti-Hu syndrome." Anti-Hu associated PSN-PEM is an immune disorder in which both cell-mediated and humoral mechanisms are involved. Patients are considered affected by Anti-Hu associated PSN-PEM when they develop clinical signs and symptoms of CNS dysfunction and/or sensory neuropathy not caused by metastases or other disorders, and serum or cerebrospinal fluid is positive for Hu abs. SCLC is found in more than 90% of patients with cancer and positive Hu abs. Individual patients with Hu abs associated to SCLC may suffer PSN-PEM, limbic encephalitis, brainstem encephalopathy, opsoclonus-myoclonus, paraneoplastic cerebellar degeneration or myelopathy. Hu abs have a specificity of 99% and sensitivity of 82% in detecting paraneoplastic neurological syndromes. There are two types of treatment: the first is to treat the cancer, the second is to suppress the immune reaction with the use of corticosteroids, cyclophosphamide, azathioprine, plasma exchange, intravenous immunoglobulin and immunoadsorption; however, treatment of paraneoplastic syndromes is generally unsatisfactory.
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PMID:Paraneoplastic syndromes associated with anti-Hu antibodies. 1134 32

When treating patients for metastatic cancer, there is always a balance between the benefits of treatment and resulting side-effects. Peripheral sensory neuropathy (PSN) is a side-effect of many anticancer agents used in routine practice. Oxaliplatin is a relatively new agent currently licensed in over 50 countries including France, Germany and the UK for the treatment of metastatic colorectal cancer. Although it is a new agent, it is from the same family of drugs as cisplatin, an agent that has been used for many years. PSN is the most commonly discussed side-effect associated with oxaliplatin. Oxaliplatin-induced PSN is characterized by two distinct syndromes: a transient acute dysaesthesia and a cumulative distal neurotoxicity. Importantly, both are generally reversible after stopping treatment. Oxaliplatin-induced acute PSN is triggered and exacerbated by cold and can be greatly reduced in affected patients simply by avoiding cold conditions. Oxaliplatin-induced cumulative PSN may also be managed by temporary cessation of treatment.
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PMID:An overview of chemotherapy-induced peripheral sensory neuropathy, focusing on oxaliplatin. 1195 4

Oxaliplatin, a platinum compound characterized by a diaminocyclohexane (DACH) platinum carrier ligand, has proven its efficacy in first- and second-line advanced colorectal cancer (CRC) treatment. Acute reversible and cumulative peripheral sensory neuropathy has been observed frequently with oxaliplatin treatment and limits its use. Its synergism with other drugs, as well as its different mechanism of action and toxicity profile make it an attractive candidate for combination studies in CRC. It can be combined safely with 5-fluorouracil (5-FU)+/-folinic acid (LV), irinotecan, raltitrexed, multitarget antifolate LY231514 (MTA), and oral 5-FU prodrugs. These combinations confer both an increased response rate compared to that of any single agent and an increased secondary surgical resection of initially unresectable metastases, possibly leading to prolonged survival. In three prospective randomized phase III studies in advanced CRC, oxaliplatin plus 5-FU/LV improved significantly progression-free survival without a significant increase in median survival time and without affecting quality of life, compared to treatment with 5-FU/LV. Ongoing clinical trials will define its role in the adjuvant setting.
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PMID:Oxaliplatin: results in colorectal carcinoma. 1239 98

The effectiveness and toxicity of many drugs can vary depending on the time of administration in relation to 24-hour rhythms of biochemical, physiological and behavioural processes under the control of the circadian clock. Such chronopharmacological phenomena are influenced by not only the pharmacokinetics but also pharmacodynamics of medications. Chronotherapy is especially relevant when the risk and/or intensity of the symptoms of disease vary predictably over time as exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke and peptic ulcer disease. Morning, once-daily administration of corticosteroids results in little adrenocortical suppression, while the same daily dose split into four equal doses to coincide with daily meals and bedtime results in significant hypothalamus-pituitary-adrenal axis suppression. In a randomised, multicentre trial involving patients with previously untreated metastases from colorectal cancer, the chronomodulated infusion of oxaliplatin, fluorouracil and folinic acid was compared with a constant-rate infusion method. Adverse effects such as stomatitis and peripheral sensory neuropathy were lower and objective response was higher with chronotherapy as compared with the fixed-rate infusion. The merit of chronomodulated infusion is supported by the 24-hour rhythm of DNA synthesis and the activity of dehydropyrimidine dehydrogenase, which brings about the intracellular catabolism of fluorouracil. On the other hand, haloperidol and selective serotonin reuptake inhibitors have diverse effects on sleep continuity and nocturnal arousals. Although interferon also alters the clock function, this disruptive effect can be overcome by devising an administration regimen that minimises adverse drug effects on clock function. Thus, one approach to increasing the efficiency of pharmacotherapy is the administration of drugs at times at which they are most effective and/or best tolerated.
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PMID:Changes in toxicity and effectiveness with timing of drug administration: implications for drug safety. 1458 62

Metastatic renal cell cancer is one of the immuno-sensitive tumors. Apart from the immuno-modulating agents IFNalpha and IL-2, thalidomide has been reported to be effective in this type of cancer. However, bone metastases and bulky metastases, show limited response to immunotherapy, are often site of recurrent disease and are therefore often treated later with radiotherapy. In this phase II study, we evaluated toxicity and efficacy of the combination of continuous low dose (1 mIU/m2) s.c. IL-2 and thalidomide (200 mg once daily) in 22 patients with progressive metastatic renal cell cancer. In addition, 13 soft tissue lesions and two bone metastases in 13 patients were concurrently treated with fractionated radiotherapy. T cell number and activation in blood was measured by immunoflowcytometry. Nearly all patients developed grade 1-2 toxicity consisting of fatigue, sensory neuropathy, constipation and dizziness. Five patients had a grade 3-4 toxic event: four patients with deep venous thrombosis requiring anticoagulant therapy, and one patient who developed radiation myelopathy. On systemic response evaluation ten patients showed ongoing SD with a mean progression free survival of 9 months. One patient showed a PR (at an irradiated site). Regarding local response to irradiation, seven lesions showed a PR for a mean time period of 8.7 months, whereas seven were stable for 6 months. The radiation response of one lesion was not evaluable. Immunoflowcytometry showed an increase in number and activation of lymphocytes (mainly Natural Killer--NK-cells), which was absent or even decreased in irradiated patients. The combination of sc. low dose IL-2, thalidomide and radiotherapy is feasible, but relatively toxic and does not lead to higher responses at non-irradiated sites. The combination of immunotherapy and concurrent radiotherapy is effective at 60% of the relatively large evaluable sites. Progressive myelopathy developed in one patient, possibly due to radiotherapy in combination with thalidomide.
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PMID:Prolonged low dose IL-2 and thalidomide in progressive metastatic renal cell carcinoma with concurrent radiotherapy to bone and/or soft tissue metastasis: a phase II study. 1590 25


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