Clinical, Pathological, and Molecular Characteristics of Diffuse Spinal Cord Gliomas
Garcia, Mekka R; Feng, Yang; Vasudevaraja, Varshini; Galbraith, Kristyn; Serrano, Jonathan; Thomas, Cheddhi; Radmanesh, Alireza; Hidalgo, Eveline T; Harter, David H; Allen, Jeffrey C; Gardner, Sharon L; Osorio, Diana S; William, Christopher M; Zagzag, David; BouÃ©, Daniel R; Snuderl, Matija
Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64â€‰years (range 1-82) and the overall median survival was 397â€‰days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (pâ€‰=â€‰0.366) or radiation (pâ€‰=â€‰0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.
Clinical value of DNA methylation in practice: A prospective molecular neuropathology study [Meeting Abstract]
Galbraith, Kristyn; Shen, Guomiao; Serrano, Jonathan; Vasudevaraja, Varshini; Tran, Ivy; Movahed-Ezazi, Misha; Harter, David; Hidalgo, Eveline; Wisoff, Jeffrey; Orringer, Daniel; Placantonakis, Dimitris; Gardner, Sharon; William, Christopher; Zagzag, David; Allen, Jeffrey; Sulman, Erik; Golfinos, John; Snuderl, Matija
Perioperative team communication through a mobile app for improving coordination and education in neurosurgery cases
Ber, Roee; London, Dennis; Senan, Samya; Youssefi, Yasmin; Harter, David H; Golfinos, John G; Pacione, Donato
OBJECTIVE:Miscommunication and poor coordination among surgical teams are known causes of preventable medical harms and operating room inefficiencies and inhibit surgical training. Technology may help overcome these challenges. This study used the personal experience of one of the authors as a former Air Force F-15 pilot to design a combat aviation pre- and postoperative communication workflow in the neurosurgery department and tested its effect on safety, efficiency, and education. The authors hypothesized that the adoption of this workflow through a tailored technological platform will increase compliance and improve the chances of sustainability. METHODS:Data were prospectively collected from neurosurgery cases before (January-May 2020) and after (June-October 2020) implementation of this workflow. Briefing and debriefing were executed using a custom mobile platform and were defined as nonmandatory for all participants. All faculty and residents who operated at NYU Langone Medical Center (Tisch campus) during the intervention period were enrolled on the platform. Primary outcomes were morbidity and mortality per the department's criteria, and intraoperative last-minute requests as reported by operating room staff in a double-blinded fashion. Secondary outcomes were user responses on the subjective questionnaires. RESULTS:Data were collected from 637 and 893 cases during the preintervention and intervention periods, respectively. The average briefing rates for residents and surgeons were 71% and 81%, respectively, and the average debriefing rates for residents and surgeons were 67% and 88%. There was no significant difference in preoperative risk score between the preintervention and intervention patient populations (p = 0.24). The rate of intraoperative last-minute requests significantly decreased from 16.6% (35/211) to 10.5% (35/334, p = 0.048). There was no significant change in morbidity and mortality between the preintervention and intervention periods. On subjective questionnaires there was a statistically significant improvement in safety, efficiency, and educational aspects of the cases during the intervention period. CONCLUSIONS:Implementation of aviation-like structured team communication practices in the neurosurgery department through a technological platform improved education and communication between surgical teams and led to a reduction in last-minute surgical requests that could impact costs.
Dural Tear During Thoracic Laminectomy Using Craniotome With Footplate Attachment
Houten, John K; Harter, David H; Schwartz, Amit Y
Laminectomy can be accomplished using the craniotome with a footplate attachment, and the technique has been advanced as a superior alternative to using a high-speed drill-driven burr and Kerrison rongeurs. Laminectomy can be accomplished more rapidly and with less bone destruction, an advantage when planning laminoplasty. There is, however, scant literature describing complications of dural laceration using this technique. A 48-year-old male underwent T7-10 laminectomy for resection of an intramedullary spinal cord tumor. During the upward cut of the hemi-lamina at T7-9, a dural laceration occurred that proved not amenable to direct suture closure. The dural was closed with a dural patch placed along the inner surface of the dura and a fat graft on the outer surface with adjunctive use of a lumbar drain. While the footplate laminectomy technique has merits touted in prior publications, including the ability to open the spinal canal quickly at numerous levels and an enhanced ability to achieve an osteoplastic laminoplasty, surgeons should be cognizant of the risk of associated dural laceration. We believe that it is important to emphasize that the initial placement of the lip of the footplate must be well-seated under the inferior aspect of the lowest lamina and over the ligamentum flavum and that the footplate should not be directed beyond the border of the laminae and facet, as this can result in dura and root injury.
Orbital Rosai-Dorfman disease initially diagnosed as IgG4-related disease: a case report
Iyengar, Nishanth S; Golub, Danielle; McQuinn, Michelle W; Hill, Travis; Tang, Karen; Gardner, Sharon L; Harter, David H; Sen, Chandranath; Staffenberg, David A; Thomas, Kristen; Elkin, Zachary; Belinsky, Irina; William, Christopher
Inflammatory orbital lesions include a broad list of diagnoses, many of them with overlapping clinical and radiographic features. They often present a diagnostic conundrum, even to the most experienced orbital specialist, thus placing considerable weight on surgical biopsy and histopathological analysis. However, histopathological diagnosis is also inherently challenging due to the rarity of these lesions and the overlaps in histologic appearance among distinct disease entities. We herein present the case of an adolescent male with a subacutely progressive orbital mass that generated a significant diagnostic dilemma. Early orbital biopsy was consistent with a benign fibro-inflammatory lesion, but corticosteroid therapy was ineffective in halting disease progression. After an initial substantial surgical debulking, histopathological analysis revealed several key features consistent with IgG4-related disease (IgG4-RD), a systemic fibro-inflammatory process typically accompanied by multifocal tumor-like lesions. Surprisingly, within months, there was clear evidence of clinical and radiographic disease progression despite second-line rituximab treatment, prompting a second surgical debulking. This final specimen displayed distinctive features of Rosai-Dorfman disease (RDD), a systemic inflammatory disease characterized by uncontrolled histiocytic proliferation. Interestingly, certain features of this re-excision specimen were still reminiscent of IgG4-RD, which not only reflects the difficulty in differentiating RDD from IgG4-RD in select cases, but also illustrates that these diagnoses may exist along a spectrum that likely reflects a common underlying pathogenetic mechanism. This case emphasizes the importance of surgical biopsy or resection and histopathological analysis in diagnosing-and, ultimately, treating-rare, systemic inflammatory diseases involving the orbit, and, furthermore, highlights the shared histopathological features between RDD and IgG4-RD.
Intra-reservoir administration of alteplase to treat a distal ventriculo-atrial shunt obstruction
Delavari, Nader; Mureb, Monica C; Yaun, Amanda; Wisoff, Jeffrey H; Harter, David H; Hidalgo, E Teresa
BACKGROUND:Ventriculoatrial shunts can be afflicted with distal malfunctions due to thrombus formation at the distal tip. Distal tip thrombus formation may occur more commonly in oncologic patients who are predisposed to hypercoagulability. CASE DESCRIPTION/METHODS:A patient who had a ventriculo-atrial shunt placed for leptomeningeal carcinomatosis presented with headaches and confusion and was found to have a partial distal shunt obstruction. Intra-reservoir administration of alteplase resulted in resolution of her symptoms. Nuclear medicine shunt patency test demonstrated restoration of distal flow. CONCLUSIONS:Intra-reservoir administration of alteplase can be a useful non-operative treatment strategy for ventriculo-atrial shunt malfunction. This strategy may be particularly useful in cases with higher peri-operative risk, such as patients with advanced metastatic cancer.
Intracranial Angiomatoid Fibrous Histiocytoma [Meeting Abstract]
Spino, Marissa; Delavari, Nader; Harter, David; Jour, George; Snuderl, Matija
Prospective feasibility and safety assessment of surgical biopsy for patients with newly diagnosed diffuse intrinsic pontine glioma
Gupta, Nalin; Goumnerova, Liliana C; Manley, Peter; Chi, Susan N; Neuberg, Donna; Puligandla, Maneka; Fangusaro, Jason; Goldman, Stewart; Tomita, Tadanori; Alden, Tord; DiPatri, Arthur; Rubin, Joshua B; Gauvain, Karen; Limbrick, David; Leonard, Jeffrey; Geyer, J Russel; Leary, Sarah; Browd, Samuel; Wang, Zhihong; Sood, Sandeep; Bendel, Anne; Nagib, Mahmoud; Gardner, Sharon; Karajannis, Matthias A; Harter, David; Ayyanar, Kanyalakshmi; Gump, William; Bowers, Daniel C; Weprin, Bradley; MacDonald, Tobey J; Aguilera, Dolly; Brahma, Barunashish; Robison, Nathan J; Kiehna, Erin; Krieger, Mark; Sandler, Eric; Aldana, Philipp; Khatib, Ziad; Ragheb, John; Bhatia, Sanjiv; Mueller, Sabine; Banerjee, Anu; Bredlau, Amy-Lee; Gururangan, Sri; Fuchs, Herbert; Cohen, Kenneth J; Jallo, George; Dorris, Kathleen; Handler, Michael; Comito, Melanie; Dias, Mark; Nazemi, Kellie; Baird, Lissa; Murray, Jeff; Lindeman, Neal; Hornick, Jason L; Malkin, Hayley; Sinai, Claire; Greenspan, Lianne; Wright, Karen D; Prados, Michael; Bandopadhayay, Pratiti; Ligon, Keith L; Kieran, Mark W
Background/UNASSIGNED:Diagnosis of diffuse intrinsic pontine glioma (DIPG) has relied on imaging studies, since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods/UNASSIGNED:Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG. Surgical biopsies were performed after enrollment and prior to definitive treatment. All subjects were treated with conventional external beam radiotherapy with bevacizumab, and then stratified to receive bevacizumab with erlotinib or temozolomide, both agents, or neither agent, based on O6-methylguanine-DNA methyltransferase status and epidermal growth factor receptor expression. Whole-genome sequencing and RNA sequencing were performed but not used for treatment assignment. Results/UNASSIGNED:Fifty-three patients were enrolled at 23 institutions, and 50 underwent biopsy. The median age was 6.4 years, with 24 male and 29 female subjects. Surgical biopsies were performed with a specified technique and no deaths were attributed to the procedure. Two subjects experienced grade 3 toxicities during the procedure (apnea, n = 1; hypertension, n = 1). One subject experienced a neurologic deficit (left hemiparesis) that did not fully recover. Of the 50 tumors biopsied, 46 provided sufficient tissue to perform the study assays (92%, two-stage exact binomial 90% CI: 83%-97%). Conclusions/UNASSIGNED:Surgical biopsy of DIPGs is technically feasible, associated with acceptable risks, and can provide biologic data that can inform treatment decisions.
Integrated Liquid Biopsy Analysis for Pediatric Brain Tumor Patients Using Detection of ctDNA and Circulating Tumor Cells [Meeting Abstract]
Zhu, Kaicen; Barnett, Katherine; Shen, Guomiao; Mohammed, Hussein; Panicucci-Roma, Tania; Serrano, Jonathan; Harter, David; Wisoff, Jeffrey; Yaun, Amanda; Wang, Shiyang; Gardner, Sharon; Snuderl, Matija
Automated cell enrichment and digital cell sorting using dielectrophoretic arrays for isolation of circulating tumor cells in pediatric brain tumor patients [Meeting Abstract]
Barnett, K; Zhu, K; Shen, G; Serrano, J; Harter, D; Wisoff, J; Yaun, A; Wang, S; Gardner, S; Snuderl, M
INTRODUCTION: Liquid biopsy has the potential to revolutionize diagnosis and management of cancer. In brain tumors, detection of cell free tumor DNA (ctDNA) and circulating tumor cells (CTC) is challenging due to low level of the circulating material. We present a novel workflow for detection and capture of CTCs. METHODS: Peripheral blood was obtained from five pediatric patients with astrocytoma (n=2), ependymoma (n=1), dysembryoplastic neuroepithelial tumor (n=1), and medulloblastoma (n=1) at initial resection (n=3) and relapse (n=2). Samples were enriched using the Clear-Bridge ClearCell FX1 system and the suspension stained with antibodies against CD56 and CD45. Samples were analyzed using Silicon Biosystems DEPArray to capture single and pooled CTCs. CTCs were identified by CD56 positivity, while leukocytes were positive for CD45 and NK cells double-positive for CD56 and CD45. RESULTS: CTCs were identified in all 5 patient samples. The number of CD56-positive cells isolated from each sample ranged from 1 to 25 (mean 9). The CD56-positive cells were on average 11.8 mum in diameter (range 9.0-15.7 mum), and CD45-positive cells were on average 10.8 mum in diameter (range 8.9-15.9 mum). Single CTCs and CTC pools are amenable to molecular analysis after whole genome amplification. CONCLUSION: We report a novel integrated workflow for capturing CTCs in pediatric patients with brain tumors. While rare, CTCs circulate in peripheral blood of patients with brain tumors regardless of their grade and are amenable for molecular analysis. This method has the potential to serve as a non-invasive diagnostic and monitoring method for pediatric brain tumors