Immunotherapeutic treatment strategies for glioblastoma (GBM) are under investigation in clinical trials. However, our understanding of the immune phenotype of GBM-infiltrating T cells (tumor-infiltrating lymphocytes; TILs) and changes during disease progression is limited. Deeper insight is urgently needed to therapeutically overcome tumor-induced immune exhaustion. We used flow cytometry and cytokine assays to profile TILs and peripheral blood lymphocytes (PBLs) from patients with GBM, comparing newly diagnosed or recurrent GBM to long-term survivors (LTS) and healthy donors. TCR sequencing was performed on paired samples of newly diagnosed and recurrent GBM. We identified a clear immune signature of exhaustion and clonal restriction in the TILs of patients with GBM. Exhaustion of CD8 TILs was defined by an increased prevalence of PD-1, CD39, Tim-3, CD45RO, HLA-DR marker expression, and exhibition of an effector-/transitional memory differentiation phenotype, whereas KLRG1 and CD57 were underrepresented. Immune signatures were similar in primary and recurrent tumors; however, restricted TCR repertoire clonality and a more activated memory phenotype were observed in TILs from recurrent tumors. Moreover, a reduced cytokine response to PHA stimulation in the blood compartment indicates a dysfunctional peripheral T-cell response in patients with GBM. LTS displayed a distinct profile, with abundant naïve and less exhausted CD8 T cells. TILs and PBLs exhibit contrasting immune profiles, with a distinct exhaustion signature present in TILs. While the exhaustion profiles of primary and recurrent GBM are comparable, TCR sequencing demonstrated a contracted repertoire in recurrent GBM, concomitant with an increased frequency of activated memory T cells in recurrent tumors. .

OBJECT Intramedullary spinal cord metastases (ISCM) represent a small proportion of intramedullary tumors. However, with the lifespans of patients with malignant tumors increasing, incidents of ISCM are on the rise. Due to threateningly severe disabilities in patients, accompanied by limited life expectancy, every attempt should be made to treat these tumors the same way as metastases elsewhere in the CNS, with the goal of complete removal of the ISCM and preservation of neurological functions. The object of this study is to retrospectively analyze the experiences of 22 patients who were surgically treated for ISCM over a 22-year period. METHODS Hospital charts of 22 patients, who were surgically treated for ISCM between 1992 and 2014, were reviewed retrospectively. Demographic data, histopathological diagnoses of primary cancer, chronological sequence of the disease, and neurological status using the simplified McCormick functional classification were collected and reanalyzed. RESULTS The most frequent histology was metastasis of lung cancer, followed by brain and breast cancers. The time span from primary cancer diagnosis to the development of symptomatic spinal metastases ranged from 0 to 285 months, with a mean interval of 38 months. The leading presenting sign was dysesthesia (77% of the population), followed by paresis (68%). Only 5 patients (23%) showed urinary retention. Initial performance status represented by the McCormick Scale was on average 2.47. Total or near-total removal was achieved in 87% of cases. Compared with the clinical status 1−2 days after surgery, there was an improvement in the McCormick Scale grade at the last follow-up from 2.47 to 2.12 (p = 0.009). Likewise, an improvement was detected when comparing the preoperative status with the last follow-up (from 2.45 to 2.12; p = 0.029). The mean survival time after surgery was 11.6 months. CONCLUSIONS These results suggest that surgery for intramedullary metastases—with all of the challenges of a rare and potentially risky procedure—can be beneficial to patients with advanced stages of cancer. Surgery can be performed with minimal new morbidity and results in maintaining neurological performance status.

Context Craniopharyngioma is a rare neoplastic entity of the central nervous system. Childhood-onset craniopharyngioma is the subject of frequent research whereas the information on adult-onset craniopharyngioma is scarce. Objective The objective of this study was to examine the level of daily impairment in adult patients suffering from craniopharyngioma. Design Noninterventional patient registry indexed as PV4842 with the local ethics committee. Setting The study is set in a hospitalized and ambulatory setting. Patients 148 patients with adult-onset craniopharyngioma were recruited from 8 centers, 22 prospectively and 126 retrospectively. Mean follow-up was 31 months. Interventions No interventions performed. Main Outcome Measures Complications, symptoms, body mass index (BMI), and quality of life (QoL; EORTC QLQ C30 and BN20) were recorded preoperatively and at follow-up. The hypotheses tested were generated after data collection. Results Complications were more frequent after transcranial than transsphenoidal approaches (31 % vs. 11%; P < 0.01). Preoperative obesity was present in 0% papillary and in 38% of all adamantinomatous craniopharyngiomas (P = 0.05), and diabetes insipidus was more frequent for papillary craniopharyngioma (36.8% vs. 16,7%; P < 0.05). Hormone deficits at follow-up were reduced in 16.9%, equal in 31.4%, and increased in 63.6% (P < 0.001). BMI increased from 28.7 ± 7.4 kg/m2 before surgery to 30.2 ± 7.4 kg/m2 at follow-up (P < 0.001). In QoL, a decrease of future uncertainty (62.5 vs. 36.8; P = 0.02) and visual disorders (38.9 vs. 12.0; P = 0.01) were observed in the prospective collective after surgery. Conclusions Adult craniopharyngioma is associated with a complex sociological and psychological burden and hypothalamic dysfunction, warranting further investigation and emphasizing the need for a wider treatment approach.

ObjectiveOur aim was to identify the impact of different surgical strategies on the incidence of C5 palsy.BackgroundDegenerative cervical spinal stenosis is a steadily increasing morbidity in the ageing population. Postoperative C5 nerve root palsy is a common complication with severe impact on the patients´ quality of life.MethodsWe identified 1708 consecutive patients who underwent cervical decompression surgery due to degenerative changes. The incidence of C5 palsy and surgical parameters including type and level of surgery were recorded to identify predictors for C5 nerve palsy.ResultsThe overall C5 palsy rate was 4.8%, with 18.3% of cases being bilateral. For ACDF alone the palsy rate was low (1.13%), compared to 14.0% of C5 palsy rate after corpectomy. The risk increased with extension of the procedures. Hybrid constructs with corpectomy plus ACDF at C3-6 showed significantly lower rates of C5 palsy (10.7%) than corpectomy of two vertebrae (p = 0.005). Multiple regression analysis identified corpectomy of C4 or C5 as a significant predictor. We observed a lower overall incidence for ventral (4.3%) compared to dorsal (10.9%) approaches (p<0.001). When imaging detected a postoperative shift of the spinal cord at index segment C4/5, palsy rate increased significantly (33.3% vs. 12.5%, p = 0.034).ConclusionsExtended surgical strategies, such as dorsal laminectomies, multilevel corpectomies and procedures with extensive spinal cord shift were shown to display a high risk of C5 palsy. The use of extended procedures should therefore be employed cautiously. Switching to combined surgical methods like ACDF plus corpectomy can reduce the rate of C5 palsy.