Prediction of very short survival in patients with brain metastases from breast cancer.

AIMS: Current prognostic models are not accurate enough to identify brain metastases patients with very short survival, i.e. <2 months, who are unlikely to derive major benefit from whole brain radiotherapy. Our aim was to develop a more reliable model. MATERIALS AND METHODS: This was a retrospective analysis of a German database, which was used to develop a score, and an additional database from Norway, which was used for validation purposes. RESULTS: The groups included 67 and 32 patients, respectively. An analysis of prognostic factors resulted in a risk score based on performance status, extra-cranial metastases, the interval from breast cancer to brain metastases and a need for corticosteroid treatment, which classified 63 of 67 test patients correctly. However, the validation failed and unfortunately the risk score that performed best in the Norwegian patients (31 of 32 correctly predicted) was not applicable to the German patients. CONCLUSIONS: The prediction of short survival is associated with several caveats and seems to result in an unacceptable risk of withholding radiotherapy in patients who actually survive for longer than 2 months.

Migratory pattern of fetal rat brain cells and human glioma cells in the adult rat brain.

The migratory behavior of two human glioma cell lines (D-54MG and GaMG) and fetal rat brain cells grafted into the adult rat brain was studied. To trace the implanted cells, they were stained with the carbocyanine vital dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate before injecting them into the white matter above the corpus callosum. The animals were sacrificed 2 h and 7 and 21 days after injection, and the brains were removed and cryosectioned. Fluorescence microscopy showed that both the 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-stained fetal and tumor cells had the same migratory pattern. Implanted cells were found along myelinated fibers in the corpus callosum and in the perivascular space. After immunostaining for several extracellular matrix (ECM) components (laminin, fibronectin, collagen type IV, and chondroitin sulfate), laminin deposits were observed in the border zone between the host tissue and implanted tumor cells as well as fetal cells. By using two different types of antibodies against fibronectin, it is shown that the fibronectin expression observed in the tumor matrix may be host derived. This was further supported by the fact that tumor spheroids obtained from the two glioma cell lines were negative when immunostained for these ECM components. Several of the ECM components may be host derived. This can be caused by neovascularization and repair synthesis or by a local production of guiding substrates which are important for tumor cell locomotion. The present data suggest that the migratory patterns of fetal and glioma cells are indistinguishable when transplanted into the adult rat brain. Thus, glioma cells may be routed by the same ECM components that play a major role during brain development.

Prognostic models predicting survival of patients with brain metastases: integration of lactate dehydrogenase, albumin and extracranial organ involvement.

AIMS: To explore the role of expanded assessment of metastatic extracranial organ involvement, as well as albumin and lactate dehydrogenase (LDH), i.e. surrogates of disease extent, in survival prediction models for patients with brain metastases. MATERIALS AND METHODS: A retrospective analysis of 189 patients treated with whole brain radiotherapy was carried out. Uni- and multivariate analyses included recursive partitioning analysis classes, basic score for brain metastases and diagnosis-specific graded prognostic assessment (DS-GPA). RESULTS: Elevated LDH correlated significantly with extracranial organ involvement, low albumin with primary tumour type and primary tumour control. Elevated LDH, low albumin and a combination of both correlated significantly with overall survival. LDH, albumin and the number of extracranial organs involved (none, one, two or more harbouring metastases) were independent prognostic factors in multivariate analyses (if added to the three established scores mentioned above and also if added to individual parameters such as age, performance status, etc.). A combination of these three new prognostic factors predicted very short survival (median 0.7 months if all three were present). CONCLUSION: We have previously defined patient groups in whom foregoing radiotherapy was unlikely to compromise survival. These were patients with a DS-GPA score of 0-1.5 points and age ≥75 years or Karnofsky performance status ≤50 or uncontrolled primary tumour with extracranial metastases to at least two organs. Patients with a combination of three new adverse features (elevated LDH plus low albumin plus extracranial metastases to at least two organs) might also be considered for best supportive care. Furthermore, it appears warranted to study whether scores such as DS-GPA can be optimised by integrating information on these three parameters.

Surviving extreme hypercalcaemia--a case report and review of the literature.

We report a case of extreme hypercalcaemia associated with a parathyroid adenoma in a young man. The patient presented with classical symptoms of a hypercalcaemic syndrome, and serum calcium and parathyroid hormone levels were 6.92 mmol L(-1) and 70.2 pmol L(-1) respectively. After stabilizing the patient and reducing the calcium level, a parathyroidectomy was performed. The postoperative course was uneventful with rapidly resolving clinical symptoms. Hypercalcaemic crisis is a rare but life-threatening complication of primary hyperparathyroidism. It should be suspected in acutely ill patients complaining of muscular weakness, gastrointestinal and cerebral symptoms. To reduce mortality, it is essential to correctly diagnose the condition without delay and provide appropriate emergency management correcting hypercalcaemia and dehydration. Successful parathyroidectomy quickly relieves symptoms and prevents recurrence.

Interactions between fetal rat brain cells and mature brain tissue in vivo and in vitro.

Fetal as well as mature neural cells were homografted into the right cerebral hemisphere of adult BD-IX rats. The animals were sacrificed 7 d after implantation, and the localization of implanted cells was visualized by fluorescence and light microscopy. The cell implants were prestained with the fluorescent vital dye 1,1'-Dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) to discriminate between implanted cells and host brain tissue. At the implantation site, the fetal brain cells as well as the cells from immature brain cell aggregates showed diffuse infiltration into the surrounding host brain tissue of up to 0.5 mm. Extensive cell migration along the corpus callosum for up to 5 mm in the coronal and to a lesser extent in the sagittal plane was also observed. In addition, fetal cells were distributed in the subarachnoid space of both cerebral hemispheres and showed a distinct association with larger blood vessels. Cells from mature brain aggregates did not migrate as far as fetal cells and showed only a local infiltration into the host neuropil. Fluorescent microspheres as well as fixed fetal brain cells were implanted, either alone or in combination with vital cells to distinguish between active cell migration and passive cell displacement. The microspheres and the fixed cells were found either localized to the implantation pathway or distributed in the corpus callosum for up to 2 mm in the coronal plane without any dispersion in the sagittal plane. The microspheres also showed an extensive displacement in the subarachnoid space. In vitro co-culture experiments between two immature aggregates showed a complete fusion of the two aggregates during a 96 h culture period. In co-cultures between two mature aggregates complete fusion was not prominent, although the confrontation zone appeared diffuse. Confrontations between a mature and an immature aggregate showed the same pattern of interaction as seen for the two mature aggregates. It is concluded that carbocyanine dyes may be used as a tracer for transplanted cells. Cells from fetal rat brain cell aggregates, opposed to those from mature aggregates, showed extensive migration along well defined anatomical structures in the mature along well defined anatomical structures in the mature brain. Some of the spread of cells following implantation is probably due to passive movement since inert microspheres will spread into certain areas of the CNS.