Intradural spinal tumors in adults-update on management and outcome.

Among spinal tumors that occur intradurally, meningiomas, nerve sheath tumors, ependymomas, and astrocytomas are the most common. While a spinal MRI is the state of the art to diagnose intradural spinal tumors, in some cases CT scans, angiography, CSF analyses, and neurophysiological examination can be valuable. The management of these lesions depends not only on the histopathological diagnosis but also on the clinical presentation and the anatomical location, allowing either radical resection as with most extramedullary lesions or less invasive strategies as with intramedullary lesions. Although intramedullary lesions are rare and sometimes difficult to manage, well-planned treatment can achieve excellent outcome without treatment-related deficits. Technical advances in imaging, neuromonitoring, minimally invasive approaches, and radiotherapy have improved the outcome of intradural spinal tumors. However, the outcome in malignant intramedullary tumors remains poor. While surgery is the mainstay treatment for many of these lesions, radiation and chemotherapy are of growing importance in recurrent and multilocular disease. We reviewed the literature on this topic to provide an overview of spinal cord tumors, treatment strategies, and outcomes. Typical cases of extra- and intramedullary tumors are presented to illustrate management options and outcomes.

Neuro-oncology biotech industry progress report.

The Brain Tumor Biotech Center at the Feinstein Institute for Medical Research, in collaboration with Voices Against Brain Cancer hosted The Brain Tumor Biotech Summit at in New York City in June 2015. The focus was once again on fostering collaboration between neuro-oncologist, neurosurgeons, scientists, leaders from biotechnology and pharmaceutical industries, and members of the financial community. The summit highlighted the recent advances in the treatment of brain tumor, and specifically focused on targeting of stem cells and EGFR, use of prophage and immunostimulatory vaccines, retroviral vectors for drug delivery, biologic prodrug, Cesium brachytherapy, and use of electric field to disrupt tumor cell proliferation. This article summarizes the current progress in brain tumor research as presented at 2015 The Brain Tumor Biotech Summit.

Superselective intraarterial cerebral infusion of cetuximab after osmotic blood/brain barrier disruption for recurrent malignant glioma: phase I study.

Objective To establish a maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of Cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol, and examine safety of the procedure in patients with recurrent malignant glioma. Methods A total of 15 patients with recurrent malignant glioma were included in the current study. The starting dose of Cetuximab was 100 mg/m(2) and dose escalation was done to 250 mg/m(2). All patients were observed for 28 days post-infusion for any side effects. Results There was no dose-limiting toxicity from a single dose of SIACI of Cetuximab up to 250 mg/m(2) after osmotic BBB disruption with mannitol. A tolerable rash was seen in 2 patients, anaphylaxis in 1 patient, isolated seizure in 1 patient, and seizure and cerebral edema in 1 patient. Discussion SIACI of mannitol followed by Cetuximab (up to 250 mg/m(2)) for recurrent malignant glioma is safe and well tolerated. A Phase I/II trial is currently underway to determine the efficacy of SIACI of cetuximab in patients with high-grade glioma.

Multifunctionalization of cetuximab with bioorthogonal chemistries and parallel EGFR profiling of cell-lines using imaging, FACS and immunoprecipitation approaches.

The ability to derivatize antibodies is currently limited by the chemical structure of antibodies as polypeptides. Modern methods of bioorthogonal and biocompatible chemical modifications could make antibody functionalization more predictable and easier, without compromising the functions of the antibody. To explore this concept, we modified the well-known anti-epidermal growth factor receptor (EGFR) drug, cetuximab (Erbitux®), with 5-azido-2-nitro-benzoyl (ANB) modifications by optimization of an acylation protocol. We then show that the resulting ANB-cetuximab can be reliably modified with dyes (TAMRA and carboxyrhodamine) or a novel synthesized cyclooctyne modified biotin. The resulting dye- and biotin-modified cetuximabs were then tested across several assay platforms with several cell lines including U87, LN229, F98EGFR, F98WT and HEK293 cells. The assay platforms included fluorescence microscopy, FACS and biotin-avidin based immunoprecipitation methods. The modified antibody performs consistently in all of these assay platforms, reliably determining relative abundances of EGFR expression on EGFR expressing cells (LN229 and F98EGFR) and failing to cross react with weak to negative EGFR expressing cells (U87, F98WT and HEK293). The ease of achieving diverse and assay relevant functionalizations as well as the consequent rapid construction of highly correlated antigen expression data sets highlights the power of bioorthogonal and biocompatible methods to conjugate macromolecules. These data provide a proof of concept for a multifunctionalization strategy that leverages the biochemical versatility and antigen specificity of antibodies.

Expanding the borders: the evolution of neurosurgical approaches.

In this article the authors discuss the development of neurosurgical approaches and the advances in science and technology that influenced this development throughout history. They provide a broad overview of this interesting topic from the first attempts of trephination by ancient cultures to the work of the pioneers of neurosurgery and the introduction of microsurgery.

Industry progress report on neuro-oncology: Biotech update 2013.

For the second time, The Brain Tumor Center of the Weill Cornell Brain and Spine Center, in collaboration with Voices Against Brain Cancer, hosted The Brain Tumor Biotech Summit in New York City in June 2013. After a very successful first summit in 2012, this innovative event has established a platform for intensive networking between neuro-oncologists, neurosurgeons, neuroscientists, members of the biotechnology and pharmaceutical communities, members of the financial community and leaders of non-profit organizations. This year's summit highlighted dendritic cell vaccines, novel antibody, heat shock protein and targeted therapies as well as exosome technologies, MRI-guided therapies and other novel drug delivery tools. This report presents a short overview of the current progress in brain tumor research and therapy as presented at the 2013 Brain Tumor Biotech Summit.

Vincent du Vigneaud: following the sulfur trail to the discovery of the hormones of the posterior pituitary gland at Cornell Medical College.

In 1955, Vincent du Vigneaud (1901-1978), the chairman of the Department of Biochemistry at Cornell University Medical College, was awarded the Nobel Prize for Chemistry for his research on insulin and for the first synthesis of the posterior pituitary hormones-oxytocin and vasopressin. His tremendous contribution to organic chemistry, which began as an interest in sulfur-containing compounds, paved the way for a better understanding of the pituitary gland and for the development of diagnostic and therapeutic tools for diseases of the pituitary. His seminal research continues to impact neurologists, endocrinologists, and neurosurgeons, and enables them to treat patients who had no alternatives prior to du Vigneaud's breakthroughs in peptide structure and synthesis. The ability of neurosurgeons to aggressively operate on parasellar pathology was directly impacted and related to the ability to replace these hormones after surgery. The authors review the life and career of Vincent du Vigneaud, his groundbreaking discoveries, and his legacy of the understanding and treatment of the pituitary gland in health and disease.

Results and risk factors for recurrence following endoscopic endonasal transsphenoidal surgery for pituitary adenoma.

BACKGROUND: Endoscopic endonasal (EE) transsphenoidal surgery is an important surgical approach to the treatment of sellar pathology, particularly for pituitary adenomas. Risk factors for the radiographic recurrence of pituitary adenomas resected using a purely endoscopic approach have not been established. This study investigates outcomes and identifies risk factors for recurrence following EE transsphenoidal surgery for pituitary adenoma. METHODS: We performed a retrospective review of 64 patients with pituitary adenomas undergoing EE surgery by a single, right-handed surgeon preferentially operating through the right nares. Post-operative MRI studies were utilized to monitor for residual disease or disease recurrence. RESULTS: Residual tumor was found in 31.2% of patients. Over a median follow-up period of 23.1 months (range 4-62.5), 4 (20%) of these patients showed recurrence. Two patients with inconclusive post-operative imaging had subsequent imaging consistent with recurrence, making the total recurrence in our series 9.4%. While no statistically significant effects of gender, age or history of previous treatment were seen, amenorrhea on presentation and maximum tumor diameter >10 mm were significant risk factors for radiographic recurrence (p = 0.044 and 0.005, respectively). No predominant side of residual tissue was identified in these tumors operated through the right nares. CONCLUSIONS: Only 20% of patients with residual tumor developed recurrent disease over a median follow up of 23.1 months. This recurrence rate may be an important consideration in cases where gross total resection is not feasible. Preferentially operating from the right does not seem to influence the location of residual tumor.

Conservative management of cavernous sinus cavernous hemangioma in pregnancy.

Cavernous sinus cavernous hemangiomas in pregnancy are extremely rare lesions. The precise management of these lesions remains unknown. The authors present a case of a cavernous hemangioma in pregnancy, centered within the cavernous sinus that underwent postpartum involution without surgical intervention. A 34-year-old pregnant patient (gravida 1, para 0) presented to an otolaryngologist with persistent headache and left-sided facial pain and numbness in the V1 distribution. While being treated for sinusitis, her symptoms progressed to include a left-sided oculomotor palsy and abducens palsy. Magnetic resonance imaging without contrast revealed an expansile mass within the left cavernous sinus consistent with a cavernous hemangioma. The patient was evaluated by a neurosurgeon who recommended close follow-up and postpartum imaging without surgical intervention. Although the lesion enlarged during pregnancy, the patient was able to undergo an uncomplicated cesarean section at 37 weeks. All facial and ocular symptoms resolved by 9 months postpartum, and MRI showed a decrease in lesion size and reduced mass effect. The authors conclude that nonsurgical management may be a viable approach in patients who have an onset or exacerbation of symptoms associated with cavernous sinus cavernous hemangiomas during pregnancy because postpartum involution may negate the need for surgical intervention.