Wojciech Kloc

Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array.

Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.

Validation and cross-cultural adaptation of the Polish version of the Oswestry Disability Index.

Study Design. Validation of a translated, culturally adapted questionnaire. Objective. To translate and culturally adapt a Polish version of the Oswestry Disability Index (ODI) and to validate its use in Polish patients. Summary of Background Data. The ODI is among the most popular questionnaires used to evaluate back pain–related disability. To our knowledge no validated Polish version of the index was available at the time our study was initiated. Methods. The questionnaire was translated and culturally adapted by 2 independent translators and approved by expert committee. Final version was included in the booklet consisting in addition of a previously validated Roland–Morris disability questionnaire, VAS for low back and leg and 3 Likert scale questions (pain medications, pain frequency, disability). It was tested on 169 patients with chronic low back pain, 164 (97%) of them were enrolled, and 84 of 164 (53%) returned the completed retest booklet within 2 to 14 days after the baseline test. There were no differences between the 2 groups in demographic and clinical parameters. Test-retest reliability, internal consistency, and construct validity were investigated. Results. The mean ODI (standard deviation [SD]) was 48.45 (18.94); minimum 2, maximum 94. The Cronbach &agr; for baseline questionnaires (n = 164) was 0.90. Concurrent validity, measured by comparing ODI responses with the results of the Roland–Morris disability questionnaire score was very good (r = 0.607, P < 0.001). The correlation with VAS back was fair (r = 0.37, P < 0.001) and with VAS leg was good (r = 0.56, P < 0.001). The tested ODI had excellent test-retest reliability, the intraclass correlation coefficient was 0.97 and standard error of measurements was 3.54, the resulting minimal detectable changes at the 95% confidence level was 10. Conclusion. The results of this study indicate that the Polish version of the ODI is a reliable and valid instrument for the measurement of disability in Polish-speaking patients with lower back pain.

Direct Vertebral Rotation Versus Single Concave Rod Rotation: Low-dose Intraoperative Computed Tomography Evaluation of Spine Derotation in Adolescent Idiopathic Scoliosis Surgery.

Study Design. A comparative clinical study of two main corrective manoeuvres in scoliosis surgery. Objective. To compare the effectiveness of two main corrective manoeuvres: single concave rod rotation (SCRR) and direct vertebral rotation (DVR) in regard to apical vertebral rotation (AVR) and rib hump correction in adolescent idiopathic scoliosis (AIS) surgery. Summary of Background Data. It remains unclear whether SCRR manoeuvre alone causes apical vertebral derotation (AVD) and rib hump correction. Although the influence of DVR on AVD and rib hump change has been described, it has been evaluated mainly with indirect methods. This is the first study to evaluate separately the derotational effectiveness of these two manoeuvres during the low-dose intraoperative computed tomography (ICT). Methods. A study group consisted of 38 AIS patients treated by posterior scoliosis surgery (PSS) with all pedicle screw constructs. All examined patients had dow-dose ICT evaluation (before correction, after SCRR, and after DVR). Results. We found SCRR ineffective – mean postcorrectional AVR increased insignificantly 1.5° (16.1% worsening) P = 0.170. On the contrary, an average postcorrectional AVR after DVR decreased significantly mean 3.1° (33.3% improvement) P = 0.049. Precorrectional rib hump angle was 19.3°, after SCRR 15°, and after DVR 12.3°. It was found that despite the lack of true derotation after SCRR there was a significant 22.3% decrease of the rib hump P = 0.043. Although the rib hump decreased significantly 36.3% after DVR as well P = 0.023. There was also significant difference between a rib hump angle after SCRR and DVR (P = 0.049). Conclusion. SCRR does not lead to AVD. The true spinal derotation is possible only when DVR systems are used. The decrease of rib hump is achieved after both SCRR and DVR, but the improvement is significantly better after DVR. Level of evidence: 3

Śluzowiak zatoki czołowej penetrujący do jamy czaszki

We discuss a case of 49-year-old man admitted to our Department with headache and tumor of frontal region since 3 months. We report clinical features and imaging data of mucocele of frontal sinus that penetrates into cranial cavity. The mucocele had damaged anterior and posterior walls of frontal sinus with intracranial penetration. There was intact dura of anterior fosse. External approach with coronal incision was performed, mucocele was evacuated and mucosa was removed. Then frontal sinus was cranialized with reconstruction of anterior wall and finally wide nasal drainage was performed. Intracranial mucocele of the frontal sinus is rere evidence. The key difficulties may be related to dura preservation and reconstruction of anterior wall of frontal sinus.

Reactive astrocytic S1P3 signaling modulates the blood–tumor barrier in brain metastases

Brain metastases are devastating complications of cancer. The blood–brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood–tumor barrier (BTB) when brain metastases form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy by limiting drug uptake. Here, we report that experimental breast cancer brain metastases of low- and high permeability to a dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic sphingosine-1 phosphate receptor 3 (S1P3) is upregulated in the neuroinflammatory response of the highly permeable lesions, and is expressed in patients’ brain metastases. S1P3 inhibition functionally tightens the BTB in vitro and in vivo. S1P3 mediates its effects on BTB permeability through astrocytic secretion of IL-6 and CCL2, which relaxes endothelial cell adhesion. Tumor cell overexpression of S1P3 mimics this pathway, enhancing IL-6 and CCL-2 production and elevating BTB permeability. In conclusion, neuroinflammatory astrocytic S1P3 modulates BTB permeability.When brain metastases form, the blood–brain barrier morphs into the blood–tumor barrier (BTB), surrounded by neuroinflammatory response. Here, the authors show that S1P3 is upregulated in neuroinflammatory response in highly BTB permeable lesions, and modulation of S1P3 could impact BTB permeability.

Malignant Gliomas as Second Neoplasms in Pediatric Cancer Survivors: Neuropathological Study

This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.

Primary Spinal Intradural Mesenchymal Chondrosarcoma with Several Local Regrowths Treated with Osteoplastic Laminotomies: A Case Report

Mesenchymal chondrosarcomas (MCSs) are rare malignant tumors of the bone and soft tissues. Only a few cases of such tumors originating from the spinal canal meninges have been described in the literature. The authors report on a case of a 22-year-old woman with MCS of the arachnoid at the T12-L1 level with a 14-year-long observation. The tumor was totally resected using osteoplastic laminotomy with reconstruction of laminar roof. This small spindle cell tumor was initially microscopically suspected of synovial sarcoma, but correctly verified with widened immunophenotyping and molecular studies as MCS. At its first recurrence, the neoplasm showed microscopically a typical bimorphic pattern of small round cell component with foci of hyaline cartilage. The patient experienced three local recurrences: 4, 6, and 10 years after the initial resection, respectively. The techniques of laminotomy and relaminotomy were also used during three following operations. The repeated surgical removal, radiotherapy, and chemotherapy were the methods of complex oncological treatment. The patient remains now in complete remission, fully self-dependent with slight motor disturbance, and mild sensory deficits. Current views on the clinicopathological characteristics and treatment modalities of the chondrosarcomas of the spinal canal are discussed.

Transient Monoplegia as a Result of Unilateral Femoral Artery Ischemia Detected by Multimodal Intraoperative Neuromonitoring in Posterior Scoliosis Surgery: A Case Report

AbstractThis is to report a case of 16-year-old girl with transient right lower limb monoplegia as a result of femoral artery ischemia detected by multimodal intraoperative spinal cord neuromonitoring (MISNM) during posterior correction surgery of adolescent idiopathic scoliosis.A patient with a marfanoid body habitus and LENKE IA type scoliosis with the right thoracic curve of 48° of Cobb angle was admitted for posterior spinal fusion from Th6 to L2. After selective pedicle screws instrumentation and corrective maneuvers motor evoked potentials (MEP) began to decrease with no concomitant changes in somato-sensory evoked potentials recordings.The instrumentation was released first partially than completely with rod removal but the patient demonstrated constantly increasing serious neurological motor deficit of the whole right lower limb. Every technical cause of the MEP changes was eliminated and during the wake-up test the right foot was found to be pale and cold with no popliteal and dorsalis pedis pulses palpable. The patient was repositioned and the pelvic pad was placed more cranially. Instantly, the pulse and color returned to the patients foot. Following MEP recordings showed gradual return of motor function up to the baseline at the end of the surgery, whereas somato-sensory evoked potentials were within normal range through the whole procedure.This case emphasizes the importance of the proper pelvic pad positioning during the complex spine surgeries performed in prone position of the patient. A few cases of neurological complications have been described which were the result of vascular occlusion after prolonged pressure in the inguinal area during posterior scoliosis surgery when the patient was in prone position. If incorrectly interpreted, they would have a significant impact on the course of scoliosis surgery.

EPIDERMOID CYST OF THE CRANIOVERTEBRAL JUNCTION - A CASE REPORT

Abstract Introduction An epidermoid cyst (EC) is a congenital, benign, and nonifiltrating tumor which originates from the central nervous system (CNS) as a result of neural tube defects (NTD). The presence of lesion may cause CNS symptoms by means of mass-effect, when compressing the adjacent structures, or rupture and secondary aseptic inflammatory process. Within the CNS, EC is most frequently located in: pontocerebellar angle, suprasellar region, posterior cranial cavity, and spinal canal. The clinical symptoms can be general, like headache or dependent on the lesion location: dizziness, nystagmus, damage to the cranial nerves within the pontocerebellar angle and brain stem, disturbed fields of vision, and epileptic seizures. Magnetic resonance imaging (MRI) allows for visualizing the lesion which is shown as a heterogenic iso- or hypointense mass in relation to the cerebrospinal fluid. Using diffusion weighted images (DWI) is a helpful tool in differentiating tumor mass from cerebrospinal fluid. In computed tomography (CT) scans, EC has the same or almost the same density as the cerebrospinal fluid which makes the image difficult to differentiate from an arachnoid cyst. Treatment of choice is to remove the lesion in a possibly complete spectrum. In asymptomatic patients or patients exhibiting a mild intensity of symp, it is possible to wait and observe which solution could be chosen. Aim The aim of this paper was to present a case report concerning treatment of an EC located in the craniovertebral junction. Materials and Methods A clinical management concerning a patient diagnosed and treated both in an outpatient clinic and in hospital at the departments of neurology and neurosurgery has been described. Case study A 69-year old female patient came to the Neurology Outpatient Clinic complaining of headaches, pain in her neck, and balance disturbances. These symptoms had intensified for 2 years. An MRI scan of the cervical spine revealed a large lesion in the posterior cranial cavity. An MRI scan of the head showed a multicystic tumor located in the posterior fossa in the projection of cerebellomedullary cistern, which did not undergo contrast intensification. The patient was treated surgically. Following surgery, headaches, pain in the neck as well as neurological symptoms subsided. Results and discussion Microsurgical removal of the lesion is the treatment of choice for EC. A total removal should be strived for, preferably en block, although leaving part of the cyst is not a mistake. Postoperative mortality may reach 8.9%, whereas recurrences amount to 4.5% during an 8-year long observation period. EC untreated surgically can, through dermal fistulas, cause bacterial meningitis. Thus, treatment limited to the observation of the lesions may pose a threat, and surgical treatment should be decided upon quickly. Conclusions Surgical treatment with the use of microscopic technique aided with neuromonitoring allows for removing tumors of the cholesteatoma type safely and radically.