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Open access

Ahmed Mohyeldin, Jayakar V. Nayak and Juan C. Fernandez-Miranda

Over the past three decades, endoscopic endonasal surgery has unlocked new corridors to treat a wide spectrum of ventral skull base lesions. Tuberculum sella meningiomas represent one of the most ideal pathologies for ventral skull base access. Traditionally, these lesions were approached primarily through various subfrontal and frontal-lateral transcranial approaches that have unfortunately been shown to be associated with worsening visual decline postoperatively. The endoscopic endonasal approach is now being attempted by more surgeons and leverages an infrachiasmatic trajectory that provides direct access to the tuberculum sella where most of the vascular supply for these lesions can be taken early, facilitating more efficient surgical resection and mitigating the risk of optic nerve injury. Here we review a challenging case of a large (∼3 cm) tuberculum sella meningioma, encasing critical vessels off the circle of Willis and resected via an endoscopic endonasal approach. We discuss the technical nuances and relevant surgical anatomy of this approach and highlight important considerations in the safe and successful removal of these meningiomas. We show that certain tumors that appear to encase the supraclinoidal carotid artery can be fully resected via an endonasal approach with precise surgical technique and adequate exposure. Furthermore, this case illustrates the risk of injuring a key perforating vessel from the anterior communicating artery complex, called the subcallosal artery. Injury to this vessel is highly associated with tumors like the one presented here that extend into the suprachiasmatic space between the optic chiasm and the anterior communicating complex. Meticulous surgical dissection is required to preserve this perforating vessel as well as branches from the superior hypophyseal artery. Finally, we review our current closure techniques for these challenging approaches and discuss the use of a lumbar drain for 3 days to lower CSF leak rates.

The video can be found here: https://youtu.be/mafyXi5B0MA.

Full access

Ahmed Mohyeldin, Russell R. Lonser and J. Bradley Elder

OBJECT

The object of this study was to assess the feasibility, accuracy, and safety of real-time MRI-compatible frameless stereotactic brain biopsy.

METHODS

Clinical, imaging, and histological data in consecutive patients who underwent stereotactic brain biopsy using a frameless real-time MRI system were analyzed.

RESULTS

Five consecutive patients (4 males, 1 female) were included in this study. The mean age at biopsy was 45.8 years (range 29–60 years). Real-time MRI permitted concurrent display of the biopsy cannula trajectory and tip during placement at the target. The mean target depth of biopsied lesions was 71.3 mm (range 60.4–80.4 mm). Targeting accuracy analysis revealed a mean radial error of 1.3 ± 1.1 mm (mean ± standard deviation), mean depth error of 0.7 ± 0.3 mm, and a mean absolute tip error of 1.5 ± 1.1 mm. There was no correlation between target depth and absolute tip error (Pearson product-moment correlation coefficient, r = 0.22). All biopsy cannulae were placed at the target with a single penetration and resulted in a diagnostic specimen in all cases. Histopathological evaluation of biopsy samples revealed dysembryoplastic neuroepithelial tumor (1 case), breast carcinoma (1 case), and glioblastoma multiforme (3 cases).

CONCLUSIONS

The ability to place a biopsy cannula under real-time imaging guidance permits on-the-fly alterations in the cannula trajectory and/or tip placement. Real-time imaging during MRI-guided brain biopsy provides precise safe targeting of brain lesions.

Open access

Ahmed Mohyeldin, Peter Hwang, Gerald A. Grant and Juan C. Fernandez-Miranda

Pediatric craniopharyngiomas that were once thought to be inoperable or considered only for salvage medical therapy are now being reconsidered for aggressive surgical resection via endoscopic endonasal approaches. Here we review the operative video case of an 11-year-old with a giant complex craniopharyngioma that was resected via an endoscopic endonasal approach. Due to the extent of tumor burden near the basilar apex, a transclival approach was necessary. To accomplish this, a wide sphenoidotomy, posterior ethmoidectomy, and resection of the middle turbinate were necessary to create enough working space for the resection. We also highlight several key innovations in pediatric endoscopic endonasal surgery management and underscore a multidisciplinary approach that allows for the safe and successful treatment of these lesions. Our multidisciplinary team involves an experienced fellowship-trained endoscopic skull base surgeon and otolaryngologist, as well as a pediatric neurosurgeon, pediatric endocrinologist, pediatric anesthesiologist, and pediatric intensivists who play important roles in the preoperative, intraoperative, and postoperative phases of care of the patient. Finally, we discuss critical surgical decision points including pituitary transposition, which has a lot of conceptual appeal when it is anatomically feasible but unfortunately, in our experience, has low functional preservation rates. Initially, we always aim to utilize pituitary transposition for tuberoinfundibular craniopharyngiomas, and once the relationship between the tumor and the stalk is determined, a decision on whether to preserve or sacrifice the stalk and pituitary gland is made. In this particular case, there was a salvageable stalk and the transposition was performed knowing that the chances for functional preservation were low.

The video can be found here: https://youtu.be/ClL73FU5QIU.

Restricted access

Wesley Hsu, Ahmed Mohyeldin, Sagar R. Shah, Colette M. ap Rhys, Lakesha F. Johnson, Neda I. Sedora-Roman, Thomas A. Kosztowski, Ola A. Awad, Edward F. McCarthy, David M. Loeb, Jean-Paul Wolinsky, Ziya L. Gokaslan and Alfredo Quiñones-Hinojosa

Object

Chordoma is a malignant bone neoplasm hypothesized to arise from notochordal remnants along the length of the neuraxis. Recent genomic investigation of chordomas has identified T (Brachyury) gene duplication as a major susceptibility mutation in familial chordomas. Brachyury plays a vital role during embryonic development of the notochord and has recently been shown to regulate epithelial-to-mesenchymal transition in epithelial-derived cancers. However, current understanding of the role of this transcription factor in chordoma is limited due to the lack of availability of a fully characterized chordoma cell line expressing Brachyury. Thus, the objective of this study was to establish the first fully characterized primary chordoma cell line expressing gain of the T gene locus that readily recapitulates the original parental tumor phenotype in vitro and in vivo.

Methods

Using an intraoperatively obtained tumor sample from a 61-year-old woman with primary sacral chordoma, a chordoma cell line (JHC7, or Johns Hopkins Chordoma Line 7) was established. Molecular characterization of the primary tumor and cell line was conducted using standard immunostaining and Western blotting. Chromosomal aberrations and genomic amplification of the T gene in this cell line were determined. Using this cell line, a xenograft model was established and the histopathological analysis of the tumor was performed. Silencing of Brachyury and changes in gene expression were assessed.

Results

The authors report, for the first time, the successful establishment of a chordoma cell line (JHC7) from a patient with pathologically confirmed sacral chordoma. This cell line readily forms tumors in immunodeficient mice that recapitulate the parental tumor phenotype with conserved histological features consistent with the parental tumor. Furthermore, it is demonstrated for the first time that silencing of Brachyury using short hairpin RNA renders the morphology of chordoma cells to a more differentiated-like state and leads to complete growth arrest and senescence with an inability to be passaged serially in vitro.

Conclusions

This report represents the first xenograft model of a sacral chordoma line described in the literature and the first cell line established with stable Brachyury expression. The authors propose that Brachyury is an attractive therapeutic target in chordoma and that JHC7 will serve as a clinically relevant model for the study of this disease.

Restricted access

Ahmed Mohyeldin, Clifton L. Dalgard, Huasheng Lu, Thomas Mcfate, A. Sasha Tait, Viral C. Patel, Kondi Wong, Elizabeth Rushing, Subhojit Roy, Geza Acs and Ajay Verma

Object

The hypoxia-inducible pleiotropic hormone, erythropoietin (EPO), has recently been found to promote the development and survival of neurons and astrocytes. Since hypoxia has been implicated in the malignant progression of some human cancers, the authors investigated whether EPO signaling influenced the malignant properties of human astrocytoma cells.

Methods

Reverse transcriptase–polymerase chain reaction, Western blot analysis, and immunohistochemical studies were used to measure EPO and its receptor (EPOR). Cell viability, Matrigel invasion assays, metalloprotease assays, EPO neutralizing antibodies, and EPOR overexpression were used to study the biological actions of EPO.

Expression of both EPO and EPOR was observed in the hypoxic regions and invasive margins of glioma specimens obtained at biopsy, and expression of EPOR correlated with the stage of the tumor. The EPOR was also functionally upregulated by hypoxia in cultured glioblastoma multiforme (GBM) cells. Both hypoxia and EPO protected cultured GBM cells from cisplatin cytotoxicity and promoted the invasiveness of GBM cells through Matrigel by potentiating metalloprotease activity. Hypoxia-enhanced cell invasion was attenuated in cells that overexpressed a nonfunctional EPOR.

Conclusions

Hypoxia-inducible autocrine and paracrine EPO signaling participates in the malignant progression of GBMs.

Restricted access

Daisuke Yamashita, Joshua D. Bernstock, Galal Elsayed, Hirokazu Sadahiro, Ahmed Mohyeldin, Gustavo Chagoya, Adeel Ilyas, James Mooney, Dagoberto Estevez-Ordonez, Shinobu Yamaguchi, Victoria L. Flanary, James R. Hackney, Krishna P. Bhat, Harley I. Kornblum, Nicola Zamboni, Sung-Hak Kim, E. Antonio Chiocca and Ichiro Nakano

OBJECTIVE

Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism.

METHODS

Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry.

RESULTS

Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core.

CONCLUSIONS

Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.