Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease.

We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR and TCR) sequences from the blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires were associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation, and counterregulation by the co-receptors BTLA, Tim-3, PD-1, TIGIT, and CD73. Tfh, Th17-like, and nonconventional (but not classical antiviral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.

Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma.

Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors1,2. Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4+ T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.

Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.

The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying glioblastoma phenotypes. We aimed to characterize DNA methylation subclass heterogeneity during progression and assess its clinical impact. Matched tissues from 47 glioblastoma patients were subjected to DNA methylation profiling, including CpG-site alterations, tissue and serum deconvolution, mass spectrometry, and immunoassay. Effects of clinical characteristics on temporal changes and outcomes were studied. Among 47 patients, 8 (17.0%) had non-matching classifications at recurrence. In the remaining 39 cases, 28.2% showed dominant DNA methylation subclass transitions, with 72.7% being a mesenchymal subclass. In general, glioblastomas with a subclass transition showed upregulated metabolic processes. Newly diagnosed glioblastomas with mesenchymal transition displayed increased stem cell-like states and decreased immune components at diagnosis and exhibited elevated immune signatures and cytokine levels in serum. In contrast, tissue of recurrent glioblastomas with mesenchymal transition showed increased immune components but decreased stem cell-like states. Survival analyses revealed comparable outcomes for patients with and without subclass transitions. This study demonstrates a temporal heterogeneity of DNA methylation subclasses in 28.2% of glioblastomas, not impacting patient survival. Changes in cell state composition associated with subclass transition may be crucial for recurrent glioblastoma targeted therapies.

A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups.

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.

Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.

Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models. Rhiz counteracted glioblastoma cell proliferation by inducing apoptosis, G2/M-phase cell cycle arrest, and inhibition of autophagy. Proteomic profiling followed by bioinformatic analysis suggested suppression of the Akt pathway as one of the major biological effects of Rhiz. Suppression of Akt as well as IGF-1R and MEK1/2 kinase was confirmed in Rhiz-treated GBM cells. In addition, Rhiz pretreatment resulted in a more pronounced inhibitory effect of γ-irradiation on the growth of patient-derived glioma-spheres, an effect to which the Akt inhibition may also contribute decisively. In contrast, EGFR upregulation, observed in all GBM neurospheres under Rhiz treatment, was postulated to be a possible sign of incipient resistance. In line with this, combinational therapy with EGFR-targeted tyrosine kinase inhibitors synergistically increased the efficacy of Rhiz resulting in dramatic inhibition of GBM cell viability as well as a significant reduction of neurosphere size in the case of combination with lapatinib. Preliminary in vitro data generated using a parallel artificial membrane permeability (PAMPA) assay suggested that Rhiz cannot cross the blood brain barrier and therefore alternative drug delivery methods should be used in the further in vivo studies. In conclusion, Rhiz is a promising new candidate for the treatment of human glioblastoma, which should be further developed in combination with EGFR inhibitors.

Influence of microbiological diagnosis on the clinical course of spondylodiscitis.

PURPOSE: This study sought to recognize differences in clinical disease manifestations of spondylodiscitis depending on the causative bacterial species. METHODS: We performed an evaluation of all spondylodiscitis cases in our clinic from 2013-2018. 211 patients were included, in whom a causative bacterial pathogen was identified in 80.6% (170/211). We collected the following data; disease complications, comorbidities, laboratory parameters, abscess occurrence, localization of the infection (cervical, thoracic, lumbar, disseminated), length of hospital stay and 30-day mortality rates depending on the causative bacterial species. Differences between bacterial detection in blood culture and intraoperative samples were also recorded. RESULTS: The detection rate of bacterial pathogens through intraoperative sampling was 66.3% and could be increased by the results of the blood cultures to a total of 80.6% (n = 170/211). S. aureus was the most frequently detected pathogen in blood culture and intraoperative specimens and and was isolated in a higher percentage cervically than in other locations of the spine. Bacteremic S. aureus infections were associated with an increased mortality (31.4% vs. overall mortality of 13.7%, p = 0.001), more frequently developing complications, such as shock, pneumonia, and myocardial infarction. Comorbidities, abscesses, length of stay, sex, and laboratory parameters all showed no differences depending on the bacterial species. CONCLUSION: Blood culture significantly improved the diagnostic yield, thus underscoring the need for a structured diagnostic approach. MSSA spondylodiscitis was associated with increased mortality and a higher incidence of complications.

Carbon fiber-reinforced PEEK versus titanium implants: an in vitro comparison of susceptibility artifacts in CT and MR imaging.

Artifacts in computed tomography (CT) and magnetic resonance imaging (MRI) due to titanium implants in spine surgery are known to cause difficulties in follow-up imaging, radiation planning, and precise dose delivery in patients with spinal tumors. Carbon fiber-reinforced polyetheretherketon (CFRP) implants aim to reduce these artifacts. Our aim was to analyze susceptibility artifacts of these implants using a standardized in vitro model. Titanium and CFRP screw-rod phantoms were embedded in 3% agarose gel. Phantoms were scanned with Siemens Somatom AS Open and 3.0-T Siemens Skyra scanners. Regions of interest (ROIs) were plotted and analyzed for CT and MRI at clinically relevant localizations. CT voxel-based imaging analysis showed a significant difference of artifact intensity and central overlay between titanium and CFRP phantoms. For the virtual regions of the spinal canal, titanium implants (ti) presented - 30.7 HU vs. 33.4 HU mean for CFRP (p < 0.001), at the posterior margin of the vertebral body 68.9 HU (ti) vs. 59.8 HU (CFRP) (p < 0.001) and at the anterior part of the vertebral body 201.2 HU (ti) vs. 70.4 HU (CFRP) (p < 0.001), respectively. MRI data was only visually interpreted due to the low sample size and lack of an objective measuring system as Hounsfield units in CT. CT imaging of the phantom with typical implant configuration for thoracic stabilization could demonstrate a significant artifact reduction in CFRP implants compared with titanium implants for evaluation of index structures. Radiolucency with less artifacts provides a better interpretation of follow-up imaging, radiation planning, and more precise dose delivery.

Bacterial adhesion characteristics on implant materials for intervertebral cages: titanium or PEEK for spinal infections?

PURPOSE: Surgical intervention with intercorporal stabilisation in spinal infections is increasingly needed. Our aim was to compare titanium and polyetheretherketon (PEEK) cages according to their adhesion characteristics of different bacteria species in vitro. METHODS: Plates made from PEEK, polished titanium (Ti), two-surface-titanium (TiMe) (n = 2-3) and original PEEK and porous trabecular structured titanium (TiLi) interbody cages (n = 4) were inoculated in different bacterial solutions, S.aureus (MSSA, MRSA), S.epidermidis and E.coli. Growth characteristics were analysed. Biofilms and bacteria were visualised using confocal- and electron microscopy. RESULTS: Quantitative adherence of MSSA, MRSA, S.epidermidis and E.coli to Ti, TiMe and PEEK plates were different, with polished titanium being mainly advantageous over PEEK and TiMe with significantly less counts of colony forming units (CFU) for MRSA after 56 h compared to TiMe and at 72 h compared to PEEK (p = 0.04 and p = 0.005). For MSSA, more adherent bacteria were detected on PEEK than on TiMe at 32 h (p = 0.02). For PEEK and TiLi cages, significant differences were found after 8 and 72 h for S.epidermidis (p = 0.02 and p = 0.008) and after 72 h for MSSA (p = 0.002) with higher bacterial counts on PEEK, whereas E.coli showed more CFU on TiLi than PEEK (p = 0.05). Electron microscopy demonstrated enhanced adhesion in transition areas. CONCLUSION: For S.epidermidis, MSSA and MRSA PEEK cages showed a higher adherence in terms of CFU count, whereas for E.coli PEEK seemed to be advantageous. Electron microscopic visualisation shows that bacteria did not adhere at the titanium mesh structure, but at the border zones of polished material to rougher parts.

Posterior vertebral column resection as a safe procedure leading to solid bone fusion in metastatic epidural spinal cord compression.

OBJECTIVE: Cancer is one of the leading causes of death and greatly decreases a patient's quality of life. Vertebral metastases often lead to epidural spinal cord compression (ESCC) requiring surgical therapy. It has previously been shown that in patients with metastatic ESCC (MESCC), a surgical intervention leads to an improved outcome. Although the treatment paradigms in spinal metastases have changed and separation surgery followed by stereotactic radiosurgery is considered the best strategy, there are still cases in which 360° decompression with stabilization is indicated. In these patients, a proper bone fusion should be the treatment goal to guarantee good clinical results in extended survival times through progressions in oncological therapies. The aim of this study was to examine the safety and feasibility of posterior vertebral column resection (pVCR) in everyday clinical practice, achievement of bone fusion, and midterm outcome in patients with MESCC. METHODS: All patients treated with pVCR due to MESCC between 2013 and 2020 were enrolled in this observational single-center study. Demographics, outcome parameters, numeric rating scale (NRS) score, Frankel grade, and Karnofsky Performance Scale (KPS) score were evaluated. Radiological images routinely acquired during follow-up were reviewed and screened for the presence of bone fusion. RESULTS: Sixty-six patients were treated by eight surgeons. The mean follow-up period was 549 ± 739 days. At baseline, the average age was 64.4 ± 10.9 years. Reported NRS scores (preoperative 6.2 ± 1.7 vs postoperative 3.4 ± 1.6) and segmental kyphosis as measured on sagittal CT images (preoperative 13.5° ± 8.6° vs postoperative 3.8° ± 5.4°) decreased significantly (p < 0.001). In only 2 patients (3%), the Frankel grade worsened postoperatively, whereas in 12 patients (18.2%) an improvement was documented. The KPS score remained constant during the observation period (preoperative 73.2% ± 18.2% vs 78.3% ± 18% at last follow-up). Bone fusion was observed in 26 patients (86.7%) receiving CT more than 100 days after the index surgery. CONCLUSIONS: pVCR is a reliable surgical technique in daily clinical practice, which proves to be beneficial in terms of short- as well as midterm outcome, as judged by the KPS and NRS. The overall improvement in the Frankel grade shows patient safety. A bone fusion was observed regularly in oncological patients undergoing pVCR. The authors therefore conclude that pVCR is a safe, fast, and efficient strategy to achieve stability and pain relief by achievement of bone fusion in cancer patients.

Intraoperative blood loss in oncological spine surgery.

OBJECTIVE: Intraoperative blood loss in patients undergoing oncological spine surgery poses a major challenge for vulnerable patients. The goal of this study was to assess how the surgical procedure, tumor type, and tumor anatomy, as well as anesthesiological parameters, affect intraoperative blood loss in oncological spine surgery and to use this information to generate a short preoperative checklist for spine surgeons and anesthesiologists to identify patients at risk for increased intraoperative blood loss. METHODS: The authors performed a retrospective analysis of 430 oncological patients who underwent spine surgery between 2013 and 2018 at the university medical spine center. Enrolled patients had metastatic tumor of the spine requiring surgical decompression of neural structures and/or stabilization including tumor biopsy using an open, percutaneous, and/or combined dorsoventral approach. Patients requiring vertebro- and kyphoplasty or biopsy only were excluded. Statistical analyses performed included a multiple linear regression analysis. RESULTS: The mean intraoperative blood loss in the study patient cohort was 1176 ± 1209 ml. In total, 33.8% of patients received intraoperative red blood cell transfusions. The statistical analyses showed that tumor histology indicating myeloma, operative procedure length, epidural spinal cord compression (ESCC) score, tumor localization, BMI, and surgical strategy were significantly associated with increased intraoperative blood loss or risk of needing allogeneic blood transfusions. Anesthesiological parameters such as the American Society of Anesthesiologists (ASA) Physical Status classification score were not associated with blood loss. Multiple linear regression analysis demonstrated good predictive value (r = 0.437) for a five-item preoperative checklist to identify patients at risk for high intraoperative blood loss. CONCLUSIONS: The analyses performed in this study demonstrated key factors affecting intraoperative blood loss and showed that a simple preoperative checklist including these factors can be used to identify patients undergoing surgery for metastatic spine tumors who are at risk for increased intraoperative blood loss. ABBREVIATIONS: ABT = allogeneic blood transfusion; ASA = American Society of Anesthesiologists; ESCC = epidural spinal cord compression; KW = Kruskal-Wallis; MET = metabolic equivalent of task; RBC = red blood cell.

CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis.

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.

Clonality of circulating tumor cells in breast cancer brain metastasis patients.

BACKGROUND: The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. METHODS: Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). RESULTS: CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. CONCLUSION: The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment.

Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units and can be assessed by the Richmond Agitation and Sedation Scale (RASS) in principle. However, the role of agitation in patients with aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a retrospective analysis to identify risk factors for the development of a hyperactive delirium and its functional consequences for neurological outcome. Three hundred thirty-eight patients with SAH were screened in this study resulting in 212 patients which reached at least once a RASS of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up. We provide four independent risk factors for the development of agitation in SAH patients. Our study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients.

Optical Barcoding for Single-Clone Tracking to Study Tumor Heterogeneity.

Intratumoral heterogeneity has been identified as one of the strongest drivers of treatment resistance and tumor recurrence. Therefore, investigating the complex clonal architecture of tumors over time has become a major challenge in cancer research. We developed a new fluorescent "optical barcoding" technique that allows fast tracking, identification, and quantification of live cell clones in vitro and in vivo using flow cytometry (FC). We optically barcoded two cell lines derived from malignant glioma, an exemplary heterogeneous brain tumor. In agreement with mathematical combinatorics, we demonstrate that up to 41 clones can unambiguously be marked using six fluorescent proteins and a maximum of three colors per clone. We show that optical barcoding facilitates sensitive, precise, rapid, and inexpensive analysis of clonal composition kinetics of heterogeneous cell populations by FC. We further assessed the quantitative contribution of multiple clones to glioblastoma growth in vivo and we highlight the potential to recover individual viable cell clones by fluorescence-activated cell sorting. In summary, we demonstrate that optical barcoding is a powerful technique for clonal cell tracking in vitro and in vivo, rendering this approach a potent tool for studying the heterogeneity of complex tissues, in particular, cancer.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

Impact of spinal cord compression from intradural and epidural spinal tumors on perioperative symptoms-implications for surgical decision making.

Spinal cord or cauda equina compression (SCC) is an increasing challenge in clinical oncology due to a higher prevalence of long-term cancer survivors. Our aim was to determine the clinical relevance of SCC regarding patient outcome depending on different tumor entities and their anatomical localization (extradural/intradural/intramedullary). We retrospectively analyzed 230 patients surgically treated for SCC. Preoperative status for pain and neurological impairment were correlated to the degree of compression, tumor location, and early as well as short-term follow-up outcome parameters. Interestingly, we did not observe any differences between intradural-extramedullary compared to extradural tumors. Unilaterally localized tumors were likely to present with pain (72.9 %, p < 0.01), whereas concentric growth was associated with motor deficits (41.0 %, p < 0.01, as primary symptom, 49.3 % on admission, p < 0.05). In concentric tumors, the pain pattern was diffuse (40.5 % vs. 17.5 in unilateral disease, p < 0.01), whereas unilateral tumors resulted in localized pain (61.4 % local axial or radicular, p < 0.01). Diffuse pain, patients without a sensory or motor deficit, progressive disease, cervical localization, and a higher degree of stenosis were identified as beneficial for an early improvement in pain (p < 0.05). Notably, 29 % of patients with unchanged pain and 30.8 % with unchanged neurologic function at day 7 postoperative improved during follow-up (p < 0.001). Our data demonstrate that the preoperative tumor anatomy in patients with SCC was closely related to their presenting symptoms and early clinical outcome. The detailed analysis elucidates the biology of SCC and might thereby aid in determining which patients will benefit from surgery.

Cervical vertebroplasty for osteolytic metastases as a minimally invasive therapeutic option in oncological surgery: outcome in 14 cases.

OBJECTIVE The treatment of cervical spinal metastases represents a controversial issue regarding the type, extent, and invasiveness of interventions. In the lumbar and thoracic spine, kypho- and vertebroplasties have been established as minimally invasive procedures for patients with metastases to the vertebral bodies and without neurological deficit. These procedures show good results with respect to pain reduction and low complication rates. However, limited data are available for kypho- and vertebroplasties for cervical spinal metastases. In an effort to add to existing data, the authors here present a case series of 14 patients who were treated for osteolytic metastases of the cervical spine using vertebroplasty alone or in addition to another surgical procedure involving the cervical spine in a palliative setting to reduce pain and restore stability. METHODS Fourteen patients consisting of 8 males and 6 females, with a mean age of 64.7 years (range 44-85 years), were treated with vertebroplasty at the authors' clinic between January 2015 and November 2016. In total, 25 vertebrae were treated with vertebroplasty: 10 C-2, 5 C-3, 2 C-4, 2 C-5, 3 C-6, and 3 C-7. Two patients had an additional posterior stabilization and 5 patients an additional anterior stabilization. In 13 cases, the surgical approach was a modified Smith-Robinson approach; in 1 case, the cement was injected into the corpus axis from posteriorly. Patients with osteolytic defects of the posterior wall of the vertebral body did not undergo surgery, nor did patients with neurological deficits. Preoperatively, on the 2nd day after surgery, and at the follow-up, neck pain was rated using the visual analog scale (VAS). RESULTS Twelve patients were examined at follow-up (mean 9 months). Neck pain was rated as a mean of 6.0 (range 3-8) preoperatively, 2.9 on Day 2 after surgery (range 0-5), and 0.5 at the follow-up (range 0-4), according to the VAS. The mean Neck Disability Index at follow-up was 3.6% (range 0%-18%). CONCLUSIONS Anterior vertebroplasty of the cervical spine via an anterolateral approach represents a safe and minimally invasive procedure with a low complication rate and appears suitable for reducing pain and restoring stability in cases of cervical spinal metastases. Vertebroplasties can be combined with other anterior and posterior operations of the cervical spine and, in the axis vertebra, can be performed transpedicularly from posteriorly. Thus, in cases in which the posterior wall of the vertebral body is intact, vertebroplasty represents a less invasive alternative to vertebral replacement in oncological surgery. Prospective randomized trials with a longer follow-up period and a larger patient cohort are needed to confirm the encouraging results of this case series.

Keyhole approaches to intradural pathologies.

OBJECTIVE Spinal tumors account for 2%-4% of all tumors of the central nervous system and can be intramedullary, intradural extramedullary, or extradural. In the past, wide approaches were used to obtain safe access to these tumors, as complete resection is the goal in treating most tumor entities. To reduce surgical complications due to large skin incisions and destabilizing laminectomies, minimally invasive approaches were established. In this study, the authors share their experience with mini-open approaches to intradural tumor pathologies. METHODS The authors retrospectively reviewed cases involving patients with intramedullary and intradural extramedullary lesions treated between 2009 and 2016. They present their surgical mini-open approach to the spinal cord as well as unique characteristics, key steps, and postsurgical complications for specific tumor subgroups (meningioma, neuroma, and intramedullary tumors). RESULTS A total of 245 intradural tumors were surgically treated during the study period. Of these lesions, 151 were intradural extramedullary meningiomas (n = 79) or neuromas (n = 72). Nine (12.5%) of the neuromas were dumbbell neuromas. Ninety-four tumors were intramedullary. The mean age of the patients was 51.4 years, and 53.9% were female. The mean duration of follow-up was 46.0 months. All meningiomas and neuromas could be resected using a mini-open keyhole approach, but only 5.3% of the intramedullary lesions could be accessed using this technique. Of the 94 patients with intramedullary tumors, 76.6% required a laminotomy, 7.4% required a hemilaminectomy, and 10.6% required a 2-level laminectomy. Only 2 of the patients with intramedullary tumors needed stabilization for progressive cervical kyphosis during follow-up. None of the other patients developed spinal instability after undergoing surgery via the mini-open (keyhole/interlaminar) approach. There were significantly more surgery-associated complications in the large exposure group than in the patients treated with the mini-open approach (19.1% vs 9.6%, p < 0.01). CONCLUSIONS Intradural extramedullary and in selected cases intramedullary pathologies may safely be resected using a mini-open interlaminar approach. Avoiding laminectomy, laminotomy, and even hemilaminectomy preserves spinal stability and significantly reduces comorbidities, while still allowing for complete resection of these tumors.

The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma.

The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 ± 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts.