Left Internal Carotid Artery Arising from the Right Cavernous Internal Carotid Artery: A Case Report.

Anatomical variations involving the internal carotid artery are uncommon. Herein, we present a very rare origin of the internal carotid artery. An adult female presented to the emergency department after falling. Imaging revealed that the left internal carotid artery arose from the contralateral cavernous segment of the internal carotid artery. Such a variation should be kept in mind by radiologists and surgeons who interpret and operate in this area, respectively.

Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis.

IMPORTANCE: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. OBJECTIVE: To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. DATA SOURCES: Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. STUDY SELECTION: Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. MAIN OUTCOME AND MEASURES: Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. RESULTS: The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. CONCLUSION AND RELEVANCE: This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Onyx-HD 500 Embolization of a Traumatic Internal Carotid Artery Pseudoaneurysm after Transsphenoidal Surgery.

BACKGROUND AND PURPOSE: Traumatic intracranial pseudoaneurysms present a challenge for treatment. Traditionally these lesions have required a deconstructive approach consisting of vessel sacrifice since their fragile nature often makes direct microsurgical repair or coil embolization hazardous. As a high-viscosity liquid embolic agent that results in immediate, vessel sparing aneurysm occlusion, Onyx-HD 500 represents a uniquely efficacious tool for this clinical situation. CASE SUMMARY: We report the case of a 56-year-old right-handed gentleman who suffered a vascular injury to the ICA during revision transsphenoidal surgery for a recurrent pituitary macroadenoma. The patient was initially treated with nasal packing, but after recurrent episodes of epistaxis and a CT angiogram demonstrating a large traumatic ICA pseudoaneurysm, the patient was referred for invasive treatment. Given the presumed fragility of the lesion, embolization with Onyx-HD 500 was chosen in order to safely achieve immediate aneurysm occlusion without the need for vessel sacrifice. After an early recurrence due to incomplete initial embolization, the patient went on to complete occlusion without further hemorrhage. CONCLUSION: This case illustrates the utility of a high-viscosity liquid embolic agent in providing immediate protection from rehemorrhage by occluding a large ruptured pseudoaneurysm of the proximal intracranial ICA, while sparing the parent artery.

Detection of circulating tumor cells in the cerebrospinal fluid of a patient with a solitary metastasis from breast cancer: A case report.

Brain lesions identified following the diagnosis and eradication of primary cancers are often ambiguous in origin, existing as a solitary metastasis or an independent primary brain tumor. The brain is a relatively common site of metastasis with breast cancer, although determining whether metastases have originated from the breast or brain is often not possible without invasive biopsies. In the current case report, a patient presented with a brain lesion identified by radiography and was without systemic disease. The patient had previously exhibited a complete response to chemotherapy and surgery for a poorly differentiated invasive ductal carcinoma. The origin of the brain lesion could not be determined by magnetic resonance imaging, giving rise to a diagnostic dilemma with diverging treatment options. We previously reported a method to isolate and enumerate tumor cells of epithelial origin in the cerebrospinal fluid (CSF). CSF tumor cell analysis of the patient revealed massive CSF tumor cell burden of epithelial origin, indicating that the brain lesion was likely of breast origin. The current case report highlights the use of CSF tumor cell detection as a differential diagnostic tool, in addition to its previously demonstrated use as a marker of disease burden and therapeutic response.

COX-2 drives metastatic breast cells from brain lesions into the cerebrospinal fluid and systemic circulation.

Breast cancer is among the most common malignancies that metastasize to the brain, with 15% to 20% of patients with metastatic breast cancer eventually developing brain metastases. We previously reported a method to enumerate tumor cells in the cerebrospinal fluid (CSF) of patients with breast cancer with central nervous system (CNS) metastases, a setting that lacks sufficiently informative biomarkers. Here, we show that breast cancer cells can spontaneously disseminate into the CSF from brain lesions in mice in a COX-2-dependent manner and can escape from the CNS to systemic circulation. Enumeration of tumor cells in the peripheral blood (circulating tumor cells, CTC) and CSF (cerebrospinal fluid tumor cells, CSFTC) of nine breast cancer patients with brain metastases revealed dynamic changes in tumor cell burden in both the peripheral blood and CSF compartments that correlated with clinical disease progression. Interestingly, four of the enrolled patients exhibited rapid intercompartmental transitioning of the disease reflected in the CTC and CSFTC counts that preceded corresponding evidence by clinical imaging or neurologic symptoms. Two of these patients had systemic disease recurrence involving the primary malignant site. Intercompartmental cycling of tumor cells may represent an important mechanism for disease persistence and recurrence that may involve tumor self-seeding. Our findings demonstrate the involvement of COX-2 in the genesis of CSFTCs and suggest that COX-2 inhibitors should be investigated in patients with breast cancer with brain metastases for their ability to reduce CSFTC counts and prevent systemic recurrence.

Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.

Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.

Endovascular embolization by parent artery reconstruction of a symptomatic fusiform posterior cerebral artery aneurysm using Onyx HD-500: a neurointerventional report.

BACKGROUND AND PURPOSE: Posterior cerebral artery aneurysms are treatment challenge for the neurosurgeon. Parent artery occlusion, trapping and bypass have been the classic treatment options for aneurysms in this location. With the introduction of newer embolic agents such as Onyx®, endovascular intervention is now a viable therapy for these aneurysms. CASE SUMMARY: We report the case of a 60-year-old man who presented with a symptomatic, though unruptured, fusiform left posterior cerebral artery aneurysm. Given the distal location of this dominant sided aneurysm, post-operative visual deficits and aphasia were a concern if parent vessel occlusion were to be performed. Therefore, an endovascular reconstruction using Onyx HD-500 and two closed-cell stents was performed. CONCLUSIONS: This report illustrates the ability of a high-density liquid embolic agent to provide immediate reconstruction of a fusiform aneurysm in a distal location.

Identification and enumeration of circulating tumor cells in the cerebrospinal fluid of breast cancer patients with central nervous system metastases.

The number of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer patients is now an established prognostic marker. While the central nervous system is a common site of metastasis in breast cancer, the standard marker for disease progression in this setting is cerebrospinal fluid (CSF) cytology. However, the significance of CSF cytology is unclear, requires large sample size, is insensitive and subjective, and sometimes yields equivocal results. Here, we report the detection of breast cancer cells in CSF using molecular markers by adapting the CellSearch system (Veridex). We used this platform to isolate and enumerate breast cancer cells in CSF of breast cancer patients with central nervous system (CNS) metastases. The number of CSF tumor cells correlated with tumor response to chemotherapy and were dynamically associated with disease burden. This CSF tumor cell detection method provides a semi-automated molecular analysis that vastly improves the sensitivity, reliability, objectivity, and accuracy of detecting CSF tumor cells compared to CSF cytology. CSF tumor cells may serve as a marker of disease progression and early-stage brain metastasis in breast cancer and potentiate further molecular analysis to elucidate the biology and significance of tumor cells in the CSF.

Impact of tracheostomy timing on outcome after severe head injury.

BACKGROUND: The influence of tracheostomy timing on outcome after severe head injury remains controversial. METHODS: The investigation was based on data prospectively collected by the Pennsylvania Trauma Society Foundation statewide trauma registry from January 1990 until December 2005. RESULTS: 3,104 patients met criteria for inclusion in the study (GCS ≤ 8 and tracheostomy). Early Tracheostomy Group (ETG) patients, defined as tracheostomy performed during hospital days 1-7, were more likely to be functionally independent at discharge (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI), 1.16-1.82, P = 0.001) and have a shorter length of stay (adjusted OR 0.23, 95% CI, 0.20-0.28, P < 0.0001). However, Late Tracheostomy Group (LTG) patients, defined as tracheostomy performed >7 days after admission, were approximately twice as likely to be discharged alive (adjusted OR 2.12, 95% CI, 1.60-2.82, P < 0.0001). Using a Composite Outcome Scale, which combined these three measures, there was a non-significant trend toward a higher likelihood of a poor outcome in LTG patients. When this analysis was repeated using only those patients in relatively good condition on admission, LTG patients were found to be approximately 50% less likely to have a good outcome (adjusted OR 0.46, 95% CI, 0.28-0.73, P = 0.001) when compared to ETG patients. CONCLUSIONS: These results indicate a complex relationship between tracheostomy timing and outcome, but suggest that a strategy of early tracheostomy, particularly when performed on patients with a reasonable chance of survival, results in a better overall clinical outcome than when the tracheostomy is performed in a delayed manner.