Leptomeningeal dissemination in pediatric brain tumors

Leptomeningeal disease (LMD) in pediatric brain tumors (PBTs) is a poorly understood and categorized phenomenon. LMD incidence rates, as well as diagnosis, treatment, and screening practices, vary greatly depending on the primary tumor pathology. While LMD is encountered most frequently in medulloblastoma, reports of LMD have been described across a wide variety of PBT pathologies. LMD may be diagnosed simultaneously with the primary tumor, at time of recurrence, or as primary LMD without a primary intraparenchymal lesion. Dissemination and seeding of the cerebrospinal fluid (CSF) involves a modified invasion-metastasis cascade and is often the result of direct deposition of tumor cells into the CSF. Cells develop select environmental advantages to survive the harsh, nutrient poor and turbulent environment of the CSF and leptomeninges. Improved understanding of the molecular mechanisms that underlie LMD, along with improved diagnostic and treatment approaches, will help the prognosis of children affected by primary brain tumors

Novel Technique for C1–2 Interlaminar Arthrodesis Utilizing a Modified Sonntag Loop-Suture Graft With Posterior C1–2 Fixation

Objective Conventional techniques for atlantoaxial fixation and fusion typically pass cables or wires underneath C1 lamina to secure the bone graft between the posterior elements of C1–2, which leads to complications such as cerebrospinal fluid (CSF) leak and neurological injury. With the evolution of fixation hardware, we propose a novel C1–2 fixation technique that avoids the morbidity and complications associated with sublaminar cables and wires. Methods This technique entails wedging and anchoring a structural iliac crest graft between C1 and C2 for interlaminar arthrodesis and securing it using a 0-Prolene suture at the time of C1 lateral mass and C2 pars interarticularis screw fixation. Results We identified 32 patients who underwent surgery for atlantoaxial with our technique. A 60% improvement in pain-related disability from preoperative baseline was demonstrated by Neck Disability Index (p<0.001). There were no neurologic deficits. Complications included 2 patients CSF leaks related to presenting trauma, 1 patient with surgical site infection, and 1 patient with transient dysphagia. The rate of radiographic atlantoaxial fusion was 96.8% at 6 months, with no evidence of instrumentation failure, graft dislodgement, or graft related complications. Conclusion We demonstrate a novel technique for C1–2 arthrodesis that is a safe and effective option for atlantoaxial fusion

Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus

Tumor interferon (IFN) signaling promotes PD-L1 expression to suppress T cell-mediated immunosurveillance. We identify the IFN-stimulated non-coding RNA 1 (INCR1) as a long noncoding RNA (lncRNA) transcribed from the PD-L1 locus and show that INCR1 controls IFN gamma signaling in multiple tumor types. Silencing INCR1 decreases the expression of PD-L1, JAK2, and several other IFN gamma-stimulated genes. INCR1 knockdown sensitizes tumor cells to cytotoxic T cell-mediated killing, improving CAR T cell therapy. We discover that PD-L1 and JAK2 transcripts are negatively regulated by binding to HNRNPH1, a nuclear ribonucleoprotein. The primary transcript of INCR1 binds HNRNPH1 to block its inhibitory effects on the neighboring genes PD-L1 and JAK2, enabling their expression. These findings introduce a mechanism of tumor IFN gamma signaling regulation mediated by the lncRNA INCR1 and suggest a therapeutic target for cancer immunotherapy