RESUMEN
Aberrant expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) proteins alters human immunoresponse and promotes tumor development and progression. We assessed the expression status of PD-1 and PD-L1 in spinal chordoma tissue specimens and their association with clinicopathological characteristics of patients. Formalin-fixed paraffin-embedded tumor samples from 54 patients with spinal chordoma were collected for immunohistochemical analysis of PD-1 and PD-L1 expression. The association of the expression levels of PD-1 and PD-L1 with clinicopathological variables and survival data were statistically analyzed. Lymphocyte infiltrates were present in all 54 patient samples. Of 54 samples, 37 (68.5%) had both positive PD-1 and PD-L1 expression in tumor cell membrane. Moreover, 38 (70.4%) and 12 (22.2%) had positive PD-1 and PD-L1 expression in tumor-infiltrating lymphocytes (TILs), respectively. Tumors with positive PD-L1 expression were significantly associated with advanced stages of chordoma (p = 0.041) and TIL infiltration (p = 0.005), and had a borderline association with tumor grade (p = 0.051). However, positive tumor PD-L1 expression was not significantly associated with local recurrence-free survival (LRFS) or overall survival (OS). PD-1 expression in TILs was associated with poor LRFS (χ(2) = 10.051, p = 0.002, log-rank test). Multivariate analysis showed that PD-L1 expression only in TILs was an independent predictor for LRFS (HR = 0.298, 95% CI: 0.098-0.907, p = 0.033), and OS (HR = 0.188, 95% CI: 0.051-0.687, p = 0.011) in spinal chordoma patients. In conclusion, PD-L1 expression in TILs was an independent predictor for both LRFS and OS in spinal chordoma patients. Our findings suggest that the PD-1/PD-L1 pathway may be a novel therapeutic target for the immunotherapy of chordoma.
RESUMEN
OBJECTIVE: To report multiple cases and investigate etiology of initially single fungal spondylodiscitis that progressively spread to adjacent segments following lumbar discectomy, resulting in multiple spinal involvements. METHODS: From January 2005 to May 2013, ten adult patients were admitted or referred to our institution with postoperative discitis. Fungal infections were confirmed by microbiologic and pathologic examinations. The clinical appearance, radiographic features, and treatments of this pathology were investigated. RESULTS: All the patients were previously healthy. The average interval between the occurrence of symptoms and primary lumbar discectomy was 61 days (range, 15-120 days). All the patients were treated with anterior surgical debridement, interbody fusion, and prolonged antifungal therapy. Three patients additionally received combined posterior instrumented fusion. Despite aggressive surgical debridement and antifungal therapy, spread of the infections to adjacent multiple discs was observed. No deaths, severe neurologic deficits, or deterioration of neurologic status were noted. The infections were completely resolved in all cases with spontaneous fusion within an average follow-up of 32.4 months. CONCLUSION: Fungal spondylodiscitis after surgery represents an intractable and troublesome complication, and surgical debridement may not impede the progression of the infection in cases where an insufficient course of antifungal treatment is administered. Such cases may require prolonged antifungal treatment with regular consultation by an infectious disease specialist.