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.

Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients, as well as future applications of recent laboratory and translational studies. Methods: Review of the literature. Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-ALA and ICG), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine can be used for rapid tumor detection and pathological tissue examination. Other emerging agents such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed. Conclusion: We are standing on the doorstep of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/β-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.