Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.     

The assessment of development of binding antibodies to interferon beta during interferon beta 1a treatment of multiple sclerosis

The importance of binding antibodies (BAb) that develop during the treatment of multiple sclerosis with interferon beta has not been fully explained yet. However, they are generally regarded as one of factors that may diminish treatment efficacy. The aim of the study was to evaluate firstly, BAb occurrence in interferon beta 1-a (IFN beta 1-a)-treated MS patients and secondly, BAb impact on clinical efficacy of this medication. In the 36-month study participants were 21 patients with relapsing-remitting multiple sclerosis, RR-MS, (14 women, 7 men, aged 29.6 +/- 8.5). All the patients were receiving intramuscular IFN beta-1a (Avonex) for 24 months, in the dose of 30 micrograms per week. Clinical parameters and serum BAb levels (the EIA method) were estimated every 3 months. Two control groups, examined only once, included 20 RR-MS patients without IFN-beta therapy and 20 healthy volunteers. While before treatment a high BAb level was found in 2 patients (9.5%), at 6 months of treatment it was found in 8 patients (38.1%). A similar number of patients with high BAb levels was seen throughout the study during the IFN-beta treatment. On therapy completion serum BAb levels decreased very rapidly. After 2 years of treatment, disability as measured by the EDSS scale was more pronounced in patients with serum BAb, but the differences were statistically not significant. No statistically significant relationship was found either between elevated BAb levels and the number of relapses during the IFN-beta treatment (including relapses that required steroid therapy).     

Outbreak of measles in Kielce--June 2001

Kielce area has had a very low incidence of measles. The outbreak of measles was reported in June 2001 and included a cumulative number of 12 cases, of whom 11 have been lab confirmed. Nine cases belonged to Gypsy community and were less than 16 years of age. Remaining 3 cases were medical care workers of age 29-31. None of the children involved in the outbreak have been previously vaccinated against measles.     

Pharmacological effects of lavandulifolioside from Leonurus cardiaca

Lavandulifolioside was detected for the first time in Leonurus cardiaca var. vulgaris [Moench] Briquet (Lamiaceae). The isolation was performed from the butanolic extract of the aerial parts and the identification by NMR and MS. The pharmacological properties of lavandulifolioside consist of significant negative chronotropism, prolongation of the P-Q, Q-T intervals and QRS complex, and decrease of blood pressure. Contrary to the butanolic extract lavandulifolioside did not reduce the spontaneous locomotor activity. In conclusion, the pharmacological pattern of lavandulifolioside did not explain the pharmacological effects of L. cardiaca L. alone.     

Difficulties in stereotactic biopsies of brain tumors

MATERIAL: 28 stereotactic biopsies of organic brain processes (brain tumours) were performed in the years 1997-2000 in the Department of Neurosurgery, Medical University of Warsaw. In this series the lesions were located in corpus callosum in 5 patients, in basal nuclei in 9, and deeply in the white matter of cerebral hemispheres in 14. METHOD: The Baklund biopsy kit and Leksell's stereotactic frame were used, target localisation was based on the CT scan. Histological verification was based on hematoxillin--eosin staining, completed with histochemical evaluation if necessary. In 9 patients intraoperative smear evaluation was performed. RESULTS: Sensitivity of stereotactic biopsies was 86% (24/28), although the rate of conclusive biopsies was lower, being 60% (17/28). False negative results were observed in 14% of the patients (4/28). Analysis of the results revealed, that the sensitivity was not dependent on the size, neither on the location of the tumour, but was related to its morphology. The false negative results were obtained in the tumours with significant necrosis (as seen on CT scans). There were no surgical complications in this series. CONCLUSIONS: 1. Difficulties in stereotactic biopsies of brain tumours are associated mainly with tumour morphology. In tumours with marked necrosis, other degenerative changes or cystic ones, higher risk of non-conclusive biopsy may be expected. 2. Size of the tumour and its location do not affect the diagnosis based on the stereotactic biopsies. 3. In the polymorphic tumours, the policy to take biopsy material from different tumour sites, should be a rule, as different parts of the lesion may represent different stages of malignancy and histological evaluation of separate parts of the tumour may lead to inadequate oncological treatment.     

Yolk-sac carcinoma of extra-embryonic origin in the 129 Sv/Sl mouse

Displacement of the visceral yolk-sac in fetectomized rats and hamsters does not only induce benign teratomas but may also lead to the development of malignant yolksac carcinoma. In the mouse, displacement of this extraembryonic membrane readily induces teratoma but until now yolk-sac carcinoma has never been observed in this species. In the present study we report the development of yolk-sac carcinoma in 129 Sv/Sl mice after a long latent period (8 months). The tumor is composed of visceral and parietal patterns in the primary neoplasm and in its metastases. It develops from the extra-embryonal part belonging to normal (+/+), heterozygous (SI/+) or sterile (SI/SI) embryos, which proves that these yolk-sac carcinomas are not of germ-cell origin.     

Influence of smoking on metallothionein level and other proteins binding essential metals in human milk

Aim: To assess the influence of smoking on the level of total protein, metallothionein (MT), albumin and lactoferrin in human breast milk. Methods: Samples of whole milk and supernatants of milk after centrifugation at 10 000×g and 105 000×g were analysed. Cadmium was determined by graphite furnace atomic absorption spectrometry (GFAAS). The concentration measurements employed the following methods: total protein by Lowry, albumin by colorimetry, cotinine and lactoferrin by ELISA tests, metallothionein by ¹⁰⁹Cd/haemoglobin assay. Results: The assessment of tobacco smoke exposure was based on concentrations of cotinine in breast milk (197±98 ng/ml in smokers and 23±11 ng/ml in non-smokers; p≤0.001) and serum (179±87 ng/ml and 32±19 ng/ml, respectively; p≤0.001). The level of cadmium was four times higher in the milk of smoking women than in non-smokers. The concentration of total protein was lower in smoking (37.3±10.6 mg/ml) than in non-smoking mothers (51.8±13.8 mg/ml; p≤0.02). No significant differences between albumin and lactoferrin concentrations were observed. The level of metallothionein was over twice as low in smokers (5.1±1.9 μg/ml) than in non-smokers (13.4±3.0 μg/ml; p≤0.001), and an inverse correlation between MT level and cadmium concentration (r=-0.86; p=0.001) was noticed.

Conclusions: The breast milk of smoking mothers might be of lower nutritive value. The amount of MT transported by milk to the mammary gland is smaller in smokers than in non-smokers, which may prove to be advantageous to an infant because of the higher toxicity of the Cd-MT complex than that of inorganic Cd salts.     

Quantitative assessment of mRNA TGF-beta1 in liver tissue in connection with serum mean daily level of TGF-1 in chronic hepatitis B patient

Monitoring of fibrosis process with the use of histopathologic studies on liver's bioptates is limited, so it is attempted to find reliable, obtained with less invasive methods, sensitive and reflecting fibrosis dynamics markers of this process. The aim of the study was simultaneously to assess liver's expression as well as circadian and mean daily TGF-betal concentration in serum of patients with chronic hepatitis type B in comparison to control group. Studies were performed on 50 patients (9 women, 41 men) aged 45.9 +/- 2.3 years with chronic hepatitis type B. Control group consisted of 20 patients (mean age 38.6 +/- 3.7 years), in which so called minimal changes without fibrosis were observed in histophatologic bioptate of liver. Blood for studies was collected every 4 houres during the day. Serum concentration of TGF-betal was assessed with the use of ELISA method, and expression of mRNA TGF-betal in liver with QRT-PCR method. No significant difference between circadian as well as mean daily serum TGF-betal concentration beetwen control group and the group with chronic hepatitis type B was shown. Increased expression of mRNA, TGF-betal in bioptate of liver of patients with chronic hepatitis type B in comparison to control group was noted. In "minimal changes" control group presence of significant positive correlation between expression of mRNA TGF-beta1 in liver and concentration of this cytokine in serum was shown, in the group of patients with chronic hepatitis B this connection was not noted.