Survey of treatment recommendations for elderly patients with glioblastoma.

INTRODUCTION: Glioblastoma, which is the most commonly diagnosed primary CNS neoplasm, is more frequent in individuals aged 65 years or more. Our purpose is to identify how glioblastoma diagnosed in elderly population is treated by Spanish oncologists. MATERIAL AND METHODS: A survey was emailed to all members of Spanish Group for Neuro-oncology Research (GEINO). RESULTS: Twenty-six neuro-oncologists from 26 hospitals completed the survey. The answers were different depending on the age, performance status, and MGMT methylation status. Patients between 65 and 70 years of age are mainly treated with Stupp treatment. For patients between ages of 70 and 80 years, 46.2% made recommendations for Perry regimen, for both methylated and non-methylated patients. For patients older than 80  years, monotherapy treatment is considered more frequently. In cases of non-MGMT promoter methylation, systemic therapy with temozolomide is still recommended in many hospitals. CONCLUSION: Our research demonstrates there is no uniform approach to the management of elderly patients with glioblastoma among academic neuro-oncologists.

SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017).

Glioblastoma (GB) is the most common brain malignancy and accounts for over 50% of all high-grade gliomas. Radiotherapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy is the current standard of care for patients with newly diagnosed GB up to age 70. Recently, a new standard of care has been adopted for elderly patients (≥ 65 years) based on short course of RT and TMZ. Several clinically relevant molecular markers that assist in diagnosis and prognosis have recently been identified. The treatment for recurrent GB is not well defined, and decision-making is usually based on prior strategies as well as several clinical and radiological factors. The presence of neurologic deficits and seizures can significantly impact quality of life.

[Spinal granuloma in a patient receiving a spinal infusion of morphine and clonidine]. / Granuloma intradural en un paciente con infusión espinal de morfina y clonidina.

Patients treated with long-term spinal infusion of high doses of morphine develop a granuloma at the location of the catheter tip. Diagnosis is based on a steady increase in intrathecal morphine dosage after a relatively prolonged period of stability, on the gradual development of neurologic signs and symptoms suggesting radicular or spinal cord compression, and on magnetic resonance images. We describe a man with central neuropathic pain after removal of a tumor. The presence of all 3 of the aforementioned diagnostic criteria led to suspicion of a spinal granuloma.

Brain abscess due to Panton-Valentine leukocidin-positive Staphylococcus aureus.

Panton-Valentine leukocidin (PVL) is a cytotoxin produced by Staphylococcus aureus that exhibits highly specific lytic activity against polymorphonuclear cells, monocytes, and macrophages. A 34-year-old man admitted for right parietal brain abscess and thickened dura mater in close proximity to a lytic bone lesion is presented. The abscess culture yielded methicillin-sensitive S. aureus that produced PVL. The patient did well after surgery and antibiotic treatment. A hematogenous infection, route of bone infection with progression to dura mater and brain parenchyma was hypothesized. To our knowledge this is the first reported case of a brain abscess due to PVL-positive S. aureus.

[How is iron prescribed in French ICUs: a practice survey]. / La prescription martiale en réanimation aujourd'hui : une enquête de pratique.

OBJECTIVE: To evaluate the practice concerning the iron prescription by French intensivists. TYPE OF STUDY: Survey during an intensive care-national congress. METHODS: Interviewed practitioners were separated in two groups (prescribing [P] iron once time or more per week; or not [NP] less than one time per month). Iron-treatments (iv or oral) efficacy and tolerance were quoted from 1 to 10. RESULTS: All the 128 interviewed intensivists (73% male; mean age 36+/-8 years) considered having anaemic patients and 94% considered having patients with iron deficiency. For 72% of them, the iron deficiency was judged frequent (concerning >10% of their patients) and 25% were P. Intravenous iron, oral iron or both were used by, respectively, 20, 35 and 44% of the interviewed intensivists. Intravenous iron was considered more efficient (7+/-2 versus 6+/-2; p<0.001) and better tolerated (7+/-2 versus 6+/-2; p<0.001) than oral iron. There was no demographic difference between P and NP. P answered more often having patients with iron deficiency (p=0.04), but they did not perform biological tests for diagnosis of iron deficiency more often and did not consider iron-treatment efficacy or tolerance higher than NP. CONCLUSION: Intensive-care anaemia and iron deficiency were considered to be frequent and iron treatments to be efficient and quite well tolerated. But only 25% of the interviewed intensivists were frequent-iron prescribers. This survey underscore that iron prescription in ICU seems to rely more on clinical feeling than on strong evidence: it's time to investigate!

Transclival cerebrospinal fluid fistula in a patient with Marfan's syndrome.

Marfan's syndrome is a disease associated with reduced structural integrity of connective tissues. We report a 36-year-old patient with Marfan's syndrome who presented with rhinorrhoea, occipital headache and vomiting. Physical examination revealed typical Marfan's syndrome features including dolicocephalous, mandibular micrognathia, tall stature, disproportionately long limbs and digits, and hypermobility of the joints. A high-resolution CT scan demonstrated pneumoencephalous, cerebrospinal fluid (CSF) filling the sphenoidal sinus, and a small bone defect of the clivus. Surgery performed through a transsphenoidal approach revealed the sphenoid sinus to be filled with CSF and a small fenestration in the clivus. The arachnoid diverticulum and the fenestration were repaired and covered with a graft of abdominal fat. In this patient, a deficiency in bone development associated with Marfan's syndrome gave rise to a clival fenestration and a transclival CSF fistula. Although abnormalities of the spinal meningeal membranes have been reported in Marfan's syndrome, to our knowledge, this is the first report of a fistula located in the cranial base in this condition.

Serum anticholinergic activity in patients following cardiac surgery and healthy individuals following amitriptyline application.

The serum anticholinergic activity (SAA) is used as a marker for cognitive impairment. Here, two studies have been performed characterizing the SAA profile. In Study 1 the endogenous SAA in relation to the total serum protein concentration was monitored for 24 h in five healthy individuals and compared with that in four inpatients following cardiac surgery. In Study 2 the SAA of seven healthy individuals was assessed following a single amitriptyline dose. In both studies SAA was assessed by an ex vivo assay. In Study 1, the absolute SAA varied in a wide range of 1.2 and 14.5 atropine equivalents (AEs) over 24 h. A circadian pattern was not observed. The mean total serum protein concentration, but not the SAA, was significantly lower in inpatients than in healthy individuals. In Study 2, the SAA increased following amitriptyline to a maximum. The mean SAA increased by 6.39 AE at the amitriptyline peak concentration. High SAA variability showed a low statistical relation to amitriptyline concentrations. Both studies characterize the SAA as an individual parameter not affected per se by surgery or clinical care and poorly correlated with the total serum protein concentration. The relation with amitriptyline concentration helps to quantify SAA values towards a better understanding of the clinical implications and limitations of SAA changes.

Spontaneous cerebrospinal fluid fistulae associated with empty sellae: surgical treatment and long-term results.

OBJECTIVE: To evaluate the accuracy of different diagnostic tools for cerebrospinal fluid fistulae (CFFs) associated with empty sellae and to assess the long-term results after surgical treatment. METHODS: Records were retrospectively reviewed for 38 of 44 patients who were treated for CFFs associated with empty sellae between 1972 and 1996. Glucose and radioisotope analyses of nasal fluids were used to establish the CFF diagnosis. Computed tomography, magnetic resonance imaging, and cisternography were used to localize the sites of the CFFs. Treatment was performed using three different approaches, i.e., subfrontal approach, transsphenoidal approach, and lumboperitoneal shunt placement. RESULTS: Glucose and radioisotope analyses of nasal fluids confirmed CFFs in 97 and 100% of the cases, respectively. For localization of the sites, a leak in the sella was suggested in 32% of the cases using gammagraphy, in 50% using computed tomography or magnetic resonance imaging, and in 75% using computed tomographic contrast cisternography. After surgery, rhinorrhea ceased for 34 patients (89%), but 14 (41%) patients experienced recurrences of the rhinorrhea 6 months to 20 years after surgery (mean, 4.2 yr). Cure rates for the subfrontal approach, transsphenoidal approach, and shunt placement were 94, 85, and 86%, and the recurrence rates were 43, 33, and 50%, with mean times of 7.8, 4.2, and 0.8 years, respectively. CONCLUSION: In this series, confirmation of CFFs was easy, although localization of the sites remained difficult. Recurrences were more numerous and occurred sooner after treatment with shunts; packing of the sella through a craniotomy achieved better and more stable results, although differences were not statistically significant.

T-cell evaluation in patients with colon cancer: dinitrochlorobenzene skin testing versus plasma levels of sIL-2r and sCD8.

BACKGROUND: Developing reliable methods to test the T-cell system may be important in the treatment of colon cancer patients with 5-fluorouracil/levamisole. In a pilot study we explored whether DNCB (dinitrochlorobenzene) skin testing correlated with plasma levels of soluble interleukin-2 receptor (sIL-2r) and soluble CD8 (sCD8) and, secondly, whether the application of DNCB had any influence on the production of sIL-2r and sCD8. METHODS: In 10 patients with advanced colon cancer and in 10 healthy volunteers, plasma levels of sIL-2r and sCD8 were measured before and 10 days after the application of 2 mg DNCB on the inner side of the forearm. RESULTS: As expected, colon cancer patients showed a depressed immune system compared to healthy volunteers (DNCB skin test: P = .005, sIL2r [medians 700 vs 295, P = .002], sCD8 [medians 158 vs 90, P = .03], M-W test). The plasma levels for sIL-2r and sCD8 were significantly lower in the skin-positive cases (P = .01 and P = .03, M-W test). However, a large overlap in plasma levels could be observed between the two skin categories. DNCB had no influence on the production of sIL-2r and sCD8; median change skin-negative and skin-positive -10 vs +25, P = .14, respectively; 48 vs 0, P = .32 (M-W test). CONCLUSIONS: DNCB skin testing and plasma levels of sIL-2r and sCD8 seem to be equally useful in evaluating the T-cell system and can be used simultaneously.

Choroid plexus papillomas of the III ventricle in infants. Report of three cases.

The III ventricle is an uncommon location for choroid plexus papilloma at any age. We describe three new cases of choroid plexus papillomas of the III ventricle (CPPs). All children were boys under 4 months of age and all presented with increased intracranial pressure, hydrocephalus and macrocephaly. The three were examined by preoperative computed tomography (CT) and ultrasonography. Two of them were investigated with magnetic resonance imaging (MRI). The first case was treated with a right corticofrontal transventricular approach and subtotal resection, so that he required a second operation through a transcallosal approach. In the other two cases a transcallosal approach was used. Two children needed permanent ventriculo-peritoneal shunts. The average follow-up of 4.3 years has revealed no neurological deficits in any case. The timing of and the need for shunting are major considerations. Clinical and imaging follow-up (CT and/or ultrasonography) are very helpful in controlling postoperative hydrocephalus and subdural effusion, avoiding unnecessary shunting in many cases. The operative approaches, transcortical and transcallosal, are discussed.

Abnormal A-type lamin organization in a human lung carcinoma cell line.

We have studied the expression of lamins A and C (A-type lamins) in a lung carcinoma cell line using type-specific monoclonal antibodies. Using immunofluorescence and immunoblotting studies it was noted that several irregularities in lamin expression exist in the cell line GLC-A1, derived from an adenocarcinoma. First, the expression of the A-type lamins was lower than in other adenocarcinoma cell lines of the lung. Also the ratio between lamins A and C proteins was 1:8 instead of the 1:1 ratio seen in the other cell lines. Northern blotting confirmed the altered level of A-type lamin expression. Secondly, an abnormal localization of lamin A was observed. Intensely fluorescing lamin A aggregates were observed in the nucleus, rather than the typical perinuclear staining pattern. Confocal scanning laser microscopy revealed that the lamin A aggregates were indeed present throughout the internal nucleus. When these cells were extracted with Triton X-100 the nucleoplasmic aggregates disappeared, which indicates that the A-type lamins are not properly incorporated into the lamina. The A-type lamins in other cell lines derived from adenocarcinomas remained present in the nuclear periphery after extraction with the non-ionic detergent. Immunoblotting studies of the Triton X-100 soluble and insoluble fractions showed that lamin A and an apparently truncated product, which was detected with the lamin A antibody, were present in the insoluble fraction of GLC-A1. This truncated product is partly Triton X-100 soluble since it was also detected in the detergent soluble fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Medulloblastoma in adulthood: prognostic factors influencing survival and recurrence.

Thirty adult patients presenting with medulloblastoma between 1974 and 1991 were studied and treated at Puerta de Hierro Clinic. After diagnosis, all patients were treated by surgery followed by radiotherapy and eight of them received adjuvant chemotherapy. We have studied the influence of some factors such as age, sex, location of tumour in the cerebellum, amount of surgical resection and histological variants on survival and recurrence of the disease. Only the histological type has a statistically significant influence on survival and recurrence: we have found that patients presenting classic medulloblastoma have a long survival and a long relapse-free interval.

Our approach towards developing a specific tumour-targeted MRI contrast agent for the brain.

This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The prepared magnetite particles bound to dextran, were also shown to be of appropriate size by electron microscopy. After their intravenous injection into rats with blood-brain barrier disruption, the lesion was strongly enhanced by T2-shortening. Furthermore, monoclonal antibodies directed against small cell lung carcinoma, proved to be able to penetrate into tumours, which had been raised by implantation of the small cell lung carcinoma cells into the brains of nude rats. As to the essential step, it was demonstrated in vitro that magnetite particles coupled to monoclonal antibodies by the biotin-streptavidin binding, could be bound to the target cells of the antibody, changing the relaxation rates of the latter. Finally it could be shown in vitro that an alternative approach, using lymphocytes to be targeted to tumour cells, also proved feasible, in that these lymphocytes could be labelled with magnetite that had been incorporated into liposomes. Further developments will be the in vivo assessment of the acquired progress in experimental animals, before clinical application is warranted.

Proliferation rate of colonic mucosa in normal subjects and patients with colonic neoplasms: a refined immunohistochemical method.

An increased colonic epithelial proliferation rate and an increase of the cryptal proliferative zone are probable markers of increased susceptibility to colonic cancer. In this study an immunohistochemical method using 5-bromo-deoxyuridine (BrdUrd) to measure the proliferation rate of colonic mucosa in vitro was used. Fresh endoscopic colonic biopsy specimens were incubated with BrdUrd and then processed for immunohistochemistry using a monoclonal antibody. Essential procedures with respect to the equal distribution of nuclei stained with BrdUrd in the biopsy specimens proved to be the cutting of the specimens before incubation and the use of a microwave oven at the beginning of incubation. The use of the procedure of the running average showed that 12 length cut crypts are sufficient to determine reliably the proliferation rate, expressed as the labelling index (LI). This was determined in the biopsy specimens of 10 subjects without organic colonic disease, eight patients with adenomatous colonic polyps, and in six patients with (recent) colonic carcinoma. Mean LI in the controls was significantly lower than in patients with colonic polyps and in those with colon cancer. It is concluded that this method is promising for screening persons at risk for colon cancer and will be of great potential in performing dietary intervention studies in these subjects.

Characterization of a human small cell lung carcinoma cell line with acquired resistance to cis-diamminedichloroplatinum(II) in vitro.

A 6.4-fold cis-diamminedichloroplatinum(II) (CDDP) resistant human small cell lung carcinoma cell line (GLC4-CDDP) was developed to study acquired CDDP resistance in vitro. Compared to the sensitive cell line (GLC4), the GLC4-CDDP showed an increase in doubling time and a decrease in cloning efficiency, cellular size, double minutes per cell, cellular protein, and nuclear protein content. While a complete cross-resistance for tetraplatin and a partial cross-resistance for doxorubicin, melphalan, cadmium chloride, carboplatin, and cis-dichloro-trans-dihydroxo-cis-bis(isoprolylamine)platinum (IV) (resistance factor, respectively,4.0,5.8,2.1,1.5,2.9) was found, no cross-resistance for vincristine was found. In the GLC4-CDDP line in comparison to the GLC4 line, glutathione and total amount of sulfhydryl compounds was significantly increased, while glutathione S-transferase and glutathione reductase was the same. The platinum content in cells and nuclei was lower in the resistant line, but after correction for cellular protein or volume no difference was found. The amount of platinum bound to DNA was significantly lower in the GLC4-CDDP line. After a 1-h incubation with CDDP, the amount of Pt-GG adducts was the same and the amount of interstrand cross-links was reduced in the GLC4-CDDP line as compared to GLC4. In conclusion, in the GLC4-CDDP line the phenotype and genotype are changed and various mechanisms, such as decreased Pt-DNA binding, elevated glutathione, and reduced interstrand cross-links, play a role in the development of the CDDP resistance.

Two small cell lung cancer cell lines established from rigid bronchoscope biopsies.

Two new, good growing cell lines (GLC-8, GLC-11) have been established from biopsies of small cell lung cancer (SCLC). Tumor biopsies were procured by rigid bronchoscopy from tumor recurrences at the site of the primary lesions. Both tumors were clinically resistant to chemotherapy. Cytogenetic analysis revealed deletions in the short arm of chromosome 3. GLC-8 shows amplification of N-myc. Both cell lines show SCLC differentiations; neurosecretory granules were present and the SCLC related hormones dopa-decarboxylase and creatine kinase were elevated. Both cell lines behave as so-called 'classic' SCLC cell lines.

Simultaneous immunohistochemical demonstration of antigen expression and 5-bromodeoxyuridine incorporation in plastic embedded sections.

In this study a double immunohistochemical staining procedure is described for the simultaneous demonstration of antigen expressing cells and replicating cells in rat thymus. As markers for cell surface antigen expression a monoclonal antibody against Ia-expressing cells (His 19) and a monoclonal antibody against cells of the monocyte-macrophage lineage (ED2) were used. Replicating cells were demonstrated by the incorporation of 5-bromodeoxyuridine (BrdUrd). Tissue pieces were fixed in a periodate-lysine-paraformaldehyde fixative and embedded in glycol methacrylate. To demonstrate Ia-expressing cells or ED2-positive macrophages in plastic embedded sections a digestion with trypsin is necessary. The staining procedure was applied sequentially and was performed with a peroxidase and an alkaline phosphatase labeled reagent yielding respectively a brown and a blue reaction product. Results with this staining procedure on plastic embedded sections of rat thymus, an organ with a high DNA synthesizing capacity, showed incorporation of BrdUrd predominantly in the cortex. ED2-positive macrophages were only found in the cortex. The Ia-positive epithelial reticular cells demonstrated extremely well their stellate form.

Intermediate filament expression in small cell lung cancer; poor correlation to in vitro data.

A panel of monoclonal antibodies, detecting different intermediate sized filament proteins, was prospectively applied on all specimens derived from S.C.L.C. patients attending our clinic in 1985. Reactivity with the antibodies was subsequently correlated to clinical data. The results indicate a heterogeneous pattern of reactivity of the assessed antibodies. However this heterogeneity is not a straightforward extension of the intermediate sized filament expression in SCLC cell lines.