Does lumbar spinal decompression or fusion surgery influence outcome parameters in patients with intrathecal morphine treatment for persistent spinal pain syndrome type 2 (PSPS-T2).

OBJECTIVES: Intrathecal morphine pump (ITMP) infusion therapy is efficient in managing chronic pain refractory to standard treatment. This study evaluates pain relief and improvement of quality of life in chronic pain patients after intrathecal morphine pump implantation for treatment of persistent pain after lumbar spinal fusion surgery and lumbar spinal decompression alone. METHODS: Forty three chronic pain patients that received an ITMP at our department between 2009 and 2019 were retrospectively analyzed divided into 2 cohorts (lumbar spinal fusion surgery and lumbar spinal decompression alone). Pain intensity was evaluated using the numeric rating scale (NRS), quality of life was assessed by EQ-5D-3L, mental health was assessed by Beck Depression Inventory (BDI-V), and Pain Catastrophizing Scale (PCS). Morphine dosage was assessed over time. Data was collected preoperatively, 6 and 24 months postoperatively. Statistical analysis was performed using Friedman's analysis of variance to evaluate the development of NRS, PCS, BDI and EQ-5D-3L over time and Mann-Whitney-U-test for the differences between these parameters in the different cohorts. A two-sided p-value <0.05 was considered statistically significant. RESULTS: Median age was 64 years (IQR25-75 56-71 years). NRS, EQ-5D-3L, BDI-V, and PCS showed a significant overall improvement after 6 and 24 months compared to baseline data (p<0.001). No statistically significant differences between patients with lumbar spinal fusion surgery and lumbar spinal decompression alone were seen. Furthermore, no statistically significant differences for age and gender were seen. The initially administered median morphine dosage was significantly higher in the fusion group (3.0 mg/day; IQR25-75 1.5-4.2 mg/day) compared to the decompression-alone group (1.5 mg/day; IQR25-75 1.0-2.6 mg/day); (p=0.027). CONCLUSIONS: This retrospective study showed that ITMP have a major long-term impact on pain relief, improve the quality of life, psychological distress, as well as pain catastrophizing in patients with chronic pain following lumbar spinal surgery independent of the previous surgical procedure. After ITMP implantation initial median morphine dosage seems to be significantly higher after spinal fusion compared to decompressive surgery alone.

ZEB1 induces N-cadherin expression in human glioblastoma and may alter patient survival.

The present study investigated the expression of epithelial-mesenchymal transition (EMT)-related factors zinc finger E-box-binding homeobox 1 (ZEB1), cadherin-1 (CDH1), cadherin-2 (CDH2) and the cell cycle modulating kinase cyclin-dependent kinase 1 (CDK1) in human glioblastoma (GBM) compared to normal brain tissue, as well as whether the levels of expression were associated with the overall and progression-free survival of the GBM patients. In 44 GBM and five normal brain tissue specimens, the expression levels of ZEB1, CDH1, CDH2 and CDK1 were evaluated by real-time PCR and immunostaining, and the results were correlated with clinical data. The expression levels of all investigated genes as detected by immunostaining were significantly higher in the GBM when compared to the normal brain tissues. There was no influence on survival. A linear correlation between ZEB1 and CDH2 and CDK1 expression was observed in GBM. Moreover, ZEB1 was involved in EMT (e.g., signaling in human GBM) and high ZEB1 levels were linked to an aberrant cell cycle processing, marked by CDK1 overexpression.

FGFR3-TACCs3 Fusions and Their Clinical Relevance in Human Glioblastoma.

Oncogenic fusion genes have emerged as successful targets in several malignancies, such as chronic myeloid leukemia and lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein-FGFR3-TACC3 fusion-is prevalent in 3-4% of human glioblastoma. The fusion protein leads to the constitutively activated kinase signaling of FGFR3 and thereby promotes cell proliferation and tumor progression. The subgroup of FGFR3-TACC3 fusion-positive glioblastomas presents with recurrent clinical and histomolecular characteristics, defining a distinctive subtype of IDH-wildtype glioblastoma. This review aims to provide an overview of the available literature on FGFR3-TACC3 fusions in glioblastoma and possible implications for actual clinical practice.

Tumor treating fields therapy is feasible and safe in a 3-year-old patient with diffuse midline glioma H3K27M - a case report.

Since high grade gliomas are aggressive brain tumors, intensive search for new treatment options is ongoing. For adult patients with newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM), low intensity intermediate frequency alternating electric fields, known as tumor treating fields (TTFields) have been established as a new treatment modality. Tumor treating fields significantly increase survival rates in combination with adjuvant temozolomide (TMZ) in adult and GBM patients. Here, we report about feasibility and safety of treatment on a pediatric patient with diffuse midline glioma who is receiving TTFields therapy in combination with temozolomide.

Antiproliferative effect of GTS-21 in glioblastoma cells.

Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. The poor prognosis and short median overall survival of patients with GBM is associated with resistance to therapy after surgical and adjuvant treatment. The expression of various acetylcholine receptors (AChR) in GBM has been widely reported. The present study aimed to investigate the expression of cholinergic system-related genes in primary GBM and to explore the antiproliferative effect of 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21) in GBM cell lines. Therefore, the expression of 28 genes associated with the cholinergic system was detected using a customized RT2 Profiler PCR Array in 44 GBM and 5 healthy control brain tissue samples. In addition, the activity of GTS-21, an alpha 7 subunit nicotinic AChR (α7 nAChR) agonist, and that of α-bungarotoxin (α-BTX), an α7 nAChR antagonist, was determined in primary and established GBM cells. Therefore, the A172, U87 and G28 cell lines and primary GBM cells were treated with GTS-21, ACh or nicotine. Cell viability was evaluated using MTT assay at 24, 48 and 72 h following cell treatment with the corresponding compounds. The results revealed that the expression of cholinergic system-related components was notably downregulated, except that of cholinergic receptor nicotinic alpha 7 subunit (CHRNA7), in primary GBM and U87 cells. However, the dominant-negative duplicate form of CHRNA7 was also downregulated. Furthermore, A172 and G28 cells exhibited a heterogeneous gene expression pattern. Additionally, GTS-21 inhibited the proliferation of GBM cells in a dose- and time-dependent manner. Interestingly, treatment with α-BTX restored the proliferation of U87 cells, but not that of A172 and G28 cells. Collectively, the findings of the present study suggested that GTS-21 may inhibit the proliferation of GBM cells and may therefore serve as a novel therapeutic approach to the treatment of GBM, which warrants further investigation.