Outcomes in a consecutive series of 111 surgically treated plexal tumors: a review of the experience at the Louisiana State University Health Sciences Center.

OBJECT: The authors conducted a retrospective study of 107 consecutive patients with 111 brachial plexus tumors surgically treated at the Louisiana State University Health Sciences Center (LSUHSC). METHODS: During a 12-year period, from 1986 to 1998, 371 patients with lesions of the brachial plexus underwent surgery at LSUHSC. Among this group, 107 patients harbored 111 tumors of the brachial plexus. Neural sheath tumors were the most commonly found and included 33 neurofibromas (20 of which were associated with von Recklinghausen disease), 36 schwannomas, and 12 malignant neural sheath tumors. Of the non-neural sheath tumors, 13 were benign and 17 were malignant. Presenting symptoms included pain (59%), palpable mass (52%), paresthesias (30%), and paresis (29%). Anterior supraclavicular (82%) or posterior subscapular (18%) approaches were used to achieve gross-total (79%) or subtotal (21%) resection of tumor. The average follow-up period was 38.3 months or 3.2 years. Seventy percent of patients with benign neural sheath tumors became free from pain postoperatively or reported improvement in their preoperative pain status. Function remained intact or improved in 50% and remained stable postoperatively in another 20% of cases. Preservation of function was more likely in patients who presented intact and in those who had not undergone a previous attempted biopsy procedure or resection than in those in whom such manipulation had occurred. CONCLUSIONS: Resection of most plexal tumors is technically feasible and associated with acceptable morbidity and mortality rates.

Effect of pharmacologic doses of zinc on the therapeutic index of brain tumor chemotherapy with carmustine.

To evaluate the potential differential effect of pretreatment with pharmacologic doses of the trace element zinc on the chemosensitivity of glioma cells and bone marrow cells for carmustine (BCNU), we performed in vitro and in vivo studies of zinc toxicity as well as of the combined treatment with zinc and the anticancer drug. We studied the in vitro effects on established human and rat glioma cell lines using a microcolorimetric growth assay and on murine bone marrow using a clonogenic assay for committed progenitor cells of the granulocyte-monocyte lineage. Zinc exposures of up to 100 microM for 120 h did not influence the growth of six of seven human glioma cell lines. Only U87MG demonstrated statistically significant toxicity during high zinc exposure (100 microM over 120 h). Dose-response growth curves generated for BCNU did not show protection against the anticancer agents by a 48-h pretreatment with different zinc concentrations. The clonogenic capacity of bone marrow cells was slightly reduced by in vitro culture for 24 and 48 h. Although this effect appeared to be more prominent in the presence of zinc supplementation, overall a statistically significant inhibition was seen only after exposure to a concentration of 100 microM zinc over 48 h. As compared with chemotherapy alone, in vitro pretreatment with 50 microM zinc over 48 h followed by chemotherapy resulted in an increased number of colony-forming unit-granulocyte monocyte (CFU-GM): CFU-GM increased by a factor of 2 for BCNU (60 microM x 2 h). This statistically significant in vitro chemoprotection would translate into a dose-protection factor of 1.5, i.e., for the same level of myelosuppression, zinc pretreatment would allow administration of a 50% increased dose of BCNU. The in vivo studies were performed in an s.c. xenograft model of the human glioma cell line U87MG in athymic mice. The maximal tolerable pretreatment with zinc was determined to be a 10-day course of daily i.p. injections of 10 mg/kg ZnCl2. The subsequent i.p. administration of the dose lethal to 10% of the mice (LD10) and of a 1.5 x LD10 dose of BCNU resulted in less bone marrow toxicity in pretreated animals than in non-zinc-pretreated mice as determined in a CFU-GM assay. Glioma colony-forming efficiency (CFE) assays, on the other hand, did not show any zinc-related difference in the BCNU sensitivity of U87MG.(ABSTRACT TRUNCATED AT 400 WORDS)

Metallothionein and anticancer agents: the role of metallothionein in cancer chemotherapy.

Metallothioneins (MTs) are intracellular proteins containing the highest amount of thiol groups within the cytoplasm. These thiol groups are able to bind several cytotoxic agents, such as platinum compounds and alkylating agents. Increased levels of MT are one mechanism of resistance to these anticancer drugs, as intracytoplasmic binding of MT prevents the active molecules from reaching their target, the intranuclear DNA of tumor cells. MT synthesis can easily be induced by physiologic heavy metals such as zinc and copper. Pharmacological modulation of MT levels has been used to increase the MT pool in normal tissues and decrease their susceptibility to the toxicity of anticancer drugs. In the case of tumors arising in the brain, where the inducibility of MT synthesis is low, this approach would allow protection of normal tissues without decreasing the antitumor activity of the cytotoxic agents. The interaction of MT with cytotoxic agents is not limited to covalent binding. A correlation between MT synthesis and amplification of oncogenes such as ras has been reported. Furthermore, the cytotoxic drugs are bound by MT after competition with zinc and copper; these metals are cofactors of numerous metalloenzymes, some of which are involved in the metabolism of nucleic acids. Competitive displacement of these metals might modify nucleic acid metabolism and influence cellular proliferation. On the other hand, increased MT levels could provide a zinc cofactor reserve that increases the cell's reparative potential when faced by DNA damage by cytotoxic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunohistochemical demonstration of proliferating cell nuclear antigen in glioblastomas: pronounced heterogeneity and lack of prognostic significance.

In order to evaluate a possible significance of the expression of proliferating cell nuclear antigen (PCNA) as clinically useful prognostic parameter, we retrospectively investigated a series of 40 glioblastomas by means of immunohistochemistry and compared the results to patient survival. All glioblastomas included in the study had been treated by operation, radiotherapy and intraarterial ACNU [3-(4-amino-2-methyl-5-pyrimidinylmethyl)-1-(2-chloroethyl)-1-nitr osourea] chemotherapy. Patient survival ranged from 2 months to 42 months (mean: 14.2 months). PCNA values varied widely, ranging from 0.5% to 75% (mean: 24.9%). Statistical analysis revealed no significant correlation between PCNA index and patient survival. Our study thus indicates that the expression of PCNA appears not to be a useful prognostic parameter for glioblastoma patients.

[MRT in syringomyelia--follow-up control after syringo-arachnoid shunt surgery with clinical correlation]. / MRT bei Syringomyelie--Verlaufskontrollen nach syringosubarachnoidalen Shuntoperationen mit klinischer Korrelation.

In 8 patients with syringomyelia, MR long-term follow-ups (observation period 25-46 months) were done after syringosubarachnoidal shunt operations. MR showed directly after surgery in 6 cases an extensive collapse of the syringomyelias and in 2 cases a lesser reduction of the diameter of the syrinx. During the subsequent course the size of the cavities increased again in 3 cases. The size of the syrinx visualised by MR did not correlate with the clinical status during the follow-up studies. This seems to point to an insufficient representation of the disease process by the morphological visualisation of the size of the syrinx.

Primary Ewing's sarcoma of the calvarial skull.

Primary Ewing's sarcoma of the calvarial skull was diagnosed in a 10-years-old girl. Detailed angiographical investigations were performed in this large tumor, and although the larger part of the neoplasm was supplied by the external carotid artery, an unusual feature was the presence of a very thick arterial feeder, originating from the left callosomarginal artery. The tumor was radically resected. Adjuvant chemotherapy was given, and no recurrence or metastasis occurred during two years, after which the girl was lost for follow-up.

Effects of recombinant human tumor necrosis factor on rodent gliomas and normal brain.

In a study examining the possible therapeutic effects of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) on malignant gliomas without expression of tumor necrosis factor (TNF)-receptors, RG-2 glioma cells were tested in vitro as well as in a rat experimental glioma model. A growth inhibition assay revealed no inhibiting effect in vitro up to a concentration of 20 micrograms/ml rHuTNF-alpha. Receptor-binding studies showed that RG-2 cells did not present specific receptors for rHuTNF-alpha. The pharmacokinetics of rHuTNF-alpha after intravenous injection were studied with respect to serum, tissue, and brain tumor concentrations and showed increased glioma concentrations of (mean +/- standard error of the mean) 0.47 +/- 0.18 ng TNF/mg brain compared to 0.15 +/- 0.05 ng TNF/mg brain in the normal contralateral hemisphere. No therapeutic effect on solid RG-2 gliomas could be observed after stereotactic injection of 7.3 micrograms rHuTNF/10 microliter buffer solution into the tumor in 10 animals. Immunohistochemical studies after stereotactic injection of rHuTNF-alpha showed total disappearance of the substance after 24 hours without internalization into tumor cells. Stereotactic injection of 7.3 micrograms rHuTNF 10 microliters into normal brain resulted in marked inflammatory response around the injection track, including microvascular thrombosis. These results demonstrate that rHuTNF has neither direct nor indirect cytotoxic activity on RG-2 glioma cells. Furthermore, before clinical use of rHuTNF-alpha in malignant gliomas, the authors suggest that receptor studies be done in each patient. In receptor-positive patients undergoing treatment with rHuTNF-alpha, precautions should be taken to prevent local encephalitic reactions.

Brain and brain tumor uptake of L-3-[123I]iodo-alpha-methyl tyrosine: competition with natural L-amino acids.

SPECT studies with L-3-[123I]iodo-alpha-methyl tyrosine (IMT) were carried out in 10 patients with different types of brain tumors--first under fasting conditions (basal) and a week later during intravenous infusion of a mixture of naturally-occurring L-amino acids (AA load). An uptake index (UI) was calculated by dividing tissue count rates by the integral of plasma count rates. The UI decreased by 45.6% +/- 15.4% (n = 10, p less than 0.001) for normal brain and by 53.2% +/- 14.1% for gliomas (n = 5, p less than 0.01) during AA load compared to basal conditions, while two meningiomas and a metastasis showed only a minor decrease (23.9 +/- 5.7%, n.s.). Two pituitary adenomas could not be delineated on the SPECT scans. These data indicate that IMT competes with naturally-occurring L-amino acids for transport into normal brain and gliomas. Transport characteristics of IMT into tumors of nonglial origin appear to be different from those of gliomas. For both types of tumors, it is advisable to perform IMT-SPECT under fasting conditions.

Clinical experience with a pressure-adjustable valve SOPHY in the management of hydrocephalus.

Seventy-four patients with hydrocephalus due to a variety of causes were treated with a cerebrospinal fluid (CSF) shunt, incorporating a recently developed pressure-adjustable valve SOPHY (PAVS). The PAVS may be changed percutaneously with the help of an externally applied magnet in order to select a high-, medium- or low-valve opening pressure, whenever the need for a change in pressure characteristics seems necessary to the neurosurgeon. The percutaneous pressure adjustment obviated up- or downgrading of a medium pressure position by surgical means in half of our patients during the follow-up time (up to 39 months; mean follow-up 16.7 months). In 66 patients (89%) decreased ventricle volume and improvement of the clinical sign of increased intracranial pressure were established. In 11 patients a valve or a catheter infection occurred; in 6 of these patients the valve had to be removed. Half of this group consisted of patients under 2 years of age. Significant technical complications related to the PAVS did not occur in our series but until a somewhat smaller PAVS is available, we cannot recommend its use in neonates or in small infants. In all other patients the PAVS is a very valuable instrument in the surgical management of hydrocephalus because it makes shunt revisions for inadequate valve pressure obsolete in individual patients.

SPECT studies of brain tumors with L-3-[123I] iodo-alpha-methyl tyrosine: comparison with PET, 124IMT and first clinical results.

L-3-[123I]iodo-alpha-methyltyrosine (123IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of 124IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). 124IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with 123IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, 123IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.