Publications by authors named "Constantinos Hadjipanayis"

76 Publications

Fluorescence-Guided Surgery: A Review on Timing and Use in Brain Tumor Surgery.

Front Neurol 2021 16;12:682151. Epub 2021 Jun 16.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Fluorescence-guided surgery (FGS) allows surgeons to have improved visualization of tumor tissue in the operating room, enabling maximal safe resection of malignant brain tumors. Over the past two decades, multiple fluorescent agents have been studied for FGS, including 5-aminolevulinic acid (5-ALA), fluorescein sodium, and indocyanine green (ICG). Both non-targeted and targeted fluorescent agents are currently being used in clinical practice, as well as under investigation, for glioma visualization and resection. While the efficacy of intraoperative fluorescence in studied fluorophores has been well established in the literature, the effect of timing on fluorophore administration in glioma surgery has not been as well depicted. In the past year, recent studies of 5-ALA use have shown that intraoperative fluorescence may persist beyond the previously studied window used in prior multicenter trials. Additionally, the use of fluorophores for different brain tumor types is discussed in detail, including a discussion of choosing the right fluorophore based on tumor etiology. In the following review, the authors will describe the temporal nature of the various fluorophores used in glioma surgery, what remains uncertain in FGS, and provide a guide for using fluorescence as a surgical adjunct in brain tumor surgery.
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http://dx.doi.org/10.3389/fneur.2021.682151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245059PMC
June 2021

Current knowledge on the immune microenvironment and emerging immunotherapies in diffuse midline glioma.

EBioMedicine 2021 Jul 19;69:103453. Epub 2021 Jun 19.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai,10 Union Square East, 5th Floor, Suite 5E, New York, NY 10003, USA; Department of Oncological Sciences, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Diffuse midline glioma (DMG) is an incurable malignancy with the highest mortality rate among pediatric brain tumors. While radiotherapy and chemotherapy are the most common treatments, these modalities have limited promise. Due to their diffuse nature in critical areas of the brain, the prognosis of DMG remains dismal. DMGs are characterized by unique phenotypic heterogeneity and histological features. Mutations of H3K27M, TP53, and ACVR1 drive DMG tumorigenesis. Histological artifacts include pseudopalisading necrosis and vascular endothelial proliferation. Mouse models that recapitulate human DMG have been used to study key driver mutations and the tumor microenvironment. DMG consists of a largely immunologically cold tumor microenvironment that lacks immune cell infiltration, immunosuppressive factors, and immune surveillance. While tumor-associated macrophages are the most abundant immune cell population, there is reduced T lymphocyte infiltration. Immunotherapies can stimulate the immune system to find, attack, and eliminate cancer cells. However, it is critical to understand the immune microenvironment of DMG before designing immunotherapies since differences in the microenvironment influence treatment efficacy. To this end, our review aims to overview the immune microenvironment of DMG, discuss emerging insights about the immune landscape that drives disease pathophysiology, and present recent findings and new opportunities for therapeutic discovery.
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http://dx.doi.org/10.1016/j.ebiom.2021.103453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220552PMC
July 2021

Student Survey Results of a Virtual Medical Student Course Developed as a Platform for Neurosurgical Education During the Coronavirus Disease 2019 Pandemic.

World Neurosurg 2021 08 28;152:e250-e265. Epub 2021 May 28.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address:

Background: Before the coronavirus disease 2019 (COVID-19) pandemic, medical students training in neurosurgery relied on external subinternships at institutions nationwide for immersive educational experiences and to increase their odds of matching. However, external rotations for the 2020-2021 cycle were suspended given concerns of spreading COVID-19. Our objective was to provide foundational neurosurgical knowledge expected of interns, bootcamp-style instruction in basic procedures, and preinterview networking opportunities for students in an accessible, virtual format.

Methods: The virtual neurosurgery course consisted of 16 biweekly 1-hour seminars over a 2-month period. Participants completed comprehensive precourse and postcourse surveys assessing their backgrounds, confidence in diverse neurosurgical concepts, and opinions of the qualities of the seminars. Responses from students completing both precourse and postcourse surveys were included.

Results: An average of 82 students participated live in each weekly lecture (range, 41-150). Thirty-two participants completed both surveys. On a 1-10 scale self-assessing baseline confidence in neurosurgical concepts, participants were most confident in neuroendocrinology (6.79 ± 0.31) and least confident in spine oncology (4.24 ± 0.44), with an average of 5.05 ± 0.32 across all topics. Quality ratings for all seminars were favorable. The mean postcourse confidence was 7.79 ± 0.19, representing an improvement of 3.13 ± 0.38 (P < 0.0001).

Conclusions: Feedback on seminar quality and improvements in confidence in neurosurgical topics suggest that an interactive virtual course may be an effective means of improving students' foundational neurosurgical knowledge and providing networking opportunities before application cycles. Comparison with in-person rotations when these are reestablished may help define roles for these tools.
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http://dx.doi.org/10.1016/j.wneu.2021.05.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412498PMC
August 2021

3D Exoscope Navigation-Guided Approach to Middle Cranial Fossa.

Otol Neurotol 2021 Sep;42(8):1223-1227

Department of Otolaryngology-Head and Neck Surgery, Icahn School of Medicine at Mount Sinai, New York, New York.

Objective: To test the feasibility and efficacy of a 3D exoscope navigation-guided middle cranial fossa (MCF) approach to the internal auditory canal (IAC); to potentially obviate the need to use dissection landmarks and instead, use the navigation probe as a guide to find structures and drill down to the IAC.

Patients: Cadaveric dissection of six temporal bones.

Intervention: Computed tomography temporal bone was performed with fiducials on each specimen before the dissection to employ the navigation system. Using a 3D exoscope with navigation by Synaptive (Toronto, Ontario, Canada), the MCF approach was performed.

Main Outcome Measures: Navigation accuracy, ability to identify critical structures, and ability to drill out the IAC successfully.

Results: All six specimens had the IAC successfully drilled out using the 3D exoscope. All dissections were performed with navigation and did not require dissecting out the greater superficial petrosal nerve and superior semicircular canal. One specimen used landmark dissection to confirm the IAC after navigation had been used to locate the IAC first. Navigation accuracy mean was 1.86 mm (range, 1.56-2.05 mm).

Conclusion: A 3D exoscope navigation-guided MCF approach to the IAC is feasible without landmark dissection.
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http://dx.doi.org/10.1097/MAO.0000000000003185DOI Listing
September 2021

Intraoperative molecular imaging clinical trials: a review of 2020 conference proceedings.

J Biomed Opt 2021 May;26(5)

Perelman School of Medicine, Univ. of Pennsylvania, United States.

Significance: Surgery is often paramount in the management of many solid organ malignancies because optimal resection is a major factor in disease-specific survival. Cancer surgery has multiple challenges including localizing small lesions, ensuring negative surgical margins around a tumor, adequately staging patients by discriminating positive lymph nodes, and identifying potential synchronous cancers. Intraoperative molecular imaging (IMI) is an emerging potential tool proposed to address these issues. IMI is the process of injecting patients with fluorescent-targeted contrast agents that highlight cancer cells prior to surgery. Over the last 5 to 7 years, enormous progress has been achieved in tracer development, near-infrared camera approvals, and clinical trials. Therefore, a second biennial conference was organized at the University of Pennsylvania to gather surgical oncologists, scientists, and experts to discuss new investigative findings in the field. Our review summarizes the discussions from the conference and highlights findings in various clinical and scientific trials.

Aim: Recent advances in IMI were presented, and the importance of each clinical trial for surgical oncology was critically assessed. A major focus was to elaborate on the clinical endpoints that were being utilized in IMI trials to advance the respective surgical subspecialties.

Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's second clinical trials update on IMI were selected to discuss their clinical trials and endpoints.

Results: Multiple phase III, II, and I trials were discussed during the conference. Since the approval of 5-ALA for commercial use in neurosurgical malignancies, multiple tracers and devices have been developed to address common challenges faced by cancer surgeons across numerous specialties. Discussants also presented tracers that are being developed for delineation of normal anatomic structures that can serve as an adjunct during surgical procedures.

Conclusions: IMI is increasingly being recognized as an improvement to standard oncologic surgical resections and will likely advance the art of cancer surgery in the coming years. The endpoints in each individual surgical subspecialty are varied depending on how IMI helps each specialty solve their clinical challenges.
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http://dx.doi.org/10.1117/1.JBO.26.5.050901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126806PMC
May 2021

In Reply: The Role of Prophylactic Intraventricular Antibiotics in Reducing the Incidence of Infection and Revision Surgery in Pediatric Patients Undergoing Shunt Placement.

Neurosurgery 2021 06;89(1):E104

Department of Neurosurgery Icahn School of Medicine at Mount Sinai Mount Sinai Health System New York, New York, USA.

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http://dx.doi.org/10.1093/neuros/nyab145DOI Listing
June 2021

Proposed definition of competencies for surgical neuro-oncology training.

J Neurooncol 2021 May 21;153(1):121-131. Epub 2021 Apr 21.

Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany.

Objective: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established.

Methods: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology.

Result: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families.

Conclusions And Relevance: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.
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http://dx.doi.org/10.1007/s11060-021-03750-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131302PMC
May 2021

Re-evaluating Biopsy for Recurrent Glioblastoma: A Position Statement by the Christopher Davidson Forum Investigators.

Neurosurgery 2021 06;89(1):129-132

Department of Neurological Surgery, Washington University School of Medicine, St Louis, Missouri, USA.

Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.
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http://dx.doi.org/10.1093/neuros/nyab063DOI Listing
June 2021

Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration.

Front Neurol 2021 9;12:644804. Epub 2021 Mar 9.

Department of Neurosurgery, Henry Ford Health System, Detroit, MI, United States.

Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2-4 h prior to induction to anesthesia. To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data. Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented. Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4. Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.
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http://dx.doi.org/10.3389/fneur.2021.644804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985355PMC
March 2021

Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial.

J Neurooncol 2021 May 20;152(3):501-514. Epub 2021 Mar 20.

Univ. Lille, Inserm, CHU Lille, U1189 - ONCO-THAI -Laser Assisted Therapies and Immunotherapies for Oncology, 59000, Lille, France.

Purpose: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection.

Methods: Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death.

Results: There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months).

Conclusions: This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.
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http://dx.doi.org/10.1007/s11060-021-03718-6DOI Listing
May 2021

Fluorescence guided surgery for pituitary adenomas.

J Neurooncol 2021 Feb 21;151(3):403-413. Epub 2021 Feb 21.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, Mount Sinai Downtown Union Square, 10 Union Square East, Suite 5E, New York, NY, 10003, USA.

Purpose: Resection of pituitary adenomas presents a number of unique challenges in neuro-oncology. The proximity of these lesions to key vascular and endocrine structures as well as the need to interpret neuronavigation in the context of shifting tumor position increases the complexity of the operation. More recently, substantial advances in fluorescence-guided surgery have been demonstrated to facilitate the identification of numerous tumor types and result in increased rates of complete resection and overall survival.

Methods: A review of the literature was performed, and data regarding the mechanism of the fluorescence agents, their administration, and intraoperative tumor visualization were extracted. Both in vitro and in vivo studies were assessed. The application of these agents to pituitary tumors, their advantages and limitations, as well as future directions are presented here.

Results: Numerous laboratory and clinical studies have described the use of 5-ALA, fluorescein, indocyanine green, and OTL38 in pituitary lesions. All of these drugs have been demonstrated to accumulate in tumor cells. Several studies have reported the successful use of the majority of the agents in inducing intraoperative tumor fluorescence. However, their sensitivity and specificity varies across the literature and between functioning and non-functioning adenomas.

Conclusions: At present, numerous studies have shown the feasibility and safety of these agents for pituitary adenomas. However, further research is needed to assess the applicability of fluorescence-guided surgery across different tumor subtypes as well as explore the relationship between their use and postoperative clinical outcomes.
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http://dx.doi.org/10.1007/s11060-020-03420-zDOI Listing
February 2021

Guidelines in the management of CNS tumors.

J Neurooncol 2021 Feb 21;151(3):345-359. Epub 2021 Feb 21.

Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.

Introduction: Evidence-based, clinical practice guidelines in the management of central nervous system tumors (CNS) continue to be developed and updated through the work of the Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS).

Methods: The guidelines are created using the most current and clinically relevant evidence using systematic methodologies, which classify available data and provide recommendations for clinical practice.

Conclusion: This update summarizes the Tumor Section Guidelines developed over the last five years for non-functioning pituitary adenomas, low grade gliomas, vestibular schwannomas, and metastatic brain tumors.
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http://dx.doi.org/10.1007/s11060-020-03530-8DOI Listing
February 2021

The Neurosurgeon's Armamentarium for Gliomas: An Update on Intraoperative Technologies to Improve Extent of Resection.

J Clin Med 2021 Jan 11;10(2). Epub 2021 Jan 11.

Department of Neurosurgery, Mount Sinai Health System, New York, NY 10029, USA.

Maximal safe resection is the standard of care in the neurosurgical treatment of high-grade gliomas. To aid surgeons in the operating room, adjuvant techniques and technologies centered around improving intraoperative visualization of tumor tissue have been developed. In this review, we will discuss the most advanced technologies, specifically fluorescence-guided surgery, intraoperative imaging, neuromonitoring modalities, and microscopic imaging techniques. The goal of these technologies is to improve detection of tumor tissue beyond what conventional microsurgery has permitted. We describe the various advances, the current state of the literature that have tested the utility of the different adjuvants in clinical practice, and future directions for improving intraoperative technologies.
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http://dx.doi.org/10.3390/jcm10020236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826675PMC
January 2021

Medical Student Publications in Neurosurgery: At Which U.S. Academic Institutions Do Medical Students Publish Most?

World Neurosurg 2021 03 16;147:181-189.e1. Epub 2020 Dec 16.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Neurosurgery, Mount Sinai Beth Israel, New York, New York, USA. Electronic address:

Background: The neurosurgery residency match is a competitive process. While medical research offers esteemed learning opportunities, productivity is closely evaluated by residency programs. Accordingly, students work diligently to make contributions on projects within their neurosurgery departments. The present study evaluated medical student research productivity for each of the 118 U.S. neurosurgery residency programs.

Methods: A retrospective review of publications for 118 neurosurgery programs from January 1, 2015, to April 1, 2020, was performed. The primary outcome was any publication with a medical student as the first author. Secondary outcomes included number of faculty in each department, department region, and medical school ranking. The number of student first author publications was compared among programs, regions, and medical schools.

Results: Mean numbers of medical student first author publications and faculty members per institution were 16.27 and 14.46, respectively. The top 3 neurosurgery departments with the greatest number of student first author publications were Johns Hopkins University, Brigham and Women's Hospital, and University of California, San Francisco. Salient findings included a positive correlation between the number of medical student first author publications from a neurosurgery department and the number of departmental faculty (P < 0.001, R = 0.69). Additionally, the mean number of first author medical student publications at the top 30 programs was higher than the mean for the remaining programs (P < 0.0001).

Conclusions: This study is the first to evaluate neurosurgery medical student productivity in North America. By systematizing first authorships, incoming students who desire to pursue neurosurgery can be informed of institutions with student involvement, and departments that use medical student expertise can be recognized.
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http://dx.doi.org/10.1016/j.wneu.2020.12.045DOI Listing
March 2021

Orbital invasion by Esthesioneuroblastoma: a comparative case series and review of literature.

Orbit 2020 Dec 14:1-14. Epub 2020 Dec 14.

Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

To review the current literature on esthesioneuroblastoma (ENB) as it pertains to clinical features, grading systems, treatment options, and survival.: A literature search in PubMed was performed to include all articles published in English with orbit involving ENB. Only articles that included each patient's demographics, tumor stage, treatment, or survival were included. A total of 22 articles with 104 patients were considered for this literature review. We also present five cases of ENB, all encountered in our health system, between 2010 and 2020.: The median age of diagnosis of orbit involving ENB was 44.5 years. Males were more likely affected than females at 72.9%. Common presenting ocular symptoms were visual change (38.1%), periorbital pain (33.3%), and diplopia (14.3%). Common clinical exam findings were proptosis (47.6%), extraocular movement deficit (23.8%), and periorbital edema (19.0%). Twenty-seven patients (77.1%) received surgery, 22 patients (62.9%) received chemotherapy, and 30 patients (85.7%) received radiation therapy as part of their treatment. Median duration of survival was 124.0 months and 5-year overall survival (OS) was 67.1%. Hyams, Kadish, and Dulguerov T-staging showed inconsistent survival prognosis while orbital invasion and lymph node metastasis had worse outcomes. Our five cases exhibited the spectrum of disease processes evidenced above, with four involving the orbit.: ENB is a rare sinonasal tumor that can invade the orbit. Because of its rarity, no single staging system appears superior. Resection with radiation therapy has superior survival results while the benefits of chemotherapy are currently unknown.
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http://dx.doi.org/10.1080/01676830.2020.1852262DOI Listing
December 2020

Akaluc bioluminescence offers superior sensitivity to track in vivo glioma expansion.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa134. Epub 2020 Oct 10.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Background: Longitudinal tracking of tumor growth using noninvasive bioluminescence imaging (BLI) is a key approach for studies of in vivo cancer models, with particular relevance for investigations of malignant gliomas in rodent intracranial transplant paradigms. Akaluciferase (Akaluc) is a new BLI system with higher signal strength than standard firefly luciferase (Fluc). Here, we establish Akaluc BLI as a sensitive method for in vivo tracking of glioma expansion.

Methods: We engineered a lentiviral vector for expression of Akaluc in high-grade glioma cell lines, including patient-derived glioma stem cell (GSC) lines. Akaluc-expressing glioma cells were compared to matching cells expressing Fluc in both in vitro and in vivo BLI assays. We also conducted proof-of-principle BLI studies with intracranial transplant cohorts receiving chemoradiation therapy.

Results: Akaluc-expressing glioma cells produced more than 10 times higher BLI signals than Fluc-expressing counterparts when examined in vitro, and more than 100-fold higher signals when compared to Fluc-expressing counterparts in intracranial transplant models in vivo. The high sensitivity of Akaluc permitted detection of intracranial glioma transplants starting as early as 4 h after implantation and with as little as 5000 transplanted cells. The sensitivity of the system allowed us to follow engraftment and expansion of intracranial transplants of GSC lines. Akaluc was also robust for sensitive detection of in vivo tumor regression after therapy and subsequent relapse.

Conclusion: Akaluc BLI offers superior sensitivity for in vivo tracking of glioma in the intracranial transplant paradigm, facilitating sensitive approaches for the study of glioma growth and response to therapy.
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http://dx.doi.org/10.1093/noajnl/vdaa134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680182PMC
October 2020

Use of Intraoperative Fluorophores.

Neurosurg Clin N Am 2021 Jan 5;32(1):55-64. Epub 2020 Nov 5.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA; Department of Neurosurgery, Mount Sinai Beth Israel, New York, NY, USA. Electronic address:

Fluorescence-guided surgery provides surgeons with improved visualization of tumor tissue in the operating room to allow for maximal safe resection of brain tumors. Multiple fluorescent agents have been studied for fluorescence-guided surgery. Both nontargeted and targeted fluorescent agents are currently being used for glioblastoma multiforme visualization and resection. Fluorescence detection in the visible light or near infrared spectrum is possible. Visualization device advancements have permitted greater detection of fluorescence down to the cellular level, which may provide even greater ability for the neurosurgeon to resect tumors.
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http://dx.doi.org/10.1016/j.nec.2020.08.001DOI Listing
January 2021

Third Ventricle Cavernous Malformation and Obstructive Hydrocephalus Thought to Be a Colloid Cyst.

World Neurosurg 2021 01 1;145:315-319. Epub 2020 Oct 1.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Background: Third ventricle cavernous malformations (CMs) associated with ventriculomegaly and obstructive hydrocephalus are quite rare in patients. Preoperative surgical planning can be challenging due to the lesion's non-specific appearance on CT and magnetic resonance imaging that can mimic other intraventricular pathologies, such as a colloid cyst. Management of these lesions can be varied in the setting of obstructive hydrocephalus.

Case Description: The patient is a 78-year-old woman who first presented to her primary care provider with balance difficulties and inability to ambulate on her own. She also had bladder incontinence and progressive, severe headaches. Imaging of the brain demonstrated entrapment of the right lateral ventricle and obstructive hydrocephalus due to a lesion in the third ventricle obstructing the right foramen of Monro, thought to be a colloid cyst. A right frontal neuroendoscopic approach with direct visualization, however, confirmed a third ventricle CM. A septal pellucidum fenestration was performed to restore cerebrospinal fluid communication and no resection of the lesion was performed. The patient recovered well after the operation and at clinical follow-up reported no headaches and was walking well without a walker and with no neurological deficits.

Conclusions: A third ventricle CM was discovered after a neuroendoscopic approach for resection of a presumed colloid cyst in a patient with obstructive hydrocephalus. A neuroendoscopic septostomy was performed to treat the obstructive hydrocephalus and no resection was attempted. The patient suffered no complications and is at her neurologic baseline with no deficits.
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http://dx.doi.org/10.1016/j.wneu.2020.09.136DOI Listing
January 2021

The Role of Prophylactic Intraventricular Antibiotics in Reducing the Incidence of Infection and Revision Surgery in Pediatric Patients Undergoing Shunt Placement.

Neurosurgery 2021 01;88(2):301-305

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, New York.

Background: Ventriculoperitoneal shunt placement remains the primary treatment modality for children with hydrocephalus. However, morbidity and revision surgery secondary to infection remains high, even while using antibiotic-impregnated shunts.

Objective: To determine whether intraoperative injection of antibiotics is independently associated with reduced rates of infection and revision surgery in children undergoing shunt placement.

Methods: This is an analysis of a prospectively collected, multicenter, shunt-specific neurosurgical registry consisting of data from over 100 hospitals collected between 2016 and 2017. All patients under 18 yr of age undergoing first-time shunt placement for the definitive treatment of hydrocephalus were included. The primary exposure of interest was injection of intraventricular antibiotics into the shunt catheter following shunt placement and prior to closure. The use of additional surgical adjuncts, such as antibiotic-impregnated shunts, stereotactic guidance, and endoscopy was collected. The primary outcome metric was the need for additional intervention because of an infection.

Results: A total of 2007 pediatric patients undergoing shunt placement for hydrocephalus were identified. Postoperatively, 97 (4.8%) patients had additional intervention secondary to infection. In a multivariable regression model controlling for patient characteristics, etiology of hydrocephalus, prior temporizing measures, and placement of an antibiotic-impregnated shunt, injection of intraventricular antibiotics was associated with a significant reduction in postoperative infections (odds ratio = 0.29, 95% CI: 0.04-0.89, P = .038). Of those receiving intraventricular antibiotics, only 2 (0.38%) went on to undergo re-intervention due to infection.

Conclusion: These data suggest that for this select group of patients, use of intraventricular antibiotics was associated with decreased rates of re-intervention secondary to infection.
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http://dx.doi.org/10.1093/neuros/nyaa413DOI Listing
January 2021

Spinal cord injury in the United States Army Special Forces.

J Neurosurg Spine 2020 Sep 25:1-7. Epub 2020 Sep 25.

3Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio.

Objective: Spinal cord injury (SCI) is an area of key interest in military medicine but has not been studied among the US Army Special Forces (SF), the most elite group of US soldiers. SF soldiers make up a disproportionate 60% of all Special Operations casualties. The objective of this study was to better understand SCI incidence in the SF, its mechanisms of acquisition, and potential areas for intervention by addressing key issues pertaining to protective equipment and body armor use.

Methods: An electronic survey questionnaire was formulated with the close collaboration of US board-certified neurosurgeons from the Mount Sinai Hospital and Cleveland Clinic Departments of Neurosurgery, retired military personnel of the SF, and operational staff of the Green Beret Foundation. The survey was sent to approximately 6000 SF soldiers to understand SCI diagnosis and its associations with various health and military variables.

Results: The response rate was 8.2%. Among the 492 respondents, 94 (19.1%) self-reported an SCI diagnosis. An airborne operation was the most commonly attributed cause (54.8%). Moreover, 87.1% of SF soldiers reported wearing headgear at the time of injury, but only 36.6% reported wearing body armor, even though body armor use has significantly increased in post-9/11 SF soldiers compared with that in their pre-9/11 counterparts. SCI was significantly associated with traumatic brain injury, arthritis, low sperm count, low testosterone, erectile dysfunction, tinnitus, hyperacusis, sleep apnea, posttraumatic stress disorder, major depressive disorder, and generalized anxiety disorder. Only 16.5% of SF soldiers diagnosed with SCI had been rescued via medical evacuation (medevac) for treatment.

Conclusions: A high number of SF soldiers self-reported an SCI diagnosis. Airborne operations landings were the leading cause of SCI, which coincided with warfare tactics employed during the Persian Gulf War, Operation Iraqi Freedom, and other conflicts. A majority of SCIs occurred while wearing headgear and no body armor, suggesting the need for improvements in protective equipment use and design. The low rate of medevac rescue for these injuries may suggest that medical rescue was not attainable at the time or that certain SCIs were deemed minor at the time of injury.
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http://dx.doi.org/10.3171/2020.7.SPINE20804DOI Listing
September 2020

Hyperthermia treatment advances for brain tumors.

Int J Hyperthermia 2020 07;37(2):3-19

Brain Tumor Nanotechnology Laboratory, Department of Neurosurgery, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Hyperthermia therapy (HT) of cancer is a well-known treatment approach. With the advent of new technologies, HT approaches are now important for the treatment of brain tumors. We review current clinical applications of HT in neuro-oncology and ongoing preclinical research aiming to advance HT approaches to clinical practice. Laser interstitial thermal therapy (LITT) is currently the most widely utilized thermal ablation approach in clinical practice mainly for the treatment of recurrent or deep-seated tumors in the brain. Magnetic hyperthermia therapy (MHT), which relies on the use of magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs), is a new quite promising HT treatment approach for brain tumors. Initial MHT clinical studies in combination with fractionated radiation therapy (RT) in patients have been completed in Europe with encouraging results. Another combination treatment with HT that warrants further investigation is immunotherapy. HT approaches for brain tumors will continue to a play an important role in neuro-oncology.
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http://dx.doi.org/10.1080/02656736.2020.1772512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756245PMC
July 2020

Postoperative outcomes following glioblastoma resection using a robot-assisted digital surgical exoscope: a case series.

J Neurooncol 2020 Jul 9;148(3):519-527. Epub 2020 Jun 9.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, New York, NY, USA.

Introduction: Maximal extent of resection (EOR) of glioblastoma (GBM) is associated with greater progression free survival (PFS) and improved patient outcomes. Recently, a novel surgical system has been developed that includes a 2D, robotically-controlled exoscope and brain tractography display. The purpose of this study was to assess outcomes in a series of patients with GBM undergoing resections using this surgical exoscope.

Methods: A retrospective review was conducted for robotic exoscope assisted GBM resections between 2017 and 2019. EOR was computed from volumetric analyses of pre- and post-operative MRIs. Demographics, pathology/MGMT status, imaging, treatment, and outcomes data were collected. The relationship between these perioperative variables and discharge disposition as well as progression-free survival (PFS) was explored.

Results: A total of 26 patients with GBM (median age = 57 years) met inclusion criteria, comprising a total of 28 cases. Of these, 22 (79%) tumors were in eloquent regions, most commonly in the frontal lobe (14 cases, 50%). The median pre- and post-operative volumes were 24.0 cc and 1.3 cc, respectively. The median extent of resection for the cohort was 94.8%, with 86% achieving 6-month PFS. The most common neurological complication was a motor deficit followed by sensory loss, while 8 patients (29%) were symptom-free.

Conclusions: The robotic exoscope is safe and effective for patients undergoing GBM surgery, with a majority achieving large-volume resections. These patients experienced complication profiles similar to those undergoing treatment with the traditional microscope. Further studies are needed to assess direct comparisons between exoscope and microscope-assisted GBM resection.
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http://dx.doi.org/10.1007/s11060-020-03543-3DOI Listing
July 2020

Neurosurgical management of brain and spine tumors in the COVID-19 era: an institutional experience from the epicenter of the pandemic.

J Neurooncol 2020 Jun 5;148(2):211-219. Epub 2020 May 5.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital, 1468 Madison Ave., New York, NY, USA.

The challenges of neurosurgical patient management and surgical decision-making during the 2019-2020 COVID-19 worldwide pandemic are immense and never-before-seen in our generation of neurosurgeons. In this case-based formatted report, we present the Mount Sinai Hospital (New York, NY) Department of Neurosurgery institutional experience in the epicenter of the pandemic and the guiding principles for our current management of intracranial, skull base, and spine tumors. The detailed explanations of our surgical reasoning for each tumor case is tailored to assist neurosurgeons across the United States as they face these complex operative decisions put forth by the realities of the pandemic.
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http://dx.doi.org/10.1007/s11060-020-03523-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200051PMC
June 2020

Dissecting the default mode network: direct structural evidence on the morphology and axonal connectivity of the fifth component of the cingulum bundle.

J Neurosurg 2020 Apr 24;134(3):1334-1345. Epub 2020 Apr 24.

1Athens Microneurosurgery Laboratory, Evangelismos Hospital, Athens.

Objective: Although a growing body of data support the functional connectivity between the precuneus and the medial temporal lobe during states of resting consciousness as well as during a diverse array of higher-order functions, direct structural evidence on this subcortical circuitry is scarce. Here, the authors investigate the very existence, anatomical consistency, morphology, and spatial relationships of the cingulum bundle V (CB-V), a fiber tract that has been reported to reside close to the inferior arm of the cingulum (CingI).

Methods: Fifteen normal, formalin-fixed cerebral hemispheres from adults were treated with Klingler's method and subsequently investigated through the fiber microdissection technique in a medial to lateral direction.

Results: A distinct group of fibers is invariably identified in the subcortical territory of the posteromedial cortex, connecting the precuneus and the medial temporal lobe. This tract follows the trajectory of the parietooccipital sulcus in a close spatial relationship with the CingI and the sledge runner fasciculus. It extends inferiorly to the parahippocampal place area and retrosplenial complex area, followed by a lateral curve to terminate toward the fusiform face area (Brodmann area [BA] 37) and lateral piriform area (BA35). Taking into account the aforementioned subcortical architecture, the CB-V allegedly participates as a major subcortical stream within the default mode network, possibly subserving the transfer of multimodal cues relevant to visuospatial, facial, and mnemonic information to the precuneal hub. Although robust clinical evidence on the functional role of this stream is lacking, the modern neurosurgeon should be aware of this tract when manipulating cerebral areas en route to lesions residing in or around the ventricular trigone.

Conclusions: Through the fiber microdissection technique, the authors were able to provide original, direct structural evidence on the existence, morphology, axonal connectivity, and correlative anatomy of what proved to be a discrete white matter pathway, previously described as the CB-V, connecting the precuneus and medial temporal lobe.
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http://dx.doi.org/10.3171/2020.2.JNS193177DOI Listing
April 2020

Laser Ablation of Abnormal Neurological Tissue Using Robotic NeuroBlate System (LAANTERN): 12-Month Outcomes and Quality of Life After Brain Tumor Ablation.

Neurosurgery 2020 09;87(3):E338-E346

Department of Neurosurgery, Washington University, St. Louis, Missouri.

Background: Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality-of-life (QoL) data.

Objective: To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms.

Methods: Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur.

Results: A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors.

Conclusion: Results from the ongoing LAANTERN registry demonstrate that LITT stabilizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real-world registry and comparative to published literature.
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http://dx.doi.org/10.1093/neuros/nyaa071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534487PMC
September 2020

Specific causes and predictors of readmissions following acute and chronic subdural hematoma evacuation.

J Clin Neurosci 2020 May 31;75:35-39. Epub 2020 Mar 31.

Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, Mount Sinai Health System, USA; Department of Neurosurgery, Icahn School of Medicine, Mount Sinai Beth Israel, Mount Sinai Health System, USA. Electronic address:

Patients treated with craniotomy for subdural hematoma (SDH) evacuation have a higher readmission incidence when compared to other neurosurgical patients. Factors predictive of readmission following craniotomy for SDH are incompletely understood. The National Surgical Quality Improvement (NSQIP) database was queried for all patients treated by craniotomy for SDH of any etiology (e.g. acute, chronic, spontaneous, traumatic) during the study period (2012-2014). Patients requiring repeat hospitalization within 30 days of surgery were identified and classified by reason for readmission. Binary logistic regression analysis was used to identify predictors of readmission. 1024 patients met inclusion criteria, among whom 109 (10.6%) were readmitted within 30 days. The most common causes of readmission were recurrent SDH (n = 27; 33.3%), seizure (n = 8; 9.9%), new neurological deficit (n = 6; 7.4%), stroke (n = 6; 7.4%), and altered mental status (AMS) (n = 6; 7.4%). Multivariable modeling identified hypertension requiring medication (OR = 2.78, P = 0.013) and abnormal INR (OR = 2.66, P = 0.035) as significantly associated with readmission following chronic SDH, while postoperative UTI (OR = 3.64, P = 0.01) and stroke (OR = 4.86, P = 0.018) were significant predictors of readmission following acute SDH. Readmission was associated with recurrent hemorrhage after chronic/spontaneous SDH, while seizures, AMS, and neurological deficits drove readmissions after acute/traumatic SDH. Careful management of anticoagulation and antihypertensive medications may be helpful in reducing the risk of readmission following craniotomy for chronic SDH.
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http://dx.doi.org/10.1016/j.jocn.2020.03.042DOI Listing
May 2020

Patents and Innovation Among Neurosurgeons from the American Association of Neurological Surgeons.

Cureus 2020 Feb 18;12(2):e7031. Epub 2020 Feb 18.

Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, USA.

Objective Neurosurgeons have taken on the role of innovators, continuing to move the field forward over the centuries. More recently, innovation has taken the form of new technological devices and therapeutics, which require patenting. The aim of this study is to identify major areas of innovation in the field of neurosurgery by evaluating patent records. Methods This study quantifies the number of patents the American Association of Neurological Surgeons (AANS) neurosurgeons hold across different subspecialties. The United States Patent and Trademark Office (USPTO) patent database was queried using the names of 7,293 AANS members who filed patents between 1976 and 2019. Results A total of 346 (4.7%) AANS neurosurgeons hold a total of 1,025 patents. The number of patents held by each neurosurgeon ranged from one to 109. The areas that patents were filed under include cellular and genetic science (40), drug delivery (45), image guidance (82), neuromodulation (52), pain (7), peripheral nerve stimulation (24), spine (398), surgical devices (148), trauma (16), tumor (78), vascular (67), and other (68). No patents were filed under pediatrics (0). The fields with the greatest number of filed patents are spine, instruments/devices, and image guidance. Conclusion Given the technical nature of the field of neurosurgery, instruments and devices that improve localization, visualization, targeting, and spinal reconstruction are often in demand. Furthermore, since the rates of spinal procedures and implants continue to increase, higher patenting may be motivated by the opportunity to develop new products that can result in royalty payments to neurosurgeons. The advent of new technologies undoubtedly continues to push the field of neurosurgery forward.
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http://dx.doi.org/10.7759/cureus.7031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082787PMC
February 2020

Multiparametric MRI for early identification of therapeutic response in recurrent glioblastoma treated with immune checkpoint inhibitors.

Neuro Oncol 2020 11;22(11):1658-1666

UCLA Brain Tumor Imaging Laboratory, Center for Computer Vision and Imaging Biomarkers, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.

Background: Physiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM.

Methods: Inclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), Ktrans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria.

Results: Out of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, Ktrans, Vp, and Ve were not indicative of treatment response within 6 months.

Conclusions: In patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment.

Key Points: • In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response.• Interval change in rADC can be used as an imaging biomarker to determine PFS6.• Interval change in MR perfusion and permeability measures do not suggest ICI treatment response.
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http://dx.doi.org/10.1093/neuonc/noaa066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846197PMC
November 2020

Repair of a Temporal Bone Encephalocele With the Surgical Exoscope.

Otol Neurotol 2020 04;41(4):561

Department of Otolaryngology Head and Neck Surgery, New York Eye and Ear Infirmary of Mount Sinai.

Objective: We describe our experience using the extracorporeal video microscope, the "exoscope" for repair of a temporal bone encephalocele.

Method: The patient is a 69-year-old male with a right temporal lobe encephalocele herniating through a tegmen defect. He underwent definitive tegmen defect repair and bipolar cauterization of the encephalocele. The authors elected for a combined transmastoid and transtemporal approach in order to isolate the tegmen defect and provide watertight repair. The Synaptive robotic BrightMatter (Toronto, ON) drive video exoscope monitor system was used for the entirety of the case including both the transmastoid approach and transtemporal craniotomy.

Results: No intraoperative complications were encountered during either the transmastoid (mastoidectomy) or transtemporal craniotomy. The authors were able to complete the entire case without abandonment of the exoscope in favor of the traditional binocular microscope. Advantages of this technology in clinical practice includes high-resolution three-dimensional visualization, increased degrees of freedom for exoscope adjustment, and reduced surgeon fatigue in a fixed, unnatural posture. Limitations include decreased depth perception and increased operative time.

Conclusion: The exoscope system is a safe and effective alternative or adjunct to the existing binocular operating microscope for lateral skull based procedures. The exoscope provides the surgeon with a comfortable, high-resolution visualization without compromising surgical exposure and patient safety.SDC video link: http://links.lww.com/MAO/A837.
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http://dx.doi.org/10.1097/MAO.0000000000002433DOI Listing
April 2020

Review of clinical trials in intraoperative molecular imaging during cancer surgery.

J Biomed Opt 2019 12;24(12):1-8

University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States.

Most solid cancers are treated by surgical resections to reduce the burden of disease. Surgeons often face the challenge of detecting small areas of residual neoplasm after resection or finding small primary tumors for the initial resection. Intraoperative molecular imaging (IMI) is an emerging technology with the potential to dramatically improve cancer surgery operations by allowing surgeons to better visualize areas of neoplasm using fluorescence imaging. Over the last two years, two molecular optical contrast agents received U.S. Food and Drug Administration approval, and several more drugs are now on the horizon. Thus a conference was organized at the University of Pennsylvania to bring together oncologic surgeons from different specialties to discuss the current clinical status of IMI trials with a specific focus on phase 2 and phase 3 studies. In addition, phase 1 and experimental trials were also discussed briefly, to highlight other novel techniques. Our review summarizes the discussions from the conference and delves into the types of cancers discussed, different contrast agents in human trials, and the clinical value being studied.
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http://dx.doi.org/10.1117/1.JBO.24.12.120901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005471PMC
December 2019
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