OBJECTIVESpontaneous CSF leaks are rare, their diagnosis is often delayed, and they can precipitate meningitis. Craniotomy is the historical “gold standard” repair for these leaks. An endonasal endoscopic approach (EEA) offers potentially less invasiveness and lower surgical morbidity than a traditional craniotomy but must yield the same surgical success. A paucity of data exists studying EEA as the primary management for spontaneous CSF leaks.METHODSThe authors retrospectively reviewed patients undergoing spontaneous CSF rhinorrhea repair at their institution from July 2010 to August 2018. Standardized management includes EEA as first-line treatment, and lumbar puncture (LP) performed 24–48 hours postoperatively. If opening pressure on LP is elevated, CSF diversion or acetazolamide therapy is used as needed. Perioperative lumbar drains are not used.RESULTSOf 46 patients identified, the most common CSF rhinorrhea etiology was encephalocele (28/46, 60.9%), and the most common location was cribriform/ethmoid (26/46, 56.5%). Forty-three patients underwent EEA alone, and 3 underwent a simultaneous EEA/craniotomy. The most common repair strategy was nasoseptal or other pedicled flaps (18/46, 39.1%). Postoperatively, 15 patients (32.6%) received CSF diversion due to elevated ICP, with BMI > 40 kg/m2 being a significant risk factor (odds ratio 4.35, p = 0.033) for postrepair shunt placement. Twelve patients received acetazolamide therapy for treatment of mildly elevated pressures. The average opening pressure of the shunted group was 36 cm H2O and the average for the acetazolamide-only group was 26 cm H2O. Two patients underwent CSF leak repair revision, one because of progressive fungal sinusitis and the other because of recurrent CSF leak. The mean follow-up duration was 15 months.CONCLUSIONSThe paradigm of EEA repair of spontaneous CSF rhinorrhea with postoperative LP to identify undiagnosed idiopathic intracranial hypertension appears to be safe and effective. In the authors’ cohort, morbid obesity was statistically associated with the need for postoperative CSF diversion. This has implications for future surgical treatment as obesity levels continue to rise worldwide.

No abstract

Despite recent advances in cancer therapeutics, glioblastoma (GBM) remains one of the most difficult cancers to treat in both the primary and recurrent settings. GBM presents a unique therapeutic challenge given the immune-privileged environment of the brain and the aggressive nature of the disease. Furthermore, it can change phenotypes throughout the course of disease—switching between mesenchymal, neural, and classic gene signatures, each with specific markers and mechanisms of resistance. Recent advancements in the field of immunotherapy—which utilizes strategies to reenergize or alter the immune system to target cancer—have shown striking results in patients with many types of malignancy. Immune checkpoint inhibitors, adoptive cellular therapy, cellular and peptide vaccines, and other technologies provide clinicians with a vast array of tools to design highly individualized treatment and potential for combination strategies. There are currently over 80 active clinical trials evaluating immunotherapies for GBM, often in combination with standard secondary treatment options including re-resection and anti-angiogenic agents, such as bevacizumab. This review will provide a clinically focused overview of the immune environment present in GBM, which is frequently immunosuppressive and characterized by M2 macrophages, T cell exhaustion, enhanced transforming growth factor-β signaling, and others. We will also outline existing immunotherapeutic strategies, with a special focus on immune checkpoint inhibitors, chimeric antigen receptor therapy, and dendritic cell vaccines. Finally, we will summarize key discoveries in the field and discuss currently active clinical trials, including combination strategies, burgeoning technology like nucleic acid and nanoparticle therapy, and novel anticancer vaccines. This review aims to provide the most updated summary of the field of immunotherapy for GBM and offer both historical perspective and future directions to help inform clinical practice.