Kevin Kwan

Primary solitary retro-clival amyloidoma

Background: Amyloidosis encompasses a group of disorders sharing the common feature of intercellular deposition of amyloid protein by several different pathogenetic mechanisms. Primary solitary amyloidosis, or amyloidoma, is a rare subset of amyloidosis in which amyloid deposition is focal and not secondary to a systemic process or plasma cell dyscrasia. Case Description: This 84-year-old female presented with history of multiple syncopal episodes, dysphagia, and ataxia. Motor strength was 3+/5 in the right upper extremity. Rheumatoid factor, cyclic citrullinated peptide (CCP), and anti-nuclear antibody (ANA) were normal. Serum and urine immune-electrophoresis detected no abnormal bands. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a non-enhancing soft-tissue mass extending from the retro-clivus to C2 posteriorly, eccentric to the right with severe mass effect on the upper cervical medullary junction. Endoscopic trans-nasal debulking of the retro-clival mass was performed with occiput to C5 posterior instrumentation for spinal stabilization. Conclusions: Primary solitary amyloidosis, unlike other forms of amyloidosis, has an excellent prognosis with local resection. Diagnosis requires special stains and a degree of suspicion for the disease. This is the first report to document an endoscopic trans-nasal approach for removal of a primary solitary amyloidosis of the retro-clivus. Management of vertebral amyloidoma involves aggressive local resection of the tumor when feasible and spine stabilization as the degree of tumor involvement mandates. Complete evaluation for the diagnosis of systemic amyloidosis is essential for the management and prognostication. Surgeons encountering such lesions must maintain high suspicion for this rare disease and advise pathologists accordingly to establish the correct diagnosis.

Lessons Learned Using a High-Definition 3-Dimensional Exoscope for Spinal Surgery

BACKGROUNDnThe operative microscope has significantly advanced modern neurosurgical spine surgery but continues to be limited by high costs, suboptimal optics, poor ergonomics, and difficulties with maneuverability. We believe the novel 4K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX), may improve the surgical corridor through advancements in illumination, ergonomics, magnification, and depth of field and has the potential to be utilized in neurosurgical education and training.nnnOBJECTIVEnTo evaluate the surgical potential of a novel 3D EX system in spinal surgery.nnnMETHODSnRetrospective analysis over 6 mo of all patients who have undergone spinal surgery at Northwell Health using the 3D EX. Nuances of surgical theater positioning, advantages/disadvantages of the EX and clinical sequelae of the patients were analyzed.nnnRESULTSnAll 10 patients who underwent spinal surgery utilizing the EX experienced excellent surgical and clinical outcomes without complications. The low-profile EX allowed for excellent operative corridors and instrument maneuverability. The large monitor also resulted in an immersive surgical experience, and gave team members the same 3D vision as the operator.nnnCONCLUSIONnThis study demonstrates the feasibility of utilizing the 3D 4K-HD EX system and highlights potential technical assets of this novel technology in regard to optics, ergonomics, and maneuverability. Further clinical research is needed to examine the clinical effectiveness of the EX system for different surgical approaches through quantitative methodology.

Local Immunotherapy for Malignancy: A Role for Brain Tumors?

Local Immunotherapy for Malignancy: A Role for Brain Tumors? Mounting evidence suggests that the immune system can be reprogrammed for cancer eradication. Utilization of personalized antigen-specific targets is limited due to the heterogenic nature of tumors. Programming pre-existing T-cells within the tumor microenvironment to recognize and attack cancer may be a more reliable and applicable immunotherapy treatment method for tumors. Commonly, T cells that recognize tumor antigens are often tipped toward immunosuppression in established tumors, with T cell inhibitory receptor activation rather than stimulatory receptor activation.1 In this novel paper, the authors focus on relieving the negative checkpoints and stimulation of activation pathways on T cells as a novel therapeutic technique.2 Sagiv-Barfi et al2 developed a new immunotherapy by directly injecting immune activating agents into the tumor, in situ vaccination, using the tumor and its immune reactive microenvironment as an antigen source. A screening strategy for candidate immune-stimulatory agents revealed unmethylated CG-enriched oligodeoxynucleotide (CpG), a Tolllike receptor 9 ligand, could induce the expression of OX40 on CD4 + T cells in the tumor microenvironment. OX40 is a costimulatory molecule of the TNFR superfamily, and notably with activation can promote T cell activation. Furthermore, they utilized an agonistic anti-OX40 antibody to provide a synergistic stimulus to elicit an antitumor immune response. The strategy was to implant the same syngeneic tumor at two separate sites in vivo, followed by injection of the test agents, CpG and OX40 antibody, locally in one of the tumor sites. Remarkably, they demonstrate in situ vaccination with a CpG induces OX40 expression in intratumoral CD4 + T cells, as shown by flow cytometry and positron emission tomography. This effect was reproduced in a patient with follicular lymphoma treated with low-dose radiation and intratumoral injection of CpG. The effects of CpG signal to T cells appear to be dependent on myeloid-derived cell communication, emphasizing the necessity of antigen-presenting cells in the local environment. Using an A20 B cell lymphoma model, they show that in situ vaccination of CpG and an agonistic OX 40 antibody resulted in regression of tumor at both local and distant tumor sites and required the presence of both CD4+ and CD8+ T cells. In situ vaccination was shown to not only be effective against transplanted syngeneic models of lymphoma, breast carcinoma, colon cancer, and melanoma but also in a genetically driven spontaneous model of breast cancer. They establish that the low doses of these agents work by triggering an immune response in the microenvironment of the injected site rather than by diffusion of the injected agents to distal sites. Mechanistically, it seems that the therapeutic effect of systemic in situ vaccination occurs through a combination of natural killer cell activation, Treg inhibition, Teff activation all at the treated tumor site.2 These preclinical studies provide a strong rationale for translation of combinatory usage of CpG with anti-OX40 antibodies from the bench to bedside. Clinically, CpG is being investigated for clinical trial use, either as a single agent or concomitantly with other therapeutic modalities for the treatment of lymphoma. Similarly, anti-OX40 antibody is being studied in early phase clinical trials for the treatment of lymphoma, carcinoma, sarcoma, and metastatic disease.2 The authors provide evidence for combination therapy using a TLR agonist and an OX-40 antibody to activate the T cell immune repertoire within the tumor microenvironment. It is feasible that this technique could be utilized for the treatment of brain tumors intraoperatively as the situ vaccination does not require prior knowledge of the tumor antigens. Furthermore, direct injection of the tumor, with low doses of these agents, can help avoid side effects from systemic administration.3 Another potential application would be to administer the in situ vaccine at the site of the primary tumor for those patients with intracranial metastatic disease in combination withmultimodality chemoradiation treatment.