High-Dose Fluorescein Reveals Unusual Confocal Endomicroscope Imaging of Low-Grade Glioma.

Background: Fluorescence-guided brain tumor surgery using fluorescein sodium (FNa) for contrast is effective in high-grade gliomas. However, the effectiveness of this technique for visualizing noncontrast-enhancing and low-grade gliomas is unknown. This report is the first documented case of the concurrent use of wide-field fluorescence-guided surgery and confocal laser endomicroscopy (CLE) with high-dose FNa (40 mg/kg) for intraoperative visualization of tumor tissue cellularity in a nonenhancing glioma. Case Description: A patient underwent fluorescence-guided surgery for a left frontal lobe mass without contrast enhancement on magnetic resonance imaging. The patient received 40 mg/kg FNa intravenously at the induction of anesthesia. Surgery was performed under visualization with a Yellow 560 filter and white-light wide-field imaging. Intraoperative CLE produced high-quality images of the lesion 1.5 h after FNa injection. Frozen-section analysis demonstrated findings comparable to those of intraoperative CLE visualization and consistent with World Health Organization (WHO) glioma grades II-III. The patient recovered without complications. Analysis of the permanent histologic sections identified the tumor as an anaplastic oligodendroglioma, IDH-mutant, 1p/19q co-deleted, consistent with WHO grade III because of discrete foci of hypercellularity and increased mitotic figures, but large regions of the lesion were low grade. Conclusions: The use of high-dose FNa in this patient with a nonenhancing borderline low-grade/high-grade glioma produced actionable wide-field fluorescence imaging using the operating microscope and improved CLE visualization of tumor cellularity. Higher doses of FNa for intraoperative CLE imaging and possible simultaneous wide-field fluorescence surgical guidance in nonenhancing gliomas merit further investigation.

Acridine Orange: A Review of Novel Applications for Surgical Cancer Imaging and Therapy.

Introduction: Acridine orange (AO) was first extracted from coal tar in the late nineteenth century and was used as a fluorescent dye. In this paper, we review emergent research about novel applications of AO for fluorescence surgery and cancer therapy. Materials and methods: We performed a systematic search in the MEDLINE, PubMed, Cochrane library, Google Scholar, Embase, Web of Science, and Scopus database using combinations of the term "acridine orange" with the following: "surgical oncology," "neuropathology," "microsurgery," "intraoperative fluorescence," "confocal microscopy," "pathology," "endomicroscopy," "guidance," "fluorescence guidance," "oncology," "surgery," "neurooncology," and "photodynamic therapy." Peer-reviewed articles published in English were included in this review. We have also scanned references for relevant articles. Results: We have reviewed studies on the various application of AO in microscopy, endomicroscopy, intraoperative fluorescence guidance, photodynamic therapy, sonodynamic therapy, radiodynamic therapy. Conclusion: Although the number of studies on the clinical use of AO is limited, pilot studies have demonstrated the safety and feasibility of its application as an intraoperative fluorescent dye and as a novel photo- and radio-sensitizator. Further clinical studies are necessary to more definitively assess the clinical benefit AO-based fluorescence guidance, therapy for sarcomas, and to establish feasibility of this new approach for the treatment of other tumor types.

Endoscopically Assisted Targeted Keyhole Retrosigmoid Approaches for Microvascular Decompression: Quantitative Anatomic Study.

OBJECTIVE: We describe and quantitatively assess minimally invasive keyhole retrosigmoid approaches targeted to the upper, middle, and lower cranial nerve (CN) complexes of the cerebellopontine angle (CPA). METHODS: Anatomic dissections were performed on 10 sides of 5 fixed, silicone-injected cadaver heads. Surgical views through various trajectories were assessed in endoscopic videos and 3-dimensional (3D) interactive virtual reality microscope views. Surgical freedom and angles of attack to the proximal and distal areas of CN complexes of the CPA were compared among upper and lower keyholes and conventional retrosigmoid craniotomy using neuronavigation. RESULTS: Compared with keyholes, the conventional approach had superior surgical freedom to most areas except for the distal CN V, the root of CN VII, and the root of CN IX, where differences were not significant. The conventional retrosigmoid approach provided a larger horizontal angle of attack than either the upper or lower keyholes for all selected areas; however, the vertical angles of attack were not different. Splitting the petrosal fissure resulted in a significant increase in the vertical angle of attack to the root zones of CNs V and VII but not to the distal areas of these nerves or CN IX. Illustrative cases of endoscope-assisted keyhole retrosigmoid approaches for the treatment of trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia are presented. CONCLUSIONS: Targeted keyhole retrosigmoid approaches require detailed understanding of the 3D anatomy of the CPA to create appropriate locations of corridors, including skin incisions and keyholes. Endoscope assistance complements the standard microsurgical technique by maximizing the visualization and identification of the delicate neurovascular structures.

Systematic Review of Factors Influencing Surgical Performance: Practical Recommendations for Microsurgical Procedures in Neurosurgery.

BACKGROUND: Microneurosurgical techniques involve complex manual skills and hand-eye coordination that require substantial training. Many factors affect microneurosurgical skills. The goal of this study was to use a systematic evidence-based approach to analyze the quality of evidence for intrinsic and extrinsic factors that influence microneurosurgical performance and to make weighted practical recommendations. METHODS: A literature search of factors that may affect microsurgical performance was conducted using PubMed and Embase. The criteria for inclusion were established in accordance with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) statement. RESULTS: Forty-eight studies were included in the analysis. Most of the studies used surgeons as participants. Most used endoscopic surgery simulators to assess skills, and only 12 studies focused on microsurgery. This review provides 18 practical recommendations based on a systematic literature analysis of the following 8 domains: 1) listening to music before and during microsurgery, 2) caffeine consumption, 3) ß-blocker use, 4) physical exercise, 5) sleep deprivation, 6) alcohol consumption before performing surgery, 7) duration of the operation, and 8) the ergonomic position of the surgeon. CONCLUSIONS: Despite the clear value of determining the effects of various factors on surgical performance, the available body of literature is limited, and it is not possible to determine standards for each surgical field. These recommendations may be used by neurosurgical trainees and practicing neurosurgeons to improve microsurgical performance and acquisition of microsurgical skills. Randomized studies assessing the factors that influence microsurgical performance are required.