Immunohistochemical evaluation of tissues following bone implant extraction from upper and lower limb

Fractured bones can regenerate and restore their biological and mechanical properties to the state prior to the damage. In some cases, however, the treatment of fractures requires the use of supportive implants. For bone healing, three processes are essential: the inflammatory phase, the repair phase and the remodelling phase. A proper course of the first - inflammatory - stage is important to ensure a successful fracture healing process. In our study, we evaluated tissue samples immunohistochemically from the area surrounding the fractures of upper and lower limbs (bone tissue, soft tissue, and the implant-adhering tissue) for markers: CD11b, CD15, CD34, CD44, CD68, Cathepsin K, and TRAcP that are linked to the aforementioned phases. In soft tissue, higher expressions of CD68, CD34, CD15 and CD11b markers were observed than in other locations. TRAcP and Cathepsin K markers were more expressed in the bone tissue, while pigmentation, necrosis and calcification were more observed in the implant-adhering tissue. Since even the implant materials commonly perceived as inert elicit the observed inflammatory responses, new surface treatments and materials need to be developed

Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?

Aims. Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. Methods. 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evalu ated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS ≥ 3 and ≥ 4. Results. Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VI RADS ≥ 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS ≥ 4. Based on our results, we consider the optimal cut-off point to be VI-RADS ≥ 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). Conclusions. We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC.Web of Science1671908

Complex tumours genomic and transcriptomic analysis in uterine tumours resembling ovarian sex cord tumours (UTROSCT).

Background & objectives: UTROSCT is a rare entity. Most tumours behave in a benign fashion, but clinically aggressive neoplasms have been described. Our aim was to perform a comprehensive genomic and transcriptomic analysis in a series of UTROSCT to reveal clinically relevant alterations. Methods: DNA and RNA isolated from 30 UTROSCT were analysed using capture DNA NGS analysis (KAPA HyperPlus kit and a panel of 788 genes/gene parts; 2044 kbp; Roche) and transcriptome RNA-Seq (KAPA RNA HyperPrep kit; Roche), and pair-end sequenced on Next- Seq 500 or NovaSeq (Illumina). Only likely pathogenic or pathogenic (class 4/5) mutations and gene fusions were evaluated. Results: The analyses of our sample set revealed the presence of several recurrent gene fusions in the majority of the cases, including NCOA2/3. Moreover, whole transcriptome RNA-Seq revealed additional rare gene fusions such as COL6A3::FAM13B. Other alterations detected included rare class 4/5 mutations in CHEK2 and RECQL4. Conclusion: Our complex study of the molecular alterations in UTRO- SCT has revealed potentially signifcant gene fusions and genetic alter- ations in these tumours, some of which may be clinically actionable

HPV and RAD51 as Prognostic Factors for Survival in Inoperable Oral and Oropharyngeal Cancer in Patients Unfit for Chemotherapy Treated with Hyperfractionated Radiotherapy

Introduction: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway. Objective: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival. Method: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined. Results: Only two types of HPV were identified—HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year (p = 0.083), 5-year (p = 0.159), and overall survival (p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year (p = 0.083) and 5-year (p = 0.159) survival. Conclusion: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant

Sphingosine kinase‑1 predicts overall survival outcomes in non‑small cell lung cancer patients treated with carboplatin and navelbine

International audienc

Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study

Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). ----- Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. ------ Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. ----- Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy