Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and <10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology.

A Study of 179 Patients with Degenerative Stenosis of the Lumbosacral Spine to Evaluate Differences in Quality of Life and Disability Outcomes at 12 Months, Between Conservative Treatment and Surgical Decompression.

BACKGROUND This prospective study included 179 patients with degenerative stenosis of the lumbosacral spine and aimed to evaluate the outcomes of conservative treatment and surgical decompression on quality of life and disability over 12 months. MATERIAL AND METHODS The surgery group consisted of 96 patients with degenerative stenosis of the lumbosacral spine who qualified for surgical decompression, while the conservative-treatment group included 83 patients who qualified for conservative treatment. We used the Satisfaction with Life Scale questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, the Visual Analog Scale to assess the severity of pain, the Oswestry Low Back Pain Disability Questionnaire to assess the degree of disability, and the Sexual Satisfaction Scale at 0, 1, 6, and 12 months after treatment. RESULTS Statistical analysis showed a positive relationship between conservative and surgical treatment and quality of life (P<0.05). A significant reduction in the severity of pain (P<0.05) and the degree of disability (P<0.05) were both recorded during the 12-month followup period in both groups. Women of both groups declared significantly lower satisfaction than men at every time point (P<0.05). CONCLUSIONS Most patients in both groups declared an improvement in their quality of life, with the surgery group showing a higher percentage of responses that their quality of life had improved. Based on the results obtained from the FACIT-F questionnaire, degenerative stenosis of the lumbosacral spine had a non-root effect on the patients' lives in the surgery group.

Repeated assessment of suspected normal pressure hydrocephalus in non-shunted cases. A prospective study based on the constant rate lumbar infusion test.

BACKGROUND: Only a few reports have been published on the natural history of non-shunted patients suspected of having NPH. The aim of this study is to follow up a group of such cases. METHODS: It was possible to follow up 27 patients who had not been qualified for shunting after the primary diagnosis. An assessment of Hakim's triad was performed, together with an analysis of radiological parameters and the results of lumbar infusion tests (LITs), both on admission and at the later date (on average, after 5.6 months). All parameters were analyzed with respect to periventricular lucency (PVL), atrophy, type of NPH, and the age of the patients. RESULTS: There were no deteriorations and six patients improved. Those who were over 50 and who had no PVL or secondary NPH tended to improve more frequently. Significant improvement of dementia was noted (p = 0.042) in all cases, and in the group of patients without PVL (p = 0.04). The size of the ventricles did not change significantly. The values of the resistance to outflow (R), elastance (E), and ICP remained stable. CONCLUSIONS: Analysis of our series revealed that the patients suspected of having NPH who had not been qualified for shunting did not deteriorate, while some of them even improved significantly as far as the level of dementia was concerned. As the CT and LIT parameters remained stable, there were no indications for repeating these examinations, at least within the period of nearly 6 months, which followed the primary diagnosis.

Evaluation of differences in expression pattern of three isoforms of the transforming growth factor beta in patients with lumbosacral stenosis.

The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-ß-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-ß-1 and TGF-ß-3, while TGF-ß-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-ß-1, TGF-ß-2, and TGF-ß-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-ß-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-ß-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-ß-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-ß-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-ß-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-ß isoforms level for better understanding and managing degenerative spinal conditions.

Exploring Novel Therapeutic Opportunities for Glioblastoma Using Patient-Derived Cell Cultures.

Glioblastomas (GBM) are the most common, primary brain tumors in adults. Despite advances in neurosurgery and radio- and chemotherapy, the median survival of GBM patients is 15 months. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and molecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have established 13 GBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNA-seq, immunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1R132H, TP53 and PDGFRα), classical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), and the expression of pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, ß-Tubulin III) markers revealed the striking intertumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-CADHERIN and CD44 at the mRNA/protein levels suggested increased epithelial-to-mesenchymal transition (EMT) in most studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-derived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated cultures, the strongest accumulation of the apoptotic markers caspase 7 and PARP were found in WG4 cells with methylated MGMT, suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-derived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream signaling pathways. AG1478 caused decreased levels of phospho-STAT3, and thus inhibition of active STAT3 augmented antitumor effects of DOX and TMZ in cells with methylated and intermediate status of MGMT. Altogether, our findings show that GBM-derived cell cultures mimic the considerable tumor heterogeneity, and that identifying patient-specific signaling vulnerabilities can assist in overcoming therapy resistance, by providing personalized combinatorial treatment recommendations.

Identification of the immune gene expression signature associated with recurrence of high-grade gliomas.

High-grade gliomas (HGGs), the most common and aggressive primary brain tumors in adults, inevitably recur due to incomplete surgery or resistance to therapy. Intratumoral genomic and cellular heterogeneity of HGGs contributes to therapeutic resistance, recurrence, and poor clinical outcomes. Transcriptomic profiles of HGGs at recurrence have not been investigated in detail. Using targeted sequencing of cancer-related genes and transcriptomics, we identified single nucleotide variations, small insertions and deletions, copy number aberrations (CNAs), as well as gene expression changes and pathway deregulation in 16 pairs of primary and recurrent HGGs. Most of the somatic mutations identified in primary HGGs were not detected after relapse, suggesting a subclone substitution during the tumor progression. We found a novel frameshift insertion in the ZNF384 gene which may contribute to extracellular matrix remodeling. An inverse correlation of focal CNAs in EGFR and PTEN genes was detected. Transcriptomic analysis revealed downregulation of genes involved in messenger RNA splicing, cell cycle, and DNA repair, while genes related to interferon signaling and phosphatidylinositol (PI) metabolism are upregulated in secondary HGGs when compared to primary HGGs. In silico analysis of the tumor microenvironment identified M2 macrophages and immature dendritic cells as enriched in recurrent HGGs, suggesting a prominent immunosuppressive signature. Accumulation of those cells in recurrent HGGs was validated by immunostaining. Our findings point to a substantial transcriptomic deregulation and a pronounced infiltration of immature dendritic cells in recurrent HGG, which may impact the effectiveness of frontline immunotherapies in the GBM management. KEY MESSAGES: Most of the somatic mutations identified in primary HGGs were not detected after relapse. Focal CNAs in EGFR and PTEN genes are inversely correlated in primary and recurrent HGGs. Transcriptomic changes and distinct immune-related signatures characterize HGG recurrence. Recurrent HGGs are characterized by a prominent infiltration of immature dendritic and M2 macrophages.

Can infusion tests be recommended for patients with giant hydrocephalus?

BACKGROUND: The problem of adequate diagnosis of hydrocephalus followed by administration of an effective treatment has not yet been properly solved. Specifically, this pertains to the decision about the surgical insertion of a flow diverting device. AIMS: A lumbar infusion test was used to examine the compensatory parameters of intracranial space in giant hydrocephalus. The early and late results of shunt implantation were analyzed together with complications after surgery. SETTINGS AND DESIGN: In-house software was used offline to adjust the dynamic intracranial pressure (ICP) response to infusion. MATERIALS AND METHODS: Nine patients with giant hydrocephalus were the subjects for the study. We analyzed recordings of the response in ICP to the 2 ml/min infusion of saline. We performed computerized identification of outflow resistance and intracranial compliance based on the truncated (30- 100%) ICP response and assessed the stability of estimates over time. Eight out of nine patients were shunted. Monitoring of patients was followed for a period of up to 9 months. RESULTS: Five out of eight shunted patients improved within a few days of surgery. During follow-up five patients developed various complications. A definite improvement was noted in four patients. The improvement rate did not correlate with any of the compensatory parameters. Most of the patients studied exhibited a lack of intracranial space reserve, a significantly reduced rate of CSF secretion, and a slightly elevated value of outflow resistance. CONCLUSIONS: The infusion test showed itself to be more useful as a way of revealing the compensatory parameters of the intracranial space than as a prognostic tool. The outcome of shunted patients with giant hydrocephalus was uncertain, owing to the relatively high rate of complications. We may therefore suggest that the diagnosis of giant hydrocephalus is a relative contraindication to implantation, as well as to the performance of an infusion test.

Aberrantly Expressed RECQL4 Helicase Supports Proliferation and Drug Resistance of Human Glioma Cells and Glioma Stem Cells.

Anti-tumour therapies eliminate proliferating tumour cells by induction of DNA damage, but genomic aberrations or transcriptional deregulation may limit responses to therapy. Glioblastoma (GBM) is a malignant brain tumour, which recurs inevitably due to chemo- and radio-resistance. Human RecQ helicases participate in DNA repair, responses to DNA damage and replication stress. We explored if a helicase RECQL4 contributes to gliomagenesis and responses to chemotherapy. We found upregulated RECQL4 expression in GBMs associated with poor survival of GBM patients. Increased levels of nuclear and cytosolic RECQL4 proteins were detected in GBMs on tissue arrays and in six glioma cell lines. RECQL4 was detected both in cytoplasm and mitochondria by Western blotting and immunofluorescence. RECQL4 depletion in glioma cells with siRNAs and CRISPR/Cas9 did not affect basal cell viability, slightly impaired DNA replication, but induced profound transcriptomic changes and increased chemosensitivity of glioma cells. Sphere cultures originated from RECQL4-depleted cells had reduced sphere forming capacity, stronger responded to temozolomide upregulating cell cycle inhibitors and pro-apoptotic proteins. RECQL4 deficiency affected mitochondrial network and reduced mitochondrial membrane polarization in LN18 glioblastoma cells. We demonstrate that targeting RECQL4 overexpressed in glioblastoma could be a new strategy to sensitize glioma cells to chemotherapeutics.

Compensatory parameters of intracranial space in giant hydrocephalus.

BACKGROUND AND PURPOSE: The main goal of the present study is to examine compensatory parameters of intracranial space in giant hydrocephalus. We also assess the early and late outcome and analyse complications in shunted cases. MATERIAL AND METHODS: Nine cases of giant hydrocephalus characterised by the value of Evans ratio > 0.5, ventricular index > 1.5, and the width of the third ventricle > 20 mm were considered. Using the lumbar infusion test and developed software we analysed the intracranial compensatory parameters typical for hydrocephalus. Based on the Marmarou model, the method depended on a repeated search for the best fitting curve corresponding to the progress of the test was used. Eight out of nine patients were therefore shunted. Patients were followed up for 9 months. RESULTS: Five out of eight shunted patients undoubtedly improved in a few days after surgery (62%). Complications (subdural hygromas/haematomas and intracerebral haematoma) developed in 5 (62%) cases in longer follow-up. A definite improvement was noted in 4 out of 8 operated cases (50%). CONCLUSIONS: To get the stable values of compensatory parameters, the duration of the infusion test must at least double the inflexion time of the test curve. All but one considered cases of giant hydrocephalus were characterized by lack of intracranial space reserve, significantly reduced rate of CSF secretion and by various degrees of elevated value of the resistance to outflow. Due to the significant number of complications and uncertain long-term improvement, great caution in decision making for shunting has to be taken.

Decreased levels of interleukin-10 and transforming growth factor-beta 2 in cerebrospinal fluid of patients with high grade astrocytoma.

OBJECTIVE: Glioma cells can produce anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) which inhibit T cell and monocyte function. It is unknown if production of these cytokines is limited to the site of tumor or these molecules are also released to cerebrospinal fluid and blood. The goal of our study was to determine if patients with astrocytoma have increased levels of IL-10 and TGF-beta 2 in cerebrospinal fluid (CSF) and serum. METHODS: CSF and serum samples were taken from 16 patients with astrocytoma of grade III or grade IV according to the WHO classification and from 28 age- and gender-matched controls (patients with normal pressure hydrocephalus or with lumbar disk herniation). Cytokine concentrations were measured using ELISA methods. RESULTS AND DISCUSSION: There was no difference in serum levels of IL-10 and TGF-beta 2 between groups. Patients with astrocytoma had decreased levels of IL-10 (0.9 +/- 1.2 versus 3.5 +/- 9.2 pg/ml, p=0.01) and TGF-beta 2 (0.0 +/- 0.0 versus 5.4 +/- 9.4 pg/ml, p=0.05) in CSF compared to controls. Because serum IL-10 and TGF-beta 2 levels are similar in patients with astrocytoma and in controls, these cytokines are probably not directly involved in peripheral monocyte and T cell deactivation.

Effect of Social Factors on Surgical Outcomes in Cervical Disc Disease.

BACKGROUND: Daily clinical practice shows us how diametrically different surgical outcomes can occur in particular groups of patients sharing the same diagnosis and being subjected to the same treatment. Patient-reported outcomes appear to be significantly influenced by social factors and patients' emotional status. Data on such variables were collated and analyzed statistically with the aim of confirming our clinical observations. METHODS: We analyzed a group of 100 patients following cervical disc surgery. The clinical evaluation was based on a visual analog scale (VAS) for pain and the neck disability index (NDI). Non-clinical data comprised education status, employment status, body mass index (BMI), and history of depressive episodes in the period immediately preceding the surgery, which was investigated using the Beck Depression Inventory (BDI). RESULTS: Patients who had completed university or secondary school education had a significantly lower BMI and lower BDI scores and they reported less pain at 12 months postoperatively than patients with vocational or elementary school education only. Patients who were employed at the time of the study or were retired demonstrated significantly lower NDI scores both before the surgery and at 12 months postoperatively, as well as lower BDI scores compared to those who were unemployed or drew disability pensions. Factors such as age or BMI score did not exert a direct effect on treatment outcomes assessed as changes in the VAS and NDI scores. CONCLUSIONS: Surgical treatment for the cervical disc disease decreases pain and improves patients' quality of life. Treatment outcomes are also influenced by social factors and patients' emotional status.

Analysis of changes in cervical spinal curvature and intervertebral disk space height following ACDF surgery in a group of 100 patients followed up for 12 months.

We analysed 100 patients following anterior cervical discectomy and fusion with interbody stabilisation with PEEK cages. Radiographs obtained preoperatively and during the 12-month follow-up were compared to track changes in overall and local cervical lordosis and disk space height. Subsidence was defined as cage migration ≥ 3 mm into the adjacent endplates. Mean change in operated disk space height was 1.13 ±â€¯1.33 mm. Subsidence was detected in 10.23% of the operated spaces. Mean change in overall cervical lordosis was 1.31 ±â€¯5.71 degrees, and mean change in local lordosis was 0.19 ±â€¯4.71 degrees. Change in overall cervical lordosis correlated with change in local lordosis (r = 0.61, p < 0.01). The greatest changes in lordosis and disk space height were noted immediately post-surgery. Baseline values were approximated gradually over time, but the post-operative values at 12 months were still higher than baseline. Disk space height change did not correlate with changes in patient-reported pain intensity at baseline (VAS 0) vs. at 12 months post-operatively (VAS 12) (r = 0.12, p < 0.05) or changes in the Neck Disability Index (NDI) at baseline (NDI 0) vs. at 12 months post-operatively (NDI 12) (r = -0.02, p = 0.05). Changes in overall cervical lordosis did not directly influence treatment outcomes assessed by comparing VAS 0 vs. VAS 12 (r = 0.13, p = 0.24) or NDI 0 vs. NDI 12 (r = -0.0005, p = 0.96). Surgical outcomes depend primarily on adequate decompression of the spinal cord and nerve roots. Post-operative radiological changes did not directly influence patients' pain level or quality of life.

Assessment of the haemostatic system in patients surgically treated for ruptured cerebral aneurysm.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate selected markers of thrombin generation and subsequent fibrinolysis in patients with aneurysmal subarachnoid haemorrhage (SAH) and to assess the relationship between thrombin generation/fibrinolysis and clinical course and outcome. MATERIAL AND METHODS: This prospective study included 72 patients after aneurysmal SAH who underwent surgery within 72 hours after onset of symptoms. The results were compared with 84 control patients without SAH. Selected markers of thrombin generation (thrombin-antithrombin complexes, TAT), fibrinolysis (D-dimer) and fibrinogen level were examined in blood just after admission and on day 7 after surgery. The relationship between levels of those markers and selected clinical and radiological data, and outcome at 3-6 months after surgery, were assessed. RESULTS: On admission, patients with SAH had higher levels of TAT (p<0.001), D-dimer (p=0.048), and fibrinogen than the control group (p<0.001). Also, patients with severe bleeding demonstrated higher TAT (p<0.001) and D-dimer (p=0.04) levels. The admission level of TAT (higher than 24 g/l; odds ratio = 10.8) and the elevated blood fibrinogen level (odds ratio = 1.2) showed a strong correlation with mortality. Furthermore, a level of TAT higher than 24 g/l (odds ratio = 9.98) and the level of fibrinogen (odds ratio = 1.3) strongly correlated with poor outcome. There was no significant correlation between markers of coagulation on the 7th day after surgery for SAH and the outcome. CONCLUSIONS: Activation of blood coagulation as well as the fibrinolytic system occurred early in the course of SAH. Such activation was associated with poor clinical status of patients on admission, greater amount of subarachnoid blood, and poor clinical outcome. Thus, blood levels of TAT and fibrinogen are independent factors associated with mortality and morbidity after aneurysmal SAH.

Comments on 'Analysis of intracranial pressure during and after the infusion test in patients with communicating hydrocephalus'.

We comment on the paper by Juniewicz et al (2005 Physiol. Meas. 26 1039-48) which addresses problems in application of the Marmarou model for analyzing intracranial pressure changes during and after the infusion test, as well as the clinical relevance of the additional parameters obtained during prolonged infusion.

[Results of neuroendoscopic treatment of arachnoid cysts in adults]. / Wyniki leczenia torbieli pajeczynówki u doroslych przy zastosowaniu techniki endoskopowej.

BACKGROUND AND PURPOSE: Most arachnoid cysts (ACs) are asymptomatic, but some of them cause mass effect, mainly in adults. Surgery of ACs is controversial, especially regarding the choice of the best method of treatment. The authors present short- and long-term outcome of endoscopic surgery of ACs. MATERIALS AND METHODS: There were 19 adults with symptomatic ACs treated surgically in the last 6 years. 16 cysts were located supratentorially, and 3 infratentorially. Cystocisternostomy was carried out in 7 patients, cystocisternostomy with catheter implantation was performed in 5 patients, cystoventriculostomy in 3 patients, and cystoventriculostomy with catheter implantation was carried out in 2 patients. In one case additional endoscopy combined with shunt was necessary, and in another one endoscopy converted to microsurgery. Outcome was assessed by means of neurological examination and computed tomography (CT). RESULTS: During the short-term follow-up, 11 (57.9%) cases improved neurologically, and in 6 (33.0%) ACs were significantly smaller in CT. During the long-term follow-up, 14 (73.7%) patients improved significantly, and the size of ACs was reduced in 16 (84.2%). In two cases subdural haematoma was observed. CONCLUSIONS: Outcome after endoscopic surgery of ACs in adults is good, and the complication rate is low. Endoscopy should be recommended as the treatment of choice in patients suffering from ACs.

[Diagnosis and operative treatment cavernous angiomas of the central nervous system]. / Diagnostyka i leczenie operacyjne naczyniaków jamistych osrodkowego ukladu nerwowego.

UNLABELLED: Among all detected cerebral angiomas the frequency of cavernous angiomas (CAs) is 5-13%. The aim of this study is to present the diagnostic methods of CA of the central nervous system (CNS), indications for surgery and assessment of its outcome. Between 1993-2000, eleven cases of CAs were operated on at the Department of Neurosurgery, Medical College, Jagiellonian University in Krakow. In 6--seizures were observed, in 4--headache (supratentorial CAs), increasing neurological deficits in 4 (location in vertebral channel and cerebellum), hemorrhage--1 case (CA in pons combined with supratentorial lesion). Surgery was carried out by means of craniotomy, and via laminectomy in the cases of spinal channel tumours. Early and late outcome were assessed in following cathegories: very good, good, fair, bad (significant deterioration). The shortest late observation was 5 years. Direct very good surgical outcome was attained in 4 cases (36%), good in 4. (36%), fair in 2. (18%), bad in 1 case. In late observation, 7 patients were very good (64%), and 3 good (27%). In one case the neurological improvement was poor, later observed--late outcome was fair. In 6 cases they suffered from frequent epileptic seizures before surgery; they were seizure free in the late assessment. CONCLUSIONS: (1) direct surgical outcome in CA of the CNS is good and very good in the majority of cases; (2) in late observation, further neurological improvement allows to attain over 90% good and very good outcomes; (3) the high antiepileptic effectiveness after surgery of CA is observed.

[Direct surgical outcome of meningiomas obliterating the superior sagittal sinus]. / Bezposrednie wyniki leczenia operacyjnego oponiaków obliterujacych zatoke strzalkowa górna.

BACKGROUND AND PURPOSE: Aggressive surgery for parasagittal meningiomas is considered when superior sagittal sinus is totally thrombosed by the tumour. However, there is potential risk of venous outflow injury resulting in an intracerebral haemorrhage. The aim of this study is to present surgical technique and early surgical outcome of patients with meningiomas obliterating the superior sagittal sinus. MATERIAL AND METHODS: Ten patients (4 men and 6 women, mean age 58), operated for sagittal meningiomas with radiologically proved superior sagittal sinus obliteration, were analysed retrospectively. In all cases, radical surgery with the resection of invaded sagittal sinus was performed. The size of tumours varied between 35 and 100 mm; the mean was 53 mm. Five of them required reoperation because of tumour recurrence due to a previous incomplete resection. In five cases, bifrontal craniotomy was made, in four biparietal and in one parieto-occipital. Preoperative status and direct postoperative outcome were compared using the Karnofsky scale. RESULTS: Very good outcome was achieved in 6 cases--the clinical status remained unchanged. In two, the outcome was good (in the first patient hemiparesis increased and in the second there was worsening of cortical visual disturbances). In two cases with an unfavorable outcome, one patient suffered quadriparesis and mutism; the other experienced cerebral edema with hemorrhagic infarct and died despite decompressive surgery. Both these patients were totally dependent before surgery (Karnofsky < 40). CONCLUSIONS: In the radical resection of a tumour with occluded sinus, direct postoperative outcome ranges from good to very good in a significant number of cases. In dependent patients having a large tumour, there is the risk of an unfavourable outcome after radical surgery. In such cases, partial resection and further radiotherapy should be considered.

[A case of GH and TSH secreting pituitary macroadenoma]. / Przypadek makrogruczolaka przysadki wydzielacego hormon wzrostu i tyreotropin.

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

[The use of TachoComb for the rhinorrhea repair in pituitary transsphenoidal surgery]. / Zastosowanie siateczki TachoComb w zaopatrywaniu plynotoku nosowego w operacjach przysadki droa przezklinowa.

UNLABELLED: The transsphenoidal pituitary tumors surgery is often connected with intraoperative rhinorrhea. This complication might be serious if occurs again in the postoperative period. The aim of this study is to evaluate the sella reconstruction methods in patients with intraoperative rhinorrhea and comparing of their efficiency. MATERIAL AND METHODS: In the group of 259 consecutive cases operated on at the Neurosurgery Department in Cracow using the transsphenoidal approach, in 40 occured intraoperatively observed rhinorrhea. In the 26 cases we used Surgicel, artificial dura or fascia and Tissucol (I group), and in 14 TachoComb with Tissucol but in 5 also fascia or artificial dura (II group). RESULTS: Out of the 26 patients from the I group (without TachoComb) in 5 cases occurred postoperatively rhinorrhea (3-36 days after surgery). 4 patients were reoperated, 1 patient died due to the meningitis. 2 patients suffered from the visual disturbances due to the sella overpacking (7,7%), what was visualized in the control imaging studies. In 14 cases from the II group in 2 postoperative rhinorrhea was observed (in the 7 and the 30 day after operation)--14,2%. There were no signs of meningitis, and no fatal cases. The visual disturbances as well as overpacking of the sella were not observed. CONCLUSIONS: Using of the TachoComb in reconstructive surgery of the sella reduces the risk of the post operative CSF leak and eliminates the features of the sella overpacking and visual deterioration.

Thoracic Nerve Root Schwannoma Filling the Spinal Canal Almost Entirely Without any Neurological Deficits.

INTRODUCTION: Spinal tumours may be classified in three groups: 1) extradural, 2) intradural extramedullary and 3) intramedullary spinal cord tumours. Intradural extramedullary tumours arise from the leptomeninges or nerve roots and include schwannomas. A schwannoma is usually a firm grey-whitish tumour growing near a nerve trunk or ramus. It can be separated from the nerve without damaging neural tissue. Schwannomas are usually solitary tumours. CASE PRESENTATION: We present the case of a 37-year-old male who underwent surgery for a tumour in the upper thoracic segment of the spinal canal. Although the tumour filled the spinal canal almost entirely, the patient did not manifest any neurological deficits. During the surgery, the tumour was removed completely. A histological examination confirmed a benign schwannoma lesion (WHO G1). CONCLUSIONS: The question whether doctors are keen to order more diagnostic investigations (including both laboratory and imaging studies) than are necessary is often asked in clinical practice. The cost factor is also important. Not every patient with back pain is referred for an MRI study in the absence of characteristic neurological signs. The case of our patient, however, speaks in favour of early referral for such diagnostic modalities. Appropriate imaging studies, even in patients presenting with no neurological deficits, may help detect pathologies than can lead to severe disability. A spinal canal tumour filling the spinal canal almost entirely and displacing the spinal cord could cause spinal cord damage at any time with all the dire consequences such as paraplegia and loss of the ability to walk.