In this hospital treatments contains treating diseases of brain, spinal cord diseases, diseases of peripheral nerves, tumors and etcetera. In addition, animal testing can also be performed.
BACKGROUND/AIMS:To explore the feasibility and effectiveness of Tumor Destructive Mechanical Impulse (TMI) treatment of solid tumors, biomechanical preconditions for subsequent computational simulation of focused shock wave propagation within cells and tissue are investigated. This innovative "soft" approach is different from the FDA-approved high intensity focused ultrasound (HIFU)-based histotripsy, and from electrical Tumor Treating Fields (TTFs). METHODS:Atomic force microscopy investigation for cell mechanics, multiple parametric computational simulations for focused shock wave propagation, technical TMI generator and applicator design, light- and electron-microscopic evaluation of treatment effects on tumor cells and tissue. RESULTS:Individual tumor cell evaluation of physical properties as basis for multiple parametric simulations determine the optimal treatment parameters (total energy required, energy flux density, shock wave frequency) and applicator positions; design flexibility of applicator devices for extra- and intracorporeal treatment. CONCLUSION:The fundamental feasibility, effectiveness and reliability of TMI treatment of solid tumors were proven, providing a reliable theoretical basis for the broadly applicable translation into clinical practice.
BACKGROUND/AIMS:Bone metastases are a frequent and highly debilitating complication of advanced malignancies and are associated with severe pain, structural instability and loss of functional capacity. Radiotherapy, systemic antineoplastic therapy, bone-targeted agents and interventional techniques remain the clinical standard, yet a relevant proportion of patients experience only incomplete or transient pain relief. Non-invasive focal approaches are therefore being explored. Tumor-destructive mechanical impulses (TMI) - an umbrella term for shock-type, high-strain acoustic pulses generated by electrohydraulic, electromagnetic or piezoelectric systems - have a long safety record in musculoskeletal medicine and are increasingly investigated in oncology. We report the palliative use of TMI in patients with painful bone metastases. METHODS:Patient-specific DICOM data were segmented using Simpleware ScanIP® and imported into ANSYS SpaceClaim for geometry preparation, enabling coupled device-tissue simulations under clinical pressure wave forms; the resulting anatomical models were simulated in ANSYS Explicit Dynamics. In parallel, DICOM data were processed using MATLAB®/TABLIN and converted into OnScale® for high-frequency pressure wave propagation analysis, predicting pressure fields, focal volumes and attenuation through bone. The outputs of the numerical solution of the finite element (FEM) propagation models comprise total energy, energy flux density, pulse count and frequency, and the optimal placement of the TMI applicator. TMI was applied within individual healing attempts in patients in whom conventional therapy had failed. RESULTS:In two patients with metastatic prostate carcinoma described in detail, and in thirteen further patients with bone metastases, TMI applied to metastatic bone lesions was followed by relief of periosteal pain. In both index patients, follow-up Ga-68-PSMA PET-CT showed marked regression of the osseous lesions. Treatments were tolerated without device-related complications; in one patient the piezoelectric technique was not tolerated and was replaced by the electrohydraulic technique. CONCLUSION:TMI treatment combines direct mechanotransduction with controlled cavitation, potentially disrupting tumor cells and microvasculature and inducing features of immunogenic cell death. In the patients reported here, palliative TMI treatment was associated with pain relief and radiographic tumor regression, including observations compatible with a possible immunological abscopal response. These observations derive from uncontrolled individual healing attempts under concomitant systemic therapy and require prospective confirmation.
Vestibular schwannoma (VS) is a benign tumor growing from Schwann cells of the vestibulocochlear nerve (cranial nerve VIII), accounting for 6-8% of brain tumors. Cystic vestibular schwannoma (cVS) represents 10% of VS cases and is characterized by unpredictable growth and worse surgical outcomes compared to solid VS (sVS). The molecular mechanisms underlying this aggressive phenotype remain poorly understood. In this context, long non-coding RNAs (lncRNAs) are gaining increased interest as biomarkers for early diagnosis and improved clinical management. lncRNAs are RNA molecules that are longer than 200 nucleotides. They are known to regulate gene transcription and participate in chromatin remodeling through various mechanisms. However, their role in cVS is largely unexplored. In this study, we identified cVS-associated lncRNAs using patient-derived samples. Whole transcriptome analysis via RNA sequencing revealed 65 differentially expressed lncRNAs and 308 protein-coding genes (PCGs) between cVS and sVS. From these, we selected the top eight lncRNAs (TENM3-AS1, ADIRF-AS1, PCA3, RP11-108K14.12, RP11-728F11.4, AC132217.4, RP11-43F13.3, and EGFLAM-AS1), each showing significant correlation with more than 20 differentially expressed PCGs. The upregulation of PCA3 and ADIRF-AS1, and the downregulation of EGFLAM-AS1 in cVS, were further validated using qRT-PCR. Here, by transcriptome-wide approach, we demonstrate that lncRNAs are prevalent in cVS disease and are likely to play critical roles in regulating important signaling pathways involved in disease pathogenesis. We believe, that detailed future investigations on this set of identified lncRNAs can provide useful insights into the biology and, ultimately, contribute to biomarker development for this neoplasm.
Purpose Meningiomas (MNGs) occur in different histopathological subtypes. The WHO grading system classifies a subset as grade 2 and 3, indicating a more aggressive course. Recent advances in risk stratification introduces an integrated molecular-morphological score (IntS), offering improved risk prediction over the traditional WHO classification. This study aims to evaluate the prognostic utility of IntS in the context of the timing of adjuvant radiotherapy (RT). Methods This retrospective study analyzed 55 patients with histologically diagnosed WHO grade 2 and 3 MNG treated with adjuvant RT. Molecular analyses using Illumina 450k Human BeadChip and Illumina 850k EPIC stratified patients into 3 risk groups (low, intermediate and high) using an integrated model that combines WHO grading, Copy Number Variations (CNVs), and Methylation Families (MF). Results After 5 years a local failure-free survival (LFFS) rate of 0% in MF-malignant MNG contrasts with a LFFS rate of 77% and 58% in MF-benign and MF-intermediate MNG. A significant correlation between CNVs and LFFS was also observed in the adjuvant setting. The IntS model revealed distinct 5-year LFFS disparities across different risk categories, underscoring the impact of combined morphological and molecular characteristics on outcome. Conclusion The integration of DNA-methylation and CNV-profiles into the IntS unified risk score offer an enhanced prognostic differentiation of MNG patients. This approach shows a promising direction for guiding the optimal timing of adjuvant RT, offering a path toward more tailored treatment strategies for meningiomas.
BACKGROUND:Image-guided pedicle screw placement improves accuracy over fluoroscopy, but level-specific performance and independent predictors in routine care remain incompletely defined. This study aims to compare intraoperative computed tomography (iCT)-navigated vs fluoroscopy-assisted (FA) lumbar screw placement, while quantifying level-specific performance and exploring independent predictors of optimal (grade A) placement. METHODS:We performed a single-center retrospective, noncontemporaneous cohort study of 229 adults who underwent primary lumbar pedicle screw fixation, including 131 iCT navigated and 98 FA. In total, 1304 lumbar screws were graded on postoperative computed tomography (CT) using the Gertzbein-Robbins scale. Mixed-effects logistic regression estimated odds of Grade A placement with fixed effects for technique, pathology, level, side, and age. RESULTS:iCT was associated with higher accuracy than FA (grade A 97% vs 86%), with no grade C breaches under iCT (vs 2% with FA). The advantage was level dependent and most pronounced at L5 (grade A 97.3%-98.2% with iCT vs 79.3%-85.7% with FA); additional statistically significant differences favored iCT at L2 left, L3 left, and L4 left, while L3 right showed a nonsignificant trend. In adjusted analyses, FA was associated with markedly lower odds of grade A placement. Trauma was independently associated with a reduced likelihood of grade A placement, whereas revision surgery served as the reference category and was not an independent predictor; age, level, and side were not independent predictors. CONCLUSIONS:In this retrospective cohort, iCT navigation was associated with superior radiographic accuracy compared with fluoroscopy and higher rates of optimal screw placement. Traumatic pathology was associated with lower odds of optimal placement. CLINICAL RELEVANCE:iCT-based navigation was associated with an increased likelihood of achieving optimal (Gertzbein-Robbins grade A) lumbar pedicle screw placement compared with fluoroscopy in routine clinical practice. The advantage appears particularly pronounced at L5 and in anatomically challenging scenarios. However, these findings are based on radiographic accuracy only and should be interpreted cautiously, as no direct conclusions on clinical outcomes or complication reduction can be drawn. LEVEL OF EVIDENCE: 3:
