Tumor recurrence is the main challenge in glioblastoma (GBM) treatment. Gold standard therapy temozolomide (TMZ) is known to induce upregulation of IL8/CXCL2/CXCR2 signaling that promotes tumor progression and angiogenesis. Our aim was to verify the alterations on this signaling pathway in human GBM recurrence and to investigate the impact of TMZ in particular. Furthermore, a combi-therapy of TMZ and CXCR2 antagonization was established to assess the efficacy and tolerability. First, we analyzed 76 matched primary and recurrent GBM samples with regard to various histological aspects with a focus on the role of TMZ treatment and the assessment of predictors of overall survival (OS). Second, the combi-therapy with TMZ and CXCR2-antagonization was evaluated in a syngeneic mouse tumor model with in-depth immunohistological investigations and subsequent gene expression analyses. We observed a significantly decreased infiltration of tumor-associated microglia/macrophages (TAM) in recurrent tumors, while a high TAM infiltration in primary tumors was associated with a reduced OS. Additionally, more patients expressed IL8 in recurrent tumors and TMZ therapy maintained CXCL2 expression. In mice, enhanced anti-tumoral effects were observed after combi-therapy. In conclusion, high TAM infiltration predicts a survival disadvantage, supporting findings of the tumor-promoting phenotype of TAMs. Furthermore, the combination therapy seemed to be promising to overcome CXCR2-mediated resistance.

The spine is one of the organs that is most affected by metastasis in cancer patients. Since the control of primary tumor is continuously improving, treatment of metastases is becoming one of the major challenges to prevent cancer-related death. Due to the anatomical proximity to the spinal cord, local spread of metastasis can directly cause neurological deficits, severely limiting the patient’s quality of life. To investigate the underlying mechanisms and to develop new therapies, preclinical models are required which represent the complexity of the multistep cascade of metastasis. Current research of metastasis focuses on the formation of the premetastatic niche, tumor cell dormancy and the influence and regulating function of the immune system. To unveil whether these influence the organotropism to the spine, spinal models are irreplaceable. Mouse models are one of the most suitable models in oncologic research. Therefore, this review provides an overview of currently used mouse models of spinal metastasis. Furthermore, it discusses technical aspects clarifying to what extend these models can picture key steps of the metastatic process. Finally, it addresses proposals to develop better mouse models in the future and could serve as both basis and stimulus for researchers and clinicians working in this field.

CyberKnife stereotactic radiosurgery (CK-SRS) precisely delivers radiation to intracranial tumors. However, the underlying radiobiological mechanisms at high single doses are not yet fully understood. Here, we established and evaluated the early radiobiological effects of CK-SRS treatment at a single dose of 20 Gy after 15 days of tumor growth in a syngeneic glioblastoma-mouse model. Exact positioning was ensured using a custom-made, non-invasive, and trackable frame. One superimposed target volume for the CK-SRS planning was created from the fused tumor volumes obtained from MRIs prior to irradiation. Dose calculation and delivery were planned using a single-reference CT scan. Six days after irradiation, tumor volumes were measured using MRI scans, and radiobiological effects were assessed using immunofluorescence staining. We found that CK-SRS treatment reduced tumor volume by approximately 75%, impaired cell proliferation, diminished tumor vasculature, and increased immune response. The accuracy of the delivered dose was demonstrated by staining of DNA double-strand breaks in accordance with the planned dose distribution. Overall, we confirmed that our proposed setup enables the precise irradiation of intracranial tumors in mice using only one reference CT and superimposed MRI volumes. Thus, our proposed mouse model for reproducible CK-SRS can be used to investigate radiobiological effects and develop novel therapeutic approaches.

Minimally invasive posterior cervical fixation remains technically challenging due to narrow pedicle dimensions and proximity to neurovascular structures. This multicenter study evaluates the accuracy and safety of a dedicated minimally invasive cervical pedicle screw-rod system with 3D navigation guidance. Can minimally invasive cervical pedicle screw placement achieve accuracy rates comparable to open techniques while maintaining patient safety? Retrospective multicenter analysis of 46 patients (60.7 ± 17.4 years) undergoing percutaneous cervical pedicle screw-rod instrumentation at three German university centers (01/2022–04/2024). Indications included degenerative disease (n = 21), tumors (n = 13), trauma (n = 8), and inflammation (n = 4). Primary outcome was neurological status (Frankel classification); secondary outcomes included screw accuracy (Bredow classification), surgical characteristics, and complications. All procedures utilized 3D navigation based on cone-beam CT or intraoperative CT. In total, 232 pedicle screws were implanted from C2 to T2. Favorable screw position (Bredow grades 1–2) was achieved in 89.7% overall, with significantly lower accuracy at C3–C6 versus other levels (86.0% vs. 95.4%, p = 0.0297). No permanent neurological deficits occurred. Two screws required intraoperative repositioning; zero revision surgeries were needed. Mean surgical duration was 148 ± 66min with blood loss of 236 ± 183 ml. Minimally invasive cervical pedicle screw-rod instrumentation with 3D navigation achieves high accuracy and safety comparable to open techniques. In the majority of cases, the technique supplemented anterior fusion for additional stability, but it may also serve as posterior-only instrumentation for in tumor-related osteolysis or traumatic injuries. Mid-cervical levels remain particularly challenging and require heightened vigilance.

Spine surgery is one of the most frequently performed surgical procedures globally, with increasing numbers particularly among older patients. Sexual function significantly impacts quality of life, yet sexual dysfunction following spine surgery remains underexplored. This systematic review aims to summarize current research on sexual dysfunction following spine surgery, identify knowledge gaps, and clinical implications. A systematic literature search was conducted following the PRISMA-DTA guidelines. Relevant articles were identified utilizing MEDLINE and PubMed database focusing on studies reporting sexual function outcomes after elective spine surgery. Fifteen studies meeting the inclusion criteria were analyzed for study type, sample size, surgical approach, and sexual function outcomes. The majority of studies were retrospective and single-center with small sample sizes. About 62% reported no decline or improvement in sexual function after surgery, while 38% documented a decrease. Surgical approaches and patient populations varied widely. Most studies utilized the Oswestry Disability Index (ODI) to address sexual activity, though its limitations in capturing nuanced sexual dysfunction were noted. Research addressing sexual dysfunction on a deeper level, including psychological and gender-specific sexual health remained scarce. Evidence on sexual dysfunction following spine surgery currently is heterogeneous and limited. There is a critical need for high-quality, prospective, gender-specific research employing comprehensive and validated sexual function assessments. The routine evaluation of sexual function holds the potential to enhance understanding, improve patient counseling, postoperative care, and overall quality of life.