Characterization of perioperative glycemic status and dexamethasone use with associated postoperative complications in glioblastoma patients.

PURPOSE: Postoperative morbidity in glioblastoma (GBM) patients can be due to the disease course but can also come from postoperative complications. Our objective was to study the association of dexamethasone use and perioperative hyperglycemia with postoperative complications in GBM patients. METHODS: A single-center, retrospective cohort study was conducted in patients who underwent surgery for primary GBM from 2014-2018. Patients with perioperative fasting blood glucose (FBG) measurements and adequate follow-up to assess for complications were included. RESULTS: A total of 199 patients were included. More than half (53%) had poor perioperative glycemic control (FBG ≥ 7 mM for ≥ 20% perioperative days). Higher dexamethasone dose (≥ 8 mg) was associated with higher FBG on postoperative days 2-4 and 5 (p = 0.02,0.05,0.004,0.02, respectively). Poor glycemic control was associated with increased odds of 30-day any complication and 30-day infection on univariate analysis (UVA), and 30-day any complication and increased length of stay (LOS) on multivariate analysis (MVA). Higher average perioperative daily dexamethasone dose was associated with increased odds of 30-day any complication and 30-day infection on MVA. Elevated hemoglobin A1c (HgbA1c, ≥ 6.5%) was associated with increased odds of 30-day any complication, 30-day infection, and LOS on UVA. In a multivariate linear regression model, only the diagnosis of diabetes mellitus predicted perioperative hyperglycemia. CONCLUSIONS: Perioperative hyperglycemia, higher average dexamethasone use and elevated preoperative HgbA1c are associated with increased risk of postoperative complications in GBM patients. Avoiding hyperglycemia and limiting dexamethasone use in postoperative period may decrease the risk of complications. Select HgbA1c screening may allow the identification of a group of patients at higher risk of complications.

The role of bevacizumab in the treatment of glioblastoma.

Bevacizumab has been used in patients with GBM as a salvage therapy since its approval in the United States for recurrent GBM in 2009. In order to review the therapeutic effect of bevacizumab in the primary and recurrent clinical setting we have performed a systematic analysis of data from the published literature. Weighted median progression free survival and overall survival were calculated and compared to standard therapy or other experimental therapies. A qualitative analysis of the limited studies on health related quality of life and effects on steroid requirements was also undertaken. We found that the available literature supports the use of bevacizumab for prolonging PFS and OS in the recurrent setting either alone or in combination with a cytotoxic agent (P < 0.05), but does not support its use in the primary setting (P > 0.05). The survival advantage of bevacizumab compared to experimental therapy at recurrence is limited to 4 months. There is no additional benefit reported to date in health-related quality of life with the use of bevacizumab, although it may reduce steroid requirements. On average there is one side-effect event per patient and 74% of these events are grade 3 toxicity or higher. Further studies investigating the role of bevacizumab in combination with cytotoxic agents at recurrence are awaited.

Endoscopic third ventriculostomy for hydrocephalus due to tectal glioma.

BACKGROUND: Tectal gliomas commonly present with hydrocephalus from obstruction of the aqueduct of Sylvius. The creation of a ventriculostomy in the floor of the third ventricle (ETV) has been previously reported to by-pass aqueduct obstruction. The goal of this study was to determine the safety and efficacy of ETV in the presence of an obstructing tectal glioma. METHODS: We retrospectively reviewed the clinical presentation, management, and clinical outcome after ETV in patients diagnosed with tectal glioma and obstructive hydrocephalus in our institution over a period of 15 years. Shunt freedom at follow-up was the main outcome variable. Long-term clinical outcome was assessed at the most recent clinic visit. Clinical outcome was ranked as excellent, good, or poor according to resolution of symptoms and patient functional status. RESULTS: The median age at presentation was 16.5 years (range: 6.4 to 59 years) and the most common presenting symptom was headache. Eleven patients had ETV as a primary procedure and three patients underwent ETV as a substitute for shunt revision at the time of shunt failure. At follow-up (median 3.9 years, range: 2.2 to 7 years) 13 of 14 patients remain shunt independent with excellent (n=9) or good outcomes (n=5). CONCLUSIONS: In patients with tectal glioma causing obstructive hydrocephalus, ETV can be performed safely in the primary setting or as a substitute for shunt revision. A high rate of shunt freedom (78%-100%) at prolonged follow-up can be expected in this patient population.

Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: potential for targeting experimental brain tumors.

Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50nm or 120nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. FROM THE CLINICAL EDITOR: This study demonstrates the use of magnetic resonance image-guided transcranial focused ultrasound to open the BBB and enable spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS)-based molecular imaging for experimental tumor tracking.

The Role of Nursing Care in the Management of External Ventricular Drains on the Neurosurgical Ward: A Quality Improvement Project.

OBJECTIVE: The management of external ventricular drains (EVDs) is a critical aspect of patient care in the intensive care setting. However, nurses on the general floor are not commonly exposed to patients with EVD and therefore lack the necessary knowledge and skills to manage and troubleshoot EVDs effectively. The aim of this study was to evaluate the level of knowledge, comfort, and impact of EVD management among nurses on the floor after the implementation of a quality improvement (QI) tool. METHODS: This is a cross-sectional study conducted among registered nurses working on the neurosurgical floors of the Montreal Neurological Hospital. Data were collected using a questionnaire based on the plan-do-study-act model. A survey assessing the level of knowledge and comfort with EVD management was conducted before and after the implementation of the QI tool. RESULTS: Seventy-six nurses completed the questionnaire regarding their knowledge and comfort level in EVD management. Results showed that only 42% of the nurses reported feeling "comfortable" whereas 37% reported feeling "uncomfortable" in caring for patients with an EVD. In addition, only 6.5% reported being "comfortable" in troubleshooting a malfunctioning EVD. However, the level of comfort significantly improved after using the QI project. CONCLUSIONS: The results of this study highlight the need for continued training and education to support the care of patients with EVDs in the ward setting. The implementation of a QI tool can significantly improve nurses' knowledge and comfort level in EVD management, leading to improved patient outcomes and overall quality of care.

Aurora kinase B/C inhibition impairs malignant glioma growth in vivo.

Inhibition of Aurora kinase B has been evaluated as a therapy to block solid tumor growth in breast cancer, hepatocellular carcinoma, lung adenocarcinoma, and colorectal cancer models. Aurora kinase inhibitors are in early clinical trials for the treatment of leukemia. We hypothesized that Aurora B inhibition would reduce malignant glioma cell viability and result in impaired tumor growth in vivo. Aurora B expression is greater in cultured malignant glioma U251 cells compared to proliferating normal human astrocytes, and expression is maintained in U251 flank xenografts. Aurora B inhibition with AZD1152-HQPA blocked cell division in four different p53-mutant glioma cell lines (U251, T98G, U373, and U118). AZD1152-HQPA also inhibited Aurora C activation loop threonine autophosphorylation at the effective antiproliferative concentrations in vitro. Reduction in cell viability of U251 (p53(R273H)) cells was secondary to cytokinesis blockade and apoptosis induction following endoreplication. AZD1152-HQPA inhibited the growth of U251 tumor xenografts and resulted in an increase in tumor cell apoptosis both in vitro and in vivo. Subcutaneous administration of AZD1152-HQPA (25 mg/kg/day × 4 days; 2 cycles spaced 7 days apart) resulted in a prolongation in median survival after intracranial inoculation of U251 cells in mice (P = 0.025). This is the first demonstration that an Aurora kinase inhibitor can inhibit malignant glioma growth in vivo at drug doses that are clinically relevant.

Ventriculoatrial Shunts: Review of Technical Aspects and Complications.

Diversion of cerebrospinal fluid is required in many neurosurgical conditions. When a standard ventriculoperitoneal shunt and endoscopic third ventriculostomy are not appropriate options, placement of a ventriculoatrial shunt is a safe, relatively familiar second-line shunting procedure. Herein we reviewed the technical aspects of ventriculoatrial shunt placement using an illustrative case. We focused on the different modalities for inserting and confirming the location of the distal catheter tip. We discussed how to overcome typical difficulties and significant concerns, such as cardiac arrhythmias and venous thrombosis. In addition, we reviewed the current literature for the different complications associated with ventriculoatrial shunt placement.

The biological basis for modern treatment of chordoma.

Chordomas are rare malignant tumors arising in bone of the spheno-occiput, sacrum, and vertebral column which can cause neurological deficit. Current management of chordoma involves safe resection followed by radiation therapy. However, surgical resection is often subtotal and chordoma often recurs despite optimal therapy. Despite years of effort, effective adjuvant therapy for denovo, recurrent and metastatic chordoma are absent and 5-year survival is at best 65%. While no chemotherapeutic agent has been demonstrated to be effective against chordoma in vivo, a greater understanding of the genetics and molecular biology of chordoma is opening up avenues of investigation towards the rational development of targeted therapies. Although enthusiasm for the use of already established or new investigational agents will increase with greater understanding of chordoma biology, laboratory studies of these agents are important prior to incorporation into clinical human trials. The authors review the current state of knowledge regarding chordoma and offer insight into potential new therapies for this rare and challenging tumor.

Clinical outcomes after endovascular coiling in high-grade aneurysmal hemorrhage.

OBJECT: Our experience in Calgary was reviewed to determine the safety and clinical effectiveness of coiling in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH). METHODS: Patients with Hunt-Hess grades IV and V aneurysmal subarachnoid hemorrhage who underwent endovascular coiling between January 1999 and April 2009 at Foothills Medical Centre, Calgary, Alberta, Canada were reviewed. The primary outcome measure was the Modified Rankin Score after at least six months. Secondary outcome measures included extent of aneurysm occlusion and peri-procedural complications. In patients with favourable functional outcomes, Barthel's Index (BI), Re-integration to normal living index (RINL), and Zung depression scale (ZDS) were determined. RESULTS: Thirty-three patients were identified (median age of 57 years; 73% female) and 69% were Hunt-Hess grade IV subarachnoid hemorrhage and 22 % were grade V. Endovascular coiling resulted in absence of residual flow into the aneurysm fundus in 91%. Only seven procedure-related complications occurred with no deaths attributed to the procedure. Vasospasm, hydrocephalus, and pneumonia were the most common non-procedural complications. Average follow-up was 27 +/- 17 months. Overall mortality was 32%, but 53% of patients had good functional outcome (mRS<3). Nine patients completed the BI, RINL, and ZDS with average BI 99 +/- 2, RINL 89 +/- 14, ZDS 33 +/- 11, suggesting minimal deficits in function and mood. CONCLUSIONS: Endovascular coiling in patients with high-grade subarachnoid hemorrhage is safe. While the morbidity and mortality from high-grade aneurysmal subarachnoid hemorrhage remains significant, favourable radiologic and functional outcomes can be achieved in a significant proportion of these critically ill patients.

Expression of cell type incongruent alpha-cardiac actin 1 subunit in medulloblastoma reveals a novel mechanism for cancer cell survival and control of migration.

BACKGROUND: Alterations in actin subunit expression have been reported in multiple cancers, but have not been investigated previously in medulloblastoma. METHODS: Bioinformatic analysis of multiple medulloblastoma tumor databases was performed to profile ACTC1 mRNA levels. Western blot was used to verify protein expression in established medulloblastoma cell lines. Immunofluorescence microscopy was performed to assess ACTC1 localization. Stable cell lines with ACTC1 overexpression were generated and shRNA knockdown of ACTC1 was accomplished. We used PARP1 cleavage by Western blot as a marker of apoptosis and cell survival was determined by FACS viability assay and colony formation. Cell migration with overexpression or knockdown of ACTC1 was determined by the scratch assay. Stress fiber length distribution was assessed by fluorescence microscopy. RESULTS: ACTC1 mRNA expression is highest in SHH and WNT medulloblastoma among all subgroups. ACTC1 protein was confirmed by Western blot in SHH subgroup and Group 3 subgroup cell lines with the lowest expression in Group 3 cells. Microscopy demonstrated ACTC1 co-localization with F-actin. Overexpression of ACTC1 in Group 3 cells abolished the apoptotic response to Aurora kinase B inhibition. Knockdown of ACTC1 in SHH cells and in Myc overexpressing SHH cells induced apoptosis, impaired colony formation, and inhibited migration. Changes in stress fiber length distribution in medulloblastoma cells are induced by alterations in ACTC1 abundance. CONCLUSIONS: Alpha-cardiac actin (ACTC1) is expressed in SHH medulloblastoma. Expression of this protein in medulloblastoma modifies stress fiber composition and functions in promoting resistance to apoptosis induced by mitotic inhibition, enhancing cell survival, and controlling migration.

Surgical Management of Isolated Fourth Ventricular Hydrocephalus Associated with Injury to the Guillain-Mollaret Triangle.

BACKGROUND: The occurrence of isolated fourth ventricle and injury to the Guillain-Mollaret triangle in the setting of posterior fossa ependymoma represents a new association. In this case report, we discuss the clinical, theoretical, and therapeutic aspects of this problem. We describe a lateral transcerebellar trajectory and shunt valve configuration for safe fourth ventricle shunting in a patient with prior posterior fossa surgery. CASE DESCRIPTION: A 45-year-old woman underwent subtotal resection of a fourth ventricle ependymoma (World Health Organization grade III) followed by radiation therapy to control the residual tumor. Her course was complicated by a cerebral abscess and subsequent communicating hydrocephalus, for which she received a lateral ventriculoperitoneal shunt. After placement of the lateral ventricle shunt, there was a progressive increase in the volume of the fourth ventricle over the next 2 years, from 2.5 to 12.0 mL. She developed palatal myoclonus, hand incoordination, bilateral foot numbness, and progressive ataxia. Neuroimaging also revealed hypertrophic degeneration of the inferior olivary nuclei bilaterally. The isolated fourth ventricle was treated by a separate fourth ventriculoperitoneal shunt inserted through a lateral transcerebellar trajectory. A programmable variable pressure valve was implemented. CONCLUSIONS: Development of an isolated fourth ventricle and injury to the Guillain-Mollaret triangle in the setting of fourth ventricular ependymoma is a newly encountered complication. Choice of treatment modality and timing of intervention should be carefully considered on a case-by-case basis. The data presented in this report may assist in the selection of surgical treatment for isolated fourth ventricle.

Surgical treatment of intractable epilepsy associated with focal cortical dysplasia.

Focal cortical dysplasias (FCDs) are congenital malformations of cortical development that are a frequent cause of refractory epilepsy in both children and adults. With advances in structural and functional neuroimaging, these lesions are increasingly being identified as a cause of intractable epilepsy in patients undergoing surgical management for intractable epilepsy. Comprehensive histological classification of FCDs with the establishment of uniform terminology and reproducible pathological features has aided in our understanding of FCDs as an epilepsy substrate. Complete resection of FCDs and the associated epileptogenic zone can result in a good surgical outcome in the majority of patients.

Magnetic Resonance-Guided Laser Ablation for the Treatment of Recurrent Dural-Based Lesions: A Series of Five Cases.

BACKGROUND AND OBJECTIVE: Magnetic resonance-guided laser-induced thermotherapy (MR-LITT) is a minimally invasive technique that shows promise in neuro-oncology because of its superiority in delivering precise minimally invasive thermal energy with minimal collateral damage. In this analysis, we investigate initial data on the effect of MR-LITT on dural-based lesions. METHODS: Five patients were identified with dural-based lesions (4 meningiomas, 1 solitary fibrous tumor) with clear evidence of radiologic progression. In all 5 cases, the tumors were localized to the lateral convexity or paramedian locations in the supratentorial space. All patients received MR-LITT and then a follow-up magnetic resonance imaging scan at 24 hours after treatment, at 1 month, and at each subsequent follow-up visit. Local control of the ablated tumor was evaluated with radiographic follow-up and symptomatic progression-free survival was recorded. RESULTS: Five LITT treatments were performed on 5 patients with an average age of 65.2 years. The average tumor volume was 29.7 cm3 and ablation dosage was 12.4 W. On average, 80% of the pretreatment lesion volume was ablated. The mean follow-up time was 59.3 weeks. In total, 2 patients (1 with an anaplastic meningioma and 1 with a solitary fibrous tumor) had radiographic evidence of disease progression. In the observed time of the 3 patients with no progression, there was a 52% reduction in tumor volume. There were no major perioperative complications. CONCLUSIONS: MR-LITT is a promising technology for dural-based lesion treatment. This initial study demonstrates that MR-LITT is safe and offers several advantages over open surgical treatment. Randomized studies are needed to evaluate its role as a treatment adjunct.

Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance.

OBJECT: Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross-total resection (GTR) using high doses of fluorescein sodium under white light. The recent introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore. However, the ability of fluorescein to specifically stain glioma cells is not yet well understood. METHODS: The authors designed an in vitro model to assess fluorescein uptake in normal human astrocytes and U251 malignant glioma cells. An in vivo experiment was also subsequently designed to study fluorescein uptake by intracranial U87 malignant glioma xenografts in male nonobese diabetic/severe combined immunodeficient mice. A genetically induced mouse glioma model was used to adjust for the possible confounding effect of an inflammatory response in the xenograft model. To assess the intraoperative application of this technology, the authors prospectively enrolled 12 patients who underwent fluorescein-guided resection of their high-grade gliomas using low-dose intravenous fluorescein and a microscope-integrated fluorescence module. Intraoperative fluorescent and nonfluorescent specimens at the tumor margins were randomly analyzed for histopathological correlation. RESULTS: The in vitro and in vivo models suggest that fluorescein demarcation of glioma-invaded brain is the result of distribution of fluorescein into the extracellular space, most likely as a result of an abnormal blood-brain barrier. Glioblastoma tumor cell-specific uptake of fluorescein was not observed, and tumor cells appeared to mostly exclude fluorescein. For the 12 patients who underwent resection of their high-grade gliomas, the histopathological analysis of the resected specimens at the tumor margin confirmed the intraoperative fluorescent findings. Fluorescein fluorescence was highly specific (up to 90.9%) while its sensitivity was 82.2%. False negatives occurred due to lack of fluorescence in areas of diffuse, low-density cellular infiltration. Margins of contrast enhancement based on intraoperative MRI-guided StealthStation neuronavigation correlated well with fluorescent tumor margins. GTR of the contrast-enhancing area as guided by the fluorescent signal was achieved in 100% of cases based on postoperative MRI. CONCLUSIONS: Fluorescein sodium does not appear to selectively accumulate in astrocytoma cells but in extracellular tumor cell-rich locations, suggesting that fluorescein is a marker for areas of compromised blood-brain barrier within high-grade astrocytoma. Fluorescein fluorescence appears to correlate intraoperatively with the areas of MR enhancement, thus representing a practical tool to help the surgeon achieve GTR of the enhancing tumor regions.

Mechanism of action and therapeutic efficacy of Aurora kinase B inhibition in MYC overexpressing medulloblastoma.

Medulloblastoma comprises four molecular subgroups of which Group 3 medulloblastoma is characterized by MYC amplification and MYC overexpression. Lymphoma cells expressing high levels of MYC are susceptible to apoptosis following treatment with inhibitors of mitosis. One of the key regulatory kinases involved in multiple stages of mitosis is Aurora kinase B. We hypothesized that medulloblastoma cells that overexpress MYC would be uniquely sensitized to the apoptotic effects of Aurora B inhibition. The specific inhibition of Aurora kinase B was achieved in MYC- overexpressing medulloblastoma cells with AZD1152-HQPA. MYC overexpression sensitized medulloblastoma cells to cell death upon Aurora B inhibition. This process was found to be independent of endoreplication. Using both flank and intracranial cerebellar xenografts we demonstrate that tumors formed from MYC-overexpressing medulloblastoma cells show a response to Aurora B inhibition including growth impairment and apoptosis induction. Lastly, we show the distribution of AZD1152-HQPA within the mouse brain and the ability to inhibit intracranial tumor growth and prolong survival in mice bearing tumors formed from MYC-overexpressing medulloblastoma cells. Our results suggest the potential for therapeutic application of Aurora kinase B inhibitors in the treatment of Group 3 medulloblastoma.

Determinants of quality of life in patients with skull base chordoma.

OBJECT: Skull base chordomas can be managed by surgical intervention and adjuvant radiotherapy. As survival for this disease increases, identification of determinants of quality of life becomes an important focus for guiding comprehensive patient care. In this study the authors sought to measure functional outcome and quality of life in patients with skull base chordomas and to identify determinants of quality of life in these patients. METHODS: The authors carried out an internet-based cross-sectional survey, collecting detailed data for 83 individual patients. Demographic and clinical variables were evaluated. Functional outcomes were determined by Karnofsky Performance Scale (KPS) and Glasgow Outcome Scale Extended (GOSE), quality of life was measured using the 36-Item Short Form Health Survey (SF-36), and depression was assessed using Patient Health Questions-9 (PHQ-9) instrument. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Univariate and multivariate analysis was performed to identify determinants of the physical and mental components of the SF-36. RESULTS: Patients with skull base chordomas who have undergone surgery and/or radiation treatment had a median KPS score of 90 (range 10-100, IQR 10) and a median GOSE score of 8 (range 2-8, IQR 3). The mean SF-36 Physical Component Summary score (± SD) was 43.6 ± 11.8, the mean Mental Component Summary score was 44.2 ± 12.6, and both were significantly lower than norms for the general US population (p < 0.001). The median PHQ-9 score was 5 (range 0-27, IQR 8). A PHQ-9 score of 10 or greater, indicating moderate to severe depression, was observed in 29% of patients. The median ZBI score was 12 (range 0-27, IQR 11), indicating a low burden. Neurological deficit, use of pain medication, and requirement for corticosteroids were found to be associated with worse SF-36 Physical Component Summary score, while higher levels of depression (higher PHQ-9 score) correlated with worse SF-36 Mental Component Summary score. CONCLUSIONS: Patients with skull base chordomas have a lower quality of life than the general US population. The most significant determinants of quality of life in the posttreatment phase in this patient population were neurological deficits (sensory deficit and bowel/bladder dysfunction), pain medication use, corticosteroid use, and levels of depression as scored by PHQ-9.

Evaluation of epidural analgesic paste components in lumbar decompressive surgery: a randomized double-blind controlled trial.

BACKGROUND: Adjuncts for pain management in lumbar decompressive surgery are needed to reduce narcotic consumption and promote early mobility. OBJECTIVE: To evaluate the efficacy and active components of a previously described epidural analgesic paste in controlling postoperative pain and facilitating early discharge from hospital after lumbar decompressive surgery. METHODS: A randomized double-blind controlled trial was conducted. Two-hundred and one patients were randomized to 1 of 4 analgesic epidural pastes at the time of lumbar spinal surgery: combination paste (morphine + methylprednisolone), steroid paste (methylprednisolone alone), morphine paste (morphine alone), or placebo. The primary outcome measures used were analgesic consumption and the McGill Pain Questionnaire (MPQ). Secondary outcome measures were: modified American Spinal Cord Injury Association (ASIA) score, Short Form 36 General Health Survey (SF-36), Aberdeen Pain Index (ABPI), time to ambulation and time to discharge from hospital. RESULTS: Administration of combination and steroid paste, but not morphine paste, resulted in a statistically significant reduction in mean pain rating index (PRI) and present pain intensity (PPI) components of the MPQ in the first 3 days after surgery. Likewise, postoperative in-patient narcotic analgesic consumption was reduced in the combination paste and steroid paste group, but not in the morphine paste group. No difference in time to ambulation or discharge, SF-36 scores, ABPI scores, or neurologic recovery was observed. CONCLUSION: An analgesic paste containing methylprednisolone acetate is effective at reducing postoperative pain after lumbar decompressive surgery. Mixing effective doses of morphine sulfate in the paste abrogates the expected analgesic effects of epidural morphine.

High-resolution whole-genome analysis of skull base chordomas implicates FHIT loss in chordoma pathogenesis.

Chordoma is a rare tumor arising in the sacrum, clivus, or vertebrae. It is often not completely resectable and shows a high incidence of recurrence and progression with shortened patient survival and impaired quality of life. Chemotherapeutic options are limited to investigational therapies at present. Therefore, adjuvant therapy for control of tumor recurrence and progression is of great interest, especially in skull base lesions where complete tumor resection is often not possible because of the proximity of cranial nerves. To understand the extent of genetic instability and associated chromosomal and gene losses or gains in skull base chordoma, we undertook whole-genome single-nucleotide polymorphism microarray analysis of flash frozen surgical chordoma specimens, 21 from the clivus and 1 from C1 to C2 vertebrae. We confirm the presence of a deletion at 9p involving CDKN2A, CDKN2B, and MTAP but at a much lower rate (22%) than previously reported for sacral chordoma. At a similar frequency (21%), we found aneuploidy of chromosome 3. Tissue microarray immunohistochemistry demonstrated absent or reduced fragile histidine triad (FHIT) protein expression in 98% of sacral chordomas and 67%of skull base chordomas. Our data suggest that chromosome 3 aneuploidy and epigenetic regulation of FHIT contribute to loss of the FHIT tumor suppressor in chordoma. The finding that FHIT is lost in a majority of chordomas provides new insight into chordoma pathogenesis and points to a potential new therapeutic target for this challenging neoplasm.