Anti-Ri positive opsoclonus-myoclonus-ataxia in ovarian duct cancer.
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Antibodies, Neoplasm↗
Biomedical subjects
C J Vecht
Publications and source records attributed to C J Vecht.
Severe muscle weakness secondary to paraneoplastic hypophosphatemia in neuroblastoma.
We report a 28-year-old woman who presented with severe proximal muscle weakness secondary to paraneoplastic hypophosphatemia and associated with recurrent neuroblastoma. The biochemical findings included hyperphosphaturia, a reduced serum level of 1,25-dihydroxyvitamin-D3, elevated alkaline phosphatase and normocalcemia which are pathognomic for paraneoplastic hypophosphatemia. Following systemic chemotherapy and supplementation of 1,25-dihydroxyvitamin-D3 a complete remission of the neuroblastoma was achieved and all features of the paraneoplastic hypophosphatemia gradually disappeared. In the differential diagnosis of muscle weakness, hypophosphatemia should be included. Paraneoplastic hypophosphatemia associated with metastatic neuroblastoma has not been reported previously. Diagnosis, mechanism and therapy of paraneoplastic hypophosphatemia are shortly reviewed.
Adult↗
1H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration.
Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in 1H MR spectra of contrast-enhancing tumor at 5-10 min after Gd-contrast administration [Magn. Reson. Med. 37:222-225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0-5, 5-10, and/or 10-15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 +/- 3, 12 +/- 2, and 14 +/- 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.
Adult↗
Phase II study on cisplatin and ifosfamide in recurrent high grade gliomas.
27 patients with recurrent high grade glioma following surgery and radiation therapy were treated with 100 mg/m2 cisplatin and 6 g/m2 ifosfamide per cycle, administered on days 1-3 in 4 week cycles, for a maximum of six cycles. Toxicity was assessed after every cycle. Response was assessed following every second cycle, and a 50% decrease of the largest cross-sectional tumour area on contrast enhanced magnetic resonance imaging or computed tomography scan was considered a partial response (PR). A total of 95 cycles was administered; 26 patients were evaluable for response. In 5 patients (19%), a PR was obtained (median time to progression (TTP): 34 weeks). Stable disease was observed in 6 patients (23%, median TTP: 22 weeks). The most frequent toxicity was haematological: 37% of cycles were complicated by a grade 3 or 4 leucopenia. 1 patients died, probably as a consequence of increased cerebral oedema induced by the cisplatin hydration schedule. Determination of the cisplatin concentration in this patient showed a 10-fold increase in the tumour concentration as compared with that in normal brain tissue, demonstrating the absence of a blood-brain barrier in the tumour. In conclusion, generally this schedule was well tolerated, but it is of moderate activity for recurrent glioma.
Adult↗
The effect of dexamethasone on the uptake of cisplatin in 9L glioma and the area of brain around tumor.
The negative influence of dexamethasone (Dex) on the uptake of cisplatin in brain tumors was investigated in rats bearing 9L glioma. Dex or saline was given intraperitoneally prior to intravenous administration of cisplatin 5 mg/kg. Total Platinum (Pt) concentration was quantified with atomic absorption spectroscopy (AAS) in tumor, brain around tumor (BAT), normal brain and plasma. In the second experiment DNA-adducts of cisplatin were determined in tumor and BAT by AAS. In tumor, there was no difference in the Pt concentration and in the DNA-adduct level between the two treatment groups. In BAT, the Pt level in the Dex group was 0.20 microg/g (SD=0.10 microg/g), which was significantly lower than in the controls (0.53 microg/g (SD=0.21 microg/g); p < 0.001). In addition, the DNA-adduct level in BAT was 23% lower in the Dex treated rats (p=0.05). In normal brain the Pt concentration was 10-fold lower than in tumor tissue. Thus, Dex did not significantly limit the uptake of cisplatin in brain tumor nor did it influence the uptake in normal brain parenchyma. In contrast, in BAT that has a partially disrupted BBB, the concentrations of Pt and DNA-adduct formation were significantly decreased following pretreatment with Dex. The influence of Dex on limiting the effects of chemotherapy for brain tumors needs further study.
Animals↗
Steroid myopathy in cancer patients.
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Brain Neoplasms↗
[Transdermal opioid administration: the pain plaster].
A new method of administration of an opioid was recently registered: fentanyl transdermal (brand name: Durogesic), intended particularly for the indication range 'pain in cancer'. Fentanyl is lipid-soluble so that deposition in the skin takes place and the biological half-life is approximately 20 hours after removal of the plaster. It is safe to start on a basis of an equianalgesic conversion of 100:1 in relation to oral morphine, although this may entail some risk of fentanyl under dosage. The dose adjustment time is 12-24 hours before a constant fentanyl level is reached; therefore, after attaching the first sticking plaster, the original morphine dose should be continued for another 12 hours. In addition, the patient may, if necessary, be given supplementary morphine preferably as a short-acting drug. There seems to be no clear indication for transdermal fentanyl either in neuropathic pain or in chronic benign pain.
Administration, Cutaneous↗
Immunological characterization of a neuronal antibody (anti-Tr) associated with paraneoplastic cerebellar degeneration and Hodgkin's disease.
We studied an autoantibody (called anti-Tr), found in the serum and CSF of five patients with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). Anti-Tr antibodies labelled the cytoplasm of Purkinje cells of human and rat cerebellum. The molecular layer of rat cerebellum showed a characteristic dotted pattern suggestive of immunoreactivity of dendritic spines of Purkinje cells. Patients with cerebellar disorders without HD (159) or HD without PCD (30) did not harbor anti-Tr antibodies. Immunoblots of human Purkinje cells or rat and mouse cerebellum were negative. Anti-Tr antibodies, as defined in this study, appear specific for HD-associated PCD. The immunohistochemical pattern described in the rat cerebellum coupled with the absence of reactivity in the immunoblot may be used to identify anti-Tr antibodies.
Adolescent↗
Clinical characteristics of severe peripheral neuropathy induced by docetaxel (Taxotere).
BACKGROUND: Docetaxel, a semi-synthetic taxane may cause a usually mild sensory neuropathy. We describe the clinical characteristics of five patients who developed a more severe neuropathy following treatment with docetaxel. PATIENTS AND METHODS: All patients were treated in phase II studies with 100 mg/m2 docetaxel in three weekly cycles, without steroid administration. RESULTS: The clinical picture in these patients was dominated by a sensory neuropathy, but in one case severe weakness was present. Another patient developed Lhermitte's sign. Signs and symptoms are usually reversible after discontinuation of docetaxel administration, but in three patients symptoms worsened for some time after the end of treatment before improvement occurred. CONCLUSION: Severe docetaxel neuropathy may especially occur following treatment with cumulative dosage over 600 mg/m2; in patients treated with this dosage a moderate or severe neuropathy may not be rare.
Adult↗
Peripheral neuropathy induced by combination chemotherapy of docetaxel and cisplatin.
Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses.
Adolescent↗
Preclinical testing of recombinant adenoviral herpes simplex virus-thymidine kinase gene therapy for central nervous system malignancies.
OBJECTIVES: Adenoviral gene transfer and killing efficiency using the thymidine kinase (TK)/ganciclovir (GCV) mechanism was evaluated in human cancer cells occurring as central nervous system tumors. The effectiveness of this approach was tested in vitro and in experimental models for brain tumor and leptomeningeal metastases in rats in vivo. Recombinant adenoviruses with different promoters were compared. METHODS: Adenoviral vectors harboring a marker (lacZ) or a TK gene were constructed. Transcription of genes was under the control of either the adenovirus Type 2 major late promoter (MLP) or the human cytomegalovirus (CMV) immediate early gene promoter. lacZ expression and GCV killing efficiency after TK gene transfer in several human tumor cells was evaluated in vitro. The 9L rat brain tumor and leptomeningeal metastases models were used to determine the effectiveness of adeno-TK and subsequent GCV treatment in vivo. MLP and CMV containing adenoviral vectors were compared. RESULTS: Gene expression and the killing of tumor cells were very efficient in all human tumor cell lines tested. The adenovirus containing the CMV promoter showed cytopathic effects in cultured tumor cells at high multiplicity of infections but also greater cell killing efficiency after TK/GCV treatment, as compared to the MLP promoter. Although both the MLP and CMV vectors showed a significant dose-dependent therapeutic effect, animals treated with recombinant adenovirus containing the CMV promoter showed significantly longer survival time (brain tumors) or symptom-free periods (leptomeningeal metastases). CONCLUSION: This study demonstrates the therapeutic efficiency and feasibility of the TK/GCV approach in experimental brain tumors and leptomeningeal metastases. It also demonstrates that the promoter driving the transgene in an adenoviral vector influences toxicity and efficiency of treatment.
Adenoviridae↗
99mTc-SPECT in the diagnosis of skull base metastasis.
OBJECTIVE: To evaluate the role of bone SPECT in diagnosing metastasis to the skull base in cancer patients. BACKGROUND: Skull base metastasis often causes characteristic clinical syndromes. Antitumor treatment ameliorates or stabilizes symptoms in most patients. Diagnosis may be difficult when neuroimaging studies are negative (as occurs in about one-quarter of patients). Case reports have suggested a role for bone SPECT in these patients. METHODS: We reviewed the charts of all patients (1993-1996) at our institution who had skull base SPECT and at least one neuroimaging study (CT or MRI) for clinically suspected metastasis to the base of the skull. Bone SPECT, CT, and MRI were blindly re-evaluated. RESULTS: We studied 56 patients, of whom 36 had skull base metastasis. Twenty patients had other causes of the clinical syndrome, including leptomeningeal and posterior fossa metastasis, or benign causes. In 29 of 36 patients (81%) with skull base metastasis, CT or MRI clearly demonstrated the lesion. Bone SPECT identified a hot spot in the appropriate region of the skull base in 28 of 36 patients (78%). All seven patients with negative CT or MRI had positive SPECT and four of these had a response to anti-tumor treatment. CONCLUSIONS: SPECT of the skull base can demonstrate lesions not identifiable by CT or MRI. In cancer patients suspected of having skull base metastasis, we recommend SPECT of the skull base when CT or MRI studies are negative.
Adult↗
[Chemotherapy in brain tumors].
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Adrenal Cortex Hormones↗
1H MR spectroscopy detection of lipids and lactate in metastatic brain tumors.
1H MR spectroscopy was used to correlate the metabolite signals in 66 untreated metastatic brain tumors with the results of Gd-DTPA enhanced MRI. Cubic volumes containing brain metastases of lung cancer (n = 17), mammary carcinoma (n = 24), melanoma (n = 12) and those originating from other tumors (n = 13) were examined using the double spin echo technique with CHESS pulses for water suppression and TE = 135 ms. Apart from trends toward reduced signals of choline-containing compounds (Cho) and reduced post-Gd MRI contrast in lung cancer compared with the other pathology groups, the four tumor groups had similar MRI and MRS characteristics. Metastases without lipid or lactate (Lact) signal in the 1H MR spectra were comparatively small in size with homogeneous post-Gd MRI enhancement (33 +/- 5%, means +/- SEM; n = 24) and elevated Cho signals compared with normal contralateral brain tissue (70 +/- 5% of contralateral N-acetyl aspartate signal; p < 0.001). The other metastases showed either unambiguous lipid signals (n = 30) or MRS detectable Lact (n = 12) and were heterogeneous on MRI with divergent signals of Gd-enhancement (49 +/- 5% vs 14 +/- 8%, p < 0.001) and Cho (88 +/- 10 vs 47 +/- 8% of contralateral NAA; p = 0.02). Those with Lact were significantly larger compared with both other groups (p < 0.02, both). It is concluded that brain metastases can be categorized into early stage (Cho), intermediate stage (lipid, higher Cho) and late stage metastases (Lact, lower Cho).
Brain Neoplasms↗
Systemic and anti-neuronal auto-antibodies in patients with paraneoplastic neurological disease.
Sera from 23 patients with paraneoplastic disease of the central nervous system (PNS) were examined for the presence of anti-neuronal (anti-Hu, anti-Yo/PCA) and anti-Ri) and systemic auto-antibodies, including antibodies against DNA, centromeres, nRNP, Sm antigen, Scl-70, Ro(SS-A), La(SS-B), mitochondria, thyroid antigens, parietal calls, brush border antigen and rheumatoid factor. As controls, sera from 33 patients with small cell lung cancer, 33 with ovarian cancer and 7 with breast cancer and from 107 aged-matched healthy persons were used. Systemic auto-antibodies were found in 52% of patients with paraneoplastic neurological syndromes compared with only 16% (P = 0.001) in the control group with cancer only and 15% in the group of healthy controls. The relatively high percentage of systemic auto-antibodies in patients with PNS indicates that there is a genetic susceptibility to the development of auto-immune phenomena. This may provide an explanation for the relatively rare occurrence of PNS in patients with cancer.
Adult↗
Delayed radiation myelopathy: serial MR-imaging and pathology.
Clinical data, MR-scans, time-dose fractionation schemes and neuropathologic findings of two cases of delayed radiation myelopathy (DRM), are presented. Both patients, a 72-year-old diabetic woman with cervical lymphnode metastasis from a squamous cell carcinoma and a 46-year-old woman with tonsillar carcinoma, developed paraparesis followed by quadriplegia, at 7 and at 10 months following radiation. The spinal cord received 46 and 49 Gy. (Fraction dose 2.25 Gy and 2.0 Gy, 4 times/week). Serial MR-scans showed spinal cord enlargement and focally increased signal intensity (T1-gd). The second patient survived and stabilized following therapy with coumarins. The first patient died 13 months after radiotherapy. At autopsy necrosis, local calcium deposits, lipid macrophages and swollen astrocytes were observed in the white matter. There was slight hyalinosis of the intramedullary vessel walls. We conclude that serial MRI may be helpful to distinguish DRM from other causes of spinal cord injury. DRM may occur at a total dose less than 50 Gy. Additional risk factors (diabetes, hypertension), and fraction doses above 2 Gy contribute to the development of DRM.
Aged↗
Towards better pain treatment in cancer.
This review focuses on ways to ameliorate diagnosis and treatment of cancer-related pain with currently available knowledge and methods. The first part indicates how to improve pain assessment and diagnosis in the cancer patient. The second part evaluates current views for adequate pain management based on evidence of double-blind analgesic trials in cancer-related pain and deals with misconceptions in established symptomatic therapy.
Analgesics, Non-Narcotic↗
Peripheral neurotoxicity induced by docetaxel.
Docetaxel, a new semisynthetic taxoid used as an antineoplastic agent, induced a predominantly sensory neuropathy in 20 of 41 patients. We assessed neurotoxicity in all patients participating in four phase II trials conducted in our institution. The neuropathy was evaluated by a clinical sum-score for symptoms and signs and by measurement of the Vibration Perception Threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's Common Toxicity Criteria. Neuropathic symptoms were mild in most patients. However, at cumulative doses above 600 mg/m2, 3 of 15 patients developed a moderate and 1 of 15 patients a severe neuropathy. There was a significant correlation between the cumulative dose of docetaxel and the post-treatment sum-score (p = 0.002). We found no correlation between post-treatment VPT and clinical sum-score or between post-treatment VPT and the cumulative dose of docetaxel. We conclude that docetaxel produced a mild and predominantly sensory neuropathy in a high proportion of treated patients. This neurotoxicity appeared to be dose dependent and may be severe and disabling at higher dose levels. Determination of the VPT is not a reliable method to monitor docetaxel-induced neuropathy.
Adult↗