RESUMEN
OBJECTIVE: Endoscopic repair of skull base defects is required following resection of intracranial pathology via the endoscopic endonasal approach (EEA). Many closure techniques have been described, but choosing between techniques remains controversial. We report outcomes of 560 EEA procedures of skull base reconstruction performed on 508 patients over a 15-year-period. Halfway through this period, we adopted the use of a rigid, bioabsorbable extrasellar plate for reconstruction, enabling a comparison between this technique and those used previously. METHODS: All patients undergoing EEA from 2005 to 2019 at our institution were retrospectively reviewed. Demographic information, surgical pathology, tumor dimensions and radiographic features, reconstructive technique, and patient-related outcomes were collected and analyzed with univariate and multivariate statistical modeling. RESULTS: Five-hundred sixty procedures were performed on 508 patients. The series complication rate was 8.2%. Overall, cerebrospinal fluid (CSF) leak rate was 5.0% but varied significantly across closure techniques (p < 0.001). Critically, the CSF leak rate in the 272 cases prior to our 2013 adoption of the Resorb-X Plate (RXP) was 8.5%, whereas leak rate in the subsequent 288 cases was 1.7%. RXP was protective against CSF leak (p = 0.001), whereas gross total resection (GTR) correlated with increased leak rate (p = 0.001). Patient BMI was significantly associated with risk of leak (p = 0.047). Other variables did not impact leak risk. CONCLUSION: Reconstructive technique, extent of resection, and patient BMI significantly contributed to CSF leak rate. GTR was associated with increased leak risk while the RXP was protective. The bioabsorbable RXP is an effective option for rigid skull base repair with comparatively few complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1092-1098, 2023.
Asunto(s)
Procedimientos de Cirugía Plástica , Neoplasias de la Base del Cráneo , Humanos , Colgajos Quirúrgicos/cirugía , Neoplasias de la Base del Cráneo/patología , Estudios Retrospectivos , Implantes Absorbibles , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Endoscopía/métodos , Base del Cráneo/cirugía , Base del Cráneo/patología , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/cirugíaRESUMEN
BACKGROUND: Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an "abscopal effect," whereby unirradiated neoplastic cells outside treatment sites are recognized and attacked by the immune system. Radiation combined with anti-programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma clinical trials, but the mechanism and relevance of the abscopal effect during this response remain unknown. METHODS: We modified an immune-competent, genetically driven mouse glioma model (forced platelet derived growth factor [PDGF] expressionâ +â phosphatase and tensin homolog loss) where a portion of the tumor burden is irradiated (PDGF) and another unirradiated luciferase-expressing tumor (PDGFâ +â luciferase) is used as a readout of the abscopal effect following systemic anti-PD-L1 immunotherapy. We assessed relevance of tumor neoepitope during the abscopal response by inducing expression of epidermal growth factor receptor variant III (EGFRvIII) (PDGFâ +â EGFRvIII). Statistical tests were two-sided. RESULTS: Following radiation of one lesion, anti-PD-L1 immunotherapy enhanced the abscopal response to the unirradiated lesion. In PDGF-driven gliomas without tumor neoepitope (PDGFâ +â luciferase, n =â 8), the abscopal response occurred via anti-PD-L1 driven, extracellular signal-regulated kinase-mediated, bone marrow-derived macrophage phagocytosis of adjacent unirradiated tumor cells, with modest survival implications (median survival 41 days vs radiation alone 37.5 days, Pâ =â 0.03). In PDGF-driven gliomas with tumor neoepitope (PDGFâ +â EGFRvIII, n =â 8), anti-PD-L1 enhanced abscopal response was associated with macrophage and T-cell infiltration and increased survival benefit (median survival 36 days vs radiation alone 28 days, Pâ =â 0.001). CONCLUSION: Our results indicate that anti-PD-L1 immunotherapy enhances a radiation- induced abscopal response via canonical T-cell activation and direct macrophage activation in glioblastoma.