fMRI Retinotopic Mapping in Patients with Brain Tumors and Space-occupying Brain Lesions in the Area of the Occipital Lobe

Functional magnetic resonance imaging (fMRI) is a valuable tool in the clinical routine of neurosurgery when planning surgical interventions and assessing the risk of postoperative functional deficits. Here, we examined how the presence of a brain tumor or lesion in the area of the occipital lobe affects the results of fMRI retinotopic mapping. fMRI data were evaluated on a retrospectively selected sample of 12 patients with occipital brain tumors, 7 patients with brain lesions and 19 control subjects. Analyses of the cortical activation, percent signal change, cluster size of the activated voxels and functional connectivity were carried out using Statistical Parametric Mapping (SPM12) and the CONN and Marsbar toolboxes. We found similar but reduced patterns of cortical activation and functional connectivity between the two patient groups compared to a healthy control group. Here, we found that retinotopic organization was well-preserved in the patients and was comparable to that of the age-matched controls. The results also showed that, compared to the tumor patients, the lesion patients showed higher percent signal changes but lower values in the cluster sizes of the activated voxels in the calcarine fissure region. Our results suggest that the lesion patients exhibited results that were more similar to those of the control subjects in terms of the BOLD signal, whereas the extent of the activation was comparable to that of the tumor patients

A Novel Language Paradigm for Intraoperative Language Mapping: Feasibility and Evaluation

(1) Background—Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed an intraoperative language paradigm by combining classical picture naming and verb generation, which safely engaged highly relevant language functions. (2) Methods—An evaluation study investigated whether a single trial of the language task could be performed in less than 4 s in 30 healthy subjects and whether the suggested language paradigm sufficiently pictured the cortical language network using functional magnetic resonance imaging (fMRI) in 12 healthy subjects. In a feasibility study, 24 brain tumor patients conducted the language task during an awake craniotomy. The patients’ neuropsychological outcomes were monitored before and after surgery. (3) Results—The fMRI results in healthy subjects showed activations in a language-associated network around the (left) sylvian fissure. Single language trials could be performed within 4 s. Intraoperatively, all tumor patients showed DCS-induced language errors while conducting the novel language task. Postoperatively, mild neuropsychological impairments appeared compared to the presurgical assessment. (4) Conclusions—These data support the use of a novel language paradigm that safely monitors highly relevant language functions intraoperatively, which can consequently minimize negative postoperative neuropsychological outcomes

Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype

Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system

Does the distance to the cancer center affect psycho-oncological care and emergency visits of patients with IDH wild-type gliomas? A retrospective study

Background Malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas impose a high symptomatic and psychological burden. Wide distances from patients’ homes to cancer centers may affect the delivery of psycho-oncological care. Here, we investigated, in a large brain tumor center with a rural outreach, the initiation of psycho-oncological care depending on spatial distance and impact of psycho-oncological care on emergency visits. Methods Electronic patient charts, the regional tumor registry, and interviews with the primary care physicians were used to investigate clinical data, psycho-oncological care, and emergency unit visits. Interrelations with socio-demographic, clinical, and treatment aspects were investigated using univariable and multivariable binary logistic regression analysis and the Pearson’s Chi-square test. Results Of 491, 229 adult patients of this retrospective cohort fulfilled the inclusion criteria for analysis. During the last three months of their lives, 48.9% received at least one psycho-oncological consultation, and 37.1% visited the emergency unit at least once. The distance from the cancer center did neither affect the initiation of psycho-oncological care nor the rate of emergency unit visits. Receiving psycho-oncological care did not correlate with the frequency of emergency unit visits in the last three months of life. Conclusion We conclude that the distance of IDHwt glioma patients’ homes from their cancer center, even in a rural area, does not significantly influence the rate of psycho-oncological care

Validation Study for Non-Invasive Prediction of IDH Mutation Status in Patients with Glioma Using In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning

The isocitrate dehydrogenase (IDH) mutation status is an indispensable prerequisite for diagnosis of glioma (astrocytoma and oligodendroglioma) according to the WHO classification of brain tumors 2021 and is a potential therapeutic target. Usually, immunohistochemistry followed by sequencing of tumor tissue is performed for this purpose. In clinical routine, however, non-invasive determination of IDH mutation status is desirable in cases where tumor biopsy is not possible and for monitoring neuro-oncological therapies. In a previous publication, we presented reliable prediction of IDH mutation status employing proton magnetic resonance spectroscopy (1H-MRS) on a 3.0 Tesla (T) scanner and machine learning in a prospective cohort of 34 glioma patients. Here, we validated this approach in an independent cohort of 67 patients, for which 1H-MR spectra were acquired at 1.5 T between 2002 and 2007, using the same data analysis approach. Despite different technical conditions, a sensitivity of 82.6% (95% CI, 61.2-95.1%) and a specificity of 72.7% (95% CI, 57.2-85.0%) could be achieved. We concluded that our 1H-MRS based approach can be established in a routine clinical setting with affordable effort and time, independent of technical conditions employed. Therefore, the method provides a non-invasive tool for determining IDH status that is well-applicable in an everyday clinical setting

Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre

Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. Methods and results In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278). Conclusion The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly

Die Rolle von CYLD als Inhibitor des NF-kappa B Signalweges in der Entstehung von kolorektalem Karzinom, hepatozellulärem Karzinom und malignem Melanom

Diese Dissertation befasst sich mit der Rolle des Tumorsuppressorgens CYLD in der Entstehung von kolorektalem Karzinom, hepatozellulärem Karzinom und malignem Melanom. Ein Großteil der Ergebnisse wurde bereits 2007 in �Carcinogenesis� publiziert: �Reduced expression of CYLD in human colon und hepatocellular carcinomas� (Hellerbrand C. et. al., 2007). Ein Funktionsverlust von CYLD konnte erstmalig bei der familiären Variante des Zylindroms nachgewiesen werden (Bignell G.R. et al., 2000). CYLD ist ein Inhibitor des NF-kappa B Signalweges und hemmt die Aktivierung des Transkriptionsfaktors NF-kappa B, der an Immunantwort, Entzündungsgeschehen, Apoptose und Onkogenese beteiligt ist. In allen untersuchten Normalzellen des Kolons, der Leber und in Melanozyten konnte mittels PCR und quantitativer Echtzeit PCR eine deutliche CYLD-Expression auf ganzer Länge des Genes festgestellt werden. Ebenfalls lies sich CYLD auch in jeder Probe einer Normalgewebereihe nachweisen. Die untersuchten Tumorzelllinien aus kolorektalem Karzinom, hepatozellulärem Karzinom und malignem Melanom zeigen eine verminderte CYLD-Expression gegenüber Normalzellen. Hepatozelluläres Karzinomgewebe weist ebenfalls eine geringere CYLD-Expression als Normalgewebe aus demselben Organ auf. Wie in der Literatur beschrieben, konnte in Tumorzelllinien (HCT116, HepG2 und Mel Im) eine erhöhte NF-kappa B Aktivität beobachtet werden. Durch transiente Transfektion mit einem CYLD-Plasmid konnte dosisabhängig eine Senkung der NF-kappa B Aktivität in Reportergen-Assays erreicht werden. Ein Funktionsverlust von CYLD kann daher zu einer erhöhten NF-kappa B Aktivität in Tumorzellen beitragen und die Karzinogenese der untersuchten Tumorentitäten fördern. Damit könnte CYLD zukünftig ein neues therapeutisches Target in der Onkologie darstellen

Reduced expression of CYLD in human colon and hepatocellular carcinomas

CYLD was originally identified as a tumor suppressor that is mutated in familial cylindromatosis. Recent studies suggested a role for CYLD in nuclear factor-kappaB (NF-kappaB) regulation. NF-kappaB activation has been connected with multiple aspects of oncogenesis but the underlying molecular mechanisms of persistent NF-kappaB activation in tumors remain largely unknown. Thus, we evaluated CYLD transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, respectively. CYLD was downregulated or lost in all tumor cell lines investigated as compared with primary human colonic epithelial cells and hepatocytes, respectively. Further, quantitative PCR analysis revealed reduced CYLD mRNA expression in most tumor samples compared with non-tumorous tissue. Analysis on protein level confirmed these findings. Functional assays with CYLD transfected cell lines revealed that CYLD expression decreased NF-kappaB activity. Thus, functional relevant loss of CYLD expression may contribute to tumor development and progression, and may provide a new target for therapeutic strategies

Vignettes as a novel research tool in spiritual care: A methods paper

Aims: To discuss the construction and use of vignettes as a novel approach in spiritual care research and education. Design: Methods paper. Methods: In this methods paper, the authors introduce the use of vignettes in spiritual care research and provide insight into the construction of vignettes. The vignette presented was part of a study of neurosurgical nurses\u27 attitudes and responses to the spiritual needs of neuro-oncology patients. The development process, consisting of four steps, is explained in this paper. Results: Using a vignette to explore nurses\u27 attitudes towards spiritual care is an inno-vative way to understand what behaviours nurses consider appropriate in situations where the patient is seeking meaning and connection. Transparent description of the development process is crucial to ensure reproducibility. Conclusion: The use of theoretically constructed and validated vignettes in spiritual care research is new. Vignettes used in surveys have the potential to elicit nurses\u27 responses to patients\u27 search for meaning and connectedness. Implications: In order to investigate nurses\u27 attitudes and behaviours towards pa-tients\u27 spiritual needs, carefully constructed and validated vignettes are valuable re-search tools. Impact: Vignettes have proven to be a valuable research tool in the social and health sciences. So far, their use as a survey instrument in spiritual care research has not been investigated. Therefore, this method paper introduces vignettes as a novel ap-proach to spiritual care research. Our findings contribute to the further development of vignettes in nursing science, as there are similarities with case development and simulation training in nursing education.Reporting Method: Reporting guideline is not applicable.Patient or Public Contribution: No patient or public contribution

AIDS-Related Central Nervous System Toxoplasmosis With Increased 18F-Fluoroethyl-L-Tyrosine Amino Acid PET Uptake Due to LAT1/2 Expression of Inflammatory Cells

We report the case of a 40-year-old woman with a progressive right-sided hemiparesis. Standard MRI revealed a contrast-enhancing brain lesion within the left basal ganglia. 18Ffluoroethyl-L-tyrosine (18F-FET) PET showed a distinct tracer uptake (lesion-to-brain ratio [LBR]: LBRmax = 2.03, LBRmean = 1.68) with a significant larger metabolic lesion volume than contrast-enhancement in MRI, indicating cerebral glioma. Surprisingly, histopathologic analysis demonstrated central nervous system toxoplasmosis with pronounced inflammatory reaction (reactive astrogliosis, microglia activation, macrophage, and T-lymphocyte infiltration), which was associated with strong LAT1/LAT2/CD98 expression. In conclusion, inflammatory brain lesions, such as cerebral toxoplasmosis, represent a potential pitfall of 18F-FET PET mimicking a brain tumor