Paradoxical results obtained with Ki67-labeling and PHH3-mitosis index in glial tumors: a literature analysis.

Precise tiered tumor grading is essential for predicting prognosis, selecting different treatment options and for follow-up of brain tumor patients. Ki67 labeling index (LI) is widely employed in assessing aggressiveness of glial brain tumors. However, Ki67 is subject to interlaboratory variability, and its antigen is expressed on all cell cycle phases except G0, which hinders its usage as a precise criterion for assessing cell proliferation. Indeed, there exist peculiar observations pertinent to increases of Ki67 index in glial tumors following radiotherapy or treatment with tyrosine kinase inhibitors. Moreover, we have witnessed a reduced Ki67 labeling in a gemistocytic glioma during its rapid recurrence under temozolomide treatment. Therefore, we reviewed pitfalls in employing Ki67 indices for predicting glial tumor biology and tried to answer whether the mitotic marker PHH3 (phosphorylated histone H3) could provide additional information in predicting glial tumor biology. PHH3-based assessment of proliferating cell fraction provides novel potentials, but it has also its own weaknesses. It has not yet been determined whether it would be more advantageous to report: a mitotic count (MC) per unit-area (e.g., 10 high power fields (HPF)) or a mitotic index (MI) (per 1,000 tumor cells). Further, there exist peculiarities in terms of unexpectedly low or high PHH3 values in pilocytic astrocytomas and angiocentric gliomas, respectively. Indeed, we encountered almost no staining with PHH3 in our unique gemistocytic astrocytoma case. Hence, at least in some glial malignancies, PHH3 may not be necessary for cell proliferation. Awareness of the weaknesses of proliferation markers in brain tumors may improve patient monitoring and treatment.
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Microsurgical fenestration and cystoperitoneal shunt through preauricular subtemporal keyhole craniotomy for the treatment of symptomatic middle fossa arachnoid cysts in children.

INTRODUCTION: The optimal surgical treatment for symptomatic middle fossa arachnoid cyst is still controversial. The most leading therapeutic options include cyst shunting and fenestration (endoscopic, microsurgical). We present our experience on surgical treatments of arachnoid cysts. PATIENTS AND METHODS: A retrospective data review of 16 children who underwent keyhole craniotomy for microsurgical fenestration and shunting of middle fossa arachnoid cysts between 1999 and 2012 was performed after institutional review board approval. The average patient age was 6.1 years. The average follow-up period was 36.5 months. There were ten male and six female patients in the series. Indications for surgery included intractable headaches (50%), increasing in cyst size (18.75%), and seizures (31.25%). All patient records were reviewed for their clinical presentation, classification, cyst resolution, symptom resolution, and cyst outcomes. After surgery, all patients underwent assessments of clinical and radiological improvement. RESULTS: Postoperative complications were observed in two cases: progressively resolving monoparesia in one case and resolving epileptic seizure with monotherapy in the other. All patients had a satisfactory clinical outcome, and in 87.5%, there was either a decrease in the size or a complete disappearance of the MFAC. Nevertheless, three (18.75%) of all patients needed shunt revision because of shunt dysfunction. Complication related to surgical technique was cerebrospinal fluid leak which spontaneously resolved in one patient. CONCLUSION: Microsurgical fenestration with keyhole craniotomy to provide passage between cysts to basal cisterns together with cystoperitoneal shunting during the same operation is still an effective and safe method in cases with symptomatic middle fossa arachnoid cysts in children.

A Simple Technique for Bone Storage after Decompressive Craniectomy in Children.

Cranial vault reconstruction in the pediatric population is a specialized procedure, which requires additional considerations. Generally, inherent difficulties of bone storage and cranioplasty are neglected in the literature. We present a simple method of bone storage and autologous cranioplasty in a small child with severe head injury. The child underwent surgical treatment with decompressive craniectomy. A bone flap was transversally divided into two pieces and stored under the galea. Bone storage and reconstruction of the cranial vault with our surgical technique is a safe, easy and cost-effective choice excluding the surgical trauma to obtain a new subcutanous pocket for bone storage in pediatric decompressive craniectomy patients.

Decompressive craniectomy in traumatic brain injury: Transcranial Doppler sonography used as a guide.

BACKGROUND: Decompressive craniectomy (DC) is performed in the management of intracranial hyper-tension after traumatic brain injury (TBI). This study aims to investigate the effects of transcranial Dop-pler ultrasonography (TCD) measurements on the indication of decompressive surgery. METHODS: Sixteen TBI patients with a Glasgow Coma Score (GCS) <9 were included in this study. Intra-cranial pressure (ICP) monitoring and transcranial Doppler ultrasonography (TCD) measurements were recorded continuously. DC was performed according to the records of ICP and TCD. Glasgow Outcome Scale (GOS) scores were evaluated after three months. RESULTS: Mean age of the patients was 31.18±17.51; GCS ranged between three and 14 with a mean of 9.62±3.95. Mean GOS was 3.12±1.85. Craniectomy was performed in two patients (12.5%) and cra-niectomy and lobectomy together were performed in 14 (87.5%) of them. The decline in ICP (22.12±10.41, 22.62±7.35, 15.50±6.64) and pulsatility index (PI) (1.96±1.10, 1.64±0.75, 1.91±2.48) were strongly significant between days 3-5, and 1-5. The range of PI and Vmax values through five days did not present any significance. CONCLUSION: TCD, as a real-time monitor, may help for an early decision of surgical approach in the management of TBI patients.

Multimodal Intraoperative Neurophysiological Monitoring in Neurosurgical Oncology.

AIM: Neurosurgical oncology that is performed for lesions located in critical areas like the sensorimotor area has additional risk because it may cause serious neurological deficiencies. Some intraoperative neuromonitoring (IONM) modalities can effectively help the surgeons to maximize resections of this kind of lesions with or without an acceptable neurological deficiency. Our aim was to share our IONM experiences with patients who underwent intracranial lesion surgery in critical areas between September 2013 and January 2015. MATERIAL AND METHODS: This retrospective study was performed on 31 patients who underwent brain surgery for the resection of lesions located in eloquent areas. Demographic characteristics, lesion localizations, lesion pathologies, surgery, IONM recordings, and pre- and postoperative neurological examinations were reviewed. RESULTS: Five of the 31 patients had lesions in the cerebellopontine angle and 26 patients had lesions close to critical locations. Transcranial motor evoked potentials and somatosensory evoked potentials were performed in 27, electroencephalography in 31, auditory evoked potentials in 8, visual evoked potentials in 2, triggered electromyography in 8, and central sulcus determination and brain mapping in 17 patients. Motor evoked potential changes occurred in 2 patients intraoperatively. One had right hemiparesia lasting 3 days while the other had monoparesia which improved within 2 months. Permanent neurological deficit was not observed. CONCLUSION: Intraoperative neuromonitoring helps the surgeons to maximize resection of lesions in or close to eloquent areas of the brain. Using only one modality is not sufficient, whereas a combination of modalities is required to obtain a better outcome.

Whorling-sclerosing meningioma. A review on the histological features of a rare tumor including an illustrative case.

Whorling-Sclerosing variant of meningioma (WSM) is a very rare variant of meningioma and only 28 cases were previously reported in the English medical literature. The term "whorling" describes different morphological features including psammoma bodies formed by precipitated calcium or by layered whorling sheets of tumor cells in meningothelial meningiomas. In WSM, the sclerosing structures are formed by typical paucicellular or acellular collagen whorls which form the majority of tumor volume. Hence, diagnosis of these tumors is based more often on morphological and histochemical features rather than on immunohistochemical findings. WSMs often contain cells with both fibroblast-like spindle cell morphology predominantly immunopositive for vimentin and meningoepithelial cells immnunopositive for EMA. The range of their Ki-67 indices differs between 0 and 4 percent. These tumors show no focal pleomorphism, necrosis and high mitotic activity. In some WSMs, entrapped GFAP immunopositive astrocytes may be seen during invasion of the adjacent neural parenchyma. Brain invasion by WSMs may give rise to erroneous diagnoses, i.e. malignant (Grade-3) meningioma, meningiosarcoma, ganglioglioma and even astrocytoma, leading detrimental overtreatment. However; hitherto, no WSM was reported exerting any aggressive behavior. Besides reviewing the literature, we also report a new WSM with abundant uncalcified paucicellular collagen whorls forming aggregates of nodules. Unlike to previous reports, this tumor was costained with p53 and progesterone receptor. The tumor showed no morphological malignancy characteristics, e.g. cellular atypia, prominent nucleoli, hypercellularity, micronecrosis/geographical necrosis, sheeting and small cells. This rare meningioma variant should be kept in mind among differential diagnoses to avoid overtreatment that might endanger patients' outcome.

MGMT gene variants, temozolomide myelotoxicity and glioma risk. A concise literature survey including an illustrative case.

Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment. Results indicated the presence of all the rs2308321 (I143 V), rs2308327 (K178R) and rs12917 (L84F) MGMT-variants, which were previously associated with temozolomide myelotoxicity. rs12917 (L84F) variant was reported as associating with lesser risk of gallbladder tumours, yet with higher risk of non-Hodgkin lymphomas related with exposure to chlorinated solvents or hair dyes. DNA repair proteins may exert diverging effects on DNA injuries caused by different chemicals and therefore exerting complex effects on myelotoxicity, antitumour activity and carcinogenesis.

Management of Failed Cranioplasty.

AIM: Failed cranioplasty attempts may lead to numerous complications in a broad spectrum including cosmetic problems, infection, neurological deterioration and even death. Selection of the most appropriate surgical technique for second and further surgical attempts for these patients still remains a debate. We aimed to share our experience and technical pitfalls on management of failed cranioplasty, particularly for patients with large cranial defects. MATERIAL AND METHODS: A retrospective data analysis of cranioplasty cases in our series was performed including the time period between 2002 and 2012. Patients required recurrent cranioplasty were analyzed in detail. RESULTS: Totally, 101 patients underwent cranioplasty for bony defect. Of 101 patients, eleven required a revision surgery due to infection or spontaneous resorption of the bone flap. All patients underwent revision cranioplasty with pre-surgical plaster cast mold technique modified from previous studies and/or tissue expansion technique. Polymethyl-metacrylate (PMMA) was used as substitute for reconstructions. Mean follow-up was 36 months. Two out of eleven cases (18.1%) developed major complications, which led to further revision. At the end, a satisfactory reconstruction was achieved for all patients. CONCLUSION: Our modified molded plaster cast technique is a safe and cost-effective approach for the revision of failed cranioplasty. We believe that the tissue expanding techniques have also great contribution to achieve successful results.

Relation of apparent diffusion coefficient with Ki-67 proliferation index in meningiomas.

OBJECTIVE: The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and apparent diffusion coefficient (ADC) values of low-grade and atypical/anaplastic (high-grade) meningiomas. METHODS: Pre-operative diffusion-weighted imaging and histopathological evaluation of 44 patients with meningiomas were performed retrospectively. Regions of interest (ROIs) were manually drawn on the ADC images. In total six ROI measurements were taken in three consecutive slices, and the average of the mean ADC value was used. The relationship between the ADC and Ki-67 values was investigated, and the ADC values of the low-grade and high-grade meningiomas were compared. RESULTS: 31 (70%) patients had low-grade the meningiomas. 10 (23%) patients had atypical and 3 (7%) had anaplastic meningiomas. ADC values of the low-grade and high-grade meningiomas were 0.81 ± 0.12 × 10(-3) and 0.66 ± 0.08 × 10(-3) mm(2) s(-1), respectively. Ki-67 proliferation indexes were 2.19% ± 1.14% for low-grade and 11.20% ± 9.80% for high-grade meningiomas. A statistically significant negative correlation between Ki-67 proliferation index and ADC values of the low-grade and high-grade meningiomas was detected (r(2) = 0.326, p < 0.001). High-grade meningiomas had lower ADC values than that of low-grade meningiomas. There was statistically significant difference between the ADC values of the low-grade and high-grade meningiomas (p < 0.001). CONCLUSION: Our data provide an inverse correlation between the ADC and Ki-67 proliferation index values of meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning. ADVANCES IN KNOWLEDGE: The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and ADC values of low-grade and atypical/anaplastic (high-grade) meningiomas. In addition, we compared the ADC and Ki-67 proliferative index values of the low-grade and atypical/anaplastic (high-grade) meningiomas. We concluded that there was an inverse correlation between the ADC and Ki-67 proliferation index values in meningiomas, and we have found statistically significant difference between the ADC values of the low-grade and high-grade meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning.

Spinal intradural hematoma and permanent paraparesis after a lumboperitoneal shunt operation: an unusual complication.

Pseudotumor cerebri is a condition of increased intracranial pressure in the absence of clinical, laboratory or radiological pathology. Spinal intradural hematoma formation after lumboperitoneal shunt (LPS) implantation is very rare, but it can cause sudden and serious deterioration. In this report, we present a patient who developed an intradural hematoma following LPS operation. A 27-year-old male patient suffering from headaches and progressive vision loss was diagnosed with pseudotumor cerebri. He underwent LPS operation in January 2009. Four hours after the operation, he developed urinary and fecal incontinence with paraparesis (1/5). Lumbar magnetic resonance imaging identified an intradural hematoma at the level of L2-L3, and he was reoperated. The intradural hematoma was removed. Physical therapy was started because of paraparesis. Two months later, the patient's muscle strength had increased to 3/5. Surgeons must remember that, LPS implantation can cause a spinal intradural hematoma in a small percentage of patients, with catastrophic results.