Imithri Bodhinayake

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.

Erratum to: 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.

Repurposing mebendazole for the treatment of medulloblastoma.

T he current treatment for medulloblastoma—resection, radiation, and chemotherapy—negatively affects neurocognitive development and fails to ensure survival beyond 10 years for about 40% of children. Among the 4 molecular subtypes of this disease, the group 3 subtype has an especially poor prognosis. Recently, Bai and colleagues demonstrated compelling preclinical evidence for using the microtubule inhibitory drug mebendazole (MBZ) to treat several molecular subtypes of medulloblastoma, including group 3. As a long-standing antihelminthic drug, MBZ has the advantage of a low-toxicity profile in children compared with other microtubule inhibitors such as vincristine and paclitaxel. As a lipophilic agent with a low molecular weight, MBZ has the additional advantage of blood-brain barrier permeability. Previous studies suggest that MBZ acts as an inhibitor of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), the primary receptor mediating the effects of VEGF. This study reveals the antiangiogenic effect of MBZ in medulloblastoma preclinical mouse models and its encouraging impact on overall survival. The authors used 3 orthotopic models of medulloblastoma: a genetic model of the sonic hedgehog (SHH) molecular subtype consisting of allografts from spontaneous medulloblastomas in patched (PTCH)1/2, p532/2 mice; a model of therapy-resistant SHH consisting of allografts from tumors resistant to the hedgehog pathway inhibitor vismodegib; and a xenograft model with human group 3 medulloblastoma cells, D425 MB, implanted into the cerebellum. Implanted cells were transduced with firefly luciferase–expressing lentivirus for in vivo bioluminescent imaging. Mice in the treatment group received daily oral gavage of MBZ (50 mg/ kg) starting 5 days after tumor cell implantation. Tumor vasculature in brain tissue from treated animals was compared with that of phosphate-buffered saline–treated control animals by immunostaining for the endothelial marker CD31. The impact of MBZ on the kinase activity of VEGFR2 was assessed by Western blots for VEGFR2 autophosphorylation after VEGF stimulation of human umbilical vein endothelial cells and by a cell-free kinase assay.

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 Vigneauds 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.

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.

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.

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.

Neurosurgical Considerations in Macrocephaly

Head circumference (HC) or occipitofrontal circumference (OFC) serves as an important indicator of head growth. For pediatric neurosurgeons, there may be no single more important objective measure and fortunately, this is a routine part of almost every well patient visit through 2 years. The head can be considered as several interconnected compartments: the brain parenchyma, blood, cerebrospinal fluid (CSF), and the bones of the skull. An increase in the volume of any one of these compartments prior to the fusion of the sutures and fontanels results in macrocephaly, which is defined as a HC greater than two standard deviations above normal.