Nocturnal back pain; a misdiagnosed symptom of spinal tumor]

Four patients had nocturnal back pain or pain that worsened when lying down. In one of these, a 49-year-old man, the medical history mentioned a malignancy, as a result of which a spinal metastasis was suspected. In the other three patients, a 52-year old woman and two men aged 48 and 60 years, the nocturnal back pain and the back pain worsening when lying down was not recognised as indication of a spinal tumour. As objective neurological symptoms were not established at initial investigation, a long period of discomfort and frustration followed before the spinal tumour was diagnosed eventually. The importance of recognising these early complaints is stressed. Nowadays, MRI is the technique of choice to answer the question whether there is a space occupying process in the spine.     

Additive cytotoxic effect of cisplatin and X-irradiation on human glioma cell cultures derived from biopsy-tissue

Purpose: Investigation of the in vitro cytotoxic effect of X-rays, either alone or combined with cisplatin on early passage cell cultures derived from human glioblastoma multiforme biopsy tissue. Materials and methods: Fresh tumour specimens from four patients were processed to cell cultures. The U373 glioma cell line was used as a reference. Early passage cell cultures were X-irradiated (0–8 Gy) either alone or in combination with cisplatin (0.5–1 μg/ml). Cell survival was determined by either clonogenic assay or the colorimetric MTT assay. Survival curves were generated and mathematically analysed using the linear quadratic model, to obtain the radiosensitivity parameters α, β, and SF2, i.e., the Surviving Fraction after 2 Gy. Results: Two patient-derived glioma cell cultures and the U373 cell line showed rather high SF2 values of 0.61–0.72 in the clonogenic assay, indicating relative high radiation resistance. Cisplatin alone (1 μg/ml) reduced cell survival by 10–30% (n=4). When combined with irradiation, a clear additive cytotoxic effect of cisplatin was demonstrated by the unaltered value of the α-parameter for reproductive cell death. Conclusion: Cisplatin exerted an additive rather than radiosensitising cytotoxic effect in uncharacterised patient derived glioma cell cultures. Received: 5 November 1999 / Accepted: 10 May 2000     

Atheroembolic disease following administration of tissue plasminogen activator (TPA)

Atheroembolic disease is an uncommon condition with many interesting manifestations and has been reported following various procedures. Its occurrence following thrombolytic therapy is extremely rare, with only a few case reports in the literature. However, with the widespread application of thrombolysis in patients with acute myocardial infarction, its incidence is likely to increase and therefore this entity needs to be recognized. Early recognition of the illness may help avoid further expensive and unnecessary investigations. We report two cases of atheroembolic disease following the administration of human recombinant tissue plasminogen activator (TPA).     

Penetration of Idarubicin into Malignant Brain Tumor Tissue

Anthracyclines are effective in breast cancer and have in vitro cytotoxicity in glioma. In patients with glioma anthracyclines are not effective possibly because the hydrophilic drugs do not reach cytotoxic levels in tumor tissue. Idarubicin is more lipophilic than the other anthracyclines and is more cytotoxic in glioma cell lines. The uptake of idarubicin and its major metabolite idarubicinol in brain tumor tissue were measured in a patient with a brain metastasis from breast cancer and in 4 patients with malignant glioma after an oral dose of idarubicin (45 mg/m² in 1 patient; 25 mg/m² in 4 patients), given 15–24 h before brain tumor resection. The concentrations of idarubicin and of idarubicinol in tumor tissue exceeded the concurrent plasma concentrations as well as the peak plasma concentrations in all cases. The median tumor: concurrent plasma ratio of idarubicinol was 5.7 (range 1.7–18). The concentration of idarubicinol in the marginal zone between brain and tumor tissue was lower than in central tumor tissue, but was still higher than the plasma concentration in 2 of the 3 examined cases. Bone marrow suppression (platelets CTC grade 2, granulocytes CTC grade 4) occurred after a single dose of 45 ml/m². No toxicity was seen at a dose of 25 mg/m². These results, the in vitro activity of idarubicin in glioma, the convenience of oral administration, and its toxicity profile make clinical studies with idarubicin in malignant glioma, and perhaps also in brain metastases from breast cancer worthwhile.     

Treatment and outcome of brain metastasis as first site of distant metastasis from breast cancer

Twenty-eight consecutive patients with breast cancer were analyzedwho presented with a single brain metastasis asfirst site of distant metastasis. The response tosurgery with postoperative radiation therapy (RT) (9 patients)and to non-surgical therapy as first-line treatment was100% and 89% respectively with a significant differencein median recurrence-free intervals of 23 months andof 5 months respectively (p=0.033). Retreatmentof a local relapse by surgery (± RT,± chemotherapy) or by non-surgical treatment resulted ina response in 6 of the 7 operatedpatients and in 5 of the 6 non-operatedpatients with a median duration of response of7 months (range 2–20 months) and of 3months (range 2–4 months) respectively. The overall mediansurvival of the 28 patients with a singlebrain metastasis was 16 months (range 2–39 months).The median survival in the primarily operated patientswas 23 months, in the primarily not-operated group10 months, and in the never-operated group 9months. In comparison, the response to non-surgical treatmentin 20 consecutive patients who presented with multiplebrain metastases as first site of distant metastasiswas 55% with a median recurrence free intervalof 4 months. The median survival in thisgroup was 4 months, which was significantly shorterthan survival of patients with single brain metastasis(p=0.0036). These results suggest that breastcancer patients with a single brain metastasis asfirst presentation of relapse constitute a specific subgroupwith a favorable response to treatment and along survival especially if they can be treatedby surgery with postoperative RT.